A new method of ileostomy formation following surgery for colonic obstruction.
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Aged↗
Biomedical subjects
R Patel
Publications and source records attributed to R Patel.
Thromboembolic disease susceptibility related to red cell membrane fluidity in patients with polycythemia vera and effect of phlebotomies.
Thromboembolic disorders are frequent complications in polycythemia vera. In addition to thrombocytosis with hyperaggregability, leukocytosis, and high hematocrit, hyperviscosity syndrome, a new component, is described in the pathophysiology of this phenomenon. There is decreased red cell membrane fluidity with decreased deformability which increases the susceptibility to microvascular occlusion and also increases the chance of disseminated intravascular coagulation (DIC). Periodic phlebotomies improved the hematologic picture in these patients and results in the removal of the "stiff" red cells with an increased production of young red cells, greater membrane fluidity, deformability and less chance of microvascular occlusion.
Aged↗
Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis.
BACKGROUND: Cytomegalovirus (CMV) infection and disease has been found to be associated with decreased graft and patient survival among heart transplant recipients. We sought to explore the effect of CMV infection and disease on long-term survival in orthotopic liver transplant (OLT) recipients using a derivation and validation cohort. METHODS: For derivation-validation modeling, we used data collected from two prospectively followed cohorts as the basis for multivariate analyses: 167 OLT recipients from the Boston Center for Liver Transplantation (the derivation set; median follow-up: 5.5 years, mortality: 40%) and an independent cohort of 294 OLT recipients from the Mayo Clinic (the validation set; median follow-up: 4.8 years, mortality: 27%). RESULTS: Underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis, number of units of red blood cells administered during transplantation, and donor CMV seropositivity were the pre- and intratransplant variables independently associated (P<0.01) with decreased long-term survival in the derivation cohort. For variables collected up to 1 year after transplantation, the need for retransplan. tation, CMV pneumonia, invasive fungal disease, and underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis were independently associated (P<0.01) with decreased long-term survival in the derivation cohort. The magnitude of the relationship of each pre-, intra-, and posttransplant factor with survival, as measured by the relative risk, did not significantly differ between the derivation and validation cohorts. The derivation model, incorporating pre-, intra-, and posttransplant factors, had receiver operating characteristic areas of 73% and 74% for 5-year mortality in the derivation and validation cohorts, respectively. CONCLUSIONS: Data from a derivation and an independent validation cohort demonstrate that CMV factors (reflected by either donor CMV seropositivity at transplantation, CMV pneumonia, or CMV disease within the first posttransplant year) are independently associated with decreased long-term survival in OLT recipients.
Adolescent↗
Massive intrapericardial lipoma, a rare cause of breathlessness. Investigations and management.
Massive intrapericardial lipoma is a rare cause of breathlessness. We describe a case, review the literature and discuss the presentation, investigation and management of this disorder.
Adult↗
Nitrosation of uric acid by peroxynitrite. Formation of a vasoactive nitric oxide donor.
Peroxynitrite (ONOO-), formed by the reaction between nitric oxide (. NO) and superoxide, has been implicated in the etiology of numerous disease processes. Low molecular weight antioxidants, including uric acid, may minimize ONOO---mediated damage to tissues. The tissue-sparing effects of uric acid are typically attributed to oxidant scavenging; however, little attention has been paid to the biology of the reaction products. In this study, a previously unidentified uric acid derivative was detected in ONOO--treated human plasma. The product of the uric acid/ONOO- reaction resulted in endothelium-independent vasorelaxation of rat thoracic aorta, with an EC50 value in the range of 0.03-0.3 microM. Oxyhemoglobin, a .NO scavenger, completely attenuated detectable .NO release and vascular relaxation. Uric acid plus decomposed ONOO- neither released .NO nor altered vascular reactivity. Electrochemical quantification of .NO confirmed that the uric acid/ONOO- reaction resulted in spontaneous (thiol-independent) and protracted (t1/2 approximately 125 min) release of .NO. Mass spectroscopic analysis indicated that the product was a nitrated uric acid derivative. The uric acid nitration/nitrosation product may play a pivotal role in human pathophysiology by releasing .NO, which could decrease vascular tone, increase tissue blood flow, and thereby constitute a role for uric acid not previously described.
Animals↗
A mutant cell line defective in response to double-stranded RNA and in regulating basal expression of interferon-stimulated genes.
Although much progress has been made in identifying the signaling pathways that mediate the initial responses to interferons (IFNs), much less is known about how IFN-stimulated genes (ISGs) are kept quiescent in untreated cells, how the response is sustained after the initial induction, and how ISG expression is down-regulated, even in the continued presence of IFN. We have used the cell sorter to isolate mutant cells with constitutively high ISG expression. A recessive mutant, P2.1, has higher constitutive ISG levels than the parental U4C cells, which do not respond to any IFN. Unexpectedly, P2.1 cells also are deficient in the expression of ISGs in response to double-stranded RNA (dsRNA). Electrophoretic mobility-shift assays revealed that the defect is upstream of the activation of the transcription factors NFkappaB and IFN regulatory factor 1. Analysis of the pivotal dsRNA-dependent serine/threonine kinase PKR revealed that the wild-type kinase is present and is activated normally in response to dsRNA in P2.1 cells. Together, these data suggest that the defect in P2.1 cells is either downstream of PKR or in a component of a distinct pathway that is involved both in activating multiple transcription factors in response to dsRNA and in regulating the basal expression of ISGs.
Cell Line↗
A gene essential to brain growth and development maps to the distal arm of rat chromosome 12.
A recently discovered, spontaneous, autosomal recessive mutation in rats, flathead (fh), results in greatly reduced brain growth beginning in late fetal development. In this study we have mapped the fh mutation by determining the pattern of segregation of polymorphic microsatellite markers with respect to fh in 51 affected F2 offspring from a single interstrain intercross. Two markers on chromosome 12, D12Rat80 and D12Mgh6, cosegregated with the fh mutation in all 51 affected animals. The distribution of six additional markers in 40 informative meioses further localizes fh approximately 2 cM teleomeric to nos1. There are no known mutations in homologous regions of either mouse or human genomes that result in deficits in late neurodevelopment similar to that observed in fh/fh animals. The unique phenotype of fh/fh animals and the location of fh suggests the presence of a novel gene essential to normal brain development on the distal end of rat chromosome 12.
Aging↗
Imaging the spatial dynamics of calmodulin activation during mitosis.
BACKGROUND: Calcium is an important and ubiquitous signalling ion. In most cell types, changes in intracellular calcium concentrations are sensed by calmodulin, a signal transduction protein that regulates cell function through its interactions with kinases and phosphatases. Calcium signals show complex spatiotemporal patterning, but little, if anything, is known about the patterns of calmodulin activation inside cells. RESULTS: We have measured calmodulin activation continuously during mitosis in living cells with a new probe, a fluorescent adduct of calmodulin termed TA-calmodulin. We found that calmodulin was activated locally and episodically in the nucleus and mitotic spindle. The pattern of calmodulin activation was different from the pattern of calcium signals and could not be predicted from the pattern of calcium increase. Calmodulin activation was essential for mitotic progression: both entry into mitosis and exit from mitosis were blocked by a novel peptide that bound to calmodulin with high affinity and so prevented the interaction of calmodulin with its target proteins. CONCLUSIONS: These data suggest that calmodulin regulates mitotic transitions and demonstrate the utility of fluorescent adducts for studying protein activation in living cells with good temporal and spatial resolution.
Animals↗
Direct detection of 8-oxodeoxyguanosine and 8-oxoguanine by avidin and its analogues.
8-Oxodeoxyguanosine is present in DNA from many tissues. The direct demonstration of 8-oxodeoxyguanosine as a potential biomarker of oxidative DNA damage has implications for the study of mutagenesis, carcinogenesis, and free radical toxicity. Avidin is shown here to bind with high specificity to this potentially mutagenic oxidized nucleoside, 8-oxodeoxyguanosine, and to the oxidatively modified base, 8-oxoguanine. The serendipitous finding that avidin bound to the nuclei of UVA-irradiated cells has led to the development of a technique which allows detection of the damage product in a manner analogous to that of immunological techniques. The technique has been shown to be applicable to isolated DNA and to DNA in fixed cellular material and postmortem tissue. Statistically different levels of damage can be demonstrated in both isolated DNA and cultured cells exposed to free radical generating systems using a 96-well plate-based methodology. The sensitivity of this method allows the detection of 10(-19) mol of 8-oxodeoxyguanosine. This novel usage of avidin conjugates applies also to its bacterial analogue, streptavidin, and to a lesser extent to the monoclonal antibody to biotin (the ligand bound by the parent compound). This finding has tremendous potential as a simple method analogous to immunotechniques for the direct detection of 8-oxodeoxyguanosine. From structural considerations we speculate that avidin would also bind to 8-oxodeoxyadenosine.
8-Hydroxy-2'-Deoxyguanosine↗
In vitro activity of LY333328 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae.
We report the activity of LY333328 against 35 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes, as determined by PCR), 33 clinical isolates of methicillin-resistant S. aureus, and 29 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by 2 micrograms/mL LY333328, and 8 micrograms/mL LY333328 was bactericidal against all isolates tested. All isolates of methicillin-resistant S. aureus were inhibited by 1 microgram/mL LY333328, and 4 micrograms/mL LY333328 was bactericidal against all methicillin-resistant S. aureus isolates tested. All isolates of penicillin-resistant S. pneumoniae were inhibited by < 0.125 microgram/mL LY333328, and 0.25 microgram/mL LY333328 was bactericidal against all S. pneumoniae isolates tested. LY333328 is a promising new glycopeptide antimicrobial agent.
Anti-Bacterial Agents↗
Cysteine conjugate beta-lyase activity of amino acid decarboxylases.
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Aspartate Aminotransferases↗
Restorative treatment need assessment by dentally and nondentally trained subjects.
A study was carried out which compared how two groups of people, one with clinical dental experience and one without, assessed restorative dental treatment need. Using a visual analogue scale, a group of final year dental students (n = 50) and nonclinical university students (n = 50) assessed the extent to which they considered common dental imperfections, viz. spacing of the upper anterior teeth and discolouration of upper anterior teeth, warranted restorative correction. The group of dental students judged the necessity for treatment of discolouration to be more urgent than correction of spacing. The nondental group did not differentiate between the degrees of need. Data were non-normal in distribution but the use of appropriate statistical tests showed the differences in mean assessments to be significant.
Adolescent↗
Distribution of mRNAs encoding the peroxisome proliferator-activated receptor alpha, beta, and gamma and the retinoid X receptor alpha, beta, and gamma in rat central nervous system.
We report the isolation, by RT-PCR, of partial cDNAs encoding the rat peroxisome proliferator-activated receptor (PPAR) isoforms PPAR alpha, PPAR beta, and PPAR gamma and the rat retinoid X receptor (RXR) isoforms RXR alpha, RXR beta, and RXR gamma. These cDNAs were used to generate antisense RNA probes to permit analysis, by the highly sensitive and discriminatory RNase protection assay, of the corresponding mRNAs in rat brain regions during development. PPAR alpha, PPAR beta, RXR alpha, and RXR beta mRNAs are ubiquitously present in different brain regions during development, PPAR gamma mRNA is essentially undetectable, and RXR gamma mRNA is principally localised to cortex. We demonstrate, for the first time, the presence of PPAR and RXR mRNAs in primary cultures of neonatal meningeal fibroblasts, cerebellar granule neurons (CGNs), and cortical and cerebellar astrocytes and in primary cultures of adult cortical astrocytes. PPAR alpha, PPAR beta, RXR alpha, and RXR beta mRNAs are present in all cell types, albeit that PPAR alpha and RXR alpha mRNAs are at levels near the limit of detection in CGNs. PPAR gamma mRNA is expressed at low levels in most cell types but is present at levels similar to those of PPAR alpha mRNA in adult astrocytes. RXR gamma mRNA is present either at low levels, or below the level of detection of the assay, for all cell types studied.
Animals↗
Regulation of nitric oxide production by salicylates and tenidap in human OA-affected cartilage, rat chondrosarcomas and bovine chondrocytes.
OBJECTIVE: To examine the effects of non-steroidal anti-inflammatory drugs (NSAIDS) on nitric oxide (NO) and prostaglandin E2 (PGE2) production in chondrocytes from three different species. METHODS: We have estimated NO production by Griess method, and PGE2 by RIA from the supernatants of articular cartilage obtained from osteoarthritis joints (OA-affected cartilage), rat chondrosarcomas (in ex vivo conditions) and bovine chondrocytes (stimulated with cytokines + endotoxin in vitro conditions) in the presence or absence of aspirin, indomethacin, sodium salicylate, tenidap and glucocorticoids. RESULTS: NO, which was spontaneously released in ex vivo conditions by OA-affected cartilage and rat chondrosarcomas (maintained in vivo), was susceptible to inhibition by pharmacologically relevant concentrations of aspirin, sodium salicylate and tenidap, but not to concentrations of indomethacin or glucocorticoids that significantly inhibited PGE2 production under the same conditions. Similarly, the production of NO by bovine chondrocytes grown in monolayer cultures that had been stimulated with cytokines + endotoxins (in vitro) to release both NO and PGE2 (at 48-72 h post stimulation), were inhibited by aspirin, sodium salicylate and tenidap, but not by indomethacin or glucocorticoids at concentrations sufficient to PGE2 production. Inhibition of NO in the cytokines + endotoxin stimulated bovine chondrocytes (like the human OA-affected cartilage) augmented PGE2 production. CONCLUSION: These experiments demonstrate that NO production by chondrocytes across species show a similar profile of susceptibility to inhibition by selected anti-inflammatory drugs. The insensitivity of NO production to glucocorticoids is an important characteristics of these cells that merits further investigation.
Aged↗
DNA sequence resembling vanA and vanB in the vancomycin-resistant biopesticide Bacillus popilliae.
The origin of high-level vancomycin resistance in enterococci is unknown. Biopesticidal powders containing spores of Bacillus popilliae, which is vancomycin-resistant, have been used for >50 years in the United States for suppression of Japanese beetle populations. Using a polymerase chain reaction assay designed to amplify the vanB gene in enterococci, an amplicon in B. popilliae was identified and sequenced. The putative ligase gene in B. popilliae had 76.8% and 68.4%-68.9% nucleotide identity to the sequences of the vanA and vanB genes, respectively. There was 75.3% and 69.3%-69.9% identity between the translation of the putative ligase gene in B. popilliae and the translation of the vanA and vanB genes, respectively. We have identified a gene resembling vanA and vanB in B. popilliae. The gene in B. popilliae may have been a precursor to or have had an ancestral gene in common with vancomycin resistance genes in enterococci.
Amino Acid Sequence↗
Subclinical herpes virus reactivation and latency.
Although there has been considerable refinement in our understanding of the processes underlying the establishment and maintenance of latency, important research questions remain. Results from various workers imply that the establishment of latency may be a dynamic process and may offer possible therapeutic targets. The role played by the latency-associated transcripts appear to be important in both establishing latency and in aiding reactivation. Recent work has shown that reactivation in vivo is much more frequent than previously thought and leads principally to subclinical viral shedding. Factors influencing subclinical shedding for most patient groups and the response and limitation of therapy have been clearly determined.
Journal Article↗
Does renal damage occur after the administration of 32P for palliation of pain from skeletal metastases?
In normal adults, the maintenance of phosphate balance involves the reabsorption of 85-90% of filtered phosphate by the proximal tubule. At a glomerular filtration rate (GFR) of 125 ml min-1 and a plasma phosphate concentration of 1.3 mmol l-1, the filtered phosphate is approximately 235 mmol day-1. Following intravenous administration, 25-50% of 32P is excreted over 4-6 days in normal subjects. In spite of such extensive renal handling of phosphate and, therefore, of 32P, there are no data in the literature concerning possible 32P-related nephrotoxicity. Adult dosimetry values for the kidney after 32P are reported as 4.8 rad mCi-1 h-1 (0.048 mSev 37 MBq-1 h-1). The entry criteria for 32P therapy insist on a normal serum creatinine value, reflecting awareness of potential renal damage. To answer the fundamental question of whether there is demonstrable renal damage after 32P, we undertook serial measurements of GFR in patients given 32P for treatment of pain from skeletal metastases. Twenty-one patients who had normal pre-treatment renal function as shown by normal serum creatinine values were administered 32P orally in doses ranging from 277.5 to 466.2 MBq, with a mean of 425.5 MBq. Pre-treatment, GFR was estimated with 99Tcm-diethylenetriamine pentaacetate renography using the Gates protocol. Post-treatment, GFR was estimated serially as far as possible, at weeks, 1, 2, 3 and 4 and then every 4 weeks for another 3 months, at which point follow-up ceased. Serum creatinine was assessed pre-treatment and every 2 weeks until the end of follow-up, in addition to all other parameters and a clinical evaluation. Mean pre-treatment GFR was 87.5 ml min-1, with a range of 48.7-110 ml min-1. Not all patients could fulfil the entire follow-up schedule as designed, but we obtained a minimum of four follow-up tests, two before and two after 4 weeks post-treatment. GFR fell to 72% of the pre-therapy value during the first 4 weeks following therapy. By the sixteenth week, however, the mean value had returned to or exceeded the pre-treatment value. There was no change in serum creatinine values. At a time when multiple therapies are being considered, this early depression of GFR may be of importance. A closer assessment of altered renal function may be warranted and other sensitive tests of renal damage like microalbuminuria could be used.
Adult↗
DNA sequence variation within vanA, vanB, vanC-1, and vanC-2/3 genes of clinical Enterococcus isolates.
We studied the DNA sequence variation of van genes of 34 isolates of Enterococcus spp. The isolates containing the vanB gene exhibited between 0 and 41 base pair changes per 801 bp studied when the vanB sequences were compared to that of the reference strain Enterococcus faecalis V583. The isolates carrying the vanC-2 gene exhibited between 0 and 23 base pair changes per 346 bp studied when the vanC-2 sequences were compared to that of the reference strain E. casseliflavus ATCC 25788. Little variation was noted in the vanA and vanC-1 genes.
Amino Acid Sequence↗