Search PubMed⌕ Search

Biomedical subjects

S Mathur

Publications and source records attributed to S Mathur.

At least 19 recordsLinked to original sources
PubMed1999

Metastatic breast cancer diagnosed during a work-up for urinary incontinence: a case report.

Breast cancer is the most commonly diagnosed cancer among women in the USA and the second leading cause of cancer deaths in women. Breast cancer metastases to the bladder are unusual but have been reported occasionally in the literature. The majority of the reports describe bladder metastases presenting with symptomatology or occurring in the context of disseminated disease. We present the case of an 87-year-old woman with a history of breast cancer and negative routine work-up for metastatic disease. She was referred to the urogynecology division in our institution because of complaints of urinary incontinence and urinary urgency. A urethrocystoscopy revealed suspicious bladder mucosal lesions that were biopsied. The pathology findings, when compared to the original cancer specimens, were consistent with metastatic disease. This case suggests that in patients with a history of breast cancer, even subtle urinary symptoms should be thoroughly evaluated.

Aged↗
PubMed1999

Cardioprotective effects of propofol and sevoflurane in ischemic and reperfused rat hearts: role of K(ATP) channels and interaction with the sodium-hydrogen exchange inhibitor HOE 642 (cariporide).

BACKGROUND: Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane. METHODS: Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion. RESULTS: Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment. CONCLUSION: HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.

Adenosine Triphosphate↗
PubMed1998

Overexpression of elongation factor-1gamma protein in colorectal carcinoma.

BACKGROUND: Elongation factor-1 (EF-1) is a cellular protein that plays a role in protein synthesis by mediating the transfer of aminoacyl-tRNA to 80S ribosomes. It is comprised of four subunits: alpha, beta, gamma, and delta. EF-1gamma is a substrate for the maturation-promoting factor, which determines entry into the M-phase of the cell cycle in all eukaryotic cells. Previously, the authors showed that EF-1gamma RNA is overexpressed in a high proportion of colorectal carcinomas. At that time, there were no antibodies to EF-1gamma, so the EF-1gamma protein could not be examined. Because levels of RNA do not always parallel the levels of the protein it encodes, it was important to develop antibodies to EF-1gamma to examine its expression at the protein level in colorectal carcinoma. METHODS: Twenty-nine patients undergoing surgical resection for colorectal adenocarcinoma were studied. A polyclonal antibody to EF- 1gamma in rabbit was prepared. Tumors and normal-appearing mucosa distant from the tumor (> or = 10 cm) were obtained from each patient. Cytosolic proteins were extracted from the tissues and examined by Western blot analysis with the EF-1gamma antibody. Colonic tumors also were studied by immunohistochemical analysis with another EF-1gamma polyclonal antibody. RESULTS: Using Western blot analysis, the authors observed greater expression of EF-1gamma in the tumors than in the more distal normal-appearing mucosa. Overexpression was not observed in the patients with the two Dukes Stage A tumors, but was observed in four of ten patients with Dukes Stage B tumors, seven of eight patients with Dukes Stage C tumors, and six of nine patients with Dukes Stage D tumors. Overall, 17 of 29 patients (59%) were found to have overexpression of EF-1gamma. Using immunohistochemical analysis, EF-1gamma protein was shown to be located predominantly in tumor epithelium rather than the stroma or infiltrating mononuclear cells. CONCLUSIONS: Previous studies showed that EF-1gamma mRNA frequently is overexpressed in colorectal adenocarcinoma. This study showed that EF-1gamma also was overexpressed at the protein level in colorectal adenocarcinoma relative to more distal normal-appearing mucosa from the same patient. Immunohistochemical analysis demonstrated that this protein was expressed predominantly in the tumor epithelial cells and therefore was not derived from cells involved in the desmoplastic response.

Adenocarcinoma↗
PubMed1998

Intracortical chondroma.

A case of a 45-year-old woman with an intracortical chondroma of the right tibia is described. The uniqueness of this location and presentation is discussed.

Bone Neoplasms↗
PubMed1998

13-hydroxy octadecadienoic acid (13-HODE) inhibits triacylglycerol-rich lipoprotein secretion by CaCo-2 cells.

Oxidized lipids present in atherogenic lipoproteins are derived, in part, from the diet. To address the effects of an oxidized lipid on intestinal lipoprotein assembly and secretion, CaCo-2 cells were incubated with 13-HODE or its native fatty acid, linoleic acid, and triacylglycerol-rich lipoprotein synthesis and secretion were investigated. 13-HODE was readily taken up by cells and esterified to lipids. Although both fatty acids were largely esterified to neutral lipids, in comparison to neutral lipids containing linoleic acid, a greater proportion of cellular neutral lipids containing 13-HODE and/or its metabolites was secreted. Compared to linoleic acid, however, 13-HODE caused less triacylglycerol, derived from de novo synthesis, and less triacylglycerol mass to be secreted. Cells incubated with both linoleic acid and 13-HODE together secreted less triacylglycerol mass than did cells incubated with linoleic acid alone. Less newly synthesized apoB and apoB mass were secreted by cells incubated with 13-HODE without altering the abundance of apoB mRNA. The fraction of newly synthesized apoB translocated into the secretory pathway of cells exposed to 13-HODE was significantly less than that observed in cells incubated with linolenic acid, suggesting that 13-HODE interfered with the assembly and secretion of triacylglycerol-rich lipoprotein particles.

Apolipoproteins B↗
PubMed1997

Adsorption Mechanism(s) of Poly(Ethylene Oxide) on Oxide Surfaces

Adsorption of poly(ethylene oxide) (PEO) on various oxides and the flocculation behavior of PEO-coated particles was investigated to elucidate the polymer adsorption mechanism(s). It was determined that strong Bronsted acid sites on the surface interact with the ether oxygen of PEO, a Lewis base, to induce adsorption and subsequent flocculation of the substrate particles. In general highly acidic oxides of the type MO3, M2O5, and MO2 are expected to adsorb and flocculate with PEO. Accordingly, MoO3, V2O5, and SiO2 were found to strongly adsorb PEO and exhibit flocculation. On the other hand, no significant adsorption was observed on oxides with a point of zero charge (pzc) greater than that of silica such as TiO2, Fe2O3, Al2O3- and MgO thereby indicating specificity of PEO-surface bonding site interactions. The other possible mechanisms of PEO adsorption such as complexation with adsorbed ions and electrostatic interactions with a positively charged surface were found not to play a major role in the PEO adsorption onto oxide particles. In this investigation, the adsorption and flocculation behavior of oxides with PEO and the underlying adsorption mechanism(s) are discussed. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Modulation of RNase H activity by modified DNA probes: major groove vs minor groove effects.

We have previously prepared ribozyme mimics and chemical nucleases from modified DNA containing pendant bipyridine and terpyridine groups. The ability of these modified DNA probes to support RNase H cleavage of complementary RNA is described. DNA/RNA duplexes were formed using DNA probes designed to deliver metal complexes via either the major groove or the minor groove of the duplex. The duplexes were treated with Escherichia coli RNase H. Modifications in the major groove produced the same RNA cleavage pattern as unmodified DNA probes. However, minor groove substituents inhibited RNA cleavage over a four-base region. Comparison was made with a DNA probe containing a 2'-OMe modification. Our results support enzyme binding in the minor groove of a DNA/RNA duplex. We do not observe cleavage directly across from the modified nucleoside. The RNA cleavage efficiency effected by RNase H and a DNA probe decreases as follows: unmodified DNA > or = C-5 modified DNA >> c2'-modified DNA > C1'-modified DNA. Results with 28-mer RNA substrates roughly parallel those obtained with a 159-mer RNA target. The differences observed between low and high MW RNA substrates can be explained by a much higher enzyme-substrate binding constant for the high MW target.

Base Sequence↗
PubMed1997

Interaction between anesthetics and the sodium-hydrogen exchange inhibitor HOE 642 (cariporide) in ischemic and reperfused rat hearts.

BACKGROUND: Sodium (Na+)-hydrogen (H+) exchange (NHE) inhibitors are effective cardioprotective agents. The potent NHE inhibitor HOE 642 (cariporide) is being evaluated clinically in high-risk patients, including those having coronary artery bypass. Volatile anesthetics are also cardioprotective, most likely via different mechanisms. The potential interaction between anesthetics and HOE 642 was investigated. METHODS: Electrically paced isolated rat hearts were perfused at constant flow. Left ventricular developed pressure and end-diastolic pressure were monitored as determinants of function. Hearts were subjected to 60 min each of total ischemia followed by reperfusion. Isoflurane (0.93 minimum alveolar concentration [MAC]), sevoflurane (1.03 MAC), or sufentanil (1.2 nM) was added 15 min before ischemia and throughout reperfusion, either alone or in combination with HOE 642 (5 microM). The effect of HOE 642 alone was also studied. At the end of reperfusion, hearts were freeze-clamped for subsequent determination of tissue metabolites. RESULTS: In control hearts, left ventricular developed pressure recovered to 40% of preischemia values, whereas left ventricular end-diastolic pressure increased by 650% after reperfusion. Sevoflurane, isoflurane, or HOE 642 alone significantly enhanced left ventricular developed pressure recovery to more than 90%, although recovery with HOE 642 was more rapid and accompanied by significantly reduced left ventricular end-diastolic pressure. HOE 642 plus volatile anesthetics produced additive effects, with left ventricular developed pressure recovering by more that 100%, although left ventricular end-diastolic pressure was not further reduced. Sufentanil had no effect in terms of developed pressure, but protection with HOE 642 was maintained. HOE 642 with or without volatile anesthetics also preserved adenosine triphosphate levels. CONCLUSIONS: Isoflurane, sevoflurane, and HOE 642 enhance ventricular recovery, but the effect of HOE 642 is also associated with reduced contracture and adenosine triphosphate preservation. A combination of the NHE inhibitor and either volatile agent confers additive and superior protection, which could be relevant for the establishment of ideal cardioprotective strategies during surgery.

Anesthetics, Inhalation↗
PubMed1997

Effects of dorzolamide hydrochloride 2% on the retinal circulation.

PURPOSE: To study the effect of a single dose of topical dorzolamide hydrochloride 2%, a carbonic anhydrase inhibitor, on the retinal circulation of normal subjects. METHODS: Measurements of the effect of dorzolamide hydrochloride were performed in 20 normal subjects using bidirectional laser Doppler velocimetry and monochromatic fundus photography. In a double-masked randomized design, one eye received one drop of dorzolamide hydrochloride 2 % and the other eye one drop of placebo. Vessel diameter, maximum erythrocyte velocity and volumetric blood flow rate were measured in a main temporal vein of each eye before the drops, and then, 2 h later. RESULTS: Following treatment, intraocular pressure decreased by 12% in the dorzolamide-treated eye (p = 0.0004, paired Student's t-test) and by 4% in the placebo-treated eye, p = 0.04). No significant changes in venous diameter, maximum erythrocyte velocity, and volumetric blood flow rate were observed in the dorzolamide-treated eyes (0.6%, 2.6% and 1.4%, respectively) or the placebo-treated eyes (1%, 3.7% and 1.6%, respectively). CONCLUSIONS: A single drop of dorzolamide hydrochloride does not cause any significant change in any of the hemodynamic parameters measured. With the variability of our measurements, we have about 89% power to detect average 10% change in volumetric blood flow rate if significance testing is performed at p = 0.05 level.

Adult↗
PubMed1997

Inhibition of apolipoprotein B secretion by IL-6 is mediated by EGF or an EGF-like molecule in CaCo-2 cells.

Small intestinal mucosal inflammation observed in celiac disease is associated with the local release of growth factors and various cytokines. In a previous study, we investigated the effect of various cytokines on triacylglycerol and apoB secretion by CaCo-2 cells and observed that TNF-alpha, IL-1 beta, and particularly IL-6, decreased apolipoprotein (apo) B and triacylglycerol secretion. In this study, we explored possible mechanisms to explain the inhibitory effect of IL-6 on apoB secretion. IL-6, 10 ng/mL, added to the basolateral medium of CaCo-2 cells grown on semi-permeable filters, decreased apoB secretion by 42%. Adding a blocking monoclonal antibody (mAb 528) to the EGF receptor completely prevented this effect. IL-6 decreased the amount of EGF receptor protein and the binding of iodinated EGF to its receptor by 50% and 30%, respectively. Incubation of cells with various ligands to the EGF receptor, such as EGF, TGF-alpha, HB-EGF, and amphiregulin, also decreased apoB secretion. Inhibition of apoB secretion by EGF was prevented by the mAb 528 or an EGF neutralizing antibody. In a dose-dependent manner, the neutralizing antibody to EGF prevented the decrease in secretion of apoB, triacylglycerol mass, and cell-surface binding of labeled EGF caused by IL-6. Similar to the effects of IL-6, EGF decreased the secretion of triacylglycerol mass and the synthesis and secretion on newly synthesized apoB. The results suggest that, in CaCo-2 cells, IL-6 causes the release of EGF or an EGF-like molecule. By binding to cell surface EGF receptors, the molecule then causes a decrease in triacylglycerol and apoB secretion.

Antibodies, Monoclonal↗
PubMed1996

Cloning, expression, and chaperone-like activity of human alphaA-crystallin.

One of the major protein components of the ocular lens, alpha-crystallin, is composed of alphaA and alphaB chain subunits that have structural homology to the family of mammalian small heat shock proteins. Like other small heat shock proteins, alpha-crystallin subunits associate to form large oligomeric aggregates that express chaperone-like activity, as defined by the ability to suppress nonspecific aggregation of proteins destabilized by treatment with a variety of denaturants including heat, UV irradiation, and chemical modification. It has been proposed that age-related loss of sequences at the C terminus of the alphaA chain subunit may be a factor in the pathogenesis of cataract due to diminished capacity of the truncated crystallin to protect against nonspecific aggregation of lens proteins. To evaluate the functional consequences of alpha-crystallin modification, two mutant forms of alphaA subunits were prepared by site-directed mutagenesis. Like wild type (WT), aggregates of approximately 540 kDa were formed from a tryptophan-free alphaA mutant (W9F). When added in stoichiometric amounts, both WT and W9F subunits completely suppressed the heat-induced aggregation of aldose reductase. In contrast, subunits encoded by a truncation mutant in which the C-terminal 17 residues were deleted (R157STOP), despite having spectroscopic properties similar to WT, formed much larger aggregates with a marked reduction in chaperone-like activity. Similar results were observed when the chaperone-like activity was assessed through inhibition of gamma-crystallin aggregation induced by singlet oxygen. These results demonstrate that the structurally conservative substitution of Phe for Trp-9 has a negligible effect on the functional interaction of alphaA subunits, and that deletion of C-terminal sequences from the alphaA subunit results in substantial loss of chaperone-like activity, despite overall preservation of secondary structure.

Aldehyde Reductase↗
PubMed1996

Electrophoretic and isoelectric focusing analysis of human recombinant alpha 2-HS glycoprotein produced in insect cells: analysis of the post-translational events.

Alpha 2-HS glycoprotein (AHSG) is a human serum glycoprotein synthesized by liver cells. It is a natural inhibitor of the insulin receptor tyrosine kinase activity. We produced this protein in insect cells by using a recombinant baculovirus expressing the whole coding sequence of the protein. By analyzing AHSG on isoelectric focusing and on sodium dodecyl sulfate (SDS) gels, followed by immunoblot, AHSG produced in insect cells was found to be phosphorylated and to possess the connecting peptide between the A and the B chains. The same features were found in the protein produced by Hep3B, a human liver cell line that synthesizes AHSG. By contrast, no phosphorylation could be detected in AHSG present in normal human plasma, and the connecting peptide was clipped. As the protein produced in insect cells is active on insulin receptors, in contrast to the plasma protein, our results suggest that the biological activity of the protein may be associated with its single chain form together with its phosphorylation.

Amino Acid Sequence↗
PubMed1996

Acute varicella hepatitis in human T-cell lymphotrophic virus types I and II infection.

Varicella (chicken pox) is a common viral infection in children and generally runs a benign course. However, in adults, and especially in immunocompromised subjects such as those on immunosuppressant therapy or with AIDS, varicella infection is particularly severe and is associated with the formation of hemorrhagic skin lesions and visceral involvement. These patients are at an increased risk of developing varicella hepatitis, which frequently results in fulminant hepatic failure and death. In the present report, we describe for the first time the course of disease and the histological appearance of varicella hepatitis in a patient infected with the human T cell lymphotropic viruses (HTLV) I and II; these viruses have many characteristics in common with the human immunodeficiency virus (HIV). Our patient had a relatively benign illness, suggesting that varicella infection in the presence of HTLVI and II may not run as severe a course as it does in patients with HIV infection.

Acyclovir↗
PubMed1996

Reproductive Performance and Three-Dimension-Ultrasound Volume Determination of Polycystic Ovaries after Laparoscopic Ovarian Drilling

Laparoscopic treatment of polycystic ovaries is a less invasive technique than ovarian wedge resection by laparotomy and is associated with less adhesion formation. Furthermore, the results appear to be superior. The purpose of the current study was to determine the changes in the ovarian volume and the reproductive outcome after laparoscopic treatment of polycystic ovaries. We studied 34 women with polycystic ovary syndrome (PCOS) who failed to ovulate with clomiphene and who subsequently underwent laparoscopic ovarian drilling. A standard procedure was done by a single surgeon using an insulated needle electrode. In six patients, ultrasound examination was performed to determine three-dimensional volume before surgery, and 1 week and 3 weeks postoperatively. Preoperative volume was 12.2 &plusmn; 1.8 cm3 and 1 week after surgery it was 13.6 &plusmn; 1.5 cm3. The ovarian volume 3 weeks after surgery (6.9 &plusmn; 1.3 cm3) was significantly smaller than that before surgery (p <0.05). Ovulation after the procedure occurred in 30 women (88.2%). Using life table analysis, the cumulative probability of conception at 12-month follow-up was 70% (median 8.1 mo). Two patients (6%) who did not ovulate with gonadotropin previously refused further expectant treatment after surgery and conceived in the first cycle of gonadotropin treatment. Aside from these women, the majority of pregnancies (76%) occurred spontaneously, and 18% conceived with clomiphene. We observed for the first time that there is a temporary swelling of the ovary after laparoscopic ovarian drilling. Subsequently, the volume decreases to the size smaller than the preoperative volume. Laparoscopic treatment of polycystic ovaries in women with PCOS who fail clomiphene therapy is associated with an ovulation rate of 88.2% and a pregnancy rate of 70% at 12-month follow-up.

Journal Article↗
PubMed1995

Effects of meso-2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate on beryllium-induced biochemical alterations and metal concentration in male rats.

The effects of two chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane 1-sulfonate (DMPS) on the mobilization, distribution, hepatic and hematopoietic toxicity of beryllium were compared in male rats exposed to beryllium. Animals were exposed to beryllium nitrate (0.5 mg/kg, orally, daily 5 days/week) for 21 days. Twenty-four hours after the last dose they were injected with a chelating agent (DMSA or DMPS) (25 or 50 mg/kg, twice daily for 5 days). The administration of DMSA and DMPS at a dose of 50 mg/kg marginally elevated the fecal excretion of beryllium. DMPS was effective in depleting beryllium from the liver, spleen and kidneys. However, DMPS (50 mg/kg) results in the redistribution of beryllium to blood. Beryllium-induced inhibition of hepatic alkaline phosphatase and hepatic adenosine triphosphatase (ATPase) were restored considerably with the chelating agents. Also, hepatic and renal histopathological lesions were less marked in rats treated with DMPS (50 mg/kg) compared with those treated with beryllium per se and DMSA. These effects were more prominent at the 50-mg/kg dose of chelating agents than at 25 mg/kg. These results suggest that treatment with DMPS has some beneficial effects in experimental beryllium intoxication.

Animals↗
PubMed1995

The effect of nicotine on in vitro sperm motion characteristics.

UNLABELLED: PURPOSE AND STUDY PLAN: Men who are habitual smokers tend to have poor semen quality. We studied the effect of nicotine on sperm motility in vitro. Spermatozoa from 13 normal fertile nonsmoking donors, washed free of seminal plasma, were treated with medium alone (control); and, 10 mM, 5 mM, 1 mM and 0.1 mM nicotine (concentrations estimated to approximate residual concentrations of nicotine in the testes of heavy smokers). Computerized sperm motion analysis (CASA) was done at 2, 4, 6 and 24 h after incubation. RESULTS: Sperm motility, beat/cross frequency, linearity and maximum anterior lateral head displacement (ALH max.) were significantly decreased across nominal dosages (P < 0.001 by repeated measures analysis of variance). Of the concentrations tested, 0.1 mM had no effect; 1 mM significantly decreased sperm motility (P = 0.003) and linearity (P = 0.02); 5 mM decreased the beat frequency (P = 0.001) and linearity (0.02); and 10 mM markedly decreased motility (P = 0.0001), beat frequency (P = 0.0002), linearity (P = 0.02) and ALH max. (P = 0.02). The interactions between dose and time were insignificant. CONCLUSION: Nicotine at concentrations of > or = 1 mM significantly decreased sperm motion characteristics after different periods of incubation, whereas 0.1 mM concentration had the least effect.

Adult↗