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Biomedical subjects

J J Wilson

Publications and source records attributed to J J Wilson.

At least 19 recordsLinked to original sources
PubMed2001

Attention deficit hyperactivity disorder (ADHD) and substance use disorders.

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder that often continues to manifest symptoms into adulthood. In children and adults, this condition may contribute to addictive vulnerability. Several factors are common to the developmental psychopathology of these conditions, suggesting an underlying deficit in behavioral regulation as an explanation for this comorbidity. Developmentally, faulty learning processes or attempts to self-medicate dysfunctional behavior may contribute to the pathogenesis of substance use disorders. Substance abuse itself also may contribute to the development of attentional deficits and behavioral dysregulation through direct (eg, prenatal or self-inflicted exposures to neurotoxic substances) and indirect (eg, poverty, neglect, abuse) mechanisms. Because ADHD can be identified prior to the peak onset of substance use, effective treatment of this common disorder may reduce the development of substance use disorders. Adult ADHD may also contribute to the development and maintenance of substance use disorders Substance abuse patients may particularly benefit from treatment of this comorbidity.

Adult↗
PubMed2001

Investigating hepatitis C virus heterogeneity in a high prevalence setting using heteroduplex tracking analysis.

Hepatitis C virus (HCV) infection is very common among chronic hemodialysis patients. In the past, blood transfusion appeared to be the primary risk factor; however evidence of nosocomial HCV transmission in the hemodialysis setting has recently been reported. This report describes a molecular investigation of HCV isolates obtained from a population of 670 patients attending six different Seattle-King County based hemodialysis centers in order to identify potential common source infections. 733 serum specimens were collected from hemodialysis patients in 1992 and 1996, and were tested for HCV antibodies and RNA. Overall, 115 of 670 (17%) patients were positive for HCV RNA, and thus were considered actively infected by HCV. HCV genotype was determined in all cases by restriction fragment length polymorphism, and 93 patients were found to be infected by HCV genotype 1. HCV envelope genes were amplified from the 93 patients with genotype 1 infection, and were studied in further detail by heteroduplex tracking analysis (HTA) using genotype 1a and 1b specific probes derived from the envelope 1 (E1) and envelope 2 (E2) genes. Genetic relatedness between pairs of HCV envelope genes was estimated by calculating the degree of gel shift relative to homoduplex controls. Nucleotide sequencing and phylogenetic analysis was used to confirm genetic relatedness detected by HTA. When HTA was performed using the E1 gene probe, 12 apparently related infections were detected; 10 of 12 (83%) of these infections were confirmed as truly related using the gold standard method of nucleotide sequencing plus phylogenetic analysis. Using an E2 gene probe, 24 infections were apparently related, but only six (25%) were confirmed by sequencing. As a control, 41 envelope genes, which were unrelated by HTA, were sequenced; 0 of 41 (0%) were truly related. In summary, HTA provides a rapid and effective molecular technique for screening HCV genetic relatedness in population-based studies, and should prove valuable in future studies of HCV molecular epidemiology.

Genetic Variation↗
PubMed2001

Substance abuse and criminal recidivism: a prospective study of adolescents.

Studies of substance abuse among delinquents have shown mixed results on criminal recidivism. The present study evaluates personality traits associated with substance abuse and recidivism among delinquent boys, and prospectively determines the extent to which these factors are predictive of criminal recidivism. 134 incarcerated boys (x = 15.9 +/- 1.1) completed the Weinberger Adjustment Inventory and the Substance Abuse Screening Inventory. Youth were prospectively followed for up to 4.5 years following release. Among incarcerated delinquents, personality traits are predictive of a positive substance abuse screen and recidivism. A trend indicating a possible interaction between personality and treatment is observed. If these findings are replicated, personality traits may play a role in predicting substance abuse as well as individual delinquent responses to treatment.

Adolescent↗
PubMed2000

Differential regulation of mammalian brain-specific proline transporter by calcium and calcium-dependent protein kinases.

1. This study examined the role of [Ca2+]I and Ca(2+)-dependent kinases in the modulation of high-affinity, mammalian brain-specific L-proline transporter (PROT). 2. beta-PMA (phorbol 12-myristate 13-acetate), an activator of protein kinase C (PKC), inhibits PRO uptake, and bisindolymalemide I (BIM), a potent PKC inhibitor, prevents beta-PMA inhibition. Down-regulation of PKC by chronic treatment with beta-PMA enhances PROT function indicating PROT regulation by tonic activity of PKC. 3. Thapsigargin, which increases [Ca2+]I levels by inhibiting Ca(2+)-ATPase, inhibits PROT and exhibits additive inhibition when co-treated with beta-PMA. KN-62, a Ca2+/calmodulin-dependent kinase II (CaMK II) inhibitor, but not BIM (a PKC inhibitor) prevents the inhibition by thapsigargin. These data suggest that PKC and CaMK II modulate PROT and that thapsigargin mediates its effect via CaMK II. 4. Thapsigargin raises [Ca2+]I and increases PRO-induced current on a second time scale, whereas the inhibitory effect of thapsigargin occurs only after 10 min of treatment. These data suggest that Ca2+ differentially regulate PROT: Ca2+ initially enhances PRO transport but eventually inhibits transport function through CaMK II pathway. 5. Ca(2+)-induced stimulation exemplifies the acute regulation of a neurotransmitter transporter, which may play a critical role in the profile of neurotransmitters during synaptic transmission.

Amino Acid Transport Systems, Neutral↗
PubMed1999

Relationship between iron concentration and hepatitis C virus RNA level in liver tissue.

Patients with chronic hepatitis C virus (HCV) infection frequently have increased hepatic iron stores. The role of hepatitis C in hepatic iron deposition is unknown. The authors examined whether there is a relation between hepatitis C virus level in liver tissue and hepatic iron concentration. Forty-two paired samples obtained from the liver explants of five patients who underwent transplantation for liver disease due to hepatitis C were studied. Hepatitis C virus levels were measured at multiple sites within each liver by a branched deoxyribonucleic assay. Measurements of hepatic iron concentration were made at adjacent sites by a colorimetric assay. Random effects modeling showed wide intrahepatic variation in hepatic HCV ribonucleic acid (RNA) concentration (variance = 1.2 x 10(4) [mEq/g]2) and hepatic iron concentration (variance = 1.3 x 10(6) [microg/g]2). There was, however, a trend toward an association between the mean HCV level and the mean hepatic iron concentration for each liver (r = 0.30, p = 0.05). In conclusion, HCV level and iron concentration varied within and between cirrhotic livers. Variability in intrahepatic iron concentration was not related to variability in intrahepatic HCV RNA concentration. More studies are needed to determine the cause of variability in hepatic iron and HCV RNA concentration within and between livers in patients with chronic hepatitis C.

Hepacivirus↗
PubMed1999

Homeopathy in rehabilitation medicine.

Rehabilitationists must be able to assess not only the diagnostic entity, but also the person who is sick. The rehabilitation community's understanding of the holism involved in healing and the limitations of conventional therapies creates an openness to consider the usefulness of unconventional therapies. This article explores the role of homeopathy in rehabilitation medicine.

Female↗
PubMed1998

Na+-coupled alanine transport in LLC-PK1 cells: the relationship between the Km for Na+ at low [Alanine] and potential dependence for the system.

Analysis of the mechanistic basis by which sodium-coupled transport systems respond to changes in membrane potential is inherently complex. Algebraic expressions for the primary kinetic parameters (Km and Vmax) consist of multiple terms that encompass most rate constants in the transport cycle. Even for a relatively simple cotransport system such as the Na+/alanine cotransporter in LLC-PK1 cells (1:1 Na+ to substrate coupling, and an ordered binding sequence), the algebraic expressions for Km for either substrate includes ten of the twelve rate constants necessary for modeling the full transport cycle. We show here that the expression of Km of the first-bound substrate (Na+) simplifies markedly if the second-bound substrate (alanine) is held at a low concentration so that its' binding becomes the rate limiting step. Under these conditions, the expression for the KNam includes rate constants for only two steps in the full cycle: (i) binding/dissociation of Na+, and (ii) conformational 'translocation' of the substrate-free protein. The influence of imposed changes in membrane potential on the apparent KNam for the LLC-PK1 alanine cotransporter at low alanine thus provides insight to potential dependence at these sites. The data show no potential dependence for KNam at 5 micron alanine, despite marked potential dependence at 2 mm alanine when the full algebraic expression applies. The results suggest that neither translocation of the substrate-free form of the transporter nor binding/dissociation of extracellular sodium are potential dependent events for this transport system.

Adenosine Triphosphate↗
PubMed1998

Starvation depresses acylglycerol biosynthesis in bovine subcutaneous but not intramuscular adipose tissue homogenates.

The primary objective of this study was to document the effects of starvation on acylglycerol biosynthesis in homogenates of intramuscular and subcutaneous adipose tissues. Adipose tissue samples were obtained from 8th-13th thoracic rib sections from 12 Angus cattle (six steers plus six heifers). Three steers and three heifers were starved for 72 h prior to slaughter while the remainder were slaughtered 4 h after food was withheld. Fat-free 700 x g centrifugal fractions were used to measure the esterification of radiolabeled sn-glycerol 3-phosphate (G-3-P) into acylglycerols at 1.0 mM palmitic or stearic acid, or 0.2 mM oleic, linoleic, or alpha-linolenic acid. There were significant tissue x fatty acid interactions for rates of incorporation into diacylglycerols and triacylglycerols; in subcutaneous, but not intramuscular homogenates, palmitic > stearic = oleic = linoleic = alpha-linolenic acid. Subcutaneous homogenates incorporated a greater percentage of G-3-P into triacylglycerols, and a lesser percentage into phospholipid, than intramuscular homogenates (P < 0.05). In intramuscular homogenates, the primary product of G-3-P esterification to saturated fatty acids was phospholipids. When unsaturated fatty acid served as substrates, triacylglycerols and phospholipids were produced in equal proportions in intramuscular homogenates, and triacylglycerols were the predominant product in subcutaneous homogenates. Intramuscular adipose tissue homogenates exhibited no response to starvation, whereas triacylglycerol and diacylglycerol synthesis was depressed by approximately 50% in subcutaneous adipose tissue homogenates. Similarly, phosphatidic phosphohydrolase activity, initially greater in subcutaneous than in intramuscular adipose tissue, was decreased by approximately 50% by starvation in subcutaneous adipose tissue, but not in intramuscular adipose tissue. We conclude that differences in rates of diacylglycerol and triacylglycerol biosynthesis, and response to starvation, between intramuscular and subcutaneous adipose tissues were due to dissimilarities in the activity of phosphatidic phosphohydrolase.

Adipose Tissue↗
PubMed1998

Multigene tracking of hepatitis C virus quasispecies after liver transplantation: correlation of genetic diversification in the envelope region with asymptomatic or mild disease patterns.

To investigate the role of hepatitis C virus (HCV) quasispecies mutation in the pathogenesis of HCV infection, we analyzed changes in the genetic diversity of HCV genomes in 22 patients before and after liver transplantation by using heteroduplex mobility assay (HMA) technology. All patients were infected with HCV genotype 1 and developed high-titer posttransplant viremia. Each patient was classified according to the severity of posttransplant hepatitis, as assessed by standard biochemical and histological criteria. HCV quasispecies were characterized by HMA analysis of eight separate subgenomic regions of HCV, which collectively comprise 44% of the entire genome. The glycoprotein genes E1 and E2, as well as the nonstructural protein genes NS2 and NS3, had the greatest genetic divergence after liver transplantation (the change in the heteroduplex mobility ratio [HMR] ranged from 2.5 to 7.0%). In contrast, genes encoding the core, NS4, and NS5b proteins had the least amount of genetic divergence after liver transplantation (range, 0.3 to 1.2%). The E1/E2 region showed the greatest change in genetic diversity after liver transplantation, and the change in HMRs was 2.5- to 3.3-fold greater in patients with asymptomatic or moderate disease than in those with severe disease. The E1-5' region of HCV quasispecies isolated from patients in the asymptomatic group had a significantly greater degree of diversification after liver transplantation than the same regions of HCV quasispecies isolated from patients in the severe disease group (P = 0.05). While changes in the genetic diversity of some nonstructural genes were also greater in asymptomatic patients or in patients with mild disease than in patients with severe disease, the results were not significant. Data from this cohort demonstrate that greater rates of HCV quasispecies diversification are associated with mild or moderate liver disease activity in this immunosuppressed population.

Base Sequence↗
PubMed1997

Coping strategies and laboratory pain in children with sickle cell disease.

Studies have found that coping strategies are significant predictors of pain report, health care use, and psychosocial adjustment in children with sickle cell disease (SCD); however, the mechanisms of the relationship are not clear. In this study, 41 children with SCD completed a laboratory pain task to analyze their pain perception under standardized conditions. Sensory decision theory analyses were used to analyze the pain perception data. Children and their parents also completed measures of coping strategies and adjustment. Hierarchical regression analyses controlling for the child's age indicated that children who reported using active cognitive and behavioral coping strategies had a lower tendency to report pain during the laboratory pain task. Results are discussed in terms of the utility of using laboratory pain models with children and the need for future intervention studies to target coping strategies in children with SCD pain.

Adaptation, Psychological↗
PubMed1997

The stability of pain coping strategies in young children adolescents, and adults with sickle cell disease over an 18-month period.

OBJECTIVE: The current study assessed stability of pain coping strategies over an 18-month period in adults, adolescents, and young children with sickle cell disease. DESIGN: Eighteen-month longitudinal study. Assessments of coping strategies were done at baseline, 9 months, and 18 months. PATIENTS: A total of 141 patients with sickle cell disease (SCD) presenting to adult and pediatric sickle cell clinics for regularly scheduled check-ups. OUTCOME MEASURES: Coping Strategy Questionnaire subscales (Coping Attempts, Negative Thinking, and Illness-Focused Strategies). RESULTS: pearson Product-Moment correlation coefficients comparing baseline and 18-month follow-up coping data were highly significant for Coping Attempts and Negative Thinking/Illness Focused Strategies for adults. For young children, the 18-month follow-up scores on Negative Thinking were significantly correlated with baseline scores, however, no other 18-month correlations were significant. The results from the adolescent subset of subjects indicated no significant correlations on any of the coping strategies from baseline to 18-month-follow-up. Stability was also assessed using intraclass correlations, which incorporates more than two test-retest values on the same subjects. These analyses confirmed that coping strategies in adults were highly stable, whereas for children and adolescents, there was instability ANOVAs indicated that adolescents scored significantly higher than young children on Negative Thinking and Illness-Focused Strategies at baseline and follow-up. CONCLUSIONS: As compared with the highly stable coping evidenced in adults with SCD, coping in children and adolescents with SCD is more variable. Thus, interventions should target children early before maladaptive coping patterns become entrenched.

Adaptation, Psychological↗
PubMed1997

Cyclophosphamide and fluorouracil combined with mitoxantrone versus doxorubicin for breast cancer: superiority of doxorubicin.

PATIENTS AND METHODS: We conducted a randomized, multicenter study of intravenous cyclophosphamide 500 mg/m2 plus fluorouracil 500 mg/m2 combined with either mitoxantrone (Novantrone, Lederle Cyanamid Canada Ltd, Willowdale, Ontario) 10 mg/m2 (CNF) or doxorubicin (Adriamycin, Adria Laboratories of Canada Ltd, Mississauga, Ontario) 50 mg/m2 (CAF) every 3 weeks in advanced breast cancer. RESULTS: The response rate in 249 randomized patients was 36% with CNF (44 of 121) and 48% with CAF (62 of 128) (P = .054), with complete remissions in 10 patients (8.3%) on CNF and in 13 (10.2%) on CAF. If only fully assessable patients are considered, the response rate was 48% (44 of 91) with CNF and 60% (62 of 103) with CAF (P = .098). At time of analysis, all except 10 patients (one CNF and nine CAF) had died. The median survival time with CAF was longer than with CNF (15.2 v 10.9 months; P = .003), and time to progression was also longer with CAF (5.3 v 3.2 months; P < .03). Survival differences remained significant (P = .006) if patients who failed to meet all eligibility criteria were excluded. Favorable prognostic factors for survival in a Cox regression model included good performance status (P < .0001); less than two organ systems involved by tumor (P < .0001); no involvement of lung, liver, or brain (P < .003); involvement of bone or bone marrow (P < .009), prior surgery for breast cancer (P < .006); being premenopausal (P < .03); > or = 3 years from diagnosis until randomization on this study (P < .03); and treatment with CAF (P < .03). Alopecia > or = grade 3 was reported in 55% of patients with CAF and 12% of patients with CNF (P < .001), while other > or = grade 3 toxicities did not differ significantly. Priestman-Baum quality-of-life assessment was comparable on the two study arms. CONCLUSION: In patients with advanced breast cancer, CAF was associated with longer survival than was CNF, with an increase in alopecia, but not in other toxicities.

Adult↗
PubMed1997

Cognitive coping skills training in children with sickle cell disease pain.

This study was designed to examine whether brief training in cognitive coping skills would enhance pain coping strategies and alter pain perception in children and adolescents with sickle cell disease (SCD). Forty-nine participants with SCD were randomly assigned to either a cognitive coping skills condition or a standard care control condition. At pre- and posttesting, coping strategies and pain sensitivity using laboratory pain stimulation were measured. Results indicated that in comparison to the randomly assigned control condition, brief training in cognitive coping skills resulted in decreased negative thinking and lower pain ratings during low intensity laboratory pain stimulation.

Journal Article↗
PubMed1996

Suppression of renal gamma-glutamylcysteine synthetase expression in dietary copper deficiency.

A dietary deficiency of copper (CuD) is associated with a 50-70% and a 2-fold increase in hepatic reduced glutathione (GSH) concentration and synthesis, respectively, which leads to a 50-80% increase in plasma GSH. Moreover, the kidneys of CuD rats remove 40% more GSH from the blood than copper adequate (CuA) rats. These findings have led us to propose that the increase in hepatic synthesis of GSH in CuD rats is accompanied by a comparable increase in the hepatic expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate limiting enzyme of glutathione biosynthesis, and that the enhanced uptake of GSH by the kidney would lead to a compensatory decrease in renal gamma-GCS expression. In experiment I, male weanling rats (3-4 weeks) were ad libitum fed a CuD (0.5 microgram Cu/g) or CuA (5.8 micrograms/g) diet for 70 days; and in experiment II, male weanling rats were pair-meal fed the CuD or CuA diet for 35 days. In both studies, CuD diet caused a significant increase in hepatic GSH concentration, but hepatic gamma-GCS activity and mRNA abundance were unchanged. In contrast, renal GSH concentration was unaffected by the CuD diet. However, renal gamma-GCS activity was reduced 40% and this was paralleled by a 50% decrease in gamma-GCS mRNA. Moreover, the decrease in renal gamma-GCS mRNA was caused by a reduction in renal gamma-GCS gene transcription. The results of these studies indicate that the increase in renal uptake of GSH resulting from a dietary Cu deficiency is associated with a compensatory decrease in gamma-GCS expression.

Animals↗
PubMed1996

Effects of cognitive coping skills training on coping strategies and experimental pain sensitivity in African American adults with sickle cell disease.

The present study examined whether training in cognitive coping skills would enhance pain coping strategies and alter pain perception in adults with sickle cell disease (SCD). Sixty-four African Americans with SCD were randomly assigned to either a cognitive coping skills condition (three 45-min sessions in which patients were trained to use 6 cognitive coping strategies) or a disease-education control condition (three 45-min didactic-discussion sessions about SCD). Pain sensitivity to calibrated noxious stimulation was measured at pre- and posttesting, as were cognitive coping strategies, clinical pain, and health behaviors. Results indicated that, compared with the randomly assigned control condition, brief training in cognitive coping skills resulted in increased coping attempts, decreased negative thinking, and lower tendency to report pain during laboratory-induced noxious stimulation.

Adaptation, Psychological↗
PubMed1996

Tracking hepatitis C virus quasispecies major and minor variants in symptomatic and asymptomatic liver transplant recipients.

To evaluate the possibility that distinct viral quasispecies play a role in the pathogenesis of progressive hepatitis C virus (HCV) infection, we performed a detailed evaluation of HCV quasispecies before and after liver transplantation in five patients infected with HCV genotype 1, three of whom developed severe recurrent hepatitis C and two of whom developed asymptomatic posttransplant infections with high-titered viremia. HCV quasispecies were characterized by using a combination of nucleotide sequencing plus heteroduplex tracking assay of the second envelope gene hypervariable region (HVR). An average of 30 HVR clones were analyzed per specimen; an average of five specimens were analyzed per patient over a 6- to 24-month study period. The complexity of HCV quasispecies in pretransplant serum varied, ranging from one to nine genetically distinct variants for the five patients. However, in all five cases, relatively homogenous quasispecies variants emerged after liver transplantation. In the three patients who developed recurrent hepatitis, quasispecies major variants present in pretransplant serum were efficiently propagated immediately after liver transplantation and were propagated throughout the course of acute and chronic hepatitis. In contrast, in the two asymptomatic cases, we observed rapid depletion of pretransplant quasispecies major variants from posttransplant serum, followed by emergence of new quasispecies variants by posttransplant day 30. Genetic analysis suggested that in these cases, the new quasispecies variants were derived from minor variants present at relatively low clonal frequency (less than 5% of HVR clones) within the pretransplant quasispecies populations. These data demonstrate that quasispecies tracking patterns are associated with the rapidity and severity of HCV-associated liver disease after liver transplantation. Further characterization of HCV quasispecies in animal model systems is warranted.

Amino Acid Sequence↗
PubMed1996

A model for the kinetic mechanism of sodium-coupled L-alanine transport in LLC-PK1 cells.

The kinetics of sodium-dependent L-alanine transport were characterized in ATP-depleted LLC-PK1 cells, which allows experimental imposition of an interior negative diffusion potential across the plasma membrane. Under these conditions a wide range of sodium concentrations can be studied without altering the membrane potential. When Na+ is the variable substrate, the apparent maximal velocity (V max) for transport changes nearly fourfold for the five different alanine concentrations studied (0.05-2.0 mM). In contrast, at five different sodium concentrations, ranging from 10 to 135 mM, the apparent V max with variable alanine remains nearly constant at 5.3 +/- 1.2 nmol.min-1.mg cell protein-1. The ratio of the two primary kinetic parameters, Michaelis constant (Km)/V max, varies markedly no matter which solute is treated as the variable illustrate. These data are consistent with a simultaneous ordered transport mechanism in which sodium binds before alanine to the transport protein at the extracellular surface of the membrane. Alanine-dependent 22Na+ influx is more than five times faster if unlabeled intracellular sodium is present than in its absence. Sodium-dependent influx of [14C]alanine is more rapid than net alanine flux only if unlabeled Na+ and alanine are both present intracellularly. These results indicate that the cotransporter can function more rapidly in an exchange mode than when it catalyzes net solute uptake and that Na+ is the first solute to be released at the intracellular side of the membrane. A model is presented that can be used for further quantitative analysis of the kinetic and functional properties of the cotransport system.

Amino Acid Transport Systems↗