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Biomedical subjects

M Yoshikawa

Publications and source records attributed to M Yoshikawa.

At least 235 records · Page 13Linked to original sources

Inhibition of gastric emptying by triterpene saponin, momordin Ic, in mice: roles of blood glucose, capsaicin-sensitive sensory nerves, and central nervous system.

The roles of capsaicin-sensitive sensory nerves and the central nervous system in the inhibitory effect of momordin Ic, a principal saponin constituent in various Chinese and Japanese herbal medicines, such as the fruit of Kochia scoparia (L.) SCHRAD., on gastric emptying were investigated in nonnutrient meal- or nutrient meal-loaded mice. Momordin Ic (12.5-50 mg/kg) significantly inhibited gastric emptying in 1.5% carboxymethyl cellulose sodium salt test meal-loaded mice by 8.4%-60.6%, 40% glucose test meal-loaded mice by 42.8% (50 mg/kg), milk test meal-loaded mice by 36.4% (50 mg/kg), and 60% ethanol test meal-loaded mice by 37.2% (50 mg/kg). The inhibitory effect on the gastric emptying in 1.5% carboxymethyl cellulose sodium salt test meal-loaded mice was potentiated by glucose (2 g/kg, i.v. or 5 g/kg, i.p.), but markedly attenuated by pretreatment with alloxan (50 mg/kg, i.v.) and streptozotocin (100 mg/kg, i.v.), in which the activity of sympathetic nervous system was decreased, or by insulin (1 or 3 U/kg, s.c.). The effect of insulin (1 U/kg) was markedly reduced by glucose (2 g/kg, i.v.), which can directly nourish the brain, but not by fructose (2 g/kg, i.v.), which cannot be used by the brain. The effect of momordin Ic was also attenuated by pretreatment with capsaicin (75 mg/kg in total, s.c.). These results suggest that the inhibition of gastric emptying by momordin Ic is relative to serum glucose and, at least in part, mediated by capsaicin-sensitive sensory nerves and the central nervous system.

Animals↗

[A study of factors relating to aggravation of patients with pulmonary Mycobacterium avium complex disease--with special reference to malnutrition].

We examined physical and blood statuses of 24 patients with pulmonary M. avium complex disease who entered our hospital from April 1993 to March 1997. Ten patients (41.7%) were diagnosed as primary infection type and 14 patients (58.3%) as secondary infection type. Twenty-four patients were classified to the following two groups: Group A was 14 patients who converted to MAC negative within six months after the admission and group B was 10 patients who continued to excrete MAC for more than six months after the admission. We made a comparison between group A and group B as to the results of physical and blood examinations on admission. Mean value of %IBW in group B was significantly lower (group B:74.4 +/- 8.9%, group A:82.9 +/- 12.7%, p < 0.05) than that of group A. The level of serum albumin in group B was significantly lower (group B: 3.39 +/- 0.53 g/dl, group A: 3.99 +/- 0.45 g/dl, p < 0.01) than that of group A. ChE in group B was significantly lower (group B: 321.2 +/- 94.5 IU/l, group A: 442.9 +/- 148.4 IU/l, p < 0.05) than that of group A. Group B was nutritionally depleted than group A. In conclusion, these findings suggested that nutritional support should be taken into consideration in combination with conventional chemotherapy in treating chronic, intractable MAC disease.

Aged↗

Radiotherapy for large hepatocellular carcinoma combined with transcatheter arterial embolization and percutaneous ethanol injection therapy.

This study was performed to determine the effect of radiotherapy (RT) combined with transcatheter arterial embolization (TAE) and percutaneous ethanol injection (PEI) on large HCC. Between 1988 and 1996, 102 patients with unresectable, biopsy proven HCC underwent uniform pretreatment assessment followed by TAE and PEI. Of the 102 patients, 68 (67%) had more than 2 lesions in the liver, and the largest tumor sizes in each patient ranged from 3 to 8 cm in diameter. Immediately after TAE and PEI, external beam RT (36 to 70 Gy) was administered to the largest tumors only in 44 patients. The cause-specific 5-year survival rate for all patients was 39.9%. The 3-year survival rate of the RT group was better than that of the no RT group (81.1% vs. 54.6%). The cumulative local control rates of the largest treated tumors were 53.2% in the RT group and 32.7% in the no RT, respectively (p=0.006). When the survival rate was compared between patients with and without local control in the RT group, that of patients with local control was significantly better than that with local recurrences (p=0.048). No deaths or major treatment related complications occurred. RT combined with TAE and PEI did not clearly show improvement of the survival, however, it effectively controlled large HCC, and demonstrated minimal toxicity. This treatment may represent therapeutic option for some patients with unresectable large HCC.

Aged↗

Laparoscopically assisted splenectomy following preoperative splenic artery embolization using contour emboli for myelofibrosis with massive splenomegaly.

Laparoscopically assisted splenectomy with an 8- to 10-cm left upper paramedian laparotomy was performed following preoperative splenic artery embolization using painless contour emboli (super absorbent polymer microsphere) with early successful results in two men (46 and 37 years old) with myelofibrosis accompanied by massive splenomegaly. Dissection around the lower part of the spleen and the hilum initially was performed intracorporeally with the usual laparoscopic view under 12 mm Hg pneumoperitoneum. The alternating changes of viewpoints between the direct view through an 8- to 10-cm incision and the usual laparoscopic view with or without application of a retraction method were effective for safe hilar devascularization. Preoperative splenic artery embolization at the distal site was effective for safe dissection around the enlarged spleen. The patients did not complain of pain before operation. Preoperative painless embolization and laparoscopically assisted splenectomy with small laparotomy promotes the feasibility and safety of minimally invasive splenectomy for myelofibrosis with massive splenomegaly.

Adult↗

Antitumor effect of electrochemotherapy on colorectal carcinoma in an orthotopic mouse model.

Electropermeabilization was shown to markedly increase the sensitivity of murine colorectal carcinoma (CRC) cells to bleomycin (BLM), resulting in more than 2,500-fold higher susceptibility to BLM. Subsequent in vivo electrochemotherapy with BLM revealed profound antitumor effects on subcutaneous CRC tumors. Furthermore, when electrochemotherapy with BLM was employed for the treatment of orthotopic CRC tumors in mice, significantly prolonged survival priods were observed. These results indicate the feasibility of electrochemotherapy with BLM for the treatment of CRC and demonstrate that electrochemotherapy can be translated from the treatment of cutaneous and subcutaneous tumors to the treatment of internal cancers including CRC.

Animals↗

Hepatoprotective, superoxide scavenging, and antioxidative activities of aromatic constituents from the bark of Betula platyphylla var. japonica.

The 50% aqueous methanolic extract from the bark of Betula platyphylla SUKATCHEV var. japonica (MIQ). HARA was found to show potent inhibitory activity on the liver-injury induced by CCl4 or D-galactosamine (D-GalN)/lipopolysaccharide as well as O2- scavenging and antioxidative activities. From the 50% aqueous methanolic extract, two new diarylheptanoids named betulaplatosides Ia (1) and Ib (2) and a new arylbutanoid named betulaplatoside II (3) were isolated together with seventeen known aromatic constituents. 1, 2, and two known diarylheptanoids [(5S)-5-hydroxy-1,7-bis-(4-hydroxyphenyl)-3-heptanone 5-O-beta-D-apiofurano-syl-(1-->6)-beta-D-glucopyranoside (6) and aceroside VIII (7)] showed protective activity against D-GalN-induced cytotoxicity in primary cultured rat hepatocytes. Furthermore, several aromatic constituents exhibited potent O2- scavenging and antioxidative activities.

Animals↗

Hepatoprotective and nitric oxide production inhibitory activities of coumarin and polyacetylene constituents from the roots of Angelica furcijuga.

The methanolic extract from the roots of Angelica furcijuga KITAGAWA was found to exhibit protective effects on liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). From the methanolic extract, seventeen coumarins, two phenylpropanoids, and two polyacetylenes were isolated and examined their in vitro and in vivo hepatoprotective effects and inhibitory activity of NO production in macrophages. A acylated khellactone, isoepoxypteryxin, showed protective activity against D-GalN-induced cytotoxicity in primary cultured rat hepatocytes. On the other hand, six acylated khellactones (hyuganins A, B, C, and D, anomalin, isopteryxin) and two polyacetylenes [(-)-falcarinol and falcarindiol] strongly inhibited NO production induced by LPS in cultured mouse peritoneal macrophages, and also other acylated khellactones (isoepoxypteryxin, pteryxin, and suksdorfin) and a coumarin glycosides (praeroside II) were found to show the activity. By comparison of the inhibitory activities for acylated khellactones with those for other coumarins, acyl groups were found to be essential to exerting potent activity.

Acetylene↗

Colocalization of Bcl-2 and 4-hydroxynonenal modified proteins in microglial cells and neurons of rat brain following transient focal ischemia.

Bcl-2 has a role in suppressing the production of reactive oxygen species and lipid peroxidation. To explore the in situ localization of 4-hydroxy-2-nonenal (HNE)-modified proteins and the Bcl-2 oncoprotein, we used double immunofluorescence labeling and confocal imaging in the rat brain after 3 h of middle cerebral artery (MCA) occlusion followed by reperfusion. Immunoreactivity for HNE or Bcl-2 was not detected at 1 h, but appeared in some intact neurons in the boundary between the infarcted and non-infarcted zones at 12 h. At 48 h, HNE-positive microglia were colocalized with Bcl-2 in the infarcted area and the boundary zone. Bcl-2 may play an important role in the antioxidant system promoting survival of the neurons and activated microglia following reperfusion injury.

Aldehydes↗

Calibration of space-resolving VUV and soft X-ray spectrographs for plasma diagnostics.

Vacuum ultraviolet (VUV) and soft X-ray measurements are important means of diagnosing impurities in magnetically confined plasmas used in fusion research. Recently, space- and time-resolving flat-field VUV (150-1050 A) and soft X-ray (20-350 A) spectrographs have been constructed by using aberration-corrected concave gratings with varied-spacing grooves which give a wide simultaneous spectral coverage on a microchannel-plate intensified detector. Calibration experiments have been performed at beamlines 11A and 11C at the Photon Factory of the High Energy Accelerator Research Organization. The relative efficiency of the VUV spectrograph has been measured for P-polarization geometry in the spectrograph. In the soft X-ray spectrograph, efficiencies have been obtained for several different points of irradiation on the grating along the groove direction and for two (S and P) polarization geometries.

Journal Article↗

Strong synergistic anti-peroxidative effects of HDL3 and ascorbic acid against copper-catalyzed LDL peroxidation.

The aim of this study was to investigate the effects of high density lipoprotein 3 (HDL3) and ascorbic acid (AsA) in combination on copper-catalyzed low density lipoprotein (LDL) peroxidation. LDL and HDL3 were isolated from sera of healthy volunteers. LDL protein, 200 microg/ml, was incubated in phosphate-buffered saline (PBS) containing 2.5 microM CuSO4 in the absence or presence of AsA, with HDL3 protein alone, or with coincubation of HDL3, 200 microg/ml, and AsA, 20 microg/ml, at 37 degrees C for up to 24 h. As a control, the same amount of control LDL protein was added to PBS. The protective effects of the HDL3 and AsA were examined by both electrophoresis and determination of the lipid hydroperoxide (LPO) level in each sample. The concentration of AsA was also measured in samples containing AsA. The coincubation of HDL3 and AsA exerts more powerful anti-peroxidative effects against copper-catalyzed LDL peroxidation, than either of these agents alone. In addition, AsA was retained in the media by the addition of HDL3. The findings suggest that there are strong synergistic anti-peroxidative effects of HDL3 and AsA and these two may act in concert in vivo to inhibit LDL peroxidation and thus exert an anti-atherosclerotic effect.

Antioxidants↗

Inhibitory effect and action mechanism of sesquiterpenes from Zedoariae Rhizoma on D-galactosamine/lipopolysaccharide-induced liver injury.

Hepatoprotective sesquiterpenes were isolated from the aqueous acetone extract of Zedoariae Rhizoma, the rhizome of Curcuma zedoaria ROSCOE (Zingiberaceae). Principal sesquiterpenes, furanodiene, germacrone, curdione, neocurdione, curcumenol, isocurcumenol, aerugidiol, zedoarondiol, and curcumenone and curcumin were found to show potent protective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in mice. Plausible action mechanisms for their hepatoprotective activity were clarified on the basis of the inhibitory effect on D-GalN-induced cytotoxicity in primary cultured rat hepatocytes, LPS-induced NO production in cultured mouse peritoneal macrophages, and D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced liver injury in mice.

Animals↗

Immunomodulatory activity of thunberginol A and related compounds isolated from Hydrangeae Dulcis Folium on splenocyte proliferation activated by mitogens.

We investigated the immunomodulatory effects of antiallergic constituents from Hydrangeae Dulcis Folium, the processed leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO, on splenocyte proliferation in mice. Thunberginol A and hydrangenol significantly suppressed T lymphocyte proliferation induced by concanavalin A. Thunberginol A also suppressed B lymphocyte proliferation induced by lipopolysaccharide, but other constituents induced significant increases. These inhibitory effects of thunberginol A on splenocyte proliferation seemed to contribute to the suppressive effect on type IV allergy.

Adjuvants, Immunologic↗

Gene expression of alpha1-6 fucosyltransferase in human hepatoma tissues: a possible implication for increased fucosylation of alpha-fetoprotein.

The 1-6 fucosylated -fetoprotein (AFP) present in serum of patients with hepatocellular carcinoma (HCC) has been employed for the differential clinical diagnosis of HCC from chronic liver diseases. The molecular mechanism by which this alteration occurs, however, remains largely unknown. To address this issue, we purified GDP-L-Fuc:N-acetyl-beta-D-glucosaminide 1-6 fucosyltransferase (1-6 FucT), an enzyme involved in the 1-6 fucosylation of N-glycans from porcine brain, as well as from a human gastric cancer cell line, and cloned their genes. In this study, levels of 1-6 FucT mRNA expression and the activity of this enzyme for 12 human HCC tissues were examined and compared with that in surrounding tissues and normal livers. The mean +/- SD for 1-6 FucT activity was 78 +/- 41 pmol/h/mg in normal control liver, 202 +/- 127 pmol/h/mg in adjacent uninvolved liver tissues (chronic hepatitis: 181 +/- 106 pmol/h/mg; liver cirrhosis: 233 +/- 164 pmol/h/mg), and 195 +/- 72 pmol/h/mg in HCC tissues. The mRNA expression of 1-6 FucT was also enhanced in proportion to enzymatic activity except for a few cases, suggesting that 1-6 FucT expression is increased in chronic liver diseases, especially liver cirrhosis. Transfection of 1-6 FucT gene into cultured rat hepatocytes markedly increased 1-6 FucT activity and led to an increase in lens culinaris agglutinin (LCA) binding proteins in both cell lysates and condition media. When the 1-6 FucT gene was transfected into a human HCC cell line, Hep3B, which originally showed low levels of 1-6 FucT expression, 1-6-fucosylated AFP was dramatically increased in the condition media. Collectively, these results suggest that the enhancement of 1-6 FucT expression increased the fucosylation of several proteins, including AFP, and that the level of 1-6-fucosylated AFP in patients with HCC was in part caused by up-regulation of the 1-6 FucT gene expression.

Adult↗

Neurotoxicity evoked by N-methyl-D-aspartate in the organotypic static slice cultures of rat cerebral cortices: effect of GABA(A) receptor activation.

We investigated the neurotoxicity evoked by N-methyl-D-aspartate (NMDA) receptor stimulation in the organotypic static slice cultures of rat cerebral cortices. We also examined whether the gamma-aminobutyric acid (GABA)A receptor agonist muscimol has a protective effect on the NMDA-mediated neurotoxicity in this culture system. NMDA-mediated cytotoxicity was evaluated histologically and quantified by the measurement of lactate dehydrogenase (LDH) release into the culture medium. There was an NMDA-induced, dose-dependent leakage of LDH release and neuronal cell death, which were not attenuated by muscimol treatment. The results suggested that NMDA neurotoxicity is reproduced in the organotypic culture, and that GABA(A) receptor activation exerted no protective action against the NMDA cytotoxicity.

Animals↗

Acute hepatic failure due to hepatosplenic B-cell non-Hodgkin's lymphoma in a patient infected with hepatitis C virus.

We report a 75-year-old Japanese man infected with hepatitis C virus (HCV) who died of acute hepatic failure due to the hepatic infiltration of B-cell non-Hodgkin's lymphoma (NHL) cells. He suddenly developed jaundice, fatigue, fever, and hepatosplenomegaly during the course of chronic infection with HCV. Postmortem liver necropsy revealed extensive infiltration of lymphoma cells into the liver. Although the association between HCV infection and NHL has recently become a matter of concern, we believe this to be the first reported case of acute hepatic failure caused by hepatic involvement of non-Hodgkin's lymphoma in an HCV-infected patient.

Aged↗

Protective effects of oleanolic acid oligoglycosides on ethanol- or indomethacin-induced gastric mucosal lesions in rats.

We examined the effects of various oleanolic acid oligoglycosides obtained from traditional herbs on ethanol- or indomethacin-induced gastric mucosal lesions in rats and on gastric secretion in pylorus-ligated rats. Test samples were given orally to fasted rats 1 h before absolute ethanol (1.5 ml/rat, p.o.) or indomethacin (30 mg/kg, s.c.) treatment, or ligation of the pylorus. Oleanolic acid 3-O-monodesmosides [oleanolic acid 3-O-glucuronide (1, 20-50 mg/kg), momordin Ic (2, 5-50 mg/kg), and 28-O-deglucosyl-chikusetsusaponins IV (5, 10-50 mg/kg) and V (7, 10-50 mg/kg)] were found to show protective effects on ethanol-induced gastric mucosal lesions, whereas oleanolic acid 3,28-O-bisdesmosides [momordin IIc (3), chikusetsusaponins IV (4) and V (6)], oleanolic acid 28-O-monodesmoside [compound O (8)], and their common aglycon [oleanolic acid (9)] showed no such effects. Oleanolic acid 3-O-monodesmosides (1, 2, and 5) also showed protective effects on indomethacin-induced gastric mucosal lesions. 28-O-Deglucosyl-chikusetsusaponin V (7) did not inhibit the indomethacin-induced lesions, while chikusetsusaponins V (6, 50 mg/kg) had the gastroprotective effect. These active saponins (1, 2, 4-7, 10-50 mg/kg) did not decrease the gastric secretion by oral administration in pylorus-ligated rats.

Animals↗