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Biomedical subjects

A B Singh

Publications and source records attributed to A B Singh.

At least 37 records · Page 2Linked to original sources

Arginine vasotocin gene expression and secretion during osmotic stimulation and hemorrhagic hypotension in hens.

In chickens, hyperosmolality stimulates the secretion of vasotocin (AVT) and up-regulates hypothalamic AVT gene expression. Hemorrhage, on the other hand, has not been considered an effective stimulus for AVT release in this species. The effects of acute osmotic stress and prolonged hemorrhagic hypotension on AVT gene expression and secretion were studied in White Leghorn hens. Conscious hens were osmotically stimulated by administering a single ip injection of 3 M NaCl (5 ml/kg). Urethane-anesthetized hens were bled to a mean arterial pressure of 80-90 mm Hg and the pressure was maintained within this range by additional bleeding. A total of about 30% of the estimated blood volume was removed. Both experiments were terminated after 1 hr of stimulation. Plasma AVT levels in the hyperosmotic and hypovolemic hens were 4- and 2-fold higher, respectively, compared to controls. Hypothalamic AVT mRNA levels, detected by Northern blot analysis, were 2.5- and 2-fold higher in the osmotically stimulated and hypotensive groups, respectively, compared to control groups. As determined by in situ hybridization, both osmotic stimulation and hypovolemia resulted in an increase in the number of AVT mRNA-containing neurons in the supra-optic and paraventricular nuclei. Our results indicate that, under the conditions used, hypotension and hyperosmolality are equally effective in stimulating AVT gene expression and secretion of AVT.

Animals↗

Effect of gonadotrophin and sex steroid on the scotoresponses of day old chicks of Japanese quail, Coturnix coturnix japonica.

Luteinizing hormone (LH) and testosterone propionate (TP) were tested for their effects on the development of scotorefractoriness in Japanese quail. Day old chicks of both the sexes were divided into four groups and treated with normal saline, LH (1 microg/100 g body weight) and two doses of TP (100 microg/100 g body weight- TP1 and 1 mg/100 gm body weight- TP2) over a periods of 14 weeks. In the male chicks, compared to control, LH treatment advanced and low dose of TP suppressed the development of scotorefractoriness, while high dose of TP inhibited it completely and maintained the birds in scotosensitive state. On the other hand, in females, LH treatment increased the rate of sexual development resulting in the onset of egg laying earlier than that of control, but both the doses of steroid hormone suppressed ovarian development. It is suggested that, LH treatment not only induced a higher degree of reproductive development in short day quail but may also advance sexual maturity as under long daylength. Further, both the doses of male hormone had negative feedback effect on neuroendocrine axis and eliminated the attainment of scotorefractoriness i.e., reproductive development under short days.

Animals↗

The effect of erythropoietin administration on murine bone marrow chimeras.

All patients develop anemia after autologous or allogeneic bone marrow transplantation and red blood cell transfusion is almost always required in the post-transplant period. Recently Epo therapy has been employed in the setting of bone marrow transplantation. As bone marrow transplant patients typically suffer from malignancies and are immunocompromised, further immunosuppression should be avoided. Recent reports have suggested that Epo may modulate immune response. We have studied the effects of Epo on immune response in murine bone marrow chimeras. Epo administration resulted in an increase in hematocrit. There was no significant alteration in lymphocyte numbers, although a shift in lymphocytes toward T cell predominance was observed. Epo administration resulted in enhanced cell proliferation in response to T and B cell mitogens, although no alteration in cytotoxicity or natural killer cell activity was observed. No example of Epo-induced impaired immunity was observed.

Animals↗

The host response in graft versus host disease. III. The in vitro induction of regulatory cells in chronic murine graft versus host disease.

Murine graft versus host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing CGVH disease. Using an in vitro system to induce the host protective cell, we now demonstrate that two distinct Thy-1+ cells emerge which regulate CTX against the host. One cell is of host origin, radiation sensitive, and functionally resembles a veto cell. The second regulatory cell, of parental origin, is radiation resistant and restricted in its ability to suppress anti-F1 CTX. We further demonstrate that the emergence of these cells is modulated by competitive immunoregulatory influences mediated by T contrasuppressor and I-J+ cells.

Animals↗

Sensitization to Ganoderma lucidum in patients with respiratory allergy in India.

Although human sensitization to basidiomycete Ganoderma has been reported in New Zealand, North America and Europe, hypersensitivity due to this fungi is not known in India, in spite of its prevalence in the atmosphere. We have studied the atmospheric concentration of Ganoderma in different localities within Delhi and the sensitization level to this fungi amongst the Indian population. Aerobiological sampling, using a Burkard personal slide sampler, was carried out in Delhi for 2 consecutive years (October 1989-September 1991). The sampler was operated at 10 day regular intervals for 10 min to trap the spores. The peak season for Ganoderma is recorded from July to September with highest average monthly catch of 336 spores/m3 in September 1991 from south Delhi. Antigenic extracts were prepared from both, the spores and whole body of Ganoderma lucidum. The results of intradermal skin tests conducted on 172 patients revealed that 28.48% and 17.44% of patients showed marked skin reactivity to spore and whole body extracts, respectively. A significant correlation (r = 0.963, P < 0.01) was found between intradermal and skin-prick tests. More than 80% of the intradermal test positive patients had significantly (P < 0.01) elevated IgE antibodies to the fungi in question. Thus, sensitization to Ganoderma lucidum has been reported for the first time in the atopic population of India.

Adult↗

Cinnamon bark oil, a potent fungitoxicant against fungi causing respiratory tract mycoses.

Cinnamic aldehyde has been identified as the active fungitoxic constituent of cinnamon (Cinnamomum zeylanicum) bark oil. The fungitoxic properties of the vapours of the oil/active constituent against fungi involved in respiratory tract mycoses, i.e., Aspergillus niger, A. fumigatus, A. nidulans A. flavus, Candida albicans, C. tropicalis, C. pseudotropicalis, and Histoplasma capsulatum, were determined in vitro as minimum inhibitory concentration (MIC), minimum lethal concentration (MLC), inoculum density sustained, and exposure duration for fungicidal action at MIC and higher doses, as well as effect of incubation temperatures on fungitoxicity. It is concluded that these inhalable vapours appear to approach the ideal chemotherapy for respiratory tract mycoses.

Cinnamomum zeylanicum↗

Effect of photoperiod in the regulation of the annual testicular cycle of a subtropical mammal, the Indian palm squirrel, Funambulus pennanti.

In seasonally breeding subtropical mammal, the Indian palm squirrel (Funambulus pennanti), reproductive recrudescence is initiated before the winter solstice followed by sexually active condition which extends until the end of summer season. Onset of seasonal regression coincides with the annual decrease in daily photoperiod and the increased level of relative humidity resulting from the arrival of monsoon at this latitude. To test the photoperiodic responses, three groups of squirrels were exposed to natural day length (NDL), long day length (LD 15:9), and short day length (LD 6:18) over a period of one year beginning from March. Squirrels of all these groups were exposed to similar ambient temperature and humidity conditions. Initially, the rate of testicular development was similar in control and long day squirrels attaining peak values in May (0.67 cm3) and June (0.7 cm3) respectively. Thereafter, while the gonads of controls regressed, the latter maintained a plateau. On the other hand, the gonads of short day squirrels regressed sharply until June (0.21 cm3) followed by spontaneous recrudescence and finally a plateau (0.55 cm3). These results indicate that initially squirrels are photosensitive (as long days are gonadostimulatory and short days are inhibitory) in the first half of summer season but eventually become refractory to the inhibitory effect of short days. Obviously, an acyclic condition is developed under constant long as well short day conditions maintaining the neuroendocrine-gonadal-axis in a continuously active state. We suggest that in nature although gonadal growth of this species does not synchronize with the increase in daily photoperiod, it is partially regulated by an interplay of annual photocycle and humidity conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro generation of soluble suppressor factor in murine chronic graft versus host (GVH) disease.

Veto cells are cells which suppress self directed cytotoxicity (CTX) regardless of the strain of origin of the cytotoxic effector cell. The mechanism by which veto cells inhibit self directed CTX is largely unknown. We have previously described the emergence of a veto cell in murine chronic graft versus host (CGVH) disease both in vivo and in vitro. Using an in vitro system in which veto cells are induced, we now report that a soluble factor is also induced which is capable of suppressing CTX. This cytotoxicity suppressing factor (CsF) is heat labile and has a molecular weight above 50 kD. The factor prevents the emergence of a cytotoxic effector cell. but is largely ineffective once the effector cell has functionally emerged. CsF is irreversible and is not restricted in its ability to inhibit anti-self CTX.

Animals↗

The host response in graft versus host disease. I. Radiosensitive T cells of host origin inhibit parental anti-F1 cytotoxicity in murine chronic graft versus host disease.

Murine graft versus host (GVH) disease takes two forms depending on the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, auto-antibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We now report that this marked disparity in disease expression results from a radio-sensitive host mechanism which protects the F1 mouse from parental anti-F1 cytotoxicity in mice undergoing chronic GVH disease. Cellular analysis revealed that protection in chronic GVH disease is mediated by a phenotypically complex system of genetically unrestricted radiosensitive T cells of F1 origin. These cells fail to functionally emerge in mice undergoing acute lethal GVH disease.

Acute Disease↗

The host response in graft versus host disease. II. The emergence of host protective cells is in part determined by background genomic compatibility.

Murine graft versus host (GVH) disease takes two forms depending on the parental/F1 strain combination employed. In an accompanying paper (Singh et al., Clin. Immunol. 151, 1993) many of the clinical features of these two forms of GVH disease are described. In addition to these clinical characteristics, acute lethal GVH (ALGVH) disease is characterized by diminished natural killer cell activity, whereas chronic GVH disease is characterized by normal or increased natural killer cell activity. Previously we have reported that this marked disparity in disease expression can be attributed to radiosensitive host cells which protect the F1 mouse from parental anti-F1 cytotoxicity (CTX) in mice undergoing chronic GVH (CGVH) disease. These cells fail to functionally emerge in mice undergoing ALGVH disease. We now report that the background genome, presumably the minor lymphocyte stimulatory loci, of the donor cells determines whether these host cells emerge and thereby dictates the form of GVH disease which is induced. C57BL/6 (B6) cells (H-2b, minor lymphocyte stimulatory locus (Mls)b) and B10.D2 cells (H-2d, Mlsb) were found to induce ALGVH disease when adoptively transferred to [C57BL/6xDBA/2]F1 (B6D2) (H-2b/d, Mls-1a/b, Mls-2a/b) recipient mice. DBA/2 cells (H-2d, Mls-1a, Mls-2a) and Balb/c cells (H-2d, Mls-1a, Mls-2b) induced CGVH disease in B6D2 mice. Using Mls congenic strains we have demonstrated that donor cell reactivity against Mls-2a was necessary and sufficient to induce ALGVH disease as determined by anemia, lymphopenia, anti-F1 cytotoxicity, and loss of cytotoxicity against allogeneic targets. Such Mls-2a reactivity correlated with the impaired induction of a host protective cell capable of vetoing self-directed CTX. Failure of this host protective cell to emerge in turn correlated with donor anti-host CTX and the emergence of ALGVH disease.

Acute Disease↗

Tubulointerstitial nephritis and vasculitis.

In the past few years, advances in molecular and cellular immunology have greatly enhanced our understanding of the immunopathogenesis of tubulointerstitial nephritis and vasculitis. This review focuses on recent observations regarding nephritogenic tubulointerstitial antigens, their expression and presentation by tubular epithelial cells, the subsequent immune response, and the factors that serve to modulate this response. The latter part of this review summarizes recent findings regarding the role of autoantibodies in the immunopathogenesis of vasculitis.

Animals↗

Survey of airborne culturable and non-culturable fungi at different sites in Delhi metropolis.

A two year aerobiological survey for culturable and non-culturable fungi was conducted at human height at five different sites in Delhi metropolis. Burkard Personal Volumetric Sampler for petriplates and slide exposures were used for sampling the air. With simultaneous petriplate and slide exposure a total of 98 fungal forms were recorded. Cladosporium contributed for 25-40% of total airborne fungi followed by Ustilago (smuts) (24%) Aspergillus flavus (10-13%), Alternaria (11%) and A. niger (8%). Basidiomycetes contributed 7-13% at different sites. The frequency of occurrence of these types varied from 50-98%. In general fungal concentration was high from July to April with low counts in winter (January) and dry and hot summer (May-June). Quantitative variations in the spore counts were found to be statistically significant within the same urban locality.

Aerobiosis↗

Differential effects of polyamine homologues on the prevention of DL-alpha-difluoromethylornithine-mediated inhibition of malignant cell growth and normal immune response.

Natural polyamines (putrescine, spermidine, and spermine) are ubiquitous cellular cations that play an important role in cell proliferation and differentiation. Ornithine decarboxylase is the first and a rate-limiting enzyme in the biosynthesis of polyamines. Polyamine depletion using DL-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, has been shown to suppress cell growth in a variety of settings, including those of tumor and lymphocyte proliferation. The objective of the present investigation was to examine the inhibitory effects of DFMO on a variety of murine in vitro immune responses, including lymphocyte proliferation in response to T-cell mitogen (concanavalin A), B-cell mitogen (lipopolysaccharide), and alloantigen as well as cytotoxicity. DFMO-mediated inhibition of cell proliferation in these cases correlated with depletion of intracellular polyamines. The inhibitory effects of DFMO were reversed by polyamine repletion with putrescine. Putrescine also reversed the growth-inhibitory effects of DFMO on 4 tumor cell lines that we tested: 28-13-3S, YAC-1, P-815, and K562. However, putrescine homologues exhibited a differential effect in preventing DFMO-mediated inhibition of cell growth in normal lymphocytes and cancer cell lines. Only putrescine homologues containing a shorter methylene chain were effective in preventing the growth-inhibitory action of DFMO on normal immune response. In contrast, only the longer chain homologue 1,5-diaminopentane overcame the effect of DFMO on tumor cell growth. These findings suggest that supplementation with selected polyamine homologues may sustain normal immune response in DFMO-treated individuals while effectively suppressing malignant cell growth. The potential clinical relevance of these observations is discussed.

Animals↗

Suppression of annual testicular development in Indian Palm squirrel, Funambulus pennanti by 8 hr temporal relationship of serotonin and dopamine precursor drugs.

Daily injections of 5-HTP (5-hydroxytryptophan, serotonin precursor) and L-DOPA (L-Dihydroxyphenylalanine, dopamine precursor) given 8 hour apart inhibited normal testicular growth in seasonally breeding Indian Palm Squirrel, Funambulus pennanti leading to complete gonadal atrophy, which was maintained till the end of the study. HCG administration induced higher degree of gonadal development but, when the two treatments (HCG + 8 hr relationship of 5-HTP and L-DOPA) were given simultaneously no significant difference was observed compared to control. Results indicate that induced suppression of gonadal function in a fashion similar to seasonal regression leading to non-breeding condition is the consequence of specific phase relationship (8 hr) between serotonergic and dopaminergic activities and not due to Serotonin or dopamine alone. This suggestion gets support from the finding that gonadal condition of squirrels receiving only 5-HTP (5-HTP control) or L-DOPA (DOPA control) was not different from control and exhibited normal testicular growth. It also seems that neurotransmitter precursor drugs given 8 hr apart possibly inhibited the activity of neuroendocrine-gonadal axis since this effect was overpowered by stimulatory effect of gonadotrophin. The findings strongly support the hypothesis that specific phase relation of circadian serotonergic and dopaminergic oscillations account for seasonal reproductive conditions.

5-Hydroxytryptophan↗

Attenuation of murine acute lethal graft-versus-host disease by the administration of DL-alpha-difluoromethylornithine.

Intravenous injection of 5 x 10(7) C57BL/6 (B6) lymphocytes into adult (C57BL/6 x DBA/2)F1 recipient mice results in acute lethal graft-versus-host (ALGVH) disease. This disorder is characterized by anemia, a diminished number of splenocytes, impaired cytotoxicity (CTX) against third party alloantigen, and impaired natural killer cell (NK) activity. Parental anti-F1 CTX is critical to the induction of ALGVH disease, and CTX in general has been reported to be dependent upon the presence of the low molecular weight polyamines essential for cell growth and differentiation. We now report that DL-alpha-difluoromethylornithine, a specific inhibitor of polyamine biosynthesis, attenuates the clinical expression of disease in mice undergoing ALGVH disease.

Anemia↗

Ultrastructural development of chorioallantoic placenta in the Indian Miniopterus bat, Miniopterus schreibersii fuliginosus (Hodgson).

The chorioallantoic placental interhemal membrane of Miniopterus schreibersii fuliginosus has been described electron-microscopically. Morphologically there are three main types of placentae which develop in chronological sequence. They are (1) primary placenta, (2) secondary placenta and (3) tertiary placenta. In neural groove and limb-bud embryos the primary placenta consists of the following elements which separate the maternal and fetal circulations: (1) a continuous ectoplasmic layer, (2) intrasyncytial lamina, (3) syncytiotrophoblast, (4) cytotrophoblast, (5) basal lamina, (6) mesenchyme and (7) fetal endothelium. The primary placenta degenerates until term when it consists of a thin syncytiotrophoblastic layer resting on basal lamina. Mesenchyme does not show the presence of fetal capillaries. The secondary placenta is formed in early limb-bud embryos. The electron microscope has revealed that the placenta is of the endotheliomonochorial type and (1) consists of a well-developed maternal endothelium, (2) the trophoblast surrounding the maternal blood tubule is cellular, not syncytial as previously thought and the apical plasma membrane of these trophoblastic cells is in direct contact with the discontinuous interstitial membrane, (3) basal lamina, (4) mesenchyme and (5) fetal endothelium. Tertiary placenta at full term stage is of the hemodichorial type having the following elements: (1) thin ectoplasmic layer, (2) a thick intrasyncytial lamina, (3) syncytiotrophoblast, (4) cytotrophoblast, (5) basal lamina, (6) mesenchyme and (7) fetal endothelium. The definitive chorioallantoic placental barrier in this bat thus differs from the organization earlier proposed by Chari and Gopalakrishna [Proc. Indian Acad. Sci. 93: 463-483, 1984] on the basis of light-microscopic observations: (1) the absence of maternal endothelium in the primary placenta from the neural groove and early limb-bud embryos, (2) the existence of only cellular trophoblast in the secondary placenta throughout the gestation and (3) the presence of well-developed hemodichorial tertiary placenta is the unique feature of the interhemal membrane in higher Chiroptera.

Animals↗

Biological standardization of pollen allergens from India.

Standardization of allergens are achieved by in vitro and in vivo methods. Some of the allergens from Western countries are standardized using biological potency of the extracts but no attempt has been made till now to standardize any of the pollen extracts from India based on biological units. Therefore, we have attempted to standardize two important pollen allergens Ricinus communis and Holoptelea integrifolia by biological methods. Broadly the methods adopted by Dreborg and Grimmer (1983) was followed. Skin prick tests were carried out with the extracts of R. communis and H. integrifolia on 15 allergic patients in five three fold log dilutions starting with 1:10, in 50% glycerinated buffer. Glycerinated buffer (50%) and histamine dihydrochloride (1 mg/ml) were used as negative and positive controls, respectively. The mean wheal diameter obtained with different concentrations showed a gradual systematic fall with increase in dilution. The mean relative diameter (% of histamine reaction) varied from 124.1 +/- 8.9 to 33.7 +/- 6.1 and 78.9 +/- 5.5 to 21.4 +/- 3.8 with the highest and lowest concentrations of R. communis and H. integrifolia pollen antigens, respectively. The histamine equivalent concentration of antigen 1,000 Biological Units (BU) obtained for crude pollen extracts of R. communis and H. integrifolia was 1:17 and 1:22 respectively.

Adolescent↗

The effects of recombinant human erythropoietin on the cell mediated immune response of renal failure patients.

Recombinant human erythropoietin (rHuEpo) is now widely employed in correction of the anemia of end stage renal disease (ESRD). Recent reports suggest that rHUEpo, in addition to its effect on CFU-E and burst-forming-unit-erythroid (BFU-E), may stimulate granulocyte/macro-phage production and pluripotential progenitors of the myeloid and monocyte lineage. Furthermore, there is now data which demonstrate that ESRD patients who received rHuEpo have enhanced cytokine production. Taken together, these observations suggest that the administration of rHuEpo may augment the diminished immune response of renal failure patients. To evaluate the effects of rHuEpo therapy on cell-mediated immunity in hemodialysis patients, a prospective controlled study was conducted. Two parameters of immune function were tested. One was natural killer cell (NK) activity, and the other proliferation in response to the T cell mitogen concanavalin A (Con-A). NK activity of the ESRD patients was comparable with that of normal controls at the start of the study and was unaffected by rHuEpo therapy. In contrast to this, anemic ESRD patients initially demonstrated impaired mitogen driven proliferation (initial stimulation index (S.I.) = 42.5 +/- 11.9) which significantly improved following rHuEpo therapy (final S.I. = 73.3 +/- 14.7, p < 0.05). The later value exceeded the mitogen response in less anemic ESRD patients who did not receive rHuEpo (initial S.I. = 60.7 +/- 16.5, final S.I. = 61.0 +/- 16.7), but did not reach values seen in normal controls. The data suggest that rHuEpo therapy may be associated with enhanced immune responses in patients with ESRD.

Aged↗