Non-pharmacological treatment of hypertension.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to L Davis.
Explore the source record for details and available documents.
2-Amino-3-ketobutyrate-CoA ligase (EC 2.3.1.29), or aminoacetone synthetase, has been purified by a nine-step procedure from 1.0 kg of beef liver to yield 8.8 mg of homogeneous enzyme. The homogeneous form of the enzyme, a monomer of M(r) = 44,000, shows unusually high absorption at 430 nm, with a ratio of absorbance at 280 and 430 nm of 2.6. On storage a species with an additional absorption peak at 332 is formed. Neither the 430-nm peak nor the 332-430 ratio is affected by pH or substrates. The peak at 430 nm and enzyme activity are both reduced by borohydride reduction and treatment with cysteine. The first 21 amino acids at the NH2-terminal of the ligase occur in the sequence Ser-Ala-Leu-Ala-Gln-Leu-Arg-Gly-Ile-Leu-Glu-Glu-Glu-Leu-Glu-Ser-Ile-Arg- Gly-Ala - Gly. No homology is detectable in the first 20 amino acids of the Escherichia coli and beef liver mitochondria enzymes. However, homology is found around the lysine residue to which the pyridoxal 5'-phosphate is attached in the two enzymes. A very hydrophobic peptide containing pyridoxal phosphate having the following sequence Leu-Leu-Gly-Val-Met-Asp-Gln-Val-Thr-Ile-Ile-Asn-Ser-Thr-Leu-Gly-Lys(P xy)-Ala- Leu-Gly-Gly-Ala-Ser-Gly-Gly-Tyr-Thr-Thr-Gly-Pro-Gly-Ala-Leu-Val has been isolated from the ligase. Fourteen residues around the lysine to which the pyridoxal 5'-phosphate is bound are completely identical with the pyridoxal 5'-phosphate containing peptide isolated from the E. coli 2-amino-3-ketobutyrate-CoA ligase.
Explore the source record for details and available documents.
We have developed preparative in situ hybridization (Prep-ISH) of complex DNA populations to mitotic chromosomes as a means of generating chromosome region-specific DNA subpopulations. Prep-ISH is a combination of two cytogenetic techniques: in situ hybridization of DNA molecules to mitotic chromosomes and chromosome microdissection. Here, we present test cases demonstrating the feasibility of this approach on mouse and human genomes, using single nuclei, single chromosomes, or single chromosomal subregions to assess sensitivity, specificity, and representation of the Prep-ISH technique. Prep-ISH has a number of applications in studies of gene expression and genome organization, including efficient cytogenetic sorting of tissue-specific cDNAs and genomic DNA libraries. In addition, Prep-ISH is likely to dramatically reduce the number of candidate genes to aid in gene discovery efforts and to improve efficiency of developing transcription maps and YAC and cosmid contigs through defined cytogenetic regions.
L-Threonine dehydrogenase was purified 10,000-fold to a specific activity approximately 300 mumol.min-1.mg-1 protein from porcine liver mitochondria. Purification to apparent homogeneity was achieved by sequential chromatography on DEAE Sepharose FF, Affi-Gel Blue, Sephacryl S-200, Matrex Gel Red A, and Matrex Gel Green A. The subunit molecular mass was estimated as 37 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while an apparent native molecular mass of 73 kDa was shown by gel filtration chromatography, suggesting a dimeric structure. The purified enzyme was subjected to proteolytic degradation and the resulting peptides were isolated exclusively by reverse-phase high-performance liquid chromatography. Approximately 70% of the total sequence was obtained and the N-terminal amino acid sequence of the intact polypeptide chain was thus tentatively extended to residue 40.
In this study, the 3M microvascular anastomotic system was utilized for the first time to perform an end-to-end anastomosis in a non-vascular tubular structure, which was compared to the conventional microvascular suture method. The bicornuate rat uterus was the preferred structure because of its anatomic similarity to the human fallopian tube. Thirty Sprague-Dawley rats underwent 3M and conventional end-to-end anastomoses of their bicornuate uteri. At different intervals, the animals were explored and biopsies were taken for examination under light microscopy. Overall patency rate with the 3M technique was 68 percent vs. 96 percent with the conventional technique. Complication rates were 40 percent with the 3M device and 12 percent with the conventional method. This study concludes that, if this method is to be used on non-vascular tubular structures, further modifications to the system and additional research are mandatory, in order to recommend this technique for clinical application.
Explore the source record for details and available documents.
New advances in systemic radionuclide therapy have increased the number of treatment options available for patients with painful osseous metastases. This form of therapy has three major appeals: 1) it addresses all sites of involvement; 2) selective absorption into bone limits irradiation of normal tissues; and 3) as a result, toxicity may be reduced and the therapeutic ratio improved. The clinical experience with radioactive phosphorus, strontium, samarium, and rhenium are reviewed. To date, the best studied and the only Food and Drug Administration approved agent is strontium-89. About 60% to 90% of patients treated with strontium-89 respond with complete or partial relief of pain for a median duration of 6 months. Large, prospectively randomized clinical trials have established the efficacy of strontium-89 as a first-line therapy and as an adjuvant to external-beam radiotherapy. Particularly advantageous is its usefulness in situations in which external-beam radiotherapy options have been exhausted and normal tissue tolerance has been reached. Newer radiopharmaceuticals are still under investigation.
Explore the source record for details and available documents.
Cisplatin is one of the most active cancer treatment agents available. Unfortunately, however, cisplatin causes many untoward side effects. Nurses play a major role in administering cisplatin and in preventing and managing the adverse effects associated with this drug. In order to maximize the quality of life of patients undergoing cisplatin treatment, nurses need a thorough knowledge of its uses, administration, and side effects. This article is the second of a two-part series about cisplatin. Part I provided a review of the mechanism of action, current uses, and administration guidelines. Part II discusses the most common side effects of cisplatin and the appropriate nursing assessment and management of patients undergoing treatment with this agent. In addition, future directions for the use of cisplatin and the use of alternative agents will be discussed.
PURPOSE: Radiation Therapy Oncology Group 85-28 represents a Phase I/II trial of accelerated fractionation in patients with brain metastases. METHODS AND MATERIALS: Patients entered had controlled or absent primary with metastases other than brain which were stable or only brain metastases with the primary uncontrolled. Karnosfky status was required to be greater than 60. Patients received 1.6 Gy twice daily separated by 4-8 hr delivered 5 days a week. The entire brain was treated to 32.0 Gy and the boost dose escalated from 16.0 Gy to 22.40 Gy and subsequently 32.00 Gy and 42.40 Gy. RESULTS: We observed no undue toxicity with escalating dose of irradiation. An incremental, although not statistically significant improvement in survival was noted with escalating doses. Median survival ranged from 4.2 months to 6.4 months with escalating dose of irradiation. Median survival also increased in patients with controlled primary tumors, non-lung primaries and solitary metastasis. CONCLUSION: The incremental improvement in survival in patients with good prognostic factors appeared encouraging. The Radiation Therapy Oncology Group will test the 54.4 Gy study against 30 Gy in 2 weeks in a Phase III trial based on the results of this trial.
L-Threonine-serine dehydratase catalyzes the conversion of L-threonine and L-serine to alpha-ketobutyric acid and pyruvate, respectively. The enzyme has been purified to homogeneity from extracts of sheep liver. In the past, various cofactors have been suggested for threonine dehydratase from both prokaryotic and eukaryotic tissue. While some direct evidence for the presence of pyriodoxal 5'-phosphate in impure preparations is present in the literature no direct evidence for the cofactor in homogeneous dehydrogenase from mammalian tissue has been reported. The threonine dehydratase of sheep liver has been obtained in a homogeneous form and a spectral study provides clear evidence for the presence of pyridoxal 5'-phosphate. Both the physical properties of homogeneous threonine dehydratase and a study of spectral properties of its cofactor are reported in this communication.
1. Phosphatidylinositol phospholipase C (PI-PLC) treatment of rachitic rat matrix vesicles (MVs) released about 80% of membrane-bound alkaline phosphatase (ALP), AMPase, PPiase into the media. 2. About 20% hydrolytic activity was not released from MV membranes by PI-PLC treatment. 3. SDS-polyacrylamide gel electrophoresis and Western blot analysis showed only one immunoreactive protein corresponding to the molecular weight of ALP present in the soluble fraction after PI-PLC treatment. 4. The specific activity of the released ALP was at least 5-fold higher than the residual activity. 5. After PI-PLC treatment, MVs also demonstrated an 80% reduction of AMP- or beta GP-dependent calcium deposition. 6. The soluble fraction containing 80% of ALP activity was unable to support calcium deposition. The mixing of the soluble and insoluble fractions after PI-PLC treatment failed to fully restore calcium-depositing activity.
We are investigating the roles of RNA synthesis, chromatin structure and nuclear matrix organization in establishing and maintaining transcription domains, using mitogen stimulated lymphocytes as a model system. In a continuing study, the effects of the RNA polymerase inhibitor DRB and of its removal on nuclear organization have been examined by EM cytochemistry and by immunofluorescence labelling of the nuclear matrix PI1, Sm and nucleolar fibrillarin antigens. Chromatin, interchromatin granules and nucleoli were extensively restructured after DRB, as were matrix antigens. According to cytochemical staining properties, the conformation of DRB-induced condensed chromatin resembled that in partially stimulated lymphocytes. The nucleoplasmic fibrogranular RNP network appeared little altered, but the fibrillar proteinaceous interchromatinic regions, interpreted as representing the nuclear matrix in situ, were more affected. After removal of DRB, nuclei recovered the organization and transcriptional activity of controls within 8 h. These results suggest that the matrix subtending transcription domains remains stable when transcription is arrested, even though the chromatin and individual RNP components of the domains are disorganized. The data further indicate that absence of transcription is not solely accountable for the highly aggregated state of the chromatin in resting lymphocytes.
The West Virginia School of Osteopathic Medicine (WVSOM) educated and retained more primary care physicians for practice in rural Appalachia than did any other U.S. medical school from 1978 through 1990. This article describes the most important methods used at WVSOM to place physicians in rural areas: (1) The school has a focused, achievable mission (to provide primary care physicians who are trained to meet the medical needs of rural Appalachia and to improve the health care of the rural Appalachian population) that is agreed upon by the administration, faculty, and students; (2) it participates in a multistate educational exchange program with a similar mission; (3) it emphasizes personalized and interactive recruiting, admission, and placement processes aimed to attract nontraditional, rural students; (4) it provides early and long-term clinical training in rural sites (both hospitals and physicians' offices); (5) it is dedicated primarily to the education of medical students rather than to research or other goals; and (6) it is a freestanding school in a rural environment. The authors state that although WVSOM is unusual in some respects, at least some of its methods may be useful to other medical schools as they seek to produce more primary care physicians for rural and other underserved areas.
A prospective, randomized, blinded trial involving 25 adult mongrel dogs was performed to evaluate whether placement of a fat graft or local instillation of recombinant tissue-plasminogen activator gel (rt-PA) could modify the development of a postlaminectomy membrane. One component of the study involved the performance of a lumbar laminectomy and placement of gel rt-PA, free fat, or no tissue placement over the exposed dura mater. Three months later the animals were killed and sections of spine were removed en bloc, decalcified, and examined histologically. No significant differences were found in the degree of cellular fibrosis or heavy collagen production. A similar laminectomy at another lumbar level was also followed by gel rt-PA, free fat, or no tissue placement. Three months after surgery, surgery was performed again at this level immediately before death. There were no differences in the adhesiveness of the laminectomy membrane to dura mater or roots. It was concluded that the local instillation of gel rt-PA after laminectomy did not inhibit scar formation or scar adherence to the dura mater.
Explore the source record for details and available documents.