ACTH and the stress-induced changes of lysine incorporation into brain and liver proteins. When mice were subjected to footshock treatment and subsequently injected with [3H] lysine, the cerebral uptake of [3H] lysine, its incorporation into brain protein and the relative radioactivity (RR = protein radioactivity divided by amino acid radioactivity) were all increased. In the liver, footshocked mice showed decreased free lysine radioactivity, and increased protein radioactivity and relative radioactivity compared to quiet mice. The possibility that ACTH mediated these effects was investigated. The injection of saline had no effect in the brain but partially mimicked the footshock responses in the liver. Injections of ACTH 1--24 mimicked the effects of footshock in the brain, and further augmented the saline-induced effect on the RR in the liver. ACTH 4--10 increased the RR of brain protein, but produced no significant change in brain free lysine radioactivity or in any measure in the liver. Pretreatment of mice with the synthetic glucocorticoid, dexamethasone, did not enhance these effects and diminished the effect of ACTH 4--10 in the brain. ACTH treatment did not alter the profiles of brain polyribosomes. Lysine vasopressin, which is also released during stress, did not alter the incorporation of [3H] lysine into brain or liver protein, except at high doses when it decreased plasma radioactivity. These results suggest that secretion of ACTH at least partially mediates the stress-induced changes of [3H] lysine incorporation into brain and liver proteins, but that it is probably not the only factor involved.


Alterations of spontaneous neuronal activity in the caudate-putamen, nucleus accumbens and amygdaloid complex of rats produced by D-amphetamine. Changes in spontaneous neuronal activity in the caudate-putamen, accumbens nucleus and amygdaloid complex of immunobilized, locally anesthetized rats were recorded following intraperitoneal injection of 2.5 mg/kg d-amphetamine sulfate. In each site, d-amphetamine typically produced a prolonged depression of firing rate which, in most cases, occurred after an inital, brief potentiation of activity. However, the onset of the amphetamine-induced depression occurred signficantly later in the amygdala. Subsequent IP administration of either 5.0 mg/kg chlorpromazine or 2.0 mg/kg haloperidol reversed, to varying degrees, the amphetamine-induced depression of neuronal activity in each area. These results are discussed in terms of the known biochemical effects of amphetamine on catecholaminergic transmission and the alleged role of the nigro-neostriatal mesolimbic dopamine systems in the amphetamine behavioral response.


A method for simultaneous recording of eight behavioral parameters related to monoamine neurotransmission. In response to the increasing demand for refined techniques to record drug induced changes in motor activity we have designed and evaluated against observations an automatic test box that quantifies eight defined components of behaviour in rats. Activity, corresponding to the recordings from the commonly used photocell activity boxes. Total, and forward locomotion, expressing the actual distance the rat walks. Corner count, and corner time, reflecting the position of the animal in the box. Hole count, and hole time, expressing the reaction of the rat to an environmental stimulus i.e. holes in the bottom of the test box. Gnawing, which is a direct counting of the number of gnaws made by the animal. The recording parameters relate to our interest in behaviour influenced by monoamine neurotransmission and the result shows that the selected parameters are recorded with high reliability.


Atonia after carbachol microinjections near the locus coeruleus in cats. The effect of microinjections of carbachol into the dorsolateral pontine tegmentum on the behaviour of cats is investigated. Injections of small amounts (50 and 500ng) of carbachol into the pontine reticular formation induced muscular atonia in otherwise awake animals. The atonia is not due to cholinergic stimulation of the noradrenergic cells of the locus coeruleus or the dorsolateral pons, since the most effective sites were situated ventrally to the locus coeruleus and alpha- and beta-adrenergic blocking agents did not affect the antonia. The results are discussed in view of the postulated role of the locus coeruleus in paradoxical sleep.


Parallel changes in behaviour and hippocampal monoamine metabolism in rats after administration of ACTH-analogues. Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response.


Effect of stress on norepinephrine-stimulated cyclic AMP formation in brain slices. Experiments were conducted to determine if stressful procedures, which increase brain norepinephrine (NE) release in rats, lower the responsiveness of central noradrenergic receptors as measured by the catecholamine (CA)-induced cAMP accumulation in hypothalamic and cerebral cortical slices. No conclusive evidence of subsensitivity was found after either acute or chronic electric footshock or continuous restraint. Failure to find a significant reduction after stress may have resulted from several methodological problems. These include (a) the inhibition of phosphodiesterase activity with isobutylmethylxanthine, which may have obscured possible adaptive changes in cAMP degradation and/or adenosine-dependent adrenergic receptors; (b) a low initial responsiveness to NE in these animals as suggested by the greater case in inducing supersensitivity with reserpine than subsensitivity with amphetamine; and (c) the use as a test agent of exogenous NE which may stimulate a far broader population of receptive sites in brain slices than are activated during stress by the local release of endogenous NE.


L-tryptophan inhibition of epinephrine-stimulated phosphorylase activity in vivo and in vitro. The administration of L-tryptophan prevented the normal rise in blood sugar concentration that usually follows the injection of epinephrine into rats. Of the several possible mechanisms by which tryptophan could inhibit epinephrine-induced hyperglycemia, one might be that tryptophan prevented the activation of the enzyme, phosphorylase, which is an indirect result of epinephrine action on the liver. This report presents evidence supporting this hypothesis: (1) The injection of tryptophan (2.5 mM/kg) prevented epinephrine-induced glycogenolysis in the liver of rats by 100%. (2) The time courses of epinephrine-induced hyperglycemia and activation of phosphorylase in liver were nearly identical. (3) The injection of tryptophan completely inhibited (100%) the epinephrine-induced phosphorylase activation. (4) The addition of tryptophan in vitro completely inhibited (100%) the epinephrine-induced activation of phosphorylase. (5) Tryptophan inhibition of epinephrine-induced hyperglycemia occurs immediately after tryptophan administration. (6) The addition of cyclic AMP blocked the tryptophan inhibition of epinephrine-induced phosphorylase activation. This evidence suggests that tryptophan may inhibit epinephrine-induced hyperglycemia in rats by preventing the activation of liver phosphorylase.


Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,2,4-trisubstituted-5-imidazolones. Nine 1-(3,4-dimethoxyphenylethyl)-2-methyl-4-(substituted benzylidene)-5-imidazolones were synthesized, characterized by their sharp melting points, elemental analyses and infrared spectra and evaluated for anticonvulsant activity. All 1,2,4-trisubstituted-5-imidazolones at a dose of 100 mg/kg i.p. possessed anticonvulsant activity and the degree of protection observed against pentylenetetrazol-induced convulsions in mice ranged from 20 to 60%. These 1,2,4-trisubstituted-5-imidazolones selectively inhibited in vitro oxidation of the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate and NADH by rat brain homogenates while the NAD-independent oxidation of succinate remained unaltered. The anti-convulsant activity possessed by 1,2,4-trisubstituted-5-imidazolones was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates.


The psychotropic properties of estrogens. In this review article clinical literature and experimental work from biochemistry, electro-encephalography and experimental psychology will be reported. Like the androgens and progestogens reviewed earlier, estrogens have psychotropic properties comparable to those of well-known psychotropic compounds. These are: improvement of psychological test results and increase in extraversion and decrease in neuroticism according to the Eysenck Personality Model (1964). Such effects are usually associated with the psychostimulants. The immediate effect on EEG of 4 mg estradiol valerate (single oral dose, male subjects), is a standard EEG profile similar to that of the tricyclic antidepressants. High dosages of estrogens have antidepressant properties clinically. In terms of psycho-pharmacological profiles, the estrogens seem to be a new type of psychotropic compound.


Physostigmine alters onset but not duration of REM sleep in man. Physostigmine (1.0mg) or placebo were administered intravenously over 1-h period to seven male normal volunteers beginning 35 min after sleep onset. The results indicate that physostigmine induced the onset of REM sleep but did not significantly alter the duration of individual REM sleep periods. Physostigmine significantly shortened the REM latency and the duration of the second nonREM period. After inducing the onset of the first REM period(s); physostigmine also appeared to advance succeeding REM-nonREM sleep cycles relative to sleep onset even when the duration of each cycle was unaffected.


An antiserum against 9-deoxy-6,9-epoxy-PGF1alpha recognizes and binds PGI2 (prostacyclin). Antibodies were prepared against 9-deoxy-6,9-epoxy-PGF1alpha, the 5,6-dihydro analog of prostacyclin (PGI2). By using as the hapten, this structurally similar, stable analog, an antibody population was developed which recognized PGI2 and reversed its influence on platelet aggregation. The antibodies also opposed the normal effect of PGI2 on the cAMP and thromboxane B2 levels during aggregation. By anticipating the cross reaction between the analog and PGI2 and by considering it beneficial, the problem of raising antibodies against an unstable compound has been circumvented.


A rapid, simple determination of plasma cyclic AMP. Plasma cyclic AMP content was determined without being extracted, using binding protein obtained from rat liver. EDTA was suitable as an anticoagulant for cyclic AMP estimation. Cyclic AMP further added to EDTA plasma was able to be estimated. The estimated values by plasma dilution were almost the same as the expected values. It was thought that the direct assay was useful for determination of plasma cyclic AMP. Isoproterenol (50 microgram/kg, iv) produced an increase of plasma cyclic AMP level accompanied with a decrease of blood pressure and an increase of heart rate in anesthetized dogs. Cyclic AMP level of peripheral venous plasma was 18.6 +/- 1.32 p mole/ml in human (N=25), 21.6 +/- 3.04 P mole/ml in dogs (N=7) and 50.6 +/- 4.59 p mole/ml in rabbit (N=9). Plasma cyclic AMP level of rabbit was higher than those of human and dog.


[Immunological and structural properties of Rous sarcoma virus-transformed and tumor cells]. We compared the capacity of both normal and Rous sarcoma virus (RSV)-transformed chicken embryo fibroblast (CEF) cells as well as Rous sarcoma (RS) tumor cells to serve as targets in anti-tumor immunity assays. These studies showed that sera from tumor-bearing donors were able to stain transformed CEF more efficiently than RS cells as detected by immunofluorescence. In contrast, antiserum against the major viral glycoprotein, gp 85, stained a higher percentage of RS than transformed cells. Normal CEF cells, which served as controls, were essentially non-reactive with the immune system as judged by this type of assay. We observed that RS cells are considerably larger and contain far higher levels of protein than either normal or transformed CEF. Scanning electron microscopy revealed both the RS cells and transformed CEF to be rich in surface ruffles, blebs and microvilli as distinguished from the flattened, fusiform appearance of normal CEF cells.


The mecanism of cementing line formation in the bones of cestrum-fed chicks. Chicks fed a rachitogenic diet for five weeks after hatching were then treated with a daily oral dose of 1,000 I.U. Vitamin D3 or a 1% addition to the feed of powdered leaves of Cestrum diurnum for periods of 1, 2, 4, 8, 16 and 30 days. Comparative studies were made on stained sections, microradiographs of undermineralized sections and alpharadiographs of demineralized sections. The present dose of Cestrum diurnum caused at first, a rapid maturation and mineralization of the epiphyseal cartilage and an intense growth and osteocytic osteolysis in the diaphysis of the tibia and femur. After 8 days however, growth decreased and the diaphysis gradually became petrotic. Under these conditions, the osteocytes degenerated and died. The areas of polysaccharide-rich, low density matrix which surrounded them, decreased gradually to become cementing lines, persistent after 30 days.


Barbiturate dependence in mice: evidence for beta-adrenergic receptor proliferation in brain. C57BL/6J and DBA/2J inbred mice were assayed for beta-adrenergic receptor density following seven days of chronic phenobarbital intoxication. These physically dependent mice showed a greater brain receptor density than did the control, while acute intoxication to phenobarbital produced no significant effects. C57BL/6J mice showed a higher average receptor density than did the DBA/2J mice under all conditions. These findings support the hypothesis that chronic barbiturate intoxication leads to a receptor supersensitivity which may play a role in the phenomena of functional tolerance and physical dependence.


The effect of dobutamine on rat cardiac cyclic AMP, phosphorylase a and force of contraction. Dobutamine produced a dose-dependent increase in cardiac cyclic AMP, % phosphorylase a and contractile force in the isolated perfused rat heart. Cyclic AMP increased prior to the increase in % phosphorylase a and prior to or concomitant with the increase in force. Similar results were obtained with isoproterenol except that the effects of isoproterenol occurred slightly earlier. The efficacy of both amines was approximately the same but dobutamine was was about 1/45 as potent as isoproterenol.


Some characteristics of a natural infection by parainfluenza-3 virus in a group of calves. Parainfluenza-3 (Pi3) virus infection in a group of 25 calves is described. The virus was isolated from the lungs of four calve at days 6, 7, 13 and 55 after they were housed together at birth. Intracytoplasmic inclusion bodies were seen by light microscopy in bronchial and bronchiolar epithelial cells of two of these calves. Virus infected cells were detected by electron microscopy in three of the four calves. Haemagglutination inhibition antibodies to Pi3 virus were found in the sera of the calves. Despite the virus being present in the group from one week, a significant increase in antibody titre was found in only two animals although all the calves were in contact with each other during the study period. The pulmonary lesions in the four infected calves consisted of a bronchitis and bronchiolitis with infiltration of the walls and lumena of these structures by neutrophils and an adjacent neutrophil infiltration of alveoli some of which were collapsed.


[ECG signs of pulmonary embolism caused by lymphography injected contrast oil (author's transl)]. Authors have reported ECG signs of pulmonary embolism caused by lymphography injected contrast oil. Signs indicative of transitory right ventricular strain were observed in the ECG in 17 of 30 clinically symptom-free patients.


The clinical importance of anaerobic bacteria in wound infections after gastrointestinal surgery. Wound cultures from 54 patients with infections after gastrointestinal surgery were examined. Cultures from wounds after surgery on the upper gastrointestinal tract grew few organisms, mainly aerobic gram-positive cocci. Culture from wounds on the lower gastrointestinal tract grew strains of bacteria, aerobic and anaerobic gram-negative rods dominating. Indirect immunofluorescence studies on acute and convalescent phase sera showed significant immune response against Bacteroides fragilis in a majority of cases. Immune response against anaerobic cocci was seldom found. Very high antibody titres against Clostridium perfringens were often found, both in patients' and control sera.


Deviation of plasmatic aldosterone and significance of the stimulating (ACTH-cortrosyn) and inhibitory (propranolol) effects in hypertension and cardiovascular pathology. Starting from the interference between the renin-angiotensin-aldosterone (RAA) system and cardiovascular pathology in arterial hypertension (AH) we have made a correlative study of the cardiovascular system and plasmatic aldosterone in normal and hypertensive subjects under conditions of stimulation (ACTH) and inhibition (propranolol). After administration of ACTH (one of the physiologic mediators of stress) increased values for plasmatic aldosterone were found. Negative cardiovascular effect: arrhthmia, angor, AH, cardiac asthma, under the condition of preexisting cardiovascular pathology or altered steroidogensis, were also noticed. Inhibition with propranolol does not have conclusive effects in AH with normal aldosterone. The best effect were noticed in that hypertension which implies the RAA pressor system in its pathogeny, irrespective of etiology, the reduction AT occurring in parallel with decline in plasmatic aldosterone values and total peripheral resistance (RPT). Administration of propranolol in AH with activated RAA system irrespective of etiology represents a pathogenic treatment able to prevent efficiently the major complications of AH.


Pharmacokinetic and therapeutic studies of pivmecillinam in patients with normal and impaired renal function. Pivmecillinam which is the oral form of mecillinam was evaluated by treatment of 26 patients presenting various types of urinary tract infections and by prophylactic treatment of 12 patients. Pivmecillinam given in a daily dosage of 1.2 g for periods of 1 to 56 weeks was well tolerated in all of the patients including those with impaired renal function without any dose reduction. The original bacterial strain in the urine was eradicated in 100% of the cases. Two patients had a superinfection and 4 had a recurrence during a 3-month follow-up period. The oral absorption of pivmecillinam was investigated in 15 patients with normal or slightly reduced renal function and in 5 patients on maintenance hemodialysis. High serum levels were achieved within 1 to 2 h after administration. Patients with reduced renal function showed retarded elimination rates, suggesting that the dose should be adjusted in this category of patients.


Serum electrophoretic lipoprotein factors and pseudocholinesterase activity in thyroid disease. Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency.


Septicemia and meningitis caused by Fusobacterium aquatile. A case of septicemia and meningitis caused by Fusobacterium aquatile is described. The insidious onset of the megningitis and occurrence of multiple cranial nerve affections were outstanding features. In spite of adequate antibiotic treatment the course was protracted, and the outcome was permanent damage to 3 of the affected cranial nerves.


The changed epidemiology of hepatitis A infection in Scandinavia. The prevalence of antibodies against hepatitis A virus (anti-HAV) was studied in a Swedish city population. A great difference was observed in different age groups. Anti-HAV was not found in the serum of young individuals while the prevalence was high in older ages (87% in individuals 60 years or older). This pattern of hepatitis A exposure is quite different from that reported for instance from the Mediterranean area and may indicate a very low frequency of hepatitis A exposure in Scandinavia today. The high prevalence of anti-HAV in older Swedes possibly reflects hepatitis A exposure in childhood during World War I and II when hepatitis A was more common.


Effect of (+)catechin on connective tissue. The effect of (+)catechin on connective tissue was studied in organ cultures of chick embryo tibiae and after in vivo injection in rats and mice. Collagen biosynthesis and hydroxylation of 14C-Pro-labelled protocollagen in vitro by protocollagen proline hydroxylase (PPH) were inhibited. In vivo, a slight decrease in the biosynthesis of collagen and in the PPH activity in skin of rats and mice was noticed as an effect of (+)catechin. No effect of the drug was observed on the incorporation of 14C-D-glucosamine by chick embryo tibiae. Increased urinary excretion of acid mucopolysaccharide metabolites by the mice injected with (+)catechin was observed.


[Primary stenosing cholangitis].

[Primary stenosing cholangitis]. Five cases of sclerosing cholangitis are recorded from 3697 biliary operations. Two patients had a cancerous course and 1 associated ulcerative colitis. The first two cases could be classified as primary sclerosing cholangitis. They are described. The pathogenetic mechanisms and treatment of this affection are discussed.


[Surgical treatment of syndactylia].

[Surgical treatment of syndactylia]. In a review of over 100 surgical procedures on the hand in the pediatric age group during the past 4 years, experience in the treatment of syndactyly of the hand is discussed. Due to their structural differences, exogenous acrosyndactylies are to be distinguished from the genetically determined cutaneous and osseous syndactyly. Early separation of thumb, index and fifth finger ensures grip function and improves psychointellectual development. Scar syndactyly is avoidable given an appropriate technique for formation of the interdigital commissure and if triangular flaps for long digits are used.


[Progress in clinical oncology 1978].

[Progress in clinical oncology 1978]. A short survey of recent progress in the diagnosis and pharmacotherapy of neoplastic diseases is conducted, with special mention of measurement of hormone receptors, needle biopsy, tactics and strategy of drug therapy, and new drugs. The importance of several forms of cooperation is stressed: cooperation between doctor and patient, between hospital physician and town physician, interdisciplinary cooperation, and cooperative clinical studies. Adjuvant chemotherapy and immunotherapy are new methods under study. The problems arising in the wake of progress in medical oncology and the ever increasing use of chemotherapy are loss of individual initiative in physicians working with protocols, and prohibitive costs are diagnostic and therapeutic procedures become more sophisticated.


Aminophylline increases cerebral metabolic rate and decreases anoxic survival in young mice. In weanling mice treated with pharmacologic doses of aminophylline, the concentrations of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in the brain increased 44 and 36 percent, respectively, and the cerebral metabolic rate was three times that in controls. In neonatal mice, therapeutic doses of aminophylline greatly decreased the rate of anoxic survival in vivo and the duration of gasping of the isolated head. The findings suggest caution in the use of this drug and other methylxanthines in hypoxic human newborns.


[Primary hyperaldosteronism with paroxysmal arterial hypertension. Apropos of 2 operated cases]. Primary hyperaldosteronism usually causes moderate hypertension. It is rare to note as in our two patients intermittent attacks of paroxysmal hypertension. The diagnosis of aldosteronism will be suspected on the finding of persistent hypokalemia with acidosis. It will be confirmed by laboratory examinations severe fall in plasma renin activity and rise in aldosterone in the adrenal veins. To determine the affected side, one may carry out adrenal phlebography which is a difficult technic, and/or a scan using iodine cholesterol which is benign and precise. Surgery with removal of the adenomatous hyperplasia in one case and of an adenoma in the other, gave one very good result.


[Urogenital infections and mycoplasms].

[Urogenital infections and mycoplasms]. The role of genital mycoplasmas, e.g. M. hominis and U. urealyticum in urogenital infections is controversial. 120 samples were taken in 95 men and 25 women with urogenital infections and examined in the laboratory. Mycoplasmas were found in about 32% of men and 52% of women. M. Hominis is often associated with gonococcal infection and seems to play only a secondary role. The frequent isolation of U. urealyticum in various types of urethritis (gonococcal and non-gonococcal) is roughly the same. In the absence of a control investigation in healthy subjects, it is not possible to say whether it plays any role in urethritis.


[Observations apropos 500 case reports of upper gastrointestinal hemorrhages]. In this study of 500 cases of bleeding from the upper digestive tract, the importance of emergency fibre endoscopy is emphasised. It is in fact the only way to demonstrate acute gastro-duodenal lesions which are very frequent, especially during post-operative intensive care. As far as treatment is concerned, the interest of gastric lavage with ice-cold drinks is emphasised in hemostasis. As far as surgery is concerned, the indications are now well known depending on the rate of transfusion during the first few hours and the etiology. In chronic duodenal ulcers, vagotomy, pyloroplasty and suture of the ulcer have always given good results. This is also the case with acute ulcers. On the other hand, in gastric ulcers, gastrectomy remains the treatment of choice. When bleeding is due to oesophageal varices, surgery is only indicated in exceptional cases.


Ectopic adrenocorticotrophic hormone syndrome. A case report. Excessive production of adrenocorticotrophic hormone (ACTH) by oat cell carcinomas and carcinoid tumours of the lung has been well documented. Florid cases of Cushing's syndrome secondary to the excessive production of ACTH by the tumour are rare. In this article 2 cases of florid Cushing's syndrome associated with oat cell carcinoma are described.


Erythrocytosis in hepatocellular cancer. A Black patient with hepatocellular cancer and an increased red cell mass (erythrocytosis) is described. Assay of the patient's serum in ex-hypoxic polycythaemic mice showed the presence of erythropoietic activity. To determine the incidence of erythrocytosis in Southern African Blacks with hepatocellular cancer, haemoglobin and haematocrit values in 117 such patients were reviewed. Four patients (3,4%) had haemoglobin levels above the upper limit of normal and 2 (1,7%) of the patients had raised haematocrit values. Fifty-eight per cent of the patients were anaemic when they were first seen.


The subcellular distribution of [3H]-colchicine-binding activity and tubulin in pig blood platelets. The subcellular distribution of the [3H]-colchicine-binding protein, believed to be tubulin, the subunit protein of microtubules, has been investigated in mammalian blood platelets. Studies on a soluble extract from pig platelets and two particulate fractions (viz. membrane-rich and granule-rich fractions) have shown that about 98% of the colchicine-binding activity in a platelet homogenate is located in the soluble phase. This result is in agreement with polyacrylamide gel electrophoresis experiments which show that the soluble fraction contains a substantial amount of 55,000 MW tubulin, whereas the membrane and granule-rich fractions contain very little of this component. The [3H]-colchicine-binding activity of the platelet soluble phase is largely precipitated by 40-50% ammonium sulphate and also by vinblastine sulphate in millimolar concentrations. Moreover the colchicine-binding protein in the platelet soluble fraction has a sedimentation coefficient of 5.9 S, is eluted in the void volume of a Sephadex G-100 column, and binds to DEAE-Sephadex at low ionic strength and is eluted from this ion-exchanger at an ionic strength of 0.47 M-KCl. In addition, most of the colchicine-binding activity of the platelet soluble phase is associated with protein which will undergo temperature-dependent polymerization in vitro and which has a molecular weight on SDS-polyacrylamide gels of 55,000. All these experimental findings suggest that the colchicine-binding activity of pig platelet homogenates is due to the presence of the microtubule protein, tubulin, which is largely found in the soluble compartment of the cells.


Effect on platelet functions of derivatives of cyclic nucleotides. Derivatives of cyclic nucleotides were evaluated for their ability to inhibit platelet aggregation and the release reaction. Derivatives substituted in position 8 (mainly 8-Br-cyclic GMP) were more active than 3'-5' cyclic AMP, and their relative potency in inhibiting platelet aggregation and 14C-serotonin release was comparable to that of N62-0'-dibutyryl-cyclic AMP. Compounds substituted in position 6 or 2'-0 were not effective. The active compounds, which were also tested for their ability to stimulate platelet adenylate cyclase or to inhibit cyclic AMP phosphodiesterase, did not modify the intracellular levels of cyclic AMP. Since previous animal experiments have shown that these derivatives cause less side effects than cyclic AMP and its dibutyryl derivative in animals, it is suggested that modification of the cyclophosphate molecule might make it possible to find compounds active only on platelet function without interfering with other biological systems.


Studies on bovine leucosis V. A comparative study on the practical value of the agar gel immunodiffusion test, the indirect fluorescent antibody technique and the micro complement fixation test for the detection of antibodies to bovine leucosis virus. The practical value of the indirect fluorescent antibody technique (I FAT), the micro complement fixation test (M CFT) and the agar gel immunodiffusion test (AGIDT) for the detection of antibodies to bovine leucosis virus (BLV) was investigated. For this purpose 1495 serum samples were examined. There was a remarkably good agreement between the three tests in the demonstration of antibodies to BLV especially if sera with a sufficient high concentration of antibodies ("late serum") were under investigation. These positive sera were derived only from farms which exploited one or more imported animals. A disagreement of results of the three tests was observed in 38 (2.5%) cases. This was due to: (1) difficulties in reading of the test; (2) presumably by the demonstration of different classes of antibody and (3) the fact that in the AGIDT sera could be used undiluted. This discrepancy was especially evident with sera with a low concentration of antibodies ("early or incubation sera"). A drawback for the M CFT is the anticomplementary activity found in 17% of the bovine serum samples.


[Study of the biochemical and radiochemical effects of the agent MTDQ (author's transl]. The antioxidant MTDQ exhibits a radiosensitizing effect and was used in pretreatment of radiation-resistant human tumors, e.g. synoviomas, sarcomas, von Recklinghausen disease. After this premedication and fractionated radiation therapy of different kinds a permanent regression of the tumors was observed. The radiosensitizing compound is non-toxic and selectively accumulates in tumorous tissues. The chemical structure (three functional groups) and in vitro tests make probable that the main factors in the mechanism of action are peroxide decomposition, hydrol formation, polymerization and, in the course of those reactions, the in situ release of oxygen.


Chromatographic separation of vitamin D3 sulfate and vitamin D3. This paper describes a simple chromatographic technique on Sephadex LH20 for the separation of vitamin D3 sulfate from free vitamin D3 and its metabolites. This technique has been used in the study of vitamin D3 sulfate metabolism in rats. Seven hours after injection of vitamin D3 sulfate (35S or 35S and 3H) only the peak of vitamin D sulfoconjugate was found in chromatographic elution of serum extracts.


[Etiology of chronic recurring aphthous stomatitis]. 46 patients with chronic recurrent aphthae of the oral mucosa were subjected to clinical, virological and serologic examinations to evidence the assumed virus aetiology of this clinical picture. A cytopathogenic organism (classified as herpes virus hominis) could be cultivated from the aphtha sample from only one patient.


The control of endemic goitre by iodized oil in a community health programme. A programme of iodized oil injections was carried out in an area of high goitre prevalence (28.5%) in rural Zaire. The iodized oil programme was undertaken as a part of a broader, pre-existing community health programme. No complications were encountered.


Isoproterenol and propranolol: ability to cross the blood-brain barrier and effects on cerebral circulation in man. Using the "double indicator" technique the ability of 3H-isoproterenol and 14C-propranolol to cross the blood-brain barrier was studied in man. In 3 subjects extraction of isoproterenol was 3.8% in a single passage and the PS product was 2.0 ml/100g/min. In 4 patients extraction of propranolol was 63% and PS was 46.7 ml/100/min. Regional cerebral blood flow (rCBF) was studied in man with the 133Xe-intraarterial injection method. Intracarotid isoproterenol (3 migrogram/min., 6 patients) caused a significant reduction in rCBF, but after correction for a concomitant decrease in arterial PCO2 the alteration was no longer significant (59.8 -51.7/57.4 ml/100g/min.). Intracarotid propranolol (0.15 mg/kg, 11 patients) caused no significant change in rCBF, but after correction for arterial PCO2 change the lateration although on 4% was just significant, p less than 0.05. (56.3 -55.8/54.1 ml/100g/min). After propranolol the rCBF changes caused by alterations in the arterial PCO2 were normal and the focal flow increase during hand work could not be changed by simultaneous intracarotid propranolol.


Alterations of cyclic AMP in cerebral ischemia. Cyclic AMP levels were measured in brains of 21 cats after occlusion of a middle cerebral artery by a transorbital approach. Brain samples for determination of cAMP by a protein binding radioassay were obtained from the ischemic and contralateral temporal lobes before sacrifice, 1, 3, and 24 hours after occlusion of the right middle cerebral artery. At 1 hour, no difference between the 2 sides was observed; a mean of 17.4 pmoles/mg protein was observed from the side of the occlusion and 18.9 pmoles/mg protein from the contralateral side. At 3 hours, a mean value of 8.9 pmoles/mg protein on the ischemic side and a level of 21.7 pmoles/mg protein on the contralateral side were observed. At 24 hours, the cAMP level on the ischemic side remained below the nonischemic side; the values obtained were 13.7 pmoles/mg protein compared to 27.9 pmoles/mg protein compared to 27.9 pmoles/mg protein. These changes in cAMP as early as 3 hours after the onset of ischemia, when such a lesion is reversible, may indicate that in initial step in the alteration of cellular metabolism following ischemia is due to membrane perturbation and altered production of this second messenger.


Machakos project studies. Agents affecting health of mother and child in a rural area of Kenya. V. Pertussis sentypes in Kenyan children 1974--1975. Cultures of Bordetella pertussis were isolated by pernasal swabs from Kenyan children in whom whooping-cough was suspected. Serotyping of 94 of these isolates was undertaken by four laboratories in Europe, and there was very close agreement in their typing results. Each laboratory found that the incidence of type 1, 3 was the lowest of the three types, and that there were approximately equal numbers of types 1, 2, 3 and 1, 2. No new serotype was found. This distribution of serotypes was found in all age-groups; and it is in marked contrast with that currently seen in vaccinated communities, where type 1, 3 predominates. The implications of these findings for vaccination against whooping-cough in East Africa are discussed.


Serum albumin and total globulin levels in common liver diseases in Accra (Ghana). Serum albumin and total globulin were determined in 22 healthy people, 29 patients with acute viral hepatitis, 27 patients with cirrhosis and 27 patients with primary hepatocellular carcinoma to see if they might be of discriminating value. The mean serum albumin values were found to be highest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. The mean serum total globulin values on the other hand, were found to be lowest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. Both the mean albumin and mean total globulin of each group of subjects were significantly different from the respective means of the other three groups. A probable explanation for the higher serum albumin and lower globulin levels found in primary hepatocellular carcinoma, as compared to cirrhosis, is that hepatocellular carcinoma occurs in reasonably well-compensated cases of cirrhosis.


Immunization of mice against Trypanosoma cruzi: the effect of chemical treatment or immune serum on an epimastigote vaccine. Groups of long Evans and CD-1 mice were immunized with vaccines prepared from epimastigotes of Trypanosoma cruzi, strains Y and Tulahuen, modified by various chemical means, or by the addition of immune sera. Freeze-thawed epimastigotes were used as a control antigen. Freeze-thawed epimastigotes, with and without saponin as adjuvant, gave significant protection against challenge with homologous trypomastigotes. Similar levels or protection were obtained in mice vaccinated with living epimastigotes. Treatment of epimastigotes by various chemical means, including sodium perchlorate failed to increase their immunogenicity, but did not reduce it. The addition of immune serum to the antigen may have slightly increased its immunogenicity.


Bioactivity of male (sperm transmitted) mouse mammary tumor virus as influenced by donor, recipient and age at treatment. The sperm collected from mammary tumor virus (MTV)-carrying mice (C3H, BALB/cfC3H, BALB/cfRIII and RIII) was separately tested for mammary tumor-inducing activity in (BALB/c x C3Hf)F1, (BALB/c x RIIIf) F1, and BALB/c female recipients by i.p., injection of 0.1 ml of the sperm at 1-2 weeks or at 3 months of age. A total of 551 recipents was observed, including control mice. The results may be summarized as follow: 1) mammary tumor incidence in experiments with or without histocompatibility between sperm donor and recipient is the same; 2) bioactivity is related to the type of MTV (C3H, RIII) and to the type of recipient, not to the sperm donor; 3) the activity of RIII MTV released in the sperm appears to be less influenced by the age of recipients than is that of C3H MTV; 4) BALB/c recipients are  more susceptible to C3H than to RIII sperm-released MTV; 5) (BALB/c x RIIIf) F1 hybrids are resistant to sperm-released MTV, especially to C3H MTV infection, and show a 34% incidence of late spontneous lymphomas inherited by the RIIf male parent; 6) (BALB/c x C3Hf) F1 hybrids  are susceptible to both C3H and RIII sperm-released MTV and show a 30% incidence of late spontaneous mammary tumors due to genetic transmission of MTV by the C3H male parent.


Analysis of frog neuromuscular function at hyperbaric pressures. Nerve and muscle compound action potentials were measured in the frog sciatic nerve-gastrocnemius muscle preparation in a hyperbaric helium-air environment. Helium pressure to 69 ATA induced a reversible depression in muscle compound action potential amplitude without significantly affecting other parameters. Blockade other parameters. Blockade induced by tetraethylammonium while at pressure could be partially reversed by decompression. A desensitization-type of neuromuscular block produced at pressure after neostigmine infusion could also be partially reversed by decompression. These results suggest a possible involvement of the acetylcholine receptor complex in pressure-induced depression of synaptic transmission.


Hypercalciuria related to cadmium exposure. A work force has been investigated for possible cadmium intoxication. One group who are coppersmiths have an 18.5 per cent prevalence of upper urinary tract stone disease associated with a statistically highly significant hypercalciuria and reduced serum inorganic phosphate. Proof of exposure to cadmium has been confirmed in all workers. The trace element cadmium should be kept in mind when investigating stone formers who exhibit an unexplained hypercalciuria.


Anatomic effect of distention therapy in unstable bladder: new approach. The recent clinical success of distention therapy in the treatment of the unstable bladder is reviewed. Bladder stability and increased capacity as measured by cystometry following distention therapy as well as relief of symptoms have prompted this anatomic study. The neuromuscular pathways of conduction in rat and rabbit bladder wall were examined following short-term (two-hour) and prolonged (six-hour) distention. Treated and control animals were studied at fixed intervals for four months. Prolonged distention did not alter either smooth muscle cell architecture or intercellular junctions. It did produce a transient phase of degeneration among the unmyelinated nerve fibers in the bladder wall consisting of axonal swelling and lysis of organelles. A quantitative estimate of nerve injury was compiled using pooled histograms. These results suggest that bladder stability following distention therapy may be related to nerve degeneration in the bladder wall.


Value of liver scintiscan in staging of testicular neoplasm. A nineteen-year retrospective study of the usefulness of liver scanning in the staging evaluation of germinal cell testicular neoplasms was undertaken at the National Naval Medical Center. Of 94 patients, 90 (96 per cent) demonstrated accurate correlation between liver scan and histopathologic diagnosis.


Adrenal autotransplantation.

Adrenal autotransplantation. New tools for the diagnosis of adrenal diseases and the development of successful techniques to treat patients with bilateral tumors of the kidney have increased the number of procedures involving removal of both adrenals. Offering to these patients an adrenal autograft represents more than a superfluous medical exercise, since a successful outcome of the graft will relieve them of the burdens and risks of long-term postoperative steroid replacement therapy. The aim of this review is to bring to mind the possibility of autografting adrenal glands in some clinical situations and to emphasize some points that could be relevant in obtaining successful results. The available data justify clinical trials with the procedure.


[Laparoscopic diagnosis of glomus tumors]. 3 cases of glomus tumors of the stomach, small bowel and lesser omentum were examined. In one patient the tumor was manifested through intraabdominal hemorrhage, diagnosed during laparoscopy; but the source of the hemorrhage remained unrecognized. The puncture of the tumor, which proved its benign character, was performed in the second case. The biopsy taken at the laparoscopy in the third patient showed angioleiomyosarcoma. All the patients were operated.


[Testing the immunogenicity of the dermal antigen in Marek's disease virus]. An experiment was performed to study the immunogenicity of the dermal antigen of Marek's disease virus, extracted from the skin of 30-day-old chickens, infected with Marek's disease virus on the first day of life. Three kinds of samples were tested: (1) dermal antigen centrifuged at 10 000 g per 0.5 h, (2) dermal antigen centrifugated at 10 000 g per 0.5 h and 100 000 g per 1 h, (3) dermal antigen treated like sample (2) and partly purified by DEAE-cellulose chromatography. Samples (1) and (2) were inoculated to two-day-old chickens and the vaccination was repeated, using complete Freund's adjuvant, 21 days later. Sample (3) was inoculated to two-day-old chickens with DEAE-dextran. All the three groups were challenged together with the controls (non-vaccinated chickens) on the seventh day after the first vaccination. A reduction of mortality was observed in the chickens vaccinated with and re-vaccinated with sample (1) (23.07%) and in the chickens vaccinated with sample (3) (30.76%). The chickens of the latter group were the last to start dying from Marek's disease--only after the 10th week of life. In the chickens which had been vaccinated and revaccinated with sample (2) the mortality was not reduced. The study is continued, with particular emphasis on the relationship of DEAE-dextran to protection against Marek's disease.


Feminizing adrenocortical tumor. Histological and ultrastructural study. A case of a feminizing adrenocortical tumor associated with Cushing's syndrome in a 29 year old male is presented. The ultrastructural features are compared with adrenal tumors secreting aldosterone, glucocorticoids of androgens. As in adrenal carcinomas, this tumor demonstrates nuclear pleomorphism with enlarged nucleoli and nuclear pseudoinclusions. The cytoplasmic organelles show some parallels between feminizing and androgen-secreting adrenal tumors. Different types of mitochondria occur with varying amounts of smooth endoplasmic reticulum. Numerous microbodies are present. Histological and ultrastructural signs indicating probably malignancy are discussed and it is noted that most of the feminizing adrenal tumors are carcinomata. Neither local recurrence nor distant metastases have yet been detected in this case, two years after excision of the tumor.


Spheroidal filamentous inclusion body cells in von Recklinghausen's disease. Cells with spheroidal filamentous cytoplasmic bodies, distinctive by both light and electron microscopy, were found in a neoplasm arising from the sciatic nerve of a patient with von Recklinghausen's disease. Tissue fixed with formalin and embedded in paraffin for three years was deparaffinized, reprocessed, and examined with the electron microscope. The morphology of the spheroidal body cells, the close resemblance to erythrophagocytosis, and the possible significance of the changes are discussed.


B-cell nature malignant lymphoma probably caused by EB-virus infection. In cells in a haemopericardium associated with a B-cell malignant lymphoma, immature herpes type virus particles were found by electron microscopy. Epstein-Barr virus associated nuclear antigen (EBNA) and virus capsid antigen (VCA) were also found, both in the tumor cells, in the bloody pericardial fluid and in cultivated cells. Serological studies revealed high anti-toxoplasma antibody levels both in the pericardial fluid and in serum. Both EB virus and toxoplasma infections are assumed to have played an important role on the pathogenesis of the present case.


Tumour cell interactions in vitro. Evidence for the occurrence of tumour cells within other tumour cells. After addition of dibutyryl cAMP to spinner flask cultures of JB-1-E tumour cells an increase in the number of examples of emperipolesis was observed. Ruthenium red staining of the cells revealed a conspicuous staining of the cell membrane of the outer cell, while that of the inner cell was unstained. The differences in staining properties of the cell membranes of the outer and inner cells involved in emperipolesis and apparently viable inner cells make it evident that coexistence of cells--one within another--is possible.


Investigations on the presence of antibodies to alphaviruses, flaviviruses, Bunyavirus and Kemerovo virus in humans and some domestic animals. The presence of antibodies to some alphaviruses, flaviviruses, bunyaviruses and orbiviruses was studied in the sera from humans and domestic animals of biotopes "C" and "T" in the south-east of Romania. Specific antibodies were found in humans to 3 alphaviruses (eastern equine encephalitis, western equine encephalitis and Sindbis), in a very low proportion, and to 3 flaviviruses (tickborne encephalitis, West Nile and Ntaya), at a much higher percentage. Very low percentages of antibodies to Bunyavirus and Kemerovo virus were also detected. The proportion of antibodies to flaviruses (tick-borne encephalitis, West Nile and Ntaya) detected in domestic animals (sheep, cattle and swine) is much lower than that found in humans of the same biotope ("T").


Isoenzymes of lactate dehydrogenase, acid phosphatase, alkaline phosphatase and peroxidase in monkey kidney cell cultures inoculated with herpes virus type 1. The variation of lactate dehydrogenase, peroxidase, acid and alkaline phosphatase isoenzymes was studied in VERO cells inoculated with infectant and UV-inactivated herpes simplex virus type 1 (HSV--1). Infectant HSV--1 induced quantitative and qualitative modifications in isoenzyme patterns within the first 4 hours post inoculation (p.i.). The modifications caused by the UV-inactivated HSV--1 were similar, but appeared 8 hours p.i. The possibility of using isoenzyme modifications as rapid, sensitive and specific biochemical tests for virus detection and differentiation between infectant and inactivated virus is discussed.


Immunoelectrophoretic study of the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note I. Analysis of chorioallantoic membrane host antigens. The immunoelectrophhoretic analysis of two preparations of the same virus cultivated in different substrates (Sendai/egg and Sendai/KB) demonstrate that virus envelopes contain: a) identical virus-specific antigens (but also some virus antigens with only partial immunochemical identity, or even non-identity); b) antigens incorporated by the virus from the host cell, during assembly and release. The latter differ according to the host, and some of them are only partially identical with the corresponding antigens of the host cell, which suggests that host cell glycoproteins are incorporated into the virus envelope after certain virus-induced modifications.


Effects and mechanism of the interaction between ceruloplasmin and some viruses or subviral components. The results of investigations concerning the interaction between ceruloplasmin (a serum nonspecific inhibitor) and some myxo- and paramyxoviruses, as well as certain viruses with oncogenic potential (herpes virus, SV--40) are reviewed. The data presented point out the inhibiting action of ceruloplasmin on virus multiplication and the ceruloplasmin-induced modification in the antigenicity of Sendai virus and subviral fractions. The stages and mechanisms of ceruloplasmin action are discussed.


[Differential diagnosis of glomus and glomal stomach tumors]. Two cases of glomangiomas of the stomach are described in detail. Moreover 8 cases of mixed glomus tumors of the stomach were clinically observed, one of them being previously described. The analysis of clinico-radiological and morphological features of these diseases, based both on the personal authors' and literature material enabled the conclusion to be drawn on the presence of a number of signs, which could contribute to differentiating between glomangiomas (Barre-Masson tumors) and  epitheliod leiomyomas of the stomach. These differences may be of some practical value in selecting the therapeutic tactics and formulating the prognosis.


[Angiography in abdominal diseases (author's transl)]. Angiography of arteries and veins in the abdominal and retroperitoneal compartement is a valuable routine roentgenologic procedure. Its value in the diagnosis of vascular disorders is apparent. Regarding space occupying lesions in the abdomen angiography is an aid in diagnosis and differential diagnosis and provides information on the curability. Visualization of the venous system will give mainly information on the extent of a tumor. For an evaluation of portal hypertension the arterial indirect visualization of the portal venous system is superior to the direct percutaneous splenoportography. In the acute gastrointestinal bleeding selective angiography is able to demonstrate the bleeding site.


Recent advances in the understanding of acupuncture. The controversy about acupuncture is familiar to us since its recent reintroduction into this country. Much of its philosophical concepts were taken at their face values as the bases for condemnation. Since I last reviewed these antiquated concepts in the light of modern medicine, much has developed. It seems that if the effects of acupuncture were transmitted along the peripheral nerves to the central nervous system, it would be more effective if applied segmentally to the site of noxious stimulation. Disruption of extralamniscal pathways would abolish its analgesic effect. The distant and nonsegmentally located acupuncture points exert their influences through the integrative efforts of the reticular formation and the thalamus. The demonstration of transmissibility of acupuncture analgesia through blood and cerebrospinal fluid in animals implicates the involvement of humoral factors. Since such an effect can be suppressed by naloxone or by hypophysectomy, endorphins are thought to be involved. Such laboratory evidences indeed begin to shed some light on a possible neurohumoral mechanism of acupuncture. The differences between acupuncture and hypnosis are discussed. Acupuncture points were compared with referred pain, trigger points and motor points of the skeletal muscles. Its possible uses for other than pain, such as drug addiction, alcoholism, etc. are also reviewed.


[The appearance of pathognostic inclusion bodies in verruca vulgaris (author's transl)]. Pathognostic inclusion bodies develop in the nucleus. They frequently occur in the upper layers of the pathologically changed stratum spinosum. They are stained in an amphophilic or basophilic manner. Their structure is a nearly homogenous, finely grained or plaquelike one. The inclusion bodies contain masses of human wart viruses in a cristalline-like arrangement or are irregularily distributed. Feulgen staining is positive. Different pictures of inclusion bodies are demonstrated in paraffin sections. The knowledge of structural variants is very helpful in biopsy diagnosis of veruca vulgaris.


[Functional organization of monosynaptic interneuronal connections in the cerebral cortex]. A study of monosynaptic intraneuronal connections was performed in micro-regions of sensorimotor and autitory cortical areas in cats. Certain definite characteristics were found in the joint activity of neurones which persisted after the regime of microsystem activity was changed. Neurones with a lower spike amplitude discharge earlier and elicite discharges in neurones with a greater spike amplitude; feed-backs are inhibitory. It is suggested that in both cortical areas there exist microsystems with similar organization composed of different types of neurones.


[Critical remarks on the surgical treatment of syndactylia (author's transl)]. The technique of surgery for syndactylia is described in detail. The author's opinion about the optimal age for surgical correction of equally or unequally long fingers is reported. The importance of early intervention in case of complicated syndactylia is stressed. Until growth has come to an end, continuous follow-up is necessary for early recognizing late contractures.


[Antigenic activity of Bordetella pertussis during cultivation in liquid nutrient media]. The authors studied the antigenic activity of Bordetella pertussis during stab cultivation. For the first time there were revealed changes (oscillations) of antigenic activity: formation of 3 peaks of which the middle was the highest. A possibility of improving the quality of pertussis vaccine by using biomass at the height of the peak was experimentally founded.


Acute influence of LH and FSH on cyclic AMP formation in isolated granulosa cells of the rat. A technique for the mechanical isolation of granulosa cells from the rat ovary is described. Cyclic AMP formation by the isolated granulosa cells of the follicles in various stages of development was studied in response to the administration in vitro of gonadotrophins. In granulosa cells from small to medium-sized follicles FSH but no LH stimulated cAMP formation, while in cells from pre-ovulatory follicles both gonadotrophins had a stimulatory effect. The effects of both gonadotrophins were transient with a maximal response after 15 to 60 min of incubation. In the presence of the phosphodiesterase inhibitor, 3-isobutyl-methylxanthine, the action of FSH was potentiated and prolonged while the response to LH was unaffected. These data indicate that both gonadotrophins activate the adenylate cyclase system of the isolated granulosa cells while FSH in addition stimulates the phosphodiesterase activity. Consecutive determinations of cAMP during and after the pre-ovulatory LH-FSH surge, demonstrated a rise of cAMP levels in granulosa cells from the pre-ovulatory follicles following endogenous gonadotrophin release. cAMP levels remained high or increased until the time of ovulation.


Histochemical and histoenzymatic changes in mouse liver in subacute benzene intoxication. The investigations were performed on mice. They were divided into a control group and 4 experimental groups. The experimental animals were administered intraperitoneally benzene 6 X every 24 h. The animals were decapitated 30 min. 4, 12 and 24 h after the last benzene administration. During the experiment, dyeing for neutral lipids and glycogen was carried out, and the activity of NADH2-r.t., SDH, G-6-Pase, ATP-ase and ACP was estimated. A decrease of glycogen content in liver cells, deviations in the amount of neutral lipids, reversible decrease of mitochondrial enzymes activity, and intensification of the processes of intracellular catabolism were found.


The significance of the imprint cytology in breast biopsy diagnosis. Tissue biopsies of the breast with and without carcinomas were examined simultaneously by intraoperative histology and imprint cytology. In 95 per cent of the cases there was a good agreement between the histologic and cytologic diagnoses. The reliability of the imprint cytology was tested in some complicated cases such as proliferating fibroadenomas, pseudoinvasive adenosis and carcinomas. In 20.2 per cent of the cases with carcinoma, the tumor cells showed peculiar intracytoplasmic inclusions, whereas such inclusions were found only in 0.43 per cent of the biopsies of mammas without carcinoma. Their morphological variations and the histochemical pattern are discussed. The results have demonstrated that simultaneous cytologic examination of unfixed mamma biopsies can be a good screening method and that the intracytoplasmic inclusions may be an especially helpful histopathologic feature in the diagnosis of breast cancer.


[Histotopography of glycosidases in the accessory glands of the boar before and after castration]. The histochemical distribution of six glycosidases (N-acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucuronidase, alpha-galactosidase, alpha-mannosidase and alpha-fucosidase) was investigated in the prostate, glandula vesicularis and glandula bulbourethralis of castrated and non-castrated adult boars. The functions of the glycosidases in the male accessory sex glands of the boar and their androgen dependence are discussed briefly.


Plasma lipids and lipoproteins in young patients with brain infarction. Thirty-two patients aged 60 or less with brain infarction were examined with regard to possible changes in lipoprotein pattern as compared with a reference group. Except for a lower concentration of total lipids, cholesterol and high-density lipoproteins in the female patients, no difference was demonstrated in the two groups. In all patients a significant reduction in total lipids, cholesterol, triglyceride and all lipoproteins was demonstrated after the acute cerebrovascular accident presumedly due to the stress situation.


Morphological changes in CNS of rats treated with perhexiline maleate (pexid). The basic cellular lesion in CNS of suckling rats treated with Pexid was studied by light and electron miroscopy. The most pronounced abnormality, the formation of various intracytoplasmic inclusions, was found in neurons, astrocytes, oligodendrocytes, ependymal cells, endothelial cells and fibroblasts. These abnormal inclusions were generally membrane-bound, although clearly non-membrane-bound inclusions were occasionally found. The several internal patterns of the inclusions were (1) lamellar, both concentric and parallel, (2) reticular and (3) crystalloid. These alterations were completely reversed following withdrawal of the drug. The structural characteristics of the abnormal inclusions in Pexid-treated animals were similar to those found with certain hypocholesterolemic, neuroleptic, anorectic, and antimalarial drugs. This suggests that the inclusions occurring within the cells of animals treated with any of these drugs may develop in a similar manner, and that the formation of such inclusions is likely to be a form of cellular reaction common to certain metabolic disturbances.


Light and electron microscopic observations on the relationship between Hirano bodies, neuron and glial perikarya in the human hippocampus. Hippocampi from two intellectually normal and four demented subjects were examined in autopsy material. Large Hirano bodies seen by light and electron microscopy were thought to be glial in origin and not to be produced by the perikarya of neurons as has been suggested in the literature. Myelination of two Hirano bodies found in the stratum lacunosum-granulosum where neuron perikarya are rare suggests that these bodies are produced by oligodendroglia. Hirano bodies were found to be associated with neurons showing granulovaculoar degeneration. With electron microscope they were frequently seen to be divided by clefts filled with amorphous material which possibly consisted of free ribosomes.


The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors. Eighty glial and non-glial brain tumors have been studied to date using an immunologically specific and highly sensitive method of staining GFA protein which is applicable to formalin fixed and paraffin embedded tissue. Eight of these cases have been described and illustrated in some detail. GFA protein was present in all astrocytes and astrocytomas studied and in a proportion of ependymal cells and ependymomas. Some tumor cells have been demonstrated by this method to be glial despite the complete lack of blue fibrillar staining with PTAH and the absence of all morphological similarity to glial cells. In such cases the demonstration of GFA protein by this method has been valuable in establishing a diagnosis. In addition to its diagnostic value in specific cases, the method promises to shed light on unsolved problems of tumor cytogenesis.


Adrenoleukodystrophy. Preliminary report of a connatal case. Light- and electron microscopical, immunohistochemical and biochemical findings. This is the first description of a connatal case of adrenoleukodystrophy. The clinical picture consisted of severe psychomotor retardation, convulsions and hypsarrhythmia, but no obvious signs of adrenal insufficiency. Pathologically, the adrenals were small. The entire cortex was largely replaced by large round cells. Ultrastructurally, some cells in the adrenal cortex contained inclusions with electron-lucent clefts surrounded by a membrane. The anterior pituitary lobe could be demonstrated to have produced ACTH. The central nervous system showed extensive zones of demyelination in the brainstem, the cerebellum and the right-sided capsula interna. In the demyelinated areas there was sudanophilic breakdown and an intense gliosis. Ongoing demyelination could also be demonstrated by the chemical analysis. In the gray matter there waere micropolygyria of the insular cortex and swollen nerve cells in the nucleus arcuatus. Ultrastructure revealed the type of inclusions in the microglia of the same type as in the adrenals, and a different type of inclusions in unidentifiable cells, possibly neurons. These latter inclusions consisted of loosely stacked lamellar material. The findings are interpreted as further evidence of storage taking place in this disease.


Serum prolactin, FSH and LH during puberty in girls and boys. Serum prolactin, follicle-stimulating hormone and luteinizing hormone were determined in 200 girls and 80 boys. The boys have been examined on three occasions at one-year intervals and the girls twice at 1.5-year intervals. In girls, serum FSH rapidly increased in the youngest age groups (7.5-11.5 years), whereas in boys, the increase took place later and the first significant increase was seen between age groups 9.5 and 12.5 years. In girls, a rise in serum LH took place later than that of FSH (between 10.5 and 11.5 years), and LH peaked at 13.0-13.5 years. In boys, the timing in the changes of serum LH closely resembled that of FSH. The girls displayed a significant increase in serum prolactin between 7.5 and 8.5 years, and this was followed by a slow progressive increase. In the group of boys, serum prolactin did not show any significant changes. In girls, there was a correlation between serum LH and body weight, as well as calculated fat amount and body fat percentage early in puberty. There was no correlation between serum LH and chronological or bone age in this age group, which suggests that the correlation found is not due to age-related parallel phenomena.


Mechanism of the formation of megamitochondria by copper-chelating agents. V. Further studies on isolated megamitochondria. Effect of cuprizone has been studied on some biochemical properties of megamitochondria obtained from the mouse liver. (1) Contents of Ca2+, Mg2+ and Cu2+ in the blood or the liver homogenates were not altered by cuprizone intoxication, whereas those in liver mitochondria were significantly altered: after 3-4 days' intoxication, content of Ca2+ was decreased and was remarkably increased after 14-15 days' intoxication. Content of Mg2+ behaved contrarily. (2) Both cytochrome oxidase and ATPase activities were unchanged in the liver megamitochondria, but monoamine oxidase (MAO) activity was significantly decreased. Value of I50 (50% inhibition) for MAO was determined to be 0.33 mM using the control liver mitochondria. Cuprizone had almost no effect on MAO activity of kidney or heart mitochondria both in vivo and in vitro. (3) The amount of lysolecithin was increased in the liver megamitochondria. These results were discussed in the light of membrane fusion phenomenon which plays a key role in the mechanism of megamitochondrial formation.


Effects of isoprenaline on the time course of the cyclic AMP level in rat uterus. Isoprenaline markedly relaxed rat uterine muscle and increased its content of cyclic AMP. The cyclic AMP concentration reached its highest value, about ten times the control after 3 min., after which it declined rather quickly at first but later more slowly. After 60 min. the cyclic AMP content reached twice the prestimulation value. The muscle remained relaxed all the time. If the incubation medium from the uterus treated with isoprenaline for 60 min. was added to a fresh muscle, a normal response was elicited. Addition of a new dose of isoprenaline to a muscle previously incubated with isoprenaline for 60 min. only gave a minimal rise in cyclic AMP after 3 min. The presence of catechol or corticosterone, which both decreased the inactivation of isoprenaline, showed no effect on the decrease of the isoprenaline-stimulated cyclic AMP level. Nor could the decrease in the cyclic AMP response be prevented in the presence of GTP,F-, adenosine or in Ca2+-deficient medium. The addition of theophylline and puromycin both lead to a slower decline of cyclic AMP content, but after 60 min. the value returned to near that seen ater only isoprenaline. Our studies on isoprenaline-induced desensitization of rat uterus have led us to the conclusion that the change in the capacity of the preparations to accumulate cyclic AMP may be a result of either changes in the beta-adrenoceptors or in the cyclase-system.


Plasma cyclic AMP in manic-depressive illness. The postulated disturbance of cyclic AMP (cAMP) in manic-depressive illness was investigated by using plasma as the biological material. Cyclic AMP was measured by a protein-binding assay, which was found very satisfactory for the purpose of this study. In the drug-free state, depressed patients (n = 28) had significantly lower and manic patients (n = 9) significantly higher plasma concentrations of cAMP than controls. Unmedicated manic-depressive subjects had normal cAMP levels during normothymic phases (n = 7). Cyclic AMP was reduced by neuroleptics in mania and elevated by tricyclics in depression. Lithium exerted a normalizing effect on cAMP in both phases of the illness. It is concluded that manic-depressive illness is associated with a disturbance in the cAMP system. The use of plasma rather than urine for the investigation of the state of cAMP in psychiatric disorders is advocated.


Survey of serum lipid levels in Icelandic men aged 34-61 years. An epidemiological and statistical evaluation. This report presents the results of serum beta-lipoprotein, total cholesterol and triglycerides determinations in a male population surveyed 1967--'68. This was the first stage (stage I) in a prospective health survey conducted by the Icelandic Health Association. The area of study was the city of Reykjavík with adjacent suburbs and communes. The population invited was 1/3 of each of 16 year-groups of males in the age-interval 34-61 years. The population was selected from the National Roster according to birthdays i.e. the 1st, 4th, 7th,.. of each month, the total number being 2.955. The response was 75.1%. B-lipoproteins were determined with the Hyland Beta-L Test, total cholesterol and triglycerides on Technicon AutoAnalyzer (i) according to Technicon Methodology N-24a, and a modification of the method of Kessler and Lederer respectively. Control sera were run in connection with cholesterol- and triglycerides determinations. Serum cholesterol levels were similar to the highest reported from other countries contrary to the triglycerides levels which are in the low range. The mean values and lower centiles are practically independent of age whereas the higher centiles are markedly age-dependent. A seasonal variation for the cholesterol weekly mean values was found. These values were highest in winter and lowest in summer, the difference estimated to be 30-40 mg%. No seasonal variation of triglycerides was found. Centile-flowdiagrams for these blood lipids are presented and the use of similar flowdiagrams is suggested as an aid to bridge a gap between the interpretation of cross-sectional and longitudinal studies.


Early diagnosis of cancer by gastricbiopsy. On the basis of 350 gastric biopsies the difficulties of early diagnosis of cancer are discussed. The technical and morphological stumbling blocks of evaluation are reviewed. The differences between the gross and microscopic diagnoses, the more important causes of histologic error are dealt with.


Photochemical reactions of cytochrome oxidase at low temperatures. The unique of CO-cytochrome oxidase as first noted by Yonetani et al. (22) is that after its photodissociation at low temperatures recombination occurs as the sample temperature is raised, but at temperatures considerably higher than those for other CO-heme and CO-hemoprotein complexes; that is, the half recombination temperature is 180 K contrary to 25-30 K for other CO complexes. The photodissociability, however, disappeared when monomeric cytochrome oxidase was treated with pCMB to remove an intrinsic copper, the significance of which in CO complex formation was thus demonstrated. It is proposed that the copper is situated close to heme a and traps the photodissociated CO. The access of the trapped CO to the heme a to resume the original binding is effected only when sufficient energy for thermal agitation is provided by elevating the sample temperature. During the course of this study, new photo- and thermochromic properties were observed with the reduced enzyme by cooling it in liquid nitrogen after preincubation at pH 8.6 to 10.5. The characteristic bands appeared at 575 and 428 nm and diminished when this ample was illuminated at 26 K. As the sample temperature was raised these bands were restored with a half transition temperature of 80 K. When the reduced oxidase had been complexed with CO, cyanide or azide, or treated with pCMB, such a unique species did not appear. The enthalpy change of 1.16 kcal/mol for the formation of this species as well as the above-described properties suggests that the hydrogen bond between the formyl side group of heme a and one of seven sulfhydryl groups in cytochrome oxidase is responsible for the appearance and disappearance of this new species. Based on these results a schematic model has been proposed for the photo- and thermochromism of cytochrome oxidase at cryogenic temperatures and for the microenvironment of the prosthetic heme a and copper in this enzyme. On the other hand, contrary to the central dogma of Warburg that all CO-heme and CO-hemoprotein complexes are photodissociable, we observed little photodissociability with some CO-heme complexes, especially at very low temperatures, and presented a view that depending on the bond type between CO and heme iron the efficiency of photodissociation is so varied that under certain conditions practically no photodissociation occurs. According to this view a tilted arrangement of the ligated CO towards the heme plane accompanying a large extent of overlapping of the dpi(Fe) and the pi* antibonding orbital on the CO facilitates photodissociation. In addition to our own observations of photochemical properties of cytochrome oxidase and heme model compounds, recent photodynamic studies carried out by other investigator on CO-heme and CO-hemoproteins are summarized and the validity and limitation of their models are discussed.


[Psychological links and coronary diseases. II. Psychological correlations of certain physiological variables (author's transl)]. In this study, correlations were tabulated between physiological and psychological measurements drawn from a group of 21 infarct patients and a matching group of 21 normal subjects. The physiological variables taken under consideration are the number of platelets, the beta-lipoproteines and the systolic blood pressure; all these variables were tested under stress and at rest. On the top, fibrinogene at rest, cortisol under stress and heart rate under conditions of "intake" and "rejection" were also measured. The psychological assessment was achieved by the MMPI. Several psychological traits link with physiological parameters to be considered as cardiovascular risks. However, these links are mostly specific; moreover, they vary under different experimental conditions. In other words, different neuro-behavioral patterns seem to operate at rest and under stress. The links between psychological and physiological variables vary also between normal subjects and infarct patients. Normal subjects as well as infarct patients show a relationship between neurotic traits and genuine physiological reactions. However, among the formers, these neurotic traits are in closer relationship with inhibitions as among heart patients. Psychological risk factors in cardiovascular disorders appear to be related with a genuine expression of conflictual affects leading to inadequate physiological responses; when these reactions are repeated in time, functional disorders may induce organic lesions.


Lipoprotein lipase and postheparin esterase activity in primary hyperlipoproteinaemia type IV and V. In a study of the aetiopathogenesis of primary hyperlipoproteinaemias, which has not yet been elucidated, we paid attention to the heparin-activated lipolytic enzymes. Lipoprotein lipase (LPL) and postheparin esterase (PHE) activity was determined in 35 patients with primary hyperlipoproteinaemia (HLP) type IV (average age 50 years), 28 with type V (average age 48 years) and 2 with type III (57 and 62 years). Since PHE activity is correlated to sex and in women also to age, these factors had to be taken into account. The average activity values for the given enzymes in the patients group did not differ from the results in the control group. From these enzymes activities we tried to analyse the findings in individual cases in which the values were lower or higher than the control group range. The low PHE activity in some patients with type IV and V was evidently secondary and due to hepatobiliary disorder (most frequently liver steatosis). The simultaneous elevation of LPL and PHE activity in type IV and V patients with a high serum lipoprotein concentration shows that the response of patients with extreme HLP to heparin is more pronounced. The low PHE activity in type III (tested in only 2 patients) could possibly indicate the liver disorder on which this metabolic disease may be based.


Determination of alpha-amylase activity in duodenal contents with the blue starch polymer. The use of the blue starch polymer (Phadebas tablets) for the determination of duodenal alpha-amylase is described. 0.05% bovine or human albumin solutions are necessary for dissolution of substrate tablets as well as for dilution of duodenal contents. Concentration and output values of duodenal amylase before and after cholecystokinin-pancreozymin and secretin stimulation display a close correlation of the chromogenic and saccharogenic method. The average error of duodenal alpha-amylase in parallel examinations is low with both methods and their relative accuracy is practically the same. The chromogenic method is considered more simple and rapid.


Lisfranc's fracture-dislocation: a manifestation of peripheral neuropathy. Lisfranc's fracture-dislocation may be secondary to acute trauma, but on the basis of our experience with seven cases, it is more commonly a manifestation of repetitive subclinical trauma in patients with a neuropathic disorder. Separation of these two groups of patients is important, since those with acute trauma require reduction and those with a neuropathy need only be treated with non-weight bearing. All patients with Lisfranc's fracture-dislocation and without a specific history of acute trauma should be evaluated for the possibility of diabetes mellitus or another cause of sensory neuropathy.


An evaluation of the absorption spectra of antigens from Entamoeba histolytica (Ibadan strains). By means of chromatography different fractions of antigens from Entamoeba histolytica (Ibadan Strains) have been separated. All the different fractions have been tested for antigenic reactivity using agar gel diffusion technique. The intact antigen, as well as, the three antigenically reactive fractions were found to have ultra-violet absorption spectra in the region 258 and 278 millimicron. By virtue of this physico-chemical property amoebic extract(s) was found to simulate a mononucleotide Deoxy-5-methyl-cytidilic-acid. Such a unique structure of the extracts was used to suggest a mechanism for the possible low antigenicity of the organism based on its inability to induce a protective antibody response in human amoebiasis.


Fine needle aspiration biopsy in the diagnosis of mediastinal lesions. In the presence of a mediastinal mass, fine needle aspiration biopsy is an alternative to other time-consuming and expensive diagnostic procedures. We have performed a total of 25 fine needle aspiration biopsies of mediastinal lesions in 18 patients. Although our material is too limited to reach definite conclusions as to risks, we have found the technique enables a high percentage of positive diagnoses and is well tolerated by the patient.


Wilms' tumor to the heart: clinical and radiographic evaluation. The clinical and radiographic appearances of four children with cardiac extension of Wilms' tumor and four cases from the literature are described. Four of the eight children were seen for "cardiac problems" and four for "routine" Wilms' tumor. In those "routine" cases, there were no clinical suggestions of inferior vena cava or cardiac extension. Preoperative screening for tumor extension may be crucial. However, because of the rarity of cardiac extension, it would be appropriate to screen patients by noninvasive methods such as gray scale ultrasound of the abdomen, echocardiography, or computed tomography before any invasive procedure is considered.


The ultrastructure of the neonatal pig colon. The neonatal pig colon has several unique structural and developmental features. At birth it has a variable population of epithelial cells which in their arrangement on villus-like protrusions and in their capability for protein uptake into large preformed supranuclear vacuoles closely resemble neonatal ileal cells. Such villus-like protrusions and vacuolated cells are not present in the 2-day-old piglet. On the first day after birth absorptive epithelial cells which lack supranuclear vacuoles transiently accumulate a large number of lipid droplets, each separated from the cytoplasm only by a proteolipid interface. None of the much smaller lipid droplets bounded by a unit membrane of the smooth endoplasmic reticulum and characteristic of normal small intestinal fat uptake were ever seen in these cells. Very few of the large lipid drops remain on the second day after birth. This initial capacity of the colon for protein and lipid uptake never reappears. The pattern of colonic amino acid transport also changes markedly in the first four days of independent life and this may be correlated with the observation that the absorptive cells at birth have microvilli which are twice the length of those on similar cells at and after two days old. These morphological results are discussed in terms of implied functional changes in the neonatal period.


Dispersion of cisternae of rough endoplasmic reticulum in aging CNS neurons: a strictly linear trend. Dispersion of cisternae of rough endoplasmic reticulum (RER) in aging rats has been determined quantitatively for mitral cells of the olfactory bulb and Purkinje cells of the cerebellum using a recently published morphometric technique (Cruz Orive, '76). In both cell types dispersion of cisternae occurred throughout the period studied and in a linear fashion. The observed RER dispersion cannot be attributed to a decrease in the total amount of RER, since the total amount of RER was constant in Purkinje cells and increased in mitral cells during the age studied.


Dissection of a continuous distribution: red cell galactokinase activity in blacks. A significant difference between blacks and whites in the distribution of red cell galactokinase (GALK) has been found by Tedesco et al. [2]. From the shapes of the distributions, it was inferred that whites are essentially all homozygous for one allele (GALKA), but blacks are polymorphic. A second allele (GALKP), for lower GALK activity, is presented at high frequency in blacks but rare or absent in whites. This paper presents a method which, assuming the genetic model presented, estimates the genotype composition of the black sample. We make some reasonable biochemical assumptions and fit a mixture of three normal distributions to the black data to obtain an estimate of p, the frequency of GALKA in blacks. The fit of the model to the data is excellent and the best estimate of p is .217 +/- .025. Since admixture of white genes in blacks from the United States is known to be about 20%, the value of p implies that virtually all GALKA alleles were introduced by admixture, and that the ancestral black population was monomorphic for GALKP. If whites are indeed monomorphic for GALKA, they differ from unmixed blacks by a full gene substitution at the locus for GALK.


Aniridia, cataracts, and Wilms' tumor in monozygous twins. We studied the first instance of aniridia-Wilms' tumor syndrome in twins who were mentally retarded. Both of them had congenital aniridia, cataracts, and glaucoma; only one subsequently developed a Wilms' tumor. A two-allele, two-step mutation is the most likely explanation of this genetically abnormal syndrome in twins. The aniridia-Wilms' tumor syndrome in twins further documents the relationship of teratogenic malformations and neoplasias.


Collagenase in experimental carbon tetrachloride cirrhosis of the liver. The presence and distribution of collagenase in experimental CCl4 cirrhosis of the liver in rats has been studied by immunohistochemical techniques. A monospecific anti-rat uterus collagenase antibody was raised in rabbits and used for indirect immunofluorescence staining of liver sections obtained from rats in both the reversible and irreversible stages of CCl4-induced cirrhosis. Collagenase is present assoicated with connective tissue septums as long as cirrhosis is reversible, and it is not detectable in the irreversible stage. In animals sacrificed during the transition between the reversible and irreversible stages of cirrhosis, collagenase appeared bound to the outer surfaces of connective tissue septums and was absent from the deeper portions. These observation suggest that the irreversibility of experimental CCl4 cirrhosis of the liver is associated with a disturbance in the mechanisms of collagen degradation, which may be a deficiency in collagenase activity, a change in the susceptibility of the substrate, or a combination of both factors.


Mechanism of cardiac output response to hypertonic sodium chloride infusion in dogs. Hypertonic sodium chloride and tris(hydroxymethyl)amino-methane (Tris) hydrochloride (0.3 mmol/kg.min) were infused intravenously into chloralose-anesthetized dogs over a 20-min period. Cardiac output, maximum left ventricular dP/dt, and (dP/dt)/P increased by 55, 33, and 23%, respectively, during NaCl infusion, but Tris HCl infusion had no effects. NaCl infusion did not change heart rate or left ventricular end-diastolic pressure. Mean systemic and pulmonry arterial blood pressures increased, whereas total peripheral and pulmonary vascular resistances decreased. Responsiveness of cardiac beta-adrenergic receptors, as determined by serial intravenous injections of epinephrine, was not affected by NaCl infusion. Plasma catecholamine concentration, however, increased during NaCl infusion. In addition, the increases in cardiac output, maximum left ventricular dP/dt and (dP/dt)/P were abolished by prior treatment with practolol, a cardioselective beta-adrenergic receptor blocking agent. These results suggest that the hemodynamic effects of NaCl infusion were caused, at least in part, by the inotropic action of catecholamines.


Epidemiological aspects of rotavirus infection in hospitalized Venezuelan children with gastroenteritis. The prevalence of rotavirus infection in hospitalized Venezuelan children with gastroenteritis was studied during the period November 1975 to December 1976. Rotaviruses were the pathogens most frequently associated with gastroenteritis, being found in 121 of 293 (41.3%) patients and in only 3 of 66 (4.5%) controls. Other viruses (adenoviruses, enteroviruses, and small icosahedrical viruses) were detected at a lower frequency both in cases and controls. Rotaviruses were detected at a lower frequency both in cases and controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal temperature variation in a tropical country such as Venezuela. Children of all age groups examined (0-5 yr) were susceptible to rotavirus infection. The frequency of infection was slightly higher in the age group 13-24 mo, and significantly lower in children younger than 6 mo old. Rotaviruses were readily detected even after 12 days from the onset of illness. These results indicate that rotaviruses may be a major cause of infantile acute gastroenteritis in Venezuela.


New and old agents in diarrhea: a prospective study of an indigenous adult African population. We conducted a prospective study 77 indigenous African adults with acute diarrhea seeking care at the major hospital in Nairobi, Kenya, to determine the major pathogens responsible for this syndrome in adults. Fecal and blood specimens were collected and examined for enteric bacterial pathogens, viruses, and parasites. In 13 (26%) inpatients and 11 (49%) outpatients Shigella was found, and heat-labile and heat-stable forms of enterotoxigenic Escherichia coli were found in 9 (18%) inpatients and 1 (4%) outpatient. Human revirus-like agent titers rose significantly in another 3 (6%). Amebic dysentery was not seen although hemagglutination-inhibition tests for invasive Entamoeba histolytica were positive in 4 inpatients. An etiologic agent was found in 65% of patients.


Ultrastructural changes of the early visceral yolk sac layer of mouse embryos after maternal injection of trypan blue. The ultrastructural features of the early visceral yolk sac epithelium of normal mouse embryos on day 9 were compared to those whose mothers had received a single subcutaneous injection of 100mg/kg trypan blue on day 8. The following results were obtained: In normal embryos the visceral yolk sac cells are predominantly characterized by numerous membrane bounded inclusions localized in the supranuclear cytoplasm. In embryos of animals treated with trypan, blue, at about 12h after injection large single and only partly membrane bounded vacuoles are observed occupying most of the apical cytoplasm. Up to 24h after injection large cytoplasmic areas are seen which are in a stage of autodigestion possibly due to leakage of the vacuolar content. These alterations are exclusively limited to the visceral yolk sac epithelium whereas in the cells of the embryonic part, e.g. head process, no changes could be found. The observations are discussed in relation to the mechanism of the teratogenic activity of trypan blue.


Secretory antibody responses in cattle infected with foot-and-mouth disease virus. Antibody responses in serum, saliva, nasal secretions, or esophageal-pharyngeal fluid of foot-and-mouth disease virus-infected steers were examined by single radial immunodiffusion and mouse-neutralization tests. In steers infected with type O foot-and-mouth disease virus, high serum antibody titers were detected within 10 days after infection. Antibody was first detected in saliva at 30 days and gradually increased to a plateau at about 90 days. Small amounts of antibody continued to be secreted in saliva and in nasal secretions for at least 6 months. Antibody was not detected in esophageal-pharyngeal fluid. The major antibody activity in secretions was due to secretory immunoglobulin A as revealed by radioimmunoelectrophoresis.


Natural mode of transmission of the bovine leukemia virus: role of bloodsucking insects. The development of bovine leukemia virus (BLV) infection was studied in 14 noninfected young adult cattle exposed to 25 to 30 BLV-infected cows in an area of approximately 0.5 ha. Of 7 cattle (group 1) exposed beginning in July and August (midsummer) of 1976, 4 were infected by October, and all 7 by November (4 months' exposure). Of 7 cattle (group 2) exposed from February 1977 (midwinter), all remained negative for 3 months, and only 1 was positive after 6 months. By October 1977, however, 4 cattle in this group were infected, indicating that contact transmission of BLV is prevalent during the summer months. This, and the fact that BLV-infected lymphocytes were recovered from tabanids allowed to feed on a BLV-positive cow, supports the idea that bloodsucking insects play a major role in the spread of BLV.


Chemotherapy of advanced small-cell anaplastic carcinoma. Superiority of a four-drug combination to a three-drug combination. A controlled clinical trial compared three-drug and four-drug combination chemotherapy in 109 patients with advanced small-cell anaplastic carcinoma of the lung. The combination of vincristine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was significantly superior to the combination of the last three drugs alone with regard to median survival (230 versus 176 days) (P less than 0.01) and to duration of response (186 versus 112 days) (P less than 0.01). Objective response occurred in 78% and 75%, respectively. No significant difference in these values was observed in the comparison of the three subtypes of small-cell anaplastic carcinoma using the World Health Organization classification.


Adenoid cystic carcinoma with orbital and cranial metastases: case report. Adenoid cystic carcinoma of the paranasal sinuses was demonstrated in a patient who subsequently developed a metastatic lesion to both orbits resulting in total blindness. While there are reports of extension of adenoid cystic carcinoma of the lacrimal gland to the adjacent orbit, this patient is an example of orbital extension of an adenoid cystic carcinoma of minor salivary gland originating in a paranasal sinus. The frequency and classification of this tumor also is reviewed.


[Blue rubber bleb naevus and glomangiomatosis, unicity or duality? About two cases (author's transl)]. About 2 personal cases, a review concerning Blue Rubber Bleb Naevus syndrome and glomangiomatosis is presented. Attention is drawn to the different histological pictures of these disease. Importance of a clear differentiation from the viewpoint of prognosis is emphasized.


[Formation of pseudotypes of VSV after culture in a human melanoma]. Electron microscope studies showed a high production of melanosomes and viral particles budding into the cisternae of the endoplasmic reticulum in cells derived from a subcutaneous metastasis. The history of this subline (HM6B-A) has been summarized elsewhere. An amelanotic subline (provided by the same patient) did not show similar virus particles. When infected with a vesicular stomatitis virus (VSV) thermolabile mutant (tl), these cells produced a VSV pseudotype in which a thermosensitive antigen was modified. Modification of surface VSV antigens was also detected by neutralisation tests. Using these tests, the VSV-pseudotype particles could be used as a tool to detect one or more antigens to a "putative" human melanomavirus, which might be only partially expressed.


Possible biochemical basis of memory disorder in Alzheimer disease. Damage to the hippocampal formation, whether focal or diffuse, leads to severe impairment of short-term memory. The most common presenting symptom of Alzheimer disease is loss of short-term memory, and histologically the hippocampus is characteristically affected. Choline acetyltransferase, which is involved in the synthesis of acetylcholine, is depleted in the hippocampus in the disorder. Anticholinergic drugs administered to normal subjects can simulate some aspects of the memory defect seen in Alzheimer disease. It is postulated that damage to a cholinergic neuronal pathway running to or from the hippocampus underlies the memory disorder. This suggestion implies that it may be possible to improve memory in patients with Alzheimer disease by pharmacological means.


Failure to demonstrate papovavirus tumor antigen in human cerebral neoplasms. Cell cultures derived from 80 brain tumors failed to show the intranuclear tumor (T) antigen common to cells transformed by simian virus 40 (SV40) or BK or JC viruses.


Leigh's disease in an adult with evidence of "inhibitor factor" in family members. A 21-year-old man with a longstanding history of impaired visual acuity, strabismus, broad-based gait, and below-average intellectual capacity developed respiratory difficulties and intermittent generalized weakness at age 19. He subsequently showed signs of massive brainstem dysfunction and died. Postmortem examination demonstrated changes compatible with subacute necrotizing encephalomyelopathy of Leigh involving portions of the diencephalon, midbrain, pons, and medulla as well as portions of the spinal cord and optic nerves. Evaluation of family members for presence of the urinary inhibitor factor for thiamine diphosphate phosphoryl transferase revealed abnormal levels in a brother, a maternal uncle, and the maternal grandfather of the patient.