PubMed Health⌕ Search

Biomedical subjects

K P Stock

Publications and source records attributed to K P Stock.

At least 19 recordsLinked to original sources
PubMed1998

Coenzyme A disulfide reductase, the primary low molecular weight disulfide reductase from Staphylococcus aureus. Purification and characterization of the native enzyme.

The human pathogen Staphylococcus aureus does not utilize the glutathione thiol/disulfide redox system employed by eukaryotes and many bacteria. Instead, this organism produces CoA as its major low molecular weight thiol. We report the identification and purification of the disulfide reductase component of this thiol/disulfide redox system. Coenzyme A disulfide reductase (CoADR) catalyzes the specific reduction of CoA disulfide by NADPH. CoADR has a pH optimum of 7.5-8.0 and is a dimer of identical subunits of Mr 49,000 each. The visible absorbance spectrum is indicative of a flavoprotein with a lambdamax = 452 nm. The liberated flavin from thermally denatured enzyme was identified as flavin adenine dinucleotide. Steady-state kinetic analysis revealed that CoADR catalyzes the reduction of CoA disulfide by NADPH at pH 7.8 with a Km for NADPH of 2 muM and for CoA disulfide of 11 muM. In addition to CoA disulfide CoADR reduces 4,4'-diphosphopantethine but has no measurable ability to reduce oxidized glutathione, cystine, pantethine, or H2O2. CoADR demonstrates a sequential kinetic mechanism and employs a single active site cysteine residue that forms a stable mixed disulfide with CoA during catalysis. These data suggest that S. aureus employs a thiol/disulfide redox system based on CoA/CoA-disulfide and CoADR, an unorthodox new member of the pyridine nucleotide-disulfide reductase superfamily.

Bacterial Proteins↗
PubMed1993

Variability in the stereoselective disposition of ibuprofen in patients with rheumatoid arthritis.

1. Patients suffering from rheumatoid arthritis received oral doses of 600 mg racemic ibuprofen (n = 25; RAC) or 400 mg (S)-ibuprofen (n = 25; S-IBU) in a double-blind, randomized parallel-group study. 2. The pharmacokinetic parameters of (S)-ibuprofen were not statistically different between treatments (P > 0.05). Comparing (S)- and (R)-ibuprofen within the group receiving the racemate significantly higher Cmax (20.3 +/- 5.3 vs 17.7 +/- 4.4 micrograms ml-1; P < 0.02; 95% confidence interval for differences (CI): 0.5-4.6), AUC (86.2 +/- 23.5 vs 67.6 +/- 26.6 micrograms ml-1 h; P < 0.001; CI: 9.5-27.6), mean residence time (4.5 +/- 1.1 vs 4.1 +/- 1.2 h; P < 0.01; CI: 0.1-0.6) and renal clearance (0.8 +/- 0.6 vs 0.0 +/- 0.0 ml min-1; P < 0.001; CI: 0.5-1.0) values were observed for the (S)-enantiomer. 3. No difference was found (P > 0.05) between treatments in the percentage of the dose recovered in the urine as (R)- or (S)-ibuprofen plus metabolites (S-IBU: 80.2 +/- 8.47 vs RAC: 74.1 +/- 14.0%). 4. Interindividual variation in the pharmacokinetics of (S)-ibuprofen following administration of the racemate was similar to that following the administration of the single isomer suggesting that chiral inversion is not a major factor contributing to variability in the disposition of this drug.

Arthritis, Rheumatoid↗
PubMed1991

S-ibuprofen versus ibuprofen-racemate. A randomized double-blind study in patients with rheumatoid arthritis.

Ibuprofen (ibu) is a racemic 2-arylpropionic acid non-steroidal anti-inflammatory drug whose activity is due mainly to the S-enantiomer. So far only the racemic compound is in clinical use. A double-blind randomized trial was carried out for a 2-week period in 50 patients with classical rheumatoid arthritis (RA) (Steinbrocker II-III) to compare the effectiveness and tolerance of S-ibu (400 mg T.I.D.) with that of the racemic compound (600 mg T.I.D.). Ritchie-index, limitation of movement, joint pain on pressure and pain at night decreased significantly in both groups. Due to lack of effectiveness, the dose had to be increased in 3 patients from the S-ibu group as well as in 6 patients from the racemic group resulting in mean daily doses of 1220 mg S-ibuprofen and 1870 mg racemic ibu. No statistically significant difference could be found between both groups concerning efficacy and unwanted effects. Therefore, S-ibu given alone may be advantageous because the metabolic load to the human body is reduced and patients are more likely to comply with drug doses of 1.2 g/day as compared to 1.8 g/day.

Adult↗
PubMed1990

Cellular immune response toward human articular chondrocytes. T cell reactivities against chondrocyte and fibroblast membranes in destructive joint diseases.

Articular cartilage is one of the major targets in destructive joint diseases in humans. We studied cellular immune reactions against cartilage cell-surface membranes, because it has recently been suggested that these represent possible antigenic structures, based upon the observation of autoantibodies with this specificity in certain joint diseases. A striking T cell reactivity toward chondrocyte membranes was found both in blood and synovial tissue from patients with rheumatoid arthritis. This reactivity was strongly dependent on the presence of monocytes and had all the characteristics of an antigen-driven process. Clonal analysis demonstrated high precursor frequencies in peripheral blood T cells that were reactive against chondrocyte membranes. This response to chondrocyte membranes greatly exceeded the T cell stimulation induced by membranes from other sources such as fibroblasts or epithelial cells. In contrast to patients with rheumatoid arthritis, individuals with osteoarthritis showed a strong peripheral blood and synovial fluid T cell response not only to chondrocyte membranes, but also to fibroblast membrane material. However, there was no reactivity to epithelial cell membranes. Normal donors generally did not show significant responses to any membrane preparation. These data indicate that there is a strong T cell reactivity toward chondrocyte membranes in destructive joint disorders, and this may significantly contribute to the pathogenetic processes that occur in these diseases.

Adult↗
PubMed1990

Pharmacokinetics of S(+)- and R(-)-ibuprofen in volunteers and first clinical experience of S(+)-ibuprofen in rheumatoid arthritis.

S(+)-, R(-)- or racemic ibuprofen was administered orally to volunteers in doses of 150 mg, 300 mg and 500 mg pure S(+)-, 300 mg pure R(-)- and 600 mg racemic ibuprofen. The pharmacokinetic parameters in humans showed that S(+)-ibuprofen was not inverted to R(-)-ibuprofen, whereas R(-)-ibuprofen was inverted to S(+)-ibuprofen to a variable degree. S(+)-ibuprofen and R(-)-ibuprofen given alone more rapidly reached significantly higher maximal plasma concentrations than after the same doses of the racemic compound. The elimination half-lives and clearance values for all three forms of ibuprofen were comparable. The mean residence time of S(+)-ibuprofen after R(-)- and racemic ibuprofen was significantly longer than after administration of the pure S(+)-enantiomer. Judged by the AUC, the bioavailability of S(+)-ibuprofen was independent of the dose within the range tested. Administration of S(+)-ibuprofen to 6 rheumatic patients showed that the pharmacokinetic behaviour of S(+)-ibuprofen in patients was similar to that found in volunteers. S(+)-ibuprofen proved to be an effective analgesic antirheumatic drug in the dose range 1 to 1.5 g/day.

Adult↗
PubMed1989

Pharmacological differences between R(-)- and S(+)-ibuprofen.

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug exhibiting optical isomerism. Only the racemate is in clinical use. In in vitro studies it has been demonstrated that only the S(+)-enantiomer inhibits the PG synthetase system. Nevertheless, it is widely believed that the sole use of the active isomer does not comprise any advantages since the inactive isomer is converted within the human body. In a triple cross-over study (300 mg S(+), 300 mg R(-), 600 mg racemic IBU; n = 8), we could show that the converted R(-)-IBU after racemate administration provides for only one third of the AUC of S(+)-IBU obtained after S(+)-application. Highest S(+)-peak plasma levels were reached after S(+)-IBU, lower ones after racemate. We, therefore, studied 4 patients with classical rheumatoid arthritis treated with 2-3 doses of 500 mg of S(+)-IBU/day over a two week period. Significant clinical recovery (Ritchie-index p less than 0.01; analogue scale pain p less than 0.05, motion p less than 0.01) was reached after one week. The results indicate that a reduction of dose and of metabolic load is possible if the S(+)-enantiomer is administrated.

Administration, Oral↗
PubMed1985

[Immunologic and electron microscopic findings in an unusual case of Whipple's disease].

Whipple's disease is a curious disorder with the involvement of many organ systems, primarily gut, synovium and the central nervous system, characterized by the presence of numerous proliferating bacteria in tissue macrophages and other cell types. While clinically this disease entity has previously been defined by the classical triad of diarrhoea, malabsorption and weight loss, some patients do not show these features. In this report, a clinically unusual case of Whipple's disease is described presenting with high persistent fever, severe arthralgias and headaches, but without malabsorption, diarrhoea or weight loss. Nevertheless, the histological and electron microscopical pictures demonstrated the typical findings of intracellular micro-organisms along with the presence of bacteria in Schwann nerve cells, which has only once been described previously. Immunological findings before treatment demonstrated a decrease of T cells with the helper/inducer phenotype, and a concomitant rise in cells with the suppressor/cytotoxic phenotype, an elevation of "activated" Ia positive T cells and a significant reduction of T cell mitogenic responsiveness. Of special interest, after a successful treatment these immunological abnormalities shifted to normal with the exception of a still elevated number of Ia+ T cells. The discussion of this unusual case of Whipple's disease includes - besides possible cellular immunological abnormalities - genetic factors, especially since this patient was HLA-B-27-positive as was his son who is suffering from ankylosing spondylitis.

Doxycycline↗
PubMed1985

[Reduction of insulin reserves and exocrine pancreatic secretion in chronic pancreatitis].

In 11 persons with normal pancreas function and 21 patients with chronic pancreatitis serum levels of insulin and C-peptide were measured under basal conditions and after maximal stimulation with glucose-tolbutamide-glucagon. Patients with the highest excretory deficiency in the secretin-pancreozymin test had the most marked impairment in endocrine function. In patients with manifest diabetes the exocrine capacity was reduced to an average of 10% of normal. The endocrine parameters correlated linearly with the exocrine ones, most markedly C-peptide reserve with pancreatic enzyme secretion.

Adult↗
PubMed1985

Beta-cell reserve capacity in chronic pancreatitis.

The degree of correlation between exocrine pancreatic function and endocrine secretory capacity was examined in 13 chronic pancreatitis patients with secondary diabetes mellitus, 8 chronic pancreatitis patients without diabetes, and 11 healthy subjects. The two parameters were studied under maximal stimulation (volume-corrected secretin-pancreozym test and glucose-tolbutamide-glucagon provocation, respectively). A close, linear correlation was found between all endocrine variables and pancreatic acinar function (e.g. rs = 0.77 for chymotrypsin output and C-peptide release; p less than 0.0001). The correlation was less strong with pancreatic bicarbonate output (e.g. rs = 0.49 for C-peptide release; p less than 0.05). In our patients, secondary overt diabetes occurred in chronic pancreatitis when protease outputs were, on an average, reduced to about 10% of the mean maximal protease output of normal subjects.

Adult↗
PubMed1981

[Gastrointestinal hemorrhage--angiodysplasia].

Clinico-pathological conference on the clinical picture of angiodysplasia--a rare source of bleeding in the upper gastrointestinal tract. In patients with relevant hemorrhagic symptomatology (tarry stools, anemia, possibly hemorrhagic shock), the diagnosis is established with the aid of angiography and endoscopy. Treatment consists in the resection of the section of bowel involved.

Aged↗
PubMed1981

[Screening of exocrine pancreatic function (author's transl)].

The validity of oral pancreatic function tests (fluoresceine dilaurate-[FDL-], N-benzoyl-L-tyrosyl-para-amino-benzoic-acid-[PABA-]test) was assessed intra-individually in 67 patients in comparison with the secretin-pancreozymin test corrected for volume loss. Faecal chymotrypsin (CH-F) estimation was included in the comparison. According to the result of the secretin-pancreozymin test, patients were divided into those with normal pancreatic function (n = 28), those with borderline restricted function (n = 18), and those with manifest exocrine insufficiency (n = 21). Results show that in borderline decreased pancreatic function the diagnostic value of all screening tests is limited. The sensitivity (true pathological results) was 38% in the FDL-test, 40% in the PABA-test, and 31% in CH-F. In manifest exocrine pancreatic insufficiency FDL- and PABA-test as well as CH-F showed similar sensitivity of 67, 63, and 62%, respectively. Results show that oral pancreatic function tests, particularly the simple FDL-test, represent a diagnostic alternative to the relatively complicated CH-F assessment. However, none of the tests are able to replace the secretin-pancreozymin test as the most valid diagnostic investigation.

4-Aminobenzoic Acid↗
PubMed1981

[Biliary excretion of mezlocillin].

2 g of mezlocillin were given at different time intervals (1/4, 1/2, 1, 2, 4, 10, 14, 18 hours) to patients in whom endoscopic retrograde cholangiography (ERC) was scheduled for antibiotic prophylaxis. Prior to the instillation of the contrast medium 5 ml of bile were aspirated and the concentration of the antibiotic determined via agar diffusion in comparison to the serum level. Serum levels reached a peak of 105 micrograms/ml whereas bile levels reached a mean level of 4000 micrograms/ml. In patients with intact liver function mezlocillin is concentrated to a factor of 40 within bile. Complete elimination in serum occurs after 4 to 5 hours, in bile after 18 to 24 hours.

Bile↗
PubMed1981

Biological and biochemical analysis of endoscopically aspirated bile.

Selective cannulation and aspiration of bile prior to ERCP may be helpful in bacterial contamination (suppurative cholangitis), in patients with choledocholithiasis, to determine lithogenicity of bile, and in studies where antibiotic concentration of different substances are analyzed in correlation to hepato-biliary diseases. Results of appropriate examinations are presented.

Ampulla of Vater↗
PubMed1981

Tuberculosis of the pancreas.

In a case report, the rate condition of tuberculosis of the pancreas is described. There are two conceivable ways in which the pancreas may become diseased: 1. toxic-allergic reaction of the pancreas in response to generalized tuberculosis (so-called concomitant pancreatis) 2. Invasion of the pancreas by tubercle bacteria disseminated via the blood, or through penetration of the organ by adjacent caseating abdominal lymph nodes. Histologically, epithelioid cells and Langhans' giant cells are only rarely found; caseation usually develops, with subsequent calcification, which can lead to stenosis of the pancreatic duct. In patients with generalized tuberculosis and abdominal complaints, the diagnosis is most reliably established on the basis of ERCP and CAT. In the presence of pain, resection of the affected portion of the pancreas may be considered as means of treatment.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1981

[In-vitro experiments to study the role of contrast medium in pancreatitis due to ERCP (author's transl)].

The causes of hyperamylasaemia or pancreatitis, occasionally observed after the endoscopic retrograde cholangio-pancreatographie (ERCP), have been unequivocally identified as pressure, volume and the duration of contrast medium instillation. In a completely pressure free experimental model involving the perifusion of lobes of the pancreas of guinea pigs, a study has now been carried out to investigate the extent to which, in addition to these known causes, the contrast medium itself contributes to the development of enzymatic disorders. It was found that, merely as a result of stimulation through Ceruletid (Takus), the secretion of amylase was increased by more than 400%. Following the addition of 50% contrast medium to the perifusion medium, however, amylase secretion was completely suppressed. The electron-microscopic examination of the perifused pancreatic cells revealed that the contrast medium had a synthesis-enhancing effect on the production of zymogen granules in the cells of the acini, but that, however, throughout the duration of contrast medium perifusion, the extrusion of granules was suppressed. Only after the contrast medium had been washed out, an excessive secretion of amylase was observed. The findings show that, in addition to the increase of intraductal pressure, the contrast medium itself may also be possible causal factor in the development of hyperamylasaemia or pancreatitis.

Amylases↗
PubMedDate not supplied

[Therapy of non-steroidal antirheumatic drug-induced gastrointestinal lesions with misoprostol].

In a multicenter placebo-controlled double-blind study in patients with degenerative or inflammatory rheumatic diseases the prostaglandin analogue misoprostol, in a dose of 200 micrograms twice daily after meals, was administered for the treatment of NSAID-induced lesions and symptoms of the upper gastrointestinal tract. Treatment with an NSAID was continued. Misoprostol treatment was demonstrated to be clearly superior to placebo in respect of reduction of gastroduodenal lesions and gastrointestinal pain. In addition, the physician's global assessment of gastrointestinal complaints was also statistically significantly better. No difference between the groups was found with respect to antirheumatic action of the NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗