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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 1,225 records · Page 68Linked to original sources

Fetal liver infusion in aplastic anaemia.

Forty patients with severe aplastic anaemia received an intravenous infusion of 0.004 to 11.1 x 10(8) (median: 8 x 10(8) hematopoietic cells prepared from the fetal livers of 8-32 week old abortuses. Five patients, who died within 15 days of fetal liver infusion, are excluded from analysis. Twenty-two of the 35 evaluable patients (62%) responded favourably. Six of the 7 patients with good response were alive after 9 to 44 months (median: m = 20); one died 106 months after fetal liver infusion due to renal lithiasis. Four of the 7 with moderate response were alive after 9 to 31 months; 3 died within 16 months. Of 8 patients with minimal response, one was lost to follow-up and the others died in 3.4 to 10 months (m = 6). Median survival of responders was 15.7 months. Bone marrow cellularity became normal in 12 patients following fetal liver infusion. In seven patients, there was a relapse; 6 regained a normal bone marrow cellularity after a second or third fetal liver infusion. These data strongly suggest a role of fetal liver infusion in inducing bone marrow recovery. Of 13 non-responders, 4 were lost to follow-up and 9 died within 20 days-4.3 months (m = 1.6). Fetal liver infusion appears to be an effective therapy in patients with severe aplastic anaemia.

Anemia, Aplastic↗

Bone marrow recovery following fetal liver infusion (FLI) in aplastic anaemia: morphological studies.

Twenty-two of 35 patients with aplastic anaemia who received fetal liver infusion (FLI), responded to this treatment. Detailed review of bone marrow aspirates and biopsies was available in 17. There was a good correlation between clinical improvement and blood counts. The bone marrow cellularity increased to 48 percent in about 18 weeks with repopulation by both erythroid and myeloid cells. The erythroid response was predominant and the earliest to occur (1.5-61 weeks); it lasted for 7.5-100 weeks. Marked dyserythropoiesis was observed. Myeloid response occurred simultaneously in 45 percent of the responders; in the others it was delayed by 1.5 to 4 weeks. Significant dysmyelopoiesis with shift to the left, unrelated to infection, was seen 1.5 to 9.5 weeks after FLI lasting for 9-26 weeks in most cases. Megakaryocytic response either did not occur or was delayed, less marked and often transient.

Anemia, Aplastic↗

Fetal liver infusion in acute myelogenous leukaemia.

Forty-five patients with acute myelogenous leukaemia (AML) received induction chemotherapy with either a conventional dose of cytarabine and daunorubicin (27 patients) or a low dose of cytarabine (18 patients). Maintenance chemotherapy was given to all responders. In 14 of 39 evaluable patients, infusion of fetal liver cells from 10-24 weeks old foetuses was given following induction as well as maintenance therapy. Six of 14 patients (43%) achieved a complete remission; 2 showed evidence of transient engraftment documented by analysis of sex chromosomes and RBC antigens (1 patient each). Fetal liver infusion within 6 days of completing induction chemotherapy appeared more effective than when given later. Five of 25 patients (20%) who did not receive fetal liver infusion achieved a complete remission. The present work suggests that fetal liver infusion given following induction chemotherapy may increase the remission rate in AML either by temporary engraftment or by accelerating the rate of haematological recovery.

Antineoplastic Combined Chemotherapy Protocols↗

Studies on engraftment following fetal liver infusion.

Studies to find engraftment following fetal liver infusion (FLI) in aplastic anaemia (AA) and acute myeloid leukaemia (AML) were carried out in 24 patients (17 AA and 7 AML patients) out of the 56 who received FLI. HLA studies done in 13 patients (3 AA and 5 AML), repeatedly after FLI, showed no significant change in HLA antigen pattern before and after FLI. Red cell antigen studies were done in five (1 AA and 4 AML) patients, 3 weeks to 7 months after FLI. One patient with AML who was Rh negative prior to reinduction chemotherapy became Rh positive two months after FLI; six months later he was Rh negative again. In the remaining patients there was no change in red cell antigen pattern after FLI. Radio-immuno-assay to detect alpha-fetoprotein levels, carried out in 10 (8 AA and 2 AML) patients repeatedly after FLI, demonstrated no increase. In 13 patients (8 AA and 5 AML) in whom there was a sex difference between donor and recipient, bone marrow cultures for sex chromosomes revealed mixture of XX and XY cells in 3 male patients with aplastic anaemia. One male patient with AML demonstrated complete engraftment after induction chemotherapy and FLI: all the mitoses studied were of XX pattern. Engraftment was however temporary as repeated studies revealed reversion to XY pattern. The present work suggests that infusion of fetal liver cells may sometimes induce temporary chimerism or engraftment in an adult host; in the majority of cases, however, engraftment could not be established.

Anemia, Aplastic↗

HLA status following fetal liver transplantation in aplastic anaemia and acute myeloid leukaemia.

Fetal liver infusion (FLI) was tried as an alternate mode of therapy in 40 patients with aplastic anaemia and in 16 patients with acute myeloid leukaemia. The fetal HLA typing carried out on spleen and thymus cells revealed that, while it was more difficult to HLA type the thymus than the spleen cells, 'full house' antigens could be determined only in fetuses of 18 weeks or older. No special effort was made to transfuse HLA- matched or partially matched donor cells into the recipient. The recipients were HLA typed at varying time intervals following FLI in an attempt to document a possible chimerism. None of the patients revealed a 'shift' in their HLA antigen profile and there was no evidence of any donor cell engraftment. No relationship between the HLA match of donor and recipient, and the general condition, the prognosis or the total survival of the patient was evidenced. These data indicate that, even though fetal liver cells express HLA antigens, these cells are functionally incompetent to cause an apparent graft-versus-host disease in the host.

Anemia, Aplastic↗

Activity of a partially purified human BCGF on murine assays for B-cell stimulatory factors. I. BCGF II-like activity of human BCGF.

To further characterize a human B-cell growth factor (BCGF) produced by phytohemagglutinin (PHA) P-stimulated peripheral blood T cells, a partially purified preparation of this material was tested in a number of murine assays for B-cell stimulatory factors (BSF). Human BCGF lacked murine BSF-1 activity as assessed via the induction of polyclonal proliferation of anti-IgM-stimulated murine B cells; however, this material consistently augmented the proliferative response of murine B cells to anti-IgM and a saturating dose of murine BSF-1. Human BCGF also induced proliferation in unstimulated murine B cells, and augmented the proliferative response of dextran sulfate activated murine B cells. Human BCGF is therefore capable of causing proliferation of unstimulated and activated murine B cells, and by these criteria closely resembles murine BCGF II. In contrast to murine BCGF II, however, human BCGF failed to stimulate proliferation or immunoglobulin (Ig) secretion by murine BCL1 B lymphoma cells. A murine analog of this human BCGF showing the same pattern of biological responses was found in concanavalin A-stimulated supernatants of the murine MB2.1 T-cell line and D9-Cl T-cell hybridoma. The active component of the human BCGF preparation was not due to contaminating PHA, interleukin 1, interleukin 2; interferon-gamma, or endotoxin. Comparison between the above human BCGF and a commonly used source of murine BCGF II, i.e., supernatant from antigen-stimulated D10.G4.1 T cells, provided information suggestive of BCGF II heterogeneity. Both human BCGF and D10.G4.1 supernatant caused proliferation of unstimulated and dextran sulfate-stimulated murine B cells; however, only the human BCGF preparation augmented the proliferative response of murine B cells to anti-IgM and a saturating dose of murine BSF-1, and only the D10.G4.1 supernatant stimulated BCL1 cell proliferation and immunoglobulin secretion. The data therefore indicate that the different assays for BCGF II used in this study respond to different factors, and suggest the existence of two BCGF II-like activities.

Animals↗

Cross-sectional echocardiographic recognition of submitral left ventricular aneurysm.

Three cases of annular submitral left ventricular aneurysm precisely diagnosed by cross-sectional echocardiography are reported from the Indian subcontinent. The cineangiographic findings are available in all and morphologic findings in two cases. The apical four-chamber view demonstrated a characteristically large aneurysm arising below the mural leaflet of the mitral valve extending anterolaterally and posteriorly and communicating with the left ventricular cavity in all the cases. Contrast echocardiography performed during cardiac catheterisation promises to be a good technique for the qualitative assessment of the associated mitral regurgitation. Cross-sectional echocardiography is invaluable in diagnosis and assessment of results of surgery in this entity.

Adolescent↗

Comparative hemodynamic dose-response effects of five slow calcium channel-blocking agents in coronary artery disease.

A prospective, randomized study compared the hemodynamic effects of equivalent doses of five slow calcium channel blockers (verapamil, diltiazem, nicardipine, nisoldipine, and amlodipine) in 50 patients with ischemia. After a stable control period, dose-response curves were constructed for each drug with hemodynamics measured 10 minutes after intravenous boluses. Each drug reduced mean systemic arterial pressure (P less than 0.01) and systemic vascular resistance index (P less than 0.01). The heart rate increased after nicardipine, nisoldipine, and amlodipine (P less than 0.01) but was unchanged after verapamil and reduced after diltiazem (P less than 0.01). The left ventricular filling pressure increased after amlodipine (P less than 0.05) and verapamil (P less than 0.01) but was unchanged with the other compounds. Cardiac index increased substantially after the dihydropyridines (P less than 0.01), with little change after verapamil or diltiazem. Cardiac double product fell only after verapamil and diltiazem. These studies provide quantitation of the comparative actions of acute intravenous calcium channel blockade in coronary disease.

Amlodipine↗

Expression and rearrangement of the ROS1 gene in human glioblastoma cells.

The human ROS1 gene, which possibly encodes a growth factor receptor, was found to be expressed in human tumor cell lines. In a survey of 45 different human cell lines, we found ROS1 to be expressed in glioblastoma-derived cell lines at high levels and not to be expressed at all, or expressed at very low levels, in the remaining cell lines. The ROS1 gene was present in normal copy numbers in all cell lines that expressed the gene. However, in one particular glioblastoma line, we detected a potentially activating mutation at the ROS1 locus.

DNA, Neoplasm↗

Intranasal nitroglycerine attenuates pressor response to tracheal intubation in beta-blocker treated hypertensive patients.

The effect of intranasal nitroglycerine on the pressor response to laryngoscopy and tracheal intubation was studied in 40 adult hypertensive patients treated with beta-blocking drugs. Nitroglycerine 0.75 mg, administered intranasally 30 seconds before induction of anaesthesia, was compared with a placebo solution of saline. Haemodynamic variables were measured for 10 minutes after laryngoscopy and tracheal intubation. Heart rate did not change significantly in either group. Systolic as well as mean arterial blood pressure increased significantly for the first 5 minutes in the control group, whereas patients in the nitroglycerine group showed a decrease in systolic as well as in mean arterial pressure. No patient in the nitroglycerine group showed a decrease in systolic arterial pressure greater than 20 mmHg. In conclusion, intranasal nitroglycerine ameliorates the pressor response to laryngoscopy and tracheal intubation in beta-blocked patients.

Administration, Intranasal↗

Comparative sequence analysis of cDNA clones encoding I-A molecules of the CH12 B cell lymphoma: nucleotide differences do not account for their "defective" function in B cell stimulation.

The CH12 B cell lymphoma can be stimulated to secrete antibody by helper T cells that interact with I-EK but not I-AK molecules expressed on its membrane. Both molecules present antigen to the appropriate T cells. We have analyzed the mRNA by Northern blot analysis and obtained partial sequences of cDNA clones encoding A alpha and A beta of the I-A molecule to determine if deletions or mutations in the cytoplasmic or transmembrane domains account for the "defect" in triggering following interaction with I-A restricted helper T cells. The results provide no evidence for structural alterations in either A alpha or A beta which could account for these observations. The implications of these findings on the role of class II molecules in B cell activation is discussed.

Amino Acid Sequence↗