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A Chaudhuri

Publications and source records attributed to A Chaudhuri.

At least 73 records · Page 4Linked to original sources

The Duffy protein: a malarial and chemokine receptor.

A major advance towards understanding the Duffy blood group system has been achieved with the cloning of FY, a single-copy gene located in the 1q22->q23 region of chromosome 1. The product of FY Is an acidic glycoprotein (gp-Fy), which spans the plasma membrane seven times and has an exocellular N-terminal domain and an endocellular C-terminal domain. The system consists of four alleles, five phenotypes, and five antigens. FYA, FYB, FYB(ES), and FYB(WK) are the alleles; Fy(a+b-), Fy(a-b+), Fy(a+b+), Fy(a-b+(wK)), and Fy(a-b-), are the phenotypes, and Fy(a), Fy(b), Fy3, Fy5, and Fy6 are the antigens. Fy(a-b-), or Duffy-negative individuals, lack the Duffy protein on erythrocytes and are predominantly African and American blacks. They have the FYB(Es) allele with a mutation in the promoter region, which abolishes the expression of the protein in erythrocytes only. In the few cases of non-black Fy(a-b-) individuals, a nonsense mutation prevents the synthesis of gp-Fy. In Fy(a-b+(wk)) erythrocytes, the Fy(b) antigen is weakly expressed due to a reduced amount of the protein. The Fy5 antigen includes the Rh protein, and the Fy6 antigen is defined by a murine monoclonal antibody. Gp-Fy is produced in several cell types, including endothellal cells of capillary and postcapillary venules, epithelial cells of kidney collecting ducts, and lung alveoli, as well as PurkinJe cells of the cerebellum. The Duffy protein plays a role in inflammation and in malaria Infection. The protein is a member of the superfamily of chemokine receptors and is the receptor to which certain malarial parasites bind to invade red blood cells. The parasite-specific binding site, the binding site of chemokines, and the major antigenic domains are located in overlapping regions at the exocellular N terminus of the Duffy protein.

Antigens, Protozoan↗

The effects of spatial frequency overlap on face recognition.

The effects of spatial frequency overlap between pairs of low-pass versus high-pass images on face recognition and matching were examined in 6 experiments. Overlap was defined as the range of spatial frequencies shared by a pair of filtered images. This factor was manipulated by processing image pairs with high-pass/low-pass filter pairs whose 50% cutoff points varied in their separation from one another. The effects of the center frequency of filter pairs were also investigated. In general, performance improved with greater overlap and higher center frequency. In control conditions, the image pairs were processed with identical filters and thus had complete overlap. Even severely filtered low-pass or high-pass images in these conditions produced superior performance. These results suggest that face recognition is more strongly affected by spatial frequency overlap than by the frequency content of the images.

Adolescent↗

New genotypes in Fy(a-b-) individuals: nonsense mutations (Trp to stop) in the coding sequence of either FY A or FY B.

Duffy blood group antigens are carried on a glycoprotein that is predicted to pass through the erythrocyte membrane seven times and is a promiscuous chemokine receptor. The Fy(a- b-) phenotype is present in two-thirds of African-American Blacks but is rare in Caucasians. In Blacks, the phenotype is due to a non-functional GATA-1 motif in the FY B, which silences the gene in erythrocytes but not in other tissues, and these patients do not generally make anti-Fyb or anti-Fy3. We describe here the molecular analysis of FY in three unrelated Caucasians who were studied because they had strong anti-Fy3 in their serum. Each was found to have a point mutation that was predicted to change a tryptophan to a premature stop codon in the coding sequence. In one patient (patient 1), the nonsense mutation was at nucleotide 287 of the major transcript in FY A; in another (patient 2), it was at nucleotide 407 in the major transcript of FY B; and in a third (patient 3), it was at nucleotide 408 of the major transcript of FY A.

Aged↗

Molecular mechanisms that lead to reduced expression of duffy antigens.

BACKGROUND: In the Duffy blood group system, the null phenotype Fy(a-b-) has been classically associated with a mutated GATA box, while the Fy(x) phenotype weak Fy(b) is associated with Arg89Cys and Ala100Thr mutations. This report assesses the prevalence of the Duffy GATA box and the Fy(x)-associated mutations in white and African American (black) donors and investigates the molecular mechanism underlying the Fy(x) phenotype. STUDY DESIGN AND METHODS: PCR RFLP Duffy genotyping was performed on blood samples from blacks and whites. Duffy antigen expression (Fy(a), Fy(b), Fy6, Fy3) on RBCs was measured by flow cytometry. By site-directed mutagenesis, the relevance of each Fy(x)-associated mutation to Duffy (mRNA, antigen, and protein) expression was analyzed in transfectants by Northern blotting, flow cytometry, and immunoblotting. RESULTS: The mutated GATA box occurred at a high allele frequency (0.8) in blacks and was rare among whites. Conversely, the Fy(x)-associated mutations were absent in blacks, but present in 3.5 percent of whites. By flow cytometry, Duffy antigens (Fy(a) or Fy(b), Fy6 and Fy3) showed a dosage effect in RBC samples that were transcriptionally silenced by the GATA box mutation in one allele. By contrast, the reduced (10%) Duffy protein in Fy(x) RBCs was shown by heterologous expression analysis not to be due to reduced RNA levels, but to protein instability caused by Arg89Cys. CONCLUSIONS: Reduced Duffy expression can result from mutations affecting transcription (mutated GATA box in one allele) or instability of the translated protein (Arg89Cys). The frequencies of these mutations vary among populations.

Black People↗

The symptoms of chronic fatigue syndrome are related to abnormal ion channel function.

The pathogenesis of chronic fatigue syndrome (CFS) is unknown but one of the most characteristic features of the illness is fluctuation in symptoms which can be induced by physical and/or mental stress. Other conditions in which fluctuating fatigue occurs are caused by abnormal ion channels in the cell membrane. These include genetically determined channelopathies, e.g. hypokalemic periodic paralysis, episodic ataxia type 2 and acquired conditions such as neuromyotonia, myasthenic syndromes, multiple sclerosis and inflammatory demyelinating polyneuropathies. Our hypothesis is that abnormal ion channel function underlies the symptoms of CFS and this is supported also by the finding of abnormal cardiac-thallium201 SPECT scans in CFS, similar to that found in syndrome X, another disorder of ion channels. CFS and syndrome X can have identical clinical symptoms. CFS may begin after exposure to specific toxins which are known to produce abnormal sodium ion channels. Finally, in CFS, increased resting energy expenditure (REE) occurs, a state influenced by transmembrane ion transport. The hypothesis that ion channels are abnormal in CFS may help to explain the fluctuating fatigue and other symptoms.

Energy Metabolism↗

Does face recognition rely on encoding of 3-D surface? Examining the role of shape-from-shading and shape-from-stereo.

It is now well known that processing of shading information in face recognition is susceptible to bottom lighting and contrast reversal, an effect that may be due to a disruption of 3-D shape processing. The question then is whether the disruption can be rectified by other sources of 3-D information, such as shape-from-stereo. We examined this issue by comparing identification performance either with or without stereo information using top-lit and bottom-lit face stimuli in both photographic positive and negative conditions. The results show that none of the shading effects was reduced by the presence of stereo information. This finding supports the notion that shape-from-shading overrides shape-from-stereo in face perception. Although shape-from-stereo did produce some signs of facilitation for face identification, this effect was negligible. Together, our results support the view that 3-D shape processing plays only a minor role in face recognition. Our data are best accounted for by a weighted function of 2-D processing of shading pattern and 3-D processing of shapes, with a much greater weight assigned to 2-D pattern processing.

Adolescent↗

DXA body composition studies are not affected by extracellular water measurements using stable sodium bromide dilution.

Body composition studies using dual energy x-ray absorptiometry (DXA) are being increasingly reported in the literature. When DXA body composition measurements are combined with body water studies, stable bromide is often administered to measure extracellular water. Bromine attenuates x-rays significantly more than soft tissue and so could affect DXA body composition analysis. DXA scans were performed on 26 adults (12 F, 14 M) before and after the intravenous injection of 3 g sodium bromide (NaBr). No significant differences were noted pre- and post-NaBr infusion for whole-body fat mass, fat-free soft tissue mass and bone mineral content. These findings were supported by a simple mathematical analysis of the likely effect of the sodium bromide infusion. This showed that when 3 g NaBr was introduced into the body, the effect on fat mass estimates was expected to be marginally less than the precision of the DXA technique.

Absorptiometry, Photon↗

Deletion of the murine Duffy gene (Dfy) reveals that the Duffy receptor is functionally redundant.

All of the antigenic determinants of the Duffy blood group system are in a glycoprotein (gp-Fy), which is encoded by a single-copy gene (FY) located on chromosome 1. gp-Fy is also produced in several cell types, including endothelial cells of capillary and postcapillary venules, the epithelial cell of kidney collecting ducts, lung alveoli, and the Purkinje cells of the cerebellum. This protein, which spans the cell membrane seven times, is a member of the superfamily of chemokine receptors and a malarial parasite receptor. The mouse Duffy gene (Dfy) homolog of human FY is also a single-copy gene, which maps in a region of conserved synteny with FY and produces a glycoprotein with 60% homology to the human protein. The mouse Duffy-like protein also binds chemokines. To study the biological role of gp-Fy, we generated a mouse strain in which Dfy was deleted. These homozygous Dfy(-/-) mice were indistinguishable in size, development, and health from wild-type and heterozygous littermates. We also examined components of the immune system and found no differences in lymph nodes or peripheral blood leukocyte levels between knockout and wild-type mice. The gross and histological anatomy of the thymus, spleen, lung, and brain showed no significant differences between mutants and wild-type mice. There was no indication of an overall difference between the knockout and wild-type mice in systematic neurological examinations. The only significant difference between Dfy(-/-) and Dfy(+/+) mice that we found was in neutrophil migration in peritoneal inflammations induced by lipopolysaccharide and thioglycolate. In mice homozygous for the deletion, there was less neutrophil recruitment into the peritoneal cavity and neutrophil influx in the intestines and lungs than in wild-type mice. Despite this, the susceptibility to Staphylococcus aureus infection was the same in the absence and in the presence of gp-Fy. Our results indicate that gp-Fy is functionally a redundant protein that may participate in the neutrophil migratory process.

Alleles↗

Brachial vascular reactivity in blacks.

Endothelial function was studied ultrasonographically in a healthy subset of African Americans (blacks) because they have an increased risk of hypertension and vascular disease. Twenty-four healthy black and 28 well-matched white subjects were investigated. Ischemia was induced by inflating a cuff over the forearm to 40 mm Hg higher than systolic pressure for 5 minutes. Brachial artery diameter and blood flow velocity were measured at baseline and at 15, 45, and 60 seconds after deflation by use of an Acuson 128XP10 ultrasonograph with a 7.5 MHz transducer. Mean postischemic dilatation, an index of endothelial function, was 1.76+/-0.56% in blacks and 8.79+/-1.22% in whites (P<0.001). Median postischemic vasodilatation in black men [0% (0% to 2.86%)] was not significantly different to that in black women [0.82% (0% to 3.14%)], whereas white women [11.48% (8.70% to 14.29%)] dilated significantly more than white men [4.20% (2.13% to 5.56%)] (P<0.05). Both groups dilated significantly over baseline diameter to sublingual nitroglycerin administration 18.7+/-2.5% (blacks) and 20.2+/-3.2% (whites; P=NS). Mean hyperemic responses did not differ significantly between the 2 subject groups, nor did they differ between men and women of both ethnic groups. We conclude that endothelium-dependent vasodilatation is significantly impaired in healthy, young blacks compared with whites and that gender differences are not seen in blacks with regard to this phenomenon. An impairment in endothelium-dependent NO generation may be a contributing factor to future hypertension and vascular disease in healthy blacks.

Adult↗

Molecular maps of neural activity and quiescence.

The rapid accumulation of inducible transcription factors (ITFs), such as c-Fos and Zif268, in activated neurons combined with histological methods that offer detection at the cellular level are key features that have led to their wide use in visualizing activated neurons. There are two major drawbacks of ITFs that limit their use in the CNS--cell-type expression specificity and stimulus-transcription coupling uncertainty. Recent technical advances in the field of molecular activity mapping now permit dual-labeling approaches that help resolve some of these ambiguities and identify neurons that are activated by different sensory stimuli. Furthermore, the recent identification of the robl/LC7-like gene, which shows immediate-early repression after stimulation, may have utility in functional mapping where it can be used to delineate quiescent neurons and serve as a complement to molecular activity markers.

Animals↗

Control of MRSA.

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Humans↗

Novel series of non-glycerol-based cationic transfection lipids for use in liposomal gene delivery.

A novel series of nontoxic and non-glycerol-based simple monocationic transfection lipids containing one or two hydroxyethyl groups directly linked to the positively charged nitrogen atom were synthesized. The in vitro transfection efficiencies of these new liposomal gene delivery reagents were better than that of lipofectamine, a widely used transfection agent in cationic lipid-mediated gene transfer. The most efficient transfection formulation was observed to be a 1:1:0.3 mol ratio of DHDEAB (N, N-di-n-hexadecyl-N,N-dihydroxyethylammonium bromide):cholesterol:HDEAB (N-n-hexadecyl-N,N-dihydroxyethylammonium bromide) using a DHDEAB-to-DNA charge ratio (+/-) of 0.3:1. Observation of good transfection at charge ratios lower than 1 suggests that the amphiphile-DNA complex may have net negative charge. Our results reemphasize the important point that in cationic lipid-mediated gene delivery, the overall charge of the lipid-DNA complex need not always be positive. In addition, our transfection results also imply that favorable hydrogen-bonding interactions between the lipid headgroups and the cell surface of biological membranes may have some role for improving the transfection efficiency in cationic lipid-mediated gene delivery.

Animals↗

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

OBJECTIVE: To determine the effect of humanized monoclonal antibody against alpha4 integrin (reactive with alpha4beta1 integrin or very-late antigen-4) on MRI lesion activity in MS. METHODS: A randomized, double-blind, placebo-controlled trial in 72 patients with active relapsing-remitting and secondary progressive MS was performed. Each patient received two IV infusions of anti-alpha4 integrin antibody (natalizumab; Antegren) or placebo 4 weeks apart and was followed up for 24 weeks with serial MRI and clinical assessment. RESULTS: The treated group exhibited significantly fewer new active lesions (mean 1.8 versus 3.6 per patient) and new enhancing lesions (mean 1.6 versus 3.3 per patient) than the placebo group over the first 12 weeks. There was no significant difference in the number of new active or new enhancing lesions in the second 12 weeks of the study. The number of baseline-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not significantly different between the two groups. The number of patients with acute MS exacerbations was not significantly different in the two groups during the first 12 weeks (9 in the treated group versus 10 in placebo) but was higher in the treatment group in the second 12 weeks (14 versus 3; p = 0.005). The study was not, however, designed to look definitively at the effect of treatment on relapse rate. Treatment was well tolerated. CONCLUSIONS: Short-term treatment with monoclonal antibody against alpha4 integrin results in a significant reduction in the number of new active lesions on MRI. Further studies will be required to determine the longer term effect of this treatment on MRI and clinical outcomes.

Adult↗