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J R Schultz

Publications and source records attributed to J R Schultz.

At least 37 records · Page 2Linked to original sources
PubMed1996

Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids.

Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products.

Antioxidants↗
PubMed1996

Autoxidation of ubiquinol-6 is independent of superoxide dismutase.

Ubiquinone (Q) is an essential, lipid soluble, redox component of the mitochondrial respiratory chain. Much evidence suggests that ubiquinol (QH2) functions as an effective antioxidant in a number of membrane and biological systems by preventing peroxidative damage to lipids. It has been proposed that superoxide dismutase (SOD) may protect QH2 form autoxidation by acting either directly as a superoxide-semiquinone oxidoreductase or indirectly by scavenging superoxide. In this study, such an interaction between QH2 and SOD was tested by monitoring the fluorescence of cis-parinaric acid (cPN) incorporated phosphatidylcholine (PC) liposomes. Q6H2 was found to prevent both fluorescence decay and generation of lipid peroxides (LOOH) when peroxidation was initiated by the lipid-soluble azo initiator DAMP, dimethyl 2,2'-azobis (2-methylpropionate), while Q6 or SOD alone had no inhibitory effect. Addition of either SOD or catalase to Q6H2-containing liposomes had little effect on the rate of peroxidation even when incubated in 100% O2. Hence, the autoxidation of QH2 is a competing reaction that reduces the effectiveness of QH2 as an antioxidant and was not slowed by either SOD or catalase. The in vivo interaction of SOD and QH2 was also tested by employing yeast mutant strains harboring deletions in either CuZnSOD and/or MnSOD. The sod mutant yeast strains contained the same percent Q6H2 per cell as wild-type cells. These results indicate that the autoxidation of QH2 is independent of SOD.

Animals↗
PubMed1996

Numerical simulation of iodine speciation in relation to water disinfection aboard manned spacecraft I. Equilibria.

Elemental iodine (I2) is currently used as the drinking water disinfectant aboard the Shuttle Orbiter and will also be incorporated into the water recovery and distribution system for the International Space Station Alpha. Controlled release of I2 is achieved using the Microbial Check Valve (MCV), a flow-through device containing an iodinated polymer which imparts a bacteriostatic residual concentration of approximately 2mg/L to the aqueous stream. During regeneration of MCV canisters, I2 concentrations of approximately 300 mg/L are used. Dissolved iodine undergoes a series of hydrolytic disproportionation and related reactions which result in the formation of an array of inorganic species including: I-, I3-, HOI, OI-, IO3-, HIO3, I2OH-, I2O(-2), and H2OI+. Numerical estimation of the steady-state distribution of inorganic iodine containing species in pure water at 25 degrees C has been achieved by simultaneous solution of the multiple equilibrium expressions as a function of pH. The results are reported herein.

Disinfection↗
PubMed1996

Neurodevelopmental outcome of infants with viral meningitis in the first three months of life.

We prospectively evaluated the neurodevelopmental outcome of infants with documented viral meningitis to determine (1) whether deficits in physical growth, development, speech and language, hearing, or intelligence occur; and (2) if so, at what age these deficits can be detected. Sixteen infants with documented enteroviral meningitis under the age of 90 days and a control group of 13 patients matched for age, race, sex, and socioeconomic status were followed up prospectively for 3 years with annual evaluations, which included a developmental evaluation by a pediatric developmentalist, articulation and language tests by a speech-language pathologist (Sequenced Inventory of Communication Development, Receptive-Expressive Emergent Language Scale (REEL), Preschool Language Scale (PLS), Revised Peabody Picture Vocabulary Test (PPVT-R), Photo Articulation Test, audiometric screening), and intelligence tests by a psychometrist (Bayley Scales of Infant Development [BSID] and Stanford-Binet). No deficits were demonstrated in growth, development, hearing, BSID, articulation, and expressive language. Subtle but significant (P < 0.05) deficits were documented in the study group compared with the control group in the receptive component of the REEL, all subsections of the PLS, the PPVT-R, and the verbal comprehension/language-processing section (Factor II) of the Stanford-Binet. These differences could be reliably detected by 3 years of age. We conclude that viral meningitis in young infants may cause subtle deficits in language skills, particularly receptive language. We recommend that children who have had enteroviral meningitis during early infancy be monitored carefully for language development and, perhaps, receive increased language stimulation in the home prior to school entry in order to optimize their learning potential.

Analysis of Variance↗
PubMed1995

HIV-infected adolescents with hemophilia: adaptation and coping. The Hemophilia Behavioral Intervention Evaluation Project.

OBJECTIVE: It is estimated that 70% of individuals with factor VIII deficiency hemophilia who received blood products before 1985 are infected with human immunodeficiency virus (HIV). The goal of the current study was to assess how adolescents with hemophilia cope with reminders of their HIV status, because adaptation is likely to have implications for these individuals' quality of life and adherence to safer sex recommendations. METHODS: Participants included 297 HIV-positive adolescents with hemophilia who were recruited from 11 sites across the United States. Adolescents reported on the use and effectiveness of strategies for coping with reminders of their HIV status. RESULTS: A significant degree of distress was reported in response to such reminders, with anger being the most commonly reported emotion. Although a wide variety of coping strategies had been tried, participants reported using resignation (80.9%), self-calming (78.8%), and distraction (76.4%) most frequently in their attempts to cope with reminders of HIV. Self-blame (3.6%), engaging in risky behaviors (22.2%), thinking about sex (25.4%), and drug/alcohol use (29.1%) were used least. These adolescents tended to rate more active cognitive and behavioral coping strategies (eg, cognitive restructuring, seeking social support, physical activity) as most effective, whereas passive strategies (eg, wishful thinking, blaming others) were reported to be least helpful. Those individuals who reported being distressed by reminders of HIV endorsed most of the coping strategies significantly more often than the nondistressed group, although ineffective strategies were commonly chosen. Sexually active adolescents were more likely than their abstinent peers to cope by thinking about sex, engaging in risky behaviors, or using alcohol and drugs. CONCLUSION: In this population of adolescents who have known their serostatus for several years, distress about everyday reminders of HIV appears to be associated with ineffective coping strategies.

Adaptation, Psychological↗
PubMed1994

The properties of HDL in genetically engineered mice.

Genes involved in HDL structure and metabolism have been overexpressed through the introduction of transgenes or inactivated by gene targeting in mice. These new experimental substrates make it possible to address hypotheses relevant to the biology of HDL that were previously inaccessible through human studies. The in-vivo studies performed to date with these engineered mice have provided insight into structural determinants of HDL, uncovered interactions between proteins that act on HDL and clarified the role that HDL-associated proteins play in atherosclerosis. Further use of these animals, coupled with the development of new engineered lines of mice, should help unravel many questions associated with the in-vivo biological properties and metabolism of HDL.

Animals↗
PubMed1993

Protein composition determines the anti-atherogenic properties of HDL in transgenic mice.

High-density lipoprotein (HDL) contains two major proteins, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), comprising about 70% and 20% of the total HDL protein mass, respectively. HDL exists in human plasma in two main forms, one containing apoA-I with apoA-II (AI/AII-HDL) and another containing apoA-I without apoA-II (AI-HDL). A strong inverse relationship exists between total plasma HDL concentration and atherosclerosis, but the results of studies examining the relationship between AI-HDL and AI/AII-HDL and atherosclerosis have been conflicting. To determine whether these two HDL populations have different effects on atherogenesis, human apoA-I (AI) and human apoA-I and apoA-II (AI/AII) transgenic mice were produced in an atherosclerosis-susceptible strain. Following an atherogenic diet, despite similar total cholesterol and HDL cholesterol concentrations, the area of atherogenic lesions in the AI/AII mice was 15-fold greater than in the AI animals. These studies show that the protein composition of HDL significantly affects its role in atherogenesis and that AI-HDL is more antiatherogenic than AI/AII-HDL.

Animals↗
PubMed1993

Hypokalemia and anesthetic implications.

Reductions in serum potassium influence myocardial cell excitability by increasing membrane potential, diastolic depolarization, duration of refractory period and action potential, and decreasing conduction velocity. Disturbances in electrolyte balance typically involve alterations in two or more cations whose effects can be additive or antagonist. Serum magnesium and calcium have been demonstrated to influence the electrophysiologic effects of potassium imbalances. The arrhythmogenic potential of hypokalemia is thought to result from electrical inhomogeneity, alterations in conduction, changes in automaticity and disturbances in sodium pump kinetics. Potassium balance is maintained by two separate, yet interrelated, systems: distribution and the balance between intake and excretion. Cell wall integrity, osmolality, hormones and acid-base balance influence the relative concentrations of potassium between the intracellular and extracellular compartments. Renal excretion is the major route of elimination and is affected by acid-base balance, potassium and sodium intake, urinary flow rates and mineralocorticoid states. Serum potassium is not an accurate reflection of total body potassium stores. Acute hypokalemia differs from chronic, for the former results in a change in only the serum potassium concentration, whereas the latter is accompanied by a reduction in both the total body stores and serum levels. The importance of intracellular and extracellular concentrations lies in their determination of the resting membrane potential and, therefore, membrane excitability. Although experimental studies have demonstrated an association between ventricular ectopy and hypokalemia, the clinical studies to date have reported conflicting results. The arrhythmogenic role of hypokalemia has been examined in ambulatory hypertensive patients with acute myocardial infarctions and those with magnesium deficiencies, the results of which have been difficult to interpret because of differences in study design, durations, and characteristics of study population. During general anesthesia, both experimental and clinical studies have failed to demonstrate an increase in the incidence of ventricular ectopy in hypokalemic patients. The common practice of acute repletion therapy or cancellation is not warranted based on the studies to date. Repletion therapy is neither inexpensive nor benign. In one study of 4921 hospitalized patients, the frequency of dangerous complications of oral and/or intravenous potassium therapy was approximately 1 in 175. Certain patients are susceptible to hyperkalemia, so commonly prescribed medication can promote elevations in serum potassium including indomethacin, amiloride, beta-adrenergic blocking agents, and angiotensin-converting enzyme inhibitors. Evaluation of hypokalemia should include identification of the etiology precipitating the electrolyte imbalance. Examinations should include the duration and severity of the depletion, history of past and present illness, current medications, and the presence of concurrent electrolyte disturbances.(ABSTRACT TRUNCATED AT 400 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

Expression of human apolipoprotein A-II and its effect on high density lipoproteins in transgenic mice.

Apolipoproteins A-I and A-II comprise approximately 70 and 20%, respectively, of the total protein content of HDL. Evidence suggests that apoA-I plays a central role in determining the structure and plasma concentration of HDL, while the role of apoA-II is uncertain. To help define the function of apoA-II and determine what effect increasing its plasma concentration has on HDL, transgenic mice expressing human apoA-II and both human apoA-I and human apoA-II were produced. Human apoA-II mRNA is expressed exclusively in the livers of transgenic animals, and the protein exists as a dimer as it does in humans. High level expression of human apoA-II did not increase HDL concentrations or decrease plasma concentrations of murine apoA-I and apoA-II in contrast to what was observed in mice overexpressing human apoA-I. The primary effect of overexpressing human apoA-II was the appearance of small HDL particles composed exclusively of human apoA-II. HDL from mice transgenic for both human apoA-I and human apoA-II displayed a unique size distribution when compared with either apoA-I or apoA-II transgenic mice and contain particles with both these human apolipoproteins. These results in mice, indicating that human apoA-II participates in determining HDL size, parallel results from human studies.

Animals↗
PubMed1991

Small differences in Drosophila tropomyosin expression have significant effects on muscle function.

The effects of promoter deletions on Drosophila tropomyosin I (TmI) gene expression have been determined by measuring TmI RNA levels in transformed flies. Decreases in RNA levels have been correlated with rescue of flightless and jumpless mutant phenotypes in Ifm(3)3 mutant transformed flies and changes in muscle ultrastructure. The results of this analysis have allowed us to identify a region responsible for 20% of maximal TmI expression, estimate threshold levels of TmI RNA required for indirect flight and jump muscle function, and obtain evidence suggesting that sarcomere length may be an important determinant of flight muscle function.

Animals↗
PubMed1991

A muscle-specific intron enhancer required for rescue of indirect flight muscle and jump muscle function regulates Drosophila tropomyosin I gene expression.

The control of expression of the Drosophila melanogaster tropomyosin I (TmI) gene has been investigated by P-element transformation and rescue of the flightless and jumpless TmI mutant strain, Ifm(3)3. To localize cis-acting DNA sequences that control TmI gene expression, Ifm(3)3 flies were transformed with P-element plasmids containing various deletions and rearrangements of the TmI gene. The effects of these mutations on TmI gene expression were studied by analyzing both the extent of rescue of the Ifm(3)3 mutant phenotypes and determining TmI RNA levels in the transformed flies by primer extension analysis. The results of our analysis indicate that a region located within intron 1 of the gene is necessary and sufficient for directing muscle-specific TmI expression in the adult fly. This intron region has characteristics of a muscle regulatory enhancer element that can function in conjunction with the heterologous nonmuscle hsp70 promoter to promote rescue of the mutant phenotypes and to direct expression of an hsp70-Escherichia coli lacZ reporter gene in adult muscle. The enhancer can be subdivided further into two domains of activity based on primer extension analysis of TmI mRNA levels and on the rescue of mutant phenotypes. One of the intron domains is required for expression in the indirect flight muscle of the adult. The function of the second domain is unknown, but it could regulate the level of expression or be required for expression in other muscle.

Animals↗
PubMed1983

Timing of elective hypospadias repair in children.

Psychological concerns for the timing of medical procedures on children result from the longstanding realization that events and behavioral patterns of childhood have wide-ranging effects on the later behavior of the adult. A review of the literature regarding the effects of surgery on psychological development is presented. Particular reference is made to the impact of genitourinary surgery with specific emphasis on the repair of hypospadias, a congenital anomaly affecting 1:250 to 1:400 live male births. Studies of adults who underwent hypospadias repair as children suggest that they are psychologically different from their peers who did not have this surgery. Specifically, as adults they frequently have sexual difficulty despite erectile competence and they generally occupy less responsible, less competitive, and less independent professions than similarly intelligent cohorts. These findings imply that the experience of hypospadias or its surgical repair may in some way affect psychological development. By examining these experiences in light of emotional and cognitive development and the emergence of body image and sexual identity, predictions for psychologically optimal timing of surgery are made. Importance of the role of the family in the psychological outcome and a discussion of surgical considerations are also provided.

Age Factors↗
PubMed1981

Physostigmine and lithium response in the schizophrenias.

Conflicting reports concerning cholinomimetic-induced reduction of schizophrenic symptoms prompted the authors to study such changes in schizophrenic symptoms following physostigmine infusions in subgroups of patients with schizophrenic-like illness. These subgroups were defined by the presence or absence of antipsychotic response during a 2-week trial of lithium alone after physostigmine infusion. Patients who showed significant but temporary improvement in their thinking disturbance on serial Brief Psychiatric Rating Scale scores following physostigmine infusion subsequently responded to lithium; patients who failed to improve following physostigmine also failed to respond to lithium. The authors suggest that some schizophrenic-like illnesses may be biologically similar to mania both with respect to physostigmine and lithium-induced changes in symptomatology.

Adult↗
PubMed1979

Antithymocyte globulin (ATGAM) in renal allograft recipients. Multicenter trials using a 14-dose regimen.

Antithymocyte globulin (ATG, ATGAM; The Upjohn Company) was tested for efficacy and safety in controlled studies in 358 renal allograft recipients. A total of 183 patients were treated according to protocols prescribing 14 daily doses of ATG in addition to standard immunosuppressive therapy with azathioprine and prednisone, while 175 controls received no ATG. Four ATG lots were tested; results with each lot were analyzed separately, and the data were also pooled to obtain an overall impression. ATG delayed the onset of the first rejection episode during the prescribed treatment period (2 weeks). Concurrently, less i.v. steroid was required, but the steroid dosage requirement then rebounded in the 2 weeks after the end of the prescribed treatment period. ATG did not significantly improve the proportion of patients alive with functioning grafts 6 months after transplant, except with one of the four lots.

Adult↗
PubMed1979

Extended treatment with antithymocyte globulin (ATGAM) in renal allograft recipients.

Twenty renal allograft recipients were treated with antithymocyte globulin (ATGAM; ATG) for up to 16 weeks in addition to azathioprine and prednisone, while 20 controls received no ATG. The ATG group showed a lower incidence of first rejection episodes during the first month after transplantation, and also a better functional graft survival rate up to 2 years after transplantation. The results in this early ATG trial were better than those in subsequent trials which used 14-day treatment regimens. Longer treatment deserves another look.

Antilymphocyte Serum↗