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Biomedical subjects

R Verma

Publications and source records attributed to R Verma.

At least 19 recordsLinked to original sources
PubMed2003

Rheological microscopy: local mechanical properties from microrheology.

We demonstrate how tracer microrheology methods can be extended to study submicron scale variations in the viscoelastic response of soft materials; in particular, a semidilute solution of lambda-DNA. The polymer concentration is depleted near the surfaces of the tracer particles, within a distance comparable to the polymer correlation length. The rheology of this microscopic layer alters the tracers' motion and can be precisely quantified using one- and two-point microrheology. Interestingly, we found this mechanically distinct layer to be twice as thick as the layer of depleted concentration, likely due to solvent drainage through the locally perturbed polymer structure.

Bacteriophage lambda↗
PubMed2003

Does reporting of plain chest radiographs affect the immediate management of patients admitted to a medical assessment unit?

AIM: The purpose of our study was to investigate whether reporting of plain chest radiographs affects immediate management of patients admitted to a medical assessment unit. MATERIALS AND METHODS: During a 3 month period we prospectively evaluated 200 patients who had a plain chest radiograph on admission. After the post on-call ward round, an independent medical specialist registrar reviewed the notes, retrieving relevant clinical details. The plain chest films were reported independently by a trainee radiologist and consultant, reaching a consensus report. RESULTS: There was 93% agreement between trainee and consultant radiologists (95% CI=89-96%). Seventy percent had documented reports by the on-call medical team. There was disagreement between radiology and medical reports in 49% of reported films (95% CI=40-57%). The radiologist's report led to a direct change in the immediate management of 22 patients (11%). CONCLUSION: Only 70% of films had documented reports in the clinical notes despite this being a legal requirement. Radiology reporting does cause a direct change in patient management. Chest radiographs of patients admitted to a medical admissions unit should be reported by a radiologist with the minimum of delay.

Acute Disease↗
PubMed2003

Cauda-conus syndrome resulting from neurocysticercosis.

A 60-year-old male, presented with insidious onset, gradually progressive, burning paresthesia over the saddle area, sphincteric disturbance, impotence and paraparesis. Investigations revealed a ring-enhancing lesion in the conus medullaris suggestive of neurocysticercosis. This was supported by quantitative enzyme-linked immunosorbant assay from purified cell fraction of taenia solium cysticerci. On treatment with steroids he showed marked improvement.

Humans↗
PubMed2002

Magnesium sulfate and neonatal outcomes of preterm neonates.

OBJECTIVE: To determine whether in utero exposure to magnesium sulfate was associated with increased neonatal morbidity and mortality among premature neonates, and secondarily to determine the relationship, if any, between duration of magnesium sulfate exposure and neonatal morbidity and mortality. METHODS: We studied 401 neonates at our institution who were born between 23 and 34 weeks' gestation following preterm labor or preterm premature rupture of membranes. The population was stratified by exposure to magnesium sulfate and compared by various neonatal outcome variables. Similarly, the magnesium-exposed population was stratified by duration of exposure and compared for various neonatal outcome variables. Student's t test, chi2 test, Fisher's exact test and logistic regression were used for analysis. RESULTS: A total of 190 neonates were exposed to magnesium sulfate, while 211 neonates were not. The magnesium-exposed neonates were delivered at a significantly lower gestational age compared to the unexposed neonates (28.2 +/- 3.0 vs. 29.3 +/- 3.1 weeks, p = 0.001). Univariate analysis revealed no differences between groups with regard to rates of respiratory distress syndrome, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, histological and clinical chorioamnionitis, neonatal sepsis or neonatal death. However, magnesium-exposed neonates were more likely to have received antibiotics (71.6% vs. 45.0%, p = 0.0001) and antenatal steroids (95.8% vs. 61.6%, p = 0.0001), factors known to affect perinatal morbidity and mortality. Controlling for antenatal confounding factors, magnesium sulfate use was not independently associated with neonatal mortality (odds ratio (OR) = 0.66; 95% confidence interval (CI) = 0.28, 1.54; p = 0.34). Seventy-nine neonates were exposed to magnesium sulfate therapy for more than 24 h, while 111 neonates were exposed for 24 h or less. There were no significant differences between groups with respect to neonatal outcomes, with the exception of an increased rate of clinical chorioamnionitis in the group exposed to magnesium for more than 24 h (22% vs. 8.2%, p = 0.005). After adjusting for gestational age at delivery, magnesium sulfate exposure for over 24 h was independently associated with a 2.8-fold increased rate of clinical chorioamnionitis (OR = 2.8, 95% CI = 1.14, 6.90; p = 0.02). CONCLUSION: Prenatal exposure to magnesium sulfate was not associated with increased neonatal morbidity or mortality. However, prolonged exposure to magnesium sulfate may be associated with an increased risk of clinical chorioamnionitis.

Adult↗
PubMed2002

Effect of weed extracts on seedling growth of some varieties of wheat.

Allelopathic effect ofAvena fatua L., Cyperus rotundus L., Polygonum hydropiper L., and Solanum nigrum L. were examined on seedling growth of certain commonly used varieties of wheat (Triticum aestivum L.) in the Tarai region of U.P. state. The weed extracts inhibited the length of plumule in all the varieties (100%) with Solanum and it was in 12 (92%), 10 (77%) and 06 (46%) varieties with Polygonum, Avena and Cyperus, respectively. In radicle length, it was in 92% with both Polygonum and Solanum; and 85% and 69% of the varieties with Avena and Cyperus, respectively. However, all the four weed extracts reduced the dry weight of plumule, radicle and total seedling in all the varieties (100%) of wheat except in HD--2329 with Cyperus, in which it was positive. The percent reduction (percentage of control) was more than 50% in 92%, 77%, 54% and 39% of the varieties, respectively with Solanum, Polygonum, Avena and Cyperus. Among the weed extracts, the inhibitory effect on seedling growth in different varieties followed the order: Solanum > Polygonum > Avena and > Cyperus. On the basis of the present results, UP--2003 and WH--542 followed by PBW--226, Sangam and HD--248 were more susceptible to all the four weed extracts compared to the rest of the varieties of wheat.

Avena↗
PubMed2001

Arthus reaction to recombinant hepatitis B virus vaccine.

A severe, local, inflammatory, late-phase reaction accompanied by skin necrosis occurred after an infant was given an intramuscular injection of recombinant hepatitis B virus vaccine. The clinical course and appearance of the rash were typical of an Arthus reaction. Although not identical to this case, prior reported cases of complement-mediated reactions occurring after hepatitis B virus infection or vaccination provide theoretical support for this diagnosis.

Arthus Reaction↗
PubMed2001

Measurement of long-range steric repulsions between microspheres due to an adsorbed polymer.

We have measured the interparticle potential between pairs of micron-sized silica spheres induced by adsorbed polyethylene oxide polymer using a line-scanned optical tweezer. We found this long-range steric repulsion to be exponential over the range of energies (0.1k(B)T-5k(B)T) and polymer molecular weights (452,000-1,580,000) studied, and that the potential scaled with the polymer's radius of gyration R(G). The potential's exponential decay length was about 0.6R(G) and its range was about 4R(G), although both parameters varied significantly from one pair of spheres to another. The potential's exponential prefactor was greater than mean-field predictions.

Adsorption↗
PubMed2001

Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol.

Patient-tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 10(5) cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m(2) per day for 5 days every 4 weeks for 6 cycles, followed by consolidative high-dose cyclophosphamide (1.5, 2.25, or 3g/m(2)). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were cPCR positive. In contrast, flow cytometry for CD5-CD19 dual staining and kappa--lambda clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were cPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry. (Blood. 2001;97:1929-1936)

Antigens, CD↗
PubMed2001

A multidimensional electrospray MS-based approach to phosphopeptide mapping.

A new, multidimensional electrospray MS-based strategy for phosphopeptide mapping is described which eliminates the need to radiolabel protein with 32P or 33P. The approach utilizes two orthogonal MS scanning techniques, both of which are based on the production of phosphopeptide-specific marker ions at m/z 63 and/or 79 in the negative ion mode. These scan methods are combined with liquid chromatography-electrospray mass spectrometry and nanoelectrospray MS/MS to selectively detect and identify phosphopeptides in complex proteolytic digests. Low-abundance, low-stoichiometry phosphorylation sites can be selectively determined in the presence of an excess of nonphosphorylated peptides, even in cases where the signal from the phosphopeptide is indistinguishable from background in the conventional MS scan. The strategy, which has been developed and refined in our laboratory over the past few years, is particularly well suited to phosphoproteins that are phosphorylated to varying degrees of stoichiometry on multiple sites. Sensitivity and selectivity of the method are demonstrated here using model peptides and a commercially available phosphoprotein standard. In addition, the strategy is illustrated by the complete in vitro and in vivo phosphopeptide mapping of Sic1p, a regulator of the G1/S transition in budding yeast.

Amino Acid Sequence↗
PubMed2001

Selective degradation of ubiquitinated Sic1 by purified 26S proteasome yields active S phase cyclin-Cdk.

Selective degradation of single subunits of multimeric complexes by the ubiquitin pathway underlies multiple regulatory switches, including those involving cyclins and Cdk inhibitors. The machinery that segregates ubiquitinated proteins from unmodified partners prior to degradation remains undefined. We report that ubiquitinated Sic1 (Ub-Sic1) embedded within inactive S phase cyclin-Cdk (S-Cdk) complexes was rapidly degraded by purified 26S proteasomes, yielding active S-Cdk. Mutant proteasomes that failed to degrade Ub-Sic1 activated S-Cdk only partially in an ATP-dependent manner. Whereas Ub-Sic1 was degraded within approximately 2 min, spontaneous dissociation of Ub-Sic1 from S-Cdk was approximately 200-fold slower. We propose that the 26S proteasome has the intrinsic capability to extract, unfold, and degrade ubiquitinated proteins while releasing bound partners untouched. Activation of S-Cdk reported herein represents a complete reconstitution of the regulatory switch underlying the G1/S transition in budding yeast.

Adenosine Triphosphate↗
PubMed2001

Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors.

Human osteoblasts (HOBs) support the growth of human haematopoietic progenitor cells, and support the survival and limited expansion of long-term culture-initiating cells. Using human CD34+ cells and the murine myelomonocytic cell line NFS-60 as targets, we previously found that one component of HOB-derived haematopoietic activity is cell-associated granulocyte colony-stimulating factor (G-CSF). However, antibody failed to neutralize all the activity, suggesting that more than one factor supports haematopoietic cells. In the present investigations, we asked whether the HOB-derived, non-G-CSF secreted activity was as a result of other known growth factors. We found that, among the cytokines expressed by HOBs, only hepatocyte growth factor (HGF) and G-CSF stimulated NFS-60 cell proliferation. HOB cells and osteosarcoma cells secreted biologically active HGF, although the levels varied considerably. Moreover, addition of neutralizing HGF antibody to CD34+ cell/HOB co-cultures resulted in a significant reduction ( approximately 50%) in the ability of the HOBs to support haematopoietic progenitor cells. These results suggest that a major component of osteoblast-derived haematopoietic activity is HGF. Secretion of HGF, in concert with cell-associated cytokines such as G-CSF, may account for the stem cell-stimulating activities of osteogenic cells and, thereby, the unique stem cell-supporting role of the osteoblasts within the bone marrow microenvironment.

Antibodies, Monoclonal↗
PubMed2001

Signal-averaged P-wave ECG discriminates between persistent and paroxysmal atrial fibrillation.

Atrial fibrillation (Afib) has been associated with abnormal signal-averaged P wave (SAPW) parameters but whether SAPW is associated with the time course of these arrhythmias (persistent vs. paroxysmal, frequent vs. rare episodes) remains unknown. This article assesses the significance of SAPW duration in distinguishing patients with paroxysmal from those with persistent Afib. SAPW electrocardiogram was performed with a "double triggering" software system for acquisition and analysis of data. SAPW total duration (TD), X, Y, and Z leads magnitudes and vector signal magnitudes were measured offline. Optimal cutoff value between control and patient groups was determined by using a receiver operator characteristic curve. Data were analyzed to compare controls with patients groups and between patient groups according to time course of the arrhythmic history. Fifteen age-matched patients without a history of Afib and 55 patients with a history of Afib (33 with paroxysmal and 22 with persistent arrhythmia) were studied off antiarrhythmic drugs. Patients with history of persistent arrhythmia were studied within 2 days after electrical cardioversion to sinus rhythm. SAPW TD was the only parameter consistently associated with Afib. SAPW TD was 98 +/- 6 ms (mean +/- SD) in the control group, 127 +/- 19 ms in the pooled patients group (P =.0001); 122 +/- 20 ms for paroxysmal and 133 +/- 17 ms for the persistent Afib group (P =.04). Analysis of other SAPW parameters were not statistically significant. SAPW duration is a simple method to identify patients with history of Afib. A significantly longer SAPW TD characterizes patients with a history of persistent as opposed to paroxysmal Afib. Prolongation of SAPW TD possibly reflects more advanced electrophysiological changes, creating a more stable substrate that leads to persistence of the arrhythmia.

Algorithms↗
PubMed2001

Life cycle of a data warehousing project in healthcare.

Hill Physicians Medical Group (and its medical management firm, PriMed Management) early on recognized the need for a data warehouse. Management demanded that data from many sources be integrated, cleansed, and formatted. As a first step, an operational data store (ODS) was built and populated with data from the main transactional system; encounter data were added. The ODS has served its purpose well and has whetted management's appetite for more information and faster, more reliable access, all in one location. PriMed hired Annams Systems Consulting (Annams) for this effort. A team was formed, made up of consultants from Annams and members of PriMed's information services (IS) team. The "classical" approach is being taken: enhancing the ODS, which is largely normalized in structure, and integrating data from various sources, along with enforcing business rules. The team is designing and implementing data marts and a "star schema" style of data modeling--a useful tool for management to evaluate results before investing further.

California↗
PubMed2000

Source of oncofetal ED-B-containing fibronectin: implications of production by both tumor and endothelial cells.

ED-B fibronectin (FN) is a FN isoform derived from alternative splicing of the primary transcript of a single gene. Its expression on tumor stroma and neoformed tumor vasculature and its absence, with few exceptions, in normal adult tissues imply a prognostic and diagnostic value for ED-B FN. We investigated the location and source of ED-B FN because this will be of importance both in understanding its role in tumor development and in designing strategies to target this molecule. We have confirmed that ED-B FN is expressed in the majority of breast and colorectal carcinoma tissue samples, with strong immunohistochemical staining around the tumor cells and in the tumor stroma. No staining of tumor neovasculature was seen. ED-B FN is produced by a range of tumor and endothelial (both primary and transformed) cell lines, as detected by reverse transcription-PCR, but is not expressed at the plasma membrane. Strong expression of human ED-B FN is seen in tumor xenografts. These data indicate that neoplastic cells can act as the source of ED-B FN in tumors. The lack of cell surface expression on tumor cell lines has clear implications for the design of therapeutic strategies which target this molecule.

Adult↗
PubMed2000

Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes.

Ubiquitin-dependent proteolysis is catalyzed by the 26S proteasome, a dynamic complex of 32 different proteins whose mode of assembly and mechanism of action are poorly understood, in part due to the difficulties encountered in purifying the intact complex. Here we describe a one-step affinity method for purifying intact 26S proteasomes, 19S regulatory caps, and 20S core particles from budding yeast cells. Affinity-purified 26S proteasomes hydrolyze both model peptides and the ubiquitinated Cdk inhibitor Sic1. Affinity purifications performed in the absence of ATP or presence of the poorly hydrolyzable analog ATP-gamma-S unexpectedly revealed that a large number of proteins, including subunits of the skp1-cullin-F-box protein ligase (SCF) and anaphase-promoting complex (APC) ubiquitin ligases, copurify with the 19S cap. To identify these proteasome-interacting proteins, we used a recently developed method that enables the direct analysis of the composition of large protein complexes (DALPC) by mass spectrometry. Using DALPC, we identified more than 24 putative proteasome-interacting proteins, including Ylr421c (Daq1), which we demonstrate to be a new subunit of the budding yeast 19S cap, and Ygr232w (Nas6), which is homologous to a subunit of the mammalian 19S cap (PA700 complex). Additional PIPs include the heat shock proteins Hsp70 and Hsp82, the deubiquitinating enzyme Ubp6, and proteins involved in transcriptional control, mitosis, tubulin assembly, RNA metabolism, and signal transduction. Our data demonstrate that nucleotide hydrolysis modulates the association of many proteins with the 26S proteasome, and validate DALPC as a powerful tool for rapidly identifying stoichiometric and substoichiometric components of large protein assemblies.

Adenosine Triphosphate↗
PubMed2000

Azathioprine and 6-mercaptopurine for the treatment of perianal Crohn's disease in children.

Numerous adult studies show a 30-65% response rate to azathioprine (AZA) or 6-mercaptopurine (6-MP) for significant perianal Crohn's disease. The aim of this study was to evaluate whether these drugs healed pediatric perianal Crohn's disease. Records of pediatric Crohn's patients were retrospectively reviewed for significant perianal disease treated with AZA or 6-MP for > or =6 months. The patient's perianal disease was reviewed and evaluated for fistulas, drainage, induration, and tenderness. In addition, the patients were given a score using the Irvine Perianal Disease Activity Index (PDAI). Patients were retrospectively scored upon initiation of treatment and after six months of therapy. Possible scores ranged from 0-20. Twenty patients met the study criteria. Five patients were considered treatment failures. One patient required a colostomy after 1.5 months of therapy, one developed pancreatitis, and three were noncompliant with therapy. Of the remaining 15 patients who were treated for > or =6 months, 67% had an improvement in drainage, 73% in tenderness, 60% in induration, and 40% in fistula closure. The mean Irvine PDAI was 7.67 +/- 2.19 initially and 4.40 +/- 1.72 after six months of therapy. The improvement was statistically significant (p < 0.001). AZA and 6-MP are effective treatments for healing significant perianal Crohn's disease in pediatrics.

Adolescent↗