Proteoglycans of CAPD-dialysate fluid and mesothelium.
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Biomedical subjects
Publications and source records attributed to M Davies.
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The reproduction of symptoms on arthrography of the lumbar facet joint has been accepted as a screening procedure before localised spinal fusion. We studied the histology of 127 facet joints removed at operation from 84 patients, who had previously had facet arthrography. The specificity of the arthrographic results for degenerative joint disease was 75% but their sensitivity was only 59%. This gave a positive predictive value of 85%, but a negative predictive value of only 43%. We conclude that the production of symptoms during facet arthrography is of little value as a screening procedure.
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Relationships between changes in weight and blood lipids were examined in 655 subjects who had enrolled for a fitness programme. At entry data were obtained on weight, fitness, lipids, physical activity, diet, and smoking. On re-examination 2 years later approximately half the sample had maintained stable weight (+/- 2 kg), a quarter had lost (- greater than 2 kg), and a quarter had gained weight (+ greater than 2 kg). Analyses of weight change/lipid change relationships included comparisons of lipid changes in weight 'stable', 'losers', and 'gainers' groups, and multiple regression analyses controlling for the effects of age, diet, and fitness. It was found that changes in weight and lipids were significantly related, the relationship was stronger than between any other independent variable and changes in lipids, and it was stronger for men than for women. It was concluded that there is an independent cause and effect relationship between weight and lipids to an extent useful for clinical and public health purposes.
A chemiluminescence immunoassay has been developed for the measurement of albumin concentrations in human urine, as an indicator of diabetic nephropathy. The assay involved competition between analyte albumin and an acridinium ester labelled albumin tracer for binding to a rabbit (anti-human albumin) antibody. Immune complexes were separated using sheep (anti-rabbit immunoglobulin G) antibodies coupled to paramagnetic particles. The total incubation time was ninety minutes at room temperature followed by sedimentation and washing of the solid-phase using a magnetic rack. Chemiluminescence emission was quantified rapidly (2 s) using a commercially available luminometer. The assay was sufficiently sensitive (10 ng/ml) for the detection of microalbuminuria with the advantages of rapidity and use of stable reagents. The assay correlated well with both RIA and rate nephelometry.
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A study was made of the effects of stress-management courses on 595 men and women (mean age, 45 +/- 11 years) from one to seven years after they had attended such courses. The course (six 1.5-h sessions) included relaxation training, rational thinking and priority setting and assertiveness training. Evaluation comprised the Paul stress inventory of perceived stress and a questionnaire that dealt with stress and related behaviour and coping skills. The results indicated a substantial reduction in perceived stress immediately after the course which persisted until follow-up; satisfactory persistence in the use of learned coping skills; good reception of the course; and that decreases in perceived stress predicted changes in life-style, a reduced use of stress-related medications and an increased use of relaxation training. Extensive research, including controlled studies, on stress-management courses for Australians is recommended, as a basis for the development of courses which serve the needs of groups that differ in age, health status, occupation, education, and ethnic origin.
Many deaths from acute myocardial infarction occur before hospital admission. Provision of resuscitation by GPs, ambulance personnel and the general public has been shown to improve early mortality. The impact of thrombolysis on prognosis is also discussed.
(1) The degradation of glomerular basement membrane and some of its constituent macromolecules by human kidney lysosomal cysteine proteinases has been investigated. Three cysteine proteinases were extracted from human renal cortex and purified to apparent homogeneity. These proteinases were identified as cathepsins B, H and L principally by their specific activities towards Z-Arg-Arg-NHMec, Leu-NNap and Z-Phe-Arg-NHMec, respectively, and their Mr on SDS-polyacrylamide gel electrophoresis under reducing conditions. (2) Cathepsins B and L, at acid pH, readily hydrolysed azocasein and degraded both soluble and basement membrane type IV and V collagen, laminin and proteoglycans. Their action on the collagens was temperature-dependent, suggesting that they are only active towards denatured collagen. Cathepsin L was more active in degrading basement membrane collagens than was cathepsin B but qualitatively the action of both proteinases were similar, i.e., at below 32 degrees C the release of an Mr 400,000 hydroxyproline product which at 37 degrees C was readily hydrolysed to small peptides. (3) In contrast, cathepsin H had no action on soluble or insoluble collagens or laminin but did, however, hydrolyse the protein core of 35S-labelled glomerular heparan sulphate-rich proteoglycan. (4) Thus renal cysteine proteinases form a family of enzymes which together are capable of degrading the major macromolecules of the glomerular extracellular matrix.
The underlying pathophysiological mechanisms in heart failure provide an explanation of why drugs often fail to improve the prognosis while providing symptomatic relief. An understanding of these mechanisms should allow a more rational approach to therapy.
First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.
The metabolic turnover of rat glomerular proteoglycans in vivo was investigated. Newly synthesized proteoglycans were labeled during a 7-h period after injecting sodium [35S]sulfate intraperitoneally. At the end of the labeling period a chase dose of sodium sulfate was given. Subsequently at defined times (0-163 h) the kidneys were perfused in situ with 0.01% cetylpyridinium chloride in phosphate-buffered saline to maximize the recovery of 35S-proteoglycans. Glomeruli were isolated from the renal cortex and analyzed for 35S-proteoglycans by autoradiographic, biochemical, and immunochemical methods. Grain counting of autoradiographs revealed a complex turnover pattern of 35S-labeled macromolecules, commencing with a rapid phase followed by a slower phase. Biochemical analysis confirmed the biphasic pattern and showed that the total population of [35S]heparan sulfate proteoglycans had a metabolic half-life (t1/2) of 20 and 60 h in the early and late phases, respectively. Heparan sulfate proteoglycans accounted for 80% of total 35S-proteoglycans, the remainder being chondroitin/dermatan sulfate proteoglycans. Whole glomeruli were extracted with 4% 3-[(cholamidopropyl)dimethy-lammonio]-1-propanesulfonate-4 M guanidine hydrochloride, a procedure which solubilized greater than 95% of the 35S-labeled macromolecules. Of these 11-13% was immunoprecipitated by an antiserum against heparan sulfate proteoglycan which, in immunolocalization experiments, showed specificity for staining the basement membrane of rat glomeruli. Autoradiographic analysis showed that 18% of total radioactivity present at the end of the labeling period was associated with the glomerular basement membrane. The glomerular basement membrane [35S]heparan sulfate proteoglycans, identified by immunoprecipitation, have a very rapid turnover with an initial phase, t1/2 = 5 h, and a later phase t1/2 = 20 h.
Measurements of aerobic fitness, weight, blood pressure, and lipids were made in 1000 sedentary men and women entering a fitness programme, and were repeated 2 years later in 733 subjects. Cross-sectional analyses including (a) comparisons of CHD risk factors in subjects grouped as "low", "low/moderate", "moderate/high", and "high" fitness, and (b) multiple regression analyses of relationships between fitness and risk factors showed that fitter subjects had better risk profiles than less fit. Longitudinal analyses including (a) comparisons of risk factor changes in subjects grouped as fitness "losers", "stable", "small gain", and "large gain", and (b) multiple regression analyses of relationships between fitness change and risk factor changes showed that fitness change was largely unrelated to risk factor changes. The study supported the existence of beneficial associations between fitness and risk factors but not cause and effect relationships.
Ninety-one per cent of a county-wide high school population (N = 5596) completed the Eating Symptoms Inventory (ESI) and the Eating Attitudes Test (EAT). Being female, older and heavier are far more strongly associated with anorexic and bulimic symptoms than is social class. ESI approximations of the DSM-III criteria for anorexia nervosa or bulimia suggest that while both conditions are rare (less than 1%), bulimia is the more prevalent disorder.
The factors operative during normal and disease states which govern the degradation of the glomerular extracellular matrix (ECM, glomerular basement membrane and mesangial matrix) remain poorly understood. These structures consist primarily of types IV and V collagen, which are highly resistant to the action of classical interstitial collagenases. Here we report that an intrinsic glomerular cell type, the human mesangial cell, secretes: 1) a neutral proteinase with specific activity against type IV basement membrane collagen and, 2) an inhibitory protein with the characteristics of the tissue inhibitor of metalloproteinases (TIMP). The purified enzyme has a neutral pH optimum, consists of a basic (pI 8.4) protein doublet with molecular weight of 66 and 68 kilodaltons, and is inhibited by calcium and zinc chelators. The enzyme degrades both soluble and basement membrane type IV collagen, but does not specifically degrade types I or V collagen or casein. Immunohistochemistry of cultured cells demonstrated homogeneous staining for the neutral proteinase antigen, while the TIMP antigen was detected in fewer than one-third of cultured cells. These findings suggest that the synthesis of these proteins may be independently regulated. The secretion of these factors may play an important role in the turnover of the glomerular ECM under basal or pathologic conditions.