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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 415 records · Page 23Linked to original sources
PubMed1996

Effect of adenine methylation on the structure and dynamics of TpA steps in DNA: NMR structure determination of [d(CGAGGTTTAAACCTCG)]2 and its A9-methylated derivative at 750 MHz.

At TpA steps in DNA, the adenine base experiences exceptionally large amplitude (20 degrees-50 degrees) and slow (10 ms-1 microsecond) motion [Kennedy et al. (1993) Biochemistry 32, 8022-8035] which has been correlated with transitions between multiple conformational states [Lefevre et al. (1985) FEBS Lett. 190, 37-40]. The base dynamics can be detected in one-dimensional 1H NMR spectra as excess line width of the aromatic proton resonances. The magnitude of the excess line width is temperature dependent and reaches a maximum at some temperature. In order to better understand the origin of the dynamics, we have studied the effect of N6-methylation of the TpA adenine on both the line widths and its local structure. Here, solution-state 500 and 750 MHz 1H NMR data collected on [d(CGAGGTTTAAACCTCG)]2 show that the excess line width of the TpA adenine-H2 is diminished when the TpA adenine is N6-methylated and that the line width no longer experiences a maximum as the temperature is varied. The resonances sharpen upon methylation because the amplitude of base motion is restricted due to steric effects and due to other structural changes at the TpA site. Additionally, both the TpA adenine-H8 and the exchangeable imino resonance of thymine at the TpA step were also found to have excess line width that is diminished upon N6-methylation. In order to elucidate the structural features responsible for TpA base dynamics, solution-state NMR structures of [d(CGAGGTTTAAACCTCG)]2 and its A9 N6-methylated derivative were determined at 750 MHz. Comparison of the structures shows that poor base stacking at the TpA step may contribute to, or be the origin of, its base dynamics.

Adenine↗
PubMed1996

Transplant-associated autoimmune mechanisms in human hepatitis C virus infection.

In order to define factors which are important for the development of hepatitis C virus (HCV) infection and disease in transplant patients, we examined the role of class II MHC antigen restriction in viral antigen presentation to support a hypothesis of the association of this disease with an autoimmune pathogenesis. A greater degree of histocompatibility match between these donors and their HCV-negative recipients was associated with a greater predisposition to recipient HCV liver disease (ALT elevation) posttransplant. The HCV carrier state could be identified with significant amplification of autologous mixed lymphocyte reactivity (AMLR) in both long-term hemodialysis and long-term renal transplant patients, but the AMLR was absent in end-stage liver disease patients with HCV-associated cirrhosis and was insignificantly elevated in these patients with persistent infection in the first 2 years after a new liver was transplanted. There was also a moderate reduction in autologous reactivity as well as serum HCV titers among renal transplant patients who displayed biochemical evidence of chronic liver disease as opposed to those who did not. This appeared later in the course of the disease. HCV RNA could be detected in peripheral blood mononuclear cells (PBMC) of only a portion of HCV-infected renal transplant patients and these showed significantly higher autologous reactivity. In contrast, despite the fact that observations were earlier after de novo liver transplantation, HCV RNA (i.e., earlier in the course of a new or recurrent disease process) was found in PBMC of all liver transplant recipients tested. The AMLR of noninfected laboratory volunteers could be amplified by preincubating their stimulating cells (APCs) with enriched HCV possibly in immune complex (pHCV-IC). This amplification appeared only with specific combinations of HCV strains with HLA DR serotypes. In addition, HCV-primed T cells could be generated to the virus which displayed accelerated activation kinetics. Liver infiltrating lymphocytes extracted from HCV-positive end-stage diseased livers had significantly higher proliferative and cytotoxic reactivity to autologous (HCV-infected) hepatocytes than the extracted lymphocytes responding to autologous hepatocytes from HCV-negative livers. These findings offer evidence of dynamic autoimmune mechanisms in the spectrum of progression of HCV disease and may help to predict the effect of intervention at various intervals in this progression in organ transplant recipients.

Autoimmune Diseases↗
PubMed1996

Outreach to homeless mentally ill people: conceptual and clinical considerations.

This paper describes a model of outreach predicated on developing a trusting, meaningful relationship between the outreach worker and the homeless person with mental illness. We describe five common tasks inherent in this model of outreach (establishing contact and credibility, identifying people with mental illness, engaging clients, conducting assessments and treatment planning, and providing ongoing service). Other issues discussed include: (a) Responding to dependency needs and promoting autonomy; (b) setting limits while maintaining flexibility; (c) resistance to mental health treatment and follow-up service options.

Community-Institutional Relations↗
PubMed1996

Dissociation between behavioral and psychophysiological measures of response preparation.

Two measures of response preparation were compared: lateralized readiness potentials (LRPs) and reaction times (RTs) to probe stimuli. Subjects responded with the left and right hands to target S's and T's of one size, withholding responses to nontarget S's and T's of a different size. The size discrimination was more difficult than the S vs. T discrimination, so the name of a nontarget letter was expected to prime the response hand to which it was assigned. This priming had no effect on LRPs but did influence RTs to separate probe stimuli, suggesting that LRPs and probe-RTs are sensitive to different aspects of response preparation.

Adolescent↗
PubMed1996

Prostaglandin E2 gel for cervical ripening in patients with an indication for delivery.

OBJECTIVE: To determine if labor can be induced safely and efficiently in patients with a medical or obstetric indication for delivery before 41 completed weeks of gestation by pre-induction cervical ripening with prostaglandin (PG) E2 gel. METHODS: One hundred eighteen women with confirmed indication for induction of labor before 41 completed weeks were randomized in a double-blind fashion to either intracervical PGE2 gel or placebo before induction by a standard oxytocin protocol. Data regarding the change in Bishop score, interval to complete dilation, maximal oxytocin dose required to establish labor, and route of delivery were collected. Apgar scores and umbilical artery pH were also recorded. RESULTS: The maximum oxytocin dose required to establish progressive labor was significantly lower in the PGE2 group (10.06 +/- 8.50 versus 13.35 +/- 9.27 mU/minute, P = .014). The cesarean rate was also significantly lower in the PGE2 group (13.1 versus 31.6%, P = .016). CONCLUSION: Pre-induction intracervical deposition of 1 mg PGE2 gel decreased the amount of oxytocin required to induce progressive labor and decreased the cesarean rate in patients who had medical or obstetric indications for delivery before 41 completed weeks. This was accomplished without negative effect on Apgar score or umbilical artery pH.

Adult↗
PubMed1996

Cardiac and vascular responses of isolated rat tissues treated with diterpenes from Sinularia flexibilis (coelenterata: octocorallia).

The marine environment is a rich source of compounds with cardiovascular activity. This study characterizes the cardiac and vascular responses in isolated rat tissues of flexibilide, dihydroflexibilide and sinulariolide, three diterpenes isolated from the soft coral Sinularia flexibilis. On rat left ventricular papillary muscles, dihydroflexibilide and flexibilide showed similar potencies (-log EC50 = 4.69 +/- 0.05 and 4.66 +/- 0.06, respectively); the maximal response to dihydroflexibilide of 1.4 +/- 0.2 mN was 35 +/- 7% that of calcium chloride in the same muscles. All diterpenes relaxed rat thoracic aortic rings precontracted with KC1 (100 mM) with similar potencies (flexibilide, -log EC50 = 4.17 +/- 0.06). Flexibilide was further characterized and shown to increase force in isolated rat left atria by 0.8 +/- 0.5 mN at 1 x 10(-4) M, to increase rate of contraction in isolated rat right atria by 18 +/- 5 beta/min at 3 x 10(-5) M and to completely relax endothelium-denuded rat thoracic aortic rings (-log EC50 = 4.14 +/- 0.05). Toxicity as indicated by the occurrence of ectopic beats was not observed with the diterpenes at concentrations which produced complete relaxation of blood vessels, maximal positive inotropic activity and minor positive chronotropic responses. Thus, these compounds may be useful lead compounds in the search for improved treatment of cardiovascular disease, especially heart failure.

Animals↗
PubMed1996

Longitudinal induced IL-2 mRNA monitoring in renal transplant patients immunosuppressed with cyclosporine and in unmodified canine renal transplant rejection.

Immune monitoring of transplant patients to define optimal immunosuppression continues to be important, as rejection occurs despite adjustment of dosaging of CsA or even FK506 to achieve "therapeutic-range" blood levels. Because CsA is known to inhibit upregulation of IL-2 mRNA transcription, we prospectively sequentially measured (induced) IL-2 mRNA in PHA-stimulated PBMC cultures from transplant recipients of kidneys from living-related donors (n = 15) using a quantitative PCR assay, with a potential 24-hour turnaround time, to define immunologic events in real time. Reproducible individual patient sensitivity or refractoriness to CsA was determined pretransplant, by adding a range of CsA concentrations to the PBMC cultures and constructing induced IL-2 mRNA regression inhibition curves. However, this was not predictive of rejection episodes, but did correlate well with individual differences in IL-2 mRNA levels posttransplant, despite similar maintenance trough blood concentrations of CsA between patients. In this prospective study, seven patients experienced rejection episodes despite therapeutic CsA trough levels. Three of these, plus one not receiving CsA therapy, who happened to be prospectively tested at the time that rejection was clinically diagnosed, had a decrease in induced IL-2 mRNA before treatment was instituted. As a correlation to this observation in patients, induced IL-2 mRNA levels in unmodified rejection were sequentially measured in PBMC cultures in autologous vs allogeneic canine renal transplants and IL-2, IL-10, TNF-alpha, and IFN-gamma mRNA were also measured in kidney biopsies. Sequential PHA lymphoproliferation assays of [3H] thymidine incorporation on patient and dog PBMC cultures were also performed. Similar to the observations in patients, unmodified rejection in the canine renal allograft model also was accompanied by a decline of PHA-induced IL-2 mRNA in PBMCs as the serum creatinine concentrations became elevated. In the dog kidney biopsies at later phases of rejection, IL-10 mRNA levels were also significantly elevated (p = 0.032).

Animals↗
PubMed1996

Audiogenic seizures following global ischemia induced by chest compression in Long-Evans rats.

Transient global ischemia was used to produce a rat model of generalized tonic-clonic epilepsy. Controlled chest compression in ketamine-anesthesized Long-Evans rats produced transient global ischemia by mechanically preventing the heart from pumping blood. Circulation was restored by standard cardiopulmonary resuscitation techniques. With a temporal muscle (skull) temperature of 35 +/- 0.4 degrees C, 75% (76/102) of the rats survived 7 min of chest compression. Generalized seizures could be evoked in 78% (59/76) of the surviving rats by a 60 s exposure to a loud sound (bell, 110 dB) beginning 24 h after the ischemic episode. The seizure patterns seen resembled those described by Maresceaux (1987) for genetically seizure-prone Wistar rats. Susceptibility to sound-induced seizures declined with time, with wide variations in recovery rate between individuals; one rat showed a daily sound-induced seizure for over 5 months. Seizures were attenuated or blocked by treatment with carbamazepine or sodium valproate. This model is similar to the great vessel occlusion model used by Kawai et al. (1995), but is less invasive. We believe it will be useful in the evaluation of therapies for acquired generalized (grand mal) seizures.

Acoustic Stimulation↗
PubMed1996

Human immunodeficiency virus type 1-related transient neurological deficits.

PURPOSE: To characterize human immunodeficiency virus type 1 (HIV-1)-related transient neurological deficit (TND). DESIGN: A 3-year prospective study based at a tertiary referral center. METHODS: Patients with TND in the absence of an opportunistic infection, neoplasm, neurosyphilis, or seizure were recruited and further investigated. The frequency of hospital admission for these patients was compared with those who were HIV-1 seronegative and with those who were admitted for HIV-1-related thromboembolic events. RESULTS: Twenty-seven patients were identified: mean age of 39 +/- 9 years; CD4+ cell count of 130 +/- 80/microL. Seven patients had no history of an AIDS-defining illness. Hemiparesis and hemisensory disturbance occurred in 23 patients (85%); 15 had preexisting ADC, 7 stage 1 and 8 stage 2; 3 developed ADC after 18 months. Thirteen patients had multiple attacks and 5 had more than 20; 2 patients developed a cerebral infarct. No cause for the TND was identified in 8 patients (30%). Anticardiolipin antibodies were found in 70% and low protein S levels in 53% which was significantly more often than in a neurologically normal group with similarly advanced HIV-1 disease. The frequency of admission was 0.8% whereas the frequency for similar TND in HIV-1-seronegative patients was 0.4% and the frequency for HIV-1-related thromboembolic events was 0.9%. CONCLUSIONS: Transient neurological deficits occur in advanced HIV-1 disease and are often associated with ADC, elevated concentrations of anticardiolipin antibodies, and low protein S levels. Future studies will need to define the precise role of these associations in the pathogenesis of HIV-1-related TND.

AIDS Dementia Complex↗
PubMed1996

Peak torque, average power, and hamstrings/quadriceps ratios in nondisabled adults and adults with mental retardation.

OBJECTIVE: To compare isokinetic hamstring and quadriceps peak torque (Nm), average power (watts), and corresponding hamstring/quadriceps (HQ) ratios (as percentages) of adult men with Down syndrome(DS), with mental retardation without Down syndrome (NDS), and nondisabled sedentary controls (SC). DESIGN: Repeated measures analysis of variance. SETTING: Subjects were tested at a university exercise science laboratory. SUBJECTS: Volunteer sample of 35 subjects: SC(n=13), DS(n=9), and NDS (n=13). INTERVENTION: Subjects performed isokinetic strength tests at 60 degrees /sec and 90 degrees/sec using gravity effected torque procedures. Subjects with DS and NDS performed the test on two separate days with best results selected for statistical comparisons. Sedentary controls performed the test once. MAIN OUTCOME MEASURES: Isokinetic hamstring and quadriceps peak torque and average power, and corresponding HQ ratios on a Cybex 340 isokinetic dynamometer. RESULTS: In all isokinetic parameters measured, sedentary controls demonstrated significantly higher scores than subjects with DS and NDS. There was no significant difference between subjects with DS and NDS, although mean peak torque and average power scores were greater in subjects with NDS. Finally, there were no significant differences in peak torque and average power HQ ratios across groups (p> .01), although group mean peak torque HQ ratios were greatest for sedentary controls (range=61% to 63%) and approximated accepted HQ ratio norms, and lowest for subjects with DS(range=40% to 46%). CONCLUSIONS: Individuals with mental retardation are in need of progressive resistance exercise programs to improve hamstring and quadriceps strength and normalize HQ strength and power ratios.

Adult↗
PubMed1996

Effectiveness of a urinary control insert in the management of stress urinary incontinence: early results of a multicenter study.

OBJECTIVES: The purpose of this study was to test the safety and effectiveness of a urethral insert for managing stress or mixed urinary incontinence. METHODS: We performed a prospective, multicenter study of 135 female patients who were treated for 4 months with the Reliance Urinary Control Insert. The effectiveness of the insert was measured objectively at the time of first use and after 4 months' use by standardized pad weight studies. Insert effectiveness was also measured by reports of symptom improvement during patient interviews and on patient diaries. Urine microscopy and culture were obtained monthly; cystoscopy and urodynamics were conducted at study entry and at 4 months. RESULTS: Significant improvement in involuntary urine loss was observed. Objective measurement of urine loss revealed that 80% of the patients were completely dry, and 95% of the patients achieved greater than an 80% decrease in urine loss. In addition, patients' perceptions of acceptability, incontinence symptom improvement, ease of learning, comfort, and time to habituation also showed improvements. Untoward events reported during the study included hematuria, bacteriuria, and bladder irritation. These events did not require significant medical intervention and did not result in any long-term clinical sequelae. CONCLUSIONS: These preliminary results indicate that the Reliance Urinary Control Insert may be a safe, effective, and well-tolerated alternative to other available methods for the management of stress or mixed incontinence in women. Additional long-term follow-up will be required to substantiate this conclusion.

Adolescent↗
PubMed1996

Efficacy of several modes of continuous-flow insufflation for resuscitation of a canine model of acute respiratory arrest.

STUDY OBJECTIVE: To test the efficacy of several modes of continuous-flow insufflation on the maintenance of physiologic parameters in a model of respiratory arrest, and the effect of these modes on neurologic outcome. METHODS: Anesthetized dogs were slowly infused with tetrodotoxin over 75 minutes to the point of respiratory arrest. We used two different modes of continuous-flow insufflation: endobronchial insufflation (EI) of air 3 cm distal to the carina (.25 or 1.0 L.kg-1.min-1); and tracheal insufflation of oxygen (TRIO) 1 cm proximal to the carina (.08 or .2 L.kg-1.min-1). RESULTS: EI at either flow rate provided ventilation sufficient to allow the dogs to recover effective spontaneous breathing and be removed from ventilation after 4 hours. By this time, almost all cardiovascular variables and blood gas values were normal. TRIO at .2 L.kg-1.min-1 also resulted in successful recovery, although Pa02, as well as systemic and pulmonary arterial pressures and vascular resistances, remained increased at the end of the 4-hour period. TRIO at the low flow rate, however, resulted in deterioration of blood gas values and systemic arterial pressure; dogs required conventional mechanical ventilation after 45 minutes of low-flow TRIO. CONCLUSION: EI can be used to maintain oxygenation in acute respiratory arrest when conventional techniques are not feasible; TRIO at .2 L.kg-1.min-1 is also effective.

Acute Disease↗
PubMed1996

Effect of estrogen withdrawal on blood pressure and insulin resistance in sucrose-fed juvenile rats.

We have previously shown that juvenile Sprague-Dawley rats, fed a diet in which complex carbohydrates are replaced by sucrose, develop insulin resistance and hypertension. These conditions develop despite the absence of genetic predisposition to either. When studied with the euglycemic hyperinsulinemic clamp technique, these rats have reduced insulin-stimulated glucose utilization, but normal suppression of hepatic glucose output. In the young sucrose-fed rats, it was noted that the degree of blood pressure elevation was greater in males than in females. The purpose of this study was to test the hypothesis that estrogen withdrawal increases insulin resistance and hypertension. Female rats were randomized at weaning (3 weeks of life) to receive control diet or sucrose diet. Animals were assessed with weekly weight and indirect tail-cuff blood pressure. At 8 weeks of life, the sucrose-fed rats were randomized to receive bilateral oophorectomy or sham surgery (anesthesia and uterine horn exposure without removal of the ovaries). At 13 to 14 weeks of life, all animals were fasted overnight, and had an oral glucose tolerance test while conscious. Weight and weight gain were not different among the groups over the 11 week study period. Animals fed the sucrose diet developed significantly higher blood pressure than animals fed the control diet; oophorectomized animals had higher blood pressure than sham-operated animals (P <.0001). Sucrose-fed oophorectomized animals developed fasting and glucose-stimulated hyperinsulinemia. Estrogen withdrawal augments blood pressure in juvenile rats made insulin resistant and hypertensive with a sucrose diet. Estrogen withdrawal in these animals also induces fasting and glucose-stimulated hyperinsulinemia, which are signs of worsening insulin resistance. Androgen:estrogen imbalance increases metabolic dysfunction and worsens hypertension in this animal model.

Animals↗
PubMed1996

Absence of coactivation in the motor component: evidence from psychophysiological measures of target detection.

Previous research examining response time has supported coactivation under certain conditions. Other research has found more forceful responses to redundant-target than to single-target displays, suggesting coactivation in the motor component. The authors tested for motor coactivation using response time, response force, and other psychophysiological measures. Experiments 1 and 2 showed that response force is determined by the number of stimuli, not the number of targets, when target-distractor discriminations are required. In Experiment 3, 1 stimulus was presented on each trial, and the number of target features was varied. The response time results showed that coactivation occurred somewhere in the information-processing system, but no evidence of motor coactivation was found using any psychophysiological measure. These data disconfirm the motor-coactivation hypothesis for tasks that require visual discriminations.

Electromyography↗