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Biomedical subjects

A Mathur

Publications and source records attributed to A Mathur.

At least 37 records · Page 2Linked to original sources

The parental origin of the single X chromosome in Turner syndrome: lack of correlation with parental age or clinical phenotype.

We have used X- and Y-linked RFLPs to determine the origin of the single X chromosome in 25 live-born individuals with Turner syndrome. We determined that 18 individuals retained a maternal X (Xm) and that seven retained the paternal X (Xp). No occult mosaicism was detected. We found no differences in either maternal or paternal ages for the two groups. The ratio of maternal X to paternal X is just over 2:1, which is consistent with the expected proportion of meiotic or mitotic products, with equal loss at each step, given the nonviability of 45,Y. Six phenotypic or physiologic characteristics were assessed: (1) birth weight, (2) height percentile at time of testing, (3) presence of a webbed neck, (4) cardiovascular abnormalities, (5) renal abnormalities, and (6) thyroid autoimmunity. There were no significant differences in birth weights or heights between the girls who retained the maternal X or the paternal X. In addition, no differences between the groups could be appreciated in the incidence of the physical, anatomic, or physiologic parameters assessed.

Adolescent

Dengue virus-induced helper cytokine has two polypeptide chains which bear different determinants.

Dengue type 2 virus (DV) induces generation of a T cell helper cytokine (HF) in mouse spleen which enhances the antigen-specific antibody plaque forming cell count in syngeneic mice. The present study was undertaken to investigate the molecular structure of HF. It was observed that the activity of HF was abrogated by treatment with reducing agents such as glutathione, ouabain or dithiothreitol (DTT) which cleave disulphide bonds, separating the polypeptide chains. The two polypeptide chains could be purified by high performance liquid chromatography of DTT treated HF. The individual chains had no helper activity, but it could be restored by mixing the two. One chain of the HF bonded to the DV-antigen coupled immunosorbent column and the other to the anti-I-Ak antibody coupled column. Thus, DV-induced HF is a disulphide bonded double chain structure, one chain having antigen and the other having I-A determinants; the presence of both chains is essential for helper activity.

Animals

Inhibition of the presentation of dengue virus antigen by macrophages to B cells by serine-protease inhibitors.

It has been shown that macrophages (M phi) process dengue type 2 virus (DV) antigen and present it to B cells leading to their clonal expansion as shown by DV-specific IgM antibody plaque-forming cell (PFC) count in spleen. The present study was undertaken to find out the nature of enzymes responsible for the processing of DV antigen in M phi. DV-pulsed M phi were treated with seven different protease inhibitors and then assayed for antigen presentation to B cells. It was observed that maximum inhibition occurred by treatment of M phi with PMSF, a serine-protease inhibitor. The effect of PMSF was dose dependent and was abolished by using predigested antigen. PMSF inhibited presentation of DV and sheep RBC antigens but had no effect on presentation of bovine serum albumin which does not require processing. The results thus identify the serine group of proteases as the main enzymes involved in processing the DV antigen in M phi.

Animals

In vivo and in vitro regulation of IgE production in murine hybridomas.

Normal BALB/c mice injected i.p. with the IgE-secreting hybridomas B53 (epsilon, kappa anti-DNP), SE1.3 (epsilon, kappa, anti-arsonate) or A3B1 (epsilon, kappa, anti-TNP) were monitored for serum IgE concentrations and frequencies of splenic T lymphocytes with surface membrane receptors for the Fc portion of IgE (Fc epsilon R+ T lymphocytes). Mice with B53 or SE1.3 hybridomas initially developed high concentrations of IgE and CD8+ Fc epsilon R+ T lymphocytes, followed by a progressive decline in both serum IgE and expression of cytoplasmic epsilon-chains in the hybridoma cells. Serum IgE concentrations in mice with A3B1 hybridomas progressively increased without development of Fc epsilon R+ T lymphocytes nor a subsequent decline in IgE or change in cytoplasmic epsilon-chain expression in the A3B1 cells. An in vitro system in which the IgE-secreting hybridoma cells were cocultured with spleen cells harvested from mice with established B53 tumors was used to investigate the mechanisms involved in the inhibition of IgE production by the hybridoma cells. The results of these studies indicate that: 1) the induction/upregulation of Fc epsilon R on CD8+ T lymphocytes in vivo requires factors in addition to high serum IgE concentrations; 2) in addition to CD8+ Fc epsilon R+ T lymphocytes and monocytes, another, as yet unidentified, splenic cell component appears to contribute to the process by which epsilon-chain expression in IgE-secreting hybridoma cells is suppressed, and 3) a hybridoma (A3B1) that fails to induce CD8+, Fc epsilon R+ T lymphocytes in vivo and is not inhibited in IgE expression in vivo, nonetheless is inhibited in IgE expression in vitro when cocultured with spleen cells from mice with B53 tumors.

Animals

Concentrations of Na+ and K+ in serum and uterine flushings of ovariectomized, pregnant and cyclic rats when treated with extracts of Hibiscus rosa sinensis flowers.

The effect of 50% ethanol and benzene extracts of Hibiscus rosa sinensis flowers was studied on the concentration of Na+ and K+ in the serum and uterine flushings of ovariectomized, mated and cyclic rats. In ovariectomized rats, both extracts given alone did not alter the K+ content of the uterine flushings but when administered with estradiol dipropionate (EDP), a partial antagonism was observed when compared to EDP given alone. Conjoint treatment of extracts with EDP plus progesterone did not induce any significant change. In mated rats, both extracts did not alter the concentration of Na+ on the day of implantation but decreased significantly the concentration of K+ in uterine fluid. In cyclic rats, the administration of the extracts for 6 and 12 days did not cause any significant change in the concentration of K+ of uterine flushings but their administration for 18 days caused a significant decrease. In all three experiments, the concentration of Na+ in uterine flushings and of Na+ and K+ of serum did not show any significant changes.

Animals

Viral aetiology of acute respiratory infections in children in north India.

Two hundred and thirty children clinically diagnosed as suffering from acute respiratory infection were tested for four major groups of viral aetiological agents, i.e. influenza para-influenza, respiratory syncytial virus (RSV) and adenoviruses using indirect immunofluorescence technique. At least one of the respiratory viruses was identified in 51 (22 per cent) specimens, which included influenza A in 6 (3 per cent), influenza B in 3 (1 per cent), para-influenza type 1 in 3 (1 per cent), para-influenza type 3 in 13 (6 per cent), RSV in 11 (5 per cent) adenovirus in 12 (5 per cent), and dual virus infections in 3 (1 per cent) cases. Maximum number of virus identification was noted in children below 1 year of age, particularly infection with RSV followed by para-influenza and adenoviruses. Value of rapid diagnosis by indirect immunofluorescence technique is stressed.

Child, Preschool

Virological investigations of acute encephalopathy in India.

A total of 740 consecutive children aged between 6 months and 12 years who presented with acute encephalopathic illnesses during a three year period were assessed both clinically and by laboratory investigations. Cerebrospinal fluid was examined for the presence of cells or other abnormal substances, and any organisms were cultured. Blood examination included white cell count and estimations of haemoglobin, urea, glucose, and electrolyte concentrations and serum alanine aminotransferase and aspartate aminotransferase. A firm diagnosis was established in 278 patients (38%). Pyogenic meningitis (n = 134), measles encephalopathy (n = 38), and electrolyte imbalance (n = 23) were important causes in this group, cerebral malaria (n = 4) was uncommon and there were no cases of Reye's syndrome. The diagnoses of the remaining 462 were combined under the heading 'acute unexplained encephalopathy'. Altogether 394 of the 462 patients underwent virological investigations for arboviruses and 92 (23%) had one or more indicators of Japanese encephalitis. No other arboviruses could be isolated. Throat swabs from 187 patients with acute unexplained encephalopathy were studied on monkey kidney tissue cell lines of which 14 were positive (8%). These were identified as adenovirus, parainfluenza, influenza, poliomyelitis, Coxsackie, and echovirus; in two cases the virus was untypable. Japanese encephalitis is an important cause of acute childhood encephalopathy in this region. Clinical features of the illness may be mimicked by several disorders which require specific treatment. Thirty four of the 92 died (37%).

Acute Disease

Rapid diagnosis of Japanese encephalitis by immunofluorescent examination of cerebrospinal fluid.

An indirect immunofluorescent technique for rapid diagnosis of patients of Japanese encephalitis (JE) was developed by demonstrating the viral antigen in CSF cells. The CSF samples of 31 consecutive patients admitted with acute viral encephalitis during 1987 were studied. In 15 patients the diagnosis of JE virus infection was made on the same day. Classical techniques for virus detection and antibody serology were also conducted in these patients. The indirect immunofluorescence for JE virus antigen detection in CSF cells proved to be a rapid and simple procedure for making a quick diagnosis of infection.

Acute Disease

Prevalence of parainfluenza type 1 virus in Lucknow (India).

A total of 568 children suffering from acute respiratory infections were studied from September, 1986 to June, 1988 using indirect immunofluorescence technique to know the frequency of infections caused by parainfluenza viruses 1 and 3. Though sporadic cases of parainfluenza 1 (2.5%) and parainfluenza 3 (3.2%) were seen round the year, and increase in cases of parainfluenza virus type 1 infection was observed only in October, 1987 in Lucknow.

Age Factors

Alterations in iron levels in Japanese encephalitis virus infection.

Following Japanese encephalitis virus (JEV) infection in mice the serum iron concentration decreased; the decline started from day 3 and persisted up to day 9 postinfection. No significant difference was found in the total iron-binding capacity of serum in JEV-infected mice compared with that of controls. The hypoferraemia was associated with accumulation of iron in the spleen. Large amounts of stainable iron were demonstrated in splenic macrophages from day 5. This was accompanied by transient anaemia. Thus, the hypoferraemia, following intraperitoneal inoculation of JEV, was attributed to a block in the release of iron from the RES.

Animals

Clinical features & prognostic indicators of Japanese encephalitis in children in Lucknow (India).

This communication reports the clinical features of 92 children with Japanese encephalitis diagnosed on the basis of viral isolation from brain or cerebrospinal fluid and/or a 4-fold or higher rise in antibody titre in paired sera by haemagglutination inhibition (HI) test, followed by detection of specific IgM HI antibody. More than a third of the patients (38%) were from urban areas. A high incidence of fever (94.5%), coma (100%) and convulsions (84.7%) was seen. Focal neurological deficit was found in 29.3 per cent of patients and pleocytosis in the cerebrospinal fluid in 32.3 per cent. An extrapyramidal syndrome developed in 21.3 per cent patients during the convalescent stage. Thirty four (36.9%) patients died while in hospital. Mortality was significantly related to a short prodromal stage, deep coma, abnormalities in tone and breathing and decerebrate posturing. Japanese encephalitis represents a severe disease in children with a high early mortality.

Child

Antigenic competition between dengue and Coxsackie viruses for presentation to B cells by macrophages.

Macrophages (M phi) pulsed with dengue type 2 (DV) and Coxsackie B4 (CoxB) viruses present antigen to B lymphocytes leading to their clonal expansion as detected by counting antigen-specific IgM antibody plaque-forming cells (PFC). The present study was undertaken to investigate the site for competition in M phi between the two heterologous antigens, DV and CoxB, for their presentation to B cells. It was observed that DV-pulsed M phi presented antigen to B cells in mice depleted of T cells by treatment with anti-Thy 1.2 monoclonal antibodies. The B cells could not be stimulated in absence of M phi in mice treated with silica. The PFC counts for both the antigens were inhibited when M phi were pulsed simultaneously with DV and CoxB. PFC counts were increased by 53-120% by predigesting the antigens by trypsin. Inhibition of DV-specific response by CoxB was abrogated by predigesting CoxB. A marked reduction in DV-specific PFC response was observed when CoxB was superimposed on M phi pulsed with DV 24 h earlier. CoxB-specific PFC counts were not affected by superimposing DV on M phi pulsed with CoxB 24 h earlier. PFC response to the antigen given to M phi before glutaraldehyde fixation was not affected while that for the antigen given to glutaraldehyde-fixed M phi was markedly depressed. It is concluded that the competition between DV and CoxB for antigen presentation to B cells occurs in M phi at the level of antigen processing.

Animals

Effect of dengue virus-induced cytotoxin on capillary permeability.

Capillary permeability is increased in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) but its genesis is not known. Dengue type 2 virus (DV) induces production of a cytokine (CF2) by mouse macrophages. The present study was undertaken to investigate the effect of CF2 on capillary permeability. It was observed that intraperitoneal inoculation of CF2 in mice increased the capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radioactive iodine (125I) or Evan's blue dye in the peritoneal cavity. Peak leakage occurred at 30 min and the vascular integrity was restored by 1-2 h. The increase in capillary permeability was abrogated by pretreatment of mice with avil (H1 receptor blocker) but not by ranitidine (H2 receptor blocker). The findings thus show that DV-induced CF2 increases the capillary permeability via release of histamine.

Animals

Increased capillary permeability mediated by a dengue virus-induced lymphokine.

The mechanism of increased capillary permeability, seen in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), is not known. Dengue type 2 virus (DV) is known to induce production of a lymphokine, the cytotoxic factor (CF), by the T lymphocytes of mouse spleen. The data presented here show that intraperitoneal inoculation of CF in mice results in increased capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radiolabelled iodine (125I) or Evans blue dye. Peak leakage occurred 30 min after inoculation of CF and the vascular integrity was restored by 2 hr. The increase in capillary permeability was abrogated by pretreatment of mice with anti-CF antibodies, avil (H1 receptor blocker) or ranitidine (H2 receptor blocker). The findings thus show that a DV-induced lymphokine, the CF, increases the capillary permeability via release of histamine.

Animals

Evidence for latency of Japanese encephalitis virus in T lymphocytes.

Activation of latent Japanese encephalitis virus (JEV) in the spleen has been studied by co-cultivation with allogeneic or syngeneic cells. Activated virus was isolated by co-cultivation from T lymphocytes of spleen, as shown by indirect immunofluorescence or by inoculation into mice. The B lymphocytes and macrophages of latently infected mice did not reactivate the virus. A higher proportion of Lyt 1 cells than Lyt 2 cells were harbouring JEV as shown by indirect immunofluorescence. The spleen cells from latently infected mice elicited the lymphoproliferative response but this was much lower than that observed in the controls. These findings suggest the establishment of latent JEV infection in T lymphocytes.

Animals

Obligatory role of macrophages in dengue virus antigen presentation to B lymphocytes.

The study was undertaken to investigate the role of dengue type 2 virus (DV)-infected mouse peritoneal macrophages (M phi) in presentation of the DV antigen to B lymphocytes as shown by counting virus-specific IgM antibody plaque-forming cells (PFC). It was observed that heat-killed or glutaraldehyde-fixed M phi did not present the antigen. Pretreatment of M phi with the lysosomotropic compounds ammonium chloride and chloroquine inhibited the antigen presentation. Depletion of M phi from the spleen cell cultures abrogated the immune response to DV. The tryptic-digested DV antigen could stimulate immune responses in B-lymphocyte enriched (depleted of M phi and T cells) spleen cell cultures, and the digested antigen could be presented by glutaraldehyde-fixed M phi. Pretreatment of M phi with a trypsin inhibitor abrogated antigen presentation. The findings thus show that even for presentation to B cells the DV antigen must be processed by M phi by a trypsin-like protease.

Ammonium Chloride

Proteinase-like activity in the cytotoxic factor produced by T cells during dengue virus infection.

Dengue type 2 virus (DV)-induced cytotoxic factor (CF) or the virus-primed spleen cell capable of secreting CF were treated with various proteinase inhibitors and their activity was assayed. It was observed that the cytotoxic activity of CF was inhibited significantly, in a dose-dependent manner, by pretreatment with bovine pancreatic trypsin inhibitor (BPTI) and phenylmethylsulphonyl fluoride (PMSF), to a lesser extent by soya-bean trypsin inhibitor (SBTI) and leupeptin and not at all by 1,10-phenanthroline (OP). Similar effects were observed by pretreatment of DV-primed spleen cells. Amidolytic activity of CF or its purified fractions was assayed using twelve chromogenic peptide substrates and all the substrates were hydrolysed to the varying extent. The amidolytic activity of CF was also inhibited by pretreatment with proteinase inhibitors. Thus, CF could be a proteinase with the distinction of having a broad spectrum of activity.

Animals