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Biomedical subjects

D Becker

Publications and source records attributed to D Becker.

At least 217 records · Page 12Linked to original sources
PubMed1992

Diabetic ketoacidosis in cystic fibrosis.

OBJECTIVE: To differentiate the insulin-dependent glucose intolerance associated with cystic fibrosis from type I diabetes mellitus in patients with cystic fibrosis. DESIGN: Patient report. SETTING: Tertiary care referral center. PARTICIPANT: An 11-year-old boy with cystic fibrosis who developed diabetic ketoacidosis. MEASUREMENT/MAIN RESULT: Biochemical, immunologic, and molecular techniques were used to support the sporadic association of type I diabetes mellitus in a patient with cystic fibrosis. Cystic fibrosis was confirmed by sweat test and further supported by the demonstration of a heterozygous deletion of the F508 locus. Evidence for the diagnosis of type I diabetes mellitus was developed from the clinical presentation of diabetic ketoacidosis with hyperglycemia, ketonemia, and ketonuria. Immunologic evidence included the demonstration of anti-insulin antibodies. The demonstration of homozygous absence of aspartic acid at position 57 of the HLA DQ-beta chain placed this child at high risk of type I diabetes mellitus. CONCLUSION: The clinical presentation and the presence of immunologic and genetic markers characteristic of type I diabetes mellitus supports the concordance of cystic fibrosis and type I diabetes mellitus in this patient.

Cystic Fibrosis↗
PubMed1992

Morbidity among municipal waste incinerator workers.

Incinerator workers are exposed to many toxic compounds, most notably heavy metals. We evaluated medical and exposure monitoring data of an actively employed cohort of Philadelphia incinerator workers following an Agency for Toxic Substances and Disease Registry site survey and National Institute for Occupational Safety and Health (NIOSH) health hazard evaluation (HHE). Of the many airborne samples taken by NIOSH, only four of the personal breathing zone samples were above OSHA or ACGIH standards: one for lead, one for phosphorous, and two for total particulates. Because samples were taken during limited operations (only one of the two incinerators were operating), the results may underestimate historical exposures at this site. We limited our medical analysis to the 86 male workers who participated in the HHE out of the 105 active employees. The 86 employees were divided into potential high and low exposure groups based on a work site analysis done by an independent industrial hygienist. Eight individuals had at least one elevated biological index indicating exposure to a heavy metal. These elevations, however, were unrelated to the workers' exposure categories. Furthermore, no clinically significant mean blood or serum measurements were noted. Thirty-four percent of the workers had evidence of hypertension which increased the risk of significant proteinuria. Neither hypertension nor proteinuria were related to exposure group. Changes in pulmonary function related only to smoking status. Although there was some evidence of an increased risk of exposure to products of incinerator waste, we could not relate the few elevated biological tests to exposure classification. Additional studies are needed to assess the potential health effects of municipal waste incinerator by-products.

Adult↗
PubMed1992

New plant binary vectors with selectable markers located proximal to the left T-DNA border.

Five new binary vectors have been constructed which have the following features: (1) different plant selectable markers including neomycin phosphotransferase (nptII), hygromycin phosphotransferase (hpt), dihydrofolate reductase (dhfr), phosphinothricin acetyl transferase (bar), and bleomycin resistance (ble); (2) selectable markers are located near the T-DNA left border and; (3) selectable marker and beta-glucuronidase (uidA) reporter genes are divergently organized for efficient expression, and can easily be removed or replaced as needed.

Agrobacterium tumefaciens↗
PubMed1992

Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal-strength antacid.

This study tested the hypothesis that (alginic) acid may have a preferential effect on reflux in the upright position. We evaluated the effect of a compound containing alginic acid plus antacid (extra-strength Gaviscon) versus active control antacid with equal acid-neutralizing capacity on intraesophageal acid exposure following a high-fat meal (61% fat: sausage, egg, and biscuit). In random sequence, each of the 10 volunteers received either alginic acid-antacid or control antacid immediately following and 1, 2, and 3 hr after the meal. The sequence was repeated for both test drugs in the supine and upright positions with constant pH monitoring. Alginic acid-antacid significantly decreased postprandial reflux in the upright position compared to an equal amount of antacid. This effect did not occur in the supine position. These findings support the hypothesis that alginic acid is primarily effective in the upright position and the clinical observations of the effectiveness of alginic acid on daytime reflux symptoms.

Alginates↗
PubMed1992

Contact allergens modulate the expression of MHC class II molecules on murine epidermal Langerhans cells by endocytotic mechanisms.

MHC class II molecules play an important role during the sensitization phase of allergic contact dermatitis. To study the influence of contact allergens on the expression of these molecules by murine epidermal Langerhans cells (LC), we performed a flow-cytofluorometric analysis of the Ia-antigen expression after in vivo application of contact allergens. A distinct decrease in the Ia-antigen expression of the entire LC population was noticed 3 h after in vivo application of the contact allergen 2,4-dinitrofluorobenzene (DNFB). This decrease was transient and balanced 24 h after in vivo application of DNFB. A downregulation was also detectable after in vivo application of the contact allergens 1-chloro-2,4-dinitrobenzene (DNCB), oxazolone, K2Cr2O7, 2,4,6-trinitrochlorobenzene (TNCB), and toxic concentrations of the irritant compound sodium dodecyl sulfate (SDS). In vitro studies showed that freshly prepared as well as 3-d cultured LC downregulated their Ia-antigen expression in the presence of DNFB, which was used as a model compound. This decrease was not inhibited by the MHC class II molecule transport-inhibitor brefeldin A nor by the ionophore monensin. The inhibition of receptor-mediated endocytosis with hypertonic media (0.45 M sucrose) abolished the DNFB-mediated downregulation of Ia-antigen expression. An accelerated clearance of cell-surface-expressed antibody-labeled IA molecules was detectable in the presence of DNFB. Internalization studies carried out with peroxidase-labeled anti-IA-antibody complexes showed remarkable alterations in the intracellular distribution of endocytosed material under the influence of subtoxic concentrations of DNFB, DNCB, K2Cr2O7, and TNCB. The irritant substance sodium dodecyl sulfate (SDS) influenced the intracellular distribution pattern of internalized material only when used in toxic concentrations. An augmented participation of MHC class II molecules in endocytotic processes is mediated by reactive substances like contact allergens and might contribute to the processing and presentation of these compounds.

Allergens↗
PubMed1992

Increased level of intracellular MHC class II molecules in murine Langerhans cells following in vivo and in vitro administration of contact allergens.

Treatment of murine Langerhans cells (LC) with contact allergens results in increased internalization of cell membrane constituents and therefore in depressed cell-surface expression of major histocompatibility complex (MHC) class II molecules during the first hours after haptenization. In this presentation we show that this downregulation of cell-surface-expressed Ia-antigens is accompanied by an augmentation of the intracellular pool of MHC class II molecules. Rat MoAb 2G9 was developed, which recognizes IA and IE molecules of the d-haplotype. This MoAb competes with the murine MoAb MK-D6 for binding sites to IAd-molecules. After blocking the cell-surface-expressed molecules with 2G9 and permeabilizing the cell membranes this allowed us to measure selectively the intracellular amount of IA molecules by double immunofluorescence staining and flow cytometric analysis. Cell-surface expression of IA molecules was found to be depressed but their internal pool was significantly elevated following in vivo treatment with the contact allergens DNFB, DNCB, oxazolone, and K2Cr2O7 for 3 h. In vitro culture of freshly prepared LC in the presence of 1 microgram/ml DNFB yielded similar results. Blocking of protein biosynthesis with cycloheximide did not prevent this intracellular class II accumulation. An augmented representation of internalized class II molecules in haptenized LC might play an important role in the presentation of contact allergens.

Administration, Cutaneous↗
PubMed1992

Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation.

Fibroblast growth factor receptor (FGFR-1) is expressed as a single 3.5-kb mRNA transcript in normal human melanocytes and in malignant melanomas as determined upon Northern hybridization to a cDNA clone encoding the membrane-spanning form of the human FGFR-1. Polyclonal antisera directed against the chicken FGFR recognized a 145-kDa protein in primary and metastatic melanomas. Antisense oligodeoxynucleotides targeted against the translation start site and a splice donor-acceptor site of human FGFR-1, in addition to inhibiting the proliferation of normal human melanocytes and malignant melanomas, caused extensive dendrite formation and severe disruption of cell-cell contact--morphological changes that were not observed upon inhibition of the genes encoding basic fibroblast growth factor (bFGF) and retinoic acid-alpha receptor. Thus, unlike in the case of the ligand bFGF, expression of the FGFR-1 may represent a requisite to prevent human melanocytes and malignant melanomas from undergoing (terminal) differentiation.

Base Sequence↗
PubMed1992

Radiation-induced DNA damage as a function of hydration. I. Release of unaltered bases.

The release of unaltered bases from irradiated DNA, hydrated between 2.5 and 32.7 mol of water per mole of nucleotide (gamma), was investigated using HPLC. The objective of this study was to elucidate the yield of the four DNA bases as a function of dose, extent of hydration, and the presence or absence of oxygen. The increase in the yield of radiation-induced free bases was linear with dose up to 90 kGy, except for the DNA with gamma = 2.5, for which the increase was linear only to 10 kGy. The yield of free bases as a function of gamma was not constant in either the absence or the presence of oxygen over the range of hydration examined. For DNA with gamma between 2.5 and 15, the yield of free bases was nearly constant under nitrogen, but decreased under oxygen. However, for DNA with gamma greater than 15, the yield increased rapidly under both nitrogen and oxygen. The yield of free bases was described by a model that depended on two factors: 1) a change in the DNA conformation from a mixture of the A and C conformers in vacuum-dried DNA to predominantly the B conformer in the fully hydrated DNA, and 2) the proximity of the water molecules to the DNA. Irradiation of the inner water molecules (gamma less than 15) was less efficient than irradiation of the outer water molecules (gamma greater than 15), by a factor of approximately 3.3, in forming DNA lesions that resulted in the release of an unaltered base. This factor is similar to the previously published relative efficiency of 2.8 with which hydroxyl radicals and base cations induce DNA strand breaks. Our irradiation results are consistent with the hypothesis that the G value for the first 12-15 water molecules of the DNA hydration layer is the same as the G value for the form of DNA to which it is bound (i.e., the pseudo-C or the B form). Thus we suggest that the release of bases originating from irradiation of the hydration water is obtained predominantly: (1) by charge transfer from the direct ionization of the first 12-15 water molecules of the primary hydration layer and (2) by the attack of hydroxyl radicals generated in the outer, more loosely bound water molecules.

Animals↗
PubMed1992

N-linked glycoproteins associated with flagellar scales in a flagellate green alga: characterization of interactions.

Glycoproteins associated with one type of flagellar scale (p-scale) isolated from the flagellate green alga Tetraselmis striata (Prasinophyceae) were shown to bind the mannose-specific lectin GNA (Galanthus nivalis agglutinin). Enzymatic deglycosylation of the glycoproteins with N-glycosidase F led to an electrophoretic mobility shift to lower molecular masses in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and abolished GNA-binding strongly indicating that most of the scale-associated glycoproteins contain asparagine-linked oligosaccharide side chains presumably of the high mannose type. To evaluate the significance of N-linked glycoproteins for scale structure and integrity, p-scales were digested with various proteases or extracted with 8 M urea and their ultrastructure and protein composition determined. The results show that while scale-associated N-linked glycoproteins do not determine the overall structure of the scale subunits (which consist of complex polysaccharides), they are apparently involved in mediating linkages between scale subunits; we have tentatively identified one glycoprotein of Mr 280,000 which may link outer scale subunits to one another. In addition, some scale-associated N-linked glycoproteins may provide connections between the layer of p-scales and the underlying flagellar membrane.

Chlorophyta↗
PubMed1991

Progression and regression of minor coronary arterial narrowings by quantitative angiography after fenofibrate therapy.

To study the effects of fenofibrate, a lipid-lowering medication, on patients with coronary artery disease, 191 minor coronary narrowings in 42 patients with coronary artery disease were analyzed by quantitative coronary angiography using computer-assisted contour detection. Computed parameters were percent diameter reduction and percent plaque area. A prospectively formed intervention group of 21 patients treated with special diet and fenofibrate (200 to 400 mg/day) was checked every 6 weeks with regard to risk factors. After a mean interval of 21 months, coronary angiography was repeated, using the same x-ray system and nearly identical projections. The intervention group was angiographically compared at follow-up with an untreated comparison group, also comprising 21 patients. Both groups had high initial serum cholesterol (mean 311 mg/dl) and low-density lipoprotein (LDL) cholesterol levels (mean 235 mg/dl). Only among the treated patients did lipid levels change significantly: cholesterol, -19%; LDL cholesterol, -20%; high-density lipoprotein cholesterol, +19%; and triglycerides, -30%. At angiographic follow-up, the changes in percent diameter reduction and percent plaque area correlated positively with the mean serum and LDL cholesterol levels of the intervention group. Significant differences were found in the change in percent plaque area between both groups. The intervention subgroup with angiographic regressions (11 patients) had significantly lower serum and LDL cholesterol levels than the intervention subgroup with angiographic progressions (10 patients). These results indicate the beneficial effect of fenofibrate on minor coronary narrowings. Because of its high reproducibility in measuring minor narrowings, quantitative coronary angiography proved to be a suitable method for angiographic follow-up.

Cholesterol↗
PubMed1991

Biochemical properties of MHC class II molecules endogenously synthesized and expressed by mouse Langerhans cells.

The cell surface expression and biosynthesis of Langerhans cells (LC)-derived major histocompatibility complex (MHC) class II molecules from epidermal cells (EC) prepared freshly and cultured for up to 3 days was investigated. Based on the constitutive expression of MHC class II determinants by LC, a panning and magnetic bead selection procedure was employed, yielding 65% and 86% of I-A+ cells, respectively. Phenotypical and cytochemical examinations revealed that the two LC preparations were free of contaminating macrophages as well as B and T cells. Freshly prepared enriched LC were highly efficient in the stimulation of protein antigen-specific T cell clones, while LC purified from short-term cultured EC suspensions proved to be more efficient allogeneic stimulator cells than fresh LC. Comparative analysis of LC obtained from freshly prepared and from short-term-cultured EC preparations indicated an up-regulation of MHC class II determinants during short-term culture. Radioiodination analysis of LC selected by magnetic beads demonstrated prominent class II alpha and beta chain signals with only a minute fraction of invariant chains p35 and p45 being expressed at the cell surface. Unlike class II complexes derived from B cells, those from LC contained invariant chain fragment p20 in association with alpha/beta heterodimers at the plasma membrane. No qualitative differences between freshly isolated and 3-day cultured LC in cell surface expressed MHC class II components were detectable. Metabolic labeling with subsequent two-dimensional electrophoresis revealed distinct features of LC-derived MHC class II molecules with a high proportion of invariant chains in particular gamma and p40 and their extensive sialylation. While fresh and 1-day cultured LC exhibited appreciable levels of newly synthesized class II molecules, a dramatic down-regulation in class II and invariant chain synthesis was measured after 3 days of continuous in vitro culture.

Animals↗
PubMed1991

Scale formation in algae.

Scale biogenesis in algae represents a unique model system to study the transport of secretory macromolecules through the Golgi apparatus (GA) and their exocytosis. The larger scales can be visualized in the light microscope, and thus the kinetics of scale assembly, transport, and secretion can be studied in vivo. In addition, scales are osmiophilic and readily visible in conventional transmission electron microscopy; thus, details of scale assembly and sorting can be studied without invoking immunolabeling techniques. The following are distinctive features of scale biogenesis in algae: 1) transport of scales through the GA-stack occurs by cisternal progression; 2) scale secretion may be very rapid (in some cases a single GA-cisterna leaves the stack every 15-20 s); 3) sorting of different scale types does not occur in the GA, but in a post-GA-compartment. Recent progress in the analysis of scale formation in the green flagellates Tetraselmis and Scherffelia is reviewed.

Animals↗
PubMed1991

Transzygomatic approach to tumours of the parasellar region. Technical note.

A simple transzygomatic approach to the middle fossa centered on the inferior retraction of the temporal muscle hinged on the transected zygomatic arch is described. This approach allows a very low basal exposure of the middle and temporal fossa minimizing the amount of temporal lobe retraction needed to approach intra and extradural lesion in this location. The upper portion of the infratemporal fossa is also reached after removal of the middle fossa skull base. This approach is simple, easily performed, does not require extensive skull base removal, and still offers excellent visualization of the middle fossa and of the upper infratemporal fossa.

Chondrosarcoma↗
PubMed1991

Extended retrolabyrinthine transtentorial approach to petroclival lesions.

In this communication, an extension of the retrolabyrinthine approach that has permitted safe, effective access to the petrous tip and clivus is presented. The basic technique involved complete mastoidectomy, preservation of the middle and inner ear structures, removal of the sigmoid and middle fossa plates, middle and posterior fossa craniotomies, ligation of the superior petrosal sinus, and division of the tentorium. Nine cases that exemplified the versatility of this approach constituted the basis of this paper: 2 cholesteatomas, 2 basilar artery aneurysms, 2 chordomas, and 3 meningiomas. The indications for, and complications of, this method have been discussed.

Adult↗
PubMed1991

[Quantitative coronary angiography: progression and regression of coronary stenoses--an intervention study with fenofibrate].

In order to examine the effect of fenofibrate on coronary narrowings, within the framework of a prospective intervention study, we treated a total of 44 hypercholesterolemic patients (who were in our clinic to undergo PTCA) with diet and fenofibrate (200-400 mg/day) over a period of 3 years. After a mean interval of 21 months, control angiographies were performed in nearly identical projections for 21 patients on clinical grounds. The minor and medium-grade narrowings of the reangiographed patients at the beginning and at the end of the intervention interval were measured by means of digital image processing and automatic contour detection. The measuring parameters were percent diameter reduction (% DR) and percent plaque area (%PA). With regard to their angiographic progression, the 21 reangiographed patients of the intervention group were compared to a comparison group consisting likewise of 21 patients of similar age and sex distribution and persistently high lipid and lipoprotein levels. During the intervention period, the reangiographed patients of the intervention group showed the following changes of the lipid and lipoprotein levels in contrast to the outset values: cholesterol -19 +/- 8%, LDL -20 +/- 14%, HDL +19 +/- 44%, triglycerides -30 +/- 31%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗