PubMed Health⌕ Search

Biomedical subjects

R Levin

Publications and source records attributed to R Levin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Short-lived intermediates in hemoglobin/O2 systems.

The kinetics of the reaction of hemoglobin with molecular oxygen, in which rapid mixing is followed by a very fast temperature jump, is numerically simulated. Values for rate constants are used to the extent known, otherwise interpolated or extrapolated. It is shown that reaction steps not resolvable by rapid mixing can be resolved by subsequent chemical relaxation at appropriate points in time. Four different mechanisms are considered, all assuming no distinction between the two kinds of chains of hemoglobin. Bimolecular rate constants for oxygen binding are either the same for all four sites, or are governed by "frequency factors" (the kinetic equivalent of statistical factors for equilibrium constants in allosteric models). Furthermore, either the third or the fourth measured (Adair) dissociation constant is composed of the product of a "local" dissociation constant and an allosteric interconversion constant. These two pairs of choices give rise to four different mechanisms. Can these mechanisms be distinguished experimentally? As the final parameter values are so similar for the first two binding steps, discrimination is essentially impossible at low oxygen concentration levels (less than 100 microM with 50 microM hemoglobin). Discrimination becomes possible at higher oxygen concentrations, but high resolution in time and concentration amplitude are required. Much depends upon the differences in molar extinction coefficients of components over the accessible wave length range. Some of these values are as yet unknown or not known to a sufficient precision. Nevertheless, distinction between mechanistic alternatives is possible in principle.

Hemoglobins↗
PubMed1997

Short-lived intermediates in aspartate aminotransferase systems.

The kinetics of the reaction of aspartate aminotransferase with erythro-beta-hydroxy-aspartate, in which rapid mixing is followed (upon reaching a suitable stationary state) by a very fast temperature jump, is numerically simulated. Values for rate constants are used to the extent known, otherwise estimated. It is shown that reaction steps not resolvable by rapid mixing can be resolved by subsequent chemical relaxation. Since several absorption spectra of enzyme complexes overlap, use of a pH-indicator is investigated. When the pH-indicator is coupled to the protonic dissociation of free enzyme, the fast steps are easily detected in the chemical relaxation portion of the simulation. When the pH-indicator is coupled to the protonic dissociation of the (short-lived) quinoid intermediate, protonic dissociation is easily detectable in the stopped flow phase and in the chemical relaxation phase. Such transient protonic dissociation has not been detected experimentally, but is predicted by the simulation. When natural substrates are used, the magnitude of the rate constants makes it unlikely that transient proton dissociation can be detected by stopped flow alone, but a combination of stopped flow with very fast temperature perturbation allows detection of the transient proton through use of a suitable nonbinding pH-indicator. This is demonstrated by simulation for a specific case. Finally, an alternate mechanism is introduced and distinction of its kinetics from that of the original mechanism is demonstrated.

Aspartate Aminotransferases↗
PubMed1997

Protein kinase C induced calcium influx and sustained enhancement of ciliary beating by extracellular ATP.

The major purpose of this work was to determine protein kinase C (PKC) influence on ciliary beat frequency (CBF) and to assess participation of PKC in purinergic ciliary stimulation. The experiments were performed by simultaneous measurement of [Ca2+]i and CBF on tissue culture of frog esophagus epithelium. The PKC activators TPA and DiC8 produced significant elevation of [Ca2+]i and strong frequency enhancement. The calcium elevation was inhibited by lowering the extracellular calcium level, or by La3+, but was unaffected by verapamil and the phospholipase C inhibitor U-73122, suggesting that Ca2+ influx was via non-voltage-operated calcium channels. The inhibition of [Ca2+]i elevation resulted in corresponding inhibition of CBF enhancement. The effect of TPA was blocked by the selective PKC inhibitors chelerythrine, calphostin C, and GF109203X, and by the enzyme downregulation. The downregulation of PKC, or the enzyme inhibitors did not affect the immediate response to extracellular ATP but caused rapid decay of initially stimulated [Ca2+]i and CBF to the basal level. These results suggest that PKC produces CBF enhancement via activation of calcium influx through non-voltage-operated calcium channels. This calcium influx seems to be responsible for the duration of ciliary stimulation produced by the extracellular ATP.

Adenosine Triphosphate↗
PubMed1997

The effects of initial drug choice and comorbidity on antihypertensive therapy compliance: results from a population-based study in the elderly.

Approximately half of all elderly patients have elevated blood pressure, and proper treatment of this disorder leads to decreased cardiovascular morbidity in patients 65 and older. This study examined the effect of initial drug choice and comorbidity on medication compliance. We conducted a retrospective follow-up of 8643 outpatients aged 65 to 99 with newly prescribed antihypertensive therapy (AHT) from 1982 to 1988 in the New Jersey Medicaid and Medicare programs. Compliance was measured in terms of the number of days in which AHT was available to the patient during the 12 months following the initiation of therapy. Odds ratios (OR) and 95% confidence intervals (CI) for the outcome of good compliance (> or =80%) were calculated. In a logistic regression model, good compliance (> or =80%) was significantly associated with use of newer agents such as angiotensin converting enzyme inhibitors (OR 1.9, 95% CI 1.6 to 2.2) and calcium channel blockers (OR 1.7, 95% CI 1.5 to 2.1) as compared to thiazides, the presence of comorbid cardiac disease (OR 1.2, 95% CI 1.1 to 1.2), and multiple physician visits (OR 2.2, 95% CI 1.8 to 2.5). Good compliance was inversely associated with use of multiple pharmacies (OR 0.4, 95% CI 0.4 to 0.5) and number of medications prescribed overall (OR 0.8, 95% CI 0.7 to 0.9). Drug choice, comorbidity, and health services utilization were significantly associated with AHT compliance and represent important considerations in the management of high blood pressure. Noncompliance may be an important cause of treatment failure in elderly hypertensives.

Aged↗
PubMed1997

Drinking water turbidity and pediatric hospital use for gastrointestinal illness in Philadelphia.

Recent outbreaks have demonstrated that serious infectious gastrointestinal illness related to drinking water supplies remains a problem in the United States. The magnitude is unknown, but children, the elderly, and immunocompromised individuals are considered at highest risk. We examined the association between daily measures of drinking water turbidity and both emergency visits and admissions to Children's Hospital of Philadelphia for gastrointestinal illness, controlling for time trends, seasonal patterns, and temperature. We found that an interquartile range increase in turbidity levels in Philadelphia drinking water was associated with a 9.9% increase [95% confidence limits (CL) = 2.9%, 17.3%] in gastrointestinal emergency visits for children age 3 years and older 4 days later. For children age 2 years and younger, an association was found with a lag of 10 days (5.9% increase; 95% CL = 0.2, 12.0). For admissions, a similar pattern was seen. For children over 2 years old, an increase of 31.1% (95% CL = 10.8%, 55%) was seen with a lag of 5-6 days. For younger children, an increase of 13.1% (95% CL = 3.0, 24.3) was seen 13 days later. This association occurred in a filtered water supply in compliance with current federal standards.

Adolescent↗
PubMed1997

Depression in the elderly: biologic considerations.

Although support for the biologic basis and effective somatic therapy of geriatric depression is increasing, both patients and clinicians are reluctant to identify and treat the symptoms associated with late-life depression, a broad-based problem in the geriatric population. There is much clinical and biologic overlap between depression and other organic brain disorders such as dementia, with evidence that late-onset depression may sometimes be a prodrome for other organic disorders. These and other issues surrounding geriatric depression are reviewed with a focus on future research questions.

Age Factors↗
PubMed1997

Acidosis impairs rabbit trabecular smooth muscle contractility.

PURPOSE: The aim of our study was to define the effects of acidosis on the contractility of trabecular smooth muscle. METHODS: Rabbit corpus cavernosal strips were mounted in organ chambers to measure isometric tension. Additionally, intracellular free Ca2+ concentration ([Ca2+]i) and tension were measured simultaneously utilising the intracellular fluorescent dye, FURA-2, and isometric tension recordings. RESULTS: Contraction of corpus cavernosum smooth muscle following transmural electrical stimulation (TES) of constrictor nerves or exposure to norepinephrine was depressed under acidic (pH 6.9) vs. control (pH 7.4) conditions. Twenty mM K(+)-induced contractions were also inhibited by acidosis, however 40, 80, and 120 mM K+ contractions were unaffected. Relaxation responses to acetylcholine and electrical stimulation, in phenylephrine contracted tissues, were unaffected by acidosis. Tissues contracted with 20 mM K+ under control conditions, relaxed approximately 50% when exposed to an acidic environment. This relaxation was blocked by exposing the tissue to 80 mM K+. Acidic conditions inhibited basal tone and [Ca2+]i as well as normal increases in both intracellular free Ca2+ and tension upon exposure to 20 mM K+, while 80 mM K(+)-induced increases in Ca2+ and tension were comparable under both neutral and acidic conditions. CONCLUSION: Acidosis impairs trabecular smooth muscle contractility. This alteration is probably secondary to the interference of [H+] with the intra and extracellular mechanisms that regulate homeostasis of [Ca2+]i. Since acidosis is an early complication of ischemic priapism, we propose that the reduced contractility of trabecular smooth muscle may be a significant factor in the perpetuation of the ischemic state.

Acetylcholine↗
PubMed1997

Active and passive compliance of the fetal bovine bladder.

PURPOSE: Others have shown that the fetal bovine bladder is relatively noncompliant. Previous studies on compliance of fetal bovine bladders have demonstrated that the youngest fetal bladders had lowest and the oldest fetal bladders (near full-term) had greatest compliance. Our study was designed to determine the level of participation of active tension in the compliance of fetal bladders during gestation. MATERIALS AND METHODS: Fetal bovine bladders were obtained immediately after maternal harvest and crown-to-rump length was measured to determine gestational age. The fetus was inspected for genitourinary anomalies and the bladder was immediately placed in chilled M199 media. Strips (1 x 0.5 cm.) were excised from the anterior sagittal plane of the bladder and subjected to length-tension analysis in oxygenated Tyrode's buffer at 37C. Tension was measured using a force transducer and length was increased using a micropositioner. Compliance refers to the length-tension studies performed in normal Tyrode's solution and consists of a combination of active (smooth muscle tone) and passive properties. Passive compliance refers to length-tension studies performed after inactivation of bladder smooth muscle tone. Compliance with muscle tone intact was determined by incrementally stretching the strips to twice resting length in physiological buffer and then permitting them to return to resting length. Passive compliance with muscle tone ablated was determined in the same fashion after overnight incubation in calcium-free Tyrode's buffer in the presence of 5 mM. egtazic acid and 10 mM. sodium azide. An exponential function was fit to the normalized length-tension curves, where the exponential coefficient (EC) is numerically inversely proportional to compliance. RESULTS: Passive compliance was greatest in the youngest bladders (EC = 0.5 in the first trimester) and gradually decreased with increasing fetal age (EC = 1.2 in the third trimester). Active compliance demonstrated the opposite pattern, since the younger bladders were more stiff (EC = 2.1 in the first and 1.6 in the third trimesters). CONCLUSIONS: These studies demonstrate that passive compliance is greatest in the youngest bladders and progressively decreases with gestation. However, active smooth muscle tone is greatest in the youngest bladders and decreases with gestation. Thus, high active smooth muscle tone in the youngest fetal bladders results in relatively poor compliance of the early stage fetal bladder.

Animals↗
PubMed1997

The impact of thiazide diuretics on the initiation of lipid-reducing agents in older people: a population-based analysis.

OBJECTIVE: The objective of this study was to examine how often treatment for hyperlipidemia followed the use of thiazides, compared with the use of other antihypertensive drugs, in older patients. DESIGN: Retrospective follow-up of all health claims filed over a 12-month period. SETTING: New Jersey Medicaid and Medicare programs. PARTICIPANTS: A total of 9274 enrollees, aged 65 to 99, who were newly initiated on antihypertensive medications from 1981-1989. MEASUREMENTS: We measured rates of lipid-reducing agent (LRA) initiation among patients in the 2 years following antihypertensive initiation (thiazide, non-thiazide drug, or combinations of the two) compared with rates among patients not currently taking antihypertensive agents. We used Cox regression analyses to estimate relative risks (RR), accounting for switching in antihypertensive therapy and for time when drug therapy was not currently available according to pharmacy refill records. RESULTS: There were 226 patients (2.4%) in the cohort who were started on LRA during the follow-up period. After adjusting for potential confounders, we found no significant relationship between LRA initiation and overall thiazide use (RR 1.47, 95% CI 0.89-2.40), or other antihypertensive use, relative to no current exposure. However, use of high-dose thiazides (> or = 50 mg) was associated significantly with LRA initiation (RR 1.97, 95% CI 1.12-3.45). Factors associated with decreased incidence of LRA use included age > or = 85 (RR 0.59, 95% CI 0.36-0.96), black race (RR 0.58, 95% CI 0.37-0.91), and nursing home residency (RR 0.20, 95% CI 0.11-0.35). CONCLUSION: Use of low-cost and effective thiazide diuretics in older hypertensives was not associated with more common initiation of lipid-reducing agents, except with high-dose use of thiazides currently seen as inappropriate in most cases. Age and race were important determinants of LRA use.

Aged↗
PubMed1997

Actions of lidocaine on reentrant ventricular rhythms in the subacute myocardial infarction period in dogs.

The actions of lidocaine were studied in 18 dogs, 4 days after ligation of the left anterior descending artery, by computerized mapping. Lidocaine only occasionally suppressed the induction of reentry. At fast heart rates, lidocaine actually facilitated the induction of reentry. The effects on conduction and refractoriness of normal and ischemic myocardium were measured using high-resolution techniques. Lidocaine promoted reentry by a rate-dependent increase in refractory gradient, resulting in additional block, and a selective decrease in conduction velocity in ischemic tissue, resulting in additional conduction delay. Lidocaine could prevent reentry through a rate-independent differential increase in refractory period gradient at the entrance to the common pathway of the circuit, causing block of the reentrant impulse. We conclude that the proarrhythmic effect of lidocaine is due to increased conduction delay and block while the antiarrhythmic effect is due to block of the reentrant impulse by prolonged refractoriness in the common pathway.

Animals↗
PubMed1997

Inhibition of early and late events of the HIV-1 replication cycle by cytoplasmic Fab intrabodies against the matrix protein, p17.

BACKGROUND: The HIV-1 matrix (MA) protein, p17, contains two subcellular localization signals that facilitate both nuclear import of the viral preintegration complex early during infection and virus particle assembly late in infection. The dual role of MA in both the afferent and efferent arms of the HIV-1 life cycle makes it an important target for intracellular immunization-based gene therapy strategies. MATERIALS AND METHODS: Here we report, using a new bicistronic vector, that an intracellular Fab antibody, or Fab intrabody, directed against a carboxy-terminal epitope of MA from the Clade B HIV-1 genotype, can inhibit HIV-1 infection when expressed in the cytoplasm of actively dividing CD4+ T cells. RESULTS: Marked inhibition of proviral gene expression occurred when single-round HIV-1 CAT virus was used for infections. In challenge experiments using both laboratory strains and syncytium-inducing primary isolates of HIV-1, a substantial reduction in the infectivity of virions released from the cells was also observed. CONCLUSIONS: This novel strategy of simultaneously blocking early and late events of the HIV-1 life cycle may prove useful in clinical gene therapy approaches for the treatment of HIV-1 infection and AIDS, particularly when combined with genetic or pharmacologic-based strategies that inhibit other HIV-1 target molecules simultaneously.

Animals↗