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Biomedical subjects

M Hazama

Publications and source records attributed to M Hazama.

At least 37 records · Page 2Linked to original sources

[Three cases of vas deferens calcification].

Three patients with calcification of the bilateral vas deferens, revealed by plain X-ray, pelvic computerized tomography and/or vesiculography, are reported. Although they came to our department because of acute left epididymitis, right ureteral calculus and right undescended testis respectively, these diseases were not the causative factors for the calcification. Since no other probable causes including tuberculosis and diabetes-mellitus were found, the cause of disease was unknown.

Adult↗

Intranasal immunization against herpes simplex virus infection by using a recombinant glycoprotein D fused with immunomodulating proteins, the B subunit of Escherichia coli heat-labile enterotoxin and interleukin-2.

To establish a novel strategy of mucosal immunization against herpes simplex virus type 1 (HSV-1) infection, we studied the immune responses elicited by intranasal immunization with several forms of a recombinant glycoprotein D (gD) of HSV-1. A truncated gD (t-gD) co-administered with heat-labile enterotoxin B subunit (LTB) from Escherichia coli induced both a mucosal immune response involving secretion of anti-gD IgA and serum IgG production. The levels of these responses are comparable to those in mice which have recovered from intranasal HSV-1 infections. The fusion protein (t-gD-LTB), consisting of t-gD and LTB, induced the responses more efficiently than did co-administration of t-gD and LTB, although GM1 ganglioside binding activity was significantly reduced in t-gD-LTB. We found that another fusion protein, consisting of t-gD and human interleukin-2 (t-gD-IL-2), also elicited antibody responses comparable to those induced by t-gD-LTB. Immunity acquired by intranasal immunization with t-gD-IL-2 protected mice from intraperitoneal HSV-1 infections, whereas t-gD-LTB or t-gD alone failed to provide protection against infection. Even in a mouse strain that responded highly to subcutaneously administered gD, intranasally administered t-gD did not elicit antibody responses. The lack of response to gD was clearly abrogated by co-administration with IL-2, and administration of t-gD-IL-2 induced an excellent level of antibody responses in this strain. These results suggest that the IL-2 fusion strategy yields a new type of mucosal immunization, the mechanism of which differs from that speculated for the mucosal adjuvant activity of LTB.

Administration, Intranasal↗

[Clinical long-term studies of the treatment of chronic complicated urinary tract infections. Utility and recurrence after 14-day treatment by cefditoren pivoxil].

In this study, cefditoren pivoxil (ME 1207, CDTR-PI), a new oral cephem antibiotic, was given to 72 patients with non-catheterized complicated urinary tract infections (UTI) to evaluate clinical efficacy and safety, and also to investigate the rate of recurrence after completion of treatment. Daily dose of CDTR-PI was 100 mg t.i.d., and CDTR-PI was administered for 14 days. According to the criteria proposed by the Japanese UTI Committee, clinical efficacy of CDTR-PI was evaluated at day 7 and day 14. The rate of recurrence was assessed by bacterial count in urine as the marker. The following results were obtained. 1. Overall clinical efficacy rates were 68.4% on day 7 and 81.6% on day 14. The efficacy rate at day 14 was higher than the rate at day 7. 2. Bacteriologically, eradication rates were 75.5% at day 7 and 79.6% at day 14. 3. As to side effects, abdominal discomfort was observed in 1 case and its incidence was 1.6%. Incidence of abnormalities of laboratory findings was 10.4%, and these abnormalities were slight and transient. 4. Thirty-one patients were assessable to the recurrence of infections, 60% of them were judged as "cured" at 1-2 weeks and 3-7 weeks after completion of treatment. In this study, "relapsed", reappearance of causative organisms, was observed much more frequently than "reinfection". These results suggest that sufficient clinical efficacy and safety of CDTR-PI in non-catheterized complicated UTI were effected by 14 days treatment.

Administration, Oral↗

[A case of genital tuberculosis occurring in the tunica albuginea and the tunica vaginalis].

We report a case of genital tuberculosis occurring in the tunica albuginea and the tunica vaginalis. A 29-year-old man came to our department with the complaint of a nodule in the right scrotum. The physical and radiological examinations revealed no signs of pulmonary or urogenital tuberculosis. The urine and the semen were clear and negative in culture of acid fast bacteria, but the tuberculin reaction was moderately positive. Surgical exploration revealed a white yellowish soybean sized nodule in the surface of the tunica albuginea of the right testicle apart from the epididymidis, and we therefore enucleated it. No abnormalities were found in other parts of the tunica vaginalis, epididymidis or the funiculus. Histopathological examination demonstrated typical tuberculomas in the tunica albuginea and the tunica vaginalis, but the seminiferous tubules were almost intact. We diagnosed this case as tuberculosis arising in the tunica albuginea and the tunica vaginalis and started antituberculosis therapy.

Adult↗

[Two cases of renal cell carcinoma accompanied with ossification].

We report two cases of renal cell carcinoma accompanied with ossification. Case 1: A 40-year-old male visited a physician with the complaint of epigastric pain. Examination of the stomach revealed compression of the greater curvature. Abdominal radiography and CT scan revealed a left renal mass with calcification, which was a hypovascular tumor on angiography. A transperitoneal left nephrectomy was performed. The resected kidney was 700g in weight and the tumor, which was 12 x 10 x 10 cm in size and located in the upper pole of the kidney, was enveloped with a hard capsule and was extensively necrotized. Histopathological diagnosis was renal cell carcinoma (papillary type, mixed subtype). Case 2: A 69-year-old female was occasionally pointed out to have a left renal mass in ultrasonic examination. It was accompanied with calcification in CT scan and a hypervascular tumor in angiography. A transperitoneal left nephrectomy was performed. The resected kidney was 320 g in weight and the tumor located in the lower pole of the kidney, was 6 x 6 x 6 cm in size and necrotized. Histopathological diagnosis was renal cell carcinoma (alveolar type, clear cell subtype). Microscopically in both cases, ossified tissue existed among the fibrous tissue in the necrotized lesion of the tumor, but not near the cancer cells and, it was accompanied by calcification. During the ossification process, the connective tissue proliferates after the necrosis of the tumor, and metaplasia occurred from its juvenile plastic cells to osteoblastic cells.

Adult↗

A novel strategy for converting recombinant viral protein into high immunogenic antigen.

Interleukin 2 (IL-2) is a lymphokine promoting immune response and therefore has been investigated as an immunological adjuvant. In order to enhance the immunogenicity of recombinant viral protein, herpes simplex virus type 1 (HSV-1) glycoprotein D (gD), we genetically created a fusion protein consisting of gD and human IL-2. The fusion protein, without any other adjuvants, induced high antibody responses and cell-mediated immunity to HSV-1 in mice. Mice immunized with the fusion protein were protected against HSV-1 infection. The results indicate that IL-2-fusing can provide a means for converting a weak immunogenic protein into a high immunogenic antigen, and the strategy would be widely applicable to the other antigens for pathogens.

Adjuvants, Immunologic↗

[A study on the treatment duration of an antibacterial agent in complicated urinary tract infections. Utility and recurrence after 14-day treatment by fleroxacin].

In this study, fleroxacin (FLRX), a new quinolone derivative, was orally given at 300 mg once daily for 14 days to 102 patients with non-catheterized complicated urinary tract infections in order to determine the optimal treatment duration. We investigated its efficacy at day 5-7 and day 14, according to the criteria proposed by the Japanese UTI Committee, and also to the recurrence rate after the withdrawal. The results were as follows: 1. Overall clinical efficacy rates were 86% at day 5-7 and 84% at day 14. Both incidence of bacterial replacement in bacteriuria and normalization in pyuria were increased at day 14 as compared with those at day 5-7. 2. Bacteriological eradication rates were 91% at day 5-7 and 89% at day 14. 3. Clinical efficacy rates from physicians' evaluation were 86% at day 5-7 and 88% at day 14. 4. Incidence of side effects was 9.1%, and most of the cases were gastrointestinal symptoms which appeared within 4 days. Slight and transitory changes in laboratory findings were noted in 2.3% of evaluable cases. 5. With the occurrence of pyuria and bacteriuria as markers, the "no recurrence" rates were 63% at 1 week, 54% at 2 weeks, 61% at 3 weeks, 81% at 4-6 weeks after the withdrawal, and the "recurrence" rates were 4%, 4%, 6% and 5%, respectively. Remaining cases were judged as "reserved assessment". Generally, aggravation of bacteriuria was found but the aggravation of pyuria was observed in only few cases. 6. According to breakdown of cases with bacteriuria only, cure rate was 67% and recurrence rate was 33%. Re-infections were observed much more frequently than relapse based on the identification of infecting organisms. These results suggest that sufficient bacteriological eradication and clinical efficacy could be obtained by 14-day treatment of FLRX in non-catheterized complicated urinary tract infections. The efficacy of the treatment became evident around day 7. In approximately 30% of the cases in which eradication of the initial causative organisms was observed at day 14 reappearance of bacteriuria (greater than or equal to 10(3) CFU/ml) occurred after withdrawal of the antibiotic, but cases with pyuria were few, and the incidence of true recurrence was generally low. Onset of side effect after 5-day was not seen, hence FLRX seemed to be a safe agent.

Administration, Oral↗

[Clinical experience with three cases of haemorrhagic tendency--bladder carcinoma with hemophilia A, a bladder carcinoma with von Willebrand disease and a benign prostatic hypertrophy with idiopathic thrombocytopenic purpura (ITP)].

Recent understanding of the pathogenicity of haemorrhagic tendency as well as advance of management of patients with this disease makes its surgical treatment possible. Since 1979 we have experienced three male patients with haemorrhagic tendency. The first case was a bladder carcinoma with hemophilia A. He had been given 2500 unit of Conco-eight (coagulation factor VIII) before transurethral resection of bladder tumor (TUR-Bt) and was given 1000 unit of Conco-eight every eight to twelve hours for seven days postoperatively. The second case was a bladder carcinoma with von Willebrand disease. This case was also pretreated by Conco-eight before operation and we had difficulty in controlling his coagulopathy for one month postoperatively. The third case was a benign prostatic hypertrophy with idiopathic thrombocytopenic purpura (ITP). He had been given a huge dose of gamma globulin for six days before operation and on the operation day his platelet count was normalized. Since his prostate was estimated to weight over 70 g, suprapubic prostatectomy was selected. All these three cases were operated uneventfully. From this experience we believe that with proper preoperative and postoperative management, patients with haemorrhagic tendency can be operated safely.

Adult↗

Immunogenicity of a new type of yeast-derived hepatitis B vaccine consisting of M (pre-S2 + S) protein particles.

Genetically modified M (pre-S2+S; P31) protein (M-P31c) particles were formulated into a vaccine (TGP-943) through adsorption on to an alum adjuvant. The immunogenicity of this vaccine was investigated using guinea-pigs and various kinds of mice. In terms of anti-HBs(S) response, TGP-943 was found to be as immunogenic as the control plasma-derived vaccine (PDV) and yeast-derived S vaccine (YDSV) in Balb/c mice. TGP-943 induced anti-S antibodies even in S low-responder mice. In addition to the anti-S antibodies, TGP-943 was shown to elicit anti-pre-S2 antibodies dose-dependently, and the anti-pre-S2 antibodies were maintained at a high level after immunization with a high dose of TGP-943. The antibody response to pre-S2 had a tendency to appear earlier than that to S. M-P31c particles induced in vitro proliferation of TGP-943-primed lymph node cells, indicating that TGP-943 is more immunogenic than conventional vaccines in terms of T-cell levels. These results suggest that TGP-943 would be a promising candidate for a third generation hepatitis B vaccine.

Animals↗

Nucleotide sequence analysis of cDNA encoding the coat protein of cucumber mosaic virus: genome organization and molecular features of the protein.

The cDNA sequence coding for the coat protein of cucumber mosaic virus (Japanese Y strain) was cloned, and its nucleotide sequence was determined. The sequence contains an open reading frame that encodes the coat protein composed of 218 amino acids. The nucleotide and deduced amino acid sequences of the coat protein of this strain were compared with those of the Q strain; the homologies of the sequences were 78% and 81%, respectively. Further study of the sequences gave an insight into the genome organization and the molecular features of the coat protein. The coding region can be divided into three characteristic regions. The N-terminal region has conserved features in the positively charged structure, the hydropathy pattern and the predicted secondary structure, although the amino acid sequence is varied mainly due to frameshift mutations. It is noteworthy that the positions of arginine residues in this region are highly conserved. Both the nucleotide and amino acid sequences of the central region are well conserved. The amino acid sequence of the C-terminal region is not conserved, because of frameshift mutations, however, the total number of amino acids is conserved. The nucleotide sequence of the 3'-noncoding region is divergent, but it could form a tRNA-like structure similar to those reported for other viruses. Detailed investigation suggests that the Y and Q strains are evolutionarily distant.

Amino Acid Sequence↗

[A case of a complete paraplegic fathering a girl following artificial insemination after an intrathecal neostigmine injection].

A case of a 32-year-old paraplegic male who fathered a girl following artificial insemination after an intrathecal neostigmine injection is described. The patient became a complete paraplegic after injury to the spinal cord caused by a traffic accident in 1971, resulting in ejaculatory disturbance. In June, 1984 the first intrathecal neostigmine injection was tried and 2.7 ml of semen was collected and offered to artificial insemination. However, the first to ninth attempt did not result in fertilization. The tenth attempt was made in March 7, 1986, and 3 ml of semen presenting 240 X 10(6) spermatozoa per ml with 5% of motile sperms was collected. This resulted in pregnancy, and the patient's wife delivered a healthy girl weighing 2552 g by cesarean section on November 19, 1986. This is the fourth case of a paraplegic who fathered a child following artificial insemination after an intrathecal neostigmine injection in the Japanese literature.

Adult↗

[Male infertility with chromosomal abnormalities. III. 46, XYq-].

A deletion of the long arm of the Y chromosome (46,XYq-) was found in two cases with normal male habitus but with azoospermia. The first case was of a 28-year-old married man, an office worker, complaining of infertility. His height was 153 cm, weight 57 kg and distance of extended hand 152 cm. Both testes were 13 ml in size. The second case was a 32-year-old married man, a fireman, complaining of infertility. His height was 160 cm, weight 64 kg and distance of extended hand 161 cm. Both testes were 10 ml in size. In each case, the external genitalia showed a normal male type, but azoospermia was identified in semen analysis. The testicular biopsy specimens revealed spermatogenic arrest with thickening of basement membrane. Chromosomal analysis showed 46,XYq- karyotype. Basal serum levels of luteinizing hormone and follicle-stimulating hormone were slightly elevated and the serum testosterone level was within normal limits. Eight cases of 46,XYq- karyotype in the Japanese literature including our cases were reviewed.

Adult↗

[Problems in evaluating male fertility: valuable factors in evaluating male fertility and normal values of seminal parameters].

To determine the valuable factor for evaluating male fertility, a comparative study was done as to various seminal parameters between fertile and infertile groups. The fertile group consists of 57 proven fertile males and the infertile group consists of randomly chosen 67 infertile patients. Seminal parameters assessed were sperm concentration, motility, mean velocity, total sperm output, total motile sperm output, sperm morphology, acrosin activity and sperm penetration rate on zona-free hamster egg penetration assay (SPA). The infertile group was significantly different from the fertile group in every parameter except acrosin activity. However, the range of each parameter in the two groups overlapped each other. The diagnostic rate of each parameter, which is the percentage of an infertile male correctly diagnosed as infertile, was calculated by using 95% specificity threshold value of fertile males. The 95% specificity threshold values of sperm concentration, motility and % normal shaped sperm were 24.9 x 10(6)/ml, 34.9% and 55%, respectively, and they could be acceptable for the normal limit of seminal parameters. The diagnostic rate was highest in penetration rate (72.4%). In other words, penetration rate is the most valuable factor in various parameters for making a distinction between fertile and infertile males. Sperm motility and mean velocity showed the next highest diagnostic rate. On the other hand, sperm concentration showed a poor diagnostic rate (36.8%). In addition, there was no significant correlation between penetration rate and any other seminal parameters. These results suggest that the SPA will be an essential test for evaluating male fertility and penetration rate may be a marker of male fertility in the treatment of male infertility.

Adult↗

Epidermal growth factor in human seminal plasma.

In the present study, we have partially purified a characterized epidermal growth factor (EGF)-like substance(s) from human seminal plasma, and determined the concentrations of immunoreactive (IR)-hEGF in seminal plasma from normal and infertile males. Competitive binding curves of seminal plasma extracts were parallel to those of standard hEGF in both radioimmunoassay and receptor assay. Seminal IR-hEGF was similar to standard hEGF by gel exclusion chromatography, isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The concentrations of IR-hEGF in normal seminal plasma (48 +/- 9 ng/ml) did not differ from those of infertile males (41 +/- 3 ng/ml); the concentrations of seminal plasma IR-hEGF did not correlate with density, motility or morphology of sperm. These data clearly demonstrate the presence of hEGF in human seminal plasma indistinguishable from hEGF of urinary origin, and suggest that it may not play an important role in the sperm function. The tissue(s) of its origin and its physiological function in the male reproductive organs remain undetermined.

Adult↗

[Male infertility with chromosomal abnormalities. II. XX-male syndrome].

We report two cases of the XX-male syndrome, and review the literature. The first case was a 31-year-old married man, a welder, complaining of infertility. His height was 158 cm, weight 82 kg and distance of extended hand 155 cm. The external genitalia showed a normal male type, but bilateral small testes and gynecomastia were noticed. The second case was a 32-year-old married man, a shopkeeper, complaining of infertility. His height was 165 cm, weight 60 kg and distance of extended hand 167 cm. No gynecomastia was noted. The external genitalia showed a normal male type, but bilateral small testes were noticed. In each case, azoospermia was identified in semen analysis. Urethrography revealed the prostatic utricle in the second case. The testicular biopsy specimens revealed hyalinization of seminiferous tubules and proliferation of Leydig cells. X chromatin was positive in buccal smears, and Y chromatin negative in cultured lymphocytes. Chromosomal analysis showed 46, XX karyotype in the first case and 46, XXp+ in the second case. H-Y antigen was positive in each case. Basal serum levels of LH and FSH were moderately elevated and the serum testosterone level was low. Serum levels of PRL, TSH, estradiol, GH, T3 and T4 were normal. An impaired response by testicular Leydig cells to hCG was observed. The LH and FSH responses to LH-RH were almost normal. Clomiphene citrate administration resulted in a decrease in the serum testosterone and gonadotropins levels. These results indicate hypergonadotropic hypogonadism secondary to testicular failure in both XX-males. Twenty-six cases of the XX-male syndrome have been cited in the Japanese literature. The clinical features and etiology of this syndrome are discussed.

Adult↗