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Biomedical subjects

D Chandler

Publications and source records attributed to D Chandler.

At least 55 records · Page 3Linked to original sources

A polymerase chain reaction-based assay for diagnosing varicella-zoster virus retinitis in patients with acquired immunodeficiency syndrome.

PURPOSE: To develop a rapid, sensitive, and specific laboratory assay based on the polymerase chain reaction for the diagnosis of varicella-zoster virus retinitis in patients with acquired immunodeficiency syndrome (AIDS). METHODS: We developed and tested a polymerase chain reaction-based assay for the detection of varicella-zoster virus DNA in vitreous samples. We attempted to detect varicella-zoster virus DNA in 14 vitreous samples from patients with AIDS and a clinical diagnosis of progressive outer retinal necrosis syndrome. For controls, we also attempted to detect varicella-zoster virus DNA in vitreous samples from 75 immunocompetent patients with vitreoretinal disease and 88 patients with AIDS and vitreoretinal inflammatory disease not related to progressive outer retinal necrosis syndrome. RESULTS: Varicella-zoster virus DNA was detected in 11 of 14 vitreous samples from AIDS patients with progressive outer retinal necrosis syndrome. All three samples that scored negative for varicella-zoster virus DNA came from eyes that had been treated aggressively with antiviral drugs and had clinically inactive disease at the time of vitreous biopsy. Varicella-zoster virus DNA was detected in only two of 75 control vitreous samples from immunocompetent patients with vitreoretinal disease and two of 88 control vitreous samples from patients with AIDS and vitreoretinal inflammatory disease not related to progressive outer retinal necrosis syndrome. CONCLUSION: We have developed a rapid, sensitive, and specific polymerase chain reaction-based diagnostic assay for varicella-zoster virus DNA that will assist in the diagnosis of varicella-zoster virus retinitis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Disciform keratitis: a case of herpes zoster sine herpete.

PURPOSE: To describe a case of disciform keratitis in a patient with acquired immunodeficiency syndrome (AIDS) in which varicella-zoster virus was the causative agent. METHOD: Case report, Polymerase chain reaction-based assays for varicella-zoster virus, cytomegalovirus, and herpes simplex virus were used to analyze an aqueous aspirate. RESULTS: We examined a 41-year-old man with AIDS but without a history of varicella-zoster virus dermatitis who had disciform corneal edema in his left eye. Varicella-zoster virus was detected by a polymerase chain reaction-based assay in the aqueous of the left eye; however, neither cytomegalovirus nor herpes simplex virus DNA were detected by polymerase chain reaction-based assays. The corneal edema slowly resolved while the patient was treated with famciclovir. CONCLUSION: Varicella-zoster virus may cause disciform keratitis without a preceding skin eruption.

2-Aminopurine↗

A capitated model for a cross-section of severely mentally ill clients: employment outcomes.

Employment outcomes are examined in a three year controlled study of two Integrated Service Agencies (ISAs) for a cross-section of severely mentally ill clients. At each site significantly more ISA members than comparison clients obtained some paid employment. At the urban site the difference was dramatic: 73 vs 15 percent worked during the study period, and 29 percent of the ISA clients worked competitively. The significant but still limited ISA results argue for increased employment opportunities for all seriously mentally ill clients.

California↗

Evolutionary conservation of regulatory strategies for the sex determination factor transformer-2.

Sex determination in Drosophila melanogaster is regulated by a cascade of splicing factors which direct the sex-specific expression of gene products needed for male and female differentiation. The splicing factor TRA-2 affects sex-specific splicing of multiple pre-mRNAs involved in sexual differentiation. The tra-2 gene itself expresses a complex set of mRNAs generated through alternative processing that collectively encode three distinct protein isoforms. The expression of these isoforms differs in the soma and germ line. In the male germ line the ratio of two isoforms present is governed by autoregulation of splicing. However, the functional significance of multiple TRA-2 isoforms has remained uncertain. Here we have examined whether the structure, function, and regulation of tra-2 are conserved in Drosophila virilis, a species diverged from D. melanogaster by over 60 million years. We find that the D. virilis homolog of tra-2 produces alternatively spliced RNAs encoding a set of protein isoforms analogous to those found in D. melanogaster. When introduced into the genome of D. melanogaster, this homolog can functionally replace the endogenous tra-2 gene for both normal female sexual differentiation and spermatogenesis. Examination of alternative mRNAs produced in D. virilis testes suggests that germ line-specific autoregulation of tra-2 function is accomplished by a strategy similar to that used in D. melanogaster. The similarity in structure and function of the tra-2 genes in these divergent Drosophila species supports the idea that sexual differentiation in D. melanogaster and D. virilis is accomplished under the control of similar regulatory pathways.

Alternative Splicing↗

Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24.

Founder effect and linkage disequilibrium have been successfully exploited to map single gene disorders, and the study of isolated populations is emerging as a major approach to the investigation of genetically complex diseases. In the search for genetic isolates ranging from Pacific islands to Middle East deserts, the 10 million Gypsies resident in Europe have largely escaped the attention of geneticists. Because of their geographical ubiquity, lack of written history and the presumed social and cultural nature of their isolation, Gypsies are construed as not meeting the criteria for a well defined founder population. Gypsy society has a complex structure with subdivisions and stratifications that are incomprehensible to the surrounding populations. Marginalization by the health care systems in most countries results in a lack of information on causes of morbidity and mortality and little is known about hereditary disorders or the population genetic characteristics of Gypsies. This study is the first example of mapping a disease gene in endogamous Gypsy groups. Using lod score analysis and linkage disequilibrium, we have located a novel demyelinating neuropathy to a narrow interval on chromosome 8q24. We show that the disease, occurring in Gypsy groups of different identity and history of migrations, is caused by a single mutation whose origin predates the divergence of these groups.

Adolescent↗

Client outcomes in a three-year controlled study of an integrated service agency model.

OBJECTIVE: In a three-year controlled study, two California integrated service agency demonstration programs that combined structural and program reforms were tested to see if they produced improved outcomes for a cross-section of clients with severe and persistent mental illness. METHODS: Clients at an urban site and a rural site were randomly assigned to an integrated service agency program or to a comparison group who received the usual services. Data on client outcomes, were drawn from databases and client and family interviews. RESULTS: Compared with the comparison groups, clients served by the integrated service agencies had less hospital care, greater workforce participation, fewer group and institutional housing arrangements, less use of conservatorship, greater social support, more leisure activity, less family burden, and greater client and family satisfaction. Clients in the urban demonstration program, but not those in the rural program, did better than the comparison group on measures of financial stability, personal well-being, and friendship. At the urban site, 72.6 percent of clients participated in the work force during the three-year study period, compared with 14.6 percent of the clients in the comparison group. No differences were found at either site in rates of arrest and conviction and in self-reported ratings of self-esteem, symptoms, medication compliance, homelessness, and criminal victimization. The capitated costs for demonstration clients were much higher than the costs for services used by comparison clients. CONCLUSIONS: Three-year outcomes for a cross-section of clients with severe mental illness in the integrated service agencies were broadly favorable, but costs of services for those clients were high relative to costs for clients receiving the current standard of care.

Adult↗

Client outcomes in two model capitated integrated service agencies.

OBJECTIVE: Client outcomes for the first year of a three-year study were measured in two integrated service agencies (ISAs) for severely mentally ill persons to test the effectiveness of a model combining financing reform (consolidated funding and capitation) with an assertive continuous treatment team approach. METHODS: Clients referred to pilot ISAs at an urban and a rural site in California were randomly assigned to the ISA programs or to comparison groups receiving usual services. Objective data from clients' records as well as subjective information from interviews were compared. RESULTS: At both sites, demonstration clients' participation in the work force was significantly higher than that of the comparison groups. At the urban ISA, clients' participation in the work force rose from a baseline rate of 11 percent to 36 percent. Both ISAs decreased use of hospital care, particularly the rural ISA, which reduced admissions from a baseline rate of 40 percent to 21 percent in the study year. Both ISAs retained clients in treatment with significantly more success than did comparison programs, and urban ISA clients reported participating in more leisure and social activities than did clients in the comparison group. No differences were found at either site in rates of long-term hospitalization, arrest, or conviction or in measures of self-esteem, symptomatology, substance use, homelessness, or quality of life. CONCLUSIONS: After 12 months of a 36-month program, demonstration clients spent less time in hospitals, were more likely to have worked for pay, and were more likely to have remained in treatment.

Adult↗

Visualization of fast energy flow and solvent caging in unimolecular dynamics.

Energy flow in solution between physically or chemically evolving solute molecules and the surrounding solvent significantly affects the nature of chemical dynamics in liquids. It determines the extent to which the statistical theory of reaction rates is valid; the transfer of energy between solute and solvent influences the ease with which the transition state evolves into the products--the process central to transition-state theory. But analysing the energy flow in liquid-phase dynamics is difficult because these systems are so complex, and the degrees of freedom are consequently so numerous. Here we present a way to address this challenge. We introduce an approach for visualizing the energy flow directly, and apply it to the isomerization of cyclohexane (between boat and chair conformations) in liquid carbon disulphide, a process for which detailed information about the molecular motions is available from molecular dynamics simulations. Our method reveals in pictorial form the formation and relaxation of a solvent cage, and shows that the relaxation has a strong effect on energy flow to and from the transition state on sub-picosecond timescales. We anticipate that this visualization approach will be generally useful for elucidating dynamical molecular processes in solution.

Cyclohexanes↗

Apoptosis and expression of the bcl-2 proto-oncogene in the fetal and adult human kidney: evidence for the contribution of bcl-2 expression to renal carcinogenesis.

bcl-2 was identified as a transcript associated with the t(14;18) and imparts resistance to apoptotic cell death. bcl-2 is normally expressed in many tissues and exhibits remarkable structural and functional conservation. Using immunohistochemical and in situ DNA labeling techniques we examined the localization of bcl-2 in the developing human kidney. bcl-2 expression was rapidly upregulated in the induced metanephrogenic mesenchymal cells that differentiate into renal vesicles and nephrons. bcl-2 expression was undetectable in uninduced mesenchyme and in the renal ampullae and associated collecting system. The distribution of apoptotic cells within the developing kidney was inversely correlated with expression of bcl-2. The localization of bcl-2 protein in the adult human kidney also was examined. bcl-2 was expressed at high levels in all renal neoplasms examined providing a potential basis for the deregulation of apoptosis in the development and progression of these tumors.

Adult↗

Incidence of sudden infant death syndrome in infants with sickle cell trait.

The significantly higher incidence of both sickle cell trait (SCT) and sudden infant death syndrome (SIDS) in the black population suggests that SCT and SIDS may be epidemiologically related. To study this possibility, we identified, for the period of February 1990 to February 1992, all infants with SCT born in Los Angeles County whose disease was diagnosed through the California Newborn Screening Program. We matched these infants with all confirmed cases of SIDS in Los Angeles County from February 1990 to March 1993. Three cases of SCT among 589 infants confirmed to have had SIDS were identified. The incidence of SIDS was 1.25/1000 live births for the general population versus 0.58/1000 cases for the SCT group. This finding remained unchanged when rates were adjusted for ethnicity. We conclude that infants born with SCT are not at increased risk of dying of SIDS.

Black People↗