Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Role of cholinergic and serotoninergic processes in modulation of activity of the negative reinforcement system

The effect of cholinergic and serotoninergic drugs on the latency of blocking of central aversive stimulation was studied. Physostigmine and fluoxetin increased the latency of avoidance. Hyoscine and n-chloramphetamine could either increase or decrease the time of active avoidance. Fluoxetin reduced the activating and reversed the depriming effects of hyoscine. A combination of fluoxetin with physostigmine potentiated the depressant effect of the latter. n-Chloramphetamine weakened inhibitory effect of physostigmine and potentiated the action of hyoscine. An inhibitory role is suggested for cholinergic and serotoninergic mechanisms in the activity of the negative reinforcement system. Functional interconnection between these neuromediator systems is postulated.Department of Pharmacology, Academician I. P. Pavlov First Medical Institute, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 11, pp. 552–554, November, 1978.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Chemotherapy and antiangiogenesis: drug-specific effects on microvessel sprouting

Tumors are angiogenesis dependent. Some chemotherapeutics have been shown to be able to suppress angiogenesis and thus tumor growth in vivo at low, well-tolerated doses. Not much is known about the angiogenesis-modulating effects of chemotherapeutics in vivo, however. Microvessel sprouting is inherent to angiogenesis. Using the rat mesentery assay, we studied the effect of cyclophosphamide, doxorubicin and paclitaxel at a low, atoxic dose on the number of sprouts per unit tissue volume (No. SP) and their length (Le. SP) at the edge of the expanding network in VEGF165-mediated angiogenesis. A single dose of each cytotoxic drug was administered i.v. 7 days before the animals were sacrificed. Cyclophosphamide significantly lengthened the shortest Le. SP and shortened the longest Le. SP, doxorubicin did not significantly affect Le. SP, whereas paclitaxel significantly shortened both the shortest and the longest Le. SP. No correlation was found between the present results and the distinctly drug-specific results of microvessel segment number and length analyzed within central parts of the same expanding network. To our knowledge, this is the first quantitative report on the effect of chemotherapy on angiogenesis sprouting in vivo. Collectively, the data suggest that cyclophosphamide, doxorubicin and paclitaxel at a non-toxic dose primarily target different intrinsic components of the angiogenic cascade, leading to distinctly drug-specific effects.     

Experimental study of the possibility of metabolic correction of maternal, fetal, and newborn hypoxia in rats using a new amino acid composition MR-33

The status of pregnant rats, their fetuses, and progeny exposed to oxygen insufficiency are compares. By the end of pregnancy the resistance to hypoxia markedly decreases. Newborn rats during nursing are highly resistant to hypoxia. When nursing period is over, the resistance to hypoxia drops, but later is gradually restored. MR-33 preparation produces a pronounced antihypoxic effect. Administration of the drug to pregnant rats not only appreciably improves their resistance to oxygen insufficiency, but also promotes adaptation and compensatory mechanisms in the progeny, thus helping the progeny to better tolerate hypoxia, particularly when its probability is particularly high. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 451–454, October, 1997     

Changes in state of the surfactant in experimental pneumonia

The state of the lung surfactant in rabbits at different stages of development of experimental pneumonia (3–60 days) was compared with the dynamics of oxidoreductases in the alveolar epithelium and cells of the inflammatory focus of infiltration. In the initial stage (3–7 days) of activation of cell metabolism there was a brief increase in, the intensity of surfactant lipid synthesis, accompanied by relative inhibition of phospholipid synthesis. Later, development of degenerative changes and sclerosis of the parenchyma was accompanied by inhibition of synthesis of all components of the surfactant. The surface activity of the surfactant became stabilized at a low level.Laboratory Division, I. M. Sechenov Research Institute of Medical Climatology and Physical Methods of Treatment, Yalta. Department of Pathological Anatomy, Faculty of Internal Medicine, and Department of Organic Chemistry, Crimean Medical Institute, Simferopol'. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 286–288, September 1977.     

Response of different types of connective tissue to hormones

A comparative study was made of the lysosomal glycosidases of the eye tissues (sclera and cornea) and also of bone tissue and cartilage from rabbits. Intraperitoneal injection of thyrocalcitonin (TCT), deoxycorticosterone (DOC), hydrocortisone (HC), and somatotropic hormone (STH) were shown to modify the activity of -galactosidase, -glucosidase, and hyaluronidase and the functional state of the lysosomal membranes in the tissues. HC and STH stabilize, whereas DOC and large doses of TCT labilize the lysosomal membranes. After injection of HC and STH the absolute activity of the enzymes in the tissue homogenates falls, whereas DOC has the opposite action.Helmholtz Research Institute for Eye Diseases, Moscow. N. N Priorov Central Scientific-Research Institute of Traumatology and Orthopedics, Moscow. (Presented by Academicial of the Academy of Medical Sciences of the USSR M. V. Volkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 7, pp. 38–41, July, 1977.     

Hypermethioninemias of genetic and non-genetic origin: A review

This review covers briefly the major conditions, genetic and non-genetic, sometimes leading to abnormally elevated methionine, with emphasis on recent developments. A major aim is to assist in the differential diagnosis of hypermethioninemia. The genetic conditions are: (1) Homocystinuria due to cystathionine β-synthase (CBS) deficiency. At least 150 different mutations in the CBS gene have been identified since this deficiency was established in 1964. Hypermethioninemia is due chiefly to remethylation of the accumulated homocysteine. (2) Deficient activity of methionine adenosyltransferases I and III (MAT I/III), the isoenzymes the catalytic subunit of which are encoded by MAT1A. Methionine accumulates because its conversion to S-adenosylmethionine (AdoMet) is impaired. (3) Glycine N-methyltrasferase (GNMT) deficiency. Disruption of a quantitatively major pathway for AdoMet disposal leads to AdoMet accumulation with secondary down-regulation of methionine flux into AdoMet. (4) S-adenosylhomocysteine (AdoHcy) hydrolase (AHCY) deficiency. Not being catabolized normally, AdoHcy accumulates and inhibits many AdoMet-dependent methyltransferases, producing accumulation of AdoMet and, thereby, hypermethioninemia. (5) Citrin deficiency, found chiefly in Asian countries. Lack of this mitochondrial aspartate-glutamate transporter may produce (usually transient) hypermethioninemia, the immediate cause of which remains uncertain. (6) Fumarylacetoacetate hydrolase (FAH) deficiency (tyrosinemia type I) may lead to hypermethioninemia secondary either to liver damage and/or to accumulation of fumarylacetoacetate, an inhibitor of the high K(m) MAT. Additional possible genetic causes of hypermethioninemia accompanied by elevations of plasma AdoMet include mitochondrial disorders (the specificity and frequency of which remain to be elucidated). Non-genetic conditions include: (a) Liver disease, which may cause hypermethioninemia, mild, or severe. (b) Low-birth-weight and/or prematurity which may cause transient hypermethioninemia. (c) Ingestion of relatively large amounts of methionine which, even in full-term, normal-birth-weight babies may cause hypermethioninemia.     

Studies on Fusarium solani

Allergenic cross-reactivity among three Fusarium species (F. solani, F. equiseti, and F. moniliforme) was determined by crossed immunoelectrophoresis (CIE), ELISA inhibition, and immunoprint-inhibition analysis. Inhibiting immunoprint was used to assess the cross-reactivity of individual allergenic proteins in culture filtrate (CF), separated on SDS-PAGE. Dose-response inhibition of band 14 kDa in immunoprints of F. solani CF by antigens of F. solani CF, F. equiseti CF, and F. moniliforme CF demonstrated significant cross-reactivity of allergenic proteins on analysis of densitometric scans. CIE and ELISA inhibition using hyperimmune sera raised in rabbits against F. solani CF antigen also demonstrated shared antigenicity among Fusarium species. Collectively, this study revealed the presence of shared as well as unique antigenic and allergenic determinants in F. solani CF, F. equiseti CF, and F. moniliforme CF antigens.     

Effects of sex steroid hormones on lipid peroxidation and glutathione antioxidant system in rat skin

Effects of estradiol and testosterone on the intensity of lipid peroxidation and contents of glutathione redox system components in the dermis and epidermis of rat skin were studied. Only estradiol induced considerable dose-dependent and tissue-specific biphasic antioxidant effects on the skin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 663–666, December, 1999     

Ultrastructural stereological analysis of the liver of Muridae from regions with various levels of anthropogenic pollution

Ultrastructural stereological analysis revealed the fundamental reorganization of hepatocytes in Muridae from natural ecosystems exposed to anthropogenic factors. An appreciable decrease of the volume density of mitochondria and granular endoplasmic reticulum was associated with a many-fold increase of the volume density of glycogen. The detected hepatocyte glycogenosis was characterized by a redistribution of organelles and the formation of large depots of glycogen with reduced electron density. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 4, pp. 470–476, April, 1996 Presented by D. S. Sarkisov, Member of the Russian Academy of Medical Sciences     

Daily variations of epinephrine, norepinephrine, and β-adrenoceptors in the blood and lymphoid organs of intact rats

Daily variations of catecholamine concentrations in the blood and lymphoid organs in Wistar rats were revealed. Daily fluctuations of epinephrine and norepinephrine levels in the spleen and blood were synchronous. Circadian variations of epinephrine in the thymus, lymph nodes, and plasma were synphasic. A relationship between neurotransmitter concentrations and expression of β-adrenoceptors on thymic and splenic lymphocytes was noted. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 9, pp. 344–346, September, 1999     

Investigation of the effect of certain chlorinated hydrocarbons on the composition of the hepatocyte population of the rat liver

Hepatocytes in the liver of albino rats poisoned by inhalation of dichloropropane and trichloropropane were investigated cytophotometrically and karyometrically. With respect to the effect on polyploidization of the hepatocyte nuclei trichloropropane was found to be more toxic than dichloropropane. The development of polyploidization is determined by the dose of the toxic agent and the exposure to it: The smaller the dose the shorter the time required for the effect to take place.Laboratory of Morphology, A. N. Sysin Institute of General and Communal Hygiene, Academy of Medical Sciences of the USSR. Laboratory of Cytology, N. K. Kol'tsov Institute of Developmental Biology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 345–348, March, 1977.     

Advantages of dichlorotriazinylaminofluorescein conjugates isolated by one-stage gel filtration in immunofluorescence

A simple method of obtaining dichlorotriazinylaminofluorescein (DCTAF) conjugates against human immunoglobulins and of isolating their optimally labeled fractions is described. The one-stage method of liberation of the conjugates from unbound fluorochrome and of simultaneous separation of optimally labeled fractions is carried out on sephadex G-25 at pH 5.6–6.6 in an eluting solution of low ionic strength. Proteins loaded with dye are adsorbed on the gel in accordance with their isoelectric points.Laboratory of Clinical Immunology, Department of Immunology, Scientific-Research Center, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician, of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 505–506, April, 1977.     

A comparative study of the effects of dimebon,obsidan, finoptin,and cordaron on the functional state of ischemic focus and size of necrotic zone in experimental myocardial infarction

Dimebon, an antihistamine agent, exerts a moderate antianginal effect, improving the function of ischemic focus in the myocardium and decreasing the necrotic zone in experimental myocardial infarction. Dimebon is less active than obsidan, finoptin (except for the size of the necrotic zone), and cordaron. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 642–644, December, 1996     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.     

Mechanism underlying the effect of the bronchodilator troventol on histamine secretion

Molecular mechanism of the effect of the anticholinergic bronchodilator troventol on histamine secretion, the initial step in bronchospasm, is studied. Atrovent (ipratropium bromide) and atropine sulfate are used as reference preparations. Histamine secretion is induced by adding phorbol myristate acetate to cell suspension. In cells incubated for 5 min with troventol histamine secretion constitutes 52.4% of the maximum level, while atrovent and atropine have no effect on this process. Histamine secretion in mast cells is initiated by a sharp increase in cytosolic calcium. Troventol and atrovent reduce the initial rate of passive calcium entry into the cells by 56.3 and 28%, respectively, while atropine does not affect this parameter. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 11, pp. 537–540, November, 1997     

Unique cellular features in a testicular plasmacytoma

A case of testicular plasmacytoma is described at the light and fine structure level. The patient was a 54-year-old male with a history of multiple myeloma.The testicular tumor was restricted to an interstitial space growth. Plasma cells varied in differentiation with few obtaining the cartwheel nucleus and prominent Golgi of connective tissue plasma cells. Cytoplasmic inclusions were characteristic of most cells and a large number of intranuclear inclusions were present. To our knowledge, this is the first report of such inclusions in the cells of a testicular plasmacytoma. Their significance in cases of end stage myeloma is discussed.