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R Kühn

Publications and source records attributed to R Kühn.

At least 73 records · Page 4Linked to original sources
PubMed1994

Organ-sparing treatment of advanced bladder cancer: a 10-year experience.

PURPOSE: Radical cystectomy is considered as standard therapy for muscle-invasive bladder cancer. We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy +/- chemotherapy. METHODS AND MATERIALS: From 1982 through 1991, 245 consecutive patients, mean age 66 years, with invasive bladder cancer (T2-3 or poor prognostic T1, no distant metastases) entered a prospective protocol with the objective of bladder preservation. Treatment consisted of transurethral resection (complete, if possible) and definitive radiotherapy with 56 Gy maximum dose (50.4 Gy minimum target dose) in 28 fractions. Since 1985, 139 patients received a simultaneous chemotherapy on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily (79 patients) or 65 mg/m2 carboplatin (60 patients). Cystectomy was performed as salvage treatment for residual or recurrent invasive disease. The median follow-up at the date of analysis (12-31-92) was 5.9 years. RESULTS: The overall survival was 47% after 5 years and 26% after 10 years. The 5-year survival according to the initial T-category was 60% for T1 (44 patients), 64% for T2 (47 patients), 43% for T3 (127 patients), and 16% for T4 (23 patients). The most important single prognostic factor was the amount of residual tumor after TUR (5-year survival 80% after R0, 53% after R1, and 31% after R2 resection, p < 0.01). Chemotherapy increased the rate of complete remission, but had no impact on 5-year survival (52% vs. 50%). Fifty-three salvage cystectomies were performed, all without severe complications, and 192 patients (79%) maintained a normal functioning bladder. The bladder preservation rate in 5-year survivors was 83%. CONCLUSIONS: Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective. The survival in this series is as good as in any comparable cystectomy series. Eighty-three percent of long-term survivors maintained their functioning bladders.

Aged↗
PubMed1994

MHC class I expression in mice lacking the proteasome subunit LMP-7.

Proteasomes degrade endogenous proteins. Two subunits, LMP-2 and LMP-7, are encoded in a region of the major histocompatibility complex (MHC) that is critical for class I-restricted antigen presentation. Mice with a targeted deletion of the gene encoding LMP-7 have reduced levels of MHC class I cell-surface expression and present the endogenous antigen HY inefficiently; addition of peptides to splenocytes deficient in LMP-7 restores wild-type class I expression levels. This demonstrates the involvement of LMP-7 in the MHC class I presentation pathway and suggests that LMP-7 functions as an integral part of the peptide supply machinery.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not dependent on IL-4 from non-Th cells.

Interleukin 4 (IL-4) is essential for the induction of immunoglobulin E (IgE) responses in mice. Recent in vitro studies have suggested that IL-4 derived from non T helper (Th) cells, in particular from mast cells and basophils, may be essential for triggering of IL-4 expression in Th cells and may directly contribute to IgE isotype switch induction. Here, we have generated mice carrying a functional IL-4 gene only in Th cells or non-Th cells, respectively, by reconstitution of IL-4-deficient mice (IL-4T mice) with CD4+ or CD4- spleen cells from congenic wild-type animals. In mice in which only CD4+ cells are able to express IL-4, antigen-specific IgE is produced in a T cell-dependent immune response. Thus, induction of IL-4 expression in Th cells can occur in the absence of IL-4 from non-Th cells, which suggests that at least some Th cells can express IL-4 in response to another signal which has yet to be identified. No IgE is detectable, however, in mice in which only CD4- cells can express IL-4, suggesting that Th cells are the primary, if not the only source of IL-4 for initial induction of IgE synthesis.

Animals↗
PubMed1994

Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4.

Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL-2 and IL-4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL-2 and IL-4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL-2 and IL-4-deficient homozygous mice.

Animals↗
PubMed1994

Analysis of free amino acids in green coffee beans. I. Determination of amino acids after precolumn derivatization using 9-fluorenylmethylchloroformate.

For the determination of free amino acids in green coffee beans, 9-fluorenylmethylchloroformate was applied successfully as the precolumn derivatization agent. The separation of the 27 free amino acids of green coffee as yet identified or quantitatively determined is almost complete. The paper describes in detail the conditions of extraction, derivatization and resolution and presents reproducible data of standard curves and of quantitative results. It has been demonstrated that by applying the extraction procedure described, 99.8% of the free amino acids detectable by this method are extracted. On principle, Arabica and Robusta coffees contain the same main and minor amino acids. It was possible for the first time to determine the free amino acids ornithine, beta-alanine and pipecolic acid quantitatively in Arabica and Robusta coffees as well as hydroxyproline in Arabica coffees.

Amino Acids↗
PubMed1994

Dysmorphic erythrocytes in glomerulonephritis. 1. Electron microscopical and histochemical investigation.

Dysmorphic erythrocyte malformation in urine is characteristic of glomerulonephritis. The mechanisms leading to this phenomenon are still unknown. To obtain evidence of the site as well as of the process of erythrocyte damage, electron microscopical and histochemical investigations of renal biopsy materials from 19 patients with histologically defined glomerulonephritis were performed. The results suggest that the initial damage of erythrocytes in the glomerular area is reasoned by enzymatic glycocalyx destruction. On passage through the tubular system the osmotically sensitized surface altered cells undergo rapid hemolysis and losses of membrane skeletal proteins leading to dysmorphic shape transformations.

Adult↗
PubMed1994

Dysmorphic red cell formation in glomerulonephritis. 2. In vitro generation of dysmorphic erythrocytes.

In the present study influences leading to in vitro formation of dysmorphic erythrocytes were studied. Fresh and surface altered erythrocytes pretreated with several proteases were passed through different solutions representing distinct nephronís fluids. After passage of intact erythrocytes only 12-15% dysmorphic cells were observed. In case of protease treated cells the number of dysmorphic cells rose to 35-80%. The hemoglobin content was decreased. PAGE and electron microscopical findings demonstrated substantial losses of transmembrane and membrane skeleton proteins. It is assumed that surface protein degradation, loss of membrane skeleton proteins and hemolysis seem to be closely associated with dysmorphic malformation of urinary erythrocytes characteristical for glomerulonephritis.

Anisotropy↗
PubMed1994

[Kidney transplantation in patients with anomalies of the lower urinary tract].

In the transplant centre in Erlangen-Nuremberg, 1242 patients underwent renal transplantation between 1966 and 1993. In 4.5% of cases (56 patients) the renal end stage disease had been caused by severe abnormalities or functional disturbance of the lower urinary tract. Despite long-standing defunctionalization, urinary diversions and multiple operative procedures, it was possible to use the original bladder for ureterocystoneostomy in all patients. Only 1 patient needed an enterocystoplasty after transplantation. Altogether 72 transplantations have been performed in 56 patients ranging from 10.2 to 62.7 years of age. At follow up, 40 patients (71%) had a functioning graft with a mean serum creatinine level of 1.5 mg%. The 5-year transplant survival rate is 57.3%. Our results suggest that carefully planned renal transplantation in urological patients has results comparable to those obtained in other, non-risk, kidney transplant recipients. The methods of bladder reconstruction and augmentation, intermittent self-catheterization as well as anticholinergics and continuous antibiotic prophylaxis combine to make the ileal or colonic conduits needed earlier unnecessary.

Adolescent↗
PubMed1994

[Classification and prognosis of supravesical urothelioma with the new TNM classification].

We report on 149 patients with supravesical urothelioma (transitional cell carcinoma of the upper urinary tract) treated in our hospital during the years 1967-1991. The introduction shows the distribution of sex and age as well as the localization of the tumor. Main topic of this paper is a new definition of the clinical pathology of supravesical urothelioma by means of the TNM classification published 1987. Based on the pathological pioneer work of P. Hermanek our results are as follows: during the first diagnosis pT3 predominates with 30.2%, followed by pT1 with 25.5% and pTa, pT1 and pT4 with a relatively low incidence. G2 predominates with 47.7%; G1 and G3 have almost the same frequency. The G/pT ratio shows a decreasing linearity for G1 from pTa to pT4; for G2 there is equivalence of pT1-pT3; and pTa and pT4 are relatively rare. With respect to G3, pT3 predominates with 51%, followed by pT4, pT1 and finally pTa with zero frequency. The G/M ratio shows M0 only for G1, 10% M positive for G2 and 15% M positive for G3. The 10-year survival rate for patients with R0 resection and stage pTa is 64% and for pT1-pT4, 33-36%. The 10-year survival rate for patients with G1 tumor is 51%, and that for G3 tumors 30%. Multicentric occurrence and carcinoma in situ have no prognostic significance in our sample. As is well known, papillary growth has a better prognosis than solid infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Interleukin-10-deficient mice develop chronic enterocolitis.

Interleukin-10 (IL-10) affects the growth and differentiation of many hemopoietic cells in vitro; in particular, it is a potent suppressor of macrophage and T cell functions. In IL-10-deficient mice, generated by gene targeting, lymphocyte development and antibody responses are normal, but most animals are growth retarded and anemic and suffer from chronic enterocolitis. Alterations in intestine include extensive mucosal hyperplasia, inflammatory reactions, and aberrant expression of major histocompatibility complex class II molecules on epithelia. In contrast, mutants kept under specific pathogen-free conditions develop only a local inflammation limited to the proximal colon. These results indicate that the bowel inflammation in the mutants originates from uncontrolled immune responses stimulated by enteric antigens and that IL-10 is an essential immunoregulator in the intestinal tract.

Anemia↗
PubMed1993

Visualization of serotonin effects on renal vessels of rats.

We studied the effects of serotonin (5-hydroxytryptamine, 5-HT) on glomerular blood flow (GBF) and on renal vessel diameters in the hydronephrotic kidney and in vascular casts of normal kidneys of rats. 5-HT (60 min after local application of 10(-8) mol.liter-1) constricted the arcuate arteries (-10 +/- 2% to -14 +/- 2%, mean +/- SEM), dilated the interlobular arteries (+13 +/- 2%) and afferent arterioles (+17 +/- 3%), and decreased GBF (-44 +/- 5%). In contrast to normal autoregulation, reduction of renal perfusion pressure after local application of 5-HT from 118 +/- 3 mm Hg by 10 and 20 mm Hg reduced GBF by 12 +/- 2% and 23 +/- 3%, respectively. The 5-HT2 antagonist, ritanserin (60 min after local application of 10(-6) mol.liter-1), dilated all preglomerular vessels and increased GBF. In the presence of ritanserin, 5-HT lost nearly all vascular effects. During infusion of 5-HT (5 micrograms.min-1 i.v. for 20 min) vascular reactions were similar to those under local application. After cyclooxygenase inhibition with indomethacin, infusion of 5-HT failed to constrict the arcuate arteries whereas vasodilation of the small preglomerular vessels remained unaffected. Analyzing vascular casts of normal kidneys we observed considerable vascular spasms and an average vasoconstriction of the interlobar arteries of 19 +/- 9% after i.v. infusion of 5-HT. We believe that 5-HT decreases GBF by 5-HT2 receptor-mediated constriction of the large renal vessels which are modulated by the prostaglandin system, whereas 5-HT dilates the small preglomerular vessels, most likely via 5-HT1-like receptors. Furthermore, our data indicate that 5-HT impairs the myogenic component of renal autoregulation in the low pressure range.

Animals↗
PubMed1993

[Pathologic development of the kidney].

In the absence of firmly established views on the development of nephropathy, we describe in this paper the embryogenetic and clinical aspects of kidney disease. Congenital reductive nephropathy always arises in the ureteral bud and is determined by two factors, endogenous dysplasia and endogenous obstruction. The nine well-known patterns of disease that may result are described herein. The most important starting points are as follows: (a) A dysplastically disorganized and hence refluxive trigone of the bladder induces, via pyramidal-medullary deficiencies, a defect of the metanephros and thus what we term reflux nephropathy (III-V). BU and PN may supervene postnatally. (b) Similarly, obstruction of the ureteral outlet in the first trimester induces dysplastic ascending nephropathy. (c) The same obstruction beginning in the second trimester induces nondysplastic, purely obstructive nephropathy, characterized by glomerular hypogenesis and hemo-obliterative cirrhosis which varies considerably from stage to stage and from case to case and may go as far as complete loss of the parenchyma. (d) Obstruction of the pyeloureteral junction, occurring late in the embryonic phase and originating outside the urinary system, provides the clearest example of fully developed nondysplastic reductive nephropathy. The lesional process may come to a halt at any time. (e) Coincidence of early embryonic dysplastic-refluxive nephropathy and late embryonic infravesical obstruction (with no causal link) accounts for half the morbidity from valvular disease. The other half results from simple nondysplastic obstruction.

Female↗
PubMed1992

T helper cell membranes promote IL-4-independent expression of germ-line C gamma 1 transcripts in B cells.

Studies using plasma membranes from activated Th cell clones (Th membranes) to stimulate B cells have shown that both a contact-mediated activation signal plus Th-derived cytokines are required for antibody production. In order to clearly separate and define the role of these two signals in isotype switching, B cells were stimulated with Th membranes in the presence or absence of cytokines, and the transcriptional activity of the unrearranged H chain loci was determined. In the presence of Th membranes, two known switch factors were shown to specifically induce germ-line transcription of the same H chain loci as in LPS-stimulated B cells (IL-4 induced C gamma 1 and C epsilon transcription, transforming growth factor-beta induced C alpha transcription). The contact-mediated activation signal provided by the Th membranes, in the absence of any added cytokines, resulted in the specific induction of C gamma 1 germ-line transcription, and thus functioned as a switch signal for IgG1. These findings provide a mechanism for previously observed IL-4-independent isotype switching to IgG1.

Animals↗
PubMed1991

Generation and analysis of interleukin-4 deficient mice.

Interleukin-4 (IL-4) promotes the growth and differentiation of many hematopoietic cells in vitro; in particular, it directs the immunoglobulin (Ig) class switch to IgG1 and IgE. Mice homozygous for a mutation that inactivates the IL-4 gene were generated to test the requirement for IL-4 in vivo. In the mutant mice T and B cell development was normal, but the serum levels of IgG1 and IgE were strongly reduced. The IgG1 dominance in a T cell-dependent immune response was lost, and IgE was not detectable upon nematode infection. Thus, some but not all of the in vitro properties of IL-4 are critical for the physiology of the immune system in vivo.

Aging↗
PubMed1991

A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene.

Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation.

Animals↗