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Biomedical subjects

A Chatterjee

Publications and source records attributed to A Chatterjee.

At least 55 records · Page 3Linked to original sources

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

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

Agrammatic sentence production: the use of a temporal--spatial strategy.

We report the sentence production of a left-handed man with a right-hemisphere infarct. He demonstrated an inability to correctly map grammatical categories (subject, object) onto thematic roles (agent, patient) even for simple active sentences. The patient's performance appears to be the result of selective damage to the functional level (Garrett, 1980) of sentence production. His failure could not be accounted for by theories of agrammatism that implicate memory deficits, phonologic processing impairments, or deficits in processing complex transformations. The patient's performance revealed the consistent application of a temporal-spatial strategy in sentence production, despite adequate lexical-semantic abilities.

Aged

Asyntactic thematic role assignment: the use of a temporal-spatial strategy.

We report syntactic comprehension performance of a left-handed man with a right-hemisphere infarct. He was unable to accurately map grammatical categories (subject, object) onto thematic roles (agent, patient), despite demonstrating intact conceptual knowledge of these thematic roles. He performed poorly on both active and passive reversible sentences. His asyntactic thematic role assignment cannot be accounted for by a short-term memory impairment or any hypothesis that predicts selective vulnerability to passive sentence constructions. Rather than performing randomly, our patient used a temporal or spatial strategy in assigning thematic roles. Because he also had a production-mapping deficit and used the same temporal-spatial strategy in production tasks, we hypothesize that the mapping of thematic roles onto grammatical categories and vice versa may be a specific aspect of sentence processing that is common to sentential production and comprehension. We also raise the possibility that thematic roles have underlying spatial representations prior to being elaborated by grammar.

Aged

Refined mapping of caltractin in human Xq28 and in the homologous region of the mouse X chromosome places the gene within the bare patches (Bpa) and striated (Str) critical regions.

Caltractin belongs to a family of calcium-binding proteins and is a structural component of the centrosome. A human caltractin cDNA (CALT) has recently been mapped by fluorescence in situ hybridization (FISH) to Xq28. We report here refined mapping of the human CALT gene and its murine homolog between the loci DXS1104 (DXHXS1104) DXS52 (DXHXS52) by PCR and Southern analysis on YACs and somatic cell hybrids from the region in both species. These mapping studies place the gene within the critical region for the murine X-linked dominant, male lethal mutations bare batches and striated.

Animals

Effect of glutathione on sister-chromatid exchanges in normal and buthionine sulfoximine-treated mice.

Based on their ability to induce sister-chromatid exchanges (SCEs) it is evident that thiol-containing radioprotectors can induce DNA damage. However, there were contradictory findings when reduced glutathione (GSH) was tested using two cell lines. The present study demonstrated that GSH can induce SCEs and also delay in cell proliferation in mouse bone marrow cells in vivo. The presence of catalase significantly reduced GSH-induced SCE frequency down to catalase alone levels. An attempt was made to evaluate the effect of GSH treatment in buthionine sulfoximine (BSO)-treated mice (GSH-depleted mice) and the data indicate that induction of SCEs takes place without inducing a delay in cell proliferation or the generation of hydrogen peroxide. Probably, some unknown route is involved by which GSH-degraded product(s) induce SCEs in BSO-treated mice. Therefore, the induction of SCEs by GSH in normal mice may be largely due to hydrogen peroxide generation; however, the involvement of the binding ability of GSH to chromatin and the probable (unknown) route by which GSH-degraded product(s) may cause smaller fraction of SCEs cannot be ruled out.

Animals

Spatial characteristics of thematic role representation.

Humans use language to describe actions by mapping the thematic roles of agent (doer of actions) and patient (recipient of actions) on the grammatical categories of subject and object. The extent to which thematic roles can be conceptualized independent of language is not known. If nonlinguistic conceptualization of thematic roles is possible, then representation of these roles would evidence nonlinguistic characteristics. Motivated by observations in an aphasic man, we wished to learn if thematic roles are conceptualized spatially. Normally subjects were asked to draw stick figures depicting the thematic roles of agent and patient. They demonstrated a systematic spatial bias in locating agents to the left of where they located patients. This bias, somewhat mitigated by ordering effects of motor output and auditory input, was brought into clearest focus when subjects depicted thematic roles in a context stripped of surface sentential form. These data imply that, in their nascent form, the thematic roles of agent and patient are spatially represented prior to being projected on grammar.

Adult

Progression of diabetic retinopathy and rubeotic glaucoma following cataract surgery.

There has been recent interest in the progression of diabetic retinopathy following extracapsular cataract extraction (ECCE) especially with vitreous loss. It is well known that diabetic retinopathy progresses after intracapsular cataract extraction (ICCE) but was thought to be less common after ECCE. We present 7 patients with symmetrical non-proliferative diabetic retinopathy who underwent ECCE with intraocular lens (IOL) implantation. These patients ranged in age from 56 to 69 years; 2 were insulin-dependent diabetics (IDDM) and 5 non-IDDMs. Rubeosis iridis developed quickly between post-operative outpatient visits despite good diabetic control and a static retinal picture in the fellow eye. Visual loss following the onset of rubeosis was severe, with 3 patients needing cyclocryotherapy and eventually having no perception of light. The rapid onset of rubeosis between post-operative outpatient visits leads us to suggest much shorter periods between reviews than is current practice and the consideration of routine panretinal photocoagulation in the immediate post-operative period in diabetics with worsening retinopathy after ECCE and IOL. Possible causes of the increase in neovascularisation and rubeosis are discussed. The most important message highlighted by these case histories is that the surgery and follow-up of diabetic patients undergoing surgery should be undertaken by an ophthalmologist with an interest in diabetes. Where there is no recognised diabetic retinal specialist in a unit, then early referral to such an ophthalmologist is recommended when complications arise.

Aged

Arsenic in ground water in six districts of West bengal, India: the biggest arsenic calamity in the world. Part 2. Arsenic concentration in drinking water, hair, nails, urine, skin-scale and liver tissue (biopsy) of the affected people.

In six districts of West Bengal arsenic has been found in ground water above the maximum permissible limit recommended by the WHO of 0.05 mg l-1. This water is used by the villagers for drinking, cooking and other household purposes. These six districts have an area of 34,000 km2 and hold a population of 30 million. Over the last five years we have surveyed only a few small areas of these six affected districts and our survey revealed that, at present, at least 800,000 people from 312 villages in 37 blocks are drinking contaminated water and more than 175,000 people are showing arsenical skin lesions that are the late stages of manifestation of arsenic toxicity. Most of the three stages of arsenic-related clinical manifestations are observed amongst the affected people. The common symptoms are conjunctivitis, melanosis, depigmentation, keratosis and hyperkeratosis; cases of gangrene and malignant neoplasms are also observed. The source of arsenic is geological. We have analysed thousands of arsenic contaminated water samples. Most of the water samples contain a mixture of arsenite and arsenate and in none of them could we detect methylarsonic or dimethylarsenic acid. We have also analysed a large number of urine, hair and nail samples, several skin-scales and some liver tissues (biopsy samples) of the people drinking the arsenic contaminated water and showing arsenical skin lesions. Flow injection hydride generation atomic absorption spectrometry (FI-HGAAS) was used for the analysis of hair, nails, urine and skin-scale after decomposition by various techniques. The liver tissues were analysed by Zeeman corrected-ETAAS using a few milligrams of the biopsy samples.

Adolescent

Cross-over, completion and confabulation in unilateral spatial neglect.

Patients with left-sided neglect generally mis-bisect horizontal lines to the right of mid-position. However, with short lines they frequently cross over and place their marks to the left; a phenomenon not easily explained by current theories of neglect. It is difficult to ascertain whether patients neglect the ipsilateral segment of short lines, perceptually distort these lines, or extend these lines leftward at a representational level. Reading horizontally arrayed letter strings is an alternative task potentially capable of sorting between these hypotheses, providing this task could be demonstrated to be comparable to line bisections. In this study, we exploit the observation that line bisection performance may be described by a power function: psi = K phi beta, in which psi represents the subjective awareness of lines and the objective measurements of these lines. The constant and exponent are empirically derived. We have investigated whether reading task performance also subscribes to power functions. Five patients with left-sided neglect were tested on line bisections and reading tasks with stimuli of varying horizontal lengths. Performance on both tasks could be described by power functions and patients were similarly ordered by severity across both tasks. Since power function analyses established that these tasks were comparable, reading performance on short words provided insight into how patients bisected short lines. Patients reported additional letters to the left end of short words suggesting that cross-over bisections are analogously a consequence of completion or confabulation of short lines beyond their objective left end-point. Although most neglect patients have difficulties forming veridical left-sided representations, this cross-over phenomenon is interpreted as resulting from a lack of inhibition of leftward confabulatory mental representations. Since both bisections and reading tasks are described by a continuous function, it is proposed that similar lack of inhibition must also be present, albeit hidden, when patients confront stimuli with longer lateral extension. Confabulatory phenomena at the left edge of these patients' rightwardly constricted attentional window, may be far more common than hitherto appreciated.

Aged

Inactivation of rsmA leads to overproduction of extracellular pectinases, cellulases, and proteases in Erwinia carotovora subsp. carotovora in the absence of the starvation/cell density-sensing signal, N-(3-oxohexanoyl)-L-homoserine lactone.

The soft-rotting bacterium, Erwinia carotovora subsp. carotovora 71, produces extracellular enzymes such as pectate lyase isozymes (Pels), cellulase (Cel), polygalacturonase (Peh), and protease (Prt). While the extracellular levels of these enzymes are extremely low when the bacterium is grown in salts-yeast extract-glycerol (SYG) medium, the enzymatic activities are highly induced in SYG medium supplemented with celery extract. By transposon (mini-Tn5) mutagenesis, we isolated a RsmA- mutant, AC5070, which overproduces extracellular enzymes; the basal levels of Pel, Peh, and Cel in AC5070 are higher than the induced levels in the RsmA+ parent, AC5047. While Peh production is mostly constitutive in AC5070, Pel, Cel, and Prt production is still inducible with celery extract. The high basal levels of pel-1, pel-3, and peh-1 mRNAs in AC5070 demonstrate that overproduction of the pectolytic enzymes is due to the stimulation of transcription. Using chromosomal DNA flanking mini-Tn5 as a probe, we cloned the wild-type rsmA+ allele, which suppresses Pel, Peh, Cel, and Prt production in both RsmA+ and RsmA- strains. The RsmA- mutant, like its parent, produces N-(3-oxohexanoyl)-L-homoserine lactone (HSL), a starvation/cell density-sensing signal required for extracellular enzyme production. To examine the role of HSL, we constructed HSL-deficient strains by replacing hslI, a locus required for HSL production, with hslI::Tn3HoHo1-Spc. While the basal levels of Pel, Peh, Cel, and Prt are comparable in the RsmA- mutant and its HSL- derivative, these enzymes are barely detectable in the Hsl- derivative of the RsmA+ parent strain.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Butyrolactone

Identification of a global repressor gene, rsmA, of Erwinia carotovora subsp. carotovora that controls extracellular enzymes, N-(3-oxohexanoyl)-L-homoserine lactone, and pathogenicity in soft-rotting Erwinia spp.

The production of extracellular enzymes such as pectate lyase (Pel), polygalacturonase (Peh), cellulase (Cel), and protease (Prt) is activated by the cell density (quorum)-sensing signal, N-(3-oxohexanoyl)-L-homoserine lactone (HSL); plant signals; and aep genes during postexponential growth of Erwinia carotovora subsp. carotovora 71. Studies with mutants of E. carotovora subsp. carotovora 71 derepressed in exoenzyme production led to the identification of a negative regulator gene, rsmA (rsm, repressor of secondary metabolites). Nucleotide sequencing, transcript assays, and protein analysis established that a 183-bp open reading frame encodes the 6.8-kDa RsmA. rsmA has extensive homology with the csrA gene of Escherichia coli, which specifies a negative regulator of carbon storage. Moreover, the suppression of glycogen synthesis in E. coli by rsmA indicates that the Erwinia gene is functionally similar to csrA. Southern hybridizations revealed the presence of rsmA homologs in soft-rotting and non-soft-rotting Erwinia spp. and in other enterobacteria such as Enterobacter aerogenes, E. coli, Salmonella typhimurium, Shigella flexneri, Serratia marcescens, and Yersinia pseudotuberculosis. rsmA suppresses production of Pel, Peh, Cel, and Prt, plant pathogenicity, and synthesis of HSL in E. carotovora subsp. atroseptica, E. carotovora subsp. betavasculorum, E. carotovora subsp. carotovora, and E. chrysanthemi. In the E. carotovora subsp. carotovora 71, rsmA reduces the levels of transcripts of hslI, a luxI homolog required for HSL biosynthesis. This specific effect and the previous finding that HSL is required for extracellular enzyme production and pathogenicity in soft-rotting Erwinia spp. support the hypothesis that rsmA controls these traits by modulating the levels of the cell density (quorum)-sensing signal.

4-Butyrolactone