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Biomedical subjects

J Metcalf

Publications and source records attributed to J Metcalf.

At least 19 recordsLinked to original sources
PubMed2001

Defects of DNA mismatch repair in human prostate cancer.

Loss of mismatch repair (MMR) function leads to the accumulation of errors that normally occur during DNA replication, resulting in genetic instability. Germ-line mutations of MMR genes in the patients with hereditary nonpolyposis colorectal cancer lead to inactivation of MMR protein functions, and the defects of MMR are well correlated to the high rate of microsatellite instability in their tumors. Previous studies (T. Uchida, et al. Oncogene, 10: 1019-1022, 1995; S. Egawa, et al. Cancer RES:, 55: 2418-2421, 1995; J. M. Cunningham, et al. Cancer RES:, 56: 4475-4482, 1996; X. Gao, et al. Oncogene, 9: 2999-3003, 1994; H. Rohrbach, et al. Prostate, 40: 20-27, 1999) have shown that genetic instability (chromosomal and microsatellite instability) is detectable in human prostate cancer. To elucidate the role of MMR genes in the tumorigenesis of prostate cancer, we evaluated the expression of these genes in human cancer cell lines and in tumor specimens. Using Western blot analysis, we detected loss among MSH2, MLH1, PMS2, and PMS1 proteins in DU145, LNCaP, p69SV40T, M2182, and M12 cells. In addition, genomic instability in the prostate cell lines including DU145, PC3, LNCaP, p67SV40T, M2182, and M12 was detected by a microsatellite mutation assay. Significantly, immunohistochemical analysis of prostatic tissue revealed the reduction or absence of MMR protein expression in the epithelium of prostate tumor foci compared with normal adjacent prostate tissue. In contrast to hereditary nonpolyposis colorectal cancer, characterized by defects predominantly in MLH1 and MSH2, the samples we examined showed more tumor foci with loss of PMS1 and PMS2. PMS1, which is only expressed in the basal cells in normal glands, is conspicuously absent in most prostate cancer. From these results, we conclude that there are defects of MMR genes in human prostate cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A flow cytometric protocol for titering recombinant adenoviral vectors containing the green fluorescent protein.

As the use of adenoviral vectors in gene therapy protocols increases, there is a corresponding need for rapid, accurate, and reproducible titer methods. Multiple methods currently exist for determining titers of recombinant adenoviral vector, including optical absorbance, electron microscopy, fluorescent focus assay, and the "gold standard" plaque assay. This paper introduces a novel flow cytometric method for direct titer determination that relies on the expression of the green fluorescent protein (GFP), a tracking marker incorporated into several adenoviral vectors. This approach was compared to the plaque assay using 10(-4)- to 10(-6)-fold dilutions of a cesium-chloride-purified, GFP expressing adenovirus (AdEasy + GFP + GAL). The two approaches yielded similar titers: 3.25 +/- 1.85 x 10(9) PFU/mL versus 3.46 +/- 0.76 x 10(9) green fluorescent units/(gfu/mL). The flow cytometric method is complete within 24 h in contrast to the 7 x 10 days required by the plaque assay. These results indicate that the GFU/mL is an alternative functional titer method for fluorescent-tagged adenoviral vectors.

Adenoviridae↗
PubMed1998

Pharmacokinetic modeling of recombinant interleukin-2 in patients with human immunodeficiency virus infection.

A novel model was developed to characterize the time-varying clearance of recombinant interleukin-2 (IL-2). Sixty-eight patients with human immunodeficiency virus infection received 83 cycles of IL-2 either by continuous infusion or by subcutaneous injection for 5 days. IL-2 concentrations after intravenous infusions peaked at 24 hours and then declined by 55% to 78% during the remainder of the infusion. Soluble IL-2 receptors increased greater than 10-fold before gradually returning to baseline. Subcutaneous administration showed a dose-dependent decrease in area under the concentration-time curve (AUC) between days 1 and 5. A model was developed in 9 patients who had IL-2 concentrations and soluble IL-2 receptors determined by ELISA. Concentrations were fitted by an indirect stimulatory pharmacodynamic model. An additional 59 patients with only IL-2 concentrations were fitted to a simplified empiric model. Both models provided an overall r2 of 0.99 for the plot of observed versus fitted concentrations. The time-dependent increase in IL-2 clearance, likely receptor-mediated, was well described with use of an indirect-effects pharmacokinetic-pharmacodynamic model.

Adult↗
PubMed1998

Nurses as writers.

Although nurses are expected to be competent in on-the-job writing, most nurses receive little formal education in the types of writing required in practice. Thus, it is important for faculty in schools of nursing to include in the curricula various types of writing assignments to help students develop these skills. This article describes how at one university a course, "Nurses as Writers," provides opportunities for students to learn and practice the types of writing needed in their professional careers.

Curriculum↗
PubMed1997

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.

HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.

Adult↗
PubMed1997

The geoepidemiology of primary biliary cirrhosis.

There are apparently large geographical and secular variations in the prevalence of primary biliary cirrhosis worldwide. Most studies suggest that the disease is most common in Northern Europe, particularly northern Britain and Scandinavia, and that the prevalence is increasing. This comprehensive review of the literature explores to what extent these variations could be real rather than artifactual due to lack of comparability among studies. The major design flaws are examined and guidelines for better practice are outlined. It is hoped that other researches will utilize these recommendations for future studies so that true variations can be identified and hypotheses regarding disease causation may be formulated and investigated. These guidelines include: stringent case inclusion criteria; definition of date of disease onset; well-defined study period, area and population; multiple case finding methods; rigorous tracing of all possible cases. Preliminary results of the authors' study using these guidelines are described and report a point prevalence of 235 per million population in 1994 in the north of England, the highest yet reported.

Age of Onset↗
PubMed1995

Requirement for nursing care services and associated costs in acute spinal cord injury.

The purpose of this study was to analyze the requirement for professional nursing care and the nursing care costs for patients with acute spinal cord injury. This descriptive study used a convenience sample of 50 consecutively admitted spinal cord-injured (SCI) patients who agreed to participate. Trained data collectors interviewed patients daily, reviewed the chart and spoke with the patient's nurses, after which nursing diagnoses were determined and acuity calculated. The sample consisted of 26 quadriplegic (Q), 5 ventilator-dependent quadriplegic (V) and 19 paraplegic (P) SCI subjects. The median length of stay (LOS) was 16 days with an intensive care unit (ICU) LOS of 4 days. LOS in the intermediate unit was 11 days. Median hours of nursing care was 143 (translating to $2458) for the entire acute care hospitalization. Specific hours of care and consequent costs were determined for all three groups through both phases of care. Significant differences were found in the hours of nursing care required among the three groups (X2 7.18, df = 2, p < .03), even though no difference was found in the LOS. A nursing consumption ratio (hours of nursing care/hours of LOS) demonstrated that ventilator-dependent SCI patients required the greatest number of nursing care hours.

Acute Disease↗
PubMed1992

Powerlessness in acute spinal cord injury patients: a descriptive study.

The purpose of this study was to describe the frequency and characteristics of the nursing diagnosis, powerlessness, in an acute spinal cord injury (SCI) population. This descriptive study had a sample of 50 SCI patients admitted during the acute phase of injury to a model systems SCI center. Patients with a length of stay of greater than or equal to 15 days experienced a significantly higher (p less than .01) occurrence of powerlessness than did those with hospitalization of less than 15 days. Powerlessness was not found to cluster or occur in any pattern but was random throughout hospitalization. There was a statistically significant relationship (p less than .01) between the occurrence of powerlessness and patient acuity, with the occurrence increasing as acuity increased in severity. Quadriplegics and patients over the age of 60 years had a higher occurrence of powerlessness (p less than .05). This study demonstrated powerlessness was a commonly occurring diagnosis in acute SCI.

Adolescent↗
PubMed1991

Use of a new CD4-positive HeLa cell clone for direct quantitation of infectious human immunodeficiency virus from blood cells of AIDS patients.

A new CD4-positive HeLa cell line (clone 1022) with increased sensitivity for human immunodeficiency virus (HIV) isolates derived from AIDS patients could titer infectivity of HIV from most isolates at a level equal to that observed using normal human phytohemagglutinin (PHA)-stimulated lymphocyte cultures. By use of this clone with a focal immunoassay (FIA), peripheral blood mononuclear cells (PBMC) producing HIV were detected in 15% of seropositive asymptomatic patients and 23% of AIDS patients at a frequency of 1 in 2 x 10(4) to 3 x 10(6) PBMC. HIV detection by primary FIA correlated with low CD4-positive cells counts. HIV activation in cocultures with PHA blasts resulted in increasing numbers of cells releasing HIV starting 3-4 days after cocultivation. The low incidence of HIV detection by direct FIA compared with the high incidence of HIV isolation after cocultivation with PHA blasts provided quantitative infectivity data suggesting that HIV was in a state of latency or low expression in most PBMC of AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Bilateral fallopian tubal polyps: radiologic and pathologic correlation.

A case of bilateral fallopian tube filling defects found on hysterosalpingography performed on a patient for infertility work-up is presented. Repeat hysterosalpingography performed 4 years later showed no change. Microsurgical resection revealed the defects to be fallopian tubal polyps of endometrial origin.

Adult↗
PubMed1988

Common cardiac drugs and rehabilitation.

Cardiac patients are often on drugs. They invariably benefit from a rehabilitation programme where they may be seen more frequently than in a routine follow-up clinic. Rehabilitation units must keep alert for drug-induced adverse effects or symptomatic deterioration, as well as the more usual psychological and physical benefits they induce.

Adrenergic beta-Antagonists↗
PubMed1984

Evoked potentials: nursing perspectives.

An evoked potential is an electrical manifestation of the brain's response to an external stimulus. Evoked potential studies provide a sensitive, quantitative assessment of portions of the neurological system which may enhance clinical data but do not indicate specific diagnosis. Nurses, by enhancing self knowledge related to evoked potential studies, should be better able to present concise information to patient and families. The outcome will be a more knowledgeable and less anxious patient.

Brain↗