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Biomedical subjects

H Ahmad

Publications and source records attributed to H Ahmad.

At least 37 records · Page 2Linked to original sources
PubMed1998

Glutathione S-transferase of goat lens: evidence for expression of only class mu isoenzymes.

PURPOSE: It has been suggested that glutathione S-transferases (GSTs) of the mammalian ocular lens detoxify various toxicants and cataractogens; therefore, it provides protection against cataractogenesis. In this study the GST isoenzymes of goat lens have been purified and characterized. METHODS: The goat lens homogenate was subjected to affinity chromatography over GSH-linked epoxy activated Sepharose 6B. The isoenzymes of the GST were separated by chromatofocusing on a Mono-P column using FPLC. RESULTS: Two GST isoenzymes, GST 7.2 and GST 6.6, were purified to apparent homogeneity from goat lens. GST 7.2 appeared to be a heterodimer of Mr. 26,500 and Mr. 25,000 subunits, the GST 6.6 showed a homodimeric subunit structure of Mr. 25,000. Western blotting and the N-terminal region amino acid sequence analysis indicated that both isoenzymes of goat lens belong to the mu-class GST. CONCLUSION: Although they share varying degrees of structural correlation, the two isoenzymes of goat lens seem to be the products of two distinct genes. The isoenzyme expression pattern of GST in goat lens is similar to bovine lens, which also contains two isoenzymes belonging only to GST mu.

Animals↗
PubMed1997

Preferential overexpression of a class MU glutathione S-transferase subunit in mouse liver by myristicin.

The present studies were undertaken to elucidate the mechanism of induction of glutathione S-transferase (GST) in mouse liver by myristicin, an active constituent of parsley leaf. A/J albino mice, given 5 to 50 mg doses of myristicin, showed 4- to 14-fold increase in liver GST specific activity over the control. GST purified from equal amounts of control and myristicin-treated livers indicated a marked increase in the GST activity. A relatively higher increase in GST activity towards 2,4-dichloronitrobenzene and a profound increase in the levels of GST mu on Western blot analysis of the myristicin-treated mouse liver suggest a preferential induction of GST mu. Results of the study also indicate that out of the two mu class GST subunits (Mr. 26,500 and Mr. 25,000) expressed in liver only one (Mr. 26,500) is significantly elevated. Myristicin treatment caused a slight change in the GST pi levels while the levels of GST alpha showed a modest increase. These results suggest that myristicin could be an effective chemopreventive agent, particularly for carcinogens that are detoxified by the mu class GST.

Allylbenzene Derivatives↗
PubMed1997

Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria.

OBJECTIVE: This study determines the long-term efficacy of the ACE inhibitor, enalapril, in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate (AER) 20-200 micrograms/min and normal renal function followed for 5 years in a prospective randomized single-blind placebo-controlled trial. AER, blood pressure, fasting plasma glucose, and HbA1 were measured very 3-4 months and glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary urea every 12 months. RESULTS: In the patients treated with enalapril, AER decreased from 55 +/- 33 to 20 +/- 59 micrograms/min (geometric mean +/- SD), whereas in the placebo group, AER increased from 53 +/- 31 to 85 +/- 90 micrograms/min after 5 years. Within 5 years, 7.7% (4/52) of enalapril-treated subjects and 23.5% (12/51) of placebo-treated subjects progressed to clinical albuminuria defined as AER > 200 micrograms/min and at least 34% above baseline (risk reduction = 66.7%, P < 0.001). AER increased at an annual rate of 12.3% (95% CI 9.8-14.9) in the placebo group, while it declined by 16.7% (95% CI -18.3 to -15.2) in the enalapril group (P < 0.001). In addition, 8 of the 12 placebo-treated patients had evidence of coronary artery disease. The rest of the parameters remained practically unchanged in the two groups. CONCLUSIONS: After 5 years of therapy with enalapril, compared with placebo, normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria, reduced AER, and preserved GFR.

Adult↗
PubMed1996

Lupus nephritis in children: a longitudinal study of prognostic factors and therapy.

There are only a few studies in the pediatric literature that have analyzed risk factors for renal failure in childhood lupus nephritis. This study reviewed the outcome of 56 children (4 to 18 yr of age) with lupus nephritis seen at the authors' institution over a 27-yr period (1965 to 1992), in relation to risk factors and therapy. All children underwent percutaneous renal biopsy before the institution of therapy. From 1965 to 1987, treatment for Class III and IV lupus nephritis consisted of high-dose pulse methylprednisolone, 500 mg daily for 10 days, followed by oral prednisone. From 1987 to 1992, IV cyclophosphamide was given monthly for 6 months and then every 3 months for a period of 3 yr for patients with Class III and Class IV disease. Of 56 children, 42% had Class IV and 21% had Class III histology at onset. The mean follow-up period was 4 yr and ranged from 0.5 to 20.3 yr. Life-table analysis showed that the cumulative proportion of patients surviving was 82.8% at 5 yr and 67.7% at 10 yr. Renal survival was 44.4% at 5 yr and 29% at 10 yr, after the initial diagnosis of lupus nephritis was made. Age at diagnosis, race, sex, initial serum creatinine level, and the presence of proteinuria, hypertension, and DNA antibody titers were reviewed with respect to disease progression, as was the histological class at diagnosis. The effect of the different therapies was also examined. Univariate analysis revealed a significant association of progression to ESRD with an elevated serum creatinine level (P = 0.021), decreased C3 complement (P = 0.024), hypertension (P = 0.053), and histological classification of Class IV lupus nephritis (P = 0.031). Multivariate analysis demonstrated that progression to ESRD was independently associated with an initial Class IV histology (relative risk, 1.78; P < 0.003), hypertension at presentation (relative risk, 1.67; P < 0.003), and a low C3 complement level in conjuction with a high creatinine level (relative risk, 1.52; P < 0.028). Among children with lupus nephritis, those with Class IV disease, hypertension, high creatinine levels, and low C3 complement levels at the time of diagnosis are at increased risk for ESRD. Initial histological classification of lupus nephritis was the most reliable prognostic factor for disease progression. This study was unable to detect a difference in outcome for the two treatment groups.

Adolescent↗
PubMed1995

Lingual thyroid: tongue-splitting incision for transoral excision.

Two patients presenting to the Central Military Hospital of Beirut with symptomatic lingual thyroid are reported. I131 thyroid scanning revealed the lingual thyroid to be the only functional thyroid tissue present in each patient. Subsequent CT scanning demonstrated the large size of these ectopic thyroids causing significant mechanical obstruction. These were excised transorally using a posterior midline tongue-splitting incision and reimplanted in the rectus abdominis muscles. Details of this modified tongue-splitting surgical approach are described. A brief review of the literature concerning lingual thyroid and its surgical treatment is also presented as well as three patients operated on for lingual thyroid at the American University of Beirut Medical Centre between 1975 and 1994 using an external neck incision.

Adult↗
PubMed1995

Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis.

Short-term cyclosporine (CsA) has been shown to reduce the proteinuria in refractory nephrotic syndrome, but the effect on disease progression has not been evaluated. This study was undertaken to evaluate whether maintenance CsA therapy in steroid-resistant focal segmental glomerulosclerosis (FSGS) will prevent progression to ESRD. Twenty-one black and Hispanic children (mean age, 8.4 +/- 4.5 yr) with biopsy-proven, steroid/cyclophosphamide-resistant FSGS were treated with CsA (initiated at 6 mg/kg per day and titrated to the serum cholesterol level to achieve a response). The mean CsA dose was 7 (4 to 20) mg/kg per day, the duration of CsA therapy was 27.5 (3 to 97) months, and the duration of follow-up was 8.5 +/- 4.7 yr. At the end of CsA therapy, the mean (+/- SE) proteinuria fell from 6.2 +/- 0.2 to 2.0 +/- 0.1 g/24 h (P < 0.001), the mean albumin rose from 1.95 +/- 0.04 to 3.41 +/- 0.04 g/dL (P < 0.001), the mean cholesterol decreased from 472 +/- 12.7 to 257 +/- 5.3 mg/dL (P < 0.005), and the mean creatinine rose from 0.79 +/- 0.02 to 1.16 +/- 0.03 mg/dL (P < 0.005). Seven children continue to receive maintenance CsA therapy, and 14 patients have had CsA stopped: 6 for an increase in serum creatinine and/or continued proteinuria, 5 for sustained remission, 2 for noncompliance, and 1 for pregnancy. Five (24%) of the 21 patients progressed to ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗
PubMed1994

Beware the anomalous portal vein.

Portal vein thrombosis is an unusual potential complication of liver resection. In our case it was due to ligation of the right branch of the portal vein during right hepatectomy in a patient without portal vein bifurcation. Hepatic angiography can delineate this abnormality and influence the choice of surgical management.

Cholangitis↗
PubMed1993

Interactions of glutathione S-transferase-pi with ethacrynic acid and its glutathione conjugate.

Ethacrynic acid, a diuretic drug known to be an inhibitor of glutathione S-transferases (GSTs), has been shown to enhance the cytotoxicity of the alkylating agent class of chemotherapeutic drugs in cultured cancer cells resistant to alkylating agents. This action of ethacrynic acid is presumably mediated by inhibition of GSTs which are implicated in detoxification of alkylating agents. In addition to being an inhibitor of GSTs, ethacrynic acid also interacts with GSTs as a substrate for conjugation with GSH to yield an ethacrynic acid-GSH conjugate. This conjugate is formed both enzymatically and non-enzymatically and itself is a GST inhibitor. Since ethacrynic acid-GSH conjugate is itself likely to be able to mediate reversal of alkylating agents through GST inhibition, we have synthesized and purified the ethacrynic acid-GSH conjugate, studied the kinetics of inhibition of human lung pi-class GST by ethacrynic acid and the conjugate, and compared the kinetics of the enzymatic and non-enzymatic formation of the conjugate using an HPLC method. Results of our studies showed that the ethacrynic acid-GSH conjugate was a more potent inhibitor of human lung GST-pi than ethacrynic acid (Ki = 1.5 vs. 11.5 microM, respectively) and that their mechanisms for GST inhibition were distinct (competitive and non-competitive, respectively). Comparison of enzymatic and non-enzymatic rates of conjugate formation in vitro indicated that GST-pi catalyzed a rapid conjugation of ethacrynic acid with GSH at a concentration of ethacrynic acid an order of magnitude above that required to nearly completely inhibit GST catalyzed conjugation of 1-chloro-2,4-dinitrobenzene. However, because of the rapid non-enzymatic reaction, and the inhibition of GST-pi with the accumulation of the conjugate in the reaction mixture, the overall quantity of the conjugate formed after 150 min was nearly identical in the presence or absence of GST-pi. Results of these studies suggest that inhibition of GSTs by ethacrynic acid-GSH conjugate may be the main mechanism through which ethacrynic acid reverses alkylating agent resistance.

Alkylating Agents↗
PubMed1993

Glutathione S-transferases of human skin: qualitative and quantitative differences in men and women.

Glutathione S-transferase (GST) isozymes of male and female leg skin have been characterized. GST activities and protein have been quantified in a number of male and female skin samples and the results indicate that as compared to the male skin, female skin contains a higher amount of GST activity as well as protein. Both male and female leg skin contain three GST isozymes with pI values 9.9, 9.1 and 4.8. In accordance with previous findings the major isozyme, pI 4.8 belongs to the pi-class, whereas the two minor forms pI 9.1 and 9.9 belong to the alpha-class. Each of the three isozymes is more abundant in female skin. Surprisingly, the specific activities and Kcat values of the female skin GSTs, particularly of the pi-class isozyme were found to be significantly higher as compared to those of male skin isozyme. Studies into the kinetics of inhibition by hematin also indicated differences in male and female skin GSTs. Whereas we confirm the presence of an alpha-class GST, pI 9.9, in human skin with an apparently higher subunit M(r) value as compared to other human alpha-class GSTs, contrary to the previous report (Del Boccio et al. (1987) Biochem. J. 244, 21-25), the results of the present studies show that the N-terminus of this alpha-class GST is blocked.

Amputation, Surgical↗
PubMed1993

Characterization of two novel subunits of the alpha-class glutathione S-transferases of human liver.

More than 85% of the complete amino-acid sequence of the alpha-class glutathione S-transferase omega (GST omega) of human liver, described for the first time in this communication, show that GST omega is a heterodimer of two closely related novel alpha-class GST subunits. The sequences of these subunits, omega 1 and omega 2, have over 97% homology between them and are also highly homologous to the two alpha-class subunits characterized previously. Characterization of these two novel alpha-class subunits described in this report would explain the molecular basis for high degree of heterogeneity observed among the alpha-class human GSTs.

Amino Acid Sequence↗
PubMed1993

Comparative studies on the effect of butylated hydroxyanisole on glutathione and glutathione S-transferases in the tissues of male and female CD-1 mice.

1. Male CD-1 mice had about 1.6-fold higher glutathione (GSH), 2-fold higher glutathione S-transferase (GST) activity and 2.8-fold higher GST protein in their livers as compared to the female mice. 2. When mice were fed a diet containing 0.75% BHA for 2 weeks, a 1.8-fold increase was observed in GSH levels of female mice liver as opposed to only 1.2-fold increase in male mice. BHA caused 10-fold increase in GST activity and protein in livers of female mice as compared to only about 3-4-fold increase in livers of males. Differential induction of GSH and GST in males and females was also observed in other tissue besides liver but was not as remarkable. 3. Sex-related differences were also observed in the induction of the alpha- and mu- and pi-classes of GSTs by BHA; most noticeable being GST pi, which was induced to about 10-fold in female liver as opposed to only 3.4-fold in male liver.

Animals↗
PubMed1992

Reversed-phase chromatographic method for specific determination of glutathione in cultured malignant cells.

A chromatographic method for the specific determination of glutathione in malignant cell lines is described. The method is based on the ability of glutathione-S-transferase to specifically and quantitatively conjugate glutathione to 1-chloro-2,4-dinitrobenzene and chromatographic quantitation of the resultant conjugate, dinitrophenyl-S-glutathione, by reversed-phase liquid chromatography. The assay can be performed on 20,000 g supernatants of cell homogenates without acid extraction. 2-Mercaptoethanol, a sulfhydryl compound often used as a thiol-protective agent to preserve enzymatic activities of a number of enzymes, did not interfere with glutathione determination by this method. The dinitrophenyl-S-glutathione isolated from either standard glutathione samples or from cell homogenates was shown to be identical to authentic dinitrophenyl-S-glutathione using mass spectrometry. Recovery of glutathione in standard samples by the current method was identical to that determined using 5,5'-dithiobis(2-nitrobenzoic acid). Exogenous glutathione added to supernatants of cell homogenate in the presence or absence of 2-mercaptoethanol was also completely recovered.

Chromatography, High Pressure Liquid↗
PubMed1992

Gender related differences in the expression and characteristics of glutathione S-transferases of human colon.

In the present study, the expression of glutathione S-transferase (GST) isozymes was compared in human male and female colon tissues. GST isozymes were purified and quantified in five male and five female colon tissue samples. Noticeable differences were observed in the isoelectric focusing profiles (IEF) of the GSTs, from male and female colon tissues. Both male and female colon tissues had three common GST peaks with pI values of 9.2, 6.7 and 4.8. An additional GST peak with a pI value of 6.2 found in all females was not found in males. Based on kinetic, immunological and structural properties, these isozymes were classified into alpha (pI 9.2), mu (pI 6.7 and 6.2) and pi (pI 4.8) classes. Activity of the alpha-class GST in male colon was approx. 2-fold higher than the corresponding isozyme in female colon. The pi-class GST 4.8 was the most predominant GST in both the sexes and its activity with CDNB as substrate was more abundant (about 1.6-fold) in female colon as compared to that in male colon. Significant differences were seen in substrate specificities between male and female colon GST 4.8. Sex related differences were also observed in the inhibition kinetics of GST pi from male and female colon in the presence of hematin. In addition, GST pi isolated from female colon was more thermostable as compared to the corresponding male isozyme. The thermostability of purified GST pi isozyme from males or females was not affected by incubation of the enzyme with either estrogen, testosterone or progesterone.

Amino Acid Sequence↗
PubMed1992

Glutathione S-transferases of mouse liver: sex-related differences in the expression of various isozymes.

Sex-related differences in the expression of glutathione S-transferase (GST) isozymes of mouse liver have been described. There were no apparent qualitative differences in the isoelectric focusing profiles of the GST isozymes from male and female mouse liver. Both male and female mice have at least four GST isozymes in their liver with pI values of 9.8, 8.7, 6.4 and 5.7. Kinetic, immunological, and structural properties including the N-terminal region amino acid sequences of these isozymes have been determined and they have been classified into alpha, mu, and pi classes. The most cationic isozyme (pI 9.8) belongs to the alpha class and is comparatively more abundant in female liver. The isozyme having pI 8.7 belongs to the pi class and is more abundant in male liver. The mu class GST pI 6.4 as well as the isozyme having pI 5.7 which corresponded to the a class isozyme GST 8-8 of rat liver were more abundant (about 1.5-fold) in male mouse liver as compared to the female. Interestingly, present studies reveal sex-related differences in the heat stabilities of the alpha and pi class GSTs of mouse liver. The alpha class GST pI (9.8) isolated from female mouse liver was more thermostable as compared to the corresponding enzyme from male mouse liver. On the contrary, the pi class GST (pI 8.7) from male mouse was more thermostable as compared to the corresponding enzyme from the female mouse.

Amino Acid Sequence↗