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Biomedical subjects

K Koyama

Publications and source records attributed to K Koyama.

At least 127 records · Page 7Linked to original sources
PubMed1999

Characterization of a surface membrane molecule expressed by natural killer cells in most inbred mouse strains: monoclonal antibody C9.1 identifies an allelic form of the 2B4 antigen.

A newly generated monoclonal antibody (mAb C9.1) described in this study identifies a surface membrane molecule that is involved in the lytic programme of activated natural killer (NK) cells. This conclusion is based on the facts that, first, this antigen was expressed on the vast majority of surface immunoglobulin (sIg)- CD3- CD4- CD8- spleen lymphocytes, albeit it was also present on minor subsets of sIg+ B (approximately 7%) and CD3+ T (approximately 2%) lymphocytes; second, that all splenic NK activity was contained within the C9.1+ cell population, and was almost totally abolished by treatment of spleen cells with mAb C9.1 and complement; third, that mAb C9.1 was capable of increasing interleukin-2-cultured and in vivo polyinosinic:polycytidylic acid-activated, NK cell-mediated, antibody-redirected lysis, but not freshly isolated NK cell-mediated killing. Furthermore, the strain distribution of the C9.1 antigen was shown to be antithetical to that of the 2B4 antigen already described as a molecule associated with major histocompatibility complex-unrestricted killing mediated by activated NK cells. The gene encoding C9.1 antigen was linked to the Akp1 isozyme locus on chromosome 1 close to the 2B4 gene. Although C9.1 and 2B4 were monomeric glycoproteins of 78 000 MW and 66 000 MW, respectively, removal of N-linked sugars from both antigens by endoglycosidase F yielded identical protein backbones of 38 000 MW. Thus, all of these results suggest that mAb C9.1 recognizes an allelic form of the 2B4 antigen. However, the detection of mAb C9.1-reactive antigen on a minor subset of B cells may suggest a possible reactivity of mAb C9. 1 with some product of other members of the 2B4 family genes.

Animals↗
PubMed1999

Correlation between the motility of frozen-thawed epididymal spermatozoa and the outcome of intracytoplasmic sperm injection.

The purpose of this study was to investigate if the outcome of ICSI was influenced by epididymal sperm motility in frozen-thawed specimens. A total of 18 ICSI treatment cycles using spermatozoa retrieved by microsurgical epididymal sperm aspiration (MESA) were analysed retrospectively. Cryopreservation of epididymal spermatozoa was performed when enough epididymal aspirates were collected. Sixty-nine out of 126 oocytes injected with spermatozoa retrieved by MESA were fertilized, giving a fertilization rate of 54.8%. Out of 18 embryo transfer cycles, 6 (33.3%) achieved pregnancies. Fresh epididymal spermatozoa were used in 5 cycles while frozen-thawed epididymal spermatozoa were used in 13 cycles for ICSI. The fertilization rates were 68.6% (35/51) in the former group and 45.3% (34/75) in the latter group, respectively. There was a significant difference between the two groups (p < 0.05). In ICSI treatments using fresh epididymal spermatozoa, the cells used for injection were all motile. However, motile epididymal spermatozoa could be used in only five ICSI treatment cycles after freeze-thawing. In 6 cycles, only immotile sperm were used for injection of frozen-thawed spermatozoa. The fertilization rate in each group was 68.4% (13/19) and 31.6% (12/38), respectively. There was a significant difference between these groups (p < 0.01). These results indicate that the outcome of ICSI was influenced by sperm motility in frozen-thawed epididymal specimens. When no sperm motility could be recovered after freeze-thawing even with chemical treatments, consideration should be given to retrieving fresh epididymal spermatozoa again to achieve a better fertilization rate in such patients.

Epididymis↗
PubMed1999

Novel experimental model using free radical-induced emesis for surveying anti-emetic compounds from natural sources.

A novel experimental model of free radical-induced emesis for screening anti-emetic compounds from natural sources was established. 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) dissolved in liposome induced emesis in young chickens, and the emesis was prevented by antioxidants including N-(2-mercaptopropionyl)-glycine (MPG), alpha-tocopherol, and L-ascorbic acid. Tropiseton, a serotonin receptor antagonist, also prevented emesis induced by AAPH. Known anti-emetic drugs and anti-emetic principles from natural sources also showed significant retching inhibition in the experiment using this system.

Amidines↗
PubMed1999

Prenatal sonographic diagnosis of a fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo.

Here we report the first case of prenatally diagnosed fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo. A 37 year old woman, having immunological infertility, was treated by in-vitro fertilization (IVF) and embryo transfer. Following unsuccessful IVF using fresh embryos, the patient conceived after transfer of cryopreserved-thawed embryos. The chromosomal analysis identified a normal karyotype at 16 weeks' gestation when amniocentesis was performed. The pregnancy course was uneventful until 28 weeks' gestation when polyhydramnios associated with fetal renal tumour was detected using ultrasonography. A male infant weighing 2564 g was born via Caesarean section at 34 weeks' gestation. A left nephrectomy was performed 5 days after delivery and the tumour was identified histologically as a mesoblastic nephroma. The postoperative course was uncomplicated to this point.

Adult↗
PubMed1999

Successful pregnancy in an infertile patient with conservatively treated endometrial adenocarcinoma after transfer of embryos obtained by intracytoplasmic sperm injection.

A rare case of successful pregnancy in a woman with early-stage endometrial adenocarcinoma conservatively treated is presented. The patient, having polycystic ovaries, was initially diagnosed with hyperplasia of the endometrium and treated with several cycles of ovulation induction following intrauterine insemination. Then dilatation and curettage were carried out when hysteroscopy was performed. The histology report identified a well-differentiated adenocarcinoma of the endometrium. After repeated endometrial curettage, in-vitro fertilization and embryo transfer were introduced for immediate treatment of the patient's infertility in order to avoid the risk of recurrence of neoplastic endometrial lesions by oestrogens. A single pregnancy was achieved after transfer of the embryos obtained after intracytoplasmic sperm injection. This was performed due to the poor semen characteristics (asthenozoospermia). The patient delivered a healthy normal male infant at term. A transvaginal ultrasound examination 2 months after delivery showed a smooth, linear endometrium. Moreover, the histology report after endometrial biopsy was free of any malignancies. The patient now desires another pregnancy. We conclude that conservative treatment of early-stage endometrial adenocarcinoma in young women wishing to preserve fertility should be considered in carefully selected cases. Assisted reproductive technologies may be helpful for immediate achievement of pregnancy in such patients.

Adenocarcinoma↗
PubMed1999

Cisplatin-5-fluorouracil therapy with remarkable effect and 5-year survival for paraaortic lymph node metastases of rectal carcinoma in females: a case report.

A 68-year-old woman was admitted because of a rectal carcinoma with huge paraaortic lymph node metastases. Low anterior resection with regional lymph node dissection was performed, leaving the paraaortic mass. After the operation, cisplatin-5-fluorouracil therapy was used as supplemental chemotherapy. The metastatic lymph nodes shrank remarkably in response to anticancer drugs. We evaluated the effect of chemotherapy as a partial response. The physical condition of the patient was well controlled for more than 4 years until she was admitted again because of cardiac failure accompanied by relapse of abdominal lymph node swelling. She died of cardiac failure 5 years and 3 days after the operation.

Adenocarcinoma↗
PubMed1999

A pilot study of CPT-11 and cisplatin for ovarian clear cell adenocarcinoma.

BACKGROUND: Ovarian clear cell adenocarcinoma is known to have poorer prognosis than ovarian serous cystadenocarcinoma. Cyclophosphamide plus cisplatin has been the standard therapy for ovarian cancer, but ovarian clear cell adenocarcinoma dose not respond to this therapy. The treatment for ovarian clear cell adenocarcinoma has not been established. We planned a pilot study of CPT-11 and cisplatin for the treatment of ovarian clear cell adenocarcinoma. METHODS: First, three patients were administered 70 mg/m2 of cisplatin intravenously on day 1 and 60 mg/m2 of CPT-11 intravenously on days 1, 8 and 15. Treatment was repeated every 4 weeks. Other patients were administered 75 mg/m2 of cisplatin intraperitoneally on day 1 and 60 mg/m2 of CPT-11 intravenously on days 1, 8 and 15. Treatment was repeated every 4 weeks. RESULTS: A total of 10 patients were entered in this study and a total of 43 courses were administered. 1 CR, 1 PR and 1 PD were observed in patients with measurable lesion. Grade 3 leukopenia was experienced in seven patients, grade 3 thrombocytopenia in two and grade 3 anemia in five. Grade 3 liver toxicity was observed in one patient and grade 3 diarrhea in one patient. No grade 4 toxicity was experienced. CONCLUSION: CPT-11 plus cisplatin is feasible and has efficacy for ovarian clear cell adenocarcinoma. This regimen should be explored in a phase II study.

Adenocarcinoma, Clear Cell↗
PubMed1999

CAG repeat length in the androgen receptor gene of infertile Japanese males with oligozoospermia.

We analysed the CAG repeat length in exon 1 of the androgen receptor gene in 59 idiopathic Japanese infertile males with oligozoospermia; 36 fertile males were also analysed as controls. The number of CAG repeats in infertile males ranged from 14 to 32 (mean 21.2+/-4.2), whereas the number of CAG repeats in fertile males ranged from 16 to 31 (mean 21.4+/-3.5). Among infertile males, six possessed a short form of 14 CAG repeats and three possessed 15 CAG repeats. On the other hand, fertile males did not possess the short form of 14 or 15 CAG repeats. The incidence of infertile males with 14 and 15 CAG repeats was significantly higher (P<0.05) than that of fertile males. Although the sample size is small, the results suggest that the reduction of CAG repeats in exon 1 of the androgen receptor is closely related to impaired spermatogenesis in infertile Japanese males.

Adult↗
PubMed1999

Expression of recombinant human zona pellucida protein 2 and its binding capacity to spermatozoa.

The human zona pellucida (ZP) is composed of three major glycoproteins: ZP1, ZP2, and ZP3. The aim of this study was to clarify the role of ZP2 by focusing on the polypeptide structure. We produced in Escherichia coli a recombinant human ZP2 protein (rec-hZP2) corresponding to amino acid sequence 1-206 of the mature protein. The final yield of rec-hZP2 protein was 80 microg/ml Luria Broth medium. After 2-h incubation of human spermatozoa with rec-hZP2 in vitro, an immunofluorescent study indicated that rec-hZP2 bound only to acrosome-reacted spermatozoa. The binding site migrated from the acrosome to the midpiece of the spermatozoa. Rabbit and mouse antisera produced against rec-hZP2 stained native human ZP in the immunofluorescent study, and significantly blocked human sperm binding and penetration into human ZP as compared to control values. The N-terminal polypeptide portion of human ZP2 was shown to contain a binding site for acrosome-reacted spermatozoa and to play an important role in secondary sperm binding and penetration into the ZP.

Acrosome↗
PubMed1999

Inhibitory effect of ND2001 on spontaneous multiple metastasis of NC 65 tumors derived from human renal cancer cells intradermally transplanted into nude mice.

The NC 65 tumor cell line derived from human renal cell carcinoma was selected from among nine human cell lines by determining the inhibition of invasion by ND2001 (sodium D-glucaro-delta-lactam) in vitro. The efficacy of this agent against these tumor cells was investigated in an experimental metastatic model of human tumors in vivo. Although ND2001 did not inhibit growth of NC 65 cells intradermally transplanted into male KSN mice (nu/nu), this agent inhibited multiple spontaneous metastasis.

Animals↗
PubMed1999

Frameshift mutation of the STK11 gene in a sporadic gastrointestinal cancer with microsatellite instability.

Germline mutations of the STK11 gene lead to emergence of hamartomas in the gastrointestinal tract of patients with Peutz-Jeghers syndrome, who bear an increased risk of malignancies of the gastrointestinal tract, genital tract, and other organs. We analyzed 80 sporadic colorectal cancers, six small-intestinal cancers, and 40 gastric cancers for somatic mutations of STK11 by SSCP methods. Among them only one colorectal cancer, which showed a phenotype of microsatellite instability, was found to possess a deleterious mutation in this gene, a frameshift involving deletion of one base at codons 279-281. This region of the gene contains a mononucleotide-repeat sequence, CCCCCC. The other allele of STK11 had been lost in this tumor. If the STK11 gene is one of the mutational targets of microsatellite instability, its inactivation may be associated with tumor development in a small proportion of colorectal cancers.

AMP-Activated Protein Kinase Kinases↗
PubMed1999

Analysis of APCL, a brain-specific adenomatous polyposis coli homologue, for mutations and expression in brain tumors.

We recently identified a novel homologue of the adenomatous polyposis coli (APC) tumor suppressor gene, APCL, whose abundant and specific expression in the central nervous system indicated an important role in neuronal proliferation and differentiation. To investigate possible involvement of APCL alterations in brain tumors, we first analyzed the expression of APCL mRNA in seven glioma tissues by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, and in nine glioma cell lines by northern blotting. APCL expression was reduced significantly in most of the glioma tissues and all nine cell lines in comparison with normal brain tissue. However, single-strand conformation polymorphism (SSCP) analysis and DNA sequencing of the entire coding region of APCL detected no mutations in any of the glioma cell lines, or in any of the 35 astrocytic gliomas and five medulloblastomas examined. Our results suggested that some epigenetic mechanism is responsible for the decrease in APCL expression in our panel of brain tumors.

Brain Neoplasms↗
PubMed1999

Induction of epithelial Na+ channel in rat ileum after proctocolectomy.

In patients with colectomy, epithelial transport function in the remnant small intestine can be regulated in response to the increased fecal electrolyte and fluid loss. Using a rat colectomy model, we investigated the Na+ and K+ transport mechanisms underlying the intestinal response. Proctocolectomy with ileoanal anastomosis was performed on rats. The small intestinal mucosa was mounted in Ussing chambers; then short-circuit currents and 22Na+ fluxes were measured. mRNA expression of the epithelial Na+ channel (ENaC) was determined by Northern blotting. Amiloride-sensitive, electrogenic Na+ absorption appeared in the ileum after proctocolectomy. This functional change was accompanied by the chronological induction of mRNAs for alpha-, beta-, and gamma-subunits of the ENaC in the ileum. Tetraethylammonium-sensitive short-circuit current was also activated. We conclude that electrogenic Na+ absorption and probably K+ secretion are induced in the ileum after proctocolectomy. This induction of electrogenic Na+ absorption is probably mediated by the increase in the mRNA levels for all three types of subunits of the ENaC and may contribute to the recovery from the increased fecal Na+ loss.

Aldosterone↗
PubMed1999

Effect of positive end-expiratory pressure on left and right ventricular diastolic filling assessed by transoesophageal Doppler echocardiography.

The effect of positive end-expiratory pressure (PEEP) on left and right ventricular diastolic filling dynamics was assessed by transmitral and transtricuspid flow patterns. Using transoesophageal Doppler echocardiography in fourteen ASA physical status 1 female patients, the following measurements were performed at baseline (0 cm H2O PEEP) and at 5, 10, 15, and 20 cm H2O PEEP: 1. peak velocity of early filling (peak E velocity), 2. peak velocity of atrial contraction (peak A velocity), 3. the ratio of the peak E to A velocity (peak E/A velocity ratio), 4. isovolumic relaxation time (IRT), 5. acceleration half-time (AHT), 6. deceleration half-time (DHT) of early filling, and 7. end-diastolic and end-systolic areas of both ventricles. Increasing PEEP progressively deceased peak E velocity of both ventricles. In contrast, peak A velocity did not change and the peak E/A velocity ratio decreased significantly with PEEP. IRT and AHTs remained unchanged, but DHTs of both ventricles increased following PEEP. End-diastolic and end-systolic areas of both ventricles decreased gradually and significantly with PEEP. It is concluded that PEEP was associated with decreased preload as well as reduced compliance of both ventricles, which was considered to contribute to the changes in diastolic ventricular filling.

Adult↗
PubMed1999

A toxicokinetic analysis in a patient with acute glufosinate poisoning.

Incidents of poisoning in humans caused by the ingestion of the glufosinate ammonium containing herbicides are gradually increasing in Japan. This poisoning is characterized by various neurological symptoms such as disturbances of consciousness, convulsions and apnea which appear after an asymptomatic interval of several hours. We studied the toxicokinetics of glufosinate in a patient with this poisoning successfully treated without extracorporeal hemopurification. A 65-year-old male ingested BASTA, which contains 20% w/v of glufosinate ammonium, about 300 ml, more than the estimated human toxic dose. Four and a half hours after ingestion, he showed speech ataxia and systemic tremor. He was prophylactically intubated before the occurrence of serious respiratory failure. After 5 days of artificial ventilation he was extubated and discharged without any sequelae. We studied the serial change of serum glufosinate concentration every 3-6 h and assessed the urinary excretion of glufosinate every 24 h. The absorbed amount of glufosinate was estimated from the cumulative excreted in urine. Toxicokinetic analysis was performed using the two-compartment model. The changes in serum glufosinate concentration exhibited T1/2alpha of 1.84 and T1/2beta of 9.59 h. The apparent distribution volume at beta-phase and the total body clearance were 1.44 l/kg and 86.6 ml/min, respectively. Renal clearance was estimated to be 77.9 ml/min. The indication for extracorporeal hemopurification for this poisoning has been discussed.

Aged↗
PubMed1999

A substitutional mutation in the DNA binding domain of the androgen receptor causes complete androgen insensitivity syndrome.

DNA analysis of the androgen receptor gene in a patient with complete androgen insensitivity syndrome identified a substitutional mutation (tyrosine converted to cysteine at position 571) in the DNA binding domain. In vitro transfection experiments with the patients' androgen receptor gene, indicated normal expression of the androgen receptor in transfected COS-7 cells compared to the wild type gene. There was also no evidence of impaired thermal stability of the 5 alpha-dihydrotestosterone-androgen receptor complex. However, the capacity of the androgen receptor to activate target gene transcription was found to be completely disrupted in a luciferase assay. These results confirmed that only one substitutional mutation in the DNA binding domain was related to the pathogenesis of the complete androgen insensitivity syndrome.

Adult↗