Clinical science and molecular medicine最新文献

1. The properties of inactive and active renin in human plasma and amniotic fluid were studied chromatographically. Activation was achieved at pH 3.3 with and without added pepsin. 2. Acid activation of renin was time- and temperature-dependent but was inhibited by dilution of the sample. The dilution effect was corrected by adding pepsin. Such characteristics indicate that activation at low pH is catalysed by intrinsic enzymes. 3. Separation and/or dilution of the activating enzyme during ion-exchange chromatography concealed the eluted position of inactive renin and reduced the amount recovered. Only after full activation of the eluted renin was achieved with added pepsin was a distinct peak of inactive renin exposed. 4. At pH 7.5 inactive renin carried a lower negative charge than the active enzyme. This charge difference was lost after activation. 5. No molecular-weight differences between active, inactive renin or the International Renin Standard were detected by gel filtration. No renin of larger molecular weight was present. 6. These findings will be helpful in purification studies of human inactive renin.

1. Renin release from isolated dog renin granules was limited to within 20% of the total renin during incubation at 37 degrees C in isotonic medium and did not depend on the external concentration of renin. 2. Although the renin granules were osmotically and mechanically fragile, they were quite stable at 0 degrees C in isotonic medium. 3. The bulk of renin activity appeared in the supernatant when the granules were ruptured by osmotic lysis. About 8% of the total renin still remained in the membrane fraction of the granules after treatment by freezing and thawing. 4. Therefore stored renin in the granules can be described as comprising three components: a readily released soluble form; a soluble but hard-to-release form; a membrane-bound form.

1. Filters comprising multiple layers of rabbit renal tubular basement membrane were constructed with conventional pressure filtration chambers. The effects of concentration-polarization on the behaviour of these filters was assessed by studying the filtration of proteins and of serum under turbulent (stirred) and unstirred conditions. 2. With stirring bovine serum albumin was effectively rejected by the filter barriers (sigma = 0.95) but rejection was diminished (sigma = 0.18) without stirring. The hydraulic permeability of the filters also fell without stirring. 3. In the presence of horse immunoglobulin G, a wholly rejected protein, the rejection of cytochrome c was increased and hydraulic flux was reduced. 4. Filtration studies of serum showed that serum protein was effectively rejected with stirring (sigma greater than 0.999) but rejection diminished when stirring ceased (sigma = 0.98). Albumin was the only protein detected in the filtrate with stirring but alpha- and beta- globulins appeared when stirring ceased. 5. These results show that concentration-polarization markedly affects the behaviour of these basement membrane filters in vitro, since without stirring a polarization layer of rejected protein is formed, which reduces hydraulic permeability and results in increased protein permeation through the filter.

1. Intravenous doses of bilirubin (3.4 mumol/kg) were given to normal subjects and patients with Gilbert's syndrome. Both groups displayed an identical initial disappearance of a substantial proportion of the bilirubin but, late in time, the Gilbert's patients exhibited reduced clearance with a sustained elevation of the plasma bilirubin and no reflux into the plasma space of conjugated bilirubin. Increasing the dose in normal subjects (by factors of 3 and 6) failed to reproduce the response found in the Gilbert's patients. 2. In the the bile-containing duodenal aspirates of Gilbert's patients the average proportion of bilirubin found as bilirubin diglucuronide was 68% (normal 88%) and of bilirubin monoglucuronide, 23% (normal 7%). Both differences were significant at the P less than 0.001 level. In the Gilbert's patients restriction of caloric intake to 1569 kJ/day for 2 days characteristically raised the serum bilirbuin with no modification of the biliary pigment pattern; phenobarbital (180 mg/day for 2 weeks) decreased the plasma bilirubin to the normal range with, concomitantly, a reversion of the biliary pigment pattern towards normal. 3. We conclude that there is no hepatic uptake defect in Gilbert's syndrome but that there is decreased activity in the conjugation process underlying the addition of the second glucuronic acid moiety to bilirubin, to form bilirubin diglucuronide.

1. We have measured muscle blood flow by a 133Xe clearance technique, and its response to noradrenaline in baboons before and 2 weeks after ligation of the bile ducts when they were jaundiced. 2. In the normal baboons, the response to noradrenaline was a dose-dependent decrease in muscle blood flow. 3. Bile-duct ligation caused no significant alteration in skeletal muscle blood flow but the response to noradrenaline in the jaundiced baboons was significantly attenuated. This effect was not observed in four sham-operated baboons.

1. The cerebral depressant effect of 30 ml of aqueous ethanol diluted to 25% and administered orally to 16 volunteer subjects was compared with a control group of 15 volunteer subjects. 2. The two parallel forms of the Watson--Glaser Critical Thinking Appraisal tests were employed as a measure of cerebral function. 3. The control group showed a small but statistically insignificant improvement on retesting with Watson--Glaser test form ZM after preliminary administration of form YM. 4. The relationship between the blood alcohol time curve and the alcohol effect was analysed for each individual subject, each subject being used as his own control. 5. The main peak cerebral depressant effect was substantial and occurred on average 25.5 min before the attainment of the peak blood alcohol concentration. 6. There was no significant correlation between blood alcohol concentration and contemporaneous cerebral impairment (r = -0.01). 7. There was a highly significant correlation (r = 0.60) between the effect upon cerebral function and the gradient of the blood alcohol curve at that time.

1. Normal synovial membrane contains approximately equal proportions of two genetically distinct forms of collagen, types I and III. The proportion of these two collagens is unchanged in rheumatoid synovium but in addition a small amount of basement membrane collagen is present. Tissue culture of rheumatoid synovium confirms the synthesis of both type I and III collagens. 2. In young normal synovium both type I and type III collagens are stabilized by a reducible keto cross-link, which is replaced in adult tissue by an as yet unknown non-reducible cross-link. During the proliferation of the collagen in adult rheumatoid synovium a high proportion of the keto cross-link is present. This cross-link is not susceptible to cleavage by D-penicillamine, nor does the drug have any effect on the rate of synthesis in vitro. The mode of action of D-penicillamine in rheumatoid arthritis does not appear to involve a direct effect on the synovial membrane collagen.

1. Data have been combined from three previous series to provide revised standards for the prediction of physiological dead-space volume (VD), arterial oxygen tension (Pa,O2), alveolar-to-arterial oxygen-tension difference (PAO2--Pa,O2) and venous admixture fraction (QVa/Qt) in the sitting position. 2. These standards, based on measurements in 96 healthy men and women aged from 20 to 74 years, largely confirm conclusions drawn from the first series of 48 subjects. 3. VD is best predicted on age, height, tidal volume and the reciprocal of respiratory frequency. Pa,O2,(PA,O2--Pa,O2) and Qva/Qt are adequately predicted on age alone.

1. Human alpha1-antitrypsin was isolated with preserved microheterogeneity from subjects of Pi types M, S and MMalton. The M-protein was partially (20%) and completely desialylated. The proteins were labelled with either 125I or 131I. 2. The disappearance rate of these alpha1-antitrypsins was studied after simultaneous injection of the two types of labelled protein into Pi M subjects. The fractional catabolic rates of S- and MMalton-protein were 0.36 and 0.34 day(-1) respectively compared with 0.28 day(-1) for M-protein. The ratio of extravascular to plasma pools was 1.4 for S- protein and 1.6 for MMalton-protein. The 20% desialylated M-protein showed an increase of about 100% in its fractional catabolic rate. The disappearance rate of completely desialylated alpha1-antitrypsin was extremely rapid. 3. The slightly higher fractional catabolic rate of S- than of M-protein can only partly explain the 40% lower plasma concentration in subjects of Pi type S. Similarly the slight increase in catabolic rate of Pi MMalton- protein is too small to explain why the alpha1-antitrypsin content of the blood in Pi MMalton subjects is only 15% of that normally found. A low hepatic secretion seems to be the major cause of the low alpha1-antitrypsin concentration found in subjects of types Pi S and MMalton, as in Pi type Z.