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Biomedical subjects

K Nelson

Publications and source records attributed to K Nelson.

At least 145 records · Page 8Linked to original sources

Evolutionary genetics of the proline permease gene (putP) and the control region of the proline utilization operon in populations of Salmonella and Escherichia coli.

Virtually complete sequences (1,467 bp) of the proline permease gene (putP) and complete sequences (416 to 422 bp) of the control region of the proline utilization operon were determined for 16 strains of Salmonella, representing all eight subspecies, and 13 strains of Escherichia coli recovered from natural populations. Strains of Salmonella and E. coli differed, on average, at 16.3% of putP nucleotide sites and 17.5% of control region sites; the average difference between strains was much larger for Salmonella strains (4.6% of putP sites and 3.4% of control region sites) than for E. coli (2.4 and 0.9%, respectively). There was no difference in the distribution of polymorphic amino acid positions between the membrane-spanning and loop regions of the permease molecule, and rates of synonymous nucleotide substitution were virtually the same for the two domains. Statistical analysis yielded evidence of three probable cases of intragenic recombination, including the acquisition of a large segment of putP by strains of Salmonella subspecies VII from an unidentified source, the exchange of a 21-bp segment between two strains of E. coli, and the acquisition by one strain of E. coli of a cluster of 14 unique polymorphic control region sites from an unknown donor. An evolutionary tree for the putP and control region sequences was generally concordant with a tree for the gapA gene and a tree based on multilocus enzyme electrophoresis, thus providing evidence that for neither gene nor for enzyme genes in general has recombination occurred at rates sufficiently high or over regions sufficiently large to completely obscure phylogenetic relationships dependent on mutational divergence. It is suggested that the recombination rate varies among genes in relation to functional type, being highest for genes encoding cell surface and other proteins for which there is an adaptive advantage in structural diversity.

Amino Acid Sequence↗

Influence of ramipril on plasma atrial natriuretic peptide, antidiuretic hormone, angiotensin II and aldosterone in patients with chronic congestive heart failure.

UNLABELLED: In an open trial 5 mg ramipril daily for 2 weeks was administered to 11 patients with congestive heart failure. 24-hour plasma profiles of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), angiotensin II (Ang II) and aldosterone (Aldo) were determined before and on days 1 and 15 of ramipril treatment, respectively. Urinary sodium excretion was also measured at the same time points. There were no relevant differences in the 24-hour profiles of ANP and ADH. Ang II values dropped as expected on the first day of ramipril treatment from 11.2 pg/ml to 2.9 pg/ml at 3 h post administration and from 6.7 pg/ml (predose) to 1.8 pg/ml at 2 h post administration on day 15. Plasma aldosterone values increased slightly from day 1 to day 15, sodium excretion increased from 125.9 mmol to 166.5 mmol/24 h; however, both changes in the 24-hour profiles were nonsignificant. A clinically relevant improvement in the severity of CHF was observed. From a total of 121 reported symptoms according to McKee et al., 35 showed an improvement; 81 remained unchanged, in only 5 symptoms a deterioration was observed. According to the NYHA-classification 5 patients improved from grade III to II, 6 remained unchanged. CONCLUSION: ACE inhibition does not induce changes in ANP or ADH levels in the resting state while Ang II decreases. A slight increase in aldosterone levels may be due to increased sodium excretion.

Aged↗

Influence of two guar preparations on glycosylated hemoglobin, total cholesterol and triglycerides in patients with diabetes mellitus.

Guar smoothens postprandial glucose peaks and reduces serum cholesterol. Both properties are advantageous for diabetic patients and can be realized, in part, by adding fiber to the diet. Depending on the blood glucose concentration, a small portion is incorporated into hemoglobin (HbA1), building a largely irreversible complex, making it a long-term indicator of blood glucose status. HbA1 may increase from a normal value of about 5% to as much as 20% of total hemoglobin in diabetics. This study tested the efficacy of two guar preparations in diabetic patients over 3 months by measuring HbA1, cholesterol and triglycerides. Forty diabetic patients with HbA1 > 10% ingested either 3 x 4 g daily of a new guar preparation (GU-052, Steigerwald, Darmstadt, Germany) or 3 x 5 g daily of Glucotard (Boehringer, Mannheim, Germany) for 12 weeks. Before and after 30, 60 and 90 days of treatment, HbA1, cholesterol and triglycerides were determined. After 90 days of treatment, GU-052 caused a reduction in HbA1 from 12.6 +/- 2.6% to 10.5 +/- 1.5% (-15.6 +/- 9.0%) in the GU-052 group and from 12.0 +/- 2.6% to 10.9 +/- 1.82% (-8.6 +/- 7.2%) in the Glucotard group. Cholesterol was reduced from 269 +/- 28 mg/100 ml on day 0 to 227 +/- 18 mg/100 ml on day 90 in the GU-052 group and from 261 +/- 40 to 235 +/- 26 mg/100 ml in the Glucotard group. Both GU-052 and Glucotard had little effect on plasma triglycerides. Fewer unpleasant side effects were reported for the GU-052 preparation than for Glucotard.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunoreactive parathyroid hormone after volume change in normo- and hypotensive hemodialysis patients.

The effects of reduced blood volume during hemodialysis on circulating immunoreactive parathyroid hormone (PTH) were determined in relation to changes in blood pressure and heart rate in normo- and hypotensive patients with end stage renal failure. During dialysis the plasma concentration of PTH did not change in normotensives, while PTH increased significantly in patients with a fall in blood pressure during a 25% reduction in effective intravascular volume. The blood volume was measured continuously during hemodialysis using the authors' hemoglobin measurement system. The decrease in blood volume in both groups was comparable. The results suggest that secretion of PTH during hemodialysis may play a role in hemodynamic instability during hemodialysis.

Adult↗

Effect of deoxyribonucleic acid ploidy status on survival of patients with carcinoma of the endometrium.

This retrospective study was performed to determine the clinical usefulness of deoxyribonucleic acid (DNA) ploidy and the amount of DNA in the nucleus of the tumor cell on the prognosis of patients with carcinoma of the endometrium. Five year follow-up study was obtained for 121 patients. Flow cytometric analysis was used to determine tumor cell ploidy from paraffin-embedded specimens. Patients were grouped according to ploidy, clinical stage and grade and whether or not they received postoperative radiation. The data were subjected to a Cox proportional hazards regression analysis, and only ploidy status and clinical stage were significantly associated with survival time. Of the 121 patients observed, 44.6 per cent were aneuploid and 55.4 per cent, euploid. Preliminary chi-square analysis indicated a strong survival advantage to those patients with euploid endometrial carcinoma. The over-all five year survival rate for patients with aneuploid tumors was 53.7 per cent, as opposed to 80.6 per cent for patients with euploid tumors (p less than 0.01). Eighty-seven patients were Stage I, 39 aneuploid, 48 euploid. The five year survival rate for patients with Stage I aneuploid was 71.8 versus 85.4 per cent for those who were euploid. Twenty-one patients were Stage II; seven aneuploid and 14 euploid. The five year survival rate for aneuploid patients was 14.3 versus 85.7 per cent for euploid patients. The over-all five year survival rate for those with Stage I and II was 85.5 per cent euploid and 63.0 per cent aneuploid, p less than 0.05. Patients with Stage III or IV had poor outcome regardless of ploidy status. These data show that patients with euploid Stage I and II carcinoma of the endometrium have a significant survival advantage over patients with aneuploid tumors. We, therefore, believe that ploidy status may be used to facilitate the determination of prognosis in carcinoma of the endometrium.

Adenocarcinoma↗

Characterization and clonal distribution of four alleles of the speA gene encoding pyrogenic exotoxin A (scarlet fever toxin) in Streptococcus pyogenes.

Streptococcus pyogenes strains producing pyrogenic exotoxin A (scarlet fever toxin) have recently caused episodes of streptococcal toxic-shock-like syndrome (TSLS). We exploited knowledge of genetic diversity and relationships among exotoxin A-producing patient strains provided by multilocus enzyme electrophoresis to select strains for comparative sequencing of toxin genes. Our analysis identified four alleles of speA in natural populations, one of which (speA1) occurs in many distinct clonal lineages and is probably old. Two other alleles (speA2 and speA3), characterized solely by single amino acid substitutions, were each identified in single clones that together have caused the majority of TSLS episodes. It is unlikely that these alleles have had a long association with S. pyogenes clones. A fourth allele (speA4) also is present in a single phylogenetic lineage and is 9% divergent from the other three toxin alleles. An absence of synonomous (silent) nucleotide changes in speA2 and speA3 is unusual and suggests that the allelic variation is not selectively neutral, which implies that the toxins are not functionally equivalent. These results may be important in helping to understand the recent increase in frequency and severity of disease caused by S. pyogenes.

Alleles↗

Declining seroprevalence and transmission of HTLV-I in Japanese families who immigrated to Hawaii.

This study examined the seroprevalence and transmission of human T cell lymphotropic virus type I (HTLV-I) in Japanese families who originated in Okinawa, an area in which HTLV-I is endemic, and who were currently residing in Hawaii, a nonendemic area. Among a cohort of Japanese men whose sera were collected in Hawaii in 1967-1975, those of Okinawan ancestry had an HTLV-I seroprevalence of 11.4%. This study, conducted in 1987-1988, sampled 142 index subjects from this male cohort and tested them along with their wives, children, and spouses of the children for HTLV-I antibodies. Seropositivity in their wives was 11.4% and 41.2% among the seronegative and seropositive index subjects, respectively; seropositivity also increased from 29.4% to 35.3% to 58.8% with the husbands' increasing antibody levels by tertiles. Elevated antibody levels may be a marker for infectivity, which is associated with more efficient sexual transmission of HTLV-I. The age-adjusted odds ratio for the association of seropositivity between husband and wife, however, was four times lower than that reported among native Okinawans. In addition, a substantially low seroprevalence (1.3%) was found among their offspring. The decline in HTLV-I transmission in this migrant population may be due to low infectivity in the parent generation who live in a nonendemic environment, increasing numbers of offspring marrying outside of the Okinawan community, and improved living circumstances.

Aged↗

Nucleotide polymorphism and evolution in the glyceraldehyde-3-phosphate dehydrogenase gene (gapA) in natural populations of Salmonella and Escherichia coli.

Nucleotide sequences of the gapA gene, encoding the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, were determined for 16 strains of Salmonella and 13 strains of Escherichia coli recovered from natural populations. Pairs of sequences from strains representing the eight serovar groups of Salmonella differed, on average, at 3.8% of nucleotide sites and 1.1% of inferred amino acids, and comparable values for E. coli were an order of magnitude smaller (0.2% and 0.1%, respectively). The rate of substitution at synonymous sites was significantly higher for codons specifying the catalytic domain of the enzyme than for those encoding the NAD(+)-binding domain, but the nonsynonymous substitution rate showed the opposite relationship. For Salmonella, statistical tests for nonrandom clustering of polymorphic sites failed to provide evidence that intragenic recombination or gene conversion has contributed to the generation of allelic diversity. The topology of a tree constructed from the gapA sequences was generally similar to that of phylogenetic trees of the strains based on multilocus enzyme electrophoresis, but the level of divergence of gapA in Salmonella group V from other Salmonella and E. coli strains is much greater than that indicated by DNA hybridization for the genome as a whole.

Amino Acid Sequence↗

Streptococcus pyogenes causing toxic-shock-like syndrome and other invasive diseases: clonal diversity and pyrogenic exotoxin expression.

Genetic diversity and relationships among 108 isolates of the bacterium Streptococcus pyogenes recently recovered from patients in the United States with toxic-shock-like syndrome or other invasive diseases were estimated by multilocus enzyme electrophoresis. Thirty-three electrophoretic types (ETs), representing distinctive multilocus clonal genotypes, were identified, but nearly half the disease episodes, including more than two-thirds of the cases of toxic-shock-like syndrome, were caused by strains of two related clones (ET 1 and ET 2). These two clones were also represented by recent pathogenic European isolates. A previous report of a relatively high frequency of expression of exotoxin A among isolates recovered from toxic-shock-like syndrome patients in the United States was confirmed; and the demonstration of this association both within clones and among distantly related clones supports the hypothesis that exotoxin A is a causal factor in pathogenesis of this disease. Near identity of the nucleotide sequences of the exotoxin A structural gene of six isolates of five ETs in diverse phylogenetic lineages was interpreted as evidence that the gene has been horizontally distributed among clones, presumably by bacteriophage-mediated transfer.

Bacterial Proteins↗

The growth response of BG-1 ovarian carcinoma cells to estradiol, 4OH-tamoxifen, and tamoxifen: evidence for intrinsic antiestrogen activation.

The influence of estrogen (E) and antiestrogen (AES) on the in vitro growth of BG-1 ovarian carcinoma cells, which express steroid receptors was examined (K. R. Geisinger, T. E. Kute, M. J. Pettenati, C. E. Welander, Y. Dennard, L. A. Collins, and M. E. Berens, Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors, Cancer 63, 280-288, 1989). All determinations were simultaneously referenced under similar conditions to MCF-7 cells, a well-established cell line for modeling hormonal responses in breast cancer. In "complete" media containing fetal calf serum (FCS, 10%), MCF-7 cell numbers increased approximately 7 x in 7 days, remaining at this level Days 8-15. In contrast, BG-1 cells achieved similar numbers by Day 7, but showed apparent exponential growth over Days 8-15 to 15-20 x. Phenol red-free media containing 10% FCS (less than 20 pg estradiol (E2)/ml by RIA) was used to assess responses to E and AES. Growth of both MCF-7 and BG-1 cells slowed in E-free media. E2 (10 nM) stimulated the growth of both cell lines, yet was responsible for exponential increases during Days 8-15 only in BG-1 cell numbers (50-70 x). The metabolically active AES (4OH-tamoxifen, 50 nM) reduced E2-stimulated MCF-7 growth to 3-4 x, while tamoxifen (50 nM) had no effect. Rescue with 10 microM E2 fully overcame the AES inhibition of MCF-7 proliferation. In contrast, BG-1 cells experienced significant E2-stimulated growth reductions in the presence of either 4OH-tamoxifen or tamoxifen. E2 was observed to rescue BG-1 cells from both of these antagonists. We conclude that BG-1 ovarian carcinoma cells respond in vitro to E and AES. Moreover, by virtue of responses to tamoxifen, BG-1 cells may have an intrinsic capacity to hydroxylate tamoxifen to its active metabolite. This property of ovarian carcinoma cells might be worth exploiting in the design of more effective combination chemotherapy regimens.

Carcinoma↗

The Association of Teachers of Preventive Medicine's recommendations for postgraduate education in prevention.

The Guide to Clinical Preventive Services, prepared in 1989 by the U.S. Preventive Services Task Force, assesses the effectiveness of 169 types of preventive interventions. In 1990, the Association of Teachers of Preventive Medicine formed a panel to review the guide and recommend ways it could be used to enhance both undergraduate and postgraduate medical education. This paper outlines the panel's recommendations of the types of knowledge and attitudes on which postgraduate medical education in prevention should be built. Detailed recommendations are presented, based on the summary findings of the guide, for residency education in prevention. Implementation of these recommendations will integrate preventive services into the continuum of medical care. These recommendations are presented to achieve the goal of educating physicians to approach the total patient, putting the patient's health rather than the disease process in the forefront of primary medical care.

Education, Medical, Graduate↗

Pulmonary effects of ischemic limb reperfusion: evidence for a role for oxygen-derived radicals.

OBJECTIVE: To evaluate the lung as a reperfusion target after limb ischemia-reperfusion, and to measure specifically the oxygen radical response to this reperfusion. DESIGN: Paired simple randomized, with continuous interval data in dependent variable and both continuous and nominal independent variables. SUBJECTS AND INTERVENTION: Sprague-Dawley male rats (n = 195) were anesthetized and both hind limbs occluded for 3.75 hr, the overnight LD50. Alveolar lavage was performed on the animals 1 hr after reperfusion or on survivors 20 hr after reperfusion. Groups were either undosed or pretreated with alpha-tocopherol as an antioxidant (50 mg/kg.day) 2 days before ischemia. MEASUREMENTS AND MAIN RESULTS: Luminol-enhanced chemiluminescence was measured in both phorbol myristate acetate-stimulated and unstimulated macrophages. Nanomoles of superoxide radicals per 10(6) alveolar cells/min were also measured using a cytochrome c reduction assay. A significant (p less than .01, Student's t-test), time-dependent increase in response of cells from ischemic-reperfused rats was seen. Pretreatment with antioxidant had no effect at 1 hr, but significant differences were seen in the 20-hr survivors. CONCLUSIONS: These studies show that alveolar lavage cells, 95% macrophages, reflect the reperfusion of ischemic-reperfused hind limbs by a significant increase in oxygen radical activity, an effect partly suppressed in antioxidant-dosed survivors.

Animals↗

Influence of ramipril on renal function in patients with chronic congestive heart failure.

Ramipril was administered to 13 patients, aged 49-80 years, weighing 53.5-90.3 kg, with congestive heart failure (CHF) for 2 weeks in an open trial. One patient dropped out after day 1 and another accidentally received another angiotensin-converting enzyme (ACE) inhibitor, so that 11 patients remained for analysis. Each patient received 5 mg of ramipril daily for 2 weeks, followed by a 1-week washout period. Urine was collected in 4-h fractions for 12 h followed by a 12-h fraction on days 1, 8, and 15. Creatinine clearance, as well as the excretion of albumin and the urinary brush border enzymes gamma-glutamyl transferase (GGT), alanine aminopeptidase (AAP), N-acetyl-beta-D-glucosaminidase (NAG), and lactate dehydrogenase (LDH) were determined. The values for albumin excretion, creatinine clearance, GGT, AAP, NAG, and LDH obtained for the various days during the time course before and during multiple dosing were subjected to an analysis of variance followed by Scheffe's test for means. Daily albumin excretion decreased during treatment with ramipril from 23.8 +/- 27.4 mg/24 h (baseline) to 12.9 +/- 15.1 (day 1), 10.8 +/- 15.6 (day 8), and 12.4 +/- 12.7 mg/24 h (day 15). The differences were significant (alpha = 0.05) when compared to pretreatment albumin excretion. Creatinine clearance increased from 78.8 +/- 38.3 ml/min (baseline) to 82.4 +/- 34.6 (day 1), 85.1 +/- 28.5 (day 8), and 91.7 +/- 36.4 ml/min (day 15). The change on day 15 was significant (alpha = 0.05) when compared to pretreatment values.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosamine↗