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Biomedical subjects

K Hermann

Publications and source records attributed to K Hermann.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Contamination of heparin by histamine: measurement and characterization by high-performance liquid chromatography and radioimmunoassay.

Plasma samples which were collected in the presence of heparin contained 12.83 +/- 0.34 ng/ml histamine-immunoreactive material (n = 10). In contrast, histamine-immunoreactive material in plasma samples which were collected in the presence of EDTA/phenanthroline contained 0.32 +/- 0.01 ng/ml (n = 10). Histamine-immunoreactive material was found as a contaminant in three different heparin formulations with unrelated batch numbers. The concentrations of the histamine-like material were 32.82, 81.93, and 280.23 ng/ml, respectively. Octadecasilyl-silica (ODS) cartridges were used to purify histamine from other constituents in the heparin preparations. The histamine-immunoreactive material in the three preparations could be characterized as histamine with cation-exchange high-performance liquid chromatography (HPLC) on a TSK SP-5 PW column with NaH2PO4, pH5.0, as a mobile phase and gradient elution. For the accurate measurement of histamine in plasma samples with heparin as an anticoagulant, one should be aware of a possible contamination of heparin formulations by histamine.

Chromatography, High Pressure Liquid↗

Human leukocytes contain angiotensin I, angiotensin II and angiotensin metabolites.

Angiotensin I (ANG I) and angiotensin II (ANG II) were measured radioimmunologically in human leukocytes extracted with a mixture of acetone, 1N HCl and water (40:1:10 vol). The analytical recoveries of 125I-ANG I and 125I-ANG II, which were added prior to extraction, were 92.00 +/- 3.10 and 99.19 +/- 0.91% (mean +/- SEM; n = 12). The concentration of ANG I- and ANG II-like material in leukocytes from healthy volunteers was 32.04 +/- 3.64 and 13.05 +/- 1.26 fmol/mg protein (n = 24). The immunoreactive material could be characterized on HPLC as Ile5-ANG I, Ile5-ANG II and angiotensin metabolites such as Ile4-ANG III, Ile3-ANG II hexapeptide, Ile2-ANG II pentapeptide and Ile1-ANG II tetrapeptide. From the ANG I-immunoreactive material determined in the extracts, 26% could be characterized on HPLC as Ile5-ANG I. The ANG II-immunoreactive material present in the extracts could be separated on HPLC into 44% Ile5-ANG II, 14% Ile4-ANG III, 7% Ile3-ANG II hexapeptide, 4% Ile2-ANG II pentapeptide and 8% Ile1-ANG II tetrapeptide. Patients with a history of anaphylactic reactions to bee or wasp venom showed significantly reduced ANG II concentrations in their leukocytes as compared to controls (6.76 +/- 0.76 fmol ANG II/mg protein, n = 22, vs. 13.05 +/- 1.26 fmol ANG II/mg protein, n = 24; p < 0.05). A significant correlation between the severity of clinical symptoms and the ANG II levels was found for grade I and II reactions (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Increased urinary excretion of angiotensin during anaphylactoid reactions.

Immunoreactive angiotensin I (ANG I) and angiotensin II (ANG II) were measured in human urine, after purification on octadecasilyl-silica cartridges. The total daily excretion of ANG I and II in healthy volunteers was 292.2 +/- 62.5 and 12.2 +/- 2.5 pmol/24 h (mean +/- SEM; n = 14). No differences in the concentrations of ANG I or II were detected between females and males. Although lower levels of ANG I and II were found during the nighttime, no clear-cut circadian rhythm in the excretion of the peptides was found. ANG II was not degraded in acidified urine which shows the effective inhibition of ANG-II-degrading enzymes. Oral provocation tests (OPT) in patients with a history of anaphylactoid reactions (AR) to drugs, foods and food additives were associated with elevated ANG I and II concentrations when symptoms of anaphylaxis occurred. The excretion of ANG I increased by a factor of 7.8 +/- 2.4 and the excretion of ANG II by a factor of 6.1 +/- 1.6 (mean +/- SEM; n = 15). In patients with negative OPT and no clinical symptoms of anaphylaxis, the levels of ANG I and II remained unchanged (n = 26). It is concluded that angiotensin peptides play a role during the events of AR. The peptides may be considered as counteracting factors which stabilize cardiovascular functions.

Adolescent↗

Histamine, tryptase, norepinephrine, angiotensinogen, angiotensin-converting enzyme, angiotensin I and II in plasma of patients with hymenoptera venom anaphylaxis.

Markers of immediate-type hypersensitivity such as histamine and tryptase were measured in the plasma of nonallergic volunteers and patients with a history of hymenoptera venom anaphylaxis. No significant differences in histamine or tryptase were found between patients and controls. Norepinephrine, an important compound involved in the control of cardiovascular functions and blood pressure, was the same in patients and nonallergic volunteers. In addition, components of the renin-angiotensin system were determined. Patients with hymenoptera venom anaphylaxis showed significantly lower plasma angiotensinogen concentrations as compared to healthy nonallergic controls (p < 0.007), whereas plasma ACE activity was the same. Likewise, the plasma levels of angiotensin I and angiotensin II were significantly reduced in patients as compared to controls (p < 0.04 and p < 0.003, respectively). These findings suggest that the renin-angiotensin system may play an important role as a counteracting factor in hymenoptera venom anaphylaxis.

Adult↗

Plasma concentrations of arginine vasopressin, oxytocin and angiotensin in patients with hymenoptera venom anaphylaxis.

The plasma concentrations of arginine vasopressin, oxytocin, angiotensin I and II were studied in patients with hymenoptera venom anaphylaxis (n = 50) and healthy volunteers (n = 25). There was no difference in arginine vasopressin: 5.52 +/- 0.45 fmol/ml vs. 3.99 +/- 0.41 fmol/ml or oxytocin: 28.10 +/- 1.13 fmol/ml vs. 26.24 +/- 1.80 fmol/ml between patients and controls. No correlation between the severity of clinical symptoms and the plasma levels of arginine vasopressin and oxytocin was found in patients. However, patients with a history of hymenoptera venom anaphylaxis showed significantly reduced angiotensin I and angiotensin II plasma levels as compared to controls (ANG I: 9.51 +/- 0.61 fmol/ml vs. 22.91 +/- 1.73 fmol/ml; ANG II: 2.84 +/- 0.16 fmol/ml vs. 6.95 +/- 0.33 fmol/ml). A significant inverse correlation between the severity of clinical symptoms and the plasma levels of angiotensin I and angiotensin II was observed; the lower the concentrations the more severe the clinical symptoms. Oxytocin immunoreactivity eluted from the HPLC column as a single peak with the same retention time as synthetic oxytocin. The vasopressin immunoreactive material could be characterized on HPLC as arginine-vasopressin and two other peptides of unknown nature which crossreacted with the vasopressin antibody. These findings suggest a possible role of angiotensin I and angiotensin II in hymenoptera venom anaphylaxis while arginine vasopressin and oxytocin are most likely not involved.

Adolescent↗

The renin angiotensin system and hymenoptera venom anaphylaxis.

Components of the renin angiotensin system, namely renin, angiotensinogen, angiotensin I and II and aldosterone were measured in plasma of patients with hymenoptera venom anaphylaxis (n = 50) and healthy non-allergic controls (n = 25). Patients with a history of anaphylactic reactions to hymenoptera venom who did not undergo immunotherapy showed significantly reduced renin, angiotensinogen, angiotensin I and angiotensin II in plasma as compared with controls (P < 0.05). There was no difference in the aldosterone concentration between patients and controls. Angiotensin I, angiotensin II, renin and angiotensinogen levels were the same in male and female patients. There was also no difference in the angiotensin I, II, renin or angiotensinogen levels between young and older patients. A significant inverse correlation between the severity of clinical symptoms and the plasma levels of renin (r = -0.382, P < 0.001), angiotensinogen (r = -0.567, P < 0.0001), angiotensin I (r = -0.656, P < 0.0001) and angiotensin II (r = 0.0762, P < 0.0001) was found: the lower the levels the more severe the clinical symptoms. No correlation was found for aldosterone. Hymenoptera venom allergic patients with repeated anaphylactic reactions during hyposensitization did not tolerate the sting of a living insect (n = 6). In these patients, renin, angiotensinogen, angiotensin I and II remained significantly lower than in healthy non-allergic controls. Patients with successful immunotherapy (n = 27) who tolerated the sting of a living insect had renin, angiotensin I and II significantly higher than patients without immunotherapy. These findings suggest a possible role of the renin angiotensin system in hymenoptera venom anaphylaxis.

Adolescent↗

Measurement and characterization of histamine and methylhistamine in human urine under histamine-rich and histamine-poor diets.

A radioimmunoassay for histamine was used to measure histamine and 1-methylhistamine (MH) in human urine samples. The detection limit of this assay was 2 ng/ml for histamine and 0.5 ng/ml for MH. Cation exchange high performance liquid chromatography (HPLC) on a Bio-Gel TSK SP-5 PW column with gradient elution was capable of separating histamine from its precursor L-histidine and its metabolites MH and 1-methylimidazole acetic acid (MIAA). The concentration of MH-immunoreactive materials in healthy volunteers with no dietary restrictions was 202 +/- 92 micrograms/24 h (mean +/- SD; n = 14). The excretion of MH-like material, expressed as micrograms of MH per 24 h, was not significantly different before or after the intake of histamine-rich food: 217 +/- 88 vs. 276 +/- 135 micrograms/24 h (n = 10). However, in urine samples collected in individual fractions, the levels of MH immunoreactivity were significantly increased after a histamine-rich meal in comparison to the corresponding fractions which were taken a day earlier at the same time intervals after a histamine-low diet (p < 0.03). HPLC characterization of MH immunoreactivity revealed the presence of histamine, MH and a compound with the same retention time as MIAA. The ratio of histamine, MH and MIAA in controls without dietary restrictions, as determined by HPLC analysis, was 50 +/- 6, 47 +/- 5 and 3 +/- 1%, respectively. After a histamine-rich meal the ratio was 97 +/- 2% for histamine, 1% for MH and 2 +/- 1% for MIAA.

Adult↗