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Biomedical subjects

D Becker

Publications and source records attributed to D Becker.

At least 181 records · Page 10Linked to original sources

Indications for a more aggressive disease process in newly diagnosed insulin-dependent diabetic children in northern than in southern Europe.

Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3-4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden ('North') and Pittsburgh were younger (< 10 years old) at diagnosis compared with those in the other clinics in Europe (P < 0.05 versus P < 0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (< 8 days; P < 0.001) and higher blood glucose (> 20 mmol/l; P < 0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%; P < 0.01) or in France (70%; P < 0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (< 0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.

Adolescent↗

[Clinical aspects and therapy of early lepromatous leprosy with a case example].

Taking into account the increase in worldwide human migration, leprosy is of growing importance in the differential diagnosis of dermatological diseases encountered in Central Europe. We report on the case of a young man from Ghana who developed hypopigmented maculae and plaques on his trunk and proximal limbs. The diagnosis of lepromatous leprosy could be made in consideration of the histological pattern of infiltrating leucocytes and detection of numerous acid-fast mycobacteria on skin biopsy. The results of the physical examination as well as routine laboratory and immunological parameters were consistent with this form of leprosy. Due to glucose-6-phosphate-dehydrogenase deficiency, treatment with dapsone was contraindicated. With high-dose rifampicin and clofazimine therapy, the skin changes cleared over the course of 11 months following a leprosy reaction type II (erythema nodosum leprosum) that developed during a phase of discontinued therapy due to low patient compliance.

Adult↗

Fertile transgenic wheat from microprojectile bombardment of scutellar tissue.

A reproducible transformation system for hexaploid wheat was developed based on particle bombardment of scutellar tissue of immature embryos. Particle bombardment was carried out using a PDS 1000/He gun. Plant material was bombarded with the plasmid pDB1 containing the beta-glucuronidase gene (uidA) under the control of the actin-1 promoter of rice, and the selectable marker gene bar (phosphinothricin acetyltransferase) under the control of the CaMV 35S promoter. Selection was carried out using the herbicide Basta (Glufosinate-ammonium). From a total number of 1050 bombarded immature embryos, in seven independent transformation experiments, 59 plants could be regenerated. Putative transformants were screened for enzyme activity by the histochemical GUS assay using cut leaf material and by spraying the whole plants with an aqueous solution of the herbicide Basta. Twelve regenerants survived Basta spraying and showed GUS-activity. Southern-blot analysis indicated the presence of introduced foreign genes in the genomic DNA of the transformants and both marker genes were present in all plants analysed. To date, four plants have been grown to maturity and set seed. Histochemically stained pollen grains showed a 1:1 segregation of the uidA gene in all plants tested. A 3:1 segregation of the introduced genes was demonstrated by enzyme activity tests and Southern blot analysis of R1 plants.

Acetyltransferases↗

Transgenic cereal (tritordeum) plants obtained at high efficiency by microprojectile bombardment of inflorescence tissue.

Transgenic cereal plants expressing the beta-glucuronidase (uidA) and neomycin phosphotransferase (neo) genes were obtained via microprojectile bombardment of immature inflorescence tissue of tritordeum (the fertile Hordeum x Triticum amphiploid, HchHchAABB). A total of 17 independent transgenic plants were recovered from 32 bombardments (on average four inflorescences per shot). Of the bombardment and culture parameters tested, explant preculture had the most influence on stable transformation frequency. The uidA and neo genes were supplied on two separate plasmids (co-transformation) and 88% of the transgenic plants recovered expressed both genes. Southern analysis confirmed the results of histochemical GUS and NPT II assays. Transgenic plants were grown to maturity and flowered and set seed. Pollen from four T0 GUS+ plants analysed showed GUS activity and T1 seedlings derived from one of the transgenic plants showed a segregation of 2.75:1 (GUS+:GUS-) for uidA gene activity.

Culture Techniques↗

[Follow-up of vena cava filters with color Doppler ultrasound].

In 49 patients, colour-coded Duplex sonography was performed after implantation of a Greenfield caval filter. A plain film radiograph of the abdomen was taken additionally. The examination could be assessed free of artifacts in the longitudinal and transverse section in a total of 41 patients (84%). The procedure facilitates not only a diagnosis of thrombotic changes in the vena cava but can also display the topographical position of the filter and the venous flow. Caval thrombosis was verified in 5 patients. In 7 cases there was a decentral position of the filter apex with tilting. The penetration of filter struts through the vein wall eluded sonographic diagnosis as did morphological changes to the filter (e.g. filter fracture). In combination with the plain film radiograph, colour-coded Duplex sonography can replace cavography or computed tomography in the investigation of position and venous flow.

Adult↗

Influence of oxygen on the repair of direct radiation damage to DNA by thiols in model systems.

Here the reactions of thiols with DNA primary radical intermediates formed after gamma-irradiation of frozen (77 K) anoxic and oxic solutions of DNA/thiol mixtures are investigated. Through analysis of the experimental composite spectra at each annealing temperature, the relative concentrations of individual radicals present are estimated and reaction sequences inferred. In all samples the primary DNA radical anions and cations (DNA.+ and DNA.-) are suggested to be the predominant radicals at low temperatures. In anoxic samples, TH. (5,6-dihydrothym-5-yl radical), .RSSR.- and, in glutathione samples, .GSH [gamma-glu-NHC(CH2SH)CO-gly] radicals are observed as the temperature is increased. The presence of oxygen efficiently suppresses the formation of RSSR.- and .GSH; instead, in oxic samples, O2.-, DNAOO., RSOO. and RSO. are observed at higher temperatures. The photolytic conversion of RSOO. to RSO2. is used to verify the presence of RSOO. in gamma-irradiated DNA/thiol systems and confirm that the computer analysis employed yields reasonable estimates of the relative DNAOO. and RSOO. concentrations. From the relative concentrations of radicals present, it is clear that the radicals observed at higher temperatures originate from the radical reactions of the primary DNA.+ and DNA.- radicals. Based on the reaction sequences inferred and previous work with thiols alone, it is concluded that TH., DNAOO. and RSOO. (in part) originate largely with DNA.-, whereas RSSR.-, .GSH and RSOO. (in part) originate largely with DNA.+. The possible roles of DNAOO., RSOO., RSO., RSO2. and .OOGSH in the chemical oxygen enhancement effect at biologically realistic temperatures are discussed.

Animals↗

Isolation and analysis of novel human melanocyte-specific cDNA clones.

Human melanoma represents a neurocrest-derived malignancy, occurring in 10% of cases within the setting of a familial predisposition and in 90% of cases with sporadic onset. It is estimated that more than 85% of familial melanomas and about 40% of sporadic melanomas arise from melanocytic precursor lesions. In an attempt to isolate genes that may play a role in human melanocytic progression, we applied subtractive cDNA hybridization, involving repeated rounds of subtraction. This was followed by amplification of the remaining enriched cDNAs, which led to the isolation of several human melanocyte-enriched cDNA clones. Evidence is provided suggesting that these melanocyte-enriched cDNA probes may be derived from novel genes whose expression is significantly up-regulated in normal human melanocytes compared to early and advanced-stage human melanomas.

Cells, Cultured↗

Psychopathology and cognitive decline in dementia.

This study investigated the correlation between the degree and quality of cognitive impairment and the presence and degree of severity of psychopathology. Sixty-four demented outpatients were rated for cognition by the Mental Status Questionnaire and for psychopathology by the BEHAVE-AD Reisberg questionnaire. A statistical analysis of the correlations between the cognitive and psychopathological parameters was performed. The study indicated a high rate of psychopathology (as high as 83% of the patients). No significant correlation was found between the cognitive grading score and the presence of psychopathology, except in the space of declined spatial orientation and the occurrence of hallucinations. Psychopathology is a common phenomenon occurring in the course of dementia in the form of Alzheimer's disease or multi-infarct dementia. There is a certain increase in the degree of psychopathology that correlated with cognitive impairment. The high correlation between impaired spatial orientation and the presence of hallucinations seems to point to a common neuropathological substrate.

Aged↗

Chronicle of an announced death (thoughts on mid-adulthood).

Middle age can be considered not as the onset of decline, but as a stage of expansion. There has been very little written in the literature on the developmental stages man can expect to experience during his adult life. The criteria and parameters for identifying the level of maturity have relied on terms extracted from developmental theories of childhood. This article deals with the crucial issues and developmental tasks of middle adulthood and the need to define developmental lines based on clinical and epidemiological investigation. The psychotherapeutic problems involved in treating adults in middle age will be presented, including the counter-transference dilemma. It is the author's belief that middle adulthood is a period of transition which opens up options of change and growth once one has worked through the limitations of age and the awareness of one's own death.

Adaptation, Psychological↗

ESR detection at 77 K of the hydroxyl radical in the hydration layer of gamma-irradiated DNA.

Previous ESR reports of gamma-irradiated DNA at low temperatures have suggested that hydroxyl radicals are not formed in the first hydration layer of DNA. In this report we show that hydroxyl radicals are produced in low yield. Due to the glassy nature of this hydration layer at low temperature, the hydroxyl radical gives a broad ESR resonance which is not easily detected. Low-field ESR spectra of hydroxyl radicals in an irradiated 6 M CsF aqueous glass are shown to be nearly identical to those found in DNA; however, the yields in the aqueous glass (G = 0.087 to 0.13 mumol/J) are found to be greater than those in DNA's first hydration layer (G = 0.035 +/- 0.02 mumol/J). A large kappa value for destruction of the OH in DNA's hydration layer limits the yield of OH at high doses. The yield of H2O2 (which likely results from hydroxyl radical recombinations that occur both during irradiation and upon annealing) is found to 0.0035 mumol/J in the dose range 65 kGy to 195 kGy. The amount of H2O2 formed corresponds to most of that expected from recombination of the OH trapped at 77 K at the equivalent dose. The low yield of trapped OH radicals in the first hydration layer has implications for possible hole transfer to DNA.

DNA↗

The influence of hydration on the absolute yields of primary free radicals in gamma-irradiated DNA at 77 K. II. Individual radical yields.

In this report we present an electron spin resonance (ESR) investigation of the yields of the individual free radicals formed in gamma-irradiated frozen DNA as a function of hydration and dose at 77 K. Analysis of the ESR spectra taken at low hydration shows that the ion radical composition remains nearly constant with dose and that few secondary radicals are formed even at high doses (above about 50 kGy). For fully hydrated samples, the radical composition changes dramatically with dose. Thymine anion radical (T-.) is found in abundance at low doses but nearly disappears at higher doses, with a corresponding increase in the N-3 deuterated cytosine anion radical (CD.). Guanine cation radical (G+.) decreases at high doses, with a concomitant increase in secondary radical species (S.). Analysis of the dose-response data for G values (the yields in microM/J), k values (the destruction constants) and k' values (a new constant that characterizes the change in G with dose) was performed for each of the DNA base free radicals present at 77 K. The G value for each of the base radicals increases with the hydration level. The k values for CD. and G+. increase slightly with hydration; however, that of T-. increases substantially. Destruction constants for neutral radicals such as TH. and CD. are found to be substantially smaller than those for ion radicals and provide an indication of the radical charge state. A negative k' value for T-. and a positive k' value for CD. are explained in terms of radiation effects that result in the formation of a deuterated cytosine base, i.e., C(N3)D+, which greatly increases cytosine's electron affinity. The ratio of anion radical to cation radical concentrations is found to be about 1.6 and is invariant with hydration. A speculation on the imbalance based on hole-hole combinations in spurs is presented.

DNA↗

Synthesis and utilization of saccharide intermediates.

A new method has been developed for preparation of partially pivaloylated saccharides in one step from readily available starting materials. These intermediates were used in the synthesis of disaccharides and a glucosteroid.

Carbohydrate Conformation↗

Evidence for N-linked glycosylation in Toxoplasma gondii.

In this paper we report experiments demonstrating the presence of N-linked oligosaccharide structures in Toxoplasma gondii tachyzoites, providing the first direct biochemical evidence that this sporozoan parasite is capable of synthesizing N-linked glycans. The tachyzoite surface glycoprotein gp23 was metabolically labelled with [3H]glucosamine and [3H]mannose. Gel-filtration chromatography on Bio-Gel P4 columns produced four radiolabelled N-linked glycopeptides which were sensitive to peptidase-N-glycanase F, but resistant to endoglycosidases H and F. Using chemical analysis and exoglycosidase digestions followed by Dionex-high-pH anion-exchange chromatography and size fractionation on Bio-Gel P4 we show that gp23 has N-linked glycans in the hybrid- or complex-type structure composed of N-acetylgalactosamine, N-acetylglucosamine and mannose and devoid of sialic acid and fucose residues. In addition, the sensitivity of glycopeptides from glycoprotein extracts to endoglycosidases H and F revealed the in vivo synthesis of oligomannose-type structures by T. gondii tachyzoites. We have extended these findings by demonstrating the ability of T. gondii microsomes to synthesize in vitro a glucosylated lipid-bound high-mannose structure (Glc3Man9GlcNAc2) that is assumed to be identical with the common precursor for N-glycosylation in eukaryotes.

Amidohydrolases↗

Effects of fenofibrate on angiographically examined coronary atherosclerosis and left ventricular function in hypercholesterolemic patients.

Within the framework of a prospective lipid-lowering intervention study 44 patients were treated over a period of 3 years with a lipid-lowering diet and 200-400 mg fenofibrate daily. The intervention led to statistically significant decreases in total cholesterol (Chol), low density lipoprotein cholesterol (LDL-Chol) and triglycerides levels, and to a significant increase in high density lipoprotein cholesterol (HDL-Chol) levels. Despite intervention, in 8 patients the HDL-Chol levels decreased by up to 20 mg/dl, where these were mainly patients with high initial values. Likewise, the triglycerides of 4 patients whose initial levels were relatively low increased (up to 49 mg/dl) and the LDL-Chol levels of 8 patients whose initial levels were also low increased (up to 49 mg/dl). Only minor success was achieved through the 6-week diet, but this was still slightly significant for Chol and LDL-Chol levels. A total of 21 patients underwent repeat angiography within 3 years for clinical reasons. For the evaluation of the angiographic progress a total of 98 minor and moderate stenoses was measured using digital image processing and automatic contour finding. The change in the angiographic parameters 'percent diameter reduction' (%DR) and 'percent plaque area' (%PA) correlated with on-treatment LDL-Chol levels (%DR change with LDL-Chol: r = 0.67, P = 0.0005; %DR change with Chol: r = 0.61, P = 0.002; %PA change with LDL-Chol: r = 0.40, P = 0.037; %PA change with Chol: r = 0.38, P = 0.044), while for HDL-Chol and triglycerides no influence on the angiographic progress could be demonstrated. On the basis of the reproducibility of the measuring methods the patients were classified in the categories 'regression', 'unchanged' and 'progression'. The patients classified as 'regression' (parameter: %DR change) showed an LDL-Chol mean value of 162 +/- 9 mg/dl, whereas those classified as 'unchanged' or 'progression' showed values of 189 +/- 25 mg/dl and 199 +/- 21 mg/dl, respectively (P = 0.014). A negative correlation appeared between the angiographic progress parameters and the initial degree of stenosis. The left ventricular ejection fraction in the second angiography showed relationships to lipoprotein levels and angiographic progress parameters.

Coronary Angiography↗

Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.

To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.

Alleles↗