Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 937 records · Page 52Linked to original sources

PubMedDate not supplied

A western blotting procedure for detection of metallothionein.

A method to detect metallothionein (MT) by Western blotting technique is described. Cadmium-containing rat MT-I and -II were subjected to sodium dodecylsulfate/polyacrylamide gel electrophoresis (SDS-PAGE) without prior reduction by 2-mercaptoethanol (2-ME), because prior reduction of MTs by 2-ME resulted in diffused bands. After SDS-PAGE, MTs in the gel were reduced by incubating in buffer containing 2-ME, and then electrophoretically transferred to a polyvinylidene fluoride membrane. Non-reduced MTs were not found to be immobilized on the membrane. Prior to electrophoresis the zinc, in zinc-containing MT samples, must be replaced with cadmium by addition of excess cadmium chloride. MTs immobilized on the membrane were detected by two methods, (1) binding of radioactive cadmium and (2) immunochemical staining using protein-A/colloidal gold conjugate, the detection limits of which were 0.4 and 0.06-0.16 micrograms, respectively.

Animals↗

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MRI in thorotrastosis.

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed in four patients with thorotrastosis. On CT scan, Thorotrast (thorium oxide) deposition was shown as high-density areas in the liver and spleen and the abdominal lymph nodes. These deposits were not found on MRIs. Splenic volume was significantly small due to atrophy. The contrast-noise ratio in the spleen on T1-weighted images was significantly lower. Thorotrast deposition does not affect MRI appearance; therefore it may be useful for the early detection of malignant tumors as a complication of thorotrastosis.

Aged↗

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Modulated cytokine production from cervical lymph node cells treated with B[a]P and PCB.

To investigate the effects of Benzo[a]pyrene (B[a]P) and polychlorinated biphenyls (PCB) on in vitro cytokine production, we isolated cervical lymph node cells from ovalbumin (OA)-primed mice and the lymph node cells were cultured with various concentrations of B[a]P or PCB in the presence of antigen presenting cells (APC) and OA. B[a]P significantly increased the levels of interleukin-4 (IL-4) and -6(IL-6) in the culture supernatants. However, the levels of interferon-gamma (IFN-gamma) were decreased by treatment with PCB. These findings indicate that in vitro treatment with B[a]P or PCB modulate cytokine production from lymph node cells.

Animals↗

PubMedDate not supplied

Radiotherapy during pregnancy: effects on fetuses and neonates.

To optimize the efficacy of radiotherapy for cancer patients who are pregnant, the following factors must be considered: the potential effects of the therapy on fetuses and neonates, the stage and prognosis of the mother's disease, and the possible risks to the patient of restricting cancer treatment. Malformations and mental retardation are the most serious consequences of fetal exposure to radiation that are observed after birth. The sensitivity to radiation is high from 2 to 8 weeks after conception for malformations and from 8 to 25 weeks (particularly up to week 15) for mental retardation; the risk of mental retardation declines rapidly after the 25th week of gestation. When a pregnant patient requires radiation therapy, the physician should consider fetal sensitivity to radiation in light of gestational age and the expected dose of radiation and should then calculate the risk to the fetus versus the benefits to the mother. The risk is negligible if fetal exposure does not exceed 0.1 Gy, preferably remaining below 0.05 Gy, during gestation. Furthermore, it is safest to administer radiotherapy during or after the 25th week of gestation.

Abnormalities, Radiation-Induced↗

PubMedDate not supplied

RNA interference may be more potent than antisense RNA in human cancer cell lines.

1. RNA interference (RNAi) is a newly discovered cellular pathway for the silencing of sequence-specific genes at the mRNA level by the introduction of the cognate double-stranded (ds) RNA. Because antisense (AS) mechanisms have similar effects, we compared these two effects in human cancer cell lines, considering a possible application of RNAi for cancer therapy. 2. We tested RNAi effects by transfecting human hepatoma and pancreatic cancer cell lines with AS and sense (S) RNA expression plasmids corresponding to the exogenous luciferase gene or the endogenous c-raf gene in the form of complexes with a cationic lipopolyamine or a tumour-targeting peptide vector we developed. In addition, we compared the effects of small interfering RNA and AS oligoDNA complexed with the peptide vector. 3. From the viewpoint of AS actions, the effect of the AS RNA may be cancelled by the S RNA, although, interestingly, we found that the combination of the AS and S RNA expression plasmids was more effective than the AS RNA expression plasmids alone in reducing target gene expression, whereas the S RNA expression plasmids had no effects. The combination of the luciferase AS and S RNA had no effects on the expression of either the beta-galactosidase gene or the c-raf gene. In the presence of 2-aminopurine (an inhibitor of dsRNA-activated protein kinase), the inhibitory effect of the combination of AS and S RNA on gene expression did not change in the case of the endogenous c-raf gene, but was reduced in the case of the exogenous luciferase gene. The effect of 22 nucleotide RNA duplexes corresponding to the luciferase gene was by one order stronger than that of the phosphorothioate AS DNA. 4. Thus, it is suggested that RNAi may be more potent than AS RNA in reducing target gene expression in human cancer cell lines, regardless of the length of dsRNA. With further studies on the RNAi phenomenon in cancer cells, RNAi could provide a novel approach for cancer gene therapy.

2-Aminopurine↗

PubMedDate not supplied

Docetaxel in combination with carboplatin for chemo-naive patients with epithelial ovarian cancer.

We conducted a study of docetaxel-carboplatin combination therapy to confirm the efficacy and toxicity in chemotherapy-naive patients with ovarian cancer. Docetaxel 70 mg/m2 and carboplatin (area under the concentration-vs.-time curve of 5) were administered consecutively on day 1 of a 21-day cycle for five planned cycles in chemo-naive patients with the International Federation of Gynecology and Obstetrics stage IC to IV ovarian cancer with or without successful cytoreductive surgery at staging laparotomy. Twenty-six patients (median age, 53 years; range, 34-76 years) were enrolled into this trial at Niigata University Hospital. The major toxicity with this regimen was neutropenia. The incidence of grade 3 and 4 neutropenia were 27% (7/26) and 69% (18/26), respectively. However, the neutropenia was brief and reversible with G-CSF support. Nausea/emesis, fatigue, arthralgia/myalgias, and alopecia were the most common nonhematologic toxicities, in which no grade 3 or 4 toxicity was observed. Neurotoxicity was infrequently observed. Nine of 11 assessable patients responded to the regimen. We conclude that the combination of carboplatin and docetaxel seems to be highly active in ovarian cancer with the major toxicity of neutropenia, and the extremely low incidence of clinically significant neurotoxicity. Randomized controlled clinical trials should be conducted to define a role for this regimen in ovarian cancer.

Adult↗

PubMedDate not supplied

Low risk endometrial cancer: a study of pelvic lymph node metastasis.

The aim of our study was to find preoperative or intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy. A retrospective review of the medical records of 107 patients with endometrioid adenocarcinoma, FIGO grade 1 or 2 tumor, myometrial invasion <or=50%, and no intraoperative evidence of macroscopic extrauterine spread was performed. Clinicopathologic risk factors were analyzed with Fisher 's exact test with regards to pelvic lymph node metastasis. The median age of the patients was 54 years. Pelvic lymph node metastasis was observed in five of 107 patients (4.7%), where two patients with small tumors of 2 cm or less had positive pelvic lymph nodes. The presence of positive pelvic lymph nodes did not correlate with depth of invasion, histologic grade, cervical invasion, peritoneal cytology, menopausal status, preoperative serum CA125 level, or primary tumor diameter. Only lymphvascular space involvement (P < 0.0001) was significantly correlated to pelvic lymph node metastasis. We suggest that all patients with endometrial cancer who are taken to the operating room for primary therapy should be prepared to undergo extended surgical staging, except when clinical or operative factors increase patients' morbidity.

Adenocarcinoma↗

PubMedDate not supplied

An unexcluded paternity case investigated with hypervariable DNA loci.

A paternity case involving a putative father, a child, and the mother was referred to our laboratory for testing. Parentage was not excluded with 23 kinds of standard blood group markers and HLA, but the putative father requested more-affirmative evidence of paternity. Seven kinds of DNA probes that recognize hypervariable loci were applied. On the basis of the allelic frequencies and their confidence intervals previously reported among unrelated Japanese individuals, as well as confirmed codominant segregation of the polymorphism, the exclusion probability and paternity index were calculated for this case. The cumulative paternity index from the seven DNA probes was 1.4 x 10(6), which was 316 times higher than that from the 23 standard blood group markers and HLA. Accordingly, DNA polymorphism is considered to be informative enough for paternity testing.

Blood Grouping and Crossmatching↗

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Sensitizing effects of gallium citrate on hyperthermic cell killing in vitro.

The lethal effects of gallium citrate in combination with heat were studied using four cell lines, L5178Y, FM3A, P388 and HeLa. Cells were incubated with different concentrations (0.2 2 mM) of gallium citrate at 37 degrees C for 24 h and heated at a range of temperatures from 40-44 degrees C for various time periods up to 6 h in the absence of gallium citrate. Survival and cell viability were determined by clonogenic assay and the dye-exclusion test, respectively. All of the cell lines tested were insensitive to heat below 41 degrees C, but were very sensitive to heat above 43 degrees C. Gallium citrate was cytotoxic to these cell lines at different levels: P388 and HeLa were far more sensitive than L5178Y and FM3A. The killing effects of heat at 41 degrees C were greatly enhanced by gallium citrate in L5178Y and P388 cells. The Arrhenius analysis for the lethal effect of heat, determined by clonogenic assay, in L5178Y cells showed that the transition temperature was remarkably decreased for the gallium-treated cells from approximately 43 degrees C to 41 degrees C. The mechanism for this decrease in the transition temperature may be attributable to the additional effects of gallium citrate on energy metabolism. Preincubation with 0.05 mM gallium citrate at 37 degrees C for 7 days also enhanced heat sensitization at 41 degrees C in L5178Y. This preincubation condition may correspond to the condition for the continuous infusion of gallium that is clinically used for cancer treatment. In contrast, treatment with gallium did not greatly enhance the sensitivity of FM3A or HeLa cells to heat at 41 degrees C, but the effects of gallium were significant.

Adenosine Triphosphate↗

PubMedDate not supplied

Levels of fructosyllysine in collagen are low compared with the loss of lysine in diabetic rats: involvement of oxidation in increased cross-linking.

1. It is thought that early glycation products on lysine residues of collagen are re-arranged to form collagen cross-links (advanced glycation end-products), which are increased in hyperglycaemia. We have previously reported that 4 week vitamin E supplementation in diabetic rats protected against the development of increased collagen cross-linking. In the present study we analysed early glycation products as fructosyllysine and amino acid content of tail tendon collagen in rats. 2. The amount of lysine residues in early collagen glycation products in diabetic rats was estimated to be less than 0.2 mol/mol type I collagen, whereas in the diabetic rats the loss of lysine residues was estimated to be 2.5 mol/mol. However, vitamin E supplementation protected against the loss of lysine residues without affecting early glycation products. 3. Thus, it is demonstrated that the amount of early collagen glycation products is quite small compared with the loss of lysine residues in diabetic rats and we suggest that the oxidative modification of lysine residues may be involved in the increased cross-linking observed in hyperglycaemia.

Amino Acids↗

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Complete response to docetaxel and carboplatin combination chemotherapy for a stage IV uterine papillary serous carcinoma: a case report.

We report a case of a stage IV uterine papillary serous carcinoma (UPSC) with multiple organ metastases. The patient was treated with docetaxel and carboplatin combination chemotherapy. After five courses, uterine tumor, Douglas tumor, lymphadenopathy, and distant metastases on magnetic resonance imaging or computed tomography scan were completely resoluted. Moreover, endometrial biopsy showed no carcinoma tissues after six courses. We suggest that this regimen may be effective for treatment of advanced-stage UPSC.

Adult↗

PubMedDate not supplied

Placental site trophoblastic tumor presenting as subaponeurotic metastasis.

Cases of metastatic placental site trophoblastic tumor (PSTT) have a very poor prognosis because these tumors tend to be less sensitive to chemotherapy than other types of gestational trophoblastic disease. We describe the case of a 25-year-old woman who presented with occipital tumor and abnormal vaginal bleeding. Hysterectomy, bilateral salpingo-oophorectomy, and occipital tumor removal revealed a primary PSTT in the uterus, with ovarian and occipital subaponeurotic metastases. She received etoposide, methotrexate, actinomycin-D/cyclophosphamide, vincristine chemotherapy and had a complete clinical remission. Fifteen months later, she had a recurrent subaponeurotic occipital tumor invading the cranium and underwent tumor removal along with cranial bone followed by local irradiation. She was then treated with etoposide, cis-platinum/etoposide, methotrexate, actinomycin-D chemotherapy and again had a remission for 5 months. The patient, however, had a left parietal subaponeurotic tumor, invading the dura mater, and received local irradiation. Soon after, she developed left orbital bone metastasis, treated by local irradiation. These bone metastases responded to the radiation completely. However, multiple organ metastases were found, and she died of the disease. This represents the first case of PSTT with initial subaponeurotic metastasis in a living patient. New modalities of treatment for high-risk or metastatic PSTT need to be developed.

Adult↗

PubMedDate not supplied

Effect of human granulocyte colony-stimulating factor on neutropenia induced by radiotherapy and chemotherapy.

This study was designed to test the effect of human granulocyte colony-stimulating factor (hG-CSF) in patients at risk for neutropenia caused by radiotherapy plus chemotherapy. Twelve patients with advanced esophageal tumor were treated after operation with 'sandwich' radiochemotherapy (successive treatment with chemotherapy-radiotherapy-chemotherapy). hG-CSF was given subcutaneously at a dose of 2 micrograms/kg/day for 3-5 days after the white blood cell counts decreased to less than 3,000/mm3. Neutrophil counts significantly recovered to normal levels within 5 days in all patients treated with hG-CSF. No significant changes in the lymphocyte, platelet and red blood cell counts were shown. No side effects were observed. These results indicate that hG-CSF is a useful tool for the treatment of neutropenia induced by radiotherapy and chemotherapy.

Aged↗

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Changes in phosphorus distribution during total parenteral nutrition.

To investigate the mechanism of hypophosphatemia during total parenteral nutrition (TPN), changes in phosphate (P) contents in the liver and muscle of rats supported by TPN for 2 days at 270 cal/g were studied in 39 Sprague Dawley rats (200 g body weight), divided into 5 groups as follows: G-I: starved for 24 hr (n = 7); G-II: TPN (5 mEq P/1000 cal) after 24 hr starvation (n = 7); G-III: starved for 4 days (n = 7); G-IV: TPN (5 mEq P/1000 cal) after 4 days starvation (n = 9); G-V: TPN (35 mEq P/1000 cal) after 4 days starvation (n = 9). P contents of the tissues were measured colorimetrically. Results indicated that muscle P content decreased in the depleted rat supported by TPN with low P intake, while an increase in P content in the liver was a constant finding in each TPN group. Increase in P intake tended to preserve the P content in the muscle. These findings suggest that the changes in P distribution in major body tissues must be considered in addition to the changes in the serum inorganic P levels to evaluate an adequate P requirement for TPN.

Animals↗

PubMedDate not supplied

Comparison of ultrastructural changes in thyrotrophs of the rat pituitary between intermittent and continuous treatments with sulfadimethoxine.

To clarify relationships between serum thyroid-stimulating hormone (TSH) levels and ultrastructural changes in thyrotrophs caused by intermittent or continuous treatments with antithyroid compound, male Fischer-344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN) were given water containing 0.1% sulfadimethoxine (SM) for 8 wk and then sacrificed (Group 1). Additional groups were examined 2 wk after withdrawal (Group 2), after 4 wk retreatment following a 2-wk withdrawal period (Group 3), and after 14 wk continuous exposure (Group 4). Control rats (Group 5) remained untreated for 8 wk after the DHPN initiation. Microscopic examination revealed hypertrophy of thyrotrophs and depletion of TSH-positive material in Groups 1, 3, and 4 but a return to normal in Group 2. Electron microscopic examination of thyrotrophs in the anterior pituitary in Groups 1, 3, and 4 revealed dilated rough endoplasmic reticulum (ER) cisternae with intracisternal dense granules as well as diminished numbers of intracytoplasmic secretory granules, these changes being most marked in Group 1 and least pronounced in Group 4. The number of intracytoplasmic secretory granules in Group 3 was much lower than in Group 4, as demonstrated by morphometric analysis. In Group 2, thyrotrophs showed dilated rough ER cisternae without intracisternal dense granules and essentially the same component of intracytoplasmic secretory granules as Group 5. The present study suggest that while prolonged continuous treatment with SM results in gradual acclimation to an increased demand for TSH, intermittent treatment elicits a persistent state of reduced TSH storage in thyrotrophs due to a continued strong feedback through the hypothalamus-pituitary-thyroid axis.

Animals↗

PubMedDate not supplied

The present status of active tuberculosis in a general hospital; a study of 186 cases.

To study the present status of TB in a general hospital, we reviewed the records of 186 patients with TB at the Saga Medical School Hospital. Ninety-two patients (49.5%) had extrapulmonary tuberculosis and 59 patients (31.7%) had complicated severe diseases. The variety of TB lesions and underlying diseases often caused diagnostic delay and misdiagnosis. In fact, 16 cases were not identified to be TB until after death. The TB prevalence was significantly high in malignant disease, diabetes mellitus, collagen disease and chronic renal failure among the total number of patients discharged. Twenty-one patients developed TB while on an intensive therapy for underlying diseases. Unfortunately, 22 patients with TB died in our hospital. These findings suggest that special care must be taken to prevent TB in a general hospital. We emphasize that early diagnosis of TB depends on the suspicion of this infection on the part of the physician.

Adult↗

PubMedDate not supplied

Effectiveness of intrathoracic chemothermotherapy for malignant pleurisy due to Ewing's sarcoma: a case report.

This paper describes a case of malignant pleurisy which showed evidence of the effectiveness of a new mode of cancer treatment, intrathoracic chemothermotherapy (ICT). ICT consisted of a bolus intrathoracic injection of 50 mg cis-diamminedichloroplatinum (CDDP) and local heating using 8 MHz radiofrequency waves for 60 min. A patient with multiple lung metastases and malignant pleurisy on both sides due to Ewing's sarcoma was treated on the right side with ICT, along with concomitant systemic administration of 50 mg CDDP. Intrathoracic temperatures were monitored by insertion of thermocouple temperature sensors, and temperatures of 43 degrees C or over were successfully maintained for about 40 min during each of three treatments. Although the patient died 3 months later of advanced metastases in the left lung and malignant pleurisy on the left side, lung metastases in the right lung were stable on radiographs, and autopsy results showed no cancerous lesions in the right thoracic cavity, which had been treated with ICT. Since no effective response had been obtained clinically or histologically before starting ICT, despite frequent administration of anti-cancer drugs, we conclude that heat acted synergistically with CDDP on drug-resistant cells in this case.

Adult↗

PubMedDate not supplied

Enhancement of thermoradiotherapy by glucose administration for superficial malignant tumours.

The effect of hyperglycemia on the thermoradiotherapy of superficial malignant tumours was investigated. Glucose administration alone (500 ml of 10% glucose by intravenous drip infusion) reduced the tumour blood flow, when measured by laser Doppler flowmetry, to 66.1% of the baseline level at 30 minutes after the beginning of glucose infusion. Forty patients received glucose in tandem during the hyperthermia and radiotherapy (group A), and 38 patients received thermoradiotherapy alone (group B). The mean Tave (the average temperature of all intratumoural sensors) in group A was 43.4 +/- 1.1 degrees C while that in group B was 42.5 +/- 1.2 degrees C, i.e., glucose administrations significantly increased the tumour temperature (p < 0.01). In group A, complete tumour response (CR) was observed in 12 patients (30.0%), partial response (PR) in 25 patients (62.5%) and no response (NR) in three patients (7.5%). In group B, seven (18.4%), 20 (52.7%) and 11 (28.9%) patients showed CR, PR and NR, respectively. The tumour response rates were significantly different between two treatment groups (p < 0.05). The frequency of side effects of hyperthermia in groups A and B were 22.5 and 21.1%, respectively. This study suggests that hyperglycemia enhances the effectiveness of thermoradiotherapy.

Adult↗