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Biomedical subjects

K Hermann

Publications and source records attributed to K Hermann.

At least 19 recordsLinked to original sources

Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12.

BACKGROUND AND AIMS: As integral membrane proteins, claudins form tight junctions together with occludin. Several claudins were shown to be up-regulated in various cancer types. We performed an expression analysis of genes encoding tight junction proteins to display differential gene expression on RNA and protein level and to identify and validate potential targets for colorectal cancer (CRC) therapy. PATIENTS AND METHODS: Amplified and biotinylated cRNA from 30 microdissected CRC specimen and corresponding normal tissues was hybridized to Affymetrix U133set GeneChips. Quantification of differential protein expression of claudin-1, -8 and -12 between normal and corresponding tumour tissues was performed by Western blot analyses. Paraffin-embedded CRC tissue samples, colon cancer cell lines and normal tissue microarray were analysed for protein expression of claudin-1 by immunohistochemistry (IHC). RESULTS: Claudin-1 (CLDN1) and -12 (CLDN12) are frequently overexpressed in CRC, whereas claudin-8 (CLDN8) shows down-regulation in tumour tissue on RNA level. Quantification of proteins confirmed the overexpression of claudin-1 in tumour tissues, whereas changes of claudin-8 and -12 were not significantly detectable on protein level. IHC confirmed the markedly elevated expression level of claudin-1 in the majority of CRC, showing membranous and intracellular vesicular staining. CONCLUSIONS: Differential expression of genes encoding claudins in CRC suggests that these tight junction proteins may be associated to and involved in tumorigenesis. CLDN1 is frequently up-regulated in large proportion of CRC and may represent potential target molecule for blocking studies in CRC.

Aged↗

Adsorption geometry and core excitation spectra of three phenylpropene isomers on Cu(111).

Theoretical C 1s near edge x-ray absorption fine structure (NEXAFS) spectra for the C(9)H(10) isomers trans-methylstyrene, alpha-methylstyrene, and allylbenzene in gas phase and adsorbed at Cu(111) surfaces have been obtained from density functional theory calculations where adsorbate geometries were determined by corresponding total energy optimizations. The three species show characteristic differences in widths and peak shapes of the lowest C 1s-->pi(*) transitions which are explained by different coupling of the pi-electron system of the C(6) ring with that of the side chain in the molecules as well as by the existence of nonequivalent carbon centers. The adsorbed molecules bind only weakly with the substrate which makes the use of theoretical NEXAFS spectra of the oriented free molecules meaningful for an interpretation of experimental angle-resolved NEXAFS spectra of the adsorbate systems obtained in this work. However, a detailed quantitative account of relative peak intensities requires theoretical angle-resolved NEXAFS spectra of the complete adsorbate systems which have been evaluated within the surface cluster approach. The comparison with experiment yields almost perfect agreement and confirms the reliability of the calculated equilibrium geometries of the adsorbates. This can help to explain observed differences in the catalytic epoxidation of the three molecules on Cu(111) based on purely geometric considerations.

Journal Article↗

Spectroscopic analysis of small organic molecules: a comprehensive near-edge x-ray-absorption fine-structure study of C6-ring-containing molecules.

We report high-resolution C 1s near-edge x-ray-absorption fine-structure (NEXAFS) spectra of the C6-ring-containing molecules benzene (C6H6), 1,3- and 1,4-cyclohexadiene (C6H8), cyclohexene (C6H10), cyclohexane (C6H12), styrene (C8H8), and ethylbenzene (C8H10) which allow us to examine the gradual development of delocalization of the corresponding pi electron systems. Due to the high experimental resolution, vibrational progressions can be partly resolved in the spectra. The experimental spectra are compared with theoretical NEXAFS spectra obtained from density-functional theory calculations where electronic final-state relaxation is accounted for. The comparison yields very good agreement between theoretical spectra and experimental results. In all cases, the spectra can be described by excitations to pi*- and sigma*-type final-state orbitals with valence character, while final-state orbitals of Rydberg character make only minor contributions. The lowest C 1s-->1pi* excitation energy is found to agree in the (experimental and theoretical) spectra of all molecules except for 1,3-cyclohexadiene (C6H8) where an energy smaller by about 0.6 eV is obtained. The theoretical analysis can explain this result by different binding properties of this molecule compared to the others.

Journal Article↗

[Brain natriuretic peptide for postoperative monitoring of the fluid balance in a cardiac surgery patient].

Brain natriuretic peptide is a neurohormone used for estimation of left ventricular wall tension and volume overload. We describe the use of this parameter in a postoperative cardiac surgery patient for detection and monitoring of left ventricular failure in a postoperative intensive care unit at a tertiary care center. Left ventricular failure was detected by brain natriuretic peptide levels, while x-ray and values obtained by the pulmonary artery catheter were inconclusive.

Aged↗

Immunocytochemical and biochemical identification of angiotensin II in human nasal tissue.

Angiotensin II (ANG II) was identified immunocytochemically and biochemically in biopsy samples of human nasal tissue. Staining for ANG II was predominantly found in structures similar to a string of pearls with consecutive short varicose areas, which is characteristic for neuronal tissue. The localization of ANG II in neurons was confirmed by positive staining of adjacent tissue sections with a specific antibody to neurofilament or doublestaining with both antibodies in one section. Likewise, ANG II-like material was also determined radioimmunologically in nasal tissue extracts. The concentrations of ANG II varied form 1.28 to 332.78 fmol/g wet tissue weight with an average concentration of 79.61+/-44.09 fmol ANG II/g wet tissue weight (mean+/-SEM, n=7). The ANG II-immunoreactive material was further characterized biochemically by HPLC on a reversed phase C(18) column in an acetonitrile and methanol gradient as Ile(5)-ANG II and ANG II metabolites such as Ile(4)-ANG III, Ile(3)-ANG II(3-8)hexapeptide and Ile(2)-ANG II(4-8)pentapeptide.

Angiotensin II↗

The NIST Surface Structure Database -- SSD version 4.

SSD-4, the fourth version of the NIST Surface Structure Database, has appeared in early 2002 as a significant upgrade to both the database and graphics software; it now also includes nearly 1300 structures published through the end of 2000. SSD is an interactive PC-based database of critically selected surface structures determined with a variety of experimental techniques. The data include not only atomic coordinates, bond lengths and bond angles, but also information about experimental preparation, measurement and analysis methods. The software provides advanced search and display facilities, as well as interactive three-dimensional color visualization and analysis tools of great flexibility. In addition, the program can generate publication-quality color or grayscale prints of any structure, with a host of user-selectable options (such as view angle, perspective, colors, ball and bond styles, and labels).

Computer Graphics↗

UV-induced skin changes due to regular use of commercial sunbeds.

BACKGROUND/AIM: Increased pigmentation and thickening of the epidermis are the most important photoprotective skin reactions induced by ultraviolet (UV) radiation. The present study was designed to find out what changes are induced by regular use of commercial sunbeds twice weekly over a period of 6 weeks. METHODS: The parameters analysed were skin pigmentation measured by chromametry, minimal erythema dose (MED) as a parameter of light sensitivity, epidermal thickening as determined by histology, induction of keratinocyte apoptosis as determined by TUNEL staining and antioxidant metabolism as measured by changes of cis- and trans-urocanic acid (UCA) content of the skin. RESULTS: As expected, chromametry confirmed the clinically obvious increased skin pigmentation. However, no increase in MED was observed. In addition, neither epidermal thickening nor sunburn cells were seen. Significant detectable changes in proportion of the UCA isomer content of the UV-exposed skin were seen. The total UCA and cis-UCA content increased significantly between nearly all points of measurement. The amount of trans-UCA first decreased, then increased significantly between the different time points. CONCLUSION: Our data indicate that sunbed-induced tanning is non-protective, which has to be addressed for persons looking for this effect before planning a stay in a sunny climate. However, sunbed-induced tanning may influence immunological reactions.

Adolescent↗

Oligodendrogliomas.

PURPOSE: To study the pattern of contrast enhancement in MR and CT of oligodendrogliomas and to compare this with other imaging findings and with histopathological grading criteria. MATERIAL AND METHODS: 20 patients with oligodendrogliomas (12 low-grade WHO II and 8 anaplastic WHO III) were reviewed. 20 complete MR investigations, 20 non-enhanced CT studies and 16 CTs after contrast enhancement were estimated blindly without knowledge of the tumour histological grades. RESULTS: All anaplastic oligodendrogliomas showed tumour contrast enhancement on MR and CT images. Also in 6/12 low-grade oligodendrogliomas the contrast was enhanced on MR imaging. In 5 of these, tumour calcifications were detected by CT. The remaining 6/12 WHO grade II cases showed no significant MR contrast enhancement. Of the oligodendrogliomas grade II, CT showed contrast uptake in 3 cases and no enhancement in 6, while in 3 cases postcontrast CT was not available. A comparison of contrast enhancement with tumour grade resulted in a p-value of 0.042 for MR and of 0.011 for CT. A combined statistical test of tumour grade and calcifications detected by CT compared with MR contrast enhancement showed a significant correlation (p=0.014). CONCLUSION: These data demonstrated that a clear grading of oligodendrogliomas based on the image criterion MR contrast enhancement was not possible. We suppose that, besides tumour neovascularisation, additional factors such as calcifications may disturb the blood-brain barrier.

Brain Neoplasms↗

Analysis of histidine and urocanic acid isomers by reversed-phase high-performance liquid chromatography.

The qualitative separation performance of a C18, C8 and C4 reversed-phase column was investigated for the separation of histidine and its metabolites histamine, 1-methyihistamine and trans- and cis-urocanic acid. Trans- and cis-urocanic acid were baseline separated from their precursor histidine on all three columns using isocratic elution with a mobile phase composed of 0.01 M aqueous TEAP pH 3.0 and acetonitrile at a ratio of 98:2 (v/v). However, histidine was not separated from histamine and 1-methyihistamine. Selecting the C8 column and introducing 0.005 M of the ion pairing reagent 1-octanesulfonic acid sodium salt into the aqueous solution and acetonitrile at a ratio of 90:10 (v/v), significantly improved the separation. The separation was also followed by a change in the retention times and the order of elution. The sequence of elution was histidine, cis-urocanic acid, trans-urocanic acid, histamine and 1-methylhistamine with retention times of 5.58 +/- 0.07, 7.03 +/- 0.15, 7.92 +/- 0.18, 18.77 +/- 0.24 and 20.79 +/- 0.21 min (mean +/- SD; n=5). The separation on the C8 column in the presence of the ion-pairing reagent was further improved with gradient elution that resulted in a reduction in the retention times and elution volumes of histamine and 1-methylhistamine. The detection limits of histidine and trans-urocanic acid at a wavelength of 210 nm and an injection volume of 0.05 ml were 5 x 10(-8) mol l(-1) (n=3). The kinetic of the in-vitro conversion of trans- into the cis-isomer after UV irradiation was depending on the time of exposure and the energy of the light source. UVB light induced a significantly faster conversion than UVA light. TUCA and cUCA samples kept at -25 degrees C were stable for up to 50 weeks. Samples, eluted from human skin showed various concentrations of histidine and trans- and cis-urocanic acid with an average of 1.69 +/- 0.33 x 10(-5) mol l(-1), 1.17 +/- 0.43 x 10(-5) mol l(-1) and 1.67 +/- 0.33 x 10(-5) mol l(-1), respectively (n=8).

Adult↗

Comparison of the effects of two early intervention strategies on the health outcomes of malnourished hemodialysis patients.

OBJECTIVE: To determine the efficacy and cost-effectiveness of providing oral supplementation early in the course of malnutrition for hemodialysis (HD) patients. DESIGN: The study design consisted of 3 groups: an experimental group, a control group of patients with mild hypoalbuminemia (HA) (serum albumin [SA] = 3.5 to 3.7 g/dL), and a comparison group of patients with moderate to severe HA (SA = 2.5 to 3.4 g/dL). SETTING: Ten outpatient hemodialysis centers in southeast lower Michigan. PATIENTS: Treatment and control groups consisted of 32 HD patients with mild HA. Fourteen HD patients with moderate to severe HA comprised the comparison group. INTERVENTION: The experimental group received diet counseling and oral supplementation, and the control group received diet counseling only. The comparison group received physician-prescribed oral supplements and dietary counseling to permit comparison of the experimental treatment with current supplementation practices. MAIN OUTCOME MEASURES: Differences between groups in the number of patients reaching nutritional repletion, change in SA levels at the end of the study, and follow-up periods, were tested using chi-square analysis. Analysis of variance was used to compare group differences in treatment duration to repletion and number of hospitalization days. RESULTS: During the study period, significantly more patients reached nutritional repletion in the experimental group and control group (50% and 57%, respectively) than in the comparison group (7%). Overall, repletion occurred more quickly in the experimental group (3.2 +/- 1.7 months) than in the control group (3.5 +/- 1.2 months), with a larger number of patients in the experimental group repleted by month 2 of the study phase. During follow-up, patients in the experimental group were far more likely to maintain nutritional repletion or continue to improve (61%) than patients in the control group (14%). Although too few patients were hospitalized to show statistical significance, there was a trend toward greater numbers of hospital days in more malnourished patients (208 days for the comparison group), followed by those with mild HA who did not receive oral supplements (107 days), and the experimental group (71 days). CONCLUSION: Although the sample size for this study was too small for the results to be conclusive, it appears that use of nutritional supplements early in the course of malnutrition may provide benefits such as, attaining nutritional repletion more quickly, which results in less product usage. It is also more likely that good nutritional status will be maintained after supplementation is discontinued.

Aged↗

Immunohistochemical detection of simian immunodeficiency virus (SIV) in rectal mucosa of experimentally infected rhesus macaques (Macaca mulatta).

Experimental simian immunodeficiency virus (SIV) infection is the most appropriate animal model for human HIV infection. Eight male rhesus monkeys (Macaca mulatta) were intravenously or intrarectally infected with SIVmac251/MPBMC to comparatively investigate the distribution and spread of the virus within the rectum during the course of the disease. SIV-positive cells were immunohistochemically detected in rectal biopsies obtained at days 3 and 7 and week 2, 4 and 12 postinfection. SIV-expressing cells were detected for the first time at one week after experimental infection and were present in the lamina propria and lymph follicles. Numbers of positive cells per individual animal varied strongly in time, with a more rapid rise in animals with rapid progression of the disease. Differences were not observed between intravenous and intrarectal infection. Our observations support the significance of the intestinal tract as target organ in initial pathogenesis of SIV infection.

Animals↗

Determination of histidine and urocanic acid isomers in the human skin by high-performance capillary electrophoresis.

Histidine was baseline separated from histamine, 1-methylhistamine and cis- and trans-urocanic acid using high-performance capillary electrophoresis (HPCE) on a fused-silica column (50 cm x 75 microm) with 0.05 M NaH2PO4 buffer, pH 5.0, and 12 kV. The detection limit of histidine, trans- and cis-urocanic acid was 10(-6) M at a wavelength of 214 nm. The detection limit of the urocanic acid isomers was slightly enhanced to 5 x 10(-7) M at 267 nm. The transformation of the trans-urocanic acid standard in vitro into the cis-isomer was dependent on the time of exposure and the energy of the light source. UVB light induced a significantly faster conversion than UVA light. The HPCE method was used for the characterization and measurement of histidine and urocanic acid in human skin eluates. The concentrations of histidine, trans- or cis-urocanic acid in ethanol washes from the skin of healthy, non-allergic volunteers were 2.22+/-0.40 x 10(-5) 0.96+/-0.26 x 10(-5) and 1.04+/-0.30 x 10(-5) M, respectively, (mean+/-SEM, n=8). The results obtained by HPCE correlated well with data obtained by HPLC. Correlation coefficients of r2=0.981, r2=0.814 and r2=0.956 were found for histidine, trans- and cis-urocanic acid, respectively.

Electrophoresis, Capillary↗

Urinary apo(a) excretion is not altered by changes in glomerular filtration rate and renal plasma flow in healthy males.

Lipoprotein(a) (Lp(a)) is an independent risk factor for atherosclerotic disease. However, information concerning the site of Lp(a) catabolism and breakdown is scarce. Several studies have shown that, in renal insufficiency, plasma Lp(a) levels are elevated, and that after normalisation of kidney function they return to normal. We have recently shown that fragments of apo(a) are found in the urine of healthy individuals. Despite this evidence that apo (a) is excreted into the urine, the mode of excretion of apo(a) remains unclear. Since it has been reported that intravenous infusion of somatostatin can reduce glomerular filtration rate (GFR) and renal plasma flow (RPF), we analysed urinary apo(a) excretion in ten healthy volunteers receiving somatostatin infusions. The infusion of somatostatin led to reversible changes in GFR and RPF. Apo(a) excretion was constant in all 10 individuals over the entire time course when normalised for creatinine. There was a highly significant correlation between plasma Lp(a) levels and urinary apo(a) values. Changes in renal plasma flow and glomerular filtration rate did not alter urinary apo(a) excretion. We conclude that a constant amount of apo(a) is excreted into urine, depending on plasma Lp(a) levels, and that urinary apo(a) excretion is not altered by changes in GFR and RPF in healthy males.

Adult↗

Quantitative assessment and correlation of sympathetic, parasympathetic, and afferent small fiber function in peripheral neuropathy.

We compared three neurophysiological methods for assessing small nerve fiber function in 40 patients with peripheral neuropathy to determine the various manifestation types of peripheral small fiber neuropathy. Heart rate variation tests were used to assess cardiac parasympathetic small fiber function. Cutaneous vasoconstrictor responses (sympathetic C fibers) induced by deep inspiration were examined with laser Doppler flowmetry. Cutaneous afferent C fiber function was assessed by measurement of axon reflex vasodilatation induced by histamine iontophoresis. All test parameters were significantly lower in patients with peripheral neuropathy than in control subjects. Comparison of the three small fiber systems revealed that functionally different systems are damaged independently, and isolated affection of each fiber type was frequently observed. The three tests are useful noninvasive tools with which to evaluate sympathetic, parasympathetic, and afferent small fiber function in patients with peripheral neuropathy. In many patients functionally different small fiber systems are affected selectively. To diagnose small fiber neuropathy and to evaluate the individual type of manifestation complementary testing of several small somatic and autonomic fiber systems is necessary.

Adult↗

Treatment outcomes for female octogenarians with breast cancer.

Scant information is available comparing the treatment outcomes of minor surgery (lumpectomy) versus extensive treatment (radical and simple mastectomy or lumpectomy and radiation) in octogenarians with breast cancer. Medical records of women (ages 80-89) who received treatment for breast cancer from 1984 through 1994 were reviewed. All patients were stage T1 or T2, and none had palpable lymph nodes. The recurrence rate, disease-free interval, and death rate for both groups were compared. Of the 41 patients representing 43 minor surgeries, 12 per cent (5 of 41) of patients developed recurrence, all of which were related to the primary breast tumor. The mean disease-free interval was 28.6 +/- 24.7 months (range, 6-65). Forty-six per cent (18 of 39) of patients died, 10 per cent (4 of 39) from recurrence and metastatic disease from breast cancer and 36 per cent (14 of 39) from other causes. Of those who underwent extensive treatment, 14.6 per cent (7 of 48) of patients experienced recurrence, all related to the primary breast tumor. The mean disease-free interval was 24.0 +/- 21.9 months (range, 2-71). Forty-eight per cent (23 of 48) of patients died, 10 per cent (5 of 48) from recurrence and metastatic disease from breast cancer and 37 per cent (18 of 48) from other causes. None of the differences between the minor surgery versus extensive treatment groups were statistically significant. The recurrence rate, disease-free interval, and death rate from recurrent disease are similar for patients undergoing minor surgery compared with those undergoing extensive treatment.

Aged↗

Pasteurella multocida toxin increases endothelial permeability via Rho kinase and myosin light chain phosphatase.

Pasteurella multocida toxin (PMT) has been shown to induce actin reorganization through activation of the GTPase Rho. Here we investigated the involvement of the Rho target proteins Rho kinase and myosin light chain (MLC) phosphatase in the PMT-induced increase in endothelial permeability and the underlying actin reorganization of endothelial cells. Stimulation of endothelial layers with PMT enhanced transendothelial permeability > 10-fold, and this was abolished by pretreatment with the specific Rho inactivator C3 transferase from Clostridium botulinum. The PMT-induced increase in endothelial permeability was associated with 1) inactivation of MLC phosphatase, 2) an increase in MLC phosphorylation, and 3) endothelial cell retraction and actin stress fiber formation. PMT-stimulated actin reorganization could be prevented by 1) pretreatment of cells with C3 transferase, 2) microinjection of the Rho binding domain and the pleckstrin homology domain of Rho kinase, and 3) microinjection of constitutively active MLC phosphatase. Together, these results suggest that PMT activates Rho/Rho kinase, which inactivates MLC phosphatase. The resulting increase in MLC phosphorylation causes endothelial cell retraction and a rise in endothelial permeability.

Bacterial Proteins↗

Normative values of vibratory perception in 530 children, juveniles and adults aged 3-79 years.

Impaired vibratory perception is an early and frequent finding in various neuropathies. Quantitative vibratory threshold assessment refines the diagnosis of neuropathies but is based on psychophysical techniques requiring patient cooperation. Large, age and sex matched normative data bases are needed to better identify abnormal vibratory perception. In this study vibratory perception was tested at the second metacarpal bone and above the first metatarsal bone of 530 children, juveniles and adults aged 3.3-79.2 years. Thresholds assessed with a 128 Hz graded Rydel-Seiffer tuning fork, TF, were compared to three Vibrameter values, the vibration perception thresholds, VPT, determined with increasing vibration stimuli, the vibration disappearance threshold, VDT, determined with decreasing supraliminal stimuli, and the vibration threshold VT which equals the mean of VPT and VDT. The influence of gender, age, body height, weight and skin temperature at the tested site on thresholds was studied. Retest reliability was tested in 73 children aged 3.3-6.9 years and in 20 volunteers aged 5.2-66.1 years who were also tested for the influence of pretest skin warming on thresholds and for differences between results of the left and right body side. TF, VPT, VDT, VT were closely correlated with each other (Spearman: -0.67<Rs<-0.47; P<0.01). The skin temperature, body side, weight and height did not influence thresholds. In adults, thresholds increased with age and were higher in men above the age of 50 than in women of the same age. Thresholds at the feet were higher than at the hands (Wilcoxon: P<0.001). Retest reliability was high and did not depend on the retest interval. The study provides important normative data for the widespread use of quantitative vibration testing.

Adolescent↗

Magnification survey and spot view mammography with a new microfocus X-ray unit: detail resolution and radiation exposure.

The aim of our study was to evaluate a mammography unit capable of magnification of up to fourfold at an equivalent or lower dose than with current systems. A prototype mammography tube with an electron-beam-focusing technology resulting in a focal spot size of 40-120 micro m was combined with a highly intensifying screen-film system. To evaluate contrast-detail resolution, phantom radiographs were performed with the prototype magnification mammography system using a magnification factor of 1.7 for survey views and a magnification factor of 4.0 for spot views. They were compared with unmagnified survey views and magnification spot views (magnification factor 1.9) of a state-of-the-art mammography system. The radiation exposure was measured and mean glandular doses were calculated. The contrast-detail resolution with both prototype (m = 1.7) and conventional (m = 1.1) survey views was equivalent while the entrance dose and the mean glandular dose were approximately 50 % lower with the prototype. For spot views, the contrast-detail resolution was substantially higher for the prototype than for conventional magnification while the dose was equivalent. Dose reduction and improved detail resolution are possible with this new technology.

Acrylic Resins↗