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Biomedical subjects

R Gandhi

Publications and source records attributed to R Gandhi.

At least 19 recordsLinked to original sources
PubMed2006

Anti-idiotype-mediated epitope spreading and diminished phagocytosis by a human monoclonal antibody recognizing late-stage apoptotic cells.

Apoptotic cells are considered an important auto-antigenic source in diseases such as systemic lupus erythematosus (SLE). A human monoclonal antibody demonstrating exquisite specificity towards late-stage apoptotic cells was generated from an SLE patient. Polyreactive recognition of ribonucleoproteins Ro52 and Ro60 was observed. The antibody significantly diminished the phagocytosis of apoptotic cells and a concomitant decrease in transforming growth factor-beta (TGF-beta) secretion was observed. Light and heavy chain sequencing revealed the antibody to be in essentially germline configuration. Elicited anti-idiotypic antibodies bound distinct self-antigens and showed augmented reactivity towards apoptotic cells as well. Thus, near-germline encoded antibodies recognizing antigens externalized during the process of apoptosis can mediate a variety of potentially pathogenic effects; decreases in the phagocytic uptake of dying cells would constitute a disease-perpetuating event and stimulation of the idiotypic network could lead to intermolecular epitope spreading, increasing the range of molecular targets..

Antibodies, Monoclonal↗
PubMed2001

Defining the learning curve for the Focused Abdominal Sonogram for Trauma (FAST) examination: implications for credentialing.

Focused Abdominal Sonogram for Trauma (FAST) examination is being used increasingly for the torso evaluation of injured patients. In a controlled setting using peritoneal dialysis patients as models for injured patients with free fluid we hypothesized that more experienced providers would perform FAST with greater accuracy. Twelve fellow or attending level trauma surgeons, two radiologists, and one ultrasound technician were studied for their ability to detect intraperitoneal fluid (0-1600 cm3) in nine peritoneal dialysis patients with two different volumes of dialysate/patient. FAST experience with injured patients was defined as minimal (<30 patients examinations), moderate (30-100), or extensive (>100). All surgeons had participated in a didactic/practical course before the study. Test results were reported as "+" or "-" by the participant; "+" results were further quantified by volume. The sensitivity of those in the minimal-, moderate-, and extensive-experience to detect <1 L was 45, 87, and 100 per cent, respectively; the accuracy in detecting dialysate volume within 250 cm3 was 38, 63, and 90 per cent, respectively. In this controlled setting the accuracy of FAST particularly in diagnosing smaller volumes, as well as the ability to quantify volume, improves with experience. The learning curve for FAST starts to flatten out at 30 to 100 examinations. Training and credentialing policies should consider these findings to optimize patient care.

Abdominal Injuries↗
PubMed2001

Regeneration from leaf protoplasts of Arabidopsis thaliana ecotype estland.

Protoplasts (2 x 10(7)/g fresh wt) were isolated from leaves of A. thaliana ecotype estland, with a viability of more than 90%. Protoplasts cultured in calcium alginate beads or layers showed division while culture in liquid or agarose beads failed to elicit any division. Effect of culture density showed highest frequency of division occurring at 5 x 10(5) while no division was seen when cultured at a density of 5 x 10(4). Culture in MS medium resulted in higher division frequency and better sustenance of microcolonies as compared to B5 medium. Under optimized conditions, macrocolonies were formed at a frequency of 1.8%. Shoot regeneration was seen in 50% of microcalli transferred to shoot induction medium for regeneration. Shoots were rooted and plantlets transferred to pots. The plants produced flowers and were fertile.

Arabidopsis↗
PubMed2001

What's new with IL-2?

Explore the source record for details and available documents.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Genetic and molecular analysis of wings apart-like (wapl), a gene controlling heterochromatin organization in Drosophila melanogaster.

Mutations in the X-linked gene wings apart-like (wapl) result in late larval lethality associated with an unusual chromosome morphology. In brain cell metaphases of wapl mutants, sister chromatids of all chromosomes are aligned parallel to each other instead of assuming the typical morphology observed in wild type. This effect is due to a loosening of the adhesion between sister chromatids in the heterochromatic regions of the chromosomes. Despite this aberrant chromosome morphology, mutant brains exhibit normal mitotic parameters, suggesting that heterochromatin cohesion is not essential for proper centromere function. On the basis of these observations, we examined the role of wapl in meiotic chromosome segregation in females. wapl exhibits a clear dominant effect on achiasmate segregation, giving further support to the hypothesis that proximal heterochromatin is involved in chromosome pairing during female meiosis. We also examined whether wapl modulates position-effect variegation (PEV). Our analyses showed that wapl is a dominant suppressor of both white and Stubble variegation, while it is a weak enhancer of brown variegation. wapl maps to region 2D of the X chromosome between Pgd and pn. We identified the wapl gene within a previously conducted chromosomal walk in this region. The wapl transcriptional unit gives rise to two alternatively spliced transcripts 6.5- and 5-kb long. The protein encoded by the larger of these transcripts appears to be conserved among higher eukaryotes and contains a tract of acidic amino acids reminiscent of many chromatin-associated proteins, including two [HP1 and SU(VAR)3-7] encoded by other genes that act as suppressors of PEV.

Animals↗
PubMed2000

Assessing the need for reintubation: a prospective evaluation of unplanned endotracheal extubation.

OBJECTIVE: Unplanned endotracheal extubation (UEE) is a common complication in medical intensive care units but very little data about UEE in surgical populations are available. Our hypothesis is that the surgical intensive care unit (SICU) population requires reintubation less frequently compared with the medical intensive care unit population. We prospectively gathered data on patients in a SICU in an attempt to identify the incidence of UEE and to study the need for reintubation after UEE. METHODS: During an 18-month period, we prospectively identified SICU patients from a quality improvement database who required ventilatory support. All patients who self-extubated were included in the study. RESULTS: Fifty-eight of 1,178 intubated patients experienced unplanned extubation 61 times during the 18-month period. A total of 22 patients (36%) required reintubation, whereas 39 patients (64%) did not. Thirty-three patients self-extubated while being actively weaned from ventilatory support. Of these, only 5 patients (15%) required reintubation and 28 patients (85%) did not (p < 0.01). CONCLUSION: A total of 85% of patients who self-extubate during the weaning process did not require reintubation in our study. Those who have an FiO2 >50%, a lower PaO2/FiO2 ratio, had UEE occur by accident, or were not being weaned when UEE occurred required reintubation more frequently. These data suggest that some of our SICU patients are intubated longer than necessary, which may translate into more ventilator related complications, longer ICU stays and increased cost.

Adult↗
PubMed2000

Safety and cost of low-molecular-weight heparin as bridging anticoagulant therapy in subacute cerebral ischemia.

BACKGROUND AND PURPOSE: Anticoagulation with intravenous unfractionated heparin (IVUH) while awaiting therapeutic oral anticoagulant levels is a common practice in patients with acute and subacute cerebral ischemia. A promising alternative strategy is to use bridging subcutaneous low-molecular-weight heparin (LMWH), which may have a favorable risk-benefit profile compared with IVUH and may permit earlier discharge with completion of transition to warfarin therapy as an outpatient. METHODS: A LMWH, enoxaparin 1 mg/kg BID, was used as bridging anticoagulation therapy in 24 consecutive patients admitted to a university stroke center in whom the treatment plan included transition from acute to chronic anticoagulation. The LMWH group was contrasted with the preceding 24 patients transitioned to warfarin with IVUH at the same center. RESULTS: Fewer patients in the LMWH bridging therapy group experienced neurological worsening than in the IVUH bridging therapy group (2/24 versus 8/24; P:=0.033). Fewer total adverse events were noted in the LMWH group than in the IVUH cohort (3 versus 20; P:=0. 002). Fifteen of the 24 LMWH patients (62.5%) were discharged while still receiving LMWH and completed transition to warfarin as outpatients, receiving an average of 3.6 days of outpatient transitional therapy. In these 15 patients, use of LMWH was associated with a net savings of $2197 per patient. CONCLUSIONS: In this pilot cohort with subacute cerebral ischemia, bridging LMWH appeared to be safer than bridging IVUH and was associated with reduced hospital stay and reduced total cost of care.

Adult↗
PubMed2000

Oxidant-antioxidant status in acute and chronic renal failure.

Present study was carried out to evaluate oxidant-antioxidant status and effect of hemodialysis in acute and chronic renal failure. Serum MDA levels increased while serum SOD found decreased significantly. This study indicates the existence and increased production of an oxidizing stress resulting from hemodialysis and disturbance in antioxidant enzyme system.

Acute Kidney Injury↗
PubMed1999

Extrusion and spheronization in the development of oral controlled-release dosage forms.

The concept of multiparticulate dosage forms was introduced in the 1950s. With the increasing use of multiparticulate controlled release (CR) oral dosage forms, in recent times there has been a rise in interest in the methods of preparing these dosage forms. A method that has gained increased usage over the past few years is that of extrusion and spheronization. It has been extensively explored as a potential technique and also as a future method of choice for preparation of multiparticulate CR dosage forms. In this review an attempt is made to outline the general process of extrusion and spheronization and to assess its importance in the development of multiparticulate CR oral dosage forms.

Journal Article↗
PubMed1999

IgY antiporcine endothelial cell antibodies effectively block human antiporcine xenoantibody binding.

Avian IgY antibodies are structurally different from mammalian IgGs and do not fix mammalian complement components or bind human Fc receptors. As these antibody-mediated interactions are believed to play significant roles in both hyperacute rejection (HAR) and acute vascular xenograft rejection (AVXR), IgY antibodies to xenoantigen target epitopes may inhibit these rejection processes. In this report, we show that chicken IgY antibodies to alpha-Gal antigen epitopes and to other porcine aortic endothelial cell (PAEC) antigens block human xenoreactive natural antibody binding to both porcine and rat cardiac tissues and porcine kidney tissues. Chicken IgY antibodies blocked complement-mediated lysis of PAECs by human serum, and inhibited antibody-dependent cell-mediated lysis of PAECs by heat-inactivated human serum plus peripheral blood leukocytes. Binding of IgY to porcine endothelial cells did not affect cell morphology nor expression of E-selectin. These results suggest that avian IgYs could be of potential use in inhibiting pig-to-human xenograft rejection.

Animals↗
PubMed1999

Multidrug resistant Salmonella.

A total of 326 salmonella strains was isolated and studied from suspected enteric fever cases in Mumbai (Bombay) during a 2 year period from May 1992 to July 1994. These were identified using standard biochemical and serological tests. Bacteriophage typing, antibiotic sensitivity and conjugation experiments were also carried out. S. typhi was the most common serotype accounting for 75.46% of the strains. Among S. typhi strains 87% were biotype I and 13% were biotype II. 9.5% strains were of S. paratyphi A, 5.52% of S. typhimurium, 4.60% of S. worthington, 4.30% of S. havana and 0.62% of S. enteritidis. The commonest bacteriophage type of S. typhi was E1, and of S. paratyphi A type 1, whereas 88.88% strains of S. typhimurium were untypable. Most of the strains were multidrug resistant including commonly used antibiotics such as chloramphemicol, ampicillin, and cotrimaxazole. Quinolone derivatives such as Ciprofloxacin were found to be the most effective drugs. In the conjugation experiments there was direct transfer of resistance pattern and enbloc transfer of resistance was observed in most strains. Salmonella typhi is still the most commonly encountered species. There is an alarming increase in multidrug resistance.

Anti-Bacterial Agents↗
PubMed1998

Molecular and functional characterization of a calcium-sensitive chloride channel from mouse lung.

A protein (mCLCA1) has been cloned from a mouse lung cDNA library that bears strong sequence homology with the recently described bovine tracheal, Ca2+-sensitive chloride channel protein (bCLCA1), bovine lung endothelial cell adhesion molecule-1 (Lu-ECAM-1), and the human intestinal Ca2+-sensitive chloride channel protein (hCLCA1). In vitro, its 3.1-kilobase message translates into a 100-kDa protein that can be glycosylated to an approximately 125-kDa product. SDS-polyacrylamide gel electrophoresis from lysates of mCLCA1 cDNA-transfected transformed human embryonic kidney cells (HEK293) reveals proteins of 130, 125, and 90 kDa as well as a protein triplet in the 32-38 kDa size range. Western analyses with antisera raised against Lu-ECAM-1 peptides show that the N-terminal region of the predicted open reading frame is present only in the larger size proteins (i.e. 130, 125, and 90 kDa), whereas the C-terminal region of the open reading frame is observed in the 32-38 kDa size proteins, suggesting a posttranslational, proteolytic processing of a precursor protein (125/130 kDa) into 90 kDa and 32-38 kDa components similar to that reported for Lu-ECAM-1. Hydrophobicity analyses predict four transmembrane domains for the 90-kDa protein. The mCLCA1 mRNA is readily detected by Northern analysis and by in situ hybridization in the respiratory epithelia of trachea and bronchi. Transient expression of mCLCA1 in HEK293 cells was associated with an increase in whole cell Cl- current that could be activated by Ca2+ and ionomycin and inhibited by 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid, dithiothreitol, and niflumic acid. The discovery of mCLCA1 opens the door for further investigating the possible contribution of a Ca2+-sensitive chloride conductance to the pathogenesis of cystic fibrosis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

The murine calcium-sensitive chloride channel (mCaCC) is widely expressed in secretory epithelia and in other select tissues.

The tissue and cellular expression pattern of a recently cloned murine calcium-sensitive chloride channel (mCaCC) was determined. In situ hybridization was performed on formalin-fixed, paraffin-embedded murine tissues using digoxigenin-labeled, single-stranded RNA probes. The data were substantiated with northern blot and reverse transcriptase-polymerase chain reaction analyses. All three assays consistently indicated strong expression in tissues with secretory or ion regulatory functions, such as mammary gland, respiratory and intestinal epithelia, gall bladder, pancreas, kidney, uterus, and epididymis. Additional mCaCC expression was observed in germinal centers of lymphatic tissues, in spermatids, and in keratinocytes of the skin, esophagus, and cornea. The results are in accordance with previous electrophysiological reports on calcium-activated chloride conductances in various murine exocrine secretory epithelia and suggest a role of mCaCC in transepithelial ion transport. However, expression in other than secretory tissues indicates a more complex function.

Animals↗