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Biomedical subjects

M A Shah

Publications and source records attributed to M A Shah.

At least 19 recordsLinked to original sources
PubMed1992

Oxidation of peptidyl lysine by copper complexes of pyrroloquinoline quinone and other quinones. A model for oxidative pathochemistry.

Various o- and p-quinones were assessed as oxidants of peptidyl lysine in elastin and collagen substrates in the presence and absence of divalent copper as paradigms of protein-lysine 6-oxidase (lysyl oxidase) which contains both quinone and copper cofactors. Pyrroloquinoline quinone was among the most active in the absence and the most active of the o- and p-quinones tested in the presence of copper. The optimal rate of elastin oxidation occurred at a 2:1 PQQ/Cu(II) ratio while Cu(II) itself oxidized elastin relatively slightly. Elastin oxidation by 2:1 PQQ/Cu(II) required aerobic conditions consistent with oxygen-dependent turnover of this catalytic pair. Dimethylsulfoxide and catalase individually or in combination inhibited elastin oxidation by PQQ/Cu(II) by approx. 50%, suggesting that oxygen free radical species participate in the reaction. Amino-acid analysis of elastin and collagen substrates oxidized by 2:1 PQQ/Cu and then reduced with borohydride revealed that alpha-aminoadipic-delta-semialdehyde and lesser amounts of covalent cross-linkages were generated by this oxidant. In contrast, lysine oxidase produced aldehydes and significantly greater quantities of cross-linkage products, consistent with the known specificity of the enzyme. These data, thus, indicate the potential for free quinones, such as PQQ, particularly when stimulated by appropriate metal ions, to act as adventitious oxidants of lysine side-chains in proteins.

Anaerobiosis↗
PubMed1990

Structural and catalytic properties of copper in lysyl oxidase.

The spectral and catalytic properties of the copper cofactor in highly purified bovine aortic lysyl oxidase have been examined. As isolated, various preparations of purified lysyl oxidase are associated with 5-9 loosely bound copper atoms per molecule of enzyme which are removed by dialysis against EDTA. The enzyme also contains 0.99 +/- 0.10 g atom of tightly bound copper per 32-kDa monomer which is not removed by this treatment. The copper-free apoenzyme, prepared by dialysis of lysyl oxidase against alpha,alpha'-dipyridyl in 6 M urea, catalyzed neither the oxidative turnover of amine substrates nor the anaerobic production of aldehyde at levels stoichiometric with enzyme active site content, thus contrasting with the ping pong metalloenzyme. Moreover, the spectrum of the apoenzyme was not measurably perturbed upon anaerobic incubation with n-butylamine, while difference absorption bands were generated at 250 and 308 nm in the spectrum of the metalloenzyme incubated under the same conditions. A difference absorption band also developed at 300-310 nm upon anaerobic incubation of pyrroloquinoline quinone, the putative carbonyl cofactor of lysyl oxidase, with n-butylamine. Full restoration of catalytic activity occurred upon the reconstitution of the apoenzyme with 1 g atom of copper/32-kDa monomer, whereas identical treatment of the apoenzyme with divalent salts of zinc, cobalt, iron, mercury, magnesium, or cadmium failed to restore catalytic activity. The EPR spectrum of copper in lysyl oxidase is typical of the tetragonally distorted, octahedrally coordinated Cu(II) sites observed in other amine oxidases and indicates coordination by at least three nitrogen ligands. The single copper atom in the lysyl oxidase monomer is thus essential at least for the catalytic and possibly for the structural integrity of this protein.

2,2'-Dipyridyl↗
PubMed1990

Socioeconomic and health care determinants of child survival in Kuwait.

This paper analyses the socioeconomic and health care determinants responsible for the decline over the last two decades in infant mortality in Kuwait. Published data and the results of a national health survey conducted in 1984-85 show the following. With the overall affluence of the society, health care in terms of immunization has improved dramatically and more than 90% of all children are covered. Of all births, 99% now occur in a hospital or clinic. About half of the mothers continue to breast-feed their babies for about 16 months. Despite these favourable conditions, differences still exist between social classes. The risk of stillbirth remains much higher among the poorer women, those without any education and those who gave birth at home. These findings are consistent with developed countries like the USA and Japan, where the social class differences in mortality still persist.

Cross-Sectional Studies↗
PubMed1990

Development of tolerance to the effects of vigabatrin (gamma-vinyl-GABA) on GABA release from rat cerebral cortex, spinal cord and retina.

1. The effects of acute and chronic vigabatrin (gamma-vinyl-GABA) (GVG) administration on gamma-aminobutyric acid (GABA) levels and release in rat cortical slices, spinal cord slices and retinas were studied. 2. GVG (250 mgkg-1 i.p.) administered to rats 18 h before death (acute administration) produced an almost 3 fold increase in GABA levels of the cortex and spinal cord and a 6 fold increase in retinal GABA. The levels of glutamate, aspartate, glycine and taurine were unaffected. 3. When GVG (250 mgkg-1 i.p.) was administered daily for 17 days (chronic administration) a similar (almost 3 fold) increase in cortical GABA occurred but the increases in spinal and retinal GABA were reduced by approximately 40%. 4. Acute administration of GVG strikingly increased the potassium-evoked release (KCl 50 mM) of GABA from all three tissues. This enhanced evoked release was reduced by about 50% in tissues taken from rats that had been chronically treated with GVG. 5. Acute administration of GVG reduced GABA-transaminase (GABA-T) activity by approximately 80% in cortex and cord and by 98% in the retina. Following the chronic administration of GVG, there was a trend for GABA-T activities to recover (significant only in cortex). Acute administration of GVG had no effect on glutamic acid decarboxylase (GAD) activity in cortex or spinal cord. However, chronic treatment resulted in significant decreases in GAD activity in both the cortex and cord (35% and 50% reduction respectively). 6. The K-evoked release of glutamate, aspartate, glycine and taurine from cortical slices and the Kevoked release of glycine from spinal slices and retinas were not affected by either acute or chronic GVG treatment. 7. These experiments indicate that GVG treatment increases specifically the K-evoked release of GABA and that tolerance can develop to this enhancing effect of GVG on central GABA release. This tolerance may result from increased feedback inhibition of GAD with a consequent reduction of presynaptic GABA stores.

4-Aminobutyrate Transaminase↗
PubMed1990

Pediatric trauma triage: review of 1,307 cases.

To assess patterns of pediatric trauma triage and patient transfer to the pediatric trauma centers, the records of 1,307 patients 14 years old or less who were admitted or died during resuscitation at eight Level II Trauma Centers from January 1987 through December 1988 were reviewed retrospectively. Cases were analyzed according to the following criteria: age, diagnosis, mechanism of injury, admitting service, pediatric trauma score (PTS), length of stay in the intensive care unit (ICU) and in the hospital, and outcome. Forty-three patients were transferred to pediatric trauma centers based on local criteria. Of the remaining 1,264 patients kept at the Level II Trauma Centers, the average patient age was 8.34 year; PTS, 9.74; and length of stay, 4.46 days. Two hundred fifty-eight patients (19.7%) required ICU care for an average length of stay of 2.86 days. Twenty-four patients (1.8%) died; all 24 had a PTS less than or equal to 8. In comparing the data to the guidelines in Appendix J of the American College of Surgeons' Hospital and Prehospital Resources for Optimal Trauma Care of the Injured Patient for transfer to a Level I Pediatric Trauma Center, we found that children with a PTS greater than 8 and who either require ICU care and/or have altered states of consciousness can safely be treated in the adult ICU of a Level II Trauma Center.

Adolescent↗
PubMed1990

Allied health manpower in Kuwait: issues and answers.

This article focuses on the salient issues and problems regarding allied health manpower in Kuwait, an oil-rich Gulf country. The health system in Kuwait has expanded very rapidly since the country's independence 29 years ago. A major feature of the health system is its heavy reliance on expatriate workers, constituting 80% of all doctors and over 90% of all nurses. Local training facilities have started producing some of the required allied health professionals. Continued shortages of indigenous allied health professionals are, however, inevitable in most areas. The presence of a highly diverse expatriate workforce raises serious problems, concerning worker conflict, differential skills and competencies, and adjustment to the Kuwaiti culture. Standardizing local training facilities, curricular expansion to accommodate emerging health concepts, and improving the system of hiring expatriates are needed.

Allied Health Personnel↗
PubMed1989

Immunocytochemical evidence that vigabatrin in rats causes GABA accumulation in glial cells of the retina.

Vigabatrin (gamma-vinyl-GABA, GVG) is an irreversible inhibitor of GABA-aminotransferase (GABA-T) that is under clinical trial as an antiepileptic drug. Rats were injected (i.p.) with GVG and killed 18 h later. GVG administration reduced retinal GABA-T activity to undetectable levels and increased the GABA content 5-fold. Immunocytochemistry using a GABA antiserum clearly revealed the presence of GABA-IR in the glial Muller cells of retinas from GVG-treated rats but not from controls. This experiment indicates that the administration of drugs which inhibit GABA-T may cause the accumulation of GABA in retinal cells that do not normally possess enough endogenous GABA to be detected by immunocytochemistry.

Aminocaproates↗
PubMed1989

Immunochemical reactivity of native and modified preparations of pig kidney diamine oxidase.

This paper describes the antigenicity of pig kidney diamine oxidase [EC 1.4.3.6] and the possible role of constituent amino acids in the epitope structure of the enzyme. The loss of 62% of the biological activity after DAO-anti-DAO antibodies interaction was attributed to the steric hindrance caused by binding of antibody to the enzyme molecule. A gradual loss in antigenicity during ultraviolet (UV) irradiation was observed without any significant conformational change, demonstrating the destruction of antigenic determinants. However, ethoxyformylation of nine histidyl residues with complete inactivation caused no change in immunoreactivity. The results indicate that the antigenic sites and catalytic sites are located at different positions along the polypeptide chain. Moreover, the results of lysine residue modification were suggestive of possible involvement of lysine in the antigenic determinants of DAO.

Amine Oxidase (Copper-Containing)↗
PubMed1989

Baclofen and phaclofen modulate GABA release from slices of rat cerebral cortex and spinal cord but not from retina.

1. The effects of (-)-baclofen, muscimol and phaclofen on endogenous gamma-aminobutyric acid (GABA) release from rat cortical slices, spinal cord slices and entire retinas were studied. 2. The spontaneous resting release of GABA from the three tissues was 3 to 6 pmol mg-1 wet wt 10 min-1. Depolarization of cortical slices with KCl (50 mM) (high-K) produced an 8 fold increase in GABA release but high-K did not evoke an increased release of GABA from spinal slices or retinas. 3. When rats were injected with gamma-vinyl-GABA (250 mg kg-1 i.p.) (GVG) 18 h before death, the tissue GABA stores were increased 3 to 6 fold and high-K then evoked striking Ca-dependent releases of GABA from all three tissues. Thus, in subsequent experiments, unless otherwise stated, the nervous tissues were taken from GVG-treated rats. 4. (-)-Baclofen (10 microM) significantly reduced the K-evoked release of GABA from cortical and spinal slices but retinal release was not affected, even at a concentration of (+/-)-baclofen of 1 mM. For cortical slices, the IC50 for baclofen was approximately 5.2 microM. The inhibitory effect of baclofen on GABA release from cortical slices also occurred in slices prepared from saline-injected rats, indicating that GVG treatment did not qualitatively affect the results. 5. The inhibitory effect of (-)-baclofen on the K-evoked release of GABA from cortical and spinal slices was antagonised by phaclofen (500 microM), confirming that baclofen was producing its effects by acting at the GABAB-receptor. 6. Phaclofen (500 microM) increased the spontaneous resting release of GABA from cortical slices taken from GVG-treated rats but not from saline-injected rats. Phaclofen did not increase GABA release from spinal slices or retinas taken from GVG-treated rats. 7. Baclofen (10 microM) significantly reduced the K-evoked release from cortical slices of glutamate, aspartate, glycine and taurine. 8. Muscimol (10 microM) and delta-aminolaevulinic acid (10 microM) had no effect on either the resting or Kevoked release of GABA from cortical slices prepared from saline-injected or GVG-treated rats. 9. The results obtained with cortical and spinal slices are consistent with the presence of inhibitory GABAB-autoreceptors. The phaclofen-induced increase in GABA release from cortical slices taken from GVG-treated rats, but not from saline-injected rats, implies that under conditions of high GABA release, considerable feedback inhibition is occurring via activation of the GABAB inhibitory autoreceptors. No evidence was found for GABAB-autoreceptors on retinal GABAergic amacrine cells or for GABAA-autoreceptors in cortical slices or spinal cord slices.

Amino Acids↗
PubMed1989

Role of disulfides in biological activity and conformational stability of pig kidney diamine oxidase: evidence for two disulfide states.

Six disulfides are found to be present in pig kidney diamine oxidase and all of these are available to reducing agents under nondenaturating conditions. Disulfide reduction with dithiothreitol followed by carbamidomethylation indicated two states of disulfides, each containing three groups, distinguishable by pH dependence. The first group of three disulfides has a functional role in catalytic activity. The another class of three disulfides showed accessibility only at higher pH values and appears to be important in maintaining the three dimensional structure of the molecule. The disulfides for these two activities appear to be independent of each other. Almost similar behaviour was noticed with copper depleted apo-enzyme.

Amine Oxidase (Copper-Containing)↗
PubMed1988

The glycoprotein nature of pig kidney diamine oxidase. Role of disulphide groups and arginine residues in the concanavalin A-diamine oxidase interaction.

Pig kidney diamine oxidase (DAO) was found to contain 5% (w/w) natural hexose, 3.25% glucosamine, 2.61% N-acetylglucosamine and 0.25% N-acetylneuraminic acid. The enzyme exhibited strong affinity towards concanavalin A (Con A) with a stoichiometry of 1:4.6. The kinetics of interaction approached an apparent first-order rate, with a rate constant (Kapp.) value of 1.5 x 10(-2) min-1. The enzyme reduced with dithiothreitol followed by alkylation with iodoacetamide showed an increase in the stoichiometry of the Con A-DAO interaction. Similarly arginine modification by phenylglyoxal caused decreased affinity, with an altered Kapp. value of 9.09 x 10(-3) min-1. The results suggest that, besides the carbohydrate content, the protein moiety of the enzyme also plays a significant role in the Con A-DAO interaction.

Amine Oxidase (Copper-Containing)↗
PubMed1983

Acute sporadic non-A, non-B hepatitis in India.

A total of 293 sporadic cases of acute viral hepatitis were identified in Kashmir, India, from April 1979 to December 1981; 44 (15%) were found serologically to be hepatitis A, 94 (32%) hepatitis B, and 155 (53%) non-A, non-B type. The non-A, non-B hepatitis observed was a disease of young adults (29.8 +/- 15 years) with slight male predominance (1.4:1). Six of the 155 non-A, non-B cases had history of prior parenteral exposure, while 51 (33%) had a recent contact with another case of jaundice, suggesting that this form of hepatitis was spread by person-to-person contact. Fulminant hepatic failure occurred in 19 cases, and six (31.5%) of the 19 cases occurred in pregnant women. None of 90 non-A, non-B cases followed up six months later had developed chronic hepatitis. The acute sporadic non-A, non-B hepatitis described in Kashmir resembles epidemic non-A, non-B hepatitis epidemiologically and seems to be distinct from the non-A, non-B hepatitis described in the West.

Adolescent↗
PubMed1981

Comparative review of early and intermediate patency rates of polytetrafluoroethylene and autogenous saphenous vein grafts for lower extremity ischemia.

One hundred nine primary bypass operations were performed on 97 patients who had limb ischemia caused by arteriosclerosis obliterans, over a 32-month period starting in January, 1978. The majority of those procedures were done for rest pain or gangrenous changes. The greater saphenous vein was used whenever possible (44 of 109 procedures), and a polytetrafluoroethylene (Gore-Tex) prosthesis was used in 65 of 109 procedures. Average follow-up was 9.3 months. The cumulative patency rate in all vein grafts was 93.1% at 1 month and 73.4% after 31 months, whereas the cumulative patency rate for polytetrafluoroethylene was 83.3% at 1 month and 51% at 31 months. The difference is not statistically significant (0.10 less than P less than 0.25). In above-knee procedures for claudication, polytetrafluoroethylene performed identically to vein (P greater than 0.50), although vein appeared to perform better in above-knee procedures done for rest pain or necrosis. A limited number of below-knee revascularizations were performed, and although no conclusions of statistical significance can be drawn, cumulative patency of vein appeared to be better than polytetrafluoroethylene. For additional comparative analysis, this study was compared to a previous study in which Dacron was used in femoropopliteal arterial reconstructions. Patency rates in above-knee revascularizations appeared to be comparable in Dacron and polytetrafluoroethylene. Diabetes did not appear to alter age of onset of disease or patency rates, although smokers became symptomatic 10 years earlier than nonsmokers. Although the early and long-term results of arterial reconstructions in the ischemic extremity are known, the availability of new alternate arterial prostheses raises the question of the optimum material depending on the specific clinical circumstances.

Actuarial Analysis↗