PubMed Health⌕ Search

Biomedical subjects

S M Blake

Publications and source records attributed to S M Blake.

At least 37 records · Page 2Linked to original sources
PubMed2000

FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis.

OBJECTIVE: To characterize a novel secreted frizzled-related protein (SFRP) and determine its tissue distribution at the mRNA and protein level. METHODS: The FrzB-2 gene was identified by expressed sequence tag (EST) analysis of human tissue-derived libraries. Tissue distribution of FrzB-2 mRNA was determined by Northern blot analysis and in situ hybridization. FrzB-2 protein reactivity was localized in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody against a peptide sequence unique to FrzB-2. Apoptosis was detected in articular cartilage sections using Tunel staining. RESULTS: ESTs corresponding to FrzB-2 were found in osteoblast, chondrosarcoma, osteosarcoma, osteoclastoma and synovial fibroblast libraries. FrzB-2 mRNA is expressed in a number of tissues and cell types including bone-related cells and tissues such as primary human osteoblasts and osteoclastoma. In situ hybridization studies showed strong FrzB-2 mRNA expression in human chondrocytes in human osteoarthritic (OA) cartilage but negligible levels in normal cartilage chondrocytes. The FrzB-2 cDNA encodes a secreted 40 kDa protein consisting of 346 amino acids. FrzB-2 is 92. 5% identical to the rat orthologue, DDC-4, which has been shown to be associated with physiological apoptosis. FrzB-2 protein was selectively detected in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody. Consistent with its potential role in apoptosis, positive FrzB-2 staining and Tunel positive nuclei staining were detected in chondrocyte clones in sections of human OA cartilage. CONCLUSION: These data suggest that FrzB-2 may play a role in apoptosis and that the expression of this protein may be important in the pathogenesis of human OA.

Amino Acid Sequence↗
PubMed1999

Activation of the p38 mitogen-activated protein kinase pathway by Epstein-Barr virus-encoded latent membrane protein 1 coregulates interleukin-6 and interleukin-8 production.

The Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) is a pleiotropic protein the activities of which include effects on gene expression and cell transformation, growth, and death. LMP1 has been shown to induce nuclear factor (NF)-kappaB and c-Jun NH2-terminal kinase/AP-1 activities in target cells, and in this study we demonstrate that LMP1 also engages the p38 mitogen-activated protein kinase cascade, leading to activation of the transcription factor ATF2. Mutational analysis of the LMP1 cytoplasmic COOH terminus revealed that p38 activation occurs from both the tumor necrosis factor receptor-associated factor (TRAF)-interacting, membrane-proximal COOH-terminal activating region (CTAR)1 domain (amino acids 186-231) and the extreme tumor necrosis factor receptor-associated death domain (TRADD) binding CTAR2 region (amino acids 351-386). Because LMP1 also engages signaling on the NF-kappaB axis through CTAR1 and CTAR2, we have examined whether these two pathways are overlapping or independent. We have found that inhibition of p38 by the highly specific inhibitor SB203580 did not affect NF-kappaB binding activity. Conversely, although the metabolic inhibitor D609 blocked NF-kappaB activation, it did not impair the ability of LMP1 to signal on the p38 axis, suggesting that these two LMP1-mediated pathways are primarily independent. Divergence of signals must, however, occur downstream of TRAF2 as a dominant negative TRAF2 mutant that blocks LMP1-induced NF-kappaB activation also inhibited p38 signaling. In addition, we have found that p38 inhibition significantly impaired LMP1-mediated interleukin-6 and -8 expression. Thus, p38 may play a significant cooperative role in regulating at least some of the pleiotropic activities of LMP1.

Activating Transcription Factor 2↗
PubMed1999

Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2.

The transforming Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) activates signalling on the NF-kappaB axis through two distinct domains in its cytoplasmic C terminus, namely, CTAR1 (amino acids [aa] 187 to 231) and CTAR2 (aa 351 to 386). The ability of CTAR1 to activate NF-kappaB appears to be attributable to the direct interaction of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), while recent work indicates that CTAR2-induced NF-kappaB is mediated through its association with TNF receptor-associated death domain (TRADD). LMP1 expression also results in activation of the c-Jun N-terminal kinase (JNK) (also known as stress-activated protein kinase) cascade, an effect which is mediated exclusively through CTAR2 and can be dissociated from NF-kappaB induction. The organization and signalling components involved in LMP1-induced JNK activation are not known. In this study we have dissected the extreme C terminus of LMP1 and have identified the last 8 aa of the protein (aa 378 to 386) as being important for JNK signalling. Using a series of fine mutants in which single amino acids between codons 379 and 386 were changed to glycine, we have found that mutations of Pro379, Glu381, Ser383, or Tyr384 diminish the ability of LMP1 CTAR2 to engage JNK signalling. Interestingly, this region was also found to be essential for CTAR2-mediated NF-kappaB induction and coincides with the LMP1 amino acid sequences shown to bind TRADD. Furthermore, we have found that LMP1-mediated JNK activation is synergistically augmented by low levels of TRADD expression, suggesting that this adapter protein is critical for LMP1 signalling. TRAF2 is known to associate with TRADD, and expression of a dominant-negative N-terminal deletion TRAF2 mutant was found to partially inhibit LMP1-induced JNK activation in 293 cells. In addition, the TRAF2-interacting protein A20 blocked both LMP1-induced JNK and NF-kappaB activation, further implicating TRAF2 in these phenomena. While expression of a kinase-inactive mutated NF-kappaB-inducing kinase (NIK), a mitogen-activated protein kinase kinase kinase which also associates with TRAF2, impaired LMP1 signalling on the NF-kappaB axis, it did not inhibit LMP1-induced JNK activation, suggesting that these two pathways may bifurcate at the level of TRAF2. These data further define a role for TRADD and TRAF2 in JNK activation and confirm that LMP1 utilizes signalling mechanisms used by the TNF receptor/CD40 family to elicit its pleiotropic activities.

Amino Acids↗
PubMed1999

Factors associated with occupational exposure and compliance with universal precautions in an urban school district.

Factors associated with occupational exposure and universal precautions (UP) compliance were assessed among employees in one urban school district. Half of the employees surveyed reported responding to bleeding injuries and cleaning blood or other body fluids (e.g., vomit, urine) during the previous school year. Also, 1 in 4 custodians and 1 in 10 teachers/teacher's aides had direct contact with blood or body fluids without protection. In multivariate logistic regression analyses, direct contact was most likely among secondary school employees in unpredictable situations who did not have protective equipment or comply with UP. UP compliance was greater among those who had protective equipment available and felt self-confident. Self-confidence was associated with having received training or protective equipment. Routine communications between administrators and employees, staff training, provision of protective equipment, and exposure incident monitoring are essential to effective implementation of UP policies in schools and work settings where occupational exposure could occur.

Analysis of Variance↗
PubMed1999

Idoxifene, a novel selective estrogen receptor modulator, is effective in a rat model of adjuvant-induced arthritis.

Idoxifene, a selective estrogen receptor modulator, was evaluated in male and female rats with adjuvant-induced arthritis (AA). AA was induced in Lewis rats with Mycobacterium butyricum in paraffin oil injected into the base of the tail, and the animals were treated with idoxifene prophylactically (days 0-21) or therapeutically (days 10-21). Efficacy was determined by measurements of paw inflammation, bone mineral content, and bone mineral density (BMD) with dual X-ray absorptiometry and by histological evaluation. Serum interleukin-6 levels were measured as a marker of the anti-inflammatory effects of the compound. Estrogen was included for comparison and was administered at 5 mg/kg, three times a week s.c. Prophylactic treatment of male AA rats with idoxifene at 10, 3, and 1 mg/kg and estrogen at 5 mg/kg significantly inhibited paw inflammation. There was improved joint integrity measured by BMD and reduced serum interleukin-6 levels in animals treated with 10 mg/kg/day idoxifene. Idoxifene and estrogen were as effective for AA in female Lewis rats as in male rats, significantly inhibiting paw inflammation and improving BMD. Histological evaluation of the tibiotarsal joints of female rats treated with 10 mg/kg showed protection of bone, cartilage, and soft tissue. Therapeutic treatment with either idoxifene or estrogen (starting on day 10 of disease) of male and female Lewis rats also was effective in reducing paw inflammation in these animals, although the effect was much less than that observed with the prophylactic dosing protocol.

Animals↗
PubMed1996

Effects of theophylline and rolipram on antigen-induced airway responses in neonatally immunized rabbits.

1. The effects of the xanthine, theophylline, a non-selective phosphodiesterase (PDE) inhibitor, and the phosphodiesterase type 4 (PDE 4) inhibitor, rolipram, were evaluated in a model of antigen-induced airway responses in the allergic rabbit. 2. Adult litter-matched NZW rabbits (2.5-3.9 kg), immunized within 24 h of birth with Alternaria tenuis antigen, were pretreated twice daily for 3 days with theophylline (3 mg kg-1, i.p) or rolipram (1 mg kg-1, i.p) prior to antigen challenge (Alternaria tenuis). For each drug-treated group, a parallel group of rabbits were pretreated with the appropriate vehicle. In all groups airway responsiveness to inhaled histamine and bronchoalveolar lavage (BAL) was performed 24 h before and after antigen-challenge. 3. Basal lung function in terms of resistance (RL, cmH2O 1(-1)s-1) and dynamic compliance (Cdyn, ml cmH2O-1) were unaltered by pretreatment with theophylline or rolipram compared to their respective vehicles 24 h prior to or post antigen challenge. 4. The acute bronchoconstriction induced by inhaled Alternaria tenuis aerosol was unaffected by pretreatment with theophylline or rolipram. 5. Airway hyperresponsiveness to inhaled histamine was indicated by reduced RL PC50 (2.4-3.5 fold) and Cdyn PC35 (2.5-2.6 fold) values 24 h after antigen challenge. Treatment with rolipram, but not theophylline, prevented the increase in responsiveness to inhaled histamine 24 h after antigen challenge. 6. Total cells per ml of BAL fluid increased 24 h after antigen challenge due to the recruitment of neutrophils and eosinophils. Antigen-induced increases in pulmonary neutrophils were unaffected; however, eosinophils were reduced 57.5% in theophylline and 82% in rolipram-treated rabbits. 7. Inhalation of Alternaria tenuis aerosol elicits an acute bronchoconstriction, followed 24 h later by an increased responsiveness to inhaled histamine and pulmonary neutrophil and eosinophil recruitment in the immunized rabbit. With the dosing regimes used, both rolipram and theophylline inhibited eosinophil recruitment, whilst only rolipram prevented the development of airway hyperresponsiveness. Neither agent inhibited the acute bronchoconstriction due to inhaled antigen.

Airway Resistance↗
PubMed1996

Effect of the glucocorticosteroid budesonide and a novel phosphodiesterase type 4 inhibitor CDP840 on antigen-induced airway responses in neonatally immunised rabbits.

1. The effects of the inhaled corticosteroid budesonide and a novel PDE 4 inhibitor CDP840 given systematically, were evaluated in a model of antigen-induced airway inflammation in the rabbit. 2. Adult litter-matched NZW rabbits (2.4-3.5 kg) immunised within 24 h of birth with Alternaria tenuis antigen were pretreated with budesonide (total dose 100 micrograms, inhaled over 2 days) or CDP840 (total dose 7 mg kg-1, i.p. over 3 days), before antigen challenge. For each drug-treated group a parallel group of rabbits was pretreated with the appropriate vehicle. In all groups airway responsiveness to inhaled histamine was assessed and bronchoalveolar lavage (BAL) performed 24 h before and after antigen challenge. 3. Basal lung function in terms of total lung resistance (RL; cmH2O l 1s-1) and dynamic compliance (Cdyn; ml cmH2O-1) were unaltered by pretreatment with budesonide or CDP840 compared to their respective vehicles 24 h before or after antigen challenge. 4. The RL component of the acute bronchoconstriction induced by inhaled Alternaria tenuis aerosol was unaffected by pretreatment with budesonide. However, budesonide prevented the fall in Cdyn due to antigen. Treatment with CDP840 significantly reduced antigen-induced acute bronchoconstriction in terms of both RL and Cdyn. 5. Airway hyperresponsiveness (AHR) to inhaled histamine was indicated by reduced RL PC50 (2.4-4.5 fold) and Cdyn PC35 (2.1-3.9 fold) values 24 h after antigen challenge. Treatment with either budesonide or CDP840 abolished the antigen-induced increase in responsiveness to inhaled histamine. 6. Total cells recovered per ml of BAL fluid increased 24 h after antigen challenge. Antigen-induced pulmonary eosinophilia was reduced (93%) in budesonide and (85%) in CDP840 treated rabbits. Antigen-induced increases in neutrophil numbers were reduced (76%) with budesonide but not CDP840 pretreatment. 7. Inhalation of Alternaria tenuis aerosol elicited an acute bronchoconstriction, followed 24 hours later by an increased responsiveness to inhaled histamine and pulmonary neutrophil and eosinophil recruitment. CDP840 was more effective than budesonide in preventing the antigen-induced increase in total lung resistance (RL); however, both drugs prevented the antigen-induced reduction in dynamic compliance (Cdyn). CDP840 and budesonide also prevented antigen-induced AHR and eosinophilia in the immunised rabbit.

Administration, Inhalation↗
PubMed1994

The effect of recombinant human interleukin 1 receptor antagonist on the induction phase of antigen induced arthritis in the rabbit.

OBJECTIVE: To determine if systemic administration of human interleukin 1 receptor antagonist (IL-1ra) to rabbits during the induction phase of antigen induced arthritis (AIA) could block inflammation and cartilage proteoglycan loss. METHODS: Recombinant human IL-1ra was administered every 6 h to rabbits beginning 1 h before induction of arthritis. Joint swelling was monitored for 72 h and then animals were killed 6 h after the last dose of IL-1ra. Leukocyte accumulation in the joint space and synovial lining was determined and the proteoglycan content and capacity for synthesis was assessed in the articular cartilage of the control and arthritic joints. RESULTS: Administration of IL-1ra had no detectable effect on the induction of arthritis. Swelling proceeded with a similar time course to untreated AIA animals and at 3 days the cellular infiltrate into synovial fluid (SF) was similarly high, the proteoglycan content of SF was also high and cartilage proteoglycan content was depleted. The biosynthesis of proteoglycan in cartilage was also similarly inhibited. No changes were detected in the cartilage and synovium or SF of the contralateral joints of animals receiving IL-1ra. CONCLUSION: IL-1ra given at a dose shown to block synovitis and proteoglycan loss induced by a bolus injection of recombinant IL-1 in rabbits was unable to inhibit the induction of AIA. Our results suggest that the action of IL-1 is not the major factor responsible for the induction of arthritis in this animal model of inflammatory joint disease.

Animals↗
PubMed1992

Uridine diphosphoglucose dehydrogenase activity in synovial lining cells in the experimental antigen induced model of rheumatoid arthritis: an indication of synovial lining cell function.

Uridine diphosphoglucose dehydrogenase (UDPGD) is the enzyme responsible for the production of uridine diphospho(UDP)-glucuronate, an essential monosaccharide in the biosynthesis of hyaluronan, which is found in high concentrations in normal synovial fluid. Synovial lining cells have been implicated in the synthesis of hyaluronan, but the degree to which they are adapted metabolically to this function in normal and inflamed synovium has not been established. Using a quantitative cytochemical method it was shown that synovial lining cells from chronically inflamed rabbit synovium had significantly lower UDPGD activity per cell than the lining cells of normal synovium. These findings suggest that the lining cells of normal non-inflamed synovium may be enzymatically adapted for the synthesis of hyaluronan and that this may be an indication of a specific role of synovial lining cells in the maintenance of normal joint function.

Animals↗
PubMed1991

The effect of menadione epoxide on the experimental immune arthritis in the rabbit.

It was shown previously that the experimentally induced arthritis in the rabbit can be largely nullified by subsequent treatment with menadione (by gavage). It is now shown that menadione epoxide, as is produced in the vitamin K cycle, also exerts a beneficial effect histologically and biochemically. Such treatment decreased both the glucose 6-phosphate dehydrogenase and the 6-phosphogluconolactonase activities in the synovial lining cells of the challenged joints towards values found in the unchallenged joints; it had only equivocal effects on the 6-phosphogluconate dehydrogenase activity. The results indicated that the epoxide might be interfering primarily with the lactonase activity.

Animals↗
PubMed1990

Amelioration by menadione of the experimental chronic immune arthritis in the rabbit.

The immunological induction of arthritis in the knee of the rabbit is well established as a model for human rheumatoid arthritis. It has the special advantage of allowing the development of the condition, and the effect of disease-modifying agents, to be followed. Attention has been focussed on the activity of glucose 6-phosphate dehydrogenase in the synovial lining cells since the fourfold elevation of this activity was shown to be fundamental in the human condition. An equal elevation of this activity has now been demonstrated in the rabbit model. Furthermore, it has been shown that the oral administration of menadione decreases this activity towards normality with a concomitant decrease in the degree of inflammation.

Animals↗
PubMed1989

Differences in smoking cessation strategies between men and women.

This descriptive research was designed to identify differences in smoking cessation strategies between men and women in a cross-sectional population sample of current smokers in the upper Midwest. Data on the number of previous quit attempts, the success and persistence in quit attempts, future intentions to change smoking habits, and strategies planned for cessation were obtained from 1669 smokers. Log-linear analyses controlling for age and the number of cigarettes smoked revealed significant gender differences. Men and women appear to approach smoking cessation differently. Women were more tentative and less committed to quitting smoking entirely. Women were also less successful in sustaining smoking cessation attempts for longer than one week. Efficacy expectations and differential attributions for failure were suggested as possible explanations for the results, however further research will be necessary to confirm or disconfirm these hypotheses.

Adult↗
PubMed1987

The reactivity of various free radicals with hyaluronic acid: steady-state and pulse radiolysis studies.

The reactions of the primary water radicals with the biopolymer hyaluronic acid have been studied by pulse radiolysis. Bimolecular rate constants, expressed in terms of the disaccharide repeating sub-unit of hyaluronic acid, for OH., H. and eaq- were found to be 7 X 10(8) M-1 X s-1, 5 X 10(7) M-1 X s-1 and less than 5 X 10(6) M-1 X s-1, respectively. By comparing the viscosities of samples, gamma-irradiated in the steady state under a variety of conditions, with unirradiated controls, the efficiencies with which selected radicals cause chain breakage have been determined. Efficiencies of 30%, 15%, 0%, 0.2% and 5% were estimated for OH., H., eaq-, methanol radicals and tert-butanol radicals, respectively. The presence of oxygen during irradiation increased the extent of chain breakage by a factor of 1.75.

Electrons↗
PubMed1986

Type A behavior in children: demographic, behavioral, and physiological correlates.

This article provides descriptive data on the Type A behavior pattern from an urban, biracial sample of 8 to 10-year-old children from Minneapolis. Type A behavior was assessed using the Matthews Youth Test for Health (MYTH). High MYTH scores were more prevalent in males relative to females and in black males relative to white males. Parent self-reports suggested that Type A children were more outgoing, talkative, and physically active than Type B children; they were more aggressive in their interactions with others and were more likely to experience a greater number of aversive significant life events than Type B children. No differences in resting heart rate, diastolic or systolic blood pressures were found between Type A and Type B children; there were no differences on measures of the family environment. These results provide additional evidence for the construct validity of the MYTH and offer new information on the correlates of Type A behavior in children.

Blood Pressure↗
PubMed1985

Cardiovascular responses in type A children during a cognitive challenge.

The few studies which have examined stress-induced cardiovascular reactivity among Type A children have had equivocal results. In the present study, 41 extreme Type A and 46 extreme Type B children were monitored for heart rate and blood pressure during a challenging cognitive task under clear or ambiguous performance standards. Significant heart-rate and blood-pressure responses were observed, but no effects could be attributed to the behavior pattern or performance standards. Type A's were more self-involved, generally attributing their performance to effort. Under ambiguous performance standards, they perceived themselves more negatively and attributed performance to luck and task difficulty. These results do not support the exaggerated cardiovascular response hypothesis but do suggest that Type A children look toward external cues in the evaluation of both themselves and their performance, particularly when the external standards for performance are ambiguous.

Achievement↗
PubMedDate not supplied

Aortic valvuloplasty: potential nursing diagnoses.

The use of transluminal balloon angioplasty has become widespread in the treatment of cardiovascular diseases. Since critical care nurses are responsible for the assessment and management after the procedure in the critical care unit, the authors provide information on the pathophysiology and potential nursing diagnoses for these patients. In this way, the critical care nurse can support the patient before, during, and after the procedure.

Aged↗
PubMedDate not supplied

The shape up challenge: a community-based worksite exercise competition.

PURPOSE: To assess organizational and employee participation during three community-wide worksite exercise competitions in two communities. DESIGN: A one-group, posttest-only design was used. Lack of controls, exercise baseline, and the short-term nature of the interventions were limitations. SETTING: The Minnesota Heart Health Program conducted annual exercise campaigns between 1982 and 1989 within three intervention communities to reduce behavioral risk for cardiovascular disease. The Shape Up Challenge was a worksite exercise competition designed, in conjunction with other campaign activities, to increase levels of physical activity. SUBJECTS: A total of 119 participating companies in two Minnesota communities, and 17,626 employees within these worksites, composed the subjects in this study. INTERVENTION: Eligible worksites were invited to participate in a month-long competition during which employees recorded minutes spent daily in aerobic activities. Incentives were established to promote intragroup cooperation and intergroup competition. Companies competed for awards that were based on average minutes of exercise per employee versus per participant. MEASURES: Numbers of companies recruited and participating, campaign activities, minutes of exercise, and costs were recorded on implementation logs. Companies completed surveys describing business type, number and sex of employees, existing health promotion programs, and perceived benefits of participation. RESULTS: Of the 365 companies invited to participate, 33% participated (range 15% to 50%). Participating companies were more likely than nonparticipating companies to offer other health promotion programs and perceived greater benefits from participation. Women and smaller companies had significantly greater participation rates than men and larger companies. Average employee participation rates ranged from as high as 84% in smaller organizations to as low as 16% as organization size increased. CONCLUSIONS: Community-based worksite exercise competitions appear to be a viable strategy for promoting employee exercise, particularly in smaller companies. Group-based contingencies applied in natural work units may facilitate employee participation. Further research is needed to assess the relative efficacy of this approach, compare alternative incentives, and identify strategies to enhance exercise maintenance after the intervention has ceased.

Chi-Square Distribution↗