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R Kühn

Publications and source records attributed to R Kühn.

At least 19 recordsLinked to original sources
PubMed1999

In vitro study concerning the efficiency of the frequency-doubled double-pulse Neodymium:YAG laser (FREDDY) for lithotripsy of calculi in the urinary tract.

BACKGROUND AND OBJECTIVES: In a preclinical study we have tested both in vitro and in vivo, a new type of pulsed solid-state laser system that has not been applied in urology so far and has been developed for optimized intracorporal lithotripsy of biliary, salivary, and urinary calculi. STUDY DESIGN/MATERIALS AND METHODS: Sixty one calculi from the human urinary tract were split in vitro into fragments with a remaining particle size of </= 2 mm using the prototype of a short-pulsed passively Q-switched and frequency-doubled double-pulse Neodymium:YAG laser. In a supplementary animal test, the bladder mucosa of five rabbits was directly exposed to a highly rated laser beam to be able to assess the tissue lesion potential of the system. RESULTS: All the 61 urinary calculi with different composition were successfully split in vitro within a short period of time (2.5 +/- 4.6 minutes). During histopathologic examination of the exposed bladder walls of the rabbits only a small tissue lesion potential with urothelium changes exclusively at the surface was ascertained. CONCLUSION: The high degree of fragmentation efficiency, the purchase and maintenance costs, which due to its design are substantially lower in comparison to other laser lithotriptors, and the high degree of safety during application make this new laser a real alternative not only to the present laser lithotripsy systems but also to common ballistic lithotriptors.

Animals↗
PubMed1999

Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes.

Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic gene polymorphism at codon 192 (glutamine/arginine) has been associated with coronary artery disease (CAD). To further evaluate the role of this paraoxonase gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase genotype in 288 type 2 diabetic patients (170 with and 118 without angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was assessed using polymerase chain reaction followed by AlwI digestion. The frequency of the Gln allele was 0.656 in the CAD patients and 0.746 in the controls (chi2 = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age-adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects carrying at least one Arg allele. In the multivariate analysis, this association was even stronger after correction for the possible confounders age, sex, smoking history, and hypertension. Among current and former smokers, the odds ratio (OR) for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P < 0.01). The paraoxonase Arg allele was not associated with the history of myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not myocardial infarction in type 2 diabetic patients, a risk factor further modified by cigarette smoking. This risk could possibly be explained by a reduced ability of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.

Arginine↗
PubMed1998

Csk controls antigen receptor-mediated development and selection of T-lineage cells.

The development and function of alphabetaT lymphocytes depend on signals derived from pre-T and alphabetaT cell receptors (preTCR and alphabetaTCR) (reviewed in refs 1, 2). The engagement of these receptors leads to the activation of Lck and Fyn, which are protein tyrosine kinases (PTKs) of the Src family. It remains unclear to what extent the activation of Src-family PTKs can direct the differentiation steps triggered by preTCR and alphabetaTCR. Here we show that the inactivation of the negative regulator of Src-family PTKs, carboxy-terminal Src kinase (Csk), in immature thymocytes abrogates the requirement for preTCR, alphabetaTCR and major histocompatibility complex (MHC) class II for the development of CD4+ 8+ double-positive and CD4+ single-positive thymocytes as well as peripheral CD4 alphabetaT-lineage cells. These data show that Csk and its substrates are required to establish preTCR/alphabetaTCR-mediated control over the development of alphabetaT cells.

Animals↗
PubMed1998

IL-10 regulates liver pathology in acute murine Schistosomiasis mansoni but is not required for immune down-modulation of chronic disease.

We have used IL-10 gene knockout mice (IL-10T) to examine the role of endogenous IL-10 in the down-modulation of hepatic granuloma formation and lymphocyte responses that occurs in chronic infection with the helminth parasite Schistosoma mansoni. Although IL-10-deficient animals showed 20 to 30% mortality between 8 and 14 wk postinfection, they displayed no alterations in their susceptibility to infection and produced similar numbers of eggs as their wild-type littermates. The IL-10T mice displayed a significant increase in hepatic granuloma size at the acute stage of infection, which was associated with increased IFN-gamma, IL-2, IL-1beta, and TNF-alpha mRNA expression in liver and elevated Th1-type cytokine production by lymphoid cells. Despite developing an enhanced Th1-type cytokine response, the IL-10T mice showed no consistent decrease in their Th2-type cytokine profile. Surprisingly, although granulomatous inflammation was enhanced at the acute stage of infection, the livers of IL-10T mice displayed no significant increase in fibrosis and underwent normal immune down-modulation at the chronic stage of infection. Moreover, the down-modulated state could be induced in IL-10T mice by sensitizing the animals to schistosome eggs before infection, further demonstrating that the major down-regulatory mechanism is not dependent upon IL-10. We conclude that while IL-10 plays an important role in controlling acute granulomatous inflammation, it plays no essential role in the process of immune down-modulation in chronic schistosome infection.

Acute Disease↗
PubMed1998

Efficacy of radiochemotherapy with platin derivatives compared to radiotherapy alone in organ-sparing treatment of bladder cancer.

PURPOSE: Presently, for muscle-invasive bladder cancer, radical cystectomy is considered to be the standard treatment. Bladder preservation, in the interest of quality of life, is secondary to the primary treatment goal of curing the patient. We present a 14-year multivariate analysis of prognostic factors influencing survival and bladder preservation after transurethral resection of the bladder (TURB) and radiotherapy (RT) +/- chemotherapy. METHODS AND MATERIALS: From May 1982 to May 1996, sequential cohorts of 333 patients with bladder cancer (mean age: 66 years) were treated by either RT alone (128 patients), or with platin-based concomitant radiochemotherapy (RCT, 205 patients) after TURB. Patients (282) with muscle-invasive or T1 high-risk cancers (Grade III, residual tumor after TURB, multifocality, tumor diameter > 5 cm, associated Tis or Ta, multiple recurrences or lymph node metastases), who received a minimal target dose of 45 Gy were selected for analysis (med. follow-up = 7.5 years): after October 1985, 115 patients received cisplatin (25 mg/m2) and 69 patients carboplatin (65 mg/m2) before every treatment fraction (1.8 Gy) on Days 1-5 and 29-33 of conventional fractionated RT. RESULTS: Complete remission rate was 20% (55 of 282 patients) after radical TURB, 57% (56 of 98) after TURB plus postoperative RT, and 80% (145 of 181 patients) after TURB plus RCT (85% after concomitant cisplatin and 70% after RCT plus carboplatin). These differences were significant in multivariate analysis (p = 0.003-0.05). The strongest impact on initial response had T-category (p < 0.0001) and R-status after TURB (p < 0.0003). Cause-specific survival (CSS) was 59 and 43% after 5 and 10 years; 79% of patients survived with preserved bladder. Five-year CSS after RT, RCT-Cis, and RCT-Carbo was 40, 64, and 54%, 10-year CSS 31, 48, and 27%, respectively (p = 0.04-0.045, univariate). R-status after TURB was the only independent prognostic factor for survival and bladder preservation. For relapsed patients after cystectomy, the 5- and 10-year CSS were 40 and 33%. CONCLUSIONS: TURB followed by RT/RCT is an alternative treatment option to primary cystectomy for patients with muscle-invading bladder cancer. Compared to historic controls, the addition of cisplatin or carboplatin leads to significantly more complete remissions and better survival. Survival rates are similar to those achieved by primary cystectomy and possibly even better for selected subjects, such as patients with T3b and T4 tumors. Cystectomy should be restricted to only those patients who fail after RCT.

Adult↗
PubMed1998

Radiotherapy alone or radiochemotherapy with platin derivatives following transurethral resection of the bladder. Organ preservation and survival after treatment of bladder cancer.

PURPOSE: Multivariate analysis of prognostic factors influencing survival and bladder preservation after radiochemotherapy for bladder cancer following transurethral resection of the bladder (TURB). PATIENTS AND METHODS: At the University Hospital of Erlangen 333 patients with bladder cancer were treated with either radiotherapy alone (RT, n = 128) or platin based radiochemotherapy (RCT, n = 205) after TURB between 5/1982 and 5/1996. Two-hundred and eighty-two curative patients, with either muscle invasive or T1-high risk cancer, were analyzed. Median age was 66 years, median follow-up is 7.5 years. Uni- and multivariate analysis was performed for age, grade, R-status after initial TURB, T-category and treatment modality relevant to the endpoints initial response, survival and bladder preservation. RESULTS: Treatment related mortality was below 1%. Complete remissions were achieved at 57%, 70%, and 85% after RT or RCT with carboplatin or cisplatin. This difference was multivariately significant. Further significant prognostic factors were pT-category and R-status. For all patients survival was 59% and 43% after 5 and 10 years. 79% of survivors could keep their own bladder. Five-year survival rates after RT alone, RCT with carboplatin or cisplatin were 47%, 57%, and 69%, respectively. This was univariately significant. The only multivariately significant factor for survival and bladder preservation was the R-status after initial TURB. CONCLUSIONS: Treatment of bladder cancer by TURB and RT/RCT is an alternative to primary cystectomy. The addition of chemotherapy leads to significantly more complete remissions and better survival. Initial TURB is recommended to be as radical as possible.

Adult↗
PubMed1998

Effect of testosterone replacement after neonatal castration on craniofacial growth in rats.

Neonatal castration precludes the pubertal increase in serum testosterone and reduces general and craniofacial growth in the male Wistar rat. This study aimed to determine whether exogenous testosterone given at an age beyond the normal pubertal peak restores general and craniofacial growth in male, neonatally castrated rats. The design was a randomized, double-controlled, cross-sectional trial. Male Wistar rats were assigned by weighted randomization to be either castrated early after birth (n = 35) or not (n = 15). On day 57, a 1.5-cm Silastic tube with testosterone was implanted in 18 of the castrated rats. On day 70 and day 110, body length, weight, and craniofacial growth were measured together with the weight of the prostate, and blood samples taken. The exogenous testosterone resulted in a significant increase in serum testosterone and prostate weight. All measures of general and craniofacial growth had higher mean values in the non-castrated control group than in the castrated group, while in the testosterone-implant group the mean values lay between these of the castrated animals and the non-castrated controls. Two-way ANOVA indicated a significant effect of the testosterone administration on lower-incisor growth and the size of the total skull vault.

Analysis of Variance↗
PubMed1998

Rhythmic variation in beta1-adrenergic receptor mRNA levels in the rat pineal gland: circadian and developmental regulation.

In the rat pineal gland noradrenaline is released in large quantities from sympathetic nerve endings at the onset of darkness, thereby driving rhythmic melatonin synthesis with elevated levels at night-time. Upon release, noradrenaline interacts with postsynaptic beta1-adrenergic receptors to activate the cyclic AMP signalling pathway. Well characterized third messengers of this signalling cascade affect cyclic AMP-inducible genes that are crucially involved in initiation, maintenance and termination of hormone production. Among these third messengers are CREB (cyclic AMP responsive element binding protein) as an activating and ICER (inducible cyclic AMP early repressor) as an inhibitory transcription factor. Because a cyclic AMP-inducible promoter element is present on the beta1-adrenergic receptor gene, the expression of the receptor itself may be under control of the cyclic AMP-signalling pathway. By in situ hybridization, Northern blot analysis and RT-PCR we demonstrate a day/night rhythm in beta1-adrenergic receptor mRNA in the rat pineal gland with elevated levels during the dark period. As this rhythm persists, under constant darkness but is abolished upon removal of the sympathetic innervation, it is truly circadian. A marked day/night difference in the levels of beta1-adrenergic receptor mRNA becomes evident only after postnatal day 10, coinciding with the appearance of a functional cyclic AMP signalling pathway in the rat pineal gland. Furthermore, targeting ICER expression by transfection of pinealocytes with an antisense ICER construct, clearly indicates that the levels of the beta1-adrenergic receptor mRNA are regulated by the cyclic AMP-signalling pathway in a feedback mechanism.

Animals↗
PubMed1997

Analysis of granuloma formation in double cytokine-deficient mice reveals a central role for IL-10 in polarizing both T helper cell 1- and T helper cell 2-type cytokine responses in vivo.

In response to i.v.-injected eggs of Schistosoma mansoni, normal mice develop a dominant type 2 response, whereas IL-10-deficient animals generate a mixed type 1/type 2 cytokine profile and show reduced pulmonary granuloma formation. IL-4-deficient mice, while displaying diminished type 2 responses and granulomatous inflammation, also do not fully default to a type 1 cytokine profile. Strikingly, mice doubly deficient in IL-4 and IL-10 are completely defective in pulmonary granuloma formation and develop a highly polarized type 1 cytokine pattern. In analogous fashion, mice deficient in both IL-12 and IL-10 generate highly exacerbated type 2 cytokine responses, whereas in wild-type animals, IL-12 depletion minimally effects egg-induced cytokine production. Together, these results argue first that IL-10 is an important endogenous down-regulator of type 2 as well as type 1 cytokine synthesis, and second, that its induction is critical for type 2 response polarization in vivo.

Animals↗
PubMed1997

Generation of Cre recombinase-specific monoclonal antibodies, able to characterize the pattern of Cre expression in cre-transgenic mouse strains.

Transgene-encoded Cre recombinase can target alteration of loxP-tagged genes to specific cell types and developmental stages in mice, depending on the pattern of transgene expression. To facilitate determination of the latter, we have generated monoclonal anti-Cre antibodies which are specific for distinct epitopes on the recombinase and detect Cre both on immunoblots and intracellularly by immunofluorescence. We demonstrate the usefulness of these antibodies by an analysis of Cre expression in mice carrying a cre-transgene under B cell-specific control.

Animals↗
PubMed1997

In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death.

Gene targeting experiments have demonstrated that the expression of immunoglobulin heavy chain in the pre-B cell receptor (pBCR) and of heavy and light chains in the B cell antigen receptor (BCR) marks checkpoints in early B cell development that the cells have to pass to survive. To investigate whether the persistence of mature B cells in the peripheral immune system also depends on BCR expression, we have generated a transgenic mouse in which the BCR can be inducibly ablated through V region gene deletion. Ablation leads to rapid death of mature B lymphocytes, which is preceded by down-regulation of MHC antigens and up-regulation of CD95 (Fas) and can be delayed by constitutive bcl-2 expression.

Animals↗
PubMed1997

[Advantages and limitations of intraoperative mechanical autotransfusion in al prostatectomies].

UNLABELLED: Intraoperative autotransfusion (MAT), preoperative autologous blood donation, and preoperative normovolaemic haemodilution are three different methods to avoid homologous blood transfusion during surgical procedures. The controversial use of MAT via cell saver in tumour surgery as well as contamination of the operative field with urine illustrate the particular difficulties of autologous blood transfusion in connection with radical prostatectomy. We investigated changes in the osmotic resistance of the retransfused red blood cells (RBC), bacterial contamination, changes in coagulation parameters, and the presence of tumour cells. PATIENTS AND METHODS: After written informed consent, 24 patients who presented for radical prostatectomy were randomly allocated to either a group that used MAT or a group that used homologous transfusion. The patients received "balanced anaesthesia" with midazolam, fentanyl, atracurium, and nitrous oxide/oxygen. The analysed parameters from the preoperative period to the 3rd postoperative day are shown in Table 1. The Haemonetics 3 Plus Cell Saver was used for autotransfusion. RESULTS: Our results showed that the haematologic parameters, coagulation factors, and serum chemistry did not differ between the two groups (Tables 2-4). However, there were significant differences during the investigated period. The osmotic resistance of the salvaged RBCs was higher than that preoperatively. Furthermore, there were no tumour cells in the autologous salvaged RBCs. CONCLUSION: Our results showed no decrease in the quality of the autotransfused RBCs, urine was not retransfused; and there were no significant differences between the groups postoperatively. Although there were no tumour cells in the salvaged blood, the possibility of blood irradiation is discussed. We concluded that because of the risk of infection of homologous blood products, MAT is a safe possibility to reduce the amount of homologous blood transfusion required in connection with radical prostatectomy.

Aged↗
PubMed1997

A comparative histopathological study of the influence of chemo- and radiotherapy on human prostatic carcinoma grown in nude mice.

Histological investigations were carried out to determine the effects of various kinds of treatment on the heterotransplanted prostatic carcinoma PC EW in athymic nude mice. Morphological changes after chemotherapy, radiotherapy, and combined radiochemotherapy were analyzed qualitatively and quantitatively. Effects of chemo- and radiotherapy like reduction of mitotic activity and increase of necrotic resp. fibrotic areas cumulated under the combined therapy. Results after radiotherapy or combined therapy corresponded to those reported for human prostatic carcinoma. Our observations indicate that the heterotransplanted tumor line PC EW represents a well suited preclinical test system for treatment of human prostatic carcinoma.

Adenocarcinoma↗
PubMed1997

Advances in gene targeting methods.

Gene targeting in embryonic stem cells is commonly used for gene inactivation and the generation of mouse mutants. The combined use of methods for site-specific and homologous DNA recombination expands the potential of gene targeting in embryonic stem cells considerably and offers the opportunity of conditional gene targeting in mice.

Animals↗
PubMed1996

Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse.

Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to IgE in the mouse. Here we report that IL-4-deficient (IL-4-/-) and wildtype mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4-/- mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4-/- mice and controls, but the levels of productive epsilon transcripts (p epsilon) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4-/- mice as compared with controls. Induction of g epsilon after anti-IgD treatment of IL-4-/- mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor alpha chain. Infection of IL-4-/- mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of g epsilon transcription and switch recombination to p epsilon.

Animals↗
PubMed1996

Light-induced expression of transcription factor ICER (inducible cAMP early repressor) in rat suprachiasmatic nucleus is phase-restricted.

The mammalian hypothalamic suprachiasmatic nucleus (SCN) harbors an intrinsic circadian oscillator driving a variety of endogenous rhythms. SCN activity is entrained to environmental lighting conditions by photic information from the retina. Light-induced phase shifts involve cAMP and Ca2+ as second messengers and are linked to transcriptional and translational processes. Using in situ hybridization with a cDNA fragment of the cAMP responsive element modulator (CREM) isoform inducible cAMP early repressor (ICER) we demonstrate a light-induced upregulation of CREM mRNA in rat SCN during the second half of the night. Notably, ICER is the only member of the CREM family which is transcriptionally inducible. We suggest that a stimulus-induced upregulation of ICER expression can inhibit cAMP-inducible genes in rat SCN via its trans-repressing potency.

Animals↗
PubMed1996

Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.

We have characterized the progressive stages of chronic intestinal inflammation that develops spontaneously in specific pathogen-free (SPF) mice with a targeted disruption in the IL-10 gene (IL-10-/-). Our longitudinal studies showed that inflammatory changes first appear in the cecum, ascending and transverse colon of 3-wk-old mutants. As the disease progressed, lesions appeared in the remainder of the colon and in the rectum. Some aged IL-10-/- mice also developed inflammation in the small intestine. Prolonged disease with transmural lesions and a high incidence of colorectal adenocarcinomas (60%) was observed in 6-mo-old mutants. Mechanistic studies have associated uncontrolled cytokine production by activated macrophages and CD4+ Th1-like T cells with the enterocolitis exhibited by IL-10-/- mice. A major role for a pathogenic Th1 response was further suggested by showing that anti-IFNgamma antibody (Ab) treatment significantly attenuated intestinal inflammation in young IL-10-/- mice. When weanlings were treated with IL-10, they failed to develop any signs of intestinal inflammation. Interestingly, IL-10 treatment of adults was not curative but did ameliorate disease progression. Our studies have also shown that inheritable factors strongly influence the disease susceptibility of IL-10-/- mice. In 3-mo-old mutants, intestinal lesions were most severe in IL-10-/- 129/SvEv and IL-10-/- BALB/c strains, of intermediate severity in the IL-10-/- 129 x C57BL/6J outbreds, and least severe in the IL-10-/- C57BL/6J strain.

Aging↗