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Biomedical subjects

S Kapur

Publications and source records attributed to S Kapur.

At least 163 records · Page 9Linked to original sources

Passive acquisition of leukocyte proteins is associated with changes in phosphorylation of cellular proteins and cell-cell adhesion properties.

In this report, we show that interaction of neoplastic epithelial cells with vesicles derived from leukocytes results in passive acquisition by tumor cells of a diverse group of leukocyte proteins. Vesicles shed from leukocytes were heterogeneous and exhibited the specific proteins expressed on leukocyte subsets. Accordingly, epithelial cells differentially acquired leukocyte proteins associated with vesicles. Ultrastructural localization demonstrated that acquired proteins were associated with the plasma membranes of the epithelial cells. The binding of tumor cells that passively acquired leukocyte proteins to immobilized intercellular adhesion molecule-1 and to endothelial cells was significantly increased. Furthermore, passive acquisition of proteins on the plasma membranes of epithelial cells was associated with modulation of overall phosphorylation of proteins in the range of 20-65 kd and consisted of both increased as well as decreased phosphorylation of specific protein species in the cells. These findings demonstrate that leukocyte proteins that are shed in association with vesicles passively coat the plasma membranes of target epithelial cells. Passive acquisition of proteins by cells modulates the constitutive properties endowed upon cells by their native plasma membranes and is associated with changes in phosphorylation of cell proteins.

Cell Adhesion↗

Expression of mRNA for interleukin 6 by cells infiltrating epiretinal membranes in proliferative vitreoretinopathy.

We have investigated the expression of mRNA for interleukin 6 (IL-6) in cells infiltrating 12 epiretinal membranes, and the presence of biologically active IL-6 in vitreous humour available from five corresponding eyes. The results showed that nine of the 12 membranes (75%) contained cells expressing mRNA for this cytokine. Although in two of the specimens pigmented cells were identified as some of the cells expressing mRNA for IL-6, we did not identify the nature of IL-6 mRNA-producing cells infiltrating the membranes. Interestingly, two vitreous samples from eyes whose membranes did not contain cells with mRNA for IL-6 exhibited significant concentrations of IL-6 (315 and 28 micrograms/ml). Parallel study of mRNA for IL-6 in PVR biopsies and of IL-6 levels in corresponding vitreous may indicate how cytokine-mediated pathways of inflammation are involved in the pathogenesis of epiretinal membrane formation.

Base Sequence↗

Malignant schwannoma with melanocytic and neuroepithelial differentiation in an infant with congenital giant melanocytic nevus: a complex neurocristopathy.

We describe an infant girl, born with a pigmented giant nevus, who developed a malignant schwannoma in the retroperitoneum at 16 months of age. At birth the nevus covered over 50% of her body and histologically was a compound nevus with extension into the deep dermis surrounding dermal appendages. The malignant schwannoma was biphasic with areas composed of spindle and round cells. Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell phenotype, but neuroepithelial and melanocytic cells were identified as well. We believe that this constellation of findings represents a form of neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409-429, 1974), is a disease that results from aberrations in the migration, growth, or cytodifferentiation of neural crest tissues. These diseases may be simple (a singular pathologic process, usually localized) or complex (multiple neuroectodermal lesions). We report this case because the occurrence of retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a pigmented giant nevus is unique, and may represent a previously undescribed form of a complex neurocristopathy.

Female↗

Electroconvulsive shock increases tyrosine hydroxylase and neuropeptide Y gene expression in the locus coeruleus.

Electroconvulsive seizures (ECS) increase tyrosine hydroxylase (TH) activity in the locus coeruleus (LC) but not in the substantia nigra (SN). To determine whether new enzyme synthesis contributes to the increase in TH activity, we carried out in situ hybridization histochemistry to determine the effect of ECS on TH mRNA levels in the LC and SN. The effect of ECS on neuropeptide Y (NPY) mRNA levels in the LC was also studied because NPY coexists with norepinephrine in the LC neurons and has been implicated in depressive disorders. A significant increase was observed in TH mRNA and NPY mRNA levels in LC neurons in the ECS group. There was no difference between TH or NPY mRNA levels in the left and right LC. No change was observed in TH mRNA expression in the SN compacta or SN reticulata. We conclude that the regionally selective increase in TH activity after ECS is at least partly due to increased gene expression and that NPY gene expression is regulated in a similar fashion following ECS.

Animals↗

Chlamydial cervicitis: role of culture, enzyme immunoassay and Giemsa cytology in diagnosis.

Three different laboratory tests were carried out to find the occurrence of chlamydial infections in a selected group of 150 female patients presenting clinically with cervicitis. The tests included isolation using a cell culture system, enzyme immunoassay (EIA) for antigen detection and Giemsa cytology of endocervical smears. Contrary to earlier reports on cytological diagnosis of chlamydial cervicitis, endocervical smears stained by Giemsa stain and EIA for antigen detection were found to be of comparable sensitivity and specificity (73.1% and 86.3% for smear, and 76.1% and 90.9% for EIA, respectively) when cell culture was used as the gold standard.

Animals↗

The case for a services-based approach to payment for mental illness under national health care reform.

In this position paper drafted by the committee on psychopathology of the Group for the Advancement of Psychiatry, the authors discuss merits and disadvantages of three different approaches to equitable coverage of mental illness: coverage for selected psychiatric diagnoses, coverage based on severity of impairment, and coverage of services. They believe that coverage of selected disorders has political appeal but is discriminatory and arbitrary; it is also impractical because clinicians may overdiagnose conditions covered by insurance and underdiagnose excluded conditions. Coverage based on severity of impairment, or disability, has similar limitations. The authors believe services should be the principal basis for coverage, as under general medical insurance. The approach is nondiscriminatory, and costs can be controlled through such means as managed care, changes in the payment system, or benefit design.

Community Mental Health Services↗

Screening for genital chlamydial infection in symptomatic women.

During a two year period, the prevalence of genital chlamydial infection was assessed by Papanicolaou and Giemsa cytology of endocervical specimens from 396 women attending a gynaecology outpatient department in a Delhi hospital, with symptoms of lower genital tract infection and primary or secondary infertility. The results of cytological examination were confirmed by isolation in a cell culture system. Prevalence was found to be 41 per cent (93 of 227) in patients presenting with vaginal discharge and 36 per cent (61 of 169) in infertility women. Genital chlamydial infection is prevalent in gynaecological patients in this region.

Chlamydia Infections↗

Expression of transforming growth factor-beta isoforms in small round cell tumors of childhood. An immunohistochemical study.

The transforming growth factor (TGF)-betas are a highly conserved group of potent multifunctional cell regulatory proteins with variable effects on cell growth and differentiation. Most of the small round cell group of childhood tumors are thought to arise from either primitive mesenchyme or neuroectoderm and show evidence of skeletal muscle or neural differentiation, and rarely both. To investigate the possibility that the TGF-betas have a role in the growth or differentiation of these neoplasms, we used antibodies specific for peptide sequences of the three known mammalian TGF-beta isoforms (TGF-betas 1, 2, and 3) to probe for TGF-beta protein expression in a total of 49 cases. TGF-beta 1 immunoreactivity was present in 16/17 (94%) of rhabdomyosarcomas, and the staining intensity was usually strong. TGF-beta 1 was also present in three of three ectomesenchymomas. In contrast, TGF-beta 1 was absent in all but one out of nine poorly differentiated neuroblastomas. Differentiating neuronal cells of ganglioneuroblastomas, however, were strongly positive for TGF-beta 1. Ewing's sarcomas and peripheral primitive neuroectodermal tumors had a less consistent, but usually positive, staining pattern. TGF-beta 3 staining patterns were very similar to those of TGF-beta 1. TGF-beta 2 immunoreactivity was only rarely detected in this group of tumors. The results suggest different roles for TGF-betas 1 and 3 in neuroblastoma and rhabdomyosarcoma. Expression of TGF-betas 1 and 3 is associated with neuronal differentiation of neuroblastoma. In contrast, these proteins may promote the growth of rhabdomyosarcoma by suppressing differentiation.

Adolescent↗

Role of the dopaminergic system in depression.

A hypothesis implicating dopamine in depression was proposed over 15 years ago (Randrup et al 1975). The identification of multiple new subtypes of dopamine receptors and evolving views regarding the function of the dopamine systems in the brain require a reexamination of this hypothesis. Results from studies in depression, Parkinson's disease, and animal models of depression suggest a deficiency of dopamine in depression. Dopamine precursors, dopamine agonists, and dopamine reuptake inhibitors show therapeutic efficacy in depression. Electroconvulsive therapy (ECT) and standard pharmacological antidepressants enhance dopamine function. Studies using receptor-specific drugs in clinical trials and neuroimaging studies are needed to further clarify the role of dopamine in depression.

Animals↗

A strategy for resection of Wilms' tumor with vena cava or atrial extension.

Resection of a Wilms' tumor that extends into the vena cava or right atrium results in excellent survival when combined with adjuvant therapy. Preoperative identification of the presence of intravascular tumor thrombus and the level of vascular involvement is essential. It facilitates safe surgical resection, with cardiopulmonary bypass immediately available for retrohepatic and atrial tumors. Six patients with intracaval or intracardiac tumor thrombus were treated over a 5-year period with no perioperative deaths. Preoperative chemotherapy was useful in two patients with extensive tumors and pulmonary metastases. Our results using an integrated management plan suggest that an aggressive surgical approach is justified for this extensive variant of Wilms' tumor.

Algorithms↗

Effect of cyclosporine on adrenocortical response to injury and infection.

The effects of cyclosporine administration on the adrenocortical response to the severe stress of burn wound sepsis were studied in Wistar rats. Animals were treated with cyclosporine (10 mg/kg/day) or saline by gavage for 10 days, then subjected to 30% scald burns with wound inoculation with Pseudomonas. Animals were sacrificed on Postburn Days (PBDs) 1, 4, and 7 for determination of serum corticosterone and ACTH levels and adrenal weights and histology. Adrenal glands from animals sacrificed on PBD 7 were also analyzed for DNA, RNA, and protein content. Cyclosporine treatment without injury had no significant effect on body weight gain, adrenal mass, or baseline ACTH or corticosterone levels. During sepsis, cyclosporine-treated animals demonstrated a significantly diminished adrenocortical response compared to those given only saline. Serum corticosterone levels in the cyclosporine group were 45, 53, and 62% lower on PBDs 1, 4, and 7, respectively, than in saline-treated controls (P < 0.01 on each day). ACTH levels were 43 and 36% lower in cyclosporine-treated animals on PBDs 4 and 7, respectively, compared to the saline-treated group (P < 0.05 on each day). Adrenal hyperplasia occurred in both groups by PBD 7, but increases in adrenal mass and in histologic changes associated with hyperplasia (lipid depletion, vascular dilation) were less pronounced in cyclosporine-treated animals compared to those receiving saline, while adrenal composition remained similar between the two groups. Thus, cyclosporine administration is associated with an attenuated adrenocortical response to the stress of sepsis due to diminished circulating levels of ACTH.

Adrenal Cortex↗

Effects of 9-ene-tetrahydrocannabinol on uterine estrogenicity in the mouse.

Several early (Phase I) and late (Phase II) estrogenic effects of 9-ene-tetrahydrocannabinol (THC) were examined in the adult mouse uterus. An injection of THC (2.5 or 10 mg/kg body wt) in ovariectomized mice neither stimulated uterine water imbibition or accumulation of [125I]bovine serum albumin (Phase I responses) at 6 h, nor antagonized these Phase I responses elicited by estradiol-17 beta (E2). With respect to Phase II responses, although single injections of THC (2.5, 5.0 and 10 mg/kg body wt) alone were ineffective in influencing uterine weight at 24 h or incorporation of [3H]thymidine at 18 h, this drug interfered with these responses elicited by E2 in a dose-dependent manner. In contrast, an injection of THC in progesterone (P4)-primed ovariectomized mice modestly enhanced (61%) uterine incorporation of [3H]thymidine. However, E2-stimulated uterine thymidine incorporation in P4-primed ovariectomized mice was antagonized by THC treatment. Effects of THC on blastocyst implantation were examined. Single or multiple injections of various doses of THC neither induced implantation in P4-primed delayed implanting mice, nor interfered with E2-induced implantation. Furthermore, daily injections of THC (10 mg/kg body wt) during the peri-implantation period had no apparent adverse effects on implantation, or on experimentally induced decidualization (deciduomata). The data suggest that THC is neither pro- nor antiestrogenic with respect to Phase I responses. However as regards Phase II responses, THC is modestly pro-estrogenic in the P4-treated uterus, but is anti-estrogenic in the presence of E2. These estrogen agonistic/antagonistic effects of THC on uterine Phase II responses do not adversely affect the process of implantation and decidualization.

Animals↗

Expression of insulin-like growth factor-I (IGF-I) and its receptor in the peri-implantation mouse uterus, and cell-specific regulation of IGF-I gene expression by estradiol and progesterone.

This study describes the expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) genes in the mouse uterus during the peri-implantation period (Days 1-6 of pregnancy), as well as effects of estradiol (E) and progesterone (P) on cell-specific IGF-I gene expression in the uterus of the ovariectomized adult mouse. Northern blot analysis showed that IGF-I mRNA levels were low but readily detectable in the uterus on Day 1 of pregnancy and steadily increased, reaching high levels just before (Day 4) and after initiation of implantation (Days 5 and 6). In general, IGF-IR transcripts were present in low abundance in uterine RNA throughout the peri-implantation period. However, six sizes of uterine IGF-IR transcripts were detected, and the relative abundance of two of these transcripts varied significantly during the peri-implantation period. Cell-specific expression of the IGF-I gene was examined by in situ hybridization to mRNA and immunohistochemical detection of protein. The results indicated that the synthesis of IGF-I on Days 1 and 2 was most predominant in glandular and luminal epithelial cells. However, on Days 3 and 4, stromal cells, and on Days 5 and 6, decidual cells appeared to be the predominant sites of synthesis of this growth factor. Uterine IGF-I gene expression was stimulated by ovarian steroids. Northern blot analysis showed that IGF-I transcripts were rare in the ovariectomized adult mouse uterus, but an injection of P and/or E caused a rapid accumulation of these transcripts. Analysis of the cell-specific expression of uterine IGF-I showed that E induced IGF-I gene expression primarily in epithelial cells, whereas P did so in the stroma. Superimposition of E on the P-primed uterus further stimulated IGF-I expression in the stroma. The results of these studies are consistent with an autocrine/paracrine function of uterine IGF-I, and indicate that ovarian steroids regulate the cell-specific and temporal patterns of expression of this gene in the peri-implantation mouse uterus.

Animals↗

Clozapine for the treatment of adolescents with schizophrenia.

Despite recent reports that clozapine is useful for the treatment of chronic schizophrenics resistant to neuroleptics, no studies have been reported in adolescents with schizophrenia. Despite the risk of potentially fatal agranulocytosis, clozapine's use in adolescents may become important because of its lack of extrapyramidal side effects or association with tardive dyskinesia, and reports that suggest that schizophrenic adolescents resemble chronic adult schizophrenics. The authors report three successful trials of clozapine in adolescents with schizophrenia who did not respond to conventional neuroleptic treatment.

Adolescent↗