Macrophage colony-stimulating factor (M-CSF) is known to play an important role in osteoclast formation. However, its actions on mature cells have not been fully characterized. We now report that M-CSF dramatically stimulates osteoclastic motility and spreading; osteoclasts responded to a gradient of M-CSF with orientation, and random cell polarization occurred after isotropic exposure. M-CSF also supported the survival of osteoclasts by preventing apoptosis. Paradoxically, M-CSF inhibits bone resorption by isolated osteoclasts. We found that this was effected predominantly by reduction in the number of excavations. Thus, M-CSF showed a propensity to suppress resorption through a reduction in the proportion of cells that were resorbing bone. Our data suggest that apart from the established role of M-CSF in the provision of precursors for osteoclastic induction, a major role for M-CSF in bone resorption is to enhance osteoclastic survival, migration, and chemotaxis. It seems appropriate that during these processes resorptive functions should be suppressed. We suggest that M-CSF continues to modulate osteoclastic activity once osteoclasts are on resorptive sites, through regulation of the balance between resorption and migration, such that not only the quantity, but the spatial pattern of resorption can be controlled by adjacent M-CSF-secreting cells of osteoblastic lineage.

Animals↗

PubMed1993

The academic base for general practice: the case for change.

University departments of general practice and the postgraduate education system for general practice have developed separately over the past 30 years. This separation is now impeding the academic development of the discipline and causes difficulties with recruitment and career progression. These problems could be eased by the creation of integrated departments. This would establish a critical mass for research and educational development, allow human and other resources to be used more flexibly and effectively, and provide a strong base for undergraduate education, vocational training, higher professional training, and continuing education. It could encourage collaborative ventures with other disciplines and also lead to higher standards of patient care.

Education, Medical, Graduate↗

PubMed1993

Health promotion in general practice. Room for improvement in data collection.

Explore the source record for details and available documents.

Data Collection↗

PubMed1993

Highly sensitive fluorimetric enzyme immunoassay for prostaglandin H synthase solubilized from cultured cells.

A highly sensitive fluorimetric enzyme immunoassay was developed for prostaglandin H (PGH) synthase, an intrinsic membrane protein, using n-octyl beta-D-glucopyranoside for solubilization of the synthase from the endoplasmic reticulum membrane. An anti-PGH synthase IgG-coated polystyrene ball was reacted with a PGH synthase standard or crude detergent extract of cells, washed to remove the detergent, and then incubated with anti-PGH synthase Fab'-beta-D-galactosidase conjugate. The bound beta-D-galactosidase activity was quantitated with 4-methylumbelliferyl-beta-D-galactoside, a fluorogenic substrate. The detection limit for the PGH synthase standard was found to be 1.0 pg/assay. The sensitivity of this assay is increased by about 2-3 orders of magnitude over those of previously reported radioimmunoassay or colorimetric enzyme immunoassay. The high sensitivity of the fluorimetric enzyme immunoassay allowed reliable detection of low levels of human PGH synthase present in small samples of cultured cells. Our studies with this fluorimetric immunoassay for the synthase developed a general method for determination of membrane-bound proteins at ultrasensitive levels.

Animals↗

PubMed1993

Homomeric assemblies of NMDAR1 splice variants are sensitive to ethanol.

Studies have shown that the neuronal NMDA receptor is a target for the actions of ethanol. Recently, a number of subunits of the NMDA receptor have been cloned and functionally expressed in various combinations. We have expressed four splice variants of the NMDAR1 subunit in Xenopus oocytes, and find that homomeric assemblies of this subunit, in the absence of other subunits, exhibit ethanol sensitivity comparable to that seen in neurons. In the presence of calcium, the reduction of total current was greatest in the NMDAR1-LL splice variant, and was significantly less in the NMDAR1-SS variant. The increased sensitivity of NMDAR1-LL may be attributed to a particularly sensitive slow current 'hump' which is more pronounced in NMDAR1-LL than in NMDAR1-SS. The reduction of NMDA-evoked current by ethanol was significantly different when calcium was replaced by barium in the external medium. In this case, the slow current hump was significantly reduced, current through NMDAR1-LL was less reduced by ethanol, and the percent reduction of NMDAR1-LL and NMDAR1-SS currents was similar. NMDA-evoked currents in heteromeric receptors formed by coinjection of the mouse epsilon-1 subunit with the NMDAR1 splice variants responded to ethanol similarly to homomeric assemblies.

Animals↗

PubMed1993

Cell cycle regulated expression of nucleolar antigen P120 in normal and transformed human fibroblasts.

Normal and SV40 virus-transformed WI-38 human lung fibroblasts were serum starved and refed, or synchronized by double thymidine block and released from the block. At different time points in the cell cycle, steady state levels of P120 mRNA and P120 protein content of the cells were determined by densitometric scans of Northern and Western blots. At the same time points, [3H]thymidine uptake was measured and flow cytometric analysis performed for DNA content and P120 antigen staining. Levels of P120 protein and P120 mRNA were approximately 4 times greater in non-synchronous, exponentially growing transformed cells than in similarly growing normal cells. Early G1-phase cells, synchronized either with serum deprivation or with metabolic block, contained only a trace amount of P120 protein and mRNA. The P120 gene was transcribed early in G1 and P120 protein synthesis initiated in middle G1. A dramatic increase of P120 protein level occurred in S-phase with a corresponding mRNA peak preceding the P120 protein peak. These results indicate that P120 is overexpressed in transformed WI-38 cells and that P120 is temporally regulated during the cell cycle of both transformed and normal fibroblasts. The dramatic increase in P120 protein expression at the G1 to S boundary suggests that P120 may play a role in the regulation of cell cycle and increased nucleolar activity that is associated with cell proliferation.

Blotting, Western↗

PubMed1993

Reliability of the Columbia scale for assessing signs of Parkinson's disease.

Inter- and intrarater reliability in scoring the signs of Parkinson's disease using the original Columbia scale and a modified version of this, the Sydney scale, were assessed in five neurologists participating in a long-term study of Parkinson's disease. Scoring was done on video recordings of 41 patients whose disability ranged from mild to severe. Although all the neurologists were familiar with the scales and had received training designed to produce uniformity of scoring, interrater reliability was poor. The mean score for the Columbia scale varied from 18.6 to 30 and for the Sydney scale from 15.2 to 23.2. By contrast, intrarater reliability was good. This study highlights the limitations of clinical rating scales in Parkinson's disease when more than one rater is used. In designing clinical trials, every effort should be made to ensure that the same patient is always assessed by the same rater.

Analysis of Variance↗

PubMed1993

Effect on herd health and productivity of controlling tsetse and trypanosomosis by applying deltamethrin to cattle.

A large cattle ranch was established in 1954 in a heavily tsetse infested part of north-east Tanzania. Trypanosomosis was controlled for 30 years by prophylactic drugs but in 1988 drug resistance seemed to be developing as cases of trypanosomosis were being confirmed 4 or 5 weeks after treatment with isometamidium chloride (Samorin). Herd health had deteriorated and productivity was uneconomically low. In order to control the tsetse population the 8,000 cattle, grazing over 250 km2, were regularly dipped in the synthetic pyrethroid deltamethrin (Decatix Cattle Dip and Spray formulation). Within a year the tsetse population, as monitored by traps, had decreased by more than 90%. Disease mortality decreased by 66% and a range of productivity measures such as calving percentages and weaning weights were raised to levels above those prevailing before the decline in herd health.

Abortion, Veterinary↗

PubMed1993

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing. RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens. CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.

Adolescent↗

PubMed1993

A prospective study to identify high-yield criteria associated with acute intracranial computed tomography findings in head-injured patients.

We conducted a multicenter, prospective study of head-injured patients to identify high-yield clinical criteria for acute intracranial injuries. Emergency patients with a history of blunt head trauma occurring within 2 weeks and who underwent nonenhanced cranial computed tomography (CT) were entered onto the study during a 12-month period. Of the 264 patients, 32 (12%) had abnormal CT findings. Nine high-yield variables were associated with abnormal CT findings: alcohol use before injury, antegrade amnesia, prolonged loss of consciousness, anisocoria and/or fixed and dilated pupils, abnormal Babinski reflex, focal motor paralysis, cranial nerve deficit, Glasgow coma scale score of less than 15, and clinical signs of basilar skull fracture. Patients 2 years old or younger or older than 60 years of age showed a significantly greater prevalence of abnormal CT findings than patients of other ages.

Acute Disease↗

PubMed1993

A quantitative evaluation of the aetiological role of betel quid in oral carcinogenesis.

Computer aided search and review of bibliographies of published papers and monographs revealed 17 case control studies of oral cancer and betel quid chewing from 1933 to 1990. Studies were assessed and site specific risk of oral cancer associated with chewing betel quid with and without tobacco in the quid among smokers and non-smokers was computed. Tobacco smoking and chewing betel quid containing tobacco arose as important risk factors for oral cancer, betel quid without tobacco significantly increased risk in only one study. Heterogeneity in estimates of risk among studies was reduced by restricting analysis to those with more exact definition of exposure and site of the cancer. Variation in risk among studies reflects bias in selection and inadequate definition of exposure and tumour site and an inability to control effectively for confounding. Further studies, addressing these issues are advised, to clarify the role of betel quid without tobacco as a carcinogen, alone and in combination with tobacco smoke.

Areca↗

PubMed1993

Meeting report (with extended abstracts). CEIR Forum on the effects of cytokines on radiation responses.

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Accidents↗

PubMed1993

Differences in serum lipids in Australian children: is diet responsible?

A total of 5211 schoolchildren aged 10-15 years participated in an Australia-wide sample survey conducted in 1985 and completed dietary and demographic assessment, and the measurement of body mass index: 1017 children aged 12 and 15 years gave blood for serum lipid analysis. Group mean differences in serum lipids and body mass index with age, sex, socioeconomic status and ethnic origin were determined. Nutritional analysis generated group mean values for daily energy intake, per cent kilo-joules from total fat, saturated fat, monosaturated fat and polyunsaturated fat, as well as the polyunsaturated:saturated fat ratio and nutrient density of fibre. In multiple regression analyses, socioeconomic and gender based differences in serum lipids could be explained by differences in diet, whereas age group differences could not. Although there were statistically significant differences in dietary fat intake on the basis of ethnic origin, these were not reflected in differences in serum lipids. For girls, dietary fat variables were more important predictors of serum lipids than body mass index. For boys, the reverse was true. These results suggest that class differences in cardiovascular risk arise from dietary differences that are present from an early age. Sex-based differences in serum lipids seem to reflect different mechanisms in girls and boys. In the former, dietary differences are of importance but for the latter, anthropomorphic (possibly exercise-linked) differences are the most important. These findings imply that cardiovascular risk preventive programmes for children need to take into account the mechanisms of social inequality and sex-based differences.

Adolescent↗

PubMed1993

Effects of exercise on total and segmental colon transit.

To investigate the effect of aerobic exercise on total gastrointestinal and segmental colon transit, 16 male health care workers with a sedentary life-style were studied during 1 week of rest and 1 week of exercise. The exercise phase consisted of walking 4.5 km on a level treadmill for 1 h on each of 3 days. Total gastrointestinal and segmental colon transit times were measured using radiopaque markers ingested on each of 3 consecutive days with an abdominal radiograph obtained on the fourth day. With exercise, total gastrointestinal transit time decreased in 5, increased in 6, and did not change in 5 subjects. Using a paired t test, total transit did not show a significant change from rest (24.5 +/- 21.8 h) to exercise (20.9 +/- 16.8 h), p = 0.50. These observations support our previous findings that physical activity to the extent that average people consider routine exercise does not necessarily improve gastrointestinal transit. Therefore, the role of such exercise in the management of chronic constipation can be seriously questioned.

Adult↗