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Biomedical subjects

K Hermann

Publications and source records attributed to K Hermann.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front.

Sixty to eighty percent of all colorectal cancers are characterized by mutations in the APC tumor suppressor gene. Recently, it was shown that these mutations lead to a nuclear overexpression of beta-Catenin by disruption of the wingless/WNT signal pathway. Since nuclear beta-Catenin functions as a transcriptional activator of hitherto unknown tumor genes, this form of beta-Catenin is now considered a major oncoprotein in colorectal cancer. Using immunohistochemistry, we investigated the distribution of overexpressed beta-Catenin within individual colorectal carcinomas. In the majority of the tumors, we found no homogeneous staining, but a strong nuclear expression of beta-Catenin predominantly localized at the invasion front with strongest nuclear staining of isolated, scattered tumor cells. In contrast, cells in the tumor center often showed no nuclear staining, but retained a membranous expression of beta-Catenin, comparable to normal colon epithelium. It is, therefore, likely that in addition to the overexpression of beta-Catenin caused by defects in the APC locus, regulatory events in the tumor itself lead to a different distribution of this oncoprotein. Possibly, surrounding tissue at the invasion front can give signals to the tumor cells, leading to a nuclear translocation of beta-Catenin, where it may play a direct role in tumor invasion processes.

Cell Nucleus↗
PubMed1998

GeneGenerator--a flexible algorithm for gene prediction and its application to maize sequences.

MOTIVATION: We developed GeneGenerator because of the need for a tool to predict gene structure without knowing in advance how to score potential exons and introns in order to obtain the best results, pertinent in particular to less well-studied organisms for which suitable training sets are small. GeneGenerator is a very flexible algorithm which for a given genomic sequence generates a number of feasible gene structures satisfying user-defined constraints. The specific implementation described in detail requires minimum scoring for translation start and donor and acceptor splice sites according to previously trained logitlinear models. In addition, potential exons and introns are required to exceed specified minimal lengths and threshold scores for coding or non-coding potential derived as log-likelihood ratios of appropriate Markov sequence models. RESULTS: A database of 46 non-redundant genomic sequences from maize is used for illustration. It is shown that the correct gene structures do not always maximize the considered target function. However, in most cases, the correct or nearly correct structures are found in a small set of high-scoring structures. A critical review of the generated structures sometimes allows the choices to be narrowed by considering additional variables such as predicted splice site strength or local optimality of splice site scores. Summary statistics for prediction accuracy over all 46 maize genes are derived under cross-validation and non-cross-validation training conditions for the Markov sequence models. The algorithm achieved exon sensitivity of 0.81 and specificity of 0.75 on an independent set of 14 novel maize genomic segments. AVAILABILITY: GeneGenerator runs under Borland-Pascal 7.0 using MS-DOS and C on UNIX work stations. The source code is available upon request. CONTACT: jkleffe@euler.grumed.fu-berlin-de

Algorithms↗
PubMed1998

Distribution and kinetics of amylin in humans.

The aim of the study was to determine the apparent volume of distribution (VTOT), total body clearance (CL), fractional clearance, and mean residence time (MRT) of the beta-cell hormone amylin. We therefore performed an intravenous injection of 50 micrograms of human synthetic amylin (amlintide) in nine healthy male subjects during suppression of endogenous amylin release by intravenous somatostatin (0.06 microgram.kg-1.min-1). The plasma levels of amylin concentrations over time were analyzed using three-exponential curves. VTOT was 173 +/- 16 ml/kg and was not different from that of insulin reported in the literature (157 ml/kg). MRT was 27.7 +/- 2.1 min and thus two times the reported value for insulin (14.1 min) and C-peptide (16.4 min). CL and fractional CL were 6.2 +/- 0.2 ml.kg-1.min-1 and 0.038 +/- 0.003 min-1, respectively. Fractional CL is therefore definitely lower than that reported for insulin (0.12-0.2 min-1) but is, however, in the range of that of C-peptide (0.05 min-1). In conclusion, clearance of amylin is similar to that reported for C-peptide and much slower than insulin, indicating that the commonly used molar insulin-to-amylin ratio does not reflect the correct relationship of the two peptides.

Adult↗
PubMed1997

The renin-angiotensin system in patients with repeated anaphylactic reactions during hymenoptera venom hyposensitization and sting challenge.

Patients with a history of anaphylactic reactions to hymenoptera venom who tolerated the hyposensitization and the sting provocation without problems (n = 10) had angiotensin I (ANG I), angiotensin II (ANG II), angiotensinogen and renin similar to the values found in healthy nonallergic controls (n = 11). In contrast, patients who repeatedly experienced anaphylactic reactions during hyposensitization and who displayed anaphylactic reactions to sting provocation with a living insect (n = 6) showed significantly lower renin (p < 0.05), angiotensinogen (p < 0.05), ANG I (p < 0.05) and ANG II (p < 0.05) plasma levels as compared to healthy nonallergic controls (n = 11). Sting provocation with a living insect induced clinical symptoms of anaphylaxis in all of the 6 patients. A decrease in ANG I was found in 4 of the patients (67%) after provocation as compared to the concentration before the sting challenge. Angiotensinogen decreased in 3 of the patients (50%) whereas renin activity decreased in 2 of the patients (29%). In all cases a decrease in ANG II was noticed (100%). It is concluded that patients at high risk of developing anaphylactic reactions possess a dysfunctional renin-angiotensin system (RAS) which is not stimulated and does not respond appropriately. These findings point to an important role of the RAS as a defense mechanism in response to anaphylactic reactions.

Adolescent↗
PubMed1996

Logitlinear models for the prediction of splice sites in plant pre-mRNA sequences.

Pre-mRNA splicing in plants, while generally similar to the processes in vertebrates and yeast, is thought to involve plant specific cis-acting elements. Both monocot and dicot introns are typically strongly enriched in U nucleotides, and AU- or U-rich segments are thought to be involved in intron recognition, splice site selection, and splicing efficiency. We have applied logitlinear models to find optimal combinations of splice site variables for the purpose of separating true splice sites from a large excess of potential sites. It is shown that plant splice site prediction from sequence inspection is greatly improved when compositional contrast between exons and introns is considered in addition to degree of matching to the splice site consensus (signal quality). The best model involves subclassification of splice sites according to the identity of the base immediately upstream of the GU and AG signals and gives substantial performance gains compared with conventional profile methods.

Algorithms↗
PubMed1996

Object-oriented sequence analysis: SCL--a C++ class library.

SCL (Sequence Class Library) is a class library written in the C++ programming language. Designed using object-oriented programming principles, SCL consists of classes of objects performing tasks typically needed for analyzing DNA or protein sequences. Among them are very flexible sequence classes, classes accessing databases in various formats, classes managing collections of sequences, as well as classes performing higher-level tasks like calculating a pairwise sequence alignment. SCL also includes classes that provide general programming support, like a dynamically growing array, sets, matrices, strings, classes performing file input/output, and utilities for error handling. By providing these components, SCL fosters an explorative programming style: experimenting with algorithms and alternative implementations is encouraged rather than punished. A description of SCL's overall structure as well as an overview of its classes is given. Important aspects of the work with SCL are discussed in the context of a sample program.

Algorithms↗
PubMed1996

Effect of renin on brain arterioles and cerebral blood flow in rabbits.

There is evidence of an intrinsic renin-angiotensin system in the brain. The goal of the study was to determine whether stimulation of endogenous angiotensin production by applying renin to the brain surface has an effect on pial arteriolar caliber and CBF. Pial vessel diameters were measured through a closed cranial window in anesthetized rabbits. Percent changes of blood flow in the cortical area under the cranial window were simultaneously measured by laser-Doppler flowmetry. Topical application of 0.01-0.1 U/ml renin induced maximum dilation of 18.9 +/- 4% (mean +/- SD) of pial arterioles within 2 min. Arteriolar calibers thereafter decreased slowly. Flow gradually increased to peak at 38 +/- 15% 50 min after renin application. Angiotensin I levels in jugular blood, as measured by radioimmunoassay, increased to a peak 40 min after topical renin application. Angiotensin II levels in jugular blood and both angiotensin I and II levels in blood samples from the femoral artery did not change. Diameter and flow changes were inhibited by intravenous pretreatment with the converting enzyme blocker captopril (10 mg/kg body wt i.v.). Captopril did not affect the vasodilation and flow increase in response to hypercapnia. Topically applied captopril (10(-5) M) blocked renin-induced arteriolar dilation. We conclude that renin increases pial arteriolar diameters and cortical blood flow in the rabbit brain. Stimulation of angiotensin production is likely to be a mediator of this response.

Administration, Topical↗
PubMed1995

Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matched-pair analysis. The Berlin-Frankfurt-Münster Study Group.

It is unclear how best to treat children with acute lymphoblastic leukaemia (ALL) who are in a second remission. Treatment with bone-marrow transplants from HLA-identical siblings results in a statistically greater likelihood of leukaemia-free survival than does chemotherapy. Less than 25% of relapsed patients are able to benefit from this therapy due to a lack of matching donors; chemoradiotherapy or autologous BMT are considered for the rest. We compared treatment results for children who underwent autologous BMT with those who had chemotherapy. All patients were registered between 1983-94 in the multicentre trials. We selected groups of patients by matching variables associated with treatment outcome and duration of second remission. 52 matched-pairs were studied. The probability of event-free survival at 9 years was 0.32 (SD 0.07) for patients receiving chemotherapy versus 0.26 (SD 0.07) for patients who underwent autologous BMT. For two groups--children with prognostic factors indicating high risk of relapse and those with factors indicating lower risk--the outcome from transplantation did not differ significantly from that of chemotherapy: no advantage of autologous BMT over chemotherapy as post-induction treatment for children with ALL in a second remission could be detected with regard to event-free survival. Because autologous BMT has been used as the final step of treatment it is possible that its relative ineffectiveness has been due to the lack of continuation therapy after transplant. Attempts should be made to complement autologous BMT by subsequent immunotherapy, molecular biotherapy, chemotherapy, or a combination of these.

Adolescent↗
PubMed1995

Association between the renin angiotensin system and anaphylaxis.

Patients with hymenoptera venom anaphylaxis before immunotherapy (n = 50) showed significantly lower renin, angiotensinogen, angiotensin I and angiotensin II as compared to healthy non-allergic controls (n = 25) (p < 0.05). A significant inverse correlation between the severity of clinical symptoms and the plasma levels of renin, angiotensinogen, angiotensin I and angiotensin II was found: the lower the levels the more severe the clinical symptoms. Hymenoptera venom allergic patients with repeated anaphylactic reactions during hyposensitizatin did not tolerate the sting of a living insect (n = 6). Sting provocation with a living insect induced clinical symptoms of anaphylaxis in all of the 6 patients. Renin, angiotensinogen, angiotensin I and II remained significantly lower in these patients as compared to healthy non-allergic controls. Likewise, no stimulation of the renin angiotensin system occurred during the anaphylactic reaction. The values of angiotensin II were similar or lower than the values before the anaphylactic reaction. In contrast, patients with successful immunotherapy (n = 27) who tolerated the sting of a living insect, renin, angiotensin I and II were significantly higher than in patients without immunotherapy. After immunotherapy, the values for renin, ANG I and ANG II were similar to the values found in healthy non-allergic controls. Patients with a history of hymenoptera venom anaphylaxis (n = 22) showed significantly lower ANG II concentrations in their leukocytes as compared to healthy non-allergic controls (n = 24). Successful immunotherapy induced a significant 9-fold increase in ANG II as compared to patients without immunotherapy. These findings suggest a possible role of the renin angiotensin system in hymenoptera venom anaphylaxis.

Adolescent↗
PubMed1995

DNASTAT: a Pascal unit for the statistical analysis of DNA and protein sequences.

DNASTAT is a collection of Pascal routines for researchers who develop their own application programs for statistical analysis of DNA and protein sequences. Dynamic and file-based data structures allow users to process sets of sequences by simple loop control without limitations on the number of sequences and their individual sizes. This frees the programmer from potentially error-prone tasks like dynamic memory allocation and controlling array sizes. Sequences can be stored in databases along with biological and statistical attributes. Individual sequences can be accessed by column name and row number as with spread-sheets. DNASTAT allows large sets of sequences to be processed using a PC with standard configuration. Its small size, simplicity and free availability make it attractive to students of mathematical biology. Use of DNASTAT is illustrated by two sample programs that generate a database of coding regions from the GenBank entry of the tobacco chloroplast genome. A version of DNASTAT written in ANSI-C for PCs and Unix workstations is also available.

Base Sequence↗
PubMed1995

Origin of angiotensin in human leukocytes.

The capability of human leukocytes to synthesize angiotensin peptides was studied. Leukocytes which were prepared from heparinized blood by sedimentation in dextran were incubated for 0, 1, 2, 4, 6, 8, and 24 h at 37 degrees C with the 3H-labeled amino acid isoleucine. At the various time points the washed cells were extracted with 0.1 M acetic acid. The extracts contained radioactive material which eluted from a Bio Sil TSK 125 gel filtration column in the low-molecular-weight range with the same retention time as synthetic angiotensin I (ANG I) or angiotensin II (ANG II). The extracted radioactive material also bound to anti-ANG I and anti-ANG II antibodies. However, excess of unlabeled synthetic ANG I or ANG II failed to displace the bound radioactivity. Rechromatography of the radioactive material which eluted in the low molecular weight fractions of the gel filtration column could be characterized as non-incorporated 3H-isoleucine on a reversed phase C18 column with an acetonitrile gradient. These findings demonstrate the lack of an angiotensin-generating pathway in human leukocytes. Further studies are necessary to determine the origin of angiotensin peptides in human leukocytes.

Adult↗