Pancreatic stellate cells mediate fibrosis in chronic pancreatitis. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)-1 and -2 are crucial modulators of fibrosis. Transforming growth factor-beta (TGF-beta) is a key regulator of extracellular matrix production and myofibroblast proliferation. We have examined MMP and TIMP synthesis by transformed cultured pancreatic stellate cells and their regulation by TGF-beta 1. By Northern analysis they expressed mRNAs for procollagen 1, TIMP-1, TIMP-2, and MMP-2. Expression of membrane type-1 MMP was confirmed by Western blotting. By immunohistochemistry these enzymes localized to fibrotic areas in human chronic pancreatitis. Active TGF-beta 1 constitutes 2 to 5% of total TGF-beta 1 secreted by pancreatic stellate cells; they express TGF-beta receptors I and II. Exogenous TGF-beta 1 (10 ng/ml) significantly increased procollagen-1 mRNA by 69% and collagen protein synthesis by 34%. Similarly TGF-beta 1 at 0.1, 1, and 10 ng/ml significantly reduced cellular proliferation rate by 37%, 44%, and 44%, respectively, whereas pan-TGF-beta-neutralizing antibody increased proliferation by 40%. TGF-beta1 (10 ng/ml) down-regulated MMP-9 by 54% and MMP-3 by 34% whereas TGF-beta 1-neutralizing antibody increased MMP-9 expression by 39%. Pancreatic stellate cells express both mediators of matrix remodeling and the regulatory cytokine TGF-beta 1 that, by autocrine inhibition of MMP-3 and MMP-9, may enhance fibrogenesis by reducing collagen degradation.

A cross-sectional survey of an age- and sex-stratified random sample of the elderly population living in Southampton was undertaken with the object of measuring the frequency of cardiovascular disease by questionnaire and examination, and assessing cardiac anatomy and physiological function by noninvasive methods. The response rate was 64% and 259 men and women aged between 65 and 95 years were interviewed and examined and had a twelve-lead ECG and chest radiograph. Forty per cent of men and 47% of women reported a diagnosis of one or more cardiovascular diseases, of which high blood pressure 33%, coronary heart disease 14% (angina pectoris 11% and myocardial infarction 8%), peripheral arterial disease of the lower limbs 7%, and cerebrovascular disease 6% occurred most frequently. With the exception of high blood pressure, which women reported more frequently than men (40% vs 27%), the prevalence of these diagnoses by sex was similar. The self-administered WHO questionnaires gave point prevalence estimates for angina pectoris of 13%, possible myocardial infarction 7% and intermittent claudication 5%, which were similar to reported prevalences of these diseases, although disagreement in the classification of individuals for each disease was common. When comparing the WHO chest pain questionnaire with the doctors' independent diagnosis of angina pectoris in this population, the sensitivity of the WHO questionnaire was 79%, with a specificity of 98% and a predictive value of 88%. For each sex the sensitivity of the WHO chest pain questionnaire was similar but specificity and predictive value were both lower for women.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid artery massage was carried out in a cross-section of 95 healthy elderly subjects (51 men and 44 women, mean age of 74 years) to assess the heart rate response and associated symptoms. These subjects were drawn from a larger group of randomly selected healthy elderly people living in Southampton. They had no history of myocardial infarction or stroke and were not taking any drugs that might enhance the carotid sinus reflex. A continuous distribution of response to carotid artery massage was seen with a median percent change in RR interval of 11.6% (IQR 22.9%); 66% had a percent change in RR interval of < 20%, 90% had a change of < 50%, and 9.5% a change of > 100%. Carotid sinus hypersensitivity (sinus arrest > 3 s) was found in 4 previously asymptomatic subjects; a prevalence of 4.2% (95% CI 1.2%-10.4%), and this was associated with dizziness in 2 of these 4 subjects. Dizziness also occurred in one other subject who had a change in RR interval of 178%. The definition of an abnormal carotid sinus reflex is arbitrary given the continuous RR interval response to carotid artery massage. In diagnosing carotid sinus syndrome, the RR interval response to carotid artery massage alone is not sufficient, as this maneuver must also reproduce the patient's presenting symptoms.