Search PubMed⌕ Search

Biomedical subjects

G R Smith

Publications and source records attributed to G R Smith.

At least 91 records · Page 5Linked to original sources
PubMed1997

A novel method for structure-based prediction of ion channel conductance properties.

A rapid and easy-to-use method of predicting the conductance of an ion channel from its three-dimensional structure is presented. The method combines the pore dimensions of the channel as measured in the HOLE program with an Ohmic model of conductance. An empirically based correction factor is then applied. The method yielded good results for six experimental channel structures (none of which were included in the training set) with predictions accurate to within an average factor of 1.62 to the true values. The predictive r2 was equal to 0.90, which is indicative of a good predictive ability. The procedure is used to validate model structures of alamethicin and phospholamban. Two genuine predictions for the conductance of channels with known structure but without reported conductances are given. A modification of the procedure that calculates the expected results for the effect of the addition of nonelectrolyte polymers on conductance is set out. Results for a cholera toxin B-subunit crystal structure agree well with the measured values. The difficulty in interpreting such studies is discussed, with the conclusion that measurements on channels of known structure are required.

Adenosine Triphosphatases↗
PubMed1997

Advances in mucosal immunology.

HIV infection is likely to remain a significant medical and scientific problem well into the twenty-first century. During the first 15 years of the epidemic, much has been learned about the biology of HIV infection, but the majority of biomedical research has focused on the peripheral circulation. It is likely that the behavior of the virus within the unique immunologic environment of the intestinal mucosa differs from that which is observed in the periphery. Many clinical and epidemiologic features of HIV infection offer compelling reasons to encourage further examination of the mucosal immune system's role in AIDS pathogenesis. This article has touched on most of the significant observations concerning the mucosal immune system and HIV infection, and it is clear that much remains to be done. As mentioned earlier, the mucosal abnormalities observed in HIV infection are likely to have many causes. Careful evaluation of patients with early disease and fewer confounding variables may provide fresh insight into AIDS pathogenesis. Similarly, prospective evaluation of selected patient populations may be more informative in characterizing the progressive alterations in mucosal immune function than random cross-sectional studies of poorly defined groups. It is equally important for immunologic assessment to be correlated with nutritional and symptomatic evaluation. Finally, the success or failure of future antiretroviral therapies will be critically related to the impact of such agents on lymphoid reservoirs of HIV infection such as the gastrointestinal tract, which are at present refractory to treatment.

Antigen-Presenting Cells↗
PubMed1997

Region-specific meiotic recombination in Schizosaccharomyces pombe: the rec11 gene.

Mutations in the rec11 gene of Schizosaccharomyces pombe reduce meiotic recombinant frequencies by as much as a factor of 300 on chromosome III but less than a factor of 4 in the intervals tested on chromosomes I and II. To gain insight into the function of this region- (or chromosome-) specific activator of recombination, we have cloned and sequenced the rec11 gene. Meiotic crosses with rec11 disruption mutations placed the rec11 gene 6 cM from ade6 on chromosome III. Transcripts of rec11 accumulated transiently at 2-3 h after induction of melosis in a pat1-114 (Ts) mutant. Reverse transcriptase/polymerase chain reaction (RT-PCR) analysis of these transcripts revealed eight introns. The spliced RNA is predicted to encode a polypeptide of 923 amino acids with only very limited homology to reported proteins. The transient accumulation of rec11 transcripts and the phenotype of rec11 mutations suggest that the novel rec11 gene product acts early in meiosis to activate recombination preferentially on chromosome III.

Base Sequence↗
PubMed1997

Gene replacement with linear DNA fragments in wild-type Escherichia coli: enhancement by Chi sites.

During conjugation and transduction of Escherichia coli even numbers of recombinational exchanges are required for replacement of a gene on the circular chromosome. We studied gene replacement using a related method of gene transfer (transformation with 6.5-kb linear DNA fragments) as an experimental model for conjugation and transduction. Two properly situated Chi sites, 5' GCTGGTGG 3', stimulated gene replacement approximately 50-fold, more than the sum of the stimulation by the individual Chi sites. Gene replacement was dependent on RecA and RecB functions. Similar results were obtained with an alternative experimental model in which linear DNA fragments were generated from phage lambda by intracellular EcoRI restriction following infection. Dual Chi site-stimulation of these RecA-, RecB-dependent recombination events thus did not depend upon the mode of delivery of the linear DNA into the cells. A single DNA fragment with two Chi sites was sufficient for gene replacement. These results support a one Chi-one exchange hypothesis ("long chunk" gene replacement), stemming from studies with purified RecBCD enzyme, and argue against models in which Chi converts RecBCD enzyme to a state capable of promoting multiple exchanges on one DNA molecule. These results also provide a method for gene targeting in wild-type E. coli and suggest a method for gene targeting in other organisms.

Bacterial Proteins↗
PubMed1997

The Schizosaccharomyces pombe rec16 gene product regulates multiple meiotic events.

Previously isolated meiotic recombination (rec) mutants of Schizosaccharomyces pombe define 16 complementation groups. The rec genes cloned and sequenced to date reveal little amino acid sequence identity to other reported proteins. We examined the rec mutants for alterations in meiotic events other than recombination to gain insight into the rec gene functions and to assess whether they affect recombination directly or indirectly. While mutations in the rec6-12, 14, 15 and 19 genes appeared to affect only meiotic recombination, a mutation in rec16 delayed meiotic DNA synthesis and, in some instances, reduced its amount; mitotic DNA synthesis was not detectably altered, indicating that the rec16 effect is limited to meiosis. In the rec16 mutant some meiotically induced transcripts (e.g., rec7 and 15) were significantly reduced in abundance, whereas others (e.g., rec10 and exo1) were induced and degraded with normal timing and extent during meiosis, indicating that the rec16 mutation leaves the basic meiotic program intact. These results indicate that the rec genes other than rec16 have their primary effect on meiotic recombination. In contrast, the rec16 gene product is essential for normal meiotic replication, recombination, and induction of some transcripts. These meiotic events may be coupled via a dependence of recombination and transcription on replication or via a cascade of gene expression.

DNA, Fungal↗
PubMed1997

A WD repeat protein, Rec14, essential for meiotic recombination in Schizosaccharomyces pombe.

Mutations in the Schizosaccharomyces pombe rec14 gene reduce meiotic recombination by as much as a factor of 1000 in the three intervals tested on chromosomes I and III. A DNA clone complementing the rec14 mutation was shown by genetic and physical analysis to contain the rec14 gene, which was functional in plasmid-borne inserts as small as 1.4 kb. The rec14 gene contains two exons separated by a 53-bp intron, which was confirmed by analysis of rec14 transcripts. The spliced transcript encodes a protein product of 302 amino acids, which contains six WD repeat motifs found in the G-beta transducin family of proteins and other proteins, including the Saccharomyces cerevisiae Ski8 (Rec103) protein. Although the rec14 transcripts were present in mitotically dividing cells, rec14 mutations had no detectable effect on mitotic recombination. The pattern of expression of rec14 differes from that of previously analyzed S. pombe rec genes. Based upon mutant phenotypes and amino acid sequence similarities, we propose that S. pombe Rec14 is a functional homologue of S. cerevisiae Rec103.

Amino Acid Sequence↗
PubMed1997

Classification of human and animal strains of Fusobacterium necrophorum by their pathogenic effects in mice.

Forty-six strains of Fusobacterium necrophorum, 24 from animals and 22 of human origin, were examined by pathogenicity tests in mice, while the same strains were being examined in laboratories elsewhere by other methods. The pathogenicity tests consisted of (1) subcutaneous inoculation with a large dose of a pure culture, (2) subcutaneous inoculation with a small dose of F. necrophorum mixed with a large but relatively harmless dose of Staphylococcus aureus, and (3) intravenous inoculation with a large dose of a pure culture. Fourteen strains, all of animal origin, showed the characteristic behaviour of biotype A. Twenty-eight strains, 10 of animal origin and 18 from man, were classified as biotype B. The remaining four strains, all from man, produced a distinct type of infection in mice; these strains were referred to as 'A2433-like' because of their resemblance to a strain described in an earlier study. It would appear that biotype A strains, responsible for classical necrobacillosis in animals, do not infect man; that biotype B strains occur in both man and animals; and that 'A2433-like' strains are probably confined to man.

Animals↗
PubMed1997

Implementing outcomes management systems in mental health settings.

Outcomes management has received considerable attention in the literature on mental health services delivery. However, relatively little practical information is available on how to implement an outcomes management system in the mental health care setting. The authors review seven key issues that must be addressed in planning such a system: involving senior organizational leaders in ownership of the project, securing the support of clinicians and patients, selecting personnel to operate the system, choosing outcomes assessment instruments, developing data collection procedures, selecting techniques for data management, and using the data to improve outcomes. Ultimately, an outcomes management system is intended to generate data that can be used to stimulate discussion, to guide clinicians in tailoring treatments, and to identify efficient treatment approaches.

Data Collection↗
PubMed1997

Principles for assessment of patient outcomes in mental health care.

With the dramatic changes that are occurring in mental health and substance abuse treatment systems, it is imperative that the field keep its focus on the patient and the patient's outcomes of care. Outcomes management systems that measure the processes of care, the patient's characteristics, and the patient's outcomes of care can be helpful in maintaining this focus. To facilitate the development of these systems, the Outcomes Roundtable, a group of mental health consumer, professional, service, and policy-making organizations, has articulated a set of 12 broadly applicable principles of outcomes assessment. The principles call for outcomes assessments that are appropriate to the question being answered, that use tools with demonstrated validity and reliability and sensitivity to clinically important changes over time, and that always include the consumer perspective. In addition, the principles recommend outcomes assessments that create minimal burden for respondents and are adaptable to different health care systems, that include general health status as well as mental health status, and that include consumers' evaluation of treatment and outcomes. Outcomes assessment tools should quantify the type and extent of treatment, should include generic and disorder-specific information, and should measure areas of personal functioning affected by the disorder. Outcomes should be reassessed at clinically meaningful points in time. Outcomes assessment should use appropriate scientific design and representative samples and should examine outcomes of consumers who prematurely leave treatment as well as those who continue in treatment.

Humans↗
PubMed1997

Assessing the effectiveness of mental health care in routine clinical practice. Characteristics, development, and uses of patient outcomes modules.

The health care delivery system faces continually increasing pressure to be accountable for the historically unparalleled amount of resources it utilizes. This article discusses one set of recently developed tools known as outcomes modules that are used to assess how treatment affects outcomes in patients with a given disorder. These tools currently are being used to inform administrative decisions about how to improve the quality of care, and can potentially influence decisions by patients, providers, and payers of care as well. The critical components of outcomes modules, as well as their administration and applications are described, using modules for psychiatric conditions as examples.

Data Collection↗
PubMed1997

Validation of the Panic Outcomes Module.

This article discusses the validation of a module designed to evaluate the outcomes of clinical care for panic disorder. The research utilized a longitudinal design to examine cross-sectional relationships and change over time within and between subjects. Baseline, follow-up, and test-retest data were collected on 73 patients. The initial field test indicates that the Panic Outcomes Module measures outcomes and case-mix characteristics with acceptable levels of measurement error for group data. The module's measure of change in panic severity demonstrated encouraging agreement with the structured interviewer's judgement of change. This module, completed in approximately 20 minutes, is short enough to incorporate into outpatient mental health settings. We recommend that providers and administrators interested in monitoring the outcomes of specialty care for panic disorder seek assistance from health services researchers to use the Panic outcomes module. Further research is needed to validate this module for use in primary care populations.

Adult↗
PubMed1997

An instrument for measurement of outcomes of care for schizophrenia. Issues in development and implementation.

To advance effectiveness research in mental health, we need common, standardized, validated instruments that can be used easily in routine practice settings. The Schizophrenia Outcomes Module is a relatively brief, comprehensive instrument for monitoring and assessing the outcomes of treatment for schizophrenia in clinical care settings. The module was developed with the guidance of a multiinstitutional, multidisciplinary expert panel; the clinical and theoretical considerations that framed the expert panel's deliberations and determined the module's content and characteristics are described. Initial field testing of the instrument involved longitudinal observation of 100 individuals with schizophrenia over a 6-month period. To our knowledge, it is the only brief and easily administered instrument that encompasses the four major outcome domains defined by the National Institute of Mental Health's Plan for Research on the Severely Mentally Ill. As such, it is a promising tool for effectiveness research in schizophrenia.

Adolescent↗
PubMed1997

Effectiveness of care and improvement of quality of life in patients with panic disorder.

To investigate how practice guidelines or recommendations can be applied in the assessment of quality of care, 72 subjects beginning specialty treatment for panic disorder were enrolled. The Panic Outcomes Module assessed symptoms, health status, and treatment at baseline and after 8 weeks. Using published guidelines, the authors developed specific criteria to rate whether subjects' reports reflected appropriate treatment, including antipanic medication or three or more subsequent visits that involved antipanic behavioral therapy elements. Sixty-nine subjects (96%) completed the Panic Outcomes Module at both baseline and follow-up. Improvement in symptoms and health status was not different between subjects receiving appropriate and inappropriate care.

Adolescent↗
PubMed1997

Measuring outcomes and costs for major depression.

This article addresses briefly the measurement of multidimensional outcomes and costs for major depression. We emphasize the importance of measuring outcomes in a variety of domains, including the broader issues of improvement or decline in functioning and impairment based on domains known to be affected by major depression. We emphasize the importance of measuring the economic costs of illness, both the direct total health care costs and indirect costs. Direct costs include mental health treatment costs and all other health care costs. Indirect costs include such varied factors as lost wages for the depressed individual and caregiver burden. We demonstrate the usefulness and importance of using these measures with several examples from our own research.

Arkansas↗
PubMed1996

Cost-effectiveness of clozapine monitoring after the first 6 months.

BACKGROUND: Clozapine is effective in treating patients with schizophrenia who do not respond to conventional neuroleptic drugs. The drug is unique in that it is available only with a US Food and Drug Administration-mandated system for weekly monitoring of patients' white blood cell counts. No study has been conducted to evaluate the cost-effectiveness of this mandatory monitoring system. METHODS: A benchmark case was established by utilizing cumulative incidence rates of agranulocytosis from a recent study with a large sample of clozapine-treated patients. We assumed a 20% mortality among patients with agranulocytosis, $30.61 in monitoring costs each week, and 14.4 years of remaining life expectancy after detection of agranulocytosis. Based on these bench-mark assumptions, cost-effectiveness ratios in dollars per quality-adjusted life-year were calculated for the first, second, and third 6-month periods during which a patient was receiving clozapine. Sensitivity analyses were performed with more conservative assumptions in 5 alternative scenarios. RESULTS: In the benchmark case, costs per quality-adjusted life-year gained were $61,694, $925,418, and $420,644 for the first, second, and third 6-month periods of clozapine treatment, respectively. In the alternative scenarios, these costs ranged from $7923 to $46,056 for the first 6-month period and from $54,025 to $690,850 for the second and third 6-month periods. CONCLUSIONS: While the costs of monitoring patients with schizophrenia in the first 6-month period of clozapine treatment seem to be justifiable, monitoring thereafter may not be cost-effective because of the very low incidence of agranulocytosis in the later periods.

Adult↗