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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 235 records · Page 13Linked to original sources
PubMed1996

Factors affecting DNA-binding proteins and pcbC transcript levels in Penicillium chrysogenum.

Proteins extracted from Penicillium chrysogenum grown in either complex or defined medium were used in electromobility shift assays. With a probe DNA covering the region -10 to -132 relative to the pcbC translation start codon, four protein/DNA complexes (designated A-D) were reproducibly observed. Two of the four DNA/protein complexes routinely detected in extracts from liquid cultures (A and B) were also detectable with protein extracts from P. chrysogenum spores. Generally, with proteins from liquid cultures, there was a correlation between increased levels of the complexes and increased levels of the pcbC transcript. In addition, the detectable levels of the complexes and the pcbC transcript showed some relationship to the extracellular pH of the medium. In defined medium, with glucose as the carbon source, the pcbC transcript was not detectable in extracts from the wild-type strain at any time, whereas with the high penicillin-producing strain P-2, a pcbC transcript was detected. In complex medium, the pcbC transcript was detectable during the exponential phase of cultures of the wild-type or P-2, even when glucose levels were as high as 2.5% (w/v).

Blotting, Northern↗
PubMed1996

Future directions for resuscitation research. III. External cardiopulmonary resuscitation advanced life support.

This discussion about advanced cardiac life support (ACLS) reflects disappointment with the over 50% of out-of-hospital cardiopulmonary resuscitation (CPR) attempts that fail to achieve restoration of spontaneous circulation (ROSC). Hospital discharge rates are equally poor for in-hospital CPR attempts outside special care units. Early bystander CPR and early defibrillation (manual, semi-automatic or automatic) are the most effective methods for achieving ROSC from ventricular fibrillation (VF). Automated external defibrillation (AED), which is effective in the hands of first responders in the out-of-hospital setting, should also be used and evaluated in hospitals, inside and outside of special care units. The first countershock is most important. Biphasic waveforms seem to have advantages over monophasic ones. Tracheal intubation has obvious efficacy when the airway is threatened. Scientific documentation of specific types, doses, and timing of drug treatments (epinephrine, bicarbonate, lidocaine, bretylium) are weak. Clinical trials have failed so far to document anything statistically but a breakthrough effect. Interactions between catecholamines and buffers need further exploration. A major cause of unsuccessful attempts at ROSC is the underlying disease, which present ACLS guidelines do not consider adequately. Early thrombolysis and early coronary revascularization procedures should also be considered for selected victims of sudden cardiac death. Emergency cardiopulmonary bypass (CPB) could be a breakthrough measure, but cannot be initiated rapidly enough in the field due to technical limitations. Open-chest CPR by ambulance physicians deserves further trials. In searches for causes of VF, neurocardiology gives clues for new directions. Fibrillation and defibrillation thresholds are influenced by the peripheral sympathetic and parasympathetic nervous systems and impulses from the frontal cerebral cortex. CPR for cardiac arrest of the mother in advanced pregnancy requires modifications and outcome data. Until more recognizable critical factors for ROSC are identified, titrated sequencing of ACLS measures, based on physiologic rationale and sound judgement, rather than rigid standards, gives the best chance for achieving survival with good cerebral function.

Animals↗
PubMed1996

Local perinuclear calcium signals associated with mitosis-entry in early sea urchin embryos.

Using calcium-sensitive dyes together with their dextran conjugates and confocal microscopy, we have looked for evidence of localized calcium signaling in the region of the nucleus before entry into mitosis, using the sea urchin egg first mitotic cell cycle as a model. Global calcium transients that appear to originate from the nuclear area are often observed just before nuclear envelope breakdown (NEB). In the absence of global increases in calcium, confocal microscopy using Calcium Green-1 dextran indicator dye revealed localized calcium transients in the perinuclear region. We have also used a photoinactivatable calcium chelator, nitrophenyl EGTA (NP-EGTA), to test whether the chelator-induced block of mitosis entry can be reversed after inactivation of the chelator. Cells arrested before NEB by injection of NP-EGTA resume the cell cycle after flash photolysis of the chelator. Photolysis of chelator triggers calcium release. TreatmenT with caFfeine to enhance calcium-induced calcium release increases the amplitude of NEB-associated calcium transients. These results indicate that calcium increases local to the nucleus are required to trigger entry into mitosis. Local calcium transients arise in the perinuclear region and can spread from this region into the cytoplasm. Thus, cell cycle calcium signals are generated by the perinuclear mitotic machinery in early sea urchin embryos.

Animals↗
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↗
PubMed1996

Intratracheal administration of hepatocyte growth factor/scatter factor stimulates rat alveolar type II cell proliferation in vivo.

Alveolar epithelial injury occurs universally in common respiratory illnesses associated with diffuse lung damage. After alveolar injury, type II cells proliferate and reestablish epithelial integrity, thereby restoring normal lung structure and function. However, the regulation of type II cell proliferation and alveolar epithelial repair is poorly understood. Hepatocyte growth factor/scatter factor (HGF/SF) is a heparin-binding growth factor that has been shown to be mitogenic for cultured alveolar type II cells. In this study, we determined the effect of intratracheal instillation of rhHGF/SF on type II cell proliferation in vivo. To quantify the alveolar type II cell proliferative response, we developed a double-label immunohistochemical technique to detect replicating alveolar type II cells in formalin-fixed lung sections that utilized the identification of proliferating cells by bromodeoxyuridine (BrdUrd) incorporation into DNA and alveolar type II cells by 3F9 immunoreactivity. BrdUrd detection was optimized by enzymatic antigen recovery and silver intensification of the horseradish peroxidase reaction product. Intratracheal instillation of rhHGF/SF induced a time- and dose-dependent increase in type II cell proliferation. The type II cell labeling index increased to 12.3 +/- 6.0% 48 h after 1.0 mg/kg rhHGF/SF administration, compared with 2.6 +/- 0.9% after PBS instillation. To compare the normal type II cell reparative response with the level of proliferation after exogenous rhHGF/SF administration, we measured the specific alveolar type II cell labeling index in rat lung sections obtained from animals exposed to hyperoxia for 50 h and then allowed to recover in room air. After 1 day of recovery, the alveolar type II cell labeling index was 0.45 +/- 0.2%. The specific labeling index increased to 5.4 +/- 1.3% at 2 days and then declined to 0.31 +/- 0.16% 5 days after hyperoxia exposure. In animals not exposed to hyperoxia, the alveolar type II cell labeling index was 0.6 +/- 0.14%. These studies demonstrated that intratracheal instillation of rhHGF/SF promoted alveolar type II cell proliferation in vivo. The maximal level of type II cell proliferation after rhHGF/SF administration was more than twice that reached during recovery from hyperoxia exposure. Thus, intratracheal instillation of HGF/SF may provide a potential strategy to promote type II cell proliferation and augment alveolar epithelial repair after lung injury.

Animals↗
PubMed1996

Occupational dose to the radiographer in dual X-ray absorptiometry: a comparison of pencil-beam and fan-beam systems.

The introduction of advanced dual X-ray absorptiometry (DXA) scanners with fan-beam geometry, improved image definition and faster scan times raises the question as to whether there is a significant radiation dose to the radiographer. We have measured the radiation dose to the operator from studies performed on four DXA systems; the Lunar DPX, Hologic QDR-1000, QDR-2000 plus and QDR-4500. The results were compared with the radiographer dose from 99Tcm-MDP radionuclide bone scanning, where it is not usual to use a radiation barrier between the patient and the operator, and 18F-FDG positron emission tomography (PET) scanning where it is usual to protect staff. Ambient dose equivalent rate averaged over 1 h at 1 m from the patient with the DXA systems working at maximum patient throughput were 0.012, 0.12, 2.1 and 2.4 microSv h-1, respectively, for the DPX, QDR-1000, QDR-2000plus and QDR-4500. Annual operator dose for the DPX and QDR-1000 was well below the 1 mSv limit for members of the public recommended by the International Commission on Radiological Protection (ICRP) (1990). Results for the QDR-2000plus and QDR-4500 were similar to a radionuclide bone scan (2.2 microSv h-1), but smaller than for a PET scan (8.9 microSv h-1), and were close to the 5 mSv year-1 limit for a supervised area defined in the 1985 Ionising Radiation Regulations. Precautions to reduce radiographer dose with fan beam DXA include placing the operator at least 2 m from the patient, scanning the right hip instead of the left and using scan modes with short scanning times.

Absorptiometry, Photon↗
PubMed1996

Concordance and precision of dual X-ray absorptiometry with a 10 s scan.

Development of dual energy X-ray absorptiometry (DXA) scanners with multidetector array technology has resulted in greatly shortened scanning times. The Hologic QDR-4500 includes an ultrafast (10 s) "turbo" scan mode recommended by the manufacturer for fast screening studies or as an aid to positioning the patient prior to scanning using the normal fast (30 s), medium (1 min) or high definition (2 min) modes. The suitability of the turbo mode for use in routine clinical studies was assessed by examining the concordance of bone mineral density (BMD) measurements obtained in this mode with measurements obtained using the three normal scanning modes. Studies in 151 female patients showed statistically significant discrepancies in four out of the six scan sites studied with systematic differences of 2.9% and 3.1% being observed for the posteroanterior (PA) spine and intertrochanteric region of the hip, respectively. In vivo precision for the 10 s scan found by performing duplicate measurements on 37 patients had a coefficient of variation of 1.3% for PA spine and 2.5% for femoral neck BMD. An investigation of the dependence of precision on body mass index (BMI) shows that the precision of spine and hip BMD was adversely affected with increasing BMI but the trend was statistically significant only in the spine. It was concluded that turbo mode scans are acceptable for routine clinical studies of the spine and hip but should not be used for longitudinal studies or patients with BMI greater than 30 kg m-2.

Absorptiometry, Photon↗
PubMed1996

Luminescent oxygen channeling assay (LOCI): sensitive, broadly applicable homogeneous immunoassay method.

Luminescent oxygen channeling assay (LOCI) is a homogeneous immunoassay method capable of rapid, quantitative determination of a wide range of analytes--including high and very low concentrations of large and small molecules, free (unbound) drugs, DNA, and specific IgM. Assays have been carried out in serum and in lysed blood. Reliable detection of 1.25 microU/L thyrotropin (TSH) and 5 ng/L hepatitis B surface antigen (HBsAg) corresponds to detection limits approximately 3- and approximately 20-fold lower, respectively, than those of the best commercially available assays. An assay of chorionic gonadotropin is capable of quantification over a 10(6)-fold range of concentrations without a biphasic response. Latex particle pairs are formed in the assay through specific binding interactions by sequentially combining the sample and two reagents. One particle contains a photosensitizer, the other a chemiluminescer. Irradiation causes photosensitized formation of singlet oxygen, which migrates to a bound particle and activates the chemiluminescer, thereby initiating a delayed luminescence emission. Assay times range from 1 to 25 min.

Antigens, Viral↗
PubMed1996

Comparison of sutured and stapled closure of loop ileostomy after restorative proctocolectomy.

Twenty consecutive stapled loop ileostomy closures in patients treated by restorative proctocolectomy were compared with the previous 20 sutured loop ileostomy closures in a non-randomised audit. Complications occurred in six of 20 stapled closures compared with seven of 20 sutured closures. Operating time and hospital stay were similar. The additional expense of stapling does not seem justified as complication rates, operating time and hospital stay are similar to sutured closures.

Adolescent↗
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↗