The anti-inflammatory actions of tilorone hydrochloride. Tilorone suppressed inflammation induced by immune (direct passive Arthus reaction) as well as by non-immune agents (carrageenam-induced paw edema and abscess formation), if the compound is given 24 hr prior to the proinflammatory agonists. The non-immune anti-inflammatory effect is independent of the adrenals. A surprising findings was that total serum hemolytic complement is markedly elevated 24 hr after a single dose of tilorone.


Transmission of Creutzfeldt-Jakob disease to the stumptail macaque (Macaca arctoides). The successful transmission of Creutzfeldt-Jakob disease from both affected human and chimpanzee brain to stumptail macaques has been accomplished. The incubation period of 5 yr was the same for both animals; however, the course of the disease was longer in the animal receiving the human brain. In both cases, initial mild symptoms slowly remitted only to reappear some 4 mo later. Muscle biopsies revealed changes suggestive of a mild neuropathy. In addition, there appeared to be an increased ability to incorporate 3H-thymidine in untreated cultures of lymphocytes from peripheral blood.


Dichloroacetate-induced changes in liver of normal and diabetic rats. Dichloroacetate (DCA) was administered orally to normal (nondiabetic) and streptozotocin-diabetic rats in a dose of 1000 mg/day/kg rat wt. One group of diabetic animals received DCA both orally and intraperitoneally. DCA therapy lowered the blood glucose values of diabetic animals but did not alter values in nondiabetic rats. The hepatic activity of glucokinase and pyruvate kinase were significantly lower in both DCA-treated nondiabetic and DCA-treated diabetic animals than values observed for untreated animals. However, DCA therapy was accompanied by remarkable increases in the activities of glucose-6-phosphate dehydrogenase and malic enzyme in both nondiabetic and diabetic animals. Glucose-6-phosphate dehydrogenase was 3-fold higher in DCA-treated nondiabetic animals whereas malic enzyme activity was 10-fold higher in the treated animals than observed in the untreated animals. Similar changes, although smaller in magnitude, were observed for these enzymes in the DCA-treated diabetic animals. Although DCA therapy was accompanied by a significant increase in the wet weights of the liver for both nondiabetic and diabetic animals, no morphological changes were seen by light or electron microscopy. Our observations coupled with those of previous investigators suggest that DCA therapy may have an important role in pyruvate metabolism and may lower the blood glucose concentration by inhibiting hepatic gluconeogenesis.


Hyperthermia induced by amphetamine, p-chloroamphetamine and fenfluramine in the rat-1. Hyperthemia was elicited in rats by the subcutaneous injection of 4 mg/kg (+)-amphetamine, 4 mg/kg (+)-p-chloroamphetamine, or 8 mg/kg fenfluramine. This hyperthermia could be abolished by oral pretreatment with 300 mg/kg p-chlorophenylalanine. Cyproheptadine, at a dose of 0.05 mg/kg, completely inhibited the response induced by p-chloroamphetamine, but a dose of 0.4 mg/kg was necessary in the case of amphetamine and fenfluramine. Protection against hyperthermia by p-chloroamphetamine was also provided by chloroimipramine. Hypothalamic turnover of 5-HT was enhanced by all three amphetamines. alpha-Methyltyrosine and disulfiram had no effect on the hyperthemia induced by the amphetamines, FLA-63 seemed even to enhance it. Haloperidol, in the dose range of 0.1 -0.4 mg/kg, attenuated the hyperthermia induced by amphetamine and p-chloroamphetamine, but not that induced by fenfluramine. The results point to a central origin of the hyperthemia induced by amphetamine, p-chloroamphetamine and fenfluramine. In the mediation of this effect, 5-HT and, to a lesser degree, dopamine seem to play an important role.


Expanded role for the physical therapist. Screening musculoskeletal disorders. The primary purpose of this study conducted at two army hospitals was to evaluate the feasibility of using the physical therapist as the primary 'screener' for patients presenting with a complaint of low back pain. The study was organized into two phases. A base line phase consisted of a data collection period under standard operating conditions. Patient waiting times, treatment times, and total care times were measured for patients presenting to various clinics with a complaint of low back pain. The same data were collected during a screeing phase in which all patients presenting with a complaint of low back pain were referred directly to the physical therapist for primary evaluation. An assessment of physical therapist and patient satisfaction and acceptance was made. The quality of care rendered in the screeing clinic was assessed through patient interviews, physician interviews, and record reviews. This concept and the quality of care rendered were found to be acceptable to the patient, the physician, and the physical therapist.


The changes of thyroglobulin in the lysosomal particles of thyroid during the postnatal period in rats. The distribution of radioactivity and protein-SH groups was studied in neonatal rats injected with 125-I- in the 15,000 g pellets of thyroid glands to obtain information about the colloid which undergoes phagocytosis by lysosomes. The 15,000 g pellet was solubilized in Triton X--100. The soluble portion was enhanced on the 16th day of age, whereas the portion of the insoluble fraction remained almost unchanged. The content of protein-SH groups in the insoluble fraction decreased with age and was increased in the soluble fraction. The concentration of immunoreactive thyroid stimulating hormone (TSH) in the pituitary and in the blood of rats during ontogenesis was higher on the first day after delivery, then decreased within the first seven days and again markedly increased during the third postnatal week. It was concluded that higher amounts of Triton soluble thyroglobulin occurring during the postnatal period in rats reflects the availability of more substrate, i.e. thyroglobulin for pinocytosis and partially depends upon the TSH level. These findings also support the suggestion on maturation of the pituitary-thyroid system during the postnatal period in rats.


Eelectrophysiological correlates of pecking. Electrophysiological correlates of pecking were studied in 50 freely moving pigeons. With the backward averaging technique average motor potentials (AMPs) were found in all subdivisions of the striatum. The AMPs appeared significantly earlier (40 msec before pecking) in the Wulst than in the neostriatum, ectostriatum, and archistriatum (18 to 28 msec before pecking). Their amplitude could be reduced by monocular occlusion. Average visual responses (AVRs) in the optic tectum were decreased at brief peck-flash intervals, reached maximum with 100 to 200 msec peck-flash delays and then again decreased at intervals corresponding to the occurrence of the next peck (300 msec). A head-mounted microdive system and a miniature FET probe were employed to record unit activity with glass microelectrodes. Out of 280 examined neurones, 83% were activated and 6% inhibited by pecking. The pre- and post-pecking histograms indicated that hyperstriatal neurones are activated earlier and for a longer time than the neostriatal units. It is concluded that rostral parts of striatum play an important role in the functional organisation of pecking.


Septal rage: mitigation by pre-surgical treatment with p-chlorophenylalamine. Destruction of the septum leads to a well known hyperirritability syndrome. However, the intensity of this syndrome is modifiable by certain presurgical treatments. Injections, prior to surgery of para-chlorophenylalanine (PCPA) for two days or insulin for five days has no effect on septal rage. However, injections of PCPA five days prior to surgery leads to a marked reduction in septal hyperirritability.


Effect of foreign innervation on contractile and histochemical properties of the transplanted levator ani muscle of the rat. Heterotopic transplantation of the levator ani (LA) muscle into the bed of the fast tibialis anterior (TA) or slow soleus (SOL) muscle respectively results in transformation of contractile and histochemical properties of the muscle dependent on the new "foreign" innervation. This transformation is observed after transplantation of minced muscle tissue and of free grafts. The result of transformation is more pronounced in the case of free LA-TA grafts which show progressive shortening of contractile response, whereas the LA-SOL shows slight shortening. The heterotopically transplanted free LA-SOL and the LA-TA grafts become relatively faster than the respective original muscle, suggesting operation of myogenic factors related to the fast LA muscle. Maximal tetanic tension output of the free heterotopic grafts 60 days after transplantation recovers to only about a quarter of the correspondong control muscles. Recovery of speed of contraction in the transplanted LA muscle is similar to that observed after selfreinnervation after crushing the pudendal nerve close to its entry into the muscle. In the heterotopically transplanted muscles the reversal of the originally uniform histochemical fibre pattern to a mixed fibre pattern in respect to ATPase and SDH activity is dependent on the type of innervation. After selfreinnervation of the LA muscle by the pudendal nerve a uniform fibre pattern is maintained with regeneration of the nerve.


Inhibition of thyroxine binding to adenohypophysial proteins in vitro by 2,4-dinitrophenol administered in vivo. Male and female rats were given oestradiol benzoate (1 mg as a microcrystal aqueous suspension i.m. twice a week), 0.0033% 2.4-dinitrophenol (DNP) in their food (about 1 mg/rat/day), or 0.1% DNP in their food (about 30 mg/rat/day), or both oestradiol and DNP. The smaller DNP dose mildly stimulated food consumption and did not affect body weight. The larger dose strongly inhibited food consumption in the first two weeks of the experiment; consumption then returned to the control level, but body weight fell markedly at the same time. After 3 weeks' administration of both the small and the large dose of DNP, adrenal weight in the males was raised and the weight of the gonads was unchanged. The large DNP dose severely reduced the weight of the seminal vesicles and the uteri. It also inhibited the accumulation of radioiodine in the thyroid of both males and females. Isolated administration of the oestrogen raised adrenal weight in the males and ovarian and uterine weight in the females; it reduced the weight of the testes and seminal vesicles. These reactions were not affected by DNP. A pronounced oestradiol-induced increase in the weight of the adenohypophyses was accompanied by raised thyroxine binding to the adenohypophysial proteins in vitro. DNP inhibited the growth reaction of the adenohypophysis to the oestrogen only slightly and non-significantly, but significantly inhibited the thyroxine binding reaction to the adenohypophysial proteins in vitro. By itself, DNP had no effect on adenohypophysial weight, but reduced thyroxine binding to the adenohypophysial proteins in vitro, especially in males. The effect of DNP was similar to that of thyroxine observed in earlier experiments; nothing is known of its mechanism.


Cardiovascular, respiratory and glottic effects of sodium salicylate administered into different parts of the circulation in rabbits. The authors studied the effect of sodium salicylate administered into different parts of the circulatory system on various cardiovascular, respiratory and glottic parameters in Pentobarbital-anaesthetized rabbits. The results show that apnoea, bradycardia and hypotension, followed by hypertension, can also be caused by the extrathoracic action of salicylate. Cardiovascular responses induced by injecting salicylate into the carotid circulation are qualitatively the same, even after vagotomy, as in injection into the femoral vein. Salicylate injected into the common carotid artery, the internal carotid artery or the femoral vein causes inspiratory apnoea in rabbits, with powerful electrical activity of the diaphragm and an intrapleural pressure shift to marked inspiratory values. Laryngoconstriction occurs simultaneously, despite inspiratory apnoea. The injection of salicylate into the common carotid artery after bilateral vagotomy induces expiratory (not inspiratory) apnoea, indicating that the vagi play an important role in the origination of inspiratory apnoea in rabbits.


An attempt to characterize certain parameters of the radiorenographic curve in children with intact kidneys and urine passages. The authors evaluated 48 curves for the right and left kidney of 24 children free from any disorder of the uropoietic system, in whom radiorenography formed part of a general examination. In the recordings they evaluated the "secretory" (ta) and "excretory" (td) parts of the curves and percentual differences in the recordings for times ta and td and at 5, 10 and 15 minutes. The percentual differences in the curves were compared with the findings in a group of 64 children with cystopyelonephritis. Times ta and td for the whole group of investigated children were normal. Percentual differences between the curves for the right and left kidney were significantly smaller in the "healthy" group than in the children with cystopyelonephritis. Comparison of the results in the two groups showed that the differences were statiscally significant or highly significant. The drop in the recordings at 5, 10 and 15 minutes corresponded to the normal findings in adults.


Radioprotective and toxic effects of a mixture of AET and 5-methoxytryptamine in mice. The authors studied the radioprotective efficacy and toxicity of an AET + 5-methoxytryptamine mixture and its effect on the course of respiratory exchange, using different weight ratios of the two components. The optomum was found to be 150 mg AET/kg b.w + 25 mg 5-MOT/kg b.w. This mixture gave very good protection in the supralethal exposure range and markedly prolonged its duration. The high toxicity of this mixture was abolished by the pre-administration of glutathione. Raised and longer protection was also manifested in the course of respiratory exchange, showing that an association exists between changes in energy metabolism and raised radioresistance of the organism.


Effect of sex and season on the production and deposition of lipid and glycid reserves in the intermittently starving golden hamster. In golden hamster adapted to intermittent starvation (with access to food for 3 days a week only), the glycogen and lipid content of the liver, total body fat and RQ values measured in vivo were investigated. These parameters were studied in dependence on the duration of the adaptation period (6 weeks versus 20 weeks), season of the year (winter versus summer) and sex. The liver glycogen content in intermittently starved males and females increases after 6 weeks of adaptation during winter. In summer an increase was found after long-term adaptation, but only in males. Male hamsters also exhibited a higher ability to accumulate liver lipids during both seasons. In spite of their lower weight intermittently starving males have a higher percentage of body fat in comparison with females, a stimulating effect being observed in winter. Increased lipogenesis in golden hamsters adapted to intermittent starvation may be concluded from the increased RQ values when compared with relative data gained in controls fed daily ad libitum. Significant differences between RQ measurements according to season and sex were not found.


Maternal milk intake by infant rats temporarily denied acces to other food sources. The onset of the weaning period for infant rats was artificially postponed to the 24th day of life by denying the young access to solid food and/or water. Study of 85-Sr transfer in the maternal milk showed that the artificial shift in the initiation of weaning did not influence the time of its termination. The weaning period, defined as the time between the first intake of solid food and the last intake of maternal milk, was shortened to about 4 days in these young. We also found that the young did not compensate the lack of solid food by a higher maternal milk intake, but that they tried to do so by drinking more water.


The ability of collecting veins to sustain sympathetic constriction. The collecting femoral vein is capable of sustaining contraction even for 15 minutes provided sympathetic stimulation frequency is low or moderate. At a frequency of 15 Hz, however, the collecting vein gradually relaxes after having reached a maximum contraction in spite of continuing stimulation. The ability of the relaxing venous smooth muscle to develop further contraction to exogenous noradrenaline has been proved. It seems probable that the relaxation is due to the decline in the amount of transmitter released from nerve terminals as a result of prolonged high rate stimulation.


Effect of brain, liver and muscle cytosols on in vitro incorporation of labelled amino acids into the ribosomes of these organs during protein depletion. The functional state of the rat liver, brain and muscle proteosynthetic apparatus during developing protein depletion was studied, with special reference to the effect of brain cytosols on the synthetic capacity of liver and muscle ribosomes. The results indicate that both stimulant and inhibitory agents (so far unidentified) may be present in brain cytosols during protein depletion.


Effect of glucose on the utilization of palmitate 1 14C by rat kidney cortex slices. The authors studied the effect of glucose on the uptake and utilization of palmitate 1 14C by rat kidney cortex slices. They found that its inhibitory effect on free fatty acid (FFA) uptake was caused by inhibition of the incorporation of 1 14C-labelled palmitate into the total lipids and FFA and by reduced oxidation to 14CO2. Glucose has a regulative function in the utilization of FFA by the kidneys.


Effect of antiandrogen cyproterone acetate on the action of testosterone on mouse kidney. The loss of endogenous testosterone in castrated male mice leads to a marked decrease in seminal vesicle and kidney tissue weight. 21 days' administration of exogenous testosterone abolished the effect of castration on the seminal vesicles and kidney tissue. The antiandrogen cyproterone acetate produced significant changes in the target tissue for androgens, i.e. in the seminal vesicles. In every case it blocked the action of both exogenous and endogenous testosterone on the seminal vesicles, but failed to block the "renotropic" action of testosterone, expressed as relative kidney weight. Contrary to its effect on the seminal vesicles, it did not influence relative kidney weight in normal animals. It likewise did not block the effect of exogenous testosterone on kidney tissue. The mechanism of the action of cyproterone acetate in androgen-dependent tissues is known to consist in inhibition of androgen binding to specific cell receptors in the target tissues. Some of the specific androgen receptors in mouse kidney are evidently different in character from those in the accessary sex glands, that being the reason why cyproterone acetate has an antiandrogenic, but not an antirenotropic effect. In agreement with experiments on rats, adrenal weight also decreases in mice after the administration of cyproterone acetate.


The expiration reflex in man.

The expiration reflex in man. After anaesthetizing the oral, pharyngeal and epiglottal mucosa, the authors stimulated the vocal folds mechanically with a nylon fibre, by means of indirect laryngoscopy, in 58 human subjects. They found that stimulation of the vocal folds also produced in man the same typical expiratory reaction, not preceded by inspiration, which they previously observed in experimental animals.


The expiration reflex in the mouse.

The expiration reflex in the mouse. The authors determined the elicitability of the expiration reflex and the mechanoreceptive sensitivity of the respiratory tract in 35 anaesthetized albino mice. They found that the expiration reflex could be elicited from both the oral and the tracheal end and that its intensity was statistically significantly higher in elicitation from the oral end. The only other pronounced respiratory reflexes evoked by mechanical stimulation of the airways were the sneeze reflex and the aspiration reflex, which is present in most animals. The mechanoreceptors of the tracheal and bronchial mucosa were less sensitive to stimulation. In most cases they did not react at all, or with just a single forced inspiration, and at other times only by a change in respiration frequency and amplitude.


The expiration reflex during ontogenesis in the rat. The authors studied the elicitability of the expiration and aspiration reflex and of the respiratory reaction from the tracheobronchial area in 131 anaesthetized rats (aged 1-15 days, adult and biologically old). They found that the expiration reflex could be elicited, in the rat, from the first day of life, at a time when other respiratory reflexes were not yet stable. In young rats, the expiration reflex was often followed by a cough reaction which was absent in adult animals. The findings indicate that the expiration reflex is one of the most important respiratory reflexes of the early postnatal period in the rat, because the aspiration reflex and the respiratory reaction from the bronchi were not stable until the 15th day of life. In biological old rats, the expiration reflex is less frequently elicited and its intensity attains about half the value found in adult animals. The aspiration reflex and the respiratory reaction from the bronchi are likewise less readily elicited than in adult animals, but when the intensity of their maximum expiratory effort is increased, it is far greater.


Carrageenin-induced experimental pneumonia in rats. The authors verified the possibility of modelling pneumonia by the intratracheal administration of carrageenin solution into the lungs of rats. The most satisfactory dose was found to be 0.5 ml 0.7% carrageenin solution administered at 40 degrees C. The disease, evaluated by the morphological and functional signs, culminated after two days. Both macroscopically and histologically the lungs displayed typical signs of catarrhal suppurative aspiration bronchopneumonia. Functionally, marked tachypnoea (mean 180 cycles/min as against 110 c/min in the conscious controls) and raised functional residual capacity were found. A drop in the respiration rate and in FRC after bilateral cervical vagotomy indicated that a reflex component participates in the origin of the above two signs.


The effect of the parasympathetic autonomic nervous system on auditory fatigue. Volunteers with normal hearing were tested for vegetative balance with the aid of vegetative reflexes and with the aid of the atropine test. The effect of white noise stimulated on hearing thresholds was then investigated together with their recovery. The vegetative system was affected experimentally by intravenous administration of atropine, and the beginning and recession of hearing fatigue was observed. Atropine caused a small change only. In a similarly arranged experiment, 1% pilocarpin administered subcutaneously in a dose of 1.4 minus 1.6 ml, resulted in increased hearing fatigue and retarded recovery at higher frequencies. The effect of pilocarpin is explained by the fact that it supports the inhibitory processes checked by the parasympathetic nervous system on the periphery.


One-stage reconstruction for exstrophy of the bladder in girls. In an African female infant with exstrophy who was a candidate for complete reconstruction of the urinary tract, pelvis, and abdominal wall, the treatment program was simplified by performing iliac osteotomies at the same time as the other repairs, using a single transverse lumbosacral incision for access. A series of 3 wire loops held the symphysis in apposition. A plaster spica, followed by a plaster girdle, minimized the tension on the pubic wires. We believe that we obtained, by this method, superior strength and a better appearance of the abdominal wall and perineum.


Studies on the energy metabolism during anaerobic fermentation of glucose by baker's yeast. As a result of the intimate association of ADP phosphorylation with alcoholic fermentation, resulting in the synthesis of 2 mole ATP per mole glucose fermented, it may be calculated that a minimum of 672 mucal heat development may be expected for every mm-3 CO2 developed during alcoholic fermentation. When all ATP produced would be fully de-phosphorylated to ADP + Pi (e.g. by ATP-ase activity) a maximum heat development of 1200 mucal per mm-3 CO2 could be expected. Using the LKB-Flow-Microcalorimeter for measurement of heat development and at the same time the Warburg technique for measuring CO2 development during anaerobic glucose fermentation of a baker's yeast suspension, the heat development per mm-3 CO2 produced was calculated over a fermentation period of 90 min. Maintenance of strict anaerobic conditions in the Flow-Microcalorimeter vessel was complicated by diffusion of traces of oxygen via the Teflon transport lines, resulting in excessive heat development values, not representative for the alcoholic fermentation. This problem could be circumvented by removal of traces of oxygen by means of addition of the enzyme glucose-oxidase. Poisoning the respiratory enzyme system of the yeast by addition of KCN or azide, or using respiratory-deficient mutants of the yeast also resulted in heat development values, inherent with alcoholic fermentation. The values obtained were very close to the minimum of 672 mucal per mm-3 CO2, at least during the initial phases of fermentation, indicating that ADP regeneration from ATP, essential for maintaining the high fermentation rate, is not primarily the result of ATP-ase activity, but must be due to participation of ATP in energy-requiring synthetic reactions.


Growth of motor end plates and histochemistry of intrafusal myofibres in neonatal piglets. Between birth and 10 days the mean growth rate of peroneus longus motor end plates was 0-298 mum/day. A similar rate was found in seven other muscles from different anatomical regions. At birth, sartorius spindles contained three types of intrafusal myofibres; (i) large diameter with conspicuously strong acid-stable, and moderate or strong alkali-stable adenosine triphosphatase (ATPase) reactions; (ii) large diameter with weak or negligible acid-stable and alkali-stable ATPase; (iii) small diameter with weak or negligible acid-stable, and strong alkali-stable ATPase. All had a high mitochondrial enzyme content and positive PAS reaction. With the exception of some large diameter fibres, all reacted positively for phosphorylase. The frequency distribution of diameters was unimodal at birth but by 9 or 10 days was bimodal.


Electron microscopic demonstration of a saccharide moieties in the hypophase of the alveolar surfactant system. For electron microscopic demonstration of complex carbohydrates and simple sugars in the mouse lung, anionic dye and lectins were used. After immersion fixation of small lung tissue blocks, the alveolar surfactant system was destroyed and only membrane bound carbohydrates (cell coat) could be demonstrated by means of colloidal iron and ruthenium red. Fixation of the whole lung via the visceral pleura preserved the alveolar surfactant system. Only this technique afforded a distinction between cell coat components and hypophase components. After performance of the Concanavalin A-peroxidase technique and after incubation in ferritin-labed Concanavalin A, Lens culinaris lectin or Ricinus communis lectin, various saccharide moieties were demonstrable by immune electron microscopy in the hypophase of the alveolar surfactant system.


A comparison of the effector cells involved in cell-mediated lympholysis and antibody-dependent cell-mediated cytotoxicity in man. Some physical and mechanistic properties of cytotoxic lymphocytes and antibody-dependent killer cells were compared. Cytotoxic lymphocytes were measured by the cell-mediated lympholysis (CML) technique after sensitization of human peripheral blood leukocytes (PBL) in unidirectional mixed leukocyte culture (MLC). Killer cells were measured before and after MLC in an antibody-dependent cell-mediated cytotoxicity (ADCMC) assay using 51-Cr-labeled mouse mastocytoma cells as targets. Quantitative analysis of the cytotoxic activity of populations separated by velocity sedimentation at 1 g indicated that cytotoxic lymphocytes in MLC were a relatively heterogeneous population of rapidly sedimenting cells that corresponded morphologically to lymphoblasts. Further studies in which PBL were separated before MLC suggested that such cytotoxic lymphocytes were derived from small lymphocyte progenitors. Analysis of ADCMC in separated populations showed that most killer cells in PBL had the sedimentation properties of small lymphocytes. After stimulation of PBL in MLC, increased ADCMC activity was detected, and the increased activity was associated with a population of rapidly sedimenting cells, Comparison of the sensitivity of cytotoxic lymphocytes and killer cells to inhibition by EDTA, cytochalasin B, and dimethyl sulfoxide showed no significant differences between the two types of effector cells.


Disappearance of specifically mlc-responsive lymphocytes in cba mice injected with cells from the h-2-compatible, m-antigen-incompatible strain c3h. The mixed lymphocyte culture (MLC) response of lymphocytes from CBA mice injected with spleen cells from the H-2-compatible strain C3H was studied. The response of CBA lymphocytes against C3H cells was higher than that obtained against H-2-disparate strains. Intravenous injection of C3H cells resulted in a markedly increased MLC response in lymph nodes but not in the thymus during the first 1 to 3 days. Thereafter, the specific MLC response decreased drastically, far below that of nonimmunized animals. Reactivity was back to normal in the thymus after approximately 4 weeks but remained suppressed in lymph nodes for more than half a year. A decreased response was also noted in spleen, Peyer's patches, and the peripheral blood lymphocyte population. Such a state of relative unresponsiveness was achieved by injecting as few as 10-4 C3H spleen cells. This exhaustion of the specific MLC response could not be explained by production of blocking serum factors or of cells that can inhibit the MLC response. The strong MLC response obtained by lymphocytes from nonimmunized animals may be due to disparity at the newly detected M locus. This antigenic system is characterized by strong MLC stimulatory capacity and no detectable production of humoral antibodies or development of effector cells capable of killing M-antigen-bearing cells. A possible explanation of the results is that the CBA mice become chimaeric for a long time after injection of C3H cells. This prolonged exposure to a foreign transplantation antigen may lead to exhaustion of the specifically responsive lymphocytes.


The treatment of low differentiated germinal cancers of the testis using mithramycin. Twenty-six patients with metastases from a germinal cancer of the testis were treated with Mithramycin. After an observation time of between one-half-3 one-half years, 18 are still alive, of which 12 appear to be free from cancer. The 2-year survival rate is 50% (5/10). The side effects of Mithramycin therapy are described and discussed.


ATP-ase activity of lymphocytes from patients with carcinomas of the urinary bladder. In 13 out of 26 patients with urinary bladder carcinomas in various stages of malignancy, the ATP-ase activity of circulating lymphocytes was found significantly elevated. A decline in the ATP-ase activity was demonstrated in 14 of 17 patients re-investigated after treatment, while the activity remained unchanged in 2 and rose in 1 patient. No correlation between the clinical tumour stage and the lymphocyte ATP-ase activity was found, but the activity was closely correlated to the histological grade of malignancy. In 11 of the 17 patients the clinical effect of the treatment was closely correlated to a decline in ATP-ase activity. Determination of lymphocyte ATP-ase activity is suggested as an additional and simple help in the diagnosis of bladder carcinoma and in the follow-up control after treatment of patients with this disease.


Genetic problems in tumours of the gastrointestinal tract. The role of heredity in the production of gastrointestinal tumours is reviewed. The rare forms showing Mendelian inheritance are described, with special reference to oesophageal cancer and to familial polyposis of the colon. The high risks in these disorders are contrasted with the generally low risks to family members for the common cancers of the digestive tract. The part played by genetic factors in production of the premalignant state is critically discussed, with emphasis on gastric and hepatic cancer. The various experimental genetic approaches to the causation and early detection of cancer are outlined, and it is concluded that both genetic and environmental factors should be considered together when the etiology is being investigated.


[Treatment of primary and secondary liver tumors using a combination of chemotherapy and surgery]. The results obtained with protracted intra-arterial chemotherapy infusions in 60 case of primary or secondary liver tumor are discussed. The treatment should if possible be associated with surgical excision of the dominant tumor mass. Subjective improvement is obtainable in 75% of cases and objective improvement (including longer survival) in 50%. In some exceptionally favourable cases complete histologic disappearance of the metastases has also been achieved. Carcinoembryonic antigen determination appears to be the most reliable follow-up test.


HL-A LD (lymphocyte defined) typing: a rapid assay with primed lymphocytes. When human lymphocytes are cultured for 9 to 14 days with stimulating cells of a family member differing by a single HL-A haplotype they become "primed" to recognize specific HL-A LD (mixed lymphocyte culture) antigens. These primed lymphocytes respond specifically and rapidly when "restimulated" with cells of a person that contain the same LD antigens as those of the priming haplotype. Specific HL-A LD antigens can be detected within 24 hours by this primed LD typing.


Adenosine diphosphate effect on contractility of human muscle actomyosin: inhibition by ethanol and acetaldehyde. Magnesium adenosine triphosphate (Mg-2+-ATP) is known to produce dissociation of muscle actin and myosin in vitro, while its hydrolysis leads to reassociation. The interaction of purified actin and myosin from human muscle, in the presence of Mg-2+-ATP, was stimulated by minute amounts of adenosine diphosphate (ADP), a product of ATP hydrolysis. By contrast, the dissociation of the actomyosin complex was inhibited by ADP. These data suggest that ADP serves to modulate muscle contraction. Ethanol and its primary metabolite, acetaldehyde, inhibited these effects of ADP. The inhibition was reversible when the preparations were freed of these compounds. The effects of ethanol and acetaldehyde on the response of actomyosin to ADP may play a role in the pathogenesis of alcoholic myopathy and cardiomyopathy.


A case of Marfan's syndrome with absent right coronary artery complicated by aortic dissection and right ventricular infarction. The first patient to be reported with Marfan's syndrome and an absent right coronary artery is described. Dissection of the ascending aorta was associated with right ventricular infarction which was probably due to the coronary artery anomaly and caused his death.


[Early thrombogenic problems in the sparks-prothesis (author's transl)]. Some patients with Sparks arterial bypass graft show just during the operation a thrombosis in the prothesis. After the rubber rod has been pulled off, thrombogenic substances can be washed out of the prothesis-lumen. They shorten the clotting time of the patients' venous blood. 1000 ml 0.0% NaCl prevent this early thrombosis in the arterial bypass graft.


[Coronaro-myocardial interplay determining the instantaneous mean ventricular shape (author's transl)]. A working hypothesis on the mechanism of diastolic chamber expansion based on functional anatomy and physiology is developed. It should be a major determinant of the momentary average chamber width. The sum of all intramyocardial fluid-filled spaces and the myocardium itself are considered in the working hypothesis as the hydraulic medium of a process which can be summarised under the term "cavernous body mechanism". The most important factor of this hydraulic system should represent the intramural fluid volume (hydraulic medium) and the contractile-elastic tension development in the transmural direction of the chamber wall. Morphological analysis of myocardial structure shows that an endoepicardial direction of force in the myocardial net can be recognised. The "motor" of circular fibres of the middle layer is surrounded by the spiral course of the fibres of the inner and outer layers of the chamber wall (uvula mechanism). It is interwoven by very dense bifurcating myocardial fibres (structural principle of the tongue). By these means, the width of the chamber cone is influenced decisively by an active decrease in wall thickness. The coronary perfusion pressure is thought to have a chamber dilating influence in the sense of a "cavernous body mechanism". The hypothesis presented helps us to understand pathological chamber dilation secondary to transmural myocardial fibrosis. Such a narrow functional coronary-myocardial interaction gives the myocardium two functions; besides haemodynamic pumping, the cardial muscle must function as an internal antagonist to favour diastolic chamber dilation.


[On the mechanism of valve plane (author's transl)]. A detailed description of the functional sequence and mechanism of the valve plane movements is given as an extension of the studies on the functional morphology of cardiac movements. The valve plane mechanism is driven in the small, rapidly beating heart by the contraction of the external and internal spiral fibres of the myocardium which decreases the width of the chamber. The atrium is enlarged during systole by the descent of the valvular ring towards the apex. The auricular apendices must act as a compensation reservoir giving the atrial wall the necessary freedom of movement within the pericardial dome. Under these working conditions (hypovolaemia, decreased venous return pathophysiological consequences are discernible as subendocardial bleeding secondary to increased sliding movement of the inner layer of the myocardium against the middle layer. Chamber dilation as a consequence of endocardial fibrosis is explained as a result of progressive rigidity of endo-epicardial fixation. These structural changes progressively impair the systolic-diastolic changes in wall thickness.


[Light- and electronmicroscopic findings in nine auto-alloplastic vascular grafts (Sparks-Mandril) (author's transl)]. Auto-alloplastic arterial prostheses with a dacron mesh of 1 or 2 layers according to Sparks were investigated by light and electron microscopy after variable times of incorporation and perfusion. At the end of the organization-period the characteristic structure of the wall is composed of three layers. The interior layer is adapted to the form of the mandril, which holds the place of the lumen, the medial layer is formed according to the inforcing dacron-mesh. With increasing duration of incorporation the granulation tissue shows somewhat less inflammatory cells and capillaries and more collagen fibres. There were some characteristic disturbances of healing only partly due to infection, which resulted in focal or total necrosis of the granulation tissue: Not all of these findings were of clinical importance. Already after a perfusion time of 10 months an atherosclerosis of variable degree was found. This atherosclerosis started from mural thrombi and showed in the electron microscope proliferations of modified smooth muscle cells. Advantages and disadvantages of the autoalloplastic arterial prostheses are discussed.


Relationship between P wave form and left atrial pressure and volume in mitral valve disease. The P wave of the ECG, recorded with both conventional and special techniques, was compared with left atrial (LA) pressure and volume in 22 patients with mitral valve disease. The patients were also compared with 2 groups of normal subjects as to the P wave, recorded with the special technique. Changes in the P wave, such as increased duration, increased bipeak interval or P terminal force were significantly more common in the patients than in normal subjects. Among the patients, no significant correlations were found between degree of LA pressure elevation, LA enlargement and P wave changes. It is concluded that for the diagnosis of increased LA load it is more useful to study the terminal vector of the P wave than signs of increased atrial asynchrony. Recordings with high amplification and paper speed as in the present special technique are of advantage for such measurements. However, the special leads by themselves were not ideal for study of an increased terminal vector directed to the left and backwards.


Hydraulic studies of aortic cannulation return nozzles. An in vitro investigation of 8 different types of clinical aortic return nozzles was conducted. The importance of cannula geometry, tip location and direction was demonstrated in preventing abnormal flow conditions in the major aortic arch arteries. Alternative methods to correct these abnormalities were studied. This report has presented a preliminary study of the flow conditions produced by aortic cannulae during cardiopulmonary bypass. More detailed analysis of the pressure field as well as in vivo studies of the effects of a non-rigid geometry of the flow behavior are needed to confirm the findings of this investigation.


Umbilical cord vein fistula for vascular access in hemodialysis. Human umbilical cord vein allografts (HUCVAG) were modified by sequential treatment with 95% ethanol and 1.3% dialdehyde starch and stored in 70% ethanol. Tensile strength measurements of HUCVAG were found to range between canine aorta and bovine heterograft. Surface clotting was prolonged to 4 times that of pre-clotted dacron velour and 2 times that of bovine carotid heterograft. Inferior vena cava implants of HUCVAG remained patent for a period of 10 to 14 days while 4 of 5 bovine carotid heterografts clotted in 2 hrs ans one within 3 days. Micrpscopic examination showed a smooth intimal surface with no fibrin deposition and no evidence of rejection, providing excellent basic qualities as a vascular substitute. Using "14 gauge cannula, 180 repetitive percutaneous punctures were made in 10 heparinized dogs with HUCVAG fistulas between the carotid artery and external jugular vein. With exception of one instance in any preparation over a 4 month period. These results suggest the valueless. unbranched modified umbilical cord vein in unlimited supply is suitable as an arteriovenous fistula for blood access in maintenance hemodialysis.


Development of skin interfacing cannula. The skin interfacing potential of various velours, felts, foams and rough cast surfaces of some polymers was investigated by bonding these substances to solid core silastic rods using Dow-Corning Medical Adhesive Type A. These dummy cannulae were implanted as skin penetrating rods onto the dorsum of canines, goats, and swine. Vitreous carbon buttons were also investigated as to their potential. Over 200 individual implants were made and some retained in place for 2 yrs. Only the nylon and dacron velours held much promise as a long-term interfacing material. A "growth phenomenon" was observed using the velour material and this, we feel, is related to a permanent marriage between basal cells and adjacent monofilament fibers. Subsequent maturation of these cells carries the monofilament fibers to the surface causing the entire cannula to "grow". Since the maturation rate is apparently slower in humans, it does not detract from their potential application. The maturation rate is also much more rapid on the dorsum than on the ventral surfaces.


Telemetric monitoring device to detect thrombosis in the external arteriovenous shunt. A telemetric monitoring system of the external arteriovenous shunt for long term hemodialysis was deviced. Analysis of the arteriovenous shunt bruit showed that frequency distribution of the bruit ranged between 25 and 500 Hz. An air transmission type microphone with an optimum frequency at 200 Hz was designed. The monitoring system, including the microphone, a small FM transmitter and an FM receiver with an alarm system by the transmitter. The signals received by the FM receiver were amplified and selected by a bandpass filter. After being all-wave rectified, and averaged for one min by the averaging circuit, the signals were finally balanced by the standard signal and the precision comparator. When the arteiovenous shunt bruit ceased for more than one min, the alarm system went off. The system frequently detected obstruction of blood flow due to flection of the forearm during sleep and by other causes, thereby preventing clotting of the arteriovenous shunt flow. Thrombosis in the arteriovenous shunt was detected 5 times by the telemetric device while the patients were alseep at home, and declotting was successful in all the cases. The system has proven to be available for early detection of shunt obstruction and of clot formation inside the arteriovenous shunt.


The effect of fenbendazole on nematode parasites in experimentally infected lambs. Fenbendazole given orally to experimentally infected lambs at a dose rate of 5 mg per kg was found to be 100 per cent effective against three and 10-day larave and also against 20-day adults of H contortus, O circumcincta, N battus and T colubriformis. The same dose was also 100 per cent effective against 10-day, 17-day larvae and 27-day adult D filaria.


Electron microscopic cytochemical characterization of bile canaliculi and bile ducts in vitro. Electron microscopic cytochemical localization of Mg++-activated adenosine triphosphatase (Mg++-ATPase) and 5-nucleotidase (AMPase) was investigated in bile canaliculus-rich and bile duct-containing fractions isolated from rat liver. Comparative cyochemical studies between prefixed and non-prefixed fractions revealed that the activity of both enzymes could be detected in the fractions under appropriate experimental conditions. However, the cytochemical activity of AMPase was much more sensitive to glutaraldehyde than that of Mg++-ATPase. Mg++-ATPase and AMPase reaction products were localized primarily on bile canalicular microvilli, that is, along the outer (luminal) surface of canalicular plasma membranes, but they were never observed on bile ductal microvilli. AMPase was also detectable on lateral hepatic plasma membranes. Mg++-ATPase demonstrated by the cytochemical technique described is a reliable enzyme marker for isolated bile canalicular membranes. At high magnification, Mg++-ATPase reaction product was also observed on the microfilaments surrounding isolated bile canaliculi. The possibility that the reaction product on the pericanalicular microfilaments may result from the hydrolysis of ATP byan actomyosin ATPase-like enzyme associated with these filaments is briefly discussed.


[Relationship between Chemical Constitution and Theraeutic Activity of alpha, beta-unsaturated Aldehydes in the Ehrlich-Solid-Tumor of the Mouse]. Biochemical and biological effects and chemical properties of three alpha,beta-unsaturated aldehydes [acrolein (I), 4-hydroxypentenal (II), and 4-hydroxyundecenal (III)] were compared. These three substances inhibited the incorporation of -3H-thymidine in Ehrlich-ascites-tumor cells in vitro in the following order: I is greater than III is greater than II. For reactivities with glutathion in vitro the order was: I is greater than II is greater than III is greater than. We concluded there from that the high activity of I, as to its inhibition of thymidine incorporation and its toxicity, was related to its high activity against SH-groups. With respect to therapeutic effects and hydrophilia the following order: II is greater than I is greater than III was observed. In our opinion the high hydrophilia of II is responsible for the significant and good inhibition of tumour growth.


[ct-Mode of Action in the Teratogenic Experiment]. The doses of 10 and 20 mg/kg N-methyl-N-nitrosourea which were teratogenetically effective after a single dose were distributed over 12,24, 48, and 96 hrs during the embryonic developmental phase of the rat. It turned out that the effects were enormously increased when both doses were given in ten single doses during 12 hrs. The number of fetuses that had died down during gestation was increased considerably, the surviving fetuses bore, without exception, the marks of extreme malformations, as, for example, big haemorrhagic cysts instead of the mandible and the tongue. The distribution of the doses over 24 hrs showed, as far as quantity is concerned, comparable teratogenic effects, which, however, during the time of treatment varied in quality according to the variation of the critical sensitivity of the developmental phase. The distribution over even longer periods of time gradually weakened the effect. There were also some other symptoms that became manifest. So it can be said that N-methyl-N-nitrosourea is according to its teratogenic effects also a typical ct-poison (Druckrey) with the maximum of cumulation after distributing the dose over 12 hrs of the gestation.


[Quantitative Cytochemical and Morphometric Investigations on Uterine Angiomatosis (Endolymphatis Stromal Myosis) and Stromal Sarcoma]. The angiomatosis uteri shows a low scattering of nuclear DNA content; an euploid DNA stem line suggests a benign behavior in these tumors. This evidence is supported by clinical experiences. The endometrial stromal sarcoma and the angioblastic sarcoma are characterized by a high scattering of nuclear DNA content, an aneuploid DNA stemline and a substantial irregularity of the nuclear area. These difference, suggest the malignancy of stromal and angioblastic sarcoma.


[Morbus Hodgkin in autopsies today (author's transl)]. In Hodgkin's disease, good clinical results are obtained by the modern combined treatment with irradiation and chemotherapy. An examination of autopsy findings show in the period 1955-1964 a mean survival time (measured from first biopsy until death) of 22 month, in the period 1965-1973 of 42 month. In contrast to first biopsies, autopsies have a prevalence to the reticular "Hodgkin-sarcoma" .41% of all cases are of this type. 12 of these cases had changed from the lymphocytic predominaut type or from nodular sclerosis, to the reticular type. This augmentation of the reticular type is seen as a consequence of modern therapy. In 18 autopsies, histologic classification was rendered impossible by massive scarring. 8 cases of the period 1965-1973 did not show any lymphogranulomatous tissue and could be morphologically defined as "cured". Therapeutic damages were found in 15 cases. 6 cases had diffuse pulmonary fibrosis. The therapy provoked scars could be differentiated histologically from the hyalinizations occurring in nodular sclerosis and in diffuse fibrosis.


Epoxide hydrase activity in mouse skin eidermis. By fractionation of mouse epidermis a "microsomal" fraction may be obtained with a specific EH-activity at least 6-7 times higher than that of epidermis homogenates. Such enrichment allows to utilize the radioassay with 7--3H-styrene oxide as substrate which normally is too insensitive for organs with low levels of EH-activities. By the procedure developed the unambiguous demonstration of EH-activity in the epidermis of mouse skin is possible.


Transaminase level (GOT, GPT) in rats under treatment with diethylnitrosamine. Transaminase levels (GOT, GPT) of Sprague-Dawley-rats were not increased during long-term oral application of diethylnitrosamine (DENA) in doses of 0.1 and 3.0 mg/kg/day respectively. Only rise of the daily dose to 12.0 mg/kg/ (4% of LD50) resulted in a significant increase of enzymatic activities after 2-3 months of treatment. By the determination of transaminases the process of liver cancerization cannot be discovered. The present method is also too insensitive to indicate the formation of smaller quantities of nitroso compounds from their precursors (amines plus nitrite) in vivo.


[Curative effects of diverse, centrally active drugs in rats poisoned with 3-methylcholanthrene (author's transl)]. Drugs like picrotoxine, apomorphine, ephedrine and strychnine, affecting the central nervous system, cured rats after surgical removal of methylcholanthrene tumours. Picrotoxine was most effective, in the dosage of 0.6 mg/kg s.c., all rats were cured. The therapeutic range of picrotoxine was remarkably small. Variations of only plus or minus 0.1 mg/kg of the optimal dosage, caused a 50% reduction of survival rate. Stimulation of the immune system could be excluded as an influence on survival. All animals treated with methylcholanthren showed changes in the EEG, starting after 24 hrs and persisting for 3 months, the time of the last recording. It is suggested that methylcholanthren caused some central damage. Central stimulation is suggested as the cause of the improved cure rate.


[The carcinogenic action of n-nitroso-compounds fourth communication: n-nitroso-o,n-diethyl-hydroxylamine (author's transl)]. N-Nitroso-O,N-Diethylhydroxylamine was given orally to male SD rats 100 mg/kg twice a week. 25 out of 28 evaluable animals developped after 276 plus or minus 15 days multiple carcinoma of paranasal sinus, lung and stomach.


Diagnosis of experimentally induced bronchogenic tumours in the european hamster with bronchographs. Four groups of European hamsters were treated subcutaneously once weekly for life with 1/20 or 1/40 the diethylnitrosamine LD 50. Three animals from each treatment group and the two control groups were examined every three weeks by means of bronchographic technique. In four of the animals the bronchograms showed early neoplastic alterations of the bronchial system. The results demonstrate that bronchography is a suitable method for the diagnosis of bronchogenic tumours in the European hamster and that it also allows for the detection of displacing neoplasms of non-bronchogenic origin in the region of the tracheal bifurcation.


The in vivo inhibition of tumor growth by ruthenium red: its relationship with the metabolism of calcium in the tumor. Ruthenium red shows antitumor activity on experimental tumors. This growth inhibition seems to be related with the impairment of Ca-2+ transport both at the mitochondrial and at the cell membrane level. A sex influence modifying this inhibition and the systemic effects has been observed.


HL-A antigens in carcinoma of the breast, ovarium, cervix and endometrium: possible association of haplotype HL-A10-W18 with carcinoma of the breast. 24 HL-A antigens were determined in a total of 163 Caucasien cancer patients (60 breast cancers, 64 cancers of the cervix uteri, 19 cancers of the endometrium and 20 cancers of the ovary). The comparison of the antigen frequencies with the analogous values from 1000 healthy controls yielded no outstandingly significant deviations for cancer of the cervix, endometrium and ovary. In breast cancer patients, however, there might be an association with the antigens HL-A10 and W18 or the haplotype HL-A10-W18, as indicated by the results of a combined evaluation of our data together with the results of four different HL-A studies in breast cancer patients.


Susceptibility of gerbils (Meriones unguiculatus) to weekly subcutaneous and single intravenous injections of N-diethylnitrosamine. Weekly s.c. (24, 12, and 6 mg/kg b.w.) or a single i.v. (100 or 50 mg/kg b.w.) injections of N-diethylnitrosamine (DEN) to gerbils (meriones unguiculatus) resulted in tumours of the respiratory tract and liver. Carcinomata of the nasal olfactory region or respiratory-olfactory mucosal junction were most common; papillomata of the tracheobronchial system and adenomata or carcinomata of the lungs appeared in significantly lower incidences. The neoplasms of the liver were of cholangiocellular and in a few cases of hepatocellular origin.


Metabolism of nitrosamines in vivo IV. Isolation of 3-hydroxy-1-nitrosopyrrolidine from rat urine after application of 1-nitrosopyrrolidine. After i. p. application of 6 mg/30 muCi/kg 2,5- and 3,4--14C-nitrosopyrrolidine about 20% of the radioactivity is exhaled as 14-CO2 and about 7% is found in the urine. One of the urinary metabolites was identified by thin layer chromatography, combined GC/MS spectrometry and ultraviolet absorption as 3-hydroxy-1-nitrosopyrrolidine.


[Experimental investigations on the effectiveness of fenbendazole in parasitic helminths of the stomach, intestines and lung of cattle (author's transl)]. Helminth-free bulls were injected artificially with Ostertagia ostertagi (120 000 L3), Cooperia oncophora (240000 L3), Haemonchus spec. (1 000 L3) and/or Dictyocaulus viviparus (60 L3/kg) orally or intraruminally. The animals were treated with fenbendazole during the prepatent period or after having reached maturity. The effect of 5 mg fenbendazole/kg p.o. on 3-d, 10-d- and adult stages of Ostertagia ostertagi, Haemonchus spec. and Cooperia oncophora ranges between less than 94% and 100%. Particularly noticeable was the effect on 10-d-old Ostertagia ostertagi with less than 94%. 5 mg/kg fenbendazole orally removed nearly 100% of 6-d-, 13-d-, and adult stages of Dictyocaulus viviparus. Fenbendazole may be administered as a drench or as medicated feed. The safety of the compound permits the administration of excessively high doses without clinical signs.


[Sulphated glycosaminoglycans as virus inhibitors. 2nd communication: Inhibitory effect of glycosaminoglycanpolysulphates on yellow fever virus 17 D in animal experiments (author's transl)]. Glycosaminoglycanpolysulfates (GAGPS) have virus inhibiting properties demonstrable by means of tissue culture in the plaque method. In brain preparations of children who had died of a hyperpyretic toxicosis, cell necroses were found corresponding to the picture of tissue culture plaques. The question arose from these observations whether this inhibiting effect of GAGPS can perhaps also be demonstrated in vivo. In animal experiments, cell necroses corresponding to those of the infant brain could be observed during the course of a 17 D yellow fever encephalitis in mice. The Luitpoldt-Werk Munich placed to our disposal 13 different GAGPS for tests. Each of these substances was tested in 210 mice (fig. 1). Virus dilutions (LD 50/ml) were mixed to the same volume with the indicated concentrations of substance directly before vaccination. The differing LD 50 doses is due to the fact that each ampoule contains a different content of virus.) The toxicity of all substances is practically zero (table 2a, 2b). The effect of the inhibiting substances was evaluated at first by means of a deviation of the rate between alive and dead animals (table 1). The statistical significance of the effect of some substances was that high so that an inhibition of the virus replication has obviously to be considered. The significance for L1 and L4 - they are chemically very similar - is higher than 0.001 (table 4). The virus inhibiting effect of the substances was controlled by histopathology. 31 brains of mice were dissected and histologically evaluated; the lesions of the brains were examined and recorded (table 3). The effect of the substances was measured by absence or diminution of the lesions. The most effective substance was L1 as far as its concentration was higher than the critical limit of 625 gamma/ml.


On the mechanism of activation of CaATPase by a single univalent cation. It has been demonstrated with ox-brain microsome membranes that the mechanism of CaATPase activation by a single univalent cation is different in case of Na+-ont he one hand-and K+ and its congeners-on the other. Whereas Na+ increases the amount of 32-P protein (phosphorylated intermediate), K+ causes only an insignificant increase or decrease compared to the Ca-2+-containing sample. Our findings support the assumption that the altered activity of the Na-K-ATPase (modified by the presence of Ca-2+) is responsible for the univalent cation activation of the CaATPase.


Regional cerebral blood flow in patients with chronic subdural hematomas. Cerebral blood flow (CBF) was measured by the intra-arterial 133Xenon method in seven patients, aged 55 to 76 years, with chronic subdural hematomas. Before operation, CBF was reduced to an average of 31 ml/100g/min, range 24-38 ml/100g/min. One to 3 weeks after operation, when all had improved, CBF averaged 38 ml/100g/min, range 34-43 ml/100g/min. The reduction of CBF was probably secondary to a reduced metabolic demand. Clinical improvement continued for months after operation.


Diabetogenic effects of n-nitrosomethylurea in the chinese hamster. To evaluate the role of the glucose residue of the diabetogenic substance streptozotocin, the effect of its aglucone derivate N-nitrosomethylurea was tested in Chinese hamsters. At a dose of 50 mg/kg body weight of N-nitrosomethylurea a triphasic blood glucose curve was recorded with an initial hyperglycaemic peak after 3 hours followed by a decrease at 6 hours. After 24 hours and during the following days the values were moderately elevated. There was a high mortality in the diabetic animals, about 80 per cent of them dying within one week. The approximate L.D. 50 of N-nitrosomethylurea injected intraperitoneally in non-fasting adult animals was about 125 mg/kg body weight at an observation time of 48 hours. On light microscopy, degenerative changes with nuclear pyknosis were seen after 3 hours in the pancreatic islet cells, followed by cellular disintegration. Both beta-, alpha2- and alpha1-cells were obviously affected. Pretreatment with 500 mg nicotinamide/kg body weight given intraperitoneally 10 minutes before the injection of N-nitrosomethylurea inhibited and hyperglycaemia and seemed to prevent the injurious effects of N-nitrosomethylurea on the islet cells. The results show that the glucose residue of the streptozotocin molecule is not necessary for the induction of diabetes in Chinese hamsters, but it seems to increase the selectivity of the toxic effects for the islet cells. This is a clear advantage in studies of experimental diabetes, especially when longer observation periods are desired.


Effects of ethanol on brain metabolism.

Effects of ethanol on brain metabolism. The influence of acute or chronic ethanol administration on the biochemical processes in brain and cerebral metabolic pathways has been discussed. Ethanol seems to affect cerebral carbohydrate metabolism mainly through increased glycogenolysis, although the possibility of decreased cerebral glucose utilization remains eminent. Ethanol affects the consumption of oxygen by the brain tissue presumably through alterations in the brain cell membranes. Inhibition of Na+-K+-ATP-ase observed during ethanol intoxication is suspected to result in alterations in the membranes of the nerve cells. Isotope studies in addition to total respiratory carbon dioxide production strongly suggest the inhibition of citric acid cycle function during ethanol metabolism. Although synthetic pathways for lipids do not seem to be affected by ethanol, lipid oxidation in the cerebral tissue is significantly inhibited. In addition to above mentioned alterations in the cerebral metabolic processes, ethanol also affects ionic transport processes, adenine nucleotides, and amino acid and protein metabolism. The metabolic consequences of such effects of ethanol have been discussed.


CSF homovanillic acid: an index of dopaminergic activity. Although CSF HVA is derived from brain DA metabolism the value of its determination as an index of brain DA turnover and dopaminergic activity is limited, as other factors can affect CSF concentrations. These include the partitioning of HVA between different routes of elimination from the brain, the rates of transport from CSF to blood and from the lateral ventricle to the lumbar sac, CSF space volumes, and methodologic problems. The uses and limitations of CSF HVA determination is illustrated by findings in Parkinson's disease, Huntington's chorea, motor neuron disease, disseminated sclerosis, and hepatic coma. Finally, preliminary results on the effect on CSF HVA of the DA agonist CB 154 are described.


Echocardiography in acute myocardial infarction. Sixty-four patient with acute transmural myocardial infarction had daily echocardiograms while in the coronary care unit. Patients with previous infarction were excluded. The electrocardiographic site of infarction was anterior wall in 28, inferior wall in 33 and both anterior and inferior wall in 3 patients. Echocardiograms satisfactory for interpretation were obtained in 92 percent of cases. Abnormal left ventricular wall motion corresponding to the electrocardiographic site of infarction was seen in the echocardiogram in 84 percent of cases. Exaggerated normal motion in noninfarcted areas was seen in 30 percent. The left ventricular internal dimension correlated with clinical heart failure (P less than 0.005) and was increased in 50 percent. Abnormal mitral valve closure, which reflects increased left ventricular end-diastolic pressure, was present in 33 percent. This finding did not correlate significantly with clinical heart failure. By combining the measurements of left ventricular internal dimension and mitral valve closure, it was possible to predict hospital mortality from the echocardiograms. The results indicate that echocardiography is a useful technique in the study and management of patients with acute myocardial infarction.


Echocardiography in aortic root dissection and dilatation. Six patients with aortic root dissection proved by angiography, surgery or autopsy, and six patients with aortic root dilatation were studied by echocardiography. Echocardiography was diagnostic in five or six patients with dissection and suggestive in the sixth, disclosing anterior and posterior dissection in three, anterior dissection in one and posterior dissection in one. The recording of a double echo in the aorta was the diagnostic feature. Angiography was diagnostic in four of the six patients, yielded a false negative result in one and was not performed in one. Six patients with dilatation had an enlarged aortic root by echocardiography. Left ventricular size, stroke volume, ejection fraction, aortic regurgitant flow and velocity of circumferential fiber shortening were calculated in 11 patients. Echocardiography was extremely helpful in the diagnosis, management and follow-up in patients with aortic dissection or dilatation.


Echocardiographic differentiation of infundibular from valvular pulmonary stenosis. Echocardiographic tracings of the pulmonary valve were examined in 24 normal subjects, 16 patients with valvular pulmonary stenosis and 3 patients with infundibular pulmonary stenosis. In normal subjects, atrial contraction produced a slight posterior opening motion of the pulmonary valve leaflet (a wave). This presystolic opening motion (a wave) varied with respiration, and maximal a wave depth recorded during quiet inspiration (Amax) averaged 3.7 plus or minus 1.2 (standard error of the mean) mm (range 2 to 7 mm). In the 10 cases with moderate or severe valvular pulmonary stenosis, increased force of right atrial contraction and elevated right ventricular end-diastolic pressure resulted in an increased posterior or opening motion of the pulmonary valve leaflet, and Amax averaged 9.6 plus or minus 2.0 mm (range 8 to 13 mm, P less than 0.001 versus normal). When both anterior and posterior leaflets were recorded, presystolic opening or doming of the valve was observed. In six cases of mild valvular pulmonary stenosis, Amax averaged 4 plus or minus 2.5 mm (not significant). In patients with infundibular pulmonary stenosis, marked chaotic systolic fluttering of the valve leaflet, which lies in the turbulent stream of blood distal to the obstruction, was recorded. This finding was never seen with valvular pulmonary stenosis. In two cases of mild infundibular pulmonary stenosis, the amplitude of presystolic opening motion was within the normal range of 3 and 7 mm. In one case of severe infundibular pulmonary stenosis, no presystolic opening motion was recorded, thus suggesting that the small pressure changes produced by atrial systole failed to reach the valve leaflets. Echocardiography, therefore, should be of use in differentiating valvular from infundibular pulmonary stenosis.


Right ventricular volume in congenital heart disease. With use of the Frank lead system, still loop and timed vectorcardiograms were recorded in more than 5,000 patients subjected to complete right and left heart catheterization and selective coronary cineangiography. Data so obtained demonstrated clinical superiority of the vectorcardiogram over the standard 12 lead scalar electrocardiogram. Specific advantages of the vectorcardiogram include (1) recognition of undetected atrial and ventricular hypertrophy, (2) greater sensitivity in identification of myocardial infarction, and (3) superior capability for diagnosis of multiple infarctions in the presence of fascicular and bundle branch blocks. The timed biplane vectorcardiogram is as useful as any number of simultaneously recorded electrocardiographic leads for the analysis of complex arrhythmias and beat to beat changes in intraventricular conduction. Since the validity and usefulness of this technique have been established, it should become part of the routine noninvasive evaluation of patients with cardiovascular disorders.


Advances in clinical vectorcardiography. With use of the Frank lead system, still loop and timed vectorcardiograms were recorded in more than 5,000 patients sujected to complete right and left hear catheterization and selective coronary cine angiography. Data so obtianed demonstrated clincila superiority of the vectorcardiogram over the standard 12 lead scalar electrocardiogram. Specific advantages of the vectorcardiogram include (1) recognititin of undetected atrial and ventrcular hypertropy, (2) greater sensitivity in identification of myocardial infaraction, and (3) superior capability for diagnosis of multiple infaractions in the presnece of  fascicular and burnany number of simultaneously recoreded electrocardiographic leadsfor the analysis of complex arrhythmias and beat to beat changes in intraventricula conduction. SINCE THE VALIDITY AND USEFULNESS OF THIS TECHNIQUE HAVE BEEN ESTABLISHED, IT SHOULD BECOME PART OF THE ROUTINE NONINVASIVE EVALUATION OF PATIENTS WITH CARDIOVASCULAR DISORDERS.


Mosaic double aneuploidy of X and G chromosomes. Three cases having typical mongoloid features and few or no features of Turner's syndrome were reported. Four distinct stem lines of cells 45,X/46,X,+G/46,XX and 47,XX,+G were found to be present in the lymphocytes of two females. In the third case, only three stem lines were found, the 45,X line being absent. The proportion of cell lines was different in each case. Possible mechanisms for the mosaicism were suggested.


Circulating gonadotropins, estrogens, and androgens in polycystic ovarian disease. Serum gonadotropin, estrogen, and androgen levels were measured in samples obtained from 19 patients with polycystic ovarian disease (PCO) and from 10 normal women on day 2 to 4 of their menstrual cycles. In patients with PCO, the mean (plus or minus S.E.) concentration was significantly higher (P smaller than 0.001) than the concentrations found in the normal subjects for LH (35 plus or minus 4.6 vs. 12.7 plus or minus 2.6 m.I.U. per milliliter), but not for FSH (10.3 plus or minus 0.7 vs. 8.7 plus or minus 0.9 m.I.U. per milliliter). Estrone (E1) levels (92 plus or minus 4 vs. 52 plus or minus 5 pg. per milliliter) were also significantly higher (P smaller than 0.001), while estradiol (E2) concentrations (58 plus or minus 4 vs. 63 plus or minus 8 pg. per milliliter) were comparable. Testosterone (T) (468 plus or minus 41 vs. 325 plus or minus 34 pg. per milliliter, P smaller than 0.05), androstenedione (delta) (2,083 plus or minus 138 vs. 1,123 plus or minus 153 pg. per milliliter, P smaller than 0.001), and dehydroepiandrosterone sulfate (3.4 plus or minus 0.4 vs. 2.0 plus or minus 0.37 mug per milliliter, P smaller 0.02) were also significantly increased over the values in normal controls. The mean dehydroepiandrosterone (DHEA) was elevated in the patients with PCO (11.3 plus or minus 1.7 vs. 7.5 plus or minus 1.2 mug per milliliter), but was not significantly different. A positive correlation was found between LH levels and both E2 and E1 concentrations in the patients with PCO. These data show a distinct profile of gonadotropin, estrogen, and androgen levels in patients with PCO.


Permanent sterilization by hysteroscopic cauterization. A small series of 22 patients who underwent hysteroscopy cauterization is reported. The uterus was distended with CO2 and dextran. Cauterization was done with a 6 mm. long, active-tip, No. 4 electrode: There was a 27 per cent failure rate for the controlled cases, this dropping to 11 per cent after recauterization. A significant complication, small bowel perforation, was treated by resection and anastomosis with complete recovery. The uterine distention with CO2 is safe but ostium visualization is not very good; Dextran distention is more cumbersone but gives excellent visualization and exposure of the ostium because higher intrauterine pressures are developed.


A fluid-filled intrauterine device: initial clinical trials. Initial clinical trials of a saline-filled IUD were conducted with 697 women (397 nulliparas and 307 multiparas) experiencing 6,672 woman-months of use. The cumulative rates for multiparas were: pregnancy 1.5, expulsion 10.5, medical removal 10.9, continuation 68. For nulliparous women the rates were: pregnancy 4.3, expulsion 19.4, medical removal 14.3, continuation 58. Efforts are being made to modify the geometry and content of this IUD to decrease the expulsion rate and removals for bleeding.


Fetal bile acid levels in pregnancies complicated by maternal intrahepatic cholestasis. Cholic and chenodeoxycholic acids were determined in 42 cord plasma samples after pregnancies complicated by maternal intrahepatic cholestasis and in 20 cord plasma samples after uncomplicated pregnancies with a gas-chromatographic method. The mean total amount of these bile acids was 1.8 mug per milliliter after uncomplicated pregnancies as compared to 5.6 mug per milliliter (P less than 0.001) in the cholestasis group. These bile acids were also determined in six maternal plasma samples where, as compared to the cord plasma of their babies, higher levels were found in every case. These results show that in addition to changes in the maternal circulation, maternal cholestasis elevates bile acid levels in fetal circulation. A more frequent occurrence of signs of fetal distress during pregnancy or labor was found in those cholestasis cases where cord plasma bile acid levels were high. The relationship of fetal bile acid levels to fetal steroid hormone metabolism was studied by correlating total bile acid levels with the concentrations of a number of steroid sulfates in cord plasma. An interesting finding was a negative correlation between fetal bile acid levels and concentrations of 16-oxygenated steroid sulfates, which are important estriol precursors produced by the fetus. These observations led to the conclusion that bile acids or other substances which are retained in maternal circulation as a result of cholestasis may, after transplacental passage, cause some kind of distress to the fetus.


Sequential amino acid measurements during experimental diabetic ketoacidosis. This study was designed to investigate the sequential amino acid response to acute insulin deprivation. Male Wistar rats were made severly diabetic by the intravenous injection of streptozotocin, 150 mg/kg, and maintained on insulin for 7 days. Insulin was then withheld, and measurememts of whole blood and plasma amino acid concentrations were made at 24-h intervals until 120 h, by which time animal mortality was 80%. Alanine and the other gluogenic amino acids displayed a biphasic response to insulin deprivation, decreasing in plasma and whole blood until 72 h after the last insulin injection then increasing in concentration until 120 h. The branched-chain amino acids valine, leucine, and isoleucine remained constant until 72 h after insulin, after which time their concentrations increased dramatically. It was concluded that the first phase represented enhanced gluconeogenesis and in the second phase amino acid uptake for gluconeogenesis was exceeded by net peripheral amino acid release. Enzymatic measurements showed a progressive increase in erythrocyte;plasma distribution ratios for glutamate in ketoacidosis.


Limitations to the neuroregulation of enzymes in mammalian skeletal muscle. Muscle fibers of the sternomastoid and the tongue of the rat were characterized histochemically according to mitochondrial distribution (succinic dehydrogenase), as well as reactivity for the alkali- and acid-stabile "myofibrillar" adenosine triphosphatases. The principal fiber types of the sternomastoid was the large, "white" AalphabetaM fibers and the smaller, "intermediate" BbetaD and "red CalphaL fibers (figs. 1, 2, 3). The unusual musculature of the tongue was populated by diminutive AalphaM and CalphaM fibers, and variants thereof; all with relatively high mitochondrial content (figs. 4, 5, 6). Reinnervation of the sternomastoid muscle by the hypoglossal nerve caused most fibers of the sternomastoid to assume histochemical profiles reminiscent of those commonly observed in the tongue. However, the BbetaD fibers of the sternomastoid persisted in near usual numbers and disposition (fig. 17), despite their reinnervation by a nerve normally destined for a muscle lacking that particular fiber type. Thus, there are as yet unrecognized factors, possibly of neural origin, though more likely of muscle origin (genetic), that impose restrictions on the metabolism-regulating functions of substitute motoneurons.


Controlled test of anthelmintic activity of levamisole administered to calves via drinking water, subcutaneous injection, or alfalfa pellet premix. A controlled test of the activity of 3 formulations of levamisole, at the dose level of approximately 8 mg/kg, against naturally occurring infections of gastrointestinal parasites and lungworms was made in 24 calves allotted to 4 groups of 6 calves each. Levamisole was administered to group I calves in the drinking water, to group II calves by subcutaneous injection, and to Group III calves by feeding alfalfa pellets mixed in corn silage; group IV calves were nontreated controls. Group I calves consumed the medicated water between 4 hours and 20 minutes and 9 hours and 40 minutes; group III calves consumed the medicated feed within 2 hours and 15 minutes. For calves of group I, II, and III, removals of 4th-stage Ostertagia sp were 64, 23, and 0%; of mature Ostertagia ostertagi, 90, 93, and 83%; and of mature Trichostrongylus axei, 92, 99, and 92%, respectively. For all 3 treated groups of calves, removal was 100% for 4th-stage Cooperia sp and for mature Trichostrongylus colubriformis, Cooperia oncophora, Cooperia punctata, and Oesophagostomum radiatum. Removals of Dictyocaulus vivipara were 90, 90, and 94% for calves of groups I, II, and III, respectively. There was no evidence of toxicosis. At necropsy, 2 calves in group II had small areas of edema at the sites of injection of levamisole.


Recurring hemolytic anemia, babesiasis, and influenza A viruses in a yak at low altitude in Nepal. Episodes of hemolysis and leukocytosis which were associated with Babesia bigemina followed each of 3 challenge exposures to influenza A viruses. It is possible that viral infection altered the immunologic host-parasite equilibrium. Acute thrombocytopenia and rouleaux formation were also observed. Death, attributed to liver flukes, occurred 168 days after the yak was transferred from high to low altitude. A 2nd yak died of foot-and-mouth disease, thus supporting the Nepali belief that yaks will not survive at the lower altitudes of Kathmandu.


Long-term follow-up of epidural blood patch. Epidural blood patch (EBP) was performed for the treatment of severe postlumbar puncture cephalalgia in 118 young patients. Following the first EBP, 105 patients had relief of headache. Eleven of the 13 in whom it failed had a second EBP, with adequate relief in 10, giving an overall success of 97.5 percent. Lumbar epidural, caudal, and spinal procedures were successful in 3 patients 105 to 380 days after EBP. Soon after EBP, one patient developed facial paralysis and one complained of episodes of vertigo, dizziness, tinnitus, and ataxia without headaches. Residual complications included backache and/or back stiffness in 22 patients and paresthesia in two. Two-year follow-up revealed 95 percent patient acceptance of the procedure. EBP was found to be a safe, effective method for treating severe postlumbar puncture cephalalgia, provided a proper diagnosis is made and there is no contraindication.


Peritoneoscopy: a valuable staging tool in ovarian carcinoma. Peritoneoscopy was done within 1 month of exploratory laparotomy in 30 consecutive patients, with ovarian carcinoma as part of their pretreatment evaluation. Six of the 7 patients who were thought to have ovarian carcinoma localized to the pelvis (stages I and II) were found to have advanced disease (stage III) at peritoneoscopy and thus required a change in therapy. Metastatic diaphragmatic involvement in ovarian carcinoma is common and was found in 77 percent of all patients studied. The routine shielding if the liver area ordinarily used with total abdominal radiotherapy would select these patients for therapeutic failure. Peritoneoscopy supplied reevaluable finding in 2 of 7 patients having normal physical, roentgenologic, and laboratory examinations, as well as in 93 percent of all patients stuided. "Second look" peritoneoscopy precluded the need the laparotomy in 5 to 13 patients achieving as apparent clinical remission.


Immune complex nephropathy i schistosomiasis. In a patient with chronic hepatosplenic schistosomiasis a segmental sclerosing nephropathy led to terminal renal failure. The demonstration of glomerular capillary deposition of immunoglobulin and complement with electron dense deposits and lucent deformities of the glomerular basement membrane and the presence of antischistosome adult worm antibody in serum suggested that this was an example of immune complex nephropathy. Successful renal transplantation followed by niridazole treatment of the schistosomiasis induced a transient relapse of renal dysfunction with proteinuria and a fall in serum complement. The pathogenic schistosomal adult worm antigen was identified by immunofluorescence in the mesangium of the transplant; complement and immunoglobulin were present also in that site.


Late infection in Dacron arterial grafts. We report a series of cases of late infection in Dacron arterial grafts. Late infection is defined as that presenting de novo 6 months or more after the patient's discharge from hospital with a clean healed wound. One hundred and ten patients were followed up and 6 cases of this type of infection occurred. The diagnosis was made on clinical grounds and usually pain, suppuration in the line of graft, or graft exposure were the presenting features. Secondary haemorrhage, common in early infection, did not occur. Conservative management failed in most cases and removal of the infected graft was necessary. The difficult problems associated with revascularization are discussed.


Effect of tilorone treatment on intracellular microbial infections in specific-pathogen-free mice. Specific-pathogen-free CD-1 mice were treated orally with the drug tilorone (2,7-bis[2-diethylaminoethoxy]fluoren-9-one hydrochloride) at dosages of 10 or 100 mg per kg of body weight. Drug was given 24 h before challenge and then every other day for up to 15 days. Growth of sublethal doses of Listeria monocytogenes, Mycobacterium bovis (BCG Montreal), M. tuberculosis H37Rv, and Salmonella enteritidis in the livers and spleens of intravenously challenged mice was significantly increased compared with that in control animals receiving distilled water orally. Tilorone given every other day at a dosage of 10 mg/kg reduced (but did not completely ablate) the tuberculin response to the mycobacterial infections. Both tuberculin hypersensitivity and anti-mycobacterial resistance returned to normal values within days of stopping the drug treatment. Tilorone treatment at the 100-mg/kg dose level increased the growth of S. enteritidis in both intravenously and intragastrically challenged mice; this effect seemed to be due to the reduced ability of the host to express the normal granulomatous response to the microbial infection within the liver and spleen.


Effect of oral niridazole treatment on some bacterial infections in mice. Treatment of specific-pathogen-free CD-1 mice with oral doses of 10 or 100 mg of niridazole per kg of body weight given 24 h before challenge and then every other day for up to 15 days altered the growth curves for Listeria monocytogenes, Mycobacterium bovis (BCG Montreal), M. tuberculosis H37Rv, and Salmonella enteritidis seen in the livers and spleens of the treated animals. Niridazole in an oral dosage of 10 mg/kg reduced (but did not eliminate) tuberculin hypersensitivity in the mycobacteria-infected mice. Both delayed hypersensitivity and antimycobacterial resistance quickly returned to normal levels once the drug treatment was stopped. Niridazole treatment reduced the growth of S. enteritidis in both intravenously and intragastrically challenged mice; this seemed to be due to the antibacterial action of the drug on the salmonellae both in vitro and in vivo.


Treatment of psoriasis with 6-aminonicotinamide. Topical applications of a 1.5 percent aqueous solution of 6-aminonicotinamide for four weeks resulted in substantial improvement or complete clearing of plaques of psoriasis in 27 of 34 patients. These results were clearly superior to those that were obtained with the solvent alone. Dermatitis or marked itching occurred in five of 34 patients. Topically applied thionicotinamide also produced improvement or clearing of some psoriatic lesions in an initial screening trial. The toxic hazards of 6-aminonicotinamide to the central nervous system are discussed.


Acne aestivalis.

Acne aestivalis. This is the first American report, to our knowledge, of a case of acne aestivalis, which occurred in a woman with a recurrent acneform eruption in summertime. The histopathologic sequence was very similar to that found in cases of steroid acne; namely, local necrosis of the follicular epithelium was followed by the formation of a comedo. No cause was found. Treatment with tretinoin brought about regression of the lesions.


Size of adipose cells in infancy.

Size of adipose cells in infancy. Seventy-three samples of adipose tissue from 59 infants, aged from 25 weeks' gestation to 18 months of age, were obtained at necropsy, or at operations, or by needle biopsy. Adipose cell size was measured by microscopy. During fetal life the mean cell diameter increases from about 40 mum at 25 weeks' gestation to 50-80 mum at term. Adipose cells from the buttocks are larger than those from abdominal wall. After birth, adipose cell size continues to increase so that by 3 months the mean cell diameter is about 90 mum. Observations made on infants that had been born preterm showed that the growth of adipose cells proceeds at the same rate whether development in intrauterine or extrauterine.


Acute myelofibrosis in children with Down's syndrome. Two boys with Down's syndrome, recognized at birth, developed acute myelogibrosis at the ages of 19 and 21 months. The disorder presented with anaemia and splenomegaly, and clinically resembled acute leukaemia, but bone marrow histology showed a bizarre pattern with generalized fibrosis, markedly increased reticulin, large reticulum cells, and giant cells resembling megakaryocytes. The children survived 6 and 11 months from diagnosis. A third case is quoted (Hillman and Forrester, 1968) which was also studied at this hospital; the features of all 3 cases are similar. There appears to be an increased incidence of acute myelofibrosis in children with Down's syndrome, which may be a further example of the instability of the haemopoietic system in the disease. In children with Down's syndrome and unusual leukaemia-like illness, histological examination of the bone marrow may be diagnostic.


[Family studies for detection of latent psoriatics by assay of alterations in steroid metabolism (author's transl)]. In psoriasis changes of the DHEA metabolism could be demonstrated. These genetically determined basic alterations may represent an important factor for the manifestation of psoriasis. They consist of a decreased penetration of DHEA through the cell membrane and an increased reduction of DHEA to ADIOL, leading to a reduced DHEA/ADIOL ratio. In the present investigations the question was whether the assay of these parameters may aid in the detection of latent psoriasis. For this purpose 31 members form 6 unselected families of psoriatics (8 manifested psoriatics, 18 potential psoriatics, 5 clinically and anamnestically healthy family members by marriage) as well as 6 further controls were examined. It could be shown that those changes in the DHEA metabolism, which are evident in manifested psoriatics also occur at least in part of potential psoriatics. However, both parameters investigated do not always behave the same way. Hence, from the present data a satisfactory diagnosis of latent psoriasis does not seem possible. Still, the estimation of the above parameters may aid in the attempts to define latent psoriasis. Further investigations of such families are warranted for final elucidation of this problem.


Prevention of peritoneal adhesions in the rat. The effects of dexamethasone, methylprednisolone, promethazine, and human fibrinolysin. Peritoneal adhesions were created in rats by brisk scrubbing of the terminal part of the ileum. Adhesions were graded by total number and the presence of small bowel obstruction. Adhesion prophylaxis was evaluated using dexamethasone, methylprednisolone sodium succinate, promethazine hydrochloride, and human fibrinolysin (Thrombolysin) in various combinations, doses, and routes of administration. Methylprednisolone and dexamethasone, depending on the route of administration, modified the total number of adhesions but did not modify their severity when compared to control animals. Promethazine by itself modified peritoneal adhesions in the rat. Used together, methylprednisolone and promethazine also modified adhesions, but were not substantially better than the combination of dexamethasone and promethazine. Methylprednisolone, promethazine, and human fibrinolyzin, when used in combination intraperitoneally, virtually eliminated adhesion formation.


[Vascular degeneration in otosclerosis and its influence on the mesenchymal reaction of the mucoperiost]. 38 samples of middle ear mucosa were taken from different patients during stapes surgery in otosclerosis. The samples were studied light-and electronmicroscopically without decalcification. Considerable pathologic changes in the organisation of the capillaries (endothelial hydrops, proliferation of the intima and of the adventitia, total obliteration o the vessels) cause pathologic reactions on the mesenchymal elements of the submucosa. Next to fibrolysis or hyalinosis of the collagen fibers the fibrocyts show features of undergoing lysis. Free and cellular bound calcium deposits are located in these lytic areas. The epithelial lining also shows unusual inclusions as glycogen and acid mucopolysaccharides and an alterated basement membrane. We belive that the changes of the connective tissue and of the epithelium are secundary to the capillary obstruction.


Transplantation of islets of Langerhans. Transplantation of insulin-secreting tissues is currently being evaluated as a possible method of treating diabetic patients. Isolation of islets of Langerhans from the rat pancreas is now routinely accomplished, and methods for islet isolation from the human pancreas are being explored. Transplantation of isolated islets into isologous rats is capable of reversing streptozotocin-induced diabetes. Unfortunately, isolated islets are not immunologically privileged and various immunosuppression regimens have not effectively obviated the rejection phenomena seen in rat allograft experiments.


The localisation of sorbitol pathway activity in the rat renal cortex and its relationship to the pathogenesis of the renal complications of diabetes mellitus. A series of in vivo and in vitro investigations was performed to examine the localisation of sorbitol pathway activity in the rat renal cortex and to investigate the possible relation that the acculumation of sorbitol pathway intermediates in renal cortical tissue may have to the pathogenesis of renal complications in diabetes mellitus. Neither of the sorbitol pathway intermediates, sorbitol or fructose, were detected either in intact glomeruli which had been isolated from rats rendered chronically diabetic with streptozotocin, or in metabolically active glomeruli which had been incubated in vitro in high glucose media. Such data agreed with previously published observations that the enzyme aldose reductase is not present in renal glomeruli, and suggested that changes in sorbitol pathway activity cannot be directly related to the pathogenesis of diabetic glomerulosclerosis. Sorbitol was detected in low concentrations (3.1 mu-mol/g protein) in cortical tubules which had been isolated from the renal cortex of rats rendered chronically diabetic with streptozotocin. This concentration of sorbitol was higher than that in the intact renal cortex of the diabetic animal (0.3 mu-mol/g protein) or in the cortical tubules of non-diabetic animals (0.5 mu-mol/g protein). It is apparent that the renal cortical tubule is a major site of sorbitol pathway activity in the renal cortex. However, there is presently no obvious causal relationship between the accumulation of such relatively low concentrations of sorbitol in the renal cortical tubule and the pathogenesis of glomerulosclerosis or cortical tubular lesions in diabetes.


Separation of a proteoglycan fraction from Kurloff cells stimulating protein synthesis in macrophages. Proteoglycan from Kurloff cells, when present in the medium in low concentrations, increased the incorporation of (3-H)leucine into trichloracetic acid-precipitable material by macrophages from peritoneal exudates, in addition to inhibiting their migration from capillary tubes, as observed previously. After treatment with 0.5 M-NaOH, followed by dialysis or ultrafiltration, material with the distinctive u.v. and i.r. spectra of the whole proteoglycan appeared in the diffusate, and biological activity was lost from the proteoglycan which remained in the dialysis residue. The diffusible material absorbed near 260 nm and had i.r. bands at 805 cm-minus-1 and 1260 cm-minus-1, but did not display the i.r. bands characteristic of chondrotin 4-sulphate. It contained little sulphate, no hexosamine and less than 1% of the uronic acid present in the whole proteoglycan, and there were only trace amounts of amino acids, xylose and galactose. However, significant amounts of ribose and organic phosphate were present, each representing about 1% of the whole proteoglycan. After proteolysis and chondroitanase digestion of the proteoglycan, a fraction with absorbance at 260 mn was eluted from Dowex 1 with water which stimulated the incorporation of (3H)leucine by macrophages and inhibited their migration from capillary tubes.


Plasma membranes from experimental granulation tissue. 1. A procedure was developed for the preparation of plasma membranes from experimental granulation tissue of the rat without the addition of enzymes. The yield is better than 20% and the purification at least tenfold. 2. Values are given for the activities of 5'-nucleotidase, Na-+, k-+-activated Mg-2+dependent adenosine triphosphatase and leucine beta-naphthylamidase, for lipid composition, and for the gel-electrophoretic patterns of proteins and glycoporteins in the membrane preparations. 3. The plasma membranes from the mature granulation tissue contain proportionally more protein in the lipid phase, but the specific activities of 5'-nucleotidase and Na-+,K-+-activated Mg-2+-dependent adenosine triphosphatase are smaller than in the proliferating tissue. Certain differences were repeatedly observed in the gel-electrophoretic patterns of the developmental phases. 4. The plasma membranes from the granulation tissue were compared with those from rat peritoneal macrophages and from embryonic-chick tendon cells.


Lipid requirement of the membrane sodium-plus-potassium ion-dependent adenosine triphosphatase system. The dependence of the (Na-++K-+)-dependent ATPase (adenosine triphosphatase) (EC 3.6.1.3) on lipid has been examined in a number of different ways, with the use of various preparations from kidney tissue. The main findings were as follows. (1) The ATPase activities of the preparations examined were closely correlated with their total phospholipid content. (2) Extraction of the ATPase with deoxycholate or Lubrol W, combined with suitable salt-fractionation and washing procedures, removed phospholipid, cholesterol and enzymic activity in parallel; but activity was completely lost before all lipid had been removed. (3) The loss of activity could not be attributed to inhibition by residual detergent. (4) No selective removal of any particular phospholipid class by detergent could be detected. (5) Consistent reactivation of the Lubrol-extracted enzymes was obtained  by adding dispersions of exogenous phospholipid, but only some, bearing a net negative charge, such as phosphatidylserine and phosphatidylglycerol, were effective. (6) The degree of reactivation was correlated with the amount of residual activity remaining after lipid depletion. (7) Partial purification of the ATPase, giving a 50-fold increase in specific activity, was not accompanied by selective enhancement of any particular class of phospholipid. We conclude that although the ATPase is dependent on phospholipid, only the reactivation results provide evidence for specificity.