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A Chaudhuri

Publications and source records attributed to A Chaudhuri.

At least 37 records · Page 2Linked to original sources
PubMed2003

A protein interaction map of Drosophila melanogaster.

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

Animals↗
PubMed2003

Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome.

Fatigue is a common symptom of neurological diseases that affect basal ganglia function. We used proton magnetic resonance spectroscopy ((1)H MRS) to study the metabolic functions of the basal ganglia in chronic fatigue syndrome (CFS) to test the hypothesis that fatigue in CFS may have a neurogenic component. (1)H MRS of left basal ganglia was carried out in eight non-psychiatric patients with CFS and their results were compared to age- and sex-matched healthy asymptomatic healthy controls. A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group (p < 0.001). In the absence of regional structural or inflammatory pathology, increased choline resonance in CFS may be an indicator of higher cell membrane turnover due to gliosis or altered intramembrane signalling.

Adult↗
PubMed2003

Single histidine residue in head-group region is sufficient to impart remarkable gene transfection properties to cationic lipids: evidence for histidine-mediated membrane fusion at acidic pH.

Presence of endosome-disrupting multiple histidine functionalities in the molecular architecture of cationic polymers, such as polylysine, has previously been demonstrated to significantly enhance their in vitro gene delivery efficiencies. Towards harnessing improved transfection property through covalent grafting of endosome-disrupting single histidine functionality in the molecular structure of cationic lipids, herein, we report on the design, the synthesis and the transfection efficiency of two novel nonglycerol-based histidylated cationic amphiphiles. We found that L-histidine-(N,N-di-n-hexadecylamine)ethylamide (lipid 1) and L-histidine-(N,N-di-n-hexadecylamine,-N-methyl)ethylamide (lipid 2) in combination with cholesterol gave efficient transfections into various cell lines. The transfection efficiency of Chol/lipid 1 lipoplexes into HepG2 cells was two order of magnitude higher than that of FuGENE(TM)6 and DC-Chol lipoplexes, whereas it was similar into A549, 293T7 and HeLa cells. A better efficiency was obtained with Chol/lipid 2 lipoplexes when using the cytosolic luciferase expression vector (pT7Luc) under the control of the bacterial T7 promoter. Membrane fusion activity measurements using fluorescence resonance energy transfer (FRET) technique showed that the histidine head-groups of Chol/lipid 1 liposomes mediated membrane fusion in the pH range 5-7. In addition, the transgene expression results using the T7Luc expression vector convincingly support the endosome-disrupting role of the presently described mono-histidylated cationic transfection lipids and the release of DNA into the cytosol. We conclude that covalent grafting of a single histidine amino acid residue to suitable twin-chain hydrophobic compounds is able to impart remarkable transfection properties on the resulting mono-histidylated cationic amphiphile, presumably via the endosome-disrupting characteristics of the histidine functionalities.

Cell Line↗
PubMed2003

'Proximal-type' epithelioid sarcoma: is Agent Orange still at large?

BACKGROUND AND AIMS: Proximal-type epithelioid sarcomas of the perineum are extremely rare. The authors provide an overview of this condition in relation to the history of exposure to Agent Orange. PATIENT AND METHODS: A 54-year-old man presented with a rapidly growing perineal subcutaneous mass that was shown to be a proximal-type epithelioid sarcoma. The case is discussed. An Internet Medline search was performed and the current literature reviewed. RESULTS: Only 4 primary perineal sarcomas have been described in the literature. Epithelioid sarcomas are uncommon, aggressive tumours with a propensity for locoregional recurrence. They are recognised by the US Veterans Affairs department as linked to exposure to Agent Orange, an organochlorine defoliant containing the contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, the role of Agent Orange in sarcomagenesis is still controversial. CONCLUSION: Unusual soft tissue swellings in a background of chemical exposure should be investigated thoroughly with a view to early, appropriate treatment.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2002

Single-dose metronidazole versus 5-day multi-drug antibiotic regimen in excision of pilonidal sinuses with primary closure: a prospective randomised controlled double-blinded study.

BACKGROUND AND AIMS: This pilot study examines whether single-dose intravenous metronidazole preoperatively is at least as effective as a broad-spectrum multi-drug regimen in preventing infection-related wound complications following excision of pilonidal sinuses with primary closure. PATIENTS AND METHODS: A double-blinded study with 50 patients randomised to receiving either a single drug (intravenous metronidazole 500 mg) prophylaxis preoperatively or multi-drug cover (intravenous cefuroxime 1.5 g and metronidazole 0.5 g preoperatively, and oral co-amoxiclav 375 mg 8-hourly postoperatively). They will be reviewed 1, 2 and 4 weeks postoperatively. The wound will be graded as: I, healthy; II, redness and swelling of edges; III, abscess related to a suture; IV, spreading wound infection; V, wound breakdown. Other factors considered are the distance from the lowest wound margin to the anal verge, and previous pilonidal sinus surgery. RESULTS: Results awaited. CONCLUSION: Single-dose metronidazole seems an appropriate and low-cost antibiotic to consider for prophylaxis in pilonidal sinus surgery. This study will form the base for a trial to be conducted in larger numbers as a randomised controlled trial in order to have statistical power.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2002

Diagnosis and treatment of viral encephalitis.

Acute encephalitis constitutes a medical emergency. In most cases, the presence of focal neurological signs and focal seizures will distinguish encephalitis from encephalopathy. Acute disseminated encephalomyelitis is a non-infective inflammatory encephalitis that may require to be treated with steroids. Acute infective encephalitis is usually viral. Herpes simplex encephalitis (HSE) is the commonest sporadic acute viral encephalitis in the Western world. Magnetic resonance imaging of brain is the investigation of choice in HSE and the diagnosis may be confirmed by the polymerase chain reaction test for the virus in the cerebrospinal fluid. In this article, we review the diagnosis, investigations, and management of acute encephalitis. With few exceptions (for example, aciclovir for HSE), no specific therapy is available for most forms of viral encephalitis. Mortality and morbidity may be high and long term sequelae are known among survivors. The emergence of unusual forms of zoonotic encephalitis has posed an important public health problem. Vaccination and vector control measures are useful preventive strategies in certain arboviral and zoonotic encephalitis. However, we need better antiviral therapy to meet the challenge of acute viral encephalitis more effectively.

Acute Disease↗
PubMed2002

Molecular mimicry in type 1 diabetes: immune cross-reactivity between islet autoantigen and human cytomegalovirus but not Coxsackie virus.

Type 1 diabetes is caused by a T cell-mediated autoimmune destruction of the pancreatic beta cells. Molecular mimicry between viral pathogens and beta cell protein has been a popular theory to explain loss of tolerance in type 1 diabetes. However, functional data in support of this hypothesis have been lacking, presumably because the homologies were defined on the basis of linear similarities in peptide sequences, which ignores the criteria of HLA versus T cell receptor contact residues in peptide epitopes required for T cell recognition. We applied a HLA-binding dedicated peptide microarray analysis using autoreactive T cell clones specific for the autoantigen GAD65 to determine the algorithm of T cell recognition by this given T cell clone. The subsequent database search identified a 100% fit with cytomegalovirus peptide, which was subsequently shown to be recognized by these clonal T cells. However, T cell clones reactive with linear homologies previously described as putative candidates for T cell cross-reactivity between GAD65 and Coxsackie virus peptide were unable to recognize the homologous counterparts.

Amino Acid Sequence↗
PubMed2001

Novel non-glycerol-based cytofectins with lactic acid-derived head groups.

We report herein the design, synthesis, and transfection biology of a novel series of non-glycerol-based cationic lipids with lactic acid-derived head groups The synthetic procedure adopted herein for preparing 1-hydroxy-prop-2-yl head-group-based monocationic transfection lipids 1-7 is fairly straightforward and potentially applicable in designing other cationic lipids with lactic acid-derived head groups. A striking anchor-length dependency was observed in NIH3T3 cells in the sense that except lipid 4, all the other lipids were essentially transfection-inefficient. Ethidium bromide assay for the lipid:DNA interactions is consistent with the general observation that significant lipid:DNA interactions do not guarantee on improved transfection efficiency cationic lipid mediated gene delivery. Given its remarkable transfection properties and low cellular toxicity, lipid 4 is likely to find future use in the area of liposomal gene delivery.

3T3 Cells↗
PubMed2001

Toxic megacolon due to Salmonella: a case report and review of the literature.

BACKGROUND AND AIMS: Salmonella colitis is an unusual cause of toxic megacolon. We provide an overview of this condition and report a single case. PATIENTS AND METHODS: A 62-year-old man underwent subtotal colectomy with ileostomy formation for toxic megacolon due to Salmonella enteritidis phage type 4 colitis, followed by reversal with an ileorectal anastomosis. RESULTS: Twenty-seven cases have been described in the literature. These were first treated conservatively, with antibiotics and systemic/local steroids, and some proceded to surgery. CONCLUSION: Salmonella is a rare cause of toxic megacolon, but it can behave opportunistically in patients with ulcerative colitis. S. enteritidis phage type 4 is typically transmitted via raw or uncooked eggs in most cases of salmonellosis attributed to this organism. The disease is rapidly progressive, and death may ensue due to septicaemia and/or perforation. Toxic megacolon is treated aggressively, initially medically, with high-dose steroids and attention to fluid balance, ulcerative colitis being the usual working diagnosis. Once Salmonella is cultured, appropriate antibiotics are commenced. Non-surgical decompression may be appropriate in some cases, but early surgical intervention is required for failed response to these measures or rapid deterioration in the patient's condition. Following initial surgery - often subtotal colectomy and ileostomy formation - continuity may be restored. For most patients with ulcerative colitis ileal pouch anal anastomosis is the operation of choice, but ileorectal anastomosis may be safely performed for Salmonella-induced toxic megacolon. Prevention is better than cure, and therefore health education needs to reinforce avoidance of use of raw or uncooked eggs.

Humans↗
PubMed2001

Design, synthesis, and transfection biology of novel cationic glycolipids for use in liposomal gene delivery.

The molecular structure of the cationic lipids used in gene transfection strongly influences their transfection efficiency. High transfection efficiencies of non-glycerol-based simple monocationic transfection lipids with hydroxyethyl headgroups recently reported by us (Banerjee et al. J. Med. Chem. 1999, 42, 4292-4299) are consistent with the earlier observations that the presence of hydroxyl functionalities in the headgroup region of a cationic lipid contributes favorably in liposomal gene delivery. Using simple sugar molecules as the source of multiple hydroxyl functionalities in the headgroup region of the transfection lipids, we have synthesized four novel simple monocationic transfection lipids, namely, 1-deoxy-1-[dihexadecyl(methyl)ammonio]-D-xylitol (1), 1-deoxy-1-[methyl(ditetradecyl)ammonio]-D-arabinitol (2), 1-deoxy-1-[dihexadecyl(methyl)ammonio]-D-arabinitol (3) and 1-deoxy-1-[methyl(dioctadecyl)ammonio]-D-arabinitol (4), containing hydrophobic aliphatic tails and the hydrophilic arabinosyl or xylose sugar groups linked directly to the positively charged nitrogen atom. Syntheses, chemical characterizations, and the transfection biology of these novel transfection lipids 1-4 are described in this paper. Lipid 1, the xylosyl derivative, showed maximum transfection on COS-1 cells. All the lipids showed transfection with cholesterol as colipid and not with dioleoylphosphatidylethanolamine (DOPE). Radioactive quantitation of free and complexed DNA combined with ethidium bromide exclusion measurements suggest that though nearly 70% of the DNA exists as complexed DNA, the DNA may not have condensed as was observed with other cationic lipids. Presence of additional (more than two) hydroxyl functionalities in the headgroup of the cationic lipids appears to have improved the transfection efficiency and made these lipids less cytotoxic compared to two-hydroxyl derivatives.

Animals↗
PubMed2001

Antiviral pathway activation in patients with chronic fatigue syndrome and acute infection.

Gene expression of key enzymes in 2 antiviral pathways (ribonuclease latent [RNase L] and RNA-regulated protein kinase [PKR]) was compared in 22 patients with chronic fatigue syndrome (CFS), 10 patients with acute gastroenteritis, and 21 healthy volunteers. Pathway activation in the group of patients with infections differed significantly from that of the other 2 groups, in whom there was no evidence of upregulation. Therefore, assay of activation is unlikely to provide the basis for a diagnostic test for CFS.

Acute Disease↗
PubMed2001

Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase.

Antigens of pathogenic microbes that mimic autoantigens are thought to be responsible for the activation of autoreactive T cells. Viral infections have been associated with the development of the neuroendocrine autoimmune diseases type 1 diabetes and stiff-man syndrome, but the mechanism is unknown. These diseases share glutamic acid decarboxylase (GAD65) as a major autoantigen. We screened synthetic peptide libraries dedicated to bind to HLA-DR3, which predisposes to both diseases, using clonal CD4(+) T cells reactive to GAD65 isolated from a prediabetic stiff-man syndrome patient. Here we show that these GAD65-specific T cells crossreact with a peptide of the human cytomegalovirus (hCMV) major DNA-binding protein. This peptide was identified after database searching with a recognition pattern that had been deduced from the library studies. Furthermore, we showed that hCMV-derived epitope can be naturally processed by dendritic cells and recognized by GAD65 reactive T cells. Thus, hCMV may be involved in the loss of T cell tolerance to autoantigen GAD65 by a mechanism of molecular mimicry leading to autoimmunity.

Antigens, Viral↗