Loss of heterozygosity studies and deletion mapping identify two putative chromosome 14q tumor suppressor loci in renal oncocytomas.

Renal oncocytoma is considered to be a benign tumor that shares some phenotypic features with chromophobe renal cell carcinoma (RCC). Recently, we described high frequencies of allelic loss at 1p, 2p, 6p, 10p, 13q, 14q, 17p, and 21q, which correlate significantly with the chromophobe subtype of RCC. To investigate the genetic relationship between these two entities, we examined 12 oncocytomas for loss of heterozygosity (LOH) at these regions. In addition, we included markers for 3p, 5q, 7q, 11p, and 22q. The only chromosomal region showing similarly high frequencies of allelic loss for both subtypes was 14q. Therefore, a genetic relationship between renal oncocytoma and chromophobe RCC seems questionable. Eight of 12 oncocytomas (67%) showed LOH at 14q, a frequency that was significantly higher (P < 0.001, chi(2) test) than the frequencies of LOH in all other regions. To define regions potentially harboring novel tumor suppressor genes, we performed multifluorescence microsatellite analysis with 13 markers spanning 14q. Interstitial deletions at different regions of 14q were detected, with the highest frequencies at D14S258 (14q23-24.3) and D14S292 (14q32.1-32.2). 14q LOH might be associated with advanced-stage RCCs or other tumors, but it does not seem to indicate progression in oncocytomas. Its role in pathogenesis of renal oncocytomas remains to be clarified. Here, we provide evidence for two distinct tumor suppressor gene loci at 14q in renal oncocytoma, which will be useful for further fine-mapping studies of these critical regions.

Allelic losses at chromosomes 1p, 2p, 6p, 10p, 13q, 17p, and 21q significantly correlate with the chromophobe subtype of renal cell carcinoma.

We analyzed 50 sporadic renal cell carcinomas (RCCs) for loss of heterozygosity (LOH) at the chromosomal regions 1p, 2p, 6p, 7q, 10p, 11p, 13q, 14q, 17p, 21q, and 22q. Histologically, the tumors were distinguished into clear cell, chromophilic, and chromophobe carcinomas. Whereas LOH at 14q was identified in 42-64% of all three tumor types, only the chromophobe tumors showed high frequencies of LOH (73-91%) at 1p, 2p, 6p, 10p, 13q, 17p, and 21q. These findings provide substantial evidence that the chromophobe subtype of RCC represents a distinct genetic entity. Thus, specific LOH patterns may define the histogenesis and oncogenesis of chromophobe RCC and may be useful in tumor diagnosis and clinical prognosis.

[Comparison of the bioavailabilities of erythromycin estolate and erythromycin ethylsuccinate dry suspension preparations in steady state]. / Vergleich der Bioverfügbarkeiten von Erythromycinestolat bzw. Erythromycinethylsuccinat enthaltenden Trockensaft-Zubereitungen im steady state.

Relative bioavailability of erythromycin was determined after multiple-dose administration of erythromycin estolate in comparison to erythromycin ethylsuccinate both given as oral suspensions to twelve healthy volunteers. The daily erythromycin dose of erythromycin ethylsuccinate was 50% higher than the respective dose of erythromycin estolate; the dosage interval tau was 12 h for erythromycin estolate and 8 h for erythromycin ethylsuccinate. This scheme was planned in accordance to advices of the respective manufactures. Results of the study confirm the differences in extent of bioavailability of both erythromycin derivatives known from single-dose investigations. Furthermore, the experimental data show that a twice daily administration of 1000 mg erythromycin as erythromycin estolat resulted in sufficiently high plasma concentration of the active compound.