Effect of hyperbarism on collagenous protein metabolism in granulation tissue. Rats with subcutaneously implanted polyurethane sponges were exposed 6 hours daily for 7 days to high ambient atmospheric pressures (1.5, 2, 2.5 and 3 ATA). Another group was exposed 4 hours daily for 4 weeks to 3 ATA before inducing granulation tissue formation. 14C-proline was administered 16 hours before terminating the experiment. Free hydroxyproline, soluble and insoluble collagen and total noncollagenous protein were isolated from the 7-day granuloma and the amount and radioactivity of 14C-hydroxyproline and 14C-proline were determined. Seven days' graduated hyperbarism did not affect collagen synthesis; the maturation of collagen to insoluble forms was inhibited at 2 and 2.5 ATA, but not at 3 ATA. Stimulated degradation of collagen (free hydroxyproline) was observed at 2, 2.5 and 3 ATA. In animals subjected to long-term exposure at 3 ATA pressure, the collagen in the granuloma matured to insoluble forms more quickly. Biochemical changes were correlated with changes in the fine structure of the granulation tissue. The appearance of the fibroblast proteosynthetic apparatus was not influenced by hyperbarism. Progressive spherical transformation, fusion of mitochondria and lysosomal activation in the pericapillary fibroblasts occurred at 2, 2.5 and 3 ATA. In short-term experiment, the formation of cytosegresomes and cellular necrosis also contributed to the effect at 3 ATA, which is thus already a toxic pressure for granulation tissue.


The effect of adrenal cortical hormones on the calcium content of rat aorta. The administration of prednisone in a dose of 10 mg/kg b.w. per os and of deoxycorticosterone in a dose of 10 mg/kg i.p. to rats weighing 200--220 g 24 hours before the experiment did not affect significantly the calcium content of the aortic vascular tissue. Metopiron, which influences biosynthesis of the adrenal hormones, likewise did not affect the calcium content when administered i.p. in a dose of 500 mg/kg b.w. and did not inhibit reserpine-induced calcium depletion. The results thus failed to confirm the hypothesis that reserpine influences the calcium content of the vascular wall via stimulation of corticold release.


The effect of antidepressants on the calcium content of the aorta of reserpine-treated rabbits. The pre-administration of reserpine in a dose of 5 mg/kg b.o. i.v. 24 before the experiment reduced the calcium content of the thoracic aorta of rabbits weighing 1,000--1,500 g. It had no effect on the calcium level in older animals. The calcium content also fell after 10 days' administration of reserpine in daily doses of 0.1 mg/kg b.w. Pre-administration of the monoaminooxidase inhibitors phenelsine and nialamide inhibited the reserpine-induced decrease in the calcium content of the vascular wall, although by themselves they had no effect on it. Prothiadene, a thymoanaleptic, likewise inhibited, the decrease in the calcium content when administered per os in a dose of 5 mg/kg b.w. 5 hours before reserpine.


Biological properties of rat serum hydrolases splitting N-acetyl-L-tyrosine ethyl ester. An increase in the level of activity splitting N-acetyl-L-tyrosine ethyl ester (ATEE) was found in the plasma of rats with experimentally induced rheumatoid inflammation. The level of this activity rose paralled with development of the inflammation. Homogenate of inflamed rat paws was found to contain a raised content of the high molecular weight fraction. Which was found to contain a raised content of the fraction I (splitting ATEE) causes an increase in vascular permeability and releases active kinins from plasma kininogens. These properties were also found, on a smaller scale, in serum fraction II. The results show no parallel between ATEE-splitting activity and the magnitude of the biological response.


Antiphlogistic action of phenylbutazone in normal and adrenalectomized rats of different ages relation to the 5-hydroxytryptamine blood concentration. The authors have attempted to demonstrate the effect of bilateral adrenalectomy on carrageenin-induced oedema and on the antiphlogistic action of phenylbutazone in relation to the changes of blood 5-hydroxtryptamine (5-HT) in rats of different ages (21 days, 42 days, 3 months and 18 months old). It was found that the influence of adrenalectomy on the antiphlogistic action of phenylbutazone and on the blood 5-HT concentration is related to the age of rats. The lowest antiphlogistic action of phenylbutazone was found in 21-day-old rats and highest in the 18-month-old ones. In adrenalectomized 21- and 42-day-old rats the antiphlogistic action is decreased  and fully suppressed in rats 3 and 18 months old. Adrenalectomy does not influenced basal values of blood 5-HT concentration. Blood 5-HT in adrenalectomized rats with inflammationadrenalectomized rats 42 days and 3 months old with inflammation after injection of phenylbutazone an increase of 5-HT was observed, but in 18-month-old animals in which antiphlogistic action is highest a decrease of 5-HT was observed.


Superior olivary complex in psychotic patients. A study of the neuropathology of the superior olivary nucleus and its relationship to schizophrenia or auditory hallucinations was undertaken.  No relationship was found to exist between them, but atrophy of the superior olivary nucleus was found in all the patients who had presented with seizures during life.  The aetiology of superior olivary atrophy is discussed.


Pattern of intellectual impairment in Huntington's chorea. Cognitive function was evaluated in 11 patients with Huntington's chorea, using eight subtests of the WAIS, and their performance was compared with that previously reported for a normal aged population.  The pattern of impairment was similar in the two groups.  Tests of immediate memory were given to nine of these patients, and to 10 healthy but aged subjects.  In both groups, there was a significant correlation between the performance of individuals in these tests and their IQ, suggesting that the choreic patients had no selective impairment of immediate memory.  The clinical and psychological records of the 11 patients revealed no evidence of focal deficits, and the majority of patients were fully orientated and retained insight to their condition.  These observations are discussed in relation to the pattern of intellectual impairment seen in other presenile dementias.


[Effect of p-chlorophenylalanine on the reproduction of the rat (author's transl)]. The effect of p-chlorophenylalanie (p-CPA) --300 mg/kg-- on reproduction has been studied in the female rat. Groups of animals were injected with a dose of 300 mg/kg of p-CPA 48 hours before proper copulation conditions at different moments along the ovarian cycle. Presence of spermatozoa in the vaginal frotis was negative in treated rats; in the control groups however, positivity was found in variable proportions according to the phase of the ovarian cycle: 30 ad 90% in diestrus and proestrus respectively. Treated animals showed continuous diestrus phases and diffuse luteinitation of the ovary. The results may indicate that a decrease of cerebral 5-HT, caused by p-CPA, lessens the reproductive behaviour of the female rat through mechanisms depending probably on the liberation of gonadrotrophins.


[Urinary excretion of 11-deoxy-17-ketosteroids during the normal menstrual cycle (author's transl)]. Urinary excretion of 11-deoxy-17-ketosteroids was studied in 20 to 22 women with normal menstrual cycles on the 7, 10, 14 and 20th days of their cycles. The fraction studied showed a significant cyclic variation with a type of pattern for Androsterone and Aetiocholanolone and another one for the Dehydroepiandrosterone. The possibity of one metabolic path for the former metabolites and a different one for the latter, plus its close conection with the functional changes of the ovary, were arrived at.


Myopathy in experimental uremia.

Myopathy in experimental uremia. M. quadriceps and diaphragm were studied in Wistar rats 2, 3, und 4 weeks after 5/6 nephrectomy. Control animals were sham operated and pair fed. In 10 mu transverse cryostat sections, the following histochemical reactions were performed: NADH-dehydrogenase, myofibrillar ATP-ase, modified trichrom stain, hematoxylin-eosin. Three fibre types (I, II, intermediate) were analysed quantitatively by planimetry. Sarcolemnal nuclei per unit area and fibre cross section area were determined. In muscle specimens from uremic animals, a uniform atrophy of all three fibre types could be demonstrated. In contrast to findings in man, preferential atrophy of one of the three fibre types, increase of sarcolemnal nuclei per fibre cross section area or structural abnormalities within single muscle fibres could not be detected. Neurogenic damage could be excluded (electrophysiology, sciatic nerve planimetry). The fibre changes point to a primary disturbance of muscle metabolism.


Pain in the back: An attempt to estimate the size of the problem. British morbidity statistics are reviewed to try to estimate the size of the problem of the painful back. National Insurance figures yield an estimated 13.2 million working days lost in one year, though only 68% of this is identified in routinely published statistics. Other bodies of data (G.P. consultations, outpatient and inpatient flows, spinal supports supplied) indicate use of services by sufferers. The difficulties in retrieval caused by the structure of the international Classification of Diseases (ICD) and the effects of the latest revision of it are examined.


Towards a better understanding of low-back pain: a review of the mechanics of the lumbar disc. By measurement of intradiscal pressure in vitro, the hydrostatic properties of the nucleus pulposus of normal lumbar intervertebral disc was established. The stress distribution within normal discs subjected to vertical load was also explained, demonstrating the high tangential strains occurring in the posterior part of the annulus fibrosus. Intravitally performed measurements of disc pressure have demonstrated how the load on the lumbar disc varies according to the position of the subject's body. Compared to the pressure or load in the upright standing position, reclining reduces the pressure by 70%, while unsupported sitting increases the load by 40% and forward leaning and weight lifting by more than 100%. Similar relatively large augmentations of the load were observed in subjects performing various commonly used muscle-strengthening exercises. Measurement of intradiscal pressure is instrumental in explaining, from a mechanical point, the occurrence of posterior ruptures in the lumbar discs, and provides a basis for the rational treatment of patients with low-back pain in so far as these exhibit increase of pain on increased mechanical loads. For the majority of patients with low-back pain, the cause is unknown, although most evidence so far presented links the lumbar intervertebral disc to the pain syndromes. Results of recent studies have shown that both chemical and mechanical factors are probably of importance. So far we cannot successfully treat the chemical part of the disc syndrome. Since all our patients exhibit more pain when the spine is mechanically loaded, knowledge gained from intravital disc-pressure measurements provides a basis for successfully treating the mechanical part of the condition. Since none of the frequently prescribed and more spectacular remedies has ever been proved statistically superior to any of the others, it is most fair to our patients and to ourselves to use simpler, less expensive, and less dangerous programmes, such as bed-rest, administration of salicylates, and proper ergonomic advice. Based on a scientific approach, the low-back-pain school is intended to help the patient to be able to cope with these back troubles, to avoid excess therapy, and to decrease the cost both for the individual and for Society.


HL-A 27 and the diagnosis of back problems. Too much of the information required for rigorous assessment of the diagnostic value of a positive HL-A 27 test is not available. Certainly there would seem to be no case for population screening, not least because effective prophylaxis is not possible. At present sacroiliac radiographs have greater value in the clinical situation, and it seems unlikely that the contribution they make to diagnosis will be challenged. The absence of the HL-A 27 antigen may have some value as an exclusion test, but careful prospective studies are required, as well as a more detailed cost-benefit appraisal of this test.


Histochemical and neurophysiological studies of autotransplanted cat muscle. Free autologous transplants of previously denervated whole muscles in adult cats were studied with histochemical and electromyographical methods. The transplants were placed in contact with normal intercostal muscles in intercostal spaces and removed at intervals from 5 days to 44 weeks after transplantation. Normal muscles as well as transplanted muscles without previous denervation and muscles denervated and left in situ were also studied.. The fibres of the previously denervated grafts survived the first avascular period, but a de-differentiation of enzymatic characteristics of the red and white fibres occurred and endured during the first 6 weeks after grafting. The first signs of reinnervation could be identified with electromyography after 4 weeks and with histochemical techniques after 6. Reinnervation of most of the fibres of the transplants was completed about 14-18 weeks after grafting. No fibrillations were then found electromyographically and in the histochemical preparations most fibres had attained near-normal staining characteristics. Type grouping was apparent but less pronounced than reported after reinnervation through the motor nerve. There was conclusive evidence that previously denervated muscles survived transplantation and became structurally and enzymatically mature whereas muscles transplanted without previous denervation undergo extensive fibrotic changes.


[Localized malignant mesethelioma of the peritoneum revealed by a parietal mass]. A report is presented on a rapidly evolving, fatal case of localized malignant mesothelioma of the peritoneum revealed by an abdominal wall mass. Although the tumor was at an advanced stage, a large excision of the primary mass and its metastases was attempted. On the basis of this observation the authors point out the main features of these rare tumors, the diagnostic difficulties they involve, and their possible relationship to asbestos dust exposure.


[Spectinomycin.  Indications and undesirable effects]. Modern chemotherapy postulates highly active drugs without unwanted side effects.  In the treatment of gonorrhea spectinomycin meets even the strictest requirements: maximal obtainable cure rates, no masking of concomitant syphilitic infections, and excellent tolerance.  In animal experiments no sensitizing effect of spectinomycin was found even when maximation procedures were applied.  Anaphylactoid activity of spectinomycin is low, as has been documented by personal investigational series.


High-resolution scanning electron microscopy of bacteriophages 3C and T4. An account is presented of the design and operation of a new scanning electron microscopic, and its first application to the study of biological samples. Bacteriophages were chosen because much of their ultrastructure is beyond the resolution of the conventional scanning electron microscope. The new instrument permits examination of bulk samples with a resolution that exceeds, by at least a factor of 2.5, the resolution obtained in the best secondary electron scanning electron microscopes using high brightness guns, and exceeds by an order of magnitude the resolution of standard scanning electron microscopes using tungsten filament guns. It also permits examination of biological samples in scanning transmission mode at resolutions similar to conventional transmission electron microscopes.


Chelation therapy in lead nephropathy.

Chelation therapy in lead nephropathy. Although treatment has been well defined for childhood lead poisoning and for industrial lead exposure, the treatment of lead nephropathy has been poorly studied. The available chelating agents are reviewed and the results of treatment in 17 cases of lead nephropathy are shown. It is concluded that lead nephropathy should be recognized early and treated energetically, as this may stabilize or improve renal function. Since EDTA is excreted much like creatinine, the dosage must be reduced proportionately in response to elevated serum creatinine levels in the patient with renal failure.


Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis. Hypersensitivity pneumonitis, a disease caused by repetitive inhalation of nonviable organic dust, is increasingly recognized as a cause of acute and chronic lung disease in both children and adults. Twenty-one of 32 children and adults who went on a hay ride in Arkansas developed this disease. These cases are reported. The clinical manifestations, pathology, differential diagnosis, treatment, and immunologic aspects of the disease are reviewed.


Gold therapy in rheumatoid arthritis.

Gold therapy in rheumatoid arthritis. Forty patients with active rheumatoid arthritis were treated with intramuscular injections of gold salts. A significant response was shown by 67,5% of the patients. Treatment was discontinued owing to side-effects in 35%. Dermatitis and proteinuria from renal damage were the commonest complications of treatment. The method of treatment and its side-effects are discussed.


Augmented antibody-dependent cell-mediated cytotoxicity following sensitization or nonspecific stimulation of human effector cells. Human peripheral blood leukocytes were stimulated in vitro with mitogens (poke-weed mitogen, concanavalin A, and phytohemagglutinin) or allogeneic cells. Each form of stimulation augmented the cytotoxic effector cell activity of lymphoid cells in a 4-hr test for antibody-dependent cell-mediated cytotoxicity. This augmented activity did not involve release of detectable nonspecific toxins, nor did it require the presence of mitogen during the cytotoxicity test. Stimulated attacking cells appeared more cytotoxic either because of a more potent cytotoxic mechanism per individual cytotoxic cell or because of an increased percentage of cytotoxic cells.


Bone marrow transplantation between mixed lymphocyte culture-reactive individuals. A 13-year-old boy with acute myelogenous leukemia resistant to conventional chemotherapy received a bone marrow transplant from his HL-A-identical, mixed lymphocyte culture-reactive sister. The recipient was prepared for transplantation with cyclophosphamide and total body irradiation. Despite cytogenetic evidence of engraftment, graft-versus-host disease was not observed. The patient died 38 days post-transplantation of Gram-negative bacteremia sepsis and recurrent leukemia of recipient origin.


A new micromethod for the detection of HL-A antigens on cultured human tumor cells. A rapid microcytotoxicity assay for the detection of HL-A antigens on tissue culture cells derived from human solid tumors is described. Tumor cells were prelabeled with 125Iododeoxyuridine. Isotopically labeled tumor cells were reacted with up to 37 highly selected HL-A antisera and diluted rabbit complement. Results of the HL-A typing of nine human tumor cell lines are reported. Three melanoma cell lines showed individually distinct HL-A profiles at the first HL-A locus which agreed with the antigenic pattern of the tumor donor's autologous lymphocytes. Less reactivity was noted with HL-A antisera defining second locus specificities on the three melanoma cell lines, whereas some other cell lines showed more HL-A reactions than required to present a "full house". This method obviates the necessity for visually enumerating residual tumor target cells.


Mouse lymph node activating factor released during contact of HL-A-different blood lymphocytes. Ten-fold concentrated supernatants from the 4-hr mixed cultures of lymphocytes from two humans different at two haplotypes were inoculated s.c. into the hind footpad of mice. Twenty-four to forty-eight hours later, the cellularity and the synthesis of ribonucleic acid increased significantly in the popliteal lymph nodes draining the site of injection. The supernatants from cultures of HL-A-identical cells of cells different at one haplotype lacked this activity. The results suggest that human imcompatible lymphoid cells upon mutual contact liberate a soluble mediator capable of activating the draining lymph nodes; i.e., it is able to trap cells from the circulation and to stimulate them. The mediator is species-nonspecific; the activity produced by human lymphocytes can be tested on mice.


Strong mixed lymphocyte reaction associated with the LA or first locus HL-A. Bidirectional strong stimulation in one-way mixed lymphocyte cultures (MLC) is reported between an HL-A recombinant and sibling, apparently differing only at the LA or first locus HL-A. The strong MLC reaction may represent a second strong MLR-S locus associated with the LA or first locus HL-A. Alternative explanations are discussed. A second example of a recombinant HL-A haplotype transmitted to progeny is also reported.


[Karyotype of the lizard Eumeces taeniolatus]. Using bone marrow cell preparations, the karyotype of Eumeces taeniolatus Blyth was examined. The diploid chromosome set of E. taeniolatus is found equal to 28 (24 meta- and 4 submetacentrics), NF=56. Sex chromosomes do not differ morphologically.


Nicotine effects on the acid mucopolysaccharide content of chick embryo cardiac jelly. Histochemical studies were made on the developing chick embryo heart to determine the effects of nicotine on acid mucopolysaccharide content during the critical stages of the cardiac morphogenesis. Two-day old embryos were injected with the dosages of nicotine ranging from 1.5 to 3 mg per embryo. The embryos were studied on the 3rd and 4th days of incubation. For an evaluation of acid mucopolysaccharides, the staining procedures of Mowry (1958) and Saunders (1964) were employed. It was found that nicotine decreases the content of acid mucopolysaccharide in the developing cardiac jelly. In the control embryos, the cardiac tissues picked up very intense coloration. At lower dosages (Group A; 1.5 mg/egg), the staining response of the treated heart tissues containing acid mucopolysaccharides was moderate as compared to the control embryos. At higher dosages (Group B; 3 mg/egg), the cardiac tissues were faintly colored as compared to the embryos of Group A. It is possible that the cardiac lesions previously reported in the chick embryos following the administration of nicotine (Gilani, 1971) are due to the reduction of the amount of acid mucopolysaccharides in the developing cardiac jelly--a susceptible period of the genesis of heart.


Hypertrophic non-obstructive cardiomyopathy caused by disorder of the myofiber texture. A case of hypertrophic non-obstructive cardiomyopathy caused by a disorder of the myofiber texture was observed in a 10 year old boy. The heart weighed 390 g and showed concentric hypertrophy of the left and right ventricles as well as of the ventricular septum. Additional findings consisted in an abnormal septum membranaceum and a accessory tricuspid valve leaflet. Severe cardiac hypertrophy was associated with prominent interstitial and subendocardial fibrosis, and pronounced intimal fibrosis of the intramural arteries. Electron microscopy revealed various degrees and stages of hypertrophy of the myocardial cells combined with severe degenerative changes. Additional changes of the sinus node and conduction system were responsible for a tachycardia-bradycardia syndrome, complete left bundle branch block and final total AV-block.


[On the structural changes induced in adenomyosis uteri and endometriosis externa by hormonal therapy (author's transl)]. This study was undertaken to determine whether the hormonal sensitivity of the endometrium might be a measure of the effectiveness of hormonal therapy for adenomyosis and endometriosis. Accordingly, the effects of endogenous and exogenous hormones on the endometrium, adenomyosis, and endometriosis were correlated. The results revealed that, depending on where the ectopic endometrial tissue was located and on the type (duration and intensity) of hormonal treatment, the functional response of the endometriosis varied from that of the endometrium. The variations, however, can be predicted. The response of adenomyosis to hormonal stimulation was most like that of the endometrium. Endometriosis of the ovary often revealed an excessive response to stimulation, especially after gestagens. The other types of extrauterine foci of endometriosis, however, reacted only weakly to hormonal therapy. Important prognostic consequence for therapy can be drawn from the results.


[Clinical, biochemical, morphological and electrophysiological studies of glycogenosis Type II in childhood with double deficiency of enzymes (author's transl)]. The clinical, biochemical, morphological and electrophysiological findings in a 13-month-old child, who died of glycogenosis type II, is presented. In addition to the deficiency of alpha-1,4-glucosidase, which is typical for the disease, a deficiency in hyaluronidase could be detected for the first time in the skeletal and heart muscles and in the liver. On the other hand, the beta-glucoronidase and beta-acetylglucosaminidase activity was highly increased. Deposits of a substance, most probably an acid mucopolysaccharide, which could be differentiated from glycogen by chromography and electronmicroscopy, could be detected in the muscle. A pathogenetical connection with the hyaluronidase defect is imminent.


Ultrastructure of ovarian teratomas in LT mice. Stem cells of these tumors formed nests consisting of undifferentiated embryonic cells in the center with more differentiated cells towards the periphery. A type viral particles were seen in the cisternae of rough endoplasmic reticulum. Ultrastructurally the stem cells of ovarian teratomas did not differ from stem cells of testicular or embryo-derived teratomas. They were however distinct from the cleavage stage embryonic cells and/or the unfertilized ovum, they stemmed from. They correspond both cytologically and developmentally to ectodermal embryonic cells from the egg-cylinder, the most advanced developmental stage of parthenotes observed previously in the ovary of LT mice.


Additional chromosomal indication for the unicellular origin of chronic myelocytic leukemia. In a female patient with chronic myelocytic leukemia (CML) the translocation 9q +; 22q  was constantly found to involve only the variant chromosome 9 with an unusually long secondary constriction. The finding indicates a unicellular origin of CML.


Plaque development by vaccinia-viruses on the chicken chorio-allantois under the influence of cyclophosphamide. The development of Vaccinia-virus plaques on the chorioallantois of embryonated eggs was studied under the influence of active cyclophosphamide metabolites. The viruses were inoculated on the 9th or the 13th incubation day. Cyclophosphamide was injected in doses of 62.5--500 mug in 0.2 ml NaCl into the yolk sac either 7 hrs after the virus inoculation or 3, 6, or 9 hrs in advance. The plaque development was not influenced when cyclophosphamide was given after the virus inoculation. But in treating the embryos before the infection a decrease dependent on the dose in the number of embryos with recognizable plaques occurred. This decrease was more marked with cyclophosphamide treatment 6 or 9 hrs, than with cyclophosphamide treatment 3 hrs before the virus inoculation. When the embryos were inoculated on the 13th day and treated with cyclophosphamide 9 hrs in advance, the mean effective dose was 316 mug/egg. The range of effective doses corresponds with that of the inhibitory effective doses of cyclophosphamide on transplantation tumors grown on the chorio-allantois of embryonated eggs.


The metastatic spread of "head and neck" tumors in men (an autopsy study of 371 cases). The investigation was performed by using 371 autopsy records collected by the Department of Pathology at Roswell Park Memorial Institute from 1956 till 1967. Only the "head and neck" tumors were taken into consideration. Two hypotheses were tested, i.e. whether metastases diffuse directly from the primary tumor throughout the body or if the metastatic process takes place in steps, requiring, in other words, that one or more organs be seeded first, before any generalized metastasis occurs. It appeared that the lungs and the lymphnodes of the neck are the two organs responsible for generalized metastases in the cancers of the "head and neck" area. The importance of the neck and lungs metastases in disseminating the disease was discussed in the text. It appeared that when metastases are present in the lymphnodes of the neck, the cancer is already generalized with and without metastatic deposits in the lungs. However, the absence of metastases in the neck is no guarantee that the disease is still localized to the "head and neck" area.


Proceedings: Prognosis of non-Hodgkin's lymphomas with special emphasis on the staging classification. The prognosis of the non-Hodgkin's lymphomas is determined by 1. the pattern of origin and spread which can be demonstrated in a staging classification, 2, the histopathological type, and 3. the effectiveness and scope of the treatment methods, particularly radio- and chemo-therapy. In the following paper the Ann Arbor Classification, which was originally conceived of for both disease groups (Hodgkin's and non-Hodgkin's lymphomas), is discussed particularly with respect to the applicability and prognostic evaluation for the non-Hodgkin's lymphomas. The Ann Arbor Classification may in essence reflect the oncological characteristics of the non-Hodgkin's accurately; there are, however, a number of findings with qualitative and quantitative differences which defy integration into the Ann Arbor Classification. The qualitative differences consist of the differing lymphatic and extralymphatic origins and their consequence for spread and prognosis. The quantitative differences refer to the varying patterns of distribution of the different stages of spreading, whereby the dissemination stages in the non-Hodgkin's lymphomas are more dependent on the histological form than is the case with the Hodgkin's lymphomas, and thus must play a greater role in the prognostic evaluation and indication for treatment. Suggestions have been made for a modification of the Ann Arbor Staging Classification for the non-Hodgkin's lymphomas.


Ribose conformations in the common purine(beta)ribosides, in some antibiotic nucleosides, and in some isopropylidene derivatives: a comparison. With the use of PMR the ribose conformations have been studies in the temperature range -60 to +40 degrees C in ND3 solutions of adenosine (A), guanosine (G), inosine (I), xanthsine (X), purineriboside (PR), 2-aminopurineriboside (2amPR), N6-isopentenyladenosine (N6ipA), 8-bromoadenosine (iA), and isopropylideneguanosine (iG). The aanlysis is based on the two-state S in equilibrium N model of the ribose moiety proposed by Altona and Sundaralingam. The compounds studied can be classified into two groups: 1. A, I, G, X, PR, 2amPR, N6ipA, and T show a small temperature dependence of thnd F have a stronger temperature dependence and [S] approximately 0.8. Within these two groups the similarities observed are greater than observed in the solid state. Some thermodynamic conclusions about the S in equilibrium N and the syn in equilibrium anti equilibria are presented. The results support the previously proposed correlation of the S state of the ribose with the syn conformation of the base and of the N state of the ribose with the anti conformation of the base. Furthermore, it is derived that the gg rotamer is correlated with the S state of the ribose and therefore stabilizes the syn conformation of the base.


Biochemical synthesis of stereospecifically hydrogen labeled compounds on a preparative scale, VI1-3 Synthesis of further substrates of NAD(P)-linked dehydrogenases of high specific tritium content. The preparation of (R) and (S) [2(-3)H]lactate as well as (S) [2(-3)H] glutamate via the coupled exchange reaction catalyzed by NAD linked dehydrogenases and NADH: lipoamide oxidoreductase (diaphorase) is described. The specific radioactivity of the hydrogen ions of the 3HOH/H2O can be obtained in the substrates (100% exchange) if equilibrium isotope effects are disregarded. By the exchange procedure substrates with higher specific radioactivity are obtained from positionally [3H]labeled racemic mixtures prepared by chemical reductions with [3H]labeled hydrides. The tritium content of one of the enantiomeres is "washed out" into water. As examples are presented the preparation of (R) [2-3H] (S) [2-H]malate as well as the corresponding carnitine, glutamate and (R) and (S) lactate.


[Studies on a resonance of carcinogenic benzpyrene (author's transl)]. The alpha- and p-states of 3.4-benzpyrene are calculated by use of common parameters and of a parameter set which predicts the quasi-degeneracy of these states. The quasi-degeneracy will be represented by the breadage of pairing theorem and is to be described as a correlation effect, caused by an asymmetric potential. An external field represents an external perturbation, introduced by interaction with the bioreceptor. The calculation shows a sensitive dependence of probability amplitudes for different configurations which participate in the quasi-degenerated resonance states. Thereby the dipole moment may quickly be changed so that excitons are produced. The resonance phenomenon may lead to the carcinogenic effect.


Studies on the nature of the primary reactions of photosystem II in photosynthesis. I. The electrochromic 515 nm absorption change as an appropriate indicator for the functional state of the photochemical active centers of system II in DCMY poisoned chloroplasts. The field indicating electrochromic 515 nm absorption change has been measured under different excitation conditions in DCMU poisoned chloroplasts in the presence of benzylviologen as electron acceptor. It has been found: 1. The amplitude of the 515 nm absorption change is nearly completely suppressed under repetitive single turnover flash excitation conditions which kinetically block the back reaction around system II (P. Bennoun, Biochim. Biophys. Acta 216, 357 [1970]). 2. The amplitude of the 515 nm absorption change measured under repetitive single turnover flash excitation conditions which allow the completion of the back reaction during the dark time between the flashes (measuring light beam switched off) amounts in the presence of 2 mum DCMU nearly 50% of the electrochromic 515 nm amplitude obtained in the absence of DCMU. In DCMU poisoned chloroplasts this amplitude is significantly decreased by hydroxylaminhydrochloride, but nearly doubled in the presence of CDIP+ascorbate. 3. The dependence of the 515 nm amplitude on the time td between the flashes kinetically resembles the back reaction around system ?II. The time course of the back reaction can be fairly described either by a second order reaction or by a two phase exponential kinetics. 4. 1,3-dinitrobenzene (DNE) or alpha-bromo-alpha-benzylmalodinitril (BBMD) reduce the 515 nm amplitude in DCMU poisoned chloroplasts, but seem to influecne only slightly the kinetics of the back reaction. 5. The dependence of the 515 nm amplitude on the flash light intensity (the amplitude normalized to 1 at 100% flash light intensity) is not changed by DNB. Based on these experimental data it has been concluded that in DCMU poisoned chloroplasts the amplitude of the 515 nm absorption change reflects the functional state of photosystem II centers (designated as photoelectric dipole generators II) under suitable excitation conditions. Furthermore, it is inferred that in DCMU poisoned chlorplasts the photoelectric dipole generators II either cooperate (probably as twin-pairs) or exist in two functionally different forms. With respect to BBMD and DNB it is assumed that these agents transform the phtooelectric dipole generators II into powerful nonphotochemical quenchers, which significantly reduce the variable fluorescence in DCMU-poisoned chloroplasts.


[2-anilino-1,3,4-thiadiazoles, inhibitors of oxidative and photosynthetic phosphorylation (author's transl)]. 2-anilino-1,3,4-thiadiazoles carrying various substituents in the 5-position as well as in the benzene-ring were synthesized. The compounds were tested with rat-liver-mitochondria and with spinach-chloroplasts and revelaed to be potent uncouplers of both, oxidative and photosynthetic phosphorylation, with pI50-values rangeing from 6.79 to 4.05. At higher concentrations all compounds are inhibitors of the Hill-reaction. In mitochondria a fair correlation exists between pKa of the acidic NH-group and the uncoupling activity; a maximum is obtained around pKa equals 6.8, whereas in chloroplasts activity is shifted to more acid pKa-values. The compounds meet the requirements for uncouplers according to the chemi-osmotic theory, being lipophilic weak acids. N-methylation causes total loss of activity in mitochondrial oxidative phosphorylation. The ingibitory action on photosynthetic electron transport is located within photosystem II. This latter activity is almost independent of substituent effects in contrast to uncoupling of either respiratory- or photo-phosphorylation.


Studies on the nature of the primary reactions of photosystem II in photosynthesis. II. The modification of the functional integrity of the photochemical active centers of system II by a alpha-bromo-benzyl-malodinitril and accompyaning effects on chloroplasts. The effect of alpha-bromo-alpha-benzylmalodinitril (BBMD) on the oxygen evolution and on the absorption changes at 515 nm and 704 nm has been investigated in spinach chloroplasts. It has been found: 1. Under repetitive flash excitation conditions, where the back reaction around system II is practically excluded for kinetical reasons, BBMD does not resotre the 515 nm absorption change in DCMU poisoned chloroplasts. 2. Under single flash excitation conditions, where the back reaction around system II becomes prominent in the presence of DCMU, BBMD moderately inhibits this back reaction. The deleterious effect is pronounced by preillumination with short flashes during the BBMD incubation period of the chloroplasts in the absence of DCMU. 3. Incubation of the chloroplasts with BBMD leads to an activity loss of oxygen evolution which increases with the time td between the repetitive short excitation flashes and with the dark incubation time. Preillumination during the incubation period with tbbmd significantly enhances the effect. 4. In the absence of artificial electron acceptors BBMD suppresses in DCMU poisoned chloroplasts the 704 nm absorption change reflecting an internal cyclic electron flow around system I. On the other hand the linear electron transport at system I mediated by DCIP plus ascorbate as electron donor couple and benzylviologen as electron acceptor is not distrubed by BBMD. 5. BBMD incubation of chloroplasts accelerates the decay rate of the field indicating 515 nm absorption change. Based on these experimental findings the conclusion has been drawn, that -- in contrast to the assumption of Brandon and Elgersma (Biochim. Biophys. Acta 292, 753--762 [1973]) -- BBMD does not accept electrons from the primary electron acceptor X 320 of system II in DCMU poisoned chloroplasts. BBMD rather acts as a system I electron acceptor. Furthermore, BBMD exerts deleterious effects on the center of photosystem II, accompanied by a weak ADRY-effect on the water-splitting enzyme system Y. As a tentative explanation of the BBMD-action on system II it is assumed that BBMD transforms the photochemical centers of system II into dissipative energy sinks.


Transport and processing of ribosomal RNA in plant cells after treatment with cycloheximide. In freely suspended cells of parsley (Petroselinum crispum) protein synthesis is inhibited nearly totally by 5 mug/ml cycloheximide within 10 min. This very low dose has a slight effect on the rRNA synthesis too. During an incubation period of 60 min with [32P] orthophosphate in the presence of the inhibitor (5 mug/ml) at least 65-70% mature rRNA are synthesized compared with the control. After 120 min the synthesis is progressively reduced to 60-65%, and after 240 min to 30-40%. Cycloheximide causes a delay of the prn addition to the 2.3 X 10(6) daltons RNA, normally detectable in pulse experiments, two further precursor molecules do emerge which undernormal circumstances apparently are shortlived. Their molecular weights are 2.0 X 10(6) and 0.9 X 10(6) daltons. The pulse-chase technique and cell fractionation into nuclear and ribosomal parts enables us to demonstrate a rapid transfer of labelled 18S and 25S RNA during a 15 min chase treatment to the mature cytoplasmic ribosomes. Under these conditions no differential transport of the two components takes place. The cells possess a pool of proteins. Therefore the formation of RNP-particles or ribosomes respectively and the transport from the nucleus to the cytoplasm are indipendent from protein synthesis for some time.


[Influence of immobilized ribonuclease on the cell-free protein synthesis in the wheat system (author's transl)]. In order to increase the efficiency of different mRNAs from wheat seedlings in carrying out cell-free protein synthesis in the wheat system, efforts were made to remove endogenous mRNA. In this direction, we checked the possibility of using immobilized RNase. Treatment of the cell-free system or its components with this enzyme caused a large decrease in the efficiency of poly tu-directed incorporation of labeled amino acids. This effect did not coincide with an equivalent degradation of RNA, as has been shown by analysis of ribosomes and polysomes. The results are discussed in the light of recent findings of some authors.


Temperature sensitive events between photoreceptor and circadian clock? The phase shifting action of low temperature pulses of 6 degrees C and 2 h duration administered to the various phases of the Drosophila pseudoobscura circadian rhythm and the action of light pulses given 30 min after the beginning of these low temperature pulses have been investigated. The phase response curve obtained from experiments with light pulses during low temperature cannot be explained on the basis of a straightforward and sequential phase shifting of the oscillation by the various transitions in the pulses. The response curve, after the slight phase shifting action of the temperature pulses is corrected for, resembles the standard phase response curve4 for light pulses (at 20 degrees C) in its wave form but not in its time course. Our curve is shifted in time in a manner that indicates that the light pulses accompanying the low temperature pulses arrived at phase points 1.5 h later than the actual phases at which they were given. We attribute this delay to a slowing down of the information that is apparently transmitted by a process that is temperature dependent.


[Characterisation of RNA from synchronously growing yeast cells (Saccharomyces cerevisiae) as separated by columns of methylated albumin on Kieselgur (MAK) (author's transl)]. Total RNA, extracted from synchronously growing yeast cells by the method of Georgiev-Mantieva, was separated by columns of methylated albumin on Kieselgur (MAK). By comparison with definited RNA's in discelectrophorese and after pulse labelling with [3H]methionine the following fractions are identified: t-RNA, 5.8S RNA, m-RNA, 18S and 25S R-RNA and their precursors 20S, 27S and 35S. High molecular fractions of RNA between 40S and 70S were also found.


Conversion of D-lysine via L-pepecolic acid in Neurospora crassa. Neurospora crassa converts D-lysine to L-pipecolic acid and the latter to L-lysine by a pathway outlined herein and different from mechanisms hitherto known to be involved in interconversions of enantiomers of amino acids.


Testosterone metabolism in streptomyces hydrogenans. After cultivation of Streptomyces hydrogenans in the presence of 3H-labelled testosterone, radioactive steroids were extracted separately from the cytosolic, ribosomal and cell wall-membrane fraction of the cells and from the culture medium, respectively. The separation of the steroids was performed by one- and two-dimensional thin layer chromatography (TLC). The identification of the main metabolites was achieved by crystallization to constant specific staining procedures and acetylation. The oxidation of testosterone to androst-4-en-3,17-dione is by far the predominating reaction, which is almost finished after 3 h cultivation. Androst-4-en-3,17-dione is mainly transferred into the culture medium and partly accumulated within the cell wall-membrane fraction. High polar steroid metabolites and androstane derivatives are present in very smahl amounts only.


[About the importance of paranodal structures of the Ranvier node for the impulse regeneration (author's transl)]. The site of the pulse regeneration in myelinated nerve is generally assumed to be the unmyelinated part of the axon membrane in thr Ranvier node. To check this, a micro-irradiation technique using laser pulses (lambda equals 347 nm, t equals 20 ns) was used to produce morphological lesions of about 1 mum diameter in various regions of the Ranvier node. The electro-physiological functions were monitored parallel to the irradiation. Depending on the localizing of the lesions two types of changes in these functions were observed: 1. If a definite site in the paranodal myelin sheath was damaged without affecting the axon, an action potential could no longer be elicited, although the resting potential as well as the stationary current-voltage behaviour remained unchanged. 2. A damage of the axon resulted in a break down of membrane potential and resistance. In most of the cases the excitability recovered after spontaneous or current induced restitution of the membrane resting potential and resistance. These observations indicate, that structures in the paranodal region are vital for the Na+-activation and inactivation. The membrane potential and stationary current-voltage behavior can be attributed to the axon membrane. A new hypothesis concerning the mechanism of the Na+-activation-inactivation process is suggested.


A model of pheromone molecule-acceptor interactin. Multiple binding interactions between odor molecules and acceptors are formulated by means of the Boltzmann statistics and intermolecular bond energies. Number, spatial arrangement and electronic properties of binding positions of the acceptor can be defined such that the specificity of sex pheromone receptors in male noctuid moths is quantitatively described.


Structure-response relationships in noctuid sex pheromone reception. An introductory report. Electroantennogram (EAG) data reflecting response spectra of male pheromone receptors have been analyzed for 16 species of Noctuidae (Lepidoptera). The test compounds included 100 pheromone analogues, altered in chain length, in position and configuration of double bond(s), and in the functional end groups. On comparison of amounts of substance required to elicit an equivalent EAG response, a single compound was determined to be most effective on a given species: these structures, either known or proposed as the natural sex pheromones of the species, were cis-7-dodecen-1-y1 acetate, cis-7-tetradecen-1-y1 acetate, cis-9-tetradecen-1-yu acetate, trans-9-tetradecen-1-y1 acetate, cis-11-hexadecen-1-y1 acetate, cis-9, trans-12-tetradecadien-1-y1 acetate, cis-9-tetradecen-1-y1 formate, and cis-9-tetradecen-1-ol, respectively. Elongation (shortening) of the chain by 1 or 2 methylene groups, the movement of a double bond 1 carbon from the optimum, a change to the opposite geometrical isomer, or the introduction of a second double bond invariably reduced EAG responses to 1.8 to 56 times below that observed with the most stimulating compound, in all 16 species. Further alterations in chain length or in double bond position caused even greater reduction in activity, as did certain in end group (Tables I and II). A set of distinct rules could be derived from these structure-response relationships; one of these rules concerns the optimum position of the double bond(s) in relation to chain length, and another one the ratios in activity values produced by end group variations, irrespective of chain length. The same rules described here for 16 noctuid species held also for the structure-response relationships observed within various additional groups of Lepidoptera. From EAG values determined in this study, an attempt has been made to calculate physicochemical propteries of underlying acceptor structures.


[CNA-synthesis in gamma-platlets of wheat (author's transl)]. Plants, arising from irradiated (300 kR) caryopses of wheat, exhibit a low incorporation of [3H]thymidine into the DNA, which, as shown by sedimentation on sucrose gradients, does not indicate tendencies of normalization.


[Isolation and characterization of ribosomal RNA from the phycomycete Allomyces arbuscula (author's transl)]. The ribosomal RNA of the gametophyte of Allomyces arbuscula contains two components with sedimentation coefficients of approximately 25S and 18S. The percent base composition of 25S rRNA is 31/28/24/17 (U/G/A/C), that of 18S rRNA 34/28/22/16.


Effect of alkali chlorides on human chromosomes studied by the method of poly-L-lysine binding. Human metaphase chromosomes A1 and A3 did bind more tritiated poly-L-lysine ([3H]PL) when they were isolated from lymphocyte cultures treated with LiCl rather than with NaCl or KCl. A2 chromosome did not show this differential behavior and in all three cases did bind more [3H]PL than the control A2 chromosome. The effect was dependent on the time of exposure of cells to the salts in tissue culture and on the degree of chromosomal contraction. The observed differences in [3H]PL binding are probably due to differences in surface morphology of the three chromosomes caused by treatment with alkali metal salts.


Receptor and interneuron light-adaptation in the dragonfly visual system. Intracellular recordings show that the receptors and second-order interneurons of the dragonfly compound eye change their sensitivity in response to maintained illumination. Comparison of receptor with interneuron shows that neural mechanisms act to ensure that the modulation of interneuron membrane potential that is set up by contrast changes is independent of background intensity.


[Protection of mice against Friend leukemia by active and passive immunization with isolated viral glycoprotein and its antiserum respectively (author's transl)]. Mice could be protected against Friend leukemia virus infection by innoculation with highly purified viral glycoprotein GP71 or its specific antiserum.


[Histological studies on the healing of mandibular osteotomies in the dog following stable osteosynthesis with the cold polymerizing polymethylmethacrylate "Kallokryl K"]. The disadvantages of methods of accomplishing stable osteosynthesis of mandibular fractures are described and the possibilities of jacketing the fragments with Kallokryl K plastic material, which is a cold-polymerizing polymethyl methacrylate, pointed out. After six months from the surgical operation, the healing under Kallokryl K was clinically and histologically evaluated on canine mandibles subjected to osteotomy and with the periosteum removed from the lower jaw bone. The reaction of both soft tissue and bone to the plastic material attached thereto was also evaluated. The results are discussed in the light of what is presently known about primary and secondary bone healing.


[The development of the anterior segment during the milk tooth period]. The behaviour of interdental gaps is checked during the milk teeth period on denture models of 33 regular gap milk dentures and 49 milk dentures with protrusion of the upper incisivi. A "physiological gap" could be found in only 2.3% of cases.


[Contribution to the subacute necrotic myelitis (Foix-Alajouanine) (author's transl)]. A case of a 54 years old man with an acute lumbalgia in result of heavy labour is described.  With in 7 years he developed a progressive paralysis of the upper and lower motor neuron type and an insensibility of the inferior extremities.  The protein content of the cerebrospinal fluid was increased.  The cells were insignificantly increased in number.  No tumour was detected.  The man died at the age of 62 on intoxication by infected decubitus and focal pneumonia.  Autopsy revealed subacute necrotic myelitis (Foix-Alajouanine) with enlarged, varicose, and thickened extramedullary veins of the sacral, lumbal, and lower thoracic spinal cord, which was soft and diminished in size.  In the grey and white matter of the cord, there were found more numerous and more prominent vessels like an angioma capillare et venosum; complete and incomplete necrosis was observed, partially with plasmatic infiltration.  Some nerve cells were still present.  Nerve fibres without myelin mantle were found in the spinal cord as well as in the spinal roots.  The authors support the suggestion that the subacute necrotic myelitis results from a dysgenesis of the spinal venous vessels.


The Sézary syndrome cell: surface ultrastructural characteristics. Peripheral blood mononuclear cells from a patient with Sézary syndrome which lacked E-rosette-forming ability and surface immunoglobulins, and which displayed a markedly depressed response to a variety of mitogens, were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) on 3 occasions.  The first peripheral blood sample (smooth) differed significantly from two later samples (moderate numbers of microvilli) when surface characteristics were examined by SEM; these differences were confirmed by TEM.  The Sézary syndrome cells in this patient may be related to a T lymphocyte which has lost certain surface markers and mitogen response characteristics through a process of de-differentiation.


Histochemical distribution of acid mucopolysaccharides during circadian rhythm in the cerebellum of Serranus scriba. Histochemical analysis of AMPS (AB-staining materials) in Serranus scriba brain showed its irregular distribution in different brain regions. The highest AMPS content was observed in the optocoele and ependymal cells lining it, above the marginal telencephalon and optic tectum as well as the molecular cerebellum layer. Particularly significant AMPS concentrations were noted in Purkinje cell regions. The telencephalon and optic tectum showed AB-negative-staining materials. Following histochemical changes during a 24 h period, AMPS concentrations were shown to follow circadian variations, especially in the Purkinje cell region. The highest AMPS content was noted during the morning and the lowest during the evening hours. The above changes were discussed in the context of the role of AMPS in neural functions.


Elevated lymphocyte ATP-ase activity in patients with cancer of the uterine cervix. Elevated lymphocyte Adenosine Tri-Phosphatase (ATP-ase) activity was found in 23 och 28 patients with cervical uterine carcinomas of various stages. Treatment with external irradiation and radium insertion was followed by a decline in the lymphocyte ATP-ase activity in 22 patients, while the activity remained unchanged in one patient. No correlation between the tumour stage and the lymphocyte ATP-ase activity was demonstrated. In 24 patients the clinical effect of the treatment was well correlated with the decline in ATP-ase activity. It is suggested that the determination of lymphocyte ATP-ase activity could be valuable in screening for cervical carcinoma and for follow-up after radical treatment.


Studies on citrate metabolism in liver injuries. 1. Fasting blood citrate level in chronic hepatitis and liver cirrhosis. For the purpose to study the citrate metabolism in liver diseases, blood citrate, blood glucose and serum non-esterified fatty acids (NEFA) in fasting state were measured in the subjects with chronic hepatitis and with liver cirrhosis. Citrate and glucose were measured by the enzymatic methods. NEFA was measured colorimetrically. Fasting blood citrate level was investigated in relation to the type and extent of these liver diseases. Results revealed the following: 1. Fasting blood citrate level rose with the severity of liver diseases, especially in decompensated liver cirrhosis. 2. No significant difference in fasting blood citrate level was found between the subjects with and without glucose intolerance. 3. Fasting blood citrate level had a closer correlation with serum NEFA level than with blood glucose level. From these results, it has been concluded that the increase in blood citrate level in liver diseases is due to the impaired uptake of citrate by the liver and the increased release of citrate from peripheral tissues.


Mechanism of sound susceptibility in organ of Corti - inference of contrary recruitment phenomenon (hypothesis) and the application to diagnosis -. In order to make the mechanism concerned with the sound-susceptibility in the organ of Corti clear, we observed the organ of Corti with the phase-contrast microscope, after the microdissection of the cochleae in human, dogs, guinea pigs and hamsters by Engstroöm's surface preparation technique. As a result, we have formulated a hypothesis for the mechanism of the sound-susceptibility in the organ of Corti. Further, we have inferred the contrary recruitment phenomenon (hypothesis), by explaining theoretically such a clinical fact as the recruitment phenomenon or the cochlear hearing loss by applying our first formula of hypothesis. Finally, we described the application of the contrary recruitment phenomenon (hypothesis) to the early discovery or diagnosis of the false normal ear or cochlea, in other words, latent hearing loss.


Menaquinone (vitamin K2) therapy for bronchial asthma. I. Mechanism of action menaquinone on allergic reactions. The mechanism of action of the drug was investigated from various points of view. The findings may be summarized as follows: 1. In the experiments of the degranulation of mesenteric mast cells of rats, menaquinone proved to significantly inhibit the degranulation either in active or passive sensitization with the reagin-like antibody. 2. Menaquinone did not inhibit the formation of the reagin-like antibody. 3. In the experiements of the degranulation of basophilic granulocytes from patients of bronchial asthma, the rate of appearance of A form basophilic cells upon addition of the antihuman IgE goat serum was not markedly but significantly inhibited in the patients treated with menaquinone for long periods, as compared with that in the control, whereas the in vitro addition of menaquinone did not exert a significant inhibitory action.


Studies on citrate metabolism in liver injuries. 2. Response of liver citrate to glucose load. The effect of glucose load on the levels of blood glucose, serum non-esterified fatty acids (NEFA) and liver citrate was investigated in carbontetrachloride-intoxicated (injured) rats and compared with non-intoxicated controls. The citrate level in the liver from injured animals showed 15-fold of the value of the control. Glucose load on these animals caused gradual decrease in the citrate level, whereas similar administration to the control caused inverse results. The serum NEFA levels were lowered by glucose load in both of injured and control animals. The pattern of changes in the citrate level after glucose load in the liver from injured animals was similar to that in the muscle from the control, suggesting a similarity on citrate metabolism between the injured liver and the muscle. The possible mechanisms for these results were discussed in relation to the difference in citrate metabolism between the liver and the muscle.


Cytochemical study of exfoliated cells of oral mucosa. I. The glycogen deposition and keratinization. Cytochemical studies of glycogen of oral mucosa cells have been made on the smears by freeze-drying and PAS staining. The specimens were obtained from different areas of oral cavity of 77 human subjects and an attempt was made to find some interrelation amoung glycogen deposition, keratinization and inflammation. The largest glycogen deposition was found in the mucosa cells from mouth floor and cheek, a little in those from gingiva and quite a small or no glycogen in those from mucosa of hard palate and tongue. In gingiva the cells showing much more keratinization were less in glycogen contents, and vice versa. In inflammation some increase in glycogen contents were found in the gingivitis and the highest glycogen content in the cases of denture irritation of the palate as far as the present observation is concerned.


Establishment of five cell lines from normal adult rat livers in vitro. Cells isolated by trypsin were cultured from the liver of normal rats of the Donryu strain. Cells were collected from five animals of different age groups from 40 days to 12 months. All five cell collections produced different cell lines according to animal age. The establishment of these cell lines was not dependent upon the method of perfusion by Ca++-and Mg++-free phosphate buffered saline. Minor morphological variations were observed among the five lines. All cell lines showed epithelial figures under phase contrast microscopy. An increase in cells with trisomy of No. 1 chromosome was found after two to three months of cell culture.


Time-lapse changes in the concomitant immunity of lymphocytes from different sites of mice isografted with methylcholanthrene-induced tumor. As a step in the elucidation of the mutual relationship between the degree of cancer progress and the antitumor activity of lymphocytes from different sites in cancer-bearing body, we isografted methylcholanthrene-induced tumor (MC-tumor) subcutaneously on the back of mice. The regional axillary lymph nodes, spleen and distant mesenteric lymph nodes were removed from these animals one, two, three, and four weeks later. We mixed lymphocytes prepared from these lymphatic tissues with primary MC-tumor culture cells and cultured together to estimate antitumor acitivity of lymphocytes from different sites. It has been found that a strong antitumor activity can be seen only in those regional axillary lymph node cells taken out one or two weeks after tumor transplatation and such an activity is weakened by three or four weeks. On the other hand, distant mesenteric lymph node cells one or two weeks after the transplantation have no antitumor activity as yet, while at the terminal cancer stage of four weeks there appears a stronger antitumor activity than that of regional lymph nodes. In the spleen, a strong antitumor activity can be observed in the third week after tumor transplantation, but the activity disappears by the fourth week. These findings support our previous findings in that for the tumor onset after the transplantation the antitumor activity seems to appear first in the regional lymph nodes, and when the tumor grows beyond a certain size, such an activity diminishes while it appears in further distant lymphatic tissues.


An electron microscopic study of the vascular factor in hemorrhagic diathesis. Experimental diapedetic hemorrhage (oozing) was produced by streptokinase in rabbits and the fine structures of mesenterial microvessels were observed. Diapedesis of erythrocytes was seen in the venular side of microcirculation. On the contrary, no diapedesis was seen in true capillary on the arteriolar side. Sticking of erythrocytes to venular wall prior to diapedesis was proved, electron microscopically, to be the state in which red blood cells were trapped in the gaps on the endothelial junction. It was considered to be the morphological findings of the prediapedetic state. Erythrocytes passed through gaps on the endothelial junctions with high plasticities under any diapedetic conditions mentioned above. Furthermore, in author's experiments by ruthenium red staining, erythrocytes were observed just passing through the basement membrane under electron microscopy, in spite of its high speed process. It was found that the basement membrane is a very important barrier in erythrocyte diapedesis.


The effect of products of fibrinogen digestion by plasmin (P-FDP) on the central nervous system. Low molecular peptides, derived from fibrinogen digested by plasmin and injected either intraperitoneally or into the brain lateral ventricle, were found to act depressively on the CNS in active rats, while in fairly active rats they showed stimulatory effects. Fractionation of P-FDP on Sephadex G-25 showed that the most active peptides had a molecular weight lower than 5,000.


Diagnostic accuracy of an ultrasonic multiple transducer cardiac imaging system. Eighty patients with various forms of heart disease were studied with the use of a newly developed ultrasonic system having 20 transducers arranged in a linear array. This system allows visualization of the heart in two dimensions in real time. All 15 patients with the mitral valve prolapse syndrome, 13 patients with mitral stenosis, five patients with pericardial effusion, four patients with atrial septal defect, and one patient with left ventricular dyssynergy were properly recognized with this system. One of five patients with hypertrophic myopathy and one of four patients with congestive myopathy were not recognized with this system. Criteria for the recognition of these system. Criteria for the recognition of these conditions are presented as well as the probable cause for false-positive and false-negative diagnoses in this series. Since only qualitative criteria were used, it was not possible to differentiate patients with coronary artery disease or patients with left ventricular volume overload from patients without cardiac pathology. The accuracy of this new system was judged against the clinical examination, conventional echocardiography, cardiac catheterization, and left ventricular angiography. It is assumed that the criteria for diagnosis developed during this study will be supplemented and the equipment improved in the future; however, the ease of operation of this system and the relative accuracy of diagnosis at this stage of its development are extremely interesting. It presents an excellent opportunity to obtain additional information about the cardiac patient without using invasive procedures and without risk.


Echocardiography.

Echocardiography. We have discussed the evolution of selected areas of echocardiography in an attempt to illustrate the capabilities and limitations of this method of study. As information has accumulated, some concepts of the specificity of certain echocardiographic patterns have had to be revised. Awareness of the potential for false positive and false negative results has increased rather than decreased the usefulness of the echo method. Equipment deficiencies which existed in past years have largely been corrected, thereby reducing the likelihood of repeating some of the earlier mistakes. Two years ago, we suggested that more patients with left ventricular disease should be studied, the results from different laboratories should be compared, a large number of patients with congenital disease should be evaluated, and the limitations of the technic be more precisely defined. Obviously much has been accomplished in all of these areas. Much more can be done. There is every reason to believe that the next few years will bring many new and important developments in diagnostic echocardiography.


Electrical axis and voltage criteria on left ventricular hypertrophy. The voltage criteria of left ventricular hypertrophy were studied in 229 hypertensive patients undergoing treatment and 62 patients who were not treated. The limb-lead voltage criterion (R Lead aVL greater than or equal 11 mm.) was found more frequently in patients with radiographic evidence of cardiomegaly than other voltage criteria. This may have been due to a more negative axis in patients with cardiomegaly than in patients without cardiomegaly. It is possible that dilatation of the left ventricle to the left and posteriorly accentuates limb-lead criteria at the expense of V-lead criteria. Left anterior hemiblock occured in less than 10 per cent of the hypertensive patients. In 10 out of 16 patients with left anterior hemiblock, the hemiblock disappeared after treatment of the hypertension for 4 years whereas all five hemiblocks in untreated hypertensives persisted. Development of left anterior hemiblock subsequently occurred in only one patient with treatment and one without treatment over a 4-year period.


Relationships of the tricuspid valve to the membranous ventricular septum in Down's syndrome without endocardial cushion defect: study of 28 specimens, 14 with a ventricular septal defect. The commissure between the anterior and medial leaflets of the tricuspid valve is commonly absent in Down's syndrome without endocardial cushion defect (19 of 28 specimens). As a result, aneurysm of the membranous ventricular septum may develop (eight of 14 specimens with ventricular septal defect limited to the membranous ventricular septum) and the potential for left ventricle-to-right atrial communication is increased.


Effect of preconditioning visual stimulus duration on visual-evoked responses to a subsequent test flash in Down's syndrome and nonretarded individuals. Visual-evoked responses to a visual test flash preceded by three different durations of a visual conditioning flash having the same intensity and form were recorded from 8 Down's syndrome subjects and 9 nonretarded CA-matched control subjects. Both groups showed a significant decrease in visual-evoked response perimeters to the test flash as the duration of the visual conditioning flash increased from 1 to 100 msec. For the 1000-msec condition, perimeters of Down's syndrome subjects showed a significant increase, and this was significantly greater than the nonretarded group. These results suggest that Down's syndrome individuals have deficits in their neural processing of sensory information.?23Author


The metabolic clearance rate of dehydroisoandrosterone sulfate. III. The effect of thiazide diuretics in normal and future pre-eclamptic pregnancies. The present study reports that the metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) is decreased by thiazide diuretics during normal and future pre-eclamptic pregnancies. This observation supports the thesis that diuretics represent a potential hazard to the fetus by decreasing placental perfusion.


Discovering the lifestyle of the physically disabled. The "discovery process" learned in the Leadership Training Institute sponsored by the American Occupational Therapy Association was used as the foundation for a course offered to senior occupational therapy students.  The students had completed required courses in the curriculum and had returned from six months of field work experience.  They had little or no exposure to patients outside a hospital setting.  The objectives of the course were: (1) To offer the student an experience in which he could gain an understanding of a physically disabled person's natural environment and the forces exerted on him within that environment; and (2) to offer the student an opportunity to develop issues relevant to that physically handicapped person's life style and, by using that person's natural abilities, assist him to adapt to or change his environment.  The process that evolved between the students and the handicapped people that they visited in the community is discussed.


Immune complex type glomerulonephritis in cirrhosis of the liver. Glomerular lesions were detected in 9 of 10 patients with liver cirrhosis: these lesions consisted of a) thickening of basement-membrane-like material, b) electron-dense deposits in mesangial areas and in capillary walls, c) round areas of rarefaction in the membrane-like material and in some deposits, and d) presence of IgA, with IgG and/or IgM and/or C3, in the deposits. The association of these four abnormalities seems to be characteristic of "cirrhotic glomerulonephritis." The deposits could be the result of precipitation in the glomeruli of either aggregated immunoglobulins or circulating immune complexes.


Rat myocardial mechanics during pressure-induced hypertrophy development and reversal. Moderate cardiac hypertrophy (CH) was produced in rats by abdominal aorta constriction for 5, 8, 15, 21, and 28 days. Aortic constriction release after 5, 8, and 15 days led to CH regression, which was complete within 15 days. A study of left ventricular papillary muscle mechanics during CH development demonstrated an early but transitory decrease in both maximum isometric force (Po) and maximum muscle shortening velocity (max V); in addition, the time-to-peak tension increased, and there was a decrease in isometric relaxation rate and in force-frequency relationship (negative staircase.) After CH regression, isometric relaxation and negative staircase were similar to controls, whereas the prolonged duration of contraction persisted. After release of the aortic constriction at 8 and 15 days, Po and max V were normal; however, after the earlier release (5 days), Po was higher than control, when muscle thickness was taken into consideration. These findings suggest 1) that an alteration in muscle mechanics may be related to the hypertrophy itself; 2) that anomalous excitation-contraction coupling might persist after CH regression.


Adaptation of actomyosin ATPase in different types of muscle to endurance exercise. Higher concentrations of actomyosin were found in the red portion of the vastus lateralis and in the white portion of the vastus lateralis muscle than in the soleus or heart in rats. A strenuous program of treadmill running lasting 18 wk or longer did not significantly affect the amount of actomyosin recovered from the different types of muscle. No changes in actomyosin ATPase occurred in fast-twitch white (white vastus) or heart muscles in response to the exercise training. In contrast, a decrease of approximately 20% occurred in the specific activity of actomyosin ATPase of fast-twitch red (red vastus) muscle (0.635 +/- 0.029 mumol Pi/min per milligram for sedentary vs. 0.529 +/- 0.021 mumol Pi/min per milligram for trained), while the actomyosin ATPase activity of slow-twitch red (soleus) muscle increased about 20% (0.209 +/- 0.033 vs. 0.257 +/- 0.031 mumol Pi/min per milligram). There was a close correlation (r = 0.99, P less than 0.001) between actomyosin ATPase activity and phosphofructokinase activity in the three types of skeletal muscles and in heart muscle of exercise-trained and untrained animals, providing further evidence in support of the concept that the glycogenolytic capacity of a muscle and its actomyosin ATPase activity are regulated in parallel.


Role of medullary Na-K-ATPase in renal potassium adaption. Since recent studies have shown that chronic potassium loading stimulates the specific activity of Na-K-ATPase in renal tissue, experiments were performed to determine whether increased enzyme acitivity correlated with renal adaptation for accelerated potassium excretion. The Na-K-ATPase activity in different renal zones was correlated with the maximum rate of potassium excretion during the intravenous infusion of KCl in animals with normal and reduced renal function, animals on a varied potassium diet and animals treated with methylprednisolone or deoxycorticosterone acetate. The enhanced ability to excrete a potassium load was associated with increased enzyme activity in the outer or red medulla, whether the change in Na-K-ATPase was caused by chronic potassium loading, methylprednisolone treatment, or partial nephrectomy. There was no evidence that a rise in enzyme activity in the cortex influenced the rate of potassium secretion. Moreover, stimulation of Na-K-ATPase in the inner medulla-papilla did not augment the rate of potassium excretion above that found in animals with an increase in enzyme in the outer medulla alone. These experiments provide evidence that links Na-K-ATPase to the mechanism of renal potassium adaptation and suggest that the major increment in potassium secretion by the adapted kidney occurs in the outer medulla.


Biosynthesis of glycosaminoglycans by mammalian corneal epithelium and fibroblasts in vitro. II. Approach to specify the GAG from the two cell types. 35S- as well as 3H-labeled glycosaminoglycans (GAG) produced by cultivated epithelium and fibroblasts of the rabbit cornea were treated with testicular hyaluronidase, leech hyaluronidase and chondroitinase-ABC or -AC. The fractionation-patterns of enzyme-treated GAG were compared with blanks not exposed to enzymes. The epithelial GAG revealed to be generally more resistant to the enzymatic degradation than the GAG synthesized by the fibroblasts, but--depending on the enzyme--in the GAG of both cell types the same fractions were attacked. The decline of the radioactivity in the fractions of enzyme-treated GAG allows the conclusions that both cell types produce relatively small amount of keratan sulfate but mainly chondroitin sulfates with a different degree of sulfation. In addition GAG, not present in the normal cornea, are synthesized: hyaluronic acid chiefly by fibroblasts and probably dermatan sulfate. The possible role of the fibroblastic and epithelial GAG in corneal wound repair is discussed.


Biosynthesis of glycosaminoglycans by mammalian corneal epithelium and fibroblasts in vitro. I. Isolation and fractionation-differences of GAG from the two cell types. Labeled glycosaminoglycans (GAG) were isolated and fractionated from cultured rabbit corneal epithelium, rabbit or bovine corneal fibroblasts and rabbit bone fibroblasts that had been previously incubated with either Na235SO4 or D-glucosamine-6-3H precursors. Thus it was demonstrated that the epithelium produces GAG. The fractionations indicated that the epithelial cells predominantly synthesize GAG with a lower degree of sulfation than those produced by corneal fibroblasts. The GAG-fractionation-patterns of the corneal epithelium and bone fibroblasts were similar.


Enzyme changes in lichen planus.

Enzyme changes in lichen planus. Untreated cases of lichen planus have been studied by histochemical techniques. The acid phosphatase reaction in the transitional zone has been quantitatively estimated and compared with the adjacent relatively normal epidermis. It was found that despite a thickened and accentuated granular layer as seen by routine histological methods there was a marked reduction in the intensity of the acid phosphatase reaction. The glucose-6-phosphate dehydrogenase reaction was marked in the upper layers of the epidermis in active lesions of lichen planus. This is similar to psoriasis, but different from normal human epidermis. The suggestion by other authors that lichen planus is an inborn error of metabolism is discussed. The dendritic cells of the epidermis as studied by the ATPase reaction are virtually absent in regions of active lichen planus and the possible significance of this is mentioned. The horny layer gives a dense reaction for phospholipids in lichen planus and this is similar to psoriatic keratin. The significance of this finding is considered.


[Ultrastructure of the epidermis in seborrhoic dermatitis (author's transl)]. Electronmicroscopical investigation on 12 cutaneous biopsies of different localisation showed that the seborrhoic dermatitis is not comparable to a psoriatic tissue-reaction. Both, the cyto-morphological feature and the demonstrated localisation of the acid phosphatase are distinctly different from that of the psoriatic epidermis. The described changes are clearly more similar to the well known ultrastructural pictures of eczemateous reactions. In spite of the "eczema-like" ultrastructural picture seborrhoic dermatitis apparently can be separated from the allergic and irritant contact-dermatitis. Nevertheless, the epidermal alterations are also similar to chronic nummular eczema. They therefore are unspecific and do not allow any conclusion regarding the etiopathogenesis or nosological classification of this skin disease.


Host resistance in sepsis and trauma.

Host resistance in sepsis and trauma. Host resistance to infection was measured by the in vivo response to 5 delayed hypersensitivity antigens and to sensitivity and challenge by dinitrochlorobenzene (DNCB) in 55 seriously ill or injured patients and in 50 preoperative patients. A close correlation between infections, septicemia, death related to infection and anergy was found in the postoperative and post injury patients and was predictive of these complications in the patients studied preoperatively. Decreased body cell mass was noted in both the anergic and non-anergic patients which was consistent with protein-calorie malnutrition but the two groups were not significantly different. A serum factor which inhibited cellular immunity in vitro was found in 4 patients. This factor disappeared in the two patients who recovered. The study suggests the therapeutic value of the in vivo measurement of delayed hypersensitivity in seriously ill and especially preoperative patients in whom specific or non-specific stimulation of cell mediated immunity might alter the risk of infection.


The early diagnosis of gram negative septicemia in the pediatric surgical patient. Ninety-three postoperative patients 1 day to 13 years of age had blood cultures, limulus lysate assay, determination of fibrin degradation products, white blood cell and platelet counts. Seven groups were studied. The limulus lysate assay was often positive (64%) in the presence of gram negative septicemia but there were false positives and negatives. The tests for fibrin degradation products were inconsistent. The white blood cell count was low in babies with gram negative septicemia. One hundred per cent of the infants with gram negative septicemia had a platelet count below 150,000; 71% below 100,000 (average 67,000 septic babies, 257,000 non-septic babies). The drop in platelet count with gram negative septicemia was abrupt---as much as 222,000 in 24 hours. Platelets increased when therapy was effective. Two children with gram negative septicemia had platelet counts of 50,000 and 20,000. The platelet count for patients with gram positive septicemia was 299,000, and above 150,000 in all children with ruptured and non-ruptured appendicitis and major surgery without gram negative septicemia. It was concluded that serial measurements of platelet count in the postoperative infant and child was a rapid and reliable method for early detection of gram negative septicemia and changes in platelet count in response to treatment was an indicator of the effectiveness of therapy.


Apparent coexistent valvular and subvalvular left ventricular outflow tract obstruction. A patient is presented in whom coexisting bicuspid valvular aortic stenosis and asymmetrical septal hypertrophy were suggested by echocardiography. A focal area of hypertrophy noted at operation was excised. Subsequent histological examination did not reveal evidence to support the echographic and surgical observations. The necessity for careful intraoperative assessment of the degree and nature of subvalvular muscular hypertrophy is stressed. The absence of classic echographic findings in these patients is noted.


Giant intrathoracic tumor masquerading as an enlarged cardiac silhouette. This report describes a relatively asymptomatic 52-year-old man who had a markedly enlarged cardiac silhouette on chest roentgenogram when first seen. Clinical studies confirmed the presence of a mass, and thoracotomy revealed a huge intrathoracic tumor. The lesion was interpreted as an intrapulmonary hamartoma that had undergone malignant degeneration.


Chemical structure and pharmacological (curarizing) properties of various indole alkaloids extracted from an African Strychnos. The chemical separation and identification of ten alkaloids extracted from the roots of Strychnos usambarensis are described. The elucidation of their structure by means of elementary analysis, I. R., U.V, and mass spectrometry allows their classification into bistertiary amines, hybrid and bisquaternary ammonium derivatives. This classification is reflected in the pharmacological properties. One of the tertiary amine alkaloids (usambarensine) presents atopine-like and spasmolytic activities while the bisquaternary ammonium compounds (dihydrotoxiferine, calebassine, C-curarine and afrocurarine) are competitive neuromuscular blocking agents.


Pharmacologic effects of apomorphine in rats with altered level of brain serotonin. The influence of inhibitors and precursors of serotonin synthesis on motor stimulation, hypothermia and apomorphine-induced stereotypy was studied. The results are discussed with reference to the previously expressed suggestion of a modulating role of serotonin on the mechanism of apomorphine-induced motility and in apomorphine-induced hypothermia.


Alzheimer degeneration in Down syndrome. Electrophysiologic alterations and histopathologic findings. Progressive electroencephalographic disorganization and decreased voltage amplitude in the late components of the averaged visual evoked potentials were recorded in the last two years of life of a patient with Down disease and Alzheimer degeneration. Taken together with quantitative histopathologic findings, the electrophysiologic alterations are interpreted in terms of recent evidence from an experimental animal model of dementia. Neurons with neurofibrillary degeneration become electrically inactive and contribute to the loss of voltage generators associated with neuron death in Alzheimer disease. Loss of voltage generators may result in disfacillitation and disinhibition of surviving neurons, thus causing the loss of normal rhythms.


Extraction of D-beta-hydroxybutyrate by brain in diabetic rats. Statistically significant cerebral arteriovenous differences of D-beta-hydroxybutyrate were found in rats made diabetic by administration of streptozotocin. The amount of D-beta-hydroxybutyrate extracted by the brain in diabetic animals increased with increasing arterial concentrations and the extraction ratios were comparable to those found in animals and humans with ketosis due to other causes.


Silent mitral regurgitation.

Silent mitral regurgitation. The occurrence of significant mitral regurgitation whithout the characteristic auscultatory signs, particularly the holosystolic murmur and the third heart sound, is unusual. It becomes of considerable importance when it occurs in combined lesions of the mitral valve, and more so in those areas where the treatment of mitral stenosis is by closed mitral valvotomy. Two cases of silent mitral incompetence are presented. The features that should have indicated the coexistence of regurgitation with mitral stenosis were cardiomegaly with considerable dilatation of the left atrium, and lesser degrees of right ventricular hypertrophy on electrocardiography for the severity of mitral stenosis and evidence of biventricular hypertrophy.


A study of the number and phage patterns of Staphylococcus aureus in an abattoir. Two hundred and forty-seven samples were taken from various areas within an abattoir and the levels of Staphylococcus aureus determined. Sixty-one phage patterns were found in the 141 samples containing coagulase-positive staphylococci. The incidence of coagulase positive staphylococci increased as processing progressed. Articles such as mesh gloves, hands and aprons which were either difficult to effectively clean or maintained at elevated temperatures harboured the greatest numbers of staphylococci. Over 50% of the positive samples contained multiple phage patterns of staphylococci.


Differential response in cardiomyopathy of chicks and turkeys to furazolidone toxicity. Dietary furazolidone (500 ppm or higher) significantly slowed the growth of chicks fed either a conventional or a purified diet and of turkeys fed a conventional diet. Deaths were significantly increased in turkeys fed 500 ppm and in chicks fed 700 ppm in the purified diet. Ratio of heart to body weight was significantly increased by furazolidone in turkeys, but not in chicks. Furazolidone did not induce anemia in either species. Turkeys and chicks differed markedly in cardiac response to toxic levels of furazolidone.


Effect of furazolidone on heart weights and myocardial moisture content in turkey poults. Furazolidone (FZ) at 700 ppm in feed mixtures fed turkey poults from 2 to 5 weeks posthatching significantly increased the ratio of heart weight to body weight (p less than 0.001) and myocardial moisture content (p less than 0.05). The increase in myocardial moisture content is believed to be related to increased glycogen deposition under the influence of FZ since FZ removal from the diet decreased myocardial glycogen levels and moisture content to normal levels.


Chalone-like effect abrogated by dextran sulphate and heparin polyanion pretreatment of target cells. Chalone prepared from primary BALB/c mouse embryo fibroblasts caused a 33% reduction in incorporation of tritiated thymidine in the cultures of the second in vitro passage of BALB/c embryo fibroblasts, whereas chalone prepared from thymus, skin and spleen was without effect. Pretreatment of BALB/c secondary fibroblasts with the polyanions dextran sulphate and heparin abrogated the chalone effect. The polycations DEAE-dextran and polybrene were without effect. The effect of incubation with the dextran sulphate polyanion was reversed when followed by incubation with DEAE-dextran polycation.


Stimulation of syngeneic and allogeneic lymphoid cells by tumour cells in vitro. August and Wistar rat lymph node cells were found to respond well to PHA stimulation and in mixed lymphocyte culture, as determined by an increased incorporation of 3H-thymidine. August rat lymph node cells were also stimulated by incubation with irradiated syngeneic tumour cells. Allogeneic Wistar rat lymph node cells produced a larger response to the August tumour cells. The response of syngeneic and allogeneic lymph node cells was reduced by pretreating the tumour cells with a Wistar anti-tumour serum. Pretreating the tumour cells with sera from normal or tumour bearing rats also reduced the response of syngeneic lymph node cells but did not reduce the response of allogeneic lymph node cells.


Cytochemical identification of ATPase-positive langerhans cells in EDTA-separated sheets of mouse epidermis. Sheets of epidermis for incubation to demonstrate ATPase activity were obtained from specimens of mouse footpad using EDTA as the separation medium. The use of EDTA in place of the NaBr method previously described, resulted in a greatly reduced incubation time, precise localization of reaction product and preservation of ultrastructural detail. A population of closely and regularly spaced ATPase-positive dendritic cells was demonstrated by light microscopy. Electron microscopy demonstrated that, with short incubation times, reaction product was found only in the extracellular space adjacent to dendritic cells, the majority of which possessed the typical ultrastructural features of Langerhans cells.


The sebum excretion rate in rosacea.

The sebum excretion rate in rosacea. The sebum excretion rate (SER) was measured in fifty-five patients with rosacea and 126 control subjects. The mean SER in the patients with rosacea was not increased, nor was there any correlation between SER and severity of rosacea. Our data suggest that seborrhoea plays no part in the pathogenesis of rosacea.


A new formulation of 0.1% hydrocortisone cream with vasoconstrictor activity and clinical effectiveness. A new formulation of hydrocortisone with vasoconstrictor activity has been shown to be effective clinically and was more effective in a 0.1% concentration than 1.0% Hydrocortisone Cream BPC. Its use should obviate the adverse effects of fluorinated steroids.


Hazards of steroid therapy in hepatic failure. Three patients with extensive skin disease and liver failure are described. Two were treated with large amounts of topical corticosteroids and one with a small oral dose of betamethasone. The former two patients developed Addisonian crises when they failed to apply the topical steroids and all three patients developed aseptic necrosis of bone. This report emphasizes that the hazards of steroid therapy may be increased in patients with hepatic failure.


The dissociation constant of the actin-heavy meromyosin subfragment-1 complex. We measured the binding of [14C]iodoacetamide labeled heavy meromyosin subfragment-1 (S-1) to F-actin by sedimenting the actin-S-1 complex and assaying the radioactivity remaining in the supernatant. The apparent dissociation constants (Kd) at 25 degrees, pH 7.0, were 0.01 to 0.04 muM at 0.027 and 0.08 ionic strengths and 0.07 to 0.14 muM at 0.14 ionic strength. Kd was not altered when the troponin-tropomyosin complex was bound on the actin, nor was it affected by free calcium concentration in the range 10(-4) to 10(-9) M. Measurements of the displacement of labeled S-1 from actin by native S-1 showed labeling had not altered Kd. In control experiments we found that at the low actin concentrations used (0.001-0.5 muM) not all of the actin sedimented and, furthermore, the data suggested that some of the S-1 in the supernatant was bound to supernatant actin. Our estimation of Kd, based on the assumption that all the supernatant S-1 was free, therefore resulted in an apparent Kd greater than the true Kd. We minimized the effect of the supernatant actin artefact by using only the data for high ratios of S-1 to actin, where no less than 75% of the actin sedimented; we estimate that the true Kd values could not be less than half the apparent Kd values.


Kinetic mechanism of the activation of human plasminogen by streptokinase. A method of determining the initial rate of plasminogen activation has been developed. The method has been used to investigate the mechanism of activation of human plasminogen by streptokinase. Plasmin formation follows saturation kinetics. Inhibition of plasmin formation by epsilon-aminocaproic acid is uncompetitive with a Ki of 0.6 mM. A model consistent with the data is that streptokinase induces a conformational change in the plasminogen molecule, producing an active center which cleaves an internal peptide bond to produce plasmin. Thus, streptokinase functions as a catalytic allosteric effector.


Differentiation between mutants of Escherichia coli K defective in oxidative phosphorylation. Hybrid membrane particles from two mutants of Escherichia coli K12, Bv4 and K11, defective in oxidative phosphorylation, have been prepared, in which ATP-driven membrane energization is restored. A soluble factor of mutant K11 was found to have properties similar to parental crude coupling factor, ATPase (EC 3.6.1.3). Membrane particles of this mutant could not be reconstituted by parental coupling factor. Either parental coupling factor, or the soluble factor of mutant K11 could reconstitute both respiration-driven and ATP-driven energization to membrane particles of mutant Bv14 or to parental particles depleted of ATPase. Mutant Bv4 was found to be devoid of coupoing factor activity, while retaining the ability to hydrolyze ATP. Both mutants possess an ATPase with an altered binding to the membrane. Mutant K11 is impaired in respiration-driven amino acid transport, in contrast to mutant Bv4. The three major subunits of parental Escherichia coli ATPase have been isolated and antibodies have been prepared against these subunits. Antibodies against the largest subunit (alpha component) or against the intact catalytic subunits (alpha + beta components) inhibit both ATP-Pi exchange in the parent organism as well as ATP hydrolytic activity in parent and mutants. Antibodies against the two other subunits (beta or gamma components) also inhibit these two reactions, but were found to be less effective. Mutant N144, which lacks ATPase activity, shows no precipitin lines with anti-alpha, anti-beta, anti-gamma, or anti (alpha + beta) preparations. In contrast, mutants Bv4 and K11, exhibit cross-reactivity with all of the antisera.


Immunological and fluorescence studies with the coupling factor ATPase from Rhodospirillum rubrum. 1. Purification of the coupling factor ATPase from Rhodospirillum rubrum has been achieved by a combination of a previously described procedure with chromatography on DEAE-Sephadex A50. 2. Identification of the coupling factor ATPase during purification, and estimation of the relative amount of the enzyme in each fraction was greatly simplified by utilization of its unusual fluorescence. 3. Preparations of R. rubrum coupling factor ATPase injected into rabbits yielded antisera which were suitable for following the course of purification. 4. Judged by immunoelectrophoretic analysis and polyacrylamide gel electrophoresis the final preparation was pure. Under standardized conditions, apparently pure preparations showed fluorescence ratios at 300/350 nm of 3-6, which are considerably higher than those reported for pure CF1 from chloroplasts. 5. The enzyme lost its activity and changed its immunological identity during prolonged storage and by treatment with urea. Antisera against urea-treated enzyme showed the presence of two distinct antigens in the modified preparations.


Electron microscopic studies of plasmic degradation products of fibrinogen. Implications for the disulfide structure of fibrinogen. Fibrinogen, coagulable plasmic derivatives (Fragments X) and Fragments Y, D and E were studied by negative staining electron microscopy. Fragment X obtained from Stage 1 digests and fibrinogen were both globular, while Fragment X of Stage 2 digests appeared as a nodular filament. The Stage 1 and Stage 2 Fragment X preparations had approximately the same molecular weight, but could be differentiated by several subtle differences in polypeptide chain structure. Fragments Y and D were also filamentous, although shorter than Fragment X (Stage 2), and Fragment E appeared as a small, compact or folded filament. These results agree with the concept that fibrinogen consists of a strand of nodules connected by thin strands, folded into a compact, spherical shape. The molecule opens up when stabilizing bonds are disrupted or liberated by plasmin. The data are compatible with a fibrinogen molecule in which the two halves are linked by a single locus of disulfide bonds at the amino terminus and with the asymmetric hypothesis of plasmic degradation to Fragments X, Y, D and E.