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Biomedical subjects

L Andrade

Publications and source records attributed to L Andrade.

At least 55 records · Page 3Linked to original sources

Lifetime comorbidity of panic attacks and major depression in a population-based study. Symptom profiles.

BACKGROUND: The co-occurrence of panic disorder and major depression in the same individual is common. A question to be answered is whether the comorbid disorder is a distinct one or may resemble one or other disorder. In this paper we examine whether the comorbid disorder is a distinct condition. METHOD: We examined the symptom profiles and rates of comorbidity of panic attacks and DIS/DSM-III major depressive disorder in a population-based sample from four sites of the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program (n = 12,668). RESULTS: The co-occurrence of panic attacks and major depression over the lifetime was 11 times higher than expected by chance (OR = 11.4, 95% CI 9.5 to 13.6). Subjects with both panic and depression had worse symptoms than those who had only one disorder. However, the pattern of symptoms was remarkably similar, after overall severity was taken into account. Depressive symptoms associated with more severe forms of depression (e.g. guilt, suicidal thoughts or attempts, and motor disturbance) were more frequent in the comorbid group. CONCLUSIONS: These findings may indicate a worse severity when the two disorders occur in the same individual.

Adolescent↗

Preferential VH/V lambda pairings occur in the available B cell repertoire of adult BALB/c mice.

To gain insights into the composition of the B cell repertoire, we have investigated VH gene family expression associated with individual light chains. For this purpose, we have examined the use of 12 VH gene families in a large collection of hybridomas expressing one of the four lambda light chains [lambda 1 (V1J1), lambda 2 (V2J2 and V x J2) and lambda 3 (V1J3)]. Our results show that the distribution of the VH families is very different from one lambda subtype to another. This suggests that a few substitutions between VL regions are sufficient to generate very different associated repertoires by strong selection mechanisms. Moreover, we assume that the global VH expression pattern is not random but rather composed of many preferential VH/VL associations.

Animals↗

Renal abnormalities in microfilaremic patients with Bancroftian filariasis.

To determine the frequency of renal abnormalities occurring with Bancroftian filarial infections and to assess the effects of treatment on such abnormalities, we initiated a prospective, hospital-based study of 20 microfilaremic and five amicrofilaremic patients with Wuchereria bancrofti infections. Thorough clinical evaluations and detailed renal assessments were made prior to treatment and at multiple time points for 60 days following a standard twelve-day course of treatment with diethylcarbamazine (DEC). There were two important findings. First, even prior to DEC treatment, almost half of the microfilaremic patients had hematuria and/or proteinuria. Second, treatment with DEC induced these same abnormalities in almost all of the remaining microfilaremic patients. However, this DEC-induced hematuria and/or proteinuria was transient, and the long-term response to DEC in all of the microfilaremic patients was resolution of the abnormal renal findings during the two-month followup period. In the amicrofilaremic study patients, no hematuria or proteinuria was detected before, during, or after treatment with DEC.

Adolescent↗

Biased VH gene expression in murine CD5 B cells results from age-dependent cellular selection.

Flow cytometry-purified, peritoneal and splenic CD5+ and CD5- B cells from neonatal and adult C57BL/6 mice were studied for expression of VH and Vx gene families in RNA colony blot assays, and for frequencies of clones secreting antibodies to bromelain-treated mouse red blood cells (BrMRBC), single-stranded DNA, trimethyl ammonium and bovine gamma-globulin, by limiting dilution. The results show few overall differences between the two B cell subsets, which both manifest ontogenic D-proximal VH preferences that are lost with age. Biased VH11 expression in CD5 B cells is high in adult peritoneum and spleen but absent in newborns. It only partly correlates with the selection of anti-BrMRBC reactivity, which is considerably higher in peritoneum than in spleen. No particular Vx bias was observed in any of the populations studied with the possible exception of Vx22 in peritoneal CD5+ B cells. We conclude that the antibody repertoire expressed by peritoneal CD5+ B cells of adult mice is not the result of a genetic program, but rather the consequence of local, age-dependent cellular selection mechanisms.

Aging↗

Clonal persistence of B lymphocytes in normal mice is determined by variable region-dependent selection.

Many adult splenic B cells die within 1 week in the spleen of adoptive adult recipient mice; in contrast, the cellular environment of newborn recipients allows for their expansion and persistence for several weeks. In the present study, we show that the local environment of adult peritoneal cavity also allows adult splenic B cells to persist for over 2 weeks after intraperitoneal transfer. In order to determine whether the persistence of donor B cells in newborn hosts and in the peritoneum of adult recipients results from a selection process involving the clonal specificities expressed, the variation in time of VH gene family repertoires of donor B cells was analyzed in the hosts. At different times after the transfer of splenic cells from lipopolysaccharide (LPS)-reactive mice into LPS-non responder histocompatible recipients, mRNA colony blot assays were performed. The results show that among the donor adult LPS-reactive B cells, the VH genes are differently used by the expanding or persisting B cells, in both kinds of recipients. Thus, cells expressing J558 or VH11 gene families are, in particular, positively selected, while those expressing D-proximal or J606 and 36-30 VH gene families are less selected. These findings demonstrate that the propensity of B cells to persist and expand is determined by their selection through their immunoglobulin variable regions, rather than by genetic properties linked to particular B cell subsets.

Animals↗

Multidrug resistance gene and P-glycoprotein expression in gastric adenocarcinoma and precursor lesions.

Overexpression of the Multiple Drug Resistance gene (MDR1) has been proposed as a major mechanism related to both intrinsic and acquired resistance to chemotherapeutic agents. The gene product is a membrane protein (P-glycoprotein), that acts as an energy-dependent drug efflux pump decreasing drug accumulation in resistant tumor cells. We have characterized MDR1 and P-Glycoprotein expression in human gastric adenocarcinoma and in precursor lesions. MDR1 mRNAs, analyzed by dot-blot technique, were detected in 9 of 10 non-tumoral gastric mucosae and in 8 of 10 gastric adenocarcinomas. Immunohistochemical analysis, using the MRK16 monoclonal antibody, revealed heterogeneous expression of P-Glycoprotein in individual cells. The P-Glycoprotein was found on the surface of cells of gastric areas with intestinal metaplasia subtype III. This type of intestinal metaplasia, also called "colonic metaplasia", has been strongly associated with a high risk for the development of gastric cancer. The fact that the P-Glycoprotein was detected in this precursor lesion is consistent with the intestinal metaplasia-dysplasia and carcinoma sequence proposed in the histogenesis of this tumour. The finding that P-Glycoprotein was heterogeneously expressed in malignant cells of some gastric adenocarcinomas also suggests that this transporter system probably contributes to primary and secondary multidrug resistance in this neoplasm.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Itraconazole versus placebo in the management of vaginal candidiasis.

A randomized double-blind trial was carried out with itraconazole versus placebo in the treatment of vaginal candidiasis, confirmed by clinical evaluation, direct microscopic examination and Sabouraud culture. Fifty patients were studied, 25 in the itraconazole group and 25 in the placebo group. Both groups received two capsules once daily (100 mg itraconazole/cap) for 3 days. One week after treatment patients were re-evaluated according to the same parameters as in selection. The scores for clinical symptoms, leukorrhea, vulvar pruritus, vaginitis and vulvitis, were compared in both groups before and after treatment. Statistically significant differences were found for the itraconazole group in pruritus and vaginitis (P less than 0.05) and vulvitis (P less than 0.001), with no significant difference for leukorrhea. As to the mycological evaluation, 7 days after treatment there were negative results for the itraconazole group in 92% of the patients in comparison to 52% in the placebo group (chi-square, P = 0.005).

Adult↗

Metabolic alterations in obstructive jaundice: effect of duration of jaundice and bile-duct decompression.

We examined the effect of prolonged bile duct obstruction, and subsequent biliary decompression, on biochemical and metabolic parameters, using a reversible jaundice model in male Fischer 344 rats. The animals were studied after biliary obstruction for varying periods (4 days, one week, and two weeks) and following decompression. They were sacrificed one or two weeks following decompression. All the rats were compared to sham operated, pair-fed, controls. Obstructive jaundice rapidly increased bilirubin, liver enzymes, serum free fatty acid, and triglyceride levels. Glucose levels were significantly decreased in the jaundice rats compared to their pair-fed controls. Only after two weeks of jaundice was significant hypoalbuminemia observed. Following decompression, all biochemical and metabolic values gradually returned to normal levels, except for albumin. Hypoalbuminemia was not reversed within the two-week post-decompression period. The rats jaundiced for two weeks had significantly higher mortality, compared to the other groups. We conclude that prolonged jaundice adversely affects the metabolic capacity of the rats, with albumin concentration being markedly decreased, and that biliary decompression could not reverse completely all the alterations seen with cholestasis, especially following two weeks of bile duct obstruction.

Animals↗

In vitro differentiation of Wuchereria bancrofti (Filariidae).

Wuchereria bancrofti microfilariae were isolated from blood of infected individuals and cultured in vitro under several conditions. RPMI 1640 and TC-199 media supplemented with fetal or human serum were able to support the microfilariae for periods up to 35 days at 37 degrees C (viability greater than 85%). In contrast, in minimal essential medium the microfilariae did not survive for more than 48 h. In cultures kept at 28 degrees C, where viability was much lower (approximately 10% on day 15), microfilariae differentiated into type IV larvae ("sausage" form). The in vitro maintainance of microfilarial larval forms is particularly important in the case of W. bancrofti due to the absence of an experimental model for the disease.

Animals↗

All VH11 genes expressed in peritoneal lymphocytes encode anti-bromelain-treated mouse red blood cell autoantibodies but other VH gene families contribute to this specificity.

We have studied the relationship between B cell reactivity to bromelain-treated autologous mouse erythrocytes (BrMRBC) and expression of the VH11 gene family in splenic, peritoneal and pleuropericardial cell populations from normal C57BL/6 mice. B lymphocytes producing antibodies to BrMRBC were selectively enriched or depleted from normal populations by rosette formation with BrMRBC, followed by centrifugation over density gradients. This selection method, based on the presence of functional receptors (membrane IgM), is harmless for the cells and allowed subsequent cloning in agar (colony-forming unit-B). The utilization of the 10 VH gene families was then scored in mRNA colony blot assays. The analysis of greater than 650 anti-BrMRBC clones and greater than 350 VH11-expressing colonies indicates that about half of those antibody reactivities are encoded by VH11 genes. Furthermore, it appears that all VH11-expressing B cells in the peritoneal cavity produce anti-BrMRBC antibodies.

Animals↗

Immunoglobulin VH gene expression following hemorrhage.

Hemorrhage has multiple effects on immunologic response, including alteration of B cell repertoires. In limiting dilution studies, decreased absolute frequencies of splenic clonal precursors specific for bacterial antigens were found after blood loss. In order to better define the effects of hemorrhage on B cell function, we examined immunoglobulin VH gene family expression following blood loss using both in situ hybridization and the RNA colony blot technique. No changes in VH gene family utilization were found after hemorrhage. These results demonstrate that the hemorrhage induced alteration in B cell function involves all VH gene families, without modifying distributive frequencies in VH gene family expression.

Animals↗

Selection of VH gene repertoires: differentiating B cells of adult bone marrow mimic fetal development.

In the present study we have compared by in situ hybridization and by a CFU-B colony assay VH family usage in the pre-B and B cell compartments of the bone marrow of adult BALB/c and C57BL/6 mice. We have found that the position dependent increased expression of the VH 7183 family, observed in neonatal mice, is characteristic of early differentiating B cells of adult mice. The quantitative analysis for each VH family of the number of pre-B and B cells produced daily and the number of mature B cells present in the peripheral immunocompetent cell pool of adult BALB/c demonstrates the existence of selecting mechanisms operating within the bone marrow at the level of the emergent repertoire and at the level of export of newly formed cells into the periphery. This selective process results in the decreased peripheral representation of the VH 7183 family and in the accumulation of cells belonging to the other VH families. Selection of VH family usage in peripheral repertoires may be determined according to lymphocyte life-span, as we have found a preferential utilization of the VH J558 family in populations of partially enriched, long-lived B cells.

Age Factors↗

Indiscriminate representation of VH-gene families in the murine B lymphocyte responses to Trypanosoma cruzi.

The utilization of the nine major homology families of VH-genes was quantitated in the B lymphocyte response to Trypanosoma cruzi infection of C57BL/6 mice. Normal and infected mice at various times after parasite inoculation were compared for VH-gene distribution of CFU-B produced by activated blasts recovered from spleen and lymph nodes, and for relative hybridization of total spleen RNA with each of the family probes. T. cruzi infection results in large increases of splenic RNA in the various homology families, and the numbers of activated CFU-B, reflecting the massive B lymphocyte responses. In acute phase, all nine families are expressed in roughly the same proportions as in normal mice, whereas in chronic infection, B cells expressing S107 and 7183 VH-genes might be preferentially stimulated. These results establish the polyclonal nature of the host response to T. cruzi infection.

Animals↗

Immunoglobulin VH gene expression in Ly-1+ and conventional B lymphocytes.

Lymphocyte populations in which Ly-1 B cells are differentially represented were studied for the expression of ten VH gene families, either by an RNA colony blot assay or by in situ hybridization of single cells, in BALB/c and C57BL/6 mice. The comparisons of cells from lymph nodes, Peyer's patches and adult spleen (poor in Ly-1 B cells) with cells from peritoneal cavity and neonatal spleen (rich in Ly-1 B cells) were confirmed by the analysis of adult peritoneal Ly-1- and Ly-1+ B cells sorted on the fluorescence-activated cell sorter. The results indicate that the peritoneal Ly-1+ B subset uses the whole spectrum of known VH gene families, and shows a preferential utilization of CP12 VH genes, most likely as a result of a selective process during life.

Age Factors↗

Comparative study of VH gene family usage by newborn xid and non-xid mice, newborn NZB and adult NZB mice, and by splenic and peritoneal cavity B cell compartments.

RNA from 170 different Ig-secreting hybridomas was hybridized with VH gene probes 7183, QUPC52, S107, J558, J606, 36-60, V31, X-24 and V-GAM 3.8, with the aim of comparing xid to non-xid mice, neonatal NZB to adult NZB, and the peritoneal cavity with the splenic compartments for VH gene family expression. Our results indicate that (a) defective F1 male xid mice express with high frequency 36-60 and J606 5' proximal VH families, when compared to non-xid F1 females of the same matings. (b) Neonatal NZB mice express 3' proximal 7183 and QUPC52 families with high frequency, when compared to adult mice and to the expected values derived from VH complexity. (c) Natural antibodies against cytoskeleton proteins, DNA, rabbit IgG and 2,4,6-trinitrophenyl did not appear to prefer a particular VH family. The only difference found is related to age; neonatal clones preferentially employ 7183 and QUPC52 while J558 predominates among adult clones. (d) All the 15 antibodies directed against bromelin-treated mouse red blood cells failed to hybridize with any of the nine VH probes employed. These results confirm previous findings indicating the highly homogeneous pattern of these latter antibodies, and suggest that they are encoded by a new VH family (VH11).

Animals↗

Most B cells in acute Trypanosoma cruzi infection lack parasite specificity.

The specificity of B lymphocytes activated in the acute phase of murine Trypanosoma cruzi infection was analysed in a panel of immunoglobulin-secreting hybridomas derived by fusion of lymph node cells 7 days after intraperitoneal parasite inoculation. The immunoglobulin isotype distribution of the hybrids reflected the total plaque-forming cell (PFC) response in the animal at this point, with a predominance of IgG2a, IgM, and IgG2b. Screening of the hybridoma antibodies on parasite antigens by three independent methods (western blot, ELISA, and immunofluorescence) revealed only one (out of a total of 51) that bound a parasite molecule with an apparent molecular mass of 180 kDa. In contrast, antibodies of both IgM and IgG classes were found to react with a panel of autologous antigens. These results establish that most B cells activated by T. cruzi infection are not specific for parasite antigens and therefore indicate the relevance of analysing the totality of host responses to infection.

Acute Disease↗