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Biomedical subjects

J G Wilson

Publications and source records attributed to J G Wilson.

At least 19 recordsLinked to original sources
PubMed2002

Challenges encountered in measuring outcome for a rural psychiatric residential program.

Evaluation of outcome measures can provide policymakers with valuable information on the effectiveness of psychiatric rehabilitation. Two specific challenges in collecting outcome measures for psychiatric rehabilitation programs are heterogeneity of outcomes and difficulty with follow-up. These two challenges were illustrated in the process of evaluating Rose Hill Center, a rural residential psychiatric rehabilitation program. The original design was to conduct interviews with former residents and family members and verify healthcare utilization. The difficulty of locating people and their reluctance to participate conspired to lower the follow-up rates. The design was modified to improve the follow-up rate but decrease the details of specific outcomes. The results showed a high but biased follow-up rate, with more information obtained for people who graduated from the program. The residents with planned discharge showed excellent outcomes in terms of living situation, working situation, healthcare utilization, and low severity of current symptoms. High compliance with medication spoke to the program's philosophy of including the residents in the decision-making process. The dual challenges of heterogeneity of outcomes and difficulty in follow-up that limit efforts to document the value of psychiatric rehabilitation are discussed.

Adult↗
PubMed2001

Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages.

The nuclear oxysterol receptors LXRalpha (NR1H3) and LXRbeta (NR1H2) coordinately regulate the expression of genes involved in the transport and catabolism of cholesterol. In macrophages, LXR stimulates the transcription of genes encoding transporters involved in cholesterol efflux, which may limit the transformation of these cells into foam cells in response to lipid loading. Here, we report that natural and synthetic LXR ligands induce the expression of the LXRalpha gene in primary human macrophages and differentiated THP-1 macrophages. This regulation was not observed in primary human adipocytes or hepatocytes, a human intestinal cell line, or in any mouse tissue or cell line examined. The human LXRalpha gene was isolated, and the transcription initiation site delineated. Analysis of the LXRalpha promoter revealed a functional LXR/RXR binding site approximately 2.9 kb upstream of the transcription initiation site. We conclude that LXRalpha regulates its own expression in human macrophages and that this response is likely to amplify the effects of oxysterols on reverse cholesterol transport. These findings underscore the importance of LXR as a potential therapeutic target for the treatment of atherosclerosis.

Animals↗
PubMed2001

Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis.

Using solid-phase, parallel-array synthesis, a series of urea-substituted thioisobutyric acids was synthesized and assayed for activity on the human PPAR subtypes. GW7647 (3) was identified as a potent human PPARalpha agonist with approximately 200-fold selectivity over PPARgamma and PPARdelta, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will be a valuable chemical tool for studying the biology of PPARalpha in human cells and animal models of disease.

Animals↗
PubMed2001

Retrospective review of selective serotonin reuptake inhibitors and falling in older nursing home residents.

We compared the rate of falling in older nursing home residents who had been prescribed selective serotonin reuptake inhibitors (SSRIs), other classes of antidepressants, and no antidepressants. Data were obtained from pharmacy records, medical records, fall logs, and incidence reports for one nursing home (1995 data). Older adults on SSRIs were more likely to fall than older adults not on antidepressants (p = .003) and were more likely to have an injurious fall (p = .03). The association with falling remained significant even when including potential confounders (p = .007). Older nursing home residents should be treated for depression. However, SSRIs may also carry an increased risk for falling.

Accidental Falls↗
PubMed2000

Effect of buprenorphine on CYP3A activity in rat and human liver microsomes.

Buprenorphine is a partial opioid agonist available in France as an alternative to methadone in the treatment of opiate-dependent individuals. Twenty deaths have been reported in patients who have ingested buprenorphine in combination with benzodiazepines. Since buprenorphine and many benzodiazepines are CYP3A substrates, the effect of buprenorphine on CYP3A activity was examined in order to assess the likelihood of a pharmacokinetic interaction. The formation of 6beta-hydroxytestosterone was measured in dexamethasone-induced rat liver microsomes and in human liver microsomes under control conditions and in the presence of buprenorphine. Buprenorphine was found to be a weak inhibitor of CYP3A with a 50% decrease in enzyme activity occurring at a concentration of 118 microM (IC50) in human liver microsomes. IC50 was 0.3 microM for ketoconazole in the same system. Since the IC50 for buprenorphine is roughly 2000 times higher than typical plasma concentrations, this drug is unlikely to cause clinically significant inhibition of CYP3A in patients. Excessive CNS depression due to the combination of buprenorphine and benzodiazepines is most likely due to additive or synergistic pharmacologic effect unrelated to a pharmacokinetic interaction between the drugs.

Animals↗
PubMed2000

Progesterone inhibits glucocorticoid-induced murine thymocyte apoptosis.

Sex and sex hormones modulate immune development and responses. A primary target of their effects is the structure and cellularity of the thymus; therefore, we examined the effects of sex and sex steroids on thymocyte apoptosis. We demonstrate initially that male DBA mice have a significantly higher percentage of glucocorticoid-induced apoptotic thymocytes (46.1+/-3.8%) than their female counterparts (31.6+/-3.1%; P=0.012). We postulated that this gender difference was due to differential modulation of glucocorticoid-induced apoptosis by sex hormones such as estrogen, testosterone or progesterone. Both estrogen and testosterone increased in vitro thymocyte apoptosis. In contrast, progesterone not only inhibited spontaneous in vitro thymocyte apoptosis, but also prevented in vitro glucocorticoid-induced apoptosis. Progesterone administration also suppressed glucocorticoid-induced in vivo thymocyte apoptosis. These results suggest that anti-apoptotic effects of progesterone may influence T cell development and subsequent immune responses.

Animals↗
PubMed2000

A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.

Bile acids repress the transcription of cytochrome P450 7A1 (CYP7A1), which catalyzes the rate-limiting step in bile acid biosynthesis. Although bile acids activate the farnesoid X receptor (FXR), the mechanism underlying bile acid-mediated repression of CYP7A1 remained unclear. We have used a potent, nonsteroidal FXR ligand to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain. SHP-1 represses expression of CYP7A1 by inhibiting the activity of liver receptor homolog 1 (LRH-1), an orphan nuclear receptor that is known to regulate CYP7A1 expression positively. This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis.

Animals↗
PubMed1999

Quantitative alleles of CR1: coding sequence analysis and comparison of haplotypes in two ethnic groups.

The quantitative expression of complement receptor type 1 (CR1) on erythrocytes is regulated by two CR1 alleles that differ in having genomic HindIII fragments of either 7.4 or 6.9 kb and that determine high (H allele) or low (L allele) CR1 expression, respectively, across a 10-fold range. To investigate whether the product of the L allele may contain amino acid substitutions that make it more susceptible to proteolysis, cDNA sequence spanning the CR1 coding region was analyzed in two donors who were homozygous for the H and L alleles and differed by 7-fold in their mean numbers of CR1 per erythrocyte. Sequence differences were detected at 10 nucleotide positions, including 6 that would cause amino acid substitutions. The HindIII RFLP and 3 of the latter 6 sites were analyzed in genomic DNA of 85 Caucasians and 75 African Americans; sites encoding the other amino acid substitutions were analyzed less extensively. Two major haplotypes defined prototypic H and L alleles in both ethnic groups, suggesting that these alleles existed before the African and European populations diverged. Decreased erythrocyte CR1 expression is associated with impaired clearance of immune complexes from blood. Persistence of the L allele in all populations that have been analyzed may suggest a compensatory survival advantage, perhaps related to malaria or another infectious disease.

Alleles↗
PubMed1998

Analysis of complement receptor type 1 (CR1) expression on erythrocytes and of CR1 allelic markers in Caucasian and African American populations.

CR1 expression on erythrocytes (E) is regulated by an element that is tightly linked in Caucasians to the site of an RFLP of the CR1 gene. Genomic HindIII fragments of 7.4 and 6.9 kb identify alleles that are expressed in high (H allele) or low (L allele) amounts, respectively. When age-fractionated E of donors heterozygous for both the H and L alleles and for CR1 allotypes of differing molecular weights were analyzed in Western blots, the product of the L allele appeared to have an increased rate of loss during cell aging. A coding sequence polymorphism of CR1 predicted to cause a Pro-->Arg substitution in its proximal extramembranous region was tightly linked in Caucasians to the site of the HindIII RFLP. However, neither this polymorphism nor the HindIII RFLP correlated with CR1 expression among African Americans. Relative instability of CR1 encoded by the L allele thus may derive from another coding sequence polymorphism, or may require both the Pro-->Arg substitution and epistatic effects of another polymorphic gene.

Alleles↗
PubMed1997

Adhesive interactions in hemopoiesis.

Blood cells developing in the bone marrow exhibit adhesive interactions with stromal reticular cells and specialized macrophages, and with several defined components of the extracellular matrix. Receptors that are known to participate in these interactions include certain integrins, selectins, members of the immunoglobulin superfamily, and CD44, and this list may be expected to grow. Specific inhibitors of some integrins and of CD44 have been shown to disrupt hemopoiesis in vitro; thus the function of adhesive receptors appears critical to blood cell development. The capacity of such receptors to transmit signals through the plasma membrane suggests that they regulate not just the physical interactions of hemopoietic cells, but also the responses of the cells to their environment.

Animals↗
PubMed1996

Iron chelates bind nitric oxide and decrease mortality in an experimental model of septic shock.

The hydroxamic acid siderophore ferrioxamine B [FeIII(HDFB)+] and the iron complex of diethylenetri-aminepentaacetic acid [FeIII(DTPA)2-] protected mice against death by septic shock induced by Corynebacterium parvum + lipopolysaccharide. Although FeIII(DTPA)2- was somewhat more effective than FeIII(HDFB)+, the iron-free ligand H4DFB+ was significantly more effective than DTPA. The hydroxamic acid chelator has a much higher iron affinity than the amine carboxylate, allowing for more efficient formation of the FeIII(HDFB)+ complex upon administration of the iron-free ligand. Electrochemical studies show that FeIII(DTPA)2- binds NO stoichiometrically upon reduction to iron(II) at biologically relevant potentials to form a stable NO adduct. In contrast, FeIII(HDFB)+ is a stable and efficient electrocatalyst for the reduction of NO to N2O at biologically relevant potentials. These results suggest that the mechanism of protection against death by septic shock involves NO scavenging and that particularly effective drugs that operate a low dosages may be designed based on the principle of redox catalysis. These complexes constitute a new family of drugs that rely on the special ability of transition metals to activate small molecules. In addition, the wealth of information available on siderophore chemistry and biology provides an intellectual platform for further development.

Animals↗
PubMed1996

Soluble intercellular adhesion molecule 1 (ICAM-1) antigen in sera of bronchial asthmatics.

Previous studies have suggested that intercellular adhesion molecule 1 (ICAM-1, CD54) may be involved in the pathogenesis of asthma. In addition, a soluble form of ICAM-1 (sICAM-1) has been detected in increased concentrations in the sera of patients with certain inflammatory conditions. To determine whether bronchial asthma is associated with increased levels of sICAM-1 in serum and to assess the effects of therapy on these levels, the concentrations of sICAM-1 were measured in sera of healthy donors and asthmatic patients. The mean (+/- SD) level of serum sICAM-1 for 60 asthmatic patients (304.0 +/- 82.5 ng/mL) was significantly higher than that for 39 healthy volunteers (260.9 +/- 67.2 ng/mL; p = 0.004). Twenty-two patients considered to have atopic asthma and 24 patients with nonatopic asthma did not differ in their levels of sICAM-1. In 14 patients, serum concentrations of sICAM-1 were higher during asthma attacks than in the same patients during remission (p = 0.035). Serum sICAM-1 levels were lower in nine patients during treatment with oral prednisolone (2.5 to 40 mg/d) than during periods without systemic corticosteroid therapy (p = 0.002). Thus, active bronchial asthma is associated with the presence of increased levels of sICAM-1 in serum, and these levels may be modulated by corticosteroid therapy.

Acute Disease↗
PubMed1996

Adult respiratory distress syndrome induced by a Chinese medicine, Kamisyoyo-san.

We report the first case of Kamisyoyo-san-induced adult respiratory distress syndrome (ARDS). A 59-year-old female was given Kamisyoyo-san for treatment of seborrheic dermatitis. She then presented with a respiratory illness having clinical, radiologic and functional characteristics of ARDS. Bronchoalveolar lavage fluid showed an increased number of lymphocytes, neutrophils and eosinophils. The lymphocyte stimulation test with Kamisyoyo-san was positive.

Bupleurum↗