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Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 217 records · Page 12Linked to original sources

Urinary undiversion for pelvic actinomycosis: a long-term follow up.

BACKGROUND: A 43-year-old woman who had been using intrauterine contraceptive devices for the past 10 years underwent an emergency operation for bowel and urinary obstruction. METHODS/RESULTS: Frozen section analysis showed undifferentiated adenocarcinoma. Incomplete tumorectomy, ileal resection, partial cystectomy, colostomy and bilateral ureterocutaneostomy were palliatively performed. Postoperatively, periodic acid-Schiff and Grocott-Gomori methenamine tests revealed Actinomyces and the final diagnosis was pelvic actinomycosis. Treatment with penicillin G administered intravenously relieved her symptoms and the lesion was dramatically improved. The patient underwent colostomy closure and urinary undiversion. CONCLUSIONS: Five years after urinary undiversion, the patient's renal function has been maintained and she can void without incontinence and dysuria.

Actinomycosis↗

Patient-reported quality of life after radical prostatectomy for prostate cancer.

BACKGROUND: Increasingly, quality of life (QOL) assessments are receiving greater attention in the management of malignancies, including prostate cancer. We evaluated the impact of radical prostatectomy on patient QOL 12 months or longer after surgery. PATIENTS AND METHODS: We evaluated the impact of radical prostatectomy on QOL in 60 patients with prostate cancer. The patients comprised two groups: the first group (n = 32) was evaluated 12 months or longer after radical prostatectomy; the second group (n = 28) was evaluated while awaiting radical prostatectomy. General health-related QOL was measured with the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire. Sexual function was assessed with the Sapporo Medical University Sexual Function Questionnaire. A newly developed instrument assessing urinary function was prepared only for the postoperative group. RESULTS: No differences between the two groups were seen in comparisons of general health-related QOL subscales. Men who underwent surgery reported significant deterioration in sexual function (decreased quality of erection, decreased sexual activity and decreased satisfaction with sex life) than those awaiting surgery. Of the 32 postoperative patients, 26 (81%) did not use pads at all, five (16%) used one or fewer pads per day due to occasional spotting and only one patient (3%) used two to four pads per day to deal with urine dripping. Twenty-six postoperative patients (81%) stated that, given the choice, they would undergo radical prostatectomy again. CONCLUSIONS: General health-related QOL does not appear to be compromised following radical prostatectomy. Patients are willing to accept some morbidity for a perceived survival benefit. Although minimal urinary dysfunction was reported, most patients were dissatisfied with postoperative sexual function. In preoperative counselling, greater emphasis should be placed on the risk of postoperative impotence.

Aged↗

Isolation and cloning of rat poly(ADP-ribose) glycohydrolase: presence of a potential nuclear export signal conserved in mammalian orthologs.

Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme of poly(ADP-ribose) degradation. To understand its structure-and-function relationship, we purified Parg from rat testis 9,740-fold using an improved affinity column; the purified product was a 60 kDa protein. Based on the determined sequences of three peptide fragments, degenerated primers were synthesized and a Parg cDNA comprising 3,974 nucleotides, encoding a 109 kDa protein, was isolated. The 60 kDa Parg purified from rat testes corresponded to the C-terminal half of the 109 kDa deduced peptide. When recombinant rat Parg was expressed as a glutathione S-transferase fusion protein in Escherichia coli, Parg activity was observed for the full-length and C-terminal half proteins but not in for the N-terminal half protein. Taken together, these data indicate that the catalytic domain of Parg is located in the C-terminal half. Further, we newly identified the presence of a potential nuclear export signal in the N-terminal half in addition to the previously reported nuclear localization signals in rat and other mammalian Pargs. Northern blot analysis showed the ubiquitous expression of a single 4.0 kb Parg mRNA in various rat tissues. The findings suggest that the 60 kDa Parg is produced by post-transcriptional processing.

Amino Acid Sequence↗

Reduced expression of p53 and cyclin A in intraductal mucin-hypersecreting neoplasm of the pancreas compared with usual pancreatic ductal adenocarcinoma.

OBJECTIVE: Intraductal mucin-hypersecreting neoplasm (IMHN) of the pancreas, a slow-growing malignancy with a favorable prognosis, is distinctly categorized from the high-grade malignancy of the more common ductal adenocarcinoma. The aim of the present study was to clarify the molecular differences underlying the biological differences between IMHN and ductal adenocarcinoma of the pancreas. METHODS: The expression of p53 and cyclin A in IMHN was compared with that in ductal adenocarcinoma of the pancreas immunohistochemically. RESULTS: In IMHN, the incidence of p53 and cyclin A ascertained by positive nuclear staining was significantly lower than that in ductal adenocarcinoma. Furthermore, in ductal adenocarcinoma, p53 and cyclin A are topographically coexpressed. CONCLUSIONS: These results suggest that the overexpression of p53 and cyclin A plays a role in the tumorigenesis of pancreatic ductal adenocarcinoma, and sparse expression of both antigens in IMHN may partly contribute to its low-grade malignant characteristics.

Adenocarcinoma↗

Erythromycin inhibits transcriptional activation of NF-kappaB, but not NFAT, through calcineurin-independent signaling in T cells.

The molecular mechanism of the anti-inflammatory effect of erythromycin (EM) was investigated at the level of transcriptional regulation of cytokine gene expression in T cells. EM (>10(-6) M) significantly inhibited interleukin-8 (IL-8) expression but not IL-2 expression from T cells induced with 20 ng of phorbol 12-myristate 13-acetate (PMA) per ml plus 2 microM calcium ionophore (P-I). In electrophoretic mobility shift assays EM at 10(-7) to 10(-5) M concentrations inhibited nuclear factor kappa B (NF-kappaB) DNA-binding activities induced by P-I. Reporter gene assays also showed that EM (10(-5) M) inhibited IL-8 NF-kappaB transcription by 37%. The inhibitory effects of EM on transcriptional activation of IL-2 and DNA-binding activity of nuclear factor of activated T cells (NFAT) were not seen in T cells. On the other hand, FK506, which is also a macrolide derivative, inhibited transcriptional activation of both NF-kappaB and NFAT more strongly than EM did. The mechanism of EM inhibition of transactivation of NF-kappaB was further investigated in transiently transfected T cells that express calcineurin A and B subunits. Expression of calcineurin did not render transactivation of NF-kappaB in T cells more resistant to EM, while the inhibitory effect of FK506 on transactivation of NF-kappaB was attenuated. These findings indicate that EM is capable of inhibiting expression of the IL-8 gene in T cells through transcriptional inhibition and that this inhibition is mediated through a non-calcineurin-dependent signaling event in T lymphocytes.

Anti-Bacterial Agents↗

Failure of high-dose chemotherapy with peripheral blood stem cell support for refractory placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease. The metastatic and refractory cases have a very poor prognosis. To our knowledge, this is the first report of the application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for the treatment of refractory metastatic PSTT. A 36-year-old woman had a metastatic PSTT refractory to several lines of chemotherapy. She was treated with high dose of carboplatin and etoposide with autologous PBSCT. She showed only a temporary response to high-dose chemotherapy with PBSCT support and died of disease.

Adult↗

A kinetic model of mitochondrial aspartate aminotransferase transmigration in hepatobiliary disorders.

A hypothetical kinetic model of transmigration of mitochondrial aspartate aminotransferase (m-AST) from liver to blood and its elimination from blood was constructed and assessed for prediction by computer simulation. The elimination of m-AST from plasma in healthy rats followed first-order kinetics. Depletion of m-AST from the liver after induction of hepatobiliary disorders in rats with alpha-naphthylisothiocyanate (ANIT) also followed first-order kinetics. In contrast, the changes in metabolic rate in the liver after ANIT administration, as estimated from the plasma indocyanine green clearance, approximated to a second-order time function. Based on these data, the time-dependent change in plasma m-AST activity after ANIT administration was simulated by computer according to a hypothetical kinetic model. The result of computer simulation of the change in plasma m-AST coincided well with that obtained experimentally, suggesting that continuous measurements of m-AST may be helpful to the clinical diagnosis of liver injury.

1-Naphthylisothiocyanate↗

Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HCS) deficiency is a metabolic disorder that causes a biotin-responsive multiple carboxylase deficiency. We analyzed the kinetic properties of seven mutant HCS proteins. Two of these enzymes harbored mutations within the putative biotin-binding region of HCS and showed elevated Km values for biotin compared with that of the wild-type form (Km mutant; Gly581Ser: 45 times, delThr610: 3 times). The remaining five mutations (Arg183Pro, Leu216Arg, Leu237Pro, Val333Glu, and Val363Asp) were located outside the biotin-binding region. The enzymes containing these mutations showed normal or low Km values for biotin (non-Km mutant). Symptoms of patients who have the non-Km, mutants, as well as those of patients who have the Km, mutants, responded to biotin therapy. This is probably because the Km value for biotin of normal HCS is higher than the physiologic concentration of biotin in human cells. The Vmax values of all mutant HCS proteins were considerably decreased, but to a variable degree. The responsiveness to biotin supplementation of propionyl-CoA carboxylase activity in cultured cells bearing the mutations correlated well with the degree of reduction in the Vmax of HCS. Patients who have mutant HCS proteins with lower Vmax showed poorer clinical and biochemical responses to biotin therapy. These observations suggest that the reduction of Vmax is an essential factor for pathophysiology and prognosis of HCS deficiency under treatment with large amounts of biotin. The determination of HCS genotype can be valuable for characterizing the clinical phenotype in HCS deficient patients.

Biotin↗

Cytotoxicity and mutagenicity of UVB assessed using cultured rat fibroblast.

A retroviral vector carrying both positive (neo) and negative (herpes simplex virus thymidine kinase or HSV-tk) selection markers was constructed as a substrate for mutational assay in mammalian cells. Using a population of rat fibroblast cells carrying a single copy per cell of retroviral DNA randomly integrated in their chromosomes, we examined the cytotoxic and mutagenic activities of ultraviolet light (UV) at four wavelengths (254, 290, 300, and 320 nm). The action spectra for these activities are similar to some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing, and mouse skin carcinogenesis, except at 290 and 320 nm. At 290 nm, no significant mutagenicity was observed. At 320 nm, both cytotoxic and mutagenic activities were 10 times higher than the values expected from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of some of the HSV-tk mutants obtained after irradiation with 300 and 320 nm UV revealed partially different patterns of mutation specificity, suggesting the involvement of multiple molecular mechanisms in the genotoxicity associated with this range of UV.

Animals↗

[Short-term fluctuation of blue-on-yellow perimetry in normal eyes].

PURPOSE: To evaluate short term fluctuation (SF) of blue-on-yellow perimetry (B/Y) as compared with white-on-white perimetry (W/W) in normal eyes. SUBJECTS AND METHOD: One eye each of 25 healthy persons underwent B/Y and W/W perimetry repeated 5 times each. The test subjects had no previous experience of perimetry. An automated perimeter, Humphrey Field Analyzer, model 750, was used throughout. RESULTS: The SF at the first session of B/Y perimetry averaged 2.02 dB. This value was significantly different from those of the subsequent 4 sessions. Each of SF of B/Y perimetry at the first two sessions was significantly different from that of W/W perimetry at the first two sessions. The SF of B/Y perimetry showed wider fluctuations than those of W/W perimetry at each session. CONCLUSION: B/Y perimetry in normal eyes showed individual differences as well as fluctuations between the initial and consecutive sessions. This feature has to be considered in interpretation of the findings.

Adolescent↗

[Diagnosis of magnetic resonance imaging (MRI) for blowout fracture--three advantages of MRI].

INTRODUCTION: Magnetic resonance imaging (MRI) gives a much more detailed picture of the soft tissue than computerized tomography (CT). In blowout fracture cases, it is very easy to observe the incarcerated orbital tissue. SUBJECTS: We performed MRI in 19 blowout fracture cases. RESULTS: After evaluating the images, we found three advantages of MRI. The first is that even small herniation of the orbital contents can easily be detected because the orbital fatty tissue contrasts well around the other tissues in MRI. The second is that the incarcerated tissues can be clearly differentiated because a clear contrast between the orbital fatty tissue and the extraocular muscle can be seen in MRI. The third is that the running images of the incarcerated muscle belly can be observed because any necessary directional slies can be taken in MRI. CONCLUSION: These advantages are very important in the diagnosis of blowout fractures. MRI should be employed in blowout fracture cases in addition to CT.

Adolescent↗

A model of port-site metastases of gallbladder cancer: the influence of peritoneal injury and its repair on abdominal wall metastases.

BACKGROUND: Recent surgical literature contains several reports of wound metastases of unexpected gallbladder cancer after laparoscopic cholecystectomy. We hypothesized that peritoneal injury caused by trocar insertion potentiates wound metastases. This study was designed to determine the effect of peritoneal injury on tumor implantation. METHODS: Cultured human gallbladder cancer cells were injected into the peritoneal cavity of mice immediately after surgical procedures. In a peritoneal injury group muscle and the peritoneum were perforated; in a peritoneal injury and repair group each muscle and peritoneal wound was sutured carefully; in a laparoscopic model group animals underwent peritoneal insufflation with carbon dioxide gas and tumor cell injection and then the abdominal wall was perforated. Some mice (controls) were not subjected to any surgical procedure. All mice (n = 178) were killed 2 weeks after tumor cell injection and were examined for tumor implantation. RESULTS: Although no control mice showed intraperitoneal tumor, all mice in the peritoneal injury group showed tumors at the injured sites. In the laparoscopic model group, 90% of injured sites had tumors. The traumatized site-specific implantation rate in the peritoneal injury and repair group was only 40%, whereas it was 100% in the peritoneal injury group (P < .001). CONCLUSIONS: Peritoneal injury enhances peritoneal implantation of carcinoma cells. Repair of injured peritoneum at trocar sites may reduce the frequency of wound metastases in laparoscopic surgery for unexpected gallbladder carcinoma.

Abdominal Muscles↗

[CT findings of nasal non-Hodgkin's lymphomas associated with prognosis].

X-ray CT images of the head obtained from thirteen patients (9 men and 4 women) among 33 patients (19 men and 14 women) with nasal non-Hodgkin's lymphoma (NHL) who had been seen at Kitasato University Hospital during the period from April 1975 to March 1995 were retrospectively reviewed to search for useful prognostic image factors for nasal NHL. Extracavitary subcutaneous tumor extension into the nasal wing or cheek, and tumor penetration through the nasal septum revealed on X-ray CT images seemed to be likely indicators of a poor prognosis for patients with nasal NHL.

Female↗

[Current status and future prospects of 3D treatment planning in radiation therapy, focusing on IMRT].

The ultimate goal of radiation therapy is to confine a high dose to the target area while sparing the surrounding normal structures in order to increase the delivered dose and decrease the likelihood of organ injuries. In Japan, the rotational conformal technique, which is a combination of gantry rotation and dynamic movement of multi-leaf collimators (MLC), has been widely used as a standard method for high-precision radiation therapy. The non-coplanar technique in which radiation beams are given in three dimensions has the advantage of dose concentration as well as organ sparing. In intensity modulated radiotherapy (IMRT), an uneven intensity map within a beam is generated with various methods such as "sliding window technique" and "stop and shoot technique". Several intensity modulated beams are combined to create arbitrary dose distribution including concave distribution. Although a substantial number of proton therapy facilities are planned in this country, IMRT should be considered as a competitive rival from the viewpoint of cost-benefit analysis as well as clinical effectiveness.

Humans↗

Genetic polymorphism of CYP2D6 in the Japanese population.

The frequencies of CYP2D6 mutations in a Japanese population were investigated. Individuals were classified into three groups: control individuals, cancer patients and Parkinsonians. Genotyping for CYP2D6*3, CYP2D6*4 and CYP2D6*18 was carried out using the polymerase chain reaction, and that for CYP2D6*5 was also carried out using XbaI restriction fragment length polymorphism. The frequencies of the CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*18 mutant alleles were 0%, 0.77%, 4.10% and 0.53% in more than 256 Japanese control individuals, respectively. Based on these data, the population frequency of the CYP2D6 poor metabolizer phenotype was estimated to be 0.29%. The distribution of the four mutated alleles was not significantly different between control individuals and cancer patients or Parkinsonians.

Alleles↗