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Biomedical subjects

S Gulati

Publications and source records attributed to S Gulati.

At least 181 records · Page 10Linked to original sources

Effect of cadmium on lipid composition of the weanling rat brain.

The effect of early postnatal cadmium exposure (cadmium injected at dose levels of 1 and 2 mg cadmium/kg body weight on 3rd, 10th and 17th day after birth) on various lipid fractions of the weanling rat brain was studied. The results suggest that cadmium treatment (a dose of only 2 mg Cd/kg) results in an appreciable decrease in myelin-specific lipids like nonesterified cholesterol, ethanolamine-containing lipids, cerebrosides and sulfatides leading to hypomyelination. The lower dose of cadmium (1 mg Cd/kg) did not have any significant effect.

Animals↗

L-phenylalanine mustard-dianhydrogalactitol and hyponatremia.

The incidence of hyponatremia in 34 patients following administration of high-dose L-phenylalanine mustard (L-PAM) and dianhydrogalactitol (DAG) was determined. Two consecutive daily levels of 133 mEq/l or less were observed in 12 patients. These episodes coincided with the advent of diarrhea about 10-12 days after drug administration. The hyponatremia was not due to the syndrome of inappropriate antidiuretic hormone secretion.

Diagnosis, Differential↗

Characterization of antigens from nontypable Haemophilus influenzae recognized by human bactericidal antibodies. Role of Haemophilus outer membrane proteins.

Major outer membrane antigens, proteins, and lipopolysaccharides (LPSs), from nontypable Haemophilus influenzae were characterized and examined as targets for complement-dependent human bactericidal antibodies. Outer membranes from two nontypable H. influenzae isolates that caused otitis media and pneumonia (middle ear and transtracheal aspirates) were prepared by shearing organisms in EDTA. These membranes were compared with membranes prepared independently by spheroplasting and lysozyme treatment of whole cells and found to have: similar sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns of the proteins; identical densities (rho = 1.22 g/cm3); and minimal d-lactose dehydrogenase activity indicating purity from cytoplasmic membranes. Outer membranes were solubilized in an LPS-disaggregating buffer and proteins were separated from LPS by molecular sieve chromatography. The SDS-PAGE patterns of outer membrane proteins (OMPs) from the two strains differed in the major band although other prominent bands appeared similar in molecular weight. LPS prepared by hot phenol water extraction of each of the strains contained 45% (pneumonia isolate) and 60% (otitis isolate) lipid (wt/wt), 49% and 50% carbohydrate (wt/wt), respectively, and less than 1%, 3-deoxy-manno octulosonic acid. Immunoglobulin M (IgM) purified from normal human serum (NHS) plus complement was bactericidal for both strains. Purified immunoglobulin G (IgG) from NHS killed the middle ear isolate and immune convalescent IgM from the serum of the patient with pneumonia killed his isolate. NHS or convalescent serum were absorbed with OMPs and LPS (0.6-110 micrograms) from each of the strains and immune specific inhibition of bactericidal antibody activity by each antigen was determined. OMPs from the pulmonary isolate inhibited bactericidal antibody activity directed against the isolate in both NHS (1.5 microgram of antigen) and immune serum (0.75 microgram of antigen). OMPs (60 micrograms) from the ear isolate also inhibited bactericidal activity in the respective immune serum. LPSs exhibited minimal inhibition (greater than 110 micrograms). Three human sera (two normal, one immune) were selectively depleted of 80% of antibody activity against OMPs (measured by enzyme-linked immunosorbent assay) by affinity chromatography using OMPs from the pulmonary isolate coupled to a solid phase. These OMP antibody-depleted sera also showed an 88% reduction of bactericidal activity against this strain. Immunopurified antibody against OMPs eluted from the solid phase was bactericidal.

Adult↗

Allogeneic bone marrow transplantation for patients with acute nonlymphocytic leukemia.

Seventy patients with acute nonlymphocytic leukemia (ANLL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Thirty patients underwent transplantation in first remission, 11 in second remission, 3 in third remission, and 26 in relapse. At a median follow-up of 30 mo, 17 of those in first remission and 7 of those in second remission survive in continuous remission, compared to 1 in third remission and 3 in relapse. The 3-yr Kaplan-Meier probability of disease-free survival among the various groups was 55% (+/- 9.2%) for the first remission transplants, 64% (+/- 14.5%) for second remission, 33% (+/- 20%) in third remission, and 10.3% (+/- 6.3%) in the relapse group. Statistical analysis showed a similar survival in the first and second remission groups that was significantly better than that seen in the third remission and relapse groups (p less than 0.01). The improved survival seen in the early remission groups was due to a significant decrease in the incidence of relapse posttransplant (p less than 0.01). These results confirm observations that a significant number of patients transplanted in first remission may achieve extended disease-free survival and document similar results for patients transplanted in second remission.

Acute Disease↗

Defective interleukin 2 production in patients after bone marrow transplantation and in vitro restoration of defective T lymphocyte proliferation by highly purified interleukin 2.

Using OKT3 monoclonal antibody as a mitogen, we have studied interleukin 2 (IL2) production and proliferation in peripheral blood mononuclear cells (PBMC) of 23 patients receiving bone marrow transplants. Twenty patients were recipients of allogeneic bone marrow for treatment of hematologic malignancies, aplastic anemias (AA), or severe combined immunodeficiencies (SCID). Three patients with Hodgkin's disease or neuroblastoma received autologous bone marrow. Endogenous IL2 production was not detectable (less than 0.2 U/mL) in PBMC of 18 patients and was very low in PBMC from five patients (0.5 to 1.5 U/mL), as compared to normal controls (median 3.5 U/mL) or pretransplant patients (median 1.5 U/mL). The low IL2 production was associated with defective OKT3-induced proliferation of PBMC in 19 of 23 patients studied. In the first 6 months after BMT, 14 of 15 patients (93%) showed defective proliferation of PBMC as compared to five of eight patients (63%) tested between 7 and 18 months after BMT (P less than .1). In all but three patients, addition of highly purified human lymphocyte IL2 (hpIL2) restored OKT3-induced proliferation of PBMC to within the normal range. This study demonstrates that PBMC in patients after BMT have a defect of IL2 production but are able to express IL2 receptors in response to OKT3 antibody and to proliferate normally upon addition of hpIL2. PBMC of all patients showed similar functional defects, whether or not they received additional therapy, including various conditioning regimens prior to BMT and immunosuppressive therapy after BMT. These observations suggest that T cell defects after BMT are most likely secondary to quantitative or qualitative defects of transplanted T lymphocytes or their precursors.

Anemia, Aplastic↗

ABH incompatible bone marrow transplantation: removal of erythrocytes by starch sedimentation.

Nineteen patients with acute leukaemia underwent bone marrow transplantation despite major ABH incompatibility between donor and recipient. The marrow inoculum was prepared prior to infusion by admixture with hydroxyethyl starch to sediment the incompatible erythrocytes, which were then discarded. The infusion was well tolerated with two patients developing transient haemoglobinuria, seven patients developing low grade fever and 10 experiencing no reaction. Durable haematopoietic engraftment was achieved in the 18 evaluable patients and was not influenced by pre-transplant isohaemagglutinin titres. No difference in time to engraftment, incidence of GVHD or in overall survival was found, compared to ABH compatible transplants. Therefore, the presence of incompatibility did not appear to influence transplant outcome adversely. The technique described is a rapid and safe method for overcoming the ABH barrier in marrow transplantation.

ABO Blood-Group System↗

Allogeneic bone marrow transplantation for patients with acute lymphoblastic leukemia.

Fifty-two patients with acute lymphoblastic leukemia (ALL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Twenty-two patients were in second remission, 15 in a later remission, and 15 were in relapse at the time of the transplant. At a median follow-up of 24 mo, 14 of those in second remission survive in continuous remission compared to 5 in later remission and 4 in the relapse group. Statistical analysis showed an improved disease-free survival for the second remission group (p = 0.09). Patients transplanted in later remission or relapse had a similar survival. The improved survival in second remission resulted from a decreased relapse rate posttransplant, as the early mortality from nonleukemic causes was similar among the groups (p = 0.01). In the second remission patients, no characteristics of the initial leukemia were identified that significantly affected outcome. In the combined later remission and relapse group, poor prognosis posttransplant was associated with initial WBC greater than 20K, age at diagnosis older than 10, or initial remission duration less than or equal to 1 yr. These results suggest that extended disease-free survival may be achieved by second remission transplantation and that improved therapy is necessary for later remission or relapse transplants due to the high rate of posttransplant relapse.

Adolescent↗

Macroscopic and microscopic measurement of myocardial infarct size. A comparison.

Infarct size measured by microscopic method is consistently larger than that measured macroscopically, indicating that certain areas of infarction are missed when observed macroscopically. Existence of a good correlation between the two methods, however, suggests that macroscopic estimation of infarct size would be enough for initial screening of the interventions designed for salvation of ischemic myocardium, as it is an easy method. An additional advantage of this method is that it can be utilized to measure infarct size as early as 72 h after production of infarction. Comparison of weight and volume method of macroscopic estimation of infarct size has shown that they do not give significantly different results. Weight method being less cumbersome and less time-consuming, may be adopted for initial screening of cardioprotective agents.

Animals↗

Portal hypertension in north Indian children.

Etiological factors associated with portal hypertension in children influence the decision about therapy and the prognosis. This cross-sectional observational study was performed at a tertiary care centre in northern India from January, 1990 to December, 1994. Children below the age of 14 years with suspected portal hypertension were prospectively assembled into a cohort to determine the etiology and clinical profile of portal hypertension. Of the 115 patients with portal hypertension, 76.5% had extrahepatic portal hypertension (EHPH). Remaining 23.5% of the cases had intrahepatic and post-hepatic causes of portal hypertension. Children with EHPH had a significantly earlier onset of symptoms as compared to those with intrahepatic portal hypertension (p = 0.002) and bled significantly more frequently (p = 0.00). Forty per cent of patients with chronic liver disease (CLD) never had jaundice. History suggestive of potential etiological factors could be elicited in only 7% of EHPH patients. The commonest site of block in splenoportal axis was at the formation of the portal vein. An inverse relation of bleeding rates with duration of illness was seen in EHPH. Of the 10 CLD patients in whom liver biopsy could be done, cirrhosis was present in 6 patients. Understanding the natural history of EHPH and portal hypertension due to other etiologies may have significant implications in choosing the appropriate intervention and predicting the outcome.

Adolescent↗

The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis.

Neisseria gonorrhoeae and Neisseria meningitidis have evolved intricate mechanisms to evade complement-mediated killing. Sialylation of gonococcal lipooligosaccharide (LOS) results in conversion of previously serum sensitive strains to unstable serum resistance, which is mediated by factor H binding. Porin (Por) is also instrumental in mediating stable serum resistance in gonococci. The 5th loop of certain gonococcal PorlAs binds factor H, which efficiently inactivates C3b to iC3b. Factor H glycan residues may be essential for factor H binding to certain Por1A strains. Por1A strains can also regulate the classical pathway by binding to C4b-binding protein (C4bp) probably via the 1st loop of the Por molecule. Certain serum resistant Por1 B strains can also regulate complement by binding C4bp through a loop other than loop 1. Purified C4b can inhibit binding of C4bp to Por 1B, but not Por1A, suggesting different binding sites on C4bp for the two Por types. Unlike serum resistant gonococci, resistant meningococci have abundant C3b on their surface, which is only partially processed to iC3b. The main mechanism of complement evasion by group B meningococci is inhibition of membrane attack complex (MAC) insertion by their polysaccharide capsule. LOS structure may act in concert with capsule to prevent MAC insertion. Meningococcal strains with Class 3 Por preferentially bind factor H, suggesting Class 3 Por acts as a receptor for factor H.

Blood Bactericidal Activity↗