[Measuring the age dependent psychophysical functional status of elderly humans].
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Biomedical subjects
Publications and source records attributed to W Paul.
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In 16 CF-patients (age: 7-23 years; 7 females, 9 males) we analysed the serum concentration of uric acid after a standard meal and pancreatic enzyme supplementation by PANKREON FORTE or PANGROL 400 "neu" (both 2800-3000 U lipase/kg body mass/meal). Simultaneously we measured the uric acid excretion into the urine. We found an effective digestion and subsequent resorption of triglycerides and glucose but no significant changes of the uric acid serum levels during the 8-hours-test period. The uric acid excretion was lower than in the nocturnal period before the test. We conclude that a dangerous hyperuricemia and/or hyperuricosuria do not usually occur in pancreatic enzyme supplementation.
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A number of expression vectors have been constructed to allow over-production of selected gene products in Klebsiella pneumoniae and other enteric bacteria. The plasmids use the strong hybrid trp-lac (tac) promoter for gene expression, which is regulated by the lacIQ allele of the lac repressor carried on the vector. This provides very tight regulation of gene expression, which is important for over-production of proteins which may be detrimental to cell growth. The vectors carry the standard mp18 cloning nest in which all the restriction sites are unique to the plasmid (with the exception of EcoRI in pDK7). Derivatives were constructed carrying kanamycin, chloramphenicol or ampicillin resistance as selectable markers, the first two of which are advantageous in K. pneumoniae due to the high inherent beta-lactamase activity of this organism.
A 1.4-kb PstI-HpaI DNA fragment carrying the Klebsiella pneumoniae nifM gene has been sequenced; nifM has been shown to encode a 30.6-kDa polypeptide. Two other open-reading frames were identified upstream of nifM. The one immediately upstream of nifM encodes a 16.6-kDa polypeptide which has been identified by in vitro transcription/translation in an Escherichia coli 30,000 x g supernatant system; we propose to designate this gene nifZ. The sequence of the second open reading frame is incomplete but it does not correspond to nifV, the gene previously thought to be immediately upstream of nifM, and may therefore identify another new nif gene. Both nifM and nifZ have functional nif promoters with the characteristic-24, -12 consensus sequence, we find no evidence for a nifM upstream activator sequence. The role of nifZ in nitrogenase biosynthesis is unknown but its identification calls into question previous assertions that only nifM and nifH are required for the synthesis of nitrogenase Fe protein.
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Ten normal subjects participated in a placebo-controlled, randomized, parallel study to determine the effects on thyroid hormones of chronic (4 wk) propranolol or nadolol, including observation for 2 wk after their discontinuation. Subjects took placebo for 1 wk, then propranolol or nadolol doses increased weekly to 240 mg/day by 3 wk. After 1 wk of placebo, after 2 wk of the highest dose of propranolol or nadolol, and 2, 4, 6, 9, and 13 days after their discontinuation, thyroid hormone levels were measured by radioimmunoassay and heart rate responses to exercise were assessed. Both drugs induced equal and high degrees of exercise tachycardia inhibition. Propranolol decreased 3,3'5-triiodothyronine (T3) levels, increased 3-3'-5'-triiodothyronine (rT3) levels, tended to increase thyroxine levels, but did not increase thyroid-stimulating hormone levels. After discontinuation of propranolol, rT3 levels slowly (day 6) returned to values after placebo, suggesting delayed recovery of 5'-deiodination. There was no evidence of any rebound in T3 levels after withdrawal of propranolol. Nadolol induced no significant changes in the thyroid hormones measured. The data agree with the known effects of propranolol on thyroid hormones in normal man and show that nadolol does not have these effects when given chronically at an equivalent beta-blocking dose. The likely explanation is that the membrane-stabilizing activity of propranolol alters thyroid physiology by interfering with 5'-deiodinase.
The effect of different potassium, calcium and magnesium concentrations in the perfusate on the hormone secretion of the isolated dog pancreas was investigated. A potassium concentration above 15 mMol/l shortly stimulates the insulin and glucagon secretion. Potassium ions (greater than or equal to 15 mMol/l) completely inhibit the early phase of glucose-induced insulin release. At a low Ca2+-level (0.25 mMol/l) the glucose-stimulated insulin secretion is reduced to basal values. On the other hand, the glucagon release is stimulated under these conditions. An increase of magnesium ions from 1.0 mMol/l to 2.5-7.5 mMol/l strikingly inhibits insulin and glucagon release by approximately 50%, which is compensated for insulin by increasing the Ca2+-content of the medium. Perfusates for normothermic pancreas perfusion should contain electrolyte concentrations within the physiological range.
The ether-linked phospholipid, Paf-acether (AGEPC) is released from a variety of inflammatory cell types and has properties consistent with those of a mediator of inflammation. We have examined the effects of locally administered Paf-acether on cellular accumulation in the skin of experimental animals and man by histological evaluation of sequential skin biopsies and quantification of accumulation of radiolabelled blood elements. In guinea-pig skin, immediate extravasation of plasma protein and intravascular accumulation of platelets and neutrophils was succeeded by a persistent mixed cellular infiltrate predominantly of neutrophils but also containing lymphocytes and histiocytes. Radiolabelling studies were consistent with these observations. Intradermal Paf-acether elicited persistent clinical and histopathological responses in human skin. The finding that Paf-acether is able to initiate cutaneous cellular accumulation may be important in the pathogenesis of inflammatory dermatoses.
Cutaneous responses to synthetic platelet activating factor (Paf-acether) have been studied in guinea-pig and human skin. Intradermal injection of Paf-acether elicited an acute inflammatory response in guinea-pig skin (assessed by means of radioisotopic techniques) and acute oedema formation in human skin (assessed by means of weal volume and flare area). Acute inflammatory responses in guinea-pig and human skin are potentiated by the presence of serum albumin, a phospholipid carrier. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are slightly modified by the H1-receptor antagonists, mepyramine and chlorpheniramine. These results indicate that the acute inflammatory response induced by Paf-acether is independent of cyclo-oxygenase products of arachidonic acid and that histamine release has a minor contribution to the inflammatory response induced by Paf-acether.
PAF-acether (AGEPC) is released from a range of inflammatory cell types and has properties consistent with those of a mediator of inflammation. Intradermal injection of PAF-acether in experimental animals causes immediate extravasation of plasma protein, accompanied by intravascular accumulation of platelets and neutrophils; this is followed by persistent extravascular accumulation of neutrophils and mononuclear cells. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early (weal and flare) response is succeeded, in 60% of subjects, by a late-onset area of erythema at the site of the resolved weal, reminiscent of the dual response to allergen in sensitized individuals. The time course and dose-response relationship of the early response was determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. The weal response to PAF-acether was not inhibited by concurrent administration of chlorpheniramine. Histopathological examination of serial elliptical biopsies revealed accumulation of both neutrophils and mononuclear cells in response to intracutaneous PAF-acether. We would suggest that PAF-acether is likely to be a mediator of both acute and persistent inflammation.
For 18 years we have analysed several parameters directly or indirectly involved in immunologic functions in 713 children (age: 0-14 years) suffering from CNSRD (frequently relapsing bronchitis, chronic bronchitis, frequently relapsing or chronic obstructive bronchitis, asthma bronchiale, cystic fibrosis). In all 6,067 data were evaluated. The estimation of the immunoglobulins (in serum and secretions) and the serum level of alpha-1-antitrypsin (alpha-1-AT) had the highest relevance for diagnosis and prognosis of CNSRD. Immunodeficiencies were detected in form of humoral antibody deficiency syndromes as well as local secretory IgA deficiency (MALT insufficiency). The results suggest that the MALT-insufficiency during early childhood is a high risk factor for the development of CNSRD, especially of obstructive lung diseases. In chronic bronchitis the mean levels of serum-IgA were significantly increased (p less than 0.001) and reactively increased serum mean levels of IgM and/or IgG were observed in some chronic bronchitis forms but not during the whole childhood. In homocygote and heterocygote defective alpha-1-AT types the prognosis of chronic lung disease (chronic obstructive bronchitis and/or bronchial asthma) was especially poor. Despite BCG vaccination in the neonatal period most children had negative tuberculin skin tests. This suggests that also the cellular immunofunctions may be depressed in children with CNSRD. Blood group, isoagglutinins, Zn and Fe serum levels had only limited importance for diagnosis and prognosis of the CNSRD. We recommend the estimation of these parameters in special cases only.
In vivo platelet aggregation has been studied using a novel, minimally invasive technique. No aggregatory effects of heparin were observed on normal circulating platelets nor was there enhancement of aggregation of platelets during activation by intravenous injection of ADP, collagen, PAF acether or thrombin. On the contrary, high doses of heparin were found to inhibit platelet accumulation induced by ADP, collagen or PAF-acether. Inhibition of these responses necessitated doses of heparin in excess of those required for anti-coagulant effects. The present experiments do not establish a mechanism for such inhibition. Extension to other species, including man, is needed before attributing clinical relevance to the present observations.
Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) sulfate and glucuronide reflect, in part, central norepinephrine activity while urinary 3-methoxy-4-hydroxymandelic (VMA) reflects peripheral norepinephrine activity. Urinary MHPG and VMA were measured, together with homovanillic acid (HVA), in 20 symptomatic and seven asymptomatic postmenopausal women and 10 premenopausal control women. Urinary HVA reflects, in part, central dopamine metabolism. After nine of the symptomatic women were treated for 2 months with 0.625 mg of conjugated estrogens, urinary catecholamine measurements were repeated. Serum estrogen levels were not different in symptomatic and asymptomatic patients. Urinary MHPG, VMA, and HVA were similar in symptomatic women before and after estrogen treatment and were not different from levels of asymptomatic postmenopausal and control subjects. The ratios of MHPG:VMA, MHPG:HVA, and VMA:HVA also were similar. While body weight and estrogen did not correlate with urinary catecholamines, there was a significant positive correlation between MHPG and age in postmenopausal subjects (r = 0.56, p less than 0.005).
The effect of synthetic Paf-acether has been studied in guinea-pig skin, following intradermal injection, and in guinea-pig lung, following intravenous administration. Histopathological responses to Paf-acether were assessed by both light microscopy and electron microscopy. In addition, plasma protein extravasation and platelet accumulation were quantitatively assessed using radiolabelling techniques. Intradermal injection of Paf-acether, but not lyso-Paf, elicited acute increased vascular permeability, accompanied by intravascular accumulation of platelets and neutrophils. There was evidence, 2-8 h after intradermal injection of Paf-acether, of perivascular infiltration with neutrophils. At 24 h there was a mixed cellular infiltrate comprising mononuclear cells in addition to neutrophils. Following systemic administration of Paf-acether, aggregates of platelets in close association with neutrophils were evident within the pulmonary vasculature. Intravenous injection of Paf-acether, but not lyso-Paf, caused intrathoracic accumulation of radiolabelled platelets. These results suggest that Paf-acether has properties consistent with those of a mediator of inflammation.