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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 109 records · Page 6Linked to original sources
PubMed1995

Acrolein mercapturates: synthesis, characterization, and assessment of their role in the bladder toxicity of cyclophosphamide.

Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP. The objectives of this study were to prepare and characterize synthetic standards of the GSH acrolein adduct (3-oxopropyl)glutathione (3-oxoPrGSH), the acrolein mercapturates S-(3-oxopropyl)-N-acetylcysteine (3-oxoPrMCA) and 3-hydroxyPrMCA, and the S-oxidation product of 3-oxoPrMCA (3-oxoPrMCA S-oxide). In addition, the release of acrolein from, and the bladder toxicity of, these conjugates was determined. 3-OxoPrGSH and 3-oxoPrMCA were prepared with a 99% yield by condensing acrolein with GSH and N-acetylcysteine, respectively. 3-HydroxyPrMCA was prepared with a 63% yield by refluxing 3-chloropropanol and N-acetylcysteine in a basic medium. Oxidation of 3-oxoPrMCA with H2O2 was used to prepare 3-oxoPrMCA S-oxide. By decreasing the reaction time to 1 h, and adjusting the ratio of 3-oxoPrMCA to H2O2, the yield of 3-oxoPrMCA S-oxide was increased to 96%. The anhydrous aldehyde, 3-oxoPrMCA, afforded characteristic aldehydic proton resonances (1H NMR) in deuterated dimethyl sulfoxide. New resonances were observed in deuterated water, indicating a 75% hydration of the aldehyde to the corresponding geminal diol. This phenomenon was enhanced with 3-oxoPrMCA S-oxide where approximately 100% hydration of the aldehyde to the corresponding geminal diol was observed. When incubated at 25 degrees C in 100 mM potassium phosphate buffer containing 1 M KCl, pH 8.0, 3-oxoPrMCA released approximately 6% and 3-oxoPrMCA S-oxide released approximately 16-18% of the theoretical maximum yield of acrolein after 30 min, as indicated by an increase in absorbance at 210 nm and confirmed by trapping this aldehyde as a semicarbazone. There was less than a 2% yield of acrolein from 3-hydroxyPrMCA or 3-oxoPrGSH under similar conditions. At pH 7.4 the release of acrolein from 3-oxoPrMCA and 3-oxoPrMCA S-oxide was decreased by 50%. An assay where aldehydes are reacted with m-aminophenol in acid media produced fluorescence consistent with 72%, 46%, 23%, and 1% yields of acrolein from 3-oxoPrMCA S-oxide, 3-oxoPrMCA, 3-oxoPrGSH, and 3-hydroxyPrMCA, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcysteine↗
PubMed1995

Growth attenuation in a human prostate cell line mediated by a phorbol ester.

Human prostatic cancer cells JCA-1 were induced with a phorbol ester 12-o-tetradecanoylphorbol-13-acetate (TPA), and cell growth differentiation were analyzed. Within hours of exposure to TPA, cell proliferation decreased and reached approximately 80% reduction after 3 days, as determined by [3H]thymidine incorporation and cell counting. Cell cycle analysis revealed a blocking of cells entering into the replicating S and G2M phases from the G1 phase. The TPA induced cells had a reduced growth rate but remained viable. The growth-modulating activity of TPA was similarly observed with LNCaP cells. Agarose gel electrophoresis of the chromosomal DNA from induced cells exhibited a non-fragmented pattern excluding the possibility of cell apoptosis. In parallel to the growth reduction, the TPA induced cells became larger in size showing dendrite like cytoplasmic extensions. Furthermore, JCA-1 cells treated with TPA acquired the expression of cytokeratin 18 and increased the expression of actin and vimentin by 300%. These results indicate an induced growth reduction accompanied by cellular differentiation of the prostatic cancer cells.

Cell Cycle↗
PubMed1995

An analysis of serum estradiol and serum progesterone in postmenopausal women of karachi suffering from breast cancer.

The cancer patients (39) and control (12) were subjected to postmenopausal hormonal evaluation in which serum estradiol and serum progesterone values were found to be 54.56 +/- 10.20 pg/ml as compared to 18.66 +/- 6.31 pg/ml and 0.170 +/- 0.01 ng/ml as compared to 0.229 +/- 0.01 ng/ml respectively. Consequently it was inferred that in cancer postmenopausal patients when serum estradiol level increases the serum progesterone level decrease and vice versa.

Breast Neoplasms↗
PubMed1995

Pilot study of all-trans retinoic acid as post-remission therapy in patients with acute promyelocytic leukemia.

Chemotherapy may decrease relapses of acute promyelocytic leukemia (APL) following induction with all-trans retinoic acid (ATRA), however the optimal timing of these two modalities remains to be determined. We treated eight patients with morphologic evidence of APL with intensive induction chemotherapy followed by ATRA (45 mg/m2/d for 10 weeks). All eight patients achieved a complete remission following chemotherapy. After a median follow-up of 29.0 months, seven patients remain in complete remission; one patient relapsed at 26.9 months. RT-PCR analysis for the PML/RAR alpha rearrangement was performed to monitor patients for evidence of minimal residual disease. Both of the patients with persistence of this rearrangement after induction chemotherapy converted to negative following ATRA. Toxicity of ATRA given in the post-remission setting was mild and consisted of headache, dry skin, and elevations of triglycerides and transaminases. No patient developed evidence of the retinoic acid syndrome. The administration of ATRA after intensive induction chemotherapy is associated with durable remissions and minimal toxicity in patients with APL. Disappearance of the PML/RAR alpha rearrangement after ATRA suggests that ATRA is effective against minimal residual disease.

Adult↗
PubMed1994

Urologic complications of high-dose chemotherapy and bone marrow transplantation.

OBJECTIVE: This study reviews the incidence and management of cyclophosphamide-induced hemorrhagic cystitis in a group of patients who received high-dose chemotherapy and bone marrow transplantation. METHODS: The records of 217 consecutive patients undergoing bone marrow transplantation were reviewed. The incidence, degree, and management of hematuria in this group of pancytopenic and immunocompromised patients were recorded. RESULTS: Despite prophylaxis, cystitis developed in 58 of these 217 patients (27%). In 12 patients (6%) the cystitis was severe. These patients had gross hematuria, clot retention, and drop in hematocrit necessitating blood transfusion. These patients were managed with continuous bladder irrigation, alum irrigation, and when less aggressive approach was unsuccessful, with intravesical formalin instillation. Alum irrigation was used in 5 patients, and was successful in only 1 patient. Six patients required intravesical formalin instillation to control the hematuria. Formalin solution 2-5% was instilled initially. When lower-concentration formalin failed, 5-10% formalin was used progressively. CONCLUSIONS: Patients with bone marrow transplantation in whom severe hemorrhagic cystitis develops should be managed aggressively early. Intravesical formalin appears to be the most effective regimen in controlling profuse, persistent hematuria.

Adolescent↗
PubMed1994

The combined use of soybean agglutinin and immunomagnetic beads for T lymphocyte subset depletion of bone marrow allografts: a laboratory analysis.

The prevention of graft-versus-host disease by T-lymphocyte depletion of allografts prior to bone marrow transplantation has resulted in an increase in graft failure/rejection and relapse of disease. Evidence for the selective roles of specific T-lymphocyte subsets in each of the engraftment, graft-versus-host disease, and disease relapse processes has been presented, but sufficient clinical verification to support any hypothesis in this regard is lacking. In this paper we describe a convenient and highly flexible clinical laboratory method for depletion of specific T-lymphocytes in controllable quantities by the use of select monoclonal antibodies. Almost 3 log10 removal of CD2+ and CD8+ cells without significant loss of hematopoietic progenitors (CFU-GM, BFU-E, and CD34+ cells) can be reproducibly achieved. This method, employing soybean agglutination and immunomagnetic beads, is potentially adaptable to depletion of any cell subset or any tumor cell for which unique cell-surface antigen characteristics have been defined. In addition, our protocol is equally suited to the positive selection of stem cells and hematopoietic progenitors bearing the CD34 surface antigen.

Bone Marrow Transplantation↗
PubMed1994

Heparin prevents antigen-induced airway hyperresponsiveness: interference with IP3-mediated mast cell degranulation?

We hypothesized that heparin, because of its antiallergic and/or anti-inflammatory properties, modifies airway hyperresponsiveness (AHR). We studied the effects of inhaled heparin on AHR induced by specific antigen or by platelet-activating factor (PAF), a proinflammatory mediator. Specific lung resistance (sRL) was measured in 17 allergic sheep before, immediately after, and serially for up to 2 h after airway challenge with either specific antigen or PAF. Airway responsiveness was expressed as the cumulative provocative dose of carbachol that increased sRL to 4 cmH2O/s [PD4, in breath units (BU; 1 BU = 1 breath of 1% carbachol solution)]. PD4 was determined on a baseline day and on various experimental days 2 h after airway challenge with antigen or PAF, without or after pretreatment with inhaled heparin (1,000 U/kg). Pretreatment with inhaled heparin prevented antigen-induced bronchoconstriction and postantigen AHR. PD4 was 26 +/- 2.6 (SE), 12 +/- 1.7, and 22 +/- 2.8 BU on baseline, antigen control, and postheparin days, respectively. Heparin given immediately after the antigen challenge failed to modify the magnitude and/or duration of antigen-induced bronchoconstrictor response or postantigen AHR. Heparin also failed to prevent PAF-induced changes in sRL and AHR. In vitro heparin inhibited anti-immunoglobin E- and 1,4,5-inositol triphosphate-mediated degranulation of rat peritoneal mast cells without attenuating the effects of the Ca2+ ionophore A-23187. These data suggest that in "acute responders" heparin prevents antigen-induced bronchoconstriction and AHR, possibly by inhibiting 1,4,5-inositol triphosphate-dependent mast cell mediator release and not by its anti-inflammatory action.

Animals↗
PubMed1994

Simultaneous occurrence of chronic myelogenous leukemia and signet-ringed adenocarcinoma of the rectum. A case report with a review of the literature.

Chronic myelogenous leukemia (CML) is a pluripotent stem cell malignancy with an incidence of 1.3 per 100,000. Occasionally this uncommon disease occurs concomitantly with other neoplasia including various lymphoproliferative disorders. Its association with solid tumors, especially in young people, is decidedly rare. We report the simultaneous occurrence of CML and signet-ringed adenocarcinoma of the rectum in a 20-year-old male. A review of the literature pertinent to this topic will be briefly discussed, emphasizing characteristics of rectal carcinomas in younger age-groups as well as the unexpected association of CML with solid tumors.

Adult↗
PubMed1994

Incidence and treatment of tumor lysis syndrome in patients with acute leukemia.

Tumor lysis syndrome (TLS) is a complication associated with electrolyte abnormalities that is observed in patients with acute leukemia who are receiving intense doses of chemotherapy. Forty-one patients with acute leukemia were treated with high-dose combination chemotherapy and were evaluated for TLS. A grading system developed for the evaluation of these patients was applied. Grade I tumor lysis was observed in 22 patients, grade II TLS in 2 patients and grade III in 1 patient. All patients were treated with intravenous fluids, mannitol, allopurinol and in some patients, aluminum-based antacids. Treatment for TLS prior to intensive chemotherapy reduced morbidity and mortality associated with high-dose chemotherapy for acute leukemias.

Adolescent↗
PubMed1994

Allogeneic marrow transplantation for myelodysplastic syndrome complicating autologous bone marrow transplantation.

A patient with refractory relapsed Hodgkin's disease underwent an autologous bone marrow transplant in July 1987 and achieved remission of Hodgkin's disease. He had complete hematological recovery but developed pancytopenia 3 years post bone marrow transplantation with morphological evidence of myelodysplasia. High-dose cyclophosphamide, 200 mg/kg, chemotherapy followed by an allogeneic bone marrow transplant from a HLA-matched sibling was performed in April 1991 with complete hematological recovery. Allogeneic bone marrow transplantation was thus used successfully to treat a potential complication of autologous bone marrow transplantation.

Adult↗
PubMed1994

Treatment of gancyclovir resistant cytomegalovirus with foscarnet: a report of two cases occurring after bone marrow transplantation.

Cytomegalovirus (CMV) infection is common in patients who undergo allogeneic bone marrow transplantation. Gancyclovir is useful in treating CMV infections. Resistance to gancyclovir is rare and has, thus far, not been reported in the setting of BMT. Two patients with CMV infections unresponsive to gancyclovir were successfully treated with foscarnet. 10-15% of CMV infections are resistant initially or develop resistance to gancyclovir. Both patients had an adequate trial of gancyclovir and resistance developed over time. While we did not document resistance in the laboratory there was dramatic clinical improvement with foscarnet.

Adult↗