Search PubMed⌕ Search

Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 127 records · Page 7Linked to original sources
PubMed2001

Smoking cessation in China: findings from the 1996 national prevalence survey.

OBJECTIVES: To describe patterns of smoking and smoking cessation in China within the context of the stages of change model, using data from the 1996 national prevalence survey. DESIGN: A cross sectional survey was carried out using the 145 preselected disease surveillance points, which provide a representative sample for the entire country. A standardised questionnaire on smoking was interviewer administered. SETTING: The country of China. SUBJECTS: 122,220 people aged 15-69 years. MAINTENANCE MEASURES: Smoking cessation patterns, as defined by smoking status (current or former) and stage of change (precontemplation, contemplation, and action). RESULTS: The sample included 45,995 ever smokers of whom 4336 had quit. About 72% of current smokers reported not intending to give up their smoking behaviour, and about 16% of current smokers said they intended to do so, but have not taken any action. Of all ever smokers, the percentage of former smokers was 9.5%, and 12% of current smokers had quit at least once, but relapsed by the time of the survey. The patterns were similar in men and women with regard to the stated intent to quit. Among males, the percentage of former smokers increased with age but the percentage intending to quit was constant at about 15% across age strata. The most common reason for quitting was illness. Participants with a university education were more likely to have made an attempt to quit. CONCLUSIONS: The percentage of smokers contemplating quitting was low in China in 1996. The study shows that smokers in China must be mobilised to contemplate quitting and then to take action.

Adolescent↗
PubMed2001

Community-based education improves stroke knowledge.

BACKGROUND AND PURPOSE: Despite advances in stroke therapy, the public remains uninformed about stroke, and few stroke patients present to the hospital in time to receive treatment. Health education campaigns can increase community awareness and may decrease time to hospital presentation among stroke patients. METHODS: We conducted a community-based education campaign utilizing television and newspapers to inform the residents of King County, Wash., USA, about stroke and the need to call 911. The effectiveness of the campaign was assessed, using a pretest-posttest design, through telephone interviews with residents of King County. RESULTS: Prior to the education campaign, 59.6% of persons in King County could name a risk factor for stroke, but only 45.2% knew that the brain was the organ of injury. And while 68.2% of persons stated that they would call 911 in the event of stroke, only 38.6% could name a symptom of stroke. The knowledge deficit was greatest among Asian-Americans, men, the less educated and low-income residents. There was a significant increase in stroke knowledge following the education campaign; respondents were 52% (p = 0.005) more likely to know a risk factor for stroke and 35% (p = 0.032) more likely to know a symptom of stroke after the campaign. CONCLUSIONS: Baseline knowledge about stroke among the public is poor, but can be increased through public education campaigns.

Aged↗
PubMed2001

The canine ERBB2 gene maps to a chromosome region frequently affected by aberrations in tumors of the dog (Canis familiaris).

The dog offers an increasingly important model for several human diseases, including cancer. Accordingly, the results of canine gene mapping studies will be of considerable significance. Herein, we have addressed the mapping of the canine gene ERBB2 (alias HER2, NEU). ERBB2 is a protooncogene encoding a tyrosine kinase receptor protein, the overexpression of which correlates with a more rapid progression and a worse prognosis in breast cancer. In addition, it apparently plays a role in the development of other tumors as well. By fluorescence in situ hybridization (FISH), we have mapped the canine ERBB2 to 1q13.1. Cytogenetic studies of canine tumors revealed that this region is very often affected by clonal chromosome aberrations in tumors of the dog.

Animals↗
PubMed2001

Antibody to the alpha4 integrin decreases infarct size in transient focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Inflammation, a process that involves neutrophils, lymphocytes, and monocytes, contributes to cerebral ischemic injury. Blockade of neutrophil adhesion to endothelium improves outcome after experimental stroke. In this study we sought to assess the contribution of lymphocytes and monocytes to ischemic brain injury. METHODS: Male Lewis rats underwent 3 hours of middle cerebral artery occlusion followed by 45 hours of reperfusion. Two hours after the onset of ischemia, one group of animals received an intraperitoneal injection of antibodies to the alpha(4) integrin (n=16); another group was injected with an isotype control antibody (n=11). Neurological examination, body temperature, and body weight were assessed at different time points after stroke. Animals were killed 48 hours after the onset of ischemia for determination of infarct volume and leukocyte counts. RESULTS: There were no significant differences in body temperature or weight at any time. Neurological scores (deficits) were significantly less in animals treated with anti-alpha(4) antibodies at 24 (2.0+/-1.2 versus 3. 0+/-0.4; P:=0.006) and 48 (2.0+/-1.2 versus 3.0+/-0.8; P:=0.011) hours after ischemia. Peripheral blood leukocyte counts were significantly higher in anti-alpha(4)-treated animals (6.8+/-2.2 x 10(9) versus 2.9+/-1.9 x 10(9); P:=0.001) and revealed a lymphocyte/monocyte predominance (86.0+/-16.2% versus 71.0+/-15.6%; P:=0.008). Infarct volume was significantly less in animals treated with antibodies to alpha(4) (120.1+/-51.21 versus 173.7+/-42.29 mm(3); P:=0.012). CONCLUSIONS: These data support a role for lymphocytes and monocytes in cerebral ischemic injury and show that blockade of alpha(4), even when instituted after the onset of ischemia, can improve neurological outcome and decrease infarct volume.

Animals↗
PubMed2001

Antioxidant status and nitric oxide in the malnutrition syndrome kwashiorkor.

The pathophysiology of kwashiorkor, a severe edematous manifestation of malnutrition, is still poorly understood. The syndrome is, however, known to be associated with alterations in redox metabolism. To further elucidate the role of oxidative stress in kwashiorkor, we carried out a longitudinal study on the major blood antioxidants at the St. Joseph's Hospital, Jirapa, Ghana. All kwashiorkor patients (K) were followed up for 20 d. In comparison with local healthy controls (C), the plasma total antioxidant status was reduced to less than 50% in the patients (C, 0.87 +/- 0.21 mM; K, 0.40 +/- 0.20 mM; p<0.001). Similarly, the major plasma antioxidant albumin (C, 40.9 +/- 2.5 g/L; K, 19.1 +/- 7.4 g/L; p < 0.001) and erythrocyte glutathione (C, 2.39 +/- 0.28 mM; K, 1.01 +/- 0.33; p < 0.001) were decreased, whereas the levels of bilirubin and uric acid were not significantly altered. Nitrite and nitrate were found to be increased by a factor of 2 in kwashiorkor (C, 120 +/- 46 microM; K, 235 +/- 107 microM; p < 0.001). Over the observation period, the trends of albumin and glutathione levels were related to clinical outcome. These concentrations rose in patients who recovered and fell in patients who did not. Our study strongly supports the hypothesis that oxidative and nitrosative stress play a role in the pathophysiology of edematous malnutrition. Prophylactic and therapeutic strategies should aim at the careful correction of the reduced antioxidant status of the patients.

Adolescent↗
PubMed2001

[How can the effectiveness of multimodality therapy concepts be evaluated? From the viewpoint of the pathologist].

Prognostically relevant histopathological grading of tumor regression (grades I-III) is possible, although laborious. Morphological changes after chemotherapy indicate a specific response to treatment with central fibrosis and residual tumor islands in the periphery. Prognostic factors, such as TNM categories, UICC-R status, tumor size, and lymphangiosis, which are not intrinsic part of regression grading still correlate with patient survival.

Combined Modality Therapy↗
PubMed2000

The thioredoxin system of the malaria parasite Plasmodium falciparum. Glutathione reduction revisited.

In most living cells, redox homeostasis is based both on the glutathione and the thioredoxin system. In the malaria parasite Plasmodium falciparum antioxidative proteins represent promising targets for the development of antiparasitic drugs. We cloned and expressed a thioredoxin of P. falciparum (pftrx), and we improved the stable expression of the thioredoxin reductase (PfTrxR) of the parasite by multiple silent mutagenesis. Both proteins were biochemically characterized and compared with the human host thioredoxin system. Intriguingly, the 13-kDa protein PfTrx is a better substrate for human TrxR (K(m) = 2 microm, k(cat) = 3300 min(-)(1)) than for P. falciparum TrxR (K(m) = 10.4 microm, k(cat) = 3100 min(-)(1)). Possessing a midpoint potential of -270 mV, PfTrx was found to reduce the disease-related metabolites S-nitrosoglutathione and GSSG. The rate constant k(2) for the reaction between reduced P. falciparum thioredoxin and GSSG was determined to be 0.039 microm(-)(1) min(-)(1) at 25 degrees C and pH 7.4. The k(2) for thioredoxins from man, Drosophila melanogaster, and Escherichia coli was approximately 5 times lower. Our data suggest that GSSG reduction can be supported at a high rate by the TrxR/Trx system in glutathione reductase-deficient cells; this may be relevant for certain stages of the malarial parasite but also for cells containing high [GSSG] of other organisms like dormant forms of Neurospora, glutathione reductase-deficient yeast mutants, or CD4(+) lymphocytes of AIDS patients.

Amino Acid Sequence↗
PubMed2000

Kinetic characterization of glutathione reductase from the malarial parasite Plasmodium falciparum. Comparison with the human enzyme.

The homodimeric flavoenzyme glutathione reductase (GR) maintains high intracellular concentrations of the antioxidant glutathione (GSSG + NADPH + H(+) <--> 2 GSH + NADP(+)). Due to its central function in cellular redox metabolism, inhibition of GR from the malarial parasite Plasmodium falciparum represents an important approach to antimalarial drug development; therefore, the catalytic mechanism of GR from P. falciparum has been analyzed and compared with the human host enzyme. The reductive half-reaction is similar to the analogous reaction with GR from other species. The oxidative half-reaction is biphasic, reflecting formation and breakdown of a mixed disulfide between the interchange thiol and GSH. The equilibrium between the E(ox)-EH(2) and GSSG-GSH couples has been modeled showing that the Michaelis complex, mixed disulfide-GSH, is the predominant enzyme form as the oxidative half-reaction progresses; rate constants used in modeling allow calculation of an K(eq) from the Haldane relationship, 0.075, very similar to the K(eq) of the same reaction for the yeast enzyme (0.085) (Arscott, L. D., Veine, D. M., and Williams, C. H., Jr. (2000) Biochemistry 39, 4711-4721). Enzyme-monitored turnover indicates that E(FADH(-))(S-S). NADP(+) and E(FAD)(SH)(2).NADPH are dominant enzyme species in turnover. Since the individual forms of the enzyme differ in their susceptibility to inhibitors, the prevailing states of GR in the cell are of practical relevance.

Animals↗
PubMed2000

The putative glutathione peroxidase gene of Plasmodium falciparum codes for a thioredoxin peroxidase.

A putative glutathione peroxidase gene (Swiss-Prot accession number Z 68200) of Plasmodium falciparum, the causative agent of tropical malaria, was expressed in Escherichia coli and purified to electrophoretic homogeneity. Like phospholipid hydroperoxide glutathione peroxidase of mammals, it proved to be monomeric. It was active with H(2)O(2) and organic hydroperoxides but, unlike phospholipid hydroperoxide glutathione peroxidase, not with phosphatidylcholine hydroperoxide. With glutathione peroxidases it shares the ping-pong mechanism with infinite V(max) and K(m) when analyzed with GSH as substrate. As a homologue with selenocysteine replaced by cysteine, its reactions with hydroperoxides and GSH are 3 orders of magnitude slower than those of the selenoperoxidases. Unexpectedly, the plasmodial enzyme proved to react faster with thioredoxins than with GSH and most efficiently with thioredoxin of P. falciparum (Swiss-Prot accession number 202664). It is therefore reclassified as thioredoxin peroxidase. With plasmodial thioredoxin, the enzyme also displays ping-pong kinetics, yet with a limiting K(m) of 10 microm and a k(1)' of 0.55 s(-)1. The apparent k(1)' for oxidation with cumene, t-butyl, and hydrogen peroxides are 2.0 x 10(4) m(-1) s(-1), 3.3 x 10(3) m(-1) s(-1), and 2.5 x 10(3) m (-1) s(-1), respectively. k(2)' for reduction by autologous thioredoxin is 5.4 x 10(4) m(-1) s(-1) (21.2 m(-1) s(-1) for GSH). The newly discovered enzymatic function of the plasmodial gene product suggests a reconsideration of its presumed role in parasitic antioxidant defense.

Amino Acid Sequence↗
PubMed2000

FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation.

Fas is a cell surface death receptor that signals apoptosis. Several proteins have been identified that bind to the cytoplasmic death domain of Fas. Fas-associated death domain (FADD), which couples Fas to procaspase-8, and Daxx, which couples Fas to the Jun NH(2)-terminal kinase pathway, bind independently to the Fas death domain. We have identified a 130-kD kinase designated Fas-interacting serine/threonine kinase/homeodomain-interacting protein kinase (FIST/HIPK3) as a novel Fas-interacting protein. Binding to Fas is mediated by a conserved sequence in the COOH terminus of the protein. FIST/HIPK3 is widely expressed in mammalian tissues and is localized both in the nucleus and in the cytoplasm. In transfected cell lines, FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction. Although Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3, cell death is not affected. These results suggest that Fas-associated FIST/HIPK3 modulates one of the two major signaling pathways of Fas.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Channelized fluid flow in oceanic crust reconciles heat-flow and permeability data

Hydrothermal fluid circulation within the sea floor profoundly influences the physical, chemical and biological state of the crust and the oceans. Circulation within ridge flanks (in crust more than 1 Myr old) results in greater heat loss and fluid flux than that at ridge crests and persists for millions of years, thereby altering the composition of the crust and overlying ocean. Fluid flow in oceanic crust is, however, limited by the extent and nature of the rock's permeability. Here we demonstrate that the global data set of borehole permeability measurements in uppermost oceanic crust defines a trend with age that is consistent with changes in seismic velocity. This trend-which indicates that fluid flow should be greatly reduced in crust older than a few million years-would appear to be inconsistent with heat-flow observations, which on average indicate significant advective heat loss in crust up to 65 Myr old. But our calculations, based on a lateral flow model, suggest that regional-scale permeabilities are much higher than have been measured in boreholes. These results can be reconciled if most of the fluid flow in the upper crust is channelized through a small volume of rock, influencing the geometry of convection and the nature of fluid-rock interaction.

Journal Article↗
PubMed2000

Assembly and functional expression of murine glutathione reductase cDNA: a sequence missing in expressed sequence tag libraries.

Glutathione reductase (GR) is a chemotherapeutic target. Murine GRcDNA, which contains 85% GC in the 38 codons following the start codon, was assembled from the PCR-amplified exon 1 and a downstream cDNA prior to expression in Escherichia coli as a His(6)-tagged protein. Recombinant GR, an FAD-containing homodimer, corresponds in its enzymic and spectral properties to GR isolated from murine Ehrlich ascites tumor cells. Another cDNA, representing GR with a mitochondrial targeting sequence, yielded two distinct enzymically active expression products.

Animals↗
PubMed2000

Characterization of the T cell receptor repertoire in patients with common variable immunodeficiency: oligoclonal expansion of CD8(+) T cells.

Common variable immunodeficiency is characterized by an impairment in antibody production of at least two immunoglobulin isotypes, and abnormalities of both B and T cells have also been described. In this study, a profound alteration of the T cell receptor repertoire was noted, especially in CD8(+) T cells, in CVID patients when compared to a control group. However, the higher number of oligoclonally expanded populations seen in the patient group was not dependent on age, whereas in the control group an age-related accumulation of these populations was noted. Expansion of CD8(+) CD28(-) T cells in these patients is strongly correlated with T cell receptor repertoire restriction. Furthermore, analysis of cytokine production showed a statistically significant increase in IFN-gamma secretion in the patient group. Lastly, CD94 and perforin were expressed at increased frequencies on CD8(+) T cells in the patient group when compared to the control group. We speculate that these findings support the concept that CD8(+) T cells may play an important regulatory role in CVID.

Adult↗
PubMed2000

[Volumetry of the urinary bladder with implantable ultrasound sensors].

Experimental studies revealed that the contractile response of the urinary bladder to sacral anterior root stimulation depends on the actual bladder volume. Furthermore, no clinical relevant technique is available for continuous monitoring of the bladder wall distension respectively bladder volume in paraplegic patients. The presented study investigates the reliability of especially developed implantable ultrasound sensors as a sensoric system for continuous monitoring of the bladder volume. In six anaesthesized pigs two ultrasound sensors, one transmitter and one receiver, were implanted on the bladder wall at different locations (latero-lateral, dorsal-ventral, rostral-caudal). After closing the abdominal wall, the bladder was filled in 50 ml steps up to 250 ml. After each filling step the running time of the ultrasound signal was measured. In all experiments reproducible results and a high correlation of the measured running times with bladder volume were observed. The latero-lateral configuration of the sensors seemed to be most confidential. The presented study indicates that bladder volumetry with implantable ultrasound sensors is possible with minimal technical prerequisites. This promising technique for continuous bladder volumetry could play an important role in the development of an intelligent and autoadaptive neurostimulator of the urinary bladder in paraplegic patients.

Animals↗
PubMed2000

Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction. I. Evaluation of the normal status in an animal model.

OBJECTIVE: A new approach, combined static-dynamic MR urography is evaluated to determine its potential utility for the functional-morphological diagnosis of paediatric urinary tract obstruction. In this initial investigation we sought to evaluate the procedure by imaging the urinary tract of piglets. MATERIALS AND METHODS: Twenty-nine healthy piglets were studied with MR urography (MRU), 99mTc-MAG3 diuretic renal scintigraphy (DRS), ultrasound (US) and excretory urography (EU). The functional and morphological findings were compared. For MRU we combined a respiration-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA injection. RESULTS: MRU depicted the complete urinary tract with superior image quality compared to EU. Calculation of time-intensity curves from the dynamic sequence permitted determination of single kidney function from parenchymal ROIs and urinary excretion using the whole kidney ROI. MRU and DRS showed significant agreement in the assessment of both single kidney function and urinary excretion. Disturbances of urinary drainage were generally caused by an overfilled bladder. CONCLUSIONS: Combined static-dynamic MRU is well suited for the depiction of the complete urinary tract and for the determination of individual kidney function and urinary excretion in the piglet.

Animals↗
PubMed2000

Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction. II. Findings in experimentally induced ureteric stenosis.

PURPOSE: To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction in the piglet. MATERIALS AND METHODS: In 20 piglets unilateral ureteric stenosis was created operatively. Post-surgery repeated comparative examinations were obtained with MRU, diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US). MRU was performed as a combination study with a static 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA with frusemide administration. RESULTS: MRU allowed complete depiction of the prestenotic urinary tract and of the stenosis in all cases. In 43 comparative studies MRU was superior to EU in 36, EU to MRU in 2. When single kidney function was calculated with both MRU and DRS, results were highly correlated (r = 0.92). When urinary excretion was compared, significant agreement was achieved with concordant findings in 86% and slightly discordant results in 12%. CONCLUSIONS: Static-dynamic MR urography permits excellent depiction of experimentally induced urinary tract obstruction in piglets and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out--it does not require radiation and it permits functional-morphological correlation.

Animals↗