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Biomedical subjects

R Mathew

Publications and source records attributed to R Mathew.

At least 19 recordsLinked to original sources
PubMed1992

Murine mucosal T cells have VIP receptors functionally distinct from those on intestinal epithelial cells.

Reports suggest that vasoactive intestinal peptide (VIP) binds to lymphocytes and modulates immune responses. The intestines are richly innervated with VIP-producing nerves. Thus, VIP from nerves or other sources may participate in mucosal immunoregulation. To explore this hypothesis further, murine intestinal mucosal inflammatory cells were scrutinized for functional VIP receptors. An [125I]VIP competitive binding assay characterized VIP receptors. Unfractionated lamina propria inflammatory cells bound [125I]VIP specifically. This binding was abrogated by T cell depletion. The VIP receptor on lamina propria T cells was of a single class with a Kd of 9.08 x 10(-9) M. It bound PHI and other peptide analogs poorly. The intestinal epithelial cell had a high-affinity VIP receptor (Kd 4.17 x 10(-10) M) that bound one VIP analog with moderate affinity. Both VIP and ConA stimulated mucosal inflammatory cells to release interleukin-5 (IL-5). Mucosal inflammatory cells depleted of T cells did not release IL-5 in response to VIP or ConA. It is concluded that: (1) some murine mucosal T lymphocytes have VIP receptors that may be distinct from those displayed on mucosal epithelial cells; (2) VIP affects mucosal T lymphocyte function.

Animals↗
PubMed1992

Activity staining of endoglucanases in polyacrylamide gels.

The endoglucanases of Penicillium funiculosum were analyzed for the presence of multiple forms using a modified version of the Congo red method. Postelectrophoretic slab gels were directly incubated in a solution of carboxymethylcellulose for a period as short as 15 min and then the activities were visualized by staining with Congo red. Ten distinct bands of clearances were obtained indicating the presence of at least as many multiple forms.

Acrylic Resins↗
PubMed1992

Role of cGMP mechanisms in response of rat pulmonary arteries to hypoxia.

We have demonstrated previously that in response to hypoxia, isolated rat pulmonary arteries show an initial endothelium-dependent relaxation followed by an endothelium-independent transient contraction. In the presence of increased extracellular Ca2+, both of these responses were enhanced in endothelium-intact arteries. Nitro-L-arginine, a blocker of the biosynthesis of endothelium-derived relaxing factor (EDRF), abolished the initial endothelium-dependent relaxation and Ca(2+)-induced enhancement of hypoxic contraction in endothelium-intact arteries but did not alter responses in endothelium-denuded vessels. Inhibition of prostaglandin formation with indomethacin had no effect on the hypoxia-elicited responses. Preincubation with LY 83583, an inhibitor of guanylate cyclase activation, abolished the initial hypoxia-elicited relaxation and subsequent contraction. M & B 22948, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, decreased tone under O2 but not under N2, causing an apparent enhancement of the contraction to hypoxia. Thus the modulation of hypoxic responses by the endothelium is dependent on changes in EDRF production, and a decrease in smooth muscle cGMP not involving an EDRF mechanism appears to mediate the endothelium-independent hypoxic contraction observed in the isolated rat pulmonary artery.

Aminoquinolines↗
PubMed1991

Quantitation of microsomal alpha-hydroxylation of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is activated to DNA alkylating species via two different alpha-hydroxylation pathways. Methylene hydroxylation leads to DNA methylation, whereas methyl hydroxylation yields DNA pyridyloxobutylation. We have developed a high-pressure liquid chromatography assay utilizing radiochemical detection that permits the determination of the extent of metabolism through each pathway in microsomal preparations. Levels of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) were used to measure the extent of methyl hydroxylation, whereas levels of the aldehyde, 4-oxo-1-(3-pyridyl)-1-butanone (OPB), were used to quantify the extent of methylene hydroxylation. Incubations of [5-3H]NNK with microsomes and cofactors were conducted in the presence of 5 mM sodium bisulfite to trap the reactive OPB. The inclusion of bisulfite did not affect the rate of NNK metabolism. Trapping the aldehyde also inhibited its further oxidation to the corresponding acid or reduction to HPB. Furthermore, the conversion of HPB to OPB made only a minor contribution to the OPB levels under our incubation conditions. Analysis of incubation mixtures containing [5-3H]NNK, cofactors, and either A/J mouse liver or lung microsomes demonstrated that OPB was a significant metabolite of NNK. The OPB:HPB ratio was greater in liver (1.5) than in lung (0.2-1) microsomal preparations. Apparent Km values for OPB and HPB formation in lung microsomes were 23.7 and 3.6 microM, respectively, whereas the corresponding values for liver microsomes were 19.1 and 73.8 microM, respectively. These data are consistent with the involvement of more than one cytochrome P-450 isozyme in the activation of NNK to DNA reactive species.

Animals↗
PubMed1991

In vivo and in vitro persistence of pyridyloxobutyl DNA adducts from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

The persistence of pyridyloxobutyl DNA adducts in lung and liver of F-344 rats treated with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated. The levels of these adducts were determined at various time points up to 4 weeks post s.c. injection of [5-3H]NNK (0.8 mg/kg body wt). Maximal levels of the adducts were observed between 4 and 24 h in both tissues. The disappearance of the adducts from lung and liver DNA was multiphasic with initial half-lives of 50 and 38 h respectively. In both cases, detectable levels of the pyridyloxobutyl adducts were observed at 4 weeks post injection. The in vitro rate of adduct disappearance was studied using calf thymus DNA reacted with 4-(acetoxymethylnitrosamino)-1-(3-[5-3H]pyridyl)-1-butanone in the presence of esterase. Adduct levels were measured for up to 2 weeks after the initiation of the experiment. The decomposition of these adducts was triphasic with half-lives of 6, 120 and 430 h. The multiphasic disappearance of the pyridyloxobutyl adducts suggests that there is more than a single adduct generated upon pyridyloxobutylation of DNA and that at least one of these adducts has a significant lifetime in DNA.

Animals↗
PubMed1991

O2 and rat pulmonary artery tone: effects of endothelium, Ca2+, cyanide, and monocrotaline.

The present study examines the influence of the endothelium (E), Ca2+ concentration, cyanide and monocrotaline (MCT) pretreatment on the responses of isolated rat hilar pulmonary arterial rings (PA) to hypoxia. In PA precontracted with phenylephrine, hypoxia induced an initial E-dependent relaxation phase followed by an E-independent transient contraction and a final relaxation. An increase in Ca2+ concentration from 1.5 to 2.5 mM produced an E-dependent reduction in tone generation under O2 and a significant enhancement of the hypoxia-elicited initial relaxation and the transient contractile responses. Addition of cyanide (0.1 mM) to precontracted PA produced a transient contraction similar to that caused by hypoxia. Preincubation with cyanide led to inhibition of tone generation and abolition of the contraction to hypoxia. However, the final relaxation response to hypoxia was not inhibited by cyanide. Thus, hypoxia produces an E-independent contraction via a mechanism that appears also to be activated by cyanide, and this response is not altered by MCT. The endothelium alters the response to hypoxia in a Ca(2+)-dependent manner.

Acetylcholine↗
PubMed1989

Cystic fibrosis in Saudi Arabia.

Cystic fibrosis (CF) is generally believed to be rare or nonexistent in Saudi Arabia. The aim of this report is to document the occurrence of CF in Saudi Arabia. Thirteen Saudi children were diagnosed as having CF, evidenced by typical clinical features and elevated sweat chloride concentrations (greater than 60 mmol/l). Duration of symptoms prior to diagnosis varied from 1 month-5 years (mean 23 months). The main clinical manifestations of the children were abdominal distention, failure to thrive, steatorrhoea, hepatomegaly, rectal prolapse and recurrent respiratory infections, often with Pseudomonas aeruginosa. In addition, eight patients with symptoms and a family history highly suggestive of CF, but without confirmatory sweat test results are presented. We hope that this report will increase the awareness of CF and ensure an earlier diagnosis of the disease in Saudi Arabia.

Child, Preschool↗
PubMed1989

Strain differences in pulmonary hypertensive response to monocrotaline alkaloid and the beneficial effect of oral magnesium treatment.

Magnesium therapy has been shown, by us, to attenuate monocrotaline (MCT)-induced pulmonary artery hypertension (PAH), right ventricular hypertrophy and pathological changes in the pulmonary vasculature in 75% of Sprague-Dawley rats. We studied Wistar rats to determine if there was a strain difference in response to MCT and magnesium therapy. Wistar rats were given 60 mg/kg of MCT and studied 3 weeks later, following a protocol similar to that for Sprague-Dawley rats. There was 100% mortality in Wistar rats weighing less than 230 g. The mortality rate in Sprague-Dawley rats of a similar weight range was significantly less (15%). With 40 mg/kg of MCT, Wistar rats developed pulmonary hypertension and right ventricular hypertrophy comparable to those seen in Sprague-Dawley rats administered 60 mg/kg MCT. The percent weight gain over a 3-week period was significantly higher in the Wistar control group than that in the Sprague-Dawley controls (61 vs. 39%; p less than 0.05). Oral magnesium therapy (magnesium aspartate HCl) attenuated pulmonary hypertension and right ventricular hypertrophy in 100% of the Wistar rats studied. A group of Sprague-Dawley rats was given 40 mg/kg of MCT and studied 3 weeks later. PAH and right ventricular hypertrophy in this group were not significantly different from the rats of the same strain injected with the higher dose of MCT. In conclusion, faster growing rats (Wistar) appear to be more sensitive to MCT. Both strains show a significant attenuation of cardiopulmonary changes induced by MCT when treated with oral magnesium.

Animals↗
PubMed1989

Effect of inhalation of insecticide spray on learning and memory in rats.

Acute exposure to insecticide (Baygon-spray; 5 ml/animal/5 min) inhalation in rats did not affect the learning process but produced a significant loss of memory (P less than 0.01 less than 0.001) whereas chronic exposure (one exposure per day for three weeks) produced a significant delay in learning (P less than 0.05) and memory (P less than 0.01). Acetylcholinesterase activity in brain after acute and chronic exposure declined significantly (P less than 0.01) during the learning process but returned to normal after 24 hr.

Acetylcholinesterase↗
PubMed1988

Magnesium aspartate hydrochloride attenuates monocrotaline-induced pulmonary artery hypertension in rats.

1. The effect of oral magnesium aspartate hydrochloride on monocrotaline (MCT)-induced pulmonary arterial hypertension was evaluated in rats. 2. A single subcutaneous injection of MCT, a pyrrolizidine alkaloid of plant origin, induces significant morphological changes in pulmonary vessels, pulmonary arterial hypertension and right ventricular hypertrophy in rats by 3 weeks. 3. Two groups of rats (Mg2+ control and Mg2+ + MCT) were started on oral Mg2+ (15.4 g/l magnesium aspartate hydrochloride dissolved in deionized water) 2 weeks before the MCT injection. The rest were given deionized water. At the start of the experiment, the control groups (deionized water and Mg2+) were given normal saline subcutaneously; the other groups (deionized water and Mg2+) were given MCT (60 mg/kg) subcutaneously. 4. Pulmonary artery pressure, right ventricular hypertrophy, lung pathology, organ weights and serum electrolytes were assessed 3 weeks after a single subcutaneous injection of MCT. Seventy-five per cent of the rats treated with MCT and oral Mg2+ (12 out of 16) showed significant reduction in pulmonary arterial hypertension, arterial pathology and right ventricular hypertrophy. 5. Our data indicate that Mg2+ attenuates experimentally induced pulmonary hypertension, possibly either by modulating the intracellular Ca2+ level and/or by directly affecting the pulmonary endothelial cell-smooth muscle cell complex involved in metabolism and maintenance of pulmonary vascular resistance.

Animals↗
PubMed1988

Magnesium and the lungs.

Recently, there has been considerable interest generated in the possible importance of magnesium ions (Mg2+) in the regulation of bronchial smooth muscle tone and pulmonary vascular tone. These factors have aroused interest in the possible utilization of Mg salts in the treatment of lung diseases (e.g., asthma, allergies, and pulmonary hypertension). Evidence is reviewed which indicates that Mg2+ can influence bronchial vasomotor tone, both indirectly and directly, as well as pulmonary vascular muscle contractility, mast cell granulation and neurohumoral mediator release. In addition, new experimental data suggest that Mg2+ influences a variety of lung structures and chemicals (e.g., capillary endothelial cell integrity, number of type II epithelial cells, surfactant, etc.). Surprisingly, pulmonary arterial muscle cells have a lower Mg content compared to other types of blood vessels and the myocardium, which might point to the vulnerability of the lung vasculature to lower than normal dietary intake of Mg. Several clinical reports point to the salutary actions of Mg2+ in asthma and asthma-like conditions. Very recent experimental findings in rats indicate that Mg2+ treatment can prevent development of experimental chemically induced pulmonary hypertension. Hypoxic pulmonary vasoconstriction has been reported to be attenuated by Mg2+. Although it is not clear as to whether dietary Mg2+ deficiency plays a role in development of some asthma-like conditions or pulmonary hypertension, Mg salts certainly appear to be potentially useful therapeutic avenues for these conditions and should be thoroughly investigated, both from clinical as well as experimental points of view.

Female↗
PubMed1985

Nephrocalcinosis due to primary hyperoxaluria: case report from Saudi Arabia.

Two Arab siblings with nephrocalcinosis and renal failure secondary to primary hyperoxaluria are presented. Percutaneous renal biopsies obtained from both siblings showed marked oxalate deposition in the renal medulla. Primary hyperoxaluria should be considered in the differential diagnosis of renal failure in infancy and early childhood especially when evidence of obstructive uropathy is lacking.

Child, Preschool↗