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Biomedical subjects

Y Imamura

Publications and source records attributed to Y Imamura.

At least 145 records · Page 8Linked to original sources
PubMed1997

Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses.

Tryptase Clara, a trypsin-like protease localized exclusively in and secreted from Clara cells to the bronchial epithelium of rat, proteolytically activates the infectivity of influenza A virus [H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma (1992) J. Biol. Chem. 267, 13573-13579]. We report here that human mucus protease inhibitor (MPI), a major inhibitor of granulocyte elastase in the lining fluids of the human respiratory tract, significantly inhibited proteolytic activation of the infectivity of influenza A and Sendai viruses by tryptase Clara in vitro and multi-cycles of mouse-adapted influenza A virus replication in rat lungs in vitro. Recombinant MPI and the C- but not the N-terminal domain of the MPI inhibited both the proteolytic activity of tryptase Clara and the activation of virus infection. The 50% inhibitory concentrations of recombinant MPI and the C-terminal domain for tryptase Clara with Sendai virus envelope glycoprotein as substrate were 7.4 and 61.6 nM, respectively. These results indicate that MPI is a defensive compound against virus infection. Since there is evidence suggesting that concentrations of MPI in respiratory fluids are insufficient for prevention of virus infection, administration of MPI in the airway may be useful for treatment of these virus infections.

Animals↗
PubMed1997

Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors.

The structural requirements of acetohexamide reductases purified from rabbit liver, kidney, and heart for substrates and inhibitors were examined. Acetohexamide, an oral antidiabetic drug with a ketone group, and analogs of it with various alkyl groups instead of the cyclohexyl group were used as substrates for these three enzymes. The results obtained as to substrate specificity suggested that the nature of the substrate-binding region of the heart enzyme is markedly different from those of the substrate-binding regions of the liver and kidney enzymes. Tolbutamide, which has no ketone group within its chemical structure, strongly inhibited the heart enzyme, whereas it had little ability to inhibit the liver or kidney enzyme. The inhibition of the heart enzyme by tolbutamide was competitive with respect to acetohexamide and uncompetitive with respect to NADPH. Furthermore, tolbutamide analogs with n-pentyl and n-hexyl groups instead of the n-butyl group exhibited very pronounced inhibition of only the heart enzyme. Therefore, it is reasonable to postulate that the heart enzyme, unlike the liver and kidney ones, has a cleft of a strongly hydrophobic nature near its substrate-binding region, and that this hydrophobic cleft plays a critical role in the interaction of the heart enzyme with the cyclohexyl group of acetohexamide.

Acetohexamide↗
PubMed1997

Isolated collagen IV retains the potential to form an 18-nm sided polygonal meshwork of the lamina densa.

Polygonal meshworks were revealed in the aggregates reconstituted from isolated collagen IV as well as in the lamina densa of mouse pancreas by the quick-freezing and deep-etching technique. Collagen IV solution with acetic acid from the bovine lens capsules and that isolated from the pepsin-solubilized fraction of human placenta reconstituted polygonal meshworks, which were dimensionally similar to the meshwork seen in the lamina densa of mouse pancreas. The average lengths between branching points in the lamina densa, and the meshworks of collagen IV derived from the bovine lens capsules and from the human placenta were 20.1 +/- 7.7 nm (mode = 18 nm), 21.6 +/- 11.3 nm (mode = 14 nm), and 21.6 +/- 9.0 nm (mode = 18 nm), respectively. These observations suggest that collagen IV can, in the absence of other macromolecules including laminins, comprise a skeletal meshwork similar in dimensions to that of the lamina densa.

Animals↗
PubMed1997

Trichoblastoma with rippled-pattern.

The following is a case study of a 36-year-old Japanese man with a trichoblastoma which exhibited a rippled-pattern on the left temporal region of the scalp. The histological findings of the tumor revealed lobular aggregations composed of immature follicular basaloid cells, lobules of squamous eddy-like foci of incomplete keratinization or small keratinous cysts, and multiple papillary mesenchymal bodies similar to hair germ. Interestingly, a rippled-pattern of basaloid cells and hyalinized matrixes resembling the Verocay bodies of neurilemmoma was also observed. We propose that the rippled-pattern of the basaloid cells and hyalinized matrices is caused by the characteristic stromal induction of trichoblastoma.

Adult↗
PubMed1997

Pigmented epidermal cyst.

A 58-year-old Japanese woman with a pigmented epidermal cyst on the upper arch of the right external ear is described. The blue appearance of the cyst was striking and uncommon in Japanese. Histologically, abundant melanin pigment was observed in the keratinous mass of the cavity, and epithelial cells showed epidermoid keratinization. Increased numbers of melanocytes in the basal layer, large globular cells of melanocytic origin in the spinous layer, and hair-germ-like aggregates of basaloid cells and melanocytes were also observed. The blue clinical appearance is probably due to the rich melanin granules in the cyst, keratinous mass, keratinocytes, and hair-germ-like structures.

Ear, External↗
PubMed1997

Detection of numerical chromosomal aberrations in malignant melanomas using fluorescence in situ hybridization.

To evaluate the numerical chromosomal aberration in malignant melanoma, we have applied fluorescence in situ hybridization (FISH) with repetitive DNA probes specific for chromosomes 1, 6, 7, 9, 10, and 17 on 24 fresh malignant melanomas (primary: 14, metastatic: 8). We defined a tumor that had copies with more than 3 spots as chromosomal gain. Chromosomal copy number gain was found in 40.9% of the cases for chromosome 7, 27.2% for chromosome 6, 27.2% for chromosome 17, 22.7% for chromosome 9 and 10, and 4.5% for chromosome 1. Monosomy was found in 54.5% of the cases for chromosome 10, 36.5% for chromosome 9, 27.2% for chromosome 6, 22.7% for chromosome 17, and 18.1% for chromosome 1 and 7. The most frequent numerical alterations were seen in chromosomes 6, 7, 9 and 10. Gain of chromosome 6 and 7 and/or losses of chromosome 9 and 10 may play an important role in the tumorigenesis and development of malignant melanomas.

Adult↗
PubMed1997

Individual variation of acetohexamide reductase activities in liver microsomes and cytosol of rats.

We examined individual variations in acetohexamide reductase activities in liver microsomes and cytosol of rats. Large differences among individuals were observed for acetohexamide reductase activity in liver microsomes of male Fischer-344 (Fischer), Sprague-Dawley (SD) and Wistar rats at 9 weeks of age, except in the Wistar-Imamichi (Wistar-IM) strain. These four strains of female rats did not exhibit any microsomal enzyme activity. Although acetohexamide reductase activities were fully detectable in liver cytosols from all the strains of male and female rats, there was neither strain-related difference nor considerable individual variation in the cytosolic enzyme activity. In liver microsomes of male Fischer rats at 4 weeks of age, acetohexamide reductase activity was not detectable. The microsomal enzyme activity in male Fischer rats markedly increased at 6 weeks of age to approach the levels at 9 and 12 weeks of age, with large individual variations.

Aging↗
PubMed1997

Inhibitory effect of drugs with a ketone group on reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney.

The reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney was inhibited by befunolol, moperone, levobunolol, daunorubicin and loxoprofen, which have a ketone group within their chemical structures and are substrates for the enzyme. A significant correlation was observed between the common logarithm of Vmax/Km values of the enzyme for befunolol, moperone, levobunolol and daunorubicin and the percentage inhibition of the enzyme, confirming that these drugs are competitive substrates of the enzyme with respect to acetohexamide. However, the plot for loxoprofen, a nonsteroidal anti-inflammatory drug with a ketone group, was apparently distant from the regression line obtained. Although nonsteroidal anti-inflammatory drugs with a ketone group such as suprofen and fenbufen were not reduced by the enzyme, they strongly inhibited the reduction of acetohexamide catalyzed by the enzyme.

Acetohexamide↗
PubMed1997

[Myocardial adrenergic nerve activity in valvular diseases assessed by iodine-123-metaiodobenzylguanidine myocardial scintigraphy].

Iodine-123-metaiodobenzylguanidine (MIBG) imaging was used to assess myocardial adrenergic nerve activity in patients with heart failure MIBG planar images were obtained in 94 patients. The uptake of MIBG, calculated as the heart-to-mediastinum activity ratio in the immediate image (15 min), showed a significant decrease only in patients with severe heart failure due to cardiomyopathy, but was not changed in those with valvular diseases. Storage and release of MIBG, calculated as the percentage myocardial MIBG washout from 15 min to 4 hours after isotope injection, was substantially accelerated in both patients with cardiomyopathy and valvular diseases in proportion to the severity of heart failure. These data suggest that, in severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. Also, myocardial adrenergic nerve activity is accelerated in proportion to the severity of heart failure independent of the underlying cause. MIBG images were analyzed in 20 patients with mitral stenosis with the same methods to clarify whether myocardial adrenergic nerve activity is different in patients with heart failure without left ventricular volume or pressure overload. Myocardial uptake of MIBG did not show any significant difference. The percentage myocardial MIBG washout was increased in patients with severe heart failure. The closest correlation was between myocardial washout and cardiac output. In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. Decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification.

3-Iodobenzylguanidine↗
PubMed1997

Metyrapone reductase purified partially from liver microsomes of male rats: the enzyme differs from acetohexamide reductase.

An enzyme catalyzing the reduction of metyrapone, a diagnostic drug with a ketone group, was partially purified from liver microsomes of male rats. The partially purified metyrapone reductase had no ability to reduce acetohexamide, an oral antidiabetic drug with a ketone group, even though both metyrapone and acetohexamide are reduced in liver microsomes of male rats. These results clearly indicate that the reduction of these two drugs can be catalyzed by different enzymes. The partially purified metyrapone reductase was found to reduce aldehydes, ketones and menadione. The substrate specificities were in fair agreement with those of carbonyl reductase. However, the partially purified enzyme was strongly inhibited by inhibitors of aldehyde reductase, such as barbital, phenobarbital and sodium valproate.

Acetohexamide↗
PubMed1996

Melatonin. A possible role in pathogenesis of adolescent idiopathic scoliosis.

STUDY DESIGN: The serum melatonin levels during 24-hour periods were compared between patients with idiopathic and age-matched normal control subjects. OBJECTIVE: To find if the melatonin deficiency may have some role for progression or etiology of idiopathic scoliosis in humans. SUMMARY OF BACKGROUND DATA: Experimentally induced scoliosis in chicken by pinealectomy can be attributed to the defect in melatonin metabolism. METHOD: Blood samples were correlated every 3 hours during 24-hour periods, and serum melatonin levels were measured and statistically analyzed. RESULTS: The level of melatonin, integrated concentration through 24 hours and night time (0:00 am-6:00 am), in the patients who had progressive curve (more than 10 degrees of progression in the previous 12 months) was significantly lower than the level in the patients who had a stable curve (less than 10 degrees of progression in the previous 12 months) or in the control subjects (P < 0.05). CONCLUSION: The study suggests that normal melatonin synthesis or metabolism may have crucial role in regulating normal spine growth. The level of melatonin appears to be a useful predictor for progression of spine curvature in idiopathic scoliosis.

Adolescent↗
PubMed1996

High-resolution magnetic resonance imaging of the intraorbital optic nerve and subarachnoid space in patients with papilledema and optic atrophy.

OBJECTIVE: To evaluate the orbital portion of the optic nerve and the subarachnoid space using fast spin-echo magnetic resonance imaging in normal subjects and in patients with papilledema or optic atrophy. DESIGN: Measurements of the optic nerve complex on coronal images were made using high-resolution magnetic resonance imaging with fast spin-echo sequences. PATIENTS: Twenty-one patients, including 5 patients with papilledema due to congenital hydrocephalus, intracranial tumors, or meningitis, as well as 16 patients with optic atrophy, were studied. Sixteen healthy volunteers served as controls. MAIN OUTCOME MEASURES: The longitudinal diameter of the optic nerve, the longitudinal outer diameter of the subarachnoid space, the diameter ratio, and the area of the subarachnoid space were determined. RESULTS: In normal subjects, the ring-shaped area of high signal intensity that represented the subarachnoid space was widest behind the globe, then narrowed toward the orbital apex. In patients with papilledema, the area of the subarachnoid space was markedly dilated, the optic nerve was compressed, and the nerve sheath was widened, resulting in a small diameter ratio compared with that of controls. Patients with pallor of the temporal aspect of the optic disc appeared to exhibit dilation of the subarachnoid space; the size of the optic nerve was decreased more than that of the nerve sheath, resulting in a small diameter ratio compared with controls. Patients with complete pallor of the disc, however, exhibited hyperintense optic nerve complexes without a ring-shaped appearance toward the orbital apex. CONCLUSION: Fast spin-echo magnetic resonance imaging appears useful for objectively evaluating the optic nerve and surrounding subarachnoid space in patients with papilledema and optic atrophy.

Adolescent↗
PubMed1996

Myocardial adrenergic nervous activity is intensified in patients with heart failure without left ventricular volume or pressure overload.

OBJECTIVES: To clarify whether myocardial adrenergic activity is different in patients with heart failure without left ventricular volume or pressure overload, we used iodine-123 metaiodobenzylguanidine (MIBG) imaging to study patients with mitral stenosis. BACKGROUND: In patients with heart failure due to cardiomyopathy or to valve diseases with volume or pressure overload, or both, myocardial adrenergic nerve activity is accelerated independent of underlying cause. However, it is not clear whether this change in myocardial adrenergic nerve activity is present in patients without left ventricular volume or pressure overload. METHODS: The study patients were 20 men and women with normal left ventricular function and heart failure due to mitral stenosis. Planar MIBG images obtained from these patients were compared with images from nine age-matched healthy subjects (control group). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. All 20 study patients underwent echocardiography, and 16 underwent right heart catheterization. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) did not show any significant difference between the patient and control groups. Myocardial washout was increased in patients with severe heart failure. The level of myocardial washout correlated with left atrial diameter (r = 0.51, p = 0.02) and mitral valve area calculated with Doppler echocardiography (r = -0.61, p < 0.01) and mitral valve area calculated with cardiac catheterization (r = -0.62, p = 0.02). The closest correlation existed between myocardial washout and cardiac output (r = -0.80, p < 0.01). CONCLUSIONS: In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. A decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification.

3-Iodobenzylguanidine↗
PubMed1996

Inheritance of acetohexamide reductase activities in liver microsomes and cytosol of rats.

The inheritance patterns of acetohexamide reductase activities in liver microsomes and cytosol of rats were determined by using the inbred Wistar-Imamichi and Fischer-344 strains as a model of low and high metabolizers, respectively. A simple Mendelian genetic analysis for the frequency distribution of acetohexamide reductase activity in liver microsomes of male rats led us to conclude that the phenotype is genetically regulated by an autosomal co-dominant fashion. Female rats, unlike male rats, did not exhibit microsomal enzyme activity in parental, first filial (F1) and second filial (F2) generations, indicating that the inheritance of the microsomal enzyme activity is sex-limited. On the other hand, the frequency distribution of acetohexamide reductase activities in liver cytosol of male and female rats was unimodal in all generations and there was no significant difference among these cytosolic enzyme activities.

Alcohol Oxidoreductases↗
PubMed1996

Function of Ca2+ in phosphatidylcholine-hydrolyzing phospholipase D activation in osteoblast-like cells.

We investigated the function of Ca2+ in the activation of phosphatidylcholine (PC)-hydrolyzing phospholipase D (PLD) in osteoblast-like MC3T3-E1 cells. Fetal calf serum (FCS) stimulated the formation of choline in a dose-dependent manner in the range between 0.6% and 10%. The effect of a combination of FCS and 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C (PKC) activator, on the formation of choline was additive. Staurosporine, an inhibitor of protein kinases, enhanced the formation of choline induced by FCS. BAPTA/AM, a chelator of intracellular Ca2+, inhibited the formation of choline induced by FCS. The depletion of extracellular Ca2+ by EGTA markedly reduced the FCS-induced formation of choline. SK&F 96365, an inhibitor of receptor-operated Ca2+ entry, significantly inhibited the choline formation induced by FCS. On the other hand, nifedipine, an inhibitor of L-type voltage-dependent Ca2+ channels, had little effect on the choline formation. TMB-8, an inhibitor of Ca2+ mobilization from intracellular Ca2+ store, significantly inhibited FCS-induced choline formation. These results strongly suggest that Ca2+ mobilization, through both the influx via receptor-operated Ca2+ channel and the release from intracellular Ca2+ store, plays an important role in the activation of PLD in osteoblast-like cells.

3T3 Cells↗
PubMed1996

Purification and catalytic properties of a novel acetohexamide-reducing enzyme from rabbit heart.

An enzyme catalyzing the metabolic reduction of acetohexamide [4-acetyl-N-(cyclohexyl-carbamoyl)benzenesulfonamide], an oral antidiabetic drug, was purified to homogeneity from the cytosolic fraction of rabbit heart. The molecular mass of the purified enzyme was estimated to be 110 kDa by gel filtration and nondenaturing PAGE and 28 kDa by SDS-PAGE, suggesting that the enzyme is composed of four identical-size subunits. 4-Benzoyl-pyridine and p-nitroacetophenone, typical substrates of carbonyl reductase [EC 1.1.1.184], were not reduced by the enzyme. Of drugs with a ketone group tested, only acetohexamide was a good substrate of the enzyme. the enzyme effectively reduced analogs substituted with various alkyl groups instead of the cyclohexyl group in acetohexamide, although it had little or no ability to reduce analogs substituted with various alkyl groups instead of the methyl group in acetohexamide. The enzyme was inhibited not only by quercetin, a well-known inhibitor of carbonyl reductase, but also by phenobarbital, a potent inhibitor of aldehyde reductase [EC 1.1.1.2]. These results indicate that the enzyme purified from rabbit heart is a novel enzyme responsible for the reduction of acetohexamide and its analogs.

Acetohexamide↗