Liquorkomplement und Multiple Sklerose

Zusammenfassung 1. In 239 Liquores, darunter 47 MS-Fälle und 91 normale Kontrollen, wurden Komplement und Komplementfaktoren (C₁, C₂, C₃ und C₄) bestimmt.2. Im normalen Liquor ist in der Regel keine Gesamtkomplementaktivität vorhanden. Dagegen ist die C₁- wie C₄-Aktivität praktisch immer und C₂-sowie C₃-Aktivität in über der Hälfte der Fälle zu finden. Das Komplementmuster im Liquor ist daher im Gegensatz zum Serum unvollständig.3. Bei erhöhtem Eiweiß zeigt der Liquor dagegen häufig Gesamtkomplementaktivität. Je höher das Liquoreiweiß ist, um so höher ist der Gehalt an C₂, C₃ und Gesamtkomplement. Diese Beziehungen zwischen Gesamteiweiß und Komplementaktivität gelten für normalen wie pathologischen Liquor einschließlich der MS-Fälle.4. Im MS-Liquor sind C₂, C₃ und Gesamtkomplement seltener zu finden als bei den Kontrollen. Bei den MS-Patienten ist C₂ und C₃ im akuten Schub herabgesetzt. C₃ nimmt im Verlauf der Erkrankung wahrscheinlich ab.5. Mit Antikomplementserum wurde _1C-Globulin, ein Teilfaktor von C₃, im Liquor von 55 MS-Patienten und 42 Kontrollen bestimmt. Es besteht kein Unterschied zwischen MS und Kontrolliquor. Auch bei akut entzündlicher MS ist _1C nicht vermindert.6. In der Diskussion wird auf widersprechende eigene Befunde über _1C-Inaktivierung im Serum während der akut entzündlichen MS-Phase hingewiesen.

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Summary 1. Complement and complement factors (C₁, C₂, C₃ and C₄) were determined in 239 specimes of cerebrospinal fluid (CSF) including 47 cases of Multiple Sclerosis (MS) and 91 normal controls.2. In general, total complement activity is absent in normal specimens while that of C₁ and C₄ can be found practically always and that of C₂ and C₃ in more than half of the cases. Therefore, the pattern of complements in the CSF is incomplete as opposed to that of serum.3. In contrast, samples with increased protein content frequently yield total complement activity. The higher the protein content of CSF the higher the content of C₂, C₃ and total complement. This relationship between amount of total protein and complement activity applies both to normal and pathological CSF specimens including those from MS.4. In cerebrospinal fluid from patients with MS, C₂, C₃ and total complement are found less frequently than in that from controls. C₂ and C₃ are diminished in patients with an acute exacerbation of MS. C₃ decreases probably in the course of the disease.5. _1C-globulin, a component of C₃, was determined with anticomplement sera in specimens from 55 patients with MS and from 42 controls. There is no difference between CSF of MS and controls. Even in acutely inflammatory cases of MS, _1C is not diminished.6. Discussing his results the author points out discrepancies concerning the nactivation of _1C in serum during acutely inflammatory episodes of MS.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Ultrastructural studies of concanavalin A receptors and 5′-nucleotidase localization in normal and injured mouse cerebral microvasculature

Summary Plant lectin concanavalin A conjugated with ferritin (Con A-F) injected i.v. was used for the detection of the specific monosaccharide residues (-d-mannosyl and -d-glucosyl) on the luminal surface of endothelial cells (ECs) in brain micro-blood vessels (MBVs). Both normal mice and animals with mechanically damaged blood-brain barrier (BBB) were used in this study. In addition, the activity of 5-nucleotidase (5N), the putative receptor for Con A, was studied cytochemically.Various methodologic experiments indicated that the reaction product formed on the luminal plasmalemma of ECs after incubation of samples in the cytochemical medium for the detection of 5N activity results from the action of unspecific phosphatase hydrolyzing both specific and nonspecific substrates. The abluminal side of the wall of MBVs seems to be a major location of 5N activity. Thus, no correlation between cytochemically demonstrable 5N activity and Con A receptor sites on the luminal surface of ECs was noted.After damage of the BBB, extensive internalization of the luminal plasmalemma forming the limiting membranes of pinocytotic vesicles, vacuoles, and endothelial channel-like structures was observed. This process was represented by a relatively rapid translocation of Con A receptors from luminal surface into the interior of the ECs and to the abluminal side of the vessel wall.Abbreviations AP Alkaline phosphatase - 5N 5-nucleotidase phate - AMP adenosine 5-monophosphate - CMP cytidine 5-monophosphate - GMP guanosine 5-monophosphate - UMP uridine 5-monophosphate - Con A concanavalin A - BBB blood-brain barrier - EC endothelial cell - HRP horseradish peroxidase - MBVs micro-blood vessels - NDPase nucleoside diphosphatase Supported in part by a grant from NINCDS No.17271-03     

Life events and syndromes of depression in the general population

Summary Brown and Harris (1978) contend that life events have causal significance for both psychotic and neurotic depression. This contradicts the psychiatric tradition. Neurotic depression has been regarded as a consequence of life-stress, while psychotic depression has been regarded as a consequence of processes intrinsic to the organism. Empirical evidence is presented to support the view that life events have a differential effect, within the general population. It is argued that Brown and Harris's (1978) conclusion follows from an inappropriate approach to classification. It is argued further that their data lend support to the traditional view. It is noted that their approach may inhibit the development of explanatory models linking life-stress, vulnerability factors and depression.     

Autonomic neuropathy in patients with HIV: Course, impact of disease stage, and medication

The purpose of this article is to examine the prevalence, degree, and natural course of pupillary neuropathy (PANP), cardiovascular autonomic neuropathy (CANP), and sensorimotor neuropathy (SNP) and to study the impact of disease stage and medication on neuropathy in 61 consecutive patients with HIV. PANP, CANP, and SNP were assessed by standardized test procedures. Overall prevalence of PANP, CANP, and SNP were 66%, 15%, and 15%, respectively. The maximal pupillary area (pupillary measure, p<0.0001) and the lying-to-standing ratio (cardiovascular measure, p<0.0001) were abnormal as compared with control subjects. The changes in CD4+ T-lymphocytes and respiratory sinus arrhythmia percentile during 2 years of follow-up correlated significantly (r=0.758, p=0.007). Patients with CANP were more often in an advanced disease stage than patients without CANP (p=0.004). SNP, but not PANP or CANP, was associated with the intake of the neuropathogenic drugs dideoxycytidine, dideoxyinosine, and 2,3 didehydro-2,3 dideoxythymidine (p<0.05). Autonomic and sensorimotor neuropathy are frequent in patients with HIV, and progression of CANP may put patients at risk for unexpected cardiorespiratory arrest.     

Membrane alterations in human glioblastoma

Summary Plasma membrane-enriched fractions were isolated from human gliomas and brain white matter. These membrane fractions were characterized by electron microscopy and by the distribution of the membrane marker enzymes (Na⁺K⁺)-ATPase and 2,3-cyclic AMP-3-phosphohydrolase. The comparison of the membranes from tumor and control material by SDS gel electrophoresis reveals an altered tumor membrane. Two proteins of a molecular weight of about 70,000 dalton and 30,000 dalton are found to be more expressed in the tumor membrane.     

Heterologous supersensitization between serotonin2 and alpha2-adrenergic receptor-mediated intracellular calcium mobilization in human platelets

Summary Recent reports suggest that serotonin (5-HT)₂ receptor-mediated second messenger systems are enhanced in platelets of affective disorders. To make the mechanism of the enhanced response clear, we investigated 5-HT₂ and alpha ()₂-adrenergic receptor-induced intracellular calcium (Ca²⁺) mobilization in platelets of healthy volunteers, using fura-2. 5-HT₂ and ₂-adrenergic receptor-mediated Ca²⁺ mobilization was enhanced by prior exposure to the other type of agonist, so called heterologous supersensitization. The supersensitization was due to the enhancement of maximal response without change in agonist affinity. Chelating extracellular Ca²⁺ did not diminish the supersensitization. This enhancement of Ca²⁺ mobilization was not inhibited by H-7, an inhibitor of protein kinase C. However, this supersensitization was inhibited by pretreatment with sodium fluoride which directly activates guanine nucleotide binding regulatory proteins (G proteins). These results suggest that the supersensitization was caused from intracellular Ca²⁺ storage sites through a G protein-coupled pathway.Abbreviations fura-2/AM 1-(2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy)-2-(2-amino-5-methylphenoxy)-ethane-N,N,N, N-tetraacetic acid, pentaacetoxymethyl ester - H-7 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride - EGTA ethylenedioxybis(ethylamine)-N,N,N,N-tetraacetic acid - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - NaF sodium fluoride - Fmax maximal fluorescence intensity - Fmin minimal fluorescence intensity     

Induction of glutathione S-transferase,placental type in T9 glioma cells by dibutyryladenosine 3′,5′-cyclic monophosphate and modification of its expression by naturally occurring isothiocyanates

Summary The effect of dibutyryladenosine 3,5-cyclic monophosphate (dibutyryl cAMP) on the expression of glutathione S-transferase placental type (GST-P) was examined in rat glioma cell line using an immunohistochemical technique. Cultured T9 glioma cells were negative for GST-P activity under normal conditions. However, treatment with 1 mM dibutyryl cAMP produced GST-P expression in about 50% of the cells, as well as some morphological changes. The expression of GST-P was increased with addition of dibutyryl cAMP together with 1 g/ml allyl isothiocyanate (AITC) or 0.1 g/ml benzyl isothiocyanate (BITC). With these combinated treatments, almost all cultured cells showed a strong positive reaction for GST-P, although AITC or BITC alone elicited GST-P in only 5% of the cultured cells. The results of the present study indicate that dibutyryl cAMP causes functional as well as morphological differentiation of T9 glioma cells.     

In situ hybridization with digoxigenin-labeled probes: sensitive and reliable detection method applied to myelinating rat brain

Summary A method for in situ hybridization of digoxigenin-labeled cDNA and cRNA probes to myelin protein mRNA is described. This technique has dual advantages of high structural resolution and high sensitivity and avoids problems associated with handling of radioactive materials. Furthermore, it can be readily combined in double labeling with immunocytochemical protein detection. We have used this technique to detect and locate mRNA for myelin basic protein (MBP), proteolipid protein (PLP), 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) and myelin-associated glycoprotein (MAG) in oligodendrocytes of 7-day-old and adult rat brains. PLP and MAG mRNA were restricted to the perinuclear cytoplasm, whereas MBP and CNPase mRNA was additionally present in peripheral oligodendrocyte processes.Supported by the Science Research Fund, Austria, P 7740M     

Human acoustic neurinomas: Nervous system specific biochemical parameters

Summary A series of 24 human acoustic neurinomas from 24 patients has been assayed for several biochemical parameters characteristic of the nervous system. S 100 protein, 2, 3-cyclic nucleotide 3-phosphohydrolase activity, and the myelin lipids galactosylceramide and sulfogalactosylceramide (sulfatide). Myelin basic protein was not detected. These findings further support the neuroectodermal origin of the human acoustic neurinoma, and provide additional biochemical markers for further study.     

Association analysis of a neural nitric oxide synthase gene polymorphism and antipsychotics-induced tardive dyskinesia in Chinese schizophrenic patients

Summary. Recent findings from rodent studies with chronic administration of antipsychotic drugs have indicated the role of neural nitric oxide synthase (NOS1) on the susceptibility of tardive dyskinesia (TD). In the present study, the association between a 3-untranslated region C267T (3-UTR C267T) polymorphism of the NOS1 gene and TD as well as TD severity was investigated in 251 Chinese schizophrenic patients with long-term antipsychotic treatment (TD: 128, non-TD: 123). After adjusting the effects of confounding factors, there was no significant association between NOS1 3-UTR C276T genotypes and TD occurrence (p=0.758). With in the TD group, we could not discover a significant correlation between NOS1 3-UTR C276T genotypes and the scores of abnormal involuntary movement scale (AIMS) (p=0.219 and 0.774). We concluded that the NOS1 3-UTR C276T polymorphism might not play a major role in the susceptibility of TD development, or on the severity of TD.     

The repetition of parasuicide in Edinburgh 1980–1981

Summary We prospectively studied all Edinburgh hospital-referred parasuicides admitted in 1980 until the end of 1981, with regard to their repetition of parasuicide. For those 259 who repeated during this time, parasuicide status at the key 1980 admission was significantly related to age group, the veterans being older than first-timers. Similarly, the total number of episodes of parasuicide in the follow-up period was significantly related to age-group and parasuicide status: those over 45 years and first-timers were less prone to repetition. Survival analysis of all 1980 admissions revealed that veterans were significantly more likely than first-timers to be admitted with a repetition from as little as 4 days after a given episode. This difference was maintained from then until the end of the follow-up period.     

A process analysis of Bender Gestalt Test performance in childhood emotional disorder: A single-case study

This study involves an analysis of the Bender Gestalt Test performance of a young, severely disturbed boy emphasizing the origins of and processes mediating the emergence of deviant responses. Deviant responses are considered to reflect a conflict between primitive motor impulses and an emergent, visually-mediated organization of the designs, corresponding to the several stages of sensory-motor adaptation. The manner of the resolution of visuo-motor conflict may prefigure later dispositional trends significantly embedded within aspects of childhood emotional disorder. Finally, analogy is drawn between specific aspects of performance and the boy's behavioral organization.     

Effect of castration on the concentration of adenosine 3′, 5′-monophosphate in the rat pineal organ

Summary The concentration of adenosine 3, 5-monophosphate (cAMP) was investigated in the rat pineal organ after bilateral orchidectomy. Orchidectomy caused a decrease in pineal cAMP concentration.This paper has been supported by a grant of the Polish Academy of Sciences, No. 10.4.2.01.5.6.     

Group psychotherapy and the mosaic adolescent society

Discussion of the influence of peer group mores and values on the adolescent patient's dysfunctional behaviors and treatment outcome. When the group therapist thinks peer, the group will focus on important issues such as inclusion, acceptance and awareness of the contrasting beliefs of the numerous peer subcultures within adolescent society. Strategies and approaches to create a therapeutic group milieu and structure are outlined to enable unwanteds to enter peer groups which support rather than impede the attainment of treatment goals. The need for leadership to be responsive to group members who have not experienced negentropic or functional systems is emphasized.     

Ganglioside mapping of a human medulloblastoma xenograft

Summary The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE-671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed by fast atom bombardment mass spectometry following permethylation. Identification of individual gangliosides was also performed by immunostaining of high-performance thin-layer chromatography-separated bands. Total ganglioside levels of 0.20 mol/g of tissue were obtained, consistent with those reported for human glioma cell lines grown as xenografts; predominant monosialogangliosides of TE-671 xenografts were II³--NeuAc-LacCer (GM3) and II³--NeuAc-GgOse₃ Cer (GM2) but there were also relatively large proportions of IV³--NeuAc-LcOse₄Cer (3-isoLM1), IV³--NeuAc-nLcOse₄Cer (3-LM1) and a further ganglioside of the neolactoseries with an extra lactosamine moiety. The only oligosialoganglioside detected was IV³, II³--NeuAc₂-GgOse₄Cer (GD1a).Abbreviations: The gangliosides have been designated according to Svenerholm [18] GM3 II³--NeuAc-LacCer - GM2 II³--NeuAc-GgOse₃Cer - GM1 II³--NeuAc-GgOse₄Cer - 3-LM1 IV³--NeuAc-nLcOse₄Cer - 3-isoLMI IV³--NeuAc-LcOse₄Cer - Fuc-3-isoLMI IV³--NeuAc, III⁴-Fuc-LcOse₄Cer - GD1a IV³, II³--NeuAc₂-GgOse₄Cer - FAB-MS Fast atom bombardment-mass spectometry - GC-MS gas chromatography-mass spectometry Supported by NC1 RO1 CA11898 to Dr. Bigner and B8803X-00627-24B from the Swedish Medical Research Council to Dr. L. Svennerholm     

Lectin histochemistry of scrapie amyloid plaques

Summary Peroxidase-labeled lectins were used for detection of specific monosaccharide residues in amyloid plaques in brains of scrapie-infected mice. The lectins tested recognize the following residues: -d-galactosyl (Ricinus communis agglutinin 120, RCA-1), -d-galactosyl and -d-galactopyranoside (Bandeirea simplicifolia aggl., BSA), -d-mannosyl and -d-glucosyl (Concanavalin A, Con A), N-acetylglucosaminyl and sialyl (Wheat germ aggl., WGA), sialoglycoconjugates (Limulus polyphemus aggl., LPA), -l-fucosyl (Ulex europeus aggl., UEA-1 and Tetragonolobus aggl., TPA), N-acetyl-d-galactosaminyl (Helix pomatia aggl., HPA). The most intense staining reaction in amyloid plaques was observed with BSA and WGA; it was less intense with RCA-1, Con A, and HPA. This indicates that the plaque material contains glycoproteins with abundance of accessible residues of - and -galactose, N-acetyl-d-glucosamine and N-actyl-d-galactosamine, and some types of sialoglycoconjugates recognized by WGA. Such residues, like -l-flucosyl recognized by UEA-1 and TPA, were almost undectectable in the examined plaques.There were also some differences in the staining intensity between small and large plaques (WGA and HPA) and between central and peripheral areas of the plaques.In the wall of micro-blood vessels relatively strong staining reaction was observed with RCA and BSA and less intense with WGA and Con A.Support in part by grant no. 5PO1 AG 04220-03 from the National Institute of Aging, NIH     

Prevalence of known and hidden alcoholism in the revisited lundby population

Summary Using the new data from a second followup of the Lundby 1947 cohort, the aim of the present paper has been to analyze some relationships between known and hidden alcoholism in a Swedish general population sample. Information was collected by psychiatrists trough free, exploratory field interviews checked against documentary records. Alcoholism was medically defined for present purposes. Information was obtained for 98% of the 952 men surviving the cross-section date July 1, 1972. The distribution of alcoholism and other psychiatric disorders in the total population and in age subgroups was analyzed epidemiologically. The true prevalence of alcoholism in the adult men was 9.5%, comprising 7.2% known and 2.3% hidden. The proportion of hidden to known cases was 0.301 (Temperance Boards 0.871, Psychiatric Agencies 0.961, Drinking and driving offences 4.31). The main finding that about 70% of male alcoholics in Lundby appears to be known to the agencies is at variance with current views that there is an iceberg under the tip, though consistent with Rubington's suggestion that so-called hidden alcoholism is not totally but partially invisible in welfare societies.     

Dose-dependent pharmacokinetics of α-methyl-p-tyrosine (α-MT) and comparison of catecholamine turnover rates after two doses of α-MT

Summary Groups of rats were injected i.p. with 0.407 or 1.02 mmoles/kg of D, L--methyl-p-tyrosine methylester HCl (-MT). The time-courses for-MT in plasma and brain were followed together with the endogenous brain dopamine (DA) and noradrenaline (NA) contents.The elimination of-MT from plasma and brain was markedly delayed after the high-MT dose compared with the low dose. At 40 hours after the injection of 1.02 mmoles/kg of-MT both plasma and brain levels were high, whereas no-MT could be detected in plasma or brain at 16 hours after the lower dose.The brain catecholamines were decreased to very low values after the higher-MT dose (DA 14% and NA 10% of controls at 8 and 24 hours respectively). There was no complete recuperation at 40 hours of any of the amines. After the lower-MT dose, the DA concentration was back to control levels at 16 hours and NA at 12 hours. Between 16–40 hours after the high-MT dose a majority of the rats showed prominent signs of sedation, weight loss and dehydration. No such signs were observed in rats receiving 0.407 mmoles/kg. During the first hour after the-MT injection the declines of DA and NA respectively were almost identical for both-MT doses. When the whole time-course (0–8 hours) after the high dose was considered, biphasic declines were obtained for both DA and NA, suggesting at least two different catecholamine pools. However, due to toxic effects after the high-MT dose, turnover data have to be interpreted with caution.     

Work and mental health

Abstract. Background: Studies investigating the psychological correlates of types of occupation have focused on such disorders as stress, depression, suicide and substance abuse. There have also been some models proposed to allow understanding of factors common to different types of occupations. We sought to provide an overview of research related to work and mental health and consider future research directions. Methods: A literature search was conducted using the Medline, PsycInfo, Embase and PubMed databases. The key words occupation or work were searched in combination with the key words mental health, risk factors, disorders, depression, suicide, trauma, stress or substance use. Results: Studies of stress tend to be more applicable to specific workplace issues. While some of the studies relating to onset of depression, suicide, substance abuse and trauma pertain to specific occupational issues and results are often not generalizable, they have progressed our understanding of risk factors to those disorders. There are workplace factors involving exposure to danger and crisis that lead to posttraumatic stress disorder (PTSD), substance abuse (including stimulants) and depersonalization. Workplace risk factors for depression involve situations promoting lack of autonomy, and involving caring for others as part of the work role, particularly where there is dependence on others for their livelihood. Risk factors for alcohol abuse include workplaces with access to alcohol and where use of alcohol is sanctioned. There appears to be a bi-directional relationship between personality and work, so that people are drawn to particular occupations, but the occupations then have an effect on them. An interactional model is proposed to consider this. Conclusion: The research questions pertaining to mental health are varied and will determine what mental health issues are of interest and the models of work applicable. There need to be more longitudinal studies and consideration of factors which the worker brings to the workplace (psychosocial issues, personality traits), as well as interpersonal issues and consideration of systemic, organizational, political and economic factors, including leadership styles.     

The light-flash-evoked response as a possible indicator of increased intracranial pressure in hydrocephalus

Surgical treatment of infantile hydrocephalus by shunt implantation may result in suboptimal intracranial pressure. Major neurological impairments and death are usually prevented by shunt treatment, but minor sequelae may persist or develop. The introduction of adjustable shunts has improved the possibilities of optimizing shunt function and minimizing the risk of such impairments. However, it is still impossible to determine the intracranial pressure without invasive measurements. Clinical findings and procedures such as computed tomography (CT) are not always enough to allow a conclusion as to whether a child's signs and symptoms are the result of suboptimal intracranial pressure (shunt dysfunction) or are of another etiology. With the aim of reducing the number of invasive pressure measurements and CT scans, we investigated the effect of increased intracranial pressure on the visual evoked response (VER). Binocular light flash stimuli of supramaximal intensity were used and VER recordings were performed from Oz and Cz. The VER results from a group of 31 infants and children with hydrocephalus and 2 children with pseudotumor cerebri were compared with responses from a control group of 35 healthy children. The results show that a subpotential, P (P-prime), usually just preceding P1 (P100), has an increased latency (>96 ms) in all hydrocephalic children before surgery. The P latency in this group was usually even above 110 ms. The latencies of other VER potentials were also increased but not as consistently as P. After surgical intervention the VER latencies decreased and usually normalized. The P latency in four children in the control group was just above the borderline latency, but was less than 110 ms. In the remaining 31 children the VER P latency was 96 ms or below. The VER provides information about the physiological condition of the visual system and seems to be related to intracranial pressure. The method was found to be useful in the clinical examination of hydrocephalic children. In addition, the VER may be used to monitor patients' clinical condition and the effect of treatment, e.g., in cases of pseudotumor cerebri or traumatic brain injury.