Immunodiffusion test in avian encephalomyelitis. II. Detection of precipitating antibody in infected chickens in comparison with neutralizing antibody. The sensitivities of double-immunodiffusion (DID) and neutralization tests to detect avian encephalomyelitis (AE) antibody in chickens were studied. Two antigens were employed in the tests. Concentrated antigen gave a higher titer of antiserum than crude antigen, which reacted only to serum having a neutralization log-index (NI) of 3.4approximately4.0 or more. Antibody responses were examined in four growing chick groups inoculated with AE virus by the intracerebral, subcutaneous and oral routes by the DID test with concentrated antigen and by the neutralization test for 1 or over 2 years after inoculation. When concentrated antigen was used, most sera having an NI of over 1.0 were positive for precipitating antibody. Therefore, the sensitivity of the DID test was nearly equal to that of the neutralization test. The DID test was considered to be applicable to the diagnosis of AE and an antibody survey in the field.


Nuclear localisation of DNA polymerase alpha and DNA synthesis in polyoma virus infected mouse cells. Studies using inhibitors of DNA synthesis have shown that DNA polymerase alpha is located in nuclei of polyoma virus infected mouse cells to the same degree as these nuclei are engaged in DNA replication. These results indicate that either the enzyme is actively transported into nuclei concomitant with the onset of DNA synthesis, or that it is bound much more strongly in nuclei during DNA replication. In any case, these observations support the hypothesis that DNA polymerase alpha is involved in the replication of cellular and viral DNA.


The effect of eugenol on nerve transmission. Because of its long-time use as a sedative or anodyne in dental procedures, eugenol was studied to determine its effect on evoked nerve impulse transmission. The sciatic nerve of the bullfrog was stimulated in a nerve chamber, and the compound action potential was visualized on and recorded from an oscilloscope screen. It was determined that eugenol concentrations ranging from 100 per cent to 0.01 per cent extinguished the impulse-transmission capabilities of the nerve within 3 hours. No reversal was observed within this time frame.


Radiographic manifestations of a lung carcinoma with metastases to the anterior maxilla. Radiographic examination of the facial bones frequently reveals osteolytic and osteoblastic changes. A case of undifferentiated large-cell carcinoma of the lung with metastasis to the anterior maxilla is reported. Intraoral dental radiographs revealed an ill-defined lytic area in the left anterior maxilla. The periphery of the lesion revealed saberlike extensions of bone extending into the lytic defect. Cytologic and biopsy studies of the oral mucosa led to identification of the tumor as an undifferentiated large-cell carcinoma of the lung.


Method for the determination of protein evolution rates by amino acid composition. Evolution rate of actins. A method has been developed to determine the actin evolution rate. The method is based on amino acid compositon. The actin evolution rate has been established to be extremely low. Only three or less amino acid changes per hundred amino acid residues have accumulated for a 100 million years. One can explain the conservative nature of actin evolution as a sequence of its unique tightly fitted structure rich in biologically active centres at short distances from each other. The peculiar invariability of polar amino acids leads to a conclusion that some given distribution of charges is necessary for the unique functioning of actin molecules.


[A new antigonadotropin in the treatment of precocious puberty and pubertal gynaecomastia (author's transl)]. A synthetic steroid compound derived from testosteron (isoxazol-ethisterone), Danazol, with gonadotropin-depressing activity, was used in the treatment of 4 cases of idiopathis sexual precocity (age 2 1/2 to 4 years) and in 10 cases of severe pubertal gynaecomastia. In sexual precocity the suppression of menstruation as well as of breast-enlargement was good, while the suppression of acceleration of longitudinal growth and bone maturation was inferior compared with cyproteron-acetate. In most boys with gynaecomastia a marked regression of breast enlargement occurred within a few weeks or months. With the dosage used (200-300 mg/day in the sexual precocity patients, 300-400 mg in the gynaecomastia patients) the changes in plasma hormone levels (LH, FSH, progesterone, estradiol, testosterone) were within a non significant range. Depression of testosterone seemed to be a rather regular finding. No untoward side-effects of the medication were noticed in the 14 patients studied. In summary, Danazol did not show any advantages compared with the compounds used in the treatment of isosexual precocity sofar. In contrast, the drug proved to have useful effects in pubertal gynecomastia, a condition which in severe degrees certainly deserves medical treatment.


Response of gonadotropins to stimulation with luteinizing hormone -- releasing hormone (LH-RH) in children with precocious puberty before, during and following therapy with cyproterone acetate or an ethisterone derivate. 9 children with precocious puberty were treated over a period of 6 months to 6 3/12 years with Cyproteron acetate or an Ethisterone derivate. LH-RH tests with radioimmunological estimations of LH and FSH were performed before therapy was begun, during and after completion of treatment. In children with untreated precocious puberty the mean basal LH levels were the same as in normal prepubertal children but the increase and the peak values after i.v. LH-RH were found to be considerably greater than in normals. In the treated patients this stimulatable LH release was suppressed; after completion of therapy it was again elevated. The basal FSH levels in untreated children were elevated; however the increase and the peak values were comparable to the collective norm. Results were not altered considerably by therapy, however these parameters were given elevated after completion of therapy. Despite the marked suppression of stimulatable LH by therapy acceleration of bone age is practically not affected. After completion of therapy this drug-induced suppression of gonadotropines is promptly reversible.


[Investigations of the urinary cAMP-excretion in pseudohypoparathyroidism (author's transl)]. Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs and clinical and laboratory symptoms of hypoparathyroidism which is resistant however to parathyroid extract. ALBRIGHT and coworkers supposed that this resistance was caused by an inability of the renal tubules to respond to parathyroid hormone. On three children, suffering from PHP, we could demonstrate that parathyroid extract-resistance disappears during treatment with vitamin D. Measurements of urinary excretion of cAMP, the second messenger for parathyroid hormone, in the same patients showed low basal levels of this nucleotide, which could not be stimulated by parathyroid extract either before or during vitamin D-treatment. This constantly low and by parathyroid extract not stimulable cAMP-excretion is now the symptom with the most diagnostic value for PHP. Beyond this the finding of this defective urinary excretion of cAMP in PHP was able to explain the hitherto unknown pathogenesis of this disorder: the parathyroid hormone -- sensitive adenylcyclase system is here unable to mediate the action of parathyroid hormone on its target cells, so causing a peripheral block of parathyroid-hormone activity. Therefore GREENBERG and coworkers justly term PHP a disease of the second messenger.


Isolation of polioviruses from paralyzed  children in the province of Isfahan, Iran. Viral studies were carried out in 47 children with clinical features of paralytic poliomyelitis. Forty-seven healthy children matched in age and sex were used as controls. Fourteen cases of polioviruses were isolated from the paralyzed children. Of these, 10 isolates were of type one, 2 type two and 2 type three. Among the healthy children two polioviruses were isolated, one type 1 and one type three. The importance of vaccination against poliomyelitis is emphasized.


The action of collagenase on K-type Bence-Jones proteins. The proteolytic action of a bacterial collagenase on two Bence-Jones k chains has been studied and the localization of the cleavage sites accomplished. The implications of this enzymatic attack are discussed.


Transient effects of norepinephrine on myocardial oxygen balance. In conscious dogs with experimental atrioventricular block and with ventricles paced at constant rate the effects of norepinephrine (NE) and isoproterenol (ISO) on coronary flow, coronary resistance, and myocardial O2-balance were investigated. Myocardial O2-S balance, as estimated from continuous measurement of coronary venous O2-S saturation, was used for the discrimination of coronary dilation induced either directly by vascular beta-adrenoreceptor stimulation or indirectly by increased myocardial metabolism. Following bolus injection of NE (0.3 microgram/kg) or ISO (0.1 microgram/kg) into the pulmonary artery, coronary venous O2-S saturation increased from a control of 25 +/- 2% O2-S saturation (mean +/- S.D.) transiently to 51 +/- 5 and 62 +/- 5% O2-S saturation respectively. After beta1-adrenoreceptor blockade these increases were reduced to 33 +/- 4 and 41 +/- 3% O2-S saturation, respectively. The remaining increase after NE was abolished when atropine was given in addition to beta1-b blockade. After beta1 + 2-adrenoreceptor blockade neither NE nor ISO injection had an effect on coronary venous O2 saturation. After beta1-b blockade was superimposed on ganglionic blockade NE injection led to a decrease in coronary venous O2-S saturation indicating a latent alpha-a activity of NE. NE seems to act directly via beta1-a adrenoreceptors, since no differences were observed in the time courses of changes in coronary venous O2-S saturation after left atrial injection of NE when compared to adenosine. It is concluded that circulating NE like ISO is able to improve myocardial oxygen balance by a direct vasodilating effect on canine coronary vessels mediated by vascular beta1-adrenoreceptors.


[Multiplication of murine C-type viruses in mouse teratocarcinoma cell lines]. The host-virus interactions of several murine C type viruses with cell lines established in vitro from a mouse teratocarcinoma were studied. The cells used in this study were the multipotential stem cells, or embryonal carcinoma cells, and the differentiated cells derived from a same tumor.


Hypothalamic-pituitary function tests: current status. Pituitary disorders can be diagnosed more readily and precisely as a result of two recent advances: development of radioimmunoassays for direct measurement of each pituitary hormone in blood, and availability of hypothalamic hormones for use in provocative tests for secretion of thyroid-stimulating hormone, prolactin, and gonadotropic hormones.


Van Buchem disease.

Van Buchem disease. Van Buchem disease is a hereditary sclerosing dysplasia of bone. Both dominant and autosomal recessive modes of transmission have been described. The dominant form tends to be a benign disorder and symptoms are usually confined to those associated with the enlargement of the jaw. The recessive forms tend to have a greater morbidity and symptoms arise from pressure on cranial nerves by hyperostotic bone at the base of the skull. Patients of the dominant families have often had a torus palatinus. No haematological changes are found. The alkaline phosphatase may be raised--even if the total level is not elevated, the bone fraction may be increased. The radiological appearances are regarded as characteristic. The jaw is enlarged and thickened to an extent not seen in other bone dysplasias such as osteopetrosis. The cortices of the diaphyses are thickened and the medullary cavities are encroached upon but not obliterated. Abnormal modelling of the bone ends is not found in van Buchem disease. In long bones the distribution is predominantly diaphyseal but the bone ends are also affected.


[The significance of the local oxygen pressure and of the PO2 histogram for the evaluation of the state of oxygen supply to various organs (author's transl)]. Theoretical and experimental investigations have shown that the oxygen pressure field of an organ reflects the state of the oxygen supply of a tissue. Unfortunately it is practically impossible to measure the total oxygen pressure field. Meaurements of arterial and venous PO2 or of the mean tissue PO2 do not reveal the local tissue situation. Measurements together with K. Kunze and M. Kessler lead us to the conclusion, that the oxygen pressure field can be characterized sufficiently well by a PO2-histogram. Under normal conditions the PO2-histogram is bell shaped with a steeper left side. The form and position is rather consistent. In hypoxia low PO2 values increase causing a leftward shift of the histogram; in hyperoxia the bell shaped form is destroyed and the form becomes broader and irregular. The form of the histogram gives also information about the state of the regulation of the microflow. It can be measured by PO2 microelectrodes as well as by multiwire surface electrodes. Both techniques have been applied successfully with patients.


Collagenase-released non-collagenous proteins of cortical bone matrix. Two distinct groups of non-collagenous components were isolated from rat cortical bone gelatin which had previously been digested with purified bacterial collagenase. One component was disulfide-bonded, strongly acidic, trypsin-labile glycoprotein aggregate with a molecular mass of more than 100,000 daltons. When reduced with beta-mercaptoethanol this protein disaggregated into subunits with a molecular mass of about 60,000 daltons. The other components consisted of a group of polypeptides with a molecular mass of about 5,000 daltons. The latter group was present in collagenase digests prepared from normal bone gelatin but was hardly detectable or absent in digests of gelatin prepared from either autolyzed, trypsinized or lathyritic bone, or from the residue of neutral salt extracted rat tail tendon.


A modified method for the preparation of agarose. A simple procedure for the preparation of agarose suitable for electrophoresis is developed in which anionic polysaccharides are removed by extracting the agar gel-granules with phosphate buffer (0.03 M, pH 6.8) containing urea (4 M), followed by electrophoresis in the same buffer system. Further, alkali treatment in the presence of sodium borohydride, eliminates electroendosmosis, giving essentially a neutral agarose, as judged by the electrophoretic behaviour of basic substances like crystal violet and cytochrome C. The purified agarose with yields 60-65%, has a sulphur content less than 0.1%, and forms rigid, transparent gels.


[Influence of methylcobalamin and cyanocobalamin on the neoplastic process in rats]. The effect of methylcobalamine (5.6-dimethylbenzimidazolyl-Co-methylcobamide, CH3-B12) and cyanocobalamine (5,6-dimethylbenzimidazolyly-Co-cyanocobamide, CN-B12) on the growth of Walker's carcinosarcoma and longevity of white noninbred rats with implanted Zajdela ascites hepatoma was studied. The two agents exerted a similar effect. They 1) reduced the survival of rats with implanted Zajdela ascites hepatoma and Walker's carcinosarcoma; 2) did not increase the cell concentration in ascites; and 3) increased the total volume of ascites.


Mechanisms of amitriptyline induced hypothermia in the rat. Effects of amitriptyline on rectal temperature of male rats were studied at the ambient temperature of 25 degrees C. Drugs were administered intraperitoneally. Amitryptyline elicited a dose related hypothermia. The hypothermia was attenuated by phenoxybenzamine 10 mg/kg, haloperidol 2 mg/kg, diphenhydramine 5 mg/kg, atropine 20 mg/kg, and cyproheptadine 5 mg/kg. Propranolol, at a dose of 5 mg/kg, had no effect on the hypothermia. Theophylline 50 mg/kg and dibutyryl cyclic AMP 20 mg/kg inhibited the hypothermia produced by anitriptyline. Pretreatment with parachloroamphetamine (PCA), 2 or 5 mg/kg daily for 3 days, strongly antagonized the hypothermia. In addition, pretreatment with parachlorophenylalanine (PCPA), 100 mg/kg daily for three days, reduced the brain 5-hydroxytryptamine (5-HT) concentration to 20% of the control level and completely blocked the hypothermia response. When brain 5-HT concentration recovered to 50% of the control level in PCPA treated rats following the administration of 10 mg/kg 5-hydroxytryptophan (5-HTP) the hypothermia induced by amitriptyline was restored. However, the administration of 5-HT, 5 mg/kg, to PCPA treated rats did not increase brain 5-HT concentration or restore the amitriptyline induced hypothermia (AIH). Results suggest that amitriptyline interacts with several transmitter substances to produce hypothermia. Since the ability of amitriptyline to produce hypothermia was correlated with brain 5-HT content, 5-HT might play an important role in the mediation of AIH.


Role played by the adenylcyclase-cAMP system of the rat septal area on Na+, K+ and water renal excretion. In this study, the participation of the adenylcyclase--cAMP system of the rat septal area in the mediation of the natriuretic, kaliuretic and diuretic effects of noradrenaline (NA) was investigated. The intraseptal injection of 20 nmol of NA caused a significant increase in the urinary excretion of Na+ and K+ as well as in the urinary volume during the 2 hr period following the intracerebral injection which was blocked by 40 nmol of phentolamine, locally injected, 30 min before the catecholamine. In contrast, pretreatment with propranolol (100 nmol) potentiated the effects of NA on salt and water renal excretion. The intraseptal injection of 3.12 to 50 nmol of dibutryrl cyclic adenosine monophosphate (db cAMP) caused dose-dependent increase in natriuresis and kaliuresis, but a decrease in urinary volume. Under the same experimental conditions, caffeine administration (6.25 to 100 nmol) also induced dose-dependent increases in Na+ and K+ urinary output. These results indicate that the saluretic effect of NA may be mediated by an alpha receptor-induced activation of the adenylcyclase--cAMP system in the septal area.


Actinomycin D peritonitis in rats: a tool for the study of early events in inflammation. The injection of 50 microgram i.p. of actinomycin D produces, in rats, a biphasic inflammatory reaction. The first short lasting phase (approximately 24 h) is characterized by the decrease of the peritoneal cells number, by the increase of the levels of both cAMP and cGMP in the peritoneal cells and by the increased synthesis and release of lysosomal enzymes from these cells. The second long lasting phase (greater than 120 h) is characterized by the exudate formation, intense cellular immigration, continuous release of lysosomal enzymes, return to or below the normal values of the intracellular levels of cyclic nucleotides. The treatment of rats with a steroidal drug reduces the beta-glucuronidase release and, concomitantly, the intracellular cyclic nucleotides levels. Indomethacin is ineffective.


Role of brain monoamines in the anticonvulsant effect of imipramine in albino rats. The role of brain monoamines in the anticonvulsant effect of imipramine was investigated in albino rats, against maximal electroshock-induced seizures, by using drugs with well-defined effects on brain monoamines. The results suggest a definite role for noradrenaline in imipramine anticonvulsant action. Dopamine and 5-hydroxytryptamine do not appear to be involved in this effect of imipramine.


Voluntary ethanol drinking by the RAT: effects of 2-aminoethylisothiouronium Salt, a modifier of NAD:NADH and norelegnine, a beta-carboline derivative. Voluntary intake of ethanol solution (ETOH) was decreased in rats administered 2-aminoethylisothiouronium bromide hydrobromide (AET), an agent reported to alter NAD:NADH ratios in rat liver. Repeated administration of same dose of AET to ETOH-naive rats produced a significant inhibition of liver aldehyde dehydrogenase. Ethanol intake was decreased in rats given noreleagnine (NLG), a beta-carbone derivative reported to inhibit monoamine oxidase. Repeated administration of NLG exerted a significant inhibitory effect on liver alcohol dehydrogenase activity. It is concluded that the observed reduction of ethanol under AET which inhibits liver aldehyde dehydrogenase may reflect an antabuse-like reaction and the reduction of ethanol intake under NLG may be due, in part, to a build-up of alcohol in the blood and brain through inhibition of ethanol metabolism. The results are discussed in reference to the possible mechanism of action underlying voluntary intake of ethanol in rats, implicating alteration of NAD:NADH ratios in the biochemical processes underlying alcohol intake of rats.


Angiographic diagnosis of endocrine tumors of the pancreas. The angiographic findings in 18 patients with endocrine tumors of the pancreas are analyzed. A literature review (262 cases) is performed in order to assess the accuracy of angiography in diagnosing islet cell tumors, in particular multiple and small (less than 1 cm) lesions. Problems of differential diagnosis of pancreatic and extrapancreatic structures and lesions are discussed.


Hormonal influences on RNA and DNA synthesis in developing rat brain. In recent years, authors' interest was focussed on the role of hormones in the brain biochemical maturation during the early postnatal life. One-day-old rats were used in the investigation of the following hormones: thyroxine (T4), hydrocortisone, aldosterone and ACTH, in unique or repeated administration. Dynamics of cerebral RNA and DNA synthesis, a realiable indicator of central nervous system (CNS) maturation, was investigated. Authors' research led to the following conclusions: In infant rats, cerebral RNA and DNA synthesis exhibits a continuous increase, with a peak between 7 and 14 days after birth. Hydrocortisone induces a significant inhibition of cerebral RNA and DNA synthesis, more important in 7-day-old rats. In ACTH-treated newborn rats, RNA and DNA synthesis presents a high stimulation in 7- and 14-day-old rats. Aldosterone elicits an enhancement of brain nucleic acid synthesis, more marked in 7- and 14-day-old rats. Thyroxine administration induces a marked stimulation of cerebral RNA and DNA synthesis, greatest at 7 and 14 days after birth. The results confirm the important, even decisive, role of endocrine secretions during the early postnatal life, as far as the subsequent individual development is concerned.


Activation of cAMP-dependent protein kinase without a corresponding increase in phosphorylase activity. The effect of prostaglandin E1(PGE1) and epinephrine on glycogen metabolism has been investigated in the perfused rat heart. Both agents produced increases in cAMP and the cAMP-dependent protein kinase activity ratio. When dosages were adjusted to give equal increases in the protein kinase activity ratio from a basal value of 0.15 to as high as 0.40, only epinephrine caused a significant increase in phosphorylase activity. When used together, PGE1 did not effect the ability of epinephrine to increase phosphorylase activity.


Enhanced affinity of opiate receptors for naloxone in striatal slices of morphine-dependent mice. Slices of corpus striatum were allowed to accumulate 3H-morphine and then they were placed in a small chamber and superfused with Krebs-Ringer bicarbonate solution. 100 to 1 pM of naloxone caused an immediate increase in the release of morphine from the slices when it was placed in the superfusion fluid at 0, 5 or 15 min after the the start of the superfusion. Slices from morphine-dependent mice were more sensitive to the naloxone-induced release of morphine than those of control mice. The data suggest that the affinity of the opiate receptors in the corpus straitum for naloxone is increased in morphine-dependent mice.


Cyclic AMP and cyclic GMP levels in glandular stomach of restrained rats. Cyclic AMP and cyclic GMP were measured in glandular stomach of rats subjected to saline administration, cold (4 degrees C), restraint and restraint+cold after 15, 30, 60, 90 and 120 minutes. All animals subjected to restraint+cold had gastric ulceration after 2 hours. A significant but transient decrease in cAMP was observed 15 minutes after restraint+cold. A marked, sustained and significant decrease of cGMP was observed in the same group of animals. It is concluded that it seems unlikely to be a correlation between cAMP and cGMP changes of the stomach and the restraint-induced gastric ulceration.


[Bifocal bronchial granulocellular myoblastoma (Abrikosov's tumor)]. To the 44 observations of endobronchial granular cell myoblastoma described in the world literature can be added the case of a 52-year-old patient who presented with bifocal localization of this rare tumor of enigmatic origin. The two tumors were isolated from each other, one being situated at the level of the bronchus of the left superior lobe without implantation on the main bronchus, and the other at the bifurcation of the anterior segmental bronchus and left apico-dorsal segmental bronchus. The irreversible chronic-inflammatory peripheral lesions necessitated pneumonectomy. The patient is in excellent health 17 years after pneumonectomy. This is the fifth case of bifocal bronchial granular cell myoblastoma to be published.


[Serum lipids in diminished kidney function, during hemodialysis and after kidney transplantation]. Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27).


[Antiviral activity in the serum of patients with acute myelocytic leukemia: prognostic significance. Preliminary report]. In view of suggestions that acute myeloblastic leukemia (AML) may be of viral etiology, sera of 31 patients suffering from AML were investigated for antiviral activity. Fowl plague virus (FPV), vesicular stomatitis virus (VSV), BT 20 mammary carcinoma cells and chicken embryo fibroblasts (CEF) were used as assay systems. In the FPV-BT20 system, 19 of 20 patients whose blood sample was taken when they were in complete remission showed antiviral activity in their sera. These patients stayed in complete remission for at least three months after the blood sample was taken. In the sera of 11 patients no antiviral activity could be found with the FPV-BT20 assay system. 3 of the 11 were in relapse, 5 had a relapse within 3 months and 3 stayed in remission more than 3 months after the blood sample was taken. In the FPV-CEF and in the VSV-BT20 system antiviral activity was also found. The activity in the FPV-CEF system corresponded well with the FPV-BT20 assay and the disease status, whereas the activity detected by the VSV-BT20 system did not. The nature of the antiviral activities in the sera of AML patients against FPV and VSV is not yet clear. Interferon and specific antiviral antibodies can probably be ruled out. The antiviral activity against FPV appears to be a biological index of the activity of the disease and might eventually be used to determine intensity and length of treatment.


[Hereditary myeloperoxidase deficiency. Clinical, biological and genetic study]. A case is reported of hereditary myeloperoxidase deficiency in a diabetic patient suffering from a Candida albicans hepatic abscess. Myeloperoxidase (MPO) is completely absent from the neutrophils and monocytes, although it is present in the eosinophils. Functional granulocyte studies have revealed normalchemotactic and phagocytic activity, although the bacterial activity is partially diminished with regard to Staphylococcus aureus and is almost nil with regard to Candida albicans. The granulocytic metabolism, when stimulated by zymosan, is characterized by greatly increased oxygen consumption. Genetic investigations have been conducted in 28 members of the patient's family. Cyto- and biochemical determination of MPO is clearly diminished in close relatives of the patient. Genetic analysis indicates recessive autosomal transmission with variable expressivity of the gene for the heterozygote state.


Somatotrophic, thyrotrophic and adrenocorticotrophic functions of the anterior pituitary in obesity. The basal plasma level of GH, TSH and ACTH and the reserve capacities of the adenohypophysis in the secretion of these hormones was investigated radioimmunologically in 80 patients with excessive weight (from 15.3% to 180.0%) and a group of healthy subjects. It is shown that obesity is accompanied by diverse changes of the anterior pituitary GH, TSH and ACTH functions, which may be explained by their varied participation in the fatty metabolism. The pituitary somatotrophic function is weakened in obese subjects and its disorders advance with increase of the grade of obesity. Reduced pituitary thyrotrophic function in obesity causes weakening of thyroid function; disorders of the thyroid regulation occur at the hypothalamic level. The increased blood plasma concentration of ACTH in obese subjects has a compensatory character. The reserve capacities of the adrenocorticotrophic function of the pituitary are diminished in obestiy. Disturbances of the anterior pituitary GH, TSH and ACTH functions show a single-direction character both in alimentary-constitutional and in hypothalamic obesity.


[Selection of patients with breast cancer with regard to endocrine therapy]. Predictive tests assisting in selection of breast cancer patients for endocrine therapy have been reviewed. Information gained from histologic sections, such as degree of the tumor differentiation, degree of elastosis, Barr-body count and the DNA content, are valuable predictors of prognosis and response to endocrine therapy. The length of time between mastectomy and recurrence of metastasis is an important factor in predicting response to ablative endocrine surgery. The presence of various enzymes in the tumor tissue, blood groups, immunologic competence, altered metabolism of tryptophan, urinary excretion of steroids and  in vitro hormonal responsiveness of the tumor tissue have not been widely used as predictors of tumor response to endocrine therapy. The determination of hormone receptors in primary or metastatic breast tumors is at present the most reliable test in selecting breast cancer  patients for endocrine therapy. Future developments in hormone receptor assay may provide a means of tailoring endocrine therapy to the individual patient.


Pituitary nuclear 3,5,3'-triiodothyronine and thyrotropin secretion: an explanation for the effect of thyroxine. An excellent correlation was observed between nuclear triiodothyronine (T3) and the ensuing suppression of thyrotropin (TSH) after a single intravenous injection of T3 to thyroidectomized (hypothyroid) rats. At 1 and 2 hours after injection of thyroxine (T4), in amounts equally potent to the administered T3 in terms of acute suppression of TSH, the same quantities of T3 were found in the pituitary nuclei. Virtually no nuclear T4 was present, and plasma T3 was negligible at these short intervals after T4 injection. These results suggest that suppression of TSH release in hypothyroid rats occurs by interaction of T3 with the nuclear receptor of the thyrotroph. After T4 injection, the T3 found in the nucleus is derived from rapid intrapituitary monodeiodination.


Stereospecific and nonstereospecific effects of (+)- and (-)-morphine: evidence for a new class of receptors? The unnatural (+) enantiomer of morphine had minimal activity in three opiate assays in vitro: the rat brain homogenate binding assay, the electrically stimulated guinea pig ileum assay, and the inhibition of adenylate cyclase in neuroblastoma X glioma hybrid cell homogenates. When (+)-morphine was microinfected into the periaqueductal gray (a site known to mediate morphine analgesia) of drug-naive rats, there was only minimal analgesia, but the hyperresponsivity usually observed after microinfection of (-)-morphine occurred. Also, when (+)-morphine was microinfected into the midbrain reticular formation of drug-naive rats, rotation similar to that following microinjection of (-)-morphine occurred. These behaviors were not blocked by naloxone. Significantly, they typically occur in precipitated abstinence in morphine-dependent rats. These observations suggest that there are at least two classes of receptors, one stereospecific and blocked by naloxone and the other only weakly stereospecific and not blocked by naloxone, and that precipitated abstinence may be due, in part, to a selective blockade of receptors of the former class but not of the latter.


Cyclic nucleotides injected intracellularly into rat superior cervical ganglion cells. Intracellular iontophoresis of either adenosine 3',5'-monophosphate or guanosine 3',5'-monophosphate produces a membrane depolarization and an increased membrane conductance in sympathetic ganglion cells of the rat superior cervical ganglion. Since adenosine 3',5'-monophosphate did not cause a membrane hyperpolarization, it is difficult to assign it a second messenger role in the mediation of the slow inhibitory postsynaptic potential. However, these results do not rule out the possibility that the cyclic nucleotides, at the intracellular concentrations attained in these experiments, participate in cellular processes that contribute to conductance changes which result in depolarization of the ganglion cell membrane.


Coagulation abnormalities in liver disease. The decreased capacity of the liver to synthesize proteins is the main cause of decreased blood levels of clotting factors II, V, VII, IX, X and of antithrombin III in patients with liver disease. Therefore, determination of the activity or concentration of these coagulation proteins is a useful test of liver function and guide to prognosis, provided that other mechanisms which may influence the blood level are carefully considered. Clotting factor assays have an only limited value for the differential diagnosis in liver disease.


Primary Epstein-Barr virus infection in a renal transplant recipient. A young girl with familial nephronophthisis and chronic renal failure contracted a primary Epstein-Barr virus infection after renal transplantation. During the illness she developed a clinical picture of fever and pneumonitis which closely resembled the posttransplantation syndrome usually associated with cytomegalovirus, although she had no evidence of cytomegalovirus infection. A younger sibling with the same renal disease was found retrospectively to have apparently had an earlier subclinical Epstein-Barr virus infection.


Vibrometry and uremic peripheral neuropathy. The vibratory sensation threshold (VST) was measured with a vibrometer to assess the progression of neuropathy in patients with end-stage renal disease. Normal patients and patients receiving chronic hemodialysis were studied. We found that the longer the patients were dialyzed, the lower their VST (P less than 0.01). Regression equations were established to predict threshold values versus age of both groups, and VST versus months on dialysis in the patient population. Vibrometry was an important addition to the assessment of peripheral neuropathy in our dialysis patients. It offers low cost, little patient preparation, and requires little professional time for examination and interpretation.


Review of 18 years' experience with pituitary tumors. The presenting signs, symptoms, roentgenographic findings, endocrine evaluations, treatment, and results in 68 cases of presumed pituitary adenomas treated over an 18-year period are discussed. The most common symptoms were headache, acromegalic changes, visual symptoms, and amenorrhea. Most common physical findings were obesity, acromegaly, and visual field defects, usually bitemporal hemianopsia. Roentgenographic evidence of sellar erosion was almost universal but angiography and pneumoencephalography were required to evaluate suprasellar extension. Brain scan was not considered a particularly useful diagnostic tool. Endocrine status was best evaluated by a battery of tests including 17-OH, 17-KS, T3, T4, PBI, ACTH stimulation, and FSH and STH levels. (Prolactin levels are currently being obtained, also). Surgical specimens were obtained in 29 patients, with subsequent diagnoses of 22 chromophobe adenomas, five eosinophilie adenomas, one cystic adenoma, and one necrotic tumor. All five eosinophilic tumors came from acromegalic patients. Patients treated by operation alone or operation followed by radiotherapy generally had less "medical morbidity" than did patients who received radiotherapy alone.


The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom. Clinacanthus nutans Burm, a herb reputed in Thailand and Malaysia to be "snakebite antidote" has been tested in vitro and in vivo for antivenin activity. The aqueous extract of C. nutans leaves has been found to have no effect on the inhibition of neuromuscular transmission produced by purified Naja naja siamensis neurotoxin in isolated rat phrenic-nerve diaphragm preparations. The extract of C. nutans, when given orally or intraperitoneally, are ineffective in prolonging the survival time of experimental mice receiving lethal doses of N.n. siamensis crude venom. Oral administrations of the herb extracts pretreated with alpha-amylase or beta-amylase also fail to protect the animal. It is concluded that the extract of C. nutans can not antagonize the action of cobra venom.


Genetics of the mammalian phenylalanine hydroxylase system: I. Isolation of phenylalanine hydroxylase-deficient tyrosine auxotrophs from rat hepatoma cells. Cultured rat hepatoma cells, H4-II-E-C3, are known to possess a phenylananine hydroxylating system which is sufficient to enable them to grow in tyrosine-depleted medium. Using standard procedures of auxotroph enrichment with this cell line, we have isolated tyrosine auxotrophs for the first time. We report in this paper the class of auxotrophs with (a) reduced (15-64% of wild type) or (b) absent activity of phenylalanine hydroxylase, an enzymic component of the phenylalanine hydroxylating system. This class of auxotroph presumably contains either lower (a) [or zero (b)] levels of normal phenylalanine hydroxylase protein than wild type, or mutant phenylalanine hydroxylase protein with lowered (or zero) activity. The two subgroups of auxotrophs (a) and (b) differ from each other in their revertibility and their growth behavior in the tyrosine-free medium. Over a 12-month period of testing, the auxotrophs have been highly stable with respect to their phenylalanine hydroxylase activity and growth phenotype in tyrosine-free medium. Such auxotrophs should facilitate genetic and biochemical study of the genes controlling the phenylalanine hydroxylation system and the study of phenylketonuria.


Increased polyethylene glycol-mediated fusion competence in mitotic cells of a mouse lymphoid cell line. Spontaneous mitotic cells of the mouse leukemic cell line GF7 are preferentially included in cell fusion products after treatment with polyethylene glycol (PEG). This implies a unique configuration of the natural mitotic membrane which is particularly vulnerable to induction of fusion by PEG. Colcemid-arrested GF7 mitotic cells, however, are excluded from PEG-induced cell fusion products, suggesting that colcemid reverses the membrane configuration which is susceptible to the action of PEG. When Sendai virus is used as the fusogenic agent, both colcemid-arrested and spontaneous mitotic cells are selectively fused. There must, therefore, be an essential membrane-fusogen reaction which is characteristically different for each of these agents.


The control of cell proliferation by preformed purines: a genetic study. I. Isolation and preliminary characterization of Chinese hamster lines with single or multiple defects in purine "salvage" pathways. Sublines with single or multiple defects in purine "salvage" enzymes were isolated from the Chinese hamster fibroblastic line GMA32 through single or successive one-step selections for resistance to purine analogs. They were examined for their ability to incorporate purine bases and nucleosides into macromolecules, for their sensitivity to growth inhibitory purines, and for their rescue by exogenous purines from deprivation imposed by metabolic inhibitors of endogenous synthesis. The results show that a deficiency of either adenosine kinase (EC 2.7.1.20), adenine phosphoribosyltransferase (EC 2.4.2.7) or hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) abolishes the ability of adenine to cause cell death by interfering with pyrimidine synthesis; on the other hand, the pyrimidine starvation caused by adenosine is fully prevented only by a deficiency of adenosine kinase.


Extracranial metastases of glioblastoma multiforme confirmed by electron microscopy. A case of glioblastoma multiforme which metastasized to the pleura and the lymph nodes of the neck is described. The metastases were detected during the life of the patient. The glial nature of the metastases was confirmed by electronmicriscopic demonstration of typical 90-100 angstrom wide glial fibrils occupying the tumor cell cytoplasm. Electronmicroscopy is recommended to prove the astrocytic nature of a metastatic glioblastoma multiforme. A review of the literature of histologically documented extracranial metastases of glioblastoma multiforme reveals an increase in frequency in recent years. Increased efforts at detection and documentation or an increase in occurrence caused by new methods of treatment are the two possible explanations for this trend.


Clinical characteristics of the lethal cytomegalovirus infection following renal transplantation. An ongoing prospective study of the role of viruses in renal transplant recipients has provided identification of two patterns of cytomegalovirus (CMV) infection.  In both patterns, fever and leukopenia occur within 6 months after transplant. In addition, the benign form is characterized by renal biopsy evidence of rejection and brisk Antibody responses to CMV. The lethal syndrome runs a typical 4 week course, beginning with prostration, orthostatic hypotension, mild hypoxemia and progressing to severe pulmonary and hepatic dysfunction, muscle wasting, central nervous system depression, and death. antibody responses to CMV are minimal, and renal biopsy does not show rejection despite elevation of serum creatinine. At autopsy, CMV is found in lung, liver, kidney, gastrointestinal tract, and brain. Successful management of the potentially lethal kidney, gastrointestinal tract, and brain.  Successful management of the potentially lethal CMV syndrome requires rapid clinical recognition and immediate reduction of immunosuppressive therapy. future prospects for control include development of a CMV vaccine and specific antiviral chemotherapy.


Regional hyperplastic lymph nodes in breast cancer: the role of lymphocytes and nodal macrophages. An immunological study with a five-year follow-up. Five stage I and stage II breast cancer patients with sinus histiocytosis in two or more enlarged regional lymph nodes were studied. Peripheral lymphocytes, serum, and nodal lymphocytes were tested in vitro for cytotoxicity against autologous normal and tumor cells. Nodal macrophages were incubated with autologous peripheral lymphocytes and these "activated" lymphocytes then were tested in vitro for cytotoxicity against autologous normal and tumor cells. Peripheral lymphocytes (L) were not cytotoxic to autologous tumor (T) cells at 25:1 L/T ratios. Nodal lymphocytes were specifically cytotoxic to autologous tumor cells. Macrophages from hyperplastic regional lymph nodes transferred tumor specific inmunity to peripheral lymphocytes. Macrophages from small, nonhyperplastic regional lymph nodes did not transfer tumor specific immunity. With the advent of adjuvant chemotherapy and its attack on systemic immunity, a quantitative, immunopathological classification of breast cancer patients is needed in order to properly select patients for further therapy.


Evolution of surgical treatment of bilateral Wilms' tumor. Bilateral Wilms' tumor (stage V) accounts for 10 to 15% of patients with nephroblastoma. Heretofore, surgical resection in many of these children presented insoluble technical problems. Ex vivo renal perfusion with "bench" surgical excision and revascularization has been applied in the management of a child with bilateral Wilms' tumor unresectable by conventional techniques. Complete extirpation of tumor was accomplished. Furthermore, the autotransplanted kidney was removed from the field of radiation therapy given after operation. By selective application of this technique, the child with bilateral Wilms's tumor can be approached with a greater expectation of cure.


[The immunity against challenge with swine fever virus of piglets from sows vaccinated with C-strain virus (author's transl)]. The protective value of maternal antibodies against exposure by contact to virulent swine fever virus was investigated in a group of 40 piglets at the age of 33-40 days. The piglets were from a single farm and derived from 10 sows which had been vaccinated once with C-strain virus 5.5 months before farrowing. Four contact controls of approximately the same age as the test-groups and born from non-vaccinated sows died 4-10 days (av. 7.5 days) after the onset of symptoms. Three pigs from the group under test succombed to swine fever after an illness of 12 to 16 days (av. 14 days) and one animal died from coli-enteritis. A febrile reaction (av. duration 2.9 days) was observed in more than 75% of the piglets that survived the challenge and all survivors showed a serological response. There was no relationship between the serum-neutralisation titer before challenge and the presence or absence of fever. Attempts to isolate swine fever virus by means of leucoyte cultures, bonemarrow cultures and plasma clot cultures from tonsils, spleen and lymphnodes of surviving piglets 5-7 weeks after the start of the experiment were not successful. It is concluded that a high proportion of the piglets born from dams vaccinated with C-strain virus are protected against contact exposure till the age that they can successfully be vaccinated themselves.


Molecular composition of lecithins in the primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene. The lecithins of the primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (DAB) and host liver of rat were isolated, and the individual molecular species were estimated quantitatively by combined thin-layer and gaschromatographic analysis and specific enzymic hydrolysis. The DAB-hepatoma lecithins appeared to have more specific positioning of fatty acids than the transplanted hepatoma lecithins which have been reported by Dyatlovitskaya et al. (1974). However, there were some striking differences to be noted between the DAB-hepatoma and host liver lecithins. The usual type of molecular species of lecithin, saturated-unsaturated species, was the main component in the hepatoma and host liver. The amounts of the unusual species having impaired positional specificity in fatty acid such as the saturated-saturated and the unsaturated-saturated species were high in the DAB-hepatoma when compared with host liver, although the content of the unsaturated-unsaturated species of lecithin were almost similar in both the tissues. The formation of the unusual species of lecithin in tumor tissues was discussed in relation to the impairing in the enzyme systems involved in lecithin synthesis.


Immunological and biochemical investigations on the fluorocarbon-treated antigens obtained from placenta and from cancer tissues. Biochemical and immunological investigations were made on the nature of fluorocarbon-treated antigens obtained from placenta and cancer tissues. 1) By the diffusion in gel method, a specific antigen common to cancer tissues was found in placental tissue, but not in normal tissue. Immunoelectrophoretically, a characteristic precipitate line was found in alpha2-globulin region. 2) Further purification of the placental antigens was carried out by DEAE-cellulose chromatography. Four fractions positive to Folin reaction were detected. 3) Immunoelectrophoresis revealed that the active component was concentrated in a fraction eluted with 0.1 M NaCl in 0.05 M phosphate buffer, pH 5.8 (5.8-fraction). 4) Further purification of the active component was performed by using polyacrylamide gel electrophoresis. Chemical analysis indicated that it belonged to glycoprotein. 5) This substance did not induce anemia in rabbits and had no influence on the osmotic fragility of erythrocytes. These results indicate that this substance is different from the anemia-inducing substance which was previously reported by us.


alpha-L-Iduronidase activity in established lymphoblastoid cells from patients with Hurler and Scheie syndromes transformed by Epstein-Barr virus. alpha-L-Iduronidase activity was determined in established lymphoblastoid cells, which were transformed in vitro by Epstein-Barr virus, of lymphocytes-rich cell populations isolated from peripheral blood of patients with Hurler and Scheie syndromes. alpha-L-Iduronidase activities in established lymphoblastoid cells from patients were undetectable, while activities of control subjects were clearly detected. These results suggest that established lymphoblastoid cells are useful for the enzymatic study of genetic mucopolysaccharidoses.


[Change in the hybridization characteristics of rapidly-labelled ribonucleic acids during tumor "progression"]. The hybridization properties of in vivo rapidly labeled with 14C-orotate both nuclear and mitochondrial ribonucleic acids from the MD hepatoma were investigated. During tumour progression the repression of nuclear genome found at its early stages (5th to 6th passages) is replaced by the increase of hybridizability of nuclear DNA with a population of 14C-RNA's as well as by the appearance of new classes of pulse labeled RNA's. In other words, at late stages of tumour progression (60th passage) there occur a de-repression of nuclear genome. The hybridizability of mitochondrial RNA with nuclear DNA remains almost the same at different tumour progression stages. The results obtained are discussed in the light of literature data available.


[Analysis of substances released from Zajdela ascites hepatoma cells exposed to UV radiation of different wavelengths. III. Release of nucleoproteins and carbohydrates]. Irradiation of the Zaidela ascite hepatoma cells with physiological doses of shortwave length (254 nm) and longwave length (300-380 nm) UV light (far and near UV radiation) is accompanied by the release of ribonucleoproteins (RNP) from the cells, whose amounts increase with dose. Irradiation with far and near UV light leads to the release of high-molecular and low-molecular RNP, respectively. No deoxyribonucleoprotein were found among the released substances. Non-protein fractions, released from irradiated cells, contain carbohydrate-like substances. At maximum far and near UV doses the amounts of these substances constitute 180-190% of the control and 6% of their amount in intact cells. After irradiation with far UV light, relatively high-molecular carbohydrates are released, while near UV light treatment induces the release of low-molecular carbohydrates. The criteria tested show that the efficiency of far UV light exceeds that of near UV light by one order.


[Effect of light deprivation on enzymic activity of synaptosomes and mitochondria of rabbit cortex visual region]. The specific activity of markers-enzymes in the subcellular fractions of the rabbit visual analyzer cortical end, the synaptosomes and mitochondria of nerve cells, changed under the effect of early long deprivation. For cytochromoxidase and Na+, K+-ATPase it lowers considerably in all subfractions, for monoaminoxidase and Mg2+-ATPase it rises mainly in synaptosomes; the activity of acetyl cholinesterase lowers per 1 g of tissue. In the light two weeks later a tendency is observed to normalization of the studied indexes. The specific activity of cytochrome oxidase (except for free mitochondria) and Na+, K+-ATPase reaches the control, that of monoaminoxidase also partially normalizes, but not competely; Mg2+ATPase in all the subfractions is more inhibited than in the control. This evidences for the effect of light deprivation on the activity of the enzymes associated with different cycles of metabolic processes, first of all, of oxidation and ion transport. These changes are reversible when visual impulsation is recovered. Disturbances in chemism at the subcellular level are specific for different enzymic systems and are not the same in certain subfractions of great hemispheres.


[Metabolism and content of proteins in rat tissues under the effect of sodium ribonucleate in experimental hypercorticism]. Experimental hypercorticism induced by multiple injections of ACTH-zinc-phosphate inhibits the incorporation of 1-14C-alanine and 3H-methionine into proteins of the liver, spleen, musculus quadratus femoris, blood and nuclear plasma, mitochondria, microsomas and cytosol of the liver as well as decreases the protein content in them. Under the effect of ACTH-zinc-phosphate in combination with enteral administration of sodium ribonucleate, the deviations from the normal level in the incorporation of the labelled amino acids into proteins and in the protein content of the tissues under study are less pronounced than under the effect of the hormone only. An opinion is advanced that enteral injection of sodium ribonucleate may be more preferable than parenteral administration of this preparation with hypercorticism under clinical conditions.


[Effect of "carbostimulin", vitamin D 3 and their mixture on bone tissue regeneration]. Healing of the bone injury in rabbits was studied as affected by carbostimulin and its mixture with vitamin D3. Some biochemical indexes: the content of sialic acids, calcium and citric acid in blood serum of the animals, intensity of 14C incorporation from NaH14CO3 into the regenerated bone tissue and its proteins as well as histological studies, data, evidence for a positive effect of the mentioned preparations on the bone substance regeneration in the animals under experiment. So. the content of sialic acids in blood serum normalizes on the 10th day after the operation mostly in the animals which were administered the mixture of the preparations and in which the most pronounced hypercalcemia is observed. Incorporation of 14C from NaH14CO3 into the regenerated tissue and its proteins is most intensive in the same animals.


Angiographic features of lateral cervical masses. An audible bruit may represent a clue to the vascular nature of the lesion. Angiography is definitely indicated in the presence of pulsatile cervical masses with or without an associated bruit, and should be more widely utilized in the future for evaluation of cervical masses. In addition to the nature of the mass, angiography may also be of value in outlining the extent of the mass and its relationship to major vessels. Magnification and subtraction angiographic techniques with their improved detail may play an important role in clarifying the etiology of cervical masses, and hence facilitate the plan of therapy. If reasonable uncertainty as to the clinical diagnosis exists, angiography should be considered a diagnostic aid.


Melanotic neuro-ectodermal tumour of infancy (melanotic progonoma) in two calves. Large unilateral tumours involving the mandible in two calves were composed of melanin-containing cells and small lymphocyte-like cells in a cellular fibrous stroma. These neoplasms resembled the melanotic neuro-ectodermal tumour of infancy.


Cranal computed tomography: application to otolaryngology. Cranial computed tomography (CT) is an effective radiologic method for the evaluation of extracranial and intracranial pathology. Representative cases of extracranial and intracranial pathology of otolaryngic interest are selected from 6,000 CT scans. Pathology of the nasal cavities, paranasal sinuses, orbits, and cerebellopontine angles is demonstrated.


[Biological properties of the dermopathic bovine herpes (Allerton-mammillitis) virus]. The dynamics of accumulation and localization of the virus antigen in cells of calf kidney (line CK) was followed by means of immunofluorescence technique. The antigen was detected eight hours (at the very earliest) after infecting the cells. Studied was the immune response of calves vaccinated with an inactivated virus and the addition of an adjuvant. Two weeks following revaccination high titres of virus-neutralizing and complement-fixing antibodies were established in the blood serum of the calves. These results made it reasonable to believe that the inactivated virus is suitable as a vaccinal antigen.


[Morphological changes in the kidneys of pigs with an adenovirus infection]. Dystrophic and necrobiotic changes developed in the epithelium of the kidney tubuli of sucking pigs spontaneously and experimentally infected with adenoviruses. The epithelial cells showed hyperchromatosis of the nuclei, breaking up of the chromatin, and formation of nuclear function bodies. The swelling of the dystrophic cells produced certain amount of pressure on the adjacent capillaries. The pale colour of the kidney itselt was due to the dystrophy of the epithelium and the compression anemia. After the desquamation of the degenerated epithelial cells and their carrying away with the urine the capillaries became strongly dilatated. Groups of adjacent capillaries became macroscopically visible and assumed the appearance of a petechia. Edema in lymphoidcell proliferation were established in the interstitial tissue.


[Studies of the CFT in the diagnosis of Aujeszky's disease virus in swine]. It was found that the complement-fixation test is a prompt and suitable method in the diagnosis of the Aujeszky's disease virus, the antigen employed being a cell culture virus. A virulent virus, a slightly virulent one, and the vaccinal mutant strain MK have shown a good complement-fixing activity and they detect specific complement-fixing antibodies in the immune serum. By means of cross CFT an antigenic relation has been established between some strains of the Herpes group and the Aujeszky's disease virus, it being predominantly unilatera. In Aujeszky's disease antisera neutralizing and complement fixing antibodies have been deomonstrated in titres up to 1:64, and in MK antisera--CF-antibodies only. In blood sera from farms with a moderate course in the manifestation of Aujeszky's disease the titre of the CF-antibodies has been 1:8.


[Attempts at specific immunoprophylaxis against herpes mammillitis]. A live cell culture adsorbate vaccine was produced against herpes mammillitis in cattle. Comparative investigations were carried out on the immunogenic properties of four vaccines having different adjuvants--aluminum hydroxide, saponin, arlacell, and Freund's adjuvant. All tested vaccines proved harmless and immunogenic for sensitive cattle, the highest immunogenic effect being produced by the vaccine that contained aluminum hydroxide and Freund's adjuvant. The vaccinated animals reacted to immunization with the formation of specific antibodies that showed a highest titre between the 21st and 28th day following treatment. Immunity was checked through challenge on the 45th day, all immunized heifers being fully protected against Bovid herpesvirus infection 2 infection. When necessary the vaccine can be used successfully in a dose of 3-6 cm3, subcutaneously, in the region of the dewlap.


[Pathogenesis of Aujeszky's disease].

[Pathogenesis of Aujeszky's disease]. Results are presented of studies on the various localization of the virus of Aujeszky's disease (the avirulent mutant strain MK and the virulent strain 2) in the organism of experimentally infected pigs. At the oral infection of pigs with strain MK the virus has been isolated from the submandibular lymph nodes of the animals only, the pigs being killed on the second and fifth day following infection with a low plaque-forming titer. However, from pigs that have been infected subcutaneously no virus was isolated. In experiments with the virulent strain 2, 15 out of 20 pigs have died up to the seventh day following infection. The examination has revealed that a virus of a high plaque-forming titer was present in almost all organs. Histologic investigations in the experiments with the virulent strain 2 have revealed the presence of a strongly manifested nonsuppurative encephalitis, interstitial pneumonia, necroses, and nuclear inclusion bodies. In the experiments with strain MK these changes have been much more slightly expressed, and after the tenth day of infection they tended to disappear. In the authors' opinion the changes are due to the 'interaction' between the viral particles of the vaccinal virus and the competent cells, being the cytologic manifestation of the enhanced immunobiologic status of the host organism. This is an expression of the cell manifestation of immunogenesis and not of the toxic injury of cells which has been observed in experiments with the virulent strain.


[Relationship between the chemical structure and the biological activity of antibodies against the foot-and-mouth disease virus]. Investigated was the effect of various amino agents (stained and phthalic anhydride and sulfopicric acid) on the complement-and antigen-fixing activity of IgG and IgM antibodies isolated from guinea pig sera, the donor animals being hyperimmunzed with type O, strain Polyana, of the foot-and-mouth disease virus, At the moderate modification (75-86 per cent acetylation, and 36-40 per cent 'phthalation') of the primary amino groups the foot-and-mouth disease antibodies retained only half of the conjugation caused greater and complete loss of this activity. IgG and IgM showed almost equal specificity with regard to the antigen that had induced them. The lowered complement-fixing capacity was shown to have no specific effect on the primary relation of the foot-and-mouth disease virus to the antibody. Chemical modifying agents inactivated the specific small, strongly defined complement-fixing zones in the Fc-fragment of the foot-and-mouth disease antibody molecule.


Histologic variants of lipid-secreting carcinoma of the breast. Ten new cases of so-called lipid-secreting carcinomas of the breast are presented. Histopathologic analysis suggests three different microscopical patterns which are all characterized by abundant intracytoplasmic neutral fat deposits. Review of the literature yielded only 15 well-documented cases. Diagnostic problems are emphasized, with special regard to the secretory differentiation of normal and neoplastic mammary cells.


[Changes in organelle-specific enzyme activity and the ultrastructure of liver cells in cholelithiasis]. Activities of organelle specific enzymes (succinate dehydrogenase, glucose-6-phosphatase, acidic DNAase, acidic RNAase, acidic and alkaline phosphatases) were measured in homogenates and subcellular fractions of liver tissue of patients with cholelithic disease. Liver tissue samples analyzed were investigated also by light and electron microscopy. The data obtained were considered in connection with localization of cholelith in biliary system, type of inflammation, presence of subhepatic cholestasis and of accompanying syndrome of pancreatitis. Typical alterations were observed in the activity of organelle specific enzymes and in the ultrastructure of mitochindria, lysosomes and endoplasmic reticulum in cholelithic disease. The most distinct alterations in the enzymatic activities were found in choledocholithiasis as well as in subhepatic jaundice.


[Interrelationships between lipids and scleroproteins in silicosis caused by crystalline and condensed modifications of silicon]. Accumulation of lipids, including phospholipids, in lungs was accompanied by a proliferative-cellular reaction. The proliferation of cells was caused by accumulation of lipids. One of possible mechanisms of interrelation between lipids and collagen synthesis was as follows: in silicosis degradation of macrophages was accompanied by secretion into the medium of phospholipids, which inhibited free radical oxidation; in this case the decreased formation of cytotoxic products caused the cell proliferation, including fibroblasts, which produced collagen. The importance of lipids in collagen formation was corroborated: by accumulation of lipids, which preceded the hydroxyproline increase (scleroproteins, collagen), by development of the proliferative-cellular reaction together with the higher phospholipid-hydroxyproline level as compared with control, by formation of earlier sclerosis of silicotic nodes in "condensed" silicosis with the simultaneous increase in absolute content of phospholipids and total lipids. This role of lipids was also supported by the observed correlation between the absolute contents of scleroproteins and lipids within all steps of "quartz" silicosis development.


[Lipid metabolism of neonatally thymectomized rats of different sexes]. Content of cholesterol, its esters, total beta-lipoproteins and free fatty acids was increased in blood serum of rats, subjected to thymectomia after birth. The distinct sex variations were found in alterations of these patterns. Content of cholesterol was increased only in thymectomized males at the age of 3 months; content of beta-lipoproteins in males was elevated earlier and to higher level as compared wtih females. Alteration in content of blood serum lipids did not depend on manifestations of exhaustion syndrome (typical consequence of neonatal thymectomia) but it was related to ablation of thymus; this suggests that thymus participates in regulation of lipid metabolism. Sex differences in alterations of lipid metabolism patterns enabled to assume the existence of endocrine interrelations between thymus and sex glands.


[Age and changes in the activity of several energy metabolism enzymes in the rabbit aorta]. Age alterations in the activity of several key enzymes of glucose oxidative breakdown (hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and cytochrome c oxidase) were studied in extracts from rabbit aorta. The hexokinase activity was measured also in mitochondrial fraction. The activity of all the enzymes studied in rabbit aorta (calculated either per 1 g of the tissue or per 1 mg of proteins) was the highest at the age from 1-2 weeks to 1 month. The minimal activity was observed in adult animals, which were 1-2 years old, In aorta of 3,5-4 years old rabbits an increase (per 1 g of the tissue) in the activity of the enzymes was observed.


[Activity of enzymes of glycolysis and gluconeogenesis in primary hepatomas induced by diethylnitrosamine]. Activities of the key enzymes of glycolysis and gluconeogenesis were studied in soluble fraction of primary hepatoma, induced by diethyl nitrosamine (DENA) in rats and mice of C3HA strain. Histological structure of the tumors studied showed that they belonged mainly to highly differentiated hepatocellular adenomas. Liver tissue of the animals which were not treated with DENA, was used as a control. The hexokinase activity was increased about 2-fold in the rat hepatomas and 3-fold--in the mice hepatomas. In primary hepatomas the glucokinase activity was unaltered or slightly decreased; the fructokinase activity was distinctly decreased (in several cases down to zero). The activity of key enzymes of gluconeogenesis--glucose-6-phosphatase and fructose-1,6-diphosphatase--was distinctly decreased, especially the activity of the former enzyme, which constituted in hepatomas about 1/6 of the activity found in liver tissue.


[Effect of radiation on the activity of lactate dehydrogenase and acid phosphatase isoenzymes of Zajdela hepatoma]. In cells of ascites Zajdela hepatoma in different terms after irradiation of the abdominal region in tumor-bearing rats (doses of 500, 700 and 1000 rad) there were found a reduction of highly active and an increase of insignificantly active normal isoenzymes of lactate dehydrogenase and also disorders in the content of acid phosphatase.


[Advantages of the Eagle medium over saline solutions in the studies of the metabolic parameters of tumor cells in vitro]. In two media (krebsringer phosphate and phosphate-enriched Eagle medium) the indices of energetic metabolism (respiration, glycolysis. ATP content) were determined and the metabolism of macromolecular compounds (c-RNA) of Ehrlich carcinoma ascitic cells was investigated. The results of studies of ascites tumor cells metabolism have indicated considerable advantages of phosphate-enriched Eagle medium over krebs ringer phosphate buffer.


[Effect of pepsin on low density serum lipoproteins]. Native lipoproteins of low density from human blood serum were intensively hydrolyzed by pepsin in 0.1 M solution of beta-alanine-HCl at pH 1.9. About 50% and 90% of all the protein part of the substances were split off within 60 min and 22 hrs, respectively. Analytical ultracentrifugation showed that the proteolysis occurred in several steps with formation of discrete intermediates (sedimentation coefficients 2.9 S and 2.3 S at solution density 1,012 g/ml).


[Interfering and interferonogenic activity of attenuated and original para-influenza viral strains]. A higher interfering activity of attenuated (vaccine) strains of parainfluenza virus types 1, 2 and 3 which had undergone a long-term adaptation to cell cultures as compared to the original viruses was established. The interferon-inducing activity of vaccine parainfluenza virus types 2 and 3 was also higher than that of the original viruses. The high interfering and interferon-inducing activity of attenuated parainfluenza virus strains of type 2 and 3 correlated with reduced virulence of these variants for man. These tests may be used for the assessment of virulence of parainfluenza virus strains type 2 and 3 in the laboratory.


[Characteristics of the biological properties of a Kemerovo group arbovirus isolated in Transcarpathia]. A strain of an arbovirus named Mircha was isolated from Ixodes ricinus L. ticks (30 incompletely engorged females) collected in May, 1972 from cows pastured in a forest near the village of Mircha of the Velikobereznyansky district of the Zakarpathye region of the Ukrainian SSR. The strain was found to be pathogenic for newborn white mice and rats by the intracerebral and intraperitoneal routes and for chick embryos inoculated into the yolk sac, to replicate in chick embryo fibroblast culture producing a marked cytopathic effect to be relatively stable to ethyl ether and sodium deoxylate. On the basis of the results of serological identification (CFT) it was classified into arboviruses of the Kemerovo group, the antigenic subgroup Kemeroxo-Tribec. The factors of natural focality are described briefly, and the results of the study of virus persistence in adult white mice, rats, and guinea pigs and of its immunodepressive effect are presented.


[Isolation and characteristics of messenger RNA for antiviral protein]. Experimental data on the induction and isolation of functionally active mRNA's for antiviral protein (AVP) from interferon-treated cells are presented. The dynamics of mRNA-AVP translation in homologous cells and sedimentational distribution of the total and poly(A)-containing preparation of mRNA-AVP in sucrose density gradients were studied.


[Abortive myxovirus infection in Ehrlich's ascitic carcinoma cells. Further study of the nature of the virus-specific structures produced by heterokaryons]. Fowl plague virus-infected cells of Ehrlich ascitic carcinoma produce a noninfectious virus which is defective in fragility of its membranes. An attempt has been made to produce nondefective virus by fusion of infected Ehrlich cells with permissive cells: infected and non-infected chicken fibroblasts. The fusion of FPV-infected and 3H-uridine labeled Ehrlich ascitic carcinoma cells with infected unlabeled chicken fibroblasts using inactivated Sendai virus resulted in production of two types of labeled virus particles: with a buoyant density in cesium chloride gradient of 1.29 g/cm3 characteristic of particles produced by infected Ehrlich cells and buoyant density 1.22 g/cm3 typical of standard influenza virus. Both types of particles has infectious activity which was greater in the virus with the density of 1.22 g/cm3. However, particles with the density of 1.22 g/cm3 are not found upon the fusion of infected Ehrlich cells with uninfected chicken fibroblasts, with chicken fibroblasts early after infection, or with chicken fibroblasts treated with actinomycin D before infection. Infected chicken fibroblasts in hybrids were shown not to use the radioactive pool of Ehrlich cells and, accordingly, the virus with the density of 1.22 g/cm3 if formed from components pre-existing in Ehrlich cells. It is suggested that the standard virus buds on the areas of membranes of permissive cells which are parts of the hybrids.


[Biochemical methods in the assessment of activity in rheumatoid arthritis (author's transl)]. An investigation was carried out in 120 patients with classical rheumatoid arthritis (RA). Prolylhydroxylase activity was determined in the synovial membrane and serum and compared with the level of collagen-like protein in plasma and the hydroxyproline-creatinine quotient in urine. The data were related to the activity of RA as measured according to Voit and Gamp and also according to Lansbury. Activity was, furthermore, also assessed on the basis of newly defined criteria considering clinical, biochemical and histological findings. Prolylhydroxylase activity was significantly correlated to the activity of the RA assessed according to each of these systems. The significance of the known parameters, collagen-like protein in plasma and hydroxyproline-creatinine quotient in urine were confirmed in this larger series of patients. The positive correlation between prolylhydroxylase activities in the synovial membrane, as well as in serum, and the level of collagen metabolites in plasma and urine corroborated the value of biochemical methods in the assessment of activity of RA in order to undertake differentiated therapy.


[Use of immune electron microscopy for detecting the hepatitis A virus]. Attempts were made to isolate and identify hepatitis A virus by the method of immune electron microscopy using also biophysical methods and the transfection procedure of cell cultures by nucleic acid preparations. In fecal specimens from patients with infectious hepatitis A, virus-like particles 25-30 nm in diameter were found which reacted with convalescent antisera and could be detected by the immune electron microscopy method. By the same method virus-like particles 22-25 nm in diameter were detected in the blood serum of the patients collected early in the disease. A method for their purification and concentration in cesium chloride density gradients has been developed. Attempts at transfection of the cell cultures with preparations of nucleic acids failed. In the course of the study, however, data were obtained which would subsequently facilitate isolation of the causative agent of hepatitis A.


[Pz peptidase activity in serum (author's transl)]. Synthetic PZ peptide, synthesized by Wünsch and Heidrich, was used as substrate to determine PZ peptidase activities in the sera of man, rabbit, guinea pig and mouse. The PZ peptidase from rabbit serum was purified 200 fold and characterized. The enzyme has an isoelectric point of 5.0 and pH optima at pH 7.2 and pH 7.9. Its behaviour on gel filtration points to a molecular weight of 60.000 dalton. The peptidase is inhibited by heavy metal ions, SH reagents and serum. Ca ions are EDTA are without any effect. In contrast to collagen peptidases from micro-organisms, the enzyme from rabbit serum does not attack native, but only denatured collagen. The results suggest that PZ peptidases participate in collagen breakdown by cleaving the collagen fragments which are released by the collagenases.


[Study of the synthesis of Rous virus-specific RNA in chick embryo cells]. The presence of virus-specific RNA in commercial chick embryos and its lack in chick embryos of leukemia-free chicken farm of the USSR AMS Oncological Research Center as well as in cell cultures from RIF-free chicken infected with Marek's disease virus was demonstrated by hybridizationof 3H-DNA-product of Rous sarcoma virus synthesized in vitro in the presence of actinomycin D with the total preparation of cellular RNA.


[Study of the vaccinating properties of 2 variants of Marek's disease virus]. The vaccinating properties of two variants of Marek's disease virus, Kekava strain (MDV-Kekava) have been studied. One of them is naturally attenuated, the other has been produced as a result of attenuation of the pathogenic MDV-Kekava by long-term passages in chick embryo fibroblast (CEF) culture. The vaccinating properties of the naturally attenuated strains (MDV-Kekava 83) were first studied in an experiment in which the blood of chicken No. 1683 was used as the vaccine. In paralled. the MDV-Kekava 83 variant was isolated from the blood of this chicken in CEF culture. Vaccination of chickens with the blood of this chicken as well as with 1000-3000 PFU MDV-Kekava 83 which had undergone 16, 24, 45, and 46 passages in vitro produced in the chickens resistance to Marek's disease. According to the combined data of 4 experiments, altogether 9 out of 101 vaccinated chickens developed Marek's disease. Among the controls inoculated with the pathogenic MDV alone 51 out of 137 chickens developed the disease. Attenuation of the pathogenic MDV-Kekava 55 in CEF culture occurred very slowly. The virus of the 45th passage in vitro had no vaccinating properties. Vaccination of the chickens with 1000-2500 PFU MDV-Kekava 56 which had undergone  73 a94 passages in CEF culture produced resistance to Marek's disease. Among the vaccinated chickens 20 out of 113 had Marek's disease whereas in the control group 74 out of 122 were observed to develop the disease. Among the chickens vaccinated with MDV, 3-4% developed the disease. Possible causes of the disease in this group of chickens are discussed.


[Gestagen therapy in bladderneck adenoma. III. Clinicochemical findings and course controls in patients with bladderneck adenomas under gestagen therapy]. It is reported on clinico-chemical examinations in 30 carriers of adenomas, who underwent a gestagen therapy lasting 3 months. The treatment was performed in group I in 15 patients with progesterone depot and in group II with depostate. After the end of the treatment in group I an increase of the content of the sodium ions was found. The infections of the urinary tract improved. Neither in negative sense nor in positive sense an influence of the therapy on the other examination parameters was found.


[The rhagocyte (author's transl)].

[The rhagocyte (author's transl)]. The "rhagocyte" (Delbarre) was defined with the aid of own results and results from the literature as an unity of structure and function of phagocytic cells in synovial fluids. Rhagocytes are an ubiquitous phenomenon in most cases of inflammation in joints detectable with nonspecific methods and are not a specific sign for the diagnosis of rheumatoid arthritis. The inclusion bodies of rhagocytes were demonstrated as immunoglobulin complexes with fixation of complement (IgG/IgM/C) by means of the immunofluorescence technique. In these specific preparations the rhagocyte has an importance as rheumatoid arthritis cell (R.A. cell) as defined by Hollander. --A definition of the rhagocyte and a description of histochemical results is given in a synopsis of characteristical properties of inclusion body cells. Moreover, a representation of the morphogenesis and value of the rhagocytes in a concept of the pathogenesis of rheumatoid arthritis, the in vitro and in vivo reproduction of rhagocytes and its value for the diagnosis in diseases of joints is given.


[Effect of deprivation of the "rapid" phase of sleep on self stimulation of the hypothalamus and septum in white rats]. 26 rats with bipolar electrodes in lateral hypothalamic and septal areas were learned to press the bar for electrical stimulation of the brain (monopolar square pulses, 0.1 msec, 100 cps, train length 250 msec). After stabilization of self-stimulation (SS) responses, the animals were deprived of rapid eye movement sleep (REM) for up to 4 days by confinement to a small platform surrounded by water. The rats were allowed to SS for 40 min per day during and after REM deprivation up to 1 month. It was found that REM deprivation strongly increased hypothalamic SS rates but failed to change SS thresholds. As to the septal SS, its rate either increased, with threshold unchanged or lowered (1st type), or remained steady (2nd type), or decreased, with threshold unchanged or risen. In most cases the deprivation led to alteration in the shape of SS rate/intensity curve, which remained during the whole experimental period (1 month).


[Luteoma of the ovary during pregnancy (author's transl)]. The tumor of lutein cells of the ovary during pregnancy was first described by Sternberg (1963) as "luteoma of pregnancy". Up to 1973/74 66 cases were published. This benign tumor occurring only during pregnancy probably arises under stimulation of chorionic gonadotropin and may cause a virilization of the mother and female infant. After birth the ovarian tumors regress spontaneouly. Lutein cell tumors are usally discovered incidentally at laparotomy (cesarean section) in late pregnancy  and require no radical surgical treatment. The feature of these tumors and some related questions are discussed on the basis of on own observation being, to our knowledge, the first case of this type in Central Europe.


[Disintegration of enzymatically pretreated cartilage after subcutaneous implantation]. The influence of previous digestion  of cartilage proteoglycans and collagen on cartilage resorption in implants was studied. After implantation for 1, 2, 3, and 4 weeks the morphology of the implants was studied by light microscopy. It was found that enzymatic treatment of cartilage with hyaluronidase, collagenase as well as the combination of both enzymes slightly increased the resorption by granulation tissue. From these studies it can be concluded, that cartilage depletion of proteoglycans facilitates cartilage degradation, however it is not the only reason for the severe cartilage destruction seen in arthritic joints.


[Core and coat of the hepatitis b-virus and cytoplasmic viruslike particles in chronic hepatitis. An electron microscopic study (author's transl)]. In the second liver biopsy material of a seropositive patient receiving immunosuppressive therapy (Corticosteroid + Imuran) for chronic active hepatitis (CAH), intranuclear, ring-shaped, 20--25 nm in diameter non-coated particles (core) of liver cells and intracisternal filaments, 23 nm in diameter (coat) of the soft ER in the "ground-glass" hepatocytes were demonstrated by electron microscopy. Core-particles in the cytoplasm were seen occasionally. Dane-particles could not be visualized. Cytoplasmic spherical and ring-shaped virus-like structures (circ. 80 nm in diameter) different from B-virus components and Dane-particle were also found (second virus-infection?). The role of immuno-suppression in the appaerance of viral structures is considered because such particles could not be detected in the first biopsy before therapy when CAH and antigenaemia were already present.


[Cellular mechanisms of conditioned reflex integration]. The paper deals with the formation of cellular mechanisms of integration in the course of conditioned reflex elaboration. Primary integration consists in an interaction between the effects of the conditioned (CS) and unconditioned (US) stimuli on neurons, which leads to a stable connection between them. The subsequent, final integration consists in the joining up of these cells into special populations with common functional properties in relation to the paired stimuli. Primary integration is achieved either by the mechanism of addition of the elaborated reaction to the CS to the response to the US, or by joining an adequate reaction to the CS of the elaborated response to the US. The final integration is apparently achieved by the mechanisms of transmition from one neuron to another of the formed connection between the paired stimuli along one path common for the association as a whole.


An epidemiological study on paramyxovirus antibody titers in multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. The present epidemiological study concerned and evaluation of the level of measles antibodies (hemagglutination inhibition (HI) assay) and para-influenza-1 (Sendai) antibodies (complement fixation (CF) test) in serum of 107 control individuals (38 women), 176 multiple sclerosis (MS) patients (93 women), 717 relatives to MS patients (361 women), 9 patients with systemic lupus erythematosus (SLE) (all women), 46 relatives to SLE patients (28 women), 57 patients with rheumatoid arthritis (RA) (37 women), and 143 relatives to RA patients (85 women). In MS and their relatives the HI titer value was significantly raised and the CF titer only insignificantly increased. In SLE the HI titers were insignificantly raised but the CF values significantly decreased. In RA HI values were insignificatly raised, but the CF values were significantly decreased among females lacking rheumatoid factor in serum. In the individuals under study, HI values did not correlate with CF values. In MS two groups of patients could be treated, i.e. one group with raised HI values and one with normal distribution of titers. The data obtained are discussed in light of the theory, that all three disease entities may be "Slow Virus Diseases".


[Biologic-economic study of processes for cultivating Clostridium perfringens. II. Comparison of the effectiveness of actual and predicted processes for cultivating microorganisms]. The authors analyzed the efficacy of actual and prognosticated processes of Cl. perfringens, type A, cultivation: periodic, semicontinuous, continuous, and combined monocyclic. Comparative study permitted to choose the economically optimal processes, without any expenditure for their realization. Monocyclic combined process which could provide a great amount of active toxin at short periods proved to be the most advantageous among the cultivation processes studied.


GnRH action in rat anterior pituitary gland: regulation of protein, glycoprotein and LH synthesis. The effect of synthetic GnRH on the synthesis of proteins and glycoproteins in the anterior pituitary and in vitro release of LH into the medium was studied. A maximal dose (25 ng/ml) of of synthetic GnRH caused optimum release of radioimmunoassayable LH into the medium after 2 h of incubation. A concomitant increase in cyclic AMP accumulation in the tissue and LH in the incubation medium was also observed under the influence of GnRH during different periods of incubation time. Incubation of the rat anterior pituitary with GnRH stimulated the incorporation of [3H] proline into acid precipitable proteins in a time- and dose-dependent manner, similar to radioimmunoassayable LH released into the medium. Similar results were obtained when pituitary was incubated with dibutyryl cyclic AMP. LH, in addition, enhanced the incorporation of [3H] glucosamine and [3H] amino acids mixture into acid-precipitable proteins suggesting that proteins including glycoproteins are synthesized by the rat anterior pituitary under the influence of GnRH. Approximately 10% of the radioactivity associated with proteins comigrated with radioimmunoassayable LH on the gels. GnRH also enhanced the incorporation of [3H] glucosamine and [3H] amino acid mixture into immunoprecipitable LH. The GnRH-induced incorporation of [3H] proline into anterior pituitary proteins was abolished by specific translation inhibitors.


Ionic effects on the uptake of chloromercuribenzene-p-sulphonic acid by pancreatic islets. Effects of inorganic ions on the uptake of chloromercuribenzene-p-sulphonic acid (CMBS) were studied in microdissected pancreatic islets of non-inbred ob/ob-mice. Na2SO4 stimulated the total islet cell uptake of CMBS but decreased the amount of CMBS remaining in islets after brief washing with L-cysteine. CaCl2 stimulated both the total and the cysteine-nondisplaceable uptake; the stimulatory effect of CaCl2 on the cysteine-non-displaceable CMBS uptake was counteracted by Na2SO4. NaCl, KCl or choline chloride had no significant effect on the total islet cell uptake of CMBS, whereas LiCl was stimulatory. It is concluded that beta-cells resemble erythrocytes in having a permeation path for CMBS that is inhibited by SO4(2-). By analogy with existing models of the erythrocyte membrane, it is suggested that the SO4(2-) sensitive path leads to sulphydryl groups controlling monovalent cationic permeability in beta-cells.


[The so-called minimal cancers of the breast (author's transl)]. In situ lobular carcinoma, intraductal carcinoma and papilliferous non-invasive carcinoma are three non-invading cancers that present clinically as the other malignant tumors of the breast. Between January 1, 1973 and August 31, 1976, ten patients were operated at the institut Bordet for such tumors. Surgical treatment varied between radical mastectomy according to Madden and partial mammectomy. Follow-up reveals no recurrence over periods extending from zero to three years. The choice of treatment depends on the histology and the probability of evolution of the actual cancer.


Insulin stimulation tests in pituitary dependent Cushing's syndrome after complete adrenalectomy. The present study shows that in a group of 6 euadrenal patients, previously treated by complete adrenalectomy for pituitary dependent Cushing's syndrome, the stress stimulus of insulin induced hypoglycaemia is followed by a plasma ACTH response which is of similar magnitude as the response obtained with lysin-vasopressin. Both observations indicate that the central nervous system-pituitary axis is basically normal in pituitary dependent Cushing's syndrome as assessed by insulin induced hypoglycaemia. It is concluded that non-responsiveness of the pituitary-adrenocortical system to insulin induced hypoglycaemia in untreated patients with pituitary dependent Cushing's syndrome does not represent a fundamental defect of the stress mechanism, but is due to hypercorticism per se.


Hypophysis and function of pancreatic islets. IV. Effect of treatment with growth hormone and corticotrophin on insulin secretion and biosynthesis in isolated pancreatic islets of normal rats. The effects of the recognized diabetogenic hormones, growth hormone and ACTH, administered in vivo, on (pro-)insulin biosynthesis and secretion in isolated islets of normal rats were studied. Rats were treated with these hormones for 4 weeks. Afterwards, their collagenase-isolated islets were incubated with [3H]leucine for 3 h. (Pro-)Insulin biosynthesis was estimated for the incorporation data into islet protein fractions. Islets of treated rats released significantly more insulin and incorporated significantly less [3H]leucine into proinsulin and insulin compared with controls when tested at 100 mg glucose/100 ml. At 200 mg glucose/100 ml, no significant differences were found. The findings demonstrate an impact of these hormones on the B-cells derived from normal pancreas of intact rats. The alterations are, however, not very pronounced and can be easily compensated under a strong glucose stimulus. It appears that the mechanisms for (pro-)insulin biosynthesis and release in rats are more resistant against the diabetogenic actions of pituitary hormones than in other species.


Longitudinal study of the behaviour of certain hormonal parameters in women undergoing treatment with cyproterone acetate. A study has been made of the behaviour of certain hormonal parameters (LH, FSH, PRL, HGH, ACTH, cortisol and testosterone) in five women aged from 17 to 28 years, during two successive menstrual cycles, the first under basal conditions and the second while under treatment with cyproterone acetate (CPA) 100 mg/day), given from the fifth to the twenty-fifth day of the cycle. On the first day of the initial cycle and the twenty-ninth day of the second cycle, the secretion of gonadotropins, prolactin, and somatotropin were measured before and after stimulation with GnRH (50 microgram, i.v.), sulpiride (200 mg, i.m.) or insulin (0.1 U/kg). During treatment with CPA the ovulatory peak of LH was abolished, with a reduction in the levels of gonadotropin and testosterone. No changes were observed for PRL, HGH, ACTH or cortisol. The study of the pituitary reserves showed a reduced response of LH but not of FSH to GnRH. There were no changes in the response of PRL and HGH to stimulation. The data obtained confirm the inhibitory effect of CPA on gonadotropin and testosterone secretion, while the other parameters studied did not vary significantly.


Content and composition of urinary glycosaminoglycans in the patients with myoclonus epilepsy with and without Lafora bodies. Content, composition and molecular weight distribution of the urinary glycosaminoglycans (GAG) were determined in five patients with progressive myoclonus epilepsy (PME). In one patient (Family B) this syndrome was associated with cerebral Lafora bodies and in four siblings of Family A, no Lafora bodies were present in brain biopsy. Only one of the five patients had a moderate increase of urinary GAG excretion as expressed by 24-h output or creatinine. The heparan sulfate component of the GAG was moderately increased in two other patients. The molecular weight distribution of the urinary GAG was normal. The results do not support the contention that urinary GAG excretion is abnormal in PME. Among nine lysosomal enzymes in leucocytes, only the activity of alpha-mannosidase was increased 3-fold in the four siblings.


Cerebral calcinosis with late onset encephalopathy. Unusual type of pseudo-pseudohypoparathyreoidism. A family from Western Norway is described in which 5 out of 9 members in one generation developed a progressive encephalopathy in middle life. Massive, symmetrical calcifications located in basal ganglia, dentate nuclei and cerebral sulci of the brain were seen on roentgenograms of the skull. All affected members exhibited a clinical syndrome which included mental deterioration, extrapyramidal motor deficit, cerebellar ataxia and tremor. The biochemical investigation showed normal serum calcium and phosphorous and concentration of immunoreactive parathyroid hormone was normal. The Ellsworth-Howard test with exogenously administered parathyroid extract revealed a subnormal phosphorous diuresis while urinary excretion of cyclic AMP was normal. Thus, the defect appears to be an insufficient intracellular response to cyclic AMP. The late onset of symptoms is compatible with the slight disturbance in calcium-phosphorous metabolism we have demonstrated. The family probably represents an unusual type of pseudo-pseudohypoparathyroidism of which only one other family has been reported earlier. The investigations and pedigree analysis of the present kindred is suggestive of an autosomal recessive inheritance of the disorder.


[Preliminary observations on the results of treating malignant lymphoma with Lycurim]. The authors gave Lycurim to 30 patients with malignant lymphoma (LLC--12 cases, Hodgkin's disease - 15 cases, reticulosarcoma - 2 cases and lymphosarcoma - 1 case). The patients were divided into three groups. Group I received only Lycurim, group II - Lycurim and prednisone, group III - Lycurim and Solcoseryl. Significant improvement was observed in 22 patients, with complete remission in 5 cases and partial in 17 cases. Leucopenia and thrombocytopenia precluding treatment were never observed in cases treated simultaneously with prednisone or Solcoseryl. The authors believe that the proportion of remissions may be increased combining Lycurim with vincristine, procarbazine and glycocorticosteroids (LOP or LOPP).


[Current therapy of juvenile nasopharyngeal angiofibroma]. The nasopharyngeal angiofibrom continues sometimes to challenge the otolaryngologists because of the difficult radical surgery owing to the deep anchorage of the tumor in the base of the skull. In these cases, when possible, the embolization followed by surgery or the radiotherapy are the two better treatments. Without embolization, radiotherapy must be preferred because of the life threatening surgery that cannot eradicate the tumor.


Hepatocellular carcinoma and chronic persistent hepatitis. The morphologic type of cirrhosis that is followed most frequently by hepatocellular carcinoma is posthepatitic cirrhosis. Furthermore, HB AG is detected in a high rate among cases with hepatocellular carcinoma suggesting the intimate causal relationship between hepatitis b virus and hepatocellular carcinoma. It has been considered that hepatocellular carcinoma might develop during destruction and regeneration of fully developed liver cirrhosis. However, hepatocellular carcinoma is combined with not only liver cirrhosis but also with mild liver fibrosis. An attempt was made to determine HBs Ag in the liver tissue of liver fibrosis with hepatocellular carcinoma. HBs Ag was found in non-cancerous liver tissue of 40 percent of those cases. Therefore, it may be concluded that, at least some of those fibrosis is caused by chronic viral hepatitis and hepatocellular carcinoma may develop not only on posthepatitic cirrhosis but also on chronic persistent hepatitis. This evidence also suggests the carcinogenicity of hepatitis B virus.