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Biomedical subjects

M Yadav

Publications and source records attributed to M Yadav.

At least 19 recordsLinked to original sources
PubMed2006

The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency.

CPSI deficiency is an inborn error of metabolism caused by mutations in the first, rate-determining enzyme of the urea cycle. Our mutation detection data from this disorder suggest that a significant number of mutant alleles cause RNA instability, most likely through the nonsense-mediated decay pathway. We identified 26 non-consanguinous CPSID patients with an available RNA source (liver tissue or cell line) and screened both genomic DNA and RNA for the identification and classification of mutations. Out of 52 total alleles screened from these patients, 21 (40%) have strong evidence for RNA processing mutations demonstrated by absent/minimal heterozygosity in patient cDNA sequences despite heterozygous genomic changes. These 21 alleles are a heterogenous group primarily composed of splicing defects and frameshifts that form premature termination codons which should subsequently elicit the nonsense-mediated decay pathway. This study provides evidence for the high prevalence of RNA instability mutations in genetic disease and underscores the importance of accounting for them in mutation-screening strategies.

Alleles↗
PubMed2006

Nitric oxide radicals in leucocytes and vaginal washes of Trichomonas vaginalis -infected symptomatic and asymptomatic women.

The clinical spectrum of Trichomonas vaginalis infection varies from asymptomatic to mild, moderate or severe vaginitis. Nitric oxide and other reactive nitrogen radicals produced by immune effector cells are important cytotoxic and cytostatic mediators against several microorganisms including parasites. In the present study, inducible nitric oxide synthase (iNOS) and reactive nitrogen intermediates (RNI) were determined in leucocyte cultures (stimulated with T. vaginalis in vitro) and vaginal washes (VWs) of 22 symptomatic and 20 asymptomatic T. vaginalis-infected and 20 healthy women by immunoblotting and Griess method respectively. The iNOS protein was detected in leucocytes and VWs of all the symptomatic and asymptomatic women, but was not detected in any of the samples from healthy women. Mean iNOS protein band intensity was significantly higher in leucocytes as compared to VWs (P<0.001) of both symptomatic and asymptomatic women and was also higher in leucocytes of asymptomatic as compared to symptomatic women (P<0.05). Mean RNI concentration was also significantly higher in leucocytes (P<0.01) and VWs (P<0.05) of asymptomatic as compared to symptomatic women, and was also higher in samples of infected as compared to healthy women (P<0.001). These results suggest that reactive nitrogen radicals may have a role in limiting T. vaginalis infection in asymptomatic women.

Animals↗
PubMed2005

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR=3.7, 95% CI 1.2-12.1) and increased progressively with C282Y allelic dose (RR=1.7, 95% CI 0.4-6.8 in heterozygotes; RR=8.6, 95% CI 1.5-48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.

Adult↗
PubMed2005

Kinetics of immunoglobulin G, M, A and IgG subclass responses in experimental intravaginal trichomoniasis: prominence of IgG1 response.

Trichomoniasis, the most common nonviral sexually transmitted disease, is caused by infection with the protist Trichomonas vaginalis. The clinical spectrum varies from an asymptomatic state to mild, moderate or severe symptoms. However, the exact factors leading to varied symptomatology have not been well elucidated. The mouse is a useful experimental model for intravaginal trichomoniasis, for understanding the role of local immune responses in the pathogenesis and varied symptomatology of this disease. The present study reports anti-Trichomonas IgG, IgM, IgA and IgG subclass antibody responses on different post-infection days (3rd, 7th, 14th, 21st and 28th) in serum and vaginal washes of mice infected intravaginally with T. vaginalis isolates from 15 symptomatic and 15 asymptomatic women. Successful intravaginal infection was established by inoculating T. vaginalis in BALB/c mice pre-inoculated with Lactobacillus acidophilus and pretreated with oestradiol. A significant increase in parasite load was observed on the 14th post-infection day (p.i.d.) in mice inoculated with T. vaginalis isolates from symptomatic women as compared to asymptomatic women (P < 0.001), followed by reduction until the 28th p.i.d. (P < 0.05). A significant increase in specific IgG (P < 0.001) and in particular IgG1 (P < 0.001) and IgM (P < 0.01) responses was observed on the 14th p.i.d. in serum and vaginal washes of mice infected with T. vaginalis isolates from symptomatic women as compared to asymptomatic women. Significant increases in specific IgG, IgM and IgG1 responses was observed on the 14th p.i.d. in serum samples as compared with vaginal washes of mice infected with T. vaginalis isolates from symptomatic and asymptomatic women (P < 0.01), whereas no significant difference was observed in IgA, IgG2a, IgG2b and IgG3 antibody responses. The study indicates that specific IgG, particularly IgG1 and IgM, may be playing a role in establishing symptomatic infection.

Animals↗
PubMed2002

A study of prevalence of health problems in asymptomatic elderly individuals in Delhi.

A survey was conducted in asymptomatic aged individuals (> or = 60 years) in The National Capital Territory of Delhi for the prevalence of major health problems like hypertension, diabetes mellitus and respiratory diseases. A total of 200 individuals (100 males and 100 females) were studied over a period of three months in 1998-99. Hypertension was defined as BP > or = 140/90 mmHg (JNC VI criteria), while diabetes mellitus was diagnosed if fasting whole blood sugar was 120 mg/dl or more (WHO criteria). Diagnosis of other health problems was based on relevant history and physical examination. Prevalence of hypertension in the study group was 32.5 per cent (more in males). Of these 18 per cent and 4.2 per cent had isolated systolic and diastolic hypertension, respectively. Prevalence of diabetes mellitus in the same population was 13.0 per cent. Both diseases were more prevalent in urban population. A high prevalence of respiratory disorders was observed (pulmonary tuberculosis 16 per cent, COPD 10 per cent, asthma 4.5 per cent). Cataract was present in 7.5 per cent while 1.5 per cent had symptoms of urinary tract infection. History of Jaundice was present in 3.5 per cent. Three per cent each had a history suggestive of IHD and TIA, respectively. Proteinuria and glycosuria was seen in 22.2 and 7.6 percent, respectively. A large percentage of the study group (34.4 per cent) had asymptomatic ECG abnormalities.

Aged↗
PubMed2001

Detection of amplified int-2/FGF-3 gene in primary breast carcinomas using differential polymerase chain reaction.

Amplification of int-2/FGF-3 gene was investigated by differential polymerase chain reaction (dPCR) in 440 archival primary breast carcinoma tissues. Of these, 23 were comedo ductal carcinoma in situ (DCIS), 18 were non-comedo DCIS, 41 were comedo DCIS with adjacent invasive ductal carcinomas, 19 were non-comedo DCIS with adjacent invasive ductal carcinomas, 270 were invasive ductal carcinomas, 33 were invasive lobular carcinomas, 21 were colloid carcinomas and 15 were medullary carcinomas. Int-2 was amplified in 22% (96/440) of the primary breast carcinomas. It was shown that int-2 was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 29% (12/41) of the adjacent invasive ductal carcinomas, 26% (71/270) of the invasive ductal carcinomas, 18% (6/33) of the invasive lobular carcinomas, 10% (2/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. In contrast, int-2 was not amplified in non-comedo DCIS and invasive ductal carcinomas with adjacent non-comedo DCIS lesions. A significant association was observed between int-2 amplification in the in situ components and adjacent invasive lesion (P<0.05). All tumors with int-2 amplification in the in situ lesions (7/7) also demonstrated same degree of amplification in the adjacent invasive components. However, 9% (5/53) of the tumors with no amplified int-2 gene in the in situ components showed int-2 amplification in the adjacent invasive lesions. A significant relationship was noted between amplification of int-2 and lymph node metastases (P<0.05) and poorly differentiated tumors (P<0.05) but not with estrogen receptor status (P>0.05) and proliferation index (Ki-67 and PCNA) (P>0.05). In Malaysia, majority of the patients belong to younger age group (<50 years old) but a comparison of the age groups showed that the amplification of int-2 was not statistically associated with patient age (P>0.05). These observations indicate that amplification of int-2 tends to strengthen the view that int-2 may have the potential to be an indicator of poor prognosis regardless of the age of the patient. Moreover, the presence of int-2 amplification in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that int-2 could be a marker of genetic instability occurring in early and late stages of tumor development.

Adult↗
PubMed1999

Anti-tumour promoter activity in Malaysian ginger rhizobia used in traditional medicine.

Zingiberaceae rhizomes commonly used in the Malaysian traditional medicine were screened for anti-tumour promoter activity using the short-term assay of inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells. The inhibition of TPA-induced EBV-EA was detected using the indirect immunofluorescence assay (IFA) and Western blot technique. The indirect IFA detected the expression/inhibition of EBV-EA-D (diffused EA antigen), whereas the Western blot technique detected the expression/inhibition of both EBV-EA-D and EA-R (restricted EA antigen). Seven rhizomes were found to possess inhibitory activity towards EBV activation, induced by TPA; they are: Curcuma domestica, C. xanthorrhiza, Kaempferia galanga, Zingiber cassumunar, Z. officinale, Z. officinale (red variety), and Z. zerumbet. A cytotoxicity assay was carried out to determine the toxicity of the Zingiberaceae rhizome extracts. The rhizome extracts that exhibited EBV activation inhibitory activity had no cytotoxicity effect in Raji cells. Therefore, the present study shows that several Zingiberaceae species used in Malaysian traditional medicine contain naturally occurring non-toxic compounds that inhibit the EBV activation, which, if further investigated, could contribute in the development of cancer prevention methods at the tumour-promoting stage.

Anticarcinogenic Agents↗
PubMed1999

Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa.

Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, if any, cross-reactivity between antibodies to these two gamma viruses.

Adolescent↗
PubMed1999

Function of the central domain of streptokinase in substrate plasminogen docking and processing revealed by site-directed mutagenesis.

The possible role of the central beta-domain (residues 151-287) of streptokinase (SK) was probed by site-specifically altering two charged residues at a time to alanines in a region (residues 230-290) previously identified by Peptide Walking to play a key role in plasminogen (PG) activation. These mutants were then screened for altered ability to activate equimolar "partner" human PG, or altered interaction with substrate PG resulting in an overall compromised capability for substrate PG processing. Of the eight initial alanine-linker mutants of SK, one mutant, viz. SK(KK256.257AA) (SK-D1), showed a roughly 20-fold reduction in PG activator activity in comparison to wild-type SK expressed in Escherichia coli (nSK). Five other mutants were as active as nSK, with two [SK(RE248.249AA) and SK(EK281.282AA), referred to as SK(C) and SK(H), respectively] showing specific activities approximately one-half and two-thirds, respectively, that of nSK. Unlike SK(C) and SK(H), however, SK(D1) showed an extended initial delay in the kinetics of PG activation. These features were drastically accentuated when the charges on the two Lys residues at positions 256 and 257 of nSK were reversed, to obtain SK(KK256.257EE) [SK(D2)]. This mutant showed a PG activator activity approximately 10-fold less than that of SK(D1). Remarkably, inclusion of small amounts of human plasmin (PN) in the PG activation reactions of SK(D2) resulted in a dramatic, PN dose-dependent rejuvenation of its PG activation capability, indicating that it required pre-existing PN to form a functional activator since it could not effect active site exposure in partner PG on its own, a conclusion further confirmed by its inability to show a "burst" of p-nitrophenol release in the presence of equimolar human PG and p-nitrophenyl guanidino benzoate. The steady-state kinetic parameters for HPG activation of its 1:1 complex with human PN revealed that although it could form a highly functional activator once "supplied" with a mature active site, the Km for PG was increased nearly eightfold in comparison to that of nSK-PN. SK mutants carrying simultaneous two- and three-site charge-cluster alterations, viz., SK(RE24249AA:EK281.282AA) [SK(CH)], SK(EK272.273AA;EK281.282AA) [SK(FH)], and SK(RE248.249AA;EK272.273AA:EK281.282AA+ ++) [SK(CFH)], showed additive/synergistic influence of multiple charge-cluster mutations on HPG activation when compared to the respective "single-site" mutants, with the "triple-site" mutant [SK(CFH)] showing absolutely no detectable HPG activation ability. Nevertheless, like the other constructs, the double- and triple-charge cluster mutants retained a native like affinity for complexation with partner PG. Their overall structure also, as judged by far-ultraviolet circular dichroism, was closely similar to that of nSK. These results provide the first experimental evidence for a direct assistance by the SK beta-domain in the docking and processing of substrate PG by the activator complex, a facet not readily evident probably because of the flexibility of this domain in the recent X-ray crystal structure of the SK-plasmin light chain complex.

Amino Acid Sequence↗
PubMed1998

Expression of c-erbB3 protein in primary breast carcinomas.

Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.

Adult↗
PubMed1998

Rice-starch oral rehydration therapy in neonates and young infants.

Rice-starch based oral rehydration solution (ORS) has been shown to be a suitable alternative to glucose-based ORS in the treatment of both choleragenic and non-choleragenic dehydration in older infants and children. However, in young infants, the wider use of rice-starch ORS has been impeded because of theoretical concern about the poor digestibility of starch. The present study was conducted to evaluate the safety and efficacy of rice-starch ORS in the rehydration of acute diarrhoeal dehydration in infants below 6 months of age. Sixty-three infants with clinical features of acute gastroenteritis were randomly allocated to two groups. Group A, comprising 31 infants, received a rice-starch ORS and group B, comprising 32 infants, received a glucose-based ORS. The response to treatment was monitored by weight gain, stool frequency, and decrease in vomiting. The mean weight gain in moderately dehydrated and mildly dehydrated infants in both groups A and B were closely similar at 12, 24, and 48 h after treatment with the respective ORS solution. The infants without dehydration receiving rice-starch ORS had significantly greater weight gain at 12 h compared to those receiving glucose ORS. However, this difference was not observed at 24 and 48 h. The results of this study show that rice-starch ORS is as safe and efficacious as glucose-based ORS in young infants.

Dehydration↗
PubMed1997

Detection of human herpesvirus 7 in salivary glands.

The prevalence and cellular distribution of human herpesvirus 7 (HHV-7) in archival labial salivary glands was analysed for virus-specific DNA sequences by polymerase chain reaction (PCR) and in situ hybridization signals. In addition, the cellular expression of HHV-7-encoded protein was detected by immunohistochemical staining with a virus-specific monoclonal antibody. Eleven of 20 samples were positive for the HHV-7 DNA sequence by PCR. Eighteen of 20 tissues analysed by in situ hybridization showed signals in ductal, serous and mucous cells. Some nuclei of these cells and also the myoepithelial population were positive. In immunolocalization studies, all 20 salivary glands consistently showed HHV-7-expressed protein in the cytoplasm of ductal cuboidal and columnar cells. The protein was also found in the cytoplasm of mucous and serous acinar cells that were immunopositive for HHV-7. The observations are consistent with the suggestion that the labial salivary gland is a site for virus replication, potential persistence and a source of infective HHV-7 in saliva.

Adolescent↗
PubMed1997

Detection of HHV-6 genotypes by in situ hybridization with variant-specific oligonucleotide probes.

Human herpesvirus-6 exists in two forms, HHV-6A which has not been clearly associated with any disease, and HHV-6B, the causative agent of exanthem subitum. The two variants have been distinguished by techniques such as dot blotting and restriction fragment length polymorphism of PCR products. This study aims to establish the prevalence of HHV-6A and HHV-6B in carcinoma tissues using variant-specific oligonucleotide probes. A total of 73 archived carcinoma biopsies from the oral, salivary gland, larynx, breast and cervix were obtained with seven histologically normal controls. In situ hybridization was carried out with nonradioactively labelled variant-specific probes. Samples that hybridized with both variant A and B probes were subjected further to nested PCR and digested with HindIII to distinguish the variants. A hybridization signal was observed in 76.2% of oral carcinoma tissue and 75.0% of salivary gland carcinoma tissue. In contrast, only 33.3% of cervical carcinoma tissue were positive for HHV-6 DNA. A hybridization signal was noted in all 4 laryngeal carcinoma tissues studied. However, the 10 breast carcinoma tissues studied were negative, as was the histologically normal tissue. The virus possesses tumourigenic potential and demonstrates virus transactivating properties. The frequency of HHV-6 variants in certain tumours suggest a cofactorial role in multistep carcinogenesis. While PCR amplifies selectively the predominant variant in a sample, this was not seen by in situ hybridization. The in situ hybridization technique allowed the localization of both HHV-6A and HHV-6B in the nuclei of transformed regions.

DNA, Viral↗
PubMed1997

Dual detection of human herpesvirus-6 and human papillomavirus type 16 and 18 in cervical carcinoma.

Introduction It is widely accepted that certain 'high risk' human papillomavirus (HPV) genotypes, particularly HPV 16 and 18 are aetiological agents in the development of neoplasia of the uterine cervix. The long latent period between initial HPV infection and emergence of carcinoma suggests that HPV alone is insufficient for malignant transformation and additional factors are required for the progression of HPV infected cells to a neoplastic phenotype. Cells with integrated HPV express viral E6 and E7 oncoproteins which are crucial for immortalisation of epithelial cells via their action on host p53 protein. It is therefore of particular interest to elucidate the molecular mechanisms that alter the expression of E6/E7 proteins during HPV-associated tumorigenesis. Recently, human herpesvirus-6 (HHV-6) has been shown to infect a HPV-immortalised cervical epithelial cell line and transactivate HPV 18 promoters, upregulating gene expression of E6 and E7 HPV oncoproteins (Chen et al., 1994; DiPaolo et al., 1994). HHV-6, first isolated from peripheral blood mononuclear cells of patients with AIDS and lymphoproliferative disorders, is the causative agent of exanthem subitum, heterophile-negative infectious mononucleosis and other febrile illnesses. HHV-6 has recently been detected in oral carcinomas (Yadav et al., 1994). HHV-6 also contains DNA sequences which can transform epithelial cells in culture.

Journal Article↗