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A Korn

Publications and source records attributed to A Korn.

At least 19 recordsLinked to original sources

Enhancement of uptake of lipopolysaccharide in macrophages by the major outer membrane protein OmpA of gram-negative bacteria.

Monoclonal antibodies (MAb) to lipopolysaccharide (LPS) and to the major outer membrane protein OmpA from Proteus mirabilis were generated and used to monitor the kinetics of uptake in macrophages of LPS as well as LPS bound to OmpA. Uptake was measured by a modified enzyme-linked immunosorbent assay (ELISA) in a microtiter culture system. The MAb were of various immunoglobulin G subclasses and showed strong reactivities with their antigens. Four hybridoma clones recognizing LPS and three recognizing OmpA from P. mirabilis 19 were selected for the present study on the basis of reactions in ELISA and Western blot (immunoblot) analyses. In the uptake assay, it was possible to differentiate between antigen on the cell surface and antigen which had been internalized. Uptake of LPS by macrophages was relatively rapid during the first 4 h of culture and then progressed more slowly over the remaining 24-h observation period. The level of detection of LPS in this assay system was in the nanogram range. When macrophages were pulsed with LPS for 30 min and subsequently washed to remove antigen not bound to the cells, the amount of LPS detectable on the macrophage surface decreased progressively for 3 h after the pulse, which indicated internalization of the antigen. Thereafter, LPS rose to an increased level on the cell surface. The rate of uptake of LPS was more rapid when it was in complex with OmpA. When the fate of OmpA was monitored in the same LPS-protein complexes by use of MAb to OmpA in a pulse experiment, the level of protein measured on the cell surface decreased after an initial rise, which again indicated internalization, but the protein did not reappear on the cell surface in a form detectable with the MAb. Compared with the LPS monitoring system, detection of OmpA associated with macrophages was weak, although the MAb to OmpA reacted strongly with the protein in the ELISA and Western blot analyses.

Acute-Phase Proteins

Myocardial m-[123I]iodobenzylguanidine scintigraphy for the assessment of adrenergic cardiac innervation in patients with IDDM. Comparison with cardiovascular reflex tests and relationship to left ventricular function.

Cardiac imaging using m-[123I]iodobenzylguanidine (mIBG) reflects sympathetic myocardial innervation. In patients with insulin-dependent diabetes mellitus (IDDM), the following were studied: 1) the prevalence of derangements of cardiac autonomic innervation as detected by mIBG scintigraphy in comparison with cardiovascular reflex tests and 2) the relationship between adrenergic cardiac innervation and left ventricular (LV) function. Twenty-four patients with IDDM without overt heart disease were studied after silent coronary artery disease was excluded by 201Tl scintigraphy. Cardiac innervation was evaluated by both mIBG scintigraphy (tomographic imaging) and cardiovascular reflex tests. Systolic (ejection fraction [EF] percentage) and diastolic (peak filling rate [PFR] defined as end-diastolic volumes per second [EDV/s]) LV function were determined by equilibrium radionuclide angiography at rest and during bicycle exercise. mIBG scintigraphy was also performed in 10 control subjects. All control subjects exhibited a normal myocardial mIBG distribution. Among diabetic patients, only six had normal mIBG scans (group 1), whereas 18 had evidence of regional adrenergic denervation (group 2). Reflex tests suggested cardiac autonomic neuropathy in only seven of these patients (P < 0.01 vs. mIBG). All patients had a normal EF at rest. However, group 2 showed an impaired response to exercise as indicated by a smaller increase in EF (5 +/- 6 vs. 13 +/- 5%, P < 0.05) and a lower PFR (5.9 +/- 0.8 vs. 7.3 +/- 1.2 EDV/s, P < 0.01). Myocardial mIBG scintigraphy reveals that in patients with IDDM, sympathetic myocardial dysinnervation is much more common than previously thought. Furthermore, subclinical LV dysfunction is related to derangements of adrenergic cardiac innervation.

3-Iodobenzylguanidine

[Hepatitis C].

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Adult

Clinical evaluation of a new epidural pressure monitor.

Comparative measuring of epidural pressure using the Spiegelberg probe 1 and ventricular fluid pressure was carried out in 15 neurosurgical intensive-care patients. Deviations in both directions were established, with a trend toward overestimating ventricular pressure in epidural pressure measuring (r = 0.77). Individual pulsations, spontaneous wave courses and therapy-induced pressure changes were reflected without delays. There were no complications observed with probe implantation periods for up to 6 days. The system has been shown to be mechanically stable and easy to implant. We believe the device to be fit for trend monitoring of intracranial pressure. As with other epidural pressure monitoring systems, false assessments of ventricular pressure may lead to wrong decisions as to required therapy.

Adult

The 39-kilodalton outer membrane protein of Proteus mirabilis is an OmpA protein and mitogen for murine B lymphocytes.

Partial amino acid sequence analysis of a major outer membrane protein of Proteus mirabilis (39-kDa protein) indicates that it is an OmpA protein. The mitogenic activities of the 39-kDa protein for murine lymphocytes were also investigated with T lymphocytes isolated by passing spleen cells over columns of nylon wool fiber and B lymphocytes obtained by treating spleen cells with monoclonal antibodies to Thy1 plus complement. The 39-kDa protein showed little activity in stimulating T cells to proliferate but was strongly mitogenic for B cells.

Amino Acid Sequence

Dose relationship of stimulated insulin production following intravenous application of glimepiride in healthy man.

This study evaluates stimulated insulin production rate (incremental AUC x MCR (metabolic clearance rate) of C-peptide) and blood glucose (BG) response after i.v. administration of glimepiride (Hoe 490, GLI, CAS 93479-97-1) (0.25, 0.50, 0.75, 1.00, 1.25, 1.50 mg) in healthy man (27 +/- 4 yrs). It was shown that i.v. bolus administration of GLI (0.25, 0.50, 1.25 and 1.50 mg) caused a dose-related rise in insulin production from 18 +/- 17 to 25 +/- 13, 36 +/- 14 and 54 +/- 34 pmol/kg body weight, respectively. This effect did not yet plateau at 1.5 mg GLI and was paralleled by a fall in BG (decremental area below BG baseline) by 40 +/- 36, 69 +/- 20, 161 +/- 47 and 113 +/- 62 mmol.min/l. It is concluded that insulin release is increased by i.v. GLI in a dose related manner, while a parallel decline in BG was induced only up to 1.25 mg GLI. The less marked fall of BG after injection of 1.50 mg GLI may reflect interference by insulin-counterregulatory hormones secondary to induced hypoglycaemia.

Adult

Absence of interaction between tenoxicam and warfarin.

The influence of tenoxicam on plasma warfarin concentrations and on its anticoagulant effect has been studied in healthy volunteers. Tenoxicam did not alter the plasma warfarin concentration versus time profile. Treatment with it for 14 days had no effect on the average dose of warfarin required to maintain the prothrombin time within a specified range. The coumarin dose index, an indicator of warfarin sensitivity, remained unchanged during tenoxicam administration. The results demonstrate the lack of a clinically relevant effect of tenoxicam on warfarin-induced anticoagulation.

Adult

Biochemical effects of high single doses of moclobemide in man: correlation with plasma concentrations.

The effects of high single doses of moclobemide (300, 450 and 600 mg given at the end of a standardized meal) on plasma levels of several catecholamines and their deaminated metabolites, and on plasma levels of pituitary hormones were determined in eight healthy young male volunteers in a randomized, double-blind, placebo-controlled study. Assessment of the i.v. tyramine potentiation and determination of the plasma levels of moclobemide were also performed. The tyramine sensitivity factor at 2 h after dosing was about 2.1, with no significant differences between the doses used. The inhibitory activity of moclobemide on MAO-A was reflected in significant reductions of plasma concentrations of DHPG and 5-HIAA. No clear differences were detected between the moclobemide doses. Prolactin plasma concentrations were only slightly increased after the two higher doses. The plasma concentrations of moclobemide were very much in agreement with those found in previous studies under similar experimental conditions. Thus, single oral doses of 300, 450 and 600 mg moclobemide demonstrated marked inhibition of MAO-A activity, whereas a single dose of 300 mg induced a near-maximum effect.

Adult

External ventricular drainage for treatment of rapidly progressive posthemorrhagic hydrocephalus.

Twenty-seven newborn infants (birth weight, 1503 +/- 776 g; gestational age, 31 +/- 3 wk) (mean +/- standard deviation) with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure were treated by external ventricular drainage. The progression of hydrocephalus was arrested during the drainage period in each patient. The drainage was kept in place for 23 +/- 9 days, the longest drainage period being 48 days. In 16 of 23 surviving patients, progressive ventricular dilation recurred after removal of the drainage, requiring a definitive shunt implantation (nine ventriculoatrial, seven ventriculoperitoneal). For the remaining seven infants, no further therapy was necessary. Implantation of the permanent shunt was done days 28 to 88 (body weight, 2400 +/- 950 g). Bacterial cultures from cerebrospinal fluid and/or the tip of the ventriculostomy catheter were negative in 175 instances and positive in 11 instances (7 patients). No clinical or biochemical evidence of ventriculitis was noted. Four of the 27 patients died of causes unrelated to external ventricular drainage. Twenty-three infants survived. Seventeen of 23 survivors suffered from intraventricular hemorrhage Grade 3; in 7, neurological and developmental outcomes were classified as normal; 9 patients experienced mild to moderate paresis and/or mild to moderate developmental delay; and only 1 patient was severely retarded. Six patients with parenchymal lesions had severe motor and/or developmental handicaps. We consider external ventricular drainage an effective and safe therapy in newborn infants with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure. The ultimate outcome, however, depends mainly on the mode and the extent of the primary brain lesion.

Brain Damage, Chronic

Proliferation in pituitary adenomas: measurement by MAb KI 67.

The monoclonal antibody MAb KI 67 reacts with a nuclear antigen throughout the entire cell cycle and allows easy evaluation of proliferating tumour cells on routinely prepared smear and frozen sections. 120 pituitary adenomas were investigated by use of the monoclonal antibody KI 67 in a two-step avidin-biotin-peroxidase complex (ABC) technique. The KI 67 labelling index (LI) ranged in all adenomas from 0.2 to 4.6%. In 90 cases of transphenoidally operated adenomas the dura of the sella floor was investigated histologically. Adenomas with histologically proven dural infiltration showed a statistically significant higher KI 67 LI (p less than 0.001) compared to non-invasive adenomas.

Adenoma

In vivo studies on alpha-adrenergic receptor subtypes in human veins.

We studied in vivo responsiveness of venous alpha 1- and alpha 2-adrenoceptors, measuring the diameter changes in superficial veins in response to alpha-adrenergic agonists and antagonists in healthy human volunteers. The dorsal hand vein technique was used because it permits complete dose-response studies of venous constriction without confounding reflex alterations. Local infusions of all agonists studied induced dose-dependent contraction of the hand vein; the maximal effects (Emax) were: norepinephrine (88% +/- 10%), methoxamine (97% +/- 5%), phenylephrine (95% +/- 6%), clonidine 54% +/- 12%), and azepexole (68% +/- 26%). Clonidine reduced the norepinephrine-induced venoconstriction by 11% +/- 10%. Oral doses of 1 mg prazosin antagonized the venoconstriction induced by norepinephrine, methoxamine, and clonidine, but not by azepexole. Yohimbine-antagonism was observed against all agonists studied. Inhibition by yohimbine of clonidine-induced venoconstriction was irreversible over 60-180 min. Results show that the in vivo effects on veins of alpha-adrenergic agonists are in good agreement with results from in vitro experiments. Agonists with alpha 1- and alpha 2-adrenoceptor subtype selectivity cause venoconstriction in vivo, but alpha 2-receptor mediated constriction is intrinsically weaker. Clonidine acts as a partial antagonist against norepinephrine, presumably on postsynaptic alpha 2-receptors. At high doses, alpha 2-adrenoceptor subtype selectivity of clonidine and yohimbine appear to be partially lost in vivo.

Adrenergic alpha-Agonists

Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus.

To determine the therapeutic effect of the carinitine palmitoyltransferase I (CPT-I) inhibitor, etomoxir, eight hospitalized obese non-insulin-dependent diabetes mellitus (NIDDM) patients were studied (body mass index [BMI], 28.7 +/- 1.3 kg/m2; age, 54 +/- 8 years [means +/- SE]) at baseline (placebo = t1), and after oral etomoxir (50 mg/d = t2, 100 mg = 3, 150 mg = t4, 200 mg = t5, placebo = t6). Fasting blood glucose (mmol/L), triglycerides (mmol/L), cholesterol (mmol/L), free fatty acids (mumol/L), beta-hydroxybutyrate (mumol/L), and alanine aminotransferase (GPT, U/L) were determined (t1 to t6), as were glucose utilization (M value; indirect calorimetry) and hepatic glucose production during a 10 mU/kg.min euglycemic clamp (t1 and t4). A dose-dependent decrease was induced by etomoxir in fasting blood glucose (t1 to t5: 9.5 +/- 0.7, 8.7 +/- 1.0, 8.3 +/- 1.1 [P v t1 less than .05], 7.8 +/- 0.9, [P v t1 less than .01], 7.9 +/- 1.1 [P v t1 less than .05]), which was reversible in t6 (9.9 +/- 1.1). Mean plasma lipids were reduced (t1 v t5) for triglycerides (-54%, P v t1 less than .01), cholesterol (-24%, P v t1 less than .05), and beta-hydroxybutyrate (-44%, P v t2 less than .01), while free fatty acids increased by 52% (P v t1 less than .05), as did GPT (t1: 17 +/- 3; t5: 32 +/- 7 U/L [P v t1 less than .01]).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid

Primary defect in alpha-adrenergic responsiveness in patients with varicose veins.

Responsiveness of superficial hand veins to local infusions of noradrenaline was compared in patients with primary varicose veins and in healthy volunteers by use of the dorsal hand vein technique. Patients with varicose veins required significantly higher doses of noradrenaline for half-maximal venoconstriction than the dose required by control subjects (geometric mean, 11.6 ng/min in patients compared with 4.8 ng/min in control subjects; p = 0.006). Noradrenaline responsiveness in varicose veins was not significantly different from hand vein responsiveness in the same patients. Our findings indicate a constitutional decrease in venous alpha-adrenergic receptor responsiveness in patients with varicosities. Dilation of varicose veins does not further affect noradrenaline-induced venoconstriction.

Adult

Normal responsiveness of superficial hand veins to alpha- and beta-adrenergic stimuli in allergic asthma: effects of terbutaline and prednisolone on beta-adrenergic responsiveness.

Impaired function of the adrenergic-receptor system has been postulated to contribute to the pathogenesis of bronchial asthma. Using the dorsal hand-vein compliance technique, we compared the changes in diameter of superficial hand veins in response to phenylephrine, an alpha-adrenoceptor agonist, and to isoproterenol, a beta-adrenoceptor agonist, in 14 untreated patients with allergic asthma and in 16 nonatopic control subjects. There were no significant differences in the median effective dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) or in the maximal response (Emax) between the two groups. Bronchial hyperreactivity (assessed by methacholine-challenge tests) in the patients with asthma was uncorrelated with the ED50 or Emax of isoproterenol. These results demonstrate no evidence for a generalized change in alpha- or beta-adrenergic responsiveness on smooth muscle cells in asthma. Hand-vein responsiveness to isoproterenol was unchanged after treatment for 7 days with oral terbutaline (5 mg three times per day). Thus, unlike leukocytes, smooth muscle appears not readily susceptible to beta-adrenoceptor desensitization in vivo. Local infusions of prednisolone or dexamethasone during 2 hours and systemic administration of dexamethasone (24 hours) caused a significant fall in the Emax for isoproterenol. The mechanism of attenuation of beta-adrenoceptor responsiveness by corticosteroids remains to be determined.

Adrenergic alpha-Antagonists

ACE inhibition with cilazapril improves myocardial perfusion to the ischemic regions during exercise: a pilot study.

This study was performed to examine whether cilazapril, a novel nonsulfhydril angiotensin-converting enzyme (ACE) inhibitor, may improve regional myocardial perfusion at exercise in patients with coronary heart disease (CHD). In a single-blind, nonrandomized trial, 5 mg cilazapril or placebo was administered to eight patients with documented CHD and stable exertional angina. Multistage bicycle exercise tests were performed and each patient served as his own control. At peak exercise, as well as at rest, [99mTc]hexakis-2-methoxy-2-isobutylisonitrile myocardial images were obtained. Percent myocardial activity differences (%AD) between exercise and resting images were compared (cilazapril versus placebo). Heart rate and blood pressure were not significantly different between trials. However, after cilazapril administration, %AD was higher than after placebo, with relative differences between trials of greater than 30%, along with alleviation of clinical symptoms in seven of eight patients. These data suggest that in patients with stable-effort angina, ACE inhibition with cilazapril is able to redistribute myocardial blood flow and to improve regional oxygen supply to the ischemic myocardium.

Angina Pectoris

Lack of effect of tenoxicam on dynamic responses to concurrent oral doses of glucose and glibenclamide.

1. In a single-blind, placebo controlled study the influence of tenoxicam on responses of glucose, insulin and C-peptide to oral doses of glucose and glibenclamide was examined in 16 healthy male volunteers. 2. The subjects received once daily doses of 2.5 mg glibenclamide for 12 days. From day 5 through 12 eight subjects received concomitantly 20 mg tenoxicam once daily and the remaining eight subjects received placebo. 3. On days 1, 4, 5 and 12 glibenclamide was taken with 75 g glucose and blood glucose, serum insulin and C-peptide were measured over 5 h. Plasma levels of glibenclamide and tenoxicam (where appropriate) were followed over 10 h. 4. Characteristic parameters of blood glucose and insulin and C-peptide responses did not change significantly with time (day) and there was no difference between both treatment groups. 5. Baseline insulin increased from 11.7 mu l-1 on day 1 to 15.6 mu l-1 on day 4 (P = 0.009), likewise baseline C-peptide increased from 478 pmol l-1 to 530 pmol l-1 (P = 0.05), but there was no further change in the subsequent treatment period. 6. The AUC of the glibenclamide plasma concentration-time curve did not show changes with time or differences between treatment groups. The mean (s.d.) oral clearance of tenoxicam was 2.5 (1.5) ml min-1 and appeared slightly higher than in previous studies. 7. It was concluded that tenoxicam did not affect overall glycoregulation in healthy subjects under glibenclamide steady state conditions.

Adult