Search PubMed⌕ Search

Biomedical subjects

Y Yamagishi

Publications and source records attributed to Y Yamagishi.

At least 19 recordsLinked to original sources
PubMed2001

A Japanese herbal medicine, Sho-saiko-to, prevents gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats.

BACKGROUND AND AIM: We have reported that gut ischemia/reperfusion (I/R) causes hepatic microvascular dysfunction. Nitric oxide (NO) has been found to be a modulator of the adhesive interactions between leukocytes, platelets, and endothelial cells. Sho-saiko-to (TJ-9), a Japanese herbal medicine, is reported to have protective effects against liver injury and to regulate NO production. The objective of this study was to determine whether TJ-9 affects hepatic microvascular dysfunction elicited by gut I/R, and to investigate the role of NO. METHODS: Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment and the number of non-perfused sinusoids (NPS). Plasma tumor necrosis factor (TNF)-alpha and alanine aminotransferase (ALT) activities were measured. In another set of experiments, TJ-9 (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma TNF-alpha and ALT activities, and these changes were mitigated by the pretreatment with TJ-9. Pretreatment with an NO synthase inhibitor diminished the protective effects of TJ-9 on the increase in leukostasis in the pericentral region, NPS, and plasma TNF-alpha levels, but not its effect on the increase in leukostasis in the midzonal region, total number of stationary leukocytes, or plasma ALT activities. Pretreatment with TJ-9 increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. CONCLUSIONS: These results suggest that TJ-9 attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-alpha production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect like corticosteroid effect.

Animals↗
PubMed2001

[Medical education for students in compulsory education: the conception of the preparation of three graded textbooks and preliminary evaluation of lectures using these textbooks].

The school pharmacist in our hospital pharmacy used three graded textbooks about medicine for students at the Sukagawa School for the Health-Impaired (Fukushima Medical University Hospital Branch (H. I. school)). A revised textbook for 4th-6th grade elementary school students containing 12 important items of information about medicine, a new picture textbook for 1st-3rd grade elementary school students, and a new textbook containing practical data for junior high school students were prepared by supplementing original information with illustrations, simplified expression and large type face. Additionally, the pronunciation of Chinese characters was included in the textbook for the 1st-3rd grade elementary school students. In this study, 9 students from H. I. school and 37 students from Koyase junior high school took part in a questionnaire and an examination evaluating the usefulness of the lectures, and these textbooks, in regard to the student's recognition and understanding of medicine. Most students answered that the lectures and textbooks helped them to understand medicine. Furthermore, the results of the examination indicated that the students had a general understanding of medicine. In conclusion, we suggest that it is important for students in compulsory education to learn about medicine, and that according to the preliminary result of questionnaires and examinations, both the lectures and textbooks were useful to help the students to understand more about medicine.

Adolescent↗
PubMed2001

FR198248, a new anti-influenza agent isolated from Apsergillus terreus No 13830. I. Taxomony, fermentation, isolation, physico-chemical properties and biological activities.

A novel anti-influenza agent, FR198248, was isolated from the cultured broth of a fungal strain No.13830. The strain was identified as Aspergillus terreus from morphological characteristics. FR198248, a new type of hydroxyl benzaldehyde compound, showed antiinfluenza virus activity in Madin-Darby canine kidney (MDCK) cells in vitro. The mode of action of FR198248 against influenza virus A could be ascribed to an inhibitory effect on the stage of virus adsorption. Furthermore, FR198248 possessed potent in vivo anti-influenza activity in a murine model of respiratory tract infection.

Animals↗
PubMed2000

V642I APP-inducible neuronal cells: a model system for investigating Alzheimer's disorders.

APP is a precursor of beta amyloid deposited in Alzheimer's disease (AD). Although genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not vehicle, killed most cells within a few days, with rounding, shrinkage, and detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that apoptosis occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders.

Alzheimer Disease↗
PubMed2000

Cell cycle arrest enhances the in vitro cellular toxicity of the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch.

Machado-Joseph disease (MJD) is an inherited neurodegenerative disorder caused by the expansion of the polyglutamine stretch in the MJD gene-encoded protein, ataxin-3. Using a series of deletion constructs expressing ataxin-3 fragments with expanded polyglutamine stretches, we observed aggregate formation and cell death in cultured BHK-21 cells. The cytotoxic effect of N-terminal-truncated ataxin-3 with the expanded polyglutamine tract was enhanced under serum starvation culture, in which cells were arrested in the G(0)/G(1)phase. Coexpression of p21 (waf1/cip1/sdi1), a cyclin-Cdk inhibitor that induced cell cycle arrest in the G(1)phase, also increased the cell death susceptibility produced by the mutant ataxin-3 fragment in BHK-21 cells. The elevated susceptibility to cell death in the G(0)/G(1)phase was confirmed in nerve growth factor-treated, postmitotic neuronal PC12 cells compared with undifferentiated proliferating PC12 cells. These results strongly suggest that the cellular toxicity of truncated ataxin-3 with an expanded polyglutamine stretch is enhanced by cell cycle arrest in the G(0)/G(1)phase. Mutant ataxin-3 may confer a higher susceptibility to cell death on cells in the G(0)/G(1)phase.

Animals↗
PubMed2000

Hepatic microvascular dysfunction in endotoxemic rats after acute ethanol administration.

BACKGROUND: A high concentration of ethanol is reported to cause hepatic microvascular dysfunction. However, little is known about the effect of ethanol on hepatic microcirculation in endotoxemic animals. The objective of this study was to determine whether endotoxemia enhances the hepatic microvascular dysfunction induced by acute ethanol administration. METHODS: Intravital videomicroscopy was used to monitor leukocyte recruitment, number of nonperfused sinusoids, and flow velocity of erythrocytes (RBC) labeled with fluorescein isothiocyanate (FITC) in the livers of male Wistar rats that were administered ethanol (20%, 3 g/kg; or 40%, 6 g/kg) from a gastric tube. Flow velocity of RBC in sinusoids was measured with an off-line velocimeter. Plasma tumor necrosis factor (TNF)-alpha levels were also measured. In some experiments, rats were injected with 2 mg/kg of lipopolysaccharides (LPS) intraperitoneally at 16 hr before the experiments, and the same protocol was performed. RESULTS: Although FITC-RBC velocity was initially increased by both 20% and 40% ethanol in control rats, it was reduced by only 40% ethanol at 60 min. In LPS-treated rats, the FITC-RBC velocity also was increased initially but was reduced at 60 and 30 min by 20% and 40% ethanol, respectively. Only 40% ethanol caused leukostasis in the pericentral region of control rats. In LPS-treated rats, however, leukostasis was noted in the midzonal and pericentral regions of liver after both 20% and 40% ethanol administration. Ethanol increased plasma TNF-alpha levels only in LPS-treated rats. CONCLUSIONS: These results suggest that LPS synergistically enhances ethanol-induced hepatic microvascular dysfunction and liver injury, especially in the midzonal region via coagulation, which may be mediated by TNF-alpha.

Animals↗
PubMed2000

Role of nitric oxide in endotoxin-induced hepatic microvascular dysfunction in rats chronically fed ethanol.

BACKGROUND: Nitric oxide (NO) appears to be involved in the pathogenesis of endotoxin-induced liver injury. However, little is known about how NO acts on the hepatic microcirculation, especially in alcohol-fed animals. We examined the roles of NO in endotoxin-induced hepatic microvascular dysfunction in control and ethanol-fed rats. METHODS: One lobe of the liver was observed with an intravital microscope. Flow velocity of fluorescein isothiocyanate-labeled erythrocytes in sinusoids was measured with an off-line velocimeter. Portal pressure and mean arterial pressure also were measured. RESULTS: After administration of endotoxin to control, the flow velocity decreased after 30 min. Portal pressure increased after 45 min. However, in ethanol-fed rats, both the flow velocity and portal pressure temporarily increased in the early phase. Thereafter, the flow velocity decreased and portal pressure increased. At 30 min after administration of the endotoxin, pretreatment with 10 mg/kg of an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), enhanced the endotoxin-induced decrease in the velocity of erythrocytes in the midzonal region of both control and ethanol-fed rats. Although 0.5 mg/kg of L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the midzonal region of ethanol-fed rats, L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the pericentral region of control rats. At 60 min after the endotoxin administration, L-NMMA did not affect the endotoxin-induced decrease of erythrocyte velocity in either control or ethanol-fed rats. Although 10 mg/kg of L-NMMA increased mean arterial pressure both in control and ethanol-fed rats, 0.5 mg/kg of L-NMMA did not change mean arterial pressure in either control or ethanol-fed rats. CONCLUSIONS: These results suggest that NO is involved in endotoxin-induced hepatic microvascular dysfunction, which may contribute to the sequential liver injury, especially in alcohol-fed animals.

Animals↗
PubMed1997

Human lymphotoxin mutein lacks hypotensive activity but has higher in vivo antitumor activity than lymphotoxin or tumor necrosis factor.

A serious drawback of tumor necrosis factor alpha (TNF) as a clinical antitumor agent is that it also has hypotensive activity. To overcome this problem, derivatives of its sister cytokine lymphotoxin (TNF-beta or LT) were prepared. One of them, mutein 2 (Mut2) has a deletion of amino acids 1-7 but contains substituted amino acids, Met-Phe-Pro at positions 8-10 of the mature human LT. This mutein has no hypotensive activity at the maximum dose (10 mg/kg) tested on rats. In contrast, a much lower dose (1 mg/kg) of TNF and LT caused a significant blood pressure drop. In vivo studies revealed that Mut2 was more effective than TNF or LT against MethA (a mouse tumor line) as judged by the therapeutic ratio [calculated as LD50 (dose that kills 50% of the animals)/ED50 (dose that reduces the tumor size by 50%)]. With five other different mouse tumors and two different human tumors, Mut2 was also effective and the effectiveness was comparable or superior to that of TNF or LT. These results suggest the possibility that this derivative may be usable as a clinical antitumor agent without the serious side effects associated with TNF.

Animals↗
PubMed1997

Three types of recombinant human granulocyte colony-stimulating factor have equivalent biological activities in monkeys.

Three types of rhG-CSF are commercially available (non-glycosylated: filgrastim, glycosylated: lenograstim and N-terminal mutated: nartograstim). It has been reported that higher in vitro or in vivo efficacy was found in glycosylated or N-terminal mutated rhG-CSF than in non-glycosylated rhG-CSF. We reported that glycosylated or N-terminal mutated rhG-CSF showed equal efficacy to non-glycosylated rhG-CSF in vivo. In this study, we carried out a direct comparison of pharmacokinetics and pharmacological effects of three rhG-CSFs. We used commercially obtained rhG-CSF products whose activities are guaranteed by the manufacturers. Monkeys have been selected as the experimental animals because of their close relationship to humans concerning drug disposition and daily doses were in accordance with the clinical use of rhG-CSFs. Normal cynomolgus monkeys were given 1.5 or 5 micrograms/kg of rhG-CSF either intravenously or subcutaneously for 5 consecutive days. After intravenous injection, the serum concentration-time profiles of nartograstim were almost identical to those of filgrastim at both doses but the concentrations after lenograstim administration decreased faster. Following subcutaneous administration, no marked differences were observed between the three rhG-CSFs, although lenograstim showed lower serum concentrations than both filgrastim and nartograstim. In spite of some small differences in the pharmacokinetics of the three rhG-CSFs, the pharmacodynamics were identical.

Animals↗
PubMed1997

Mitochondrial DNA analysis of Phialophora verrucosa.

Restriction fragment length polymorphism (RFLP) of mitochondrial DNA (mtDNA) was examined in 32 isolates of Phialophora verrucosa (eight isolates from Japan, 10 from China, four from the USA, six from Venezuela and four from Colombia) and in three of Phialophora americana using five restriction enzymes. P. verrucosa isolates were divided into 10 mtDNA types based on RFLP patterns. Phylogeny constructed on sequence divergence of mtDNA indicated that P. verrucosa is a single species and isolates are clustered into three groups. Japan and the USA contained Group A and Group B isolates, China Group B isolates and South America Group B and Group C isolates. RFLP patterns of P. americana mtDNA were identical to those of Type 1 or Type 4 of P. verrucosa mtDNA, suggesting that both are identical. RFLP patterns of P. verrucosa were distinct from those of other dematiaceous fungi including Exophiala jeanselmei, E. moniliae, E. dermatitidis, E. spinifera, Cladophialophora (Cladosporium) carrionii, Fonsecaea pedrosoi, and Hortaea werneckii. These results indicate that RFLP analysis of mtDNA is a useful method for the identification, taxonomy, typing, epidemiology and phylogeny of P. verrucosa.

DNA, Fungal↗
PubMed1997

Gangliocytoma with immature neuronal cell elements in the pituitary of a rat.

A spontaneous pituitary gangliocytoma with abundant, immature neuronal cell elements was found incidentally in a 109-week-old female Fischer 344 rat. The pituitary parenchyma was largely occupied by a tumor nodule with necrotic and hemorrhagic foci and cyst. The tumor was composed of mature ganglion-like (M) cells, small immature ganglion (I) cells and transitional (T) cells, with a fibrillar matrix. The I and T cells were intermingled with the M cells or were arranged in compact clusters, in which the I cells formed perivascular rosette-like structures, sometimes with mitotic figures. Immunohistochemically, all types of tumor cells were positive for neuron-specific enolase, and only the M cells was positive for chromogranin A. This result may be correlated with the degree of cytodifferentiation.

Animals↗
PubMed1996

Demonstration of alkaline phosphatase participation in the mineralization of osteoblasts by antisense RNA approach.

MC3T3-E1 cells grown with ascorbic acid express sequentially osteoblastic marker proteins such as alkaline phosphatase (ALPase) and then form a mineralized extracellular matrix (ECM) as a consequence of osteoblastic differentiation. To explore the functional roles of ALPase in the process of osteoblastic maturation, an inducible expression vector for antisense ALPase RNA was constructed and stably transfected into MC3T3-E1 cells. The expression of antisense ALPase RNA in the differentiated MC3T3-E1 transfectants reduced markedly the ALPase activity, which resulted in a significant decrease in the deposition of minerals upon prolonged culture. These findings demonstrated directly that ALPase participated in the mineralization of ECM.

Alkaline Phosphatase↗
PubMed1996

Spontaneous lesions detected in the common cotton-eared marmosets (Callithrix jacchus).

Spontaneous lesions in the common cotton-eared marmosets (Callithrix jacchus), which were maintained in our laboratory or were purchased from a commercial breeder, were examined histopathologically. There were 39 males and 22 females, between the ages of 7 and 100 months. The most interesting finding noted was extramedullary hematopoiesis, which was observed in the mesenteric lymph nodes, spleen, liver, kidney, adrenal gland, and cerebral choroid plexus. Megakaryocytes were frequently observed in the blood vessels of the alveolar wall of the lung. It is important to distinguish extramedullary hematopoiesis which occurs accidentally from that induced by repeated blood sampling or that resulting from administration of chemicals. Extramedullary hematopoiesis was easily distinguishable from inflammation or hematopoietic neoplasms, because of the various cellular elements present, including megakaryocytes. In the weak and dead animals, enterocolitis was found at a high frequency. Other common findings included thymic involution, prominent vacuolation of liver sinusoidal cells, which were probably Ito-cells, and basophilic changes in the renal tubular epithelium. The liver and the kidney are frequently affected by toxic effects of chemicals. Therefore, it is important to distinguish the toxic changes from the spontaneous ones. Proliferation of apocrine glands in the cervical skin was an interesting finding; however, neither inflammatory change nor cellular atypia was noted in this structure. Although its function is unclear, this structure may be a marmoset-specific tissue.

Adrenal Glands↗