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Biomedical subjects

Y Hosoi

Publications and source records attributed to Y Hosoi.

At least 55 records · Page 3Linked to original sources

Primary culture of cells from hyperfunctioning thyroid adenoma with an activating mutation of G alphas.

We analyzed cultured cells from hyperfunctioning thyroid adenoma and its surrounding thyroid tissue from a Japanese woman and determined the nucleotide sequences of genes encoding the alpha subunit of the stimulatory G-protein 1 (G alphas) and thyrotropin (TSH) receptor in its tumor tissue. Primary culture of cells from hyperfunctioning thyroid adenoma and its surrounding thyroid tissue revealed that cAMP production was constitutively activated while intracellular Ca2+ concentration was suppressed both at the basal level and in the response to TSH stimulation in the cells from tumor tissue compared with those from non-tumor tissue. Nucleotide sequence analysis demonstrated the somatic missense mutation at codon 201 (CGT(Arg)-CAT(His)) of G alphas gene in tumor tissue but not in its surrounding tissue. No mutation was observed in the transmembrane region of TSH receptor. These results suggest that cAMP regulatory cascade is constitutively activated while phospholipase C-Ca2+ signaling cascade is suppressed in hyperfunctioning thyroid adenoma with an activating mutation of G alphas gene in the present case.

Adenoma↗

Sensitization of cells to ionizing radiation by chlorin e6Na.

We have investigated whether a hydrophilic photosensitizer, chlorin e6Na (Ce6Na), can sensitize cells to ionizing radiation. When V79-1 cells were pretreated with Ce6Na for 2 hr before receiving a dose of 2-14 Gy of irradiation, the cells became sensitive to X-irradiation. The sensitizing effect of Ce6Na depended on the dose of Ce6Na. The sensitizing effect also depended on the length of the treatment period before X-irradiation up to 4 hr, but not on the length of a treatment period after X-irradiation. Intracellular concentrations of Ce6Na were increased linearly after incubation with Ce6Na for periods of up to 4 h. The dose-modifying factor calculated from the survival curve was 1.25.

Animals↗

Northern analysis of type II iodothyronine deiodinase mRNA in rat Harderian gland.

It has been known that type II iodothyronine deiodinase activity is present in rat Harderian gland and the activity is significantly increased by isoproterenol administration. We have performed Northern analyses to study whether the transcript for type II iodothyronine deiodinase is expressed in rat Harderian gland and whether the isoproterenol stimulation of type II iodothyronine deiodinase activity in rat Harderian gland is due to the change in its mRNA level. Northern analyses have demonstrated that type II iodothyronine deiodinase mRNA, approximately 7.5 kb in size, is expressed in rat Harderian gland, and the mRNA levels as well as the deiodinase activities are greater in hypothyroid rats than those in euthyroid rats. Type II iodothyronine deiodinase mRNA levels and the deiodinase activities in Harderian gland were increased by isoproterenol administration, and the increase in the mRNA levels preceded that in the deiodinase activities. These results indicate that 7.5 kb transcript for type II iodothyronine deiodinase is expressed in rat Harderian gland and beta-adrenergic stimulation of type II iodothyronine deiodinase activity is due at least in part to the increase in its mRNA level.

Actins↗

[Lack of evidence that inducible nitric oxide synthase participates in the development of ischemic brain damage].

We have already reported that the concentration of nitric oxide (NO) increases during and after cerebral ischemia and a selective inhibitor of neuronal NO synthase (nNOS) suppresses this increase and subsequently mitigates brain damage in rats. Although the selective inhibition of nNOS is a promising pharmacological strategy for the treatment of stroke, the role of inducible NOS (iNOS) remains to be clarified. Toward this end, we investigated temporal alterations in iNOS mRNA by the RT-PCR method in a rat model of middle cerebral artery (MCA) occlusion. We found that iNOS mRNA in the ischemic hemisphere began to increase at 3 hr and reached the maximum level at 24 hr of reperfusion following 3 hr of MCA occlusion. However, quantitative analysis revealed that no significant difference existed between 6 hr or 24 hr reperfusion group and their respective time-matched sham operation group. In addition, neither Western blotting nor immunocytochemical study disclosed an apparent induction of iNOS at any time points examined. Similar results were obtained at 24 hr of permanent MCA occlusion. Taken together, these data indicate that iNOS induction during and after MCA occlusion may be not a critical event for the development of infarction caused by ischemia itself.

Animals↗

Expression and nocturnal increase of type II iodothyronine deiodinase mRNA in rat pineal gland.

It has been demonstrated that thyroxine deiodinating activity is present in rat pineal gland, and its activity increases significantly during the night time. We have studied whether mRNA for type II iodothyronine deiodinase is expressed in rat pineal gland and whether the nocturnal rise of pineal T4 deiodinating activity is due to the change in type II iodothyronine deiodinase mRNA level. Reverse transcription-polymerase chain reaction amplification and Northern blot analyses have demonstrated that type II iodothyronine deiodinase mRNA is expressed in rat pineal gland and its mRNA level increases markedly at midnight. These results suggest that the nocturnal rise in pineal T4 deiodinating activity is due to the change in type II iodothyronine deiodinase mRNA level.

Animals↗

Effect of combination treatment of 15 cGy total body irradiation and OK-432 on spontaneous lung metastasis and mitogenic response of splenocytes in mice.

We investigated whether the combination treatment of 15 cGy total body irradiation (TBI) and a streptococcal preparation, OK-432, synergistically suppresses spontaneous lung metastasis and augments phytohemagglutinin (PHA) and concanavalin A (Con A) responses of splenocytes in WHT/Ht mice. TBI with 15 cGy was carried out 20 days after subcutaneous injection of squamous cell carcinoma cells into a hind leg. Lung colony number was counted 40 days after tumor injection. For PHA and Con A responses, mice were killed 4 hr after 15 cGy TBI. The combination treatment of 15 cGy TBI and OK-432 was most effective when OK-432 was administered 2 days before 15 cGy TBI. The combination treatment decreased the lung colony number to 29.9% of the control number. OK-432 slightly increased the PHA and Con A responses, and 15 cGy TBI did not increase them. However, when these two were combined, the PHA and Con A responses were significantly increased to 393% and 278% of the control levels, respectively. It was suggested that TBI and OK-432 acted synergistically in suppressing the lung metastasis and mitogenic response of splenocytes.

Animals↗

A new method for the assessment of venous insufficiency in primary varicose veins using near-infrared spectroscopy.

PURPOSE: Patients with chronic venous insufficiency (CVI) were evaluated from the aspect of ambulatory venous function using near-infrared spectroscopy (NIRS). METHODS: Seventy-two primary varicose veins of 59 patients (varicose group) and 20 normal limbs of 13 volunteers (normal group) were studied. The affected limbs of the patients were divided into three groups according to the classification advocated by an International Consensus Committee in 1995: mild CVI with class 2 or 3 (50 limbs); moderate CVI with class 4 (11 limbs); and severe CVI with class 5 or 6 (11 limbs). All of the patients underwent a treadmill walking test, during which NIRS was applied. Oxygenated hemoglobin (OxyHb) and deoxygenated hemoglobin (DeoHb) were continuously measured by NIRS during exercise. The ambulatory venous retention index (AVRI) obtained from serial changes in DeoHb was assessed comparatively in the four groups (normal and mild to severe CVI). In addition, 19 limbs in 13 patients were evaluated with air plethysmography for comparison with the data obtained by NIRS. RESULTS: Two distinct patterns of DeoHb change were observed. During exercise, the DeoHb level decreased in the normal group as a result of calf muscle contraction, whereas in the varicose group the DeoHb level rose because of an apparent venous reflux into the calf muscles. AVRI studies demonstrated a significant difference (p < 0.0001) among groups. Although there was no apparent relationship between AVRI and ejection fraction, AVRI showed a significant correlation with the venous filling index (r = 0.61) and a weak correlation with the residual volume fraction (r = 0.41). CONCLUSION: NIRS is useful for accurately assessing ambulatory venous dysfunction in patients with primary varicose veins.

Adult↗

Decreased pulmonary perfusion in hypersensitivity pneumonitis caused by Shiitake mushroom spores.

Hypersensitivity pneumonitis is an occupational hazard of mushroom workers. We describe a patient with severe hypersensitivity pneumonitis caused by spores of the Shiitake mushroom (Lentinus edodes) who showed a marked decrease in pulmonary perfusion, as demonstrated by pulmonary scintigraphy. This patient was treated successfully with prednisolone. These results suggest that pulmonary vasculitis may be associated with patients with hypersensitivity pneumonitis, and that steroid therapy may be clinically useful in treatment.

Alveolitis, Extrinsic Allergic↗

Single dose radiocurability of four murine solid tumors and a predictive assay for the curability in situ.

Correlations between radiocurability and kinetic parameters were investigated in four transplantable tumor types in WHT/Ht mice. The radiation dose to achieve 50% tumor control at 120 days after irradiation, i.e., TCD50/120, was 30 Gy for squamous cell carcinoma H, 32 Gy for squamous cell carcinoma NOS, 46 Gy for rhabdomyosarcoma KAS, and 63 Gy for fibrosarcoma YAS. The tumor cell kinetic parameters investigated were specific growth delay, volume doubling time, 125I-iododeoxyuridine (IUdR) uptake rate, and specific cell loss rate. The specific cell loss rate was defined as the ratio of cell loss rate in non-irradiated tumors to the rate in irradiated tumors, and was obtained by measuring the retention rate of radioactivity in the tumors. No correlations were found between specific growth delay, volume doubling time, 125I-IUdR uptake rate, and TCD50. However, the specific cell loss rate correlated with the TCD50. Therefore, the 125I-IUdR labeling method may be useful as an in situ predictive assay for tumor radiocurability.

Animals↗

X-ray- and ultraviolet-radiation-induced mutations in Muta mouse.

To evaluate the usefulness of the transgenic Muta mouse for investigating radiation-induced mutations in vivo, we have examined the effects of whole-body X irradiation and compared them to the effects of ultraviolet light. The spontaneous mutation frequencies in young adults were about 7 x 10(-5) in the spleen, liver and skin. The mutation frequencies 1 week after a lethal dose of X radiation (8 Gy) were 3.2, 2.6 and 2.7 times the spontaneous levels in the spleen, liver and skin, respectively. When the skin was irradiated with 10 kJ m-2 of UVB, the mutation frequency increased about 6 times. The mutation frequencies induced by an acute dose of 4 Gy or by a fractionated dose of 11.7 Gy (0.15 Gy x 78 times, 3 times/week) in the spleen and liver were less than 2-fold the spontaneous levels at 16 weeks after irradiation. A comparison of X and UV radiation was also conducted with cultured cells derived from the mouse embryo. UVC of 5 J m-2 raised the mutation frequency to 15 times that of unirradiated cells, while 10 Gy X rays raised it 2.6 times. The findings indicate that the Muta mouse is less sensitive to X-ray-induced mutation than UV-induced mutation.

Animals↗

[Effects of combination chemoradiotherapy with daily low-dose CDDP for esophageal cancer--results of a randomized trial].

Between 1994 and 1996, 24 patients with esophageal carcinoma were entered in a randomized clinical trial comparing radiotherapy (RT) only (arm A) versus RT and a daily low dose of CDDP (5 mg/m2) (arm B). For arm B group, CDDP was injected within 30 min after irradiation. All patients were irradiated with a total dose of 60 Gy /30fr. at first, and some patients were boosted. An overall response rate of 75.0% (complete response rate of 25.0%) was observed in arm A and 91.7% (complete response rate of 16.7%) in arm B, respectively. The survival rate at 1 year was 23.8% in arm A and 40.0% in arm B. Median survival time was 7 months in arm A and 9 months in arm B. Toxicity was acceptable and no significant difference was noted between arm A and arm B.

Aged↗

Thymic hyperplasia in patients with Graves' disease. Identification of thyrotropin receptors in human thymus.

Thymic size and density were studied in 23 untreated patients with Graves' disease and 38 control subjects using computed tomography. Both thymic size and density were higher in untreated patients with Graves' disease than in control subjects in the age-matched group. After treatment with antithyroid drugs, both thymic size and density were significantly reduced, with a concomitant decrease in thyrotropin receptor antibodies. PCR of human thymic cDNA using primers for human thyrotropin receptor amplified a fragment in a size expected for the receptor, and its nucleotide sequence was identical to human thyrotropin receptor cDNA in the thyroid. Northern blot analysis of human thymic poly(A)+ RNA demonstrated the presence of the full length form of thyrotropin receptor mRNA. Western blot analysis of human thymic membrane using anti-thyrotropin receptor peptide antibodies demonstrated a band of 100 kD that was also observed in the thyroid membrane. Immunohistochemistry of thymic tissue using mouse antihuman thyrotropin receptor monoclonal antibodies demonstrated the immunostaining of epithelial cells. These results indicate that thymic hyperplasia is apparently associated with Graves' disease and suggest that thymic thyrotropin receptor may act as an autoantigen that may be involved in the pathophysiology of development of Graves' disease.

Adult↗

[Trial of bladder sparing for patients with invasive bladder cancer by transurethral resection and intra-arterial chemotherapy].

BACKGROUND: We reviewed our experience with bladder conservative treatment for invasive bladder cancer in 20 patients to investigate which type of tumor was suitable for organ conservation. METHODS: We performed radical transurethral resection with dissection to deep layer of the muscle plus intra-arterial chemoinfusion of the cis-platinum at a dose of 80-100 mg/body twice at least, and the recurrent tumor was treated by the same procedure. There were 13 cases of stage T2 and 7 cases of stage T3a. All patients were pathologically diagnosed transitional cell carcinoma with 9 cases of grade 2 and 11 cases of grade 3. RESULTS: With a follow-up of 36 months (range 18 to 82), 15 (75%) of 20 patients were survived and 10 (50%) of 20 patients were free of tumor. Of 5 patients with residual or recurrent tumor, 2 patient underwent cystectomy and the others were required transurethral resection. Of 5 patients died, 4 patients died of cancer all with distant metastasis (lung meta: 2 cases, liver meta: 2 cases). In reference to tumor characteristics, all 4 patients had over 3 cm diameter tumors with non-papillary surface and 3 of 4 patients had invasive tumors extended to bladder neck and prostatic urethra. Of 15 patients alive, 7 (47%) patients had non-papillary tumors, 9 (60%) had grade 3 tumors, 5 (33%) had T3a tumors, but invasion of the prostate urethra was recognized in only 3 patients (20%). CONCLUSION: We had possibility of doing organ prevention therapy for the patients with invasive bladder cancer, even though it was non-papillary or grade 3 tumor. On the other hand, it was thought that a conservative approach should not be considered in patients with large non-papillary tumors that extended to bladder neck and prostatic urethra.

Adult↗

[Hemodynamic study for the assessment of atherosclerotic occlusive disease].

Of all modalities used for the assessment of the severity of ischemic limbs none has proved to be more simple, reliable and reproducible than Doppler ultrasonography. The critical level that endangers the leg in patients with arteriosclerosis obliterans will be defined around 0.3 of ankle brahcial index by Doppler pressure measurement. Concerning the evaluation of the severity of intermittent claudication Doppler study may provide some standards to predict the state of muscle ischemia after exercise from the value measured at resting state. Near infrared spectroscopy is capable of direct continuous monitoring for the change of the state of oxygenated haemoglobin and deoxygenated one in the ischemic calf muscle during exercise. NIRS can be a new modality to asses the muscle ischemia during exercise in ASO patients. The objective diagnostic techniques should be reproducible, capable of intrinsic standardization, easily employed, relatively rapid to perform, adaptable to current recording equipment, and applicable to studies during and after exercise.

Arteriosclerosis Obliterans↗

Enhanced proliferation and IL-1 production of mouse splenocytes by low-dose whole-body X-irradiation.

To elucidate the stimulative effect of low-dose whole-body X-irradiation on the immune system, in vivo, we studied its effects on some immune functions of mouse splenocytes. Results show that Concanavalin A (Con A) and phytohemagglutinin (PHA) responses of splenocytes were significantly increased by irradiation of 2.5 cGy and 5 cGy, whereas lipopolysaccharide (LPS) response was significantly depressed by irradiation of 5 cGy. By irradiation of 2.5 cGy, Con A response was significantly accelerated at each concentration of Con A, but the optimum concentration of Con A shifted to a higher value of 4 micrograms/ml from 2 micrograms/ml in the control group. When blood plasma obtained from 2.5 cGy irradiated mice was added into the medium at 0.005-1%, the Con A response of splenocytes in another un-irradiated mouse was significantly accelerated over that where the plasma added came from the sham-irradiated control mice. Furthermore, 2.5 cGy whole-body irradiation also enhanced the biological activity of intracellular interleukin-1 (IL-1) of LPS-stimulated splenocytes.

Animals↗

Decreased incidence of thymic lymphoma in AKR mice as a result of chronic, fractionated low-dose total-body X irradiation.

We have investigated whether low-dose total-body X irradiation could suppress the development of lymphoma in AKR mice. Male mice were irradiated with 5 cGy three times a week or 15 cGy two times a week from 11 weeks of age for 40 weeks. The incidences of lymphoma were 80.5% in sham-irradiated mice, 67.5% in mice irradiated with 5 cGy three times a week and 48.6% in mice irradiated with 15 cGy twice a week. Incidence of lymphoma was significantly reduced by irradiation with 15 cGy twice a week (P = 0.006). The mean survival time was significantly prolonged from 283 +/- 3 days in control mice to 316 +/- 10 days in mice irradiated with 15 cGy twice a week (P = 0.008) and to 309 +/- 14 days in mice irradiated with 5 cGy three times a week (P = 0.040). Because about 80% of male AKR mice die of lymphoma, it is likely that the prolonged life span observed in the irradiated mice is due to the reduced incidence of lymphoma.

Animals↗

An objective evaluation of muscle oxygen content in claudicants receiving drug therapy.

The effects of medical treatment with a prostaglandin I2 analog (beraprost sodium) were evaluated in 19 of 120 cases studied with near-infrared spectroscopy (NIRS) from January 1993 to September 1994. The relative changes in oxygenated (Oxy) and deoxygenated (Deo) hemoglobin (Hb) in the calf muscle were measured during a treadmill walking test and the subsequent recovery period. After medical treatment in these 19 cases, recovery time of OxyHb decreased in 10 cases, increased in 7 cases and remained unchanged in two cases. Pressure studies did not facilitate the assessment of changes in the severity of claudication. Our results demonstrate that NIRS can provide objective information regarding the effects of medical therapy in claudicants.

Aged↗