Biomedical subjects

A Yajima

Publications and source records attributed to A Yajima.

At least 37 records · Page 2Linked to original sources

PubMed2000

Enzymatic properties of dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis and its participation in virulence.

Porphyromonas gingivalis is a major pathogen associated with adult periodontitis. We cloned and sequenced the gene (dpp) coding for dipeptidyl aminopeptidase IV (DPPIV) from P. gingivalis W83, based on the amino acid sequences of peptide fragments derived from purified DPPIV. An Escherichia coli strain overproducing P. gingivalis DPPIV was constructed. The enzymatic properties of recombinant DPPIV purified from the overproducer were similar to those of DPPIV isolated from P. gingivalis. The three amino acid residues Ser, Asp, and His, which are thought to form a catalytic triad in the C-terminal catalytic domain of eukaryotic DPPIV, are conserved in P. gingivalis DPPIV. When each of the corresponding residues of the enzyme was substituted with Ala by site-directed mutagenesis, DPPIV activity significantly decreased, suggesting that these three residues of P. gingivalis DPPIV are involved in the catalytic reaction. DPPIV-deficient mutants of P. gingivalis were constructed and subjected to animal experiments. Mice injected with the wild-type strain developed abscesses to a greater extent and died more frequently than those challenged with mutant strains. Mice injected with the mutants exhibited faster recovery from the infection, as assessed by weight gain and the rate of lesion healing. This decreased virulence of mutants compared with the parent strain suggests that DPPIV is a potential virulence factor of P. gingivalis and may play important roles in the pathogenesis of adult periodontitis induced by the organism.

Amino Acid Sequence↗

PubMed2000

Association of intrauterine growth retardation with monosomy of the terminal segment of the short arm of the X chromosome in patients with Turner's syndrome.

Short stature, which may be a result of intrauterine growth retardation (IUGR), is a characteristic of Turner's syndrome. However, the loci responsible for IUGR have not been well studied. We reviewed the birth records of 74 patients with Turner's syndrome: 20 with pure X monosomy, 44 with X-mosaicisms, and 10 with X-structural abnormalities. The overall incidence of IUGR was 39.2% (29 of 74 patients). The SHOX gene is encoded in a terminal segment of the short arm of the X chromosome. In 39 patients where two copies of the SHOX gene were absent, the incidence of IUGR was 46.2% (18 of 39 patients). In 14 patients with two copies of the SHOX gene, the incidence of IUGR was significantly lower at 7.1% (1 of 14 patients). Our results suggest that SHOX influences in utero growth in Turner's syndrome.

Comorbidity↗

PubMed2000

Conization by harmonic scalpel for cervical intraepithelial neoplasia: a clinicopathological study.

The Harmonic Scalpel((R)) (HS) is a new surgical tool that cuts and coagulates by converting electrical energy into ultrasonic mechanical vibrations. The purpose of our study was to compare HS conization and the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) with respect to both clinical and pathological features. Fifty-one consecutive women conservatively treated (29 with LEEP and 22 with HS conization) for CIN III were retrospectively reviewed. The background of the patients was similar. Operative time, intra- and postoperative blood loss were not significantly different. With HS conization all specimens were removed in one piece, but with LEEP the median number of specimens obtained per patient was 3.3 (p<0.0001) with a maximum of 5. The depth of thermal artifacts at the endocervical margin was significantly less with HS conization (0.20 mm) than with LEEP (0.30 mm; p = 0.0006). This new method produced an ideal-shaped specimen without increasing complications and thermal artifacts compared with LEEP.

Adult↗

PubMed2000

Phase II study of irinotecan and cisplatin as first-line chemotherapy in advanced or recurrent cervical cancer.

Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m(2)) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m(2) i.v.) on day 1 over 90 min. The patients' median age was 57 years (range 35-75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41-74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16-62 days). The median survival was 27. 7+ months (range, 6.4-52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.

Adult↗

PubMed2000

A questionnaire survey on current surgical procedures for endometrial cancer in Japan.

The current standards for surgical procedures and lymph node dissection of endometrial cancer in Japan were investigated using a questionnaire survey. The estimated clinical stages used in the questionnaire were predicted from preoperative diagnostic imaging, histopathology of endometrial biopsies and intraoperative findings using a new classification, Federation Internationale de Gynecologie et d'Obstetrique (FIGO) in 1988. Questionnaires were mailed to 235 institutions, and 212 institutions (90.2%) responded. As a standard surgery for endometrial cancer, institutions performed simple total hysterectomy or semiradical hysterectomy and bilateral adnexectomy, which accounted for 86% of all respondents. For stage I carcinoma, simple (44%) or semi-radical (47%) hysterectomy was carried out in 91% of institutions, while radical hysterectomy was selected in 84% of institutions when stage II carcinoma was diagnosed clinically. The consensus of this survey was that dissection of both the para-aortic and pelvic lymph nodes can be omitted in G1 cases showing lesions confined to the endometrium, and that pelvic lymph nodes should be dissected, but para-aortic lymph node dissection could be omitted in G1 or G2 cases demonstrating myometrial invasion of 1/2 or less. Moreover, findings from this survey suggest that biopsy or dissection of the para-aortic lymph nodes was required in G3 cases, or in those patients diagnosed with myometrial invasion more than 1/2.

Endometrial Neoplasms↗

PubMed2000

Telomerase activity in normal ovaries and premature ovarian failure.

The average age for the onset of menopause in humans is about 51 years. On the other hand, premature ovarian failure (POF) is generally defined as the onset of menopause before the age of 40 years. Telomeres have been extensively examined as a mitotic clock. Telomeric DNA is elongated by telomerase. We analyzed the telomerase activity of 20 patients with normal ovaries and 5 patients with POF. Telomerase activity was present in the normal ovaries, however it decreased with age. Eight normal ovaries under 38 years of age showed significantly higher telomerase activity among the women with a regular menstrual cycle. Two POF patients showed high telomerase activity and 3 showed low telomerase activity. Our findings indicate that telomerase is present in the normal human ovary and that telomerase activity decreases with age. Patients with follicle dysfunction showed high telomerase activity and those with follicle depletion showed very low telomerase activity. Based on these results, we speculated that the decline of telomerase activity in the ovary is related to primordial follicle depletion with age and telomerase activity can be used as a marker of the ovarian functional age.

Adult↗

PubMed2000

Compound heterozygous mutations (PHE53/54DEL and HIS373LEU) of the P450c17 gene result in a 17alpha-hydroxylase/17,20-lyase deficient male pseudohermaphrodite with unambiguous external genitalia.

The autosomal recessive disease 17alpha-hydroxylase/17,20-lyase deficiency is characterized by mutation of the P450c17 enzyme, which catalyzes 17alpha-hydroxylation and 17,20-lysis in the steroidogenic pathways. Although 17 mutations of this enzyme have been reported, only a few of them resulted in a completely unambiguous phenotype of female external genitalia in 46, XY individuals. We report here a Japanese patient with a 46,XY karyotype, who showed such a unambiguous female external genitalia. Nucleotide sequencing of the P450c17 gene revealed the patient to be a compound heterozygote carrying two different mutations (PHE53/54DEL in exon 1 and HIS373LEU in exon 6). As these mutations have been previously detected in unrelated Japanese patients, it is confirmed that these mutations accumulate regionally. Since these mutations could be screened by a multiple genotyping method, the method is applicable when 17alpha-hydroxylase/17, 20-lyase deficiency is suspected in Japanese patients.

Adrenal Hyperplasia, Congenital↗

PubMed2000

Serum soluble fas level as a prognostic factor in patients with gynecological malignancies.

The Fas-Fas ligand system is important in apoptosis mediated by CTLs and natural killer cells. The suppression of apoptosis contributes to carcinogenesis, as well as to a resistance to chemotherapy and radiotherapy. Circulating soluble Fas (sFas), which is generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We investigated sFas levels in 64 patients with gynecological malignancies (28 cervical carcinomas, 18 endometrial carcinomas, and 18 ovarian carcinomas) and in 24 healthy female donors by using a Fas-specific ELISA. In each carcinoma group, serum sFas demonstrated a statistically significant elevation relative to levels in normal controls (P < 0.0001). Levels of serum sFas in patients with advanced cancer (FIGO stages III and IV) significantly exceeded those in patients with localized cancer (FIGO stages I and II) or those in normal control subjects (P < 0.0001). We divided the patients into two groups based on the level of serum sFas and examined the relationship between serum sFas levels and survival. No deaths occurred in the groups with cervical and endometrial cancer with a serum sFas level < 1.5 ng/ml. Survival rates in groups with cervical carcinoma, endometrial carcinoma, and ovarian carcinoma with a serum sFas level < 1.5 ng/ml exceeded those in groups with sFas levels of 21.5 ng/ml (P < 0.001, P = 0.128, and P = 0.012, respectively). Proportional hazard models demonstrated that serum sFas level was a statistically significant factor (P = 0.0196) for survival, as well as histological grade (P = 0.0168) in ovarian carcinoma.

Adult↗

PubMed1999

Complete androgen insensitivity in a 47,XXY patient with uniparental disomy for the X chromosome.

We describe a unique patient with complete androgen insensitivity syndrome and a 47,XXY karyotype. Androgen receptor assay using cultured pubic skin fibroblasts showed no androgen-binding capacity. Sequence analysis of the androgen receptor gene demonstrated two nonsense mutations, one in exon D and one in exon E. Microsatellite marker analysis showed that the patient is homozygous for all five Xq loci examined. The results suggest that the long-arms of the two X chromosomes are identical, i.e., uniparental isodisomy at least for Xq, and carry the same mutations in the androgen receptor gene. This explains how complete androgen insensitivity syndrome occurred in this 47,XXY individual.

Adult↗

PubMed1999

Superoxide dismutase in normal cycling human ovaries: immunohistochemical localization and characterization.

OBJECTIVE: To investigate the expression of manganese (Mn) and copper-zinc (Cu,Zn) superoxide dismutase (SOD) in normal cycling human ovaries throughout the menstrual cycle. DESIGN: Descriptive, controlled study. SETTING: Tohoku University School of Medicine. PATIENT(S): Twenty-four normal cycling human ovaries were obtained from patients who underwent oophorectomy and hysterectomy for squamous cell carcinoma of the uterine cervix. INTERVENTION(S): Immunohistochemistry for Mn-SOD and Cu,Zn-SOD. MAIN OUTCOME MEASURE(S): Immunostaining. RESULT(S): In the follicular stage, Mn-SOD immunoreactivity was detected in granulosa and theca interna cells of steroid-producing follicles, that is, preantral, nondominant, dominant, and atretic follicles, whereas Cu,Zn-SOD was detected in theca interna cells of these follicles and in granulosa cells of dominant follicles. In the luteal stage, immunoreactivity for Mn-SOD and Cu,Zn-SOD was observed in both luteinized granulosa and theca cells of the functioning corpus luteum. In the early degenerating corpus luteum, both Mn-SOD and Cu,Zn-SOD were positive in steroid-producing luteinized theca cells. Mn-SOD immunoreactivity was also detected in nonsteroid-producing luteinized granulosa cells and macrophages. CONCLUSION(S): Our results suggest that the expression of Mn-SOD and Cu,Zn-SOD closely correlates with steroidogenesis in the human ovary. In addition, Mn-SOD may play an important role in the process of luteal regression.

Adult↗

PubMed1999

Serologic study of human parvovirus B19 infection in pregnancy in Japan.

OBJECTIVES: To clarify the relationship between hydrops fetalis and parvovirus outbreaks in the community, seroprevalence of B19 antibody among women of childbearing age, and adverse effects of intrauterine B19 infection. METHODS: Sera were collected from 168 cases of hydrops fetalis which were diagnosed between 1987 and 1997 in Miyagi prefecture, Japan, from 232 healthy pregnant women in 1987 and 277 healthy pregnant women in 1997 in Miyagi, and from 48 women infected with B19 during pregnancy. The sera were examined for B19 IgG and IgM antibodies by enzyme-linked immunosorbent assay and for B19 DNA by polymerase chain reaction. The number of cases of erythema infectiosum in Miyagi had been monitored each month. RESULTS: Thirteen of the 168 cases of hydrops fetalis were found to be caused by intrauterine B19 infection and 12 of the 13 cases clustered in two periods of outbreaks of erythema infectiosum in the community. The positive rates of B19 IgG antibody between 1987 and 1997 were significantly different: 33% in 1987 and 46% in 1997. Nine of the 48 women infected during pregnancy showed adverse effects of the fetus: eight hydrops fetalis and one early abortion with positive B19 DNA. The fetal death rate (>12 weeks of gestation) among them was 15% (7/48), far higher than the calculated 1% among the general population. The nine mothers with adverse fetal outcomes had contact with the infectious source at the 16 weeks of gestation or earlier. CONCLUSIONS: These data clearly showed a relationship between hydrops fetalis and parvovirus outbreaks in the community, and it may be important to follow the seroprevalence for an extrapolated period time to predict occurrence of hydrops fetalis caused by B19. Also the data indicated that the gestational week infection occurred is the most important determinant of an adverse effect to the fetus as described previously.

Adolescent↗

PubMed1999

Parvovirus B19 infection induces apoptosis of erythroid cells in vitro and in vivo.

OBJECTIVE: intrauterine parvovirus B19 infection is related to non-immune hydrops fetalis, the pathogenesis of which is based on the strict tropism of B19 for erythroid precursor cells and the massive destruction of the infected erythroid cells, although the mechanism of beta19-induced cytotoxicity has not been studied in detail. The purpose of this study is to provide empirical evidence that beta19 induces apoptosis of erythroid cells both in vitro and ill vivo. METHODS: we analysed culture cells infected in vitro by B19 and tissues of nine cases of hydrops fetalis caused by B19 intrauterine infection by histological and biological methods. RESULTS: cells infected iil vitro by B19 showed nuclear changes characteristic of apoptosis by light microscopic examination and DNA extracted from the infected cells was fragmented. Electron microscopic examination showed the nuclei of infected cells contained crescent-shaped clumps of heterochromatin with increased density and double staining with anti-B1 9 antibody and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) confirmed apoptosis of individual cells. Tissues of cases of hydrops fetalis caused by B19 contained erythroid cells with nuclear inclusions and characteristic nuclear changes of apoptosis by light microscopy. The double-staining confirmed apoptosis of erythroid cells in the tissues. Immunohistochemical analysis with antibodies against cellular factors involved in apoptosis showed that caspase3, p53 and p21 were positive in infected cells.

Apoptosis↗

PubMed1999

SRY mutation and tumor formation on the gonads of XP pure gonadal dysgenesis patients.

We report three patients with XY pure gonadal dysgenesis. Two of these patients developed gonadoblastoma and associated dysgerminoma. Molecular analyses were undertaken to investigate the relationship between the formation of these tumors and Y chromosome aberrations. Deletion analyses were performed by polymerase chain reaction (PCR) amplification of Y chromosome-specific DNA sequences (PABY, SRY, DYS250, DYS254, and DYZ1). A cryptic deletion of the short arm of the Y chromosome that included the PABY, SRY, DYS250, and DYS254 loci was observed in one of the patients (22-years-old) with an associated tumor. In the other two patients who did not demonstrate such a deletion, the sequence of the SRY open reading frame was determined by the dideoxynucleotide method. Two nucleotide substitutions followed by a seven nucleotide deletion were observed in the 3' end of HMG (high mobility group)-box in the other patient (15-years-old) with an associated tumor. The patient (22-years-old) without an associated tumor did not have the cryptic deletion or mutation of SRY. A Y chromosome specific sequence (DYZ1) was demonstrated by PCR amplification of microdissected tumor tissues from these two patients. These results suggest that SRY may play a role in the formation of gonadal tumors, especially dysgerminoma.

Adolescent↗

PubMed1999

Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan.

Various risk factors were investigated in 167 cervical intra-epithelial neoplasia (CIN) case and control pairs in Japan. CIN cases showed evidence of nine known risk factors including smoking and sexual behaviour. However, after adjustment for papillomavirus infection, the highest determinant, the only remaining risk factors were: being married, early age at first pregnancy and multiparity.

Adult↗

PubMed1999

Serum carotenoids and vitamins and risk of cervical dysplasia from a case-control study in Japan.

The relationships between risk of cervical dysplasia and dietary and serum carotenoids and vitamins were investigated in a case-control study. Cases were 156 women who attended Papanicolaou test screening in nine institutes affiliated with Japan Study Group of Human Papillomavirus (HPV) and Cervical Cancer and had cervical dysplasia newly histologically confirmed. Age-matched controls were selected from women with normal cervical cytology attending the same clinic. Blood sample and cervical exfoliated cells were obtained for measuring serum retinol, alpha-carotene, beta-carotene, zeaxanthin/lutein, cryptoxanthin, lycopene and alpha-tocopherol and for HPV detection. Higher serum level of alpha-carotene was significantly associated with decreased risk of cervical dysplasia after controlling for HPV infection and smoking status (odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.04-0.62 for the highest as compared with the lowest tertile). Decreased risk for the highest tertile of serum lycopene (OR = 0.28) was marginally significant. Decreased risks observed for the highest tertiles of beta-carotene (OR = 0.65) and zeaxanthin/lutein (OR = 0.53), were not statistically significant.

Carotenoids↗

PubMed1999

Oestrogen receptor alpha and beta mRNA expression in human endometrium throughout the menstrual cycle.

We examined the localization of oestrogen receptor (ER) beta mRNA in the human endometrium throughout the menstrual cycle using non-radioactive in-situ hybridization with Brigati-tailed oligonucleotides. The findings were compared with those of ERalpha in order to examine the possible biological significance of ERbeta in the human endometrium. Both ERalpha and ERbeta mRNA expression were detected in all major human uterine cell types, including glandular epithelial cells, stromal cells and smooth muscle cells of the uterine wall, at every menstrual cycle stage. However, ERalpha mRNA expression was more prominent than that of ERbeta in all cell types throughout the menstrual cycle. In proliferative phase endometrium, ERalpha mRNA was expressed in both glandular epithelial and stromal cells, while ERbeta mRNA was expressed predominantly in glandular epithelial cells. Although the same pattern was observed in the secretory phase, both the ERalpha and ERbeta mRNA expression was relatively weaker. These results suggest that oestrogenic effects occur predominantly through ERalpha, but that ERbeta may also play a role in the modulation of oestrogenic action, especially on glandular epithelial cells in the human endometrium throughout the menstrual cycle.

Endometrium↗

PubMed1999

Phase II clinical study on the effects of recombinant human interleukin-3 on thrombocytopenia after chemotherapy for advanced ovarian cancer. SDZ ILE 964 [IL-3] Study Group.

The efficacy, safety, and optimum clinical dose of recombinant human interleukin-3 (rhIL-3) was examined in ovarian cancer patients with thrombocytopenia after cancer chemotherapy. In cases with a platelet count < 75,000/mm3 during the control observation period, rhIL-3 was administered subcutaneously at a dose of 5 or 10 micrograms/kg, once a day for 10 days starting from day 4 of the subsequent chemotherapy course. Comparison between the control observation period and the rhIL-3 administration period showed a significant improvement or a tendency toward improvement in increasing the nadir platelet count and the recovery of the platelet count. The major adverse reactions were pyrexia, fatigue, and headache, which were well controlled by the use of antipyretics, analgesics, and antiinflammatory agents. Adverse reactions were for the most part transient and disappeared quickly during or after rhIL-3 administration. Although severe adverse reactions were not observed, the incidence of grade 2 and 3 adverse reactions according to a World Health Organization (WHO) Toxicity Scale were slightly higher in the 10 micrograms/kg/d group. As a consequence, the 5 micrograms/kg/d dose was considered to have a slightly better safety profile than the 10 micrograms/kg/d dose. Although there was no significant difference in the efficacy (the platelet count) between the two doses, the safety profile of the 5 micrograms/kg/d dose was slightly better than the 10 micrograms/kg/d group. Therefore, the 5 micrograms/kg/d was considered to be the optimum clinical dose.

Adult↗

PubMed1999

Risk of recurrence of fetal chromosomal aberrations: analysis of trisomy 21, trisomy 18, trisomy 13, and 45,X in 1,076 Japanese mothers.

OBJECTIVE: To evaluate the risk of recurrence of fetal chromosomal aberrations in women who had offspring with numeric chromosomal abnormalities. SUBJECTS AND METHODS: This collaborative study consisted of 1,076 Japanese women with a history of offspring with trisomy-21, -18, -13, or 45,X. Second-trimester amniocenteses were performed, resulting in 1,248 fetal karyotypes that were analyzed with reference to prior offspring karyotypes and maternal age. RESULTS: Of the 842 women with trisomy-21 offspring, 10 conceived another such fetus. In 2 women with 3 or more such offspring, parental mosaicism of trisomy-21 was suspected. The incidence of recurrence of trisomy-21 increased with age, and significantly exceeded the incidence of trisomy-21 fetuses in the general population. None of the 170 women with trisomy-18 offspring, and none of the 46 women with trisomy-13 offspring, had another such fetus. Of the 18 women with 45,X offspring, 1 with mos 45,X/46,XX had another such fetus. CONCLUSIONS: The risk of recurrence of trisomy-21 is affected by maternal age and parental germline mosaicism. The risk of recurrence of trisomy-18 or -13 appears to be much lower than that of trisomy-21. Women who give birth to more than 1 offspring with 45,X should be examined for mos 45,X/46,XX.

Adult↗