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Biomedical subjects

D Becker

Publications and source records attributed to D Becker.

At least 109 records · Page 6Linked to original sources

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

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

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

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

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

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

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

[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

Referral and screening patterns at a clinic for anxiety disorders; implications for the planning of clinical studies.

During a two year period (1988-1990), 302 patients who were referred to our anxiety disorder clinic were evaluated and diagnosed according to a screening procedure which will be described. Of these initial referrals, 171 met a DSM-3-R diagnosis of panic disorder (with or without agorophobia) or generalized anxiety disorder; 81 patients (27% of the initial referrals) participated in a double blind placebo controlled clinical trial with a dropout rate of 12%. The implications for the planning and design of referral and screening strategies at research oriented specialized clinics are discussed.

Adult

[New principles of using biodegradable implants in the treatment of fractures].

So far the operative treatment of bone fractures has resolved itself to immobilisation and bone fragment joining with the help of metal implants such as nails, screws, plates and wires. Once the bone had healed, they had to be removed. This action bears some risk, e.g. extremity disfunction, wound infection. This requires re-hospitalization and increases social cost of the treatment. These reasons gave rise to research on new, biodegradable materials. One of them is "Biofix" manufactures as threads or nails, employed when immobilising bone fragments. Application of "Biofix" allows early rehabilitation. In 200 cases we utilized "Biofix" reinforced with a wire loop, which brought about positive results. In isolated cases there occurred inflammation of the tissues that surrounded the implant during its biodegradation. The surrounded tissues exhibited an acid reaction of pH 3-4. The biodegradable material "Biofix" is sensitive to torsion, which hinders making screws of it, hence the method of using it for nails, wire and thread. This issue is dealt with the Kampere Technical University.

Adult

Basic fibroblast growth factor in human melanoma.

Basic fibroblast growth factor (bFGF) is a major factor contributing to human melanoma cell growth. bFGF is produced constitutively by cells from each stage of the disease, but not by normal melanocytes, although the latter cells are dependent on the factor for growth in vitro. Two lines of evidence suggest that bFGF functions in an autocrine manner in melanoma: (1) inhibition of bFGF activity by bFGF-specific antibodies or antisense sequences suppresses melanoma cell growth in vitro; and (2) retrovirus-mediated transfer of a bFGF cDNA into normal murine melanocytes renders the recipient cell bFGF-independent. Constitutive production of bFGF is not by itself sufficient for the establishment of the transformed phenotype, however, since bFGF-expressing melanocytes are neither immortalized nor tumorigenic in nude mice.

Fibroblast Growth Factor 2

Excision of a Ds-like maize transposable element (Ac delta) in a transient assay in Petunia is enhanced by a truncated coding region of the transposable element Ac.

The excision of a Ds-like transposable element (Ac delta) is mediated in trans by the transposable element Ac or its derivatives in Petunia protoplasts cotransfected with two plasmid DNAs. Excision restores the activity of the beta-glucuronidase (GUS) gene that is otherwise shut off by the presence of Ac delta in its leader sequence. A transient expression assay (histochemical test) is used to detect the beta-glucuronidase activity at the protoplast to detect the beta-glucuronidase activity at the protoplast level. The number of blue-stained protoplasts is a measure of the excision frequency. With Ac delta alone a near-zero background of GUS activity is detected, which is weakly enhanced by the presence, in trans, of either the wild-type Ac or the coding region (ORFa) transcribed from the 2' promoter of Agrobacterium tumefaciens TR-DNA. A strong enhancement is observed when a truncated Ac coding region, also under the control of the 2' promoter, is supplied in trans. The truncated version has ATG10 at codon 103 in frame with ORFa and is preceded by 7 out-of-frame ATGs. The assay is quick and well suited for detection of excision frequencies above the value obtained with the wild-type Ac. The presence of empty donor sites following excision can be demonstrated by PCR amplification and direct sequencing of the appropriate DNA fragment.

Base Sequence

Mild hypoglycemia associated with deterioration of mental efficiency in children with insulin-dependent diabetes mellitus.

To assess the effects of mild hypoglycemia on cognitive functioning in diabetic children, we used an insulin glucose clamp technique to induce and maintain a hypoglycemic state. Eleven patients, 11 to 18 years of age, completed a series of cognitive tests during a baseline euglycemic state (100 mg/dl (5.5 mmol/L] and repeated those measures at the beginning and end of a hypoglycemic plateau (55 to 65 mg/dl (3.1 to 3.6 mmol/L], and again at restoration of euglycemia. At plasma glucose levels of 60 to 65 mg/dl (3.3 to 3.6 mmol/L), a significant decline in mental efficiency was found. This was most apparent on measures of mental "flexibility" (Trial Making Test) and on measures that required planning and decision making, attention to detail, and rapid responding. Moreover, complete recovery of cognitive function was not contemporaneous with restoration of euglycemia, particularly on those tests requiring rapid responding and decision making (choice reaction time). Not all subjects showed evidence of cognitive impairment during hypoglycemia. The very high degree of intersubject variability suggests that, in addition to plasma glucose values, unknown physiologic variables are responsible for triggering cognitive impairments in school-aged youngsters with diabetes during an episode of mild hypoglycemia.

Adolescent

The formation and structure of the sulfoxyl radicals RSO(.), RSOO(.), RSO2(.), and RSO2OO(.) from the reaction of cysteine, glutathione and penicillamine thiyl radicals with molecular oxygen.

This work reports an electron spin resonance study of the reactions of cysteine, glutathione and penicillamine thiyl radicals with molecular oxygen in frozen aqueous solutions at low temperatures. For all three thiols, the thiyl radical, RS., is found to react with oxygen to form the thiol peroxyl radical, RSOO(.). On the absorption of visible light, RSOO(.) photoisomerizes to the sulfonyl radical, RSO2(.), which subsequently reacts with molecular oxygen to form RSO2OO(.), the sulfonyl peroxyl radical. The identities of the sulfonyl and sulfonyl peroxyl radicals were confirmed by their production by a different route, from sulfinic acid. Sulfinyl radicals, RSO(.), are found as the final radical species in the reactions of thiyl radicals and oxygen. Parallel 17O hyperfine couplings (A parallel) are reported for each sulfoxyl radical and a correlation between the spin density on oxygen and the reactivity of the radical is suggested. As a result of this correlation sulfonyl peroxyl radicals are predicted to be far more reactive than thiol peroxyl radicals. We also report molecular orbital calculations on the nature of the spin density distribution and the molecular geometry of the model radicals CH3SO2(.) and CH3SO2OO(.).

Cysteine