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Biomedical subjects

M Osborn

Publications and source records attributed to M Osborn.

At least 37 records · Page 2Linked to original sources
PubMed1998

Diabetes care for Medicare beneficiaries. Attitudes and behaviors of primary care physicians.

OBJECTIVE: To obtain information related to primary care physician (PCP) attitudes, knowledge, and practice patterns, as well as perceptions about barriers to care and the use of materials to assist in the delivery of diabetes care for elderly patients in the office setting. RESEARCH DESIGN AND METHODS: A survey was mailed to a random sample (n = 900) of PCPs (internal medicine, family practice, and general practice physicians and endocrinologists) from the states of Alabama, Iowa, and Maryland who met selection criteria and provided diabetes care to > or = 25 Medicare beneficiaries during calendar year 1993. RESULTS: Respondents provided self-reported information regarding diabetes care for elderly patients. PCP respondents (n = 370) considered blood glucose control to be the most important treatment goal. Most respondents (92%) considered acceptable GHb values to be those < 8%. Blood pressure measurement and foot inspections for the detection of ulcers and infection were the most commonly reported routine procedures performed as part of an office visit. Laboratory tests reported to be frequently ordered included GHb, serum creatinine, and proteinuria tests. Patient nonadherence to the treatment regimen was reported to be the most common barrier to care. The majority of respondents reported using two treatment aids in caring for patients with diabetes. CONCLUSIONS: The results of this study provide some evidence that PCP self-reported attitudes, knowledge, and practice patterns in delivering diabetes care for elderly patients in the office setting more closely reflect current recommended practice than reported in previous physician surveys. Opportunities for improvement still exist.

Alabama↗
PubMed1997

Cleavage of the nuclear matrix protein NuMA during apoptosis.

NuMA is a component of the nuclear matrix which may play a structural role in the architecture of the interphase nucleus. During apoptosis NuMA is redistributed within the nucleus and is proteolysed from a 238-kDa form to a 180- to 200-kDa form. Here we show that the cleavage site leading to the stable fragment occurs between residues 1701 and 1725. Both the changes in morphology associated with apoptosis and the cleavage of NuMA were retarded by treatment with TPCK but not by treatment by other protease inhibitors including ICE inhibitor II.

Animals↗
PubMed1997

The challenges of assessing outcome in chronic pain.

Clinicians in chronic pain services are facing the need to develop meaningful and methodologically adequate measures, not only to evaluate the effectiveness of interventions and to assure quality, but also to support the continued funding and future development of such services. Explores the problems inherent in assessing outcomes in chronic pain. These include the complexity of the chronic pain syndrome itself, the multidimensional nature of interventions and the challenges of defining outcomes in the chronic illness syndrome. The complexity and challenges of assessing outcomes may lead to some reticence in facing the challenges but it is the responsibility of the clinicians to continue developing measures and to communicate to purchasers and other stake holders the complexity of assessing outcomes in chronic pain.

Chronic Disease↗
PubMed1997

Psychiatric disorder in young adults in Jamaica.

INTRODUCTION: Much research into psychiatric disorder in Jamaica has investigated psychotic illness but studies of neurotic disorders are lacking. This study investigated psychiatric disorder in a group of mainly urban, lower social class, young adults who had been regular clinic attenders as a physically healthy control group in a cohort study of sickle cell disease. METHOD: The study was cross-sectional in design. Subjects, 44 male and 45 female, were aged 18 to 20 years at the time of the study. The Psychiatric Assessment Schedule was used to determine psychiatric disorder at Index of Definition level 5. RESULTS: All subjects approached participated. Rates of psychiatric disorder were 6 (14%) in the male group and 16 (36%) in the female group. There were no psychotic disorders. In the group as a whole, psychiatric disorder was associated with female gender, unemployment, difficulties with social adjustment and number of episodes of physical illness in the 6 months prior to interview. Variables associated with psychiatric distress amongst males included not having a steady relationship, unemployment, criminal activity and difficulties with social adjustment. Variables associated with psychiatric distress amongst females included lack of domestic amenities, not having a mother at home, lack of education, unemployment and social adjustment difficulties. CONCLUSION: Rates of psychiatric disorder were higher than expected, especially for women. Larger studies are indicated to investigate the prevalence of neurotic disorders amongst young people in Jamaica, compared to similar groups in other countries.

Adolescent↗
PubMed1997

Psychiatric complications of homozygous sickle cell disease among young adults in the Jamaican Cohort Study.

BACKGROUND: This study aimed to determine the prevalence of psychiatric disorder in young adults with homzygous sickle cell (SS) disease and in controls with normal haemoglobin, and to examine factors associated with psychiatric disorder. METHOD: The study design was cross-sectional. Subjects were aged 18-20 years: 63 with SS disease and 89 controls. The Psychiatric Assessment Schedule was used to determine psychiatric disorder at index of Definition level 5. RESULTS: Psychiatric disorder was identified in 18 (29%) SS disease patients and in 22 (25%) controls. In SS patients, psychiatric disorder was not related to illness severity but was associated with leaving school early, difficulties in social adjustment, impaired cognitive function and having previous psychiatric difficulties. Male SS patients with psychiatric disorder all had low body mass index (BMI < 17.60). In controls, psychiatric disorder was associated with female gender, unemployment and difficulties in social adjustment. CONCLUSIONS: The prevalence of psychiatric disorder was similar in patients and controls, although associated factors tended to be different. The association with low BMI in SS men merits further study.

Adolescent↗
PubMed1996

Characterization of six mutations in exon 37 of neurofibromatosis type 1 gene.

Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders, with an incidence of 1 in 3,000. We screened a total of 320 unrelated NF1 patients for mutations in exon 37 of the NF1 gene. Six independent mutations were identified, of which three are novel, and these include a recurrent nonsense mutation identified in 2 unrelated patients at codon 2281 (G2281X), a 1-bp insertion (6791 ins A) resulting in a change of TAG (tyrosine) to a TAA (stop codon), and a 3-bp deletion (6839 del TAC) which generated a frameshift. Another recurrent nonsense mutation, Y2264X, which was detected in 2 unrelated patients in this study, was also previously reported in 2 NF1 individuals. All the mutations were identified within a contiguous 49-bp sequence. Further studies are warranted to support the notion that this region of the gene contains highly mutable sequences.

Adult↗
PubMed1996

NuMA: a bipartite nuclear location signal and other functional properties of the tail domain.

Nuclear Mitotic Apparatus protein (NuMA) is a 238-kDa protein of the nuclear matrix in interphase that relocates to the spindle poles in mitosis. The globular tail domain (residues 1701 to 2115) contains the nuclear targeting sequence, the site for binding to the mitotic spindle as well as a site responsible for nuclear reformation. To more precisely map these sites, we inserted full-length human NuMA and 16 derivatives with increasing truncations of the tail domain into the pCMV5 vector and induced transient expression. NuMA was found in the interphase nucleus of all transfected BHK cells expressing either full-length NuMA or NuMA mutant proteins ending at or after residue 2005. In contrast, mutants ending at or before residue 2003 remained in the cytoplasm. In the full-length NuMA molecule, point mutations at position 1988 or 1989 or a double mutation at residues 2004 and 2005 cause NuMA to accumulate in the cytoplasm of both BHK and HeLa cells. The combined results indicate a bipartite nuclear location signal involving the sequences RKR (1987-1989) and KK (2004-2005) which are separated by 14 amino acid residues. In 30% of BHK cells transfected by the full-length clone, cytoplasmic aggregates of NuMA that colocalize with the centrosomes were documented in addition to the nuclear staining. In cells with large aggregates the cytoplasmic microtubular profile was disturbed. Observation of micronuclei formation suggests that a region important for normal nuclear reformation lies in the C-terminal 130 residues. Finally, NuMA mutant proteins ending at or after residue 1800 bound to the spindle poles of mitotic cells, while NuMA proteins ending at or before residue 1750 did not.

Amino Acid Sequence↗
PubMed1996

The association of annexin I with early endosomes is regulated by Ca2+ and requires an intact N-terminal domain.

Annexin I is a member of a multigene family of Ca2+/phospholipid-binding proteins and a major substrate for the epidermal growth factor (EGF) receptor kinase, which has been implicated in membrane-related events along the endocytotic pathway, in particular in the sorting of internalized EGF receptors occurring in the multivesicular body. We analyzed in detail the intracellular distribution of this annexin by cell fractionation and immunoelectron microscopy. These studies used polyclonal as well as a set of species-specific monoclonal antibodies, whose epitopes were mapped to the lateral surface of the molecule next to a region thought to be involved in vesicle aggregation. Unexpectedly, the majority of annexin I was identified on early and not on multivesicular endosomes in a form that required micromolar levels of Ca2+ for the association. The specific cofractionation with early endosomes was also observed in transfected baby hamster kidney cells when the intracellular fate of ectopically expressed porcine annexin I was analyzed by using the species-specific monoclonal antibodies in Western blots of subcellular fractions. Interestingly, a truncation of the N-terminal 26, but not the N-terminal 13 residues of annexin I altered its intracellular distribution, shifting it from fractions containing early to those containing late and multivesicular endosomes. These findings underscore the regulatory importance of the N-terminal domain and provide evidence for an involvement of annexin I in early endocytotic processes.

Amino Acid Sequence↗
PubMed1996

Effectiveness of telephone prompts when surveying general practitioners: a randomised trial.

BACKGROUND: Response rates to recent surveys of general practitioners have ranged from 44-95%. The effectiveness of a telephone prompt by a non-medical research assistant in advance of survey mail-out was unknown at the time of this study. OBJECTIVE: To determine the effectiveness of a telephone prompt by a non-medical research assistant to enhance response rates to a lengthy survey. SUBJECTS: 364 randomly selected general practitioners randomised into intervention and control groups. OUTCOME VARIABLE: Cumulative response rate at Day 18 and Day 60. DESIGN: Intervention group received a telephone call in advance of the survey. The control group received conventional mail-outs. Non-responders in both groups were telephoned at Day 28 and sent a reminder letter and questionnaire. RESULTS: 77% of the intervention group responded to the survey compared to 64% of the control group. Intention-to-treat analysis demonstrated a significantly earlier response by Day 18 (continuity corrected chi 2 = 18.15; df = 1; p < 0.001) and a significantly higher overall response by Day 60 (continuity corrected chi 2 = 5.41, df = 1, p < 0.009) from the intervention group. CONCLUSION: A telephone prompt by a non-medical research assistant will accelerate and enhance response rates to a survey of general practitioners although the differential effectiveness of a non-medical researcher compared to a medical practitioner conducting such prompts remains unstudied.

Australia↗
PubMed1996

Prognostic significance of tumor cell proliferation rate as determined by the MIB-1 antibody in breast carcinoma: its relationship with vimentin and p53 protein.

The prognostic value of tumor cell proliferative activity as measured by the MIB-1 monoclonal antibody in invasive ductal not otherwise specified breast carcinomas was determined for 186 patients, including 111 with no axillary node involvement. The MIB-1 antibody detects the Ki-67 antigen in microwave-processed paraffin sections of the formalin-fixed tumors. The mean MIB-1 score was 16% for all tumors, 16% for the node-negative group, and 15% for the node-positive group. In univariate survival analysis, the MIB-1 score (dichotomized, </=10 versus >/=10%) predicted overall 5-year survival in all of these groups. The mean MIB-1 score was significantly higher in vimentin- and p53 protein-positive tumors (P > 0.001) than in negative ones. The impact of vimentin expression and of p53 positivity on the prognostic significance of the tumor cell proliferation rate was assessed. Vimentin was associated significantly with poor 5-year survival in the entire cohort, and a particularly strong association was found in the node-negative group. p53 had a weak but statistically nonsignificant influence on survival. In a multivariate analysis using the Cox proportional hazards model, vimentin (P = 0.0002) was the only independent prognostic factor in node-negative patients. In contrast, the MIB-1 score (P = 0.009) was the only independent prognostic factor in the node-positive group. Therefore, node-negative patients with vimentin-positive tumors and node-positive patients with tumors with high proliferation rates might be appropriate candidates for early adjuvant chemotherapy.

Adult↗
PubMed1995

Towards the finer mapping of facioscapulohumeral muscular dystrophy at 4q35: construction of a laser microdissection library.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder which has been mapped to the 4q35 region. In order to saturate this distal 4q region with DNA markers, a laser-based chromosomal microdissection and microcloning procedure was used to construct a genomic library from the distal 20% of chromosome 4, derived from a single human metaphase spread. Of the 100 microclones analyzed from this library, 94 clones contained inserts sized from 80-800 bp, with an average size of 340 bp. Less than 20% of these clones hybridized to human repeat sequences. Seventy-two single-copy clones were further characterized by Southern blot hybridization against a DNA panel of somatic cell hybrids, containing various regions of chromosome 4. Forty-two clones mapped to chromosome 4, of which 8 clones mapped into the relevant 4q35 region. Twenty of these chromosome 4-specific clones were screened against "zoo-blots"; 11 clones, of which 3 mapped to 4q35, identified conserved sequences. This is the first report to describe the isolation of potential expressed sequences derived from the FSHD region. These chromosome region-specific microclones will be useful in the construction of the physical map of the region, the positional cloning of potential disease-associated genes, and the identification of additional polymorphic markers from within the distal 4q region.

Biomarkers↗
PubMed1995

Epitope mapping and direct visualization of the parallel, in-register arrangement of the double-stranded coiled-coil in the NuMA protein.

NuMA, a 238 kDa protein present in the nucleus during interphase, translocates to the spindle poles in mitosis. NuMA plays an essential role in mitosis, since microinjection of the NuMA SPN-3 monoclonal antibody causes mitotic arrest and micronuclei formation. We have mapped the approximate position of the epitopes of six monoclonal NuMA antibodies using recombinant NuMA fragments. The SPN-3 epitope has been located to residues 255-267 at the C-terminus of the first helical subdomain of the central rod domain and several residues crucial for antibody binding have been identified. To gain insight into the ultrastructure of NuMA, several defined fragments, as well as the full-length recombinant protein, were expressed in Escherichia coli and purified to homogeneity. They were then characterized by chemical cross-linking, circular dichroism spectra and electron microscopy. The results directly reveal the tripartate structure of NuMA. A long central rod domain is flanked by globular end domains. The rod is 207 nm long and is at least 90% alpha-helical. It reflects a double-stranded coiled-coil with the alpha-helices arranged parallel and in register. The NuMA protein thus forms the longest coiled-coil currently known. Our analyses reveal no indication that recombinant NuMA assembles into filaments or other higher order structures.

Amino Acid Sequence↗
PubMed1995

New monoclonal antibodies recognizing phosphorylated proteins in mitotic cells.

Three monoclonal antibodies which showed strong staining of mitotic cells by screening on the human cell line MCF-7 were isolated. The antigens detected by the DH7 and BF6 monoclonal antibodies were located predominantly in multiple extranucleolar patches in interphase cell nuclei. In mitotic cells a strong increase in the fluorescence intensity was accompanied by its redistribution into a fine speckled form. Metaphase chromosomes were unstained. Centrosomes, spindle poles or midbodies were not stained either before or after extraction of the cells with Triton X-100 under conditions which preserve microtubular structures. In immunoblots of interphase cell extracts only very few bands reacted with DH7 whereas in mitotic cell extracts approximately 30 bands were stained. BF6 also showed an increase in the intensity and number of bands detected in mitotic compared to interphase cell extracts, and the pattern was clearly different from that obtained with DH7. The BF6 antigen were extracted by 0.5% Triton X-100, whereas the DH7 antigen was not. Dephosphorylation of the antigens strongly reduced the binding of both antibodies as measured by immunoblotting and ELISA assays. The results suggested that BF6 and DH7 detect two different phosphorylated epitopes, each of which is shared by a different subset of proteins from mitotic cells. The third antibody, BD 12, bound to several polypeptides, including one of high molecular weight that appeared to correspond to the NuMA antigen. The epitope recognized by BD 12 was not sensitive to phosphatases.

Animals↗