Masaki Yamanaka

Isolation and Characterization of a Haploid Germ Cell-Specific Novel Complementary Deoxyribonucleic Acid; Testis-Specific Homologue of Succinyl CoA:3-Oxo Acid CoA Transferase

Abstract We have isolated a cDNA clone encoding a mouse haploid germ cell-specific protein from a subtracted cDNA library. Sequence analysis of the cDNA revealed high homology with pig and human heart succinyl CoA:3-oxo acid CoA transferase (EC 2.8.3.5), which is a key enzyme for energy metabolism of ketone bodies. The deduced protein consists of 520 amino acid residues, including glutamate 344, known to be the catalytic residue in the active site of pig heart CoA transferase and the expected mitochondrial targeting sequence enriched with Arg, Leu, and Ser in the N-terminal region. Thus, we termed this gene scot-t (testis-specific succinyl CoA:3-oxo acid CoA transferase). Northern blot analysis, in situ hybridization, and Western blot analysis demonstrated a unique expression pattern of the mRNA with rapid translation exclusively in late spermatids. The scot-t protein was detected first in elongated spermatids at step 8 or 9 as faint signals and gradually accumulated during spermiogenesis. It was also detected in the midpiece of spermatozoa by immunohistochemistry. The results suggest that the scot-t protein plays important roles in the energy metabolism of spermatozoa.

Molecular Cloning and Characterization of Phosphatidylcholine Transfer Protein-Like Protein Gene Expressed in Murine Haploid Germ Cells

Abstract We have isolated a cDNA clone specifically expressed in spermiogenesis from a subtracted cDNA library of mouse testis. The cDNA consisted of 1392 nucleotides and had an open reading frame of 873 nucleotides encoding a protein of 291 amino acid residues. Computer-mediated homology search revealed that the nucleotide sequence was unique but the deduced amino acid sequence had similarity to mouse phosphatidylcholine transfer protein (PCTP). We named this newly isolated gene PCTP-like protein. Northern blot analysis revealed a 1.4-kilobase mRNA expressed in the testis, kidney, liver, and intestine with the highest level in the testis. Messenger RNA expression in the testis was detected first on Day 23 in postnatal development and then increased up to adulthood. The protein, having a molecular weight of approximately 40 000, was encoded by the mRNA and was detected at the tail of the elongated spermatids and sperm by immunohistochemical staining.

Possible association of infertility with sperm-specific abnormality of CD46.

Three infertile patients fulfilling normal or subnormal criteria on routine semen analysis showed abnormal sperm CD46 (membrane cofactor protein of complement) by SDS-PAGE/immunoblotting analysis using a panel of monoclonal antibodies. The sperm CD46 isoform has been reported to be associated with sperm-egg interaction. These three patients expressed normal CD46 isoforms on their lymphocytes and granulocytes. Sperm-specific abnormalities in these proteins thus parallel male infertility, suggesting a new category of infertility, probably due to aberrations in the molecules related to sperm-egg interaction.

Effect of Renal Transplantation on Sexual Function

This investigation was conducted to determine whether renal transplantation can improve sexual function in male patients with chronic renal failure. The authors retrospectively studied 121 men undergoing renal transplantation who complained of any type or degree of sexual dysfunction pre-operatively. Sexual function was evaluated by questionnaire which included erectile, ejaculative, and orgasmic functions. Pre- and postoperative frequency of sexual intercourse was also recorded. Patient characteristics, laboratory data, and endocrinologic profiles were analyzed to identify factors that might influence sexual function. In patients with hormonal determinations, results essentially normalized after transplantation. However, only 43 patients (35.5%) reported improvement of overall sexual function after renal transplantation, while 34 (28.1%) reported worsening. Although frequency of sexual intercourse was unaffected by transplantation, 15 of 20 patients who had no intercourse before transplantation initiated intercourse afterward. These 15 patients all underwent transplantation before 40 years of age. Comparisons of variables by sexual function showed significant differences for type of immunosuppressive treatment, interval after renal transplantation, and serum concentration of hemoglobin A1c. It is concluded that renal transplantation cannot improve sexual function in allpatients, although hormonal profiles were largely normalized, and that renal transplantation should be encouraged at a younger age.

Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients

Abstract:  Objective:  BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15‐deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living‐related renal transplantation between January 1999 and April 2003.

Climacteric-Like Disorders in Prostate Cancer Patients Treated With LHRH Agonists

We assessed long-term side effects with characteristics of female climacteric disorders in prostate cancer patients treated with luteinizing hormone-releasing hormone (LHRH) agonists. Such side effects are not considered to be serious, though they can significantly affect patient quality of life. Sixty-four prostate cancer patients treated with LHRH agonists and 30 benign prostatic hyperplasia patients, as a control group, were surveyed by questionnaire. The median age of the cancer patients was 74.9 years old, ranging from 60 to 94 years, and the median LHRH agonist dosing period was 16.5 months, ranging from 1 to 64 months. The results of the questionnaires were compared between the patients and the controls, as well as between different variables. Sixty (93.8%) of 64 patients claimed symptoms similar to female climacteric disorders. Further, more than 50% of the symptoms included in the questionnaire were reported by 14 (21.9%) of the patients. Symptoms reported by the patients were more severe than those by the controls. Hot flashes, sleep disturbance, and fatigue recorded high scores in the patient questionnaires as compared with those of the controls. In addition, as the term of LHRH agonist use increased, complaints of sweating or coldness in hands and feet increased. Patients without bone metastasis frequently experienced heaviness in the head and headaches compared to those with bone metastasis. The results of our questionnaire-based outcome study showed that side effects similar to female climacteric disorders in prostate cancer patients treated with LHRH agonists were more severe than in the control group, which could be detrimental to quality of life and general well-being.

Effect of hepatocyte growth factor on sperm motility.

PROBLEM: Hepatocyte growth factor (HGF) exists abundantly in seminal plasma and its receptor, c‐met, is expressed on spermatozoa. Considering its motogenic activity, we speculated that HGF might affect the movement ability of spermatozoa.
 METHODS: Recombinant HGF was added to washed spermatozoa and their movements were analyzed using a computer‐assisted sperm analyzer. The concentration of HGF in the seminal plasma of infertile patients (n =83) was measured by ELISA, and the data were compared with their hormonal profile and semen parameters.
 RESULTS: The HGF physiological concentration (1 ng/mL) maintained the motility of sperm after a long incubation, though the difference was not statistically significant. Recombinant HGF did not affect the linearity or frequency of movement, which suggested that it does not evoke the hyperactivation of spermatozoa. The concentration of HGF in seminal plasma did not correlate with any clinical parameter of the patients.
 CONCLUSIONS: These findings contradict the theory that HGF controls the movement of sperm. The main role of this axis in the male reproductive system might be maturation in the epididymis.

BROMOCRIPTINE FOR INFERTILE MALES WITH MILD HYPERPROLACTINEMIA: HORMONAL AND SPERMATOGENIC EFFECTS

To clarify the influence of hyperprolactinemia on spermatogenesis and steroidogenesis in infertile male patients, the serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol concentrations were and the effect of bromocriptine treatment on spermatogenesis was examined. A total of 1234 patients were evaluated and 147 men had hyperprolactinemia. Of these, only 30 had PRL concentrations more than twice the upper limit of normal and most of them had a little excess over the upper limit. For 10 of these 30, serum hormone concentrations were measured and semen was analyzed before and after bromocriptine administration. No relationship between the PRL and other hormone concentrations was found. No changes were noted in the LH, FSH, testosterone, or estradiol concentrations, or in the sperm density and motility after treatment. The mean PRL decreased from 26.5 +/- 4.5 to 1.4 +/- 1.8 ng/mL. In infertile men who are mildly hyperprolactinemic, bromocriptine administration does not improve semen analysis, although it does normalize the PRL.

Prolonged nocturnal penile tumescence caused by epinastine.

Purpose: We report a case of prolonged nocturnal penile tumescence (NPT) caused by the antiallergic agent epinastine.