Search PubMed⌕ Search

Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 19 recordsLinked to original sources
PubMed1996

Relevance and risk factors of enterococcal bacteremia following liver transplantation.

To analyze the clinical characteristics of and identify specific risk factors for enterococcal bacteremia following liver transplantation, we performed a study in 405 consecutive liver transplantation recipients prophylaxed with a selective bowel decontamination regimen. Seventy enterococcal bacteremias in 52 patients were identified. Enterococcus faecalis (50) outnumbered Enterococcus faecium isolates (18), and 49% of enterococcal bacteremias were polymicrobial. Biliary tree complications were present in 34% of enterococcal bacteremias. Of the 15 deaths (29%) among the patients with enterococcal bacteremia, 4 were directly associated with enterococcal bacteremia. In a multivariate analysis, Roux-en-Y choledochojejunostomy (P=0.005), a cytomegalovirus-seropositive donor (P=0.013), prolonged transplantation time (P=0.02), and biliary stricturing (P=0.016) were identified as significant risk factors. Other risk factors identified in a univariate analysis included primary sclerosing cholangitis (P=0.009) and symptomatic cytomegalovirus infection (P=0.008). Enterococcal bacteremia is a frequent infectious complication in liver transplantation recipients receiving selective bowel decontamination. Its association with cytomegalovirus and biliary tree abnormalities suggest specific areas for prophylactic intervention.

Anastomosis, Roux-en-Y↗
PubMed1996

Relationships between beta-amyloid (A beta) deposits and blood vessels in patients with sporadic and familial Alzheimer's disease.

The density of diffuse, primitive and classic beta-amyloid (A beta) deposits was studied in relation to the incidence of blood vessels in the superior frontal gyrus of nine cases of sporadic Alzheimer's disease (SAD), two cases of familial Alzheimer's disease (FAD) with amyloid precursor protein (APP) mutations (APP717, Val --> Ile), and eight cases of FAD not linked to chromosomes 21, 14 or 1. Stepwise multiple regression was used to determine for each patient whether variations in the density of A beta deposits along the cortex were significantly correlated with the incidence of blood vessels. In the majority of FAD and SAD cases, the density of the diffuse and primitive type A beta deposits was not related to blood vessels. However, the incidence of the larger diameter (> 10 microns) blood vessels was positively correlated with the density of the classic A beta deposits in eight (89%) SAD and two (20%) FAD cases. The data suggest that the densities of vessels and deposits were not significantly correlated between cases but only within cases, suggesting a strictly local effect. In addition, the spatial association between classic A beta deposits and blood vessels may be more apparent in SAD compared with FAD cases.

Aged↗
PubMed1996

Formation of chimeric DNA primer extension products by template switching onto an annealed downstream oligonucleotide.

Oligodeoxynucleotide sequences are described that anneal to a template downstream of a priming site. During polymerase-catalyzed extension of the primer, the extending primer shifts from the original template to a segment of the annealed oligonucleotide that acts as an alternative template. The resulting chimeric extended primer has one segment that is complementary to the template and a second segment that is complementary to the oligonucleotide. The influence of the sequence elements of the oligonucleotide and the reaction conditions on template switching have been explored. The sequence requirements for template switching are compared to those for transposon excision.

Base Sequence↗
PubMed1996

Effects of cisapride on salivary production in normal subjects.

Cisapride improves reflux esophagitis and enhances esophageal acid clearance. To test the effect of cisapride an salivary production, we enrolled 14 healthy volunteers in a double-blind, randomized, placebo-controlled study. Subjects received cisapride, 10mg per os four times a day, or placebo for three days. Saliva, collected during fasted and fed states, was analyzed for volume and buffer capacity. Buffer capacity was expressed as the volume of 0.01 N HCl needed to titrate 1 ml of saliva to pH 6.1. Both volume and buffer capacity significantly increased during the fed state as compared to the fasted on both cisapride and placebo. Cisapride significantly enhanced the postprandial salivary volume and buffer capacity compared to placebo: 29.6 +/- 11.3 ml vs 22.9 +/- 9.5 ml and 1.07 +/- 0.31 vs 0.89 +/- 0.28, respectively (P< 0.0001). Cisapride's enhancement of salivary flow rate and buffer capacity in the fed state may be another mechanism by which it exerts its beneficial effect in patients with reflux esophagitis.

Adult↗
PubMed1996

Prognostic significance and risk factors of untreated cytomegalovirus viremia in liver transplant recipients.

To study whether cytomegalovirus (CMV) viremia is a reliable marker of impending CMV disease and thus a guide for preemptive antiviral therapy, 126 consecutive liver transplant recipients were followed by routine CMV blood cultures in the absence of antiviral prophylaxis or treatment for viremia. Seventy-three patients (58%) developed CMV infections, and 36 (29%) had more than one infection episode: 29 patients (23%) had organ involvement and 45 (36%) had viremia. Within a same episode, CMV viremia was 90% sensitive and 80% specific for predicting concurrent organ involvement but preceded organ involvement in only 9 (31%) of 29 patients. In a separate analysis, untreated isolated CMV viremia in the first CMV infection episode was followed by organ involvement in a subsequent episode in 9 (33%) of 28 patients, mainly in the donor-positive, recipient-negative (D+/R-) population. The results indicate that CMV viremia is not an ideal marker to guide preemptive antiviral treatment in liver transplant recipients but is a good marker in D+/R- patients.

Adult↗
PubMed1995

Circulation of oligonucleotides by disulfide bridge formation.

An effective, convenient method for the circularization of oligonucleotides has been developed. This procedure involved preparation of an oligonucleotide with backbone-linked 5'- and 3'-terminal hexamethylenethiol groups, followed by oxidation of the thiol groups with air of oxygen to produce the corresponding circular sequence bridged via a bis(hexamethylene)-disulfide moiety. The method has been applied to the circularization of oligodeoxynucleotide sequences of varying lengths (5, 10, 15, 20, 30 and 40 bases), and the circularization process was highly efficient as shown by HPLC or gel electrophoresis of the crude reaction mixtures. Competing reactions such as dimerization were not significant except for the longer sequences (30 and 40 bases). The circularization of an eight base RNA sequence was also accomplished, as well as hexa-ethylene glycol bridged poly-T sequences capable of triplex formation.

Base Sequence↗
PubMed1995

Sequence and evolution of the blue cone pigment gene in Old and New World primates.

The sequences of the blue cone photopigments in the talapoin monkey (Miopithecus talapoin), an Old World primate, and in the marmoset (Callithrix jacchus), a New World monkey, are presented. Both genes are composed of 5 exons separated by 4 introns. In this respect, they are identical to the human blue gene, and intron sizes are also similar. Based on the level of amino acid identity, both monkey pigments are members of the S branch of pigments. Alignment of these sequences with the human gene requires the insertion/deletion of two separate codons in exon 1. The silent site divergence between these primate blue genes indicates a separation of the Old and New World primate lineages around 43 million years ago.

Amino Acid Sequence↗
PubMed1995

Suramin sodium: pronounced effects on methotrexate transport and anti-folate activity in cultured tumor cells.

Suramin is an experimental anti-neoplastic agent which has shown promising activity against prostatic carcinoma and lymphoma in clinical trials. To elucidate its mechanism of action, suramin was examined for an effect on the transport of folate compounds by tumor cells. Influx of the anti-folate methotrexate via the reduced-folate carrier system of CCRF-CEM cells was found to be highly sensitive to inhibition by suramin but not to various other arylsulfonic acids. Inhibition by suramin was competitive, and the inhibition constant Ki was 1.3 microM, a value 3-fold lower than the Kt for half-maximal influx of methotrexate. Folate binding to the membrane-associated folate-binding protein of KB cells was not affected by suramin. Growth studies revealed that the response of human CCRF-CEM, KB, PC-3 and MCF-7 cells to methotrexate was antagonized from 6- to 17-fold by pharmacological levels (10-200 microM) of suramin. Conversely, growth inhibition was additive or synergistic when suramin was combined with metoprine, a lipophilic anti-folate which enters cells by diffusion. Synergism was observed between metoprine and suramin in CCRF-CEM cells, which take up folate exclusively through the reduced-folate carrier (inhibitable by suramin), whereas additivity was observed for KB cells, which rely largely on the folate-binding protein (unaffected by suramin) for folate import. Our results indicate that inhibition of cellular transport of folate compounds may explain part of the anti-neoplastic effects of suramin on tumor cells.

Antineoplastic Agents↗
PubMed1995

Structural and functional characterization of potent antithrombotic oligonucleotides possessing both quadruplex and duplex motifs.

We report the results of a selection for single-stranded DNA oligonucleotide ligands to the serine protease thrombin using recently developed methods. This selection yielded a family of DNA sequences that conform to a consensus structure comprised of a unimolecular quadruplex motif and complementary flanking sequences capable of forming an additional Watson-Crick duplex motif. This novel quadruplex/duplex structure was not reported in a previous selection for DNA molecules which bind to thrombin [Bock et al. (1992) Nature 355, 564-566]. All quadruplex/duplex molecules tested bound to thrombin with higher affinity than quadruplex structures lacking the duplex structure. However, binding affinities did not always correlate with inhibitory potency since some molecules with high affinity were not potent inhibitors in vitro. 1H NMR spectroscopy studies demonstrated that the complementarity of bases in the duplex portion of a selected sequence allows it to form multimolecular structures. Constraining these molecules to the unimolecular quadruplex/duplex structure by bridging the 5' and 3' ends of the duplex motif with either triethylene glycol or disulfide bonds improved their thrombin inhibitory activity. All bridged quadruplex/duplex molecules were more potent inhibitors than molecules with only a quadruplex motif. Bridging the ends of these structures not only increased thrombin inhibition but also improved resistance to nucleases in serum more than 40-fold over the unbridged quadruplex. In addition, we have found that both the length and sequence of the duplex motif are important for inhibition.

Anions↗
PubMed1995

A prospective comparison of molecular diagnostic techniques for the early detection of cytomegalovirus in liver transplant recipients.

Forty-one consecutive liver transplant recipients were studied by polymerase chain reaction (PCR) of serum and peripheral blood mononuclear cells, reverse transcription (RT)-PCR of peripheral blood mononuclear cells, and viral blood culture for symptomatic cytomegalovirus (CMV) infection. The techniques were also used to predict the occurrence of CMV infection. For diagnosis of symptomatic CMV infection, the sensitivity and specificity of the different techniques were as follows: PCR of serum, 100% and 45%; RT-PCR, 25% and 97%; PCR of peripheral blood mononuclear cells, 83% and 35%; and blood culture, 83% and 86%, respectively. PCR of serum was positive in 83% of subjects with symptomatic infection before onset compared with 17% positive by blood culture. While viral blood culture was the best technique for the diagnosis of symptomatic CMV infection, PCR of serum was best at predicting the development of symptomatic CMV infection.

Cytomegalovirus↗
PubMed1995

OKT3 treatment for allograft rejection is a risk factor for cytomegalovirus disease in liver transplantation.

The role of OKT3 monoclonal antibody administration was studied as a risk factor for symptomatic cytomegalovirus (CMV) infection in 229 consecutive liver transplant recipients not receiving specific CMV prophylaxis. Twenty-six patients (11.4%) received OKT3 and 17 of them developed CMV infection, 11 (4.8%) being symptomatic. OKT3 use was a significant risk factor for symptomatic CMV infection by both univariate (relative risk [RR], 2.9; 95% confidence interval [CI], 1.5-5.8; P = .002) and multivariate time-dependent (RR, 3.4; 95% CI, 1.7-7.1; P = .001) analyses. A subgroup analysis revealed that OKT3 use was a significant risk factor for symptomatic CMV infection in CMV-seropositive but not seronegative recipients. OKT3 therapy for steroid-resistant rejection is a risk factor for symptomatic CMV infection in liver transplant recipients who are seropositive for CMV before transplantation. This group should be targeted for antiviral prophylaxis when OKT3 antirejection therapy is used.

Cytomegalovirus Infections↗
PubMed1995

Affinity, conservation, and surface exposure of hemopexin-binding proteins in Haemophilus influenzae.

Haemophilus influenzae can acquire heme from hemopexin for use as a source of both essential porphyrin and iron. In classical ligand-binding studies, we observed time-dependent, saturable, and displaceable binding of human 125I-labelled hemopexin to intact cells of H. influenzae type b (Hib) strain 760705 grown in an iron-restricted medium. From these experiments, which demonstrate that hemopexin associates with a single class of binding site, the affinities (Kds) and receptor numbers were calculated for heme-hemopexin (Kd, 205 nM; 3,200 receptors per cell) and apohemopexin (Kd, 392 nM; 4,400 receptors per cell). Thus, Hib expresses a specific hemopexin receptor which shows some preference for the heme-protein complex. Affinity chromatography on hemopexin-Sepharose 4B of detergent-solubilized membranes from Hib strain 760705 results in the copurification of three proteins with molecular masses of 57, 38, and 29 kDa. Trypsinization of whole cells of Hib 760705 abolishes hemopexin binding and correlates with the disappearance of the 57-kDa hemopexin-binding protein and appearance of a 52-kDa species which does not bind either hemopexin in ligand blot assays or a monoclonal antibody (MAbT11-30) raised against the 57-kDa protein. From immunoblotting assays and NH2-terminal amino acid sequence analysis, the 38-kDa protein isolated following hemopexin affinity chromatography was identified as the porin protein P2. These data, taken together with the receptor-binding studies which support a single class of hemopexin-binding site, suggest that P2 and the 29-kDa protein function as accessory proteins to the 57-kDa hemopexin-binding protein to facilitate the uptake of heme from receptor-bound hemopexin. To determine whether hemopexin binding and the 57-kDa protein are conserved in Haemophilus strains, whole-cell dot blots and immunoblots of the outer membrane proteins prepared from strains belonging to each of 21 different Hib outer membrane protein subtypes, six nontypeable strains, and five Haemophilus parainfluenzae strains were probed with either hemopexin or MAbT11-30. Only the H. parainfluenzae strains which lack the 57-kDa protein do not bind hemopexin. Since H. influenzae has also been shown to produce a soluble 100-kDa hemopexin-binding protein, cell-free culture supernatants were also examined for the presence of this protein. Apart from Hib 760705 and H. parainfluenzae, the 100-kDa hemopexin-binding protein was detected in all the other Haemophilus strains. The abilities of Hib 760705 to both bind and acquire heme from hemopexin without expressing a 100-kDa soluble hemopexin-binding protein show that in strain 760705, this 100-kDa protein is not essential for the utilization of heme from hemopexin.

Amino Acid Sequence↗