Search PubMed⌕ Search

Biomedical subjects

M Sheehan

Publications and source records attributed to M Sheehan.

At least 55 records · Page 3Linked to original sources

Complement inhibition by human vitronectin involves non-heparin binding domains.

Vitronectin (complement S-protein), a multifunctional glycoprotein, inhibits complement-mediated cytolysis at two identified stages of terminal complement complex (TCC) formation: blocking of C5b-7 membrane binding, and prevention of C9 polymerization. However, the functional domain(s) of vitronectin involved in these reactions remains incompletely defined. In order to identify the complement inhibition site, a 12-kD heparin binding fragment and two other internal fragments (53 kD and 43 kD) of vitronectin were isolated after cyanogen bromide (CNBr) treatment of the native molecule. Potent inhibition of guinea pig erythrocyte (GPE) reactive lysis was demonstrated with native vitronectin, total CNBr digest and the 53-kD and 43-kD fragments, but only very poorly by the heparin binding 12-kD peptide. Similarly, the 43-kD fragment blocked the binding of C5b-7 to immobilized vitronectin, whereas the 12-kD fragment had no effect. These data localize the C5b-7 binding site to a 43-kD internal region. Further characterization of the fragments was carried out in an assay which detected C9 polymerization in the presence of C5b-8. Polymerized material was separated by PAGE, detected by autoradiography and quantified after excision from the gels. Results showed that polymerization did not occur in the presence of the 53-kD and 43-kD fragments. However, the 12-kD heparin binding fragment had no effect. It is proposed that prevention of C5b-8-induced C9 polymerization resides at a site in an internal region of the vitronectin molecule.

Amino Acid Sequence↗

Women's perceptions and experience of menopause: a focus group study.

Focus groups were used to investigate women's perception and experience of menopause, hormone replacement therapy, osteoporosis and doctor-patient relationships. Forty women aged between 45 and 55 years participated in seven focus groups. Most women thought that these topics were not widely or freely discussed in the community. Nevertheless they were able to share their experiences on this occasion. Lack of reliable, accessible and current information on menopause and related topics was identified as a problem. This was compounded by the contradictory nature of the information which was available. Hysterectomy and osteoporosis were identified as specific areas in which information was inadequate and not readily accessible. Solutions suggested by the women included distributing information pamphlets with contact numbers for further information to non-health-related settings such as hairdressing salons. The need to foster open discussion between women and their doctors was highlighted, with contributions required from both parties to develop a more equal partnership. A review of doctors' and women's surveillance practices with regard to hormone replacement therapy may also be warranted. We found focus groups a useful method for accessing women's experiences and perceptions. There was particular benefit in researchers being involved as moderators and scribes, and in an early post-focus group meeting to amplify and clarify records of the discussions. Small group size and an emphasis on confidentiality were, we believe, helpful strategies in encouraging discussion of intimate topics.

Attitude to Health↗

False-positive immunoreactivity with muscle-specific actins in non-Hodgkin's lymphomas.

Antibodies to forms of muscle actin have been developed that are highly specific for tissue of myogenic origin and for which false-positive reactions are seldom reported. We studied 23 cases of B-cell malignant lymphoma by immunohistochemistry using monoclonal antiactin antibodies of two different specificities. Eight of the 23 cases were positive with an antibody against smooth-muscle actin that had been produced as ascitic fluid. Reactivity was abolished by the use of antibody from the same clone (1A4) but produced as a tissue culture supernatant. Nine of 23 cases were positive with an antibody against muscle actin (clone HHF35) produced as ascitic fluid. An antibody from the same clone (HHF35), but produced as a tissue culture supernatant, gave weak staining of both lymphoid cells and connective tissue background. Lymphoma staining by both HHF35 antibodies (and background staining) was abolished by the addition of ethylenediaminetetraacetic acid (EDTA) to the antibody. (EDTA is reported to eliminate nonspecific protein binding.) Each ascitic fluid-derived antibody stained the lymphomas in an apparently specific manner. There was intense granular deposition of reaction product localized to specific portions of the cell (plasma membrane or diffuse cytoplasmic staining and, in two signet ring cell lymphomas, globular staining of intracytoplasmic inclusions), and there was substantial concordance of the staining of the two antibodies. This finding of false-positive reactivity by two different antiactin monoclonal antibodies, both prepared as ascitic fluid, supplements recent reports of a similar phenomenon with ascitic fluid preparations of the antimelanoma monoclonal antibody HMB45.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

A new design for the department of information services.

This paper describes the structure and function of the department of Information Services at Sacred Heart Health System in Eugene, Oregon. This department has gone through a process of reorganization. The new department design features self-directed work teams with a strong customer service orientation; a mentor role stressing staff development; and a skill-based compensation system.

Computer Communication Networks↗

Centronuclear myopathy and nursing pattern caries: management of a 1 year old.

The pathognomonic open mouth of centronuclear and other myopathies can also have implications for oral health. These patients are at greater risk for gingivitis, dental caries as a result of the mouth breathing and loss of lip seal. Low tongue posture may impede the lateral expansion of the maxilla resulting in a constricted maxillary arch with resultant posterior crossbites and functional shifts. Excessive molar eruption may also occur, resulting in anterior open bites and increases in the anterior lower vertical height.

Anesthesia, Dental↗

Relative topography of biologically active domains of human vitronectin. Evidence from monoclonal antibody epitope and denaturation studies.

A panel of monoclonal antibodies to human vitronectin was used to define some epitopes for the multifunctions of this protein. Separate antibodies were identified which strongly inhibited cell spreading activity and which prevented binding to collagen. A third group interfered with the ability of vitronectin to inhibit complement-mediated guinea pig erythrocyte reactive lysis. None of the antibodies from these three groups prevented heparin binding, providing evidence that this reaction occurs at a fourth location; a different monoclonal antibody partially inhibited the binding of heparin. The relative accessibility of each biologically active epitope was assessed by the differential binding of the monoclonals to native and denatured vitronectin. Reactivity of the antibody which inhibited heparin binding greatly increased upon denaturation of vitronectin, implying that this region is normally inaccessible in the native form of the molecule. By contrast, epitopes for cell spreading, collagen binding, and inhibition of terminal complement complex lysis were destroyed by denaturation. On the basis of denaturation data and epitope mapping by competitive exclusion of monoclonal antibodies, a Venn diagram was constructed to represent overlap of monoclonal antibody epitopes in the tertiary structure. Linear epitopes for the antibodies were identified using cyanogen bromide and plasmin-derived peptides from vitronectin. The antibody which strongly inhibited cell binding reacted with a region containing the RGD site, whereas linear epitopes for collagen binding and complement inhibition appeared to reside in a 43-kDa peptide representing the internal region of the amino acid sequence, excluding the heparin-binding site. The latter two epitopes were differentiated from each other by reactivity of the antibody which inhibited collagen binding toward a smaller 20-kDa plasmin-derived peptide.

Animals↗

Training for rural general practice.

OBJECTIVE: To identify requirements for vocational training and continuing education programs in rural general practice. DESIGN: A questionnaire was sent to all 487 rural doctors and 140 metropolitan and 140 provincial city general practitioners (GPs) in Queensland. A sample of medical educators, health professional and consumer representatives and rural doctors was also interviewed. Responses were compared by geographical area, practice characteristics and level of postgraduate training. RESULTS: There are significant differences between rural and urban practice profiles. Rural doctors have to practise a range of clinical skills in an environment with restricted access to health professional support, although the need for advanced training in procedural or other skills depends on the type of rural practice. Rural and urban doctors want more influence in determining continuing medical education (CME) programs. Interactive learning methods were rated as the most effective education methods by both rural and urban GPs. Rural doctors were less likely to consider that they spent enough time on CME. CONCLUSION: Vocational training programs should accommodate various rural career objectives, including those requiring advanced levels of procedural work. There is a significant unmet demand for CME tailored to the needs of individual doctors, both rural and urban, but distance and isolation may make this more critical in rural practice. These issues need to be addressed as training opportunities can contribute to improved retention of the rural medical workforce.

Australia↗

Do psycho-social factors contribute more to symptom reporting by middle-aged women than hormonal status?

Six hundred women aged between 45 and 54 were randomly selected from the electoral roll in Brisbane, Australia. A questionnaire addressing their symptoms, hormone status and psycho-social factors was successfully administered to 381 women (64% of the original sample; 83% of those contactable). Although cardiovascular symptoms were experienced by 25% of the sample, the most common (hot flushes) ranked only tenth on a list of recently experienced symptoms. The association of hormone status with symptoms was weak in comparison with other factors. Most symptoms were reported by women who were perimenopausal, had undergone a hysterectomy, or were currently using hormone replacement therapy. A poor mental health index was strongly associated with all groups reporting symptoms. It is concluded that clinicians responding to symptoms from middle-aged women should continue to address psychosocial factors just as vigorously as those related to their hormone status.

Attitude to Health↗

A sampling framework for rural and remote doctors.

A pilot survey by telephone interview, followed by a questionnaire of all rural doctors identified in Queensland, was used develop both a definition of rural practice that distinguishes it from urban general practice and a classification of rural and remote practice which assists in sampling of rural doctors. Questionnaire responses in specific geographic areas were compared using chi-square and Mantel-Haenszel chi-square tests. Several factors were found to differentiate rural from urban general practice consistently, thereby enabling a functional definition of rural practice to be developed. Within the broad group of rural doctors, gradients in practice characteristics were found to differentiate doctors in larger rural centres from those in smaller, more remote communities. These gradients were related to the distance and time of travel from support services. They formed the basis of a complex classification of rural and remote general practice. This functional definition of rural and remote medical practice should be considered by researchers of rural medicine issues when sampling rural and remote doctors. The strategies used in this study could be adapted for use in considering practice characteristics of other rural health professions.

Humans↗

Knowledge of sunlight effects on the eyes and protective behaviors in the general community.

The knowledge of sunlight effects on the eyes and protective behaviors was assessed in the general community of Brisbane, Australia. Five hundred people were systematically sampled and surveyed via a telephone questionnaire. Of the participants, 279 (56%) were female and 258 (52%) were aged 40 years or less. Levels of knowledge were found to be lower in the older subjects, those with dark complexions and outdoor workers. Most were unaware of specific ultraviolet light related eye diseases such as cataract, pterygium and eye cancer. Three hundred and ninety (78%) wore sunglasses > 10% of the time while outdoors during the day; the most common reasons for wearing included protection from glare in 254 (65%) and driving in 60 (15%). Ninety-six (19%) never wore sunglasses, the most common reasons being inconvenience in 16 (17%), thought unnecessary in 16 (17%) and uncomfortable in 13 (14%). Promotion of sun protection to prevent ultraviolet light related diseases should include information on the eye. This information is important for establishing preventative behaviors and the selection of optimal eye protective measures.

Adolescent↗

Nerve regeneration across colorectal anastomoses after low anterior resection in a canine model.

The disappearance and subsequent return of the recto-anal inhibitory reflex following low anterior resection was investigated using manometric and histological studies. Ten female greyhound dogs were randomised into 2 groups. All underwent low anterior resection. Five had stapled EEA anastomosis of the rectum and 5 were handsewn. The recto-anal inhibitory reflex was measured before and after surgery using a microtransducer tipped catheter. Six months postoperatively the recto-anal inhibitory response was again measured and the animals sacrificed. The colorectal anastomoses were examined histologically using light microscopy to determine the pattern of innervation at the anastomotic site. Manometric studies showed the recto-anal inhibitory reflex present in all cases pre-operatively, in only 1 case on the tenth postoperative day and was present in eight cases after 6 months. Histological examination of longitudinal sections across the anastomoses showed clear evidence of regenerating nerve trunks at the anastomotic site in both stapled and handsewn groups. We conclude that the return of the recto-anal inhibitory reflex is associated with regeneration of intramural autonomic nerves across the anastomotic scar.

Anastomosis, Surgical↗

Opiate users and the first years after treatment: outcome analysis of the proportion of follow up time spent in abstinence.

This second report on a follow-up study of drug users focuses on changes that occurred on a number of variables between intake and follow-up and during the follow-up period. The length of abstinence from opiates was considered as a proportion of the total follow-up period. Overall there was a reduction in opiate use, in injecting and sharing equipment at follow-up. There had been, however, a high level of these risky activities during the follow-up period. Sustained abstinence from opiates was associated with increased employment, enhanced social stability and mental health. Intake drug use was strongly related to follow-up drug status. In particular, those who were injectors of multiple drugs at intake were far less likely to be long term opiate abstainers at follow-up than those who were not injectors at intake or injectors of opiates only.

Adult↗

An automated biotin-streptavidin procedure for progesterone evaluation.

An automated biotin-streptavidin procedure for measuring progesterone in serum is described. The method is linear up to 98.3 nmol/L and the calibration curve is stable for at least 14 days. The lower limit of progesterone detection is 0.70 nmol/L. Although serum is the preferred specimen, progesterone levels can be measured in EDTA, heparin, or citrated plasma. There is no interference from samples with monoclonal proteins or from hemoglobin and bilirubin at concentrations of 9.62 g/L and 899 mumol/L, respectively. Lipemic samples will lower the progesterone levels. Total imprecision of the method in the range of 19-80.4 nmol/L gave CVs between 4.6 and 7.3%. Progesterone values obtained with this biotin-streptavidin procedure agreed with those obtained by the DPC RIA assay (r = 0.991). The biotin-streptavidin procedure can be used as an alternative to RIA for measurement of progesterone.

Autoanalysis↗

Permanent iodine-125 implant and external beam radiation therapy for the treatment of malignant brain tumors.

Survival data of 114 patients treated for malignant brain tumors with 125I interstitial radiation therapy at Henry Ford Hospital, Detroit, Mich. (1986-1990), are presented. The first 64 patients were treated with temporary 125I implants with a total prescribed dose of 60 Gy at a dose rate of 40 cGy/h. In order to reduce the risk of injury to the surrounding normal tissue associated with high-dose brachytherapy, a new approach was initiated using permanent implants with a lower dose rate; 50 patients were treated after surgical resection with permanent implantation of 125I seeds at a lower dose rate of 4-7 cGy/h, with a total dose of 10,000-12,000 cGy, and concurrent external radiation therapy of 5,000 cGy. The rationale of this protocol was to increase the effectiveness of the low-dose-rate implant by a concurrent 'daily' boost of external radiation, thus inhibiting the proliferation of tumor cells during the protracted low-dose radiation treatment. Survival was compared between groups with permanent and temporary implants in terms of effectiveness in tumor control as well as impact on clinical condition. Low-dose-rate implant with concurrent external radiation therapy seems to offer the best chance for long-term survival without deterioration in the clinical condition.

Adult↗

Training effects of long versus short bouts of exercise in healthy subjects.

To evaluate the "threshold" duration of exercise required to produce training effects, 18 healthy men aged 51 +/- 6 years completing 30 minutes of exercise training/day were compared with 18 men aged 52 +/- 6 years completing three 10-minute bouts of exercise/day, each separated by at least 4 hours. Exercise training intensity was moderate (65 to 75% of peak treadmill heart rate). During the 8-week study period VO2 max increased significantly in both groups from 33.3 +/- 3.2 to 37.9 +/- 3.5 ml/kg/min in men performing long exercise bouts and from 32.1 +/- 4.6 to 34.5 +/- 4.5 ml/kg/min in men performing short exercise bouts (p less than 0.05 within and between groups). Adherence to unsupervised exercise training performed at home and at work by men in long and short bouts was high; total duration of training completed was 96 and 93% of the prescribed amount and total number of sessions completed was 92 and 93% of that prescribed, respectively. In both groups exercise heart rate measured by a portable microprocessor was within or above the prescribed range for greater than 85% of the prescribed duration. Thus, multiple short bouts of moderate-intensity exercise training significantly increase peak oxygen uptake. For many individuals short bouts of exercise training may fit better into a busy schedule than a single long bout.

Electrocardiography↗