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R Jain

Publications and source records attributed to R Jain.

At least 19 recordsLinked to original sources
PubMed1996

Conformational characteristics of peptides containing alpha, beta-dehydroamino acid residues.

The structural preferences of synthetic peptides containing alpha, beta-dehydroamino acid residues, as determined by theoretical studies, x-ray diffraction analyses, and spectroscopic studies, are reviewed. The role of delta ZPhe residues in stabilizing type II beta-turn structures in small peptides and in nucleating helical structure in longer peptides is exemplified by several crystal as well as solution structural studies. From the few studies reported so far it appears that delta ZLeu influences the peptide backbone, much like the delta ZPhe residue, whereas delta Ala prefers the extended conformation, suggesting that the nature of beta substituents might influence the conformation restriction behavior of the dehydroresidues. Conformational studies on synthetic peptides containing delta E, delta ZAbu, and delta Val have also been described.

Amino Acid Sequence↗
PubMed1996

Assessment of the relationship between standard probe and implantable fiber measurements of cortical bone blood flow: a canine study.

Laser Doppler flowmetry (LDF) has been used to assess cortical bone blood flow in various clinical situations, such as osteomyelitis and osteonecrosis. Standard metal-sheathed probes containing optical fibers, applied to cortical bone for perfusion measurements, require direct exposure of the bone surface for each measurement, making nonanesthetized assessments over time impractical. Implantable optical fibers offer a noninvasive method for evaluating cortical bone perfusion without repeated surgical exposure of the bone after initial surgical implantation of the fibers. In vitro studies have shown the reliability of laser Doppler (LD) fibers compared with those of the standard probe. This investigation studied the relationship between measurements of cortical bone perfusion obtained by implanted optical (LD) fibers and standard (LDF) probes in vivo. Midshaft tibial fractures were created in the right hindlimb of 11 adult, large (>25 kg) dogs and stabilized by low contact-dynamic compression plate fixation. Cortical bone blood flow was measured by LDF using standard probes and implantable fibers at five sites along the tibia prefracture, postfracture, immediately postplate application, and at 10 weeks postplating, immediately prior to euthanasia. The implantable fibers were secured onto the cortical bone via the plate and led through a percutaneous exit site. Histological examination of the inguinal and popliteal lymph nodes and soft tissue surrounding the fibers revealed mild inflammation. No significant correlation of blood flow assessed by the implantable fibers and standard probe occurred immediately postfracture (r < 0. 13, p > 0.62). However, a statistically significant correlation was seen postplate application at one of the measurement sites in the distal fracture fragment (r = 0.78, P < 0.003). The fibers remained intact and functional until an average of 3 weeks at which time they either fractured or were removed by the animals. This is the first in vivo study assessing the reliability of implantable fibers for the measurement of cortical bone blood flow. Further modification of the fibers will be necessary to improve their longevity and durability for assessment of cortical bone blood flow.

Animals↗
PubMed1996

Cost evaluation of novel therapeutics in rheumatoid arthritis (CENTRA): a decision analysis model.

This study was performed to evaluate the potential costs of a hypothetical novel biological agent (BIO) as a therapy for rheumatoid arthritis (RA), compared with oral methotrexate (MTX) and intramuscular gold (IMG). A decision analysis model was used to compare the total costs of treating a cohort of 10,000 RA patients with each agent for 6 months. Total costs included direct costs and indirect costs. Baseline estimates were subjected to sensitivity analysis. Total costs per person were: MTX, $5,430; IMG, $6,725; BIO, $9,411. In sensitivity analysis, the primary cost drivers for MTX and IMG were the indirect costs of RA and monitoring costs. In contrast, total costs of the BIO were driven predominantly by medication costs. Sensitivity analysis showed, even when efficacy and safety were optimized, costs for the BIO still substantially exceeded those of MTX and IMG. Medication costs will be an important consideration in the development of novel BIOs for RA.

Antirheumatic Agents↗
PubMed1996

Disseminated herpes simplex virus infection presenting as fever in the newborn--a lethal outcome.

The clinical course of a neonate who presented with fever and tachypnea on day 6 of life is described. He developed disseminated intravascular coagulopathy, hepatic failure, coma and expired at 14 days of age. The post mortem viral cultures from liver, adrenal and lungs were positive for HSV type 2. The fatal outcome of this case of fever, due to HSV infection, emphasizes the need for early treatment of suspicious cases of HSV infection. HSV should be considered in the differential diagnosis of the newborn with persistent fever unresponsive to antibiotics.

Fatal Outcome↗
PubMed1996

Mesenteric plexiform neurofibroma: computed tomography appearance.

Gastrointestinal involvement in von Recklinghausen's disease is usually in the form of neurofibromas and leiomyomas. Very rarely, plexiform neurofibromas may be seen involving the bowel wall and myenteric plexus with secondary minor involvement of the mesentery. This report describes the computed tomography morphology of a plexiform neurofibroma extensively involving the mesentery with minor involvement of the bowel wall.

Child↗
PubMed1995

Capillary electrophoretic separation and laser-induced fluorescence detection of the major DNA adducts of cisplatin and carboplatin.

Micellar electrokinetic capillary chromatographic separation of a dansylated mixture of normal nucleotides and platinated cross-link adducts of d(pGpG) and d(pApG) was optimized with baseline resolution. The introduction of a laser-induced fluorescence (LIF) detector overcame the lack of sensitivity characteristic of capillary electrophoresis (CE) due to the small injection volume and the short optical path length. CE/LIF was able to detect 1 adduct/10(4) normal nucleotides/micrograms DNA by fluorescence postlabeling assay. The enrichment of the adduct, prior to dansylation, enhanced the detection limit to 1 adduct/10(7) normal nucleotides/micrograms DNA. Calf thymus DNA was reacted in vitro with cisplatin and carboplatin with total input drug/nucleotide ratios of 0.05 and 0.5, respectively. A2780 human ovarian carcinoma cells were exposed in culture to 25 microM cisplatin for 2 h. The cells were incubated with drug-free medium for 3 h before harvesting. The identification of the cross-link adducts in modified DNA was confirmed by cochromatography with authentic markers. The same 1,2-intrastrand cross-link adducts were induced by both cisplatin and its second-generation drug carboplatin. This report has demonstrated, for the first time, the utility of CE/LIF as an analytical tool for assaying DNA damage [corrected].

Animals↗
PubMed1995

A density-sensing factor regulates signal transduction in Dictyostelium.

Dictyostelium discoideum initiates development when cells overgrow their bacterial food source and starve. To coordinate development, the cells monitor the extracellular level of a protein, conditioned medium factor (CMF), secreted by starved cells. When a majority of the cells in a given area have starved, as signaled by CMF secretion, the extracellular level of CMF rises above a threshold value and permits aggregation of the starved cells. The cells aggregate using relayed pulses of cAMP as the chemoattractant. Cells in which CMF accumulation has been blocked by antisense do not aggregate except in the presence of exogenous CMF. We find that these cells are viable but do not chemotax towards cAMP. Videomicroscopy indicates that the inability of CMF antisense cells to chemotax is not due to a gross defect in motility, although both video and scanning electron microscopy indicate that CMF increases the frequency of pseudopod formation. The activations of Ca2+ influx, adenylyl cyclase, and guanylyl cyclase in response to a pulse of cAMP are strongly inhibited in cells lacking CMF, but are rescued by as little as 10 s exposure of cells to CMF. The activation of phospholipase C by cAMP is not affected by CMF. Northern blots indicate normal levels of the cAMP receptor mRNA in CMF antisense cells during development, while cAMP binding assays and Scatchard plots indicate that CMF antisense cells contain normal levels of the cAMP receptor. In Dictyostelium, both adenylyl and guanylyl cyclases are activated via G proteins. We find that the interaction of the cAMP receptor with G proteins in vitro is not measurably affected by CMF, whereas the activation of adenylyl cyclase by G proteins requires cells to have been exposed to CMF. CMF thus appears to regulate aggregation by regulating an early step of cAMP signal transduction.

Animals↗
PubMed1995

Use of the CS-3000 Plus to prepare apheresed blood cells for immunomagnetic positive cell selection.

The Baxter CS-3000 Plus Blood Cell Separator was used to prepare progenitor cell components in a three-step process. The process was designed to remove platelets and plasma from a leukapheresis cell product before incubation with anti-CD34 monoclonal antibody (9C5) and to remove unbound monoclonal antibody after incubation. Fluorochrome-labeled cultured KG1a (CD34+) cells were added to the leukapheresis cell product (at 2% of total WBC) before CS-3000 processing to evaluate the CS-3000 process for preparing cells for immunomagnetic selection using the Isolex 300 (SA) Magnetic Separation system. Data were obtained using five leukapheresis products. Two percent of the nucleated cells were lost during the platelet reduction wash, and 67% of the platelets were removed. The amount of antibody initially added to the cells for incubation ranged from 3.9 to 7 mg (0.5 microgram/10(6) nucleated cells). The residual antibody in the cells after the antibody wash ranged from 11 to 40 micrograms. The antibody wash resulted in a 3% loss of nucleated cells and an additional 66% removal of platelets. The antibody-sensitized cells were then processed on the Isolex 300 (SA) system. The purity and yield of the Isolex KG1a cell product were 94% and 82%, respectively.

Antibodies, Monoclonal↗
PubMed1995

Diagnosis of abdominal tuberculosis: sonographic findings in patients with early disease.

OBJECTIVE: The diagnosis of abdominal tuberculosis is often difficult, because clinical manifestations and results of laboratory studies are nonspecific. If sonographic findings are sufficiently characteristic for diagnosis, sonography would be useful, especially in India, where abdominal tuberculosis is common and more expensive imaging techniques are not easily available. Accordingly, we performed sonography to establish the sonographic findings in cases of early tuberculosis in 56 patients with abdominal tuberculosis who had normal barium studies of the small bowel. SUBJECTS AND METHODS: Fifty-six patients with clinical features suggestive of abdominal tuberculosis (history of fever, abdominal pain, and weight loss) with no history of intestinal obstruction and normal barium studies of the small bowel had abdominal sonography. All sonograms were independently assessed by three radiologists, and the findings were tabulated by consensus. Diagnosis of tuberculosis was confirmed by sonographically guided biopsy of mesenteric lymph nodes in 19 patients, analysis of aspirated ascitic fluid in 12, and response to antituberculous chemotherapy in 25. Sonography was repeated 1, 3, 6, and 12 months after antituberculous chemotherapy was begun. Abdominal sonograms were also performed in 30 healthy volunteers, and measurements of mesenteric thickness were recorded. The mesenteric thickness was statistically compared in two groups of patients: patients at presentation with patients at the end of antituberculous chemotherapy and patients at presentation with healthy individuals. RESULTS: The mesenteric thickness in healthy individuals ranged from 5 to 14 mm. Sonographic findings in all patients with abdominal tuberculosis included an echogenic thickened mesentery (> or = 15 mm) with mesenteric lymphadenopathy. Other findings were dilated small bowel loops in 38 patients, minimal ascites in 17, matted small bowel loops in five, and omental thickening with altered echogenicity in three. Regression of these changes was noted on follow-up of all patients undergoing treatment. CONCLUSION: The characteristic sonographic features of early abdominal tuberculosis are mesenteric thickness of 15 mm or more and an increase in the mesenteric echogenicity (due to fat deposition), combined with mesenteric lymphadenopathy. Presence of dilated small bowel loops and ascites further substantiate the diagnosis.

Abdomen↗
PubMed1994

A potential role for antigen selection in the clonal evolution of Burkitt's lymphoma.

Burkitt's lymphoma (BL) is a monoclonal lymphoproliferative disorder characterized by the presence of specific chromosomal translocations that involve the c-myc proto-oncogene. Two subtypes of BL exist (endemic and sporadic) that differ in the prevalence of EBV genome expression. Although EBV infection may promote cellular proliferation in endemic BL, little is known about the forces that drive clonal expansion and evolution in the majority of EBV-negative sporadic BL. This study on an EBV-negative sporadic BL cell line derived from an AIDS patient provides evidence that antigenic stimulation may play a role in the development and/or expansion of such tumors. This cell line (BRG-P) contained a series of cellular clones that elaborated both IgM and IgA. Southern blot analyses of the line and its sublines indicated that both the IgM+ and IgA+ cells had identical c-myc and Ig JH gene rearrangements, indicating that they were derived from a common precursor, some of which eventually underwent an isotype switch. Ig VH gene sequence analyses of 21 molecular clones derived from the parental BRG BL line and two of its sublines demonstrated that all the clones used the same VH3 gene. Five unique intraclonal variants were identified at four distinct nucleotide positions (125, 161, 355, 375), which undoubtedly represented somatic mutations. Four of these five mutations occurred within complementary determining regions; all resulted in amino acid replacements. Moreover, an identical G to A nucleotide substitution that resulted in an identical amino acid change occurred at two distinct points in clonal evolution that were separated by the isotype class switch. Thus, the locations and types of the VH gene mutations, together with the occurrence of an isotype switch, are highly suggestive of an ongoing role for Ag stimulation and selection in the evolution of the malignant clone.

Adult↗
PubMed1994

Fluorescence postlabeling assay of RNA modification.

A new approach has been developed to assay RNA modification by combining enzymatic digestion of RNA to nucleoside monophosphate and fluorescence postlabeling. Nuclease P1 digestion of modified RNA affords both normal and modified nucleotides. The nucleotides are labeled in-situ with dansyl chloride via phosphoramidate derivatives with ethylenediamine following a procedure initially designed to synthesize fluorescence labeled deoxynucleotides. The postlabeled nucleotides are analyzed by HPLC using a fluorescence detector. Fluorescence postlabeling assay of 7-methylGmp in RNA exposed to dimethyl sulfate has validated the technique. In the presence of excess normal nucleotides, the limit of detection (LOD) lies between normal to modified nucleotide ratio of 10(3) to 10(4). HPLC enrichment of the modified nucleotide from the normal nucleotides prior to labeling enhances the LOD by two orders of magnitude.

Chromatography, High Pressure Liquid↗
PubMed1994

A developmentally regulated cell surface receptor for a density-sensing factor in Dictyostelium.

Conditioned medium factor (CMF) is an 80-kDa glycoprotein which is the signal in a cell density-sensing system used by developing Dictyostelium cells. CMF is slowly secreted by cells when they starve, and the extracellular level of CMF then becomes an indicator of the density of starving cells. To examine how CMF is sensed, we have made bacterially synthesized recombinant CMF and found that it has as much activity as native CMF, indicating that glycosylation is not part of the active site of CMF. Expression of recombinant fragments of CMF indicates that the active site lies within an 88-amino acid region near the N terminus. To determine whether CMF is sensed by cell surface receptors, we examined binding of iodinated recombinant CMF to live cells. We found saturable binding to 6-h starved cells at 3.9 x 10(4) molecules/cell with a KD of 2.1 nM. The binding saturates in 30 min, and a Scatchard plot indicates that there is only one class of receptor. The binding is competed off by the addition of either the native or recombinant CMF, or the 88-amino acid active fragment region; no binding competition is seen from the nonactive regions or other proteins. Very little binding to vegetative cells is seen, with maximal binding seen in cells starved for 6-8 h. The amount of cell surface CMF binding then decreases during later development. Normal levels of CMF binding are seen to CMF- cells, indicating that CMF is not required for the accumulation of its own receptor.

Animals↗