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Biomedical subjects

J Koch

Publications and source records attributed to J Koch.

At least 37 records · Page 2Linked to original sources

[Aneurysm of the internal carotid artery--a differential diagnosis of paralysis of the caudal cranial nerves].

Paralysis of the caudal cranial nerves, e. g. the nervus glossopharyngeus, vagus and accessorius, may cause disorders in swallowing and speaking leading to a reduction in the patient's quality of life. Glomus tumors or malignant lesions of the skull base are a frequent cause of such lesions. We report on the case of a 48 year old patient who presented an acute lesion of these cranial nerves in combination with paresis of the nervus hypoglossus as a result of an aneurysm of the internal carotid artery directly underneath the base of the skull. The aneurysm was treated by parent vessel occlusion. The results of this procedure were a shrinkage of the aneurysm and an improvement in the neurological symptoms.

Carotid Artery Diseases↗

Vitamin E prevents extensive lipid peroxidation in patients with hypertension.

Oxidative modification of low-density lipoprotein (LDL) increases atherogenic potential to induce the accumulation of lipids and cells in the vascular wall. Previous studies reveal that hypertensive patients have a higher susceptibility to LDL oxidation. As animal models indicate that vitamin E protects LDL from oxidation, here we study the influence of vitamin E on the resistance of LDL to oxidation (lag time) in 47 subjects (31 normotensive, 16 hypertensive) before and after oral administration of vitamin E (400 IE) daily for two months. LDL was isolated and oxidised by incubation with copper ions. The time course of oxidation was measured by continuous photometric monitoring of diene formation at 234 nm. At the beginning of this study, normotensive subjects showed a lag time of 108 +/- 26 minutes and hypertensive patients a lag time of 85 +/- 24 minutes (P<0.05). Vitamin E caused a significant increase in the lag time in both groups: normotensive subjects 128 +/- 33, hypertensives patients 114 +/- 27 minutes (P<0.01). At completion of the study, lag times in both groups were similar (P=not significant). The data presented here suggests that vitamin E protects against the increased risk of vascular disease in patients with hypertension by reducing the susceptibility to oxidative modification of LDL. Vitamin E may therefore act as an inhibitor of atherogenesis.

Administration, Oral↗

Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors.

The glycoprotein hormone receptors (thyrotrophin receptor, TSHr; luteinizing hormone/chorionic gonadotrophin receptor, LH/CGr; follicle-stimulating hormone receptor, FSHr) constitute a subfamily of rhodopsin-like G protein-coupled receptors (GPCRs) with a long N-terminal extracellular extension responsible for high-affinity hormone binding. These ectodomains contain two cysteine clusters flanking nine leucine-rich repeats (LRR), a motif found in several protein families involved in protein-protein interactions. Similar to the situation described recently in CCR5, we demonstrate here that the TSHr, as it is present at the cell surface, is sulfated on tyrosines in a motif located downstream of the C-terminal cysteine cluster. Sulfation of one of the two tyrosines in the motif is mandatory for high-affinity binding of TSH and activation of the receptor. Site-directed mutagenesis experiments indicate that the motif, which is conserved in all members of the glycoprotein hormone receptor family, seems to play a similar role in the LH/CG and FSH receptors.

Amino Acid Sequence↗

Spectroscopic determination of dynamic plasma gradients in implosion cores.

The time-dependent gradient structure of a laser-compressed, high-energy-density plasma has been determined using a method based on the simultaneous analysis of time-resolved x-ray monochromatic images and x-ray line spectra from Ar-doped D2 implosion cores. The analysis self-consistently determines the temperature and density gradients that yield the best fits to the spatial-emissivity profiles and spectral line shapes. This measurement is important for understanding the spectra formation and plasma dynamics associated with the implosion process. In addition, since the results are independent of hydrodynamic simulations, they are also important for comparison with fluid-dynamic models.

Journal Article↗

[Morphological and functional MRI studies after correction of aortic isthmus stenosis].

PURPOSE: To compare the results of different methods for postoperative assessment after coarctation repair by magnetic resonance imaging and to evaluate their reliability. The morphometric results are contrasted to functional parameters of CW Doppler, oscillometric pressure gradient and flow quantification in VEC-MRI. METHODS: 54 patients (age: 6 to 36 years) were assessed by MRI 3 to 31 years after coarctation repair. The aortic diameters were compared to growth-dependent normal values and to the diameter of the ascending (AA) and descending aorta (DA), and their mean values (MV). RESULTS: Patients after coarctation repair had mostly subnormal diameters of AA (mean value: 80% of normal) and AD (95% of normal). Compared to the control group, mean dispersion of AD diameters was significantly larger in the patient group (2.6 vs. 1.5 mm, p < 0.001). Degree of stenosis varied with the method. It was similar when using normal values and the diameter for DA, but dispersion was smaller when normal values were used. Correlation of the functional parameter to the degree of stenosis was weak. The highest correlation (r = 0.78) was reached when using normal values as the reference with mean cross-sectional velocity from VEC-MRI. CONCLUSION: The use of normal values as the reference for quantification of residual coarctation is more reliable than common methods. Since only one measurement is needed, it seems to be less susceptible to errors and more practical. MRI offers not only a tool for accurate morphologic assessment, but with VEC-MRI it is also possible to obtain a functional parameter which is superior to oscillometric pressure gradient and CW Doppler.

Adolescent↗

[CleftData. Program for minimal documentation of lip-jaw-palate clefts].

BACKGROUND: The aim of the German Study Group on Cleft Lip and Palate-Craniofacial Deformities is to develop a precise system for documentation of cleft lip and palate patients which is suitable for use in PC-databases. DOCUMENTATION: In cooperation with the medical disciplines involved in the therapy such as otolaryngology, oral and maxillofacial surgery, orthodontics and speech therapy a system of documentation was developed with regard to the international classification of diseases (ICD) and the operating procedures system (OPS). Malformations are classified with the LAHS coding system. In addition to this concept of minimal documentation photographic images in standardized projections are stored. Furthermore, each operative procedure is documented by its date and the anatomic region of malformation treated without details of operative methods or descriptions of other procedures. SOFTWARE: On behalf of the German Study Group on Cleft Lip and Palate a software to meet these purposes was developed called CleftData. Based on a relational Access database it is equipped with SQL connectivity enabling its use on all hard- and software-systems.

Cleft Lip↗

Expression of the helix-loop-helix protein ID1 in keratinocytes is upregulated by loss of cell-matrix contact.

To analyze the inhibitor of DNA-binding type 1 (ID1) in the human epidermis and in cultured keratinocytes we generated and characterized ID1-specific monoclonal antibodies. Immunohistological studies on human skin biopsies revealed that ID1 is not detectable in normal human epidermis but in lesional epidermis of bullous pemphigoid. In the latter case we found ID1 in the cytoplasm of basal and proximal suprabasal keratinocytes. Cultured normal human epidermal keratinocytes displayed ID1 in the cytoplasm; upon differentiation into a multilayered keratinocyte sheet, ID1 was no longer detectable. It was reexpressed after dispase-mediated detachment of the keratinocyte cultures from the growth substratum. In this case ID1 was localized to the cytoplasm and the nucleus. Our data indicate that after epidermal injury-in our case loss of cell-matrix contact-ID1 is upregulated in affected keratinocytes. In view of the ID1 function in other cell types, we speculate that ID1 facilitates the transition from the resting to the migrating and proliferating keratinocyte required for efficient repair of epidermal lesions by reepithelialization. Taken together we suggest that ID1 is an important player in epidermal (patho-)physiology.

Animals↗

Functional characterization of recombinant chloroplast signal recognition particle.

The signal recognition particle (SRP) is a ubiquitous system for the targeting of membrane and secreted proteins. The chloroplast SRP (cpSRP) is unique among SRPs in that it possesses no RNA and is functional in post-translational as well as co-translational targeting. We have expressed and purified the two components of the Arabidopsis thaliana chloroplast signal recognition particle (cpSRP) involved in post-translational transport: cpSRP54 and the chloroplast-specific protein, cpSRP43. Recombinant cpSRP supports the efficient in vitro insertion of pea preLhcb1 into isolated thylakoid membranes. Recombinant cpSRP is a stable heterodimer with a molecular mass of approximately 100 kDa as determined by analytical ultracentrifugation, gel filtration analysis, and dynamic light scattering. The interactions of the components of the recombinant heterodimer and pea preLhcb1 were probed using an immobilized peptide library (pepscan) approach. These data confirm two previously reported interactions with the L18 region and the third transmembrane helix of Lhcb1 and suggest that the interface of the cpSRP43 and cpSRP54 proteins is involved in substrate binding. Additionally, cpSRP components are shown to recognize peptides from the cleavable, N-terminal chloroplast transit peptide of preLhcb1. The interaction of cpSRP43 with cpSRP54 was probed in a similar experiment with a peptide library representing cpSPR54. The C terminus of cpSRP54 is essential for the formation of the stable cpSRP complex and cpSPR43 interacts with distinct regions of the M domain of cpSRP54.

Amino Acid Sequence↗

Identification of epitope regions recognized by tumor inhibitory and stimulatory anti-ErbB-2 monoclonal antibodies: implications for vaccine design.

The self-oncoprotein ErbB-2 is overexpressed in a number of malignancies. The presence of endogenous anti-ErbB-2 Ab and T cell immune responses to this protein in cancer patients has made ErbB-2 an attractive target for active immunization. However, the finding that murine anti-ErbB-2 Abs can have stimulatory, inhibitory, or no effects on cancer cell growth suggests that an inappropriately induced immune response may have an adverse effect. To ensure the induction of a beneficial Ab response, it is important to identify the epitopes recognized by these Abs. In this study we have used phage-displayed ErbB-2 gene fragment libraries and synthetic peptides to epitope-map a panel of anti-ErbB-2 mAbs. The epitopes of three mAbs, N12, N28, and L87, were successfully located to C531-A586, T216-C235, and C220-C235 of ErbB-2, respectively. It was found that while N12 inhibited tumor cell proliferation, N28 stimulated the proliferation of a subset of breast cancer cell lines overexpressing ErbB-2. The peptide region recognized by N12, (C531-A586; EP531), was used as an immunogen to selectively induce an inhibitory immune response in mice. Mice immunized with the GST fusion peptide (GST-EP531) recognized the peptide region EP531 as well as native ErbB-2. More importantly, Igs purified from mouse sera were able to inhibit up to 85% of tumor cell proliferation. In conclusion, our study provides direct evidence of the function-epitope relationship of anti-ErbB-2 Abs and also emphasizes the value of inducing a potent tumor inhibitory polyclonal Ab response by rationally selecting regions of ErbB-2 used for immunization.

Amino Acid Sequence↗

Effects of reversible inactivation of thalamo-striatal circuitry on delayed matching trained with retractable levers.

The intralaminar thalamic nuclei are characterized by their prominent projections to striatum. Lesions of the intralaminar nuclei have been found to impair delayed matching trained with retractable levers. Comparable impairments have been observed for rats with lesions of the olfactory tubercle, involving ventral areas of striatum and pallidum. We conducted two experiments to test the functional dependence of thalamic and striatal lesions on the delayed matching task. In experiment 1, we determined the effects of inactivating the intralaminar nuclei with bilateral lidocaine infusions. In experiment 2, we compared the effects of unilateral thalamic inactivations in rats with unilateral olfactory tubercle lesions. We trained rats to perform the delayed matching task to criterion and then implanted dual cannulas aimed at the bilaterally symmetrical areas in the intralaminar nuclei. Rats in experiment 2 were also given a unilateral olfactory tubercle lesion. The results of experiment 1 showed dose-dependent impairments for bilateral infusions that were qualitatively similar, although of lesser severity than delayed matching impairments observed in previous studies for rats with lesions involving extensive areas of the intralaminar nuclei. A comparable impairment was observed in experiment 2 when thalamus was inactivated on the side opposite the olfactory tubercle lesion. Performances were significantly worse when thalamus was inactivated on the contra-lesion than on the ipsi-lesion side of the brain. These results are discussed in terms of the role of ventral striatum and related thalamic nuclei in memory.

Amnesia↗

Experimental annotation of the human genome using microarray technology.

The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.

Algorithms↗

[General practice and home blood pressure measurement with fully automated device in long-term comparison].

In this prospective cohort study on 43 patients, the blood pressure patterns measured fully automatically in the doctor's practice and at home were compared over an average period of eight months. In total, a highly significant correlation was found between professional and patient measurements for both systolic and diastolic values. However, over the entire study period, the values obtained in the doctor's practice were higher than the patient's measurements (systolic +17 mmHg, diastolic +9 mmHg). The values obtained in the practitioner's office exhibited a much greater fluctuation than the patient's measurements. The majority of the values measured in the practice were above the mean of the home measurements (65% systolic and 67% diastolic). On therapy, 28 percent of the patients showing hypertensive values in the practice measured normal pressures at home. In conclusion, the study shows a minor fluctuation and a better reproducibility of the patient's own measurements versus those taken in the practitioner's office.

Adult↗

[Abdominal wall metastases as a complication of percutaneous endoscopic gastrostomy in carcinoma of the upper aerodigestive tract].

Percutaneous endoscopic gastrostomy (PEG) has become an important adjunct in the care of head and neck cancer patients. In the literature of the last 10 years, 16 cases of abdominal wall metastasis after PEG implantation were reported. We performed 387 PEG procedures in patients with head and neck cancers. In this paper, we describe two patients with advanced head and neck cancers who underwent PEG prior to cancer therapy and developed metastatic cancer at the PEG site 3 or 4 months later. Although the mechanism of spread cannot be confirmed, direct seeding from passage through the cancer seems likely. Methods of establishing enteral access which avoid tumor-contaminated fields, such as the use of an overtube during conventional PEG or PEG procedure after tumor resection, may be appropriate in head and neck cancer patients. Another possibility of origin is the hematogenous spread of cancer cells from metastases on the abdominal wall.

Abdominal Muscles↗

A helper phage to improve single-chain antibody presentation in phage display.

We show here that the number of single-chain antibody fragments (scFv) presented on filamentous phage particles generated with antibody display phagemids can be increased by more than two orders of magnitude by using a newly developed helper phage (hyperphage). Hyperphage have a wild-type pIII phenotype and are therefore able to infect F(+) Escherichia coli cells with high efficiency; however, their lack of a functional pIII gene means that the phagemid-encoded pIII-antibody fusion is the sole source of pIII in phage assembly. This results in an considerable increase in the fraction of phage particles carrying an antibody fragment on their surface. Antigen-binding activity was increased about 400-fold by enforced oligovalent antibody display on every phage particle. When used for packaging a universal human scFv library, hyperphage improved the specific enrichment factor obtained when panning on tetanus toxin. After two panning rounds, more than 50% of the phage were found to bind to the antigen, compared to 3% when conventional M13KO7 helper phage was used. Thus, hyperphage is particularly useful in stoichiometric situations, when there is little chance that a single phage will locate the desired antigen.

Capsid↗

Comparison of patients' experiences during imaging tests of the colon.

BACKGROUND: Physical discomfort, anxiety, embarrassment, and other aspects of patient experience impact on future compliance for colonic imaging tests. Therefore, a prospective study was performed comparing patient experiences during air contrast barium enema (ACBE), flexible sigmoidoscopy, and colonoscopy. METHODS: Immediately after each procedure, patients completed a questionnaire assessing pretest anxiety, difficulty with preparation, pain, cramping, bloating, overall discomfort, loss of dignity, willingness to repeat the test, and overall satisfaction. A follow-up questionnaire was administered within 48 hours. Nurses and physicians also completed questionnaires to assess the provider impression of patient experience. RESULTS: Four hundred ten patients (80 ACBE, 202 sigmoidoscopy, 128 colonoscopy) were prospectively enrolled. Sigmoidoscopy caused more pain than ACBE (Odds ratio [OR] 2.64: 95% CI [1.63, 4.27]) or colonoscopy (OR 1.83: 95% CI [1.21, 2.77]). ACBE and colonoscopy did not differ in the degree of pain. Although overall satisfaction appeared to be similar for all tests, patients were less willing to repeat ACBE than sigmoidoscopy (OR 1.85: 95% CI [1.13, 3.02]) or colonoscopy (OR 1.82: 95% CI [1.07, 3.09]). Initial and follow-up pain ratings by patients were highly correlated (Spearman correlation 0.81); however, correlation of pain assessments between staff and patients was poor (Spearman correlation 0.48). CONCLUSIONS: Sigmoidoscopy was more painful than other colonic imaging modalities. Although ACBE and colonoscopy caused similar pain, patients were less willing to repeat ACBE. In aggregate, the data suggest that patients perceive colonoscopy as the most acceptable colonic imaging procedure. Better methods are required to allow staff to adequately assess discomfort experienced by patients during these procedures.

Adult↗

Pulmonary adrenomedullin counteracts deterioration of coronary flow and myocardial performance evoked by pulmonary endothelins in experimental acute respiratory distress syndrome.

OBJECTIVES: We recently showed that pulmonary endothelins may affect coronary circulation under various experimental and clinical conditions. Here, we investigated the effect of pulmonary mediators on coronary tone in experimental acute respiratory distress syndrome. We focused particularly on pulmonary endothelin-1, a major vasoconstrictor in acute respiratory distress syndrome, and on adrenomedullin, a potent vasodilator that is up-regulated by inflammatory stimuli. DESIGN: Controlled experiment that used isolated organs. SETTING: Experimental laboratory. SUBJECTS: Wistar rats. INTERVENTIONS: The saline effluent from an isolated lung was used to serially perfuse the coronary vessels of an isolated heart. We compared serial perfusion after 2-hr pretreatment of lungs with vehicle or endotoxin (50 microg/mL), and we used the following drugs to elucidate the coronary response observed: the endothelin type A receptor antagonist BQ-123 (2 microM), the endothelin type B antagonist A-192621 (500 nM), the endothelin-converting enzyme inhibitor phosphoramidon (50 microM), the calcitonin gene-related peptide type-1 receptor antagonist hCGRP(8-37) (2 microM), and the adrenomedullin receptor antagonist hAM(22-52) (200 nM) (n = 6 each). MEASUREMENTS AND MAIN RESULTS: In controls, serial perfusion decreased coronary flow to 87 +/- 3% of baseline (p < .05). BQ-123 and phosphoramidon prevented this effect, whereas blockade of endothelin type B and adrenomedullin-binding receptors had no effect. After endotoxin challenge, coronary flow significantly increased to 110 +/- 2%. This response was augmented by BQ-123 (124 +/- 2%) and phosphoramidon (123 +/- 3%); A-192621 had no effect. Application of hCGRP(8-37) and hAM(22-52) significantly decreased coronary flow to 81 +/- 3% and 88 +/- 2%, respectively. Flow decrease after blockade of both adrenomedullin-binding receptors (73 +/- 2%) significantly deteriorated peak left ventricular pressure, to 82 +/- 6% of baseline; rate of pressure increase, to 81 +/- 5%; and rate of pressure decline, to 77 +/- 6%. Endotoxin pretreatment elevated pulmonary venous big endothelin-1 (three-fold), endothelin-1 (two-fold), and adrenomedullin (five-fold). CONCLUSION: In experimental acute respiratory distress syndrome, pulmonary adrenomedullin--via calcitonin gene-related peptide type-1 receptor and adrenomedullin receptor--outweighs the coronary vasoconstrictor impact of pulmonary big endothelin-1 exerted via endothelin type A receptors after conversion to mature endothelin-1. The consequence is prevention of flow-related deterioration of myocardial performance.

Adrenomedullin↗

Expansion of repetitive DNA into cytogenetically visible elements.

Two cases of amplified repetitive elements accidentally identified in cancer samples are reported. In both cases, repeated DNA that is normally not visible by traditional chromosome banding had increased in amount to become cytogenetically visible. In one case, an addition to the short arm of chromosome 1 was originally diagnosed. However, upon molecular analysis the diagnosis could be corrected to an amplification of the D1Z2 repeat. In the second case, a strongly DAPI-positive band was visible at the top of the short arm of chromosome 22, and the original diagnosis was add(22). Staining for telomeric repeats revealed their presence inside the DAPI-positive element, thus confirming that the element in question was truly added to the end of the chromosome. Curiously, no telomeric repeats could be detected distal to the DAPI-positive element. The identity of the DAPI-positive element could not be established, as it was not stained by any of the specific probes applied, nor in a scanning hybridization with labeled Cot-1 DNA. It thus seems to represent an expansion from some lowly repetitive AT-rich DNA translocated to the tip of chromosome 22.

AT Rich Sequence↗