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Biomedical subjects

K Hanada

Publications and source records attributed to K Hanada.

At least 127 records · Page 7Linked to original sources
PubMed1998

Enantioselective tissue distribution of the basic drugs disopyramide, flecainide and verapamil in rats: role of plasma protein and tissue phosphatidylserine binding.

PURPOSE: The stereoselective distribution of three basic drugs, disopyramide (DP), flecainide (FLC) and verapamil (VP), was studied to clarify the relationship between the tissue-to-unbound plasma concentration ratio (Kpf) and drug lipophilicity and binding to phosphatidylserine phs), which are possible factors determining the tissue distribution of these drug enantiomers. METHODS: The drug enantiomer or racemate was administered to rats by intravenous constant infusion. Their concentrations in plasma and tissues were determined using enantioselective high-performance liquid chromatography. Plasma protein binding, and buffer-octanol and buffer-hexane containing PhS partition coefficients were also determined. RESULTS: The stereoselectivity of the tissue-to-plasma concentration ratio (Kp) was partly associated with that of serum protein binding. However, the Kpf value of R(+)-VP in the lung was significantly higher than that of S(-)-VP. A linear correlation was observed between the Kpf values of these drug enantiomers in brain, heart, lung and muscle, and their buffer-hexane containing PhS partition coefficients. The in vitro data for the binding of these drugs to PhS suggest that stereoselective binding of VP to PhS may correspond to its stereoselective tissue binding. CONCLUSIONS: Our findings provide some evidence for a role of tissue PhS in the tissue distribution of basic drugs with respect to stereoselectivity of drug enantiomers distribution.

Animals↗
PubMed1998

Immediate-type heat urticaria: report of a case and study of plasma histamine release.

We report a 68-year-old man who had immediate-type heat urticaria with systemic symptoms. Immersing his hand in water at 42 degrees C (heat challenge test) produced an urticarial response, with an increase in the plasma histamine level from 0.26 to 7.64 ng/mL. Administration of oral antihistamines alone did not suppress either the urticarial response or the increase in plasma histamine. However, a combination of antihistamines and desensitization improved the skin lesions and reduced the plasma histamine level. The heat challenge test subsequently provoked a negative response and there was no increase in plasma histamine level 3 months after starting the combination therapy. These results indicate that the histamine level reflected the result of the heat challenge test and the amelioration of the skin eruption.

Aged↗
PubMed1998

Inhibitory effect of beta-thujaplicin on ultraviolet B-induced apoptosis in mouse keratinocytes.

Sunburn cells are thought to represent ultraviolet B-induced apoptotic keratinocytes. It has been demonstrated that enzymatic and nonenzymatic antioxidants effectively suppress sunburn cell formation, indicating that reactive oxygen species may play a role in the progression of ultraviolet B-induced apoptosis. Metallothionein, a cytosol protein, has antioxidant activity, and overexpression of metallothionein has been reported to reduce the number of sunburn cells in mouse skin. We have also demonstrated that overexpression of metallothionein inhibits ultraviolet B-induced DNA ladder formation in mouse keratinocytes. These findings support the hypothesis that cellular metallothionein may play an important role in the inhibition of ultraviolet B-induced apoptosis in keratinocytes through its antioxidant activity. In the present study, we investigated the effects of beta-thujaplicin, an extract from the woods of Thuja plicata D. Don. and Chamaecyparis obtuse, Sieb. et Zucc., on ultraviolet B-induced apoptosis in keratinocytes and on metallothionein induction. Topical application of beta-thujaplicin decreased the number of ultraviolet B-mediated sunburn cells and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling-positive cells in mouse ear skin. Incubation with beta-thujaplicin suppressed ultraviolet B-induced DNA ladder formation in cultured mouse keratinocytes. Histochemical analysis showed that topical application of beta-thujaplicin induced metallothionein protein in mouse skin. Northern analysis and western blotting revealed significant induction of metallothionein mRNA and metallothionein protein, respectively, in beta-thujaplicin-treated cultured mouse keratinocytes. These findings indicate that beta-thujaplicin inhibits ultraviolet B-induced apoptosis in keratinocytes and strongly suggest that the inhibitory mechanism is due to the antioxidant activity of metallothionein induced by the agent.

Animals↗
PubMed1998

Epidermal proliferation of the skin in metallothionein-null mice.

Metallothionein (MT) is a low-molecular weight metal-binding protein. Although the physiologic function of MT is not fully known, it is present in various species and various organs including the skin. MT is strongly stained in hyperplastic epidermal tissues in normal skin and in hyperplastic skin lesions, and increased expression of mRNA of the MT gene has been demonstrated in skin stimulated by proliferative agents, suggesting that MT is involved in the proliferation of epidermal keratinocytes. To improve our understanding of the role of MT in epidermal hyperplasia, mice with null mutations in their MT-1 and MT-2 genes were used in this study. We compared the epidermal hyperplasia in MT-null mice and in normal C57BL/6 J mice after treatments with cholera toxin, 12-0-tetradecanoylphorbol-13-acetate, and ultraviolet B irradiation, which stimulate epidermal proliferation. Immunostaining of MT was not detected in the skin of MT-null mice, and these mice developed significantly less epidermal hyperplasia than the normal mice after exposure to each stimulator. We determined the metal contents of skin samples by the proton-induced x-ray emission method. The zinc content of the skin of the MT-null mice was lower than that of the control mice before stimulation. After stimulation of epidermal hyperplasia, MT-null and normal mice showed significantly reduced levels of zinc. These findings indicate that cellular MT is involved in the proliferative process of the epidermis induced by cholera toxin, 12-0-tetradecanoylphorbol-13-acetate, and ultraviolet B light through its regulatory action on the metal metabolism required for cell growth.

Animals↗
PubMed1998

Novel function of metallothionein in photoprotection: metallothionein-null mouse exhibits reduced tolerance against ultraviolet B injury in the skin.

We have shown previously that injection of cadmium chloride (Cd2+) depletes the number of ultraviolet B (UVB)-induced sunburn cells in the mouse skin in vivo, and that Cd2+ treatment enhances UVB resistance in cultured keratinocytes in vitro, indicating the photoprotective role of Cd2+-induced metallothioneins (MT) with antioxidant property against UVB injury; however, there has been no direct evidence for the role of MT in UV protection. To improve our understanding of MT in photoprotection, MT-null mouse deficient in its MT-1 and MT-2 genes was studied. Skin explants were preliminarily exposed to medium alone, Cd2+ and Cd2+ plus buthionine S,R-sulfoximine, an inhibitor of glutathione synthesis. We then compared the number of UVB-induced sunburn cells and apoptotic cells in the epidermis of MT-null mice with that of control mice using organ culture systems. The skin of MT-null mice developed a greater number of sunburn cells and apoptotic cells than did that of normal mice in all experimental conditions. These findings indicate that the skin of MT-null mouse is readily injured by UVB irradiation. MT-null mouse provided direct evidence of the photoprotective effect of cellular MT in the skin.

Animals↗
PubMed1998

Reduction of caveolin-1 expression in tumorigenic human cell hybrids.

Studies on human cell hybrids of a cervical carcinoma cell line, HeLa, and normal fibroblasts have indicated that the tumorigenicity of these cells is under the control of a putative tumor suppressor on chromosome 11, although the nature of this suppressor remains unknown. We examined the expression of caveolin-1, a protein component of caveolae of the plasma membrane in these cell hybrids. The non-tumorigenic cell hybrid, CGL1, and normal fibroblast WI38 cells expressed 21-24 kDa caveolin-1, whereas in tumorigenic hybrid CGL4 as well as in the parental HeLa cells, the level of caveolin-1 was markedly reduced. Caveolin-1 expression was also reduced in gamma-ray-induced tumorigenic clones (GIMs) isolated from CGL1 cells, whereas non-tumorigenic irradiated cells expressed the same level of caveolin-1 as CGL1 cells. In accordance with these changes, the cellular level of caveolin-1 mRNA was reduced in the tumorigenic CGL4 cells and GIMs without any detectable changes in the caveolin-1 gene. However, the in vivo tumor growth of CGL4 cells was not altered when caveolin-1 was stably overexpressed through the transfection of a human caveolin-1 cDNA. These results suggest that reduction of caveolin-1 expression is necessary but not sufficient for emergence of the tumorigenic phenotypes of HeLa cell hybrids. Possible roles of the putative tumor suppressor in the control of gene expression are also discussed.

Blotting, Northern↗
PubMed1998

Hemodynamic effect of endothelin antagonists in dogs with myocardial infarction.

The hemodynamic effects of enalapril, an angiotensin-converting enzyme inhibitor, BQ-123, a selective ETA receptor antagonist, and bosentan, a nonselective ETA and ETB receptor antagonist, were studied in dogs 4 weeks after myocardial infarction (MI) produced by ligation of the left anterior descending coronary artery. Reduced arterial pressure and total peripheral resistance after administration of analapril, BQ-123, and bosentan revealed that both the renin-angiotensin system and endothelin participate in maintenance of cardiovascular function in chronic MI.

Animals↗
PubMed1998

Flagellate mushroom (Shiitake) dermatitis and photosensitivity.

Flagellate skin lesions occur in some patients after eating the mushroom Lentinus edodes, and they are called shiitake dermatitis in Japan. We describe a 44-year-old man with such skin lesions on his trunk after eating L. edodes, who developed as well photosensitive skin lesions on exposed areas. Skin phototesting with UVB did not show a decreased minimum erythema dose; UVA irradiation provoked an erythematous lesion with nonspecific histological changes. Analysis of the case histories of 94 Japanese patients with shiitake dermatitis revealed that 44 (47%) also developed dermatitis on the skin exposed to sunlight. UVA photodermatitis has not been emphasized in previous reports. The relationship to bleomycin flagellate dermatitis is discussed.

Adult↗
PubMed1998

Alterations in ultrastructural localization of growth-associated protein-43 (GAP-43) in periodontal Ruffini endings of rat molars during experimental tooth movement.

It is known that orthodontic forces induce discomfort and/or abnormal sensation after application of an orthodontic appliance in patients, suggesting the adaptation of periodontal neural elements to environmental changes. However, no morphological data have been provided. The present study investigated, by immunoelectron microscopy, the localization of growth-associated protein-43 (GAP-43) in periodontal Ruffini endings in rat molars during experimental tooth movement. In the untreated control group, immunoelectron microscopy demonstrated that GAP-43-like immunoreactivity in the Ruffini endings was confined to the Schwann sheaths around the axon terminals, and was in neither the cell bodies of terminal Schwann cells nor the axon terminals themselves. Immunoelectron microscopic observation revealed alterations in the localization of GAP-43-like immunoreactivity in the periodontal Ruffini endings during experimental tooth movement. After 1 day of treatment, the cell bodies of the terminal Schwann cells associated with Ruffini endings appeared to contain immunoreaction products for GAP-43, and retained GAP-43-like immunoreactivity during tooth movement. From 5 to 7 days, a major population of the axoplasm of the periodontal Ruffini endings, which was immunonegative in control, filled the GAP-43 immunoreactions, showing a tendency to decrease in number later, and disappeared completely at 14 days. These findings suggest that orthodontic forces easily induce the remodeling of the mechanoreceptive Ruffini endings as well as the active tissue remodeling in a close relationship. Since the ultrastructural localization of GAP-43-like immunoreactivity was drastically changed in the Ruffini endings during tooth movement, GAP-43 functions as one of the key molecules in the remodeling of mechanoreceptive Ruffini endings during tooth movement.

Acid Phosphatase↗
PubMed1998

Value of MR cholangiopancreatography in evaluating choledochal cysts.

OBJECTIVE: The aim of this retrospective study was to clarify whether MR cholangiopancreatography (MRCP) is a suitable replacement for ERCP in evaluation of the choledochal cyst. MATERIALS AND METHODS: Sixteen patients (six adult and 10 pediatric) with choledochal cysts underwent MRCP using a half-Fourier acquisition single-shot turbo spin-echo sequence. Extent of the cyst, defects within the biliary tree, and presence or absence of the anomalous junction of the pancreaticobiliary duct were evaluated. Findings were compared with those of ERCP. RESULTS: MRCP better defined the proximal biliary tree than did ERCP in two patients. Defects within the biliary tree were diagnosed correctly on MRCP in eight patients; however, two defects within the distal common bile duct were missed in pediatric patients. The presence of the anomalous junction of the pancreaticobiliary duct was revealed accurately by MRCP in all adult patients but was revealed accurately in only four of the 10 pediatric patients. CONCLUSION: MRCP appears to offer diagnostic information that is equivalent to that of ERCP for assessment of choledochal cysts in adults. In pediatric patients, MRCP should not replace ERCP; however, MRCP can play an important role as a noninvasive examination and should be considered a first-choice imaging technique for evaluation of choledochal cysts.

Adult↗
PubMed1998

The use of scanning laser ophthalmoscope microperimetry to detect visual impairment caused by macular photocoagulation.

BACKGROUND AND OBJECTIVE: To demonstrate the effectiveness of scanning laser ophthalmoscope (SLO) microperimetry in detecting retinal sensitivity and in describing areas of unstable fixation following photocoagulation therapy. PATIENTS AND METHODS: Two patients with iatrogenic vision loss resulting from photocoagulation therapy underwent a fundus examination, SLO microperimetry, and fluorescein angiography. One patient also underwent indocyanine green angiography. RESULTS: Two types of visual acuity decrease--sudden-onset and late-onset--were demonstrated following macular photocoagulation, the former resulting from incorrect identification of the fixation point, and the latter from enlarging photocoagulation scars placed in close proximity to the fovea. In one case, SLO microperimetry detected dense scotoma corresponding to the patient's symptoms and an unstable fixation point. In the other case, different retinal sensitivities were found in the photocoagulation scars. No differences were found with fluorescein angiography or indocyanine green angiography. CONCLUSION: SLO microperimetry might be effective for quantitative assessment of retinal sensitivity in photocoagulation scars and for detecting fixation points and determining their stability.

Diabetic Retinopathy↗
PubMed1997

Age-related decline in humoral immunity caused by the selective loss of TH cells and decline in cellular immunity caused by the impaired migration of inflammatory cells without a loss of TDTH cells in SAMP1 mice.

We investigated the cellular basis of the age-related decline in antibody (Ab) and delayed-type hypersensitivity (DTH) responses to sheep red blood cells (SRBC) in vivo in short-lived senescence-accelerated mouse (SAM) P1. In SAMP1 mice, age-related decreases in CD4+ T cells in the peripheral blood occurred earlier than in control mice and occurred in parallel with the age-related decline in Ab and DTH responses. In addition, the involution of the thymus was faster. The injection of thymic T cells from young mice before sensitization completely restored the Ab responses in aged SAMP1 mice. These data suggest that the age-related decline in Ab response is due to the age-related early loss of helper-T (TH) cells. On the other hand, the local transfer of spleen cells from sensitized aged donors into the footpads of naive syngeneic recipients evoked strong DTH responses, demonstrating the existence of DTH-mediating T (TDTH) cells in the spleens of aged SAMP1 mice. Moreover, the local injection of naive spleen cells from young donors, together with the antigen, into the footpads caused DTH responses in sensitized aged recipients. These findings indicate that TDTH cells were induced and were able to migrate and function as effector cells in aged mice. When naive spleen cells from aged donors were injected locally into the footpad, they restored the DTH response in aged mice, but this effect did not work if the cells were injected intravenously. This demonstrates that the inflammatory cells of the aged mice were able to work at the local site, but could not migrate there. The intravenous injection of naive spleen cells from young donors restored the DTH response in aged mice, suggesting that the endothelial cells of aged mice were not impaired and permitted the inflammatory cells to migrate into the extravascular tissues. Thus, although the age-related decline of the Ab and DTH responses occur in parallel, we found different effects of aging on TH and TDTH cells in SAMP1 mice. Furthermore, our data suggest that the reason for the low DTH response in aged SAMP1 mice is not the loss of TDTH cells, but rather the impaired migration of inflammatory cells into the local site.

Aging↗
PubMed1997

A mammalian homolog of the yeast LCB1 encodes a component of serine palmitoyltransferase, the enzyme catalyzing the first step in sphingolipid synthesis.

Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the initial step dedicated to sphingolipid biosynthesis and is thought to be a key enzyme for regulating cellular sphingolipid content. For SPT activity, the yeast Saccharomyces cerevisiae requires two genes, LCB1 and LCB2. We isolated mammalian LCB1 cDNA homologs from mouse and Chinese hamster ovary (CHO) cells and an LCB2 cDNA homolog from CHO cells. The mammalian LCB1 proteins are predicted to have about 35% amino acid identity to the yeast Lcb1 protein, whereas the CHO LCB2 protein is predicted to have about 40% amino acid identity to the yeast Lcb2 protein. Northern blot analysis of mRNA isolated from various mouse tissues revealed that the tissue distribution of both LCB1 and LCB2 messengers followed a similar pattern. Transfection of an SPT-defective CHO mutant strain with a CHO LCB1-expressing plasmid restored both SPT activity and de novo sphingolipid synthesis to the wild type levels, whereas transfection of the mutant strain with a CHO LCB2-expressing plasmid did not exhibit any recovery effects, indicating that the SPT defect in the mutant cells is specifically complemented by the CHO LCB1 homolog. Furthermore, when the SPT-defective mutant cells were transfected with a plasmid encoding a His6-tagged CHO LCB1 protein, SPT activity bound to a Ni2+-immobilized resin. These results indicate that the CHO LCB1 homolog encodes a component of SPT.

Acyltransferases↗
PubMed1997

Inhibitory effect on curcumin on mammalian phospholipase D activity.

Curcumin, the major yellow pigment of turmeric (Curcuma longa), has strong anti-carcinogenic and anti-inflammatory activities. We examined the effects of curcumin on enzyme activities of the following phospholipases in a cell-free system: G protein-mediated phospholipase D (PLD), phosphatidylinositol-specific phospholipase C, and phospholipase A2 from mouse macrophage-like cell line J774.1 cells, sphingomyelinase from bovine brain, and phosphatidylcholine-phospholipase C from Bacillus cereus. Curcumin inhibited several types of phospholipases, most effectively PLD among those tested. It also inhibited 12-O-tetradecanoylphorbol-13-acetate-induced PLD activation in intact J774.1 cells in a dose-dependent manner. These results suggest that the anti-inflammatory and anti-carcinogenic action of curcumin is partly due to the inhibition of PLD.

Animals↗