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Biomedical subjects

S Gulati

Publications and source records attributed to S Gulati.

At least 127 records · Page 7Linked to original sources
PubMed1992

Demonstration of Cu-Zn superoxide dismutase in rat liver peroxisomes. Biochemical and immunochemical evidence.

In this study, by using highly purified rat liver peroxisomes, we provide evidence from analytical cell fractionation, Western blot, and immunocytochemical analysis that Cu-Zn superoxide dismutase is present in animal peroxisomes. Treatment with ciprofibrate, a peroxisome proliferator, increased the peroxisomal superoxide dismutase activity by 3-fold with no effect on mitochondrial activity but a marked decrease in cytosolic superoxide dismutase activity, further supporting that besides cytosolic and mitochondrial localization, Cu-Zn superoxide dismutase is present in peroxisomes also. Demonstration of superoxide dismutase in peroxisomes suggests a new role for this organelle in pathophysiological conditions, such as ischemia-reperfusion injury.

Animals↗
PubMed1992

Multi-drug-resistant Salmonella typhi--a need for therapeutic reappraisal.

Enteric fever caused by Salmonella typhi resistant to all the standard first-line antibiotics is emerging as a major problem in developing countries. Fifteen such culture-proven cases were treated with ceftriaxone (6), cefotaxime (5) or ciprofloxacin (4). The earliest defervescence occurred with ceftriaxone (mean 3.3 days). Clinical cures were obtained with all three drugs with only one child having a relapse. Ciprofloxacin, by virtue of its cost and an oral route of administration, is the ideal choice in a developing country.

Cefotaxime↗
PubMed1992

Human vaccination with Escherichia coli J5 mutant induces cross-reactive bactericidal antibody against Neisseria gonorrhoeae lipooligosaccharide.

The lipopolysaccharides of enteric gram-negative bacteria and the lipooligosaccharides (LOS) of Neisseria gonorrhoeae may share antigenic determinants that are targets of bactericidal antibody. Natural (disseminated) infection with a serum-resistant gonococcal strain and immunization with Escherichia coli J5 stimulated bactericidal IgG anti-LOS antibodies that recognize different serum-resistant gonococcal LOS epitopes. In bactericidal assays, convalescent serum from disseminated infection killed only the homologous strain while post-J5 vaccination serum killed 6 of 9 additional strains. Both convalescent and post-J5 vaccination sera mediated marker (51Cr) release from liposomes sensitized with serum-resistant gonococcal LOS (homologous strain), linking acquired killing activity to cross-reacting anti-LOS antibody. Post-J5 IgG mediated 51Cr release more effectively than did convalescent IgG. Thus, bactericidal antibody elicited by J5 vaccination is more efficacious and broadly cross-reactive against serum-resistant gonococci than is antibody elicited by natural infection. Moreover, multiple LOS epitopes may serve as bactericidal targets on serum-resistant gonococci.

Antibodies, Bacterial↗
PubMed1992

Ca2+ transport in unstimulated platelets of essential hypertensives and their blood relatives.

OBJECTIVE: Intracellular free Ca2+ concentration has been shown to be elevated in platelets from essential hypertensive patients. This study was designed to characterize Ca2+ homeostasis in platelets of essential hypertensives. DESIGN: A double-blind study was carried out. Untreated and treated (propranolol therapy) essential hypertensives were studied in comparison with normotensive control subjects. First-degree blood relatives of essential hypertensives were also studied. The various procedures used in the study were already standardized and well-established methods. METHOD: For Ca2+ uptake and efflux studies, 45Ca was used. For intracellular free Ca2+ concentration studies the fluorescent Ca2+ chelator dye fura-2/acetoxymethyl ester (fura-2/AM) was used. RESULTS: The uptake of 45Ca by unstimulated platelets of untreated essential hypertensives and their relatives was significantly higher than for controls. However, essential hypertensives treated with a beta-blocker drug showed no significant difference in Ca2+ uptake compared with controls. A significantly decreased Ca2+ efflux was observed in essential hypertensives (both untreated and treated) compared with controls. Relatives also showed a depressed Ca2+ efflux compared with controls. CONCLUSIONS: It appears that the elevated intracellular free Ca2+ concentration levels in platelets (also observed by us) may be due to both an enhanced uptake into, and decreased efflux of Ca2+ from, the cell. Beta-blocker therapy may help to normalize the elevated intracellular free Ca2+ concentration levels observed in essential hypertensives. Relatives exhibit a state predisposed towards the development of hypertension.

Adolescent↗
PubMed1992

'Chest epilepsy' in a child.

Pain is a most unusual manifestation of epilepsy, and it is rarer still for chest pain to be the primary manifestation of a seizure disorder. We report here a 6 year old boy with epileptic chest pain--'chest epilepsy'--an entity not previously described in children.

Chest Pain↗
PubMed1992

Treatment of patients with relapsed and resistant non-Hodgkin's lymphoma using total body irradiation, etoposide, and cyclophosphamide and autologous bone marrow transplantation.

PURPOSE: Patients with non-Hodgkin's lymphoma (NHL) who do not achieve a complete response (CR) after induction chemotherapy or who relapse after achieving a CR are rarely cured of their disease by the usual salvage therapy. Success of high-dose cytotoxic therapy with an autologous bone marrow transplant (AuBMT) is limited. We describe the results of a prospective single-institution study using a new conditioning regimen for patients with relapsed or resistant NHL who underwent AuBMT. PATIENTS AND METHODS: Forty-four patients were reinduced with cytotoxic therapy and then evaluated for response. All patients received the conditioning regimen of hyperfractionated total body irradiation (TBI), etoposide (VP-16), and cyclophosphamide (CTX) followed by autologous bone marrow reinfusion. RESULTS: The disease-free survival (DFS) rate was 57% with a median follow-up of 42+ months. The only variable significantly associated with DFS was the patient's remission status at AuBMT. Patients who underwent AuBMT in CR had a DFS of 80%, whereas patients who underwent AuBMT in partial response (PR) or with progressive disease (PD) had a DFS of 60% and 11%, respectively (P = .002). The major toxicity was hemorrhage at the site of bulky disease, especially in patients with residual mediastinal and/or pulmonary disease. CONCLUSION: Planned reinduction cytotoxic therapy followed by TBI, VP-16, and CTX with AuBMT is an effective treatment for patients with relapsed and resistant NHL.

Adult↗
PubMed1992

Autologous bone marrow transplantation for acute myelogenous leukemia using 4-hydroperoxycyclophosphamide and VP-16 purged bone marrow.

Thirty adult patients with acute myelogenous leukemia (AML) in remission were treated with hyperfractionated total body irradiation, VP-16, and cyclophosphamide followed by infusion of autologous bone marrow purged with 4-hydroperoxycyclophosphamide and VP-16. Fifteen patients were transplanted in first remission (R1), 13 in second remission (R2), and two in third remission (R3). All patients had hematopoietic engraftment. The median time to achieve a white blood cell count of 1.0 x 10(9)/l and a neutrophil count of 500 x 10(6)/l was 32 days. The median time to achieve an unsupported platelet count of 50 x 10(9)/l was 70 days. There were four transplant-related deaths, all in patients in R2. Ten patients have relapsed, including both patients transplanted in R3. The disease-free survival (DFS) of all patients is 52%, median follow-up not yet reached. Although the number of patients in each group is small and follow-up is limited, there is a trend toward improved actuarial DFS in patients transplanted in R1 compared with patients transplanted in R2 (72 vs 39%; p = 0.081). Use of VP-16 in the conditioning regimen as well as in the purging procedure is feasible in the treatment of patients with AML.

Adult↗
PubMed1992

Serological responses to hepatitis B virus infection in multi-transfused thalassemic children.

One hundred children with beta-thalassemia major were studied prospectively. A one time analysis of serum samples was carried out for a battery of hepatitis B viral markers viz., HBsAg, anti-HBs and anti-HBc. Seven mutually different serological patterns were observed. The commonest profile seen in 49 patients was a combined seropositivity for anti-HBc and anti-HBs indicating past HBV infection with persisting immunity. Definite evidence of active HBV infection (seropositivity for HBsAg and/or HBeAg) was demonstrated in 10 cases, six of these were HBsAg positive. Anti-HBc positivity alone was detected in 17 patients. The remaining 24 children were seropositive for anti-HBs alone suggesting a possible passive transmission of anti-HBs through blood transfusion.

Blood Transfusion↗
PubMed1991

Duration of the preclinical phase of chronic myelogenous leukemia: a case report.

The molecular events that allow for clonal expansion of the malignant population in chronic myelogenous leukemia (CML) are poorly understood. Recent experiments in transgenic mice suggest a close temporal relationship between expression of the aberrant protein and manifestation of a hematologic neoplasm that resembles CML; tracing the same phenomenon in humans has not been possible. We studied a patient who underwent autologous bone marrow harvest after completion of chemotherapy and radiation therapy for advanced stage Hodgkin's disease. At the time of harvest his peripheral blood counts and bone marrow were morphologically normal. Sixteen months later he developed the clinical manifestations of CML. Detailed molecular evaluation of the harvested marrow showed that a small number of cells contained the Philadelphia chromosome. The time interval required for expansion of the malignant clone, as suggested by this particular patient, was at least 16 months although it is recognized that this figure may be variable.

Adult↗
PubMed1991

The effects of transforming growth factor beta 3 on the growth of highly enriched hematopoietic progenitor cells derived from normal human bone marrow and peripheral blood.

The effects of transforming growth factor beta 3 (TGF-beta 3) on growth in semisolid cultures of enriched hematopoietic progenitors derived from normal human marrow and blood were evaluated. Conditioned media from the Mo-T cell line (MoCM) were the source of colony-stimulating factors used to optimally stimulate primitive progenitors. To assess whether a proportion of granulocyte/monocyte (GM) progenitors were prevented from cycling, all sizes of GM aggregates were evaluated from 3 to 20 days. The activity of TGF-beta 3 on the growth of erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM) was similar to that observed for TGF-beta 1. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or 72 h after initiation of culture, did not significantly affect the total number of marrow GM aggregates at 3, 7, 14, and 20 days, but TGF-beta 3 (1,000 pmol/liter), added initially, reduced the total number of blood GM aggregates. This suggests that some blood GM progenitors might be blocked from cycling but that the great majority of marrow GM progenitors are not blocked. Whether TGF-beta 3 (10, 100, and 1,000 pmol/liter) was added initially or after 72 h of stimulation by MoCM, there was a dose-dependent reduction of marrow and blood GM colony size even when the total number of colonies was unaffected. TGF-beta 3 (10, 100, and 1,000 pmol/liter), added initially or at 72 h, reduced in a dose-dependent manner the size of marrow and blood-derived BFU-E. TGF-beta 3 (1,000 pmol/liter) was more likely to reduce the total number of marrow and blood BFU-E, and this increased sensitivity of the erythroid lineage may prevent the development of this population in colonies derived from multipotential colony-forming unit-granulocyte/erythroid/monocyte (CFU-GEM). The results suggest that the main effect of TGF-beta 3 and TGF-beta 1 is to slow the rate of proliferation of hematopoietic progenitors rather than to prevent them from beginning proliferation. This results in a reduction in colony size which prevents the identification of primitive versus mature progenitor on the basis of standard criteria of colony size.

Bone Marrow↗
PubMed1991

Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia.

4'-Demethoxydaunorubicin (idarubicin [IDR]) is a new anthracycline that differs from its parent compound by the deletion of a methoxy group at position 4 of the chromophore ring. This minor structural modification results in a more lipophilic compound with a unique metabolite that has a prolonged plasma half-life as well as in vitro and in vivo antileukemia activity. To determine its activity in acute myelogenous leukemia (AML), 130 consecutive adult patients between the ages of 16 and 60 with newly diagnosed disease were randomized in a single institution study to receive either IDR in combination with cytosine arabinoside (Ara-C) or standard therapy with daunorubicin (DNR) and Ara-C. The trial was analyzed using the O'Brien-Fleming multiple testing design that allowed for periodic inspection of the data at specific patient accession points. After accrual of 60 patients per arm, analysis showed that patients who received IDR/Ara-C had a superior response compared with those who received standard therapy: 48 of 60 patients (80%) achieved complete remission on the former arm compared with 35 of 60 patients on the latter (58%, P = .005). Logistic regression analysis of factors associated with complete response indicated that treatment with IDR/Ara-C offered a significant advantage to patients who presented with a high initial white blood cell count compared with treatment with DNR/Ara-C. The degree of marrow aplasia was approximately the same on each arm as was nonhematologic toxicity. Overall survival for patients on the IDR/Ara-C arm was 19.5 months compared with 13.5 months on the DNR/Ara-C arm (P = .025) at a median follow-up of 2.5 years. We conclude that IDR/Ara-C can effectively replace standard therapy with DNR/Ara-C in adult patients less than age 60 with newly diagnosed AML.

Adult↗
PubMed1991

Autologous bone marrow transplantation for refractory or relapsed Hodgkin's disease: the Memorial Sloan-Kettering Cancer Center experience using high-dose chemotherapy with or without hyperfractionated accelerated total lymphoid irradiation.

Fifty patients with advanced-stage Hodgkin's disease (HD) who relapsed or failed to respond to multiple regimens of combination chemotherapy were entered onto two autologous bone marrow transplantation (AuBMT) protocols. Twenty-eight patients who did not have prior radiation therapy were treated with protocol A. Protocol A consisted of reinduction with conventional doses of combination chemotherapy followed by boost local-field irradiation to areas of residual disease and hyperfractionated accelerated total lymphoid irradiation (TLI). Chemotherapy consisted of high-dose etoposide (VP-16) and cyclophosphamide followed by infusion of cryopreserved, unpurged autologous bone marrow. Twenty-two patients who have had prior radiation therapy were treated with protocol B. Protocol B consisted of reinduction with conventional doses of chemotherapy followed by involved field radiation therapy (when tolerance to residual disease has not been previously reached). High-dose chemotherapy regimen consisted of cyclophosphamide, carmustine (BCNU), and VP-16 (CBV) followed by autologous bone marrow transplantation. Of the 28 patients in protocol A, 5 patients died during the immediate peritransplant period, 5 patients progressed within six months, and 2 of them died. Two patients relapsed 13 and 39 months post transplant; 1 of them was reinduced into a complete remission (CR). Seventeen patients (61%) are disease free (16 patients in continuous complete remission), 12-54+ months (median 25+ months) following completion of therapy. Of the 22 patients in protocol B, 1 died of cytomegalovirus pneumonitis, and 11 relapsed. Ten patients (45%) are alive and disease free 16-42+ months (median 23+ months) after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗