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Biomedical subjects

M J Kelley

Publications and source records attributed to M J Kelley.

At least 19 recordsLinked to original sources
PubMed2003

Hepatitis C seroprevalence among newly incarcerated inmates in the Texas correctional system.

The seroprevalence of hepatitis C (HCV) infection was examined among a sample of incoming inmates in the Texas Department of Criminal Justice (TDCJ) prison system. Rates were compared across demographic factors and three types of prison facilities: substance abuse felony punishment units (SAFPs), state jails and prisons. The study sample consisted of 3712 incoming inmates incarcerated for any duration, dating from 1 November 1998 to 31 May 1999. Among males, inmates entering SAFPs and state jails had comparable HCV infection rates (29.7 and 27.0%, respectively) to those entering prisons (27.3%). Among females, inmates entering prisons had a higher rate of infection (48.6%) than those entering state jails (35.1%) or SAFPs (38.3%). For both genders, blacks exhibited a lower overall infection rate than whites and Hispanics, and HCV seroprevalence increased in a stepwise fashion with age. All subgroups of TDCJ inmates, including those held in alternative correctional facilities, exhibited HCV infection rates that were comparable with previous reports of inmate populations, but dramatically higher than general community samples. Given that most inmates held in alternative facilities will return to the general community in a short period of time, understanding the HCV infection rates in these subgroups holds particular public health relevance.

Adolescent↗
PubMed2001

Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33.

Chordoma is a rare tumor originating from notochordal remnants that is usually diagnosed during midlife. We performed a genomewide analysis for linkage in a family with 10 individuals affected by chordoma. The maximum two-point LOD score based on only the affected individuals was 2.21, at recombination fraction 0, at marker D7S2195 on chromosome 7q. Combined analysis of additional members of this family (11 affected individuals) and of two unrelated families (one with 2 affected individuals and the other with 3 affected individuals), with 20 markers on 7q, showed a maximum two-point LOD score of 4.05 at marker D7S500. Multipoint analysis based on only the affected individuals gave a maximum LOD score of 4.78, with an approximate 2-LOD support interval from marker D7S512 to marker D7S684. Haplotype analysis of the three families showed a minimal disease-gene region from D7S512 to D7S684, a distance of 11.1 cM and approximately 7.1 Mb. No loss of heterozygosity was found at markers D7S1804, D7S1824, and D7S2195 in four tumor samples from affected family members. These results map a locus for familial chordoma to 7q33. Further analysis of this region, to identify this gene, is ongoing.

Chordoma↗
PubMed2001

The Community Partnerships Experience: a report of institutional transition at East Tennessee State University.

The Community Partnerships Program, sponsored by the W. K. Kellogg Foundation, served as a catalyst for significant changes within East Tennessee State University (specifically its schools of medicine, nursing, and public and allied health) and the rural communities involved. The authors describe the development and implementation of the program and its effects on the students, faculty, communities, and the three participating schools over the period 1992-1999. They also review the changes the program fostered in health professions education and the resulting institutional changes at their university. The primary motivation for change at East Tennessee State University was the desire to develop primary care providers who could more effectively function in an interdisciplinary and interprofessional health care system and who would be sensitive to community needs in rural and underserved areas. The planning process, curricular transformation, implementation of inquiry-based learning, community collaboration, and interdisciplinary education involving students from the three health professions schools are described, including challenges and difficulties (e.g., student attrition; retention of volunteer community-based clinical preceptors; initial faculty resistance; a climate of competition rather than cooperation). Outcomes are described, including students' enrollment and attrition in the program over time, performances on the U.S. Medical Licensing Examination, program graduates' career choices, and the types and locations of their practices. The program's students performed as well on professional licensing examinations as did their peers enrolled in traditional programs. Program graduates have been much more likely to select primary care careers and to practice in rural locations than have their non-program peers. The development strategies and experience gained could give useful insights to other universities contemplating a community-based component for health professionals within their existing curricula.

Community Participation↗
PubMed2001

Genetic changes in contralateral bronchioloalveolar carcinomas of the lung.

OBJECTIVE: The pattern of metastases and recurrence of bronchioloalveolar carcinoma (BAC) differs from adenocarcinoma of the lung, occurring more frequently within the lung without extrapulmonary involvement. Analyses of genetic differences of contralateral BACs may help to explain these clinical differences. METHODS: We compared paired tumors from 5 patients with contralateral metachronous BACs for loss of heterozygosity (LOH) on 6 chromosomal arms (2q, 3p, 5q, 9p, 13q and 17p) and mutational analysis of p53 and K-ras. RESULTS: Two patients, patients 1 and 2, had discordant patterns of LOH on 2 and 3 of the chromosome arms, respectively. In addition, patient 2 had a detectable K-ras mutation in his initial tumor but not in his second. These results suggest that in patients 1 and 2, the contralateral tumors were clonally unrelated. Patient 3 had no mutations in the K-ras or p53 gene and no LOH on any of the 5 informative chromosome arms. Patient 4 had LOH of 9p and mutated K-ras in both the first and the second tumor, with a mutation in the p53 gene in the first but not in the second tumor. Patient 5 had LOH of 17p and the same p53 mutations in both the first and the second tumor, with a mutation of K-ras in the first tumor but not in the second. CONCLUSIONS: The preponderance of evidence suggests that in patients 3, 4 and 5, the paired tumors were clonally related. The different patterns of LOH and mutations in clinically similar contralateral metachronous BACs provide evidence of genetic heterogeneity in the tumors of this patient group.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Guidewire incidents with inferior vena cava filters.

Several authors have demonstrated that prophylactically inserted inferior vena cava filters have decreased pulmonary thromboembolic complications in selected high-risk trauma patients. Guidewire-related mishaps are potential complications of inferior vena cava filters and are likely underreported. The authors present two cases and review strategies to prevent these complications.

Aged↗
PubMed2001

Effects of mechanical stretching on trabecular matrix metalloproteinases.

PURPOSE: The homeostatic mechanisms responsible for intraocular pressure (IOP) regulation are not understood. Studies were conducted to evaluate the hypothesis that trabecular meshwork (TM) cells sense increases in IOP as stretching or distortion of their extracellular matrix (ECM) and respond by increasing ECM turnover enzymes. METHODS: Flow rates were increased in perfused human anterior segment organ cultures and the matrix metalloproteinase (MMP) levels and IOP were evaluated. Human TMs in stationary anterior segment organ culture were mechanically stretched, and MMP levels were analyzed. TM cells were grown on membranes, which were then stretched, and MMP levels were evaluated. Western immunoblots, zymography, and confocal immunohistochemistry were used to evaluate changes in MMPs and their tissue inhibitors, the TIMPS: RESULTS: Doubling the flow rate in perfused human organ cultures increased gelatinase A levels in the perfusate by 30% to 50% without affecting gelatinase B or stromelysin levels. Immediately after doubling the flow rate, the measured IOP doubled. However, over the next few days the IOP gradually returned to the initial level, although the flow rate was maintained at double the initial value. Stretching stationary organ cultures or stretching TM cells grown on membranes resulted in similar increases in gelatinase A without changes in gelatinase B or stromelysin levels. The gelatinase A increases occurred between 24 and 72 hours and were approximately proportional to the degree of stretching. Although coating the membranes with different ECM molecule affected the gelatinase A response, the optimum response occurred when the cells had been grown long enough to produce their own ECM. By Western immunoblot and confocal immunohistochemistry, the stretch-induced increases in gelatinase A were accompanied by strong decreases in TIMP-2 levels and moderate increases in one membrane type MMP, MT1-MMP. After mechanical stretching of the membrane, gelatinase A, MT1-MMP and TIMP-2 all exhibited a similar punctate immunostaining pattern over the TM cell surface. CONCLUSIONS: These results are compatible with the hypothesis that elevations in IOP are sensed by TM cells as ECM stretch/distortion. TM cells respond by increasing gelatinase A and MT1-MMP, while decreasing TIMP-2 levels. This will increase ECM turnover rates, reduce the trabecular resistance to aqueous humor outflow, and restore normal IOP levels. This hypothesis provides a regulatory feedback mechanism for IOP homeostasis.

Animals↗
PubMed2000

Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9.

The authors had previously mapped a new locus-DFNA17, for nonsyndromic hereditary hearing impairment-to chromosome 22q12.2-q13. 3. DFNA17 spans a 17- to 23-cM region, and MYH9, a nonmuscle-myosin heavy-chain gene, is located within the linked region. Because of the importance of myosins in hearing, MYH9 was tested as a candidate gene for DFNA17. Expression of MYH9 in the rat cochlea was confirmed using reverse transcriptase-PCR and immunohistochemistry. MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane. Sequence analysis of MYH9 in a family with DFNA17 identified, at nucleotide 2114, a G-->A transposition that cosegregated with the inherited autosomal dominant hearing impairment. This missense mutation changes codon 705 from an invariant arginine (R) to histidine (H), R705H, within a highly conserved SH1 linker region. Previous studies have shown that modification of amino acid residues within the SH1 helix causes dysfunction of the ATPase activity of the motor domain in myosin II. Both the precise role of MYH9 in the cochlea and the mechanism by which the R705H mutation leads to the DFNA17 phenotype (progressive hearing impairment and cochleosaccular degeneration) remain to be elucidated.

Amino Acid Sequence↗
PubMed2000

Potential of an antibacterial ultraviolet-irradiated nylon film.

The antibacterial effectiveness of an ultraviolet-irradiated nylon 6, 6 film was investigated for potential use as a food-packaging material to reduce the surface microbial contamination of foods. The film-surface analyses showed that UV irradiation induced conversion of surface amide groups to amines. Irradiation also increased the dimensional scale of the film surface topography (depth of valleys) approximately 5-fold on the scale of nanometers. The irradiated nylon demonstrated antagonistic activity against Staphylococcus aureus 25923 and Escherichia coli TV1058 with 4.5 and 6 log reductions, respectively, of an initial population of 10(6) cfu mL(-1). The irradiated nylon was ineffective against Pseudomonas fluorescens 13525 and Enterococcus faecalis 19433 under similar conditions. The film demonstrated increased antimicrobial activity against S. aureus 25923 with increasing temperatures up to 45 degrees C, the highest temperature tested. Protein and salt inhibited the antibacterial nature of the irradiated film. Amines in solution (4.31 x 10(-8) M; the calculated equivalent of amines on the film) killed at least 1 x 10(4) cfu mL(-1) E. coli TV1058, and 4. 31 x 10(-7) M amines killed up to 1 x 10(7) cfu mL(-1) E. coli TV1058. The amines in solution required similar exposure time to the bacteria for population reduction as was observed with the irradiated film.

Amines↗
PubMed2000

MEN1 gene mutation analysis of high-grade neuroendocrine lung carcinoma.

Neuroendocrine tumors of the lung consist of a spectrum of neoplasms, including typical carcinoids, atypical carcinoids, large-cell neuroendocrine carcinomas (LCNEC), and small-cell lung carcinomas (SCLC). We previously reported frequent inactivation of the gene responsible for multiple endocrine neoplasia type 1 (MEN1) in both typical and atypical carcinoid tumors. In the present study, we extend the analysis of human NE lung tumors to include 9 primary SCLCs, 36 SCLC cell lines, and 13 primary LCNECs for MEN1 gene inactivation. In SCLC, loss of heterozygosity (LOH) at the MEN1 gene on chromosome band 11q13 was detected in one primary tumor and two cell lines. The coding sequence and splice junctions of the MEN1 gene were screened for mutations in all 44 tumors and cell lines, and no mutations were detected. Northern blot analysis of 13 SCLC cell lines showed the MEN1 transcript to be present and of normal size. In LCNECs, a somatic frameshift in the MEN1 gene (1226delC) was found in one of 13 tumors, representing the first mutation observed outside the spectrum of neoplasms associated with MEN1. Interestingly, neither a deletion nor a mutation was detected in the other allele, and wild-type mRNA sequence was expressed in the tumor, suggesting that the MEN1 gene was not inactivated by a conventional two-hit mechanism. The data support the hypothesis that SCLC and lung carcinoids develop via distinct molecular pathways; however, further investigation is necessary to determine the significance of the MEN1 gene mutation observed in a single case of LCNEC. Published 2000 Wiley-Liss, Inc.

Carcinoma, Large Cell↗
PubMed2000

Autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is linked to chromosome 22q12-13.

Macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is a rare autosomal dominant disorder characterized by thrombocytopenia, giant platelets, and Döhle body-like inclusions in leukocytes. To determine the genetic basis of this disorder, we performed a genome-wide screen for linkage in three families with May-Hegglin anomaly. For the pooled analysis of the three families, three markers on chromosome 22 had two-point logarithm-of-difference (lod) scores greater than 3, with a maximum lod score of 3.91 at a recombination fraction (theta) of 0.076 for marker D22S683. Within the largest family (MHA-1), the maximum lod score was 5.36 at theta=0 at marker D22S445. Fine mapping of recombination events using eight adjacent markers indicated that the minimal disease region of family MHA-1 alone is in the approximately 26 cM region from D22S683 to the telomere. The maximum lod score for the three families combined was 5.84 at theta=0 for marker IL2RB. With the assumption of locus homogeneity, haplotype analysis of family MHA-4 indicated the disease region is centromeric to marker D22S1045. These data best support a minimal disease region from D22S683 to D22S1045, a span of about 1 Mb of DNA that contains 17 known genes and 4 predicted genes. Further analysis of this region will identify the genetic basis of May-Hegglin anomaly, facilitating subsequent characterization of the biochemical role of the disease gene in platelet formation.

Adult↗
PubMed2000

Percutaneous management of intrapulmonary air and fluid collections.

The radiologist's role in the management of intrapulmonary air and fluid collections is becoming more important. Improvements in percutaneous interventional techniques now allow the radiologist to offer patients an alternative treatment option with less morbidity and mortality than surgical resection. The use of CT allows optimal catheter placement and enables safe and effective percutaneous evacuation of intrapulmonary collections. In summary, image-guided percutaneous catheter drainage should (1) be the initial procedure performed to diagnose and treat lung abscesses not responding to conservative therapy; and (2) because of its effectiveness and safety, be considered as a treatment option in the management of symptomatic patients with intrapulmonary mycetomas.

Aspergillosis↗
PubMed2000

Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly.

May-Hegglin anomaly (MHA) is an autosomal dominant macrothrombocytopenia of unclear pathogenesis characterized by thrombocytopenia, giant platelets and leukocyte inclusions. Studies have indicated that platelet structure and function are normal, suggesting a defect in megakaryocyte fragmentation. The disorder has been linked to chromosome 22q12-13. Here we screen a candidate gene in this region, encoding non-muscle myosin heavy chain A (MYH9), for mutations in ten families. In each family, we identified one of three sequence variants within either the -helical coiled coil or the tailpiece domain that co-segregated with disease status. The E1841K mutation was found in 5 families and occurs at a conserved site in the rod domain. This mutation was not found in 40 normal individuals. Four families had a nonsense mutation that resulted in truncation of most of the tailpiece. One family had a T1155I mutation present in an affected mother and daughter, but not in the mother's parents, thus representing a new mutation. Among the 30 affected individuals, 21 unaffected individuals and 13 spouses in the 10 families, there was correlation of a variant of MYH9 with the presence of MHA. The identification of MYH9 as the disease gene for MHA establishes the pathogenesis of the disorder, should provide further insight into the processes of normal platelet formation and may facilitate identification of the genetic basis of related disorders.

Alleles↗