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Biomedical subjects

A Chatterjee

Publications and source records attributed to A Chatterjee.

At least 145 records · Page 8Linked to original sources

The chromosome localization and the HCF repeats of the human host cell factor gene (HCFC1) are conserved in the mouse homologue.

The gene encoding the human host cell factor (HCFC1) has recently been cloned and mapped to Xq28. HCFC1 codes for a family of related polypeptides that apparently arise from posttranslational processing. Six extremely conserved 19-amino-acid (aa)long motifs, unique to HCFC1 and located in the middle of the protein, could play a role in this processing or could be instrumental to the physiological role of the protein. Aternatively, these repeats could have arisen from recent duplications and may not have any specific function. To resolve this issue, we cloned the homologous region from the mouse HCFC1 gene and demonstrated that the 19-aa motifs are extremely conserved in sequence, number, and genomic organization, while the "linker" region between the third and fourth repeat is not. This suggests an important function for these repeats. In addition, by RT-PCR analysis of human RNA and comparison to the human genomic sequence, an alternative transcript including a 44-aa in-frame insertion, deriving from the 3' end of intron 18, was found. The significance of this alternative transcript is unknown, since it was not detectable in the mouse. The mouse HCFC1 gene maps to a region syntenic to Xq28, and, as in human, is in close proximity to the Renin-binding protein gene, in a 100-kb region also including the Licam and Vasopressin receptor type 2 genes.

Amino Acid Sequence↗

Comparative mapping on the mouse X chromosome defines a myotubular myopathy equivalent region.

The gene for X-linked myotubular myopathy (MTM1) has been localized to a 300-kb critical region in human Xq28 between IDS and GABRA3. As part of an effort to clone this gene, we developed a YAC contig on the mouse X Chromosome (Chr) which includes loci homologous to those within the human MTM1 critical region. The murine contig consists of 18 YACs and spans 2.5-3.0 Mb. We have aligned the human and murine physical maps by isolating conserved mouse genomic fragments, including CpG islands and trapped exons. We believe that the simultaneous isolation of genes from both mouse and human and continued comparative mapping will prove helpful in the eventual identification of MTM1 and other genes in the region.

Animals↗

The isolation of peste des petits ruminants virus from northern India.

The aetiological agent responsible for an epizootic of a rinderpest-like disease afflicting sheep and goats in three states of northern India was confirmed as peste des petits ruminants virus. To differentiate the virus from rinderpest a number of diagnostic tests were used, including immunocapture ELISA, specific oligonucleotide primers in a reverse transcriptase polymerase chain reaction, immunofluorescence with virus specific monoclonal antibodies and virus isolation. The virulence profile of one isolate in cattle sheep and goats was established. Infected animals developed specific antibody responses and excreted specific antigen in their lachrymal secretions.

Animals↗

Relationship between infrared spectra and isomorphous substitution in smectites: a computer simulation study.

Smectites, members of the 2:1 layer silicate family, share the common feature that two tetrahedral sheets sandwich a sheet of octahedrally coordinated metal ion. The diversity of the members of the 2:1 layer silicates occurs because of their capacity for isomorphous substitution of various cations in the octahedral or tetrahedral sheets. Substitution of a divalent metal ion (such as Mg2+) for the trivalent Al3+ or a trivalent metal ion (such as Al3+) for the tetravalent silicon results in a net negative charge, which then undergoes interaction with positive ions (the exchangeable cations) to form an interlayer hydrated phase. Local density functional (LDF) calculations were employed to model isomorphous substitution of Al3+ by Na+, K+, Mg2+, Fe2+, and Fe3+ in the octahedral layer of a dioctahedral smectite clay such as montmorillonite. The energies of the isomorphous substitution were then compared with the experimental observation. The ordering for successful substitution is Al3+ > Fe3+ > Mg2+ > Fe2+ > Na+ < K+. This ordering is consistent with experimental observation. The vibrational frequencies for the isomorphous substituted systems were calculated by LDF calculation and were compared with the experimental IR results. The results match very well with experiment. This understanding will help in successful prediction of the catalytic activity of smectite clays.

Aluminum Silicates↗

A comparative transcription map of the murine bare patches (Bpa) and striated (Str) critical regions and human Xq28.

The X-linked developmental mouse mutations bare patches (Bpa) and striated (Str) may be homologous to human X-linked dominant chondrodysplasia punctata (CDPX2) and incontinentia pigmenti (IP2), respectively, based on their genetic mapping and clinical phenotypes. Bpa and Str have been localized to an overlapping critical region of 600 kb that demonstrates conserved gene order with loci in human Xq28 between DXS1104 and DXS52. As part of efforts to isolate the genes involved in these disorders, we have begun to develop a comparative transcription map spanning this region in both species. Using techniques of cross-species conservation and hybridization, exon trapping, and cDNA selection we have identified four known genes or members of gene families--caltractin, a member of the gamma-aminobutyric acid (GABAA) receptor gene family, a member of the melanoma antigen gene (MAGE) family, and several members of the murine-specific, X-linked lymphocyte regulated gene (Xlr3) family. Trapped exons and, in some cases, longer cDNAs have been isolated for potentially 7-9 additional genes. One cDNA demonstrates highly significant homology with members of the Krüppel family of zinc finger transcription factors. A second novel cDNA demonstrates homology at the 3' end of the predicted amino acid sequence to a LIM domain consensus. Gene order appears conserved among those cDNAs determined to be present in both human and mouse. Three of the murine transcripts appear to be present in multiple copies within the Bpa/Str critical region and could be associated with a predisposition to genomic rearrangements. Reverse transcriptase PCR (RT-PCR) and Northern analysis demonstrate that several of the transcripts are expressed in mid-gestation murine embryos and neonatal skin, making them candidates for the Bpa and Str mutations and their respective homologous human disorders.

Amino Acid Sequence↗

Toward a neurologic model of competency: Cognitive predictors of capacity to consent in Alzheimer's disease using three different legal standards.

OBJECTIVE: To identify cognitive predictors of competency performance and status in Alzheimer's disease (AD) using three differentially stringent legal standards for capacity to consent. DESIGN: Univariate and multivariate analyses of independent neuropsychological test measures with three dependent measures of competency to consent to treatment. SETTING: University medical center. SUBJECTS: 15 normal older controls and 29 patients with probably AD (15 mild and 14 moderate). MAIN OUTCOME MEASURES: Subjects were administered a batter of neuropsychological measures theoretically linked to competency function, as well as two clinical vignettes testing capacity to consent to medical treatment under five legal standards (LSs). The present study focused on three differentially stringent LSs: the capacity simply to "evidence a treatment of choice" (LS1), which is a minimal standard; the capacity to "appreciate the consequences" of a treatment of choice (LS3), a moderately stringent standard; and the capacity to "understand the treatment situation and choices" (LS5), the most stringent standard. Control subject and AD patient neuropsychological test scores were correlated with scores on the three LSs. The resulting univariate correlates were than analyzed using stepwise regression and discriminant function to identify key multivariate predictors of competency performance and status under each LS. RESULTS: No neuropsychological measures predicted control group performance on the LSs. For the AD group, a measure of simple auditory comprehension predicted LS1 performance (r(2)=0.44, p < 0.0001), a word fluency measure predicted LS3 performance (r(2)=0.58, p < 0.0001), and measures of conceptualization and confrontation naming together predicted LS5 performance (r(2)=0.81, p < 0.0001). Under discriminant function analysis, confrontation naming was the best single predictor of LS1 competency status for all subjects, correctly classifying 96% of cases (42/44). Measures of visumotor tracking and confrontation naming were the best single predictors, respectively, of competency status under LS3 (91% [39/43]) and LS5 (98% [43/44]). CONCLUSIONS: Multiple cognitive functions are associated with loss of competency in AD. Deficits in conceptualization, semantic memory, and probably verbal recall are associated with the declining capacity of mild AD patients to understand a treatment situation and choices (LS5); executive dysfunction with the declining capacity of mild to moderate AD patients to identify the consequences of treatment choice (LS3); and receptive aphasia and severe dysnomia with the declining capacity of advanced AD patients to evidence a simple treatment choice (LS1). The results offer insight into the relationship between different legal thresholds of competency and the progressive cognitive changes characteristic of AD, and represent an initial step toward a neurologic model of competency.

Alzheimer Disease↗

Leukoencephalopathy associated with cobalamin deficiency.

Patients with cobalamin deficiency may experience cognitive impairment or neuropsychiatric symptoms. Although abnormalities of central myelin are the presumed cause of these manifestations, there is a paucity of reports of white matter lesions as shown on neuroimaging studies, and the effects of cobalamin replacement on these lesions are not known. We report a man with subacute cognitive impairment associated with cobalamin deficiency and remarkable confluent white matter abnormalities on MRI, confirmed by biopsy. With cobalamin replacement, both his cognitive deficits and imaging abnormalities partially resolved. This case indicates that leukoencephalopathy, in the absence of anemia or myelopathy, should be added to the spectrum of disorders associated with cobalamin deficiency. Early detection and treatment may be associated with a greater potential for recovery.

Aged↗

Clusters of DNA induced by ionizing radiation: formation of short DNA fragments. I. Theoretical modeling.

We have developed a general theoretical model for the interaction of ionizing radiation with chromatin. Chromatin is modeled as a 30-nm-diameter solenoidal fiber comprised of 20 turns of nucleosomes, 6 nucleosomes per turn. Charged-particle tracks are modeled by partitioning the energy deposition between primary track core, resulting from glancing collisions with 100 eV or less per event, and delta rays due to knock-on collisions involving energy transfers >100 eV. A Monte Carlo simulation incorporates damages due to the following molecular mechanisms: (1) ionization of water molecules leading to the formation of OH, H, eaq, etc.; (2) OH attack on sugar molecules leading to strand breaks: (3) OH attack on bases; (4) direct ionization of the sugar molecules leading to strand breaks; (5) direct ionization of the bases. Our calculations predict significant clustering of damage both locally, over regions up to 40 bp and over regions extending to several kilobase pairs. A characteristic feature of the regional damage predicted by our model is the production of short fragments of DNA associated with multiple nearby strand breaks. The shapes of the spectra of DNA fragment lengths depend on the symmetries or approximate symmetries of the chromatin structure. Such fragments have subsequently been detected experimentally and are reported in an accompanying paper (B. Rydberg, Radiat, Res. 145, 200-209, 1996) after exposure to both high- and low-LET radiation. The overall measured yields agree well quantitatively with the theoretical predictions. Our theoretical results predict the existence of a strong peak at about 85 bp, which represents the revolution period about the nucleosome. Other peaks at multiples of about 1,000 bp correspond to the periodicity of the particular solenoid model of chromatin used in these calculations. Theoretical results in combination with experimental data on fragmentation spectra may help determine the consensus or average structure of the chromatin fibers in mammalian DNA.

Chromatin↗

Drug abuse in Nepal: a rapid assessment study.

A rapid assessment of drug abuse in Nepal was conducted at different sites, including eight municipalities in the five development regions of the country. To interview various groups of key informants, such methods as semi-structured interviews, in-depth interviews and focus group discussions were used. A snowball sampling strategy for respondents who were drug abusers and a judgemental sampling strategy for the non-drug-using key informants were applied. About one fifth of the sample was recruited from the treatment centres and the rest from the community. Drug abusers in prison were interviewed, and secondary data from treatment centres and prisons analysed. The study revealed that the sample of drug abusers had a mean age of 23.8 years and was overwhelmingly male. Most respondents lived with their families and were either unemployed or students. About 30 per cent of the sample was married. A large majority of the sample had a family member or a close relative outside the immediate family who smoked or drank alcohol and a friend who smoked, drank or used illicit drugs. Apart from tobacco and alcohol, the major drugs of abuse were cannabis, codeine-containing cough syrup, nitrazepam tablets, buprenor-phine injections and heroin (usually smoked, rarely injected). The commonest sources of drugs were other drug-using friends, cross-border supplies from India or medicine shops. The commonest source of drug money was the family. There has been a clear trend towards the injection of buprenorphine by abusers who smoke heroin or drink codeine cough syrup. The reasons cited for switching to injections were the unavailability and rising cost of non-injectable drugs and the easy availability and relative cheapness of injectables. About a half of the injecting drug users (IDUs) commonly reported sharing injecting equipment inadequately cleaned with water. Over a half of IDUs reported visiting needle-exchange programmes at two of the study sites where such programmes were available. Infection by the human immunodeficiency virus (HIV) appears to be low among IDUs, although systematic surveillance is absent. Two thirds of the sample had experienced sexual intercourse. The last sex partners reported by respondents were commercial sex workers, wives or girl friends. Condom use was low with primary partners and relatively high with sex workers. Treatment facilities, mostly located in the central urban areas of the country, are meagre. An overwhelming majority of drug abusers felt the need to stop abusing drugs. Cost-effective drug treatment and HIV prevention programmes for IDUs are urgently needed in all areas of the country.

Adult↗

A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes.

The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5' and 3' moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organization: the transcriptional organization in "domains" described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization.

Animals↗