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Biomedical subjects

A Grover

Publications and source records attributed to A Grover.

At least 73 records · Page 4Linked to original sources
PubMed1992

Extracellular matrix receptors and mouse skin carcinogenesis: altered expression linked to appearance of early markers of tumor progression.

Interaction of cells with the basement membrane is important for cell proliferation and differentiation. Disruption of the basement membrane is an early event during progression of benign tumors to cancer. Using the techniques of immunohistochemistry and immunofluorescence, we show that cell-matrix interactions via the cell surface integrin receptors alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 4, the Mr 67,000 laminin receptor (67LR) laminin-binding protein, and the secreted matrix protein laminin are strictly regulated during differentiation of mouse epidermis. While alpha 6 beta 4 and alpha 5 beta 1 are polarized to the basal surface of basal cells in contact with the basement membrane, alpha 3 beta 1 and the non-integrin 67LR are primarily detected in the cell periphery of suprabasal cells, where cell to cell contacts are found. Sequential changes in expression of matrix receptors occur following multistage carcinogenesis of mouse skin. In an analysis of benign and malignant skin tumors induced by chemical carcinogens or oncogene transduction, we found that alpha 3 beta 1 and alpha 5 beta 1 as well as the non-integrin 67LR are sequentially down-regulated in the progression from benign to malignant, while alpha 6 beta 4 is the predominant receptor expressed in the carcinomas. Tumor expression of alpha 6 beta 4 is not polarized and is dissociated from its colocalized normal partner bullous pemphigoid antigen, which remains restricted to the basement membrane. The changes in matrix receptors are linked to appearance of keratin 13 in suprabasal regions, but always in alpha 6 beta 4 negative cells. The predominance of alpha 6 beta 4 in the proliferating cells during progression is associated with decreased expression of keratin 13 in carcinomas. These results suggest that matrix interactions with its receptors are important determinants of ordered differentiation in normal skin and show characteristic alterations during carcinogenesis that parallel changes in differentiation of the tumors.

Animals↗
PubMed1992

An immunochemical and immunocytologic study of the increase in myometrial gap junctions (and connexin 43) in rats and humans during pregnancy.

Myometrial gap junctions are thought to play a necessary role in control of parturition. In this study we evaluated the presence of gap junctions in myometrial tissues with a specific antibody to the gap junction protein, connexin 43, with immunocytochemistry and immunoblots. Immunofluorescence of rat heart showed gap junctions were localized along the intercalated disks, but no change occurred during pregnancy. Fluorescent staining of rat myometria showed punctate staining of gap junctions between muscle cells during term and preterm birth, illustrating the tremendous increase in gap junctions during labor. Similarly, staining of human myometrial tissues was present in specimens from pregnant patients but absent in tissues from nonpregnant women. Immunoblots of myometrial tissues from rat and humans confirmed the existence of high levels of connexin 43 during term and preterm labor in rats and also during late pregnancy in humans.

Animals↗
PubMed1992

Participation of health workers, school teachers and pupils in the control of rheumatic fever: evaluation of a training programme.

In a rural community block of north India we initiated a programme for control of rheumatic fever and rheumatic heart disease (RF/RHD). This included a training campaign for all 74 health workers, 773 school teachers and 12,500 older pupils (class V to X) to enable them to suspect and refer cases of RF/RHD and counsel them about secondary prophylaxis. Training material was used by project staff, medical officers and teachers to convey that this serious disease with onset between 5 and 15 years can be recognized by four simple criteria: fever with joint pain or swelling; breathlessness and fatigue; involuntary face and limb movements. One year later we evaluated awareness generated by training by administering a questionnaire to random samples in the intervention area and in a noncontiguous control area. Health workers, teachers and pupils of the intervention block were significantly better aware of the nature, severity and presentation of the disease and reported having recognized cases whom they had referred for diagnosis, prophylaxis and counselled for follow up. We conclude that a training protocol incorporating simple messages can effectively create practical awareness for RF/RHD control among teachers, health workers and pupils in a rural community.

Community Health Workers↗
PubMed1991

Synthesis and pregnancy-inhibiting activity of 7-substituted androst-5-ene derivatives.

Synthesis of 7-aryl/allyl-substituted androstene derivatives 3a through 3g has been carried out by Grignard reaction on 3 beta,17 beta-diacetoxyandrost-5-en-7-one (2) with aryl/allyl magnesium bromide. Isomeric mixture of products 3b and 3c/3e and 3f/3h was separated by column chromatography. Stereochemical assignment at C-7 has been made on the basis of 13C nuclear magnetic resonance studies and chemical considerations. Compounds 6a and 6b were synthesized by alkylation of compound 5 with beta-(N,N-diethylamino)ethyl chloride hydrochloride and 1-(2-chloroethyl)pyrrolidine hydrochloride, respectively. Compound 3g (isomeric mixture) prevented pregnancy in 60% of rats at 10 mg/kg daily dose administered orally on days 1 to 7 of pregnancy; however, its only isolable 7 beta-hydroxy isomer, 3h, was inactive at this dose.

Androstenes↗
PubMed1991

Profile of right-sided endocarditis: an Indian experience.

The clinical profile of right-sided infective endocarditis in India was studied from a review of records of patients with infective endocarditis admitted to this hospital. From November 1982 to November 1989, 109 patients with infective endocarditis showed vegetations on cross-sectional echocardiography confirming the diagnosis of infective endocarditis. In 19 (17.4%) patients, only the right side of the heart was involved: specifically the tricuspid valve alone in 10; tricuspid and pulmonary valves in 4; tricuspid valve and right ventricular outflow tract in 1; tricuspid valve and right ventricular free wall in 1; pulmonary valve alone in 2; and bifurcation of pulmonary trunk in 1. Eleven patients (57.9%) had underlying congenital heart disease whereas the remaining 8 patients (42.1%) did not have any underlying heart disease. The latter group, therefore, had isolated right-sided infective endocarditis. Previous illnesses leading to isolated right-sided infective endocarditis were: puerperal sepsis in 4; septic abortion in 1; staphylococcal pneumonia in 2; and epididymoorchitis in one. Eight out of 11 patients with congenital heart disease did not report any previous illness. In the remaining 3, right-sided endocarditis followed cardiac surgery in one; dental extraction without prophylaxis in one; and pulmonary balloon valvoplasty in one. All patients with isolated right-sided infective endocarditis had features of septicaemia, but a murmur of tricuspid regurgitation was audible in only 4 (50%) of them. We conclude that, unlike western reports, the pattern of right-sided infective endocarditis in India is different. No drug addict with right-sided infective endocarditis was seen; puerperal sepsis and septic abortion were the commonest causes of isolated right-sided infective endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Septic↗
PubMed1990

Pregnancy with heart disease. Experience at Postgraduate Institute of Medical Education and Research, Chandigarh.

Pregnant patients with heart disease seen between 1980 and 1985 were studied. The incidence of heart disease in pregnancy was 1.3%. Rheumatic heart disease was the commonest lesion (78%), followed by congenital heart disease (18.7%). In the rheumatic heart disease group, mitral stenosis was the commonest lesion (71.54%), and patients who had been or were operated on for their heart disease had less severe dyspnoea and fewer complications. The mode of delivery and the foetal and maternal mortality did not differ significantly in operated and non operated patients.

Female↗
PubMed1987

An adhesion-defective variant of F9 embryonal carcinoma cells fails to differentiate into visceral endoderm.

Adhesion-defective EC cells were isolated from a population of mutagenized F9 cells by serial transfer of cells that did not adhere to gelatin-coated dishes. The variant cells grew in suspension as multicellular clusters of loosely aggregated cells. The cells adhered to, but did not flatten on, fibroblast monolayers and extracellular matrix produced by parietal-like endoderm. Two different mutant cell lines exhibited increased sensitivity to the lectin abrin and decreased sensitivity to wheat germ agglutinin, suggesting that changes in cell surface glycosylation are associated with the mutant phenotype. These adhesion-defective mutants were used to study the relationship between cell-cell adhesion and endodermal differentiation. Unlike wild-type cells, when cultured with low concentrations of retinoic acid (RA) in suspension culture, the mutant cells did not form embryoid bodies but remained as loosely adhering strings of cells. Electron microscopic examination revealed that most of the differentiated variant cells resembled parietal endoderm, and this was confirmed by immunofluorescent staining for TROMA-3 marker. The levels of some of the markers that characterize the differentiative pathways were examined by immunoprecipitation and by enzyme-linked immunosorbent assay (ELISA). The variant line produced higher levels of laminin and type IV collagen compared to the wild-type cells. alpha-Fetoprotein (AFP) was produced at a significantly lower level by the variant compared to wild-type F9 cells during the differentiative process. The results show that variant cells differentiated toward parietal endoderm but have a very much restricted ability to differentiate to visceral endoderm. We conclude that aggregation and/or compaction provide some essential signals during the differentiation of F9 cells into epithelial layers of visceral endoderm.

Abrin↗
PubMed1987

Proteoglycan-19, laminin and collagen type IV production is correlated with the levels of mRNA in F9 cell aggregates differentiating in the presence or absence of cyclic AMP.

F9 embryonal carcinoma cells differentiate to embryoid bodies containing an outer epithelial layer of visceral endoderm cells when cultured as aggregates in medium containing retinoic acid (RA). Another pathway of differentiation to parietal endoderm is followed when dibutyryl cyclic AMP (cAMP) is added to the medium. We have measured the accumulated levels of RNA transcripts from a chondroitin sulfate proteoglycan gene (PG-19), the type IV collagen alpha 1, alpha 2 subunit genes, and laminin B1, B2 subunit genes during these differentiation processes. Laminin B2 gene is uniquely regulated among the extracellular matrix component genes studied. The level of laminin B2 RNA remains almost invariant during RA induction of differentiation but is induced 11-fold by cAMP with RA. In contrast, laminin B1, collagen IV alpha 1, and alpha 2 genes are induced in two stages with six- to sevenfold accumulation of RNA induced by RA and fourfold greater levels by cAMP (19- to 28-fold overall). All of these matrix-encoding genes except proteoglycan are expressed at low levels in unstimulated F9 cells, whereas PG-19 is completely undetectable and is observed only after 2 days of stimulation with RA. Its increased expression with RA and cAMP induction is at least 100-fold during F9 differentiation. Extracellular matrix transcripts are relatively stable and this accounts in part for high accumulated levels during differentiation. We conclude that several kinds of gene regulation occur among the matrix components and other differentiation markers, and this makes the F9 model system useful to study the differential effects of hormone treatments on cellular events leading to differentiation and loss of tumorigenicity.

Bucladesine↗
PubMed1986

Effect of liposomes on lymphocytes: induction of proliferation of B lymphocytes and potentiation of the cytotoxic response of T lymphocytes to alloantigens.

Liposomes of certain lipid composition prepared by the detergent removal method (Brunner, J. et al., Biochim. Biophys. Acta 1976. 455: 322) induced the proliferation of spleen cells from different mouse strains. Spleen cell populations enriched in B lymphocytes and those obtained from nude mice were induced to proliferate, whereas spleen cell fractions enriched in T lymphocytes and thymocytes were not. The mitogenic effect of liposomes resembled that of lipopolysaccharide (LPS) and it depended upon their lipid composition. Liposomes prepared from dimyristoyl lecithin (DML), 2:1 dimyristoyl lecithin:cholesterol (DML:C), 2:1 dioleoyl lecithin: cholesterol (DOL:C), and 2:1 egg yolk lecithin:cholesterol (EYL:C) were mitogenic, whereas liposomes prepared from egg yolk lecithin (EYL) alone were not mitogenic for spleen cells. The mitogenic effects of these liposome preparations were in the decreasing order DML greater than DOL:C greater than or equal to EYL:C greater than DML:C greater than EYL. The results suggest a correlation between the membrane fluidity of liposomes and their mitogenic effect. Although no proliferative response was induced on T lymphocytes, two of these liposomes, DML and EYL:C, had the ability to potentiate the cytotoxic response of T lymphocytes to alloantigens in mixed leukocyte culture. In responder-stimulator combinations which differed for the H-2K, H-2D or the entire H-2 region, these liposomes potentiated the cytotoxic response significantly. The results suggest that liposomes have an ability to modulate T lymphocyte response.

Adjuvants, Immunologic↗
PubMed1986

Conditions affecting the differentiation of F9 teratocarcinoma cells: potentiation of response by cyclic AMP.

F9 cells maintained in culture were shown to have a reduced ability to differentiate. The cells produced decreased amounts of alphafetoprotein when induced with retinoic acid. We show that consistent responses can be recovered after passage of F9 cells as a tumor. In addition, optimal differentiation of F9 cells to visceral endoderm may be achieved by the addition of very low concentrations of dibutyryl cyclic AMP (dbcAMP) to the medium.

Animals↗
PubMed1986

Evidence for the existence of an early common biochemical pathway in the differentiation of F9 cells into visceral or parietal endoderm: modulation by cyclic AMP.

The addition of dibutyryl cyclic AMP (dbcAMP) to aggregate cultures of F9 cells in medium containing retinoic acid (RA) directs the pathway of differentiation into parietal endoderm instead of visceral endoderm. We examined the levels of some of the markers that characterize the two pathways and studied the time of commitment of cells to either direction of differentiation by using immunoprecipitation and enzyme-linked immunosorbent assays (ELISA). For either pathway, the levels and patterns of laminin, type IV collagen, and fibronectin are the same on the first day of differentiation, characterized by slightly decreased levels of laminin and type IV collagen synthesis and an increased level of fibronectin synthesis. These levels reverse on the second day of culture when the pathways diverge markedly. The differentiation pathway, however, can be redirected into the alternate one; parietal endoderm cells become committed after 3 days, whereas visceral endoderm cells are able to change into parietal endoderm cells at any time. Thus, alpha-fetoprotein (AFP)-producing F9 embryoid bodies switched to dbcAMP-containing medium lose the capacity to synthesize AFP and start to express genes characteristic of parietal endoderm. Our results indicate that at least some visceral endoderm cells may redifferentiate into parietal endoderm cells. These phenomena thus mimic features of endoderm differentiation in the mouse embryo.

1-Methyl-3-isobutylxanthine↗