EPR study of serum ceruloplasmin and iron transferrin in myocardial infarction. Electron paramagnetic resonance (EPR) analysis of frozen serum from myocardial infarction patients has been conducted. Signal at g=4.3 was found definitively attributable to iron(III)-transferrin complex. Imcrease of serum ceruloplasmin as compared to normal was confirmed, with a concomitant decrease of iron-transferrin content. A mechanism for such correlated variation is hypothesized.


Submandibular gland tumors.

Submandibular gland tumors. Tumors involving the submandibular gland are rare. However, the incidence of malignancy is much higher than in the parotid (approaching 50 percent). In addition, the 5-year survival rate in patients with malignant tumors of the submandibular gland is much poorer in our series--28 percent versus 71.8 percent for the parotid gland. Because of the poor prognosis in patients with malignant tumors involving the submandibular gland we feel that composite resections should be carried out for all tumors except low-grade mucoepidermoid tumors. In addition, postoperative radiation should be given for specific indications (detailed in the article).


[Measurement of muscle reflex time in radicular disorders of the lumbosacral region]. The results of studies performed by the authors show that time measurements of proprioceptive muscular reflexes (triceps surae and tibialis posterior reflexes) may be considered a valuable addition to methods of topical diagnosis of radicular disturbances in the lumbosacral region. The reflexes were tested in twenty normal subjects. There were found an intraindividual constancy of the respective reflex time with a maximum deviation of 2 ms as well as a lateral variability up to 1.3 ms. Radicular compressions resulted in an increase in reflex time by 2 to 66 ms or failure of the reflex potential to be recorded. The pathological cases were compared with clinical and neurological studies, positive myelographies using radiopaque substances, and results of surgical operations. Compared with the results of surgical operations, changes in reflex time indicated damage to the reflex arc in ninety percent of the cases.


The functional pool of brain catecholamines: its size and turnover rate. Behavioral data are reviewed that give evidence for an indiscriminate involvement of brain catecholamines (CA), especially dopamine (DA), in nerve function, regardless of the time elapsed from their synthesis. Critical analysis of biochemical and pharmacological studies shows that a clear-cut distribution of brain catecholamines in two compartments ['newly synthesized' (NS) and 'main storage'] is not at all established, and moreover that there is no adequate proof that the difference in turnover rates attributed to these two supposed pools is due to a preferential extraneuronal release of NS-CA during nerve function rather than to a preferential (nonfunctional) intraneuronal deamination of NS-CA, or at least of NS-DA.


The effects of amphetamine isomers on rotarod performance. The amphetamine isomers impair the rotarod performance of rats in a dose-related manner, with (+)-amphetamine approximately four-times as potent as its (-)-isomer. At a rotation speed of 4 rpm, 60 min after i.p. administration, the TD50 values (mg/kg) were: (+)-amphetamine, 24 (21.9-26.4) and (-)-amphetamine, 96 (76.3-118.4), with the curves not deviating from parallelism. Coadministration of the peripheral cholinesterase inhibitor neostigmine salicylate (0.005 mg/kg) attenuated (+)-amphetamine neurotoxicity [30 (26.4-34.1)]. These results, in conjunction with previously reported effects of the drug on isolated nerve-muscle preparations, suggest that the muscle weakness produced by high doses of amphetamine may result from inhibition of transmission at the neuromuscular junction.


Viloxazine, sleep, and subjective feelings. The sleep of eight volunteers (mean age 55) was recorded electrophysiologically while viloxazine 200 mg was taken daily for 3 weeks, preceded and followed by a week of matching blanks. The volunteers also made ratings of their feelings on visual analogue scales. Another 15 volunteers (mean age 34) took viloxazine 300 mg daily for 3 weeks, preceded and followed by 3 weeks of matching blanks, and they also made daily ratings of feelings. The drug diminished sleep duration and caused more frequent and longer transitions into wakefulness and drowsiness. Slow-wave sleep decreased and stage 2 increased. REM sleep was markedly reduced, especially initially, and there was a withdrawal rebound. Viloxazine impaired subjective concentration mood, and quality of sleep. Three volunteers, however, had striking mood elevation. The drug caused a small loss of weight, which correlated with gastrointestinal symptoms. Three older subjects experienced withdrawal vomiting and prostration. Viloxazine shares properties with imipramine and with amphetamines.


Time-dependent disruptive effects of apomorphine and alpha-methyl-p-tyrosine on development of morphine tolerance. In rats the development of one-trial tolerance to the analgesic action of i.p. administered morphine is disrupted by the postadministration of apomorphine (30 mg/kg at 5 min but not at 3 h) or alpha-methyl-p-tyrosine (200 mg/kg at 5 min and 3 h but not at 12 h). Diethyldithiocarbamate or propranol has no disruptive effect. It is suggested that development of tolerance to the analgesic effects of morphine is mediated by sequential time-dependent biochemical processes.


[Sleep changes induced by chronic administration of S. 1694 (Survector) (author's transl)]. Five adult Macaca mulatta were studied during chronic administration (24 days) of S. 1694 (10 mg/kg, i.m.). This substance induced a significant increase of the first awakening (delaying sleep onset) and an enhancement of the duration of REM and stage 4 sleep. After withdrawal, the waking effect desappeared, but the increase in stage 4 sleep was maintained for one week and REM enhancement kept rising for 15 days. This observation of long-term action underlined the validity of drug experiments in chronic treatment: S. 1694 might set a new type of monoaminergic systems regulation.


Secretion of hormones influencing water and electrolyte balance (antidiuretic hormone, aldosterone, prolactin) during sleep in normal adult men. Renal conservation of electrolytes and water occurs normally during sleep. Antidiuretic hormone (ADH), aldosterone (ALDO), and prolactin (PRL) are hormones that may have interactive effects on kidney function. The availability of a radioimmunoassay for ADH as well as for ALDO and PRL permitted the study of the simultaneous secretion patterns of these three hormones during all-night sleep in eight normal young adult men, by blood sampling every 20 min from 2300 to 0700 on two consecutive night. ADH, ALDO, and PRL all appeared to be secreted episodically. The pulsatile release of ADH was random, and average plasma ADH levels were unchanged during the night. ALDO and PRL, on the other hand, had an approximately 90-min secretion rhythm, and average plasma concentrations of both hormones consistently increased during the hours of sleep. Average plasma sodium concentration was constant throughout the night. The nocturnal increase in plasma ALDO may be responsible for the normal reduction of urine sodium excretion during the night. The concomitant increase in plasma PRL might synergize with ALDO in influencing the renal retention of sodium, but PRL alone has little apparent effect on human kidney function. REM sleep-related decreases in urine flow have been noted both in humans and in monkeys, but ADH secretion was not REM related in out subjects. Autonomic activation during REM is one possible explanation for decreased urine flow during this stage of sleep.


Angiography in the diagnosis of liver disease in children. 75 angiographic examinations were done in 64 children aged 1 day to 16 years; 41 with various liver diseases and 23 with normal lives. The angiographic diagnosis was accurate in 95% of 44 patients where proof was established by surgery and/or biopsy. Properly used hepatic angiography is a reasonably safe procedure of great value in diagnosing and planning the surgical management of liver masses. It is also a useful tool in the diagnosis of diffuse hepatic processes of neoplastic, inflammatory or degenerative origin.


[The influence of renal artery occlusion on tumor growth of experimental nephroblastomas (author's transl)]. Nephroblastomas are induced in rats with N-Methyl-N-Nitroso-Urea, and selective renal artery occlusion is performed. This procedure has the same effect like occlusion by embolization. The effect of renal artery occlusion on the growth rate of nephroblastmas is controlled by angiography and gross and microscopic examinations up to 70 days following ischemia, the results are compared with a group of untreated nephroblastoma rats. There is a marked reduction of tumor size and a decrease in tumor proliferation. There is an immediate tumor cell death induced by acute and complete ischemia. Collateral blood vessels cause residual arterial blood supply of tumor parenchyma. There seems to be a correlation between collateral blood delivery and tumor size. Even 70 days after permanent ischemia there are areas of obviously absolute normal tumor cells. The conclusion of this experimental study demonstrated that growth rate of tumors can be reduced by ischemia although potentially malignancy still remains. Clinical embolization therapy is justified only in nonoperable patients with hypernephroma and with massive hematuria.


Postoperative nonspecific immunotherapy in primary bronchogenic carcinoma. A postoperative active nonspecific immunotherapy has been conducted in 54 patients operated on for primary bronchogenic carcinoma. The immunopotentiator used is an original product prepared from a transformed strain of a saprophytic mycobacterium: M. smegmatis ATCC 607. The patients treated show an increase in postoperative survival rates of 60% at 1 year and 50% at 2 years, with regard to the survival rates of a control group and 21 surgical series available totaling over 20,000 patients. This important increase in the survival rates is accompanied by an appreciable improvement in patient comfort.


[Respiratory gas exchange during breathing of O2 in different inert gases (author's transl)]. In 15 patients with chronic bronchitis with or without emphysema breathing of room air was compared with breathing of 20.9% O2 in helium and in argon. Minute ventilation and alveolar ventilation showed no differences, whereas the alveolar and arterial pO2 and PCO2 showed an improvement of the CO2 gas exchange and a deterioration of the O2 gas exchange. This contradictory behaviour cannot be explained by shunts or inhomogeneities or influence of gaseous or alveolo-capillary diffusion. Perhaps the physicochemical properties of the alveolo-capillary membrane change by the depletion of nitrogen. The recommendation of helium-oxygen breathing, proposed by other authors for patients with obstructive airway diseases, cannot be supported, when the gas exchange for O2 is deteriorated.


Role of alpha-adrenergic receptors in exercise-induced bronchoconstriction. The role of alpha-adrenergic receptors in exercise-induced bronchoconstriction (EIB) was studied. 9 asthmatic patients with a marked degree of EIB (group I) and 6 asthmatic patients with no or a less severe EIB (group II) were investigated and compared with 8 healthy control persons. Pulse rate, airway resistance and end-expiratory thoracic gas volume were measured at rest and immediately and 15 min after exercise. Group I subjects showed a significant inhibition of EIB after alpha-adrenergic blockade with phentolamine (10 mg as aerosol) and after cholinergic blockade with an atropine-ester (60 mg as aerosol). In 7 of 9 patients who had received phentolamine, and in 3 of 6 patients who had received atropine-ester, the EIB was completely suppressed. In group II the administration of propranolol (40 mg orally) produced a significant increase in EIB. The effect of propranolol could be inhibited by the addition of alpha-adrenergic blockade with phentolamine (10 mg as aerosol). The control subjects had no measurable EIB, even after the administration of propranolol (40 mg orally). It is concluded that, in addition to the vagal system, an activated alpha-adrenergic system is involved in the phenomenon of EIB.


[Medullary angiomas and the Klippel-Trenaunay-Weber syndrome]. 5 cases of an association of Klippel-Trenaunay-Weber syndrome and of spinal cord angiomas are reported amongst a series of 150 cases of malformation of the cord. The hypertrophic element, arterial dilatations and varices were found to be constant, in constant to cutaneous angiomatosis which was found in only 2 cases. There were intraspinal angiomas in all cases. The relationship between Klippel-Trenaunay-Weber syndrome and regional angiomatous phacomatoses are discussed.


[Attempted treatment of a voluminous tympano-jugular and retropharyngeal glomus tumor by embolization]. The authors report a case of glomus tumor effectively treated by embolisation. The very large size of this tumor, the age and very poor general condition of the patient due to swallowing difficulties represented a contraindication to classical methods of treatment. Elective devascularisation was carried out by embolisation of the tumour itself using non-resorbable inert material by way of selective catheterisation of the vessels supplying it, almost all of which arose from the external carotid. Rapid and durable disappearance of part of the left cranial nerve involvement, in particular swallowing difficulties, reflected the effectiveness of the method. 18 months after this attempt at palliative treatment, the patient's condition remains satisfactory, with no detectable evidence of any recurrence or progression of the tumour.


Urinary cyclic adenosine 3',5'-monophosphate excretion in children in short stature: effect of somatotropin. Excretion of urinary cyclic adenosine 3',5'-monophosphate (cAMP) was determined in twenty-four children of short stature and in sixteen normal children. Of the patients, eight suffered from anterior panhypopituitarism, six from isolated deficiency or somatotropin, seven had a family history of short stature, and three had growth failure of pre-natal onset. In children suffering from anterior panhypopituitarism or from isolated somatotropin deficiency, excretion of cAMP was found to be depressed. Short-term administration of purified somatotropin in normal therapeutic dose (3.4 mg per 1.7 m2 i.m. daily for 5 days) had no effect on urinary cAMP, but reduced urine volume in all patient groups. During somatotropin treatment there was a positive correlation between changes in urine volume and nitrogen balance (r = 0.67).


Conventional electromyography in myotonic dystrophy. In 31 subjects of 23 different families with unequivocal signs and symptoms of myotonic dystrophy EMG was performed with conventional technique on brachial biceps, extensor digitorum communis and tibialis anterior muscles. In 14 of these patients motor and orthodromic sensory conduction velocities were measured in median nerve as well. During full muscular effort, an interference pattern of low amplitude was seen in most of the explored muscles, while "after discharge" of different duration was present in 57-83% of the patients. At weak effort, mean potential duration was nearly always significantly reduced if polyphasic potentials were not included in the calculation; polyphasic potentials, however, exceeded the limits of normal incidence and their duration was longer than that of motor unit potentials of simple shape. At rest, spontaneous activity of short duration and positive sharp waves occurred in about 50% of the patients, but rarely in more than two places. Bursts of myotonic or pseudomyotonic discharges occurred either spontaneously or mechanically in all subjects. Conduction velocity along motor, or sensory, peripheral nerve fibres was constantly within normal values. Results were discussed in relation to the hypothesis of a primary neuronal pathogenesis of muscle wasting, and the conclusion was that nerve changes are to be considered as a collateral disorder dependent on the pleiotropic action of the gene.


Isolation and partial characterization of a glycine- and serine-rich polypeptide from human serum high-density lipoproteins (HDL). Lately, several minor polypeptides characterized by a high content of glycine and serum have been described in human serum lipoproteins. By column chromatography we have isolated a glycine- and serine-rich polypeptide from totally delipidized high-density lipoproteins, apo-HDL. The partial characterization of this polypeptide by total amino acid composition and by immunology utilizing monospecific antisera to polypeptides of human serum lipoproteins, would indicate a unique polypeptide. This low molecular weight (4900 Daltons) glycine- and serine-rich polypeptide was characterized by a mobility on polyacrylamide gel electrophoresis, similar to that of polypeptide. A-I, a blocked NH2-terminal amino acid and a terminal COOH-fragment consisting of R-Ser-Ala-Gly-Gly. There are similarities between this polypeptide and the protein moiety of a cholesterol ester-rich lipoprotein fraction, HDLsup, obtained by in vitro incubation of HDL subfractions and described in earlier publications by our group. The identity between these two polypeptides, cannot be confirmed by the present study.


Family infections by reo-like virus. Comparison of antibody titres by complement fixation and immunoelectroosmophoresis. The families of 31 index cases infected by reo-like virus were examined for gastroenteritis symptoms, virus excretion and serological evidence of infection. Excretion of virus was seen only among the children in the families, and it occurred together with gastroenteritis symptoms in 97.2% of all cases. Virtually all infected children had a significant rise in titre in paired sera. Among the parents 25.0% had a significant rise in titre associated with infections with gastroenteritis symptoms and 28.6% with symptomfree infections. A comparison between complement fixation and immunoelectroosmophoresis for detection of antibody showed that the tests gave similar results.


[Stress and sleep].

[Stress and sleep]. For this paper, psychophysiological relationships between stress and sleep are considered with reference to clinical psychiatric problems. Answers to the first question--how does sleep affect the tolerance of stress in the waking state?--are provided by sleep deprivation experiments. The latter show that total sleep deprivation has a great influence on stress. However gradual partial sleep deprivation to a sleep time of 5 hours seems well tolerated by most individuals. In some special cases we found subjects well adapted to the workaday world who could live with briefer sleeping periods. Because of experimental problems, the second question--how does stress affect sleep?--is more difficult to answer. Anxiety is one of the most important factors deteriorating sleep under conditions of stress. This reduced sleep is in turn stressful for waking behavior. Thus, the relationship between stress and sleep, two factors separated for scientific investigation, is essential and especially important in the problem of insomnia.


[Demonstration of osseous tumor micrometastases: comparison of the value of bone marrow cytology and histology]. In the course of a complete diagnostic work up ("staging") of 404 patients with solid tumors and malignant lymphomas, the bone marrow (BM) was analyzed cytologically (smears) as well as histologically (needle biopsy). 1. In this study both smear and needle biopsy showed an equal percentage of tumor metastases in the BM (14.6% and 16.1% respectively). Considerable differences exist between the various kinds of tumors, and therefore, each type must be viewed separately. 2. BM smear and BM needle biopsy complement each other. Combination of the two shows approximately 20--30% more positive BM finding as compared to each of the methods alone (19.6% positive findings), execpt in Hodgkin's disease.3. In Hodgkin's disease BM biopsy is superior to the smear in detecting BM infiltration. The biopsy yield is not improved on by smear. 4. In patients with oat cell tumors of the lung, the BM smears appear to be superior to biopsy for diagnosis of marrow invasion. The diagnostic yield of BM smears is, however, supplemented by the histology of simultaneous BM needle biopsy. 5. Direct BM examination (smear and needle biopsy) effectively supplements diagnostic radiological and isotope scanning procedures of the skeleton in searching for disseminated BM metastases in lung cancer of the oat-cell type, in non-Hodgkin lymphomas, and in prostatic cancer, but does not do so in patients with other solid tumors and Hodgkin's disease.


[The when and how of therapy for hyperlipoproteinemia]. Hyperlipoproteinemia is found in about 10--15% of the adult population. There is a strong correlation between elevated total and LDL cholesterol levels, decreased HDL cholesterol values and the incidence of coronary heart disease. Large-scale screening for this strong risk factor should be initiated at an early stage, when possible even in childhood. Dietary treatment is the basis of all lipid-lowering therapy. Lipid-lowering drugs should be given only in addition to a carefully controlled diet. Dietary and drug treatment of hyperlipoproteinemia is discussed.


[Experimental basis for the therapy of Amanita phalloides poisoning]. The experimental basis for the treatment of death-cap poisoning is reviewed. The available data suggest penicillin and silymarin as the antidotes most likely to be effective. Measures to increase the elimination of the toxins appear to be warranted.


Sodium requirement for the positive inotropic action of isoproterenol on guinea pig atria. Isoproterenol doses not elicit its characteristic positive inotropic action in contracting guinea pig atria suspended in sodium-free media. However, the ability of isoproterenol to decrease the time to peak tension development during an individual contraction cycle is still present in sodium-free solutions. Removal of sodium diminished but did not eliminate the tissues' ability to elevate adenosine 3',5'-monophosphate in response to isoproterenol. The striking absence of an inotropic action by isoproterenol on atria in sodium-free media suggests that sodium (and possibly a sodium-calcium exchange across the sarcolemma) plays an important role in the inotropic action of catecholamines.


Rearing regimen producing piglet diarrhea (rotavirus) and its relevance to acute infantile diarrhea. Piglets were weaned when 1 day old and thus were denied further access to the antibodies supplied by their dam's milk. They were placed in a nursery in which contamination by the ubiquitous rotavirus steadily increased with continuous use causing a progressive increase in the incidence of vomiting, diarrhea, and death among the piglets. A similar syndrome involving an antigenically related rotavirus and analogous management practices occurs in human infants.


Serum lipoprotein concentrations in cystic fibrosis. Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules.


Biologically active pituitary hormones in the rat brain amygdaloid nucleus. While an attempt was being made to identify the source of the growth hormone releasing factor present in cerebral spinal fluid of man, it was discovered that cells of the rat amygdaloid nucleus, grown in tissue culture, produce a material that is immunologically and chromatographically identical to growth hormone found in the pituitary. Immunoperoxidase staining revealed dense accumulation of the peroxidase-antibody to growth hormone complex in amygdala cells. Significant amounts of growth hormone and adrenocorticotropin could be extracted from this limbic structure. Extracts containing immunoequivalent amounts of growth hormone were measured by bioassay in hypophysectomized rats. Stimulation of the growth of epiphyseal cartilage by extracts of the amygdala was comparable to the stimulation by extracts of anterior pituitary glands. The stimulatory effect of amygdala extracts on adrenal and gonadal size and weight and on growth of thyroid follicular epithelium was also comparable to that of pituitary extracts.


Transovarial transmission of Japanese encephalitis virus by mosquitoes. Female Aedes albopictus and Aedes togoi mosquitoes infected with Japanese encephalitis virus either by intrathoracic inoculation or by ingestion of a virus-sucrose-erythrocyte mixture transmitted the virus to a small percentage of their F1 progeny. Adult F1 female Aedes albopictus thus infected transmitted the virus in turn to newly hatched chickens by feeding on them.


Chick embryonic skin as a rapid organ culture assay for cellular neoplasia. We used chick embryonic skin (CES) in organ culture to assess the neoplastic potential of a variety of cultured human and nonhuman cell lines. Cells derived from cancer tissues grew in CES and formed tumors in nude mice while cells derived from normal tissues grew in neither system. The CES proved to be more sensitive than the nude mouse when used to assay SV40 transformed human cells; each of four such lines grew in CES while only one of the four lines grew and formed tumors in nude mice. In addition, the patterns of invasion by inoculated cells can be easily studied in the CES. These results suggest that CES in organ culture offers an inexpensive, rapid, and reliable alternative to the nude mouse as a tumorigenicity test.


Cyclic adenosine monophosphate production by embryonic chick cells. Cells dissociated from 1-day-old chick embryos produce a pulse of cyclic adenosine monophosphate (cyclic AMP) when stimulated with cyclic AMP. There is a stimulus threshold concentration of about 10(-8) molar cyclic AMP and an upper limit, above which the response is suppressed, of about 6 X 10(-6) molar. The response occurs within 5 seconds of stimulation and corresponds to an average pulse size in the range of 10(7) molecules per cell.


Platelet factor 4: an inhibitor of collagenase. Human platelet factor 4 (PF4) is known to bind to heparin and inhibit its anticoagulant effect. This factor also inhibits the enzyme collagenase derived from cultured human skin and collagenase extracted from human granulocytes. The addition of heparin to the PF4-collagenase assay system has no effect on the observed inhibition of collagenase. Thus PF4 inhibits collagenase, in addition to neutralizing heparin.


[The effect of cancer on drug metabolism and drug action]. Over the last few years, numerous studies performed mainly in animals with a tumour but also in man with malignant disease have shown that the presence of cancer modifies gastro-intestinal absorption, tissue distribution and transformation of drugs in the liver. Consequently, malignant disease also influences the therapeutic effects and toxic effects of drugs. This effect may occur with several drugs, with or without antineoplastic properties, and appears mainly at an advanced stage of the disease.


[The lymphocyte. Model for study of cell growth control]. The absence of one essential amino-acid during lymphocyte activation by phytohemagglutinin inhibits the synthesis of macromolecules which should normally occur. The study of the kinetics of macromolecule synthesis and RNA polymerase activity during the relief of inhibition by the addition of the deficient amino-acid, shows that partial activation occurred in spite of the absence of this essential amino-acid. We use this system of reversible inhibition of lymphocyte activation to study the role of nuclear proteins in the regulation of cell growth.


[Acute granulous leukemia in multiple myeloma. Apropos of 5 cases]. The authors report five cases of acute granular leukemia which complicated the course of multiple myeloma treated by chemotherapy. They then review the literature, and discuss 30 cases which they found. The important point clinically is the long duration of the course (average 56 months) in multiple myeloma complicated by acute granular leukemia. Usually chemotherapy permitted a good quality remission and when the leukemia develops there is no longer any trace of myeloma. The mechanisms of onset of this type of leukemia during myeloma are discussed. They are probably complex and various but there is no doubt concerning the responsability of chemotherapy and in particular alkylating agents.


[Inagural lymphoblatic transformation in chronic myeloid leukemia. Clinical and cytogenetic study of one case]. A fifty-year old patient was treated for acute lymphoblastic leukemia. One month after a complete remission, a syndrome suggesting chronic myeloid leukemia led the authors to study the marrow karyotype which revealed the existence of a Philadelphia chromosome. A second lymphoblastic attack occurred rapidly and a second complete remission was easily obtained. A few weeks later, occurred lymphoblastic meningitis. A new cytogenetic study then showed duplication of the Philadelphia chromosome. One may imagine that the initial attack represented acute lymphoid transformation of chronic myloid leukemia. The theoretical and practical significance of this case is discussed.


The case against routine lipoprotein electrophoresis. We evaluate the role of lipoprotein electrophoresis as part of the routine lipogram. Analysis of 875 samples shows that it rarely provides more information than can be obtained from estimation of serum cholesterol and triglycerides with a simple test for chylomicrons. We stress the difficulties and arbitrary nature of qualitative interpretation of the electrophoretic patterns, Furthermore, electrophoretic typing is not essential for the management of patients, nor does it form the basis of current classifications of hyperlipidaemia. We argue that lipoprotein electrophoresis has a very limited place in the diagnosis and management of the individual patient.


Initiation of DNA synthesis and uptake of T antigen by chick erythrocyte nuclei in hterokaryons with SV40-transformed human cells. Nonsynchronized and hydroxyurea (HU)-synchronized SV40-transformed human cells (W98VaD) were fused with chick embryo erythrocytes (CE). The uptake of T antigen by CE nuclei was compared with initiation of chick nuclear DNA synthesis. Uptake of T antigen by CE nuclei occurred at about the same time after fusion with asynchronous as with HU-synchronized cells. CE nuclei rapidly became T antigen-positive between 16 h and 28 h after fusion and usually almost all CE nuclei were T antigen-positive by 48 h after fusion. In contrast, initiation of chick nuclear DNA synthesis occurred as a function of time after reversal of the HU block, when the host cell nuclei were also synthesizing DNA. Chick nuclear DNA synthesis occurred in many heterokaryons before the CE nuclei became T antigen-positive by immunofluorescence.


A selective system for hepatoma cells producing gluconeogenic enzymes. Gluconeogenesis is a liver-specific pathway which permits the synthesis of phosphorylated sugars from oxaloacetate, pyruvate, amino acids, or trioses. The absolute requirement for glucose or an alternative hexose which characterizes most mammalian cells probably reflects an inablility to perform gluconeogenesis rather than to generate sufficient energy by respiration alone. Cells of diverse histogenetic origins have been tested in glucose-free medium, supplemented with oxaloacetate or with dihydroxyacetone. The only cells able to grow are well-differentiated hepatoma cells which produce the relevant gluconeogenic enzymes: phosphoenolpyruvate carboxykinase, fructose diphosphatase, and triokinase. Reconstruction experiments demonstrate that glucose-free media permit the selective growth of cells producing gluconeogenic enzymes. These media should be useful for analysis of reexpression of differentiated functions in somatic cell hybrids and for the isolation of mutants.


Expression of differentiated functions in hepatoma cell hybrids: selection in glucose-free media of segregated hybrid cells which reexpress gluconeogenic enzymes. Selective glucose-free media have been used to study the reexpression of liver-specific gluconeogenic enzymes in rat hepatoma X mouse lymphoblastoma somatic hybrids. The utilization for gluconeogenesis of dihydroxyacetone or oxaloacetate requires two enzymes: fructose diphosphatase as well as either triokinase for the former or phosphoenolpyruvate carboxykinase for the latter. By sequential selection with these substrates, the reexpression of the three gluconeogenic enzymes has been dissociated. The reexpression of these enzymes is correlated with the loss of mouse chromosomes. In addition, the characterization of the parental forms of aldolase B, another liver-specific enzyme, shows that reexpression corresponds to the simultaneous production of the rat and mouse enzymes. These results demonstrate the chromosomal origin of extinction and suggest that activation of mouse silent genes which accompanies reexpression can occur without loss of the parental determinations. The hypothesis that determination involves regulatory rather than structural genes is discussed.


Adenylate cyclase and phosphodiesterase activity in the platelet release abnormality. 11 patients with histories of clinical bleeding were selected as examples of platelet release abnormality. Mean bleeding time was 18 +/- 2.6 min (normal +/- SEM; 6 +/- 0.44); mean platelet adhesiveness was 9.9 +/- 4.3% (normal +/- SEM; 30 +/- 2.2). Clot retraction and platelet factor 3 were normal. Platelet aggregation with adenosine diphosphate (ADP), epinephrine and collagen was decreased, as was 14C-serotonin release. Electron microscopic studies of platelets exposed to epinephrine showed 2 subgroups: one which failed to aggregate or have centralization of organelles and a second which developed pseudopodia and centralization of organelles, but rarely aggregated or degranulated. Measurements of activity of adenylate cyclase and phosphodiesterase under basal conditions were performed on platelets from patients and control subjects. Adenylate cyclase activity was significantly lower and phosphodiesterase activity significantly higher in the patient group. Prostaglandin E1 was a potent stimulator of adenylate cyclase in both groups, as was NaF. It was concluded that the causative defects with "platelt release abnormality" do not reside in either the activity of adenylate cyclase or of phosphodiesterase. Changes in formation and destruction of cyclic adenosinemonophosphate (AMP) may instead be regarded as a compensatory response to a defect in another effector system.


[Aujeszky's disease. Studies on the possibility of differentiating between contaminated pig-breeding farms and farms on which the pigs have been inoculated with the Bartha vaccine (author's transl)]. The serological studies reported in the present paper were done on forty-one pig-breeding farms contaminated with Aujeszky's disease and four farms that were free from this disease and on which fifty per cent of the animals had been inoculated with the Bartha vaccine. The serological studies were based on the serum neutralization test (SN test). On contaminated farms, the majority of the animals present at the time of outbreak of the disease were serologically positive. Comparison of the serological findings on farms on which there had been outbreaks of the disease from two to seven and from seven to twelve months previously, showed that there was hardly any difference in titre levels between the two groups. Of twenty-eight breeding boars used for service at the time of the outbreak, twenty-one per cent were serologically negative. Serological studies in breeding gilts showed that virulent virus was only transmitted up to two months after the outbreak of the disease.


HLA-D typing with an association of Dw2 and absent immune responses towards herpes simplex (type i) antigen in multiple sclerosis. We have confirmed that HLA-Dw2 is increased in MS patients to 47% (normals 20%). Lymphocyte transformation and antibody studies with herpes simplex antigen show that many of the DW2-positive MS patients have low or absent responses. The association of low responses to HSV and the presence of Dw2 is statistically significant at a p value less than 0.01.


Isolation of living adult Onchocerca volvulus from nodules. A technique for the isolation of adult Onchocerca volvulus from excised onchocercomata is described. The nodules are incubated in medium 199 containing 1-5 mg collagenase and 0.2 mg gentamicin per ml for 6-48 hours in a waterbath at 30-37 degrees C. A proportion of the worms can be isolated alive.


Liver monoamine oxidase (MAO) in liver homogenate of mice infected with Schistosoma mansoni and effect of certain therapeutic agents. MAO activity in liver homogenate of mice infected with Schistosoma mansoni was determined from the second till the 14th week following infection. Significant diminution of MAO activity was noticed starting from the sixth week following infection, reaching its lowest value at the eighth week, obviously denoting progress of hepatic fibrosis. Treatment of the infected, animals with four different antischistosomal agents, tarter emetic, stibophen, niridazole and hycanthone, resulted in an improvement of the enzyme level to an almost normal value. This may indicate the ease with which the lesions in the liver including fibrosis recover when the infection is successfully treated.


[Degradation and repair of rat hepatoma cell DNA following exposure to gamma rays and methylnitrosourea]. Single-strand breaks induced in DNA of ascitic hepatoma cells by gamma-rays and N-methyl-N-nitrosourea (MNU), resp., may be effectively repaired. Double-strand breaks of DNA from MNU-treated hepatoma cells are also effectively repairable in vivo. Only a small part of double-strand breaks induced by gamma-rays in DNA of these cells is repaired in the postradiation period. The combined action of gamma-rays and MNU on the hepatoma cells causes a complete inhibition of repair of DNA and its further degradation. Under these conditions, inhibition of the repair of DNA synthesis and repression of DNA polymerase I activity is observed.


[Cytochemical study of different stages in the life cycle of Toxoplasma gondii. VII. Oxidation--reduction enzymes in the cyst forms]. Dehydrogenases of glycolysis, Kreb's cycle, and pentose-phosphate shunt were detected in cystozoites of Toxoplasma gondii strain SS-119 with various degrees of activity. A mixed oxidative metabolism may be postulated on this stage of the toxoplasma life cycle. Besides, the activity of cytochrome oxidase was detected in cystozoites; the addition of cytochrome c to the incubation medium significantly intensified the reaction intensity. Of interest seems the observation of a layer of higher enzymatic activity in the host brain tissue in the immediate neighbourhood with the cyst body. This may be regarded as the host cells' (or tissue') response to the presence of the parasite's alien body.


[Effect of deep freezing on isolated rat liver lysosomes]. The level of the non--sedimentating activity of acid hydrolases (deoxyribonuclease, phosphatase, cathepsins) and electron microscopy of lysosomes has been studied after freezing to --30 degrees, --70 degrees, --140 degrees and --196 degrees. It has been found that enzyme solubilistion and lysosome ultrastructure distortion are mostly marked in the temperature range between 0 degrees and --30 degrees C. Additional membrane damage is observed in the temperature range from --140 degrees to --196 degrees C. It is suggested that not only physico-chemical changes during phase transitions of free water in the freezing medium but also recrystallization processes and the freezing-out of water structurally bound with membranes may contribute to mechanism of lysosome cryoinjury.


[Ultrastructure and function of zona fasciculata cells in the adrenal cortex of mice of differing genetic lines but physiologically normal]. Ultrastructure and function were studied of the cells of zona fasciculata of the adrenal cortex of male mice of strains CBA and C57B1. The results obtained point to potentially higher possibilities of the adrenal zona fasciculata in mice of strain C57B1. These data show the role of the genotype in determining the structure and functions of the cells of the adrenal cortex as well as an evident correspondence of the ultrastructural features to the specificity of functions and the level of activity of cells.


Epidemiologic study on enzootic bovine leukemia using serologic tests and hematologic examinations. In order to find suitable diagnostic procedures to use in an epidemiologic survey for the detection of animals infected with the bovine leukemia virus (BLV), the authors conducted an investigation on 262 Friesian dairy cattle. The results of hematologic, serologic, and electron microscopic examinations are reported. Evaluation of the results demonstrated the validity of the immunodiffusion and immunofluorescence tests and the opportunity for their use in conjunction with examination of the blood picture. From the data reported it would appear useful to extend the investigation to the herds without history of lymphosarcoma.


A murine oncornavirus marker in adenovirus 7-transformed mouse cells. The presence of oncornavirus particles in BALB/c mouse cells transformed by adenovirus 7 was investigated. The particles detected had a buoyant density of 1.16 g/cm3; both p30 and adenovirus T-specific immunofluorescence was demonstrated in the cell cytoplasm. No C-particles were shown by the electron microscope.


Quantitative comparison of milk-released C3H and RIII mammary tumor viruses in infected BALB/c hosts. The C3H and RIII mammary tumor viruses (MTV) carried by BALB/cfC3H and BALB/cfRIII breeding females have been quantified and compared in milk samples, after partial purification with a sucrose density gradient. The samples were collected at identical times during the first 3 lactation periods from individual mice (6 per strain), standardized for age at delivery and size of litter. Milk samples from 6 MTV negative BALB/c controls have also been analyzed. Data for comparison are expressed in optical density units (ODU) and refer to the protein content of the whole milk using MTV-negative Balb/c milk as blank. The results have shown 1) an increase of MTV released through milk in each MTV-carrying female from the first (average ODU, 0.542) to the second (1,351) and third (2.105) lactation, 2) individual variations, and 3) a significant difference in release between C3H and RIII MTV, the latter being more than double (average ODU, 1.801) in respect to the former (0.847). The apparent discrepancy between these results and the bioactivity in BALB/c mice of C3H and RIII MTV, significantly lower for the latter, is discussed.


Quantitative determination of mammary tumor virus in individual samples of mouse milk. The possibility to determine quantitatively the intact mammary tumor virus (MTV) in milk of mice carrying milk-transmitted MTV has been assayed by a method that allows direct comparison between individual milk samples. The method is based on (a) the measure of light scattering of partially purified MTV preparations, (b) the use of milk from genetically identical MTV free mice as blank and (c) the quantitative reference to the total protein content of whole milk. The sensitivity, specificity and reproducibility of the procedure, as well as the requirement of appropriate quantitative references, are illustrated and discussed. BALB/c (MTV free), BALB/cfC3H, and BALB/cfRIII mice have been used.


Nonrenovascular renal hypertension in children. Hypertension in children has been reported with increasing frequency because of increased awareness of its occurrence by clinicians. Renovascular lesions have been stressed in the past. However, in recent years, a number of nonrenovascular renal lesions have received attention and form the basis for this report. Unilateral chronic atrophic pyelonphritis, segmental unilateral pyelonephritis, the Ask-Upmark kidney, and unilateral renal hypoplasia have been associated with curable hypertension. The subject of juxtaglomerular cell hyperplasia, which has variably been reported in these cases, is reviewed. Ureteral obstruction, in the form of uretero-pelvic or ureterovesical junction obstruction, solitary renal cysts, the unilateral multicystic kidney, renal trauma, and renal tumors (Wilms' tumor and juxtaglomerular cell tumors) may also be associated with hypertension in children. Pheochromocytoma must be ruled out in all cases. Because of renewed interest, these nonrenovascular renal causes of hypertension are now likely to be diagnosed with increased frequency.


Pathology and natural history of urethral tumors in females: review of 65 cases. Cancer of the female urethra, although uncommon, is important because unless recognized early and treated adequately, death will ensue, preceded by much morbidity. The authors present a series of 62 patients with 70 primary tumors, and 3 patients with secondary tumors. A comprehensive classification of neoplasms of the female urethra is also included.


Fibrous histiocytoma of bladder.

Fibrous histiocytoma of bladder. A case of benign fibrous histiocytoma of the bladder is presented. The occurrence is rare, and criteria for defining malignant potential are unreliable. Careful follow-up evaluations are important.


[Immunofluorescence with PI-3 virus--preparation and evaluation of conjugates from immune sera of various animal species]. Immune sera with a high content of antibodies to para-influenza-3 (PI-3) virus suitable for production of specific conjugated immunoglobulins were prepared on conventionally reared calves, rabbits, and guinea-pigs, applying antigen in different ways. When processing the sera of the above mentioned animal species to conjugates, the sera differed in pure IgG yield, in completed conjugate, and molar F/P ratios, but their ability to demonstrate antigens of the PI-3 virus in the dilution was approximately the same. The serum prepared on a colostrum deprived calf showed the lowest antibody content and the lowest pure IgG yield, the colouring ability of the conjugate prepared being as well somewhat lower.


[Biochemical and histological studies of cows with ketosis]. Biochemical and histological investigations were carried out with cows affected with ketosis in a subclinical and clinical form. Parellel studies were performed with normal (control) cows originating from the herds with the ill animals and manifesting the same physiologic status. It was found that the blood level of glucose in the diseased cows was lowered more than 2.6 times, and the content of ketone bodies was higher-- it was increased 4.6 times, that of total lipids was 2.6 times higher, and that of free fatty acids was 3.5 times higher as compared to the same indices in the controls. The blood content of pyruvate in the affected cows was also increased. The liver glycogen in these animals was lowered from 2.1 to 4.1 times. The activity of glucose-6-phosphatase was lower, and that of glucose-6-phosphatedehydrogenase was higher as against the same indices shown by normal cows.


Peripheral nervous system affection in experimental lipidosis induced by 4,4'-diethylaminoethoxyhexesterol. A picture of generalized phosphoglyceride and cholesterol storage was induced, in keeping with literary data, by the experimental administration of 4,4'-diethylaminoethoxyhexesterol to rats. An asset of this model lies in the discovery that considerable storage occurs in the peripheral nervous system in contrast to the CNS, whose resistance to hexesterol is generally known. The significance of this finding is briefly discussed.


The incidence of antiviral antibodies in multiple slcerosis. The serological investigation of 96 multiple sclerosis (MS) patients, 61 patients with various other neurological diseases and 100 healthy controls made evident the increased incident of antimeasles and antiparinfluenza type 1 antibodies in the group of "probable" MS patients. There was no significant difference as regards antimumps antibodies. Antimeasles antibodies were detected in 7 of the 8 cerebrospinal fluid samples from "probable" MS patients, but in none of the 12 samples from patients with other neurological diseases. The significance of these results for the etiology of MS is discussed.


Interaction between cerulopasmin and Sendai virus envelope components. Note V. Serological response in the rabbit to Sendal virus and subviral fractions. Immunization of rabbits with Sendai virus and subviral fractions induced the appearance in the serum of both hemagglutinin- and neuraminidase-inhibiting antibodies. The study of the correlation between antigen characteristics and the level and kinetics of the antibodies suggests that a single antigenic glycoprotein carries both hemagglutinin and neuraminidase activities. The level of serum antibodies depends both on the size and structure of the antigens and on their organization, and reflects the role of the protein and carbohydrate moieties of the different antigen preparations used.


Parameters of RNA-dependent RNA polymerase activity in a mengovirus-infected Ehrlich ascites carcinoma cell-free system. Virus-specific RNA polymerase activity of mengovirus-infected Ehrlich ascites carcinoma (EAC) cells was maximal 7 hours after infection in a one-step growth cycle. In a cell-free system with the mitochondrial-microsomal fraction (MMF) derived from mengovirus-infected EAC cells in a nucleoside-triphosphate medium, polymerase activity increased up to 60 min (when MMF was obtained by a homogenizer) or 120 min (when MMF was prepared by sodium deoxycholate disruption). Subsequently RNA polymerase activity decreased between 150-180 min of incubation at 37 degrees C and then formed a plateau up to 300 min. The cell-free system used is able to give valuable information as regards testing of RNA polymerase inhibitors in an antiviral screening programme.


[Soluble cerebral metalloproteins. II. Superoxide dismutases of cerebral gray and white matter]. Superoxide dismutases (SOD) of high purity have been obtained from grey and white matter of bovine brain cerebral hemispheres. The SOD obtained have been shown to have three isoenzymes (a, b, c). A study of the catalytic and macromolecular properties of the SOD obtained from grey and white matter of cerebral hemispheres as well as their optical and electron paramagnetic resonance spectra indicates that both proteins possess similar properties. The possible function of SOD in grey and white matter of brain is discussed.


[Inhibition of rat heart and brain cyclic 3',5'-adenosine monophosphate phosphodiesterase under the influence of neurohormone "C"]. In vitro studies of the effect of neurohormone C on cyclic AMP phosphodiesterase activity of heart and brain showed that amounts of neurohormone equal to 5 ng inhibited significantly the activity of phos-phodiestherase in heart and even more strongly in brain. A comparison of the effect of the neurohormone with that of theophylline (10 mM) showed that very small amounts of the neurohormone brought about inhibition of enzyme activity that was equal to that observed from much larger concentrations of the theophylline. It is proposed that the inhibition of phosphodiestherase activity is of importance in the mechanism of the action of the neurohormone.


[Pathogenesis of rhinovirus infection].

[Pathogenesis of rhinovirus infection]. Rhinoviruses (RV) are the etiological factors of not only acute respiratory diseases of the common cold type but also of acute and chronic diseases of otorhinolaryngological organs. Virological and bacteriological examinations of patients with chronic pneumonia in the stages of exacerbation and incomplete remission revealed a high degree of the infection activity. Virus-bacterial associations were frequently found. RV were isolated from the lower respiratory tract (bronchopulmonary secrete, biopsy materials). The association of RV with the involvement of the lower respiratory tract in patients with chronic pneumonia was demonstrated. Rhinoviremia was detected in one child dying with acute respiratory disease. The results of studies on some factors of specific and nonspecific immunity in patients with chronic pneumonia are presented.


[Effect of Production on the serum lipid and lipoprotein level in ischemic heart disease]. The serum lipids were dynamically followed up in 39 patients with ischemic heart disease treated with Prodectin. A gradual decrease of serum cholesterin is observed during the treatment period as well as of its content in alfa lipoproteins and of alfa lipoproteins themselves. A moderate decrease of triglyceride and total lipids develops in parallel with this, whereas free fatty acids considerably increase. In more than 1/3 of the patients the profile of hyperlipoproteinemia changed in the course of the treatment: the half of them turned to normolipoproteinemia, a number of the rest--into a more favourable type--II and IV type.


[Chromosomes of 7 transplantable lines of macaque and pavian hematopoietic cells producing herpesvirus type EBV and oncornavirus type C]. Karyotypes of Su-1, Su-2, KMMA-1, and KMMA-2 (producing oncornavirus C-type), and KMPG-1, SPF-2, and SPG-3 (producing HSV, a virus of EBV type) cell lines were studied in the time course. The lines were derived from hemopoietic cells of brown macaques and baboons bearing lymphomas. Some of the lines had a paradiploid-pseudodiploid karyotype, another part aneuploid type. The selectivity of structural and numerical abnormalities of chromosomes 1, 9, 10, 11, 12, 13, 15, 18, and 20 was detected indicating a certain specificity of karyotype changes upon malignization and transformation. The number of poorly and moderately differentiating chromosomes in aneuploidy was confirmed by greater variability as compared with well-differentiating chromosomes. No parallelism between the karyotype change pattern and the type of virus produced (C or EBV) could be found thus far.


[Virus inactivation by hydrogen peroxide]. The effect of H2O2 on adenovirus types 3 and 6, adenoassociated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain Long, and coronavirus strain 229E was studied in vitro, using different H2O2 concentration and timec of exposure. H2O2 in a 3 percent concentration inactivated all the viruses under study within 1--30 min. Coronavirus and influenza viruses were found to be most sensitive. Reoviruses, adenoviruses and adenoassociated virus were relatively stable. H2O2 is a convenient means for virus inactivation.


[Stimulation of mouse encephalomyocarditis virus reproduction by non-multiplying poliomyelitis virus in several transplantable tissue culture lines]. Reproduction of mouse encephalomyocarditis virus (EMC) was studied in 5 continuous primate cell lines: HeLa, Fl, Detroit-6, P/7, and MIO inoculated with guanidine-dependent variant of poliomyelitis virus in the absence of guanidine. Poliomyelitis virus stimulated EMC virus reproduction in all cell lines under study. This stimulation effect was studied at length in HeLa and MIO cells. In HeLa cells, stimulation was observed at a low and moderate multiplicity of infection of EMC virus but not at a high (100 PEU/cell) multiplicity. Also, when EMC virus reproduction was stimulated, a shortening of the latent period of its multiplication cycle, an increase in the number of antigen-containing cells and the number of infectious centers were observed. In MIO cells, stimulation was found to occur both with low and high doses of EMC virus but not to be accompanied by a shortening in the latent period of EMC reproduction cycle, or any increase in the antigen-containing cells or number of infectious centers. In both cell types upon mixed infection the synthesis of virus-specific RNA's of EMC virus was enhanced. It is suggested that the stimulating effect of poliomyelitis virus is realized in HeLa and MIO cells at different stages of EMC virus reproduction.


[Antiviral activity of several nucleic acid components methylated in the N-position]. The degree of reproducation of Rous sarcoma, mumps, and vaccinia viruses in chick embryo cell culture incubated in the presence of 9-methyladenine was considerably lower than reproducation of these viruses in the cells propagated without this substance. 1-methyluracil and 1-methylthymine reduced considerably the amount of Rous sarcoma virus produced by the cells as compared to the controls. The presence of these substances in the maintenance medium does not prevent virus infection of the cells, and their effect appears to be associated with nonspecific action on the late stages of the virus reproduction.


[The application of guanidine hydrochloride to the treatment of degenerative nervous and muscular diseases. I. Clinical results (author's transl)]. This paper reports the results obtained on using guanidine hydrochloride in the treatment of patients with amyotrophic lateral sclerosis, degenerative diseases of the spinocerebellar system or the peripheral nervous system and dystrophic muscle diseases. A long-term effect of the substance was a diminution in the rate of progression of the diseases, with the exception of the group with dystrophic muscle diseases. Initial clinical improvement occurred in certain patients of both groups. The substance seems to be more effective in less-advanced cases than on administration in the later stages of the disease. The therapeutic dosage was 20 to 40 mg/kg/day. The most frequent side-effect was paraesthesia and sometimes gastric disturbance was reported. Therapy had to be discontinued in 3 patients due to leucopenia. In these patients the symptoms rapidly increased in severity after discontinuation of treatment. This supports the assumption that guanidine hydrochloride treatment slows down the progress of the disease.


Dissimilatory nitrate reduction in Clostridium tertium. Fermentation balance studies were carried out on Clostridium tertium grown with and without nitrate in the medium. Nitrate reduction increased the efficiency of energy produced from glucose by permitting the utilization of additional sites of substrate level phosphorylation. The effect was even more dramatic in C. tertium than in C. perfringens, with increased cell yields of about 30% being observed in the former compared with 20% in the latter. Unlike C. perfringens, C. tertium responded to the presence of nitrate in the medium with an increased growth rate. A slight increase in the Y ATP of these cultures was also observed, and quantitatively, this appeared to be consistent with the prediction of Stouthammer and Bettenhaussen that Y ATP will vary with the growth rate. Thus, C. tertium, like C. perfringens, was able to use nitrate as an electron acceptor in conjunction with its energy metabolism, suggesting that this may be widespread among the nitrate-reducing anaerobes.


[Dysostotic changes and the prognosis of Perthes' disease after operation (author's transl)]. Goff and Mau for the first time demonstrated dysostotic changes in children with Perthes' disease. Their effect on the course of the disease has not so far been determined. It was examined on 41 patients following varus-osteotomy. Follow-up after 2--6 years showed late radiologic results, measured against the total quotient (Heyman and Herndon) depended essentially on this dysostotic component. The worst results are seen in children with high-grade skeletal retardation. Final results are further influenced by age, stage of the disease at the time of surgery and pre-operative status. Age plays a part in that results are better the younger the child. There are obvious parallels between results of radiologic and histologic examination at the time of operation and the weightbearing capacity. Dysostotic changes prolong the course of Perthers's disease and cause long-term lack of firmness of the femoral head. The influence of these facts on the still controversial indication for surgery is discussed. Our findings suggest that protection against weightbearing should be prolonged after operation according to the dysostotic changes.


Paraquat suicide in a young woman: results of therapy directed against the superoxide radical. The clinical course of a young woman following two separate suicide attempts using the herbicide paraquat is reported. The patient survived an intramuscular injection of paraquat almost asymptomatically, but later exhibited a typical fatal course with fulminant proliferative pulmonary fibrosis after an intravenous injection. Fibrosis and death occurred despite a therapeutic regimen based upon a known action of paraquat, the generation of superoxide (O(2)[unk]), using superoxide dismutase, α-tocopherol, and ascorbic acid in conjunction with forced diuresis and prednisone. While treatment failed explanations for the failure of therapy in this case and current therapeutic alternatives are discussed so that they may be considered when future cases are encountered.


Characterization of a soluble NADH-independent nitrate reductase from the photosynthetic bacterium Rhodopseudomonas capsulata. The assimilatory nitrate reductase was purified 60-fold from a newly isolated, nitrate assmilating strain of the photosynthetic bacterium Rhodopseudomonas capsulata. The enzyme had a molecular weight of about 180 000 dalton and was typically prokaryotic in that it was not active with reduced pyridine nucleotides but rather with reduced flavins.


Calcium gradient dependent pyrophosphate formation by sarcoplasmic vesicles. The vesicles of the sarcoplasmic membranes synthesize pyrophosphate from inorganic phosphate. Pyrophosphate synthesis proceeds as long as a calcium gradient is maintained across the vesicular membranes. Pyrophosphate synthesis is inhibited by low concentrations of nucleoside triphosphates.


Enzymatic activity in a semi-gley soil under the floodplain forest in South Moravia. In three profiles of a semi-gley soil under the floodplain forest, variations were studied in the activities of invertase, amylase, cellobiase, cellulase, proteases, and phosphatases. In the surface soil layer, enzymatic activity was found affected by the soil moisture at a significant level, whereas in the deeper soil layers the influence of aeration was more effective. Moreover, significant correlations could be detected between the amount of available nitrogen and protease activity, while the water-soluble phosphorus acted as a represeive agent on the activity of phosphatases. Existence of correlations between the numbers of microbes and enzymes could be demonstrated for invertase and protases only.


[In vitro studies of the antiviral activity of ammonium humate against herpes simplex virus type 1 and type 2 (author's transl)]. Ammonium humate, isolated from peat water, is a higher molecular polyphenolic compound with a strong antiviral activity against herpes simplex virus type 1 and type 2. Three cell lines were chosen for examining the cytotoxicity of ammonium humate: rabbit kidney primary cells, HEp-2- and FL-cells. As the light microscopic examination of both, the monolayers and the stained cover-glass cultures, revealed, concentrations of up to 5 microgram/ml ammonium humate can be used without hesitation for rabbit kidney primary cells (Fig. 1, 2) 200 microgram/ml for HEp-2-cells (Fig. 3, 4, 5), and 2000 microgram/ml for FL-cells. Fresh prepared rabbit kidney primary cells and suspended FL-cells (Tab. 1) are most sensitive against ammonium humate than monolayers. A remarcable plaque inhibition effect on the multiplication of herpes simplex virus type 1 and type 2 has been observed in all cell systems at concentrations of 0.5-20 microgram/ml ammonium humate (Fig. 6). The inhibition of virus multiplication at concentrations of greater than 10 microgram/ml ammonium humate was independent of the incubation temperature (Fig. 8). The adsorption of the virus to the cell surface has been found to be the most humate-sensitive phase of the herpesvirus multiplication cycle (Fig. 7, 9, 10). A prophylactic effect in vitro could be observed at concentrations greater than 10 microgram/ml ammonium humate (Fig. 11, 12).


Media supplemented with nalidixic acid for the isolation of gram negative anaerobic bacteria. The minimum inhibitory concentrations (MIC) of nalidixic acid were determined for thirty-four strains of Clostridium sp. by an agar dilution technique. The MIC range of Clostridium perfringens ran from 0.03 microgram/ml to 64 microgram/ml, according to a bimodal distribution. One half of the strains was inhibited by 0.25 microgram/ml. 64 microgram/ml was able to inhibit all the strains tested. The author suggests a systematic utilization of media with and without 40 microgram/ml nalidixic acid. These two media were parallely inoculated with clinical specimens where anaerobic bacteria were suspected, and allowed the isolation of gram negative anaerobes.


[Fluorescent FAB-fragments of antibodies. Comparative assessment and utilization in immunofluorescent analysis]. The authors present the results of a comparative study of the immunofluorescent activity and the specificity of fluorescent Fab-fragments of antibodies to R. prowazeki, D. sibericus, and B. pertussis obtained by the enzymatic hydrolysis of specific immunoglobulins with papain. Fluorescent Fab-fragments of antibodies possessed the same sensitivity and specificity as the homologous fluorescent antibodies, but had an advantage of a much weaker capacity to nonspecific fluorescence and a relatively higher staining properties. Fluorescent Fab-fragments of antibodies, in contrast to the fluorescent antibodies of the same specificity, permitted to detect the antibody searched in the concentrated crude material, and thus increased the possibilities of the immunofluorescent analysis.


[Characteristics of paradoxical sleep in different types of epileptic seizures]. In 136 patients with different forms of epileptic strokes paradoxal sleep (PS) was studied. Shifts of a qualitative and quantitative character were revealed. The latter, in particular was expressed in a dissociative type of PS when muscular tension was preserved. The found changes were expressed more severely in patients with polymorphic and psychomotor strokes in the frontotemporal and frontal localization of the epileptic focus. In general, the same patients registered paroxysmal and epileptic activity in the period of PS, what was infrequently found in other forms of epileptic strokes, however, it had never coincided with the registration of rapid ocular movements. The role of PS physiological mechanisms in suppression of epileptic activity and possible ways of searching for more effective antiepileptic measures are discussed.


[Connections between spinal ganglia in the pathogenesis of reflex-distant pain syndromes]. Using the complex of the neurohistological research methods the author studied spinal ganglia, spinal cord (37 dogs) following the removal of groups of the spinal ganglia in the cervical and thoracic sections. Widely spread distant receptor-reflex systems of the connections between spinal ganglia accompanied by dendrites and axones were revealed. The fibres of these systems pass in the Bechterew intermediate regions of the posterior columns of the spinal cord. The straight interneuronal connections between the cervical and lumbar spinal ganglia were found. On the basis of the obtained data the author conducted analysis of the mechanism of the occurrence of reflex-distant pain syndromes in patients with ganglio-radiculoneuralgia in degenerative diseases of the vertebral column. The reflex-distant syndrome occurs due to irritation of spinal ganglion neurons accomplishing distant ganglion connections.


Comparative activation by AMP and cyclic-AMP of rat erythrocyte and reticulocyte glycolysis. Incubation of raty erythrocytes and reticulocytes in Tris-Ringer's medium with 5 mM cyclic-AMP or AMP increased lactate formation and glucose utilization. The glycolysis-stimulating effect of cyclic-AMP is very similar to that of AMP and, in both cases, it seems to be higher in reticulocytes than in erythrocytes. 0.5 mM norepinephrine produced a much higher lactate formation in reticulocytes than in erythrocytes, suggesting a greater adenylate cyclase activity in younger cells. 300 micrometer cyclic-AMP and AMP reverse inhibition produced by ATP (up to 1.5 micrometer) on phosphofructokinase from rat reticulocyte haemolysates. Both nucleotides are positive allosteric effectors of the enzyme as shown by displacement of F6P-saturation curve to hyperbolic kinetics. Similar results were previously obtained with rat erythrocytes. This deinhibitory effect is suggested to be responsible of the above glycolysis-stimulating effect.


Carbon balance studies with various substrates in human erythrocytes. Carbon metabolism in erythrocytes has been found to be in balance with a variety of substrates studied. The contribution of the 2,3-bisphosphoglycerate pathway to carbon metabolism depends on the rates of carbon utilization and increases with increasing metabolic rates. Net decrease of the 2,3-bisphosphoglycerate level acts as a NAD regenerating system thus facilitating uptake of polyalcohols such as xylitol.


Superoxide anion and drug-induced hemolysis. Superoxide anion, either generated during the autooxidation of dihydroxyfumaria acid or by the interaction of 1,4-naphthoquinone-2-sulfonate and intracellular hemoglobin in red cells pretreated with the intracellular superoxide dismutase inhibitor, diethyldithiocarbamate, produces structural changes in red cells hemoglobin and hypotonic lysis. No evidence for lipid peroxidation was found in red cells exposed to either 1,4 naphthoquinone-2-sulfonate in the presence of diethyldithiocarbamate or to dihydroxyfumaric acid, although the membranes of these cells exposed to either 1,4 naphthoquinone-2-sulfonate in the presence of diethyldithiocarbamate or to dihydroxyfumaric acid, although the membranes of these cells retained a green pigment. These results suggest that superoxide anion reacts with cellular hemoglobin to form hemoglobin breakdown products which bind to the red cell membrane and thereby increase the osmotic fragility of the cell.


Electron spin resonance spectra of chicken liver and hepatoma tissue embedded in paraffin. ESR spectra of chicken liver and hepatoma tissue embedded in paraffin display signals characteristic of free radicals and paramagnetic complexes. Owing to embedding the spectrum is altered as compared to that of the native tissue but remains characteristic of the respective tissues. The spectra of tissues embedded in paraffin allow no more than qualitative conclusions to be drawn concerning the spectra of the native tissues, even if appropriate controls are applied.


X-ray microanalytical studies of lead-implanted rat brains. Various cytoplasmic and intranuclear inclusions found in macrophages and astrocytes of lead-implanted rat brains were studied with an energy dispersive x-ray microanalytical technique. Cytoplasmic inclusions contained large quantities of lead, calcium and phosphorus. The proportions of these elements were different within each inclusion. Intranuclear inclusions also contained small amounts of lead and, occasionally, calcium.


Glial cell characteristics in bulk-prepared cell fractions from human brain tumours. The heterogeneity of brain tumours, especially in the glioblastoma group, makes biochemical characterization of pieces of the tumours hazardous even with extensive histological controls. This study employs a technique by which separate cell populations are subsequently isolated from the tumours by means of density gradient centrifugation. Cells isolated from glial brain tumours with low density sedimentation rates show the highest levels of glial cell characteristics, i.e. S-100 content and active uptake of the neurotransmitter GABA.


Subependymoma: a case report with ultrastructural study. A case history illustrating the potential clinical significance of subependymoma is presented. Fine structural studies indicate that the tumor is composed of cells having the cytoplasmic features of ependyma, astrocytes, and transitional cells. Its composition and structure are alike those in the adult mammalian subependymal layer.


Nasopharyngeal cancer in Greenland. The incidence in an Arctic Eskimo population. Nasopharyngeal cancer is very common among the Chinese in various parts of the world, particularly Southern China, and frequent in certain other Mongoloid groups in Southeast Asia. Also, the incidence among the Eskimos of the western Canadian Arctic and Alaska is considerably higher than would be expected. Ths paper reports for the first time the incidence of nasopharyngeal cancer among native Greenlanders, an Eskimo population with some admixture of Caucasian blood. During 1955-1976, thirty-five cases of nasopharyngeal cancer were diagnosed. Ninety-four per cent (33 cases) were squamous cell carcinomas, including lymphoepitheliomas. Incidence rates 1965-1976, age adjusted to the "world" population distribution, were 12.3 and 8.5 per 100,000 per annum for males and females respectively. These rates are among the highest recorded in the world and significantly higher than among the Caucasian population in Denmark. Compared with other high risk populations nasopharyngeal cancer among Greenlanders had an older age distribution and a lower male-to-female sex ratio. An additional 11 cases with malignant involvement, seeminly confined only to cervical lymph nodes, may have included some undiagnosed nasopharyngeal cancers. Thus the calculated incidence rates of this study could represent only minimum rates. Further research is needed especially with regard to the HL-A profile and to possible traces of Epstein-Barr virus infection.


Induction of latent Herpes simplex virus type 2 infection in human cervical epithelial cells in vitro. An in vitro method was used to induce non-productive herpes simplex virus type 2 (HSV-2) infections in human ecto- and endocervical epithelial cells. Adenine arabinoside (ara-A) could prevent the replication of HSV-2 in ecto- and endocervical cells and after removal of ara-A from growth medium a rapid destruction of explants with development of infectious virus was observed. When ara-A was not withdrawn until 4 days or later after in vitro infection the morphological, immunofluorescent and virological studies detected no infections. However, 2-3 weeks after inoculation there were in some cultures morphological as well as immunofluorescent signs of HSV infection without demonstrable infectious virus, indicating an incidental abortive nature of the infective process.


Quantitative immunoelectrophoretic studies of the L and S antigens of vaccinia virus. The L (10S) and S (7S) antigens of vaccinia virus have been characterized by their sensitivity to heat, to proteolytic enzymes and to periodate. The L antigen was heat labile and inactivated by proteolytic enzymes and periodate. Treatment with trypsin for 1 min indicated that the S antigen was built up of at least two protein subunits of about 3S and 5S. One of the subunits was highly sensitive to heat and to proteolytic enzymes. On further treatment with trypsin the other subunit was split in two components showing partial identity serologically.


Inhibition of noradrenaline-stimulated lipolysis and cyclic AMP accumulation in isolated rat adipocytes by purified phospholipase C and theta-toxin from Clostridium perfringens. Purified phospholipae C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) and theta-toxin from Clostridium perfringens both inhibited noradrenaline-stimulated lipolysis and cyclic AMP accumulation in isolated rat adipocytes in a dose-dependent manner. The action of phospholipase C was gradual in onset, while the effect of theta-toxin was almost immediate. Phospholipase C, but not theta-toxin, hydrolyzed membrane phospholipids and inhibited adenylate cyclase (EC 4.6.1.1) in a crude membrane fraction from fat cells. The inhibitory effects of phospholipase C were associated with morphological alterations detectable by electron microscopy, whereas effects of theta-toxin were observed at a time when no clearcut morphological alterations could be observed. It is concluded that the two purified principles from C. perfringens, which are both present in commercial preparations of phospholipase C, antagonize noradrenaline-stimulated cyclic AMP accumulation and lipolysis. Although their exact mechanisms of action have not been elucidated, phospholipase C and theta-toxin have different modes of attack.


Cellular action of gastrointestinal polypeptide hormones. The present state of chemistry, structure-activity relationship and cellular mode of action of gastrointestinal polypeptide hormones (gastrin, secretin, cholecystokinin-pancreozymin, caerulein and bombesin) are reviewed. Possible structure of polypeptide receptors and the mechanism of peptide--receptor interaction are described, and the role of acetylcholine and histamine in secretion discussed. The present data support the hormonal-receptor significance of cyclic nucleotides (cAMP, cGMP) in the cellular regulation of secretion.


Effect of ACTH1-24 and ACTH4-10 on distribution of 3H-noradrenaline in the brain of adrenalectomized rats. Painful stimuli led to a decrease of the radioactive catecholamine pool in adrenalectomized rats. Intraventricular administration of both tritiated noradrenaline and ACTH produced a greater decrease of the labelled catecholamine pool than in the control adrenalectomized rats in 12 to 18 hr following injection. Blocking of monoamino-oxidase activity or biosynthesis by systemic administration of Pargyline or alpha-methyl-tyrosine did not prevent the effect of ACTH on brain catecholamines. It is concluded that ACTH exerts a direct influence on the brain catecholaminergic system and that this effect might be involved in ACTH dependent behavioural responses.


The phases of sleep and wakefulness after bilateral labyrinth destruction in chronic cats. After bilateral destruction of the labyrinths, the duration of paradoxical sleep increased from 4% in the intact animals to 8% after destruction. This increase was the result of an increase from 2.2 to 2.6 in the average number of epiodes of paradoxical sleep as well as of an increase from 3.2 to 5.5 min of the duration of each episode of paradoxical sleep. One latency of the first appearance of an episode was shortened, from the 77th min at the beginning of registration to the 43rd min after destruction. During this time the duration of wakefulness decreased from 30% to 17%.


Pertussis vaccine--fact and fiction.

Pertussis vaccine--fact and fiction. The present paper indicates a number of unresolved problems in the metabolism of Bordetella pertussis and in the standardization of pertussis vaccines. The use of chemically defined media should enable the metabolic problems to be clarified. The problems concerned with the control and standardization of vaccines can largely be resolved in the laboratory with the introduction of reference preparations but the question of the reactivity of vaccine remains for the future.


Significance of the surface of crystalline silicogenic dusts in experimental silicosis. Crystalline, silicogenic quartz dusts possess a marked basic dye-binding capacity even in strong acid media (pH 1.0), which points to negative surface charges of the dusts. Presumably this surface property of the dusts may be related to their silicogenic effect. This hypothesis has been tested by pretreatment of the dusts with basic dyes for binding the negative surface charges. The dusts were administered intratracheally to rats. The results obtained after 8 and 12 months revealed that staining by basic dyes of the dusts decreases their silicogenic activity.


Special forms of initial gastric cancer. 1. Fifty-five microscopic cancer foci from 11 gastric resection preparations have been examined. Each focus than 5 mm was less in diameter. They occurred mostly in regions showing chronic atrophic gastritis, less frequently in the margin of peptic ulcer or in a polyp located in the antrum along the lesser curve. The lesions were discovered at routine histologic examination of stomachs operated upon for other primary diseases. 2. Histologically differentiated and undifferentiated types could be distinguished. They were: well differentiated adenocarcinoma, tubular adenocarcinoma, "intraluminal papillary proliferation of the glandular neck", "glandular neck displasia" mucocellular and muconodular carcinoma, and carcinoma in situ. In some cases, different histologic types within the same focus, or more foci of diverse structure in the same patient could be observed. 3. A malignant process developing from the glandular neck region or the surface epithelium could be demonstrated in each type of initial cancer.


Cerebral pseudocysts following chemotherapy of glioblastomas. Three cases of pseudocysts following surgery and chemotherapy for glioblastomas are reported. Their clinical picture was similar, consisting of intracranial hypertension without primary modification of focal signs. CT scanning has been able to detect the cystic aspect and to eliminate a true tumour recurrence. Medical treatment (steroids or Mannitol) seems inefficient. Evacuation of the cyst is the only efficient method of treatment.


The contribution of tryptophan to the regulation of the NAD+ level in mouse liver. It has been observed that the NAD level is lower in regenerating and growing mouse liver than in resting liver of adult mice. Also it has been found that in proliferating liver the NAD biosynthesis from nicotinamide and nicotinate is unchanged whereas that from tryptophan is reduced. Under these conditions the enzymatic activity of the kynureninase is decreased and the activity of the kynurenine aminotransferase as well as of the tryptophan pyrrolase is not altered. From these and other data of the literature it is concluded that the NAD biosynthesis from tryptophan is important for the regulation of the hepatic NAD level, through this pathway and the NAD degradation nicotinamide is formed which is transported to the non-hepatic tissues to act as a NAD precursor there. The possible interrelation between the NAD metabolism and the DNA synthesis is discussed.


Myocardial scintigraphy with technetrium-99m pyrophosphate during the early phase of acute infarction. To determine the sensitivity of myocardial scintigraphy with technetium-99m pyrophosphate during the early phase of acute myocardial infarction, 31 patients admitted to the coronary care unit with prolonged ischemic pain underwent imaging within 4 to 8 hours and again at 24 hours after the onset of symptoms. In 11 of 15 patients with documented acute myocardial infarction, increased focal myocardial uptake was demonstrated on early myocardial scintigraphy. Focal uptake was observed in only 2 of 16 patients with unstable angina pectoris. Three or four patients with normal early scintigrams had massive transmural myocardial infarction. Normal early scintigrams in these three patients may have reflected poor perfusion because the images were abnormal at 24 hours. In four patients the extent of technetium-99m pyrophosphate uptake increased more than 20 percent at 24 hours without other evidence of infarct extension. In the other seven patients, there was no significant change in the area of the abnormal radioactive uptake between early and delayed scintiscans. This study suggests that technetium-99m pyrophosphate scintigraphy can defect acute myocardial infarction as early as 4 hours after the onset of symptoms although the sensitivity rate (73 percent) is less than that at 24 hours.


Alpha1-antitrypsin, protein marker in oral contraceptive-associated hepatic tumors. Tissue specimens from a series of 46 hepatic tumors occurring in young female oral contraceptive users were tested for alpha1-antitrypsin deposition, utilizing immunocytochemical and histochemical methods. In two instances serum alpha1-antitrypsin phenotyping was also performed. Immunoreactive alpha1-antitrypsin deposits were demonstrated in benign lesions, including 56% of cases of focal nodular hyperplasia and 68% of cases of liver-cell adenoma, and in 89% of cases of malignant hepatoma. There was good correlation between alpha1-antitrypsin deposits and variable amounts of finely granular, or globular, diastase-resistant periodic acid-Schiff positivity within tumor cells. While quantitative differences in alpha1-antitrypsin deposits between benign and malignant cell proliferations were not observed, a qualitative continuum that linked all tumors in the study group was found. The findings suggest that alpha1-antitrypsin deficiency is not related to the hepatic tumors developing in oral contraceptive users. The tumor tissue deposits of alpha1-antitrypsin observed represent a marker protein, the significance of which is undefined.


Intraleukocytic spore formation and leukocytic vacuolization during Clostridium perfringens septicemia. The case of a patient with fulminant Clostridium perfringens septicemia and intravascular hemolysis is presented. The organisms in the blood stream were in sufficient quantity to be detected on a peripheral blood smear, and some were found to be within leukocytes. In vivo spore formation by C. perfringens is thought to be uncommon; however, in this patient probable spore formation by this organism was observed within peripheral blood leukocytes. The peripheral polymorphonuclear leukocytes from this patient were also markedly vacuolated.


Isolation of cytomegalovirus from cerebrospinal fluid of a congenitally infected infant. The isolation of cytomegalovirus (CMV) from the CSF of an infant with congenital disease is documented. Samples of urine sediments and CSF were inoculated into tissue cultures of human foreskin fibroblast cells. Cytopathology was evident within 48 hours in those tubes inoculated with CSF. The urine cultures were later positive. All viral isolates were identified by complement fixation tests using known positive CMV antiserum.


Granular cell myoblastoma: a cause of biliary obstruction. An 11-year-old boy was seen with gradual onset of jaundice. Dilated bile ducts were demonstrated by ultrasound and computerized axial tomography. The obstruction was caused by an unusual benign tumor, a granular cell myoblastoma. Cure was effected by resection and choledochojejunostomy.


Infectious mononucleosis and the Epstein-Barr virus. Recent elucidation of the relationship between the Epstein-Barr virus and infectious mononucleosis has resulted in the development of new diagnostic serological tests, and has amplified our knowledge of the epidemiological and clinical aspects of the disease. The history, epidemiology, clinical characteristics, diagnostic features, and therapy of infectious mononucleosis are reviewed. This is done in the light of recent knowledge concerning the Epstein-Barr virus as well as previous studies employing the traditional diagnostic criteria of heterophil positivity, the classical clinical symdromes, and characteristic changes in the blood cell count. Immunological studies concerning host resistance and its occasional failure are reviewed with particular reference to T and B lymphocyte activity in the disease.


Metiamide: more than an H2-receptor antagonist. The effect of metiamide on acid secretion and calcium uptake by the frog gastric mucosa was tested alone and in combination with histamine, pentagastrin, aminophylline, and dibutyrl cyclic AMP (db cAMP). Metiamide inhibited all stimulants including db cAMP which presumably acts intracellularly beyond the H2 receptor. Metiamide, therefore, actively inhibits at a point within the cell beyond the adenylated cyclase membrane receptor complexes. Metiamide also increases calcium influx into the parietal cell, suggesting yet another possible mechanism of inhibition.


Prevalence of antibody to hepatitis A and polioviruses in an unimmunized urban population. A large group of sera collected in 1954-1955 from people living in the metropolitan area of Melbourne, Australia, was tested for neutralizing antibody to polioviruses 1,2 and 3 and for antibody to hepatitis A virus by solid phase radioimmunoassay. The age-specific prevalence of antibody to each virus was remarkable similar, being highest in the elderly and in persons of low socioeconomic status. Antibody to each virus was acquired early in life, with more than half the population showing evidence of infection by the age of 15 years.


Tonsillectomy and infectious mononucleosis. Tonsillar tissue may be the primary site of infection with Epstein-Barr virus (EBV), the etiologic agent of classical infectious mononucleosis (IM). Therefore, a retrospective study of the association between tonsillectomy and IM was performed in a college student population. In the first part of the study, tonsillectomy rates were compared between 164 IM-positive students and 164 student controls who attended UCLA in 1972-1975. Although it was determined that the development of IM during college years was statistically less commin in tonsillectomized students, the difference was not inordinately large and probably had no significant biologic meaning. The authors speculate that the difference was due to the greater likelihood, and greater yield, in considering the diagnosis of IM in young adults with enlarged, inflamed tonsils. In support of this is the fact that IM-positive students who had received a prior tonsillectomy usually had the surgical procedure performed at a younger age than the control group. Conceivably, tonsillar ablation in the very young is more liable to result in incomplete removal and eventual regrowth of this tissue. Indeed, six IM-positive students who had received a tonsillectomy at six years of age or less were found to have exudate in tonsillar fossae or pillars during their IM episode. In the second part of the study, clinical and laboratory measures were found to be similar between a larger group of IM-positive students with or without a history of prior tonsillectomy.


Acute gastroenteritis among schoolchildren associated with reovirus-like agent. During early summer 1975 and spring 1976, outbreaks of acute gastroenteritis were reported from primary schools and other institutions in several districts of Japan. Outbreaks occurred in an explosive manner resembling mass food poisoning from a school lunch. The majority of patients were in the age group 6-14 years. Clinical features were generally mild, consisting of vomiting and/or diarrhea, often with low-grade fever. Reovirus-like agents in the feces were found in 27 (44%) of 62 patients. The virus found in feces of schoolchildren with acute gastroenteritis (SCGV) was related morphologically as well as serologically, not only to the agent found in infantile gastroenteritis (IGV), but also to neonatal calf diarrhea virus (NCDV). A slight difference in antigenicity between SCGV and IGV as suggested by cross complement fixation (CF) remains to be elucidated. About one-half of paired sera from 54 patients showed a significant rise in CF antibody against SCGV and/or NCDV. The pattern of neutralizing (NT) antibody against NCDV in patients' sera was similar to that of CF antibody. Most children studied had a titer of 1:4 or greater of CF and/or NT antibodies to SCGV and NCDV in acute sera. The relationship between acute gastroenteritis associated with reovirus-like agent in infants and that in schoolchildren is discussed.


Isozyme patterns in erythrocytes from human fetuses. Starch gel electrophoretic patterns of 26 enzymes (corresponding to 36 gene loci) were examined in hemolysates of erythrocytes from 11 first-trimester and mid-trimester human fetuses (65-138 gestation days). The zymograms of 16 enzymes were identical in fetal and control adult red cells. Six enzymes (enolase, guanylate kinase, lactate dehydrogenase, nucleoside phosphorylase, phosphofructokinase, hexokinase) showed differences in the staining intensity of certain isozyme zones as compared with the controls. Also, the fetal red cell zymograms, in contrast to those of adults, contained the mitochondrial forms of isocitric dehydrogenase and glutamic oxaloacetic transaminase as well as more definite zones of phosphoglucomutase-3. Finally, some of the isozymes of uridine diphosphate kinase in the fetal cells had slightly retarded mobility. These observed differences between fetal and adult red cells could reflect the expression of a different program of protein synthesis in red cells of the fetuses or the epigenetic modifications of isozymes in immature red cells.


Liver disease in renal transplant recipients. Liver disease is a common complication in renal transplant recipients. Several types of liver disease can occur. The most common are acute and chronic hepatitis. The variety of acute hepatitis include hepatitis A, hepatitis B, cytomegalovirus hepatitis, herpes simplex hepatitis and azathioprine hepatitis. The incidence of azathioprine hepatitis may not be as high as initially suggested. Chronic hepatitis is a serious problem because the disease seems to be progressive despite prednisone therapy. The causes of this chronic hepatitis are not fully known, although hepatitis B, cytomegalovirus and herpes simplex virus have been implicated. Discontinuation of azathioprine therapy has no appreciable effect on the course of chronic hepatitis.


Effects of intravenous isoxsuprine and ritodrine, with and without concomitant dexamethasone, on fetoplacental and pituitary hormones and cyclic adenosine monophosphate during late pregnancy. Beta sympathomimetic drugs are used to inhibit preterm labor and glucocorticoids to accelerate fetal pulmonary maturation. A study was designed to investigate the hormonal effects of intravenous infusion of isoxsuprine 150 to 200 mcg. per minute or ritodrine 100 to 150 mcg. per minute in a series of 28 women at 28 to 40 weeks' gestation, with and without concomitant dexamethasone therapy. Serial serum samples taken before and during the six hours of infusion were assayed for cyclic adenosine-3,5-monophosphate (AMP), estradiol, estriol, progesterone, human placental lactogen (hPL), thyrotropin (TSH), follicle-stimulating hormone (FSH), and human growth hormone (gGH). Ritodrine was more potent than isoxsuprine in increasing the circulating levels of cyclic AMP. The levels of placental steroid hormones decreased slightly, as did the ratio of progesterone to estradiol. Human placental lactogen and pituitary hormones showed no consistent changes. Simultaneous administration of dexamethasone did not modify these results.


The histogenesis of hepatoma occurring spontaneously in a strain of sand rats (Psammomys obesus). Spontaneous hepatomas and hepatic preneoplastic changes were observed in sand rats (Psammomys obesus) from two colonies. Both colonies originated from 10 sand rats captured in the Judean desert in 1969. At the age of 6 months, and increasing in multiplicity with advancing age, histologic examination revealed nodules containing hepatocytes characterized by hyperbasophilia, accumulation of glycogen, eosinophilic cytoplasm, or a mixture of these cells. In animals over 25 months old hepatocellular carcinoma was diagnosed. The histologic changes described here were reported to be characteristic of chemical hepatomagenesis in rats. No external chemical carcinogen could be demonstrated in our animal colonies, and a hereditary predisposition to tumor formation is presumed. Identity of hepatic carcinogenesis, irrespective of etiology in distantly related rodents, ie, the laboratory rat and the sand rat, which in reality is a gerbil, supports the assumption of the existence of a general law governing hepatic carcinogenesis.


Increased calcium uptake by muscle mitochondria of cold-acclimated rats. Skeletal muscle mitochondria of cold-acclimated rats have an altered morphology that is related to the occurrence of nonshivering thermogenesis. The transport of calcium by these mitochondria was studied in a search for an alteration in an energy-dissipating mechanism which might be related to the altered morphology and to the altered mode of thermogenesis in the cold-acclimated animal. The rates of calcium uptake, of calcium-stimulated respiration, and of state 4 respiration after calcium uptake were increased in the altered mitochondria. The capacity to accumulate calcium without phosphate was increased, whereas with phosphate all the calcium was removed from the medium and no difference in total uptake was seen. Spontaneous release of calcium was greater but sodium-induced release was unchanged. No effect of cyclic AMP or prostaglandin E1 on release of calcium was seen. The increase in rate of calcium uptake occurred gradually during the first 3-5 wk of acclimation to cold. The results are considered to give some support to the hypothesis that adaptive changes in the mitochondrial calcium transport cycle in skeletal muscle occur during acclimation to cold.


Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade. The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst.