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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1994

Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy.

To evaluate whether patients with subclinical hypothyroidism have a disturbance in lipid metabolism, and whether supplemental L-thyroxine (L-T4) therapy would improve their lipid parameters, we measured serum levels of thyroid hormones, TSH and lipid parameters in 34 patients with subclinical hypothyroidism before and 2 months after treatment with L-T4. Before treatment, patients with subclinical hypothyroidism had elevated serum low density lipoprotein cholesterol (LDL-C) concentrations compared with control subjects (P < 0.05). Overall, L-T4 therapy significantly decreased the serum level of TSH (P < 0.01), total cholesterol (TC; P < 0.02), high density lipoprotein cholesterol (P < 0.02), LDL-C (P < 0.05), and the ratio of apolipoprotein B to apolipoprotein A1 (P < 0.05). Lipid values in patients with basal serum TSH levels below 10 mU/l were not affected by L-T4 therapy, whereas serum levels of TC and LDL-C decreases significantly (P < 0.01) in patients with serum TSH levels above 10 mU/l. Thus, the L-T4 treatment appears to have a preventive effect on the disturbance of lipid metabolism in patients with subclinical hypothyroidism, especially in patients with serum TSH levels above 10 mU/l.

Adult↗
PubMed1994

Metabolism of 3,5,3',5'-tetrachlorobiphenyl by rat liver microsomes and purified P4501A1.

1. The metabolism of 3,5,3',5'-tetrachlorobiphenyl (TCB) was investigated with liver microsomes and purified P450 from the male Wistar rat. 2. One novel metabolite was produced after incubation with liver microsomes derived from the 3-methylcholanthrene (MC)- and 3,4,5,3',4'-pentachlorobiphenyl-pretreated rat, but not after incubation with those from the untreated or phenobarbital (PB)-pretreated rat. These results suggest that P450 isozyme(s) induced by MC-type inducers is involved in 3,5,3',5'-TCB metabolism. 3. The chemical structure of this metabolite was identified to be 4-hydroxy-3,5,3',5'-TCB by comparison of its retention time in glc and the ms with those of a synthetic sample. 4. Purified rat P4501A1, a major MC-inducible P450 isozyme, catalyzed the 4-hydroxylation of 3,5,3',5'-TCB, but P4502B1, a major PB-inducible isozyme, was inactive. 5. Reduced glutathione completely inhibited the formation of the hydroxylated metabolite, suggesting that 4-hydroxylation of 3,5,3',5'-TCB proceeded via the 3,4-epoxide.

Animals↗
PubMed1994

Sulphotransferase-dependent dehydration of atropine and scopolamine in guinea pig.

1. Enzymatic dehydration of atropine and scopolamine was studied in guinea pig. 2. The incubation of these alkaloids with guinea pig liver cytosol in the absence of cofactors gave no dehydrated metabolite. However, when atropine and scopolamine were incubated with cytosol supplemented with ATP and sodium sulphate, dehydrated metabolites, apoatropine and aposcopolamine were formed. The formation of these metabolites was confirmed by gas chromatography-mass spectrometry. 3. The reaction required ATP as well as cytosol as the obligatory factors. Deletion of sodium sulphate from the reaction mixture also resulted in a decrease of the activities, although this treatment showed limited effect when the low concentration of atropine was used. Furthermore, dehydroepiandrosterone, an excellent substrate for hydroxysteroid-sulphotransferase, effectively inhibited the in vitro activity of atropine dehydration. 4. Administration of dehydroepiandrosterone to guinea pig followed by atropine treatment caused decreased urinary excretion of apoatropine. 5. These results strongly suggested that the dehydration of atropine and scopolamine takes place via the sulphate conjugate intermediates produced from the sulphotransferase-catalysed reaction. The present finding is the first example of the sulphotransferase-dependent dehydration of a drug, and its generality in drug metabolism is discussed.

Animals↗
PubMed1994

Participation of cytochrome P450-2B and -2D isozymes in the demethylenation of methylenedioxymethamphetamine enantiomers by rats.

The cytochrome P450 isozymes in rat liver microsomes that catalyze the demethylenation of methylenedioxymethamphetamine enantiomers to the corresponding dihydroxymethamphetamine were characterized. Dihydroxymethamphetamine formation in liver microsomes from male Sprague-Dawley rats exhibited multienzyme kinetics, with Km values in the micromolar/millimolar range. The stereoselectivity [(+)-isomer versus (-)-isomer] varied from 0.78 to 1.94 after pretreatment of the rats with phenobarbital, 3-methylcholanthrene, pregnenolone-16 alpha-carbonitrile, or pyrazole, suggesting that different isozymes participate in the reaction. The low-Km demethylenation was not induced by these compounds and was not inhibited by antibodies raised against CYP2C11. Liver microsomes from female Dark-Agouti rats, a strain genetically deficient in CYP2D1, exhibited demethylenation activities that were 9% of those in microsomes from male Sprague-Dawley rats. The low-Km demethylenation was also inhibited by CYP2D substrates such as sparteine, bufuralol, or desipramine and was almost completely inhibited by antibodies against P450 BTL, which belongs to the CYP2D family. The higg-Km demethylation activity was induced by phenobarbital and pregnenolone-16 alpha-carbonitrile and the activity in both untreated and phenobarbital-induced microsomes was suppressed by anti-CYP2B1 IgG. Experiments with IgG raised against cytochrome b5 suggested that the hemoprotein contributed to the low-Km activity but not the high-Km activity. These results indicate that cytochrome P450 isozymes belonging to the CYP2D subfamily catalyze demethylenation with low Km values and that the reaction occurring with high Km values is likely to be mediated by members of the CYP2B family, but with the possible participation of other phenobarbital-inducible isoforms.

3,4-Methylenedioxyamphetamine↗
PubMed1993

[Cases of Graves' disease with falsely high TSH values due to interfering substances which cross-link with mouse monoclonal antibodies in the TSH assay kits].

It has been reported that highly sensitive two-site immunometric assays occasionally indicate falsely high serum TSH values. A possible reason for this is that heterophilic antibodies interfere with these assays. Recently we had a patient in whom the Delfia TSH kit falsely indicated an elevated serum TSH value. A 29-year-old female was diagnosed as having Graves' disease and was referred to Ito Hospital for surgical treatment. Her thyroid hormone values were distinctly high two months before admission (FT3: 20.7pmol/L, FT4: 42.3pmol/L), but her serum TSH level was normal (1.1mU/l). She was clinically hyperthyroid, and T3 and T4 values determined after ethanol extraction and T3 or T4 analog binding rates did not indicate the presence of T3 or T4 antibodies. Her TSH value became undetectable when mouse IgG was added to the assay. These results suggested that the "normal" serum TSH value was caused by interfering substances such as anti-mouse IgG antibodies which had cross-linked with mouse monoclonal antibodies in the Delfia TSH kit. Another 12 patients who were suspected of having the interfering substances were examined because of the discordance between TSH values and thyroid hormone values. All of the serum TSH values measured using the DELFIA TSH kit decreased when mouse IgG was added. In another case, the presence of serum TSH could not be detected using the Delfia TSH kit but could be measured using the RIABEAD II TSH kit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[A case of subacute thyroiditis with highly positive thyrotropin receptor antibodies and normal radioiodine uptake].

In this paper, we report on a 40-year-old female with subacute thyroiditis (SAT) who showed high levels of TSH-binding inhibitory immunoglobulins (TBII) and thyroid-stimulation blocking antibodies (TSBAb) from the early stage of the disease. Thyrotoxicosis continued for 2 months and it was subsequently followed by severe hypothyroidism. Levothyroxine was then started. At that time, both TBII and TSBAb were still positive, but they disappeared 6 months later and she remained euthyroid thereafter without treatment. When she was in a thyrotoxic phase and had a suppressed TSH level, her 24-hour radioiodine uptake was not suppressed (11%), and thyroid scan showed partial suppression of uptake in the right lobe. These observations indicate that the presence of TSH receptor antibodies (TRAb) may have modified the changes in thyroid state and the course of SAT.

Adult↗
PubMed1993

A cytochrome P450 isozyme having aldehyde oxygenase activity plays a major role in metabolizing cannabinoids by mouse hepatic microsomes.

A cytochrome P450 (designated P450 MUT-2) which catalyses the oxidation of 11-oxo-delta 8-tetrahydrocannabinol (11-oxo-delta 8-THC) to delta 8-THC-11-oic acid has been purified from hepatic microsomes of untreated male mice. Analysis of NH2-terminal sequence suggests that the isozyme is a member of the P450 2C gene subfamily. P450 MUT-2 exhibited aldehyde oxygenase activity for 11-oxo-delta 8-TH, 11-oxo-delta 9-THC, 11-oxo-cannabinol (11-oxo-CBN) and 9-anthraldehyde together with high activity for the hydroxylation of cannabinoids at the 11-position. Antibody against P450 MUT-2 significantly inhibited the microsomal formation of delta 8-THC-11-oic acid from 11-oxo-delta 8-THC, but not that of 9-anthracene carboxylic acid from 9-anthraldehyde. Major metabolic reactions of delta 8-THC, delta 9-THC and CBN with mouse hepatic microsomes were the 11-hydroxylation (all cannabinoids), 7 alpha-(delta 8-THC) or 8 alpha-hydroxylation (delta 9-THC) and epoxide formation (delta 8- and delta 9-THC). All these reactions except for 7 alpha-hydroxylation of delta 8-THC and alpha-epoxide formation from delta 9-THC were also markedly inhibited by the antibody. These results indicate that P450 MUT-2 is a major enzyme for metabolizing cannabinoids by mouse hepatic microsomes.

Animals↗
PubMed1993

Reduced Mg2+ block of N-methyl-D-aspartate receptor-mediated synaptic potentials in developing visual cortex.

Molecular cloning has demonstrated a diversity of artificially expressed N-methyl-D-aspartate (NMDA) receptors, implying a similar diversity of naturally occurring NMDA receptors in situ. Particularly significant was the success in expression of NMDA receptor classes exhibiting various sensitivities to Mg2+ block, a voltage-dependent channel blockade by Mg2+ that is essential to NMDA receptor functioning. Release from Mg2+ block often allows or facilitates the occurrence of long-term potentiation, a form of synaptic plasticity. Here we show that in the immature visual cortex, which is more susceptible to long-term potentiation than adult visual cortex, synaptically activated NMDA receptors, unlike those in the adult, have varying but clearly reduced sensitivities to Mg2+ block. We propose that the initially expressed, later-eliminated NMDA receptors exhibiting a reduced Mg2+ block may underlie the greater susceptibility to plasticity in the immature neocortex.

Age Factors↗
PubMed1993

Facilitatory effects of substance P on the susceptibility to long-term potentiation in the visual cortex of adult rats.

We studied whether substance P (SP) facilitates induction of long-term potentiation (LTP) in adult rat visual cortex slices, using intracellular recordings of postsynaptic potentials (PSPs) elicited by white matter stimulation. Tetanic stimulation in normal medium induces no change of the PSP amplitude. In SP-containing medium, by contrast, tetanization potentiated the PSP amplitude in 5 over 7 cells examined. Although the other 2 cells underwent no change, the overall effect of SP was an increase in the probability of LTP induction. This effect of SP was canceled out by bath-application of the non-peptide antagonist CP96,345 (n = 7) or intracellular application of guanosine 5'-beta-thio-diphosphate (GDP beta S; n = 7). These results suggest that SP increased LTP susceptibility of neurons in the adult rat visual cortex through SP receptor-mediated mechanisms.

2-Amino-5-phosphonovalerate↗
PubMed1993

Transient increase in endogenous basic fibroblast growth factor in neurons of ischemic rat brains.

An antiserum against basic fibroblast growth factor (bFGF) was shown to recognize an 18-kDa protein (possibly bFGF) in crude neocortical extracts by immunoblot and used to investigate the changes of bFGF immunoreactivity in neurons and astrocytes of the cerebral cortex of rats 1-21 days after unilateral occlusion of the middle cerebral artery (MCA). The mildly ischemic neocortex exhibited no signs of cell loss or degeneration in Nissl-stained sections 1-14 days after MCA occlusion, but it contained pyramidal cell bodies and processes with more intense bFGF immunoreactivity than did the control neocortex. bFGF immunoreactivity in the ischemic hemisphere gradually declined in intensity and by 21 days after MCA occlusion, it had reached the control level. On the other hand, there were many bFGF immunoreactive astrocytes in the primary olfactory cortex on the side of infarction. These findings suggest that MCA occlusion causes an increase in bFGF content not only in astrocytes but also in neurons, depending on the severity of the ischemic insult in individual cortical regions. The transient augmentation of bFGF expression or accumulation in mildly ischemic pyramidal neurons but not in astrocytes is in line with previous studies suggesting the neurotrophism of exogenously applied bFGF.

Animals↗