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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 343 records · Page 19Linked to original sources

Cystic fibrosis: diagnostic testing and the search for the gene.

Cystic fibrosis (CF) is a lethal genetic disorder inherited as an autosomal recessive at a frequency of about 1/2000 in Caucasian populations. A DNA marker genetically linked to CF was identified through a collaborative effort by random screening with a collection of RFLP markers on a set of CF families. The marker (CRI-L917) was mapped to chromosome 7. Construction of a genetic linkage map spanning the entire chromosome has led to the identification of a subset of 11 markers close to and flanking the CF locus. Using techniques of pulsed-field gel electrophoresis, which allow very large DNA fragments to be separated, we used seven probes to generate a long-range restriction map covering 12 million base pairs surrounding the CF locus. Information from the map is being used to isolate new probes closer to the CF gene. Methods being developed will allow candidate genes to be tested for their ability to correct defects in ion transport in cultured CF cells.

Chromosome Mapping↗

Social factors influence haloperidol-induced catalepsy in rat.

This study employed manipulations which presumably influence social interactions in rats: (1) paired housing with a heavier conspecific and (2) exposure to the odors of other rats. The dependent variable was the akinetic state induced by haloperidol, a neuroleptic and dopamine antagonist. In Experiment 1, adult male Long-Evans hooded rats were matched by weight and caged alone or in pairs with one rat 30 g heavier than its cagemate. All rats received haloperidol (1.5 mg/kg) and catalepsy testing. Heavy rats showed more catalepsy than the lighter member of pairs or weight-matched, singly housed controls. In Experiment 2, adult male rats were left unrecaged or were recaged into cages with bedding recently soiled by females or other adult males. After haloperidol (1.0 mg/kg), the rats exposed to bedding soiled by other adult males showed more catalepsy than did the control groups. Thus, the results of both experiments indicated that social factors can influence the akinesia induced by dopamine antagonists.

Animals↗

Evaluation and treatment of urinary incontinence in long term care.

All elderly patients with established urinary incontinence residing in an intermediate care facility during one year were evaluated for medical and urological conditions contributing to the incontinence; treatment was initiated for all diagnosed problems if possible. Unstable detrusor function (65%), sphincter weakness (13%), and overflow incontinence (10%) were all frequent urological causes, although several patients required extensive testing in addition to cystometrics to establish a complete diagnosis. Frequent nonurological causes of incontinence included behavioral problems (53%), immobility (45%), medication problems (24%), diabetes (18%), and local pathology (47%). Thirty-seven percent had three or more conditions identified. Treatment aimed at nonurological causes was more successful in ameliorating incontinence than urological medication; side effects were significant limitations to urological treatment success. Of the 22 patients who completed evaluation, treatment, and follow-up, five patients (23%) were cured, three (14%) showed at least a 65% decrease in incontinence, four (18%) showed at least a 30% decrease in incontinence, and 10 (45%) showed no change or worsened. We conclude that nonurological problems frequently contribute to urinary incontinence in long term care facilities; incontinence in some of these patients can be improved without urological therapy. Nonurological problems need careful definition and treatment; patients whose incontinence persists require comprehensive urological evaluation and therapy. A complete solution to incontinence in this setting may require safer drugs and better understanding of urinary pathophysiology.

Aged↗

Vaccinia virus-encoded ribonucleotide reductase: sequence conservation of the gene for the small subunit and its amplification in hydroxyurea-resistant mutants.

The vaccinia virus gene that encodes the small subunit of ribonucleotide reductase was localized to the HindIII F fragment by using degenerate oligonucleotide probes. DNA sequencing revealed a leftward-reading open reading frame that predicted a protein of 37 kilodaltons whose amino acid sequence was much more homologous to the mouse and clam M2 sequences (approximately 80%) than to the corresponding herpesvirus (approximately 27%) or procaryotic (approximately 19%) gene products. Vaccinia virus mutants selected for the ability to grow in high concentrations of a specific inhibitor of ribonucleotide reductase, hydroxyurea, amplified the M2 gene and harbored tandem arrays (2 to 15 copies) of the gene within the HindIII F region. RNA isolated at early times after infection with wild-type virus and probed with an internal fragment of the M2 gene indicated one major (1.2 kilobases) and two minor (4.0 and 2.1 kilobases) transcripts. S1 nuclease analysis and primer extension experiments identified an RNA start site 12 nucleotides upstream of the putative initiation ATG codon.

Amino Acid Sequence↗

Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia--a Cancer and Leukemia Group B Study.

One hundred ninety-five adult patients with refractory or first relapse acute myelogenous leukemia (AML) were randomly assigned to receive high-dose cytarabine (HiDAC), 3 g/m2 as a three-hour intravenous (IV) infusion every 12 hours for four doses, followed by 6,000 IU/m2 asparaginase (ASNase) administered at hour 42, or HiDAC without ASNase. Treatment was repeated on day 8. The median patient age was 52 years. There was an overall superior complete remission (CR) rate for HiDAC/ASNase (40%) v HiDAC (24%), P = .02. Subset analysis according to prior response and age showed the following CR rates: 54% from HiDAC/ASNase treatment of refractory AML in patients less than 60 years, and 31% in patients greater than 60 years; CR from HiDAC in the same refractory groups were 18% (less than 60) and 0% (greater than 60); 37% from HiDAC/ASNase treatment of relapsed AML in patients less than 60 years, and 43% in patients greater than 60 years; CRs from HiDAC in the same relapsed groups were 33% (less than 60) and 21% (greater than 60). Toxicity in the two treatment arms was comparable and consisted primarily of leukopenia, thrombocytopenia, mild hepatic dysfunction, diarrhea, conjunctivitis and serositis, and hyperglycemia. There was only one case of transient cerebellar toxicity and no cutaneous toxicity. Median time to full hematologic recovery was 5 weeks. There was an overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks) compared with HiDAC (15.9 weeks), P = .046, primarily attributable to effects in refractory patients. Median time to failure for refractory patients who achieved CR was 38.5 weeks with HiDAC/ASNase, and 13.3 weeks for those treated with HiDAC. For relapsed patients in CR from HiDAC/ASNase the median time to failure was 17.7 weeks and 18.3 weeks for HiDAC. The overall 42% CR rate from HiDAC/ASNase v 12% from HiDAC in patients with refractory AML indicates that HiDAC/ASNase is not cross-resistant with standard-dose cytarabine (SDAC) and anthracyclines. We conclude that HiDAC/ASNase has substantial activity in poor-prognosis AML and that this combination warrants further trials in earlier stage disease.

Antineoplastic Combined Chemotherapy Protocols↗

Transduodenal sphincteroplasty using the carbon dioxide laser.

A new method of performing a transduodenal sphincteroplasty using the carbon dioxide laser has been done in 43 patients. The advantages include more accurate incisions and exposure, less bleeding and no need for a sutured anastomosis. The procedure is particularly suited for the surgical treatment of pancreas divisum.

Ampulla of Vater↗

Computer-controlled 22-channel stimulator for limb movement.

The Nucleus multichannel implantable hearing prosthesis (Nucleus Ltd., Sydney, Australia) has been modified by computer programming (MOCO, Inc., Scituate, Mass.) into a 22-channel neural stimulator for use in functional electrical stimulation (FES). Individual or multiple channels can be sequenced and adjusted for their individual pulse amplitude, width and frequency so that activation of single and multiple nerves can be achieved. Anesthetized rabbits' sciatic nerve branches (lateral and medial) were stimulated to produce single, or co-contraction at the ankle and simultaneous bilateral joint movements. The spiral (helix) electrode was also found suitable in these experiments. In planning for the stimulator's use in paraplegic subjects, information was obtained for human lower extremity peripheral nerves. In 9 patients undergoing lower extremity amputation, threshold and maximal levels of stimulation plus nerve diameters were obtained on 21 nerves. The design for the wearable ambulation unit to control the 22-channel stimulator and electrode tresses with helix electrodes has been completed.

Animals↗

Do Xenopus oocytes have a heat shock response?

Xenopus oocytes have been reported to respond to heat shock in a unique fashion by inducing the translation of performed mRNA encoding the 70,000-Da heat shock protein (hsp70). We have reexamined Xenopus oocytes for this response by analyzing [35S]methionine-labeled oocyte proteins synthesized at ambient (22 degrees C) and at heat shock (35 degrees C) temperatures. Our objective was to use this response in studies directed at understanding how inactive messages are selected for translation. We found no evidence for the induction of hsp70 in completely defolliculated heat-shocked stage 6 oocytes, although they do appear to synthesize constitutively a 70-kDa protein which is a member of the hsp70 complex of proteins. Defolliculated oocytes were also found to be thermotolerant in vitro. Unfertilized eggs, naturally defolliculated at ovulation, also failed to induce detectable hsp70 synthesis after heat shock. In contrast, fibroblasts and the approximately 1000 follicle cells comprising the theca and follicular layers surrounding each oocyte have a classic heat shock response regulated at the transcriptional level. The hsp70 synthesized by stressed follicle cells was not transported into oocytes. We suggest that oocytes in general may represent an exception to the apparent universality of the heat shock response.

Animals↗