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Biomedical subjects

D Becker

Publications and source records attributed to D Becker.

At least 199 records · Page 11Linked to original sources

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↗

Chirality of amino acids of microorganisms used in food biotechnology.

Bacteria of the genera Acetobacter, Bifidobacterium, Brevibacterium, Lactobacillus, Micrococcus, Propionibacterium, and Streptococcus, which are used as so-called starter cultures for the large-scale production of fermented foods and beverages in food biotechnology, have been investigated for the chirality of their amino acids (AA) by gas chromatography (GC). Bacteria were grown in complex media, centrifuged, and washed with 0.85% aqueous NaCl. Aliquots were totally hydrolyzed (6 M HCl, 110 degrees C, 18 h), or extracted with 70% aqueous ethanol in order to isolated free AA. The AA were adsorbed on Dowex WX 8 cation-exchanger, eluted with 4 M ammonia and converted into their N(O)-trifluoro-acetyl(TFA) 2-propyl esters or TFA methyl esters. The AA derivatives were investigated by capillary GC using the chiral stationary phases Chirasil-L-Val, Chirasil-D-Val, and Lipodex E. Besides L-AA, in all bacteria D-amino acids (D-AA) were detected; those in the highest relative amounts were D-Ala and D-Asp (occurring in all bacteria) and, in several cases, D-Glu. Lower, but significant amounts of other D-AA such as D-Ser, D-Pro, D-Val, D-Thr. D-Ile, D-Leu, D-Met, D-Phe, D-Tyr, D-Orn, and D-Lys were also detected in certain bacteria. These findings explain the origin of D-AA found in all fermented foods and drinks produced with the aid of bacterial starter cultures.

Amino Acids↗

Amelioration of secondary ischaemic injury by perfusion with University of Wisconsin (UW) solution in rat skin flaps.

This study was designed to observe the effect of perfusion with University of Wisconsin (UW) preservation solution on skin flap survival following secondary ischaemia caused by venous obstruction in rats. An epigastric flap model was used. Saline-perfused flaps exhibited no significant improvement in survival compared to untreated animals (NS). Skin flaps perfused with UW solution, however, had a significant increase in survival to 40% (8/20) (p < 0.01) when perfused before the onset of primary ischaemia and 30% (p < 0.05) when given before the onset of secondary ischaemia. These results show that UW solution improves skin flap survival, presumably through preservation of the microvasculature.

Adenosine↗

Myb genes from Hordeum vulgare: tissue-specific expression of chimeric Myb promoter/Gus genes in transgenic tobacco.

The structures of the three Myb-related genes Hv1, Hv5 and Hv33 from barley were determined. They contain a single intron located in the second repeat unit of the Myb-related domain. By analogy to the animal MYB oncoproteins this conserved region of the gene product was shown by filter-binding experiments to exhibit nucleic acid-binding activity. Tobacco plants transgenic for chimeric Myb promoter/Gus genes express the enzyme in a developmentally controlled and tissue-specific manner. During germination and early stages of plant growth, GUS activity is seen in the root cap and adjacent meristematic tissue. At later stages of plant development, GUS activity is predominantly observed in the shoot apical meristem, the roots and the nodal regions of the stem. Within the stem at stages of secondary growth, Myb promoters are active in defined cell types. In the internode low GUS activity is displayed by the innermost cell layer of the cortex, the starch sheath, that surrounds the vascular cylinder of secondary xylem and phloem tissue, as well as in pith rays originating from vascular cambium initials. In the nodal region Myb promoter-controlled Gus expression is mainly confined to the abaxial starch sheath of the leaf trace, to the branch traces and to internal strands of primary phloem. It is suggested that in addition to their activity in meristematically active plant tissues Myb genes are expressed in conductive tissues that are closely associated with vascular bundles.

Amino Acid Sequence↗

Sequence and temporal appearance of the early transcribed baculovirus gene HE65.

We have identified the early transcribed HE65 gene by screening a cDNA library from polyadenylated RNA which was isolated at 1 h after infection of Spodoptera frugiperda cells with Autographa californica nuclear polyhedrosis virus (AcNPV). Nucleotide sequencing analysis of the HE65-specific cDNA clone reveals one open reading frame of 1,662 nucleotides from which a protein of 65 kDa in size can be predicted. The HE65 gene is located downstream of the late transcribed p80 gene and upstream of the homologous region hr4left, which overlaps the 5' sequences of the HE65 gene. An HE65-specific transcript of about 1,800 nucleotides is detectable 2 h postinfection and remains stable during the late phases of infection. RNase protection and primer extension analyses demonstrate that transcripts from the early start site of HE65 continue to accumulate from 2 to 48 h postinfection, even in the presence of aphidicolin. Furthermore, transcriptional analysis of the HE65 gene indicates a lower intensity of early transcription in comparison with the very early transcribed genes IEN, PE38, and ME53.

Amino Acid Sequence↗

An anatomicosurgical study of the temporal branch of the facial nerve.

The surgical anatomy of the temporal branch of the facial nerve was studied bilaterally in 10 embalmed cadaveric heads. Particular attention was paid to the relationships between the temporal branch, the galeal-fascial layers, and the fat pads of the temporal-zygomatic region. The temporal branch of the facial nerve pierces the parotidomasseteric fascia below the zygomatic arch. This branch travels first in the subcutaneous tissue and then, above the zygomatic arch, in the subgaleal space. The temporal branch divides into an anterior, a middle (frontal), and a posterior ramus soon after it pierces the parotid fascia. The course of the terminal twigs of the temporal branch of the facial nerve in the subgaleal space is extremely variable, with their location being at times posterior to the anterior one-fourth of the temporalis muscle. Occasionally, a twig for the frontalis muscle may run in between the two layers of the superficial temporal fascia. Because of these findings (anteroposterior variability of temporal branch twigs and recurrent intrafascial twig), Yasargil's interfascial dissection may at times fail. A combined frontotemporal scalp/superficial temporal fascia dissection is anatomically suited to preserve the temporal branch of the facial nerve.

Adipose Tissue↗

Differential expression of cyclic AMP-dependent protein kinase isozymes in normal human melanocytes and malignant melanomas.

Analysis of cyclic AMP-dependent protein kinase catalytic (C) and regulatory (R) subunits in normal human melanocytes and malignant melanomas demonstrated molar excess of regulatory over catalytic subunit in both cell types. Overall, greater catalytic activity, as a measure of C subunit, and cyclic AMP binding activity, as a measure of R subunit, were detected in metastatic compared to primary melanomas compared to normal human melanocytes. The protein kinase-specific R subunits, expressed in both melanocytes and malignant melanomas, were identified as RI-alpha and RII-alpha. Differences were noted for the ratios of RI/RII and RI holoenzyme/free RI subunit among different melanomas.

Base Sequence↗

Informed consent in demented patients: a question of hours.

Dementia, and especially Alzheimer's disease is today the subject of endless research, most of it including some kind of prolonged physical treatment. When considering such treatment, one first has to deal with the quality and validity of the consent of the demented patient suspected of impaired judgment. The term 'informed consent' involves at least two types of decisions: one regarding short-term intervention like a surgical procedure; the other concerns long-term intervention, like treatment by a new kind of drug intended to improve memory. In the latter case, the informed consent attributed to the patient raises both clinical and legal questions regarding validity of the continuing authorization given to the physician--a question which should also be examined in terms of time in fluctuating conditions, like dementia. What are the tests required to determine competency? What determines the grade of competency required in different types of research with different benefit-risk ratios? Do the changes in the cognitive function of the patient during the research demand constant assessment of competency. Where is the 'cut-off' point that dictates reassessment of the patient's consent and who is legally and practically responsible to identify this condition and decide whether to proceed? Finally, what are the alternative procedures that might simplify the decision-making process in fluctuating conditions without affecting the rights and autonomy of the patient? This article proposes several possible solutions to these legal and ethical dilemmas.

Aged↗

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

An ESR (electron spin resonance) investigation of the effect of hydration water (D2O) on the absolute yields (G) of ion radicals in gamma-irradiated DNA at 77 K is reported. The total DNA radical yield is found to increase by over fourfold on addition of the primary hydration layer (20 water molecules/nucleotide) to DNA. At hydrations greater than ca. 20 waters/nucleotide the excess water freezes into a separate and apparently radiologically independent bulk ice phase. Ice formation steals ca. 5 waters from the hydration layer which causes a proportionate (by weight) drop in the total yield of DNA radical ions. Hydroxyl radicals (.OD) are not observed even at great signal amplification in the primary hydration layer but are found only in the ice phase, which suggests efficient transfer of holes and electrons from the hydration layer to the DNA; as a consequence, DNA and its associated hydration water form the target mass for radiation damage. These results show that water of hydration is critical to radical formation and stabilization in DNA; however, the ice surrounding DNA does not contribute to direct DNA damage and is found to have the same properties as bulk ice. At 18 waters per nucleotide (gamma = 18) about one-fourth of all ion radicals produced by the radiation are trapped at 77 K. The k value for destruction is found to vary only slightly with hydration. Based on the measured G and k values for hydrated DNA, a trapped radical ion cluster size is estimated to be about 6 nm. For hydrated DNA the cluster size suggests electron migration distances of about 17 bases (for migration along the DNA strand).

Animals↗

[Functional results and survival probability of tumor patients after reconstruction of the mouth cavity and oropharynx using a microvascular radial forearm flap].

In tumor surgery of the oral cavity and oropharynx function and quality of life should be maintained and large resection margins to avoid recurrences. For these purposes the radial forearm flap has proved to be a versatile tissue transfer since it is thin and pliable and has a long vascular pedicle. From 1987 to 1991 we used the radial forearm flap in performing 70 reconstructions of the oral cavity and oropharynx after resection of squamous cell carcinomas. Forty-six patients had carcinomas of the oropharynx, while 24 patients had carcinomas of the oral cavity. The indications for these reconstructions were tumors of the oral cavity and oropharynx greater than T2 which after resection were not suitable for primary closure of the defect. Thirty-seven patients died during the follow-up period, with 36% dying within the first 2 years after operation. Fifty-five percent of these patients died of recurrences, 17% of metastases and 11% of intercurrent diseases. In 17% of cases the cause of death was unknown. The 2-year survival probability was 52% (Kaplan Meier). Our results show that reconstructions with the radial forearm flap do not improve survival rates when compared to the general survival rate in these cases despite a possibly larger resection margin allowing a more radical tumor resection. Thirty-one of the 33 patients still alive underwent following examinations. Forty-six percent of the patients with tumors of the oropharynx and 57% of the patients with tumors of the oral cavity had severe difficulties in swallowing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Environmental and familial contributions to insulin levels and change in insulin levels in middle-aged women.

OBJECTIVE: To examine familial and environmental variables associated with elevated insulin levels and changes in insulin levels in healthy, premenopausal women. METHODS: A population-based sample of 518 women (aged 42 to 50 years) completed baseline assessments of weight, cardiovascular risk factors, exercise behaviors, and glucose and insulin levels (fasting and 2 hours after a glucose load); 495 of the women were reevaluated after 3 years. RESULTS: Plasma insulin levels were related to weight, activity level, race, body fat distribution, and weight gain since age 20 years. Parental history of either diabetes or hypertension was also related to elevated insulin levels, independent of body mass index, with the highest insulin levels occurring in those women with a parental history of both diseases. Increases in plasma insulin levels over the years of follow-up were related to weight gain. CONCLUSIONS: This study suggests that importance of using family history to identify women who may have elevated insulin levels and of intervening to prevent weight gain during middle age.

Adult↗

High rates of Ac/Ds germinal transposition in Arabidopsis suitable for gene isolation by insertional mutagenesis.

Overexpression of the Activator (Ac) transposase gene in Arabidopsis thaliana resulted in a minimal germinal transposition frequency of 27% in which independent Dissociation (Ds) transposition events were observed. Molecular analysis of 45 F1 generation Ac/Ds plants indicated that high rates of somatic excision had occurred, and independent germinal insertions were identified in F2 generation progeny plants. A tandem cauliflower mosaic virus (CaMV) promoter fused to two different Ac coding sequences significantly increased the rate of Ds transposition. The CaMV-Ac fusions activated single and multiple copies of two different Ds elements, DsDHFR and Ds35S-1, and reciprocal crosses resulted in similar transposition frequencies. The improved rate of independent germinal transposition observed makes Arabidopsis an ideal system for insertional mutagenesis.

Base Sequence↗

Control of excision frequency of maize transposable element Ds in Petunia protoplasts.

The complete coding region of maize transposable element Ac and truncated but active derivatives of it were placed under the control of promoters of different strength and tested for the ability to excise transposable element Ds from a beta-glucuronidase reporter gene in a cotransfection assay in Petunia protoplasts. The highest excision values (5% of the protoplasts able to express the beta-glucuronidase gene in a control experiment) were observed with a truncated version of the Ac coding region under the control of the 2' promoter. The weak Ac promoter is sufficient to give rise to excision values not much lower than those found with much stronger promoters such as the 2' and nos promoters. A decrease in excision frequency was observed when translation of the Ac coding region was hindered by out-of-frame ATG codons in addition to the use of weak promoters. Increasing the level of Ac transposase thus does not seem to be sufficient to raise the level of Ds excision observed in this system and possibly also in maize. Therefore another factor limits the excision of Ds elements. Previously, it was reported that in tobacco cells the deletion of Ds sequence between base pairs 186 and 245 led to a decrease of the Ds excision frequency by the full-length but not by the truncated Ac product. In the Petunia assay system, however, deletion of these sequences decreased the excision rate with both the full length and the truncated Ac coding region. A cDNA construct was found similarly active as the corresponding genomic DNA.

Journal Article↗

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↗