Abnormal seasonality of schizophrenic births A specific finding?

Summary The unusual finding of an abnormal seasonal distribution of schizophrenic births, showing an excess of 10% in the winter or spring months and an equal deficit in the summer or autumn months, cannot be explained by artefacts. It has not yet been established whether the finding is specific to schizophrenia. We observed an excess of schizophrenic births of some 10% in March to May, significant at the 5% level, and a deficit of approximately the same size in June to August on the birth data of first-admission patients with the clinical diagnosis of schizophrenia. The data, obtained from the Mannheim Psychiatric Case Register, were compared with those of the Mannheim population and a control group matched by birth year and sex. The total population of mentally retarded children aged 7 to 16 years from the Mannheim population showed an excess of some 20% in April to June and an equal deficit in the last two quarters of the year, compared with the Mannheim population of the same birth years. The finding was not significant, but allowance must be made for the low case number of 415. We also compared 3409 first-admission patients with depressive syndromes (ICD 296 and 300.4) and 5615 first-admission patients with the diagnosis of neurosis and personality disorders (ICD 300–302, except 300.4, and 305–309) from the Mannheim Case Register with a control population and a parallel control group. Depressed males showed an excess of births in March to May, which was significant at the 1% level; the birth peak for females was smaller and not significant. The same findings were obtained for the category of neurosis and personality disorders, i.e. an excess of about 10% in March to May for males, significant at the 1% level, and a non-significant excess for females. Our findings are awaiting replication. Causal explanations will be discussed with great reservation. The procreational hypothesis, assuming those factors that lead to an equidirectional seasonal pattern of births with a slight deviation from the average of a year in the general population, to be reinforced in the disease categories mentioned, is regarded as the most simple and plausible explanation. It is based on the assumption that some of the parents of individuals suffering from schizophrenia, mental retardation or probably also some other mental disorders running from generation to generation, have a higher threshold in partner-seeking behaviour, which is overcome more easily in the summer months with the consequence of increased pregnancies.     

The effect of neuroleptic treatment and of high dosage diazepam therapy onβ-endorphin immunoreactivity in plasma of schizophrenic patients

Summary Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/ SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.     

Cancer mortality in relatives of retinoblastoma patients

The risk of other cancers in relatives of retinoblastoma (RTB) patients was determined by a survey of the mortality experience of siblings, parents, parental siblings, and grandparents of all U.S. or Canadian RTB patients referred to The University of Texas M.D. Anderson Hospital and Tumor Institute between 1944 and 1980. Expected mortality was ascertained by the application of age-, sex-, race-, and calendar year-specific U.S. mortality rates to the observed person-years. Among 607 relatives of 33 unilateral-sporadic RTB probands, no excess in cancer deaths was observed (observed/expected = 18/22). Among 733 relatives of 47 bilateral-familial RTB probands, a slight excess in cancer deaths was observed (41/31). A significant excess in cancer deaths was occurred in relatives under age 55 years (18/9) and in fathers (7/1) of the bilateral RTB probands. To determine whether the cancer excess was related to some unique allele associated with second tumors in RTB survivors, the cancer mortality of 203 relatives of the 14 RTB patients with second tumors was examined, and no excess was observed (11/11). To determine whether the excess might be attributable to an unexpressed RTB gene or precursor, the mortality experience was examined in 6 kindreds in which parents, unaffected by RTB, had more than 1 child with RTB. Among these 72 relatives a significant excess in cancer deaths was observed (8/2). The findings demonstrate a modest overall cancer excess in relatives of hereditary RTB patients and suggest it may be attributable to an unexpressed RTB gene or precursor in a small number of kindreds. Mechanisms for an apparent "precursor" might involve a delayed mutation, genetic mosaicism, or a submicroscopic balanced chromosomal translocation.     

Views of Dutch general practitioners about premenstrual symptoms: A qualitative interview study

BackgroundGeneral practitioners (GPs) encounter women suffering from premenstrual symptoms. Often women with premenstrual problems experience little understanding from GPs. Views of GPs will influence their approach to these women and their care. Insight into these views is lacking but could help in designing educational programmes for GPs.ObjectivesTo explore the views of Dutch GPs towards aetiology, diagnostic process, and preferred treatment of premenstrual symptoms.MethodsIn 2017, we conducted a qualitative, semi-structured, interview survey among 27 GPs, varying in age, gender, and practice setting.ResultsImportant themes emerged from the interviews: ‘no need for a symptom diary,’ ‘PMS defined as illness’ exclusively in case of disruption of normal functioning, and ‘symptomatic treatment’ as preferred approach. Most GPs considered PMS to be a physiological phenomenon, with taking history as an adequate diagnostic tool. Almost all GPs regarded a normal cyclical hormonal cycle as causal; many also mentioned the combination with personal sensitivity. Some pointed to a dividing line between physiological condition and illness if women could not function normally in daily life. Lastly, the approach GPs preferred was focussing on relieving symptoms of individual patients. In addition to explaining the hormonal cycle and lifestyle advice, all GPs advocated oral contraceptives, and if necessary psychological support. GPs expressed negative feelings about prescribing antidepressants.ConclusionGPs considered physiological changes and personal sensitivity as aetiological factors. We recommend more training to improve GPs knowledge and more insight into the burden of women with PMS. A symptom diary is an essential diagnostic tool for GPs.     

Selective effects of dietary fats on vascular 13-HODE synthesis and platelet/vessel wall interactions

Fish oil (FO) diets are associated with decreased thrombosis, which is though to be related, in part, to changes in platelet and vessel wall prostanoid synthesis. Recently, we found that 13-hydroxyoctadecadienoic acid (13-HODE) synthesized in the vessel wall from linoleic acid (LA, 18:2 n-6) via the lipoxygenase pathway, also decreases platelet/vessel wall interactions. Thus, we determined whether diets containing fish oil, walnut oil (rich in linoleic acid), black currant seed oil (rich in both linoleic and gamma linolenic acids, 18:3 n-6), or lard influenced vessel wall 13-HODE synthesis and platelet/vessel wall adhesion in rabbits. In vivo, vessel wall thrombogenicity was decreased in animals fed the black currant seed oil rich diet for 4 weeks as compared to the control "LARD" diet. This latter effect was better obtained when gamma linoleic acid was present suggesting a secondary effect of this fatty acid. The decreased vessel wall thrombogenicity in those animals, was associated with increased vessel wall 13-HODE synthesis. In contrast, ex vivo platelet adhesivity was significantly decreased in the fish oil diet fed animals, as compared to the control "LARD" diet and correlated with decreased platelet 12-HETE synthesis. We conclude that both fish oil and black currant seed oil rich diets inhibit platelet/vessel wall adhesion; the black current seed oil diet by increasing the availability of linoleic acid for 13-HODE synthesis and inhibiting vessel wall thrombogenicity; the fish oil diet, by inhibiting platelet 12-HETE synthesis and subsequent platelet adhesion.     

Pb2+ modulates the NMDA-receptor-channel complex

Summary The actions of Pb²⁺ on NMDA channel currents of acutely dissociated hippocampal CA1- and CA3-neurones from adult rats activated by aspartate plus glycine (asp/gly) were examined. A fast reversible and a slow irreversible response to Pb²⁺ were found. Pb²⁺ applied simultaneously with asp/gly decreased an inward current. The threshold concentration was below 2 M, the current was reduced > 90% at concentrations over 100 M, The decrease of the asp/gly activated current showed no voltage dependence. Opening of NMDA channels was not necessary for Pb²⁺-action, as preincubation in 50 M Pb²⁺-containing external solution for several seconds dramatically reduced the response to asp/gly/Pb²⁺. This effect was reversed within 2 to 5 s of wash. Presence of Pb²⁺ or asp/Pb²⁺ or glycine/Pb²⁺ in the external solution did not prevent recovery of the NMDA receptor/channel complex from desensitization. Prolonged perfusion of a cell with the asp/gly/Pb²⁺-containing external solution resulted in an irreversible decrease of the asp/gly current, whereas the amplitude of the asp/gly/Pb²⁺ response did not change over the duration of an experiment. We conclude that Pb²⁺ modulates NMDA channel activity via interaction with the NMDA/glycine receptor: as a result the channel current decreases.Abbreviations NMDA N-methyl-D-aspartate - LTP long-term potentiation - AP5 2-amino-5-phosphonovalerate - EGTA ethylene glycol bis(-aminoethylether)-N,N,N,N-tetraacetic acid - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid Correspondence to H. L. Haas at the above address     

Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

Predominance of a single genotype of Mycobacterium tuberculosis in countries of east Asia.

Analysis of the population structure of Mycobacterium tuberculosis strains from the People's Republic of China showed that the vast majority belong to a genetically closely related group. These strains shared the majority of their IS6110 DNA-containing restriction fragments, and also, the DNA polymorphism associated with other repetitive DNA elements, like the polymorphic GC-rich sequence and the direct repeat, was very limited. Because the majority of these strains originated from the province of Beijing, we designated this grouping the "Beijing family" of M. tuberculosis strains. Strains of this family were also found to dominate in neighboring countries such as Mongolia, South Korea, and Thailand, whereas a low prevalence of such strains was observed in countries on other continents. These data indicate that strains of the Beijing family recently expanded from a single ancestor which had a selective advantage. It is speculated that long-term Mycobacterium bovis BCG vaccination may be one of the selective forces implicated in the successful spread of the Beijing genotype.     

NRE,the major nitrogen regulatory protein of Penicillium chrysogenum,binds specifically to elements in the intergenic promoter regions of nitrate assimilation and penicillin biosynthetic gene clusters

NRE, the nitrogen regulatory protein of Penicillium chrysogenum, contains a single Cys2/Cys2-type zinc-finger motif followed immediately by a highly basic region. The zinc-finger domain was expressed to Escherichia coli as a fusion protein with -galactosidase. In order to test the putative DNA-binding ability of NRE, the intergenic promoter region of the nitrate reductase/nitrite reductase gene cluster (niiA-niaD) of Penicillium was sequenced. Our results show that NRE is a DNA-binding protein and binds to the intergenic promoter regions of the P. chrysogenum niiA-niaD and acvA-pcbC gene cluster, encoding the first two enzymes in penicillin biosynthesis. Three of the four high-affinity NRE-binding sites contained two GATA core elements. In one of the recognition sites for NRE, one GATA motif was replaced by GATT. The two GATA elements showed all possible orientations, head-to-head, head-to-tail and tail-to-tail, and were separated by between 4 and 27 bp. Missing-contact analysis showed that all three purines in both of the GATA core sequences and the single adenine residue in each of the complementary TATC sequences were involved in the binding of NRE. Moreover, loss of purines in the flanking regions of the GATA elements also affect binding of NRE, as their loss causes reduced affinity.