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Biomedical subjects

W Koch

Publications and source records attributed to W Koch.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Ileocecal invagination of a mucocele of the appendix].

HISTORY AND CLINICAL FINDINGS: A 39-year-old patient was admitted because of pain in the right mid and lower abdomen of 2 weeks duration with vomiting and postprandial nausea. He complained of changing stool habits with diarrhoea and constipation. Clinically he showed a slight tenderness in the right lower abdomen. INVESTIGATIONS: Routine laboratory test were normal including CRP and WBC. Ultrasound showed a non-compressible mass with low intensity echoes, 3.6 x 4.6 cm in diameter in the right mid abdomen, slightly tender, surrounded by a circular, intestine-like structure. A gastrografin-swallow didn't reveal any obstacle in the proximal small intestine and was inconclusive further distal. A CT scan demonstrated a ileocoecal invagination extending in the colon ascendens to the right flexure with suspicion of a tumor. At the colonoscopy on the next day the invagination was not apparent any more, but a well-rounded tumour in the appendix region was seen. DIAGNOSIS, TREATMENT AND COURSE: Suspecting a coecal tumour with remitting ileocoecal invagination a ileocoecal resection was performed on the third day. The tumour proved to be a mass of mucus with parts of a villo-mucinous cystadenoma of the UMP type. Recovery was uneventful. CONCLUSION: Mucoceles of the appendix can cause ileocoecal invagination in the adult.

Adult↗
PubMed2001

Cs(2) fixation by carbonic anhydrase model systems-a new substrate in the catalytic cycle.

The conversion of CS(2) with common carbonic anhydrase model systems has been studied using Hartree-Fock and density-functional theory methods employing the 6-311+G basis set. The calculated geometries and energetical parameters for [L(3)ZnOH](+)/CS(2) model systems (L = NH(3), imidazole) are compared with those obtained previously for the CO(2) hydration. While the same reaction mechanism applies for both heterocumulenes, the hypothetical conversion of CS(2) to give [L(3)ZnSC(O)SH](+) is characterized by a higher barrier and is much more exothermic than the corresponding CO(2) reaction cascade. Due to the increased number of heteroatoms, additional intermediates and product structures (compared with those involved in the CO(2) conversion) must be taken into account and have been analyzed in detail. The smaller electrophilicity of CS(2) is the reason for the higher activation energies, while the significantly increased exothermicity is due to the strong zinc(II)/sulfur interaction. The reversibility and therefore the existence of a catalytic cycle which could allow comparable CS(2) transformations must be questioned. Nevertheless, an interesting field of stoichiometric zinc-mediated CS(2) transformations is conceivable.

Carbon Dioxide↗
PubMed2001

Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients.

Aberrant promoter hypermethylation is common in head and neck cancer and may be useful as a marker for cancer cells. We examined whether cells with tumor-specific aberrant DNA-methylation might be found in the saliva of affected patients. We tested 30 patients with primary head and neck tumors using methylation-specific PCR searching for promoter hypermethylation of the tumor suppressor gene p16 (CDKN2A), the DNA repair gene O6-methylguanine-DNA-methyltransferase (MGMT) and the putative metastasis suppressor gene death-associated protein kinase (DAP-K). Aberrant methylation of at least one of these genes was detected in 17 (56%) of 30 head and neck primary tumors; 14 (47%) of 30 at p16, 10 (33%) of 30 at Dap-K and 7 (23%) of 30 at MGMT. In 11 (65%) of 17 methylated primary tumors abnormal methylated DNA was detected in the matched saliva samples. Abnormal promoter methylation in saliva DNA was found in all tumor stages and more frequently in tumors located in the oral cavity. Moreover, none of the saliva from patients with methylation-negative tumors displayed methylation of any marker. Of 30 saliva samples from healthy control subjects (15 smokers and 15 nonsmokers), only one sample from a smoking patient was positive for DNA methylation at two target genes. Detection of aberrant promoter hypermethylation patterns of cancer-related genes in saliva of head and cancer patients is feasible and may be potentially useful for detecting and monitoring disease recurrence. Long-term longitudinal studies are needed to evaluate this approach for early detection of head and neck cancer in at-risk populations.

Apoptosis Regulatory Proteins↗
PubMed2001

Chronic pulmonary effects of respirable methylene diphenyl diisocyanate (MDI) aerosol in rats: combination of findings from two bioassays.

Two independent bioassays are available which have examined the potential carcinogenicity of monomeric and polymeric methylene diphenyl diisocyanate (MDI) following long-term inhalation exposure in rats. These studies are not directly comparable, however, due to differences in design and conduct of the in-life phase, and differences in nomenclature used for some of the histopathological findings. This paper presents a definitive overview ofthe pulmonary toxicity of MDI developed following a thorough review of both investigations. As part of this process, the test materials and the designs of the studies were compared, and an in-depth review of lung lesions was conducted by an independent reviewing pathologist. This included the re-examination of the original lung slides, supported by an analysis of the exposure regimens, the results of which were used to develop an accurate profile of the doses received by the animals in the two studies. Histopathological findings were then combined with this information to give an overall dose-response curve for both studies as a whole. The range of total inhalation exposures to MDI was calculated as 559, 1972, 2881, 6001, 17,575 and 17,728 mgh/m3. Major pulmonary effects included increased lung weights together with bronchiolo-alveolar adenomas and hyperplasia, and interstitial fibrosis which occurred consistently in both studies, indicating a very similar qualitative response of the lungs to polymeric and monomeric MDI. The quantitative response of the lung was clearly dose-related in each study, and when the studies were considered as a whole a reasonable overall dose-response relationship was apparent for major lung lesions. Lung tumours (in low incidences) only occurred at the highest dose level in both studies (17,575 and 17,728 mgh/m3). For inflammatory and other non-neoplastic pulmonary changes, the lowest dose examined (559 mgh/m3) was regarded as a no-observed-adverse-effect-level for both polymeric and monomeric MDI. It was concluded that the results of the two studies could be combined to serve as a basis for human risk assessment of MDI.

Adenoma↗
PubMed2001

Glycoprotein Ia C807T polymorphism and risk of restenosis following coronary stenting.

Platelets are thought to contribute to development of restenosis following percutaneous coronary interventions. The glycoprotein Ia/IIa complex is a major platelet collagen receptor, its surface expression being influenced by two, linked single nucleotide polymorphisms (C807T and G873A) in the glycoprotein Ia gene. T807 is associated with increased expression of this integrin receptor. We assessed whether T807 is associated with an increased risk of restenosis in 1769 consecutive patients treated with coronary stenting. 6-month follow-up angiograms were available in 82.4% of the patients. C807T genotype distribution was CC in 35.8%, CT in 47.6% and TT in 16.6% of the patients. Restenosis (diameter stenosis > or =50% at follow-up angiography) occurred in 32.9% of CC, 31.5% of CT and 32.1% of TT patients (P=0.87). The rate of major adverse cardiac events (death, myocardial infarction or need of reintervention) within 1 yr was 21.6% for CC, 21.7% for CT and 21.2% for TT patients (P=0.98). Thus, carriage of the GP Ia T807 allele is not associated with an increased risk of restenosis or unfavorable late outcome following coronary artery stenting.

Aged↗
PubMed2001

Interleukin-10 and tumor necrosis factor gene polymorphisms and risk of coronary artery disease and myocardial infarction.

Inflammation plays an important role in the pathogenesis of atherosclerosis and acute coronary syndromes. Cytokines IL-10 and TNF-alpha exert opposite functions in inflammatory reactions, IL-10 acting predominantly as an antiinflammatory and TNF-alpha as a proinflammatory factor. Functional single nucleotide polymorphisms in the genes of IL-10, TNF-alpha, and TNF-beta are associated with gene expression and plasma levels of IL-10 and TNF-alpha. The aim of the study was to assess whether these IL-10 and TNF gene polymorphisms are related to the risk of coronary artery disease (CAD) and myocardial infarction (MI). Consecutive, angiographically examined patients with significant coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (n=998) and patients with old or acute MI constituted the group with MI (n=793). Subjects with neither angiographic CAD nor symptoms or signs of MI (n=340) served as controls. They were matched with the patients for age and sex. Genotyping was performed with techniques based on the polymerase chain reaction. Allele frequencies, genotype distributions, and frequencies of allele combinations for three IL-10 promoter polymorphisms, -1082G/A, -819C/T and -592C/A, were similar between CAD patients, MI patients, and matched controls. Similarly, genetic analysis did not reveal group-specific differences for the TNF-alpha promoter polymorphisms -863C/A and -308G/A, as well as for the TNF-beta intron 1 polymorphism 252G/A. In addition, no relationship was found between specific combinations of IL-10 and TNF alleles, indicative of low IL-10 and high TNF-alpha production, respectively, and CAD or MI. The lack of association persisted also after adjusting for other cardiovascular risk factors. Our findings suggest that six different and functionally relevant polymorphisms of the genes coding for IL-10, TNF-alpha, and TNF-beta are neither separately nor in cooperation associated with the risk of CAD or MI in angiographically examined patients.

Coronary Disease↗
PubMed2001

A simple pulmonary retention model accounting for dissolution and macrophage-mediated removal of deposited polydisperse particles.

This article describes a mechanistic two-compartmental model to simulate the disposition by dissolution and particulate clearance of particles deposited in the pulmonary region of the lung. The model provides a general solution for the size distribution of particles in the surfactant layer of the alveolar surface and in the cell plasma of alveolar macrophages. Thus it allows for different dissolution rates in the two compartments and accounts for potentially different kinetics and/or biological effects of particles and their solute in surrounding fluids. The input parameters are, among others, the size distribution density function of the deposited particles and the time constants characterizing the dissolution process as well as phagocytosis rate and particle transport by macrophages to the tracheobronchial tract. Relevant dose parameters such as retained and dissolved mass can be calculated from the temporally retained size distributions. For the first time, this theoretical presentation considers the polydispersity of aerosol particles deposited in the lung and thus provides an indispensable mathematical basis for a multicompartmental retention model that may combine particulate removal from the pulmonary region and the lymph nodes by a competition of the rates of dissolution and particulate clearance in all relevant lung model compartments.

Air Pollutants↗
PubMed2001

Inhalation studies with the Göttingen minipig.

A method for inhalative exposure of minipigs to aerosols and gases has been developed. Minipigs are exposed via mask inhalation to the test substance using a computer-controlled exposure system that permits simultaneous exposure of groups of four animals in parallel to different controlled dose levels. We studied inhalation treatment of verapamil, a cardiovascular drug, and show good absorption and favorable pharmacokinetics when compared with iv drug application. The results shown in this study encourage inhalation studies with the Göttingen minipig.

Aerosols↗
PubMed2001

[Capacity limitation and intellectual ability].

In a study examining the influence of cognitive capacity limitation on intellectual ability, 124 university students were subjected to 7 computer-based tests in which cognitive demands were manipulated by varying the number of required ordering, arithmetic, and memory operations, respectively. Intelligence data were obtained by forming a composite score from Raven's Advanced Progressive Matrices and the Berlin Intelligence Structure Test. Increases in cognitive demands led to increases in reaction times and number of errors as well as to increases in common variance and in correlations between intelligence and number of errors in 5 and 2 (of 5) comparisons, respectively, while correlations between intelligence and reaction time were found to decrease with increasing task demands in 3 comparisons. All correlations were reduced considerably when storage capacity and coordination efficiency were partialled out. These findings suggest a relationship between capacity limitation and intellectual ability.

Adolescent↗
PubMed2001

A novel protein elicitor (PaNie) from Pythium aphanidermatum induces multiple defense responses in carrot, Arabidopsis, and tobacco.

A novel protein elicitor (PaNie(234)) from Pythium aphanidermatum (Edson) Fitzp. was purified, microsequenced, and the corresponding cDNA was cloned. The deduced amino acid sequence contains a putative eukaryotic secretion signal with a proteinase cleavage site. The heterologously expressed elicitor protein without the secretion signal of 21 amino acids (PaNie(213)) triggered programmed cell death and de novo formation of 4-hydroxybenzoic acid in cultured cells of carrot (Daucus carota). Programmed cell death was determined using the tetrazolium assay and DNA laddering. Infiltration of PaNie(213) into the intercellular space of leaves of Arabidopsis (Columbia-0, wild type) resulted in necroses and deposition of callose on the cell walls of spongy parenchyma cells surrounding the necrotic mesophyll cells. Necroses were also formed in tobacco (Nicotiana tabacum cv Wisconsin W38, wild type) and tomato (Lycopersicon esculentum Mill.) but not in maize (Zea mays), oat (Avena sativa), and Tradescantia zebrina (Bosse), indicating that monocotyledonous plants are unable to perceive the signal. The reactions observed after treatment with the purified PaNie(213) were identical to responses measured after treatment with a crude elicitor preparation from the culture medium of P. aphanidermatum, described previously. The availability of the pure protein offers the possibility to isolate the corresponding receptor and its connection to downstream signaling-inducing defense reactions.

Adaptation, Physiological↗
PubMed2000

Circulating antibodies to p40(AIS) in the sera of respiratory tract cancer patients.

Studies of immune recognition in cancer have defined several tumor antigens using autologous cytotoxic T lymphocytes and by detection of serum antibodies to tumor-associated products such as p53 and HER-2/neu. The AIS gene is a p53 homologue with multiple protein products (p40, p51, p63, p73L) on chromosomal arm 3q, frequently amplified and over-expressed in squamous-cell carcinoma of the respiratory tract. We analyzed the humoral response to p40(AIS) (a core domain of AIS products without the transactivation domain) by Western blot and ELISA using bacterially synthesized p40(AIS) protein. Antibodies were detected in the sera of 17/94 (18%) HNSCCs and 13/76 (17%) lung cancers, including 5/18 (26%) squamous-cell carcinomas. Anti-p40(AIS) antibodies were not associated with factors such as sex, age, histopathological grading, extent or size of primary tumor, lymph node involvement and staging. Our results indicate that amplification and over-expression of p40(AIS) may lead to antigen recognition by an autologous host with cancer. AIS may thus represent a new group of developmentally regulated genes that are recognized as tumor antigens.

Aged↗
PubMed2000

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is not associated with restenosis after coronary stent placement.

BACKGROUND: The renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The objective of this study was to test the hypothesis that the D allele of the ACE gene is associated with a higher risk for restenosis after coronary stent placement. METHODS AND RESULTS: This prospective study included 1850 consecutive patients with coronary artery disease who underwent intracoronary stent implantation. The adverse clinical events recorded were death, myocardial infarction, and target vessel revascularization. The primary end point of the study was restenosis (>/=50% diameter stenosis at follow-up angiography performed in 84% of the patients). The secondary end point was clinical outcome 1 year after the procedure. The restenosis rate at the 6-month angiographic follow-up was 32.8% in patients with the II genotype, 34.0% for patients with the ID genotype, and 31.2% for patients with the DD genotype (P=0.62). One-year event-free survival was 77.7% in patients with genotype II, 75.2% in patients with genotype ID, and 75.5% in patients with genotype DD (P=0.54). The lack of association was also present in the subgroup of patients with a low risk for restenosis: the restenosis rate was 21.7% in II carriers, 23.4% in ID carriers, and 19.7% in DD carriers (P=0.83). CONCLUSIONS: The ACE DD genotype or D allele does not influence the 1-year clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenotic events after coronary stent placement.

Aged↗
PubMed2000

Crossed-beam study of Co+(3F4)+propane: experiment and density functional theory

A pulsed beam of Co+(3F4) crosses a pulsed beam of C3H8 or C3D8 gas under single collision conditions at collision energies of 0.01 eV and 0.21 eV. After a variable time delay t(ext) = 1-8 micros a fast high voltage pulse extracts product ions into a field-free flight tube for mass analysis. Consistent with earlier work, we observe prompt CoC3H6+ +H2 elimination products in 3:1 excess over CoC2H4+ +CH4 products at 0.21 eV on a 2-10 micros time scale. Long-lived CoC3H8+ complexes fragment predominantly back to Co+ +C3H8 reactants and to H2 elimination products on a 6-24 micros time scale. Density functional theory (B3LYP) calculations provide energies, geometries, and harmonic vibrational frequencies at key stationary points for use in a statistical rate model of the reaction. By adjusting two key multicenter transition state (MCTS) energies downward by 4-7 kcal mol(-1), we obtain good agreement with our decay time results and with the cross section versus collision energy of Armentrout and co-workers from 0.1-1.0 eV. B3LYP theory succeeds in finding relative energies of the MCTSs leading to CH4 and H2 in the proper order to explain the different product branching ratio for Co+ (which favors H2 over CH4) compared with its nearest neighbors Fe+ and Ni+ (which favor CH4 over H2).

Journal Article↗
PubMed2000

Glycoprotein Ia gene C807T polymorphism and risk for major adverse cardiac events within the first 30 days after coronary artery stenting.

The glycoprotein complex Ia/IIa (GP Ia/IIa) is a major collagen receptor on platelets and other cell types. Recently, linked polymorphisms within the coding region of the GP Ia gene (C807T and G873A) were identified that are related to GP Ia/IIa surface expression. The T807/A873 allele is associated with high expression, whereas the C807/G873 allele is associated with low surface expression of GP Ia/IIa. Subsequently, the T807 allele was found to be associated with coronary and cerebral infarction in younger patients. Platelet adhesion to the vessel wall plays a pivotal role in thrombosis after coronary artery stent placement. The goal of this study was to test whether C807T polymorphism is associated with a higher incidence of thrombotic events following coronary stenting. Consecutive patients treated with coronary stent placement (n = 1797) were genotyped for C807T polymorphism with polymerase chain reaction and allele-specific fluorogenic probes. The composite end point was defined as death, myocardial infarction, or urgent target vessel revascularization within 30 days of stent implantation. The genotype distribution of the study population was CC in 36.5%, CT in 46.7%, and TT in 16.8% of the patients. The incidence of the composite end point was 6.5% in T allele carriers and 5.3% in noncarriers (odds ratio for T allele carriage 1.23 [95% confidence interval, 0.81-1.86], P =.33). After adjusting for other baseline characteristics, the odds ratio for the composite end point was 1.15 (0.76-1.75). Therefore, C807T genotype has no significant influence on the major adverse events occurring after coronary artery stenting.

Aged↗
PubMed2000

Inverted sinonasal papilloma : a molecular genetic appraisal of its putative status as a Precursor to squamous cell carcinoma.

Inverted papilloma (IP) is a proliferative lesion of the epithelium lining the sinonasal tract. Although IP often recurs after surgical excision and is sometimes associated with squamous cell carcinoma of the sinonasal cavity (SNSCC), its presumed neoplastic nature and putative role as a precursor to squamous cell carcinoma have not been confirmed at the molecular genetic level. We analyzed the pattern of X chromosome inactivation in IPs from nine female patients. Inactivation of a single allele is seen in monoclonal proliferations and may be indicative of a neoplastic process. We also analyzed 28 IPs and 6 concurrent SNSCCs for loss of heterozygosity (LOH) on chromosomal arms 3p, 9p21, 11q13, 13q11, and 17p13. Losses at these loci occur frequently during neoplastic transformation of the upper respiratory tract and can be detected in squamous cell carcinomas and the progenitor lesions from which they arise. X chromosome analysis was informative in four of the nine IPs. All four lesions demonstrated a monoclonal pattern of inactivation. LOH was not detected in any nondysplastic areas from the 28 IPs, but LOH at one or more chromosomal loci was present in all six of the concurrent SNSCCs. We conclude that IPs are monoclonal proliferations, yet they do not fit the profile of a prototypic precursor lesion. Unlike squamous epithelial dysplasia, IPs do not routinely harbor several of the key genetic alterations that are associated with malignant transformation of the upper respiratory tract.

Alleles↗
PubMed2000

Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis.

Platelets and alterations of chemotactic and adhesive properties of endothelium play an important role in the pathophysiology of atherosclerosis. We investigated the effect of platelets on secretion of monocyte chemotactic protein-1 (MCP-1) and on surface expression of intercellular adhesion molecule-1 (ICAM-1) of cultured endothelium. Pretreatment of cultured monolayers of endothelial cells with alpha-thrombin-activated platelets significantly enhanced secretion of MCP-1 and ICAM-1 surface expression (P<0.01) that could be inhibited by interleukin-1 (IL-1) antagonists by approximately 40%. Activation of transcription factor nuclear factor-kappaB (NF-kappaB) which regulates transcription of early inflammatory response genes such as MCP-1, was significantly increased in endothelial cells treated with activated platelets via an IL-1 mediated mechanism as determined by electrophoretic mobility shift assay (EMSA) and kappaB-dependent transcriptional activity. In trans-well experiments, alpha-thrombin-activated platelets enhanced IL-1-dependent surface expression of vitronectin receptor (alpha(v)beta(3)) on the luminal aspect of endothelial monolayers and promoted alpha(v)beta(3)-mediated platelet/endothelium adhesion that could be inhibited by the antiadhesive peptides GRGDSP and c(RGDfV). We conclude that activated platelets induce significant changes in chemotactic (secretion of MCP-1) and adhesive (surface expression of ICAM-1 and alpha(v)beta(3)) properties of cultured endothelium. These findings imply a potential pathophysiological mechanism of platelets in an early stage of atherogenesis.

Blood Platelets↗