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Biomedical subjects

M Osborne

Publications and source records attributed to M Osborne.

At least 37 records · Page 2Linked to original sources

Children's AIDS-related knowledge and attitudes: variations by grade, race, gender, socioeconomic status, and size of community.

Variations of AIDS-related beliefs by grade, race, gender, socioeconomic status, and size of the community were examined for a diverse group of elementary school children (n = 609). Consistent with prior research, beliefs about HIV transmission and willingness to interact with persons with AIDS increased across grades 1 to 5. Black children living in rural communities held most misconceptions about AIDS and, relative to white peers, black children were more reluctant to interact with persons with AIDS (PWA). Support for more negative attitudes toward PWA among boys was also found. Knowledge of transmission mediated grade and sex differences in willingness to interact, but not race differences. Implications of results for AIDS prevention programs are discussed, along with directions for future research.

Acquired Immunodeficiency Syndrome↗

Microsatellite instability differences between familial and sporadic ovarian cancers.

DNA instability, reflected in altered patterns of short tandem repeat sequences (microsatellites) in dividing cells, has been described in hereditary non-polyposis colon cancer (HNPCC) and in other tumor types. Ovarian cancer (OC), although most often a sporadic cancer, can recur, with HNPCC, as part of the Lynch cancer family syndrome. In an investigation of microsatellite instability (MIN) in 90 OC cases, we found MIN in 3/28 (11%) OC cases with, and 8/62 (13%) without, a family history of cancer. For 2/3 MIN+ OC cases with family cancer history consistent with the Lynch cancer family syndrome, we found additional bands in the microsatellite patterns in tumor versus normal tissue (HNPCC-type of MIN), but no germline mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. In 7/8 MIN+ sporadic OC cases distinct MIN patterns not commonly reported in HNPCC were found. These are characterized by partial or total band shifting, leading to fewer bands and/or changes in the intensity of individual bands restricted to the tumor. In only one case was a germline change in hMSH2 or hMLH1 identified: this was subsequently found to be a polymorphism. An apparent hMLH1 somatic change confined to the tumor was found in another case. The fact that we found no germline pathologic mutations in hMSH2 and hMLH1 (predominant sites of mutation in HNPCC) in MIN+ OC cases, suggests that the genetic basis of MIN in OC can be different from that in HNPCC; our finding that distinct microsatellite banding patterns largely distinguish sporadic from familial OC, may reflect the involvement of different DNA repair genes in MIN in individual OC cases.

Adult↗

Assessing children's conceptions of AIDS.

Assessed intuitive theories of AIDS transmission through clinical method interviews in a cross-sectional design for a sample of 205 1st; 195 3rd; and 208 5th-grade students, balanced by sex and race (black/white). Analyses of relationships between the types of theories children held and their responses to closed-end questions about transmission and willingness to interact with a person with AIDS supported the validity of the interview method. Grade differences were noted for knowledge of high-risk routes, rejection of misconceptions, and cohesiveness and complexity of children's theories. Theories also differed by race and verbal abilities. Implications for most appropriate ways to assess children's understanding of illnesses and directions for future research are discussed.

Acquired Immunodeficiency Syndrome↗

Changes in haemodynamic parameters following Tai Chi Chuan and aerobic exercise in patients recovering from acute myocardial infarction.

In this study, 126 patients (90 males, average age 56 years, range 39-80) were randomised to Wu Chian-Ch'uan style Tai Chi (38), aerobic exercise (41) or a non-exercise support group (47) following acute myocardial infarction. Patients attended twice weekly for three weeks then weekly for a further five weeks. Heart rate and blood pressure were recorded before and after each session. Over the 11 sessions of exercise there was a negative trend in diastolic blood pressure only in the Tai Chi group (Rs = 0.79, p < 0.01). Significant trends in systolic blood pressure occurred in both exercise groups (Rs = 0.64 and 0.63, both p < 0.05). Only four (8%) patients completed the support group eight-week programme which was less than the number completing Tai Chi (82%; p < 0.001) and aerobic exercise groups (73%; p < 0.001).

Adult↗

Ultrastructural damage to the organ of corti during acute experimental Escherichia coli and pneumococcal meningitis in guinea pigs.

Experimental meningitis was induced in 16 pigmented guinea pigs by subarachnoid inoculation of mid log-phase 1 x 10(9) E. coli K-12 (n = 8) or 5 x 10(7) Streptococcus pneumoniae type 2 (n = 8). Animals were killed at various times between 3 and 12 h after inoculation and the ultrastructure of the organ of Corti (including the basilar membrane) was examined with high resolution scanning electron microscopy. Both E. coli and S. pneumoniae induced meningitis and invaded scala tympani. In both types of meningitis the apical surface of inner supporting cells developed craters. inner hair cell stereocilia were also disrupted. In pneumococcal meningitis both these lesions were more pronounced but in addition there were breaks in the junctions between inner hair cells and their adjacent supporting cells and there was ballooning and rupture of the apical surface of outer hair cells. Damage to the organ of Corti after bacterial invasion of the inner ear may be one of the mechanisms by which bacterial meningitis can cause deafness. The more severe cochlear lesions induced by S.pneumoniae may explain the higher incidence of deafness after pneumococcal meningitis.

Animals↗

Allocation of resources in intensive care: a transatlantic perspective.

The USA and the UK have differed substantially in approaches to health care and especially in intensive care provision. We have compared the health care systems, clinical justification for intensive care, selection of patients likely to benefit from such care, and the performance of the systems. The differences are lessening. Both countries are moving away from clinical autonomy as the driving force of medical decision-making. There is increasing recognition that not all patients will benefit from intensive care and that the doctor's obligation to the patient can be limited by constraints set by society.

Delivery of Health Care↗

A vascular hypersensitivity model of acute multifocal gastrointestinal infarction.

We have investigated the hypothesis that submucosal vasculitis may account for the patchy transmural inflammation observed in Crohn's disease. Test ferrets (N = 11) were sensitized to human albumin. Five days after the last sensitization injection, human albumin microspheres (15-150 microns diameter) were injected intraarterially into the mesenteric circulation of a defined loop of mid-gut. Six control ferrets showed no histological abnormality at either 48 hr or two weeks after intraarterial injection. At 48 hr, five of six presensitized ferrets demonstrated submucosal vasculitis with fibrinoid necrosis. In two cases there was transmural inflammation and mucosal ulceration. A further five presensitized ferrets received weekly subcutaneous human albumin injections following the mesenteric intraarterial injection of albumin microspheres: after two weeks one animal demonstrated mild perivascular inflammatory changes and another demonstrated vasculitis. One of the two animals with transmural inflammation and mucosal ulceration at 48 hr, and the animal with vasculitis at two weeks, had precipitating antibodies to human serum albumin. This model demonstrates that an immune-mediated submucosal vasculitis can sometimes result in discontinuous transmural inflammation of the intestinal wall.

Animals↗

Effect of position and support on oral-motor skills of a child with bronchopulmonary dysplasia.

The effects of position (upright vs reclining) and support (held vs chair) on the development and maintenance of feeding behavior were examined in a child with bronchopulmonary dysplasia and gastroesophageal reflux. A reclining position initially facilitated acceptance and swallowing with relatively rapid generalization to an upright position. Oral-motor skills did not differ across levels of support. Practice of emerging motor skills preceded increases in vomiting, as well as episodes of respiratory distress. This study illustrates a methodology that can be employed to elucidate complex interrelationships among oral-motor skills, gross motor skills and functioning, and symptoms of gastroesophageal reflux.

Bronchopulmonary Dysplasia↗

The effects of lithium and potassium on macromolecular synthesis in herpes simplex virus-infected cells.

All herpes simplex virus (HSV) infected cell-specific polypeptides (ICSPs) were synthesized in the presence of lithium at a concentration (60 mM) inhibitory to the production of infectious virus. Yields of certain ICSPs were increased and others, in particular glycoprotein C, decreased. HSV DNA synthesis was completely inhibited; synthesis and in vitro activities of HSV DNA polymerase and thymidine kinase were decreased but to a degree insufficient to account for the complete inhibition of HSV DNA synthesis. HSV DNA synthesis was inhibited to an equivalent degree by either incubation with 60 mM-lithium or by potassium starvation; both procedures decreased intracellular potassium by an equivalent amount as adjudged by X-ray microanalysis. We conclude that lithium inhibits HSV DNA synthesis by displacement of potassium from a potassium-dependent biochemical reaction or by other physiological changes brought about by the loss of cellular potassium. The possibility that lithium also directly inhibits a virus replicative event cannot be excluded.

Animals↗

A 1H-NMR study of the interactions between rat tissue kallikrein and two peptide inhibitors.

The 1H-NMR spectra have been obtained for rat submandibular kallikrein in the absence and presence of inhibitors. Two competitive inhibitors were investigated, the tripeptide leupeptin (a potent inhibitor with Ki 0.5 microM) and a hexapeptide (a much weaker, substrate-analogue inhibitor with Ki 380 microM). Analysis of the NMR spectra showed that binding of leupeptin to kallikrein led to a change in the conformation of the enzyme, whereas binding of the substrate analogue to the enzyme produced no such change and may have resulted in a conformational change of the inhibitor.

Amino Acid Sequence↗

Cowden's disease. A case report with analyses at the molecular level.

Cowden's disease (multiple hamartoma syndrome) is characterized by multiple hamartomas of ectodermal, endodermal, and mesodermal origin, a high incidence of malignant tumors of the breast and/or thyroid gland, and an autosomal dominant pattern of inheritance. Similar to sporadic breast cancer, chromosomal studies have not elucidated the cause of this syndrome. The authors report the case of a patient with this syndrome and analyze the pattern of amplification or rearrangement of three genes: the HER-2/neu oncogene, the ras oncogene, and the estrogen-inducible gene, pS-2. All three of these genes were present in single copies without translocations. It was noteworthy that three of the most important genes currently studied in relation to breast cancer existed in a unamplified unrearranged state in this patient. Those with clinical manifestations of Cowden's disease may be candidates for prophylactic bilateral total mastectomy, and the authors recommend that these patients undergo this procedure by their third decade of life. An alternative to this approach would entail monthly self examinations, breast examinations by the patient's physician every 3 months, bilateral mammograms every 6 to 12 months, and biopsy of any suspicious lesions. It is crucial, however, that these patients be identified by their mucocutaneous lesions and family history before an underlying malignant lesion develops.

Adult↗

Structural changes in the C-terminal region of human brain creatine kinase studied with monoclonal antibodies.

Epitopes on human brain creatine kinase (B-CK) recognized by three monoclonal antibodies have been located by chemical cleavage methods, followed by peptide synthesis or analysis of specificity for natural variants (isoforms). One antibody, CK-HTB, recognizes a conformational, or assembled, surface epitope on native CK which is also present on partially unfolded forms. It requires an Asn residue at position 300 in the amino acid sequence and will not recognize variants with Lys or His in this position. This results in a striking specificity of the antibody, which binds to B-CK only in chicken and man, but to muscle-form (M-CK) only in the rat. The results suggest that Asn-300 is exposed on the enzyme surface as part of a relatively denaturation-resistant region. Two monoclonal antibodies, CK-END1 and CK-END2, recognise epitopes within 53 amino acids of the C-terminus and bind to a synthetic hexapeptide representing the last six amino acids of human B-CK (Leu-375-Lys-380). The two antibodies show overlapping, but distinct, specificities in their binding to CK variants. CK-END1 requires Met-376 and will not tolerate Ile in this position, whereas CK-END2 requires Leu-375 and will not tolerate Met. Neither antibody binds to native CK, though both will bind to a folding intermediate and to partially unfolded states. This shows that the C-terminus of CK becomes inaccessible to the antibodies during those later stages of protein folding associated with recovery of enzyme activity and suggests that the protein may 'tuck in its tail' during one of the final steps.

Amino Acid Sequence↗

A yeast protein that binds nuclear localization signals: purification localization, and antibody inhibition of binding activity.

Short stretches of amino acids, termed nuclear localization sequences (NLS), can mediate assembly of proteins into the nucleus. Proteins from the yeast, Saccharomyces cerevisiae, have been identified that specifically recognize nuclear localization peptides (Silver, P., I. Sadler, and M. A. Osborne. 1989. J. Cell Biol. 109:983-989). We now further define the role of one of these NLS-binding proteins in nuclear protein localization. The NLS-binding protein of 70-kD molecular mass can be purified from salt extracts of nuclei. Antibodies raised against the NLS-binding protein localized the protein mainly to the nucleus with minor amounts in the cytoplasm. These antibodies also inhibited the association of NLS-protein conjugates with nuclei. Incubation of nuclei with proteases coupled to agarose removed NLS-binding protein activity. Extracts enriched for NLS-binding proteins can be added back to salt or protease-treated nuclei to restore NLS-binding activity. These results suggest that the first step of nuclear protein import can be reconstituted in vitro.

Amino Acid Sequence↗

Quantitative multiple sclerosis plaque assessment with magnetic resonance imaging. Its correlation with clinical parameters, evoked potentials, and intra-blood-brain barrier IgG synthesis.

Magnetic resonance imaging (MRI) of the cerebrum, cerebellum, brain stem, and upper cervical cord was performed in 62 individuals with clinically definite chronic, progressive multiple sclerosis (MS). The total area of MRI-demonstrated lesions was measured from film enlargements for each region using an interactive image analysis system. While the MRI was abnormal in 60 (97%) of 62 patients, the visual-evoked potentials in 51 (85%) of 60 patients, the brain stem auditory-evoked potentials (BAEPs) in 24 (46%) of 52 patients, and the somatosensory-evoked potentials (SSEPs) in 45 (89%) of 54 patients, an abnormal intra-blood-brain barrier (BBB) IgG synthesis rate, IgG oligoclonal bands, or both were found in all 62 patients. The total area of MRI abnormality in the cerebrum was significantly correlated only with the intra-BBB IgG synthesis rate, abnormal visual-evoked potentials, impaired performance on the Symbol Digit Modalities Test (SDMT), and one test of standing duration in the quantitative examination of neurologic function (QENF). The brain stem lesion area correlated with the Kurtzke expanded disability status scale and brain stem functional systems score, the ambulation index, abnormal BAEPs, and impaired performance on the SDMT as well as multiple tests of upper and lower extremity function in the QENF. The cerebellar lesion area correlated with impaired performance on the SDMT and primarily upper extremity testing in the QENF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗