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Biomedical subjects

M Maier

Publications and source records attributed to M Maier.

At least 163 records · Page 9Linked to original sources
PubMed1987

[Measuring compartment pressure of the lower leg with a microtip probe].

In the acute compartment syndrome it is difficult to decide on the basis of clinical criteria alone whether or not fasciotomy is indicated. Reliable and objective parameters are required before a treatment schedule can be devised. Measurement of the pressure inside the acute compartment can facilitate the decision as to whether operative treatment is appropriate in the case of the muscular compartment involved. We performed compartment pressure measurements in the tibialis anterior compartment in 27 healthy volunteers using a microtip probe. Clinically relevant results were obtained. It was demonstrated that this method could be used either in acute cases or for long-time measurements. We think that using a microtip probe for intracompartmental pressure measurement provides reliable data and makes the decision on fasciotomy much easier.

Anterior Compartment Syndrome↗
PubMed1986

Interaction of human low molecular weight kininogen with human mast cell tryptase.

The capacity of purified tryptase, the major neutral tryptic protease of human lung mast cells, to serve as a kininogenase was examined with purified human low molecular weight kininogen (LMWK) as the substrate. Incubating of 25 mug of tryptase with LMWK for 2 to 30 minutes, with or without heparin, yielded no net time-dependent kinin release as determined on the estrous rat uterus. The 0.4 mug of kinin seen represented less than 10% of that released from excess LMWK by 5 mug of human urinary kallikrein in 5 min. Incubation at pH 5.5 with or without heparin did not significantly alter this result. LMWK did not appear by SDS-PAGE to be cleaved by tryptase either in the presence or absence of heparin. In contrast to its action on HMWK, tryptase did not extensively cleave LMWK, or destroy its reactivity with kallikrein.

Heparin↗
PubMed1986

Urinary kallikrein excretion in healthy young infants.

Nineteen healthy hospitalized children aged between 3 weeks and 10 years and 20 others aged between one month and 16 years have been investigated for their excretion rate of active and total urinary kallikrein. Twelve hour urine samples were obtained between 7 p.m. and 7 a.m. and blood was drawn at the end of the urine collection period. Urinary kallikrein activity was measured by a synthetic substrate and a direct RIA and urinary sodium excretion, urine volume and plasma renin activity (PRA) were determined. Urinary kallikrein activity was found to be between 0 and 6 micrograms/24h and constituted approximately 10-20% of total kallikrein. When urinary kallikrein excretion rate was correlated with the sodium excretion rate the relationship was found to be positive and significant as was the correlation found between urine volume and urinary kallikrein excretion rate. No correlation could be found between PRA and urinary kallikrein excretion. Although a tendency of higher total kallikrein excretion was seen in older children, the amount excreted from all children per kilogram body weight was constant at 0.8 microgram/kg.

Child↗
PubMed1986

Urinary kallikrein excretion during inhibition of endogenous angiotensin II in the pig.

This study was performed to assess the possible contribution of endogenous angiotensin II (AII) to the regulation of urinary kallikrein excretion. The AII antagonist saralasin or the saline vehicle was infused into the aorta above the renal arteries of pigs under halothane-O2/N2O anaesthesia. Systemic and renal functional parameters were followed for 140 min and during stimulation of the reninangiotensin system by haemorrhage. Urinary kallikrein excretion, determined as kininogenase activity, was increased immediately upon both initiation and termination of the 2 h saralasin infusion into pigs not subjected to haemorrhage. Renal cortical blood flow (RCBF) was maintained, in both saline and saralasin-treated animals at blood pressures as low as 70 mm Hg, while glomerular filtration rate was dissociated during saralasin infusion. As long as RCBF was maintained, urinary kallikrein excretion rate was elevated during the progressive hypotension in both saline and saralasin-treated animals. These findings confirm a close relationship between the maintenance of RCBF and increased activity of the kallikrein-kinin system whether or not AII is antagonized, and indicate that during haemorrhage the kallikrein-kinin system is stimulated by a mechanism not involving AII.

Angiotensin II↗
PubMed1985

Osmotica, dimethyl sulfoxide, parahydroxymercuribenzoate, and cyanide change the period of the circadian clock in the pulvini of Phaseolus coccineus L.

Several substances change the period length of the circadian oscillator in the laminar pulvinus of Phaseolus coccineus L. if offered continuously via the transpiration stream to the isolated leaves in continuous light and constant temperature. The osmotica mannitol and PEG 6000 (polyethylene glycol) lengthen the circadian period from 27.9 hr (control) to about 29.5 hr. The dose-response of both substances reveal saturation curves. DMSO (dimethyl sulfoxide) lengthens the circadian period much more strongly than the osmotica. The dose-response curve reflects a curvilinear dependence of the period length from the DMSO concentration. PHMB (p-hydroxymercuribenzoate) and NaCN shorten the circadian period. The dose-response curve for PHMB is a saturation curve; saturation is reached at 80 microM PHMB with a period length of about 25.7 hr. We conclude from these results that the period of the circadian oscillator in the Phaseolus pulvinus is not directly homeostatically regulated but influenced by the intracellular milieu which can be changed by affecting membrane permeability, active transport systems or other regulatory systems within the cells.

Biological Clocks↗
PubMed1984

Comparison between vascular plasminogen activator activity and changes in blood flow in the renal cortex in pigs.

Patterns of vascular plasminogen activator activity (PAA) and of blood flow were compared in the renal cortex of pigs. The comparison was made in pigs with or without induction of hemorrhagic hypotension and continuous infusion of indomethacin (prostaglandin synthetase inhibitor) or saralasin (competitive inhibitor of angiotensin II). Blood flow was measured by radiolabelled microspheres. A significant decrease in the vascular PAA was observed only in saralasin treated animals (15% in not hemorrhaged pigs and 30% in the inner and 45% in the outer half of the renal cortex in hemorrhaged pigs). Changes in plasmin inhibitor activity in the renal cortex were not noted. No correlation could be seen between vascular PAA and changes in blood flow in the renal cortex or changes in the mean arterial blood pressure. The vascular fibrinolytic response to saralasin should be due to an effect of saralasin independent of the changes in blood flow induced by this agent.

Angiotensin II↗
PubMed1983

Purification of single-chain human low-molecular-weight kininogen and demonstration of its cleavage by human urinary kallikrein.

Human low-molecular-weight kininogen (LMWK) was purified to apparent physical and functional homogeneity by a six-step procedure consisting of ion-exchange chromatography, reverse ammonium sulfate gradient solubilization, hydrophobic chromatography on phenyl-Sepharose, gel filtration, and removal of contaminating proteins by their affinity for Affi-Gel blue and zinc. The recovery averaged 15.6% (n = 4). Purified LMWK presented as a single stained band on alkaline polyacrylamide gel electrophoresis which corresponded to the region of function in eluates from a duplicate gel. The apparent homogeneity was also observed in sodium dodecyl sulfate (SDS)-gel electrophoresis, where the protein presented as a single band of Mr = 65,000 without reduction and 68,000 with reduction. A mole of substrate released 0.8 mol of kinin in 5 min when cleaved by human urinary kallikrein (HUK), and 0.9 mol after 30 min. Cleavage of the single-chain LMWK released kinin from within a disulfide loop as indicated by the SDS-gel electrophoresis of reduced and unreduced kinin-free LMWK. The heavy chain exhibited an Mr = 62,000, which is similar to the Mr of the amino-terminal chain of human HMWK and is consistent with their antigenic relatedness. In contrast to the Mr = 64,000 procoagulant chain of human HMWK, the small (less than 10,000) carboxy-terminal chain of LMWK has no procoagulant activity and may serve only to protect the kinin moiety in the intact substrate.

Chemical Phenomena↗
PubMed1983

Kinetic analysis of the interaction of human tissue kallikrein with single-chain human high and low molecular weight kininogens.

Human low molecular weight kininogen (LMWK) and high molecular weight kininogen (HMWK) have been purified to apparent homogeneity as intact, single-chain molecules. When they interacted with homologous urinary kallikrein, 0.9 mol of kinin per mol of substrate was released from LMWK and 0.7 mol of kinin per mol of substrate was released from HMWK. These functionally and structurally intact substrates have been used to obtain the kinetic constants for kinin release by purified human tissue kallikreins. With human urinary kallikrein, apparent second-order rate constants (kcat/Km) of 1.46 X 105, 8.6 X 104, and 5.08 X 104 M-1.S-1 were obtained with LMWK, HMWK, and alpha-N-p-tosyl-L-arginine methyl ester (TAMe), respectively; with human pancreatic kallikrein, values of 8.7 X 103 and 7.3 X 104 M-1.S-1 were obtained with HMWK and TAMe. These values, which are comparable to those obtained for other enzyme-protein substrate interactions, indicate that LMWK is only slightly preferred to interactions, indicate that LMWK is only slightly preferred to HMWK as the natural substrate for urinary kallikrein and that HMWK as the natural substrate for urinary kallikrein and that HMWK is a somewhat better substrate for urinary kallikrein than for pancreatic kallikrein. Although the data obtained have been shown by NaDodSO4/polyacrylamide gel electrophoresis to reflect cleavage of the substrate at two points, the linear Line-weaver-Burk plots suggest that one cleavage is rate limiting. Because the plasma concentrations of both LMWK and HMWK are approximately 1/10th the Km values obtained, substrate concentration may also play a role in determining the rate at which tissue kallikreins release kinins from kininogen substrates either in the circulation or extravascularly.

Humans↗
PubMed1983

Effects of antiproteases (aprotinin and gabexate-mesilate) on the postischemic vascular response of the kidney.

Both under physiologic conditions and after short-term ischemia (1-3 min) kallikrein and locally synthesized prostaglandins contribute to control renal blood flow. In the present experiment the antiproteases aprotinin and gabexate-mesilate were administered to rabbits in an attempt to show whether the hemodynamic changes produced by 60 min of normothermic ischemia, i.e., postischemic hyperemia and reduction of vascular resistance, were equally mediated by kallikrein. Vascular responses were evaluated by determining renal cortical blood flow using radioactively labelled microspheres, by calculating vascular resistances, and by measuring the diameters of renal medullary vessles. Kidneys exposed to normothermic ischemia and sham-operated control organs of animals treated with aprotinin (2 X 40,000 KIU/kg body weight) and gabexate-mesilate (2 X 7 mg/kg body weight) were compared with those of rabbits which were analogously operated, but did not receive any drugs. As the antiproteases used did not significantly affect the hyperemia and the reduction of renal cortical vascular resistance seen after 60 min of normothermic ischemia, these phenomena are apparently not mediated by kallikrein. Renal medullary vasodilatation (arteriolae rectae) was significantly lower under aprotinin than in untreated ischemic kidneys, and was not longer demonstrable in gabexate-mesilate-treated animals. Thus, the effect of gabexate-mesilate was superior to that of aprotinin. Whether the antiprotease action is due to an unspecific membrane-stabilizing, to a general enzyme-inhibiting, or to a specific kallikrein-inhibiting effect, is still unclear.

Animals↗
PubMed1983

Effects of external renal hypothermia on postischemic hemodynamics.

In the rabbit model renal cortical blood flow after 60 min of normothermic ischemia is seen to rise significantly in the early reperfusion period. Under otherwise identical conditions this phenomenon is absent after hypothermic ischemia produced by surface cooling of the kidney and in sham-operated kidneys. It is still unclear whether postischemic hyperemia is a physiologic counterregulatory mechanism in response to 60-min normothermic ischemia of the rabbit kidney or a contributory factor in the development of acute postischemic renal failure.

Acute Kidney Injury↗
PubMed1983

Renal blood flow alterations after temporary ischemia. An experimental model in the rabbit.

In an effort to investigate the efficiency of various pharmacological agents in protecting the kidney against normothermic ischemia, an animal model was developed and the post-ischemic hemodynamics in the renal cortex of rabbit kidneys were studied. Renal cortical blood flow was evaluated 5-30 min after 60 min of normothermic ischemia of the left kidney using 141Ce-, 51Cr-, and 85Sr-labelled microspheres. Control groups were subjected to sham operation. The right kidneys served as individual controls. Ischemic kidneys showed a significant weight increase independent of reperfusion. Furthermore, a transient highly significant increase of cortical blood flow was found with an absolute maximum about 10 min after termination of ischemia. This increase in cortical blood flow was paralleled by a highly significant decrease of vascular resistance.

Animals↗
PubMed1983

Immunohistochemical localization of glandular kallikrein in the endocrine and exocrine human pancreas.

Fab fragments from two new monospecific anti-human tissue kallikrein sera were examined for their capacity to inhibit the functional activities of purified human urinary kallikrein and purified human pancreatic kallikrein. Fragments from a new anti-urinary kallikrein serum and from an anti-pancreatic kallikrein serum yielded mixed inhibition of kinin-generating activity and minimal inhibition of esterolytic activity. In contrast to the previously described "active site directed" anti-urinary kallikrein, these new antisera demonstrated little specificity for epitopes near the enzymatic site of urinary or pancreatic kallikrein. When used to localize kallikrein antigen in human pancreas obtained at surgery, IgG fractions of the new anti-kallikrein sera yielded moderate acinar and ductal staining in the absence of pretreatment of the tissue with trypsin or pronase. Short incubation with 0.125 mg/ml of either enzyme permitted the discrete localization of islet beta cell kallikrein antigen, while increased pronase concentrations decreased kallikrein antigen in both islets and exocrine tissue and led to islet destruction. Both antibody specificity and tissue preparation influence kallikrein localization in human pancreas.

Antibody Specificity↗
PubMed1983

Inactivation of human high molecular weight kininogen by human mast cell tryptase.

Tryptase, the major neutral protease of human pulmonary mast cell secretory granules, rapidly inactivates human high m.w. kininogen (HMWK) in vitro. HMWK (5600 nM) lost 50% of its capacity to release kinin in response to kallikrein after a 5-min incubation with tryptase (31 nM), even though kinin activity was neither generated nor, when bradykinin was incubated with tryptase, destroyed by tryptase. The procoagulant activity of HMWK (51 nM) and the purified procoagulant chain (40 nM) that is derived from HMWK were each 72% inactivated after 7 min of incubation with tryptase (0.04 nM and 0.02 nM, respectively). Human urinary and pancreatic kallikrein did not inactivate this procoagulant activity under conditions in which kinin generation occurs. Complete cleavage of native single-chain HMWK by tryptase occurred in less than 10 min as analyzed by electrophoresis in sodium dodecyl sulfate polyacrylamide slab gels. The major products formed during the initial 2 min were proteins of 100,000 and 95,000 apparent m.w., and by 10 to 30 min were fragments of 74,000 and 67,000 apparent m.w. Reduction of these cleavage products yielded two major fragments of 67,000 and 66,000 apparent m.w. that were both present by 0.17 min. The presence of lower m.w. products, thought to be primarily from the carboxy-terminal procoagulant region of HMWK, were also detected with and without reduction. The capacity of tryptase to inactivate HMWK is consistent with the ability of other mast cell-derived mediators, such as heparin proteoglycan and prostaglandin D2, to suppress blood coagulation and thrombosis, and may play an important role in the biology of mast cell-dependent events in vivo.

Blood Coagulation↗
PubMed1983

Characterization of the procoagulant chain derived from human high molecular weight kininogen (Fitzgerald factor) by human tissue kallikrein.

Human high molecular weight kininogen (HMWK), a single-chain protein with mol wt 120,000, is cleaved by human urinary kallikrein (HUK) to release kinin from within a disulfide loop and form a two-chain protein that retains all the procoagulant activity of the native molecule. Cleavage of HMWK by HUK is associated with a reduction in size to mol wt 115,000, as assessed by SDS-PAGE of unreduced protein, whereas the two chains of the reduced protein present together as a single broad band with mol wt 64,000. The 64,000 chain with procoagulant activity was chromatographically separated from the nonfunctional chain of similar size. The homogeneous procoagulant chain had an amino acid composition similar to that of smaller procoagulant ("light") chains isolated by others upon cleavage of HMWK with plasma kallikrein and elicited an antiserum that was monospecific by Ouchterlony analysis and inhibited the procoagulant function of HMWK. Thus, the limited proteolysis of HMWK by HUK has permitted, for the first time, the isolation of a stable procoagulant chain that is equal in size to the nonfunctional chain. The common terminology of "heavy" and "light" chain for kinin-free kininogen obtained with plasma kallikrein reflects the continued degradation of the procoagulant carboxyterminal chain and is not appropriate for the initial two-chain product formed when kinin is released from HMWK. It is proposed that the initial cleavage products of HMWK be designated the A-chain, the B-fragment, and the C-chain, representing the amino-terminal chain, the released vasoactive peptide containing the bradykinin sequence, and the carboxy-terminal procoagulant chain, respectively. Thus, intact HMWK would contain, in sequence, A, B, and C regions.

Amino Acids↗