Heterogeneous p27(Kip1) expression within primary renal cell cancers, their invasive margins and peritumoral renal parenchyma correlation with pathological and prognostic features.

INTRODUCTION: The expression of the negative cell cycle regulator p27(Kip1) is frequently found to be deregulated in various human cancer types. Whether expression of p27(Kip1) can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined. PATIENTS AND METHODS: For analysis of p27(Kip1) in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases. RESULTS: In univariate survival analysis, decreased expression of p27(Kip1) within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p = 0.02, log-rank test). In contrast, expression of p27(Kip1) protein within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p < 0.01), the presence of regional lymph node (p < 0.01) or distant metastases at the time of surgery (p < 0.01) as well as decreased expression of p27(Kip1) (p = 0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. CONCLUSION: Our analysis demonstrated that p27(Kip1) is heterogeneously expressed in renal cell carcinomas. Moreover, the result of the present study supports the prognostic value of p27(Kip1) protein expression for patients diagnosed with renal cell carcinoma.

Reduced Expression of the Cell Cycle Regulator p27Kip1 within the Invasion Front of Renal Cell Carcinomas Proved to be a Significant Marker for Disease-specific Survival.

BACKGROUND: The expression of the negative cell cycle regulator p27Kip1 is frequently found to be deregulated in various human cancer types. Whether the expression of p27Kip1 can be used as a prognostic marker for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression of protein within different tissue areas obtained from renal cell carcinomas, their invasion front and corresponding histologically benign renal parenchyma was determined and statistically correlated with several tumor and patient characteristics including the disease-specific long-term survival following surgical treatment. PATIENTS AND METHODS: For analysis of p27Kip1 expression in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising 1260 tissue samples each obtained from the tumor itself, the invasive front as well as the non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases In total, 88 out of 251 patients (35%) had died from tumor progression after a median follow-up of 138 (36-240) months. RESULTS: In univariate survival analysis, decreased expression of p27Kip1 within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p=0.02, log rank test). In contrast, expression of p27Kip1 within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p<0.01), the presence of regional lymph node (p<0.01) or distant metastases at the time of surgery (p<0.01) as well as decreased expression of p27Kip1 (p=0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. CONCLUSION: Our analysis demonstrated that p27Kip1 is heterogeneously expressed in renal cell carcinomas. Moreover, the results of the present study supports the prognostic value of p27Kip1 protein expression for patients diagnosed with renal cell carcinoma.

Complete nucleotide sequence of the RNA 1 of a grapevine isolate of Arabis mosaic virus.

The complete nucleotide sequence of the genomic RNA 1 of the grapevine isolate NW (Neustadt an der Weinstrasse) of Arabis mosaic virus (ArMV) was determined. It is 7334 nucleotides long excluding the poly(A) tail, and contains one long open reading frame encoding a polypeptide of 2284 amino acids. The 5' and 3' non-coding regions were 227 and 252 nucleotides long respectively, and showed stretches of high identity with the corresponding 5' and 3' non-coding regions of ArMV-NW RNA 2. The analysis of the amino acid sequence of the polyprotein encoded by the RNA 1 of the ArMV-NW showed that the conserved amino acid motifs, characteristic for the viral protease co-factor, the NTP-binding protein, the cystein protease, and the RdRp core domains, were all present. Amino acid sequence comparisons between the polyproteins encoded by the RNAs 1 of ArMV-NW and other nepoviruses showed 75% identity with the GFLV-F13, and up to 36% with other nepoviruses.

[The effects of methadone maintenance in clinical opiate dependence]. / Auswirkungen fraktionierter Methadongabe im klinischen Opiatentzug.

Comparatively few studies have examined the effects of methadone given during a clinical detoxification programme. Furthermore, their results are different especially because of changing drop-out rates. This study was carried out on a drug-detoxification ward and investigated the effects of methadone given to alleviate withdrawal symptoms. Comparisons were undertaken with patients withdrawn during a one-year period before methadone was available. No significant difference was found between drop-out rates of patients with methadone-supported detoxification (n = 113, drop-out rate: 41.6%) and patients who did not receive methadone during detoxification (n = 108, drop-out rate: 37.0%). Nevertheless the drop-out rate in the first three days of withdrawal was reduced from 15.7% to 8.0%. On average the critical drop-out moment shifted from 5.3 days to 10.1 days. Interpretations of these findings should take into account, that the number of patients who underwent a voluntary detoxification programme for the first time was nearly doubled after methadone was offered on the ward and, additionally, many more patients tried to withdraw from methadone taken within an outpatient methadone-maintenance programme.

[Rhinomanometric measurements during gradual physical exertion in subjects with normal nasal breathing]. / Rhinomanometrische Messungen unter schrittweiser körperlicher Belastung an Probanden mit normaler Nasenatmung.

28 healthy volunteers, 14 males and 14 females, aged from 18 to 45 years with normal nasal breathing were measured rhinomanometrically after physical exercise on an ergometer bicycle after increase in loads by steps of 25, 50, 75, 100, 125 and 150 watt and also 2, 5 and 10 minutes after physical exercise with 150 watt. V15 (nasal air flow related to 15 mm H2O) was registered. A new rhinomanometer with a Prandtl type tube was employed for measuring a relationship between nasal airflow (V2) and transnasal pressure (delta p) yielding a straight line in the V2-delta p-diagramm using nozzles and active anterior method. An increase of V15 up to 150 watt was measured. The average V15 value of the 28 persons for the total nose without decongestion the nasal mucosa before physical exercise at rest is 0.69 l/s and after physical exercise up to a load of 150 watt 1.09 l/s, so that the increase of V15 is 0.4 l/s. This decongestion effect of the nasal mucosa is twice to three times larger than the decongestion after xylometazolin spray 0.1% (Otriven 0.1%). The medicamentous decongestion effect of V15 = 0.14 l/s is as large as the decongestion effect caused by physical exercise with a load of 25 to 50 watt. A decrease of V15 is measured reaching a normal value within 15 minutes. The rhinomanometrical normal values under physical exercise within a load of 0 to 150 watt of healthy volunteers with normal nasal breathing are readable directly in a V15-watt diagramm for the right and left nasal cavity and the total nose based on the average values of all 28 volunteers. Individual variations of the maximal decongestion effect during physical exercise are discussed.

[Normal values of nasal airflow measured with a newly developed rhinorheomanometer with modified Prandtle-type tube and linear relations]. / Normalwerte der Nasenatmung gemessen mit einem neu entwickelten Rhinorheomanometer mit modifiziertem Prandtlschen Staurohr und linearer Kenngrösse.

A new rhinomanometer with a Prandtl type tube for measuring a square relationship between nasal airflow (V2) and transnasal pressure (delta p) yielding a straight line in the V - delta p - diagram is described. This so called rhinomanogram with straight lines is like an audiogram and gives a direct reading of V in relation to delta p. The active anterior method using nozzles is employed. 337 volunteers 185 females and 152 males aged 9-76 years with normal breathing function of the nose and normal endonasal mirror findings are examined with the above mentioned rhinomanometer. The normal values of nasal airflow in relation to 15 mm H2O in l./sec. (V15) of both nasal cavities before and after shrinkage of the nasal mucosa are measured during inspiration and exspiration. For all age groups, both male and female, the normal value of V15 of the entire nose is 0,67 +/- 0,16 l/sec before and 0.81 +/- 0.17 l/sec after shrinkage of the nasal mucosa. Slight differences in the normal values of the entire nose exist between males and females of different age groups as well as during inspiration and exspiration. V15 in females is 0.63 l/sec before and 0.77 l/sec after shrinkage, whereas V15 in males is 0.73 l/sec before and 0.86 l/sec after shrinkage. With increasing age, both in males and in females, there is slight increase of V15: V15 in the age-group of 9-16 years from 0.58 l/sec before to 0.72 l./sec. after shrinkage; in the age-group of 17-40 years it is 0.66 l./sec. before and 0.80 l./sec. after shrinkage whereas in the age-group of 41-76 years it is 0.75 l./sec. before and 0.88 l./sec. after shrinkage. During inspiration V15 is somewhat lower than during exspiration. Our normal V15-values are compared with all normal values of the nasal airflow mentioned in literature by other authors.