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E Weber

Publications and source records attributed to E Weber.

At least 19 recordsLinked to original sources
PubMed1992

CD24, a signal-transducing molecule expressed on human B cells, is a major surface antigen on small cell lung carcinomas.

Cell lines derived from human small cell carcinoma of the lung express high levels of a surface polypeptide termed the cluster-w4 antigen, which was previously identified as a potential target for toxin-based immunotherapy of lung cancer. We have cloned a complementary DNA encoding the cluster-w4 antigen from COS-1 fibroblasts transfected with a SW2 small cell carcinoma library, by panning with a mixture of the cluster-w4-specific monoclonal antibodies SWA11, SWA21, and SWA22. The sequence of the cluster-w4 complementary DNA encodes an unusually short (80-amino acid) protein identical to that recently reported for the leukocyte activation molecule CD24 except for a single valine-alanine substitution due to a single-base polymorphism within the region of the gene coding for the extracellular domain. Biochemical analyses of the cloned cluster-w4 antigen confirmed both the presence of the phosphatidylinositol tail and the extensive glycosylation reported for the CD24 molecule. Furthermore, the cloned cluster-w4 antigen expressed on COS cells was shown to react with a comprehensive panel of CD24-specific monoclonal antibodies, as assessed by indirect immunofluorescence staining. Northern blot hybridization indicated the presence of several transcript sizes for the cluster-w4 antigen that were greatly overexpressed in small cell carcinoma cell lines, compared with normal hemopoietic cells and CD24-positive cell lines. Southern blot hybridization of restriction digests of genomic DNA identified a complex pattern of bands consistent with either a complex gene structure containing many exons or the presence of a family of closely related genes.

Alanine↗
PubMed1992

Dose dependent suppression of mineralocorticoid metabolism by different heparin fractions.

One neglected side effect of heparin therapy is the inhibition of adrenal aldosterone production leading to occasionally life-threatening hyperkalaemia. This is only reported with (therapeutic) high doses (greater than or equal to 20.000 IU). The complex interplay of mineralocorticoid metabolites was studied in 29 subjects with unfractionated (UFH) and low molecular weight heparin (LMWH). Both heparins altered mineralocorticoid metabolism in a dose dependent manner. Whereas no effect was observed with UFH 2 x 5000 IU sc/day or LMWH 2500 a FXa U sc/day, higher doses significantly suppressed aldosterone and 18-hydroxycorticosterone production in plasma and urine. Three out of seven patients receiving UFH 3 x 7500 IU sc/day developed hyperkalaemia. This study shows the threshold dosage of UFH leading to suppression of mineralocorticoid metabolism in man and provides information that LMWH as well as UFH can suppress mineralocorticoid production. With respect to therapeutic implications it is important that LMWH at 2500 a FXa U sc/d had no effect on mineralocorticoid metabolism in contrast to UFH at a dosage currently used for prevention of thromboembolism (3 x 5000 IU sc/d).

Adult↗
PubMed1992

Lack of accumulation of midazolam in plasma and lipoprotein fractions during intravenous lipid infusions in patients on artificial respiration.

Severely ill patients often require total parenteral nutrition including intravenous lipid emulsions concurrently administered with lipophilic drugs. Therefore we investigated whether therapeutic application of a mixed medium chain/long chain triglyceride infusion affects the disposition of midazolam necessary for sedation in patients on artificial respiration. The concentrations of midazolam were measured in unfractionated plasma, and in lipoprotein fractions isolated from ex vivo blood samples, including determination of triglycerides and cholesterol; the albumin level was also analysed. Midazolam in the VLDL fraction was only 0.246 microgram.ml-1, whereas the total plasma concentration averaged 1.101 micrograms.ml-1, and the midazolam content of the LDL plus HDL fractions amounted to 1.771 micrograms.ml-1. Albumin in these lipoprotein fractions was just as unequally distributed. A lipid infusion resulted in a significant elevation of total triglycerides from 157 to 221 mg.dl-1 and VLDL-triglycerides from 77 to 155 mg.dl-1. The triglyceride content of the LDL plus HDL fraction rose from 102 to 139 mg.dl-1. At the same time the midazolam concentration in unfractionated plasma and in the VLDL and the LDL + HDL fractions decreased to 0.899 microgram.ml-1, 0.130 micrograms.ml-1, and 1.265 micrograms.ml-1, respectively. Cholesterol and albumin concentrations were not affected. The data show for the first time that a significant increase in plasma triglycerides during an intravenous lipid infusion does not result in accumulation of midazolam in lipoproteins, probably because albumin binding of the drug is very strong. The lack of midazolam trapping is important with respect to the safety of concurrent use of lipophilic drugs and intravenous lipid infusions.

Adult↗
PubMed1992

Measurement of drug compliance by continuous electronic monitoring: a pilot study in elderly patients discharged from hospital.

OBJECTIVE: A pilot study to assess patient compliance with medication by using a new measurement technique, continuous electronic monitoring. DESIGN: Survey. Compliance monitors were provided to eligible patients at discharge from the hospital to measure drug intake behavior prospectively for a period of 3 weeks. SETTING: Ambulant patient care after discharge from a geriatric hospital, Krankenhaus Bethanien, which is affiliated with the University Clinic, Heidelberg. PATIENTS: A consecutive convenience sample of 18 independently living elderly patients (median age 76 years) completed the study. The patients were on maintenance therapy with cardiac glycosides and/or potassium-sparing diuretics prescribed to be taken once daily. INTERVENTION: The monitoring method provides information about patients' real timing of drug use by continuously recording date and time of openings and closings of the medication containers (monitors). In addition to a standard measure, the percentage of prescribed doses taken, information about regularity of drug use is obtained. RESULTS: Compliance, percentage of prescribed doses taken, was remarkably variable; it ranged from 24% to 100%, 95% CI: 62%-84%. Mean compliance declined from the first to the third week after discharge, 85% vs 69%, 95% CI: 74%-95% and 56%-81%, respectively (P < 0.05). Omissions of doses, the predominant pattern of non-compliance, were observed in 17 of 18 patients. Regularity of dose timing, as defined by the number of interdose intervals within 24 h +/- 15%, varied from 10% to 100%, 95% CI: 46%-76%. CONCLUSIONS: Continuous electronic monitoring revealed highly variable compliance in patients prescribed maintenance therapy. Even with a once-daily regimen, persistent and high compliance cannot be assumed. The monitoring technique may be of great value to research and, possibly, to practical therapeutic management.

Aged↗
PubMed1992

Non-oral etiologies of oral malodor and altered chemosensation.

A number of non-oral causes for oral malodor have been discussed. Several well documented etiologies for non-oral malodor include renal failure, cirrhosis of the liver, and diabetes mellitus. Each of these conditions has been examined using analytical instrumentation. In addition there appear to be several other metabolic conditions involving enzymatic and transport anomalies (such as trimethylaminuria) which lead to the systemic production of volatile malodors that manifest themselves as halitosis and/or altered chemoreception. Our studies include patients who have been referred to us after being examined by numerous clinical specialists with no identification or relief from their problem. This is due in part to the intermittent nature of many of these problems as well as an apparent lack of knowledge concerning many of these metabolic problems and their relation to oral symptoms.

Acetoin↗
PubMed1992

[Mycotic aneurysm of the iliac artery caused by Salmonella infection. A case report].

Localized extra-intestinal manifestations of salmonella infections are rare, but will be encountered more frequently due to the increasing number of salmonellosis in recent years. We report a 55-year-old patient with an infected aneurysm of the right iliac artery caused by S. enteritidis. Vascular surgery with resection of the aneurysm, debridement, reconstruction with direct anastomosis of the mobilized artery was successful in combination with antibiotic therapy, but the course was complicated by a deep venous thrombosis, ileus and abdominal wall hemorrhage. A short review of the pertinent literature follows the case report, with emphasis on the surgical aspects. Autogenous reconstruction is considered the surgical treatment of choice for infected iliac aneurysms.

Aneurysm, Infected↗
PubMed1991

Sigma receptor ligand N,N'-di-(ortho-tolyl)guanidine inhibits release of acetylcholine in the guinea pig ileum.

The inhibition of stimulated contractions of the guinea pig ileum longitudinal muscle/myenteric plexus preparation by sigma receptor ligands has been previously described. In this study, the stimulated release of [3H]acetylcholine from cholinergic nerve terminals in this same preparation was monitored in the presence and absence of sigma receptor ligands. N,N'-Di-(orthotolyl)guanidine (DTG) and other compounds selective for the sigma receptor inhibited stimulated [3H]acetylcholine release. These results suggest that their inhibition of stimulated contractions in this preparation was mediated by inhibition of acetylcholine release.

Acetylcholine↗
PubMed1991

[Development of a spacer for inhaled corticosteroid. Evaluation using flunisolide metered dose aerosol].

As optimal therapy with inhaled steroids invariably demands the use of a spacer (Nolte, 1989), a specific inhalation device adapted to flunisolide metered dose inhaler was required. For this purpose, various inhalation chambers varying in geometry and material were investigated. The decisive criterion was the percentage of inhalable particles (diameter less than 8 microns) dispensed by the device. Separation of larger particles was possible in spacers with a relatively small volume. The highest dispensing rate being achieved with conical or pear-shaped inhalation chambers. An increase in spacer volume beyond 320 ml failed to improve the percentage of inhalable active substance. The results demonstrate that the spacer, dimensioned to the smallest possible volume, specially developed for Inhacort MDI has optimal dispensing characteristics for flunisolide.

Adrenal Cortex Hormones↗
PubMed1991

Dosage frequency and drug-compliance behaviour--a comparative study on compliance with a medication to be taken twice or four times daily.

The objective of the study was to investigate patient compliance with two different dosage regimens. Ethinyloestradiol 80 micrograms daily was prescribed to 35 female outpatients to be taken as 20 micrograms four times daily or 40 micrograms twice daily for 7 days. It was given to standardise cervical mucus before a sperm cervical mucus penetration-test (SCMPT) was performed. Sixty-five patients with primary infertility (mean age 29.9 y) completed the study. Compliance was assessed by microprocessor-based compliance monitoring. Besides compliance (percentage of prescribed doses taken), the adherence of the patients to the dosage schedule was evaluated--'regimen compliance'. The latter parameter of drug intake behaviour was calculated by the number of days in which 2 (BID) or 4 openings (QID) were recorded by the electronic monitor. As a third parameter, the deviation from the prescribed dosing intervals, i.e. 12 or 6 h, was also determined. Partial compliance was the predominant finding and only 9 patients (13.8%) were over-compliant. Mean compliance was 75.7% in all 65 patients as a group, range 7.1 to 143%. The mean compliance with the QID regimen was 67% compared to 85% with the BID regimen. 'Regimen compliance', the percentage of doses taken on schedule, was 36% and 63% for the QID and BID regimens, respectively. Drug-intake behaviour was more erratic with the QID than the BID regimen, as indicated by the 55% of opening intervals recorded which exceeded the range of 3-9 h (mean: 6 h), compared to only 19% exceeding 6-18 h intervals (mean: 12 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Biological assays for irritant, tumor-initiating and -promoting activities. III. Computer-assisted management and validation of biodata generated by standardized initiation/promotion protocols in skin of mice.

The initiation/promotion standard protocol 28 (protocol 28), developed and used previously as an experimental model to verify the cancerogenic process of initiation/promotion in mouse skin, was revised in three aspects: (a) statistically it was shown sufficient to use, per promoter dose group, 16 colony-outbred female NMRI mice: (b) by weekly individual records of tumor response (and health status) of each mouse in a dose group, cumulative tumor incidences (and mean and extreme body weights) are determined; from these data the collective records (tumor response, health status), the only data accessible from protocol 28, may be generated in addition; (c) the details of dose groups and all data on tumor response and health status are processed by computer using the program package PAPILLOM. The latter was developed specifically for this purpose, is written in the programming language APL and designed for easy handling by staff of animal laboratories. The program package calculates, from the individual records per promoter dose group, cumulative tumor incidences (and survival data) with confidence limits for any one exposure time, and the package may be linked to programs for statistical validations. In addition, from the collective records it calculates the tumor rates, tumor yields and survival rates for any one exposure time. These data, obtained by either of the standard protocols (16 or 28), are fully comparable. For pure compounds they may be used to calculate semiquantitative tumor-promoting potencies. These values for more than 80 polyfunctional diterpenes of the tigliane, ingenane and daphnane type, scattered in or calculated from previous papers, together with their irritancies, were compiled. Within recent years, computer-assisted standard protocol 16 has been used to handle and evaluate about 1000 promoter dose groups. Protocol 16 allows one to extract and utilize more and better toxicological information on tumor response and health status from any one dose group, utilizing significantly fewer experimental animals than required by protocol 28. Thus, the computer-assisted standard protocol 16 optimizes the utility of the experimental model of mouse skin for the amount, quality and management of experimental data as well as for the requirements of animal protection.

Animals↗
PubMed1991

Recirculating, retrograde heart perfusion according to Langendorff as a tool in the evaluation of drug-induced cardiomyopathy: effects of a high lipid diet.

A recirculating, retrograde heart perfusion according to Langendorff is described as a method for the evaluation of cardiomyopathy as an untoward side effect of a high lipid diet (addition of 10% and 25% corn oil to rat maintenance feed) in female rats. The use of glucose (5 mM) or palmitate (0.5 mM/0.1 mM BSA) as substrates during a 2-h perfusion period, and their effects on heart metabolism of control-, LL- and HL-diet fed animals were evaluated. Substrate uptake, LDH release and adenine nucleotides, creatine phosphate, creatine, lactate, pyruvate, glucose-6-phosphate, glycogen, triglyceride and phospholipid content were determined in heart tissue.

Animals↗
PubMed1991

Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukaemia.

The immunophenotype (a), ultrastructural features (b) and cell kinetics (c) of circulating megakaryoblasts have been studied in two cases of pure megakaryoblastic and one case of mixed (myeloblastic, megakaryoblastic) cell proliferation in chronic myeloid leukaemia (CML). (a) The blast cells showed early megakaryocyte differentiation antigen (HLA-DR), platelet specific GpIIIa (CD61) and GpIIb-IIIa (CD41) antigens in different percentages. (b) The megakaryoblasts were recognized by the presence of platelet GpIIIa (CD61) demonstrated by an immunoelectron microscopic method. The labelled cells were "lymphocyte-like" megakaryoblasts and cells with features of cytoplasmic maturation (demarcation membranes, alpha granules and vacuoles). (c) Cellular DNA content of the megakaryoblasts was measured by propidium iodide (PI) staining of cells expressing platelet GpIIIa (CD61). Flow cytometric (FC) DNA analysis revealed no aneuploidy and high ploidy (greater than 4N) cell population. In the two cases of pure megakaryoblastic proliferation a high percentage of the megakaryoblasts were in the S-phase, while the non-megakaryoblastic cell fraction showed no elevated S-phase compartment. It is concluded that in CML the circulating megakaryoblasts (1) have a nuclear maturation arrest and accumulation at the level of tetraploid DNA content, (2) surface antigen expression and cytoplasmic organelles show a tendency to mature and (3) in pure megakaryoblastic proliferation the myeloid cells are not in the cell compartment showing high proliferation.

Antigens, CD↗
PubMed1991

First dose hypotension with enalapril and prazosin in congestive heart failure.

Since the introduction of angiotensin converting enzyme inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the angiotensin converting enzyme inhibitor enalapril a multicenter, open, randomized, prazosin-controlled trial was designed comparing the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 mg prazosin. Subjects were 1210 inpatients with New York Heart Association functional class (I)/II and III who were not adequately compensated with digitalis and/or diuretics. In the group receiving enalapril, 3 patients (0.5%) experienced severe hypotension on day 1 and 28 patients (4.7%) moderate hypotension. In those given prazosin, 15 patients (2.6%) experienced severe hypotension and 60 patients (10.3%) moderate hypotension. The difference is statistically significant (P less than or equal to 0.000012). All patients recovered. It was concluded that treatment of patients suffering from congestive heart failure New York Heart Association functional class (I)/II or III with enalapril is comparably well tolerated.

Aged↗
PubMed1991

Radiosynthesis of sigma receptor ligands for positron emission tomography: 11C- and 18F-labeled guanidines.

A series of analogues of the potent and selective sigma receptor ligand 1,3-ditolylguanidine (DTG) were synthesized and demonstrated to have high affinity for the sigma receptor as measured by in vitro [3H]DTG displacement studies using guinea pig brain tissue. Three of these 1-aryl-3-(1-adamantyl)guanidines were radiolabeled--two with carbon-11 and one with fluorine-18. Radiochemical yields and specific activities were sufficient for these radiotracers to be used in positron emission tomography imaging of the haloperidol-sensitive sigma receptor.

Animals↗
PubMed1991

Isolation and characterization of opioid peptides from rabbit cerebellum.

The rabbit cerebellum has been shown to contain significant quantities of opioid receptors consisting of both mu- and kappa-subtypes. To determine the nature of the endogenous opioid ligands in this tissue, extracts from rabbit cerebellum were separated by various chromatography techniques and fractions were assayed initially for opioid peptides with a radioimmunoassay capable of detecting all peptides with an amino-terminal Tyr-Gly-Gly-Phe sequence. This sequence is common to all mammalian opioid peptides and is critical for recognition by all known opioid receptors. Each of the three immunoreactive opioid peptide peaks detected was purified to homogeneity and subjected to amino acid composition and sequence analysis. One peak was analyzed further by mass spectrometry. This identified the major opioid peptides in the cerebellum as [Met5]enkephalin, [Leu5]enkephalin, and heptapeptide [Met5]enkephalyl-Arg6-Phe7. The comprehensiveness of this initial detection scheme in identifying biologically active opioid peptides was substantiated through subsequent analysis. Using specific radioimmunoassays for representative opioid peptides of the three opioid systems currently known, no other peptides of either the proenkephalin, proopiomelanocortin, or prodynorphin series were detected in any appreciable amounts. Collectively, these results are consistent with the position that rabbit cerebellar opioids are derived from proenkephalin. However, given that no appreciable quantities of either [Met5]enkephalyl-Arg6-Arg7-Val8-NH2 (metorphamide) or [Met5]enkephalyl-Arg6-Gly7-Leu8 were detected suggests that rabbit proenkephalin may have a slightly altered sequence and/or is differentially processed relative to other mammalian species studied.

Amino Acid Sequence↗
PubMed1991

Plasticity of intercellular junctions of rat liver lymph capillaries in relation to functional conditions.

The junctions between endothelial cells in lymph capillaries may have different degrees of complexity and have been classified as three types: "end to end" (EE), "overlapping" (OVL), and "interdigitating" (ID). Under normal conditions, the more complex junction types (ID and OVL) are more frequent than the simple type (EE). The authors' hypothesis was that not only the folds and digitations of the endothelial profile but also the prevalence of the more complex junction types under normal conditions impart plasticity and distensibility to the endothelial wall. To verify this hypothesis they performed a transmission electron microscope study of lymph capillaries of rat liver under normal conditions and after treatment with histamine, which induces natural filling of lymph vessels. In lymph capillaries of histamine-treated animals they found a significant prevalence of the simplest (EE) junctions (50 +/- 5% versus 20 +/- 4% in controls, p less than 0.001) over the more complex OVL (28 +/- 4% versus 57 +/- 4% in controls, p less than 0.001) and ID junctions (12 +/- 3% versus 19 +/- 4% in controls, NS). The overall trend in junction types showed a highly significant shift toward the simpler types after histamine treatment (p less than .0001). There was also a significant reduction in the mean length of adjoining cell borders from 1.5 +/- 0.1 m in histamine-treated animals (p less than 0.001). These findings indicate the participation of the junctions in variations in capacity of lymph vessels in rat liver. This mobilization of cell junctions may also favor the drainage of interstitial fluids into the absorbing lymph vessels.

Animals↗
PubMed1991

N-methyl-D-aspartate receptor-mediated contractions of the guinea pig ileum longitudinal muscle/myenteric plexus preparation: modulation by phencyclidine and glycine receptors.

Glutamate evoked contractions of the longitudinal muscle/myenteric plexus (LMMP) preparation by an action at N-methyl-D-aspartate (NMDA) receptors. Other agonists at the NMDA recognition site, but not quisquilate or kainate, also contracted the LMMP, and glutamate-evoked contractions were competitively inhibited by selective NMDA receptor antagonists. Glutamate-evoked contractions were noncompetitively inhibited by MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine moleate], phencyclidine (PCP) and other compounds that bind to the PCP receptor, which is a binding site on the NMDA channel complex. Their potencies for this effect were highly correlated with their affinities for the PCP receptor. Glycine significantly shifted the glutamate concentration-response curve to the left. Glycine site antagonists caused a glycine-sensitive, noncompetitive inhibition of glutamate-evoked contractions, and their potencies for this effect were highly correlated with their affinities for the glycine binding site of the NMDA channel complex. Mg++ and Zn++ also noncompetitively inhibited glutamate-evoked contractions. The modulatory effects of glycine, Mg++, Zn++ and PCP receptor ligands were specific to glutamate-evoked contractions. MK-801 was highly selective for inhibition of glutamate-evoked contractions; MK-801 also inhibited nicotinic responses at a 500-fold lower potency. Two novel compounds are described that bind to the PCP receptor with high affinity and selectively inhibit glutamate-evoked contractions in the LMMP.

Animals↗