Search PubMed⌕ Search

Biomedical subjects

H Krause

Publications and source records attributed to H Krause.

At least 55 records · Page 3Linked to original sources
PubMed2000

The restricted expression pattern of the Hodgkin's lymphoma-associated cytokine receptor CD30 is regulated by a minimal promoter.

One of the most peculiar immunohistological characteristics of the tumour cells of Hodgkin's lymphoma, anaplastic large cell lymphoma (ALCL), and embryonal carcinoma of the testis is the expression of the CD30 antigen. Physiologically, CD30 expression is restricted to a few activated lymphocytes in normal lymphoid tissue and a small population of decidual cells. To clarify the reasons behind this highly restricted expression pattern and to learn about the combination of transcription factors involved in this regulation in Hodgkin's lymphoma and other CD30(+) malignancies, the 5'-flanking regulatory region of the cd30 gene was analysed. The major transcription start site was determined to be 270 bases upstream of the translational start codon in the Hodgkin's lymphoma-derived cell lines L591 and L428. Reporter gene assays revealed that the CD30 promoter (-413 to 84) induces a 50- to 1000-fold higher luciferase expression in CD30(+) human lymphoid cell lines (Co, Jurkat, and the Hodgkin's lymphoma-derived cell line L540) than in CD30(-) human lymphoid cell lines (DG75, SUP-T1, and U698M), CD30(-) human carcinoma cell lines (HeLa and MCF-7), or COS1 cells. Deletion analysis defined a TATA-less, minimal promoter sequence from -164 to 84. The transcription factor Sp1 and members of the Ets family induce CD30 expression, whereas the transcription factor Sp3 diminishes its induction. These data suggest that a high Sp1/Sp3 expression ratio and a peculiar expression pattern of the Ets transcription factors are involved in the overexpression of CD30 and might contribute to the transformation of CD30(+) tumour cells.

Base Sequence↗
PubMed2000

Relationships between physical activity, physical fitness, muscle strength and nutritional state in 5- to 11-year-old children.

The purpose of the present study was to assess different aspects of physical activity and fitness in order to develop a basis for sport programmes for overweight and obese children. Eighty-eight prepubertal children (49 boys, 39 girls, 4.8-11.4 years old, 61% obese, 14% overweight and 25% normal weight) were examined. Body composition was assessed by combined use of anthropometrics and bioelectrical impedance analysis. Resting energy expenditure (REE) and total energy expenditure (TEE) were measured by indirect calorimetry (IC) and individually calibrated 24-h heart rate (HR) monitoring, respectively. Activity-related energy expenditure (AEE) and physical activity level (PAL) were calculated from TEE and REE. Fitness [assessed by O2-pulse, respiratory exchange ratio (RER) at submaximal work intensities] was determined by ergometry. The maximal isometric muscle strength of the legs (m. quadriceps, Fa max, m. ischiocruralis, Fb max) was measured by computer tensiometry. Children were grouped according to their nutritional state, AEE, O2-pulse and muscle strength. When compared with normal weight children, obese and overweight children had increased fat mass (FM), fat-free mass (FFM), waist-to-hip ratio and REE, but no group differences were observed for TEE, AEE, and PAL. Obese and overweight children spent more hours per day watching TV. After correction for body weight and FFM, no group differences in REE were observed, but normal weight children had a higher O2-pulse than overweight and obese children. By contrast, RER was increased in the latter group. The fittest group had the lowest body weight, BMI, FM and FFM. Children with a low O2-pulse spent more hours per day watching TV. Grouping children according to their degree of muscle strength, younger children (4-7.5 years) did not show group differences in nutritional state, energy expenditure, physical activity and fitness. However, in the group of 7.6- to 11-year-old children, those with the greatest muscle strength and FFM had reduced BMI, skin folds, FM and FFM. FM correlated inversely with O2-pulse, but was not associated with TEE, AEE, PAL or muscle strength. By contrast TV consumption was positively associated with FM. To summarize, overweight and obese children were less fit and watched more TV than their normal weight counterparts. FM did not correspond to TEE, AEE or PAL. Muscle strength was not associated with FM in young children, but was inversely associated with FM in older children. Our cross-sectional data are consistent with the idea that increased fitness and reduced physical inactivity may prevent children from being overweight.

Body Composition↗
PubMed2000

[Complications following piercing in the oral and facial region].

The increasing distribution and social acceptance of body piercing induced us to investigate the nature and rate of complications brought about by this fashionable injury of the unscathed body. All dentists, maxillofacial surgeons and clinics within the region of the association of dentists of Bremen were asked to register all patients presenting between June and October 1998 in whom piercings of the head and neck area were visible. Response was good; 699 piercings in 273 persons were recorded and some exemplary photographs made. Some 47 persons showed local complications which ranged from keloid formation and temporary infections to cartilage necrosis and disturbances in sensibility. General diseases were described as well, mainly allergies and hepatitis. In accordance with the seriousness of the complication the medical treatment required varied. Nine persons had to be treated in hospital. In 14 cases patients suffered permanent damage. Piercings cause severe complications and considerable expense to the public health service.

Adolescent↗
PubMed2000

Telomerase activity and expression of telomerase subunits in the testicular tissue of infertile patients.

OBJECTIVE: Determination of telomerase activity and the expression of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in the testicular tissue of patients with infertility arising from various causes. DESIGN: Prospective observational study. SETTING: A university hospital. PATIENT(S): Thirty-three patients with azoospermia arising from various causes. There were 12 testicular biopsy specimens from patients with Sertoli cell-only syndrome, 9 from patients with maturation arrest, and 12 from patients with obstructive azoospermia and normal histologic findings. INTERVENTION(S): Thirty-three testicular biopsies. MAIN OUTCOME MEASURE(S): Correlation of histologic findings at testicular biopsy with telomerase activity, hTERT, and hTR. RESULT(S): All 12 biopsy specimens from patients with obstructive azoospermia were positive for telomerase activity, hTR, and hTERT. Biopsy specimens from the 9 patients with maturation arrest were positive for telomerase activity in 8 cases, hTR in 9 cases, and hTERT in 5 cases. None of the patients with Sertoli cell-only syndrome showed either telomerase activity or hTERT, but all of them showed hTR. CONCLUSION(S): Telomerase activity and evidence of hTERT in testicular tissue are highly sensitive and highly specific markers of gametogenesis, which could gain in importance as part of the fertility workup before microinjection procedures.

DNA-Binding Proteins↗
PubMed2000

No effect of gender on different components of daily energy expenditure in free living prepubertal children.

BACKGROUND: There are limited and controversial data on the influence of gender on metabolic rate in prepubertal children. OBJECTIVE: To assess the effect of gender on resting energy expenditure (REE), activity-related energy expenditure (AEE), total energy expenditure (TEE) and physical activity level (PAL) in free-living prepubertal children. DESIGN: Cross-sectional study. SUBJECTS: 40 prepubertal children (24 boys, 16 girls, 4-11 y old (mean age: 7.0 +/- 1.2 y), BMI 13.1-32.0 kg/m2). MEASUREMENTS: Energy expenditure was measured by the combination of indirect calorimetry and individually calibrated 24 h heart rate monitoring. Body composition was assessed by anthropometrics and bioelectrical impedance analysis. Socio-cultural and socio-economic factors, as well as activities of daily living, were estimated by questionnaire for the parents. Boys and girls were matched for fat-free mass (FFM, boys: 25.9 +/- 8.5 kg; and girls: 24.4 +/- 4.5 kg, n.s.) and fat mass (FM, boys: 11.6-5.9 kg; and girls: 10.8 +/- 3.3 kg, n.s.). RESULTS: We found no sex difference in REE, AEE and TEE. PAL was 1.4 +/- 0.3 for boys and 1.2 +/- 0.4 for girls. REE and TEE were significantly related to FFM (r=0.62, r=0.81, r=0.60). FFM was found to be the most significant determinant of REE (r2=0.70). REE accounted for the largest part of the variance in TEE (r2=0.46). Gender had no significant effect. CONCLUSIONS: There is no effect of gender on energy expenditure in prepubertal children.

Basal Metabolism↗
PubMed2000

Endothelial K(+) channel lacks the Ca(2+) sensitivity-regulating beta subunit.

Hyperpolarizing large-conductance, Ca(2+)-activated K(+) channels (BK) are important modulators of vascular smooth muscle and endothelial cell function. In vascular smooth muscle cells, BK are composed of pore-forming alpha subunits and modulatory beta subunits. However, expression, composition, and function of BK subunits in endothelium have not been studied so far. In patch-clamp experiments we identified BK (283 pS) in intact endothelium of porcine aortic tissue slices. The BK opener DHS-I (0.05-0.3 micromol/l), stimulating BK activity only in the presence of beta subunits, had no effect on BK in endothelium whereas the alpha subunit selective BK opener NS1619 (20 micromol/l) markedly increased channel activity. Correspondingly, mRNA expression of the beta subunit was undetectable in endothelium, whereas alpha subunit expression was demonstrated. To investigate the functional role of beta subunits, we transfected the beta subunit into a human endothelial cell line (EA.hy 926). beta subunit expression resulted in an increased Ca(2+) sensitivity of BK activity: the potential of half-maximal activation (V(1/2)) shifted from 73.4 mV to 49.6 mV at 1 micromol/l [Ca(2+)](i) and an decrease of the EC(50) value for [Ca(2+)](i) by 1 microM at +60 mV was observed. This study demonstrates that BK channels in endothelium are composed of alpha subunits without association to beta subunits. The lack of the beta subunit indicates a substantially different channel regulation in endothelial cells compared to vascular smooth muscle cells.

Animals↗
PubMed1999

6-oxa isosteres of anacardic acids as potent inhibitors of bacterial histidine protein kinase (HPK)-mediated two-component regulatory systems.

A series of 6-oxa isosteres of anacardic acids (6-higher alkyl/alkenyl-2-hydroxybenzoic acids) was synthesised and several members were discovered to be among the most potent inhibitors (IC50 values < or = 5 microM) of the bacterial two-component regulatory systems, KinA/SpoOF and NRII/NRI, reported to date. The Gram-positive antibacterial activity in selected strains is also presented.

Anacardic Acids↗
PubMed1999

[Low energy extracorporeal shockwave therapy (ESWT) for treatment of myogelosis of the masseter muscle].

Patients with functional disorders of the temporomandibular apparatus often show painful myogelosis, especially of the masseter muscle. The cause is hypertonia of the affected muscle. The aim of the presented single-blinded clinical trial was to analyze the effects of low-energy extracorporeal shock waves on patients with pain sensitivity in this region. Participating in the trial were 50 patients with painful, palpable and sonographically evident myogelosis of the masseter muscle. Half of the patients received a single application of 250 impulses of 0.04 mJ/mm2. The second half received an equivalent placebo treatment with the shock-wave impact being inhibited by a neopren insert. It was shown that in 64% of the patients significant alleviation of pain with palpable and sonographically evident softening of the myogelosis could be achieved. In 40% of the patients the therapeutic result could be conserved over a period of 2 weeks. The difference from the placebo group was statistically highly significant. ESWT is thus an easy-to-use, non-invasive method of initial pain therapy for patients with functional disorders. To preserve the long-term therapeutic result, additional functional therapy is nevertheless necessary.

Adult↗
PubMed1999

Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain.

Interleukin-15 (IL-15) is a potent inhibitor of several apoptosis pathways. One prominent path toward apoptosis is the ligand-induced association of TNF receptor 1 (TNFR1) with death domain adaptor proteins. Studying if and how IL-15 blocks TNFR1-mediated apoptosis in a murine fibroblast cell line (L929), we show here that IL-15 blocks TNFR1-induced apoptosis via IL-15Ralpha chain signaling. The intracellular tail of IL-15Ralpha shows sequence homologies to the TRAF2 binding motifs of CD30 and CD40. Most important, binding of IL-15 to IL-15Ralpha successfully competes with the TNFR1 complex for TRAF2 binding, which may impede assembly of key adaptor proteins to the TNFR1 complex, and induces IkappaBalpha phosphorylation. Thus, IL-15Ralpha chain stimulation is a powerful deflector of cell death very early in the apoptosis signaling cascade, while TNF-alpha and IL-15 surface as major opponents in apoptosis control.

Amino Acid Sequence↗
PubMed1999

Telomerase activity in malignant and benign renal tumors.

OBJECTIVES: An important characteristic of malignant cells is their unlimited replicative potential, their immortality. In conferring this immortality, the enzyme telomerase is believed to play a crucial role. The detection of telomerase activity provides new knowledge regarding the biologic growth behavior of tumors and offers new diagnostic and therapeutic tools. METHODS: In the present study the sensitive TRAP assay (telomeric repeat amplification protocol) was used to examine 44 malignant renal tumors and 8 benign tumors of the kidney and 52 specimens of normal renal tissue for telomerase activity. RESULTS: Telomerase activity was detected in 63% of tissue samples obtained from histologically confirmed renal cell carcinomas. In cases of renal cell carcinoma restricted to the kidney, telomerase activity was detected in 58%. In cases in which tumor growth has progressed beyond the limits of the organ, telomerase activity was found in 69%. This stage dependence, however, did not reach statistical significance. No correlation to tumor grading was observed. Telomerase activity was found less frequent in chromophobe renal cell carcinomas. Neither the 8 benign renal tumors (4 oncocytomas and 4 angiomyolipomas) nor the specimens of normal kidney showed any evidence of telomerase activity. CONCLUSIONS: The proportion of remarkable slow-growing renal cell carcinomas showing telomerase activity is less than in other malignancies and may correlate with biologic growth behavior. Possible explanations include the presence of an alternative pathway, called ALT (alternative lengthening of telomeres) and an association with the loss or presence of the telomerase suppressor on the short arm of chromosome 3. Prolonged follow-up will be of special interest to determine whether lack of telomerase activity predicts favorable outcome.

Adenoma, Oxyphilic↗
PubMed1999

RinoFlow nasal wash and sinus system as a mechanism to deliver medications to the paranasal sinuses: results of a radiolabeled pilot study.

Direct delivery of medication to the sinuses with standard nebulizers is difficult to achieve. The nasal inhalation of aerosolized medications is dependent on the size of the particles and the pressure with which they are delivered; when the particles are too small or the pressure is too low, the drug cannot reach the sinuses. The ability of topical medications to treat sinus disorders can be improved if the medication could be delivered directly to the sinuses. We tested the ability of the RinoFlow nasal aerosol delivery device to deposit aerosol directly to the paranasal sinuses. Five normal, healthy subjects used the device to administer technetium Tc 99m nasally. Nuclear scanning was used to detect deposition in the frontal and maxillary sinuses. Three subjects underwent additional testing after administration of a nasal decongestant. Three of the five subjects showed some evidence of direct delivery to the sinuses, although deposition was not uniform or complete. Pretreatment with a decongestant had no apparent effect on subsequent technetium delivery. We conclude that the results of this study are promising and that further study is warranted.

Administration, Inhalation↗
PubMed1998

Microsatellite analysis of plasma DNA from patients with clear cell renal carcinoma.

Deletions of DNA sequences on chromosome 3p [loss of heterozygosity (LOH)] are characteristic of clear cell renal carcinoma, which accounts for about 80% of all renal malignancies. Comparing tumor DNA to DNA from normal cells, LOH analysis of microsatellite sequences has aided in molecular diagnosis of renal carcinoma. Because clinically useful tumor markers do not exist for this cancer entity, the aim of the present study was to detect chromosome 3p microsatellite alterations (LOH and microsatellite instability) in plasma DNA from patients with clear cell renal carcinoma. Four chromosome 3p microsatellites (D3S1307, D3S1560, D3S1289, and D3S1300) were amplified by fluorescent PCR using DNA isolated from normal blood cells and plasma of 40 patients. Corresponding tumor DNA was available from 21 patients. Analyzing PCR products on an automated DNA sequencer, we found LOH in at least one locus in 25 plasma samples (63%), and 14 plasma samples (35%) exhibited LOH at more than one locus. Microsatellite instability of plasma DNA was detectable in one patient (3%). No significant association of advanced (>T2N0M0) tumor stages with LOH in plasma DNA could be demonstrated. If present, modifications of plasma DNA and tumor DNA were identical. No alterations of plasma DNA were found in healthy controls. Analysis of plasma DNA from patients with clear cell renal carcinoma reveals tumor-specific microsatellite alterations and may therefore have diagnostic potential as a molecular tumor marker.

Adenocarcinoma, Clear Cell↗
PubMed1998

Vaccination with tumor cells engineered to secrete interleukin 2-immunoglobulin G fusion protein induces tumor rejection.

Here we provide proof that the injection of tumor cells engineered to secrete interleukin 2 (IL-2)-IgG chimeric proteins locally induces potent antitumor responses, which are more effective than tumor transfection with IL-2 alone. Murine plasmacytoma cells (J558L) were stably transfected with DNA coding for a human IL-2-IgG1 or a murine IL-2-IgG2b fusion protein and were injected s.c. into syngeneic BALB/c mice. Evaluation of tumor growth and rejection patterns showed that IL-2-IgG secretion by transfected J558L tumor cells induced their rejection in all animals tested, similar to the rejection of J558L cells engineered to secrete IL-2 alone, whereas treatment with parental cells was lethal. However, mice treated with IL-2-IgG-secreting J558L cells (human IL-2-IgG1 and murine IL-2-IgG2b) exhibited a significantly stronger tumor immunity against a later challenge with parental J558L cells than mice treated with IL-2-secreting tumor cells.

Animals↗
PubMed1998

Comparison of human telomerase RNA and telomerase activity in urine for diagnosis of bladder cancer.

New, noninvasive methods for the early detection of urothelial carcinomas of the urinary bladder are needed for the diagnosis, follow-up, and screening of patients with bladder cancer. Detection of the enzyme telomerase in urine could offer these new diagnostic possibilities. The standard technique for detecting telomerase activity is the telomeric repeat amplification protocol (TRAP assay). Because of the instability of the ribonucleoprotein telomerase in an aggressive medium, such as urine, investigations conducted to date have yielded nonuniform or even contradictory findings. This study compares the detection of human telomerase RNA (hTR) by reverse transcriptase-PCR (RT-PCR) with detection of telomerase activity by the TRAP assay in the diagnosis of urothelial carcinoma of the urinary bladder. Sedimented cells obtained from urine of 30 patients with urothelial carcinoma, 15 patients with benign urological disorders, 3 patients as part of follow-up for malignant disease, and 20 healthy subjects were examined for the presence of hTR and for telomerase activity (TRAP). In patients with bladder cancer, telomerase activity was detected by the TRAP assay in only 2 of 30 specimens (7%). However, increased levels of hTR were detected by RT-PCR in 25 of the same 30 cases (83%). For patients with benign urological disorders, such as urolithiasis or urinary tract infections, hTR was detected in samples obtained from 4 of 15 patients (27%). Low hTR expression levels were found in 15% of the healthy controls. The detection of hTR by RT-PCR represents a promising new method for detecting malignant cells in urine.

Humans↗
PubMed1997

Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms.

The secretion of IL-15, a potent modulator of T, B, and NK lymphocyte functions, is likely to be tightly controlled. Here, we show that human T lymphoblasts transcribe the IL-15 gene and generate an alternative splicing product that codes for the same amino acid composition as the mature IL-15 protein, but produces an IL-15 precursor protein with a shorter signal peptide. Both alternative splicing products are transcribed by non-IL-15-secreting lymphocytes, suggesting that IL-15 secretion is not primarily controlled at the level of transcription. We generated an in vitro system for correlating the expression, translation, and secretion of IL-15 or IL-15-IgG1 fusion protein. This revealed that the two isoforms of IL-15 or a truncated IL-15 variant, both alone and fused to human IgG1, are all transcribed and translated, but not efficiently secreted. After replacing the IL-15 leader peptide with a foreign one, translation and secretion clearly increase. These results suggest that IL-15 is mainly controlled at the level of translation and secretion.

Alternative Splicing↗