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Biomedical subjects

Y Hosoi

Publications and source records attributed to Y Hosoi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Radiation therapy for loco-regionally recurrent esophageal cancer after surgery.

PURPOSE: To evaluate the treatment outcome of radiation therapy for 33 loco-regionally recurrent esophageal cancer patients. METHODS: Between 1988 and 1997, 33 patients with loco-regional recurrence of esophageal cancer after curative surgery received radiation therapy at an average total dose of 61 Gy. The site of recurrence was the supraclavicular region in 14 patients, the mediastinal region in 13 patients, and both the supraclavicular and mediastinal regions in six patients. If patients had ether distant metastasis or malignant pleural effusion, they were excluded from analysis. Patients who received prophylactic postoperative irradiation were also excluded from analysis. RESULTS: The median survival period was 7 months. The survival rates at 1, 2, and 3 years were 33, 15, and 12%, respectively. In univariate analysis, patients with a short time interval between surgery and recurrence (P=0.0098) and patients with recurrence in both the supraclavicular and mediastinal regions (P=0.036) had a worse prognosis. In multivariate analysis, the time interval between surgery and recurrence (P<0.001) and age (worse prognosis in younger patients, P=0.019) were the significant prognostic factors. Complete or partial responses were observed in nine (27%) and 21 (64%) of the patients, respectively. Changes in clinical symptoms, such as dysphagia, chest pain and back pain, could be evaluated in 11 patients, and improvement in symptoms was obtained in eight (73%) patients. CONCLUSIONS: The prognosis of patients who received radiation therapy for postoperative loco-regional recurrence of esophageal cancer is poor. However, there is symptomatic relief in a significant proportion of such patients, and long-term survival is possible in some patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Involvement of c-Jun NH2-terminal kinase-1 in heat-induced apoptotic cell death of human monoblastic leukaemia U937 cells.

PURPOSE: To determine the involvement of c-Jun NH(2)-terminal kinase-1 (JNK1) and possibly of HSP27 in heat-induced apoptosis of human monoblastic leukaemia U937 cells. MATERIALS AND METHODS: Dominant negative JNK1 (APF), in which the phosphorylation sites Thr-Pro-Tyr were changed to Ala-Pro-Phe, was overexpressed in U937 cells. Cell viability and DNA fragmentation were analysed by the erythrosin-B dye exclusion test and by agarose gel electrophoresis, respectively. Expression of activated caspase-9, phosphorylated JNK1, JNK2, p38 and HSP27 was examined by Western blotting. JNK1 kinase assay was also performed using c-Jun as a substrate. RESULTS: Loss of viability, activated cleavage form of caspase-9 and DNA fragmentation were rapid in U937 cells after 44 degrees C hyperthermia, while overexpression of dominant negative JNK1 interfered with phosphorylation or activation of JNK1 without affecting that of JNK2 or p38/SAPK, and apparently delayed or reduced cleavage and activation of caspase-9, DNA fragmentation and cell death. Heat-induced phosphorylation of HSP27, observed in parental U937 cells, was suppressed and only slightly detectable in jnk1 mutant cells. CONCLUSIONS: Prolonged phosphorylation or activation of JNK1 was considered important for heat-induced apoptosis and JNK1 may control the process possibly through phosphorylation of HSP27 and caspase-9 activation in U937 cells.

Apoptosis↗
PubMed2001

Radiological findings of accidental radiation injury of the fingers: a case report.

This case report describes the medical follow-up of a 46-y-old (at the time of exposure) man who in 1971 accidentally exposed the fingers of his right hand to gamma-ray radiation from an iridium source that was used for nondestructive testing [estimated radiation dose: 26 Gy to 90 Gy (2,600 rad to 9,000 rad)]. No prominent acute injury was detected except for leukocytopenia (800 mm(-3)) and thrombocytopenia (15,000 mm(-3)). Three years later, the first, second, and third fingers presented repeated infection and started to develop contracture. Twenty-two years after exposure, he underwent amputation of the first and second fingers, and a toe graft was done. Radiological examinations prior to and following the operation revealed atrophic change of the finger bones and arterial injuries. Angiographic findings coincided with the region and extent of radiation injury of the fingers, which indicates that arterial damage is involved in the development of this chronic disorder.

Angiography↗
PubMed2001

Expression and regulation of type II iodothyronine deiodinase in human thyroid gland.

We have studied the expression of type II iodothyronine deiodinase (DII) in human thyroid tumors and cultured human thyroid cells to elucidate the mechanisms involved in the regulation of DII expression in human thyroid gland. Three cases with hyperfunctioning thyroid adenoma, including a case that showed an activating mutation of G(s)alpha with a constitutive activation of cAMP production in cultured cells, and six cases with papillary thyroid carcinoma were analyzed in the present study. Free T(3) was increased, whereas free T(4) was within the normal range in all patients with hyperfunctioning thyroid adenoma. Thyroid tumor tissue and surrounding nontumor tissue were obtained at the time of surgery, and DII expression was compared between tumor tissue and nontumor tissue in each case. Northern analysis demonstrated the presence of DII messenger RNA (mRNA) approximately 7.5 kb in size in all of the tumor and nontumor tissues. DII mRNA and DII activity in hyperfunctioning thyroid adenoma were significantly increased compared with those in nontumor tissue in each case. In contrast, DII mRNA and DII activity in papillary thyroid carcinoma were decreased compared with those in nontumor tissue in each case. DII mRNA and DII activity in cultured human thyroid cells were significantly stimulated by TSH in a dose-dependent manner. The promoter activity of the human DII gene including the complete cAMP response element, transfected to cultured human thyroid cells, was stimulated by (Bu)(2)cAMP. In summary, these results suggest that DII expression in human thyroid gland is regulated at the transcriptional level through the TSH receptor-G(s)alpha-cAMP regulatory cascade, which may be related to the increase in circulating T(3) level in patients with Graves' disease and hyperfunctioning thyroid adenoma.

Adenoma↗
PubMed2000

Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation.

We report the p35 and p60 forms of XRCC4 protein, appearing in human leukemia MOLT-4 or U937 cells following X-irradiation or hyperthermia. p35 appeared in conjunction with the cleavage of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and the fragmentation of internucleosomal DNA, and was suppressed by Ac-DEVD-CHO. p35 was also produced in vitro by treating MOLT-4 cell lysate with recombinant caspases, suggesting that p35 was a caspase-cleaved fragment of XRCC4 in apoptotic cell death. p60 was sensitive to treatment with phosphatase or wortmannin and was undetectable in M059J cells deficient in DNA-PKcs. However, p60 was found in ataxia-telangiectasia cells after irradiation. These results indicated p60 as a phosphorylated form of XRCC4, requiring DNA-PKcs but not ataxia-telangiectasia mutated (ATM).

Androstadienes↗
PubMed2000

Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse.

Accumulation of mutation has long been hypothesized to be a cause of aging and contribute to many of the degenerative diseases, which appear in the senescent phase of life. To test this hypothesis, age-associated changes in spontaneous mutation in different tissues of the body as well as the molecular nature of such changes should be examined. This kind of approach has become feasible only lately with a development of new transgenic mice suitable for mutation assay. Here, using one of these transgenic mice harboring lacZ gene, we have shown that the age-associated increase in spontaneous mutant frequency is common to all tissues examined; spleen, liver, heart, brain, skin and testis, while the rates of increase in mutant frequency differed among the tissues. DNA sequencing of the 496 lacZ mutants recovered from the tissues of newborn and old mice has revealed that spectra of mutations are similar at the two age points with G:C to A:T transition at CpG site being a predominant type of mutation. Furthermore, some mutations in old tissues are complex type and not found in tissues of newborn mice. These results suggest that similar mechanisms may be operating for mutation induction in fetal and postnatal aging process. In addition, the appearance of complex types of mutations in the old tissues suggests a unique cause for these mutations in aging tissues.

Aging↗
PubMed2000

Radiation-induced mutations in the spleen and brain of lacZ transgenic mice.

PURPOSE: To study the dose-response and molecular nature of radiation-induced mutations in the spleen and brain of lacZ transgenic mice. MATERIALS AND METHODS: Line 60 transgenic mice containing the bacterial lacZ gene in a plasmid background were used. Mutants were selected using phenyl-beta-D-galactoside. The nature of mutants was determined by sequencing DNAs of mutant lacZ genes found in control and irradiated tissues. RESULTS: X-ray irradiation at 50 and 100 Gy showed linear dose-responses for mutation induction in both tissues. The slope, however, was about twice as steep in spleen than in brain. DNA sequence analyses showed that the predominant type of mutation induced by radiation in both tissues were large deletions. CONCLUSIONS: Radiation induces mutations in spleen and brain at different efficiencies but the molecular nature of the induced mutations are similar in the two issues.

Amino Acid Sequence↗
PubMed2000

Expression of type II iodothyronine deiodinase in brain tumors.

Type II iodothyronine deiodinase (DII) messenger ribonucleic acid (mRNA) and its activity have been demonstrated in human normal brain. Although DII activity has been demonstrated in brain tumors, expression of DII mRNA has not been studied in these tumors. To investigate the mechanisms involved in the expression of DII activity in brain tumors, we studied DII mRNA and DII activity in astrocytoma (two cases), glioblastoma (three cases), and oligodendroglioma (one case). DII mRNA, the size of which was indistinguishable from that in control cerebral cortical tissue, was demonstrated in all of the brain tumors tested, although the intensity of the hybridization signal showed wide variation among the tumors. DII activity was also detected in all tumors. DII mRNA and DII activity were highest in the tissue from oligodendroglioma. A significantly positive correlation was observed between DII mRNA and DII activity in these tumors (r = 0.94; P < 0.01), suggesting that DII expression in brain tumors is regulated at the pretranslational level. The present results demonstrate, for the first time, that DII mRNA as well as DII activity are expressed in brain tumors, and that DII mRNA is significantly correlated with DII activity in those tissues.

Adult↗
PubMed2000

DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines.

We investigated the relationship between DNA-dependent protein kinase (DNA-PK) activity and radiation sensitivity using 14 esophageal cancer cell lines, TE 1-14. DNA-PK activities differed significantly among the cell lines. The highest DNA-PK activity observed in TE-8 was more than two times higher than the lowest DNA-PK activity observed in TE-5. Significant correlation was observed between DNA-PK activity and D0 (r = 0.766; P = 0.0008). Western blots analysis revealed a significant correlation between DNA-PK activity and Ku70 expression, suggesting that the regulation in DNA-PK activity was associated with Ku70 expression. The data suggest that the measurement of DNA-PK activity and/or Ku70 expression may provide a useful way to predict radiation sensitivity.

Antigens, Nuclear↗
PubMed1999

Influence of popliteal vein thrombosis on subsequent ambulatory venous function measured by near-infrared spectroscopy.

BACKGROUND: To determine the influence of the site affected by thrombi on the subsequent venous physiology, we examined patients with postthrombotic syndrome (PTS) with respect to ambulatory venous function using near-infrared spectroscopy (NIRS). METHODS: Fifty-one limbs of 45 patients, for whom more than 1 year had passed since an acute episode of deep vein thrombosis, were studied. Seventeen limbs were asymptomatic, 27 had mild symptoms (edema only), and 7 showed severe symptoms (skin changes). The mean duration of PTS was 8.2 years. All of the patients underwent a treadmill walking test with simultaneous NIRS. Deoxygenated hemoglobin was continuously measured during exercise. The ambulatory venous retention index (AVRI) obtained from the serial deoxygenated hemoglobin changes was calculated in each patient. The location of thrombi at the onset of deep vein thrombosis was identified by venography. RESULTS: The calculated AVRI was apparently related to the clinical symptoms of PTS. The limbs initially involved with popliteal vein thrombosis showed significantly higher AVRI values than those without popliteal vein thrombosis. CONCLUSIONS: The clinical severity of PTS is correlated well with the degree of venous retention during exercise. Initial involvement of the popliteal vein is an important factor determining subsequent venous hemodynamics in patients with PTS.

Adolescent↗
PubMed1999

Stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole.

We evaluated the stimulation of Chinese hamster ovary cells expressing human thyrotropin receptors (CHO-hTSHR cell) by sera of five patients with hydatidiform mole before and after the evacuation of the mole, and compared the results with serum human chorionic gonadotropin (hCG) concentrations and serum free thyroid hormones in these patients. Significantly increased CHO-hTSHR cell stimulating activities were observed in sera from untreated patients, and the activity decreased promptly after the evacuation of the mole, concomitantly with the decrease in serum hCG and free thyroid hormones. CHO-hTSHR cell stimulating activity of sera of the untreated patients significantly correlated with serum hCG. Moreover, serum hCG stimulated CHO-hTSHR cells in a dose dependent manner similar to the dose-response curve of the stimulation by purified hCG. Sera of the patients and purified hCG did not stimulate nontransfected CHO-K1 cells. However, a significant correlation was not observed between serum-free thyroid hormones and serum hCG or between serum free thyroid hormones and CHO-hTSHR cell stimulating activities in untreated patients. These results indicate that serum hCG from patients with hydatidiform mole stimulates thyroid gland by interacting with TSH receptors, and suggest that the increase in thyroid hormones in patients may depend on both the increased serum hCG and the responsiveness of their thyroid glands to hCG.

Adult↗
PubMed1999

A retrospective study of late outcome in patients with peripheral arterial occlusive disease: an association between prosthetic vascular graft and cancer death?

The authors assessed the relationship between cause of death and treatment modality in patients with peripheral arterial occlusive disease. A total of 273 patients were treated with percutaneous transluminal angioplasty, surgical reconstruction, amputation, or medical therapy. We evaluated the outcome in various patient subgroups divided by treatments with a mean follow-up of 4.9 years. Most patients died because of cardiovascular or cerebrovascular events, and cancer was the second most frequent cause of death. Furthermore, there was a significant difference in cancer deaths between patients who received prosthetic vascular grafts and those with other types of treatment (9.3% vs. 2.8%, p<0.01, odds ratio = 3.34). It is noteworthy that patients with peripheral arterial occlusive disease succumbed to cancer, especially the patients with prosthetic vascular grafts.

Aged↗
PubMed1999

Pretranslational regulation of rhythmic type II iodothyronine deiodinase expression by beta-adrenergic mechanism in the rat pineal gland.

It has been demonstrated that type II iodothyronine deiodinase is present in rat pineal gland, and the deiodinase activity markedly increases during the hours of darkness, primarily through beta-adrenergic mechanism. We have studied the relationship between pineal type II iodothyronine deiodinase messenger RNA (mRNA) and the deiodinase activity to elucidate the mechanisms involved in the nocturnal rise in pineal deiodinase activity. Northern analysis has demonstrated that type II iodothyronine deiodinase mRNA is expressed in rat pineal gland, and the mRNA markedly increases during the hours of darkness. The nocturnal increase in pineal type II iodothyronine deiodinase activity is preceded by the increase in its mRNA. Daytime isoproterenol administration resulted in a rapid increase in pineal type II iodothyronine deiodinase mRNA followed by the increase in deiodinase activity. Propranolol treatment, bilateral superior cervical ganglionectomy, or constant light exposure significantly suppressed the nocturnal rise in type II iodothyronine deiodinase mRNA as well as the deiodinase activity. Moreover, isoproterenol or (Bu)2AMP stimulated type II iodothyronine deiodinase mRNA and the deiodinase activity in cultured rat pineal glands. These results suggest that the rhythmic change in pineal type II iodothyronine deiodinase activity is regulated at least in part at the pretranslational level by a beta-adrenergic mechanism transmitted through superior cervical ganglia.

Adrenergic beta-Agonists↗
PubMed1999

Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells.

T4, which is a major secretory product of the thyroid gland, needs to be converted to T3 by iodothyronine deiodinase to exert its biological activity. After the molecular cloning of human type II iodothyronine deiodinase (DII) complementary DNA, DII expression was unexpectedly detected in human skeletal muscle tissue. In the present study, we have identified DII activity and DII messenger ribonucleic acid (mRNA) in cultured human skeletal muscle cells and studied the mechanisms involved in the regulation of DII expression in those cells. All of the characteristics of the deiodinating activity in cultured human skeletal muscle cells were compatible with those of DII. Northern analysis has demonstrated that DII mRNA, approximately 7.5 kb in size, was expressed in cultured human skeletal muscle cells. DII mRNA and DII activity were rapidly increased by (Bu)2cAMP, forskolin, or beta-adrenergic agonists and were negatively regulated by thyroid hormones in cultured human skeletal muscle cells. Although interleukin-1beta and interleukin-6 did not decrease DII expression in cultured human skeletal muscle cells, tumor necrosis factor-alpha decreased DII expression in those cells in a dose-dependent manner. These data have demonstrated, for the first time, that DII activity and DII mRNA are present in cultured human skeletal muscle cells, and that the DII expression is stimulated by beta-adrenergic mechanisms through a cAMP-mediated pathway and is negatively regulated by thyroid hormones and tumor necrosis factor-alpha.

Adrenergic beta-Agonists↗
PubMed1999

Molecular nature of mutations induced by a high dose of x-rays in spleen, liver, and brain of the lacZ-transgenic mouse.

DNA sequences of 103 spontaneous mutants and 102 X-ray-induced mutants of the lacZ transgene from spleen, liver, and brain of the MutaMouse were examined and compared to elucidate characteristics of radiation-induced mutations in vivo. The radiation-induced mutants were isolated from genomic DNA of each tissue collected at 3.5 days after 200 Gy of whole body irradiation. Base substitution was predominant (80% or more) in nonirradiated tissues, while deletion was prevalent (about 55%) in irradiated tissues. The other types of mutation appeared at similar frequencies in both control and irradiated tissues. The size of the deletions was smaller than 438 nucleotides, with a predominance of one basepair deletions in both control and irradiated tissues. A close look at the nucleotides at the deletion endpoints revealed that many of the radiation-induced deletions did not have repeated sequences at the break point termini, whereas all deletions found in unirradiated tissues showed one or more bases of repeated sequences at the termini. Further, eight complex-type deletion mutations were found only in irradiated tissues. Comparison among the three types irradiated tissue did not reveal any tissue-specificity. The data indicate that the molecular nature of mutations induced in tissues with ionizing radiation is different from that of spontaneous mutations.

Animals↗
PubMed1999

Comparison of near-infrared spectroscopy with air plethysmography in detection of deep vein thrombosis.

BACKGROUND: As a noninvasive screening test, air plethysmography (APG) is a reliable and frequently used modality in the detection of deep vein thrombosis (DVT). Although APG is highly sensitive for the diagnosis of proximal DVT, its sensitivity for identifying calf DVT is poor. Near-infrared spectroscopy (NIRS) is a new modality which can be used to evaluate venous retention during walking. The purpose of this study was to investigate the diagnostic value of NIRS for the detection of DVT, particularly isolated calf DVT, in comparison with APG. METHODS: Fifty limbs of 39 consecutive patients with clinically suspected DVT were studied. All patients were examined by venography and APG. Patients also underwent a treadmill-walking test with simultaneous NIRS. Deoxygenated hemoglobin was continuously measured by NIRS during exercise. The ambulatory venous retention index obtained from serial DeoHb changes was calculated in each patient. RESULTS: Venography demonstrated DVT in 35 limbs, confined to the calf in 9 limbs, and with the involvement of a proximal deep vein with thrombi in 26. The overall sensitivity of NIRS and APG was 97% (34/35) and 80% (28/35), respectively. NIRS was more sensitive than APG for detecting isolated calf DVT (89% [8/9] and 22% [2/9], respectively), while both tests identified proximal DVT in all limbs. CONCLUSIONS: NIRS is a highly sensitive method for the diagnosis of haemodynamically significant DVT. NIRS may become a useful screening test because of its reliability in detecting calf vein thrombi that cannot be identified by APG.

Female↗
PubMed1998

A phosphatidylinositol 3-kinase inhibitor wortmannin induces radioresistant DNA synthesis and sensitizes cells to bleomycin and ionizing radiation.

ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) have been shown to have sequences homologous to the catalytic domains of mammalian phosphatidylinositol 3-kinase (PI3-kinase). In order to determine the contribution of ATM and DNA-PKcs to the increased sensitivity of cells to DNA-damaging agents observed in the presence of PI3-kinase inhibitors, we examined the effects of a PI3-kinase inhibitor, wortmannin, on cellular sensitivity to bleomycin (BLM), mitomycin C (MMC), X-irradiation and ultraviolet (UV)-irradiation using 2 human tumor cell lines (T98G and A172), a human fibroblast cell line (LM217), an ataxia telangiectasia (AT) cell line (AT3BISV), a scid murine cell line (SCF) and a control murine cell line (CBF). Wortmannin sensitized all of the cells, including AT3BISV and SCF, to BLM and X-irradiation, but not to MMC or UV-irradiation. Hypersensitivity to BLM and X-irradiation and normal sensitivity to MMC and UV-irradiation are characteristic phenotypes of both AT and scid mice. DNA-dependent protein kinase (DNA-PK) activity was suppressed by wortmannin to 45-65% of the control values in all of the cells except SCF, in which DNA-PK activity was not detected. Wortmannin also induced radioresistant DNA synthesis, which is a cellular phenotype of AT, in T98G and SCF cells, but did not change the DNA synthesis rates after X-irradiation in AT3BISV. Our data suggest that wortmannin decreases the activities of both the ATM protein and DNA-PK, indicating that it might be of use as a sensitizing agent for radiotherapy and chemotherapy.

Androstadienes↗