Evidence for production and functional activity of nitric oxide in seminiferous tubules and blood vessels of the human testis

Previous studies have demonstrated that nitric oxide (NO) influences Leydig cell function. Here we provide evidence for NO production and activity in seminiferous tubules and blood vessels of the human testis. By immunohistochemistry, the soluble guanylyl cyclase (sGC), the intracellular NO receptor, and the second messenger, cyclic guanosine monophosphate (cGMP), were detected in myofibroblasts of the peritubular lamina propria in Sertoli cells, as well as in endothelial and smooth muscle cells of testicular blood vessels. Performed with isolated tubules and blood vessels, the biological activity of sGC could be proved by cGMP generation in response to treatments with the NO donor, sodium nitroprusside. The endothelial and neuronal subtypes of NO synthase (NOS) were localized immunohistochemically to the same cell types that express sGC and cGMP. In isolated tubules and vessels, the presence of endothelial NOS and neuronal NOS was confirmed by immunoblotting, and NOS activity was demonstrated by decreased cGMP production upon incubation with the NOS inhibitor L-nitro arginine methylester. These findings show that peritubular cells, Sertoli cells, and testicular blood vessels may be sites of NO production and activity, possibly involved in relaxation of seminiferous tubules and blood vessels to modulate sperm transport and testicular blood flow, respectively.     

Perineal endometriosis at the site of an episiotomy scar

This study presents a case of vaginoperineal histologically verified endometriosis at the site of episiotomy scar in a 40-year female subject, 17 years after delivery. Apart from episiotomy during delivery manual revision of the uterus was performed and the cervical rupture managed. Residue symptoms occurs 8 months after the first surgical excision. Clinical data indicate that decidua implantation at the site of episiotomy occurred during the manual revision of the uterine cavity during delivery.     

Ethical, legal and medical aspects of transplantation

Tissue and organ transplantation is a very complex interdisciplinary treatment, particularly in regard to unpaired organs, and it carries numerous risks for all participants in such an action. For the purpose of minimizing the risks to the allowed level and the preservation the humanitarian goals in medicine when performing the transplantation, professional and scientific doctrines and the respect of ethical and legal principles should be strictly observed. The paper presents the basic approaches in the estimation of justification, usefulness and certain forms of responsibility in the process of transplantation. Ethical and legal postulates which support transplantation to prevent deviation, deprivation or delinquency have also been reviewed.     

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.     

A PMLRARalpha transgene initiates murine acute promyelocytic leukemia

The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha). To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice. PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.     

An efficient method of FIR filtering based on impulse responserounding

A new method of implementing efficient FIR filters is presented. It involves approximation of an equiripple FIR by a rounding operation and application of the derived impulse response by a simple recursive equation. The technique is extremely efficient for lowpass, highpass, bandpass, and bandstop filters with sharp transitions and low edge frequencies     

Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.     

The Transmogrifier-2: a 1 million gate rapid-prototyping system

This paper describes the Transmogrifier-2 (TM-2), a second-generation multifield programmable gate array (FPGA) rapid-prototyping system. The largest version of the system will comprise 16 boards that each contain two Altera 10K50 FPGA's, four I-Cube interconnect chips, and up to 8 Mbytes of memory. The inter-FPGA routing architecture of the TM-2 uses a novel interconnect structure, a nonuniform partial crossbar, that provides a constant delay between any two FPGA's in the system. The TM-2 architecture is modular and scalable, meaning that systems of various sizes can be constructed from copies of the same board, while maintaining routability and the constant delay feature. Other features include a system-level programmable clock that allows single-cycle access to off-chip memory, and programmable clock waveforms with edge resolution of 10 ns. The first Transmogrifier-2 boards have been manufactured and are functional. They have recently been used successfully in some simple graphics acceleration applications     

Method for preventing delay ambiguity

A detection error mechanism termed delay ambiguity is identified as one of the main causes of the irreducible bit error rate observed for data detection over fast fading communication channels. A periodic sequence of phase rotations applied to the phase shift keyed (PSK) transmit data symbols is proposed to prevent this type of detection error