Endocrine Profile of 45 Patients with Sertoli Cell Only Syndrome

Endokrines Profil bei 45 Männern mit Sertoli-Zell-Syndrom
Bei 45 Männern mit Sertoli-Zell-Syndrom wurden die Hormonbasiswerte für FSH, LH, Prolaktin und Testosteron mit denen von Klinefelter-Paitenten, Männern mit Oligozoospermie und gesunden, fertilen Männern verglichen. Dabei ergab sich, daß die FSH- und LH-Werte bei Sertoli-Zell-Syndrom signifikant höher lagen als bei Gesunden. Die Erhöhung der Gonadotropine bei Patienten mit Sertoli-Zell-Syndrom was allerdings nicht so hoch und Testosteron nicht so herabgesetzt wie man es bei Klinefelter-Paitenten gefunden hatte. Aus dem Resultat, daß die LH-Werte erhöhte waren, während Testosteron sich im normalen Rahmen bewegte wird die Schlußfolgerung gezogen, daß hier eine kompensierte Dysfunktion der Leydigzellen bei den Patienten mit Sertoli-Zell-Syndrom vorliegt. Für Oligozoo-spermie-Patienten ließ sich keine Differenz der Hormonwerte gegenüber Gesunden feststellen.     

Graft coronary artery disease in murine cardiac allografts: proposal to meet the need for standardized assessment.

BACKGROUND: Inconsistency exists in assessing the severity of graft coronary artery disease (GCAD) in studies that use mouse models. The central issue associated with this inconsistency is the lack of a standardized approach for assessing mouse GCAD. METHODS: We propose a new histologic definition of GCAD based on 3 successive stages (endotheliitis, premature lesion, and mature lesion) that mark the progression of this condition. In addition to these qualitative measures of GCAD, we propose including 2 additional morphometric parameters (percentage of luminal narrowing and intima-to-media ratio) and a measure of distribution (percentage of affected vessels) in the routine quantification of GCAD. RESULTS: We introduce 2 new mouse models of GCAD as examples that satisfy these criteria. CONCLUSION: The proposed assessment criteria may simplify data collection and interpretation of results in various models of GCAD.     

Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study

Background: The prognostic meaning and thus indication for adjuvanttherapy of lymphogenic micrometastases in breast cancer patientsis still under debate. Patients and methods: From 1999 to 2007, 703 patients with _cT_1–2N₀breast cancer underwent surgery including sentinel lymph nodebiopsy. Examination of sentinel lymph nodes consisted of hematoxylinand eosin and immunohistochemistry staining following serialsectioning of the sentinel node. Patients were divided intofour groups: _pN₀ (n = 423), _pN_1micro (n = 81), _pN_1a (n = 130)and _pN_1b (n = 69). Median follow-up was 40 months. Results: At the end of follow-up, 53 patients had died and 64had recurrent disease. Compared with _pN₀ and following adjustmentfor possible confounders, including adjuvant systemic treatment,overall survival was not significantly different for _pN_1microwhile significantly worse for _pN_1a and _pN_1b {hazard ratio (HR)[95% confidence interval (CI)]: 0.59 [0.14–2.58], 4.31[1.85–10.01], 10.66 [4.04–28.14], respectively}.Likewise, disease-free survival was not significantly differentfor _pN_1micro and worse for _pN_1a and _pN_1b (HR [95% CI]: 1.43[0.67–3.02], 2.79 [1.37–5.66], 7.13 [3.27–15.54],respectively). Distant metastases were more commonly observedin the _pN_1micro than in the _pN₀ group, but still not as commonas in the _pN_1a or _pN_1b group (HR [95% CI]: 4.85 [1.79–13.18],10.34 [3.82–28.00], 23.25 [7.88–68.56], respectively). Conclusion: Although the risk of distant metastases was higherin patients in the _pN_1micro than in the _pN₀ group, no statisticallysignificant differences were observed in overall or disease-freesurvival between _pN₀ and _pN_1micro. Micrometastatic lymph nodeinvolvement in itself should not be an indication for adjuvantchemotherapy in breast cancer patients. Key words: breast cancer, micrometastases, prognosis, sentinel lymph node Received for publication March 11, 2008. Revision received June 25, 2008. Accepted for publication July 1, 2008.     

Functional human transcobalamin II isoproteins are secreted by insect cells using the baculovirus expression system

Transcobalamin II (TCII) is a cobalamin (Cbl, vitamin B12)-binding protein in mammalian plasma that facilitates the cellular uptake of the vitamin. To obtain human TCII in sufficient quantity for analytical studies, the complementary DNA (cDNA) encoding TCII was inserted into the plasmid PVL 1393, and the baculovirus expressing TCII was obtained by homologous recombination in Spodoptera frugiperda (SF9) insect cells by cotransfection with the wildtype virus. Under optimized conditions, SF9 cells infected with the recombinant virus secreted 2 to 4 micrograms of TCII per milliliter of culture medium. TCII did not accumulate in the SF9 cells and seemed to be constitutively secreted as observed previously in cultured human endothelial cells. The purified recombinant TCII has the same molecular weight by SDS-PAGE as purified human TCII. The recombinant TCII cross-reacts with an antiserum to native human TCII, binds Cbl and facilitates the uptake of Cbl in eukaryotic cells by binding to the receptor for TCII-Cbl on the plasma membrane of K562 cells. Amino acid sequence analysis of the purified recombinant TCII identified two polypeptides, one identical to the amino acid sequence deduced from the cDNA and a second lacking the first and second N-terminal residues. These sequences are identical to two TCII polypeptides purified from Cohn fraction III of pooled human plasma. The two forms of recombinant TCII have the same isoelectric points as the two predominant isoprotein forms of TCII in human serum. Since the baculovirus construct contains a single cDNA that can encode only one amino acid sequence, the two isoproteins in recombinant TCII must be generated by a mechanism other than allele specific expression. A plausible mechanism for generating isoproteins of nonglycosylated peptides, such as TCII, may be by splicing of the leader peptide at alternative sites.     

Positional cloning of a gene involved in hereditary multiple exostoses

Hereditary multiple exostosis (EXT) is an autosomal dominant condition mainly characterized by the presence of multiple exostoses on the long bones. These exostoses are benign cartilaginous tumors (enchondromata). Three different EXT loci on chromosomes 8q (EXT1), 11p (EXT2) and 19p (EXT3) have been reported, and recently the EXT1 gene was identified by positional cloning. To isolate the EXT2 gene, we constructed a contig of yeast artificial chromosomes (YAC) and P1 clones covering the complete EXT2 candidate region on chromosome 11p11-p12. One of the transcribed sequences isolated from this region corresponds to a novel gene with homology to the EXT1 gene, and harbours inactivating mutations in different patients with hereditary multiple exostoses. This indicates that this gene is the EXT2 gene. EXT2 has an open reading frame encoding 718 amino acids with an overall homology of 30.9% with EXT1, suggesting that a family of related genes might be responsible for the development of EXT.      

Epidemiology of Primary Liver Cancer in Serbia and Possible Connection With Cyanobacterial Blooms

Today, the occurrence of harmful cyanobacterial blooms is a common phenomenon and a potential global health problem. Cyanobacteria can produce metabolites highly toxic to humans. More than 80% of reservoirs used for water supply in Central Serbia have bloomed over the past 80 years. A 10-year epidemiological study showed a significant increase in the incidence of primary liver cancer (PLC) in the regions where water from the blooming reservoirs was used for human consumption. At the same time, no correlation was found between the incidence of PLC and other risk factors, such as cirrhosis and hepatitis viruses. Given the strong association with PLC induction and various known possible mechanisms of carcinogenic action, it is highly possible that, cyanotoxins—acting as initiator and promoter—may be the major risk factor that acts synergistically with other risk factors to cause increased incidence of PLC. However, at present, it is still not certain whether cyanotoxins alone were sufficient to induce PLC. Therefore, additional assessment of the health risks that may arise from human exposure to cyanotoxins is advisable.