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Biomedical subjects

M Bell

Publications and source records attributed to M Bell.

At least 91 records · Page 5Linked to original sources
PubMed1997

Comparison of europium and chromium release assays: cytotoxicity in healthy individuals and patients with cervical carcinoma.

Natural killer (NK) and lymphokine-activated killer (LAK) cell activities were measured in peripheral blood obtained from healthy women to compare a standard 51Cr release assay with a nonradioactive europium (Eu3+) release assay based on time-resolved fluorescence. The two types of cytotoxicity assays were first compared in paired determinations performed on 28 samples of peripheral blood mononuclear cells obtained from healthy women who had normal pap smears or no biopsy evidence of cervical squamous intraepithelial lesions (SIL). Target cells (NK-sensitive K562 and NK-resistant Raji cell lines) were labeled with Eu3+ only, 51Cr only, or both labels and compared in cytotoxicity assays using fresh or interleukin 2 (IL-2)-activated effector cells. Spontaneous release in the Eu3+ release assay was comparable to that observed in the 51Cr release assay, but maximum Eu3+ release always exceeded that of 51Cr. In 4-h assays, specific release of Eu3+ from target cells was more rapid than that of 51Cr, consistently resulting in 30 to 40% higher levels of activity. However, a significant linear correlation (P < 0.001) was observed between cytotoxicity levels based on measurements of Eu3+ and 51Cr release in 4-h assays. The Eu3+ release assay was then used to measure NK and LAK activities in the peripheral blood of women with cervical SIL or cervical squamous cell carcinoma (SCC). Mean NK activity of women with advanced SIL (121 lytic units [LU]) or SCC (93 LU) was found to be similar to that of controls (101 LU) or patients with normal cervical biopsies (90 LU), as was the ability to generate IL-2-stimulated NK activity. However, LAK activity during 18 h of incubation in the presence of IL-2 was reduced in patients with cervical SCC (P < 0.05) compared with that in normal controls. Results of 51Cr assays performed in parallel with patient samples gave comparable results. Advantages of EU3+ release assays for routine evaluation of cytotoxicity are discussed.

Adult↗
PubMed1997

Detection of oncostatin M in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVE: To measure oncostatin M (OSM) in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: 20 samples of synovial fluid from patients with RA and 10 samples from patients with OA were examined using an OSM specific sandwich ELISA. RESULTS: OSM was detected at concentrations ranging from 2.36 to 901.82 pg/ml in 18 (90%) of 20 samples of synovial fluid from RA patients. There was no detectable OSM in synovial fluid from OA patients. In the RA patients, the OSM concentration in synovial fluid correlated significantly with the synovial fluid white blood cell count (r = 0.67, p < 0.01), but not with other laboratory parameters of disease activity. CONCLUSION: These findings suggest that OSM may contribute to joint inflammation in RA.

Adult↗
PubMed1997

Pregnancy status and feedlot performance of beef heifers actively immunized against gonadotropin-releasing hormone.

The contraceptive effect of active immunization against GnRH was evaluated in beef heifers. Crossbred heifers were randomized by breed and weight (initial weight = 227.3 +/- 1.2 kg) and assigned to one of three treatment groups. Animals in Group IB (n = 48) were actively immunized against GnRH; heifers in Groups NB (n = 48) and NN (n = 49) did not receive the anti-GnRH vaccine. Sixteen weeks after primary immunization, bulls of proven fertility were introduced into pens containing Groups IB and NB. Bulls were maintained with heifers for 2 mo. Heifers in group NN were not intentionally exposed to fertile males. At the end of the breeding period, heifers received Synovex H implants and entered a commercial feedlot. Heifers were slaughtered after 116 d of feedlot confinement. Anti-GnRH titer was evident in all heifers (48 of 48) immunized against GnRH. Gravid uteri were present at slaughter in 40 of 48 (83.3%) NB heifers. In contrast, only four (8.3%) IB and two (4.1%) NN heifers carried gravid uteri at slaughter. Although ADG did not differ between groups during feedlot confinement, ADG during the breeding period was higher (P < .05) in IB heifers than in NN control animals. Dressing percentage and longissimus muscle area were decreased (P < .05) and marbling and quality grade were increased (P < .05) in NB heifers compared with NN control heifers. Carcass traits of IB heifers were intermediate between those of the NB and NN groups. Taken together, these data indicate that active immunization against GnRH reduces the fertility of terminal heifers. These observations suggest that immunoneutralization of GnRH may be an effective management tool that will reduce the incidence of unintended pregnancy in heifers destined for feedlots.

Abattoirs↗
PubMed1997

Leukemia inhibitory factor (LIF) binding protein attenuates the phlogistic and abolishes the chondral effects of LIF in goat joints.

OBJECTIVE: To investigate the ability of murine leukemia inhibitory factor (LIF) binding protein (mLBP) to attenuate the effects of recombinant human LIF (rhLIF) in goat radiocarpal joints in vivo. METHODS: Endotoxin-free saline (1 ml) containing either 0.5 or 1 microg of rhLIF was injected into the left and right radiocarpal joints of male angora goats. One hour later the right radiocarpal joints were injected with either 1 or 5 microg of naturally occurring mLBP in 1 ml saline, while the left radiocarpal joints (controls) received 1 ml saline vehicle alone. Goat joints were examined for clinical features of inflammation and synovial fluid (SF) was aspirated on Day 0 (before injection) and Days 2 and 6 postinjection. Leukocyte counts and concentrations of keratan sulfate were determined in the SF. Proteoglycan synthesis and proteoglycan content of cartilage was determined ex vivo in cartilage explants obtained at Day 6. RESULTS: Preliminary time course studies in vitro showed that mLBP had to be added to cartilage explant cultures within 1 h of rhLIF for effective antagonism to occur. In joints injected with either 0.5 or 1 microg rhLIF significant increases in swelling, effusion volume, leukocyte counts, and SF keratan sulfate concentrations were observed relative to controls. Statistically significant depressions of ex vivo proteoglycan synthesis and in proteoglycan content of articular cartilage were also observed relative to controls. In joints injected with 1 microg rhLIF followed by 1 microg mLBP, statistically significant improvement was only observed in the rate of ex vivo cartilage proteoglycan synthesis. The observed rate did not differ significantly from that obtained in joints treated with vehicle alone. In contrast, in joints injected with 0.5 microg rhLIF followed by 5 microg mLBP, statistically significant improvement was observed in all variables. Treatment with 5 microg mLBP effectively negated the effects of rhLIF on joint swelling, effusion volume, leukocyte infiltration, and cartilage proteoglycan catabolism. CONCLUSION: Murine LBP has the ability to attenuate the phlogistic effects of rhLIF in radiocarpal joints of goats and also abolishes the stimulatory effect of rhLIF on cartilage proteoglycan catabolism and depression of ex vivo proteoglycan synthesis. These antiinflammatory and chondral effects suggest that a humanized derivative of mLBP could be a clinically useful antagonist for LIF in inflammatory diseases.

Animals↗
PubMed1996

Expression of cytokine genes or proteins and signaling molecules in lymphocytes associated with human ovarian carcinoma.

We have reported that tumor-associated T or natural killer (NK) lymphocytes purified from ascites of women with ovarian carcinoma show defective expression and function of signaling proteins, including reduced expression of TcR-zeta chains and p56(lck). In this study, the cytokine profiles of both tumor cells and tumor-associated lymphocytes (TAL) recovered from the tumor milieu were examined. Expression of cytokine genes was studied by semi-quantitative RT-PCR and Southern hybridization, and the presence of intracellular cytokine proteins was confirmed by immunostaining. Levels of mRNA encoding the cytokine genes typically transcribed in activated T lymphocytes, including IFN-gamma, IL-2 and IL-4, were markedly reduced, as was expression of the corresponding proteins, in TAL-T or TAL-NK cells relative to normal PBL-T or PBL-NK cells, respectively. Levels of TGF-beta and IL-6 were unaltered, while those of IL-10 were up-regulated. Although both tumor cells and TALs contributed to the enhanced level of IL-10 expression, a higher proportion of TAL-T lymphocytes than normal PBL-T cells expressed IL-10 protein. The altered profile of cytokine genes and proteins in TALs, TAL-T or TAL-NK cells was associated with impaired expression and/or function of signaling molecules, zeta chain and p56(lck). Our data suggest that abnormalities in signal transduction commonly seen in lymphocytes obtained from the tumor micro-environment are related to the concomitantly observed altered patterns of expression of cytokine transcripts and proteins.

Adult↗
PubMed1996

Appropriateness of primary total hip and knee replacements in regions of Ontario with high and low utilization rates.

OBJECTIVE: To compare the appropriateness of case selection for primary hip and knee replacements between two regions in Ontario: one with a high population-based utilization rate and one with a low rate. DESIGN: Random audit of medical records sampled from hospital discharge abstracts, with subsequent implicit and explicit criteria-based assessments of the appropriateness of surgery. STUDY POPULATION: People aged 60 years or over who underwent elective, single-joint, non-fracture-related, primary hip or knee replacement between Apr. 1, 1992, and Mar. 31, 1993, at one of seven hospitals in a high-rate region (comprising Brant, Huron and Oxford countries) or one of eight hospitals in a low-rate region (comprising the cities of Scarborough and Toronto). INTERVENTIONS: Structured review of hospital medical records, with additional review of information from surgeons and family physicians' office charts if necessary. Three physicians reviewed patient data and rated the preoperative pain level and functional status of patients, with agreement among at least two reviewers. The proportion of inappropriate cases was then assessed according to explicit criteria defined by a multidisciplinary panel using the delphi process. Profiles of each case were also subjected to independent implicit review by two rheumatologists and two orthopedic surgeons. OUTCOME MEASURES: Proportion of joint replacements deemed inappropriate in the high- and low-rate regions according to either the explicit criteria or the implicit review, as well as preoperative pain levels and functional status of patients in the high- and low-rate regions. RESULTS: Hip replacements were more common among patients sampled in the low-rate region than among those in the high-rate region (57.3% v. 39.3%; p < 0.002), although the patients' baseline characteristics, including severity of preoperative pain and dysfunction, were otherwise similar between the regions. Inappropriate surgery, determined by explicit criteria, was equally uncommon in the two regions (6.4% and 6.1%). On implicit review, the two rheumatologists rated fewer cases as appropriate than did the two orthopedic surgeons (63.0% v. 80.0%; p < 0.001); however, the proportion of cases rated as inappropriate by the subspecialists was similar in the high- and low-rate regions (11.4% and 11.0%, respectively, by the rheumatologists, and 6.3% and 10.4%, respectively, by the orthopedic surgeons). CONCLUSIONS: Patients selected for primary hip or knee replacement are similar in the high- and low-rate regions of Ontario. Inappropriate use of this procedure does not account for the high rate of surgery in some areas. Further studies will be required to determine which other factors account for the regional variations in the utilization rates and whether there is underservicing in low-rate areas.

Chi-Square Distribution↗
PubMed1996

Dual signal transduction through delta opioid receptors in a transfected human T-cell line.

Opiates are known to function as immunomodulators, in part by effects on T cells. However, the signal transduction pathways mediating the effects of opiates on T cells are largely undefined. To determine whether pathways that regulate free intracellular calcium ([Ca2+]i) and/or cAMP are affected by opiates acting through delta-type opioid receptors (DORs), a cDNA encoding the neuronal DOR was expressed in a stably transfected Jurkat T-cell line. The DOR agonists, deltorphin and [D-Ala2, D-Leu5]-enkephalin (DADLE), elevated [Ca2+]i, measured by flow cytofluorometry using the calcium-sensitive dye, Fluo-3. At concentrations from 10(-11)-10(-7) M, both agonists increased [Ca2+]i from 60 nM to peak concentrations of 400 nM in a dose-dependent manner within 30 sec (ED50 of approximately 5 x 10(-9) M). Naltrindole, a selective DOR antagonist, abolished the increase in [Ca2+]i, and pretreatment with pertussis toxin was also effective. To assess the role of extracellular calcium, cells were pretreated with EGTA, which reduced the initial deltorphin-induced elevation of [Ca2+]i by more than 50% and eliminated the second phase of calcium mobilization. Additionally, the effect of DADLE on forskolin-stimulated cAMP production was determined. DADLE reduced cAMP production by 70% (IC50 of approximately equal to 10(-11) M), and pertussis toxin inhibited the action of DADLE. Thus, the DOR expressed by a transfected Jurkat T-cell line is positively coupled to pathways leading to calcium mobilization and negatively coupled to adenylate cyclase. These studies identify two pertussis toxin-sensitive, G protein-mediated signaling pathways through which DOR agonists regulate the levels of intracellular messengers that modulate T-cell activation.

Adenylate Cyclase Toxin↗
PubMed1996

An evidence-based approach to prescribing NSAIDs in musculoskeletal disease: a Canadian consensus. Canadian NSAID Consensus Participants.

OBJECTIVE: To make recommendations for the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) in primary care practice, particularly for patients at high risk for NSAID-induced complications. OPTIONS: The use of misoprostol to prevent gastrointestinal ulceration and other unwanted NSAIDs effects was considered. The role of cyclooxygenase-2 (COX-2) versus COX-1 inhibiting agents was also examined. OUTCOMES: Reduction of complications associated with long-term use of NSAIDs. EVIDENCE: Evidence was gathered in late 1995 from published research studies and reviews. Position papers were prepared by faculty and advisory board members and discussed at the Canadian NSAID Consensus Symposium in Cambridge, Ont., Jan. 26 and 27, 1996. VALUES: Recommendations were based on randomized, placebo-controlled clinical trials (level I evidence) and case-control studies (level II evidence) involving NSAID use when such evidence was available. When the scientific literature was incomplete or inconsistent in a particular area, recommendations reflect the consensus of the participants at the symposium (level III evidence). Physicians were recruited from across Canada for their expertise in rheumatology, gastroenterology, epidemiology, gerontology, family practice, and clinical and basic scientific research. BENEFITS, HARMS AND COSTS: Although a reduction in complications due to inappropriate NSAID use should reduce costs of additional investigations, admissions to hospital and time lost from work, definitive cost analysis studies are not yet available. RECOMMENDATIONS: Currently, no NSAID is available that lacks potential for serious toxicity; therefore, long-term use of NSAIDs should be avoided whenever possible, particularly in high-risk patients (e.g., those who are elderly, suffer from hypertension, congestive heart failure, renal or hepatic impairment or volume depletion, take certain concomitant medications or have a history of peptic ulcer disease) (level I evidence). If NSAIDs are to be used in patients with gastric or nephrotoxic risk factors, the lowest effective dose of NSAID should be used (level III evidence); NSAIDs that are weak COX-1 inhibitors may be preferred (level II evidence). In addition, concomitant administration of misoprostol is recommended in patients at increased risk for upper gastrointestinal complications (level I evidence). However, the clinical judgement of the practising clinician must always be part of any therapeutic decision. VALIDATION: These recommendations are based on the consensus of Canadian experts in rheumatology, gastroenterology and epidemiology, and have been subjected to external peer review.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Restoration of a worn dentition using a double-veneer technique.

Restoration of dentitions affected by tooth surface loss has been a problem to the dental profession for many years. This problem is likely to increase as the population ages and retains more teeth into old age. This article describes a method of restoring teeth with non-carious loss of tooth tissue whilst conserving the remaining tooth tissue.

Aged↗
PubMed1996

Population mobility and indigenous peoples: the view from Australia.

"This paper describes an emerging field of demographic enquiry focused on the population mobility of indigenous minorities in Australasia and North America. Political, scientific and policy rationales for research on the spatial dynamics of such groups are advanced as a prelude to a review of the Australian literature. This review is structured around four complementary perspectives on mobility: the propensity to move; spatial redistribution; flows and networks; and migration careers. Comparison of the relative strengths of mobility research on the indigenous and non-indigenous populations against these four perspectives assists in identifying outstanding research needs and priorities. Commonalities in the patterns and processes of indigenous mobility in Australia, New Zealand, Canada and the U.S. suggest the value of more detailed cross-national comparisons, and also provide a basis for contemplating an indigenous variant of Zelinsky's hypothesised mobility transition."

Americas↗
PubMed1996

Oncostatin M (OSM) stimulates resorption and inhibits synthesis of proteoglycan in porcine articular cartilage explants.

Oncostatin M (OSM) is structurally and functionally similar to leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), interleukin 11 (IL-11) and ciliary neurotrophic factor (CNTF). We have previously shown that LIF stimulates proteoglycan release and suppresses proteoglycan synthesis in pig and goat cartilage explants. The aim of this study was to determine whether OSM and related cytokines influence proteoglycan metabolism in pig cartilage explants. Slices of pig articular cartilage were incubated for 6 days in serum free DMEM with or without cytokines. The total proteoglycan content in papain digested cartilage explants and medium was determined by the 1,9 dimethylmethylene blue method. Cytokine activity was assessed by determining the percentage release of total proteoglycan. To evaluate proteoglycan synthesis, cartilage was cultured for 48 h under the same conditions and in the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose dependent stimulation of proteoglycan release and suppression of proteoglycan synthesis were observed with rhOSM. IL-6, IL-11 and CNTF also inhibited proteoglycan synthesis in a dose dependent manner but the degree of inhibition was less than that for OSM and these cytokines had no significant effect on proteoglycan release. New biological effects have been identified for OSM and the related cytokines CNTF and IL-11. All three of these cytokines, like LIF and IL-6, suppress proteoglycan synthesis in pig cartilage explants. This common effect suggests that the gp130 subunit of the receptors for these cytokines may represent a common signalling pathway whereby proteoglycan synthesis is regulated. Whilst OSM and LIF stimulate proteoglycan catabolism; IL-6 IL-11 and OSM do not. Thus these effects are not always coupled and activation of gp130 alone may not be a sufficient signal for proteoglycan catabolism.

Animals↗
PubMed1996

How often do Australians move? Alternative measures of population mobility.

"Conventional census-based measures of population mobility are conceptually abstruse, ignore multiple moves and obscure the diversity of human migration experience. This paper explores three alternatives and outlines their strengths and limitations. Application of life table techniques to convert transition rates to migration expectancies generates measures that are more readily understood, automatically standardizes for age and enables the timing of mobility to be analysed methodically. Data on movement frequencies and residence duration provide new perspectives indicating substantial chronic mobility and significant differences between frequent movers and long term stayers. A number of simple summary statistics are proposed to supplement transition rates."

Australia↗
PubMed1996

Family stress and support among former Soviet immigrants.

The purpose of this qualitative descriptive study was to investigate types of family support and stress among former Soviet immigrants. Forty-two immigrants (14 males and 28 females) were interviewed about their immigration experiences, including description of current relationships with family in the resettlement country. Content analysis of interview data documented that immigrant families can be a valuable source of emotional and/or instrumental support. Immigrant families, however, can also be too overwhelmed by their own immigration demands to provide support or can generate additional stress for its members. Types of family stress included conflict from differing values and opinions, increased responsibility for family members who could not manage resettlement on their own, family members' emotional distress over immigration experiences, unmet expectations for family members' adjustment, and changes in household composition and living arrangements upon arrival in the United States.

Adult↗
PubMed1996

Children's memory for traumatic injury.

Children between 2 and 13 years who suffered traumatic injury necessitating hospital emergency room treatment were recruited as subjects. They (and adult witnesses) were interviewed a few days and 6 months later, using free and probed recall, about both injury and hospital treatment. Children at all ages were able to provide considerable information about both stressful events, although the amount of detail increased with age. They also made few commission errors. Surprisingly, children's distress at time of injury did not affect the amount or accuracy of their recall of that event, whereas distress during hospital treatment did decrease recall. A tripartite classification into 3 categories of detail was used: central, peripheral--inside the emotional events, or peripheral--outside those events. Children's recall differed depending upon detail category. Implications for children's testimony are discussed.

Adolescent↗
PubMed1995

Wisconsin card sorting test and work performance in schizophrenia.

Patients with schizophrenia have long been observed to perform poorly on the Wisconsin Card Sorting Test (WCST). Although numerous studies have established links between WCST performance and specific and diffuse structural brain abnormalities, little is known about its relationship to occupational functioning. The present study has investigated the relationship between behavior at a vocational work placement and performance on the WCST test for 89 subjects with schizophrenia or schizoaffective disorder. Multiple regression analyses that examined select WCST raw scores and that covaried out IQ and Digit Symbol Subtest scores found that Task Orientation at work was significantly related to WCST Trials to the First Category and Total Number Correct. Multiple regression analyses that examined standard scores, corrected for age and education, revealed that Task Orientation was related to Percent Conceptual Level and that Social Skills were related to Total Errors and Percent Conceptual Level. Results support the criterion-related validity of the WCST and have implications for understanding impairments in work function.

Adult↗