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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 289 records · Page 16Linked to original sources

Mechanism of the acyl-carbon cleavage and related reactions catalyzed by multifunctional P-450s: studies on cytochrome P-450(17)alpha.

It is now well-known that conventional cytochrome P-450s catalyze hydroxylation reactions using an iron mono-oxygen species, the structure of which, as inferred from chemical model studies, may be drrepresented by the following canonical forms: FeV==O<-->(.+)FeIV==O<-->FeIV--O(.). Certain multifunctional P-450s, notably those involved in steroid biosynthesis, catalyze, in addition to hydroxylation reactions, an acyl-carbon cleavage process in which the participation of an iron peroxide intermediate, FeIII--OOH, has been suggested. However the possibility still exists that the C--C bond cleavage may also occur using the FeV==O species. We have scrutinized the chemical consequences of involving either an FeV==O or an FeIII--OOH species for five different C--C bond cleavage reactions. With respect to the status as well as the origin of hydrogen and oxygen atoms, in four of the examples the mechanism involving the FeV==O species makes the same prediction as that using the iron peroxide intermediate, that is, the incorporation of an atom of oxygen from O2 into acyl part of the cleaved fragment. The fifth example, however, involving the formation, with pig testes microsomes, of 17 alpha-hydroxyandrogen (androst-5-ene-3 beta,17 alpha-diol) from pregnenolone, presents an interesting contrast--in this case different outcomes are predicted by the two mechanisms. These possibilities have been experimentally evaluated using substrates stereo- and regiospecifically labeled with heavy isotopes and incubated with pig testes microsomes under either 16O2 or 18O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Viral prophylaxis in combined pancreas-kidney transplant recipients.

The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.

Adult↗

Heat-inducible proteins that react with antibodies to chaperonin60 are localized in the nucleus of a fish cell line.

We report in the present paper that proteins which react with a polyclonal antibody (pAb) raised against the heat-shock protein chaperonin60 (cpn60) were revealed by indirect immunofluorescence in the nucleus of a fish (fathead minnow, Pimephales promelas) cell line after heat-shock. This immunoreactive cpn60 associated with the nucleolus and with discrete foci. An increased abundance of two nuclear proteins of approx. 57 and 42 kDa, present in approximately equal amounts, was detected by Western blotting using an anti-cpn60 pAb as a probe during the same time period that cpn60 was revealed in the nucleus. These proteins also reacted with a monoclonal antibody (mAb) against human cpn60 but did not react with an mAb against the cytoplasmic chaperonin, TCP1. The kinetics of translocation and pattern of nuclear localization of this immunoreactive cpn60 differed from that of stress70, another major family of heatshock proteins. We suggest that these nuclear immunoreactive cpn60 proteins are members of the cpn60 family and that they play a chaperone role in folding and assembly of proteins in the nucleus which is distinct from that of stress70.

Animals↗

Correlates of ventricular ectopic activity in isolated systolic hypertension. SHEP Cooperative Research Group.

Ventricular ectopic activity was recorded at baseline in 5.6% of the 12-lead electrocardiograms and 8.2% of the 2-minute rhythm strips of 4674 subjects with isolated systolic hypertension (systolic blood pressure 160 to 219 mm Hg, diastolic blood pressure < 90 mm Hg) participating in the Systolic Hypertension in the Elderly Program (SHEP). In this study 1.3% had 6 to 10 ventricular premature beats (VPB), and 0.7% had > 10 VPB on the 2-minute rhythm strip. Correlates of VPB presence on the 12-lead ECG were older-age male sex, presence of Q/QS pattern and higher heart rate. Participants with serum potassium < 3.5 mmol/L had a higher prevalence of VPB. Similarly, the number of VPB on the 2-minute rhythm strip was associated with male sex, increasing age, with lower serum potassium, history of palpitations, and presence of Q/QS patterns.

Aged↗

Gender differences in lipid alterations following combined pancreas-kidney transplantation.

We have previously demonstrated that the lipid profile improves following successful combined pancreas-kidney transplantation (PKT). In this study, we examined whether changes in the lipid profile were different in men than in women following PKT. Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and the TC to HDL ratio (TC/HDL) were evaluated in 47 patients (27 men and 20 women) with normal graft function following PKT. Lipids were evaluated at regular intervals 3.5 months to 2.2 years post-PKT (a total of 317 observations). After PKT, TC/HDL decreased (P < .05), TC was unchanged, and HDL increased (P < .05) in both men and women. Although TG decreased in both men and women, it reached statistical significance in men only (P < .05). There were no significant differences in any lipid parameters between men and women before PKT, but after PKT, TC, TG, and HDL were higher in women (240 +/- 11, 183 +/- 17, and 64 +/- 19 mg/dL, respectively) than in men (207 +/- 6, 143 +/- 11, and 53 +/- 2 mg/dL, P < .05 for each). When post-PKT values were analyzed for trends over time, both TC and TG decreased (P < .05 for both) without any significant difference in trends between men and women. When six individuals who had received lovastatin at any time during their postoperative course were removed from analysis, the gender differences in TG post-PKT and the decrease in TG over time were no longer statistically significant (P > .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Visual field deficits in early age-related macular degeneration.

Patients with early age-related macular degeneration (AMD) may retain good visual acuity but experience distortion and other qualitative visual changes. The purpose of the present study was to determine whether deficits of form recognition, as well as of light sensitivity, were related to retinal pigment epithelial (RPE) atrophy and/or drusen. We assessed form recognition deficits by the Amsler grid and by a perimetric test of letter recognition and sensitivity deficits by the macular threshold test of the Humphrey Field Analyzer in 59 patients with AMD and visual acuities of 20/40 or better. The number of defects on each test was compared with the area of RPE atrophy and with the area of drusen determined from fundus photographs. Multiple regression analyses based on ordinal data revealed that the number of visual field defects by each test was significantly correlated with the area of atrophy, but not with the area of drusen. There was also no significant tendency for a patient with a regional preponderance of drusen to have more impairment in the corresponding visual field. These results suggest that deficits of form recognition, as well as of sensitivity, in patients with early stages of AMD can be attributed to alteration of photoreceptor function associated with RPE atrophy, but not with drusen.

Aging↗

Cholesterol treatment facilitates spatial learning performance in DBA/2Ibg mice.

DBA/2Ibg mice were treated with cholesterol pellets for 11 days. On the seventh day after treatment, animals began 5 consecutive days of training on the spatial form of Morris water task, followed on the third and fourth days by a probe trial, and random platform training on the fifth day. DBA mice with cholesterol pellets exhibited enhanced performance compared to DBA mice that underwent a sham surgery. Our results suggest that subchronic treatment with the steroid hormone precursor, cholesterol, enhances spatial learning performance in DBA mice.

Animals↗

Mandibular form and position in 10-year-old boys.

It is unclear whether malocclusion characterized by jaw discrepancy is caused by variations in mandibular position, mandibular size, or a combination of the two. To clarify the situation, the mandibular outlines of 124 10-year-old boys, equally divided among the Angle classes, were generated from cephalograms with a computer plotting technique. The mean plots for each of the groups were superimposed on S-N and Go-Gn. These showed mandibular form and size to be similar in the Class I and Class III groups and in both divisions of Class II. The position of Class III mandibles was more anterior and rotated forward in relation to the cranial base compared with the other groups. Statistical analysis confirmed these findings. There was evidence to support the idea that Class II, Division 2 malocclusion is largely a dentoalveolar rather than a skeletal entity.

Cephalometry↗

Brief cognitive-behavioral treatment for adolescent suicide attempters and their families.

OBJECTIVE: This article describes a brief, standardized, cognitive-behavioral treatment program for adolescent suicide attempters and their families. METHOD: Successful Negotiation Acting Positively (SNAP) treatment consists of a series of structured activities that create a positive family atmosphere, teach problem-solving skills, shift the family's understanding of their problems to troublesome situations rather than difficult individuals, and build confidence in the treatment professional, thereby reducing conditions associated with future attempts. RESULTS: SNAP treatment has been systematically administered to more than 100 suicidal adolescents and their families as part of an ongoing treatment study. Although these results are not yet available, our initial experience suggests that SNAP treatment can be delivered in a reliable fashion and is well accepted by both patients and therapists. CONCLUSIONS: Although suicidality in youth constitutes a major public health problem, few therapeutic interventions have been developed specifically for suicidal adolescents. SNAP treatment addresses a number of issues critical to successful interventions with this population, including their historically poor treatment compliance, the need for family involvement in treatment, and an emphasis on coping and problem-solving strategies. Moreover, the brief, structured format of SNAP treatment is consistent with the growing trend toward standardized, empirically tested, and cost-efficient interventions.

Adolescent↗

Flow cytometric analysis of the stimulatory response of T cell subsets from normal and HIV-1+ individuals to various mitogenic stimuli in vitro.

A novel technique is described which allows the study of the responses of T cell subpopulations stimulated in bulk cultures without interfering with cell-cell interactions. The number and phenotype of lymphoblasts developing following stimulation with phytohaemagglutinin (PHA), anti-CD3, staphylococcal protein A (SPA) and pokeweed mitogen (PWM) was determined in HIV-1- and HIV-1+ patients using a new five-parameter flow cytometric method. We found that normal T cells responded faster to PHA than to any of the other mitogens tested. The peak of the PHA response occurred on day 3, followed by anti-CD3 and SPA on day 4 and PWM mitogen on day 5. Although PHA and anti-CD3 stimulated up to 95% and 80% of lymphocytes, respectively, SPA and PWM stimulated only 40% and 30% of cells, respectively. A defective T cell response was observed in lymphocytes cultured from asymptomatic HIV-1+ patients compared with negative controls. This loss of response was related to a selective mortality of T cells following mitogenic stimulation, referred to as activation-associated lymphocyte death (AALD). The results showed that stronger mitogens (PHA and anti-CD3) induced AALD in a larger proportion (50-60%) of T cells than weaker mitogens such as SPA and PWM (30-40%), and that AALD affected different lymphocyte subsets to different extents. AALD occurred more frequently in total CD8+ and CD45RO+ T cells compared with CD4+ and CD45RA+ T cells, but memory CD4+ T cells were the population most severely affected in samples from HIV-1+ donors.

Acquired Immunodeficiency Syndrome↗

The consistency of reports about feelings and emotions from people with intellectual disability.

Sixty-seven subjects with mild or moderate intellectual disability were assessed on a variety of measures of emotion. All of the measures were self-report measures and all of the data is based on reports by the subjects' themselves. The battery included the Zung Self-Rating Anxiety Scale, the Zung Depression Inventory, the General Health Questionnaire and the Eysenck-Withers Personality Test. The results reveal an impressive amount of convergent validity in the subjects' emotional systems.

Adult↗

Age, race, and gender variation in the utilization of coronary artery bypass surgery and angioplasty in SHEP. SHEP Cooperative Research Group. Systolic Hypertension in the Elderly Program.

OBJECTIVE: To assess variability in the use of coronary artery bypass grafting (CABG) and percutaneous transluminal angioplasty (PTCA) in the Systolic Hypertension in the Elderly Program (SHEP) cohort with incident coronary heart disease (CHD) by age, sex, and race. DESIGN: Retrospective analysis of a multicenter prospective cohort study. SETTING: Community-based ambulatory population in academic centers. PATIENTS: Among 4736 subjects initially enrolled in SHEP, there were 432 incident cases of CHD, excluding those patients who experienced rapid or sudden cardiac death. MAIN OUTCOME MEASURE: Incident cases of CHD who underwent CABG or PTCA. RESULTS: Of those participants > or = 60 and < 75 years of age, 7.3% underwent PTCA, compared with 3.9% of those > or = 75 years (P = 0.14). 15.4% of those < 75 underwent CABG surgery, compared with 7.8% of those 75 and older (P = 0.018). When both of these endpoints, CABG and PTCA, were combined, 22.4% of those < 75 underwent a procedure, while only 11.7% of the older cohort did (P = 0.005). Twenty-six percent of men underwent either CABG or PTCA, while only 9.1% of women did (P < 0.001). Of those < 75 years of age, 31.1% of men and 12.3% of women underwent CABG or PTCA (P < 0.001). In the 75 and older age category, 19.5% of men underwent these interventions, compared with 5.9% of women (P = 0.005). Active treatment group was significantly associated with decreased use of procedures in participants < 75 year old with CHD. Race, activity limitations, number of comorbid conditions, education level, marital status, employment status, and social support were not significantly associated with CABG or PTCA use. When the variables studied were entered into a logistic regression model, increased age and female sex remained independently associated with decreased CABG and PTCA use. CONCLUSION: In the SHEP trial older patients and women, regardless of comorbid conditions, socioeconomic status, and social support, underwent less intensive cardiovascular interventions than did younger patients and men when they developed CHD.

Age Factors↗

Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid.

The presence of ascorbic acid in gastric juice may protect against gastric carcinoma and peptic ulceration. This study examined the effect of Helicobacter pylori (H pylori) on the secretion of ascorbic acid into gastric juice by measuring fasting plasma and gastric juice ascorbic acid concentrations in patients with and without the infection and also before and after its eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than those in 10 H pylori negative controls (median 17.8, range 5.6-155.4 micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations in both groups. The median gastric juice:plasma ascorbic acid ratio in the H pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the patients with H pylori infection there was a significant negative correlation between the severity of the antral polymorphonuclear infiltrate and gastric juice ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After eradication of H pylori in 11 patients, gastric juice ascorbic acid concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml) (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows active secretion of ascorbic acid into gastric juice. Secondly, H pylori infection causes a reversible lowering of gastric juice ascorbic acid concentrations, which may predispose to gastric carcinoma and peptic ulceration.

Ascorbic Acid↗

Iris pigmentation and extent of disease in patients with neovascular age-related macular degeneration.

PURPOSE: To determine whether the extent of disease in age-related macular degeneration (AMD) varies with iris pigmentation. METHODS: The authors assessed visual function and macular appearance in the fellow eye or both eyes of 132 white patients with unilateral neovascular AMD. All patients had a visual acuity of 20/60 or better in the fellow eye. Eighty-nine of the patients were coded as having light irides (blue, green, or hazel) and 43 were coded as having dark irides (brown); the two groups of patients had comparable mean ages. RESULTS: By the Mann-Whitney test for differences in mean rank, fellow eyes with light irides showed a marginally worse visual acuity (P = .156) but significantly more visual field impairment by letter recognition perimetry (P = .011) and the macular threshold test of the Humphrey Field Analyzer (P = .043), and more retinal pigment epithelial atrophy (P = .017) and focal areas of hyperpigmentation (P = .002) than fellow eyes with dark irides. For eyes with a choroidal neovascular membrane (CNVM), those with light irides had significantly lower visual acuities (P = .006) and larger scars (P = .006) than eyes with dark irides. In addition, extent of disease in the eye with a CNVM was positively correlated with extent of disease in the fellow eye for most comparisons. CONCLUSIONS: These observations suggest that light iris pigmentation is associated with more extensive retinal disease in patients with unilateral neovascular AMD. Furthermore, in such patients, those with worse disease in the eye with a CNVM may tend to have more extensive atrophic disease in the fellow eye.

Aged↗