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H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 181 records · Page 10Linked to original sources
PubMed1995

[Pharmacokinetics of 123I-iomazenil, a benzodiazepine receptor seeker].

The biodistribution, metabolism and excretion of 123I-iomazenil have been studied in rats, rabbits and humans following i.v. administration. In all the species, 123I-iomazenil was rapidly metabolized and more than 90% of the administrated radioactivity was excreted within the first 24 hr. Dominant metabolites were acid metabolite (R-COOH), glucuronide of the acid (R-COOH-Glc) and free iodide (I-) in rats and humans. On the other hand, R-COOH, oxidative metabolite (R'-CH2COOH) and I- were found in rabbits. Thus, the possible metabolic pathways of iomazenil were hydrolysis, oxidation, conjugation and deiodination. The radioactivity was excreted into both urine and feces in rats, while primary route of excretion in rabbits and humans was from the kidneys. At 3 hr after injection, more than 97% of the radioactivity in rat brain was found in the form of the parent compound. This result indicates that metabolites of 123I-iomazenil do not cross the blood-brain barrier.

Animals↗
PubMed1994

[A five-year follow-up of two different 131I treatment methods for Graves' disease and the factors affecting the outcome].

We employed two different methods of 131I treatment for Graves' disease in 285 patients and compared the results between the two. (We also analyzed the factors affecting the treatment outcome.) A single dose of 131I adjusted to the patients' thyroid weight was administered to 180 patients in group 1, while a relatively lower dose of 131I (approximately 30Gy) was given repeatedly to 105 patients in group 2. A 5-year follow-up showed that in group 1, 34% of the patients were euthyroid, 11% hypothyroid, 11% subclinical hypothyroid and 44% still remained hyperthyroid. In group 2, 43% of the patients were euthyroid, 5% hypothyroid, 35% subclinical hypothyroid and 17% hyperthyroid. The factors affecting the outcome of the treatment in group 1 patients were their thyroid weight, the duration of the disease and TRAb levels. No significant correlation was observed between the efficacy of 131I treatment and the patients' sex, age, 24hr 131I-uptake, effective half life of administered 131I or titers of antithyroid antibodies. We conclude that the repeated low dose administration of 131I provides the best outcome in a 5-year follow-up. However, we suggest that an adjusted dose of 131I in relation to the patients' thyroid weight should be employed to obtain a faster therapeutic response.

Adult↗
PubMed1994

Protection by prosaposin against ischemia-induced learning disability and neuronal loss.

Prosaposin, the protein precursor of saposins A, B, C, and D which activate sphingolipid hydrolases, is abundant in several brain regions including the hippocampus. We infused prosaposin continuously for 7 days into the lateral ventricle of gerbils starting 3 hours before 3-min of forebrain ischemia. Using the step-down passive avoidance task, we demonstrated that ischemia-induced learning disability is prevented almost completely by prosaposin infusion. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 field of the hippocampus as well as synapses within the strata moleculare, lacunosum/radiatum and oriens of the field were significantly more numerous in gerbils infused with prosaposin infusion than in those receiving saline infusion. These findings suggest that prosaposin possesses neurotrotrophic activity to protect hippocampal CA1 neurons from lethal ischemic damage.

Animals↗
PubMed1994

Effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on N-nitrosobis(2-oxopropyl)amine (BOP)-initiated carcinogenesis in hamsters.

The effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) administration during the post-initiation phase of carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian golden hamsters were given a single s.c. injection of BOP at a dose of 10 mg/kg and then administered 3 ppm (H) or 1 ppm (L) NNK in their drinking water for the following 87 weeks. Additional groups of animals received the BOP injection alone, or only the 3 or 1 ppm NNK treatments as BOP-negative controls. At week 88 of the experiment, all surviving animals were sacrificed and development of proliferative lesions was assessed histopathologically. The results showed no statistically significant influence on pancreatic adenocarcinomas or dysplastic lesions, although the incidence and the number of atypical hyperplasias in the pancreas head in the BOP/NNK (L) group was significantly increased as compared to BOP alone group values (P < 0.05). Similarly, the NNK treatments did not affect the incidences or multiplicities of neoplastic or hyperplastic lesions in the endocrine pancreas, lung, liver or kidney. Thus, the present experiment demonstrates that the tobacco-specific carcinogen NNK does not enhance BOP-induced hamster tumorigenesis when given in the promotion phase.

Animals↗
PubMed1994

[Studies on patients with a discrepancy between free thyroid hormones and thyrotropin values].

Thyroid function has been almost exactly evaluated by the measurement of serum free thyroxine (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) concentrations. However, we occasionally experience patients who show a discrepancy between free thyroid hormones and TSH values, and the assessment of thyroid function in such cases is extremely difficult. Thyroid hormone autoantibodies (THAA) interfere with radioimmunoassay (RIA) of FT4 and FT3 by giving inappropriate values. To investigate the incidence of THAA, immune precipitation of patients' sera after incubation with labelled T4 (125I-T4) or T3 (125I-T3) analog tracer was done in 394 patients with thyroid diseases. 9 patients (2.3%) showed an increased binding of 125I-T4 or 125I-T3 analog. Heterophilic antimouse antibodies in a patient's serum (human antimouse immunoglobulin antibodies: HAMA) can interfere in two-site immunometric assays (IMA) using mouse monoclonal antibodies and result in spuriously increased serum TSH concentrations. Manufacturers now customarily add nonspecific mouse immunoglobulins into their assay kits to absorb HAMA and prevent such interference. This approach may not always be enough to prevent HAMA interference in all samples. In 14 thyrotoxic patients with inappropriately high TSH measured by an IMA kit, we measured the levels of TSH by the further addition of mouse serum into this kit. Their serum TSH levels were fully suppressed except for 2 patients with a syndrome of inappropriate secretion of TSH (SITSH). The presence of abnormal albumin in the serum also interferes with RIA of FT4 and FT3. We experienced a female case of Graves' disease treated with methimazole who showed an inappropriately high serum FT3 measured by an analog tracer RIA kit, whose serum FT4, FT3 and TSH were 1.31 ng/dl, 19.3 pg/ml and 1.9 mu U/ml respectively. Although the anti-T3 autoantibody was considered to be present initially, immune precipitation of her serum with 125I-T3 analog tracer gave a negative result. In order to elucidate this finding, Sephadex-G200 chromatography of her serum after incubation with 125I-T3 analog tracer was done. Radioactivity of her serum in albumin fraction was significantly higher than that of normal control serum to indicate the presence of abnormal albumin in the serum. In conclusion, to assess the thyroid function of a patient with a discrepancy between free thyroid hormones and TSH values, it is important to consider the presence of THAA, HAMA, or rarely, an abnormal albumin.

Adult↗
PubMed1994

cDNA cloning and sequence of CYP2C29 encoding P-450 MUT-2, a microsomal aldehyde oxygenase.

A cDNA clone encoding a cytochrome P-450 (P-450) isozyme was isolated from a mouse liver cDNA library. This P-450, designated CYP2C29, the first member of the mouse CYP2C subfamily to be reported, contained the complete coding region of 490 amino acid residues. The deduced amino acid sequence of CYP2C29 exhibited 83% identity with that of the rat CYP2C7 and had an N-terminal sequence identical to that of P-450 MUT-2, a microsomal aldehyde oxygenase. Two peptides, derived from BrCN cleavage of P-450 MUT-2, were also identical to the cDNA deduced protein of CYP2C29. These results indicate that CYP2C29 cDNA encodes P-450 MUT-2.

Amino Acid Sequence↗
PubMed1994

Nonspecific cross-reacting antigen 50/90 is elevated in patients with breast, lung, and colon cancer.

A total of 22 genes have been identified in the carcinoembryonic antigen (CEA) gene family. The protein products of this family are highly homologous and include CEA, biliary glycoprotein, nonspecific cross-reacting antigen 50/90 (NCA 50/90), NCA 95, and pregnancy-specific beta-glycoprotein. We used a monoclonal antibody with high affinity to develop a specific enzyme-linked immunosorbent assay (ELISA) method for NCA 50/90 in serum and plasma. Our calibrators were based on affinity-purified recombinant protein from a baculovirus expression system. No significant reactivity with purified CEA, recombinant NCA 95, or recombinant biliary glycoprotein was found by Western blot analysis or in the ELISA method. Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein. A cutoff value of 18 ng/ml was established based on the 95% value of serum and plasma from 147 healthy volunteers. Only 3 of 31 serum and plasma samples from patients with clinically inactive breast cancer were elevated above the cutoff value, but 44% of 136 samples from patients with clinically active breast cancer were positive. NCA 50/90 measurements were elevated in 7 of 25 patients with active breast cancer whose CEA and CA 15-3 values were below cutoff, and NCA 50/90 values do not correlate with CEA in breast cancer. In addition, we found sensitivities of 70, 39, and 42% for lung cancer, colon cancer, and leukemia, respectively. The sensitivity for non-small cell lung cancer was 85%, however, compared to 50% for small cell lung cancer. Serum from leukemia patients showed an overall sensitivity of 43%, but 71% (10 of 14) sera from patients with chronic myelogenous leukemia were positive compared to, for example, chronic lymphocytic leukemia where 0 of 7 sera had NCA 50/90 values above the cutoff. These studies suggest that NCA 50/90 may have clinical utility in the management of patients with a variety of cancers.

Animals↗
PubMed1994

Incidence of latent infection of Epstein-Barr virus in lung cancers--an analysis of EBER1 expression in lung cancers by in situ hybridization.

To evaluate the presence of Epstein-Barr virus (EBV) in lung cancers of Japanese patients, 81 lung cancers were examined using a highly sensitive in situ hybridization (ISH) method, employing an antisense oligonucleotide probe for EBV-encoded small nuclear RNA-1 (EBER). EBER1 expression was demonstrated in one poorly differentiated squamous cell carcinoma associated with marked lymphoid stroma (PDSCC-LS), two well differentiated adenocarcinomas, and two moderately differentiated squamous cell carcinomas, but was not detectable in other lung cancers, including small cell carcinomas. Unlike lymphoepithelioma-like undifferentiated carcinoma (LELC) of the lung, the PDSCC-LS consisted of poorly differentiated cells with distinct cell borders and nuclei with a coarse chromatin pattern and some prominent nucleoli. Most of the cancer cells expressed intense EBER1 signals. Although small to moderate numbers of cells positive for EBER1 were present in two adenocarcinomas and two squamous cell carcinomas, EBER1 signals varied in intensity and number in these four cases. Although polymerase chain reaction (PCR) and Southern blot hybridization with a 32P-labelled probe internal to the primers were conducted to detect the EBV genome in 24 lung cancers, including five EBER1-positive cases, the genome was found to be positive in the five cases with EBER1-positive staining, including the PDSCC-LS, two adenocarcinomas and two squamous cell carcinomas, but not in the other cases. This study indicates that the morphological features of EBV-associated lung cancers are not restricted to the typical LELC type.

Adenocarcinoma↗
PubMed1994

Promoting effects of ethinyl estradiol on development of renal proliferative lesions induced by N-nitrosobis (2-oxopropyl)amine in female Syrian golden hamsters.

The modulating effects of female sex hormones, ethinylestradiol and levonorgestrel, on the development of renal proliferative lesions after initiation with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Three groups of female Syrian golden hamsters, each comprising 30 animals, were given four weekly s.c. injections of BOP (10 mg/kg body weight) and then fed diet containing 1 ppm ethinylestradiol (group 1: BOP/EE), diet containing 10 ppm levonorgestrel (group 2) or basal diet (group 3) for the next 27 weeks. As hormone controls, two groups of 20 female hamsters each received diet containing 1 ppm ethynylestradiol (group 4) and 10 ppm levonorgestrel (group 5) from week 3 for 27 weeks without the prior initiation treatment. The severity of diffuse anisokarya, characterized by varied nuclear size and the incidence of dysplasias of the proximal tubular epithelia induced by BOP, were significantly increased in the BOP/EE group, indicating the promoting effects of the hormone. In the renal dysplastic lesions (small-cluster, cystic, clear-cell and acidophilic cell types), adenomas and nephroblastomas, increases in the numbers of argyrophilic proteins associated with nucleolar organizer regions (NOR) in the nucleus, suggesting a high proliferative activity, were seen in dysplasia of acidophilic cell types and adenomas. In addition, the number of bizarre NOR per nucleus was significantly higher in adenomas than in dysplasias and highest in nephroblastomas. This morphological change in NOR should therefore be a useful parameter for the diagnosis of malignancy of renal tumors.

Adenoma↗
PubMed1994

One-lung or two-lung ventilation during transthoracic oesophagectomy?

The purpose of this study was to determine the safety of one-lung ventilation (OLV) during transthoracic oesophagectomy. Changes in circulatory and respiratory variables during and after operation were compared in patients receiving OLV or conventional two-lung ventilation (TLV). Thirty patients undergoing transthoracic oesophagectomy were randomly divided into either the OLV or the TLV group. During thoracotomy, FIO2 was kept to 1.0. The PaO2 in the OLV group decreased from the prethoracotomy value of 467 +/- 84 mmHg to 227 +/- 162 mmHg during OLV. This decrease was greater than the decrease from 484 +/- 79 mmHg to 380 +/- 119 mmHg in the TLV group (P < 0.05). The shunt ratio increased in the OLV group from 20 +/- 7% to 35 +/- 13% during OLV which was greater than the increase in the TLV group (26 +/- 7% from 17 +/- 8%) (P < 0.05). Other variables and the incidence of the complications, however, were little different between the two groups during and after OLV and up to POD 3. It is concluded that OLV is as safe as TLV during oesophagectomy.

Anesthesia, Epidural↗
PubMed1994

Effects of continuous intravenous infusion of isosorbide dinitrate on development of tolerance to vasodilating action in human epicardial coronary arteries.

This study was performed to determine the effects of long-term intravenous infusion on the coronary vasodilating actions of continuous intravenous and bolus intracoronary administration of isosorbide dinitrate (ISDN). With quantitative coronary angiography, the coronary diameter and the vasodilating response to intracoronary ISDN (1 mg) at angiographically normal segments were studied before and after intravenous administration of ISDN, 10 to 60 micrograms/min for 1 hour, 2 days, or 5 days. The vasodilating effects of intravenous ISDN were 72% +/- 13%, 65% +/- 21%, and 6% +/- 11% of the response to intracoronary ISDN in the baseline study in each group. Irrespective of the duration of intravenous infusion, subsequent intracoronary ISDN dilated coronary arteries to extent similar to that observed in each baseline study. In conclusion, significant coronary vasodilating effects of intravenous ISDN were observed after a 2-day infusion, whereas tolerance to the vasodilating effects apparently developed within 5 days of infusion. The vasodilating response to bolus intracoronary ISDN was preserved even when the vasodilating effects of intravenous ISDN were no longer present.

Angina Pectoris↗
PubMed1994

Isolation of thyroid peroxidase from patients with Graves' disease and comparison with animal peroxidases.

1. Human thyroid peroxidase (TPO) was isolated from 280-640 g of pooled thyroid tissue resected from patients with Graves' disease. 2. Isolation was performed by an improved and simplified method. 3. The Reinheit Zahl (A412/A280) of the final preparations was in the range of 0.16-0.32. 4. The spectroscopic and enzymatic properties of Graves' TPO were compared with those of porcine TPO and bovine LPO, revealing closer resemblance to the former. 5. Graves' TPO may provide a useful substitute for normal TPO, which is very difficult to isolate.

Animals↗
PubMed1994

Development of Purkinje cell bodies and processes with basic fibroblast growth factor-like immunoreactivity in the rat cerebellum.

The development of basic fibroblast growth factor-like immunoreactivity was investigated in the nuclei, cell bodies and processes of Purkinje cells with attention to basic fibroblast growth factor-containing neuronal input to the deep cerebellar nuclei. Immunoblot analysis with the use of the antisera against basic fibroblast growth factor revealed that crude homogenate of the developing rat cerebellum exhibits a main band with the same molecular weight (18,000 mol. wt) as basic fibroblast growth factor in all the postnasal stages examined. Cerebellar cells were not labeled with the antisera during embryonic life. Under light microscopy, basic fibroblast growth factor-like immunoreactivity was detected initially in cortical cells located close to deep cerebellar fissures of the newborn rat but not in superficial cortical regions. It was difficult to determine whether or not they are Purkinje cells at the fusiform stage. On postnatal day 7, immunoreactive Purkinje cells were identified throughout the cerebellar cortex, and they expressed basic fibroblast growth factor-like immunoreactivity mainly in the apical cytoplasm and proximal dendrites. From postnatal day 14 to postnatal day 28, basic fibroblast growth factor-like immunoreactivity was noted not only throughout the cytoplasm of Purkinje cells but also in the nuclei of the immunopositive cells. Our statistical analysis showed that Purkinje cells with nuclear immunoreaction peaked on postnatal day 21. At these stages, nerve fibers immunoreactive for basic fibroblast growth factor were numerous in the cerebellar medulla and deep cerebellar nuclei. After postnatal day 42, Purkinje cells with intense immunoreactivity in the nuclei showed a marked decrease in number, and immunoreactive structures were distributed in the cerebellum in a fashion similar to that in adult rats. Electron microscopy demonstrated that immunoreactivity was located mainly in the apical cytoplasm of Purkinje cells on postnatal day 7 and throughout the cytoplasm and in the nuclear euchromatin from postnatal day 14 to postnatal day 28, as was expected from light-microscopic observations. Immunoreactivity, even though distributed diffusely in the cytoplasm, was absent from the lumen of endoplasmic reticulum and mitochondria. A small population of Purkinje cell axon terminals forming synapses with the soma and dendrites of deep cerebellar nucleus neurons began to express basic fibroblast growth factor on postnatal day 21. This is much later than the starting age for synaptogenesis between Purkinje cells and deep cerebellar nucleus neurons. The age-dependent changes in the localization of basic fibroblast growth factor within Purkinje cell nucleus, soma and processes suggest a complex transport system of this factor within Purkinje cells during postnatal development.

Aging↗
PubMed1994

Experimental induction of pulmonary fibrosis in Syrian golden hamsters by N-methyl-N-nitrosourethane.

A range finding study for experimental induction of pulmonary fibrosis in which female Syrian golden hamsters received five subcutaneous injections of 0.8, 0.6, 0.4, 0.2 or 0 mg of N-methyl-N-nitrosourethane (MNUR) once a week or once per two weeks revealed most of the animals of the 0.8 mg group to die of acute pulmonary injury due to MNUR while typical interstitial pneumonia was induced in the 0.6 mg group. Based on these results hamsters were given five subcutaneous injections of 0.6 mg/animal of MNUR once per two weeks and then reared without any treatment for 12 weeks. Marked interstitial edema and intraalveolar infiltration of macrophages due to alveolar capillary damage were seen in treated animals at week 1, and secondary diffuse fibrotic thickening of the alveolar septa, as evidenced by increased type III collagen demonstrated immunohistochemically, was marked thereafter. The content of hydroxyproline in the lung was significantly increased from week 4. The present study indicates that lung injuries attributable to primary damage of alveolar capillaries progress to diffuse alveolar fibrosis in hamsters treated with MNUR, suggesting that this animal model might be of advantage for pathogenetic analysis of the relationship between pulmonary fibrosis and lung cancer development.

Animals↗
PubMed1994

Blocking effects of synthetic trypsin inhibitor (camostat) on pancreatic carcinogenesis in hamsters initiated with N-nitrosobis(2-oxopropyl)amine.

The effects of concomitant administration of a synthetic trypsin inhibitor (camostat) on pancreatic carcinogenesis in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Thirty-two female Syrian golden hamsters were given weekly 10 mg/kg s.c. injections of BOP for 5 weeks while simultaneously receiving a 500 ppm camostat diet (BOP + camostat group). Additional groups of 30 animals received either the s.c. injections of BOP (BOP group), or the 500 ppm camostat diet (camostat group) during the same 5-week period. Thirty weeks after the first BOP administration, the incidence of pancreatic adenocarcinomas in the BOP + camostat group was significantly lower than in the group administered BOP only (p < 0.05). Similarly, the total numbers of pancreatic adenocarcinomas or dysplastic lesions were significantly decreased in the BOP + camostat group as compared with the BOP group (p < 0.01). None of the animals receiving camostat alone developed any adenocarcinomas or dysplastic lesions of the pancreas. The results of the present experiments clearly show that camostat can inhibit induction of hamster pancreatic ductal neoplasms when administered simultaneously with BOP.

Adenocarcinoma↗
PubMed1994

Effects of cigarette smoke on N-nitrosobis(2-oxopropyl)amine-induced pancreatic and respiratory tumorigenesis in hamsters.

Influences of cigarette smoke on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic duct and respiratory tract tumorigenesis were investigated using a hamster two-stage carcinogenesis model. Male 5-week-old hamsters were divided into 5 groups. Group 1 was s.c. injected with BOP at a dose of 10 mg/kg once a week for 3 weeks as an initiation treatment together with cigarette smoke exposure over the same 4-week period. Group 2 was exposed to cigarette smoke for 26 weeks after the BOP-initiation. Groups 3 and 4 were respectively given the BOP-initiation alone and the 26-week cigarette smoke exposure without initiation. Group 5 served as a sham-smoked negative control. The experiment was terminated 30 weeks after the first BOP injection. The incidence of pancreatic adenocarcinomas was significantly decreased in Group 1 as compared to the Group 3 value (P < 0.01) while the Group 2 value did not show any change. In contrast, the incidence of laryngeal and tracheal proliferative lesions (hyperplasias and papillomas) was significantly increased in Group 2 over Group 3 (P < 0.01). The incidence of pulmonary hyperplasias was also increased in Group 2 over Group 3 (P < 0.05), although that of pulmonary adenomas or adenocarcinomas was decreased in Group 2 as compared to the Group 3 value (P < 0.01). Cigarette smoke exposure in the BOP-initiation phase (Group 1) did not affect the development of respiratory proliferative lesions. No animals in Groups 4 and 5 developed any tumors in the pancreas or respiratory tract. Our results thus indicate that cigarette smoke exposure inhibits pancreatic carcinogenesis when given in the initiation phase, whereas it modulates (enhances or suppresses) the development of proliferative lesions in the respiratory tract if applied during the promotion stage to hamsters pretreated with BOP.

Animals↗