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Biomedical subjects

V Ramesh

Publications and source records attributed to V Ramesh.

At least 145 records · Page 8Linked to original sources
PubMed1996

Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients.

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by hamartomas in one or more organs, including the brain, skin, heart and kidneys. Linkage studies have shown locus heterogeneity with one TSC gene mapped to chromosome 9q34 and a second to 16p13.3. The gene on 16p13.3, TSC2, has been cloned and shown to encode a 5.5 kb transcript that is widely expressed. To facilitate the search for mutations in the TSC2 gene product, tuberin, we have designed an RT-PCR-based assay system to scan the expressed coding region of the TSC2 gene in lymphoblasts. Using 34 overlapping PCR assays we performed single-strand conformation polymorphism analysis of DNA from 26 apparently sporadic TSC cases, two TSC families non-informative for linkage analysis and two confirmed chromosome 16-linked TSC families. Of the 60 chromosomes scanned, 14 showed abnormal SSCP mobility shifts. Using direct PCR sequencing we have identified five missense mutations, one 3 bp in-frame deletion and one 2 bp frameshift deletion, one nonsense mutation, one 29 bp tandem duplication and five silent nucleotide changes that are likely to be polymorphisms. There is no apparent clustering of mutations within TSC2. The diversity of mutation types argues that TSC2 may not act in a classic tumor suppressor fashion. In addition, we saw no specific correlation between the different mutations and clinical severity or expression. These data confirm that TSC2 is indeed the relevant gene, and that a substantial number of sporadic cases arise from mutations in the TSC2 gene.

Base Sequence↗
PubMed1996

Practical problems in the management of leprosy.

The categorization of leprosy into paucibacillary or multibacillary depends on the report of slit-skin smears. Unfortunately, in many control programmes the quality of slit smears is below par. Taking the example of India, the main reasons were that the work of laboratory technicians was unrewarding as compared to serving in a general health care system. There was lack of equipment and an unrealistic patient to technician ratio. Future attempts were made by experienced workers to devise a clinical system for classifying leprosy as paucibacillary or multibacillary based on counting the number of lesions. However this method did not prove cost-effective because more paucibacillary patients were classified in the multibacillary group increasing the burden of treatment. A renewed attempt to improve slit-smear performance should be made by modifying the existing methods. This can definitely improve the situation. Patients with multiple macular lesions and those with neuritic leprosy are best treated with the MB-MDT regimen. The treatment for PB leprosy is to continue up to 6 months but in MB leprosy with a high bacterial index a longer duration of MDT may be required. Following completion of MDT many cases with deformity are accumulating and their care forms are a neglected part of many control programmes. In addition to strengthening the infrastructure, simple techniques must be imparted to those with deformities and disabilities. This involves the artful and innovative cooperation of the health worker, patient and the community. The leprosy worker should be motivated to promote such activities.

Health Services Needs and Demand↗
PubMed1996

An intelligent information systems architecture for clinical decision support on the Internet.

This paper presents a prototype of an agent-based intelligent information systems architecture that can provide clinical decision support in a distributed, heterogeneous environment such as the Internet. After presenting the architecture, a specific transaction sequence is detailed and implemented to test the architecture. A transaction sequence is a detailed analysis of all actions by all entities to accomplish the system goal. In this case, the goal is to give decision support information access to a provider in the context of a computerized patient record. Based on the results of the prototype implementation, we argue that the system is scaleable and discuss other transactions, standards, and needed development.

Computer Communication Networks↗
PubMed1996

The prevalence of transfusion transmitted diseases in renal transplant recipients.

Majority of renal transplant patients have history of blood transfusion. Out of a total of 120 renal transplant patients, 20 (16.6%) patients showed raised alanine aminotransferase (ALT) levels (> 45 IU) on 2 or more occasions at 2 weeks interval. This study was undertaken to estimate the risk of transfusion transmitted diseases (TTD) in these 20 renal transplant patients. Another 200 voluntary blood donors were also included as control. Both subject groups were screened by ELISA for HBsAg, anti HBc (IgG & IgM), anti HCV, anti CMV (IgM), anti HIV and VDRL tests for syphilis. A total of 11 (55%) patients and 3 (1.5%) blood donors showed the evidence of HBsAg positivity (p < 0.01). Anti HBc antibody was present in 12 (60%) patients and 39 (19.5%) donors which was significantly (p < 0.01) different. Anti HCV antibody was detected in 5 patients and in one blood donor (p < 0.01). However, anti CMV antibody was present in 4 (20%) patients and 3 (1.5%) donors, respectively. There was no evidence of HIV and syphilis infection in both these groups. High incidence of hepatitis markers were observed in renal transplant patients.

Biomarkers↗
PubMed1996

Synchronous oesophageal carcinoma with non Hodgkin's lymphoma, problems with management.

A case of synchronous malignancy of oesophagus with Non Hodgkin's lymphoma is presented and the rarity of such an association is discussed. The inherent difficulties encountered were initial planning of therapy keeping in view of the general condition of the patient. The patient received three cycles (every 21 days) of CHOP regimen for Non Hodgkin's lymphoma and to maintain a static state of oesophageal cancer. The patient showed more than 75 percent response to NHL counterpart, and for carcinoma oesophagus counterpart short course high dose loco-regional radiation therapy was given and the tumor was found to be resectable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Neurofibromatosis 2 gene in human colorectal cancer.

Colon cancers commonly have allelic losses of chromosome 22q, which suggests the presence of a tumor suppressor gene on 22q. The candidate tumor suppressor gene on 22q is the neurofibromatosis 2 (NF2) gene. Using single strand conformation polymorphism (SSCP) analysis, we screened 24 pairs of colorectal cancer and adjacent normal mucosa, as well as 10 colon cancer cell lines from non-NF2 patients, for mutations in the coding sequence of the NF2 gene. Two SSCP variants, one in exon 14 and another one in exon 16, were detected in two of the sporadic colorectal cancers, but not in adjacent normal mucosa samples. Sequencing of these variants in one tumor detected an A-to-G transition in bp 1459 of the NF2 cDNA, resulting in the change of Ile to Val at codon 487 of merlin, the NF2 protein product. The other tumor showed a 2-bp (CT) deletion in the intronic sequence of the alternatively spliced exon 16. These results suggest that the NF2 gene is probably involved in some colorectal tumors, but is not the critical chromosome 22q tumor suppressor gene involved in colon tumorigenesis.

Base Sequence↗
PubMed1995

Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and mouse tissues.

The recently isolated gene for tuberous sclerosis 2 (TSC2) encodes a 5.5-kb transcript that is widely expressed. The TSC2 gene product, named tuberin, is a 1784-amino-acid protein that shows a small stretch of homology to the GTPase activating protein rap1GAP. We have detected a novel variant of the TSC2 mRNA lacking 129 nucleotides, predicting an in-frame deletion of 43 amino acids spanning codons 946-988 of tuberin. This 129-bp deletion precisely corresponds to exon 25 of the TSC2 gene suggesting that alternative splicing leads to production of two forms of transcripts designated isoforms 1 and 2. Further molecular analysis revealed a third isoform exhibiting a deletion of 44 amino acids spanning codons 946-989 of tuberin. Amino acid 989 is a Ser residue encoded by the first codon of exon 26. The two isoforms also exist in newborn and adult mouse tissues, reinforcing the potential functional importance of these alternatively spliced products. These alternative isoforms should have implications for efforts aimed at identifying mutations in TSC patients. The distinct polypeptides encoded by the TSC2 gene may have different targets as well as functions involved in the regulation of cell growth.

Alternative Splicing↗
PubMed1995

Site-specific 15N-labelling of oligonucleotides for NMR: the trp operator and its interaction with the trp repressor.

A convenient and economical method is described for the site-specific 15N-labelling of the 4-amino group of individual cytidine residues in oligonucleotides. This is applied to a 20 base-pair oligonucleotide corresponding to the trp operator; this oligonucleotide and its complex with the E. coli trp repressor are studied by NMR, using 1H-15N HMQC and 15N-edited 1H-1H NOESY experiments.

Bacterial Proteins↗
PubMed1995

Medial preoptic alpha-2 adrenoceptors in the regulation of sleep-wakefulness.

Adrenergic alpha 2 agonist (clonidine) and its antagonist (yohimbine) were locally applied to the medial preoptic area (mPOA), to find out the role of alpha 2 receptors at this brain region in the regulation of sleep-wakefulness. Clonidine produced arousal, whereas yohimbine induced sleep in freely moving animals. Behavioural arousal produced by clonidine administration was accompanied by EEG synchronization. The alpha 2 receptor as the probable site of action of externally applied norepinephrine (NE), is discussed.

Animals↗
PubMed1995

Monocyte derived IL 10 and PGE2 are associated with the absence of Th 1 cells and in vitro T cell suppression in lepromatous leprosy.

Our previous studies had shown that the clinicopathological spectrum in leprosy was associated with discrete T cell subsets in circulation, with tuberculoid patients having antigen-induced Th 1, whereas lepromatous leprosy patients with antigen-specific T cell anergy possessed Th 2 cells. The present study shows that infected monocytes from lepromatous but not tuberculoid leprosy patients released soluble factors (MoF(s)) containing IL-10 and PGE2 which inhibited M. leprae induced in vitro lymphoproliferation of previously sensitised healthy or tuberculoid leprosy subjects. A strong negative correlation was observed between adherent cell derived IL-10 and IL-2 at the level of both the product and cytokine mRNA. Moreover, anti-IL-10 antibodies and indomethacin partially reversed the suppressor effects of MoF(s). Taken together these studies indicate that infected monocytes contribute to the development of T cell anergy by releasing factors that affect regulatory cytokines and T cell subset differentiation in lepromatous leprosy.

Antibodies↗
PubMed1995

Plasminogen kringle 4 binds the heptapeptide fragment 44-50 of the plasminogen N-terminal peptide.

The interaction between the plasminogen kringle 4 module and a synthetic peptide corresponding to the tryptic heptapeptide fragment Ala-Phe-Gln-Tyr-His-Ser-Lys (AFQYHSK), segment 44-50 of the plasminogen N-terminal peptide (Wiman and Wallén, Eur J Biochem 1975; 50:489-494), has been investigated by 1H-NMR spectroscopy. AFQYHSK, as well as the shorter fragments thereof, FQYHSK, QYHSK and YHSK, all bound to kringle 4 with equilibrium association constant (Ka) values ranging between 2.5 and 8.5 mM-1. The NMR evidence also indicates that binding is mediated by the canonical kringle lysine binding site and involves the C-terminal Lys residue of the ligand peptide. The results (a) support a potential interaction between plasminogen Lys-binding kringles and the N-terminal activation peptide, and (b) unambiguously demonstrate the capability of such kringles to bind polypeptides ending with C-terminal lysine.

Amino Acid Sequence↗
PubMed1995

Relationship of serum alanine aminotransferase (ALT) to body mass index (BMI) in blood donors: the need to correct ALT for BMI in blood donor screening.

A study was carried out on 1,028 voluntary blood donors to see how body mass index (BMI) correlated with the serum alanine amino transferase (ALT) activity. The mean ALT (U/l) values were 19.35, 27.63, 40.79 and 54.41 in the four BMI categories of < or = 20, 20.1-25, 25.1-30 and > 30, respectively. This study showed that the mean serum ALT level of obese subjects (BMI > 30 kg/m2), compared with the two categories of normal subjects (i.e. BMI < or = 20 and BMI = 20.1-25 kg/m2), was increased by 2.8 and 1.96 times, respectively. Compared with the BMI group < or = 20, there was a gradual per cent increase in the mean serum ALT in the three different BMI groups: 20.1-25 (+133%), 25.1-30 (+196%) and > 30 kg/m2 (+280%). This indicates the need to correct ALT values for BMI for blood donor screening, instead of using actual ALT values.

Adult↗
PubMed1995

Evidence for subarachnoid spread in the development of multiple meningiomas.

Meningiomas are among the most common human brain tumors. Occasionally patients develop multiple meningiomas. While it has been surmised that these are multiple primary meningiomas, it is possible that they represent spread of a single primary tumor. Recently, the neurofibromatosis type 2 (NF2) tumor suppressor gene has been shown to carry mutations in meningiomas. In the present study we have analyzed multiple meningiomas from two patients for point mutations in the NF2 gene by SSCP analysis and direct sequencing. We detected point mutations in the meningiomas from both patients. The first patient from which six tumors were available had a three base pair deletion in the splice donor region of exon 7. All tumors showed the identical mutation. The second patient with two independent meningiomas had a nonsense mutation in exon 8 which was the same in both tumors. Analysis of constitutional DNA revealed a wildtype DNA sequence in both cases. There was no family history of neurofibromatosis type 2 in either patient. These data provide strong evidence for a monoclonal origin of multiple meningiomas. Early subarachnoid spread is the most likely mechanism for the formation of these tumors.

Aged↗
PubMed1995

Neuropathology and molecular genetics of neurofibromatosis 2 and related tumors.

Neurofibromatosis 2 (NF2) is an uncommon, autosomal dominant disorder in which patients are predisposed to neoplastic and dysplastic lesions of Schwann cells (schwannomas and schwannosis), meningeal cells (meningiomas and meningioangiomatosis) and glial cells (gliomas and glial hamartomas). Clinical and genetic criteria that distinguish NF2 from neurofibromatosis 1 have allowed more accurate assignment of specific pathological features to NF2. The NF2 tumor suppressor gene on chromosome 22q12 encodes a widely expressed protein, named merlin, which may link the cytoskeleton and cell membrane. Germline NF2 mutations in NF2 patients and somatic NF2 mutations in sporadic schwannomas and meningiomas have different mutational spectra, but most NF2 alterations result in a truncated, inactivated merlin protein. In NF2 patients, specific mutations do not necessarily correlate with phenotypic severity, although grossly truncating alterations may result in a more severe phenotype. In schwannomas, NF2 mutations are common and may be necessary for tumorigenesis. In meningiomas, NF2 mutations occur more commonly in fibroblastic than meningothelial subtypes, and may cluster in the first half of the gene. In addition, in meningiomas, a second, non-NF2 meningioma locus is probably also involved. Future efforts in NF2 research will be directed toward elucidating the role of merlin in the normal cell and the sequelae of its inactivation in human tumors.

Humans↗