Search PubMed⌕ Search

Biomedical subjects

R Agarwal

Publications and source records attributed to R Agarwal.

At least 235 records · Page 13Linked to original sources
PubMed1996

Influence of nicotine on myocardial stiffness and fibrosis during chronic ethanol use.

Cardiomyopathy related to ethanol abuse is often accompanied by cigarette use. To examine if the major cardioactive component may intensify the abnormal function and composition induced by chronic ethanol, nicotine was administered orally, 2.5 mg bid, to a canine model receiving 36% of calories as ethanol for 6 months (group III). These animals were compared with group II receiving ethanol alone, group IV on nicotine alone, and controls (group I). In the intact, ventilated, anesthetized dog, left ventricular pressures and volumes were measured before and after dextran infusion and related to left ventricular collagen alterations. Basal heart rate, aortic pressure, and ejection fraction were comparable with controls. End-diastolic pressure and diastolic chamber stiffness (KPV) were significantly higher in the basal state and during dextran infusion in the three experimental groups, compared with group I. The increment was largest in the ethanol-nicotine group. Analysis of left ventricular myocardium revealed a rise of collagen concentrations in all three experimental groups, with an interstitial distribution on histochemical examination. Moreover, determination of advanced glycosylation endproducts, as a measure of alterations in collagen cross-links, revealed higher concentrations versus controls. The greater increase of diastolic stiffness in the nicotine-ethanol group occurred despite a similar concentration of fluorescent products as group II. Because the former had a larger increase of collage concentration, total cross-linked collagen content was presumably greater after the combined use of nicotine-ethanol. Thus, nicotine in relatively high dose when combined with ethanol, elicited a modest further increase in the left ventricular chamber stiffness and collagen concentration.

Administration, Oral↗
PubMed1996

Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.

Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.

Animals↗
PubMed1996

Cytochrome P-450 and drug development for skin diseases.

Cytochromes P-450 (CYPs) are the most versatile and important class of drug-metabolizing enzymes which are induced in mammalian skin in response to xenobiotic exposure. CYPs are the target of special interest in the development of pharmaceuticals for skin diseases because most, if not all, drugs available in the armamentarium of the dermatologist are substrates, inducers or inhibitors of this enzyme family. The functional significance of drug metabolism in the skin and the implication of CYP in skin pathology and therapy is an area for future investigation. A detailed insight into the mechanism of action of various cutaneous CYPs, being capable of modulating the drug bioavailability, will be helpful in the development of better strategies for novel therapy against constantly increasing skin disorders. This brief review puts some of these perspectives together and suggests additional research in the area of CYPs with regard to their expression and modulation in mammalian skin as well as their implication in dermatological disorders and the therapy of skin diseases.

Aryl Hydrocarbon Hydroxylases↗
PubMed1996

Effects of hemorrhagic hypotension on cerebral blood flow and perfused capillaries in newborn pigs.

We examined the effect of hemorrhagic hypotension on cerebral blood flow and perfused capillaries in newborn pigs, 2-10 days old. Cerebral blood flow was measured by using radioactive microspheres, perfused capillaries were determined by infusing a plasma marker, fluorescein isothiocyanate (FITC) - dextran (molecular mass 147,000 Da), and total capillaries were determined by staining with alkaline phosphatase. Rapid removal of 66 +/- 16 mL of blood resulted in a fall in mean blood pressure from 68 +/- 6 to 31 +/- 4 mmHg (1 mmHg = 133.3 Pa), an increase in heart rate from 137 +/- 18 to 240 +/- 34 beats/min, and a drop in arterial pH from 7.33 +/- 0.05 to 7.23 +/- 0.07. PCO2 was controlled by mechanical ventilation (36 +/- 4 mmHg before hemorrhage and 35 +/- 5 mmHg after hemorrhage) and PO2 remained stable (89 +/- 11 mmHg before hemorrhage and 94 +/- 10 mmHg after hemorrhage). Blood flow (n = 9) did not fall significantly in any brain region after hemorrhage. The percentage of perfused capillaries/mm2 (control, n = 7, hemorrhage, n = 6) was reduced in all brain regions during hypotension (cortex from 72 +/- 8 to 57 +/- 8%, cerebellum from 75 +/- 10 to 52 +/- 10%, and medulla from 76 +/- 8 to 51 +/- 9%). Similar results were seen for perfused capillary surface area We conclude that hemorrhagic hypotension resulted in a variable blood flow response with no significant reduction in cerebral blood flow but a reduction in perfused capillary number and surface area in all brain regions studied. We speculate that decreased capillary perfusion may be a contributing factor in diffuse neuronal injury after severe hemorrhagic hypotension.

Animals↗
PubMed1996

Anti-oxidant enzymes, gamma-glutamyl transpeptidase and lipid peroxidation in kidney of rats exposed to cigarette smoke.

Glutathione reductase (GR), glutathione peroxidase (GSH Px) and catalase (Cat) were determined in the kidneys of rats exposed to cigarette smoke for 3 months. Activity of the brush-border enzyme gamma-glutamyl transpeptidase (GGT), glutathione (GSH) and lipid peroxide levels (LPX) were also estimated in both, kidney homogenates and urine. Activities of GR, Cat, GGT and the levels of GSH were decreased in the kidney. However, the activities of GSH Px and LPX levels were increased. Urinary excretion of GGT, GSH and LPX were also higher. Fall in the activity of GR and rise in the activity of GSH Px, may perturb the reduced glutathione/oxidised glutathione ratio, which in turn could lead to increased LPX seen in chronic cigarette smoke exposure.

Animals↗
PubMed1996

Skin cancer chemoprevention.

Chemoprevention of cancer is a means of cancer control in which the occurrence of this disease, as a consequence of exposure to carcinogenic agents, can be entirely prevented, slowed, or reversed by the administration of one or several naturally occurring or synthetic agents. Thus, the chemoprevention of cancer differs from therapy in that the goal of prevention is to lower the rate of cancer incidence. Such chemopreventive agents are also known as anticarcinogens, and an ideal agent should have (i) little or no untoward or toxic effects, (ii) high efficacy against multiple sites, (iii) capability of oral administration, (iv) a known mechanism of action, (v) low cost, and (vi) human acceptance. With regard to naturally occurring agents, fruits, vegetables, and common beverages, as well as several herbs and plants, have been identified as rich sources of cancer chemopreventive agents. While a wide range of laboratory studies has identified many compounds, including several polyphenols, as cancer chemopreventive agents, in this article our main emphasis is on the cancer chemopreventive potential of a polyphenolic fraction isolated from green tea and silymarin, a flavonoid present in artichoke, against different stages of mouse skin multistage carcinogenesis. We also highlight studies related to retinoid effects on prevention of human skin cancers.

Animals↗
PubMed1995

Long-term culture of chronic myelogenous leukemia marrow cells on stem cell factor-deficient stroma favors benign progenitors.

Long-term culture of marrow from patients with chronic myelogenous leukemia (CML) has been reported to favor the outgrowth of bcr/abl- progenitor cells in some patients. We examined the effect of the presence of soluble or transmembrane forms of stem cell factor (SCF) in long-term cultures of CML marrow. CD34-enriched cells from CML patients in advanced chronic phase or accelerated phase were plated on immortalized fetal liver stromal cells from homozygous SCF-deficient SI/SI mice (SI/SI4) with or without the addition of soluble human SCF, SI/SI4 cells expressing high levels of the transmembrane form of human SCF (SI/SIh220), or primary human allogeneic stroma. Cells were removed from cultures and plated weekly in colony assays. The clonagenic cell output from cultures completely lacking SCF was lower over the first 2 to 3 weeks, but by 5 weeks was similar to the clonagenic cell output from the other culture conditions. Analysis of bcr/abl transcripts from individual colonies showed a lower percentage of malignant progenitors present in long-term cultures completely deficient in SCF than under the other culture conditions, particularly compared with primary human stroma-containing long-term cultures. SCF may specifically favor malignant versus benign progenitor cells present in the marrow of CML patients, and an abnormal proliferative response to SCF in very primitive cells may be an underlying defect in the pathophysiology of this disease.

Adult↗
PubMed1995

Antibody reactivity to the HRES-1 endogenous retroviral element identifies a subset of patients with systemic lupus erythematosus and overlap syndromes. Correlation with antinuclear antibodies and HLA class II alleles.

OBJECTIVE: To evaluate the correlation between the presence of antibodies to an endogenous retroviral element-encoded nuclear protein autoantigen, HRES-1, and the presence of other antinuclear antibodies and HLA class II alleles in patients with systemic lupus erythematosus (SLE) and overlap syndromes. METHODS: Antibody reactivities to native and recombinant proteins and synthetic peptides were assessed by counterimmunoelectrophoresis, enzyme-linked immunosorbent assay, and Western blotting. HLA class II alleles were determined by oligonucleotide typing. RESULTS: Forty-eight percent of the 153 patients with autoimmune disease, and 52% of the subgroup with SLE, had HRES-1 antibodies. In contrast, 3.6% of 111 normal donors, and none of 42 patients with the acquired immunodeficiency syndrome or 50 asymptomatic human immunodeficiency virus 1-infected patients, had HRES-1 antibodies. Chi-square analyses revealed a significant association between anti-HRES-1 and anti-RNP and an inverse correlation between HRES-1 and Ro/La autoantibodies in patients with SLE or overlap syndromes. Antigenic epitopes of HRES-1 and the retroviral gag-related region of the 70-kd protein component of U1 small nuclear RNP, which share 3 consecutive highly charged amino acids (Arg-Arg-Glu), an additional Arg, and functionally similar Arg/Lys residues, represent cross-reactive epitopes between the two proteins. Selective removal of HRES-1 antibodies from sera of HRES-1-seropositive/RNP-seropositive patients by absorption on recombinant HRES-1/glutathione-S-transferase-conjugated agarose beads had no effect on anti-RNP reactivities. A comparative multivariate analysis of HLA class II genes revealed a differential segregation of DQB1 alleles in HRES-1-seropositive versus HRES-1-seronegative patients (P = 0.04). While a relative increase of DQB1*0402 among HRES-1-seropositive patients was noted across ethnic groups (P = 0.02), a decrease of DQB1*0201 and DQB1*0301 was found in white HRES-1-seropositive patients (P = 0.04). CONCLUSION: Autoantibodies to HRES-1 are detectable in a distinct subset of patients with autoimmune disease, primarily in those who do not have antibodies to Ro and La. Anti-HRES-1 and anti-RNP reactivities are mediated by cross-reactive but separate antibody molecules. HLA-DQB genes, rather than HLA-DRB or DQA genes, may have a more significant influence on generation of these antinuclear autoantibodies.

Alleles↗
PubMed1995

In-hospital outcome of percutaneous transluminal coronary angioplasty for long lesions and diffuse coronary artery disease.

We performed coronary angioplasty on 151 long or diffuse lesions (120 long and 31 diffuse) in 141 patients (86% male, mean age 50 +/- 9 years). Long lesions were defined as lesions 11-20 mm in length and diffuse lesions as lesions longer than 20 mm, or three or more lesions in the same vessel. One or more adverse morphologic features were present in 131 (93%) lesions. Long balloons were used in 44%, significantly more often for diffuse disease (long lesions 39% and diffuse disease 64%; P = 0.004). Newer devices including the rotational atherectomy device (9 lesions), stents and perfusion balloons were employed in 18 (12%) lesions, more often for diffuse lesions (long lesions 8% vs. diffuse lesions 26%; P = 0.017). Lesion severity was comparable in the two groups (long lesions: 88 +/- 7%; diffuse lesions: 88 +/- 8%), but diffuse lesions were associated with significantly higher residual stenosis (long lesions: 6 +/- 8%; diffuse lesions: 12 +/- 13%, P = 0.01). Major complications occurred in five (3.5%) patients, including one death (0.7% mortality). The angiographic and clinical success rates for all patients were 99% and 96%, respectively, and were comparable for long and diffuse lesions. Judicious case selection and the use of long balloons and newer interventional devices permit coronary angioplasty for long lesions and diffuse disease with excellent success and a low risk of complications. Diffuse lesions are associated with more frequent use of long balloons and newer devices, especially rotational atherectomy and slightly higher residual stenosis as compared to long lesions.

Adult↗
PubMed1995

Inhibition of ras p21 membrane localization and modulation of protein kinase C isozyme expression during regression of chemical carcinogen-induced murine skin tumors by lovastatin.

We investigated the ras p21 membrane localization and the expression and activation of protein kinase C (PKC) isozymes in activated ras oncogene-containing tumors and assessed whether these events were related to tumor growth. We used 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted SENCAR mouse skin tumors, which were shown to contain Ha-ras oncogene activated by point mutation at codon 61, as an in vivo model for these studies. Compared with levels in epidermis, highly elevated levels of membrane-bound Ha-ras p21 were observed in growing tumors, which also showed strong expression and membrane translocation of PKC zeta and beta II and weak expression of PCK alpha. However, when ras p21 membrane localization was blocked in vivo in growing tumors by lovastatin, opposite results were evident. Compared with saline-treated animals, in which tumor growth continued, lovastatin-treated animals had significantly inhibited tumor growth, which led to tumor regression with concomitant inhibition of Ha-ras p21 membrane localization. These regressing tumors from lovastatin-treated animals also showed a decrease in the expression and membrane translocation of PKC zeta and beta II but increased expression of PKC alpha. Taken together, our results indicate that ras p21 membrane localization and the expression and activation of PKC zeta, beta II, and alpha may be the critical events in the regulation of the growth of tumors that contain activated ras oncogenes.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Efficacy of surfactant therapy in infants managed with CPAP.

Surfactant rescue therapy can be utilized effectively early in the course of respiratory distress syndrome (RDS) in infants weighing > 1,000 g and treated exclusively with continuous positive airway pressure (CPAP) therapy. Thirteen infants (BW, 1,774 +/- 580 g; GA, 31 +/- 3 weeks) comprising the CPAP/SURFACTANT group were compared with 12 infants (BW, 1,753 +/- 556 g; GA, 31 +/- 2 weeks) who comprised the intermittent mandatory ventilation (IMV)/surfactant group, and with 14 infants (BW, 1,776 +/- 332 g; GA, 32 +/- 2 weeks) treated with CPAP before surfactant was clinically available. A 5 mL/kg dose of Exosurf Neonatal (Burroughs-Wellcome) was administered to infants intratracheally when the FiO2 requirement reached 0.40 to maintain the PO2 above 50 torr. Infants in the CPAP/surfactant group were intubated solely for surfactant administration and extubated within 18 +/- 6 min of treatment. The CPAP/surfactant group was treated at a mean age of 12.3 +/- 9.3 h, and the IMV/surfactant group at 10.2 +/- 9.8 h. Alveolar-arterial oxygen gradient (AaDO2), oxygenation index (OI), and mean airway pressure (MAP) were determined immediately before and after surfactant therapy, and at comparable times for the CPAP-only group. A significant difference was found in pre-treatment AaDO2, OI and MAP between the CPAP/surfactant group and IMV/surfactant group, but not between the CPAP/surfactant group and the CPAP-only group. Similarly, a significant difference in AaDO2, OI and MAP continued post-treatment was noted. However, a significant difference was also found at this time between the CPAP/surfactant group and the CPAP-only group. In addition, a significant difference was noted in AaDO2 and OI pre- and post-treatment within each surfactant-treated group. Furthermore, in the CPAP-only group AaDO2 and OI actually worsened (212 +/- 70 vs. 239 +/- 68; 4.0 +/- 1 vs. 4.5 +/- 2, respectively). There was a significant reduction in the duration of oxygen therapy (3 +/- 2 vs. 5 +/- 2 vs. 4.5 +/- 2 days, respectively) as well as in the total days of hospitalization (30 +/- 10 vs. 42 +/- 15 vs. 43 +/- 12 days, respectively). We conclude that in this small group of infants surfactant administration was effective and safe. It appeared to improve the course of RDS and shorten the duration of oxygen exposure and days of hospitalization.

Combined Modality Therapy↗
PubMed1995

A rapid and convenient filter-binding assay for ras p21 processing enzyme farnesyltransferase.

Because it is the target for the development of anti-cancer agents, the mammalian cytosolic enzyme farnesyltransferase (FTase) has received significant attention in recent years. FTase catalyzes the transfer of a farnesyl group from farnesylpyrophosphate (FPP) to cysteine 185/186 at the carboxyl terminal end of ras proteins (ras p21), a reaction essential for the localization of ras p21 to the plasma membrane for their cellular functions including cell transformation in case of oncogenic ras p21. Here, we report the development of a rapid and convenient assay procedure for FTase using phosphocellulose paper which has a binding affinity for proteins. The FTase is assayed as the transfer of [3H]farnesyl group from [3H]FPP to the ras p21 at pH 7.4 and 37 degrees C in the presence of rat brain cytosol followed by the binding of radioactive farnesylated ras p21 to the phosphocellulose paper. The radioactivity associated with ras p21 bound to the phosphocellulose paper was determined by scintillation counting after soaking the paper in trichloroacetic acid and washing with distilled water. Utilizing [3H]FPP and recombinant Ha-ras p21 as substrates in the reaction, the FTase followed Michaelis-Menten kinetics with Km values of 1.0 and 7.69 microM for respectively [3H]FPP and recombinant Ha-ras p21. The method reported here has the advantages over the other published assay procedures of being rapid, convenient and economical, and can be successfully used for the basic assaying of FTase in different organs and distinct species and for the screening of novel inhibitors of FTase.

Alkyl and Aryl Transferases↗
PubMed1995

Effects of balloon compliance on angiographic and clinical outcomes after PTCA.

Eighty patients underwent percutaneous transluminal coronary angioplasty (PTCA) for 109 lesions. Comparison was done between two groups based on balloon compliance. The groups were comparable in their baseline characteristics. The mean inflation pressure used with compliant balloons was significantly higher; other procedural variables were not different. The occurrence rates of intimal tears and coronary dissections were not significantly different. The rates of side branch occlusions, myocardial infarction, redo PTCA or coronary stenting and death were low and similar, and likewise unaffected by balloon material. We conclude that the occurrence of adverse outcomes after PTCA is unrelated to balloon material compliance.

Angioplasty, Balloon, Coronary↗