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Biomedical subjects

S Araya

Publications and source records attributed to S Araya.

At least 19 recordsLinked to original sources

Gender differences and outcome in schizophrenia: a 2-year follow-up study in a large community sample.

This study examined gender differences in the short-term (2 years) course of schizophrenia in a sample of 200 schizophrenic (DSM-IV criteria) outpatients (74 women and 126 men). Number and length of hospitalizations during the prospective follow-up were recorded. After 2 years, men were found to have more hospitalizations and longer stays than women. Among subjects who had at least one hospitalization (12 women and 38 men), men had greater length of hospitalization. In conclusion, schizophrenic women had a significantly better short-term outcome.

Adolescent↗

The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia.

OBJECTIVE: To describe the development and validation of the Clinical Global Impression-Schizophrenia (CGI-SCH) scale, designed to assess positive, negative, depressive and cognitive symptoms in schizophrenia. METHOD: The CGI-SCH scale was adapted from the CGI scale. Concurrent validity and sensitivity to change were assessed by comparison with the Positive and Negative Symptom Severity (PANSS) and Global Assessment of Functioning (GAF) scales. To evaluate inter-rater reliability, all patients were assessed by two clinicians. RESULTS: Symptoms were assessed in 114 patients. Correlation coefficients between the CGI-SCH and the GAF and PANSS scores were high (most above 0.75), and were highest for positive and negative symptoms. Reliability was substantial (intraclass correlation coefficient, ICC > 0.70) in all but one dimension (depressive dimension, ICC = 0.64). CONCLUSION: The CGI-SCH scale is a valid, reliable instrument to evaluate severity and treatment response in schizophrenia. Given its simplicity, brevity and clinical face validity, the scale is appropriate for use in observational studies and routine clinical practice.

Adult↗

Circulating lymphocyte subsets linked to intracellular cytokine profiles in normal humans.

To determine whether there is an association between intracellular cytokine profiles and the expression of surface antigens, we performed a simultaneous flow cytometric analysis of these laboratory parameters in 11 healthy volunteers. Peripheral blood lymphocytes were double-stained for CD4 or CD8, as well as CD11a, CD25, CD26, CD29 and CD45RA or the chemokine receptors CCR3, CCR4, CCR5 or CXCR3. Portions of the cell samples were cultured for 4 h in the presence of 1 microm monensin and 20 microg/ml brefeldin A with or without stimulation by phorbol myristate acetate plus ionomycin for the detection of intracellular interferon-gamma (IFN-gamma), interleukin-2 (IL-2), tumour necrosis factor (TNF)-alpha, and IL-4. As a result, CD4+CD29high helper inducer T cells were closely associated with IFN-gamma and TNF-alpha producing CD4+ cells, while CD4+CXCR3+ cells showed a negative correlation with IL-4-producing cells, suggesting that both of these CD4+ subsets consist mainly of Th1 cells. In contrast, CD4+CD45RA+ cells were correlated inversely with IFN-gamma and TNF-alpha-producing cells, and CD8+CD11ahigh killer effector and total CCR5+ cells showed an inverse correlation with IL-2 producing cells, suggesting an immunoregulatory role for these three subsets in non-pathological conditions. Therefore, monitoring of lymphocyte subsets that express functional surface antigens could provide additional information concerning immune deviation, as assessed by the production of Th1/Th2 type cytokines. Further, this type of combined study may provide clues for the pathogenesis of immune-mediated disorders.

Adult↗

Influence of gender on social outcome in schizophrenia.

OBJECTIVE: To study the relevance of gender on social functioning in schizophrenia. METHOD: A sample of 200 schizophrenic (DSM-IV criteria) out-patients were followed-up during 2 years and were administered the following instruments: Positive and Negative Symptom Scale (PANSS), Disability Assessment Scale (DAS-sv), and Global Assessment of Functioning (GAF) Scale. A regression model was created with DAS and GAF as dependent variables, and gender, PANSS, age of onset, duration of illness and marital status as independent variables. Separate regression models were then generated for females and males. RESULTS: Gender influenced significantly on DAS and GAF, with men showing worse functioning. In gender specific analyses, we found a significant influence of illness duration and Positive and Negative PANSS on social functioning in men, and of age at onset and Negative PANSS in women. CONCLUSION: Gender had a significant influence on social functioning in schizophrenia, even after adjusting for the other independent variables.

Age Factors↗

Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis.

Thioredoxin (Trx), a redox enzyme with a conserved active site (Cys-32-Gly-Pro-Cys-35), is induced and secreted into circulation in response to inflammation. Studies here demonstrate that elevating Trx levels in circulation either by i.v. injection of recombinant Trx or stimulating Trx release in Trx-transgenic mice dramatically blocks lipopolysaccharide (LPS)-stimulated neutrophil migration in the murine air pouch chemotaxis model. Furthermore, we show that leukocyte recruitment induced by the murine chemokines KC/GROalpha, RANTES (regulated upon activation, normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) is suppressed also in Trx-transgenic mice. Addressing the mechanism responsible for this suppression, we show that circulating Trx blocks (i) the LPS-stimulated in vitro activation of neutrophil p38 mitogen-activated protein kinase, (ii) the normal down-regulation of CD62L on neutrophils migrating into the LPS-stimulated air pouch, and (iii) the in vitro adhesion of LPS-activated neutrophils on endothelial cells. However, as we also show, Trx does not alter the expression of endothelial cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD62P, and CD62E) within 3 h. Collectively, these findings indicate that elevated levels of circulating Trx interfere with chemotaxis by acting directly on neutrophils. We discuss these findings in the context of recent studies reporting beneficial effects of acutely elevated Trx in ischemic injury and negative effects associated with chronically elevated Trx in HIV disease.

Animals↗

The Spanish Version of the Quality-of-Life in Epilepsy Inventory (QOLIE-31): translation, validity, and reliability.

PURPOSE: Spanish adaptation of the Quality of Life in Epilepsy Inventory (QOLIE-31). METHODS: Internal consistency and construct validity of the Spanish translation of the QOLIE-31 were tested in 252 patients with epilepsy. Patients also were administered the General Health Questionnaire (GHQ-28), and the Nottingham Health Profile (NHP). Two weeks after the first test, a subgroup of randomly selected patients were readministered the QOLIE-31 along with a new five-option question about change in health status. Patients reporting no change in health status were included in the study of temporal stability. Sensitivity to clinical change was assessed in 31 additional patients who had successfully undergone epilepsy surgery. RESULTS: The QOLIE-31 was highly correlated with the GHQ-28 (r = -0.63) and the NHP (r = -0.69), demonstrating construct validity. Cronbach's alpha coefficient was 0.92, showing the items of the QOLIE-31 to be interdependent and homogeneous. For a 2-week test retest, both Pearson product-moment correlation and intraclass correlation coefficients were 0.90, indicating temporal stability. Sensitivity to clinical change was suggested by a significant mean difference between the global scores both before and after epilepsy surgery (-21.87, p<0.0001; 95% CI, -28.08 to -15.66). The standardized response mean of the global score was 1.67, and the effect size was 1.35, both indicating large clinical change as a result of seizure relief. CONCLUSIONS: The similarity of psychometric properties between the English and the Spanish versions of the QOLIE-31 supports their conceptual equivalence. The questionnaire's responsiveness to clinical change suggests its utility in outcome assessment of drug trials and epilepsy surgery.

Adult↗

Cis-diamminedichloroplatinum(II) augments expression of tumor-associated antigens on human gastric cancer cell line KATO-3 and increases susceptibility and binding of tumor cells to various cytotoxic effector cells.

Previous studies have demonstrated the immunomodulatory effects of cisplatin under certain conditions. The present study was designed to clarify whether cisplatin modulates the expression of surface antigens, especially human leukocyte antigen (HLA), on human tumor cell lines and/or augments the susceptibility and binding of tumor cells to cytotoxic effector cells. A human gastric cancer cell line, KATO-3, was employed. The expression of HLA and other tumor-associated antigens was analyzed by flow cytometry using FITC-conjugated monoclonal antibodies. The cytotoxicity of effector cells was determined by 51Cr release assay. The expression of HLA class I antigen, beta2-microglobulin, leukocyte function-associated antigen-1, and AC-81 adenocarcinoma-associated antigen on KATO-3 increased after exposure to cisplatin at 10 micrograms/ml for 3-6 hr; augmentation of HLA class I subtypes -B2 and -B27 was particularly prominent. Furthermore, the susceptibility and binding of KATO-3 to both lymphokine-activated killer cells and KATO-3-specific cytotoxic T lymphocytes significantly increased after cisplatin treatment. Cisplatin may modulate the expression of tumor-associated antigens on some human tumor cells. Tumor regression by cisplatin administration may depend on its direct cytotoxicity as well as on its modulating effects on the expression of tumor-associated antigens, subsequently leading to the activation of the immune surveillance system against the tumor.

Adjuvants, Immunologic↗

Anticancer chemosensitivity changes between the original and recurrent tumors after successful chemotherapy selected according to the sensitivity assay.

OBJECTIVE: The authors compare and characterize the changes in chemosensitivity between the original tumors before chemotherapy and recurrent tumors after responses. SUMMARY BACKGROUND DATA: The drug resistance in clinical chemotherapy appears to be different from that in experimental chemotherapy, and the profile and mechanisms of clinical drug resistance in recurrent tumors, especially after successful chemotherapy has scarcely been studied. METHODS: Applied chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin (ADR), mitomycin-C (MMC) and 5-fluorouracil (5-FU), singly or in combinations by a DNA synthesis inhibition assay, by which the sensitivity of recurrent tumors was assessed. Responses were defined according to the standard criteria, and successful chemotherapy indicates complete response (CR) or partial response (PR) for solid tumors and complete disappearance for malignant effusion. RESULTS: In 37 patients, the effectiveness of four agents were compared between before chemotherapy and after recurrence, and the response lasted between 2 and 26 months (mean +/- SD, 7.7 +/- 5.5). The results suggest that locally recurred tumors may become resistant to the agents previously administered; by contrast, distantly recurred tumors may not necessarily become resistant to the agents administered. The recurrent tumors are suggested to be sensitive to the agents as follows: locally recurrent solid tumors, 5-FU; distantly recurrent solid tumors, 5-FU and CDDP; locally recurrent effusion, CDDP; distantly recurrent effusion, ADR. Twenty-three of 37 recurrent tumors were re-treated with chemotherapies selected according to the sensitivity assay, singly or in combination with a biologic response modifier (BRM)--a streptococcal preparation, OK-432, or interferon-alpha. Responses were seen in 1 of 13 solid recurrent tumors and in 6 of 10 recurrent effusions. Responses were seen only when the patients were treated with a combination of chemotherapy and BRM. CONCLUSION: There may be a notable differences in the basic biologic characteristics of tumor cells with respect to local versus distant recurrences, and between effusion versus solid recurrences. Various approaches, including a combination of chemotherapy and BRM, therefore, may have to be applied to overcome these drug resistances in practical chemotherapies for recurrent tumors.

Antineoplastic Agents↗

Arrest in late G2 or prophase of cell cycle induced by 4,4-(1,2-ethanediyl) bis (1-isobutoxycarbonyloxymethyl 2, 6-piperazinedione) (MST-16) in cultured L1210 cells.

The effects of MST-16, a new antitumor agent derived from bis (2, 6-dioxopiperazine), on cell growth, cell-cycle progression and DNA synthesis, alone and in combination with other antitumor agents, were investigated in murine leukemia L1210 cells in vitro. The drug showed dose-dependent inhibition of cell growth, and this effect was cell-cycle phase-specific. Flow cytometric analysis indicated that the drug could retard-arrest the cells in late G2 phase or prophase and that it did not affect the progression from G1 to G2 phase. In the presence of MST-16, the change in 3H-thymidine incorporation was proportional to the retardation-arrest of the cells, suggesting that MST-16 has no direct action on DNA synthesis itself. MST-16 could continuously retard the cells which were arrested by etoposide (VP-16); and vincristine (VCR) could block the progression of the cells arrested by MST-16, but not vice versa. The addition of MST-16 followed by VCR was more effective than simultaneous addition of the 2 drugs on inhibition of cell growth. These results will be useful in designing a reasonable regimen of MST-16 chemotherapy for malignancies.

Animals↗

A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice.

5'-Deoxy-5-fluorouridine (5'-DFUR) is one of the oral fluoropyrimidines widely used in the treatment of gastric, colorectal and breast cancers in Japan. 5'-DFUR is converted to 5-fluorouracil by pyrimidine nucleoside phosphorylase in the tumor. 5'-DFUR has toxic effects on the intestine and may cause severe diarrhea. Trimethoxybenzoyl-5'deoxy-5-fluorocytidine (Ro09-1390) is a prodrug of 5'-DFUR, which was developed to reduce the intestinal toxicity of 5'-DFUR. The present study was designed to assess the antitumor activity and spectrum of Ro09-1390, and to compare its efficacy with that of 5'-DFUR. Six digestive organ cancer xenograft lines (two gastric, one esophageal, one colorectal, one gall bladder and one bile duct cancers) were s.c. transplanted into nude mice. The agents were orally administered daily for 14 days at doses of 0.08-0.64 mmol/kg (1-8 times the maximal clinical dose of 5'-DFUR). Both 5'-DFUR and Ro09-1390 significantly inhibited the growth of two gastric cancer lines, and the IC50's for Ro09-1390 in both lines were lower than the respective values for 5'-DFUR. The esophageal, colorectal, gall bladder and bile duct cancer lines, however, were resistant to both agents. 5'-DFUR at 0.64 mmol/kg significantly inhibited the growth of these cancers, but with high mortality, and most mice receiving this dose died within 14 days after the start of therapy, suffering from severe diarrhea and body weight loss. Ro09-1390 at the same dose resulted in low mortality, but evidenced similarly low antitumor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Fluid shear stress effects on intracellular calcium concentrations in cultured vascular endothelial cells].

Vascular endothelial cells are known to modulate their functions in response not only to humoral stimuli but also to such physical stimuli as fluid shear stress generated by blood flow. However, the mechanisms by which the hemodynamic force acts on endothelial cells are not yet well understood. We have studied how endothelial cells recognize the shear stress and mediate it to intracellular organelles. Cultured monolayers of bovine aortic endothelial cells loaded with the highly fluorescent Ca+(+)-sensitive dye Fura 2 were exposed to different levels of fluid shear stress in a specially designed flow chamber and simultaneous changes in intracellular-free Ca+(+) concentration were measured using photometric fluorescence microscopy. Application of shear stress to cells by fluid perfusion led to an immediate several-fold increase in Ca+(+) concentration within 1 min, followed by a rapid decline, and finally a plateau somewhat higher than control levels during the entire period of the stress application. The early part of the response, but no plateau, was observed even in Ca+(+)-free medium added with 2 mM EDTA, and in the presence of calcium antagonists (e.g. 2 x 10(-5) M nicardipine). Thus, endothelial cells may have a flow-sensing property which recognize the shear stress on the membrane as a stimulus and mediates the signal to increase intracellular free Ca(+)+ which is a major component of the internal signalling system of the cell.

Animals↗

Possible different mechanisms of B cell activation in systemic lupus erythematosus and rheumatoid arthritis: opposite expression of low-affinity receptors for IgE (CD23) on their peripheral B cells.

To clarify the differential state of B cell activation in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), we investigated the expression of low-affinity receptor for IgE (Fc epsilon RII; CD23) on their peripheral B cells by a cytofluorometry using H107 (CD23) and Leu-16 (CD20) monoclonal antibodies. The percentage of CD23-negative B cells in total lymphocytes was significantly greater in both groups of patients than in normal subjects, suggesting the hyperactivity of late-phase B cells in both diseases. However, the increase of CD23-negative B cells in RA was brought about by the increased number of total B cells, although that in SLE was mainly based on the relative decrease of CD23-positive B cells. The number of IgD-positive B cells was decreased, and the number of colony-forming B cells was markedly increased in SLE patients. These observations indicate that a B cell abnormality is mainly qualitative in SLE but quantitative in RA.

Adult↗

Functional differentiation and repertoire diversification of T cells derived from single progenitor cells.

Functions of T cells derived from single progenitor cells were investigated. B10. Thy-1.1 recipient mice were either whole body-irradiated and marrow reconstituted or thymus-shielded, irradiated and marrow reconstituted, and limited numbers (3 x 10(3) or 6 x 10(3] of a 1:1 mixture of bone marrow cells from C57BL/6 and B6.Lyt-2.1 mice were transferred intrathymically (i.t.). Donor-type (Thy-1.2+) cells of the thymus of a small portion of recipients which expressed the phenotype of either Ly-2.2 or Ly-2.1 but not both were regarded to be a clone of T cells derived from a single progenitor cell, and such clones were assayed for polyclonal helper (Th) and polyclonal cytolytic (CTL) activities as well as alloantigen-specific proliferative (mixed lymphocyte reaction; MLR) and CTL activities. Clones taken 4 weeks after transfer (4-week-old clones) which were generated in the thymus of whole body-irradiated recipients showed polyclonal CTL but not polyclonal Th activity, whereas 4-week-old clones generated in the thymus of thymus-shielded recipients showed both polyclonal CTL and Th activities. Similarly, 4-week-old clones generated in whole body-irradiated recipients responded with CTL to alloantigens when induced in the presence of T cell growth factors but not with MLR, whereas 4-week-old clones generated in thymus-shielded recipients showed both MLR and CTL to alloantigens. Repertoire diversification of 4-week-old clones, however, was incomplete, since clones generated in whole body-irradiated recipient did not necessarily respond with CTL to all alloantigens examined, and those generated in thymus-shielded recipients did not necessarily respond with MLR to all the antigens. On the other hand, T cell clones were shown to fully mature by 7 weeks after transfer in terms of cell function as well as repertoire diversification.

Animals↗

Comparative analysis of lymphocyte phenotypes between carriers of human immunodeficiency virus (HIV) and adult patients with primary immunodeficiency using two-color immunofluorescence flow cytometry.

A variety of phenotypic abnormalities of peripheral blood lymphocytes from 8 HIV-carriers (HIVC), 6 patients with common variable immunodeficiency disease (CVID), and 13 patients with selective immunoglobulin deficiency (SIgD) were compared using two-color flow cytometry. There was a close resemblance in phenotypic abnormalities between HIVC and the patients with CVID; i.e., increases in CD8+CD11-, Leu7+CD16- and CD3+DR+ cells, and decreases in CD4+Leu8+, CD4+Leu8-, Leu7+CD16+ and Leu7-CD16+ cells. The increase in CD3+DR+ cells was due to an increase in CD8+DR+ cells. The CD4/CD8 ratio was inverted in both groups. A strong correlation coefficient (CC) was found only between the CD4/CD8 ratio and CD4+Leu8+ cells in HIVC, while CC was also high between the CD4/CD8 ratio and CD8+CD11- cells in CVID. The phenotypic abnormalities of the patients with SIgD were various and no significant difference was found against the control, except for an increase in CD4+Leu8+ cells and a decrease in CD4+Leu8- cells, which suggests heterogeneity of immunological deficits in this group. In severe immunodeficiency, ineffective killer cells appeared to be induced as a result of an adaptive change involved in recurrent or persistent viral infections, and Leu8 molecule may be concerned in the susceptibility of CD4+ cells to HIV.

Acquired Immunodeficiency Syndrome↗

Screening of sugars inhibitory against sucrose-dependent synthesis and adherence of insoluble glucan and acid production by Streptococcus mutans.

Various sucrose derivatives and a sucrose analogue were enzymatically synthesized on the assumption that structural similarities of the sugars to sucrose would endow them with an ability to inhibit the cariogenicity of sucrose. The effect of these sugars on sucrose-dependent synthesis and adherence of insoluble glucan and on acid fermentation of sucrose by Streptococcus mutans was examined in vitro. Although none of them inhibited the acid fermentation, several sugars not only inhibited the synthesis and adherence of insoluble glucan, but were themselves only slightly fermented as well.

Acids↗