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Biomedical subjects

P Seth

Publications and source records attributed to P Seth.

At least 19 recordsLinked to original sources

Supersensitivity of spinal dopaminergic receptors in rat after chronic haloperidol.

In order to examine the effect of chronic neuroleptics on spinal dopaminergic system, rats were treated with haloperidol (0.5 mg/kg IP) for 21 days and the monosynaptic mass reflex (MMR) as well as dopamine (DA) metabolism were investigated. MMR, recorded from ventral root L6 following supramaximal stimulation to ipsilateral dorsal root L6 in spinalized rats, were found to be unaffected following chronic haloperidol treatment when compared to control. Apomorphine (0.1 mg/kg IV) caused 10-20% depression of MMR in control animals which was augmented to 40-50% in chronically haloperidol-treated animals suggesting an upregulation of DA receptors in the spinal cord. DA content of lumbar region of the spinal cord was unaffected whereas its major metabolite, homovanillic acid, was significantly reduced in chronic haloperidol-treated animals. This decreased utilization of DA may compensate the upregulation of DA receptors to maintain the physiological homeostasis of the spinal dopaminergic system.

Animals

Presynaptic dopaminergic inhibition of the spinal reflex in rats.

Dopaminergic influence on spinal monosynaptic transmission was examined in rats. Monosynaptic mass reflex (MMR) was recorded from the ventral root L6 following supramaximal stimulation (0.2 Hz; 0.1 ms) to the ipsilateral dorsal root L6 in spinalized rat under pentobarbitone sodium (40 mg/kg, i.p.) anaesthesia. MMR was inhibited by intravenous administration of the dopaminergic agonist, apomorphine (50-200 ug/kg) in a dose-dependent manner. The attenuatory effect of apomorphine (200 ug/kg i.v.) on the reflex could be reversed by the dopaminergic antagonist haloperidol (0.5 mg/kg, i.v.). Under tetanic stimulation (200 Hz; 15s), the pretetanic relative inhibition induced by apomorphine (200 ug/kg, i.v.) was increased only for a short period immediately after the cessation of tetanic stimulation. The results indicate existence of presynaptic dopamine receptors on the afferent terminals converging on the motoneurone which may functionally modulate the spinal motor output.

Animals

Detection of human papilloma virus types 16 & 18 DNA in cervical lesions of Indian women using in situ hybridization.

Fifty one biopsies from women with malignant lesions of the uterine cervix and 9 biopsies fron non-malignant lesions were examined for the presence of HPV 16 and 18 DNA sequences by in situ hybridization method using 35S-labelled DNA probes. HPV 16 DNA sequences were detected in 82.4 per cent biopsies from women with malignant lesions, whereas HPV 18 DNA was detected in only 3 biopsies which were also positive for HPV 16 DNA. Two biopsies from non-malignant lesions were positive for HPV 16 DNA only. Data were also analysed according to the histologic type of cancer. It was observed that no significant correlation existed between HPV types and different histologic types of cervical cancer.

DNA Probes, HPV

An epidemic of acute haemorrhagic conjunctivitis caused by coxsackie A24 variant.

An epidemic of acute haemorrhagic conjunctivitis (AHC) caused by a variant of coxsackie A24 (cox A24) occurred in Delhi during August to September 1988. Cox A24 antigen was detected by indirect immunofluorescence (IFA) in conjunctival cell smears of 13 of the 38 (34.2%) patients studied. Virus was isolated from conjunctival swabs in 11 (28.9%) patients and all isolates were neutralized by cox A24 antiserum. Five virus strains sent to Virology Division of Centres for Disease Control, Atlanta, USA, were confirmed as cox A24 variant. Enterovirus type 70 (EV70) was not demonstrable either by IFA or neutralization tests. Conjunctival swabs from 10 healthy laboratory controls did not show any evidence of EV70 or cox A24 virus or their antigens.

Acute Disease

Prevalence of SSPE: a serological study.

The presence of measles antibodies in serum and cerebrospinal fluid (CSF) of 340 samples from children clinically suspected of subacute sclerosing panencephalitis (SSPE) were studied. One hundred and thirty eight (40%) of these children had SSPE based on the serological evidence. The mean age group of children affected was 8.2 years. The M:F ratio was 5:1. The titres of antibodies ranged from 1:2 to 1:32 in the CSF and from 1:16 to 1:512 in the serum.

Child

Metabolic activation of sodium nitroprusside to nitric oxide in vascular smooth muscle.

Sodium nitroprusside (SNP) is thought to exert its vasodilating activity, at least in part, by vascular activation to nitric oxide (NO), but the activation mechanism has not been delineated. This study has examined the potential for vascular metabolism of SNP to NO in bovine coronary arterial smooth muscle subcellular fractions using a sensitive and specific redox-chemiluminescence assay for NO. SNP was readily metabolized to NO in subcellular fractions, and the dominant site of metabolism appeared to be located in the membrane fractions. NO-generating activity was significantly enhanced by, but did not absolutely require, the addition of a NADPH-regenerating system, NADPH per se, NADH or cysteine. A correlation analysis of NO-generating activity (in the presence of a NADPH-regenerating system) with marker enzyme activities indicated that the SNP-directed NO-generating activity was primarily membrane-associated. Radiation inactivation target-size analysis revealed that the microsomal SNP-directed NO-generating activity was relatively insensitive to inactivation by radiation exposure, suggesting that the functioning catalytic unit might be quite small. A molecular weight of 5 to 11 kDa was estimated. NO-generating activity could be solubilized from the crude microsomes with 3-[(3-cholamidopropyl)- dimethylammonio]-1-propane sulfonate, and the solubilized extract was subjected to gel filtration chromatography. NO-generating activity was eluted in two peaks: one peak corresponding to an approximate molecular weight of 4 kDa, thus confirming the existence of a small molecular weight NO-generating activity, and a second activity peak corresponding to a molecular weight of 112 to 169 kDa, the functional significance of which is unclear at present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Conversion of nitroglycerin to nitric oxide in microsomes of the bovine coronary artery smooth muscle is not primarily mediated by glutathione-S-transferases.

The pharmacological action of organic nitrate vasodilators [e.g., nitroglycerin (NTG)] is thought to be mediated through metabolic conversion to nitric oxide (NO); conversion leads to vasodilatation, whereas diminished conversion in chronic therapy may lead to pharmacological tolerance. The biochemical nature of this process, however, is poorly understood. Glutathione-S-transferases (GST) have been shown to metabolize organic nitrates in the liver, but it is not known whether these enzymes are involved in this pharmacologically relevant process. We, therefore, compared the activities of conversion of NTG to NO vs. those of GST in microsomal suspensions of bovine coronary artery smooth muscle tissue. A classical GST substrate, 1-chloro-2,4-dinitrobenzene, inhibited NO production in microsomes, suggesting possible involvement of GST in organic nitrate activation. However, GST activity derived from microsomes exhibited a different heat lability profile compared to that of NO generation. Known inhibitors of GST (viz., indomethacin and bromosulfophthalein) did not alter the NO-generating activity in microsomes. Glutathione was a critical cofactor for GST, but not for NO generation from NTG, and thiols other than glutathione (e.g., N-acetyl-L-cysteine and thiosalicylic acid) also could facilitate NO production. Moreover, comparison to a commercially available purified liver GST preparation showed that, at the same GST activity toward 1-chloro-2,4-dinitrobenzene, the microsomal incubation produced about 8 times more NO than the purified liver GST. Radiation inactivation analysis of the functional molecular sizes of GST and the NO-producing enzyme(s) suggested that the enzymes were of different molecular weights (54 kD and 160 kD, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Recovery of human immunodeficiency virus from asymptomatic prostitutes from Tamil Nadu.

Peripheral blood mononuclear cells (PBMC) from 13 asymptomatic healthy human immunodeficiency virus type-1 (HIV-1) antibody positive prostitutes from Tamil Nadu, southern India, were cocultivated with phytohemagglutinin stimulated PBMC from HIV antibody negative donors for HIV isolation. In addition, plasma samples from two antibody positive prostitutes with HIV antigenemia were processed for virus isolation. The presence of virus in the cultures was monitored by (i) assay for virus particle associated reverse transcriptase (RT) activity, (ii) HIV-antigen enzyme immunoassay, and (iii) indirect immunofluorescence test to detect expression of HIV specific core antigens p-24 and p-17 in infected cells using monoclonal antibodies to these antigens. The virus was isolated from PBMC from 2 prostitutes (86-4 and 86-5) and from plasma of one prostitute (86-20). These isolates have been characterised as HIV type-1 by dot blot hybridization using HIV-1 and HIV-2 proviral DNA probes.

DNA, Viral

HIV antibody screening of commercially available blood products in India.

In a screening of 182 vials of various commercially available blood products in the Indian market, 32 (17%) were found to contain HIV-1 antibodies. The contamination with HIV-1 antibodies was detected in all types of blood products including immunoglobulin preparations, cryoprecipitates as well as albumin. Interestingly, the contamination was seen almost exclusively in the products manufactured in the Bombay-Pune area (32 of 92, 34%). It was very low in products manufactured near Delhi (1 of 90). A single vial of imported Factor VIII concentrate tested negative.

Biological Products

Circulating immune complexes in tuberculosis.

To examine whether any correlation exists between the levels of circulating immune complexes (CICs) and the activity of tuberculosis, CICs were measured in the sera of 75 patients with active tuberculosis and in 25 control subjects using polyethylene glycol method. The effect of drug treatment on the levels of CICs was also estimated in 25 patients. It was found that levels of CICs were elevated in most of the untreated patients (96%) of tuberculosis and the CICs levels fell to control values in 64% of patients at the end of treatment.

Antigen-Antibody Complex

Acute rubella infection in pregnant women in Delhi.

Serum samples of 17 pregnant women with suspected rubella who presented at the Department of Microbiology, AIIMS, New Delhi, from March to May 1988 for confirmation of diagnosis were tested for rubella haemagglutination inhibiting (HAI) antibodies and rubella specific IgM antibodies by mu-capture ELISA. Ten of the 17 women were diagnosed to have acute rubella infection as they showed the presence of rubella specific IgM antibodies. Nine of these gave history of fever and rash whereas one woman remained asymptomatic. These observations suggest an increase in the incidence of rubella infection in pregnant women from March to May 1988 in Delhi.

Acute Disease

Isolation and characterization of non-muscle tropomyosin cDNAs of human and mouse origin.

Several cDNA clones of human and mouse non-muscle tropomyosin have been isolated. All the human clones possess a common 23 bp sequence immediate 5' of the initiation codon. However, in the further upstream regions, the nucleotide sequences diverge. Two of the mouse cDNA clones pPSI-8 and pPSI-14 have identical nucleotide sequence in the coding region sequenced. However, 5' of the initiation codon these clones have only 40 identical nucleotides and further upstream the nucleotide sequences diverge. Analysis of the genomic DNAs of mouse cells indicated the possibility of a common gene giving rise to both the tropomyosin cDNAs differing in their 5' ends.

Amino Acid Sequence

Evaluation of indirect hemagglutination and its inhibition in the differentiation between antibodies to herpes simplex virus types 1 and 2 for seroepidemiologic studies: use of a II/I index threshold of 85 and an assay of type-specific antibodies.

Two parameters, a II/I index threshold value of 85 and an assay of type-specific antibodies to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), were assessed, for seroepidemiologic purposes, for their efficacy in the establishment of past infections with HSV-1 and HSV-2 as indicated by the results of tests for indirect hemagglutination and its inhibition. Neither criterion alone established past infection with either HSV-1 or HSV-2. However, by combination of the two parameters, antibodies to HSV-1 and HSV-2 could be differentiated for seroepidemiologic studies.

Adolescent

Use of the 51chromium release test to demonstrate antigenic differences between extracellular and intracellular forms of vaccinia virus.

Complement-dependent antibody lysis of vaccinia-infected cells was examined to demonstrate the antigenic differences between extracellular (ECV) and intracellular (ICV) forms of vaccinia virus. Cytolytic antibodies present in the antisera raised against ECV or live virus (LV) were completely removed by absorption with infected cell membranes or purified ECV but not with purified ICV. Absorption with infected cell membranes also abolished the neutralizing activity of ECV and LV antisera against ECV. On the other hand, antiserum against ICV did not contain cytolytic antibodies against vaccinia-infected cells, even though its neutralizing antibody titre against ICV was high. Moreover, both ECV and ICV antisera neutralized a small proportion of the heterologous form of virus, despite using purified preparations of ECV and ICV, respectively, for raising these antisera in rabbits. In contrast, the 51Cr release test only detected the antibodies against ECV and thus can be used to differentiate between the antibody activity of a serum against ECV and ICV.

Animals

Circulating immune complexes in carcinoma of uterine cervix.

Circulating immune complexes were determined in the sera of forty-eight patients wital status by inhibition of rheumatoid factor (RF) maediated agglutination of IgG coated latex particles. The inhibitory activity was present in 63% of the sera from cervical cancer patients but only 13% of sera from control women contained this activity. Similarly, anticomplementary activity suggestive of the presence of immune complexes was present in 71% of sera from cancer patients and 13% of sera from control women. The incidence as well as the levels of immune complexes (IC) were higher in sera of patients with advanced stages of cancer as compared to those with Stage I cervical cancer. In addition, 95% of sera from cervical cancer patients had cryoblobulins, whereas only 20.8% sera from matched controls were positive for cryoprecipitates. All the cryoglobulins contained IgG type of immunoglobulin except one which had IgA immunoglobulins also. The complexes have not been characterized with regard to the nature of the antigen(s) present.

Antigen-Antibody Complex