Chinese hamster ovary cell adhesion to human platelet thrombospondin is dependent on cell surface heparan sulfate proteoglycan.

Thrombospondin is a 420-kD platelet alpha-granule glycoprotein that binds specifically to heparin. We examined adhesion to thrombospondin of CHO K1 cells and three mutant CHO lines with varying deficiencies in glycosaminoglycan (GAG) synthesis. In an experiment in which the parent line (K1) had 78% adherence to thrombospondin adsorbed to tissue culture plastic, CHO S745 cells, with less than 6% normal GAG synthesis had 11% adherence. CHO S677 cells, with decreased heparan sulfate proteoglycan but increased chondroitin sulfate proteoglycan, had 42% adherence. CHO S803 cells, with decreased heparan sulfate proteoglycan and normal chondroitin sulfate proteoglycan, had 31% adherence. Heparin inhibited K1 cell adhesion to thrombospondin, but not fibronectin, in a concentration-dependent manner. Dermatan sulfate but not chondroitin sulfate was also inhibitory. There was markedly decreased K1 cell adhesion to a thrombospondin core fragment that lacked the heparin binding NH2-terminal domain. Purified heparin binding domain, although poorly adhesive when adsorbed to substratum, inhibited cell adhesion to intact thrombospondin. Adhesion was better for all cell lines tested, including three human tumor cell lines, when thrombospondin was adsorbed at pH 4.0 compared with pH 7.4. When adsorption of thrombospondin was done at pH 7.4, cell adhesion was better when thrombospondin was adsorbed in the presence of greater than or equal to 0.6 mM calcium, compared to 0.1 mM calcium or EDTA. These findings suggest that thrombospondin can adsorb to plastic with varying degrees of exposure of a cell adhesion domain. We conclude that the thrombospondin cell adhesion receptor on CHO cells is a heparan sulfate proteoglycan, and that cell adhesion to thrombospondin depends on conformation of adsorbed thrombospondin.     

Patients' perceived problems with hypertension and attitudes towards medical treatment.

OBJECTIVE: To study perceived problems and attitudes in hypertension treatment in primary health care. STUDY POPULATION AND METHODS: A cross-sectional survey of 2219 hypertensive patients, identified by general practitioners, in 26 health centres was carried out during 1 week in 1996. A total of 1782 patients (80%) returned two questionnaires and participated in a health examination. The final study population consisted of 1561 patients currently being medically treated for hypertension and 220 patients not currently on medical treatment. The questionnaires contained 82 questions on different aspects of hypertension care and treatment, which were further elaborated using factor analysis. On the basis of reliability and internal validity analyses, 14 problem indices related to medical treatment of hypertension were formed. RESULTS: The most common perceived problem was related to lack of motivation for follow-up of hypertension (72%). Many patients had difficulties to accept being hypertensive (66%). A careless attitude towards hypertension was also common (63%). Lack of information was experienced by 56% of the patients. About 33% felt hopeless about their hypertension, reported adverse effects of hypertension treatment on sexual functions and lack of support by health care personnel. The least frequent problems were reimbursement problems and modification of dosage instructions. The number of problems identified per person varied between zero and 14 with a mean of 4.9 +/- 2.6 (s.d.). CONCLUSION: Perceived problems concerning hypertension, negative attitudes and experiences are very common among hypertensive patients in primary health care.     

Early sequential changes in serum markers of acute pancreatitis induced by endoscopic retrograde cholangiopancreatography.

BACKGROUND/AIMS: Trypsinogen activation is thought to play a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize the very early sequential changes of trypsinogen-1, trypsinogen-2, the trypsin-2-alpha1-antitrypsin complex (T2-AAT), and pancreatic secretory trypsin inhibitor (PSTI) in serum from patients with pancreatitis induced by endoscopic retrograde cholangiopancreatography (ERCP), a model for studying the early phase of the disease in humans. PATIENTS AND METHODS: The study population consisted of 659 consecutive patients with 897 ERCP procedures. Blood samples were obtained before and at different time points after the procedure. The serum concentrations of trypsinogen-1 and trypsinogen-2, PSTI and T2-AAT were determined by time-resolved immunofluorometric assays. RESULTS: ERCP-induced pancreatitis developed after 50 of the 897 ERCP procedures (5.6%). Sixty-one randomly selected ERCP patients without post-ERCP pancreatitis served as controls. Trypsinogen-1 and trypsinogen-2 showed an equally steep increase during the two first hours after ERCP in patients developing AP, but trypsinogen-1 decreased more rapidly than trypsinogen-2, which remained elevated during the 5-day study period. Serum PSTI also increased rapidly whereas T2-AAT increased more slowly peaking at 24 h. In patients developing post-ERCP pancreatitis the median concentration of trypsinogen-1 was markedly higher than in the controls already before the ERCP procedure. In the control group the concentrations of trypsinogen-1, trypsinogen-2, PSTI and T2-AAT did not change significantly. CONCLUSIONS: The rapid increase of trypsinogen-1 and trypsinogen-2 and PSTI in the early phase of AP suggests that release of pancreatic enzymes is the initial event while the delayed increase of T2-AAT may reflect that the capacity of the intrapancreatic PSTI-based inhibitory mechanism has been exhausted.     

Methodological variation in systolic time intervals

Summary. Systolic time intervals (STI) were recorded six times in 12 male students. All 72 recordings were measured twice by a physician and once by two nurses. By comparing these measurements an intra- and interobserver (= methodological) variation was obtained. For measured parameters (QS₂- interval and LVET) variation was less than 2%. For calculated parameters the variation was larger, but did not reach the level of statistical significance. Methodological variation was smaller than physiologic variation. The internal consistency was almost perfect for measured parameters and only slightly worse for calculated parameters.     

Effects of a workplace physical exercise intervention on the intensity of headache and neck and shoulder symptoms and upper extremity muscular strength of office workers: a cluster randomized controlled cross-over trial

The purpose of the study was to examine the effects of a workplace physical exercise intervention on the perceived intensity of headache and the intensity of symptoms in the neck and shoulders, as well as on the extension and flexion strength of the upper extremities. The study was a cluster randomized controlled trial. The cross-over design consisted of physical exercise intervention (15 weeks) and no-intervention (15 weeks). The subjects (n=53) were office workers (mean age 46.6 (SD 8.4)) who reported headache (n=41) symptoms in the neck (n=37) or shoulders (n=41), which had restricted their daily activities during the last 12 months. Pain symptoms were measured using the Borg CR10 scale and muscular strength with a 5RM test. Statistical analyses were based on linear mixed models. Physical exercise intervention resulted in a slight, but statistically significant, decrease in the intensity of headache and neck symptoms, as well as an increase in the extension strength of the upper extremities. The mean decrease in headache during the 5-week period was 0.64 CR10 (95% CI 0.28-1.00) (P=0.001) or 49% (95% CI 22-77), and 0.42 CR10 (95% CI 0.11-0.72) (P=0.002) or 49% (95% CI 13-85) in the intensity of neck symptoms. The mean increase in the extension strength of the upper extremities was 1.3 kg (95% CI 0.5-2.1) (P=0.001) or 4% (95% CI 1-6). The intervention had no effect on the intensity of shoulder symptoms or the flexion strength of the upper extremities. Specific exercise may be clinically important to alleviate headache and neck symptoms.     

The role of genetics and environment in lifting force and isometric trunk extensor endurance

BACKGROUND AND PURPOSE: Our understanding of what different back performance tests are measuring is limited. The purpose of this study was to investigate the relative contributions of genetics and unique and common environmental factors for 3 tests of back muscle performance in a classic twin analysis. SUBJECTS: The subjects were a population-based sample of 122 monozygotic and 131 dizygotic male twin pairs aged 35 to 69 years (mean=49.9, SD=7.7). METHODS: Variance component analysis was applied to estimate genetic and environmental influences on isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. The Cholesky decomposition genetic factor model was used to estimate genetic and environmental correlations of these variables. Path analysis was applied to study determinants of isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. RESULTS: Genetic effects accounted for 60%, 33%, and 5% of the total variance of isokinetic and psychophysical lifting forces and isometric trunk extensor endurance, respectively, and unique environmental factors accounted for 35%, 49%, and 61% of the variance. DISCUSSION AND CONCLUSION: Genetics had a dominant role in isokinetic lifting and unique environmental factors in isometric trunk extensor endurance. The relatively high role of genetics in lifting force suggests the potential to increase and sustain changes in back muscle force in the general population may be particularly challenging.     

The roles of adulthood behavioural factors and familial influences in bone density among men

BACKGROUND: A primary strategy in osteoporosis prevention is advice on exercise, smoking, and calcium intake, although its practical value is unclear. AIM: To investigate the roles of such factors on bone density (BMD) after considering the influences of familial aggregation (combined effects of genetics and familial influences) in Finnish men 35-69 years old. METHODS: We selected 105 male monozygotic twin pairs, with discordance in suspected determinants. RESULTS: Dietary calcium was associated with BMD of the femoral neck; and body weight and lifetime frequency of endurance and ball game sport activities were associated with both femoral neck and lumbar BMD. Occupational loading and smoking were associated with neither. However, age and familial aggregation explained 73% of the variance of BMD in both the femoral neck and lumbar spine; calcium intake explained 1% in femoral neck and lifetime exercise 1% in lumbar spine. CONCLUSIONS: The effects of dietary calcium and physical activity that are not 'embedded' in the familial influences had very modest effects on the variance of BMD. Thus our chances of influencing BMD in later adulthood by targeting behavioural habits are likely to be limited. Interventions focused on childhood and the family unit may achieve more beneficial long-term results.     

Gestational diabetic patients with adequate management have normal cardiovascular autonomic regulation during the third trimester of pregnancy and 3 months after delivery

ObjectiveThe aim of the present study was to evaluate the influence of gestational diabetes mellitus (GDM) on hemodynamics and cardiovascular autonomic regulation at rest and their responses to head-up tilt (HUT).Research Design and MethodsWe prospectively studied 79 pregnant women (51 with GDM, 28 without GDM) during the third trimester of pregnancy and after parturition. The maternal electrocardiogram and arterial blood pressure were noninvasively measured. Heart rate and blood pressure were measured in the supine position and in the upright position. Stroke volume was assessed from noninvasive blood pressure signals, heart rate variability (HRV) was analyzed in frequency domain, and baroreflex sensitivity by the cross-spectral and sequence methods.ResultsBetween the GDM group and control pregnant women there were no significant differences in hemodynamics and cardiovascular autonomic regulation throughout the protocol. Increased normalized low-frequency component and low-frequency to high-frequency ratio suggested a change in sympathovagal balance towards sympathetic predominance during pregnancy in both groups. The response to head-up tilt (HUT) was similar in both GDM and control pregnant women. The pregnancy modulated the response to HUT in systolic and diastolic blood pressure, stroke volume, cardiac index, peripheral resistance, total power of HRV, and its low- and high-frequency components.ConclusionsOur results suggest that pregnancy modulates cardiovascular autonomic regulation and hemodynamics equally in subjects with GDM and without GDM, suggesting that metabolic disorder during pregnancy does not result in cardiovascular dysfunction when GDM is in good balance.