Somatic hybrid of thymus leukemia (.

Somatic hybrid of thymus leukemia (. A somatic hybrid of ASL-1 leukemia cells [H-2a, thymus leukemia (TL)1,2,3, Thy-1b] and LM(TK)-cells [H-2-k, TL(-), Thy-1 (-), thymidine kinase deficient] was formed with the aid of inactivated Sendai virus. The selection of hybrid cell clones was facilitated by the inability of ASL-1 cells to grow in vitro and of LM(TK)-cells to survive in hypoxanthine/amethopterin/thymidine medium. The H-2 antigens of both parental cells were formed in approximately equivalent amounts by the hybrid cells, and they possessed a hybrid karyotype. As determined by five independent experimental procedures (antibody and complement-mediated cytotoxicity tests, the reduction of specific antibody activity of antiserum of known titer, immunofluorescent tests, mixed hemagglutination tests, and their direct isolation), TL antigens but not Thy-1 antigens were formed by the hybrid cells. TL antigens of the hybrids failed to undergo modulation under conditions leading to the modulation of TL antigens of parental ASL-1 cells. Modulation was attempted with TL 1,3, TL 2, or TL 1,2,3 antisera of high titer. thybrid cells were incubated for up to 30 hr in medium with TL antisera. Both direct and indirect immune methods were attempted. These results indicate that cellular mechanisms controlling the expression of TL antigens may be distinguished from the capacity of the cells to undergo modulation.


Genetic control of endogenous C-type virus production in pancreatic acinar cells of C57BL/He and C57BL/6J mice. Electron microscopy revealed very active production of C-type virus particles in the pancreatic acinar cells of untreated normal adult mice of the C57BL/He strain. In C57BL/6J mice, a similar picture was observed after a single intraperitoneal injection of dexamethasone. No viruses were observed in the pancreas of untreated or dexamethasone-treated BALB/c and C3Hf mice. F1 hybrids of both C57BL strains with C3Hf mice produced viruses in the same manner and quantity as the C57BL parents, whereas hybrids with BALB/c mice were entirely negative. Approximately 50% of mice of the first backcross generation of (BALB/c times C57BL/He)F1 hybrids with C57BL/He mice were active producers of C-type particles, while the other 50% were negative. It is suggested that a regulator gene that controls C-type virus production does not function in the pancreatic cells of either C57BL strain, and that BALB/c mice can provide hybrids with an active regulator.


Simian virus 40 DNA directs synthesis of authentic viral polypeptides in a linked transcription-translation cell-free system. A linked cell-free system has been developed which is capable of transcribing and translating mamalian viral DNA, and its characteristics and requirements are outlined. In this system, simian virus 40 (SV40) DNA Form I (supercoiled) directed the synthesis of discrete polypeptides up to 85,000 daltons in size. One of these products was indistingusihable from authentic major virus capsid protein VPI, as judged by mobility on sodium dodecyl sulfate/polyacrylamide gels, antibody predipitation, and peptide analyses. The cell-free products larger than VPI comprised a number of polypeptides ranging in molecular weight from 50,000 to 85,000. These polypeptides demonstrated no immunological relationship whatsoever to the structural protein VPI. However, two of these products, along with one of approximately 25,000 dlatons, were precipitated with antiserum to SV40 tumor antigen. Linear SV40 DNA generated by the cleavage of Form I DNA with the  restriction endonuclease EcoR1 was an efficient template in this system and also directed the synthesis of a polypeptide migrating with VPI on polyacrylamide gels. The potential of this system for defining a functional map of a DNA genome is discussed.


Biochemically differentiated mouse glial lines carrying a nervous system specific cell surface antigen (NS-1). Six biochemically differentiated clonal lines have been established from a transplantable glioma (tg26) of the C57BL/6 inbred mouse strain. Antibodies have been previously raised against G26 tumor cells, which define a cell surface component(s), NS-1 (nervous system antigen-1), found exclusively in the nervous system. NS-1 concentrations approximate the levels of the original G26 tumor when the clonal lines are grown as clonal tumors in vivo, but are reduced when the cells are grown in vitro. NS-1 concentrations are further reduced in vitro upon incubation of the cells with 1 mM dibutyryl 3:5-cyclic AMP. H-2 histocompatibility antigen concentration, in contrast, is unaffected by dibutyryl cAMP. In addition to expressing NS-1, the neuroectodermal origin of these cell lines is further confirmed by their synthesis of the nervous system specific acidic protein S-100 and by the high specific activity of the enzyme 2:3-cyclic nucleotide 3-phosphohydrolase. In addition, they respond to catecholamines by the elevation of intracellular 3:5-cyclic AMP levels. Whereas expression of S-100 protein is high under in vitro conditions but negligible after one passage in vivo, 2:3-cyclic nucleotide 3-phosphohydrolase is not detectable in vitro but becomes detectable again in vivo. The two membrane-bound constituents, NS-1 and 2:3-cyclic nucleotide 3-phosphohydrolase, therefore seem to be subjected to different regulatory mechanisms from that of the soluble, intracellular S-100 protein.


In vitro transformation of lymphoid cells by Abelson murine leukemia virus. Cell cultures prepared from fetal murine liver were infected by Abelson murine leukemia virus. After about 2 weeks, proliferating cells of lymphoid morphology appeared in some of the cultures. Addition of 2-mercaptoethanol to the initial culture medium greatly enhanced the appearance of the lymphoid cells. Immunoglobulin determinants were evident on the cells in some cultures. Continuous passage of the cells in certain cultures was possible and the passaged cells could form tumors after animal inoculation. Because Abelson murine leukemia virus is able to induce in vitro malignant transformation of lymphoid cells, it probably causes leukemia by directly affecting cellular growth control.


Interaction of partially purified simian virus 40 T antigen with circular viral DNA molecules. Mixing chromatographic fractions containing simian virus 40 (SV40) T antigen with SV40 [3H]-DNA I (double-stranded, circular, supercoiled) results in the conversion of the nucleic acid to a form that will bind to a nitrocellulose filter. Unlabeled SV40 DNA I successfully competes with this reaction. Under the conditions employed, the antigen-containing fractions bind a variety of circular, viral DNA molecules. Chromatography of the antigen in three systems reveals that the T immunoreactivity migrates with DNA binding activity. In a kinetic heat inactivation experiment, the antigenic reactivity disappears simultaneously with the DNA binding activity. The data indicate the presence of a discernible DNA binding activity in fractions containing T antigen and suggest that the T antigen is the DNA binding protein being measured.


Role of bovine albumin in a serum-free suspension cell culture medium. A serum-free culture medium, supplemented with 1% bovine serum albumin, supported the growth of both primary and continuous suspension-type cultures of various mammalian tumor cells. The role of albumin added to the medium was also studied. Defatted albumin failed to support cell growth, unless reconstituted with its lipid extract. Similarly, defatted albumin when combined with oleic and linoleic acids, also supported cell growth. Therefore, albumin-bound fatty acids play an important growth-promoting role in serum-free medium.


Correlation of survival from murine cytomegalovirus infection with spleen cell responsiveness to Concanavallin A. Spleen cells from nonlethally MCMV-infected weanling and adult DBA/2 mice had diminished responses to Con A stimulation. In contrast, only lethal MCMV infections were associated with a complete suppression of the Con A response. The immune response to SRBC was depressed even in asymptomatic infections of weanling and adult mice. A marked maturation of resistance to the lethal effects of MCMV infection was found to occur during the fourth week of life.


Lipids and cell fusion in vitro: effect of amphotericin B. Fusion rate of Cl-1D cells mediated by Sendai virus was decreased by preincubating the cells or the virus in the presence of lysolecithin. However, a significant increase occurred when the cells were preincubated in the presence of amphotericin B. This increase was suppressed by exogenous cholesterol.


DES-ASP1--angiotensin II: possible role in mediating responses of the renin-angiotensin system. In dexamethasone-treated dogs, both antiogensin II and its heptapeptide fragment (des-asp1-angiotensin II) stimulated the secretion of the adrenal steroids aldosterone, corticosterone, and cortisol. Further, there was no statistically significant difference in the steroidogenic potency of the two peptides. An interesting incidental finding was the decrease in PRA with both peptides, again with no demonstrable difference in the magnitude of the responses. The present data are consistent with the hypothesis that the heptapeptide mediates responses produced by the renin-angiotensin system in both the adrenals and the kidneys.


Effect of lithium ions on RNA synthesis in mammary gland explants of mice. LiC1 was found to stimulate RNA synthesis in the mammary gland in a manner similar to that of prolactin. Since LiC1 is known to inhibit adenyl cyclase and thus to reduce levels of cyclic AMP, it is concluded that a reduced level of cyclic AMP may be one step in the mechanism whereby prolactin regulates the metabolism of the mammary gland.


Brain catecholamines, spontaneous bioelectrical activity and aggressive behavior in ants (Formica rufa). The effects of dopamine (DA), 1-DOPA, diethyldithiocarbamate (DDTC) and haloperidol on aggressive behavior and spontaneous bioelectrical activity of the ant (Formica rufa) were studied. Drugs such as DA, 1-DOPA and DDTC increased mutual aggressivity in ants while it failed to change aggression directed towards other species of insects (e.g., the beetle Geotrupes sp.). The amplitude of EEG waves and the amplitude of neuronal discharges within the protocerebrum decreased after administration of both DA and 1-DOPA. Both DDTC and 1-DOPA increased the concentration of adrenaline as well as DA in the brain of ants. Haloperidol decreased intrageneric aggressivity but caused no evident changes in both EEG pattern and neuronal discharges. The present study indicates that catecholamines are critically involved in the organization of aggressive behavior in ants.


Noradrenergic role in the self-administration of morphine or amphetamine. The role of brain noradrenergic neurons in mediating the reinforcing properties of small intravenous doses of morphine and d-amphetamine was investigated by pretreatment of rats with the norepinephrine-depleting agents diethyldithiocarbamate and U-14,624, inhibitors of dopamine-beta-hydroxylase (DBH). Such treatment prevented the reacquisition of a self-administration response (bar-press) for morphine (32 mug/kg/injection) or d-amphetamine (15 mug/kg/injection) made available on a CRF schedule. Pretreatment with a DBH inhibitor also prevented the development of a secondary (conditioned) reinforcer based on primary reinforcement assosiated with either drug. Observations indicating that the orienting reflex was intact are taken as evidence that depressant effects of the DBH inhibitors were not severe enough to disrupt the associative process. Therefore, any effect on learning does not seem sufficient to explain the present results. Thus, it is inferred that the mechanisms mediating reinforcement for both morphine and amphetamine were disrupted by the inhibition of central noradrenergic functions.


Effects of arterial hypoxemia and splenic nerve stimulation on myocardial adenosine 3',5'-Monophosphate in dogs. Epinephrine infusion, 5-percent oxygen breathing, and splenic nerve stimulation were employed to increase cardiac output by 50-100% in anesthetized dogs. Epinephrine infusion as expected, increased plasma and myocardial cyclic AMP concentrations. Arterial hypoxemia increased cyclic AMP concentration in plasma but not in the heart. Practolol pretreatment abolished the increase in plasma cyclic AMP concentration and reduced the rise in cardiac output during hypoxemia. Splenic nerve stimulation was not associated with increases in either plasma or myocardial cyclic AMP. Adenylate cyclase activity was increased by addition of plasma into the incubation medium. However, splenic venous plasma obtained during splenic nerve stimulation  did not increase adenylate cyclase activity more than control plasma obtained before stimulation. We conclude that the positive inotropic action of arterial hypoxemia and splenic nerve stimulation does not depend on the adenylate cyclase-cyclic AMP system.


Evidence for adrenergic neurons in a memory access pathway. Injection of a beta-adrenergic blocker, propranolol, in rats within 5 min after training of a step-dowm passive avoidance response had no effect on performance either 2 or 6 hr later, however, when testing occurred 1, 3 or 7 days after training and injection a significant performance decrement was observed. If drug injection was postponed until 1 or 3 days after training and testing was conducted 2 hr later, again poor avoidance performance was obtained. No support for a state-dependency explanation [14] of the propranolol amnesia could be found. The amnesia that followed beta-adrenergic receptor block was identical to that previously reported when norepinephrine biosynthesis was reduced [9] and supports the hypothesis of a role for adrenergic neurons in memory formation and retrieval that is different from cholinergic neurons [4,10].


Anti-prostaglandin action of colchicine. Colchicine, given locally, inhibits urate-crystal- and CaPPD-crystal-induced inflammation. Since this inflammation is known to be mediated in part by PGE1 these observations indicate colchicine acts as an anti-PG agent. Colchicine counteracts the phlogistic action of exogenous PGE1 in both urate- and CaPPD-crystal-induced inflammation. With use of large excesses of colchicine, its anti-inflammatory action appears limited to its anti-PGE1 activity. In turn, PGE1 counteracts the antiphlogistic action of colchicine. Colchicine is less effective in reducing swelling due to CaPPD-crystals than that due to urate-crystals, a finding similar to the clinical observations that colchicine is more effective therapy for gout than for pseudogout. Some relationships are reviewed to suggest that CaPPD-crystal inflammation is a more severe membrane disorder than is urate-crystal inflammation.


Effect of ascorbic acid, sodium salicylate, and caffeine on the serum interferon level in response to viral infection. The ability of ascorbic acid, sodium salicylate, and caffeine to alter the circulating serum level of interferon was investigated in mice. The animals were singly injected subcutaneously with one of the compounds, 4-8 h later again singly injected intraperitoneally with poly I:C, and bled 6-8 h afterward. The sera from the mice were assayed for interferon titer by the use of the plaque inhibition method utilizing vesicular stomatitis virus. Ascorbic acid, sodium salicylate, and caffeine increased the serum level of interferon; however, the increase produced by sodium salicylate was dose-dependent, i.e. low doses increased interferon titers, high doses decreased the titers. Caffeine produced minimal increases in the interferon titer. These observations suggest that a potential prophylactic result may occur in virus infections from administration of the three compounds either singly or in combination at the proper concentration.


Free radical evolution in rat liver following the ingestion of DAB. The effect of the ingestion of the carcinogenic substance DAB on the density and distribution of organic free radicals in rat liver is studied by the electron spin resonance method. There is a remarkable parallelism between what is known about the evolution of the activity of mitochondria and the concentration variations of free radicals.


Caudate nucleus lesion selectively increases paradoxical sleep episodes in the rat. The EMG, ECG and the behavioral activity of seven rats were recorded for three days previous to and 24 hours after lesioning both caudate-putamen complexes. Following the lesion, the paradoxical sleep stage lengthened by about 248%, without noticeable changes in the slow wave sleep or in the waking stages. The greatest increase was obtained with lesions placed in the mediomedial portion of the caudate-putamen complex. In other six rats submitted to the above procedure except that the lesions were placed in the anterior cerebral cortex, and also in five more rats implanted in both caudate-putamen complexes but not lesioned, no change was noted in the waking, paradoxical sleep or slow wave sleep stages.


Pharmacologic interaction between cannabinol and delta9-tetrahydrocannabinol. The pharmacological activities of delta9-THC [(minus)-delta9-trans-tetrahydrocannabinol], CBN (Cannabinol) and mixtures of delta9-THC + CBN were studied in rabbits, rats and mice. CBN, although in general less active, mimicked the effects of delta9-THC in several pharmacological tests: corneal arreflexia in rabbits; climbing rope, open-field, irritability and aggressiveness after REM sleep deprivation in rats; catatonia, analgesia and sleeping time in mice. When the mixture delta9-THC + CBN was used, a synergistic effect occurred on most of the depressant effects. On the other hand CBN did not interfere with or slightly inhibited the excitatory effects of delta9-THC. In the one peripheral test used, CBN did not alter the delta9-THC effect.


Retroactive impairment of cooperative learning by imipramine and chlordiazepoxide in rats. Pairs of rats were placed in an apparatus where their sole food source hung over an electrified grid. The current was shut off only while one rat remained on a platform out of reach of the food, thus allowing his partner to eat. Mastery of the process of taking turns at eating required about 10 daily sessions. Injection of imipramine or chlordiazepoxide a few minutes after each feeding session prevented the development of this cooperative behavior. Drug injection 3 hrs after each session had no effect. Suppression of REM sleep during the first 3 hrs after training was considered the most likely mechanism of the drug-induced impairment.


Effects of early post-natal alpha-methyl-dopa treatment on behavior in the rat. 250 mg/kg of L-alpha-methyl-Dopa (alpha-m-Dopa) or saline were administered to rats for three weeks after birth. Subsequent tests revealed an increased locomotor activity and greater rate of acquisition but no disturbance in shuttle-box conditioning. The whole brain content of norepinephrine, dopamine and serotonin was not affected.


[Behavior of lipoprotein X (LP-X) in viral hepatitis]. The AA. have studied the behaviour of LP-X in fifty cases of viral hepatitis printing out a positivity in 32% of the examined cases, with a positivity of the Au-antigen in the 34% of cases. They have observed a more remarkable inclination to the cholostasis in children (40% of the cases of positivity of LP-X), concluding for a scarce specificity of such a "marker" of cholostasis.


Early experience with the EMI scanner for study of the brain. Computed tomography of the head is highly accurate new radiologic technique for the evaluation of neurologic disease. Analysis of early cases indicates that the appearance produced by CT in some conditions is unique and that increasing experience allows the neuroradiologist to predict the position and nature of disease processes with greater accuracy.


Myelographic cervical nerve root deformities. Myelograms of nerve roots and adjacent subarachnoid space were reviewed to characterize 231 cervical root deformities from both symptomatic and asymptomatic patients. Good correlation between specific features of root deformities and clinical significance could not be demonstrated. Some features were slightly suggestive of clinical significance but occurred in a sufficient number of asymptomatic patients to make them unreliable. The most accurate determinants of root deformity significance are clincal and electromyographic findings.


Retrograde hepatography and indirect lymphography of the liver: an experimental study in the dog. Retrograde infusion of large amounts of water-soluble contrast agents into the biliary system results in only a brief hepatogram. A dense hepatogram lasting for several weeks and visualization of hepatic and celiac lymph nodes equal to that in direct lymphography can be obtained after retrograde biliary infusion of Ethiodol. In serching for metastasis from tumor in the liver, gall-bladder, bile ducts, pancreas, stomach, and duodenum, radiographic visualization of these nodes may help. If proved safe, the procedure can be performed by endocopic cannulation of the common bile duct.


Congenital asymmetry (hemihypertrophy) and abdominal disease: radiological features in 9 cases. Coexistent abdominal disease was found in 9 cases of congenital asymmetry. These patients appear to be at risk of malignant neoplasms of the adrenal gland, kidney, and liver. Five of the 6 neoplasms in this group of patients were malignant. Approximately 25% of the reported cases of hemihypertrophy have been associated with hamartomas or congenital defects, especially genitourinary anomalies. Benign disorders encountered in this group included medullary sponge kidney, renal ectopia, renal cyst, nephromegaly, adrenomegaly, and hypospadius.


Steroid hormone modulation of 3H-prostaglanding E1 binding to bovine corpus leteum cell membranes. The specific binding of 3H-prostaglandin E1 (3H-PGE1) to bovine corpus luteum cell membranes was not affected by cholesterol or various progestins at concentrations of up to 9.0x10-minus-6M. At concentrations  above 2.5 x 10-minus-6M; estrone, 17beta-estradiol (but not 17alpha-estradiol or 17beta-estradiol glucuronide), estroil, equilin, D-equilenin, 17-ethynyl estradiol, diethylstilbestrol, cortisol, corticosterone, deoxycorticosterone and aldosterone inhibited specific binding of 3H-PGE1. On the other hand, testosterone and dihydrotestosterone (DHT) (but not androstenedione) significantly enhanced 3H-PGE1 binding. These findings permitted the following correlations between steroid structure and modulation of 3H-PGE1 binding: steroids with a free phenolic ring and a 17beta-hydroxyl or 17-keto group or C-21 steroids with a C-20 ketone and a C-21 hydroxy group decrease, whereas C-19 steroids with a C-17 hydroxy group enhance specific binding of 3H-PGE1. PGE receptors are heterogeneous with respect to affinity for 3H-PGE1. The steroids that decreased 3H-PGE1 binding caused a lowering to a complete loss of low affinity PGE receptors. Steroids that increased 3H-PGE1 binding caused appearance of new low affinity PGE receptors. Association rate constants for 3H-PGE1 binding were decreased by 17beta-estradiol (61%) and increased by DHT (59%).


A comparison of immunologic response to intranasal and intramuscular parainfluenza-3 live virus vaccines in beef calves challenged experimentally in the feedlot. Feeder calves were vaccinated with modified live virus (MLV) bovine parainfluenza-3 (PI-3) vaccines by the nasal and parenteral routes. Thirty days later they were challenged with the SF-4 strain of virus. Serum hemagglutination-inhibition (HI) antibodies and neutralizing antibodies in nasal secretions were compared with unvaccinated control calves. Both vaccines produced satisfactory circulating antibodies, but intranasal vaccination produced higher levels of antibodies in nasal secretions. After challenge PI-3 virus was not isolated from the vaccinated calves or two contact control unvaccinated calves but was isolated from all unvaccinated control calves isolated from vaccinated calves.


Selective inhibition of nicotinamide adenine dinucleotide dependent oxidations by substituted carbamides. Several 1-substituted acetyl-3-aryl carbamides selectively inhibited nicotinamide adenine dinucleotide (NAD) dependent oxidation of alpha-keotoglutarate and beta-hydroxybutyrate by rat brain homogenates. NAD-independent oxidation of succinate remained unaltered. The inhibition observed with 1-(N-acetylmorpholino)-3-(4-methylphenyl)carbamide was competitive in nature.


The mode of inhibition of herpes simplex and vesicular stomatitis ocular viral infections in the rabbit and hamster by an interferon inducer tilorone dihydrochloride. Ocular viral infections are a major cause of loss of vision and their effective control by applications of chemical compounds has been extensively investigated. To achieve such a control, better understanding of virus-host-drug interactions become a necessity. Two models, hamster and rabbit cornea, were selected for assays of protection afforded by tilorone dihydrochloride against herpes simplex (HSV) and vesicular stomatitis viruses (VSV). To obtain basic biologic comparison between viral interference and interferon-induction by tilorone, the hamster cornea system was first studied to produce a mutual viral interference by double infection. Furthermore, its effect against ascending herpetic ocular infection into encephalitis was evaluated in the rabbit. This compound was reported to have promising results in improving manifestations such as corneal ulceration, uveitis and conjunctivitis.


REM sleep distributions in post-addict rats relapsing to morphine self-administration: effects of naloxone subcutaneous pellets. Female Sprague-Dawley rats were prepared with chronic cortical and temporalis muscle electrodes and i.v. cannulas. They were administered i.v. injections of morphine to produce tolerance and physical dependence, then trained to lever press for i.v. self-injections of morphine (10 mg/kg) to maintain dependence. They were subsequently withdrawn for two weeks, implanted subcutaneously with one or two pellets of naloxone base, 100 mg each, or placebo pellets, returned to the experimental cages and allowed to relapse to self-administration of either saline or morphine. Rats with placebo pellets relapsed to morphine self-administration and reestablished the dependence state. However, rats implanted with naloxone and then permitted to self-administer morphine extinguished their lever pressing ("drug-seeking behavior"). Similar results were obtained with rats implanted with placebo pellets and self-administering saline. The self-injections of morphine by rats implanted with placebo pellets severely suppressed REM sleep and altered its normal distribution. Rats implanted with naloxone pellets and that subsequently extinguished their lever pressing, however, did not exhibit a change in REM sleep distributions. Similarly, self-injections of isotonic saline did not exert an effect on REM sleep distributions. These findings suggest that a correlation between REM sleep distributions, drug-seeking behavior, and morphine-naloxone interaction prevailed.


Action of phenobarbital and carbon tetrachloride on hepatic microsomal inosine diphosphatase in the rat. Pretreatment of rats with phenobarbital decreased the in vitro activity of liver microsomal inosine diphosphatase, whereas CCl4 caused an opposite effect. These actions were essentially abolished when the activity of the enzyme was assayed in the presence of optimal concentrations of triton X-100. The detergent was shown to activate and solubilize the enzyme along with membrane protein and phospholipids. During solubilization there was a tendency towards a greater phosphatidylcholine and lower phosphatidylethanolamine content in triton-soluble membranes. Microsomes of phenobarbital-treated rats were more resistant to triton solubilization, whereas those from CCl4-treated rats were more susceptible than the controls. These results demonstrated a loose association between the enzyme and the endoplasmic reticulum and that phenobarbital or CCl4 altered the activity of IDP-ase probably by affecting the binding of the enzyme to the structure skeleton of the membrane. The role of phospholipid changes in the stability of microsomal membranes is discussed.


Studies on immunisation of pigs with the Bartha strain of Aujeszky's disease virus. The K strain of Aujeszky's disease virus (ADV) grown in Vero cells was used to vaccinate pigs. Following intramuscular inoculation, the pigs remained healthy, no vaccine virus was excreted and virus could be detected only at the inoculation site. One inoculation gave good protection against challenge with a virulent strain of ADV, and the amount of virulent ADV excreted was geatly curtailed. Following vaccination only low leads of serum neutralizing antibody were detected (geometric mean titre 1/2), but three weeks after challenge very high levels were found (GMT 1/1773). Intranasal vaccination gave similar results. There was minimal excretion of vaccine virus. The clinical reaction on challenge was less severe than in the intramuscularly challenged group, although lower antibody levels were detected three wekks following challenge (GMT 1/483). A field trial, using this strain given subcutaneously, indicated that one inoculation of this vaccine is effective.


Plasma progesterone levels in sows with induced cystic ovarian follicles. Large multiple cystic ovarian follicles were induced in three sows and small multiple cystic ovarian follicles were induced in three other sows by injections of adrenocorticotrophic hormone (ACTH) during the follicular phase of the oestrous cycle. Plasma progesterone levels in sows with large cysts were relatively high, while those of sows with small cystic follicles were low. Removal of the ovaries with large cysts from one sow resulted in a precipitous drop in progesterone levels indicating that the large cysts were primarily the source of progesterone. The method by which ACTH may induced cystic ovaries was also investigated. Plasma progesterone levels in two ovariectomised sows during ACTH treatment fluctuated markedly during a 24 h period achieving peak values of 4 or 5 ng/ml. The results suggest that progesterone of adrenal cortical origin may be a factor in the development of the cystic ovarian condition.


The nasal secretion and serum antibody response of lambs following vaccination and aerosol challenge with parainfluenza 3 virus. The nasal and serum neutralising antibody responses of lambs was compared following vaccination with live or inactivated parainfluenza 3 (PI 3) virus by either intramuscular (IM) or intranasal (IN) routes. Nasal antibody was only detected following inoculation of live virus IN or inactivated virus in Freund's complete adjuvant (FCA) IM. Immunity to aerosol challenge, as assessed by viral shedding from the nose, was conferred by (1) live virus administered by either route, (2) two IM inoculations of inactivated virus in FCA, and (3) one IM injection of inactivated virus in FCA followed by IN instillation of inactivated virus.


[Unusual association of a papillary cystadenoma and a mixed tumor of the parotid]. The authors describe the exceptional association within the same parotid gland of two oncologically different tumours. This provides them with material for discussion concerning the value of pre- and per-operative histological tests and leads them to put in a plea for total parotidectomy leaving the facial nerve intact.


[2 new cases of Klippel-Trenaunay syndrome]. After a brief account of the history and pathogeny, two cases are described of sub-angiomal bone hypo and hypertrophy. Other cases in the literature are recalled. Finally, a differential diagnosis is given.


Effect of the carboxyl-terminal tripeptide of vasopressin on plasma free fatty acids and cyclic adenosine monophosphate in man. The carboxyl-terminal tripeptide of casopressin (Pro-Arg-Gly.NH2) and adrenocorticotrophic hormone (ACTH) were injected intravenously into six human subjects, and the effects of these peptides on plasma free fatty acids (FFA) and cAMP concentrations were compared with that of saline. Twenty mug of the tripetide and 100 mug of ACTH INCREASED THE PLASMA FFA CONCENTRATION TO THE SAME EXTENT, WHEREAS 200 MUG OF THE TRIPETIDE WAS WITHOUT THIS LIPOLYTIC EFFECT. ACTH and the smaller dose of the tripeptide elevated the plasma cAMP level only in the same two subjects.


Clinical conditions associated with urinary excretion of 2-hydroxybutyric acid. Urine and blood samples from patients with different clinical disorders were examined for 2-hydroxybutyric acid (2-HB) by gas chromatography and mass spectrometry. All patients with combined lactic acidosis and ketoacidosis excreted 2-HB in the urine, in amounts up to 2.3 mmol/mmol creatinine. In blood from these patients, 2-HB was present only in trace amounts. Hard physical exercise resulted in lactic acidosis and accumulation of 2-HB. The lactate to pyruvate ratio in blood and urine was markedly increased in the patients excreting 2-HB but was normal in two patients with lactic acidosis who did not excrete 2-HB. It is concluded that an increased NADH2/NAD ratio is the most important factor for the production of 2-HB.


Depresssion in narcolepsy and hypersommia. The authors studied the occurrence of depression in 100 randomly selected patients with narcolepsy and in 30 patients with hypersomnia. In the isolated form of idiopathic narcolepsy (without signs of cataplexy, sleep paralysis or hypnagogic hallucinations) depression occurred 28.6 per cent of cases. In idiopathic narcolepsy with cataplexy or other symptoms of sleep dissociation, depression was found in 17.2 per cent of cases. In idiopathic hypersomnia the occurrence of depression was 26.1 per cent. In the majority of cases the endogenous form of depression was observed. In the symptomatic form of narcolepsy and hypersomnia the occurence of depression has not been noted in any case. In most cases a parallel clincial course has been observed between the manifestation of depression and narcolepsy or hypersomnia. During a remission of the depressive state the hypersomniac symptoms decreased or disappeared totally. The authors furter discuss the possible pathophysiological mechanisms of the above mentioned symptoms. They are of the opinion that an important role is played by the secretion and metabolism of the cerebral monamines.


[Exophthalmogenic effect of thyrotropin releasing hormone (TRH) in the animal experiment]. Exophthalmos has been induced in carp by injecting thyrotropin releasing hormone (TRH) (PYRO-glutamyl-histidyl-prolinamide) into the coelom. This effect was dose-dependent (dose range 5-750 mug). It was significantly potentiated by prior administration of beta-1 minus 24 coricotropin (Synacthen, Ciba) and inhibited by prednisclone. No significant increase was obtained with 2-phenylalanine-8-lysire-vasopressin (Octapressin, Sandoz). The results show that in the fish model, TRH exerts an exophthalmogenic effect by stimulating endogenous TSH, whereas in man this is not the case. They afford further evidence that the carp model does not reproduce the conditions which occur in ophthalmic Graves' disease.


[Osteomalacia and antiepileptic drugs: study on the pathogenesis]. Severe osteomalacia with secondary hyperparathyroidism was observed in a 19-year-old mentally retarded girl, who had been treated for several years with antiepileptic drugs. Vitamin D3 orally administered in low doses led to complete reversal of all symptoms and normalization of blood chemistry, X-ray pictures demonstrated healing of all lesions. It is suggested that the alterations of vitamin-D metabolism occuring during the administration of phenobarbital and hydantion are of importance only in patients with an already lowered intake of vitamin D3 or reduced exposure to ultraviolet rays.


[Clinical problems of amebiasis].

[Clinical problems of amebiasis]. Dagnostic and therapeutic problems of amebiaiss, a disease rarely observed in this country, are discussed in the light of four own cases representing the various courses of the disease. These observations prompt the following conclusions: 1. Amebiasis should be considered in cases of unclear acute or chronic intestinal disease, even if the patient has never visited endemic regions. 2. Non-tropical forms of amebiasis may follow a severe course with complications such as liver abscess or ameboma. 3. The advice of a specialized laboratory is necessary for stool examinations on amebae. 4. Stool examinations for amebiasis should be combined with serological tests. The immunofluorescense test is of special value. False negative results are however possible, especially in cases without tissue inflitration where the infection is limited to the intestinal lumen. 5. Metronidazol (Flagyl) greatly simplifies the treatment of amebiasis as it is both efffective and better tolerated than most other antiamebic agents.


[Anti-lipoprotein autoantibodies with hypolipidemia in infectious rheumatism]. Presence of anti-lipoprotein activity, a new serological finding in inflammatory rheumatoid disease, has been established in sera and synovial fluids of 20 patients, among which were 6 cases of ankylosing spondylitis. In 18 of the patients, sera were negative for rheumatoid factor. Anti-lipoprotein activity can best be demonstrated by the hemagglutination technique. The binding activity is directed against autologous as well as homologous, however not against heterologous HDL and LDL. It has no specificity for Ag factors. Anti-LDL activity can also be demonstrated by means of double-diffusion tests, whereas no agar-precipitation has been noticeable using HDL as the antigen. Lipoprotein binding-activities were shown to be localized in the Fab fragments of IgG and, in 2 of the cases, also in IgA. We therefore assume that the underlying mechanism of the antilipoprotein activity is auto-immunization, despite of the fact that neither activation of complement nor a stoichiometric character of the binding reaction could be ascertained. Because hemagglutination and immunoprecipitation tests, respectively, were postive with apo-HDL und apo-LDL too, we consider the apo-protein to carry the antigenic site of the reaction. Sera with anti-lipoprotein autoantibodies from patients with chronic rheumatoid disease also presented another pecularity, i.e., a significant decrease of total lipids, cholesterol, and other components of the lipid spectrum. In patients with paraproteinemia, a similar combination of lipoprotein-binding activity and hypolipidemia or hypocholesterolemia was discussed in a previous paper. Regarding the pathogenesis of hypolipidemia or hypocholesterolemia in our patients with rheumatoid disorders, results of LDL turnover studies were indicative for an increase of the lipoprotein catabolism in the presence of anti-lipoprotein autoantibodies, together with a shift of the intra-extravascular distribution toward the intravascular pool. We assume the increased lipoprotein catabolism in these cases to be due to a trapping of lipoproteins by autoantibodies, and to accelerated degradation of these immune complexes. From a practical point of view, it may be of clinical importance that this new serological finding has been observed mainly in patients with chronic rheumatoid disease lacking a rheumatoid serum factor, and was frequently found in patients with ankylosing spondylitis (6 out of the 20 cases). As a screening method, we recommend systematic determinations of the total lipids and of serum cholesterol in all patients with inflammatory rheumatoid disease. In cases with low levels of total lipids and cholesterol, respectively, it may be useful to search for anti-lipoprotein autoantibodies using the hemagglutination method. Results are reported from some preliminary experiments on animals elicitation of an arthritis by means of intra-articular injections of autologous apo-HDL and apo-LDL, and demonstration of autoantibodies against HDL and LDL).


Mouse mammary tumors: alteration of incidence as apparent function of stress. Eighty to 100 percent of female mice of the C3H/He strain carrying the Bittner oncogenic virus usually develop mammary tumors within 8 to 18 months after birth when studied under the usual housing and experimental conditions. By subjecting various groups of such mice to environmental circumstances providing different degrees of chronic stress, mammary tumor incidence at 400 days was modified, with incidences ranging from 92 percent under stress to 7 percent in a protected environment. The data suggest that moderate chronic or intermittent stress may predispose such mice to an increased risk of mammary carcinoma, possibly through a resultant compromise of their immunological competence or tumor surveillance system, and that adequate protection from physiological stress may reduce mammary tumor occurrence in mice.


Cyclic AMP and cyclic GMP: mediators of the mechanical effects on bone remodeling. Compressive forces of physiological magnitude (60 grams per square centimeter) reduce the adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate content of the epiphyses of tibiae from 16-day-old chick embryos. An equivalent hydrostatic pressure applied directly to cells isolated from this tissue also affects cyclic nucleotide accumulation. The tissue response is uniform throughout the epiphysis, whereas the cell response varies according to the area of origin.


Predicting response to endocrine therapy in human breast cancer: a hypothesis. We hypothesize that the presence of progesterone receptors in human breast tumors may be a sensitive marker for predicting response to endocrine therapy. Progesterone receptors were found in 56 percent of tumors with estrogen receptors, but were absent in tumors without estrogen receptors. Preliminary clinical correlations show that only those breast tumors with progesterone receptors regressed after endocrine therapy.


Acetaldehyde oxidation by hepatic mitochondria: decrease after chronic ethanol consumption. Prolonged consumption of ethanol significantly reduces the capacity of rat liver mitochondria to oxidize acetaldehyde. This is associated with decreased mitochondrial respiration with acetaldehyde as substrate. The reduced ability of mitochondria to metabolize acetaldehyde may explain the high levels of acetaldehyde in the blood of alcoholics, which in turn could promote the perpetuation of liver injury.


Mixed tumor of female breast of unusual duration and size. A 72-year-old black woman presented with huge enlargement of the right breast beginning approximately 30 years earlier and progressively enlarging over the years. The breast was stony hard, painless, and inconvenient only because of size and weight. Simple mastectomy was done and pathologic examination showed a benign mixed tumor with large areas of pseudocartilage, osteoid, and bone formation. Preoperatively the serum calcium was 11.0 mg/100 ml and alkaline phosphatase, 550 mU/ml (SMA-12). Postoperative course was uneventful and within several weeks the alkaline phosphatase fell to a normal range (35-115 mU/ml). The case presented requires little comment other than its unusual nature and duration. Extensive bone formation was undoubtedly responsible for the elevated alkaline phosphatase and, as expected, it returned to normal limits following excision of the tumor. Simple mastectomy is considered the treatment of choice.


Osteoporosis, oestrogens and oöphorectomy. A proposed new test of oestrogenic potency. The role of oestrogens, endogenous and exogenous, in the pathogenesis of osteoporis is briefly reviewed. Aspects of research into effects of oestrogens on plasma calcium and phosphorus metabolism, conducted at Groote Schuur Hospital, are incorporated in the discussion. The current role of oestrogen therapy in the prevention of osteoporosis is presented. Evidence suggests that different oestrogenic substances produce different metabolic effects. On this basis a new test for assessment of oestrogenic potency is proposed. It is concluded that appropriate or specific oestrogens are of value in the prevention of osteoporosis, but play little or no role once the process is fully developed. A positive preventive measure recommended is conservatism with regard to ovaries during gynaecological operation on young women.


Effect of conjugated oestrogen therapy on circulating luteinising hormone in oophorectomised women. In a double-blind cross-over study, conjugated equine oestrogen (Premarin) was shown to depress the raised luteinising hormone concentration found in the plasma of oophorectomised women. A dose of 1,25 mg was as effective as 2,5 mg per day.


Sclerosing haemangioma of the lung. A case report. A case of pulmonary sclerosing haemangioma composed of blood-filled cavernous spaces separated by septa containing sheets of uniform, epithelioid-type cells and numerous mast cells is described. Although the histogenesis has not been conclusively established, the appearances in this case favour a primary vascular lesion. The variable histological patterns observed in this tumour may cause problems in diagnosis; the differentiation from haemangioma, haemangiopericytoma, pulmonary chemodectoma and benign clear cell tumour of the lung is discussed.


Focal dermal hypoplasia syndrome.

Focal dermal hypoplasia syndrome. A patient with focal dermal hypoplasia syndrome is presented.  In addition to the usual skin lesions, this patient showed two interesting features, viz. spontaneous involution of the papillomatous lesions on the lips, and osteopathic striae.


Sporadic ulcero-osteolytic neuropathy in Blacks. A report of two cases. The triad of a peripheral neuropathy, skin ulceration and destruction of bones and joints of the feet is called ulcero-osteolytic neuropathy, when other common causes of similar lesions have been excluded. Malnutrition, alcoholism and local trauma predispose to the development of the condition. It is to be differentiated from burnt-out leprosy, and is a chronic condition that eventually leads to characteristic deformities.


Colestipol, clofibrate, cholestyramine and combination therapy in the treatment of familial hyperbetalipoproteinaemia. Fifty-seven patients, mean age 26 years, suffering from familial hyperbetalipoproteinaemia (Fredrickson type lla and llb), were treated on a low cholesterol, modified polyunsaturated fat diet for a period of 6-12 weeks prior to the introduction of drug therapy.  No significant reduction in the serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol or triglyceride was found.  Fifty patients were then treated with colestipol for 6 weeks; total and LDL cholesterol decreased by 23%, but triglyceride levels were unaffected.  During the following 6 weeks, placebo was administered, and total and LDL cholesterol returned to pretreatment levels.  The patients were then randomly allocated into two groups of 16.  The first group continued with clofibrate therapy, while the second group received cholestyramine.  In the clofibrate group a reduction in total and LDL cholesterol of the order of 17% was noted, similar to cholestethat achieved in this group on colestipol.  Triglyceride levels were 15% lower on clofibrate therapy than on colestipol.  In the cholestyramine group, there was a 25% decrease in total and LDL cholesterol, compared with pretreatment levels.  This reduction was similar to that found when colestipol was administered.  Triglyceride values were significantly raised during cholestyramine therapy.  Thirteen patients were then subjected to a 6-week period of combination therapy, either clofibrate or colestipol, or clofibrate and cholestyramine.  Total and LDL cholesterol were reduced by 32% on combination therapy compared with 18% on colestipol and 23% on either clofibrate or cholestyramine alone.  Furthermore, on combined therapy, triglyceride concentrations fell by 20% when compared with the levels found when colestipol, clofibrate or cholestyramine were administered on their own.


Pseudogout--CPPD arthropathy, Case reports. Pseudogout, or calcium pyrophosphate arthropathy, is a crystalline synovitis, characterised either by acute attacks of joint pain, which usually occur in the large joints, or by a more chronic, progressive form of joint disease.  The essential features of the disease are chondrocalcinosis and the presence of pyrophosphate crystals in the synovial fluid.  The exact pathogenesis is unknown.  Case reports of 2 patients with confiemed pseudogout, and of 1 who is suspected to be suffering from the disease, as well as a summary of the outstanding aspects of the condition, are presented.


Lymphography--technique, indications and principles of interpretation. The findings in 277 patients investigated by ethiodol lymphography are reviewed, and the applications and limitations of the procedure are presented. The non-specificity of findings is the principal reason for the lack of acceptance of this procedure, and the confusing entity of tuberculous lymphadenitis is discussed.


Surgical lesions of the ovary in infancy and childhood. In 27 years, 64 patients were operated upon for ovarian lesions, 43 for tumors, 12 for nonneoplastic cysts and nine for ovarian torsion.  Of all the girls in this age group who were operated upon for appendicitis, 2 percent had ovarian lesions.  Of the girls referred for isosexual precocity in the last ten years, 4.7 per cent had ovarian lesions.  Of the girls in this age group operated upon for malignant abdominal lesions, excluding hepatic, in the last 15 years, 10.8 per cent had ovarian tumors.  Of the 11 tumors with endocrine function, four were malignant.  This association is statistically significant.  There were no operative deaths.  There were no postoperative deaths among six patients with Stage I and II lesions.  Mortality was confined to the two patients with Stage III and IV lesions.  The surgical approach was designed to conserve ovarian tissue, and adjunctive chemotherapy and radiotherapy were infrequently used.


Effects of exogenous cyclic adenosine monophosphate in hemorrhagic shock. Hemorrhageic shock produces potentially damaging alterations in the metabolism of cyclic adenosine 3',5'-monophosphate (cAMP), which is an intracellular second messenger for many hormones. The hypothesis that the administration of exogenous cAMP might have salutary effects on cardiovascular hemodynamics in shock was tested in canine experimetns. Intravenous bolus injection of dibutyryl cAMP (2 mg. per kilogram) produced hyperglycemia, but no changes occurred in heart rate, arerial pressure cardiac output, or in the first derivative of left ventricualr pressure (dp/dt). The findings were similar in conscious and anesthetized (Nembutal) normotensive dogs, in dogs after 3 hours of shock (at blood pressure of 40 mm. Hg) and after the reinfusion of shed blood. The only hemodynamic change noted was a transient hypotensionupon injection of massive doses of dibutyryl-(db-) cAMP or cAMP (greater than 10 mg. per kilogram). The implication of these findings in light of earlier reported hemodynamic effects of cAMP is discussed.


Prognosis of mammary carcinoma in young women. One hundred and sixty-two women with carcinoma of the breast, age 40 years or younger, were treated from 1950 to 1969. Mammary cancer is not uncommon in this age group. The 5 year survival rate among our operable patients was about 50 percent. The 5 year survival rate among patients 20 to 35 years of age was slightly higher than that in patients 36 to 40 years old. In stage B and more advanced breast cancer in young women, the outlook was poorer than in women 41 years and older. When axillary involvement is present during gestation or in the immediate postpartum period, the prognosis is especially poor. Young women have an unusually high proportion (35 percent) of low-grade, infrequently metastasizing tumors, such as medullary, intraductal, papillary, and lobular carcinomas. The presence of cancer in the axillary nodes at operation is the most important factor affecting prognosis in mammary cancer. From this study we can see no reason to consider carcinoma of the breast in young women a more lethal disease than that seen in their older counterparts.


The community of human malformation syndromes that shares ectodermal dysplasia and deformities of the hands and feet. Syndromes of human congenital malformation may be classified be recognizing communities of syndromes that share multiple phenotypic similarities involving their principal diagnostic features. A community of syndromes that shares various expressions of ectodermal dysplasia and various deformities of the hands and feet is proposed; these syndromes are divisible into two classes according to the presence or absence of anomalies in the nasal or labial regions of the face. The dysmorphogenetic validity of the division is supported by the fact that the syndromes without nasal or labial anomalies have a high frequency of sensorineural deafness as one expression of ectodermal dysplasia whereas those without such anomalies do not. The usefulness of such a syndromal community as a base for evolving a taxonomic scheme of dysmorphogenetic relatedness amongst different syndromes is illustrated.


[An atypical case of Aujeszky's disease in a dog (author's transl)]. Two cases of Aujeszky's disease in a cat and a dog belonging to the same owner are reported. The two animals each were five months of age. The symptoms shown by the cat were typical of Aujeszky's disease: intense itching, salivation and the head bent to one side. The main symptoms shown by the dog consisted in salivation, ptosis of one eye, a drooping ear, the head bent to one side and ataxia. As itching was not observed in the dog and the animal had spent the first months of its life in wooded surroundings, it could also have been affected with rabies, although it had been inoculated with LEP-Flury vaccine forty days prior to importation. It is of importance to the practitioner to know that itching may be absent in dogs with Aujeszky's disease and that rabies should also be suspected in these cases. Only a laboratory diagnosis will be conclusive. Studies were negative for rabies, the virus of Aujeszky's disease being found to be present in the two cases. The source of infection probably consisted in contaminated pork offal (larynges).


[I.B.R (author's transl)].

[I.B.R (author's transl)]. The clinical pictures which may be produced by IBR/IPV virus in cattle are briefly reviewed. Up to the autumn of 1972, infection occurred only sporadically in the Netherlands, no typical cases of IBR having been reported up to the fall of that year. Since the winter of 1972-1973 IBR has increasingly been diagnosed, particularly during the winter months. It may, however, be mistaken for other infections of the respiratory tract. The infection apears to be spreading. The clinical features, diagnosis, epizootiology and methods of treatment are discussed. Administration of a vaccine may be indicated in some herds where IBR-virus is present or its introduction is to be expected. In that case, inoculation of a monospecific vaccine, directed against IBR virus only is to be preferred to the use of combination vaccines.


Electroencephalographic study of an infant with phosphoribosylpyrophosphate synthetase deficiency. In a hypouricemic and mentally retarded infant due to a defect of 5-phosphoribosylpyrophosphate synthetase, electroencephalograms were recorded at the age of 4, 7, 10 and 11 months. Hypsarrhythmia was first observed at the age of 10 months, and markedly improved after ACTH therapy with concomitant increase in the enzyme activity of erythrocytes.


Reticuloendothelial system function test using 131I-labeled aggregated albumin. The reticuloendothelial system function test using 131I-labeled aggregated human albumin (131IAA) as test particle is thought to be one of the best methods for the study of RES function of human beings. This method needs a large amount of 131IAA, but 131IAA has been used as a tracer of liver scintiscanning, and we tired to study RES function by using commercially available 131IAA specially made as tracer of liver scintiscanning. Because the amount of 131IAA used in this study was smaller than the critical dosis, our interest was focussed on the catabolic activity of 131IAA phagocytized by Kupffer's cells. The plasma obtained 60 min after 131IAA injection was fractionated into two distinct peaks by gel column chromatography; ionic 131I and protein-bound 131IAA. The ratio between ionic 131I and bound 131IAA (F/B ratio) was studied in various diseases. The F/B ratios of liver cirrhosis and hepatoma were significantly lower than that of the control. The lowered F/B ratio had no correlation with other liver function tests, data of hepatic scintiscanning, or with clinical findings. The F/B ratio was also not correlated with congo red index as RES function test.


Assessment of the teratogenic potential of surfactants. Part III--dermal application of LAS and soap. The surfactant linear alkylbenzene sulphonate (LAS) was examined for embryotoxic and teratogenic potential following percutaneous administration. Solutions containing, 0.03, 0.3 and 3% LAS were applied to shaved skin during pregnancy days 2-13 in mice, 2-15 in rats and 1-16 in rabbits. Dosages employed were 0.5 ml/rat or mouse/day and 10 ml/rabbit/day. For comparison further groups of rats and mice were similarly treated with concentrations of 0.3, 3 and 30% of a standard soap solution. Marked maternal toxicity in the form of local skin reaction, irritability, weight loss and failure to maintain or establish pregnancy was evident in mice treated with LAS 3% or soap, 3 or 30%; marked local reaction and weight loss also occurred in rabbits receiving LAS 3% but the reduction in the number of pregnancies maintained was not significant. Moderate maternal toxicity was observed among mice treated with LAS, 0.3% and mild maternal toxicity in rats receiving LAS 3% or soap 30% and rabbits receiving LAS 0.3%. Effects on litter parameters were generally restricted to dosages causing marked maternal toxicity in mice, the principal effects being higher foetal loss (with consequent reduction in viable litter size) arising from an increased incidence of total litter losses. When dams showing total litter loss were excluded from the calculations, litter parameters were not unduly different from those of controls. Although LAS at 3% was considered to show marked maternal toxicity in the rabbit, the slightly higher foetal loss and lower litter size did not differ significantly from control values.


Influence of chronic exposure to cadmium on hepatic and renal cyclic AMP-protein kinase system. Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) to rats for 45 days significantly elevated the endogenous levels of cyclic AMP (cAMP) in hepatic tissue. However, the cAMP binding to hepatic protein kinase was decreased following cadmium administration, as was the kinase activity ratio. Although both doses of cadmium produced slight alterations in the cAMP-independent form of hepatic protein kinase, only the 1.0 mg/kg dose significantly depressed (24%) the activity of the cAMP-dependent enzyme. In contrast to liver, chronic exposure to cadmium significantly reduced the endogenous cAMP levels in kidney cortex. Although treatment with the lower dose (0.25 mg/kg) failed to alter either the cAMP-binding capacity of the renal enzyme or the kinase activity ratio, the higher dose (1 mg/kg) of cadmium did cause a significant increase in both parameters. In addition, cadmium treatment produced a significant decrease in both the cAMP-dependent and the independent forms of protein kinase in kidney cortex. Data suggest that the concentration of cAMP as well as its interaction with cAMP-dependent and independent forms of protein kinase, are altered in both kidney and liver following the prolonged exposure to cadmium.


Teratology studies of a mixture of tallow alkyl ethoxylate and linear alkylbenzene sulfonate in rats and rabbits. A mixture of 55% tallow alkyl ethoxylate sulfate (TAE3S) and 45% of linear alkylbenzene sulfonate (LAS) was fed to two generations of rats at dietary levels of 0.1, 0.5 or 1.0%. The rats were fed the surfactant mixture either continuously or during the organogenesis (days 6-15) period of six  pregnancies. In addition, pregnant New Zealand rabbits were given 50, 100 or 300 mg/kg doses of the surfactant mixture by intubation on days 2-16 of gestation during a single pregnancy. No adverse effects were noted on conception, fetal viability or post-natal survival in either generation of rats. There were no statistical differences among the groups of rat fetuses taken by Caesarian section and examined for birth defects. Of 1210 rat fetuses, the overall incidence of abnormal young was 9.0%. Similarly, no adverse effects were seen in rabbits treated with the surfactant mixture. Of 855 rabbit fetuses, 5.7% were abnormal, but the incidences of defective fetuses in the test groups were not significantly different from those in controls. Thus, no test related effects were seen on reproduction or embryonic development in either animal species.


Relation of the pituitary gland to gonadal hormone effects on the adrenocortical 11beta-hydroxylase system in rats. Studies were conducted to further examine the mechanisms responsible for gonadal hormone effects on the rat adrenocortical 11beta-hydroxylase system. Despite higher concentrations of cytochrome P-450 and larger 11-deoxycorticosterone (DOC)-induced difference spectra in adrenal mitochondria from females than males, no sex difference in 11beta-hydroxylase activity was observed. The pregnenolone-induced difference spectrum, indicative of cholesterol binding to cytochrome P-450, also was similar in males and females. Testosterone administration to castrated males lowered both 11beta-hydroxylase activity and mitochondrial cytochrome P-450 content. Estradiol produced the opposite effects in castrated females. However, when given to ACTH-replaced hypophysectomized rats, neither testosterone nor estradiol affected cytochrome P-450 levels or the rate of 11beta-hydroxylation. These observations, taken with the known effects of estradiol and testosterone on ACTH secretion in rats and the effects of ACTH on 11beta-hydroxylation, indicate that gonadal hormone effects on the 11beta-hydroxylase system are mediated by ACTH.


Bile composition and bile cast formation after transplantation of the liver in man. Transplantation of the liver in man is frequently complicated by biliary fistula and obstruction of the biliary tree by casts, which suggests that the composition of the bile may be abnormal. In part of the present study, bile composition was investigated in three recipients during the first few weeks after transplantation, when a T tube was in place. Supersaturation of bile with cholesterol was found in two patients immediately after surgery and during episodes of acute rejection, but bile was never lithogenic in the third. There was no evidence of bile stasis in the absence of acute rejection and bile viscosity was normal in all three patients throughout the study. Free bile acids and free bilirubin, which are relatively insoluble products of bacterial metabolism, were not present in the bile of any patient. However, chemical analysis of casts found at autopsy in a fourth recipient showed that the major component was free bilirubin. Escherichia coli was grown in cultures of the casts and the organisms were shown to possess glucuronidase activity, thus providing an explanation for the high bilirubin content. There was also some evidence in one case that damage to the bile duct mucosa has led to the precipitation of material upon it, and it is concluded that a number of factors, including infection, supersaturation with cholesterol, and mucosal damage, may be involved in bile case formation after transplantation of the liver.


Detection of hepatoma associated embryonic antigen in tumour-bearer serum. Embryonic antigen associated with an aminoazo dye-induced rat hepatoma was identified in the serum from rats bearing progressively growing tumours. Antigenic activity in serum samples was detected by their capacity to neutralize multiparous rat serum antibody reacting with surface embryonic antigens expressed upon viable hepatoma cells as assessed with use of the indirect membrane immunofluorescence test. Serum taken at various states of tumour growth from hepatoma-bearing rats was separated by Sephadex G-150 gel filtration column chromatography at pH 7.3 and pH 2.8 with use of procedures designed to identify free circulating antigen and antigen derived from immune complexes. Hepatoma-associated embryonic antigen was demonstrable in tumour-bearer serum in a free form most markedly in the later stages after implantation of tumour cells (from the end of the 2nd week to the 5th week of tumour growth). Antigenic activity in fractions derived from immune complexes was detected earlier during tumour development (from day 8 after tumour induction), and this was present in all serum samples taken up to the 5th week after tumour cell inoculation.


[Regenerative growth of asvitic hepatoma 22A]. A study was made of the recurrent growth of ascite hepatoma 22A, occurring at transplantation of 11-12-day old tumours to new hosts. The mitotic activity of the hepatoma was found to increase by 3 to 4 times (12-15 hours after inoculation). This increased cell proliferation is due mainly to a sharp shortening of all the periods of mitotic cycle. During the recurrent growth, the resting R1 cells resume their mitotic cycle. No resumption of the mitotic cycle by the resting R2 cells was observed


Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 1. animal preparation, instrumentation, and validity of model. Reduce nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to the reliable.


Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 2. effects of alterations in arterial carbon dioxide tension, blood pressure, and blood volume. The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Paco2. In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction.


[Glomus tumor of arterio-venous anastomoses]. Collected data of 74 national authors comprising 267 glomus tumors are reported. Based on these data and 49 personal authors' observations the clinic, pathogenesis, pathological anatomy and diagnosis of this rather rare lesion are described. Surgical intervention consisting in total removal of the tumor together with its capsule is the only proper method of treatment for the Barre-Masson disease.


[Serum and liver lipase activity in chickens during the 1st month of life]. Method according to DIRSTINE (1968) was employed to study the activities of serum and liver lipase in White Leghorn cockerels during early post-incubation ontogenesis; as to serum lipase, two embryo intervals were also studied (the 13th and 20th day of incubation). From the average value of 4.4 ummol (13th day), serum lipase activity increased to the average value of 7.5 ummol (20th day). The first day after hatching the average value was 3.5 ummol which remained almost unchanged until the 9th day, with the exception of a slight drop the third day; an increase of activities was observed on the 13th day (4.9 ummol), 15th day (3.5 ummol), 21st day (7.6 ummol), 22nd day (5.5 ummol), and 24th day (8.8 ummol). The minimum average activity of 2.5 ummol was measured the 32nd day. Liver lipase activity was observed to drop from the first-day starting value of 20.6 ummol to 9.8 ummol (the second day), with a subsequent increase to 14.9 ummol (the 4th day). The maximum values were recorded the 13th day (26.2 ummol) and the 15th day (28.7 ummol) whereas the minimum average value was obtained the 32nd day (6.3 ummol). Liver lipase activity drop on the second day of age and serum lipase activity drop on the third day with subsequent increase are probably associated with the change from yolk-sac nutrition to feeding per os. Some stabilization of serum and liver lipase occurs the 32nd day; the values found in adult fowl were almost the same as the 32nd day values.


Veterinary aspects of salmonid fish farming: husbandry diseases. Most disease problems affecting farmed salmonid fish are either caused or exacerbated by bad husbandry and poor environmental conditions. The aspects of water quality and nutrition which are significant in causing husbandry problems are considered. The clinical aspects of these diseases are decribed in terms of the life cycle of salmonids, and methods of prevention are discussed.


Trials with Marek's disease vaccines prepared from a turkey herpes virus and an attenuated Marek's disease virus. In field trials involving over 224,000 fowls in 11 different commercial flocks, three vaccines were used, namely a freeze-dried vaccine prepared from a turkey herpes virus, a cell-associated virus vaccine prepared from the same isolate and a cell-associated vaccine prepared from a strain of Marek's disease virus isolated from a fowl. The mortality from Marek's disease was reduced by 80 per cent to 95 per cent in birds vaccinated with the freeze-dried vaccine. Cell associated vaccines gave slightly less protection.


4-Nitrobenzoic acid reductase of Ascaris lumbricoides var suum. Substrate specificity and reaction products. 1. The substrate specificity of nitro-reductase from Ascaris lumbricoides varsum was determined. This enzyme reduced nitrobenzene, 4-nitrohippuric acid and the isomers of nitrophenol, nitroanisole, nitrobenzoic acid, nitrobenzaldehyde and nitrobenzyl alcohol. The same enzyme preparation reduced azobenzene, 4-dimethylaminoazobenzene and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene. Nitrobenzaldehyde isomers were not reduced to the alcohols. 2. The products of nitro- and azo-reduction were the corresponding amines, no hydroxylamino or hydrazo compounds were detected. 3. The pH optima and cofactor requirements were the same for both azo- and nitro-reduction and neither reaction was inhibited by oxygen. 4. Ammonium sulphate fractionation failed to separate azo- and nitro-reductase activities. The molecular weight of both azo- and nitro-reductase was about 130 000.


[Influence of fenoterol of cAMP levels and motility on the rat uterus in vitro (author's transl)]. CAMP levels of isolated rat uteri (2nmol/g wwt) were increased by Fenoterol (10(-4)--1 mug/ml) in a dose dependent manner reaching concentrations of more than 10nmol/g withing 2--5 min. AT 2 TIMES 10(-3) MUG/ML Fenoterol inhibited spontaneous contractions of the rat uterus in vitro. A 10,000 fold higher dosis of Fenoterol was needed to elicit a similar degree of inhibition, when contractions were induced by 0.6 mU/ml Oxytocin. However cAMP levels were elevated by Fenoterol in presence of Oxytocin, uterine contractions were not inhibited, i.e. the elevation of cAMP after administration of Fenoterol is correlated with a relaxant effect only in uteri contracting spontaneously.


[A spectrophotometric method for the determination of serum cholinesterase variants with succinyl choline as substrate (author's transl)]. A simple and rapid method for the estimation of the hydrolysis of succinyl choline by serum cholinesterase variants is described. Succinyl choline, as substrate for the enzyme assay, has many advantages over other substrates (acetyl choline, benzoyl choline and butyryl choline) which have no clinical application. Choline, the hydrolytic product of succinyl choline, is oxidized to betaine aldehyde by choline oxidase (EC 1.1.99.1), a rat liver mitochondrial preparation; this is coupled to the reduction of cytochrome c which is measured at 550 nm. Fifty normal sera (UU), 17 heterozygous (UA) and 8 atypical (AA) were tested with this method, and on the basis of resistance to dibucaine (Cinchocain; Kalow, W. & Genest, K. (1957) Canad. J. Biochem. Physiol. 35, 339-346) inhibition, three distinct groups could be established using succinyl choline as substrate. These results are comparable with the standard optical method of Kalow & Genest (cf. above) using benzoyl choline as substrate.


[Changes in the activity of alkaline phosphatase and the level of thiamine diphosphatase in simulations of B1 avitaminosis]. Alimentary B1 avitaminosis was attended by a declining activity of alkaline phosphatase in the brain and spleen of rats. A single administration of oxythiamine to rats in a dose of 400 mg/kg produced during the first hours an increased activity of alkaline phosphatase in the liver, brain and, to a lesser extent, in a number of other organs and reduced the thiamine-diphosphate content in the liver, brain and other tissues. The thiamin-diphosphate level in the brain returned back to normal in 12 hours, and in other tissues-towards the 3--5th day. In 24 hours after introduction of oxythiamine the activity of alkaline phosphatase was up in the liver alone, while in the brain the activity of the enzyme decreased. Thiamine, used in a dose of 400 mg/kg, exerted on the activity of alkaline phosphatase in a number of tissues an action similar to that of oxythiamine. It is suggested that the activation of alkaline phosphatase 3--12 hours following adminstration of a large dose of thiamine or oxythiamine is of a non-specific nature. Subcutaneous introduction of a commercial alkaline phosphatase preparation to rats brought down the thiamine-diphosphate level in all of the tissues under investigation. The presumed mechanisms accounting for the fall of thiamine-diphosphate and the possible part played in this process by alkaline phosphatase are discussed.


Radioimmunoassay of serum deoxycorticosterone: normal values and changes of serum deoxycorticosterone after adrenal stimulation. A sensitive radioimmunoassay for estimating serum deoxycorticosterone is described which involves descending "overrunning" paper chromatography. An ethanolic paper eluate is used as a solvent for unlabelled deoxycorticosterone in the preparation of the standard curve. The values of the water blanks (7 ng/l) are similar to the sensitivity of the standard curve (5.8 ng/l). The normal mean serum concentration of deoxycorticosterone was found to be 84 +/- 29 ng/l (n = 30) in males and 55 +/- 31 ng/l (n = 35) in females. Serum deoxycorticosterone rose in healthy subjects upon injection of ACTH, after induction of insulin hypoglycemia and after administration of metyrapone, while the rise was absent or blunted in patients with Addison's disease and in patients with pituitary failure.


[Soft tissue tumours on the back of the knee]. Soft tissue tumours behind the knee have rarely been described in literature. We have studied 74 patients with 79 tumours and pseudotumours in this area, and made a survey about pathology, clinical features, diagnosis, differentialdiagnosis and operative treatment. We have pointed out the varying nomenclature and confusion in definition ob a bursa and Baker's synovial herniation. The analysis of the casuistry showed predominantly gangliae, bursae and Baker's cysts. We have given special prominence to subfascial lipoma, malignant synovioma and nerve tumours as rare conditiones. Our own cases of synovioma and nerve tumours have been separately described.


[Compression arthrodesis of the knee joint]. The results of 42 cases of compression arthrodesis of the knee joint during a 5.5 years period are reviewed. Main indications were degenerative, rheumatoid and posttraumatic arthrosis and tuberculosis of the knee joint. Other differential indications and the operative procedure following the Charnley-Müller method are described. The complications - pseudarthrosis, infection, false rotation - are discussed.


[Vacuolisation of odontoblasts and regressive metamorphoses from viewpoint of pulp-dentin system function]. The authors, after presenting a critical definition of the problems dealt with in their present paper in addition to giving an evaluation there of from the point of view of a constant increase of knowledge, describe the biological functions of the cell with particular reference to the cell's vacuolar apparatus. They then characterize the pulpodentinal system, outlining the functional adaptation of the endodontal vascular apparatus in the light of intrascopic results, the clinical importance of which is discussed at length.


[A new butyric acid-producing bacteroides species: B. splanchnicus n. sp. (author's transl)]. Three butyric acid-producing saccharolytic Bacteroides cultures (1651/6, BM 158, and IPP 3751) were described by WERNER and REICHERTZ in 1971 (Zbl.Bakt.Hyg., I. Abt. Orig. A 217,206-216). Since then, 6 strains closely resembling 1651/6 were isolated from stool specimens and surgically removed appendices. In the present communication, strains 1651/6, S2/34, S3/38, S4/28, S6/6, A5/2 are described as members of a new species, Bacteroides splanchnicus n.sp. The strains were morphologically very similar (Gram negative non-sporing non-motile rods, 1-2.5 mu in length and 0.7 mu in width) and fermented glucose, fructose, galactose, mannose, lactose, and arabinose (pH values of 4.6-5.4, moderate gas formation). Negative reactions (pH values of 5.8-7.2) were observed with 20 other carbohydrates. The strains were positive in the glutamic acid decarboxylase test and formed indole and H2S. In peptone-yeast extract broth and peptone-yeast extract-glucose broth acetic, propionic, isobutyric, butyric, and isovaleric acids were produced. Washed cells of strains 1651/6 and S4/28 incubated anaerobically in sterile solutions of single amino acids produced butyrate from lysine only. Abundant butyric acid was also produced from glucose. The in vitro activity of 15 antibiotics on 5 strains was studied by broth dilution tests. Uniformly, the strains showed resistance to aminoglycosides and polymyxins (MIC values, 60-500 mug/ml) and susceptibility to tetracyclines, lincomycin, clindamycin, rifampicin, and erythromycin (MIC values, 0.05-0.5 mug/ml). Chloramphenicol, penicillins, and cephalosporins showed bacteriostatic activity at concentrations of 5-40 mug/ml. The serological behaviour of 5 strains was studied in cross-agglutination and gel-diffusion experiments. Cross-reactivity was pronounced in gel-diffusion tests using rabbit antisera and autoclaved extracts and extracts prepared by repeated deep-freezing and thawing of whole cell suspensions as antigens. However, antisera against the B. splanchnicus strains did not react with antigens of B. fragilis 6869, B. thetaiotaomicron AS 126, B. vulgatus AM 45 a, B. distasonis AII 104 and butyric acid-producing strains BM 158 and IPP 3751 in agglutination and gel-diffusion experiments, and there were no cross-reactions between B. splanchnicus antigens and antisera against B. fragilis 6869 and the other aforementioned strains. The new species has been confirmed by members of the ICSB Taxonomic Subcommittee for Gram negative anaerobic rods. Strains 1651/6 and S4/28 have been deposited in The National Collection of Type Cultures, London (NCTC numbers 10825 and 10826). Strain NCTC 10825 (= 1651/6) is the type of the species, B. splanchnicus.


Oxidation processes and ubiquinone localization in the branched respiratory system of mi-1 mutant of Neurospora crassa. 1. Stimulation of succinate oxidation in mi-1 mitochondria by Mg2+ and Pi is abolished on uncoupling, which points to the energy-linked activation of succinate oxidation. 2. Mitochondria exhibited respiratory control with succinate and NADH when the cyanide-insensitive oxidation was inhibited by salicylhydroxamic acid (SHAM). SHAM lowered the oxidation rate with NADH and succinate to the same level, though the NADH oxidation rate was 2.5 times as high as with succinate. 3. Despite the high stimulation of succinate oxidation via the SHAM-sensitive pathway in the active and controlled state of mitochondria, the redox state of UQ in all metabolic states remains unchanged. On inhibition of the cyanide-insensitive pathway, UQ reduction is greatly increased only in the controlled and active state. With NADH as a substrate, UQ does not respond to the metabolic states of mitochondria. 4. The redox changes of cytochrome c parallel those of UQ. 5. Branching of the respiratory chain in mi-1 mitochondria is discussed.


Universality of gonadotropic hormone effect. Effect of mammalian FSH on the ovotestis of the snail Helix pomatia. Gonadotropic hormone (FSH) stimulated markedly spermatogenesis in the ovotestis of snails. This is indicative of the presence of receptors sensitive to gonadotropic hormone in snail spermatogonia. FSH had no influence on oogenesis.


[Respiratory muscle activity in newborn children during sleep and wakefulness]. Two types of electrical activity - inspiratory and tonic (postural) ones - have been registered in the external intercostal muscles and diaphragm. Both types of the activity decrease during orthodoxical sleep as compared with the period of quiet awakefulness. During the transition of orthodoxical sleep into paradoxical one, tonic activity is completely inhibited, while inspiratory activity in the intercostal muscles remains unchanged, being increased in the diaphragm. In the period of rapid eye movements inspiratory activity of the intercostal muscles is reduced. The decreased tone of the intercostal muscles accounts for changes in respiratory movements and for the onset of asynchoronous thoracic and abdominal respiratory movements during paradoxical sleep.


[Multiple malignant tumors].

[Multiple malignant tumors]. The cases of six tumour patients are presented. One patient had four, the others three or two primary cancers in 12 years. The importance of keeping operated patients under supervision is pointed out and it is stressed that on the appearance of a new tumour the physician must not suppose incurability. In the case of gastrointestinal malignomas attention should be paid to cancer to the skin.


Short-loop feedback mechanism of luteinizing hormone: LH stimulated hypothalamic L-cystine arylamidase to inactivate LH-RH in the rat hypothalamus. The effect of the intravenous administration of several hormones on L-cystine arylamidase in the hypothalamus of the rat was examined.  The injection of 10 mug LH into adult male and female rats was followed within 90 min by an increase of the enzyme activity by 50%, while infantile animals were not affected.  When prepuberal rats were pretreated sc with testosterone and progesterone.  The iv injection of 0.1 mug oestradiol-17beta into female, and of 0.5 mug testosterone into male intact mature rats also resulted in an increase of hypothalamic enzyme activity.  The maximal increase in enzyme activity was seen 16 h after steroid treatment.  As it had previously been shown that L-cystine arylamidase inactivates LH-RH, it may be assumed that this enzyme is involved in the short-loop feedback of LH.  This assumption is based on the observation that an elevation of plasma LH brings about an activation of the enzyme system, which subsequently leads to an increased inactivation of LH-RH in the hypothalamus.  This mechanism seems to depend on the presence of certain plasma levels of oestrogen in female, and of testosterone in male animals.


The specificity and application of a radioimmunoassay for the alpha-subunit of luteinizing hormone in man. A sensitive radioimmunoassay for the alpha-subunit of LH has been developed.  Differences in the immunopotency of LH, FSH, and subunit preparations were found and are described in detail.  The assay has been applied to the measurement of circulating levels of alpha-subunit; higher levels of alpha-subunit were found in post-menopausal than in pre-menopausal women, or  men, and a rise in alpha-subunit was seen after LH-RH but not TRH administration.  Elevated levels of free alpha-subunit were found in foetal cord blood at term.  These results suggest that the alpha-subunit circulates independently of the intact pituitary and placental glycoprotein hormones.


Influence of corticotrophin on urinary 17-ketosteroid excretion in adrenalectomized females. Urinary excretion of 17-ketosteroids was measured during dexamethasone substitution followed by ACTH (Synacthen Depot, 1 mg daily) in 10 non-virilized adrenalectomized women.  No significant changes could be demonstrated indicating ovarian androgenic dependence of ACTH in non-virilized females.


The effects of LH-RH on the concentration of 3',5'-cyclic AMP and RNA synthesis in rat anterior pituitary. In an experiment performed to investigate the effect of LH-RH on the anterior pituitary of rats, we studied the changes in the concentration of 3',5'-cyclic AMP in the anterior pituitary and the uridine uptake by the anterior pituitary following the intravenous injection of 100 ng LH-RH. The results obtained are summarized as follows: 1) The tissue level of 3',5'-cyclic AMP in the anterior pituitary reached the highest peak 15 min after the injection of LH-RH. 2) The uridine uptake of the anterior pituitary began to increase 15 min after the LH-RH injection and attained a maximum level (5 to 6 times the normal level) in 30 min. 3) The fact that the uridine uptake was inhibited to a considerable extent by the addition of actinomycin D to the incubation medium suggested that uridine was incorporated into the RNA fraction.


The importance of sodium balance on the effect of angiotensin II on aldosterone production. The action of angiotensin II on the adrenal cortex can be modified by body sodium balance. The secretion rate of aldosterone was compared with the late biosynthetic pathway in dogs kept under different sodium states. The conversion of corticosterone (B) to aldosterone was significantly increased by the infusion of angiotensin II into sodium depleted dogs. ACTH infusion failed to increase the late aldosterone pathway in sodium depleted animals, even though the secretion rate increased by 10 times. These results confirm previously indirect evidence that angiotensin II has a direct stimulatory effect on the late step of aldosterone biosynthesis. This stimulation does not appear to be the result of enzyme-substrate activation by aldosterone precursors. The results favour the hypothesis that sodium balance can modulate the action of angiotensin II not only on the first steps, but that there is also a regulatory effect on the conversion of corticosterone to aldosterone.


Diurnal variations of plasma aldosterone in supine man: relationship to plasma renin activity and plasma cortisol. In order to investigate the role of renin secretion and of ACTH on the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), plasma cortisol (PC) and PA were determined at short-time intervals in 10 normal supine men. Six subjects were studied under a normal sodium intake and 4 under sodium restriction. In 4 subjects the secretion of ACTH was suppressed by dexamethasone. Under normal sodium intake changes in PA seemed to be more in parallel with changes in PC than by those in PRA as indicated by a higher significant correlation between PA and PC than between PA and PRA in 3 of the 4 subjects. In 1 subject no correlation was observed between PA and PC despite visual synchronism between the plasma concentrations of both hormones. Under dexamethasone medication fluctuations in PA were followed by those in PRA while PC was less than 2 mug/100 ml. In the sodium restricted state, changes in PA were closely paralleled and significantly correlated to PRA while no correlation was seen between PA and PC. Under dexamethasone medication the significant correlation between PA and PRA persisted. Our results indicate that in normal supine man the influence of ACTH and renin on PA may vary with different sodium intakes. Under normal sodium intake ACTH seems to be the dominant factor controlling PA, whereas under sodium restriction changes in PA are mediated through the renin angiotensin system. When the secretion of ACTH is suppressed by dexamethasone, renin controls PA both under normal and low sodium intake.


An in vitro method to study the participation of various components in autoimmune hemolytic anemia. A method is described which allows for the in vitro evaluation of various etiological components in autoimmune hemolytic anemia. As an example of the applicability of the technique, erythrocytes and serum from a patient with an autoimmune hemolytic anemia suspected to be due to poliovirus III were tested with poliovirus III and complement. Incubation of the patient's cells with complement, poliovirus and autologous serum was required for optimal in vitro fragility. The method is proposed as a practical and convenient in vitro technique for evaluating the participation of individual components in the pathogenesis of autoimmune hemolytic anemias.


Parallel tubular structures in lymphocytes. I. Occurrence in patients with Hodgkin's Disease. Investigations with the electron microscope on peripheral blood of patients with Hodgkin's disease revealed parallel tubular structures in the cytoplasm of the lymphocytes, similar to those described in the literature. In normal subjects 2-9% of the lymphocytes were found to contain these structures. The number of such lymphocytes is increased in most patients as compared to normals. A correlation between an increase of inclusions containing lymphocytes and the histological or clinical classifications could not be established. An elevation of lymphocytes with tubular structures could be found in both favourable and unfavourable histological and clinical subgroups of Hodgkin patients, but especially in all groups with an unfavourable prognosis. The origin and function of the parallel tubular structures is still unknown, but their increase in lymphocytes of patients with Hodgkin's disease is of some interest in view of the involvement of these cells.


Correlation between incorporation of myo-(2-3H)inositol into the phosphatidylinositol of lymphocytes and disability degree, stage and duration of multiple sclerosis. The present study revealed a positive correlation between the degree of disability of MS patients and the rate of incorporation of myo-(2-3-H)inositol into phosphatidylinositol of lymphocytes stimulated with basic protein (BP) and phytohemagglutinin (PHA). No correlation could be found between the response of lymphocytes to measles antigen (MA) and the degree of disability, stage and duration of multiple sclerosis. No correlation could be observed between the response of lymphocytes to the stimulants studied and the duration of the disease.


Experimental parainfluenza type 1 virus-induced encephalomyelopathy in adult mouse: a histopathological study. The pathogenicity of a strain of parainfluenza type 1 virus, isolated from the cultured brain cells from multiple sclerosis patients and designated as 6/94 virus, was studied in mouse brain. Selective degeneration of cerebral white matter, preceded by mononuclear cell infiltration, and ependymitis were prominent pathological features of the mouse intracerebrally inoculated with 6/94 virus. After inactivation by ultraviolet light the virus was still capable of producing the inflammatory and degenerative white matter lesions, although the severity of ependymitis was substantially reduced.


Nuclear characteristics of malignant lymphoma in the brain. In addition to chromatin and nucleoli, various classes of structures were often seen in nuclei of malignant lymphoma, when compared with other brain tumours. Interchromatin, perichromatin, and atypical dense granules could be ribonucleoprotein in nature on basis of their behaviours in enzymatic extraction and EDTA stain. The perichromatin fibrils became visible at the border of the condensed chromatin only after EDTA stain and might contain substrate for HnRNA. Nuclear bodies and intranuclear fibrillar rodlets also were evident.


Paradoxical sleep characteristics and cultural environment. Preliminary results. The Temiars are a tribe of negroid pygmies of basically Proto-Malaysian affinities. Field-work in the Malaysian jungle provided some observations on the sleep-wakefulness cycle of two young Temiar adults. This cycle was monophasic circumstances permitting. Their rest-activity cycle at night was similar in the jungle and in the laboratory. Polygraphic total night-sleep recordings were made with both of them in the EEG laboratory in the Hospital Besar in Kuala Lumpur. The eye-movement frequencies of PS were compared with those from young adults of the West. Although the differences were not statistically significant, the Rem-densities of the Temiars were constantly at the low side. The significance of the results are being discussed.


Morphological classification of malignant lymphomas: ultrastructural, cytochemical and immunological results. Except for tumors clearly producing immunoglobulin (e.g. plasma-cytoma), the different classes of malignant lymphomas do not correlate with a constant surface immunoglobulin pattern. Beside a prevailing IgM-surface type in a high number of different lymphoma classes even T-like or O-cells occur in most tumor types provided they are studied in a sufficient number. The possibility of dedifferentiation of immunologic cell qualities has to be envisaged. In this context intracellular lambda-chain crystals occurring in chronic lymphocytic leukaemia may provide a morphological hallmark of anaplastic deterioration of immunoglobulin synthesis. - The ambiguous significance of PAS-positive inclusions and virus-like microtubular complexes in lymphoma cells is discussed. - In conclusion the recent discovery of hairy cell leukaemia provides a good example of the value of nomenclatures based on empiricism rather than on short-lived theories.


Origin of brain macrophages and the nature of the so-called microglia. Two aspects of the so-called microglia were studied by silver impregnation and 3H-TdR ARG in light and electron microscopy. (1) So-called microglioblasts are glioblasts differentiated from matrix cells. They are progenitors of the so-called resting microglia as well as of astrocytes and oligodendroglia. (2) Brain macrophages in stab wounds, experimental Japanese encephalitis and retrograde degeneration of the facial nucleus are all found to be of hematogenous origin. Infiltrating hematogenous cells cannot stay permanently in the brain parenchyma unless pathological alterations persist indefinitely.


Primary lymphoreticuloses of the nervous system in animals. Lymphoreticular proliferative disorders occur in most species of animals including submammalian vertebrates but only occasionally affect the nervous system. Primary lymphoreticular disorders of the nervous system have been recognized in chickens as a herpesvirus-induced avian neurolymphomatosis and in mammals, patricularly in the dog, as reticulum cell sarcomas originating from perivascular mesenchymal precursor cells. Criteria have been discussed to distinguish neoplastic from inflammatory lymphoreticuloses but borderline cases exist where a clear distinction is not always possible.


Hereditary ornithine transcarbamylase deficiency. Report of two male cases with residual enzymatic activity. The authors report two male cases of liver ornithine carbamyl transferase deficiency. In one the disease occurred at 8 years of age with hyperammoniemic coma leading to death in 48 hours. In the second case, symptoms appeared on the sixth day of life but the outcome was favorable. The child is normal at 15 months. In both cases, there was a residual 6-10% OCT activity. These observations are similar to two other male cases in the literature and are different from the male neonatal fatal form in which the deficiency is virtually total. They underline the genetically heterogeneous nature of OCT deficiencies and the fact that in this X-transmitted trait, hemizygotes can preserve a functional enzymatic activity compatible with life.


Sympus monopus accompanied by nephroblastoma--A case report. An autopsy case of sirenomelia accompanied by nephroblastoma has been reported.  In this case, there were many complicating anomalies such as left renal agenesis, absence of external genital organs, imperforate anus, mass of redundant skin over sacral region, two umbilical vessels, absence of great omentum and patent ductus arteriosus.  We considered this malformation as sympus monopus.


Effect of beta-propiolactone on infectivity and haemagglutinin of the BK virus. The effect of beta-propiolactone (BPL) on the infectivity and haemagglutinating properties of BK virus was studied. No virus multiplication was observed when Vero cell cultures were inoculated with virus treated with 0.1 per cent or higher concentration of BPL. On the other hand, treatment of BK virus with 0.1 per cent or lower concentration of BPL had no apparent effect on viral haemagglutinin. BPL at a concentration of 0.1 per cent could therefore be used to prepare BK virus haemagglutinin which contains little or no infectious virus. Inactivated haemagglutinin seems to be somewhat labile against freezing and thawing, but storage at 4 degrees C had no effect on it. Identical haemagglutination inhibiting antibody titres were obtained when human sera were tested with standard haemagglutinin or with haemagglutinin inactivated with BPL.