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Biomedical subjects

R Agarwal

Publications and source records attributed to R Agarwal.

At least 307 records · Page 17Linked to original sources
PubMed1992

Purification and molecular characterization of beta-naphthoflavone-inducible cytochrome P-450 from rat epidermis.

This study was designed to characterize epidermal cytochrome P-450 (P-450) induced by skin application of beta-naphthoflavone (beta-NF). Topical application of beta-NF (40 mg/kg) to rats resulted in a 2.6-times increase in epidermal P-450 content and a 3--14-times increase in epidermal monooxygenase activities. The purified epidermal P-450 showed a major band at 54 kDa on SDS-PAGE, which comigrated with hepatic P-4501A1 and cross-reacted with monoclonal and polyclonal antibodies specific to P-4501A1. The specific content of purified epidermal P-450 was 1.53 nmol/mg protein, representing 42-times purification. HPLC analysis of the purified epidermal P-450 showed similar elution profile and retention time as that of hepatic P-4501A1. The purified preparation efficiently catalyzed-benzo(a)pyrene hydroxylation when reconstituted with purified NADPH--P-450 reductase and phospholipid. Peptide fingerprint analysis of the purified epidermal P-450 and hepatic P-4501A1 showed similar monoclonal antibody 1-7-1 reacting epitopes. Partial N-terminal amino acid sequence analysis of purified epidermal P-450 showed complete homology with the known sequence of P-4501A1. Similarly, HPLC analysis of tryptic digest of purified epidermal P-450 and hepatic P-4501A1 showed identical peptide peaks with comparable retention times. N-terminal amino acid sequence analysis of three randomly selected tryptic peptides showed complete homology with the known sequence of P-4501A1. These results indicate that rat epidermal P-450 induced by beta-NF is similar to hepatic P-4501A1.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

Photodynamic therapy of chemically- and ultraviolet B radiation-induced murine skin papillomas by chloroaluminum phthalocyanine tetrasulfonate.

Photodynamic therapy (PDT) of cancer combines irradiation of tumors with visible light following selective uptake of the photosensitizer by the tumor cells. PhotofrinR-II (Pf-II) is the only photosensitizer which is in clinical use in PDT, whereas chloroaluminum phthalocyanine tetrasulfonate (AlPcTS) has also shown promise in preclinical studies. In most such studies, the effectiveness of the photosensitizers has been assessed in implanted tumor model systems rather than in model systems where tumors are allowed to grow in their own connective tissue matrix. In this study the pharmacokinetics, tumor ablation capability and cutaneous photosensitization response of AlPcTS have been assessed in mice bearing chemically- and ultraviolet B radiation (UVB)-induced benign skin papillomas. When tumor-bearing animals were injected intraperitoneally with AlPcTS (5 mg/kg body wt), maximum tumor:normal skin ratio of 2.4 was observed at 48 h, at which time the mice were irradiated within the absorption spectrum of the photosensitizer. In tumor ablation studies with SENCAR mice bearing chemically-induced skin tumors, AlPcTS resulted in greater than 80% ablation in tumor volume at 20 days post-irradiation. In cutaneous photosensitization response, AlPcTS produced only transient effects (no effect after 24 h) in SENCAR mice. Pharmacokinetics data, tumor ablation effects and cutaneous photosensitization response of AlPcTS were comparable in SKH-1 hairless mice bearing UVB-induced skin tumors. Our data indicate that AlPcTS produces significant photodynamic effects towards the ablation of murine skin tumors, and that it does not produce prolonged cutaneous photosensitivity.

Animals↗
PubMed1992

Changing spectrum of clinical and laboratory profile of infective endocarditis.

The clinical profile of 28 consecutive patients admitted with infective endocarditis (IE) between 1987 and 1988 was studied. There were 21 males and seven females with a mean age of 24 +/- 11 years. Rheumatic heart disease (RHD) was the commonest underlying disease (68%) followed by congenital heart disease (CHD). Mitral regurgitation with aortic regurgitation were the commonest valvular lesions (47%) in those with RHD while ventricular septal defect was the commonest (43%) in those with CHD. A younger age of onset, complicated course and high mortality were seen in these six patients with acute IE. Persistently positive blood cultures during life or at autopsy were obtained in 21%. Strep viridans was the commonest isolate and was often resistant to streptomycin. 2D echocardicgram revealed vegetations in 96% of patients, the aortic valve (39%) being more commonly affected than the mitral valve (11%). ESR of more than 20 mm drop 1st hour (Wintrobe) was seen in 96%. Thrombophlebitis was a common complication of therapy and cloxacillin the commonest drug implicated. A mortality of 21% as a result of refractory congestive heart failure (CHF) (50%), uncontrolled sepsis (33%) and embolic events (17%) was seen. A rising incidence of culture negative IE, combined aortic and mitral valve disease and CHF is noted.

Adolescent↗
PubMed1991

Identification of the site of photocross-linking formed in the absence of magnesium nucleotide from SH2 (Cys-697) in myosin subfragment 1 labeled with 4'-maleimidylbenzophenone.

The site of photocross-linking between Cys-697 (SH2), prelabeled with 4'-[14C]maleimidylbenzophenone, and the 50-kDa segment of myosin S1 on irradiation in the absence of nucleotide has been determined by isolation of the 20-50-kDa adduct and subsequent tryptic proteolysis. Isolation and partial sequencing of the radioactively labeled peptide indicate that the site of cross-linking is Arg-239. This result indicates that, in the absence of nucleotide, Arg-239 resides at about 1.0 nm from SH2 and, on the basis of the recent work of Sutoh and Hiratsuka (Sutoh, K. and Hiratsuka T. (1988) Biochemistry 27, 2964-2969) places Arg-239 at no more than 1.45 nm from either Lys-184 or Lys-189 of the nucleotide-binding "glycine-rich" loop prior to the binding of nucleotide.

Adenosine Diphosphate↗
PubMed1991

The flickery block of ATP-dependent potassium channels of skeletal muscle by internal 4-aminopyridine.

We have examined the effects of 4-aminopyridine (4-AP) on single ATP-dependent potassium channels in patches excised from frog skeletal muscle. 4-AP applied to the internal face of the membrane caused a flickery block. We could not detect any flickery block when 10 mM 4-AP was applied to the external surface of the membrane. The reduction in mean unitary current by internal 4-AP was consistent with 1:1 binding with a Kd of 3.3 mM at 0 mV. The block was voltage-dependent, increasing with depolarization with an effective valency of 0.57. Rate constants for blocking and unblocking by 4-AP were obtained by fitting beta functions to the distribution of current amplitudes. Both rate constants were voltage-dependent. At 0 mV they were 17 mM-1 ms-1 and 61 ms-1. Simulation of the block using these rate constants produced a flickery block very similar to that observed experimentally.

4-Aminopyridine↗
PubMed1991

Seroepidemiology of Helicobacter pylori infection in India. Comparison of developing and developed countries.

Helicobacter pylori (previously Campylobacter pylori) is now accepted as the major cause of type B gastritis and thus what is known about the epidemiology of type B gastritis can reasonably be transferred to H. pylori. We used a specific ELISA for anti-H. pylori IgG to study the prevalence of H. pylori infection in a population of lower socioeconomic class from Hyderabad, India. The results from India were compared to studies from other parts of the world. Two hundred thirty-eight individuals ages 3 to 70 participated. The frequency of H. pylori infection increased with age (P less than 0.01) and was greater than 80% by age 20. H. pylori infection was present in 79% of the population studied; there was no gender-related difference in prevalence of H. pylori infection. IgG antibody against hepatitis A (HAV) was rapidly acquired in Hyderabad; in a subset of 58 children between the ages of 3 and 21 tested, the frequency of anti-HAV was 98.2%. The prevalence of H. pylori infection increases with age in both developed and developing countries. The high age-specific prevalence of H. pylori infection in developing countries is probably a reflection of the lower socioeconomic level of those areas.

Developing Countries↗
PubMed1991

Temperature-induced changes in the flexibility of the loop between SH1 (Cys-707) and SH3 (Cys-522) in myosin subfragment 1 detected by cross-linking.

The ability of dibromobimane to cross-link SH1 (Cys-707) in the 21-kDa C-terminal segment to SH3 (Cys-522) in the 50-kDa middle segment of the myosin S1 heavy chain has been examined as a function of nucleotide binding and temperature. The results obtained indicate that, while the reagent rapidly reacts with SH1 at both 25 and 4 degrees C, its ability to cross-link to SH3 is highly dependent on temperature. At 25 degrees C, substantial cross-linking from monofunctionally labeled SH1 to SH3 occurs, in agreement with recent work of Mornet, Ue, and Morales (1985, Proc. Natl. Acad. Sci, USA 82, 1658-1662) and of Ue (1987, Biochemistry 26, 1889-1894) and with their conclusion that a loop, allowing SH1 and SH3 to reside at the cross-linking span of dibromobimane, preexists in the protein. At 4 degrees C, however, negligible amounts of cross-linking are observed whether or not a nucleotide is present, despite indications that SH1 is labeled rapidly by the reagent at this temperature. The inability to form this cross-link is not due to an alternate cross-link between monofunctionally labeled SH1 and another thiol in the 21-kDa segment. These results indicate that this loop exists at 25 degrees C and does not exist (or exists only transiently) at the lower temperature.

Adenosine Diphosphate↗
PubMed1991

A comparative study of fracture strength, ultrasonic properties and chemical constituents of kidney stones.

Ultrasonic properties of kidney stones were studied with a double-probe-through-transmission technique, the micro hardness was studied using the Viker indentation method and the chemical composition studied using an X-ray technique. The microhardness is found to vary with chemical composition as well as ultrasonic propagation velocity. The comparative results obtained are discussed in detail.

Hardness Tests↗
PubMed1991

Antimutagenic and antitumorigenic activities of nordihydroguaiaretic acid.

Nordihydroguaiaretic acid (NDGA), which occurs in the resinous exudates of many plants is used as an antioxidant in fats and oils. In this study we show that NDGA inhibited the mutagenicity of methyl methanesulfonate, benzo[a]pyrene (BP), 2-aminofluorene, and aflatoxin B1 in Salmonella typhimurium strain TA100 or TA98 in the absence and presence of rat hepatic microsomal activation system. The addition of NDGA during and after nitrosation of methylurea (MU) resulted in a dose-dependent inhibition of mutagenicity induced by nitrosation products of MU. In a two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) as tumor promoter, pretreatment of animals with NDGA prior to DMBA application, afforded significant protection against skin tumorigenicity in female SENCAR mice. In additional studies, skin application of NDGA also inhibited the binding of topically applied [3H]BP and [3H]DMBA to epidermal DNA. When assessed in the anti-tumor promotion protocol, pretreatment of animals with NDGA before each application of TPA in DMBA-initiated mouse skin, resulted in 72% decrease in the total number of tumors when compared to non-NDGA pretreated animals. The possible mechanism(s) of the antimutagenic and anti-tumorigenic activities may be due to the multiple effects of NDGA as inhibitor of the carcinogen metabolism and DNA-adduct formation, scavenger of carcinogen free radicals, and as inhibitor of TPA-induced ornithine decarboxylase activity.

Animals↗
PubMed1991

The morphology of coronary arterial dissection occurring subsequent to angioplasty and its influence on acute complications.

We reviewed the records of 402 patients undergoing percutaneous transluminal coronary angioplasty to identify factors predicting an ischemic event with arterial disruption during an otherwise uncomplicated angioplasty. Major dissection of the coronary arteries without immediate occlusion was found in 25 patients, who exhibited 28 dissected lesions. Dissections were classified into 2 types: those producing a continuous extraluminal and parallel filling tract, and those with a continuous parallel filling tract extending into and compromising the lumen. Ischemic complications (defined as myocardial infarction, the need for repeat angioplasty, or coronary arterial bypass surgery) occurred in 6 patients (24%) within 24 hours of the completion of the procedure. The remaining 19 patients had an uncomplicated hospital course. Acute ischemic complications following dissection correlated with the percentage of luminal compromise 50 +/- 0% in those with complications as opposed to 17 +/- 21% in those without: P less than 0.001) and the development of dissection producing a filling tract which compromised at least half the lumen (100% in those with complications versus 9.1% in those without: P less than 0.001). There was a trend towards an increase in ischemic complications in patients with proximal and eccentric lesions. We conclude that patients who develop dissections which produce significant luminal compromise after an otherwise uncomplicated angioplasty are at a high risk of developing an acute ischemic complication within 24 hours of the procedure.

Acute Disease↗
PubMed1991

Involvement of singlet oxygen in chloroaluminum phthalocyanine tetrasulfonate-mediated photoenhancement of lipid peroxidation in rat epidermal microsomes.

In recent studies chloroaluminum phthalocyanine tetrasulfonate (AlPCTS) has been shown to be an effective photosensitizer for the tumor necrosis in a modality known as photodynamic therapy, but the mechanism of photodynamic effect of AlPCTS is poorly understood. In this study, in vitro incubation of rat epidermal microsomes with AlPCTS followed by exposure to red light (approximately 675 nm) resulted in an increase in ADP/iron-supported lipid peroxidation, a measure of membrane damage. This photodestructive effect was found to be dependent on both the duration of light exposure and the dose of AlPCTS. Studies employing various quenchers of reactive oxygen species revealed that scavengers of singlet oxygen (histidine, 2,5-dimethylfuran, beta-carotene and sodium azide) afforded substantial protection (up to 90%) of photoenhancement whereas the scavengers of hydrogen peroxide (catalase), superoxide anion (superoxide dismutase), and hydroxyl radical (sodium benzoate, mannitol and ethanol) were ineffective in this regard. Our data indicate that AlPCTS-mediated photodestruction mainly involves a type II reaction via singlet oxygen formation and suggest that the latter could play a significant role in the tumor necrosis evoked by AlPCTS and light.

Animals↗
PubMed1991

Inhibition of mouse skin tumor-initiating activity of DMBA by chronic oral feeding of glycyrrhizin in drinking water.

Licorice (Glycyrrhiza glabra), a Mediterranean plant, has been used as an antidote, demulcent, and elixir folk medicine for generations in China. The main water-soluble constituent of licorice is glycyrrhizin (GL), which has been shown to possess several pharmacological properties. In this study, we show that oral feeding of GL to Sencar mice resulted in substantial protection against skin tumorigenesis caused by 7,12-dimethyl-benz [a]anthracene (DMBA) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. The latent period prior to the onset of tumor development was considerably prolonged in GL-fed animals compared with animals not fed GL and resulted in significant decrease in the number of tumors per mouse, during and at the termination of the experiment. Oral feeding of GL in drinking water also resulted in inhibition in the binding of topically applied [3H]benzo[a]pyrene and [3H]DMBA to epidermal DNA. The possible mechanism(s) of the antitumor-initiating activity may be due to the involvement of GL as inhibitor of the carcinogen metabolism followed by DNA adduct formation. Our results suggest that GL possesses considerable antitumorigenic activity and could prove useful in protecting some forms of human cancer.

9,10-Dimethyl-1,2-benzanthracene↗