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Biomedical subjects

L Mishra

Publications and source records attributed to L Mishra.

At least 37 records · Page 2Linked to original sources
PubMed1998

Intratumoral cisplatin/epinephrine-injectable gel as a palliative treatment for accessible solid tumors: a multicenter pilot study.

Intratumoral injections of cisplatin/epinephrine-injectable gel were administered weekly for 4 weeks in 45 patients with malignant tumors of various histologic types. Tumors were located on the skin and subcutaneous tissue primarily of the head, neck, and trunk, and on the tongue, oral pharynx, and esophagus. Patients were not candidates for surgery, radiation, or systemic chemotherapy. Each of the treated tumors (n = 82) was evaluated 2, 4, 8, and 12 weeks after the final injection. The initial dose of cisplatin was 1 mg/cm3 tumor volume, with escalation to 6 mg/cm3 allowed, depending on observed toxicities. The mean cumulative dose per patient for the four treatments ranged from 0.56 to 380 mg cisplatin. No dose-limiting cisplatin-related toxicities, such as nephrotoxicity, neurotoxicity, or ototoxicity, were observed. The overall objective tumor response rate was 50% (41 of 82), with 40% (33 of 82) complete responses and a median response duration of 160 days. Complete responses for adenocarcinoma and squamous cell carcinoma were 58% (21 of 36) and 38% (12 of 32), respectively. These results justified further clinical trials to evaluate the role of local chemotherapy with intratumoral cisplatin/epinephrine-injectable gel in the palliative treatment of patients with selected accessible solid tumors.

Adenocarcinoma↗
PubMed1998

Identification of elf1, a beta-spectrin, in early mouse liver development.

Beta-spectrins play essential roles in cell-cell interactions and in the maintenance of cell polarity. Our aim was to identify beta-spectrin genes important for the establishment of hepatocyte polarity and differentiation. Using subtractive screening of cDNA libraries from early embryonic mouse livers (post-coital days 10, 11, and 12), we have isolated elf1 (embryonic liver fodrin 1), a differentially expressed beta-spectrin or fodrin (betaSpIIsigmaI). Elf1 encodes a 220-amino acid protein with an NH2 terminal actin-binding domain. In situ hybridization studies demonstrate elf1 expression initially in day 10 embryonic heart tissue, then in day 11-11.5 hepatic tissue. These studies suggest that elf1 may play a role in the emergence of hepatocyte polarity during liver development.

Amino Acid Sequence↗
PubMed1997

Praja1, a novel gene encoding a RING-H2 motif in mouse development.

As part of a cloning strategy to identify genes involved in early mouse liver development we have isolated Praja1, a gene with similar sequences to the Drosophila melanogaster gene goliath (gl) which is involved in the fate of mesodermal cells ultimately forming gut musculatures, fat body, and the heart. Praja1 is a 2.1 kb gene encoding a putative 396 amino acid ORF and includes a COOH-terminal RING-H2 domain. Using the Jackson Laboratory BSS panel, we have localized Praja1 on chromosome X at 36 cM, which may be a candidate gene for mouse sla (sex linked sideroblastic anemia), near the X inactivation center gene, Xist. Northern blot analysis demonstrated three transcripts (3.1, 2.6 and 2.1 kb) in mRNA from adult mouse tissues brain, liver, and kidney as well as in mRNA from developing mouse embryos (days 7, 11, 15 and 17 post coitus, p.c.). In vitro transcription/translation yielded a product with an Mr of 59 kD. Immunohistochemical staining of in vitro liver explant cultures using a heterologous antibody against praja1 demonstrated cytoplasmic staining of cuboidal cells that have hepatocyte morphology and organization. The presence of the RING-H2 domain, a proline-rich region at the COOH-end, and regions rich in acidic amino acids, leads to the hypothesis that the Praja1 product is possibly involved in mediating protein-protein interactions, possibly as part of a protein sorting or transport pathway. This is strengthened by the similarity of Praja1 to rat Neurodap1, whose product has been shown to localize to the endoplasmic reticulum and golgi in brain.

Amino Acid Sequence↗
PubMed1997

Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome.

Adenomatous Polyposis Coli↗
PubMed1996

Review of cataract intervention in Maharashtra State.

Blindness due to cataracts presents an enormous problem, not only in terms of human suffering, but also in terms of economic loss and social burden. In the absence of proven measures of primary prevention, secondary prevention in the form of surgical intervention is, currently, the remedy to the problem of blindness due to cataracts. There are various therapeutic approaches in cataract extraction. However, the conventional ICCE/SPECT and the newer ECCE/IOL are the popular approaches presently adopted on a mass scale. Maharashtra is consistently achieving the quantitative targets for cataract surgery given by the Government of India. However, the qualitative aspects of cataract surgery, the desired outcome of which is sight restoration in those blinded by cataracts, has hitherto not been monitored and assessed. The Kolhapur Circle was selected for this purpose. With the improvement of Ophthalmic Surgeons and PMOAS, the sample of cataract patients operated on in the year 1992-93 was followed. Two blocks from each of three districts in the circle were selected at random. The respondents were patients from these six blocks who had cataract surgery in the year 1992-93. 50% of the operations took place in the mobile camps while 20% took place in government fixed facilities and 30% in the private sector. Micro-analysis of the quantitative performance of cataract surgery in the Kolhapur Circle revealed that the circle is continuously delivering the intended benefits, i.e. relieving human suffering due to blindness from cataracts. The overall success rate of cataract surgery was 86% (Postoperative VA > 6/60). It seems that the investment made in cataract intervention is highly productive.

Blindness↗
PubMed1995

Antitumor and antimicrobial activities of Fe(II)/Fe(III) complexes derived from some heterocyclic compounds.

The antitumor activities of some Fe(II)/Fe(III) complexes containing 1,3-diacetyl-2H-benzimidazole-2-thione along with a few derivatives of 1,2,4-triazol, 1,3,4-oxadiazole and 1,3,4-thiadiazole as co-ligands have been investigated. Antibacterial and antifungal activities of disulfido-/dichloro-bridged dinuclear Fe(III)/Fe(II) complexes containing similar heterocycles as terminal ligands have also been investigated.

Animals↗
PubMed1993

Extracellular matrix composition influences insulinlike growth factor I receptor expression in rat IEC-18 cells.

BACKGROUND: The composition of the extracellular matrix (ECM) as well as insulinlike growth factor I (IGF-I) receptor density vary along the crypt-villus axis. We determined whether components of the ECM influence IGF-I receptor expression in IEC-18 rat small intestine crypt cells. METHODS: IEC-18 cells were cultured on plastic, collagen type IV, Matrigel, and laminin at the plateau and proliferative growth phases. Receptor affinity (Kd) and number (Bmax) were determined by competitive binding of 125I-IGF-I in the presence of increasing concentrations of unlabeled IGF-I. Receptor isolation was performed by affinity cross linking. Messenger RNA (mRNA) for IGF-I receptor was quantified by Northern analysis. RESULTS: Specific binding of IGF-I > IGF-II > insulin was observed. A 130,000-molecular weight protein was identified by cross-linking, consistent with the alpha subunit of the IGF-I receptor. Scatchard analysis revealed no effect of ECM on IGF-I binding affinity. In contrast, the Bmax was 18% lower for plateau-phase cells cultured on Matrigel vs. plastic and was 42% lower for cells cultured on laminin vs. collagen type IV. The Bmax for proliferative growth phase cells was decreased when cultured on Matrigel vs. plastic and was 10-fold less than for cells cultured at the plateau growth phase. Northern analysis revealed that IEC-18 cells cultured on Matrigel had less mRNA for IGF-I receptor than cells cultured on plastic. CONCLUSIONS: The rate of cell proliferation and the composition of the ECM influence IGF-I receptor expression in IEC-18 cells.

Animals↗
PubMed1993

In vitro cell aggregation and cell adhesion molecules in Crohn's disease.

BACKGROUND: Lack of a suitable model has hindered efforts to understand inflammation and granuloma formation in Crohn's disease. METHODS: Granulomalike aggregates of circulating mononuclear cells are produced in vitro by cultures of cells with polyacrylamide beads. To identify features of in vitro aggregates, which are similar to tissue granulomas of Crohn's disease, the gross morphology and immunohistological appearance of the aggregates produced with peripheral blood mononuclear cells from patients with Crohn's disease were analyzed, and the size of in vitro aggregates was correlated with clinical activity of the disease. Blocking antibodies were used to evaluate the role of cell-adhesion molecules in the formation of in vitro aggregates. RESULTS: The size of in vitro aggregates correlates very significantly with clinical activity (P < 0.001). In active Crohn's disease, in vitro aggregates show immunohistological features of hypersensitivity type granulomas. Blocking antibodies against leukocyte function associated antigen LFA-2 (CD2), LFA-3 (CD58), and Mac-1 (CD11b/CD18) inhibit in vitro aggregate formation. CONCLUSION: In vitro aggregates model in vivo granulomas in size and organization. Cell adhesion molecules like CD2, CD58, and CD11b/CD18 may be involved in granuloma-formation of Crohn's disease.

Antigens, CD↗
PubMed1993

Biosynthesis of colony-stimulating factor-1 (CSF-1) by mesangial cells of autoimmune mice.

The amounts of colony-stimulating factor (CSF-1) produced by the mesangial cells of the kidney may be of pivotal importance in determining the outcome of nephritis, since CSF-1 activates macrophages, and macrophages have been shown to perform an important scavenger function in removing immune complexes which localize in the kidney. To test this hypothesis, the present study examined CSF-1 production by mesangial cells of the autoimmune MRL/MpJ-lpr-lpr strain of mice and also of their normal congenic MRL/MpJ-++ counterparts. It was found that mesangial cells of autoimmune mice produced diminished amounts of functional CSF-1 when measured by a bioassay, giving validation to the hypothesis proposed. Of interest, expression of CSF-1 mRNA was discordantly increased in mesangial cells of the MRL-lpr autoimmune mice. Based on current knowledge of the pathway for CSF-1 synthesis and secretion, it would appear that there may be a block in the post-transcriptional pathway for CSF-1 biosynthesis in autoimmune mesangial cells.

Animals↗
PubMed1992

Viral hepatitis, A though E, complicating pregnancy.

Jaundice during pregnancy may be the result either of disease uniquely associated with the pregnant state or disease totally unrelated to the pregnancy. In the United States, the most common cause of jaundice in pregnant women is viral hepatitis. With the exception of hepatitis E virus infection, the clinical course and histologic findings do not differ between pregnant and nonpregnant patients.

Female↗
PubMed1991

Effect of acute intravenous alcohol on plasma lipoproteins in man.

The effect of acute administration of ethanol was determined on plasma lipoproteins and post-heparin lipolytic activities in six normal subjects. Ethanol was administered intravenously (IV) in a dose of 0.6 g/kg body weight over 1 hour and blood samples were obtained for 4 hours thereafter. In four subjects, the determinations were repeated after the infusion of an isovolumetric amount of saline. Ethanol resulted in a rapid increase in plasma triglycerides, which persisted throughout the study. Ethanol did not result in changes in high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, or apolipoprotein administration of heparin. The increase in triglycerides without changes in HDL-cholesterol after acute ethanol administration may contribute to an increased severity of cardiovascular disease in binge drinkers.

Adult↗
PubMed1991

4'-Hydroxy-3-methoxyflavones with potent antipicornavirus activity.

4'-Hydroxy-3-methoxyflavones are natural compounds with known antiviral activities against picornaviruses such as poliomyelitis and rhinoviruses. In order to establish a structure-activity relationship a series of analogues were synthesized, and their antiviral activities and cytotoxicities were compared with those of flavones from natural origin. The 4'-hydroxyl and 3-methoxyl groups, a substitution in the 5 position and a polysubstituted A ring appeared to be essential requirements for a high activity. The most interesting compound was 4',7-dihydroxy-3-methoxy-5,6-dimethylflavone possessing in vitro TI99 values of greater than 1000 and greater than 200 against poliovirus type 1 and rhinovirus type 15, respectively. This compound was also active against other rhinovirus serotypes (2, 9, 14, 29, 39, 41, 59, 63, 70, 85, and 89) tested, having MIC50 values ranging from 0.016 to 0.5 micrograms/mL. Finally in contrast to quercetin it showed to be not mutagenic in concentrations up to 2.5 mg in the Ames test.

Animals↗
PubMed1990

Effect of insulin-like growth factor I on rat alcohol dehydrogenase in primary hepatocyte culture.

The effect of insulin-like growth factor I (IGF-I) on the activity of alcohol dehydrogenase was determined in primary hepatocyte culture from male rats. Continuous exposure of hepatocytes to IGF-I (30 nM) resulted in increases in alcohol dehydrogenase activity on Days 3-6 of culture. The increase in enzyme activity was preceded by increased alcohol dehydrogenase mRNA, indicating that the effect of IGF-I was at the pretranslational level. The effect of IGF-I was observed only in the presence of pharmacological concentrations of insulin in the media. Insulin alone had no effect on alcohol dehydrogenase activity. The permissive influence of insulin was correlated with the ability of insulin to maintain a steady high number of IGF-I binding receptors in the hepatocytes during culture. The response of alcohol dehydrogenase to IGF-I is similar to that previously demonstrated for growth hormone and suggests the possibility that the effect of growth hormone on this enzyme may be mediated by IGF-I.

Alcohol Dehydrogenase↗
PubMed1990

Adeno-associated virus DNA replication is induced by genes that are essential for HSV-1 DNA synthesis.

Adeno-associated virus (AAV) DNA replication is not detectable unless cells are coinfected with a helper adenovirus (Ad) or herpesvirus or unless AAV infection is carried out in certain established cell lines that have been treated with various metabolic inhibitors or uv irradiation. In helper-dependent infections, it has been shown that AAV DNA synthesis depends on one or more early Ad genes, whereas little is known concerning any herpesvirus gene that promotes AAV DNA synthesis. In this study we tested the ability of four cloned Xbal fragments of herpes simplex virus type 1 (HSV-1) DNA to induce AAV DNA synthesis in Vero cells. Cotransfections, which were carried out with pAV1 (an infectious AAV2 plasmid), revealed that AAV DNA synthesis could be optimally induced by three of these clones (C,D, and F) plus a clone of the HSV-1 ICP4 (IE 175) gene. ICP4, an immediate early gene, was presumably required to activate expression of other HSV genes. To help identify the additionally needed HSV genes, we tested Xbal C,D, and F subclones that contain genes previously found necessary for origin-dependent HSV DNA synthesis and found that at least five of these genes (UL 5, 8, 9, 29, and 30) contributed to the induction of AAV DNA synthesis. In contrast to their absolute requirement for HSV DNA synthesis, none of these genes were strictly necessary for AAV DNA replication. Because they are all known to specify proteins that are directly involved in HSV DNA synthesis, our results suggest that some or all of their products also may directly participate in the replication of AAV DNA.

Animals↗
PubMed1989

Chemotherapeutic agents, XV. Synthesis of 4-amino-3-pyrazolo-1,2,4-triazoles as antimicrobial agents.

4-Amino-3-hydrazino-5-H/methyl-1,2,4-triazole dihydrochlorides (2a,b) were obtained by cyclization of triamino-guanidine-HCl in formic and acetic acids, respectively. Condensation of 2a with pyrazol-4-carbaldehydes in ethanol yielded 3a,b. Cyclocondensation of 2a,b with dimethylmercaptocyanoacrylonitrile, methyl dimethylmercapto-cyanoacrylate, ethoxymethylenemalononitrile and ethyl ethoxymethylenecyanoacetate individually provided 4a-d and 5a-d, respectively. The hydrazones 6a,b were obtained by refluxing 4-amino-3-(5-amino-4-ethoxycarbonyl pyrazol-1-yl)-1,2,4-triazole (5b) with aryl aldehydes in ethanol. Interaction of 2a with acetylacetone and 2-ethoxycarbonylcyclopentanone separately yielded 7 and 8 while reaction with 2-ethoxycarbonylcyclohexanone provided the bicyclic compounds 9a,b. Some of the compounds were screened for antibacterial and antifungal activities but none of them showed any significant activity.

Anti-Infective Agents↗
PubMed1989

More rapid elimination of alcohol in women as compared to their male siblings.

Sex differences in rates of ethanol elimination were investigated in natural siblings to reduce genetic variability as compared to subjects chosen at random. Ethanol was infused intravenously in a dose of 0.6 g/kg of body weight over 45 to 60 min and serial blood samples obtained for 5 hr. The mean rate of ethanol elimination was higher in seven women, not different in one, and lower in one compared with their male siblings. The mean rate of ethanol elimination for all nine women was higher at 1.93 +/- 0.12 as compared with the value of 1.69 +/- 0.17 mmoles/kg body weight/hr in the men (p less than 0.05). Higher rates of ethanol metabolism in women as compared to men may be important in the increased susceptibility of women to liver injury caused by alcohol consumption.

Acetates↗