Volume 49 (2003) No. 4

Volume 49 (2003) No. 4
Review
Selected Genetic Aspects of Male Infertility – What Animal Models Tell Us
F. LIŠKA...........................................................................129
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic
Corresponding author: František Liška, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University,
Albertov 4, 128 00 Prague 2, Czech Republic, tel. +420 224 968 147, Fax: +420 224 918 666, e-mail: fl@chl.cz.
Abstract.  
Full text. 129-141
Original Articles
Interferon Inducibility of STAT 1 Activation and Its Prognostic Significance in Melanoma Patients
V. BOUDNÝ, I. KOCÁK, L. LAUEROVÁ, J. KOVAŘÍK.....................................142 
Department of Cellular and Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Corresponding author: Jan Kovařík, Masaryk Memorial Cancer Institute, Žlutý kopec 7, 656 53 Brno, Czech Republic. E-mail: kovarik@mou.cz.
Abstract.
Full text. 142-146
Allogeneic Gene-Modified Tumour Cells in Metastatic Kidney Cancer. Preliminary Report.
G. PIZZA1, C. DE VINCI1, G. LO CONTE1, A. MAZZUCA1, G. CORRADO1, D. MENNITI1, A. BENATI1, P. ROMAGNOLI1, V. FORNAROLA1, L. BUSUTTI2, A. PALARETI3, R. CAPANNA4, V. DI MAIO1, S. RATINI1, A. GULINO5, A. VACCA5, L. MELCHIORRI6, M. FERRARI7, S. BORIANI8, R. O. BARICORDI6...........................147
1Immunotherapy Module, Operative Unit of Urology, Department of Urology and Nephrology; 2Operative Unit of Radiotherapy,
Department of Oncology,  S. Orsola-Malpighi Hospital, Bologna, Italy
3Department of Computer Science, University of Bologna, Italy
42nd Division of Orthopaedics and Reconstructive Surgery Centre, Florence, Italy
5Experimental Medicine, University “La Sapienza”, Roma, Italy
6Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Italy
7Experimental Institute of Zoo-prophylaxis, Emilia-Romagna and Lombardia Regions, Brescia, Italy
8Operative Unit of Orthopaedics, Maggiore Hospital, Bologna, Italy
Corresponding author: Giancarlo Pizza, Immunotherapy Module, Operative Unit of Urology, Department of Urology and Nephrology,
S. Orsola-Malpighi Hospital, Via P. Palagi, 9, 40138 Bologna, Italy.  Tel: +39-051-6362478; Fax: +39-051-6362476; e-mail: gpizza@med.unibo.it.     
Abstract.
Full text. 147-159
Cellular Localization of NGF and NGF Receptors in Aged Human Thymus
T. MARINOVA1, K. VELIKOVA2, S. PHILIPOV2, I. STANKULOV3, G. CHALDAKOV3,  L. ALOE4.......160
1Department of Biology, Medical University, Sofia, Bulgaria
2Department of General and Clinical Pathology, Medical University, Sofia, Bulgaria
3Division of Cell Biology, Department of Forensic Medicine, Medical University, Varna, Bulgaria
4Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy
Corresponding author: Tsvetana Ts. Marinova, Department of Biology, Medical Faculty; 2 Zdrave Street, BG-1431 Sofia, Bulgaria.
Fax: (+359 2) 9520345; (+359 2) 9520337; Tel.:(+359 2) 5166502; (+359 2) 9520311; e-mail: tmarin@medfac.acad.bg; tsvetamarin@yahoo.com.
Abstract.
Full text. 160-164
PXO Set of Recombinant Inbred Strains of the Rat: a New Strain Distribution Pattern Containing 448 Markers
D. KEMLINK1, V. JEŘÁBKOVÁ1, M. JANKŮ1, D. KŘENOVÁ1, V. KŘEN1,2....................165
1Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic
2Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Corresponding author: Vladimír Křen, Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague,
Albertov 4, 128 00 Prague, Czech Republic. Tel.: +4202 24968147; e-mail vkren(zavináč)lf1.cuni.cz.
Abstract.
Full text. 165-176

Review
Selected Genetic Aspects of Male Infertility – What Animal Models Tell Us
F. LIŠKA

Many advances have been recently made in understanding the genetic control of fertility in model systems.
This review concentrates on genetic causes of male factor infertility in mammalian models. More than 150 genes proved to be
 important for the male fertility in mammals and the list is continuously growing. Most of those genes were discovered using
gene targeting in the mouse. Here, several interesting male infertility mutations are described with regard to the pathogenesis of
 reproduction failure.
Back to content.
Original Articles
Interferon Inducibility of STAT 1 Activation and Its Prognostic Significance in Melanoma Patients
V. BOUDNÝ, I. KOCÁK, L. LAUEROVÁ, J. KOVAŘÍK

STAT 1, a member of latent cytoplasmic proteins, plays a pivotal role in mediating biological effects of interferons. Its
transducing, DNA binding and transcriptional activity requires  phosphorylation at both Tyr 701 (Y 701) and  Ser 727  (S 727)
residues. Deficient phosphorylation or constitutive activation of the STAT 1 protein were observed in some human malignancies.
Using immunoprecipitation and Western blots performed with lysates made of melanoma cells derived from patients with clinical
stage II/III and employing specific anti-STAT 1 PS 727/PY 701  immunoprobes, we show that STAT 1 activation response
induced by IFN-alfa/-gamma  is significantly impaired. On average, three quarters of patients were lacking phosphorylation at S 727.
STAT 1 PY 701 was not inducible by IFN-alfa in 63% and by IFN-gamma in 34% of samples. However, these STAT 1 activation
defects showed no correlation with the disease outcome and immunotherapy response as indicated by progression-free survival
profiles in patients treated with IFN-alfa2b.
Back to content.

Allogeneic Gene-Modified Tumour Cells in Metastatic Kidney Cancer. Preliminary Report.
G. PIZZA, C. DE VINCI, G. LO CONTE, A. MAZZUCA, G. CORRADO, D. MENNITI, A. BENATI, P. ROMAGNOLI, V. FORNAROLA, L. BUSUTTI, A. PALARETI, R. CAPANNA, V. DI MAIO, S. RATINI, A. GULINO, A. VACCA, L. MELCHIORRI,
M. FERRARI, S. BORIANI, R. O. BARICORDI

An allogeneic irradiated RCC cell line, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated
tumour cells, was used to vaccinate ten MRCC patients in progression of disease  in spite of IL-2 immunotherapy. The cells were administered subcutaneously and/or intra-tumourally. Sixty-four MRCC patients in progressive disease, not treated by vaccination but receiving similar IL-2 immunotherapy, were considered as the control group.
Patients received 4–16 injections (mean 9 ± 4), containing an average of 10.6 x 107 ± 7.7 x 107 ACHN-IL-2-transfected cells (a minimum
of 4 x 107, and a maximum of 31 x 107). Four patients also received intra-tumour injections. Vaccination was administered during
30–418 days, and the follow-up continued for 649 ± 353 days (190–1342). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were observed. One complete and
one partial tumour response were observed, as well as two stable and one no-relapse disease. All but one patient died. Responding
patients resumed progression in 4–11 months and died 18 and 36 months after beginning the vaccine therapy. In spite of the small number of treated patients, Wilcoxon’s test showed a significant (P  < 0.05) improvement of the survival in the vaccinated group compared to that of the control. The described vaccination protocol seems safe, devoid of adverse side effects and promising. It warrants further investigation.
Back to content.

Cellular Localization of NGF and NGF Receptors in Aged Human Thymus
T. MARINOVA, K. VELIKOVA, S. PHILIPOV, I. STANKULOV, G. CHALDAKOV,  L. ALOE

Recent evidence indicates that some thymic cells of developing and adult laboratory animals express the neutrophin NGF and its low-affinity p75NTR and high-affinity TrkA receptor. Less is known as to whether the thymus of adult and aged humans express these
 markers. We hypothesize that the presence and distribution of immunopositive cells for NGF and NGF receptors undergo some alterations during the involution of human thymus. Specimens from normal thymuses of old individuals were obtained from autopsy and surgery cases, and examined immunocytochemically at the light and transmission electron microscopic level. The immunoreactivity of NGF, p75NTR, TrkA and cytokeratin was found in the epithelial thymocyte microenvironment. Our results provide the first ultrastructural evidence for NGF/receptor immunocytochemical localization in human thymus. They suggest a possible immunotrophic/immunoregulatory role of NGF-p75NTR-TrkA
system for T-cell development in human thymus during senile involution.
Back to content.
PXO Set of Recombinant Inbred Strains of the Rat: a New Strain Distribution Pattern Containing 448 Markers
D. KEMLINK, V. JEŘÁBKOVÁ, M. JANKŮ, D. KŘENOVÁ, V. KŘEN

A new PXO set of RIS represents a fixed F2 population derived from polydactylous (P) congenic strain SHR.Lx and
oligodactylous (O) RI strain BXH2. The PXO strains were derived as a complementary set to current RIS  (HXB, BXH) of the laboratory rat. All PXO strains are homozygous in Lx allele and express different morphological phenotypes of the polydactyly-luxate syndrome (PLS) due to variable combinations of Lx modifying genes of either SHR or BN origin. The SDP is being built up by genotyping polymorphic microsatellite markers and several gene polymorphisms. The markers were ordered according to data from public mapping resources such as the Rat
Genome Database (rgd.mcw.edu) and current SDP of the other RI strain sets (HXB, BXH). The resulting map corresponding to the common SDP of HXB, BXH RIS sets consists of 448 markers from which 261 were proven to be polymorphic in the PXO set. The SDP of PXO
strains with polymorphic markers arranged in approximately 5 cM intervals is ready for the association analysis and interval mapping in interconnection with the SDP of HXB/BXH strains.
Back to content.