Epinephrine, cyclic AMP, calcium, and myocardial contractility. In the first part of this paper, a short review of the literature on the effects of catecholamines, Ca2+, and cyclic AMP on the biochemical, electrical, and mechanical properties of the heart is presented. It is concluded that the effects of epinephrine on activation of glycogenolysis and on the inotropic response of cardiac muscle are both mediated by the combined actions of Ca2+ and cyclic AMP. Since the inotropic response precedes the glycogenolytic response it is evident that increased energy metabolism is a consequence of increased heart work and not a causative factor. The available data suggest that increased tissue cyclic AMP levels resulting from catecholamine stimulation of adenyl cyclase activity alter cardiac mechanics by modulation of the basic calcium flux cycle of the heart. These effects may be mediated by cyclic AMP-stimulated phosphorylation of specific proteins located in the sarcolemma, sarcoplasmic reticulum, and myofilaments via one or more protein kinases, although experimental verfication of the possible relationship between protein phosphorylation and altered Ca2+ binding properties at specific sites in the membranes is at present largely lacking. The increased rate of tension development induced by catecholamines appears to be caused by an increased rate of Ca2+ influx across the sarcolemma during the plateau phase of the action potential, whereas the increased rate of relaxation is probably attributable to an increased rate of sequestration of intracellular Ca2+ by the sarcoplasmic reticulum. In the second part of the paper, data are presented using a working rat heart preparation to illustrate the effect of catecholamines in facilitating Ca2+ entry across the sarcolemma. Decreased left ventricular pressure development induced by addition of ruthenium red or verapamil to inhibit Ca2+ influx was relieved in a concentration-dependent manner by catecholamines. Curves of percentage change of left ventricular pressure against external Ca2+ concentration are presented which show that epinephrine increased the sensitivity of the heart to Ca2+ whereas verapamil decreased it. A half-maximal increase of left ventricular pressure was obtained with 0.6 mM Ca2+ in control hearts, 0.3 mM Ca2+ with epinephrine, and 2.9 mM Ca2+ with verapamil (10(-7)-treated hearts. Verapamil combined with epinephrine at the above concentrations gave a half-miximal increase of left ventricular pressure with 1.3 mM Ca2+. These results are discussed in relation to a model for the Ca2+ flux in the heart.


Regulation of calcium transport in cardiac sarcoplasmic reticulum by cyclic AMP-dependent protein kinase. A manyfold increase in phosphorylation of cardiac sarcoplasmic reticulum (SR) was seen when SR was incubated in the presence of a bovine cardiac cyclic AMP-dependent protein kinase and cyclic AMP. This phosphoprotein had stability characteristics of a phosphoester in which the phosphate is incorporated largely into serine, and its formation did not required calcium ions, unlike the formation of acyl phosphoprotein intermediate of calcium-transport ATPase which is present within the same membrane. When examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein kinase-catalyzed phosphorylation occurred at a 22,000-dalton component of the cardiac sarcoplasmic reticulum. This 22,000-dalton protein has been named "phospholamban" (lambda alpha mu beta alpha nu epsilon iota nu = to receive), based on its ability to receive phosphate from ATP. Phosphorylation of phospholamban by cyclic AMP-dependent protein kinase was associated with the stimulation of calcium transport by the cardiac sarcoplasmic reticulum. This stimulation was accompanied by an increase in the calcium-activated ATPase activity, indicating that the overall rate of calcium transport rather than its efficiency is enhanced by protein kinase. The 22,000-dalton phopholamban was susceptible to trypsin. Brief digestion with trypsin in the presence of 1 M sucrose prevented subsequent phosphorylation of phospholamban, while leaving the calcium pump apparently intact. Incubation of trypsin-treated sarcoplasmic reticulum with cyclic AMP-depentent protein kinase did not result in the stimulation of calcium transport. These results may suggest that phospholamban is a modulator of the calcium pump of the cardiac sarcoplasmic reticulum.


Increased Ca2+ binding by a cardiac cell membrane preparation after cyclic AMP-enhanced intrinsic membrane protein phosphorylation. Ca2+ binding to a sarcolemma-enriched membrane fraction from pig myocardium possessing an intrinsic cyclic AMP-dependent protein kinase occurs at several classes of low affinity binding sites and at two high affinity binding sites with binding constants  of about 1.5-1.7x10(7) M-1 (0.3 nmole of Ca2+/mg protein) and 0.9-2.9x10(6) M-1 (0.8 nmole of Ca2+/mg protein). Ca2+ binding properties are not affected by verapamil and ouabain, whereas ruthenium red depresses Ca2+ binding at the low affinity binding sites and La3+ ions strongly reduce both low and high affinity Ca2+ binding. A profound inhibition of the high affinity Ca2+ binding sites was observed in the presence of Na+ ions, half-maximal inhibition at a free Ca2+ concentration of 2x10(-8) M being achieved by 11 mM NaC1. High affinity Ca2+ binding is also diminished after pretreatment of the membranes with trypsin and phospholipase A. Phosphorylation of one or two of the membrane proteins by the endogenous cyclic AMP-dependent protein kinase leads at both classes of high affinity Ca2+ binding sites to an approximately 4-fold increase in affinity, the number of these sites remaining unchanged. The high affinity Ca2+ binding sites may possibly be involved in Ca2+ extrusion from the cell and in the relaxation process.


Effects of glucagon on cardiac cyclic nucleotides in the hypoxic heart. Isolated rat hearts were perfused with a subinotropic concentration of glucagon during an hypoxic perfusion to determine whether glucagon would enhance recovery upon reoxygenation. Rat hearts were divided into two groups: 1) those perfused with glucose-free Tyrode's solution and 2) those perfused with Tyrode's solution containing glucose. During 3 min of hypoxic exposure, untreated hearts and hearts perfused with glucagon both demonstrated a dramatic decrease in contractile force regardless of whether glucose was included in the medium. However, when glucose was present in the perfusion medium cardiac performance was better during both hypoxia and the period of reoxygenation. Furthermore, during reoxygenation, the recovery of contractile force was significantly greater in glucagon-perfused hearts than in controls. Cardiac levels of cyclic AMP and cyclic GMP were monitored at various periods of hypoxic exposure to test the existence of a correlation between the concentrations of these cyclic nucleotides and cardiac performance. During reoxygenation of untreated hearts, the hearts perfused with glucose-free medium attained 45-50 percent of the contractile force seen in glucagon-treated hearts. This enhanced recovery in the glucagon-treated hearts was associated with decreases in cyclic GMP levels at the end of the hypoxic period. At this time, the cyclic GMP levels in the glucagon-treated hearts were only 25-55 percent of the levels seen in untreated hearts that were also exposed to hypoxia. The effect of glucagon on cyclic AMP content in untreated hearts and in hearts receiving glucagon was not significantly different at 3 min of hypoxia. These studies suggest that subinotropic concentrations of glucagon exert a protective effect on the hypoxic rat heart that is not related to the direct inotropic properties of this hormone but which may involve a modulation in cardiac cyclic GMP availability.


Drug-induced changes in the superficially located stores of calcium in heart sarcolemma. Excitation-contraction coupling in heart muscle cells depends upon an inward displacement of Ca2+ from the extra- to the intracellular phase. Some of the Ca2+ which is displaced inwards is probably derived from superficially located binding sites. Drugs which increase the peak tension developed during contraction, e.g., catecholamines and the cardiac glycosides, may act by increasing the amount of Ca2+ which becomes available for participation in the events associated with excitation-contraction coupling. The catecholamines increase in the amount of Ca2+ which is displaced inward from the extracellular phase, whereas the cardiac glycosides apparently act by increasing the exchangeability of the Ca2+ which is stored at binding sites located at the plasma membrane. Other drugs, e.g., verapamil, act in the reverse manner, decreasing the amount of Ca2+ which is available for displacement from the superficially located binding sites. These observations will be discussed in terms of an hypothesis that the plasma membrane represents an important site of drug action, and that many drugs which alter the contractile performance of the heart do so because of their ability to modify the ability of the plasma membrane to accumulate and exchange Ca2+.


The effect of histamine, isoproterenol and tyramine on rat uterine cyclic AMP. Isoproterenol (10(-4) M), histamine (10(-3) M) and tyramine (10(-3) M) elevated cyclic AMP levels in incubated rat urerine segments. Promethazine (10(-6) M) an H1-receptor antagonist was ineffective in blocking the increase in cyclic AMP due to isoproterenol, histamine and tyramine. Buriamide (10(-6) M), an H2 receptor antagonist, was effective in almost abolishing the cyclic AMP elevation due to histamine, whereas burimamide did not affect the cyclic AMP levels elevated by tyramine and only slightly reduced the isoproterenol response. Propranolol was effective in reducing or abolishing the cyclic AMP accumulation by all three agonists. The respective blockade by burimamide or propranolol was overcome by increasing the concentration of the agonists. Histamine (10(-3) M) and tyramine (10(-3) M) failed to elevate cyclic AMP in uterine segments obtained from reserpine treated rats. The data supports the hypothesis that histamine, like tyramine, has an indirect effect on the rat uterus mediated through the release of endogenous norepinephrine.


Phosphodiesterase inhibition and lipolytic action of the stereoisomers of trimetoquinol. The isomers and racemate of trimetoquinol [TMQ; 6-7-dihydroxy-1-(3',4',5'-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline] as well as N-(3',4',5'-trimethoxyphenethyl)dopamine were all shown to be effective at promoting glycerol release from rat epididymal fat tissue. The rank order of potency observed for these compounds was (-)-TMQ greater than or equal to (+/-)-TMQ greater than greater than (+)-TMQ = N-(3',4',5-trimethoxyphenethyl)dopamine. (+/-)-TMQ and (-)-TMQ were the only agents capable of producing a maximal lipolytic response. None of the compounds tested were able to exhibit significant c-AMP phosphodiesterase inhibition. This study is the first report which shows that the beta-adrenoceptor activity of the isomers of TMQ does not correlate with an inhibition of c-AMP phosphodiesterase. An alternate mechanism of action for these compounds is proposed.


Infectious bovine rhinotracheitis virus: studies on the venereal carrier status in range cattle. Genital samples collected at autopsy from 193 beef cows representing 22 different herds in Northern Australia yielded only one isolate of infectious bovine rhinotracheitis (IBR) virus. Serological evidence showed 59 per cent of similar cows had prior infection with this virus and of 19 sero-positive cows tested, 11 (58-2 per cent) shed detectable IBR virus from the vagina after treatment with corticosteroids. Transitory lesions of the vagina and vulva developed in five of the treated cows. Twenty-six (65 per cent) of 40 sero-positive bulls shed detectable IBR virus into the prepuce after corticosteroid treatment. Except for one bull, virus was not isolated after corticosteroid treatment of sero-negative animals. IBR virus and mucosal disease (MD) virus were not isolated from nasal swabs before or after corticosteroid administration. No correlation was observed between initial circulating antiboyd titre and virus excretion after treatment. There were no significant changes in levels of serum antibody during the virus excretion period.


Studies on an additional pre-beta-lipoprotein, sinking pre-beta (SPB). I. Isolation and characterization. The occurrence on cellulose acetate and agarose gel electrophoresis of additional bands with the mobility of pre-beta-lipoprotein (LP) has recently been linked to ischemic heart disease (IHD). In the present study, one of these additional pre-beta-LP fractions, earlier designated as 'pre-beta-LP' and now defined on agarose gel electrophoresis, was isolated by preparative ultracentrifugation and gel filtration. The characterization of this pre-beta-1-LP revealed a 'sinking pre-beta-LP' (SPB) of density 1.050-1.080 g/ml. SPB shared its major antigenic determinant with low-density lipoproteins (LDL) and resembled closely LDL with regard to its lipid composition. Specific anti-LP(a) serum confirmed the presence of LP(a) antigen in the purified SPB preparation.


Studies on an additional pre-beta-lipoprotein, sinking pre-beta (SPB). II. Fatty acid composition of lipid moieties. The appearance of additional lipoprotein fractions with pre-beta-mobility on cellulose acetate and agarose gel electrophoresis has recently been linked with the early occurrence of ischemic heart disease (IHD). One of these fractions, designated sinking pre-beta-lipoprotein (SPB) has been isolated, purified, and identififed as synonymous with LP(a). In the present study, the lipid moieties of this lipoprotein fraction were further characterized as to their fatty acid composition. These were almost identical to those of low-density lipoprotein (LDL) lipid moieties. The acute influence on fatty acid composition of SPB lipid moieties, 5 hr after a linoleic acid-rich test meal, was a 40% increase in triglyceride linoleic acid content and only minor changes in phosphoglyceride fatty acids. Data speak against an actual conversion of chylomicron remnants into SPB but would allow a certain exchange of lipid moiety among chylomicrons, SPB, and LDL. It is therefore suggested that the origin of the SPB presumably synonymous with LP(a) is the same as for LDL: the liver.


Studies on human serum high-density lipoproteins. V. Isolation and characterization of a cholesterol ester-rich lipoprotein after in vitro incubation. Purified high-density lipoprotein (HDL), obtained by preparative ultracentrifugation at density 1.063-1.19 g/ml in the cold, were subfractionated by hydroxyl apatite column chromatography. Two of the obtained subfractions (subfractions II and III) turned turbid after incubation at 37 degrees C for 12 h. The turbid material was recovered in the supernatant of D 1.006 g/ml after centriguation at 30,000 g for 2 h. The lipoprotein fraction causing the turbidity was composed of 94% cholesterol ester and 2% apolipoprotein (by weight). On polyacrylamide gel electrophoresis the apolipoprotein moiety appeared as one polypeptide with the electrophoretic mobility of polypeptide A-I, revealed a blocked NH2-terminal amino acid, and had a total amino acid composition that differed from that of A-I and of the arginine-rich polypeptide.


Serum beta-lipoprotein subfractions in polyacrylamide gel electrophoresis associated with coronary heart disease. Subfractions of beta-lipoprotein occurred more frequently in serum from patients with coronary heart disease than in serum from patients with no sign of coronary heart disease. Two beta-lipoprotein subfractions were observed in polyacrylamide gel electrophoresis. The sera containing a beta-lipoprotein subfraction with a position close to the beta-lipoprotein band showed Lp(a) antigenic properties. Triglycerides were raised in the sera with beta-lipoprotein subfractions. The cholesterol level was significantly higher in the coronary heart disease group but was not correlated to the presence of the beta-lipoprotein subfraction. The beta-lipoprotein subfraction may possibly represent an additional risk factor in the genesis of coronary heart disease, even in the absence of other hyperlipoproteinemias.


Histochemical localization of alkaline pyrophosphate- phosphohydrolase in tooth-forming cells of rat. The activity of a pyrophosphate-splitting tissue factor in jaws, teeth and intestinal mucosa has been studied by means of histochemistry. Freeze-cut, unfixed sections of whole animals were incubated in a buffered medium (pH 8.6) containing inorganic pyrophosphate (PP) Pb2+, Mg2+, and Zn2+ at various concentrations. The effects of compound R 8231, heat, aldehyde fixation, and demineralization with EDTA were also investigated. In sections showing optimal staining, deposition of incubation products was found in the stratum intermedium and the subodontoblastic cells of the developing tooth, in the osteoblastic layers, and at the surface of the intestinal mucosa. The hard tissues were also stained except in the demineralized sections. Treatment with heat or compound R 8231 resulted in loss of originally observed soft tissue staining while short-time demineralization with EDTA enhanced the staining reaction. It is argued that a nonspecific deposition of the capturing ion, Pb2+, can hardly explain the observed soft tissue staining. The results point to the presence of a PP-splitting enzyme, and it is suggested that the enzyme exhibits features of an alkaline phosphatase with PP-phospholhydrolytic properties rather than of an inorganic pyrophosphatase.


Function of granulocytes with deficient myeloperoxidase-mediated iodination in a patient with generalized pustular psoriasis. The granulocytes of a patient with generalized pustular psoriasis (GPP) were found to have impaired ability to fix iodine after ingestion of yeast particles. Since hexose monophosphate shunt (HMS) activity was increased and the contents of 3 other lysosomal enzymes, beta-glucuronidase, N-acetyl-beta-glucosaminidase and lysozyme, were within normal range, the impaired iodination appeared to be due to a selective defect of myeloperoxidase (MPO) activity within the phagocytic cells. The deficient iodination was accompanied by a decreased intracellular killing of E. coli and C. albicans. Since hexose monophosphate shunt activity was enhanced and azide and cyanide inhibited the intracellular killing of E. coli only moderately, the patient's granulocytes may possess azide- and cyanide-resistant, MPO-independant microbicidal systems coupled to the oxidative metabolism. Assessment of granulocyte iodination and enzyme contents of the relatives of the patient revealed no hereditary transmission. Since GPP is characterized by the development of subcorneal pustules containing granulocytes, the MPO-deficiency may be the cause of or enhance the development of the disease.


Magnesium depletion and hypocalcaemia after removal of parathyroid carcinoma. A case of parathyroid carcinoma is described which presented with severe bone disease, complicated after parathyroidectomy by symptomatic hypocalcaemia and magnesium deficiency, both of which responded dramatically to the administration of magnesium. Urinary cyclic AMP assays were used to monitor parathyroid activity.


REM sleep induction by physostigmine infusion during sleep. Physostigmine (an anticholinesterase agent that increases acetylcholine at the synapse), in a dose of 0.5 milligram, was given intravenously to seven normal human volunteers. When injected during rapid eye movement (REM) sleep, physostigmine woke the subjects, and when injected during non-REM sleep, it induced REM sleep. This result suggests that cholinergic mechanisms play a role in the induction of REM sleep and in modulating cortical arousal mechanisms.


Human glyceraldehyde-3-phosphate dehydrogenase in man-rodent somatic cell hybrids. The human enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) forms heteropolymers with the rodent enzyme in man-rodent somatic cell hybrids. A gene specifying GAPDH is syntenic with the genes specifying the glycolytic enzymes triosephosphate isomerase (TPI) and lactate dehydrogenase B (LDH-B). The synteny of GAPDH, TPI, and LDH-B is the first evidence for the syntenic association of human genes that specify enzymes of the Embden-Meyerhof glycolytic pathway.


Theiler's virus-induced demyelination: prevention by immunosuppression. The effect of immunosuppression with cyclophosphamide and rabbit antiserum to mouse thymocytes on demyelination induced by Theiler's virus in SJL/J mice was ascertained from Epon-embedded sections (1 micrometer) of the central nervous system. Immunosuppression not only eliminated mononuclear cell infiltrates in the spinal cord white matter, but it also prevented the occurrence of demyelination. These results suggest that demyelination in this infection is immune-mediated.


Blockade of prolactin action by an antiserum to its receptors. A guinea pig antiserum to prolactin receptors selectively inhibited the binding of [125I] prolactin to its membrane receptors as well as prolactin-mediated incorporation of [3H] leucine into casein and transport of [14C] aminoisobutyric acid, but was without effect on the binding of [125I] insulin and insulin-mediated events in explants of rabbit mammary glands maintained in culture. These findings provide direct evidence for an obligatory functional role of a membrane receptor in mediating the action of a polypeptide hormone.


Neurotransmitter regulation of adenosine 3',5'-monophosphate in clonal nerve, glia, and muscle cell lines. Norepinephrine increases the intracellular level of adenosine 3',5'-monophosphate (cyclic AMP) in clonal cell lines of nerve, glia, smooth muscel, and skeletal muscle. The largest response is in skeletal muscle, where the cyclic nucleotide concentration is elevated more than 500-fold. Glia and muscle cells, but not nerve cells, respond to dopamine with increased cyclic AMP accumulation. This response appears to be mediated through a beta-adrenoreceptor.


[A propos of 210 emergency endoscopies in upper digestive hemorrhage]. The authors report their experience of 210 fiber endoscopies carried out as an emergency for upper digestive hemorrhage. They emphasize the necessity of early examination and only consider here examinations carried out within 12 hours from the start of the hemorrhage. In 91.4 % of cases, a correct diagnosis was possible. More than 20% of the patients had at least two lesions liable to cause hemorrhage. In cirrhosis, esophageal varices were the cause of hemorrhage in only 50% of cases.


[Endoscopic resection of colonic polyps. A propos of 45 polypectomies]. Endoscopic resection of polyps of the colon is, no doubt, a considerable therapeutic advance. It avoids surgical operation permits histological examination and makes simple biopsy unnecessary. It is indicated in the presence of pediculated polyps of a diameter or less than 3 cm, whatever the site of the polyp. Thus we were able to remove 45 polyps without complications. The method is not indicated in a large size polyp, sessile polyps or diffuse polyposis. The follow-up is still insufficient to assess : 1) the true risk of resection which can only be undertaken after long experience of colonoscopy ; 2) the frequency or recurrent adenomas. Endoscopic resection is at present the simplest method of detection and treatment of carcinoma in situ of the colon of which we observed four cases in our series. The problem of surgical reoperation is discussed.


[Routine gastric fiber endoscopy in severe head injuries]. Gastric lesions in severe cranial trauma are almost constant, whether the patients have bled or not. Routine fiber endoscopy in 63 cases permited the authors to discover various types of lesion, some in association, whether diffuse or localised, e.g. oedema or congestion, viz. congestion, purpura, various sized ulcers, usually situated high up in the stomach, sometimes in the antrum ; their course, whether rapid or not, was often intermittent. Endoscopy is the best method of diagnosis permitting appropriate treatment.


Discontinued thrombolytic treatment: initial biological results. Changes in blood coagulation following the action of intermittent treatment with streptokinase are studied : 1) Fibrinogenemia remains at a concentration slightly higher than that obtained after the first 16 hour perfusion. 2) The thrombin time becomes considerably longer on the first day, then becomes shorter and remains slightly long throughout treatment. The theoretical interest of the rise in plasminogen levels during interruption of perfusions of streptokinase is discussed.


[Intermittent thrombolytic treatment. Results during severe, chronic arterial diseases]. 38 patients with severe chronic arteritis of the lower limbs were treated with streptokinase intermittently. All had been refused for surgical operation. One patient died, 4 others had early interruption of treatment. Eleven of the 38 patients had efficient thrombolysis confirmed by arteriography. The facts confirm the possibility of thrombolysis during chronic arterial disease. The fact that the aggravation was recent was favourable factor in prognosis. The eleven patients improved, had severe aggravation of symptomes for less than 2 months. Thus thrombolytic treatment has a place of choice in the treatment of severe arterial disease where surgery is impossible, or dangerous, owing to the uncertain state of the vascular bed below the lesion. Efficacious, it permits reconstructive surgery in cases where it had been at first refused. The use of intermittent treatment, apart from advantages of confort and cost, seems to increase the efficacy of treatment.


Rare tumors of the ear, nose and throat: synovial sarcoma of the head and neck. Synovial sarcoma is a rare neoplasm of mesenchymal origin. Contrary to earlier beliefs, this tumor does not arise from the synovial lining of joints and bursae, but develops from pluripotential mesenchymal cells through abnormal differentiation into synovial neoplasms. Macroscopically there are no distinguishing features. Microscopically the tumor is characterized by a biphasic pattern of pseudoepithelial cells and a spindle cell element with fibrosarcomatous appearance. To establish a diagnosis both features must be present, yet their relative proportions vary markedly. The tumor occurs most frequently in the extremities and rarely in other areas. Only 19 cases of synovial sarcoma of the head and neck have been reported in the literature. Two additional cases, one of the hypopharynx and one of the cheek, are reported herein.


Early bilateral eighth nerve involvement in meningococcal meningitis. A male Navy recruit had hearing loss and bilateral otitis media. Meningeal signs, not initially present, developed approximately 48 hours after admission to the hospital. Type Y meningococcus was isolated from blood cultures drawn after two days of ampicillin administered orally. Permanent, bilateral, vestibular and auditory loss resulted, in spite of adequate doses of penicillin. This unusual presentation of bilateral eighth nerve involvement was thought to be due to a localized, bilateral meningococcal labyrinthitis.


The effect of dengue virus infection on the clinical sequelae of Japanese encephalitis: a one year follow-up study in Thailand. In order to determine if prior dengue virus infection reduces the severity of Japanese encephalitis (JE), we examined 127 patients hospitalized during the 1970 JE epidemic in the Chiangmai and Lampang Valleys of northern Thailand. Patients were studied during the first 30 days after onset of JE; 120 of these patients were examined one year later for residual neurologic sequelae. About 21% of patients had serological evidence of a prior dengue virus infection. Morbidity and mortality in patients with and without prior dengue virus experience were compared. These comparisons were made within two age groups to exclude differences due to age alone;


Parasitology survey in the Palu Valley, central Sulawesi (Celebes), Indonesia. A survey was undertaken in the Palu Valley, Central Sulasesi to determine whether schisto somiasis japonica was endemic in the area and to determine the prevalences rates of intestinal and blood parasites. Seven villages along the Palu River drainage system with an estimated popualtion of 18,700 were surveyed and 2,433 stools, 3,651 blood smears and 1,167 sera were collected and examined.


Portacaval shunt in two patients with homozygous type II hyperlipoproteinaemia. We report the clinical and biochemical course of 2 patients who underwent portacaval shunting for the relief of homozygous type II hyperlipoproteinaemia. In our first patient, the initial favourable clinical and biochemical response subsequently deteriorated and a splenoportogram revealed the presence of a blocked splenic vein with a large collateral blood supply to the liver. The second patient has responded quite dramatically; there has been relief of her preoperative anginal attacks and a significant fall in her plasma cholesterol concentration. The present role of portacaval shunts in the management of this conditions is discussed.


Pituitary and ovarian function in women with vesicovaginal fistuale after obstructed and prolonged labour. This study concerns 11 patients with menstrual disorders dating back to an obstructed and prolonged labour, and 5 women with similar histories but without menstrual disorders. All patients were able to secrete gonadotrophins. According to the gonadotrophin pattern, the patients could be divided into three groups: in the amenorrhoeic and in 2 normally menstruating women various degrees of suppression of basal and peak levels of luteinising hormone (LH) could be observed; patients with infrequent menstrual periods showed temporarily arrested secretion of gonadotrophins and ovarian steroids; and in polymerrhoea a non-cyclic but high secretion was seen. The gonadotrophin response to oestrogen levels was temporarily or permanently disordered in all but 3 patients in this series, whereas an ovarian refractoriness to gonadotrophins was only infrequently observed. There were 2 cases of 'ovulatory amenorrhoea' as judged by the normal profiles of ovarian steroids. Biopsies indicated inadequate endometrial transformation in many cases of amenorrhoea. Abnormal responses to the stimulatory tests of pituitary secretion of human growth hormone (HGH) and/or LH were seen in 6 patients. The study suggests that menstrual disorders after obstructed labour are associated with derangement of different hypophyseotrophic areas of the hypothalamus.


Antibacterial activity of oxidized regenerated cellulose. It has been demonstrated that oxidized regenerated cellulose promptly and markedly reduces the bacterial census of ten different strains of common pathogens when exposed to them in vitro. This was not true of two other hemostatic agents tested, namely, absorbable gelatin sponge and topical thrombin. Wounds in guinea pigs in which oxidized regenerated cellulose was placed and infected with one of three pathogens had healing per primum in 39 of 40 instances. In similar control wounds and incisions in which absorbable gelatin sponge was placed, sepsis of the wound developed in 19 of 20 of the control group and in 39 of 40 guinea pigs in the absorbable gelatin sponge group.


Orthotopic liver transplantation in ninety-three patients. During the 11 1/2 year period ending 13 months ago, 93 consecutive patients were treated with orthotopic liver transplantation. Fifty-six of the recipients were 18 years old or younger, and the other 37 were adults. The most common indications for operation were biliary atresia, primary hepatic malignant tumor, chronic aggressive hepatitis and alcoholic cirrhosis. There has been a gradual improvement in results throughout the period of study, although to a satisfactory level. Twenty-seven of the 93 patients survived for at least one year after liver replacement with a maximum of six years, and 16 are still alive after 13 to 71 months. The 11 late deaths  after one to six years were caused by chronic rejection, biliary obstruction, recurrence of hepatoma, systemic infection or hepatitis of the homograft. Rejection of the liver as judged by classical histopathologic criteria played a surprisingly small role in the heavy over-all mortality, accounting for less than 10 per cent of the deaths. Technical or mechanical problems, especially those of biliary duct reconstruction, were a far greater cause of failure, as were systemic infections. Six of the 37 adult recipients had lethal cerebrovascular accidents during, or just after, operation. When abnormalities of liver function developed in the postoperative period, the nearly automatic diagnosis of homograft rejection, in retrospect, proved to have been wrong in most instances. Further development of liver transplantation depends upon two kinds of progress. There must be reduction of operative and early postoperative accidents and complications by more discriminating patient selection, purely technical improvement and better standardization of biliary duct reconstruction. The second area will be in sharpening the criteria for the differnetial diagnosis of postoperative hepatic malfunction, including the liberal use of transhepatic cholangiography and needle biopsy. Only then can better decisions be made about changes in medication or about the need for secondary corrective surgical procedures.


Polyglactin 910 suture absorption and the role of cellular enzymes. Enzyme histochemical procedures for both hydrolase and oxidoreductase enzyme activity were applied to cryostat sections of polyglactin 910 suture implant sites. Sutures were implanted either solely in tissue or in a combination of in vitro incubation followed by implantation in vivo for total time periods of seven to 56 days. Suture absorption rates were also measured. It is concluded from the results that neither cellular nor enzyme activity is necessary for the degradation and absorption of polyglactin 910 sutures. This conclusion is based on similar absorption rates for sutures implanted solely in vivo and sutures treated in vitro and then implanted in tissue to give equivalent time spans. There were strong indications, however, that the products of suture hydrolysis are probably metabolized through the oxidative enzyme systems of cells adjacent to the suture. This mechanism of polyglactin 910 suture absorption is quite different from that observed and reported for catgut absorbable sutures.


Ascorbate inhibition of 6-aminonicotinamide teratogenesis in chicken embryos. Chicken eggs of 4 or 6 days of incubation were injected with 10 mug 6-aminonicotinamide (6-AN) or 6-AN plus various doses of sodium ascorbate, calcium ascorbate, or ascorbic acid; 11-day embryos were examined grossly and histologically. 6-AN-treated embryos had various degrees of micromelia and were reduced in overall size. All three ascorbates inhibited 6-AN teratogenesis but not completely. The extent of inhibition was dose related. Increased amounts of intercellular matrix and decreased necrosis of chondrocytes in the limb cartilage of protected embryos correlated with the gross findings.


NAD precursors as antiteratogens against aminothiadiazole. The teratogen 2-amino-1,3,4-thiadiazole (ATDA) is an antagonist of nicotinamide, and may act by interfering with the synthesis or utilization of the coenzyme nicotinamide adenine dinucleotide (NAD). Several compounds that can be converted to NAD were tested as antiteratogens against ATDA. At day 11 of gestation (sperm day = day 0) pregnant Wistar-derived rats were given single ip injections of ATDA (100 mg/kg), or ATDA immediately followed by the suspected antiteratogen ip or by gavage, or the antiteratogen alone. Compounds tested were NAD, nicotinamide, nicotinic acid, quinolinic acid, kynurenine sulfate, and L-tryptophan, in doses of 10-200 mg per animal. At autopsy (day 20) fetuses were recovered and examined. It was found that each antiteratogen significantly reduced the frequency of ATDA-induced resorptions and malformations. At certain doses each anteteratogen gave complete protection against ATDA-induced malformations in some, but not all, litters. These results support the hypothesis that ADTA interferes with the synthesis or utilization of NAD and suggest that substances converted to NAD act as antiteratogens against ATDA.


Bronchorrhoea.

Bronchorrhoea. Bronchorrohea has been defined as a condition in which more than 100 ml of sputum is produced within 24 hours, an amount in excess of that seen in chronic lung diseases. The rheological and chemical characteristics of the sputum are here described. Levels of viscosity, dry weight, N-acetyl neuraminic acid (NANA), fucose, and sulphate fall between those in saliva and mucoid sputum from chronic lung diseases. These levels were always higher in bronchorrhoea sputum than in saliva and therefore may be used in the differential diagnosis of bronchorrhoea and hypersalivation. Bronchorrhoea sputum has the constituents of a bronchial secretion but is low in acid glycoprotein. Certain other features are commonly found - a large amount of froth, increase in viscosity with time, and separation into two phases. Some cases respond to steroids, particularly when the levels of NANA in the sputum are low.


Effect of chilling on platelet cyclic adenosine 3:5-monophosphate and adenylate cyclase activity. Exposure of platelets to 1 C led to a transient increase in cyclic AMP levels (determined either by a protein binding method or by radioimmunoassay) within five to ten minutes reaching a maximum 10 to 15 minutes after chilling was begun and returning subsequently to baseline values. Addition of EDTA to the platelet suspension medium prevented this increase. Rewarming at 37 C produced a sudden reduction in platelet cyclic AMP. To determine whether the cold-induced increase in cyclic AMP was due to a transient stimulation of platelet adenylate cyclase or a rapid inhibition of phosphodiesterase, these enzymes were assayed in ruptured platelet suspensions. Platelet adenylate cyclase activity was found to possess certain characteristics similar to those of the enzyme derived from other sources but there was a marked potentiation of fluoride-stimulated adenylate cyclase activity by 0.001 M EDTA. This effect was limited to low EDTA concentrations. Exposure of platelets to 1 C for up to 60 minutes did not increase adenylate cyclase activity but lowered it substantially compared with controls kept at room temperature. Phosphodiesterase activity at 1 C was depressed sooner and to a greater extent than was adenylate cyclase. The transient rise in cyclic AMP levels in chilled platelets appears to be due to a disproportionate reduction of cyclic nucleotide phosphodiesterase activity.


[Importance of concentration factors in cryoinjury of lysosomes]. The injury degree of lysosomes isolated from the rat liver under low temperature conditions was studied with respect to nonsedimented hydrolases activities (acid RNases, DNase, phosphatase, cathepsins) taken as a biochemical criterium of lysosomal membrane stability. The lysosomal fraction was resuspended in 0.15 M NaCl solution and frozen in the liquid N2 vapours up to --30 degrees C. According to the thermographic analysis data the samples were thawed and studied at different stages of cooling. The activity of the studied hydrolases was established to increase most considerably during the water crystallization period and at the NaCl eutectic point. Hydrolytic enzymes release from lysosomes proved to be dependent on the thawing rate and NaCl concentration. The obtained data indicate to the importance of concentration factors in lysosomal membrane cryoinjury.


[The effect of standardised sodium hypochlorite solution on bacteria pathogenic for the urinary tract (author's transl)]. Stable sodium hypochlorite solution shows excellent disinfectant properties, even in higher dilution. Parallel to clinical tests in vitro experiments were made to show the changes of morphology of bacteria pathogenic for the urinary tract by scanning microscope. Two hours after incubation of the bacteria with sodium hypochlorite solution containing 40 mg available chlorine/1 severe damages of the bacterial morphology up to complete destruction were evident in all cases. Gram-negative rod-shaped bacilli were more, gram-positive cocci were less damaged.


[Activity of carbohydrate-metabolizing enzymes and content of carbohydrate and nitrogen compounds in muscles of young cattle depending on breed and sex]. The activity of glycolysis and glyconeogenesis enzymes, content of carbohydrate and nitrogen compounds were studied in muscles of 15-month cattle of different sex of the black-piebald breed and its crosses with bulls of two meat breeds Hereford and Limousine. In the muscles of bulls the activity of phosphoglucomutase, phosphohexoisomerase, aldolase and fructose-1,6-diphosphatase is considerably higher (except of the activity of phosphoglucomutase and phosphohexoisomerase in the muscles of pure-bred black-piebald animals for which difference is not statistically reliable) and the content of glycogen, glucose, fructose, lactic acid, free and phosphorylated pentoses of nonadenylic compounds is essentially lower than in the muscle tissue of heifers of analogous breed groups. A higher activity of carbohydrate metabolism enzymes (especially aldolase and fructose-1,6-diphosphate) and a higher content of total pentoses, the adenylic system pentoses, ATP phosphorus in the muscles of the cross Limousine and Hereford bulls and Limousine heifers as compared to the pure-bred black-piebald animals of the corresponding sex coincide with a greater increase in the muscular tissue and more intensive synthesis of proteins in it. A considerably lower level of glycogen, glucose, fructose and a relatively high activity of carbohydrate metabolism enzymes in the muscles of cross young cattle show that disintegration of these carbohydrates is in excess of their synthesis, that is due to an increase in the energy demand connected with a more intensive synthesis of proteins in the muscular tissue. Therefore, in the authors opinion the performed kill of the cross Limousine and Hereford bulls as well as Limousine heifers, is somewhat untimely and unreasonable. At the same time the activity of all the studied enzymes in the muscles of the cross Hereford heifers, vice versa, is considerably lower as compared to the black-piebald heifers and coincides with a low gain in live weight and muscular tissue, a more rapid accumulation of glycogen and lipids and a more delayed--of proteins in the muscular tissue, that evidences for their early maturity. Therefore the further raising of the cross Hereford heifers in the farm for obtaining meat is economically less profitable. The data obtained give grounds to recommend determination of the activity of carbohydrate metabolism enzymes, especially of aldolase and fructose-1,6-diphosphate, as a test for checking the muscular tissue growth and for prognosing the meat productivity in the growing pure-bred and cross young cattle of different sex.


[Clinical use of sodium hypochlorite for local treatment and prevention of urinary tract infections and therapy of contracted bladders (author's transl)]. A stable commercial electrolytic sodium hypochlorite solution was tested in 63 urologic patients. The complete germicidal action against all sorts of bacteria was shown in suspension-tests. Irrigation studies of the infected bladder were performed. It was found that continued bladder irrigations were necessary to stop bacterial ascension from the infected urethra. Bladder capacity was increased in 6 of 8 patients with nonmalignant contracted bladder or interstitial cystitis. Desinfection with sodium hypochlorite in urologic practice is cheap, easy to perform and diminishes the risk of hospitalism. Clinical studies confirmed the absence of general or local toxicity.


[Peculiarities of disturbances in oxidation and phosphorylation processes in rat liver under the effect of mononitrophenols]. It is determined that ortho- and n-nitrophenol introduced into the stomach (0.80 and 0.11 g/kg, respectively) inhibit the activity of cytochrome oxydase (by 21% at an average), cause an increase in the content of NADH (by 35 and 27%) and a decrease in ATP (by 38 and 36%, respectively), split the oxidation and phosphorylation processes in the rat liver tissue. The content of NAD+, AMP and ADP, lactate, the activity of K+, Na+-ATPase and lactate dehydrogenase do not change.


[Interrelation between changes in RNA transcription and glycine-14C incorporation into protein peculiar to hepatoma PC-1]. Incorporation of labelled precursor, glycin-1-14C, into the fraction and individual subfractions of blood serum immunoglobulin G (namely into protein positively reacting in the precipitation test) testifies to the fact that at early stages of the tumour development in the rat organism there occurs an intensive synthesis of protein peculiar to hepatoma PC-1. Actinomycin D in a dose blocking the appearance of the peculiar protein in the blood serum of rats with the tumour has a selective effect on the transcription of liver nuclear RNA in rats with hepatoma PC-1. Its inhibitory effect is most pronounced with respect to ribosomal RNA and one of the fractions of DNA-like RNA--RNA-85. It is observed that the fraction of DNA-like RNA--RNA-63, being stable to the effect of actinomycin D at normal state and with liver regeneration is inhibited to some extent by the antibiotic with the presence of the tumour in the rat organism.


An outbreak of acute pneumonia in young, single-suckled calves. An outbreak of acute severe pneumonia which affected six to 14-week-old single-suckled calves, resulted in 45/77 requiring treatment. The examination of paired sera from all affected calves revealed that neither an adenovirus, non infectious bovine rhinotracheitis virus nor parainfluenza 3 virus was involved. The acute exudative interstitial pneumonia found at post mortem was typical of pneumonic pasteurellosis.


Relationship of porcine cytomegalovirus and B bronchiseptica to atrophic rhinitis in gnotobiotic piglets. Both porcine cytomegalovirus (PCMV) and Bordetella bronchiseptica produced rhinitis and pneumonia when inoculated intranasally into young gnotobiotic pigs. With PCMV the nasal lesions were confirmed to the lamina propria, while Bordetella produced atrophy of the turbinate bones and hyperplasia and degeneration of the nasal epithelium. Some exacerbation of the lesions was observed in the nasal mucosa of pigs given both agents, but the degree of bone atrophy was not increased.


Initial studies on "six months disease" in sheep. Enterotoxaemia in sheep due to Clostridium welchii type D was indicated by field and laboratory investigations in Nepal. Morphological, cultural, biochemical, biological and toxin-producing characteristics observed were used to type the isolates. In anaerobic meat medium, all isolates produced pinkish discoloration of meat. All the strains fermented lactose, maltose, dextrose and sucrose whereas, salicine was fermented only by 17 strains. All but five strains were MR negative. Out of 200 isolated, 166 produced both alpha and epsilon toxins and the remaining 34 non-toxogenic strains are likely to be variants which have lost their toxogenicity. Epidemiologically the local name "Six months disease" and enterotoxaemia are considered to be identical diseases.


[Studies of the complement fixation reaction in infectious rhinotracheitis in cattle]. The complement-fixation reaction was used in the diagnosis of infectious bovine rhinotracheitis establishing its specificity and effectiveness. Highest titers of the antigens tested (up to 1:16) showed antigens that were concentrated with the use of poly ethylene glycol. In performing the test both the antigen and the complement were used in a dose that contained two units of each of them. Thus the use of the complement-fixation test proved instrumental in determining specific complement-fixing antibodies in animals that had recovered from the disease, or animals that had latent infection or had been vaccinated. The titers established usually ranged from 1:2 to 1:8, and in single cases they reached 1:128. On the infected farms some animals presented both complement-fixing and neutralizing antibodies. In Herds with positive reagents was also isolated the virus of bovine rhinotracheitis.


[Obtaining the beta-globulin fractions from swine and cattle sera and a study of their immunological activity]. The rivanol precipitation was used to obtain beta-globulin fractions from specific swine sera against edema disease, paratyph and Aujeszky's disease as well as from normal ovine and swine sera. Agar electrophoresis revealed that the preparations produced contained beta-globulin (86 per cent), gamma-globulin (5 per cent), and alpha2-globulin (9 per cent). The beta-globulin preparations were studied for the presence of antibodies against E. coli, Salmonellae, staphylococci, myxovirus parainfluenza-3, adenoviruses, and the virus of Aujeszky's disease. The beta-globulin fraction of the specific serum against edema disease was shown to contain OK and O agglutinizing antibodies against E. coli, having a titer of up to 1:3200, and the gamma-globulin titers of up to 1:12800. The beta-globulin fraction of the specific serum against typhoid contained OH and O agglutinizing antibodies against Salmonella cholerae suis with a titer of up to 1:2560. The agglutinizing antibodies against staphylococci were twice as much in the beta-globulin fraction as compared with those in the gamma-globulin fraction. The antibodies against Aujeszky's disease and the adenoviruses in the beta-globulin fractions were in negligible amounts, and the titer of the antibodies against myxovirus parainfluenza-3 ranged from 1:128 to 1:512.


[Early histoenzymologic and ultrastructural changes induced by adrenalin-thyroxine and fat diet in rabbit aorta (author's transl)]. The first stages of the atherosclerotic lesions induced in the rabbit aorta by adrenalin- thyroxine, with (or without) an hypercholesterolic diet, have been studied on the 6th, 13th, and 22nd day. Major parietal changes, barely demonstrable with light microscopic standard techniques, were detected, as soon as the 6th day, by electronmicroscopy and histoenzymology. These changes were probably due solely to the hormonal treatment. In the early stage, they consisted of some fragmentations of the elastic sheets and some smooth muscle cell lysis. The oxidative and ATPase activities were greatly reduced. The increased lysosomal hydrolase actitivities of the outer layers of the vessel could be related in the increased vascular permeability and consecutive increased perfusion gradient induced by these lesions. Later, an obvious repair process was seen. The smooth muscle cells bearing numerous processes were bound by many microfilaments and by some elastic material. The energetic enzymatic activities were increased. The part taken by the lipidic diet in these changes, apart from the increase of the esterase activity, did not seem yet of significance in this first stage of atherosclerosis. However, one cannot exclude that the intensively accumulating lipids might, at some later stages, potentiate the consequences of the vascular lesions or impede the repair process.


[Reduction of oily substances in rabbit lungs (author's transl)]. Artificial fat embolism in rabbits was caused by injection of olive oil and Lipiodol Ultrafluid into the ear vein. Electron-microscopic and histochemical observations of the lung were made. The content of nonspecific esterase was evaluated. Serious defects of blood vessels and pneumocytes as well as an increase in alveolar macrophages and capillary thrombosis were noted. The endothelial cells became considerably larger and necrosis of endothelial cells and capillary destruction even occurred. Fat appeared interstially and in the alveolus. Tissue reaction is much greater in olive oil than in contrast medium. This is due to their different chemical composition. The strong tissue reaction in olive oil is caused by glycerol and unsaturated fatty acids occurring in hydrolysis. Fat emboli are primarily eliminated by enzymatic splitting. Normally alveolar macrophages and endothelial cells contain little nonspecific esterase. After application of fatty fluids they react with an increase in the content of esterase. Alveolar epithelium seems to participate in enzymatic fat splitting.


Pigmentation and dysfunction of Gunn rat thyroid: correlation between morphological and biochemical data. The thyroid gland of homozygous Gunn rats is moderately enlarged and displays a brownish-black discoloration. Light microscopic examination discloses that the follicular cells are filled with brown granules, which are shown, under the electron microscope, to be modified colloid droplets. Most of them possess a strong acid phosphatase and a mild peroxidase activity and contain a melanin-like pigment, according to histochemical analysis. In comparison with normal Wistar rats, Gunn rats possess significantly higher plasma thyroxine and lower triiodothyronine as well as an increased plasma TSH level. The soluble protein content of the thyroid is reduced in the Gunn rat, as is the total intrathyroid iodine content. The hyperthyroxinaemia of homozygous Gunn rats is due to a hereditary deficiency in hepatic glucuronyl transferase activity. The excess circulating thyroxine is of little functional importance because it is firmly bound to plasma proteins. But Gunn rats have a slight hypothyroid goitre for reasons not yet elucidated. The functional as well as morphological data at present available suggest a modified thyroid iodine metabolism and an altered composition of the thyroglobulin which may induce abnormalities in colloid proteolysis. The observed pigment may result from peroxidation of tyrosine. These alterations are probably independent of the sole enzymatic deficiency so far encountered in these animals and may probably be ascribed to a primary enzymatic defect in the thyroid gland itself.


Mass occurrence of multilamellar bodies in myopathy. In a case of atypical myopathy submicroscopic examinations revealed intact ground structure and large number of solitaer, regular multilamellar bodies. The author suggests, in accordance with literary data, this typical alteration to be due to the applied short term Chloroquine treatment.


Concentric nuclear inclusions.

Concentric nuclear inclusions. Membrane bound concentric lamellar inclusions were found in the nuclei of pancreatic acinar cells of a patient with multiple primary neoplasms and in the parotid acinar cells of a patient with systemic lupus erythematosus. It is proposed that these inclusions form from rough cisternae sequestered in the nucleus.


Glomiform and fibrillar cytoplasmic inclusions. Glomiform inclusions, also called tubular arrays in endoplasmic reticulum, are found in the epithelial cells of glandular tissues of a patient with systemic lupus erythematosus, a patient with Reye's syndrome, and a dog. Their three dimensional structure is interpreted as a skein of contorted tubules of endoplasmic reticulum. Fibrillar inclusions found in the pancreatic acinar cells of two patients are believed to represent altered zymogen granules.


[The effect of megavolt radiation therapy on glioblastoma multiforme]. The paper deals with morphological changes in glioblastoma multiforme following megavoltage radiotherapy (1.25 and 25 MeV). Both tumour cell death and glioblastoma multiforme tissue destruction resulted from 6,000-7,500 rads megavoltage irradiation. Depending upon the time following irradiation the histological study showed the prevalance of either acute aseptic inflammation, or coagulation necrosis, or degenerative changes leading to the formation of glial and connective tissue scars and dystrophic calcification. Glioblastoma multiforme, rich in cell elements with hyperchromatic nuclei and having a high mitotic activity, proved to be the most radiosensitive tumour. The highest radioresistance was noted in tumours with a tendency to haemorrhages and necroses.


[Synthesis of virus-specific macromolecules and virion maturation in chick embryo cells infected with Sendai virus]. Synthesis and accumulation of virus-specific RNA, proteins and intracellular nucleocapsids are observed in Sendai virus-infected chick embryo cells for approximately 2 days postinfection. However, only an insignificant part of these products leaves the cell as a result of maturation of virus particles. It is suggested that the cause of the ineffective maturation of virions in the system under study may be in the observed instability of one of virus structural proteins in the infected cells, M protein. Some other suggestions on the mechanisms of nonpermissiveness of paramyxovirus systems expressed in literature earlier are also discussed.


[Identification of a hemadsorbing agent discovered in uninfected mouse L cell cultures and also the same cultures chronically infected with Sindbis virus]. Electron microscope examinations of continuous lines of mouse L cells, both uninfected (L-init) and chronically infected with Sindbis virus (L-SV) revealed accumulations of ribonucleoprotein strands and virions corresponding by their parameters to paramyxoviruses in the cytoplasms of the cells. Further studies showed L-init and L-SV cell lines to have a manifest hemadsorption effect which could be completely inhibited by antiserum to parainfluenza SV5 virus. Immunofluorescence procedures detected intensive fluorescence in the cytoplasm of these cells which was observed only after treatment of the cells with antiserum to SV5 virus. In response to inoculation of cell homogenates of continuous L-init and L-SV cultures guinea pigs developed antihemagglutinating antibody to simian parainfluenza SV5 virus. On the basis of these results it may be assumed that virus-specific structures and viruses identical by their parameters to paramyxoviruses observed in electron microscope examinations of continuous mouse L-init and L-SV cells are simian parainfluenza SV5 virus.


[Protein metabolism in chick embryo cells infected with Sendai virus]. Inocluation of chick fibroblasts with Sendai virus results in a significant increase of protein synthesis. In cytoplasmic extracts of infected cells the content of polyribosomes increased and that of free (nontranslating) 80S ribosomes decreased, the "additional" polysomes of the infected cells being involved in protein synthesis. The portion of virus-specific protein synthesis in the infected cells was about 40% of the total protein synthesis. This means that with the total increase of protein synthesis 2-fold and (in some experiments) higher, the summary synthesis of cell proteins proper is not inhibited (possibly, it is slightly increased). Quite effective synthesis of virus-specific proteins for a comparatively long period after infection and ineffective maturation of virions eventually lead to a rather considerable accumulation of virus-specific proteins in the infected cells. The total content of protein in samples prepared 2 days after infection is approximately 1-1/2 as high as in uninfected samples.


[Cytomegalovirus disease in the course of histiocytosis X (AUTHOR'S TRANSL)]. A 3 1/2 year-old boy was treated with cytostatic drugs for progressive histiocytosis X. 9 months later he acquired cytomegalovirus disease, the diagnosis being proven by liver biopsy. The causal relationship of immunosuppressive side effects of the treatment and this cytomegalovirus infection is discussed.


[Pseudohypoparathyroidism: investigations of the serum parathyroid hormone level, pte resistance and urinary camp excretion before and during vitamin d treatment (author's transl)]. Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs, oligophrenia and clinical and laboratory signs of hypoparathyroidism, which is resistant to parathyroid extract (PTE). Pseudopseudohypoparathyroidism (PPHP) is a genetically identical, partial form of PHP without hypoparathyroidism. Many hypotheses exist to explain the pathogenesis of these disorders: Albright and coworkers first demonstrated the PHP is caused by an inability of the renal tubules to respond to parathyroid hormone (PTH). Later hypotheses proposed a general defect in phosphorus transport, defects in the synthesis of PTH, the existence of antibodies to this hormone or hyperthyrocalcitonism. The possibility of measuring PTH in the peripheral serum by radioimmunoassay and improved knowledge of the role of cyclic adenosine monophosphate (cAMP) as a mediator of the action of PTH were necessary to explain the pathogenesis of PHP and PPHP. Three children suffering from PHP and two adults with PPHP were investigated as follows: measurements of PTH in the peripheral serum; assays of PTH levels during artificial hypercalcaemia; serial assays of calcium, phosphorus and PTH levels during vitamin D treatment; changes in the Ellsworth-Howard tests indicative of PTE resistance during vitamin D treatment and measurements of urinary cAMP excretion before and during vitamin D therapy. The following results were obtained: Secondary hyperparathyroidism in PHP, which could be suppressed by hypercalcaemia; normal levels of PTH in PPHP; normalization of serum calcium, phosphorus and PTE during treatment with vitamin D; abnormally low basal levels of cAMP in PHP, which could not be stimulated by PTE either before or during vitamin D treatment. The results of these investigations confirm Albright's hypothesis of endorgan resistance to PTH in PHP. This is caused by the inability of the PTH-sensitive adenylcyclase-system to mediate the action of PTH on its target cells. This is responsible for the distrubances in calcium and phosphorus metabolism and for secondary hyperparathyroidism. While this mediatorial defect seems to be total or almost total in PHP, a partial defect has to be assumed in PPHP.


[Variants of parainfluenza type 2 viruses]. A comparative study of the antigenic and biological properties of parainfluenza type 2 viruses revealed the existence of two variants among them. The first variant includes strains isolated up to 1965 inclusive, the 2nd those isolated in 1966--1974. The strains of the 2nd variant are characterized by poor interaction with antibody in immune sera to the reference virus which appears to be due to a loss of one of the antigens in them. Besides, they have comparatively low immunogenicity and the hemagglutinating activity and higher sensitivity to inhibitors. The paper emphasized the necessity of using immune sera to strains isolated in recent years, in addition to reference sera, for identification of new isolated of parainfluenza type 2 virus.


[Sensitivity of normal and Rous virus-transformed lines of Armenian hamster cells to infectious viruses]. The capacity of normal (NHET) and Rous virus-transformed cell line of armenian hamster both producing (SHET Sh-R) and not producing (SHET K-3) virus to support reproduction of vaccinia and Newcastle disease viruses was demonstrated. The former of these viruses replicated in the cell cultures with cytopathic effect, the latter did so without causing cell degeneration. The degree of Newcastle disease virus reproduction in all 3 cultures was the same whereas vaccinia virus synthesis in SHET Sh-R was inhibited as compared with NHET and SHET K-3 cultures. Interference between Rous virus and vaccinia virus in SHET Sh-R culture was not due to interferon. The infectious viruses under study caused no activation of Rous virus genome in the virogenic SHET K-3 cell line.


[Recognition of influenza and other acute respiratory virus infections and their combinations by means of immunofluorescence]. The results of postmortem examinations performed in 237 fatal cases of influenza and other acute respiratory diseases are presented. In smears of organs and tissue culture cells infected with these materials and heart blood the immunofluorescent procedure detected influenza virus antigens in 67% of the cases, antigens of other respiratory viruses in 53% including 18-19% of mixed infections. Parallel immunofluorescent studies in living patients and isolation of influenza virus and adenoviruses increased per cent of influenza case confirmation to 82%, other respiratory infections to 63%. Mixed infection was recorded in 22-28%. Antigens of influenza and parainfluenza viruses were more frequently found in smears of bronchi and trachea, antigens of respiratory syncytial virus and adenovirus in lung smears. Adenovirus antigen was also found in lymphoid cells of smears of the spleen, bronchial lymph node, tonsils. In immunofluorescent examinations of tissue cultures infected with the heart blood, virus antigen was detected most frequently in influenza and adenovirus infection (24% and 26% of cases, respectively), less frequently in respiratory syncytial virus infection (11%) and parainfluenza (5%). Virus antigens were also demonstrated in tissue culture cells infected with specimens of the liver, spleen, bronchial lymph node, tonsils, brain. The immunofluorescent studies demonstrated long-term persistence of virus antigens in the body. In a portion of cases of laboratory confirmed mixed infection there were no clinical-morphological signs of two virus diseases. In these, one of the infections was latent or was due to a previously experienced disease.


[Study of the population composition of the Rous sarcoma virus Carr-Zilber strain]. The population composition of the Carr-Zilber high titer (HT) strain of Rous sarcoma virus (C-Z-RSV) was analysed with regard to 2 features: the capacity to impart oncogenicity for syngeneic recipients to infected but untransformed cultures of mouse embryo tissue (MET), and oncogenicity for mice. With regard to these features the C-Z-RSV (HT) strain was found to be heterogenic and to consist of particles of at least two types: non-oncogenic for mice and incapable of causing early malignization of MET, and oncogenic for mice and causing early malignization.


Histochemistry and histoenzymology of the hydatid cyst (Echinococcus granulosus Batsch, 1786). I. The germinal membrane. Healthy germinal membranes of hydatid cysts from lungs of human and bovine sources were dissected and isolated for histochemical and histoenzymatic research. These techniques were performed in frozen sections and pieces of the whole membrane. Enzymatic research showed that the germinal membrane presents highly differentiated metabolic areas. These areas were topographically related with the origin and insertion of brood capsules, having differentiated structures for metabolic interchange with scolices. Taking our data into account it may be suggested that this functional differentiation could be transitory and variable for all the membrane surface. The accumulation of lipids and enzymes such as simple estarase, lipase, beta-HDH, alpha-GDH and NADPH-reductase in those areas, suggests that lipids are not a simple excretory product. This distribution probably implies that lipid metabolism or its resultant products are important in development and growth of scolices. In that sense other authors' findings and hypothesis about the possible existence of an endocrine system of the parasite, are considered. This idea being demonstrated in further researches, the lipid metabolic pathways shall bring a good pharmacological approach to the interference with parasite development.


Freeze-etching observations of trophozoites of pathogenic Entamoeba histolytica. Pathogenic Entamoeba histolytica trophozoites were studied by the freeze-etching (FE) technique of electron microscopy. Surface replicas of intact cell membranes were highly convoluted with numerous invaginations, evaginations, and undulations. Sperical depressions and elevations varying from 0.5 mu to 1.0 mu in diameter were commonly present on the external cell membrane and appeared to represent an extracellular secretory mechanism of trophozoites. Cleaved surfaces of amebae exhibited a granular and lumpy cytoplasm in which there were many vesicles and vacuoles that ranged in diameter from 0.2 mu to 9.0 mu. Some vacuoles contained tightly enveloped bacteria, while others contained bacteria and host cytocomponents. Occasional vesicles and vacuoles appeared to be fused to each other. Replicas of FE nucleus were enclosed by double nuclear membranes which were fenestrated by numerous sperical pores measuring approximately 640 A in diameter and spaced at intervals of 650 A. Counts of nuclear pores were possible and indicated 35 pores per square micron on the nuclear envelope. Golgi apparatus, mitochondria and well formed endoplasmic reticulum were absent in FE replicas. This was in agreement with electron microscope observations on thin sections previously reported by other investigators.


[Application of a demographic method for the study of adenoviruses and herpesviruses in a closed infantile community (author's transl)]. Rate of seroconversions to adenoviruses, cytomegaloviruses (CMV) and Epstein-Barr virus (EBV) was studied from 1965-1973 in 200 infants living in a closed infantile community. The transversal demographic table method was used to evaluate the results of sera examined. Seroconversion occurs earlier in the case of adenoviruses with also possess in higher intensity of infection. The intensity of seroconversions to EBV capsid antigen is a little lower, but of all three viruses examined, the spreading of infection is the slowest. On the other hand, seroconversion to CMV occurs earlier than EBV capsid antigen, but intensity of infection by this virus is lowest.


[Study of the behavior of poliomyelitis virus type 1 in diffrerent hydrous media (author's transl)]. After having analyzed several surveys on natural inactivation of viruses in water, the authors have attempted to determine the survival life of poliomyelitis virus type 1 in hydrous medium, of known composition, well-buffered and devoid of any bacterial contamination on the one hand, and on the other hand, in a similar medium with addition of organic humate-type substances. The experiment was carried out at 4 degrees C and at laboratory room temperature (18 degrees C-24 degrees C). Results tend to confirm that the presence of humate-type substances seems to have no significant influence on the development of poliomyelitis virus type 1. Moreover, under the experimental conditions used, the survival life of the virus is much longer than the one previously described. It represents an average of 296 days for a storage temperature of 18 degrees C-24 degrees C. It is longer in water kept at 4 degrees C; in fact, according to statistical calculations and to titrations carried out over a period of 550 days, the total disappearance of the virus was detected only after a period of 10 to 15 years.


[Virucidal activity of the disinfectant "gigasept" against different enveloped and non-enveloped RNA-and DNA-viruses, pathogenic for men. I. Investigation in the suspension test (author's transl)]. "Gigasept" is a highly efficient chemical disinfectant on the basis of succine dialdehyde and form aldehyde. The virucidal capacity was assayed in the suspension test procedure with different representative RNA and DNA viruses with and without an envelope, such as polio wild virus type I, coxsackie virus type B 3, adeno virus type 3, herpes virus type ) and vaccinia virus. Parameter for disinfectant activity was the virus inactivation kinetic, i. e. interdependence of titer reduction vs. disinfectant concentration and disinfectant contact time. A "minimal disinfection" was defined as a greater than or equal to 99.9% virus inactivation. A "disinfection per definitionem" must gain a titer reduction of greater than or equal to 10(3) ID 50 and absence of virus. According to these criteria all virus strains were inactivated by Gigasept regardless of absence or presence of serum, which was tested in a concentration of 40% calf serum. Disinfection per definitionem was achieved with Gigasept concentrations of 3% after 60 min. or 5% after 30 min. except for enteroviruses. This group of viruses has to be disinfected with a 10% solution for 4 hours or with a 5% solution overnight. Gigasept, on the basis of these results, can be classified as a highly effective virucidal disinfectant. As to the hepatitis virus group however, no data so far are available. An enterovirus - disinfection procedure is recommended in hepatitis risk areas, as long as test systems for hepatitis viruses are not developed.


[Cytomegalovirus antibodies in the pregnant female and in the newborn infant complement fixation and indirect hemagglutination tests (author's transl)]. 705 paired sera from mother and infant have been studied at the time of the child birth for the presence of cytomegalovirus antibodies by complement-fixation and indirect hemagglutination tests. 51.3% of those sera were found to have CF antibodies, and 72.8% to have HA antibodies. The indirect hemagglutination test is a more sensitive reaction and detects also IgM antibodies. Chosen sera were fractionated and searched for IgM-HA antibodies to detect CMV congenital infections; only one child was found to be positive. The number of mothers having been in contact with cytomegalovirus was 82.7% (having CF or HA antibodies or both). Immigrant were found to be more often positive than native women (94.3% vs 76.1%); this difference was even greater when CF antibodies alone were considered (74.6% vs 37.7%). Depending on age groups of mothers, the increased number of positives found in CF test was not noticed in HA test.


[The potentiating effects of azathioprine and azapropazone on the enzyme activity in experimental inflammation]. The influence of prednisolone, azathioprine, and azapropazone on the activity of collagen peptidase, acid phosphatase (complete), and the lactate dehydrogenase of granulation tissue was studied using a model of proliferative inflammation i.e. the cotton-granuloma in rats. The authors observed significant decreases in the activities of the collagen peptidase and acid phosphatase during treatment with prednisone and under combined treatment with azathioprine and azapropazone. In contrast, administration of either azathioprine or azapropazone by itself caused no changes in these enzyme activities as compared with a control group. These studies suggest that the last mentioned drugs potentiate each other in their inhibiting effect upon these enzyme activities. Whether or not these findings are of importance in the clinical treatment of chronic bacterial inflammations must be studied in further trials.


[Method of determinating the protective capacity of C1. perfringens toxoid]. The authors describe a model of experimental gas gangrene in guinea pigs; it was produced by the administration of the vegetative form of C. perfringens; the cells were completely washed of the lethal toxin and no toxic or necrotizing agents were added. A possibility of development of gangrenous process without any preliminary depression of the resistance of body tissues in the area of injection of the causative agent was revealed. Apart from the local process and general intoxication gas gangrene, caused by intramuscular injection of C1. perfringens to guinea pigs, was accompanied by bacteriemia and microbial contamination of the internal organs. A method of the animal infection was ascertained and the causes of their death was assessed. The method is recommended for determination of the immunological efficacy of C1. perfringens toxoids.


[Restoration of the automatic contractile activity of K+-arrested heart muscle cells in culture by means of dibutyryl-3', 5'-adenosine monophosphate]. Cultured myocardial cells of new-born rats which were arrested by 17.6-37.6 mM KCl regained their ability to contract spontaneously after perfusion with 8-10(-4)-4-10(-3) M dibutyryl cyclic AMP. This adrenaline-like action of DbcAMP is compatible with the notion that cyclic AMP is involved as a second messenger in the action of cyclic AMP-raising adrenergic agents on cardiac activity.


Biogenesis of corticosteroids in monolayer cultures of human foetal adrenal cells. Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [14C] and [3H] precursors. ACTH stimulated  corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer.


Utilization of dehydroepiandrosterone and its sulphate for oestrogen production by pregnant baboons (Papio papio). The effect of varying maternal circulating 3beta-hydroxy-5-androsten-17-one (D) and its sulphate (DS) on urinary oestrogen (Oe) excretion by baboons was determined between 65 and 174 days gestation (term = 184 days). Oe (mainly oestrone) was determined by radioimmunoassay after enzymic hydrolysis of conjugates. Increments in Oe were estimated from the difference between Oe during 5 days pre- and post-treatment. Oestradiol-17beta (5 mg in 5.0 ml saline-ethanol, 1:1) administered iv increased (P less than 0.001) Oe by 2.46 +/- 0.71, 7 (mean, mg +/- SD, number of experiments). The response to 100 mg D (3.20 +/- 1.50, 7) was greater (P less than 0.001) than that due to 100 mg DS (0.03 +/- 0.75, 7). The response to DS was not different from that due to saline-ethanol alone (-0.05 +/- 0.27, 5). Betamethasone (9alpha-fluoro-11beta,17,21-trihydroxy-16beta-methyl-1,4-pregnadiene-3,20-dione) administration (3 mg bi-daily, im) caused an approximately 90% reduction in Oe within 4 days. In animals treated chronically with betamethasone the response due to 100 mg D (2.74 +/- 1.04, 5) was again greater (P less than 0.001) that that due to 100 mg DS (0.10 +/- 0.09, 5). ACTH (8 U or 40 U, im, N = 11) produced a variable but not significant mean change in Oe at either dose level. Metyrapone (300 mg every 4 h for 6 doses) increased (P less than 0.005) Oe (0.77 +/- 0.48, 5). It is concluded that in normal pregnant animals and those treated with betamethasone, in which endogenous levels of D and DS are presumably reduced, D is preferentially used over DS for oestrogen produced. Variations in DS availability do not produce marked changes in oestrogen production. This suggest that rapid increases in oestrogen production, as occur for example close to term, may result from increased availability of D rather than DS. The variable responses to ACTH and the increase in Oe following metyrapone administration are compatible with significant foetal contributions of oestrogen precursors, the production of which is under ACTH control.


Effect of prolactin, growth hormone and insulin on the uptake and binding of dihydrotestosterone to the cultured rat ventral prostate. The effects of prolactin, growth hormone and insulin on the total uptake and specific binding of tritiated dihydrotestosterone in the cultured rat ventral prostate were examined. In similiar conditions prolactin and insulin act synergistically with testosterone on the macromolecule synthesis of the prostate, but have no effect on the conversion of testosterone to dihydrotestosterone. The total uptake of tritiated dihydrotestosterone to the tissues was slightly, but not statistically significantly, increased by prolactin, insulin and growth hormone. The majority of the radioactive dihydrotestosterone in the tissue was in free form or very loosely bound. None of these three hormones altered the binding of tritiated dihydrostestosterone to the cytoplasmic receptors. Non-radioactive dihydrotestosterone, cyproterone and cyproterone acetate in 1000 fold excess strongly decreased the binding of tritiated dihydrotestosterone to the cytoplasmic reseptors and to the nuclei. That part of the binding, which was inhibited by the hormones was considered to represent the specific binding to the receptors. Insulin stimulated both the specific and the unspecific uptake of dihydrostestosterone to the nuclei. Prolactin only stimulated the specific uptake to the nuclei while growth hormone had no effect. Autoradiography of the nuclear fraction indicated a firm binding of tritiated dihydrotestosterone to the nuclei. The radioactivity of the other contaminating cell components in this fraction appeared to be negligible.


Infectious mononucleosis in a patient with Hodgkin's disease. The case is presented of a patient, treated for Hodgkin's disease, who contracted infectious mononucleosis more than 3 years later. While Epstein-Barr virus has been considered a possible etiologic factor in Hodgkin's disease, the sequence of events reported in this case has to be interpreted as evidence against a causal relationship between the virus and Hodgkin's disease in this patient.


Cytochemical leukocyte reactions in normal children. Five cytochemical reactions in current use (MPO, PAS, LAP, SB and EST) were operated on 180 children aged 1 month to 6 years, divided into three age groups (less than 12 months, 1-3 years and 3-6 years). No significant differences are apparent from one group to another, and the mean values are identical with those of adults. On the other hand, certain variations are evident in comparison with the scores of newborn children: important decrease in LAP, increase in SB, EST and PAS. These tests should be done in investigations of inborn metabolic errors, chromosome anomalies, blood diseases, and defects in defense mechanisms.


Malignant mixed tumor of the liver: report of a case and a review of the literature. Malignant mixed tumor of the liver seen in a 4 year old girl was reported. Progressive hepatomegaly, jaundice, anemia, and extraordinarily high level of serum total cholesterol were noted clinically. Postmortem examination had disclosed that most part of the tumor was occupied by fibrosarcomatous cell growth admixed with rhabdomyosarcomatous component. In addition, carcinomatous component was distinctly recognized in a restricted part of the liver tumor. Previous reports on malignant mixed tumor of the liver were reviewed and it was emphasized that the histological diagnosis of malignant hepatic mixed tumor must be cautiously followed Edmondson's criteria; which requires existence of both epithelial and mesenchymal components of neoplastic nature and malignancy of either or both components in a hepatic tumor.


Hormone-induced diarrhea in man.

Hormone-induced diarrhea in man. In a healthy subject infusions of either secretion or glucagon caused no diarrhea. A combinations of gastrin and glucagon induced severe watery diarrhea immediately after the end of the 3 hour infusion. No diarrhea occurred from the combination of secretin and gastrin.


SV 40 related papova-viruses in human meningiomas. Human meningiomas show characteristic chromosome aberrations very similar to those reported in human cell cultures experimentally transformed by Simian virus 40 (SV 40). Three out of eight meningiomas tested showed SV 40 specific tumor antigen but no virus capsid antigen. Experiments to rescue virus were successfully performed. Electron microscopic studies of these cell cultures revealed cytoplasmic inclusions containing virus particles which corresponded in size and morphology to Papova viruses.


Further observations on the effects of lead implantation in rat brains. Lead pellets were implanted into the forebrains of adult rats. Various cytoplasmic inclusions were found in macrophages, astrocytes, pericytes and microglia. Certain macrophages and reactive astrocytes displayed intranuclear inclusions as well. The hypothalamus, in some of the animals, showed sponginess which proved to be the result of swollen axons.


Plasma lipids and lipoproteins in protein-calorie malnutrition. Plasma triglycerides, phospholipids and total cholesterol estimations and lipoprotein electrophoresis on agarose gel were done in control, Kwashiorkor, and marasmic kwashiorkor children. The beta lipoprotein percentage in both conditions is reduced to a statistically significant extent, whereas there is a statistically significant increase in plasma triglycerides in both conditions. Pre-beta fraction was present in all cases, and even increased in marasmic kwashiorkor, which is found to be significant. The results do not support the hypothesis that fatty liver in kwashiorkor is due to impaired release of triglycerides from liver.


Two cases of phosphoenolpyruvate carboxykinase deficiency. Two children are described who suffered from hypoglycemia and liver impairment. Assays of gluconeogenic enzymes in liver samples taken immediately after death demonstrated a deficiency of phosphoenolpyruvate carboxykinase, a key enzyme of gluconeogenesis. Post mortem examination demonstrated massive fat deposition in liver and kidney and to a lesser extent in other tissues. The fatty changes in liver and kidney could be explained by the absence of phosphoenolpyruvate carboxykinase, which would cause an alteration in the mitochondrial-cytosolic processes related to gluconeogenesis.


Effects of viral and mycoplasma infections on ultrastructure and enzyme activities in human skeletal muscle. The effect on skeletal muscle of acute viral and mycoplasma infections in thirteen men of ages ranging between 20-42 years has been studied. Comparisons are made with eight healthy men in the age group 22-29 years who were confined to bed for periods of time of lengths similar to the confinement to bed of the patients. Muscle samples were taken from the thigh. Glyceraldehyde-3-phosphate (triosephosphate) dehydrogenase (TPD), lactate dehydrogenase (LDH), citrate synthetase (CS) and cytochrome oxidase (cytox) activities were measured and the ultrastructure of the muscle specimens was studied by electron microscopy. Immobilization of the healthy persons induced decreased activities of CS, but those of TPD, LDH and cytox remained unaffected. Return to normal life restored the CS activity. The activities of the four enzymes were lower in the patients than in the healthy subjects after immobilization. During normal life, the activities slowly rose to levels as those seen in the healthy subjects. In connection with the acute disease, focal ultrastructural changes within the muscle were found. The changes were similar to those reported to occur in other, more specific muscle diseases.


Specificity of hormonal responsiveness in vitro. Effect of sex steroids on non-malignant rat cells compared with the effect on cells from rat tumours. Since mammary tumours and sarcomas in the rat both have been shown to be sensitive to steroid hormone in vitro, a search for a non-steroid sensitive rat tissue was made. Neonatal cerebellar medulloblasts in the rat did not respond to high concentrations of steroids if cultured as organ culture. The relevance of this finding to the specificity of steroid response assays in vitro is discussed.


Biosynthesis of unsaturated fatty acids in cultured minimal deviations hepatoma 7288 C cells. Minimal Deviation Hepatoma 7288 C cells were cultured in confluent layer with labeled linoleic, alpha-linolenic, eicosa-8,11,14-trienoic and stearic acids. The cells in culture preserved their ability to convert stearic acid to oleic acid. They also synthesized arachidonic acid from linoleic acid or eicosa-8,11,14-trienoic acid. The conversion was very low with linoleic acid and high with eicosatrienoic acid. Eicosapentaenoic acid and other homologs of the alpha-linolenic acid family were synthesized from alpha-linolenic acid. The biosynthetic patterns were the cells was modified by the fatty acid composition of the media.


Modification of synaptic efficiency, experiments in blatta orientalis. The efficiency of synapt ic transmission in a nervous pathway--metathoracic ganglia from the cockroach--can be increased by various experimental situations, i.e., removal, immobilization or denervation of the forelegs of insects in ventral position. Leg immobilization with the insect in supine position by itself determines a minor increase which is not enhanced by removal or denervation of the forelegs. Under these conditions, the insects are able to hold their antennae with a midleg immediately after any of the leg treatments. On the other hand, if the insects are allowed to be in ventral position they can hold their antennae with a midleg only when they reach the ability to stand on the remaining three legs. During the time period needed to acquire this ability, the insects make repeated and spontaneous motor effects. The increase in synaptic efficiency observed and the achievement of the insect's ability to stand on three legs occur at about the same time. These observations suggest that the self-training determines the synaptic modifications which in turn could be related to the "learnt" behavioral reaction.


Protein synthesis in adrenal mitochondrial and post-mitochondrial fractions of ACTH-treated rats. Short and prolonged administration of ACTH was used to study the effects of the hormone on protein synthesis in two subcellular fractions obtained from rat adrenals incubated in the presence of a (14C)-labelled amino acid mixture. Acute treatment with ACTH produced an increased labelling of the proteins of the post-mitochondrial (POST-MIT) fraction only. On the other hand, treatment with ACTH for 4-28 days, significantly increased the specific activity of proteins in the mitochondrial (MIT) fraction, without change in the radiolabelling of the POST-MIT fraction. The incorporation of (14C)-labelled amino acids into the proteins of the MIT and POST-MIT fractions, from control or ACTH-treated adrenals, was reduced by inhibitors of cytoplasmic protein synthesis (puromycin and cycloheximide). This suggests that the increased labelling of the MIT fraction after prolonged ACTH might be related to a translocation of cytoplasmic proteins to the mitochondrion.


Disturbances in voluntary recruitment order of low and high frequency motor units on blockades of proprioceptive afferent activity. The voluntary recruitment order of anterior tibial motor units was studied in electromyographic recordings using both low and high impedance electrodes. It was shown in previous papers, that the recruitment order in sustained voluntary contraction is normally stable and that motor units with low thresholds discharge at low, regular frequencies and that motor units with high thresholds discharge at higher and more irregular frequencies. In this paper the consequences for the discharge properties of reduced afferent inflow in sustained voluntary contraction were studied, using partial ischemic or lidocain blockades of the muscle nerve and local cooling of the muscle belly. 1. The recruitment order of certain low and certain high frequency units was reversed. 2. The muscle tension and sense of effort necessary for tonic firing were increased for certain low frequency units but decreased for certain high frequency units. 3. On severe reduction of the afferent inflow, the differences in discharge pattern between low and high frequency units were decreased. It is concluded that the recruitment of low frequency units before high frequency units in sustained voluntary contraction is partly due to proprioceptive afferent activity favouring low frequency units and disfavouring high frequency units. It is also concluded that the afferent inflow is involved in restricting certain units to low frequency discharge and others to high frequency discharge.


Effects from the vestibulospinal tract on transmission from primary afferents to ventral spino-cerebellar tract neurones. Convergence of vestibulospinal and segmental effects onto spinal interneurones which project to the ventral spino-cerebellar tract (VSCT) neurones has been studied by intracellular recording in VSCT cells. The disynaptic Ia IPSPs evoked in a group of VSCT neurones from the quadriceps nerve are monosynaptically facilitated by the vestibulospinal tract while there was no facilitation of Ia IPSP evoked from a flexor nerve. These results support the view that Ia inhibition to VSCT cells and motoneurones is mediated by common interneurones. The disynaptic inhibition evoked in other VSCT cells from the vestibulospinal tract is facilitated by volleys in the contralateral flexor reflex afferents (FRA) or bilaterally from the FRA. It is postulated that these actions are mediated by collaterals of the interneurones responsible for the analogous effects in motoneurones. Findings are reported suggesting that the monosynaptic vestibulospinal EPSP in VSCT cells in most cases is collateral to the excitatory input to the last order interneurones of reflex pathways from the FRA to motoneurones and only exceptionally to the corresponding input to Ia inhibitory interneurones. In many VSCT cells the vestibulospinal tract evoked disynaptic EPSPs which are facilitated from the FRA; the functional significance of this action is uncertain. The results are consistent with the hypothesis that VSCT neurones signal information on interneuronal transmission to motoneurones.


Rubrospinal effects on ventral spinocerebellar tract neurones. Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms.


A comparative study of the effects of cholestyramine and neomycin in the treatment of type II hyperlipoproteinaemia. A comparative study of the effects of cholestyramine and neomycin has been carried out in 35 patients with severe type II hyperlipoproteinaemia. Both agents were administered during a period of 18 weeks, the daily dosages being 12, 16 or 20 g cholestyramine and 1, 1.5 or 2 g neomycin. The mean decrease in cholesterol concentration was 22% with cholestyramine and 23% with neomycin. There was no difference in effect between the two agents and between the doses used. No significant influence on triglyceride concentration and on body weight was observed. No signs of deficiencies in fat-soluble vitamins were found. Anticoagulant requirements increased during cholestyramine medication. No signs of hyperchloraemic acidosis were observed during treatment with colestyramine. Cholestyramine was tolerated less well than neomycin: it had to be discontinued in 8 cases. Neomycin was not tolerated by 3 patients. The majority of the patients preferred neomycin.


Phosphopyridoxal complexes with histamine and histidine. (4) The kinetics of complex formation between histidine and pyridoxal 5' -phosphate in the presence of bacterial histidine decarboxylase. The dynamics of the complex formation between pyridoxal 5'-phosphate (PLP) and histidine in the presence of bacterial histidine decarboxylase was examined. Since PLP is able to form a cyclic product with histidine and histamine, the possibility of complex formation between PLP and histamine formed during a decarboxylation reaction was examined too. It was found that the cyclization reaction between PLP and histidine is equimolecular and the rate of cyclic product formation is not significantly influenced by the presence of enzyme. In the presence of bacterial histidine decarboxylase both the cyclization reaction and cyclic product formation were observed. Predominance of histamine or cyclic product formation was dependent on pH and substrate concentration. In the presence of histidine and enzymatic protein, histamine formed during the decarboxylation reaction was unable to form a cyclic product with PLP.


Metabolic investigations after xylitol infusion in human subjects. Evidence has been sought for minor degrees of thiamin and pyridoxine deficiency in patients undergoing surgery who have been infused with xylitol as a parenteral nutrient. Some metabolic changes which are associated with this practice have been studied; the findings are compared with those obtained in similar patients infused with glucose solutions. The thiamin status of all of the subjects was normal. Some of the patients showed slight biochemical evidence of pyridoxine deficiency, but there were no untoward effects of xylitol infusion. The concentration of oxalate in the blood and the excretion of oxalate in the urine did not exceed the normal range in any patient. The plasma and urine orthophosphate and urinary pyrophosphate levels decreased in association with the infusion of both xylitol and glucose. Plasma pyrophosphate and calcium levels, and the urinary calcium level, were essentially unaltered. A detailed quantitative study of the urinary organic acid excretion by means of gas chromatography/mass spectrometry showed that there was an abnormal glycolic aciduria and tetronic aciduria associated with xylitol infusion, but not with glucose infusion. There was no evidence of increased oxalate excretion in any patient by this method. The biochemical and clinical significance of these findings is discussed.