Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 433 records · Page 24Linked to original sources

PubMed1994

Drug discovery, development and deployment: a report from the 28th Joint Conference of the U.S.-Japan Parasitic Diseases Panels, Baltimore, Maryland, July 1993.

The 28th Joint Conference of the Parasitic Diseases Panels of the U.S.-Japan Cooperative Medical Sciences Program held in Baltimore, Maryland focused on current research within both countries on antiparasitic chemotherapy. This meeting report summarizes presentations of work in progress on antiparasitic drugs currently in use and drugs under development or in clinical trials, as well as reports on potentially unique parasite characteristics that may provide targets for development of future therapeutics.

Animals↗

PubMed1994

[Involvement of gene expression in drug tolerance and dependence].

The development of drug tolerance and dependence are thought to be associated with gene expression. Our studies showed that the binding activity of nuclear factors to several DNA sequences is altered by long-term treatment with methamphetamine, cocaine and morphine: 1) the binding activity of AP-1 increased markedly in the mouse brain after administration of methamphetamine and cocaine, 2) CRE-binding activity was decreased by chronic morphine treatment in the amygdala complex, cerebral cortex and hypothalamus of the mouse brain, and 3) the binding activity of single-stranded CRE binding proteins was decreased by chronic morphine treatment in the mouse cerebellum. These data suggest that the changes of DNA binding proteins can be involved in the development of drug tolerance and dependence.

Amphetamine↗

PubMed1994

[Treatment of advanced prostate cancer].

The treatment against hormone relapsing prostate cancer was examined clinically, experimentally and by a review of the literature. Conventional systemic chemotherapy should be appreciated as one of the symptomatic treatment options; and suramin might be an effective chemotherapeutic agent, if severe and the wide spectrum of side effects were concurred. Intermittent administration of suramin is beneficial at present, with monitoring of its concentration in the blood. Some patients with wide spread bone metastases, especially if they are symptomatic, would be the candidates for hemiskeletal irradiation. Low dose of fractionated radiation was found to be more effective than high dose of single radiation. Bisphosphonate was found to protect bone resorption and destruction from the inoculated prostatic cancer cells in nude mice. In the clinic, the compound would be effective to the aggravation of bone metastasis, especially in combined use with irradiation.

Animals↗

PubMed1994

Radiation therapy for patients of malignant salivary gland tumors with positive surgical margins.

PURPOSE: Surgery is an essential part of treatment for tumors of the salivary gland, yet there is increasing evidence in the literature supporting the necessity of adjuvant radiation therapy. The patients described in this report were selected to receive postoperative radiation therapy because they were found to have positive margins. We have reviewed their records to identify factors influencing the control of local disease, the development of distant metastases and overall survival, and to define the role of postoperative radiation therapy in patients with positive surgical margins. PATIENTS AND METHODS: A total of 17 patients with malignant tumors originating from the major salivary glands seen between 1970 and 1988 who were treated with surgery and postoperative radiation therapy were reviewed. All patients had positive surgical margins. RESULTS: Overall local control at five years was 65%. Classified by T-stage, local control was obtained in all two patients for T1 disease, in five of six for T2, in four of six for T3, and in none of three for T4. At five years, the ratio of patients free of distant metastases was two of two for T1 lesion, four of six for T2, three of six for T3, and none of three for T4. Five-year survival was obtained in all eight patients with T1 and T2 lesions, four of six for T3, and one of three for T4. Patients with neck nodal metastases present in the neck at admission did worse than those with negative nodes, with 0% (none of three patients) free of locoregional recurrence vs. 71% (eleven of 14), 0% (none of three) free of distant metastases vs. 63% (nine of 14), and 0% (none of three) survival at five years vs. 93% (13 of 14). CONCLUSIONS: Postoperative radiation therapy for patients with positive surgical margins was effective for T1 and T2 disease. However, patients with T3 and T4 disease require more aggressive therapy. Patients with nodal metastases in the neck at admission tended to have distant metastases and had poor prognoses. Further therapeutic measures using adjuvant chemotherapy might be explored for these patients. Patients with adenoid cystic carcinoma with positive surgical margins tended to have perineural invasion and distant metastases. However, the utility of chemotherapy for patients of adenoid cystic carcinoma with distant metastases remains uncertain, because effective drugs for adenoid cystic carcinoma do not exist and patients live for several years without chemotherapy.

Adolescent↗

PubMed1994

Effects of recombinant human soluble thrombomodulin (rhs-TM) on a rat model of disseminated intravascular coagulation with decreased levels of plasma antithrombin III.

We reported that recombinant human soluble thrombomodulin (rhs-TM) is effective for disseminated intravascular coagulation (DIC) in vivo, in mice and rats. In the present work, we investigated the effects of decreased plasma antithrombin III (ATIII) levels on anticoagulant effects of rhs-TM, as compared to findings with heparin, of which effect is lowered by the decreased plasma ATIII levels in patients with DIC. Rat plasma ATIII levels decreased when we mixed plasma with anti-rat ATIII antibody and the potential of heparin to prolong APTT or PT was markedly diminished. The potential of rhs-TM to prolong APTT and PT was not affected. In rats injected with anti-rat ATIII antibody, plasma ATIII levels decreased immediately. When the rats were infused with tissue factor (TF), DIC was induced. At doses of rhs-TM and heparin which were equally effective at inhibiting the decrease in platelet count and fibrinogen level in control rats treated with TF, only rhs-TM remained effective in preventing DIC in rats with reduced ATIII levels. Heparin was not effective when administered to these rats with reduced ATIII levels. Therefore, rhs-TM effectively inhibits coagulation independent of ATIII levels, in contrast to heparin, which depends on the ATIII level.

Animals↗

PubMed1994

Histopathological findings of the lung and trachea in sudden infant death syndrome: review of 105 cases autopsied at Dade County Medical Examiner Department.

A histopathological study of respiratory tract in sudden infant death syndrome (SIDS) was performed on the case files of Dade County Medical Examiner Department, Miami, Florida, U.S.A. over a span of 40 months from September 1989 through December 1992. Microscopic slides of the lung and trachea were collected from 105 SIDS cases and reviewed. Fifty cases of sudden infant death of recognized causes were also analyzed as a control. The microscopic findings with its severity were recorded on each case. Two major findings, namely pulmonary congestion and edema were noted in 83 and 76% of SIDS cases respectively, and in 72 and 60% of explained deaths. No differences were statistically significant between two groups despite the slight dominance in SIDS cases. Some "typical" findings such as increase of alveolar macrophages, emphysema and atelectasis mainly due to cardiopulmonary resuscitations were commonly found. However, statistical analysis of the incidence of these findings failed to disclose any significant difference. Acute and/or chronic inflammation of the trachea was noted in 21% of SIDS cases, which was consistent with the history of the affected infants stated by the guardians. Minimal to mild bronchitis and pneumonia were found in 8 and 7% of SIDS cases respectively. There were a few cases with some pneumonia which fell into "the gray area" between SIDS and explained deaths. Besides a complete autopsy, scene investigation and review of postnatal medical history of the infant are essential to make a diagnosis of SIDS.

Female↗

PubMed1994

Bactericidal activity of arbekacin against methicillin-resistant Staphylococcus aureus. Comparison with that of vancomycin.

Bactericidal activity of arbekacin (ABK) against methicillin-resistant Staphylococcus aureus (MRSA) was compared with that of vancomycin (VCM). MIC80 of VCM against 1,056 clinical isolates was 2 micrograms/ml and not a single strain of those in which MIC above 4 micrograms/ml was detected. Whereas MIC80 of ABK against the isolates was 1 microgram/ml, but a few strains of which showed MIC of 8 micrograms/ml or 16 micrograms/ml. A killing-curve study indicated that bactericidal activity of ABK was critically dependent on its concentrations. ABK, at higher concentrations, showed excellent killing effects against all the tested isolates, and the effects were superior to those of VCM because of following reasons; great reduction CFU was attained within short time incubation, and the effects were not remarkably influenced by different inoculum sizes of MRSA. At lower concentrations of ABK, between a half and four times MIC, the re-increase of CFU of MRSA with appearance of characteristic small colonies was observed. Considering the concentration of ABK in usual dose, the significance of the re-growth should be carefully assessed. It showed be recommended that the peak concentration of ABK be elevated to higher level if adverse effects do not appear.

Aminoglycosides↗

PubMed1994

Selective enhancement of metallothionein mRNA expression by copper in primary cultured liver parenchymal cells of LEC rats.

Mechanisms for the abnormal copper (Cu) accumulation in the liver of LEC rats were examined using primary cultured liver parenchymal cells prepared from mutant LEC rats and those from control LEA rats (original strain). The Cu and metallothionein (MT) mRNA levels in the liver of LEC rats were caused to decrease to the same levels as those of LEA rats by removing Cu in vivo selectively with tetrathiomolybdate. Cu was taken up by LEC rat cells to the same extent as LEA rat cells by exposure to low medium Cu and to a higher extent by exposure to high medium Cu, while the MT mRNA level in LEC rat cells increased dose-dependently at a much higher rate than that in LEA rats. MT mRNA levels in both cells were comparable by exposure to cadmium, zinc and dexamethasone. The results indicate that expression of MT mRNA is selectively enhanced by Cu in LEC cells despite the fact that uptake of Cu is comparable with normal cells.

Animals↗

PubMed1994

[Various factors influencing in vitro antifungal activities of omoconazole nitrate (OMZ), a new imidazole antimycotic].

Effects of various factors on in vitro antifungal activities of omoconazole nitrate (OMZ) were investigated with bifonazole (BFZ) as the reference drug using an agar dilution method and a broth dilution method. Composition of the culture medium significantly altered the activity as determined by minimum inhibitory concentration (MIC) of OMZ; OMZ exhibited a greater anti-Candida activity (smaller MIC values) on casitone agar (CA) than on Sabouraud dextrose agar (SDA). Anti-Candida activity of OMZ was the highest in pH 5 medium, but it was lowered by an increase of inoculum size, a prolongation of the incubation period and the addition of calf serum to the medium. Anti-Trichophyton activity of OMZ was not influenced with these factors except for the addition of calf serum. The activity of OMZ was fungicidal against Candida at pH 5.0 and against Trichophyton at pH 5.0 and 6.6. The geometric mean MIC of OMZ was lower than that of BFZ against C. albicans freshly-isolated on acid CA.

Antifungal Agents↗

PubMed1994

[A case of gauzeoma with recurrent massive hemoptysis mimicking aspergilloma].

A 52-year-old woman who had received a right upper lobectomy and thoracoplasty for the treatment of pulmonary tuberculosis 30 years prior to the present disorder, was admitted to out hospital with massive hemoptysis. We diagnosed aspergilloma clinically because chest X-ray showed a fungus ball-like mass with meniscus sign. Right middle and lower lobectomies were performed after the 7th bronchial arterial embolization for recurrent hemoptysis. The resected specimen showed a mass of old gauze, a so-called "gauzeoma". We have found no previous reports of gauzeoma with both meniscus sign and recurrent massive hemoptysis mimicking aspergilloma.

Aspergillosis↗

PubMed1994

Wide variation of probability of local failure and distant metastasis among various stages of patients with nasopharyngeal carcinoma.

PURPOSE: Although radiation therapy is the mainstay of therapy in nasopharyngeal carcinoma (NPC), the optimal dosage schemes for treating the primary tumor or cervical lymph node metastases have not been generally agreed upon. NPC is thought to be a tumor well suited to treatment with adjuvant chemotherapy because distant metastases are more common than with other head and neck sites. However, there are several reports that fail to demonstrate improved survival in chemotherapy treated patients. Careful selection of patients for chemotherapy may be required in order to show a benefit. PATIENTS AND METHODS: A total of 61 patients with nasopharyngeal carcinoma seen between January, 1972 and December, 1985 who were treated with radiation therapy alone were reviewed. We analyzed the factors influencing distant metastasis and primary control. RESULTS: The five-year survival rate for observed and relapse-free survival were 44% and 31%, respectively. The survival rates for N3 in TNM classification and for N3 in Ho's classification were significantly worse and distant metastasis rates were significantly higher as compared with N0, N1, N2. 16 of 25 patients who had distant metastases developed them following locoregional failure. No patient with N0, N1, N2a, N2b developed distant metastases without a locoregional recurrence. There were several recurrent cases in which radiation was terminated when tumor disappeared at inspection or palpation. The five-year survival rates for T4 was 0%. CONCLUSION: The patients with N3 in TNM. Ho's classification or locoregional failure may be candidates for chemotherapy, because they have a high probability of distant metastasis. CT should be used in T staging routinely to exclude tumor involvement of the base of the skull. 70 Gy may be appropriate for T3 disease, even if tumor disappeared at lower doses. More than 70 Gy may be required to treat T4 tumors. 50 Gy may be appropriate for N0, N1 and N2b and 70 Gy for N2c and N3, even if tumor was not palpable at lower doses.

Carcinoma, Squamous Cell↗

PubMed1994

Radiolabeled polymerase chain reaction assay for detection of ras oncogene point mutations in tumors.

The human ras gene plays a fundamental role in the transduction of extracellular signals to the nucleus, thereby regulating cell growth and differentiation. Point mutations in the ras gene convert it into a transforming oncogene that has been found in many solid and hematologic malignancies. We describe a rapid and sensitive assay based on a radiolabeled polymerase chain reaction followed by restriction enzyme digestion that we have adapted for differentiating between the wild-type and mutant ras genes. This assay should prove useful in the analysis of ras gene point mutations in clinical tumor specimens in which ras oncogene activation is an early event in carcinogenesis.

Base Sequence↗

PubMed1994

[Study of two cases of active pulmonary tuberculosis complicated by lung cancer].

In this study, we report on two patients diagnosed with active pulmonary tuberculosis who later developed complications of lung cancer. In both instances, lung cancer was not detected until after cessation of tuberculostatic drugs. Both patients were initially considered to be experiencing exacerbation of pulmonary tuberculosis. Patient 1 was a 77-year-old female. A roentgenogram of her chest revealed a cavitary lesion with infiltration into the right lung field. Her sputum tested positive for acid-fast bacilli. Although she was treated with isoniazid (INH), rifampicin (RFP) and streptomycin sulfate (SM), the RFP and INH treatments had to be discontinued due to liver dysfunction. Her general condition was deteriorated, and pleural effusion appeared on a subsequent chest roentgenogram. Primary squamous-cell lung cancer was confirmed by conducting a transbronchial biopsy. Patient 2 was a 59-year-old male. A roentgenogram of his chest revealed multiple cavitary lesions with infiltration into the bilateral lung field. His sputum also tested positive for acid-fast bacilli. Although he was treated with INH, RFP and SM, INH and RFP treatment had to be discontinued due to liver dysfunction and high fever. The shadow infiltrating the left lung field subsided, but a massive shadow appeared in the right lung field. Primary small-cell lung cancer was confirmed after conducting a sputum cytology. The patients was then administered cisplatin and etoposide. Patient 1 was diagnosed with lung cancer five months after being admitted to the hospital, and Patient 2 ten months after admission. Both patients succumbed due to lung cancer at seven and 26 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Expression of glutathione S-transferase P-form in primary cultured rat liver parenchymal cells by coplanar polychlorinated biphenyl congeners is suppressed by protein kinase inhibitors and dexamethasone.

Glutathione S-transferase P-form (GST-P, EC 2.5.1.18) mRNA was expressed by epidermal growth factor as well as by 3,4,5,3',4'-penta-chlorinated biphenyl (PenCB) in primary cultured rat liver parenchymal cells. The expression of GST-P was suppressed by inhibitors of protein kinase C and dexamethasone, an antagonist of AP-1 transcription factor activity, whereas expression of cytochrome P450IA2 by PenCB was not affected by these reagents. The AP-1 related transcription factor may be essential for the expression of GST-P by PenCB as also may be a protein kinase C type enzyme.

Animals↗

PubMed1993

Selective removal of copper bound to metallothionein in the liver of LEC rats by tetrathiomolybdate.

LEC rats (Long-Evans with a cinnamon-like coat color) have a genetical defect in Cu metabolism. Male LEC rats aged 10 weeks were injected ip with TTM at a dose of 5 or 10 mg/kg body weight for 8 consecutive days and killed one day after the last injection. Cu that had accumulated in the liver at a concentration of 251 micrograms/g liver was decreased to 82.7 or 74.3 micrograms/g liver respectively, by the treatment. Although most of Cu was bound to MT as a soluble form before TTM treatment, the metal remaining in the liver after the treatment was present almost exclusively in the non-soluble fraction. Zinc (Zn) present, bound to MT before the treatment, was also partly removed from the liver by TTM, and the Zn remaining in the liver after the treatment was revealed to be bound to MT (Zn-MT) by high performance liquid chromatography-atomic absorption spectrophotometry. Iron (Fe) in the liver was not affected by TTM treatment. Cu in the kidneys and spleen increased by TTM treatment, while Zn and iron were not affected. Treatment of LEC rats with severe jaundice effectively cured the animals from otherwise lethal signs by only two ip injections of TTM at a dose of 10 mg/kg body weight.

Animals↗

PubMed1993

Effect of human recombinant granulocyte colony-stimulating factor on induction of myeloid leukemias by X-irradiation in mice.

Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimulates proliferation of myeloid leukemia cells as well as normal granulocytes in vitro. We designed a method to determine if G-CSF affects the incidence of myeloid leukemias induced by irradiation and the types of leukemias induced according to the French-American-British (FAB) classification in RFM/MsNrs mice. Administration of G-CSF (2 micrograms/d for 7 days) after a single 3-Gy irradiation significantly increased the number of peripheral blood neutrophils as compared with those in control mice. Even after discontinuation of G-CSF, both the total leukocyte and neutrophil counts increased to day 10, and their levels remained elevated until day 14. The incidence of myeloid leukemia in mice exposed to a single 3-Gy irradiation was 18.6% (38 of 204), and treatment with G-CSF did not increase the incidence (15.7% [32 of 204]). In the mice with radiation-induced leukemia, those receiving G-CSF had a mean survival time of 357 days, whereas those not receiving the factor survived for 349 days. There was no significant difference of survivals between the two groups. Most of the radiation-induced leukemias in the two groups were M1 or M2, according to the FAB classification; no characteristic difference was observed among the types of leukemias. Although G-CSF stimulated the leukemia cells in vitro, G-CSF administration after irradiation did not increase the occurrence of radiation-induced myeloid leukemias. Our results show that administration of G-CSF effectively accelerates neutrophil recovery from irradiation-induced hematopoietic injury and does not enhance the induction of myeloid leukemia in RFM/MsNrs mice by irradiation.

Animals↗

PubMed1993

Proliferative and nonproliferative breast disease in atomic bomb survivors. Results of a histopathologic review of autopsy breast tissue.

BACKGROUND: The risk of female breast cancer in association with radiation dose is well established, on the basis of follow-up studies of the atomic bomb survivors and other exposed populations. This association is especially strong for women exposed before 20 years of age and appears to be much weaker among women exposed after 40 years of age. METHODS: Breast tissue samples from 88 high-dose and 225 low-dose autopsy cases from the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative and proliferative breast lesions are associated with radiation dose. RESULTS: Prevalence of proliferative disease in general and atypical hyperplasia in particular were positively associated with radiation dose. The associations were strongest for subjects who were between 40 and 49 years of age at the time of the bombing. CONCLUSIONS: It is hypothesized that the strongest association in women 40 to 49 years of age may be related to the age dependence of radiation-induced breast cancer, in that potential cancers induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers.

Adolescent↗

PubMed1993

Radiation therapy of well-differentiated neuroblastoma and central neurocytoma.

BACKGROUND: Central neurocytoma is a rare intraventricular tumor with prominent neuronal differentiation. Although reported cases of this disease are increasing, the clinical benefit of radiation therapy remains unclear. METHODS: From 1979 to 1990, two patients with central neurocytoma and five with well-differentiated neuroblastomas received radiation therapy. Five were men and two were women; the age at onset ranged from 20 to 37 years (mean age, 25.6 years). The follow-up period ranged from 14 to 134 months (median, 68 months). The initial histologic diagnosis was oligodendroglioma in five, ependymoma in one, and suspected central neurocytoma in one. Electron microscopic examination showed numerous neuronal processes containing microtubules and membrane-bound neurosecretory granules. Well-formed synaptic junctions were observed in the two cases of central neurocytoma. All patients underwent partial or subtotal tumor resection before radiation therapy (partial resection in three and subtotal resection in four). Three patients received radiation therapy locally, up to 50-60 Gy. Four cases were treated with a combination of whole brain irradiation (32-40 Gy) and local irradiation (20-32 Gy). RESULTS: Treatment results were quite favorable, and all patients are alive and well without evidence of recurrence. Computed tomography studies showed that bulky residual tumors disappeared from several months to 1 year after the completion of radiation therapy. In a patient who had surgery again, significant vacuolar degeneration was observed by light microscopic examination. CONCLUSIONS: A high level of radiosensitivity was confirmed, but additional data are required to clarify the clinical benefit of radiation therapy.

Adult↗