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Biomedical subjects

A Chopra

Publications and source records attributed to A Chopra.

At least 37 records · Page 2Linked to original sources

Decreased mRNA expression of several basement membrane components in basal cell carcinoma.

The biologic factors that control the behavior of basal cell carcinoma are poorly understood. This study was undertaken to elucidate the mechanisms responsible for the altered protein levels of several basement membrane components found in basal cell carcinoma. RNA was isolated from papulonodular basal cell carcinoma, normal human epidermal keratinocytes, and normal human skin, reverse transcribed to cDNA and amplified by the polymerase chain reaction utilizing primers specific for the 230 kDa bullous pemphigoid antigen (BPAG1), the 180 kDa bullous pemphigoid antigen (BPAG2), the alpha6 and beta4 chains of the alpha6beta4 integrin complex, and the beta3 chain of laminin 5. Southern blots probed with internal oligonucleotides confirmed that each polymerase chain reaction was specific for the basement membrane component amplified. The mRNA expressions of basement membrane components were indistinguishable between normal human epidermal keratinocytes and normal human skin, and subsequent experiments used normal human epidermal keratinocytes as controls. Quantitation of polymerase chain reaction products indicated that all basement membrane specific mRNA were significantly decreased in basal cell carcinoma as compared with normal human epidermal keratinocytes. The mean polymerase chain reaction product intensities were significantly less in the basal cell carcinoma as compared with the normal human epidermal keratinocytes at the following levels: p < 0.001 for alpha6 and beta4 integrins and the beta3 chain of laminin 5; p < 0.01 for BPAG1; and p < 0.05 for BPAG2. Our results demonstrate that decreased protein levels of basement membrane components in basal cell carcinoma are due at least partially to a downregulation of basement membrane mRNA species. We speculate that these alterations may lead to a structurally incompetent basement membrane that facilitates the basal cell carcinoma ability to invade tissues.

Antigens, CD↗

The human transcription enhancer factor-1, TEF-1, can substitute for Drosophila scalloped during wingblade development.

The human transcription enhancer factor-1 (TEF-1) belongs to a family of evolutionarily conserved proteins that have a DNA binding TEA domain. TEF-1 shares a 98% homology with Drosophila scalloped (sd) in the DNA binding domain and a 50% similarity in the activation domain. We have expressed human TEF-1 in Drosophila under the hsp-70 promoter and find that it can substitute for Sd function. The transformants rescue the wingblade defects as well as the lethality of loss-of-function alleles. Observation of reporter activity in the imaginal wing discs of the enhancer-trap alleles suggests that TEF-1 is capable of promoting sd gene regulation. The functional capability of the TEF-1 product was assessed by comparing the extent of rescue by heat shock (hs)-TEF-1 with that of hs-sd. The finding that TEF-1 can function in vivo during wingblade development offers a potent genetic system for the analysis of its function and in the identification of the molecular partners of TEF-1.

Amino Acid Sequence↗

Vaginal wall sling for anatomical incontinence and intrinsic sphincter dysfunction: efficacy and outcome analysis.

PURPOSE: A prospective cohort study was done to determine the efficacy and clinical outcome of a new technique for anterior vaginal wall sling construction to treat urinary incontinence due to intrinsic sphincter dysfunction or anatomical incontinence. MATERIALS AND METHODS: Preoperative evaluation included lateral cystography, video urodynamics, cystoscopy and incontinence staging. Postoperative subjective and objective staging outcome measures were prospectively assigned at predetermined regular intervals by a third party. RESULTS: Of the patients 95 had intrinsic sphincter dysfunction and 65 had anatomical incontinence. The repair failed in 7% of the 160 patients who had recurrent incontinence during followup and 9% had de novo urgency incontinence. Time to failure comparing patients with intrinsic sphincter dysfunction and anatomical incontinence was modeled using Kaplan-Meier survival curves, and the log rank test showed no significant difference between the groups (p > 0.05). Logistic regression covariates revealed no significant predictive factors for postoperative failures. Preoperative patient age was the only predictive factor for de novo instability (logistic regression model p < 0.05). CONCLUSIONS: Our initial results indicate that the 2 groups are indistinguishable to date based on current clinical and experimental statistics except for time to full recovery of postoperative voiding and incidence of postoperative instability (regression model p < 0.05).

Adult↗

Surgery for female stress urinary incontinence.

With the advent of magnetic resonance imaging, the treatment of female incontinence has undergone a renaissance. This change has primarily been due to superior understanding of anatomy and function of the supports of the urethra, bladder neck and bladder base in the female pelvis.

Journal Article↗

Vaginal reconstructive surgery for female incontinence and anterior vaginal-wall prolapse.

The surgical procedure of choice to correct stress urinary incontinence using a vaginal approach depends not only on the anatomic origin of the incontinence (hypermobility or intrinsic sphincter dysfunction) but also on the degree of coexistent anterior vaginal wall prolapse. The grade of coexistent cystocele and the finding of a central or lateral defect are important observations that help the surgeon plan the optimum surgical approach. Grade 4 cystocele with central and lateral defects represents the most severe form of anterior vaginal wall prolapse. In this case, the surgical goals are to correct both central and lateral defects, as well as hypermobility related to the mid-urethra and bladder neck.

Female↗

The human CD46 molecule is a receptor for measles virus (Edmonston strain).

Measles virus normally causes disease in human beings, and the host range of this virus may be determined by a specific receptor on the surface of primate cells. Human-rodent somatic cell hybrids were tested for their ability to bind measles virus, and only cells that contained human chromosome 1 were capable of binding virus. A study of lymphocyte markers suggested that the complement regulator known either as membrane cofactor protein or CD46 was the measles virus receptor. We proved this hypothesis by demonstrating that hamster cell lines that expressed human CD46 could subsequently bind virus. Furthermore, infected CD46+ cells produced syncytia and viral proteins. Finally, polyclonal antisera against CD46 inhibited virus binding and infection. These results prove that human CD46 permits cells both to bind measles virus and to support infection.

Animals↗

Geriatric assessment teams in nursing homes: do they work?

Several studies have examined the effectiveness of geriatric assessment teams in outpatient and acute care settings. This project compared medical records of 69 consecutive nursing home patients randomly assigned on arrival to team (n = 33) and nonteam (standard care, n = 36) conditions. Quality-of-care indices and healthcare service utilization were compared over a 12-month postadmission period. Team patients had a significantly greater number of diagnoses and ancillary services combined with nonsignificant trends toward decreased mortality, fewer emergency department visits, and fewer drugs prescribed. The team approach improves quality of care. Additional clinical studies evaluating the effectiveness of geriatric assessment teams should be made in other nursing homes.

Aged↗

Cloning of the guinea pig 5-lipoxygenase gene and nucleotide sequence of its promoter.

The guinea pig 5-lipoxygenase (5-LO) gene and its promoter were cloned from a guinea pig genomic DNA library. Sequencing analysis of the guinea pig promoter revealed that expression of the 5-LO gene in this rodent is probably governed by cis acting nucleotide sequences quite similar to the human gene. Nucleotide sequences that bind factors like Sp-1, AP-2, NF-kB and c-Ha-ras were identified in the guinea pig 5-LO promoter region.

Amino Acid Sequence↗

A rapid survey on substance abuse disorders in the urban slums of New Delhi.

The results are presented of a rapid survey screening method of general population for identifying dependent and non dependent drug abusers, especially in vulnerable groups such as slum dwellers. The results showed that with the help of instrument with modified DSM III and interviewing only the heads of the households it was possible to get reliable estimates of dependence disorder in the community. This method can be of assistance to health planners for a quick assessment of the magnitude of the problem leading to better allocation of funds and developing services for the affected population. The method is an improvement on key informant technique and a full fledged survey.

Adolescent↗

When outside the norm is normal: interpreting lab data in the aged.

Laboratory tests that are frequently ordered in a primary care practice include complete blood count, arterial blood gases, erythrocyte sedimentation rate, creatinine clearance, and glucose tolerance. Yet, the impact of age-associated physiologic changes on interpretation of laboratory data has only recently been elucidated. With advancing age, many laboratory parameters increase or decrease, some remain unchanged, and the effect of age on still others remains unclear. Interpreting lab data in the elderly is further confounded by the multiple disease states, polypharmacy, and atypical disease presentations commonly found in this population. Additional clinical research is needed to better establish reference laboratory values in elderly patients.

Aged↗

Genetic characterization of adenovirus transformed cell revertants resistant to methylglyoxal bis(guanylhydrazone): evidence for the involvement of three genetic loci.

Five new independent rat somatic cell mutants resistant to the antileukemic drug methylglyoxal bis(guanylhydrazone) (MGBG) were isolated after mutagen treatment. The mutants were 7- to 10-fold more resistant to MGBG than were the parental wild-type cells. When the MGBG-resistant (MGR) mutants were exposed to the drug in the presence of Tween-80, a nonionic detergent, they became as sensitive (MGS) to MGBG as the wild-type cells, indicating that they were probably permeability mutants. Genetic analysis of hybrids between MGR mutants and wild-type cells showed that MGR and the nontransformed alleles to be recessive to the MGS (wild-type) and transformed phenotype, respectively. Complementation analysis of the seven mutants revealed three functional genetic units or loci responsible not only for the MGR phenotype but also for tumorigenicity as determined in nude mice. Only the MGS hybrids produced tumors in the nude mice, whereas the MGR hybrids and mutants did not. Our results suggest the existence of cellular membrane components that are responsible both for cellular tumorigenicity and resistance to MGBG.

Adenoviridae↗

New mouse somatic cell mutants resistant to cadmium affected in the expression of their metallothionein genes.

Fluctuation tests à la Luria and Delbruck were performed with mouse LMTK cells, and the results indicate that the appearance of variants resistant to cadmium is due to random spontaneous mutations and not to epigenetic events. The rate of spontaneous mutations leading to cadmium resistance was calculated to be 0.92 x 10(-6) per cell per generation. This rate increased 14-fold on treatment with ethyl methane sulfonate. Several stable mutant cell lines resistant to cadmium were selected and characterized with respect to metallothionein (MT) induction. Based on the copy number of mt+ genes and the levels of MT proteins and mRNA, the mutants could be divided into two classes, A and B. Although group A mutants have the same number of mt1+ and mt2+ genes as wild-type cells, upon induction with cadmium, the amount of MT proteins and mRNA in the mutants are greatly increased over wild-type levels. This observation strongly suggests a mutation that regulates MT gene transcription in these cells. In group B mutants, the mt+ genes are amplified about three- to fourfold, and their MT protein and mRNA basal levels are, as expected, much higher than in the wild-type cells, under uninduced and induced conditions.

Animals↗

Cross-resistance and biochemical characteristics of second-step mutants of HeLa cells resistant to cardiac glycosides.

From ouabain-resistant (OuaR) mutants of HeLa cells which do not show any cross resistance to the digoxin analog SC4453, stable second-step mutants resistant to either SC4453 or those exhibiting increased resistance to digoxin have been isolated. The mutants obtained exhibited highly specific cross resistance towards different cardiac glycosides (CGs) and, based on their cross-resistance patterns, contained more than one type of genetic lesion. Biochemical studies with these mutants showed that cellular uptake of 86Rb was inhibited by specific CGs to which they showed increased resistance. The mutants showed reduced binding of [3H]ouabain and [3H]digoxin in comparison with the parental OuaR cells and about 50-60% of the Na+, K(+)-ATPase activity in the mutant cell extract was highly resistant to inhibition by ouabain and digoxin. In contrast to the above changes, these mutants showed no evidence of amplification, enhanced transcription, or gross alterations in the genes for the alpha or beta subunits of Na+, K(+)-ATPase. These observations indicated that these mutants involved a second-specific alteration in Na+, K(+)-ATPase. In contrast to these mutants, Chinese hamster ovary cells, which naturally exhibit comparable levels of resistance to CGs, showed no significant binding of either [3H]ouabain or [3H]digoxin and all of their Na+, K(+)-ATPase activity was resistant to inhibition by CGs.

Animals↗