Minor physical anomalies in schizophrenic patients and their siblings

OBJECTIVE: The aim of this study was to assess the frequency and type of minor physical anomalies in schizophrenic patients and their normal siblings. METHOD: Sixty adult patients with schizophrenia, 21 siblings of these patients, and 75 normal comparison subjects were assessed through use of an extended scale consisting of the Waldrop scale and 23 other minor physical anomalies. RESULTS: Patients had significantly more minor physical anomalies than comparison subjects in all body areas tested and also more minor physical anomalies in total than their siblings. Hand, eye, and mouth minor physical anomalies best discriminated patients from comparison subjects. Siblings had significantly more minor physical anomalies than normal comparison subjects. Sixty percent of the patients and 38% of the siblings, but only 5% of the comparison subjects, had a higher rate of minor physical anomalies (i.e., six or more). With the exception of ear minor physical anomalies, no association was found between minor physical anomalies in the patient and sibling in the same family. CONCLUSIONS: Higher levels of minor physical anomalies (especially in the eye, mouth, and hand/foot regions) characterize both schizophrenic patients and their normal siblings, but there is little similarity in these anomalies between patients and siblings in the same family. Thus, one or more genetic or shared environmental factors may increase the risk for development of both minor physical anomalies and schizophrenia in these families at large. Minor physical anomalies associated with schizophrenia are frequently found in, but are clearly not limited to, the head or facial region. The Waldrop scale identifies minor physical anomalies strongly associated with schizophrenia. Nevertheless, assessment of the new items clearly indicates that many additional minor physical anomalies are found in schizophrenic patients.     

Effects of milk and milk products on rectal mucosal cell proliferation in humans

The interferon (IFN)-induced protein kinase (PKR) functions as a gatekeeper of mRNA translation initiation and is, therefore, a key mediator of the host IFN-induced antiviral defense system. Many viruses have invested countermeasures against PKR. Some apparently use more than one mechanism. The influenza virus can repress PKR activity through the use of at least two factors, the cellular P58IPK protein and the viral NS1 protein. The exact mode of action of the latter has not been established. Here, using a coprecipitation assay, we found that PKR could form a complex with NS1 in crude cell extracts prepared from influenza virus-infected HeLa cells. The NS1-PKR interaction was verified by using the yeast two-hybrid system and an in vitro binding assay. Deletion analysis mapped the NS1 binding site to the N-terminal 98 residues of PKR regulatory region. Furthermore, an NS1 mutant, which lacks PKR inhibitory activity, did not bind PKR. Finally, the functional role of NS1 in PKR inhibition was substantiated using an in vivo assay for PKR activity. These results support the role of NS1 in PKR modulation during viral infection that is mediated through a complex formation between the two proteins.     

The role of cell mediated immunity in coxsackie B viral myocarditis

The role of cell mediated immunity (CMI) in the pathogenesis of coxsackie B (Cox. B) viral myocarditis in the adult were immunologically investigated. The number of types of neutralizing antibody in patients with Cox. B viral myocarditis was more than that in controls. This fact suggested that these patients had a history of previous Cox. B viral infections. In the patient with Cox. B viral myocarditis, neutralizing antibody titer was increased as 20 folds by the reinfection. And also macrophage migration inhibition test showed that CMI was enhanced not only against the same type but also against the other types of Cox.B group viruses. In conclusion, it may be essential in the occurrence of adult myocarditis that the patient has been infected by Cox.B virus and immunized against the other types as well as the same type of Cox.B group viruses. CMI may also play a critical role in the occurrence of Cox.B viral myocarditis.     

Attentional dysfunctions in neuroleptic-naive and neuroleptic-withdrawn schizophrenic patients and their siblings.

This study examined attentional deficits in 44 schizophrenic patients (24 neuroleptic-naive and 20 neuroleptic-withdrawn patients) across changes in medication status and clinical state using a 1–9 continuous performance test (CPT) with distractors. Patients' attentional selectivity scores (A′) were unchanged from the off-medication to on-medication testings (on average, 6 months later), despite significant improvement in both positive and negative symptoms. Both patient groups had significantly lower A′ scores than 44 matched healthy controls at each testing. The nonschizophrenic siblings (n?=?15) of these patients made significantly more errors of omission and commission than healthy controls. The results suggest that attentional deficits, as measured by this CPT, appear to measure stable markers of schizophrenia that may be associated with genetic vulnerability to the illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gluten sensitivity in the rectal mucosa of first-degree relatives of celiac disease patients

BACKGROUND/AIMS: Rectal gluten challenge is a simple, sensitive, and specific test of mucosal gluten sensitivity. Our aims in this study were to evaluate gluten sensitivity in a group of relatives of celiac patients and to compare these findings with those obtained on small bowel histology, celiac disease-related serology, and HLA typing. METHODS: A 4-h rectal gluten challenge was performed with 6 g of crude gluten in saline solution in 29 first-degree relatives, 20 well-diagnosed celiac patients, and 10 subjects in whom celiac disease had been excluded. The number of intraepithelial lymphocytes in pre- and postchallenge frozen rectal biopsies (pan T-cell immunocytochemistry) was quantified by computerized image analysis. RESULTS: The intraepithelial lymphocyte response after gluten instillation was significantly higher in celiac disease patients (median, 126% increase above the baseline count; 95% confidence interval: 61-213%) compared with control subjects (median, -5%; 95% confidence interval: -29-5%). Using a cut-off of 20% change in intraepithelial lymphocyte count, 14 relatives (48%) showed a celiac-like response. Two of these subjects had partial villous atrophy and increased lymphocyte counts in the small bowel mucosa. One of them also exhibited a positive celiac disease-related serology and the typical celiac human lymphocyte antibody (HLA) DQ2. The remaining 12, and all those relatives with a negative challenge, had normal small bowel mucosa and were negative for antigliadin and endomysial antibodies. The characteristic celiac HLA (DQA1 0501 DQB1 0201 heterodimer) was identified in five relatives with positive challenge (including the patient with more severe mucosal atrophy) but was also present in eight relatives with no evidence of gluten sensitivity in the rectal mucosa. CONCLUSIONS: Our study characterizes a subgroup of relatives of celiac patients who show mucosal evidence of sensitization after local instillation of gluten in the rectum but who have no other features of celiac disease.     

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.     

Persistent T cell and B cell activities in the duodenal mucosa of AIDS patients

OBJECTIVE: As HIV infection most commonly occurs via a mucosal surface, and as gastrointestinal symptoms are very frequent among HIV-infected patients, we investigated the functional properties of residual lymphocytes in the duodenal mucosa from HIV-infected individuals. DESIGN: Duodenal biopsies and blood samples were obtained from 19 HIV-infected patients [Centers for Disease Control and Prevention (CDC) stage III] and from 19 controls. METHODS: Phenotypic analysis of lymphocytes was performed by flow cytometry and/or immunocytochemistry. Interferon gamma (IFN-gamma), interleukin (IL) 4 and immunoglobulin secretions were analysed by enzyme-linked immunospot techniques. The phenotype of cytokine-producing cells was analysed by flow cytometry. RESULTS: The proportions of duodenal T lymphocytes from HIV-infected patients spontaneously secreting IFN-gamma or IL-4 were not lower than those from healthy controls. In patients with a high intestinal mucosal viral load, they were higher than in controls (P < 0.05). The proportions of immunoglobulin-secreting cells were significantly raised in HIV-infected patients for the three main isotypes. CONCLUSIONS: T- and B-cell populations of the intestinal mucosa remain functional or are even activated in patients with AIDS, even when the numbers of both mucosal and circulating CD4+ lymphocytes are strongly decreased.     

Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma

Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma. We examined cell proliferation and both double and single strand DNA damage in situ in 35 patients undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infection was confirmed in all cases by serum anti-HP antibodies, ureas testing, and histopathological examination. HP-infected gastric mucosa was classified according to the degree of inflammation and intestinal metaplasia. Ki-67, terminal deoxynucleotidyl transferase-mediated labeling, in situ nick translation, and intraepithelial neutrophil indices all increased with the progression of gastritis and were highest in glands with incomplete intestinal metaplasia. All indices were lowest in gastric glands with complete intestinal metaplasia. Significant positive correlations were observed among these markers. Increased proliferative activity in HP-associated chronic gastritis in response to cell damage or injury was clearly demonstrated, suggesting that both HP-associated toxins and intraepithelial neutrophils are important in HP-related gastric epithelial injury. Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA instability and subsequent development of intestinal-type gastric adenocarcinoma in HP-infected mucosa.     

The use of the Color-Your-Life technique with pediatric cancer patients and their siblings.

Examined the use of the Color-Your-Life (CYL) technique with 18 pediatric cancer patients (CPS), 20 siblings of pediatric patients (SIBS) and 40 controls, all aged 7–13 yrs. Findings show no differences were found between the groups for the percentages of colors. However, there were differences with respect to the way these groups represented negative emotions. SIBS tended to use the color/affect pair red/mad to indicate feelings of depression, while CPS used the absence of color, leaving white space on the paper. The Children's Depression Inventory (A. E. Kazdin, 1990) significantly correlates with the amount of blue (sad) that the Ss drew. However, this was not true for the State-Trait Anxiety Inventory for Children (C. D. Speilberger et al, 1973) and the amount of black (scared/nervous). CPS and SIBS who completed the CYL technique prior to completing the inventories had higher scores on these instruments than the children who completed the written instruments 1st. This finding was the opposite for controls, suggesting that these groups of Ss have different reactions to completing the CYL activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gluten-free diet induces regression of T-cell activation in the rectal mucosa of patients with celiac disease

OBJECTIVE: An increase in the number of intraepithelial lymphocytes (IEL) in the rectal epithelium of patients with active celiac disease has been described. No data are available about how they vary during a gluten-free diet. The aim of the study was to assess the effect of a gluten-free diet on T-cell activation in the rectal mucosa of adult patients with celiac disease. METHODS: Frozen duodenal and rectal biopsies were available in four celiac patients (one male, three female, mean age 39 yr) both before and after 7 to 24 months on a gluten-free diet. Biopsy samples were stained using monoclonal antibodies directed against CD3, betaF1, TcRdelta1, CD25, and HLADR. Numbers of IEL were estimated by counting the peroxidase-stained cells per 100 epithelial cells. Four patients without histological abnormalities were used as control subjects. RESULTS: In the four patients with active celiac disease but in none of the controls, CD25 was expressed by both duodenal and rectal lamina propria cells and HLADR was expressed by duodenal (4/4) and rectal (2/4) epithelial cells. In addition, two patients with active celiac disease had features of lymphocytic colitis, i.e., >20 IEL per 100 epithelial cells. After a gluten-free diet, the mean number of rectal CD3+ betaF1+ IEL decreased (9% vs 21%) and the expression of CD25 and HLADR was no longer present. These changes mirrored those found in the small intestinal biopsies. CONCLUSION: These results suggest that in celiac disease, gluten-driven T-cell activation is not restricted to the proximal part of the intestine but is present on the whole intestinal length. Assessment of the effectiveness of a gluten-free diet through rectal biopsies warrants investigation, as it could lessen discomfort for patients and prove more cost-effective.     

HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals

HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their HIV-seropositive partners; antibodies were not detected in low-risk controls. Envelope protein (Env) peptide-stimulated interleukin-2 (IL-2) production by peripheral blood mononuclear cells (PBMCs) was detected in 9 out of 16 ESNs, 5 out of 16 HIV-infected patients and 1 out of 50 controls. Env peptide-stimulated PBMCs of ESNs produced more IL-2 and less IL-10 compared with those of HIV-infected individuals; no differences were observed in chemokine production or in CCR5 expression. These data demonstrate that a compartmentalized immune response to pathogens is possible in humans and raise the possibility of protective roles for cell-mediated immunity and mucosal IgA in HIV-seronegative individuals exposed to HIV.     

Attenuation of cell death mediated by membrane depolarization different from that by exogenous BDNF in cultured mouse cerebellar granule cells

Membrane depolarization accompanying calcium (Ca2+) influx into neurons is thought to play an essential role in controlling the survival and death of cultured mouse cerebellar granule cells (CGCs). In this study, we sequentially controlled the survival and death of CGCs in culture and monitored the expression of several kinds of genes including brain-derived neurotrophic factor (BDNF) gene. Deprivation and subsequent induction of membrane depolarization by lowering and re-elevating the extracellular concentration of potassium chloride, respectively, led to death of CGCs and then to an attenuation of the death process depending upon the Ca2+ influx into CGCs through voltage-dependent calcium channels (VDCCs). De novo protein synthesis was critical for attenuating the death of non-depolarized CGCs. Accompanying this attenuation was an activation of c-fos and BDNF genes and an inactivation of c-jun and neurotrophin-3 (NT-3) genes. The attenuation of cell death mediated by exogenous BDNF was only partial compared to that by membrane depolarization, suggesting that not only BDNF but also other factors could be involved in the membrane depolarization-mediated attenuation of death of CGCs. In good agreement with this observation, the mode of activation of c-fos, c-jun, BDNF and NT-3 genes induced by exogenous BDNF was different from that induced by membrane depolarization. Thus, membrane depolarization effectively attenuates the death of non-depolarized CGCs, the mode of which seems to be different from that mediated by BDNF alone.