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Biomedical subjects

A Takagi

Publications and source records attributed to A Takagi.

At least 163 records · Page 9Linked to original sources

A possible role for oxidative stress in potassium bromate (KBrO3) carcinogenesis.

In order to clarify the role of oxidative stress in carcinogenesis by potassium bromate (KBrO3), 8-hydroxydeoxyguanosine (8-OH-dG) levels and cumulating replicating fractions (CRFs) were measured in the kidneys and livers of F344 rats receiving gavage doses of 100, 200 or 400 mg/kg. We used female rats in this study to allow the potential of KBrO3 for inducing alpha 2u-globulin accumulation--known to result in sustained cell proliferation and eventual promoting activity in males--to be ignored. Additional female rats were given 0.05% N-ethyl-N-hydroxyethylnitrosamine (EHEN) orally for the first 2 weeks as an initiator with subsequent administration of KBrO3 at a dose of 500 p.p.m. in the drinking water for 30 weeks. 8-OH-dG levels in the kidneys were significantly elevated with doses of 200 and 400 mg/kg, and this correlated with increases of the CRFs of proximal tubules. In the livers, however, no significant changes were found. In the promotion bioassay, the mean numbers of atypical tubules, atypical hyperplasias and renal cell tumors per rat in animals treated with KBrO3 after EHEN initiation were significantly higher than those in animals receiving distilled water after EHEN initiation. In contrast, there were no significant differences between groups in terms of liver tumors. The overall data suggest that oxidative stress generated by KBrO3 exposure might be associated with induction of cell proliferation and associated promoting activity.

8-Hydroxy-2'-Deoxyguanosine↗

Eradication of Helicobacter pylori with lansoprazole, amoxicillin, and plaunotol in duodenal ulcer patients.

Helicobacter pylori eradication therapy combining amoxicillin (AMPC), plaunotol (PL), and a proton pump inhibitor (PPI) was examined as an alternative to triple therapy, which has a high rate of side effects and low patient compliance. Thirty-two H. pylori-positive patients (24 men, 8 women) with duodenal ulcers were examined. The diagnosis of H. pylori infection was made by the urease test on specimens biopsied from two sites in the stomach. Simultaneously, the IgG antibody against H. pylori was measured by the EIA method. The therapeutic regimen was lansoprazole (LPZ) 30 mg q.d. (6 weeks) and AMPC 1,500 mg t.i.d. (2 weeks) plus PL320 mg b.i.d. (6 weeks). The rate of ulcer healing was judged endoscopically after 6 weeks. Cases that become urease-negative after the cessation of the therapy were defined as having achieved clearance, and those negative after 1 month as eradication. Within 6 weeks, 31 of 32 patients had healed ulcers. All patients were H. pylori antibody-positive before therapy. The clearance rate was 71.9% (23/32) and the eradication rate was 45.8% (11/24). Adverse effects were observed only in one case. We conclude that combination therapy with LPZ, AMPC, and PL has a high therapeutic effect on ulcer healing and moderate effectiveness for eradication of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Sensorineural hearing loss in patients with large vestibular aqueduct.

In examining 181 patients (327 ears) with sensorineural hearing loss of unknown etiology and 25 people (50 ears) with normal hearing by high-resolution computed tomography (CT), the image of the large vestibular aqueduct (VA) was defined as being a visible large aperture (> or = 4 mm), and small distance between vestibule and traceable part of the VA nearest to the vestibule (> or = 1 mm). The large VA was found in 13 patients (23 ears, 7.0%); it was relatively frequent following hypoplastic cochlea (33 ears, 10.1%) in all the inner ear anomalies detected. In patients with large VA, high-frequency hearing was affected more than low frequency, and history of sudden hearing loss was observed frequently (61% of ears with large VA), which was found to be triggered by characteristic episodes such as minor head trauma, etc. Those clinical features were observed more in those without cochlear anomaly than in those accompanying cochlear anomaly. Pathogenesis of sensorineural hearing loss and characteristic fluctuation of hearing in those patients are discussed.

Adult↗

Vestibular function in patients with a large vestibular aqueduct.

Four patients (7 ears) with a large vestibular aqueduct (VA) were examined for history of vertigo and vestibular function. Vertigo was observed in all the 4 patients. The caloric responses were significantly poorer in ears with a large VA than in the controls. On a patient with a large VA who had several attacks of sudden hearing loss and vertigo following minor head trauma, long-time exposure to sunshine, common cold, and exercise, vestibular function tests were performed several times; the caloric responses were found to fluctuate and direction changing apogeotropic positional nystagmus was observed. These findings suggest that in patients with a large VA, not only hearing but also the vestibular function are generally impaired. We believe than direct transmission of intracranial pressure changes to the inner ear or subsequent inner ear fluid movement through the large endolymphatic sac and duct have an influence on the cochlea and vestibule.

Adolescent↗

Studies of currently used and experimental cochlear implants.

Since 1987 we have inserted multichannel cochlear implants in 60 patients with severe hearing impairment. The surgical procedures were not very difficult, and few postoperative complications were encountered. Postoperative speech recognition by every patients was satisfactory. Nevertheless, some patients complained about their hearing in a noisy environment, or while listening to either TV or music. Consequently, cochlear implants needs further improvement. To improve speech recognition ability, a newly developed experimental system was constructed. Judging from the electrode activation pattern, the new system extracted the features of consonants more successfully than the present system. However, when this new system was installed in cochlear implant patients, no significant improvement in consonant recognition was obtained.

Adult↗

Disposition characteristics of recombinant human interleukin-11 after a bolus intravenous administration in mice.

The pharmacokinetics and disposition characteristics of recombinant human interleukin-11 (rhIL-11) after systemic administration of 10 to 1000 micrograms/kg was investigated in mice. After a bolus i.v. injection of 100 micrograms/kg of 111In-labeled rhIL-11, radioactivity disappeared rapidly from the circulation after a biexponential function. Plasma clearance profiles based on immunoreactivity and biological activity were identical to the disappearance pattern of radioactivity in the early phase after injection. In the range of 10 to 100 micrograms/kg, pharmacokinetic parameter estimates such as the T1/2 alpha and total body clearance were almost constant, suggesting that pharmacokinetics of rhIL-11 were linear within this dose range. 111In-labeled rhIL-11 distributed mainly to the kidney and liver; within 10 min, 40 and 20% of the dose, respectively, accumulated. On the other hand, the urinary excretion ratio was very small (ca., 1% of the dose), suggesting that rhIL-11 was cleared rapidly by glomeruler filtration followed by efficient tubular reabsorption. Pharmacokinetic analysis of the tissue distribution data demonstrated large kidney and hepatic uptake clearances. At the highest dose (1000 micrograms/kg), total body clearance significantly decreased, due primarily to saturation of hepatic uptake. These findings will provide useful information for the development of rhIL-11.

Animals↗

[Alcohol-induced hypertriglyceridemia in subjects with decreased lipoprotein lipase--improvement after cessation of alcohol intake].

We systematically investigated the effect of lipoprotein lipase (LPL) and alcohol intake on the development of primary type IV hyperlipoproteinemia which is manifested as a moderate increase in serum triglycerides as a consequence of an elevated very low density lipoprotein concentration and a normal level of serum cholesterol. Twenty six type IV hyperlipoproteinemic and 28 normolipidemic males underwent measurement of the immunoreactive LPL mass in postheparin plasma (30 unit of heparin/kg of body weight) and were interviewed as to their alcohol consumption. They were divided into 4 groups, with a LPL mass of 150ng/ml (20 percentile of the normal range) and an alcohol intake of 33g/day as the borderlines. All subjects with LPL mass less than 150ng/ml and alcohol intake of more than 33g/day were prone to manifest type IV hyperlipoproteinemia. One of the subjects in this group showed a recovery to normolipidemic state after cessation of alcohol intake. Subject whose LPL mass value was more than 180ng/ml (50 percentile of the normal range) were not susceptible to type IV hyperlipoproteinemia even though they drank alcohol more than 33g/day.

Alcohol Drinking↗

[An autopsy-verified case of Creutzfeldt-Jakob disease with codon 129 polymorphism and codon 180 point mutation].

An autopsied case of Creutzfeldt-Jakob disease is reported. A 79-year-old Japanese female showed extrapyramidal sign (resting tremor, and rigidity) and dementia. She developed myoclonus and became akinetic within one year from the onset, and then died of pneumonia at age of 81. None of the members of her family had neuromuscular disorders. CT and MRI studies revealed progressive brain atrophy. Consecutive study of EEG did not reveal periodic synchronous discharges (PSD). Codon 129 polymorphism (Met/Val) and codon 180 point mutation (Val/Ile) were detected. The autopsy revealed spongiform change of cerebral cortex and negative Kuru plaques, confirming the diagnosis of Creutzfeldt-Jakob disease. Immunohistochemical study revealed weak synaptic prion staining. Western blot analysis showed positive Proteinase K resistant prion protein. Gene analysis of autopsied brain showed the same prion DNA polymorphism and mutation. The combination of codon 129 polymorphism and 180 point mutation might associate with an atypical clinical form of CJD, which shows the extrapyramidal signs at the onset, and negative PSD in EEG.

Aged↗

Results with the currently used cochlear implant.

Over the past 7 years we have implanted the Nucleus multichannel cochlear implant in 60 patients with severe hearing impairment. The postoperative speech recognition of adult postlingually deaf patients was satisfactory. Adult prelingually deaf patients exhibited poorer speech perception than postlingually deaf patients. However, some patients showed better results than expected. The prelingually deaf patients needed a longer rehabilitation period than the postlingually deaf patients. There was considerable variation in performance among the prelingually deaf patients. As for juvenile deaf patients, some showed good speech perception ability, but postoperative rehabilitation took longer. The cooperation of doctors, audiologists, speech therapists, schoolteachers, and family members was essential, and the creation of a cochlear implant center for children is desirable to obtain better rehabilitation. On the questionnaire given to the cochlear implant patients, some complained about their hearing in a noisy environment or while listening to television or music. The present cochlear implant system obviously needs further improvement.

Adolescent↗

Surgical difficulties and postoperative problems associated with cochlear implants.

Since 1987 we have implanted 60 severely hearing-impaired adults with the Nucleus Minisystem-22 cochlear implant. In most cases, the surgical procedures were performed with satisfactory results and very few postoperative problems. The complications associated with cochlear implant surgery include difficulty in drilling the ossified cochlea, electrode displacement, and insufficient insertion of the electrode. Postoperative problems include dizziness, tinnitus, facial nerve spasm, receiver-stimulator migration or extrusion, infection of the scalp flap, and facial nerve palsy. In most cases, these complaints did not develop into serious conditions.

Adult↗

Role of oxidative stress in non-genotoxic carcinogenesis with special reference to liver tumors induced by peroxisome proliferators.

Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced carcinogenesis, the "Oxidative Stress" theory has been postulated. In this review, in order to reconsider the significance of "Oxidative Stress" to POP-induced carcinogenesis, we focus on in vivo studies examining formation of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage with mutagenic potential, after treatment of rodents with POPs. Some studies clearly demonstrated that 8-OH-dG levels in the liver DNA were increased by POP-treatments. These findings suggest that "Oxidative Stress" could contribute as one factor to POP-induced carcinogenesis. Furthermore, we refer to other multiple biological changes caused by POP-treatment presumably contributing to the carcinogenic mechanisms, and consider possible roles of "Oxidative Stress" in the carcinogenesis process.

8-Hydroxy-2'-Deoxyguanosine↗

[Creatine].

Explore the source record for details and available documents.

Adolescent↗

A case of recurrent intramural uterine stromal tumor with epithelial differentiation effectively treated with oral low-dose administration of etoposide.

A 66-year-old woman was diagnosed as having myoma of the uterus and total hysterectomy with bilateral salpingo-oophorectomy was performed. The histopathological findings were puzzling, and the case was finally diagnosed as intramural uterine stromal tumor with epithelial differentiation. Three years after the operation, a firm tumor developed in the pelvic cavity. Laparotomy failed to remove the tumor and neither CAP (cyclophosphamide 500 mg, adriamycin 50 mg, CDDP 70 mg) therapy nor radiation therapy was effective. Oral administration of etoposide (25 mg/day), however, showed PR (50% decrease) as determined by CT scanning, and ultrasonography, and no metastatic lesions were found. This tumor was coincident with the endometrial stromal tumor with epithelial elements classified by Clement and Scully. The histological feature of the tumors and the efficacy of oral etoposide therapy are discussed in this study.

Administration, Oral↗

[A study on wounds caused by cats as basic materials of cat scratch disease].

Between October, 1992 and March, 1993, the incidence of bite or scratch by the cat, was surveyed by questionnaire in 1,619 peoples who were veterinarians, veterinary technicians, students and the general population (male 652, female 967). The wound rate by cat: Veterinarians, veterinary technicians, students of veterinary college, students of veterinary technician school were significantly higher than the general population. Incidence of bite or scratch in the cat owner were significantly higher than the non cat owner, and the incidence of wounds in cat owners was more than 90%. Most injuries for veterinarians were of the occupational nature. Their injuries clearly differed from those of the other groups. In our survey 33 cases were suspected to have CSD; 19 of 102 veterinarians, 4 of 45 veterinary technicians, 2 of 517 students of veterinary college, 1 of 400 students of veterinary technicians, 7 of 555 in the general population. Of the seven cases suspected for CSD among the general population, four were proven to have cat-scratches, suggesting that injuries can be prevented by clipping the cat's nails at home. However, most of the injuries suffered by veterinarians are caused by bites, prevention poses a more serious problem. It is therefore important to educate people in all fields to fully understand sanitation and zoonosis including CSD, and teach them to handle their pets appropriately.

Adolescent↗

Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu's arteritis.

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of vascular cell injury in Takayasu's arteritis. To clarify the immunological mechanisms involved, we examined the expression of a cytolytic factor, perforin in infiltrating cells of aortic tissue samples from seven patients with Takayasu's arteritis. We also examined the expression of a 65-kD heat-shock protein (HSP-65), human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 in the aortic tissue. Immunohistochemical studies showed that the infiltrating cells mainly consisted of gamma delta T lymphocytes, natural killer cells, macrophages, cytotoxic T lymphocytes and T helper cells, and that perforin was expressed in gamma delta T lymphocytes, natural killer cells, and cytotoxic T lymphocytes. In situ hybridization analysis also revealed expression of perforin mRNA in the infiltrating cells. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly onto the surface of arterial vascular cells. We also found that expression of HSP-65, human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 was strongly induced in the aortic tissue and might facilitate the recognition, adhesion and cytotoxicity of the infiltrating killer lymphocytes. These findings provide the first direct evidence that the infiltrating cells in the aortic tissue mainly consist of killer cells, and strongly suggest that these killer cells, especially gamma delta T lymphocytes, may recognize HSP-65 and play a critical role in the vascular cell injury of Takayasu's arteritis by releasing perforin.

Adult↗

Acute, subchronic and chronic toxicity studies of a synthetic antioxidant, 2,2'-methylenebis(4-methyl-6-tert-butylphenol) in rats.

General toxicity studies on 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (MBMBP) were conducted using male and female Wistar rats. LD50 values were greater than 5 g/kg BW by oral administration for both sexes. Diarrhea was observed until 5 days. In the subchronic test, rats were fed diet containing MBMBP at 0, 0.12, 0.6 or 3.0% for 12 weeks. Severe suppression of body weight gain was observed in both sexes of 0.6 and 3.0% groups. Death accompanied by hemorrhage from nasal cavity was observed in 0.6 and 3.0% males and 3.0% females. Dose-dependent toxicity to the liver in both sexes was observed in blood chemical analysis. Histopathologically, testicular atrophy and decrease of spermatogenesis were dose- and time-dependently observed in all treated males. Atrophy of ovaries was evident in 0.6 and 3.0% females. Thymus atrophy and bone marrow hypoplasia were observed in both sexes of 0.6 and 3.0% groups. In the chronic test, rats were fed diet containing MBMBP at 0, 0.01, 0.03 and 0.1% for 18 months. Body weight gain was only suppressed in both sexes receiving 0.1%. Histopathologically, testicular atrophy and decrease of spermatogenesis were apparent in 0.1% males. No neoplastic response by MBMBP administration was noted. NOAEL was concluded to be 0.03% in the diet (12.7 mg/kg BW/day for male rats and 15.1 mg/kg BW/day for female rats).

Administration, Oral↗