Haemopoietic growth factor GM-CSF for aplastic anaemia in children.
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Biomedical subjects
Publications and source records attributed to A Hameed.
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Perforin is a marker of functionally active cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. We examined perforin expression in endometrium throughout the menstrual cycle. In addition, perforin expression was studied in endometrial leukocytes in women with anovulatory cycles with or without progesterone therapy and in postmenopausal women. In the endometrium, perforin-positive endometrial lymphocytes increased in numbers in the middle through late secretory phases. In women with anovulatory cycles, the proliferative endometrium, before estrogen withdrawal endometrial breakdown, contained less perforin-positive lymphocytes compared with the premenstrual endometrium of the normal menstrual cycle. The progestin-induced endometrial decidualization was accompanied by an extensive recruitment of perforin-positive cells. In contrast, the postmenopausal atrophic endometrium showed complete absence of perforin-positive cells. The lymphocytes isolated from secretory endometrium were CD3-, CD56+ (approximately 80%) or CD3+, CD8+ T-cell receptor (TCR)-gamma delta- (approximately 20%). Almost 90% +/- 5.5 of the CD3-, CD56+, and up to 25% +/- 7% of CD8+ T lymphocytes contained perforin. Perforin expression was further confirmed in endometrial lymphocytes by Northern blot analysis. In vitro, isolated endometrial lymphocytes exhibited NK-like cytotoxicity. After cyclic hormone withdrawal during normal menstrual cycle, these perforin-positive cytotoxic cells may be involved in endometrial stromal breakdown during menstruation.
After ovulation and in the absence of fertilization, the human corpus luteum regresses in an orderly sequence of morphological changes. This study demonstrated that luteal regression involved progressive infiltration of lymphocytes and macrophages. The inflammatory infiltrate began in the theca externa and gradually invaded granulosa cells, with maximum accumulation of lymphocytes and macrophages at the time of menstruation. Immunoperoxidase staining showed that the majority of lymphocytes were CD2+, CD3+, CD8+ T lymphocytes, and 15% of these T cells expressed perforin, a cytolytic protein implicated as a mediator of cytotoxicity. The remaining mononuclear infiltrate showed strong reactivity with monocyte/macrophage markers. These findings indicate that (a) a physiologic cell-mediated inflammatory process in the regressing human corpus luteum is mediated mainly by CD8+ T lymphocytes and cells of monocyte/macrophage lineage and (b) perforin expression in T lymphocytes supports a possible role for cytolytic T cells during the physiologic inflammatory response in human luteolysis.
The Knowledge of drugs is as old as man himself. The methods used by him to find remedies against different ailments rested to a great extent on Psychical effects and certain simple procedures like blood letting and cupping. However, attempts were also made to obtain efficient cure by drugs mainly by the vegetable and to some degree from animal and mineral kingdoms. Thus, on the basis of the historical evidences it can be said that, the history of drugs is spread over a long period and also the contribution made by the Indian physicians in this regard is not less than that of the physicians of other countries.
Nephrotic syndrome is a rare presentation of Hodgkin's disease. Majority of these cases have minimal change disease and some cases present as membranous glomerulopathy. This report presents the case of a child with nephrotic syndrome associated with Hodgkin's disease.
Autoantibodies to the saline extracts of cells are being used as diagnostic and prognostic markers in the investigation of patients with suspected systemic rheumatic disease. These are also called antibodies to the extractable nuclear antigens or anti ENA antibodies. We used saline extracts of human spleen cells and rabbit thymus extract to detect six subtypes of anti ENA antibodies, namely anti SSA (anti Sjogren's syndrome A), anti SSB (anti Sjogren's syndrome B), anti RNP (anti Ribonucleoprotein), anti Sm (anti Smith), anti Jo-1 (anti Jo-1) and anti Scl 70 (anti Systemic sclerosis 70) antibodies. Two hundred and thirty-seven patients' sera were screened in the department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, over a period of 16 months. Fifty-seven were positive for auto antibodies, of which 26 had anti SSA antibodies, 12 anti SSA+ anti RNP+ anti Sm antibodies, 7 anti RNP+ anti Sm antibodies, 6 anti SSA+ anti SSB antibodies, 5 anti SSA+ anti RNP antibodies while one patient showed only anti RNP antibody. The detection of the anti ENA antibodies was specially helpful in diagnosing patients with systemic lupus erythematosis presenting with atypical features and with mixed connective tissue disease.
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Four years data from Special Care Baby Unit revealed neonatal jaundice (NNJ) as the commonest cause of hospitalization (1944 cases of NNJ out of 6454 admitted neonates). Majority (47.5%) of babies with NNJ presented between 4-7 days of birth. One hundred and sixty infants with NNJ were positive for Glucose 6 Phosphate dehydrogenase (G6PD) deficiency, of whom 153 were males and 7 females. Eighty five G6PD deficient babies required exchange transfusion and 23 developed bilirubin encephalopathy (BE) of which 7 died.
CD68 antigen is expressed by tissue macrophages and cells of myeloid/mononuclear lineage. CD68 is recognized by many monoclonal antibodies (mAbs), including KP1, EMB11, Y1/82A, Y2/131, Ki-M6, and Ki-M7. Using the labeled strept-avidin-biotin (LSAB) immunoperoxidase technique, we examined CD68 antigen expression in human peripheral blood T cells. The anti-CD68 mAbs KP1 and EMB11 stained virtually all fresh isolated gamma/delta T cells and CD3-CD56+ natural killer (NK) cells in a granular cytoplasmic pattern. In contrast, fresh isolated CD4+ and CD8+ T lymphocytes showed no detectable reactivity with these two anti-CD68 mAbs. However, in vitro stimulation with T-cell mitogen or recombinant interleukin-2 (rIL-2) induced expression of CD68 antigen in activated CD4+ and CD8+ T lymphocytes. Similarly, the lymphokine-activated killer (LAK) cells generated after long-term (14 to 21 days) culture of peripheral blood mononuclear cells (PBMC) in rIL-2 also showed strong granular cytoplasmic staining by the anti-CD68 antibodies. This study shows that the CD68 antigen is constitutively expressed in NK cells and gamma/delta T cells and that its expression is strongly induced in activated CD4+ and CD8+ T lymphocytes as well as LAK cells.
To investigate the extent of Salmonella penetration through the egg shell, 200 eggs were dipped in red (for 3 minutes) and then in green (for 6 minutes) aqueous bland food color solution for the detection of positive penetration test areas. Each egg with positive penetration area, 5 spots of 1 cm in diameter, was marked for the attachment of steel cylinders (1 cm in diameter and height). These cylinders were filled with the test strain of Salmonella. Among 19 serotypes S. pullorum and S. gallinarum were nonmotile while the other 17 were motile. Among a total of 180 eggs (900 points) maximum (30%) penetration was in area III, where salmonellae invaded through cuticle, shell, inner and outer shell membranes, followed by area II (14.77%) and area I (4.6%). It was very well evident that penetration of salmonellae to the contents of eggs was maximum, while in area II the penetration was to outer shell membrane and in the least cases through the cuticle and shell. Penetration in area I is not significant and to some extent in area II as well, while invasion in area III is highly significant.
Anti-neutrophil cytoplasmic auto antibodies are directed against antigens in the neutrophil granules. Their detection by the indirect immunofluorescence clearly divides them into two distinct types, namely c-ANCA (Classical antineutrophil cytoplasmic antibody) and the p-ANCA (Perinuclear antineutrophil cytoplasmic antibody). These antibodies have been found to be useful as non-invasive markers to help establish the diagnosis in patients with systemic vasculitides. The antibodies also help in monitoring disease activity in some patients with systemic necrotising vasculitides. This study was aimed at demonstrating the utility of these auto-antibodies in the management of our patients presenting with systemic vasculitides. Fifty-six patients presenting with features of systemic vasculitides were examined over a six month period out of whom eight were found positive for these antibodies. The detection of these antibodies helped in early diagnosis and the institution of specific treatment. Six months follow-up in one patient with Wegener's granulomatosis, the disease activity related closely with the ANCA levels.
Accelerated arteriosclerosis is the major long-term complication of cardiac transplantation. It has been demonstrated recently that accelerated arteriosclerosis is caused, in part, by rejection-related, cell-mediated immunity. However, the role of cytotoxic T lymphocytes in this process is a subject of controversy. Perforin is a specific marker of functionally active cytotoxic lymphocytes because it is a functional component of the cytotoxic granules of these cells. We examined 11 coronary arteries from seven autopsied and four retransplanted heart transplant recipients for the presence of perforin-containing lymphocytes. Immunohistochemical stains for perforin were performed using a monoclonal antibody against human perforin. Eight of the 11 coronary arteries examined were found to contain perforin-positive cells. These perforin-positive cells were present in subendothelial spaces of the coronary arteries, and the staining seen was cytoplasmic and granular. The granules often were polarized to the endothelial surface. Furthermore, the cells identified were usually in close proximity to, or in direct contact with, coronary artery endothelial cells. These results suggest that cell-mediated endothelial injury by perforin-positive cytotoxic lymphocytes may contribute to the development of accelerated arteriosclerosis in heart transplant recipients.
The major histocompatibility complex is a group of complex genes situated on the short arm of chromosome 6 in humans. They play an important role in the regulation of the immune response. Autoimmune blistering disease provides an ideal model for studying the role of MHC in autoimmunity. The diseases are organ specific, and in some of them the relevant antigen has been cloned and sequenced. Such information on the antigen will help further define the interactions of the Ag, MHC, and TCR. Use of family studies hopefully will define and localize susceptibility alleles, so that any genetic susceptibility can be identified at the molecular level. It is from these molecular perspectives that molecular therapies could be assigned to restore the immune system.
Perforin is a potent cytolytic pore-forming protein expressed in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells. A new monoclonal antibody raised against human perforin was used to detect both in vitro and in vivo perforin expression in cytotoxic cells. Immunohistochemical analysis of human peripheral blood mononuclear cells cultured in recombinant interleukin-2 (rIL-2) showed strong granular cytoplasmic staining of the IL-2 activated cytotoxic cells. Fresh-frozen tissue sections from patients with heart allograft rejection were also stained. Strong granular cytoplasmic staining of the mononuclear inflammatory infiltrate characteristic for perforin in cardiac allograft rejection was observed. The detection and quantitative analysis of perforin-associated cytotoxic cells by the human anti-perforin monoclonal antibody will help to evaluate the significance of these functionally distinct cytotoxic cells in human tissue.
Human granzyme B antigen is expressed in cytoplasmic granules of activated cytotoxic T lymphocytes and natural killer cells. Recombinant granzyme B was generated using a prokaryotic expression vector under the control of T7 transcription and translation signals. The 25-kd recombinant protein (granzyme B) was used to develop a rabbit polyclonal antiserum. Purified anti-granzyme B antibodies were used to detect the antigen expression in cytotoxic cells in human tissues. Using the avidin-biotin-complex peroxidase technique, formalin-fixed, paraffin-embedded tissue sections from patients with acute mild or moderate allograft cardiac rejection were stained. A constant cytoplasmic staining of the lymphocytic allograft infiltrate was observed. These results provide a basis for using the anti-granzyme B antibodies for detection of cytotoxic cells in human tissues. The detection and quantitative analysis of the granzyme-associated cytotoxic cells may help to evaluate the significance of these functionally distinct cytotoxic cells in human tissues associated with increased expression of cytoplasmic granule effector molecules.
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An ethanol extract of the leaves of Ocimum sanctum was screened for its effects on the central nervous system. It prolonged the time of lost reflex in mice due to pentobarbital, decreased the recovery time and severity of electroshock- and pentylenetetrazole-induced convulsions, and decreased apomorphine-induced fighting time and ambulation in "open field" studies. Using a behavioural despair model involving forced swimming in rats and mice, the extract lowered immobility in a manner comparable to imipramine. This action was blocked by haloperidol and sulpiride, indicating a possible action involving dopaminergic neurones. In similar studies, there was a synergistic action when the extract was combined with bromocriptine, a potent D2-receptor agonist.