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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 145 records · Page 8Linked to original sources
PubMed1999

Gastroprotection by Liu-Jun-Zi-Tang (TJ-43): possible mediation of nitric oxide but not prostaglandins or sulfhydryls.

Liu-Jun-Zi-Tang (TJ-43), a herbal medicine exerting gastroprotective action, was examined for its mechanism of action in rats. TJ-43 significantly inhibited gastric mucosal damage caused by absolute ethanol at doses over 500 mg/kg in a dose-dependent way. Pretreatment with indomethacin or with N-ethylmaleimide did not affect the gastroprotective effect of TJ-43. However, pretreatment with NG-nitro-L-arginine partially but significantly reversed the protective effect of this drug. These findings suggest that the gastroprotective effect of TJ-43 occurs partly through nitric oxide but not through prostaglandins or sulfhydryls.

Animals↗
PubMed1999

Liu-Jun-Zi-Tang, a kampo medicine, promotes adaptive relaxation in isolated guinea pig stomachs.

Some patients with dysmotility-like functional dyspepsia present impaired reservoir functions such as gastric adaptive relaxation. A traditional Chinese herbal medicine, Liu-Jun-Zi-Tang, has been identified as an effective drug against dyspeptic symptoms and is widely used for therapy in such patients. In this study, we examined the effects of this drug on the gastric adaptive relaxation in isolated guinea pig stomachs. The changes in intragastric volume and pressure were recorded in the presence of atropine and guanethidine. Gastric adaptive relaxation was induced by luminal distention. Liu-Jun-Zi-Tang (100 mg/ml) induced gastric adaptive relaxation at a lower intragastric pressure and increased the % volume of the gastric adaptive relaxation and the absolute intragastric volume. Metoclopramide (2 mg/ml), trimebutine (6 mg/ml) and cisapride (2 mg/ml) did not affect gastric adaptive relaxation. It was inhibited by means of the incubation of the stomach with NG-nitro-L-arginine (100 microM). Liu-Jun-Zi-Tang (100 mg/ml), but not gastroprokinetics overcame the effect of NG-nitro-L-arginine. These results suggested that Liu-Jun-Zi-Tang promoted gastric adaptive relaxation. This effect might, at least in part, contribute to the symptom relief in patients with functional dyspepsia.

Adaptation, Physiological↗
PubMed1999

Effect of culture conditions on morphological changes of Helicobacter pylori.

The morphological conversion of Helicobacter pylori from the spiral form to the coccoid form may be the expression of a transitory adaptation to an unsuitable environment. The mechanism(s) of this conversion are not clear. In this study, we examined whether the morphological conversion of H. pylori is affected by various culture conditions, such as oxygen concentration, pH, temperature, or the presence of beta-cyclodextrin. H. pylori (NTCC11916) was cultured on Brucella agar, followed by culture in Brucella broth containing 1% agar under several conditions. Morphological conversion of individual H. pylori on the agar plate was investigated with time after incubation under phase contrast microscopy. When H. pylori was inoculated in Brucella broth containing beta-cyclodextrin, the spiral form of the organism was observed even after 6 days of incubation under standard culture conditions: 37 degrees C, pH 7, and microaerobic atmosphere (5% O2/10% CO2/85% N2) (control). The morphological conversion of H. pylori was completed on day 3 in an aerobic atmosphere (20% O2 supply) and on day 2 in an undermicroaerobic atmosphere (<0.1% O2). Its complete morphological conversion was observed at pH 8 on day 5 and at pH 4 on day 6. All of the H. pylori (100%) incubated at 20 degrees or 42 degrees C had converted from the bacillary to the coccoid form on day 4. Conditioned medium without beta-cyclodextrin caused complete conversion on day 5. These results suggest that oxygen concentration, pH, temperature, and beta-cyclodextrin may be related to the H. pylori morphological conversion from the bacillary to the coccoid form.

Culture Media↗
PubMed1998

Similarity in moth-fly specific larvicidal activity between two serologically unrelated Bacillus thuringiensis strains.

Parasporal inclusions of a Bacillus thuringiensis isolate designated 92-KU-105-9 (H14/19) exhibited unusual larvicidal activity, specific for the moth-fly, Telmatoscopus albipunctatus (Diptera: Psychodidae), similar to that of a previously reported B. thuringiensis serovar leesis (H33) strain. The LC50 value of the purified inclusions was 4.92 micrograms ml-1 for the moth-fly larvae, while no mortality was shown in the mosquitoes Culex pipiens molestus and Anopheles stephensi, at protein concentrations up to 10 mg ml-1. Morphologically, the inclusion was a homogeneous globular body surrounded by an electron-dense, thick envelope. Multilamellar inner structure was evident between envelope membrane and inclusion matrix. SDS-PAGE revealed that the inclusions consist of five proteins with molecular masses of 72, 70, 68, 56 and 30 kDa. These proteins cross-reacted with the antibodies against inclusion proteins of the serovar leesis strain. High homologies existed in N-terminal amino acid sequences between the three major proteins (72, 70 and 68 kDa) and the two established protein classes, Cry4A and Cry10A.

Amino Acid Sequence↗
PubMed1998

Age-related changes in the brains of senescence-accelerated mice (SAM): association with glial and endothelial reactions.

Twelve substrains of inbred senescence-accelerated mice (SAM) have been developed, among which the SAMP8 and SAMP10 strains show a significant age-related deterioration in learning and memory for passive and active avoidance tasks. These strains have, respectively, a low and high incidence of systemic senile amyloidosis. Although we found no amyloid deposits in their brain parenchyma, a variety of age-related alterations were identified, involving neurons, glia, and vessels in the brain tissues. Here we review the degenerative changes in aged SAMP8 and SAMP10 brains. These changes are generally similar to the pathology of aging human brain and may be characterized by their association with some specific glial reactions.

Aging↗
PubMed1998

An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model.

In order to characterize the early stage of mitochondrial dysfunction, we investigated the redox state and oxidative phosphorylation of the brain mitochondria from 2-month-old Senescence-accelerated mouse (SAM)P8 and SAMR1 mice; SAMP8 mice exhibit various signs of age-associated neurodegeneration and rapid mitochondrial dysfunction, although SAMR1 mice do not. The redox state was estimated as the reduction rate of Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), the reduction of which is closely related to the electron leakage from the mitochondrial electron transport system in the brain, using electron spin resonance spectrometry (ESRS). The oxidative phosphorylation was measured polarographically. The SAMP8 mouse brain mitochondria demonstrated higher redox state and a higher activity of mitochondrial respiration with lower respiration control ratio than the mitochondria of SAMR1 mouse brains. This indicates that an inefficient hyperactive state can exist in the mitochondrial electron transport system before the age-associated mitochondrial dysfunction develops.

Aging↗
PubMed1998

Identification of the critical portions of the human IL-4 receptor alpha chain for activation of STAT6.

Interleukin-4 (IL-4) has been shown to activate Janus kinase (Jak)-1 and Jak-3, followed by activation of STAT (signal transducers and activators of transcription) 6. This Jak-STAT pathway is central to the initiation of IL-4 activities. In this study, we identified the essential region for the proliferation signal and activation of Jak-1, Jak-3, and STAT6 in the cytoplasmic domain of the human IL-4 receptor alpha chain (hIL-4R alpha) using a mouse T cell line CTLL-2. We found that the region between amino acid 353 and 393 is critical for the proliferation signal and activation of STAT6, but not for tyrosine phosphorylation of Jaks. These results suggest that in addition to the "Box-1" portion, which is known to be essential for Jak-1 activation, the more membrane-distal region of hIL-4R alpha is also necessary for activation of STAT6.

Animals↗
PubMed1998

Lack of orally induced systemic unresponsiveness in IFN-gamma knockout mice.

Splenic T cells isolated from BALB/c mice that had been mucosally tolerized by oral administration of 25 mg of OVA revealed selective increases in IFN-gamma production with impaired levels of IL-2, IL-4, IL-5, and IL-10. These mice possessed reduced splenic OVA-specific T cell proliferative and delayed-type hypersensitivity responses when compared with nontolerized controls. Further, OVA-specific IgG Ab responses in serum and the numbers of IgG Ab-forming cells in spleen were significantly diminished following systemic challenge with OVA in CFA. When IFN-gamma-deficient (IFN-gamma-/-) mice of the same genetic background were given an oral dose of 25 mg of OVA before systemic immunization, no reduction in OVA-specific IgG Ab responses in serum and spleen was seen. Furthermore, the serum IgG Ab responses were restricted to IgG1 and IgG2b subclasses. Interestingly, although IFN-gamma-/- mice displayed a partial diminution of T cell proliferative and delayed-type hypersensitivity responses to OVA, significant responses were still present when compared with the low responses noted in IFN-gamma+/+ mice. In addition, OVA-specific T cells from IFN-gamma-/- mice produced Th2-type cytokines (e.g., IL-4), which provided help for systemic OVA-specific serum IgG1 and IgG2b Ab responses. These findings clearly indicate a central role for IFN-gamma in the induction and maintenance of mucosally induced tolerance.

Administration, Oral↗
PubMed1998

Prognostic factors in uterine carcinosarcoma: a clinicopathologic study of 25 patients.

BACKGROUND: Carcinosarcoma (malignant mixed mullerian tumor) of the female genital tract is a highly malignant neoplasm. The tumor stage and histologic grade of the carcinomatous component are among the important prognostic indicators cited in the literature for this tumor. METHODS: Twenty-five patients with uterine carcinosarcoma at 4 hospitals in the Kyoto and Nara areas of Japan were studied retrospectively. The clinicopathologic and immunohistochemical data including p53, bcl-2, Ki-67, and proliferating cell nuclear antigen (PCNA) staining were analyzed using univariate and multivariate analysis with the Cox proportional hazards model to investigate potential prognostic indicators for this neoplasm. RESULTS: The 5-year survival rate was 36.4% for all stages, 62.3% for Stage I, and 0% for Stages II-IV. From the univariate analysis, stage (P = 0.0001), endometrioid adenocarcinoma as a carcinomatous component (P = 0.0006), age (P = 0.0355), and a heterologous sarcomatous component (P = 0.0421) were found to be prognostically significant for patient survival. Stage was the only independent significant factor in the multivariate analysis (t = 2.212). None of the other factors (history of pregnancy and gestation, gross appearance of the tumors, grade of the carcinomatous component, mitotic count of the sarcomatous component, Ki-67 and PCNA reactivity, or p53 or bcl-2 positive staining) was found to be a significant prognostic indicator. CONCLUSIONS: Stage appears to be the only definite independent prognostic indicator of survival in patients with uterine carcinosarcoma. It is uncertain whether age, endometrioid adenocarcinoma as a carcinomatous component, or absence of a heterologous component in the sarcomatous area are prognostic factors. Immunohistochemical expression of p53, bcl-2, Ki-67, or PCNA is not a prognostic indicator. The immunohistochemical results of the current study may support the hypothesis of a common stem cell origin of this tumor.

Adult↗
PubMed1998

Purification and characterization of an allergy-induced melanogenic stimulating factor in brownish guinea pig skin.

We have demonstrated recently that phenylazonaphthol (PAN) allergy-induced hyperpigmentation in brownish guinea pig skin is associated with the concomitant appearance of a melanogenic soluble factor(s) that activates the intracellular signal transduction system, including phosphatidylinositol turnover subsequent to ligand-receptor binding in cultured guinea pig melanocytes. In this study we have purified and characterized the PAN-induced melanogenic stimulating factor (PIMSF) that occurs in allergy-associated hyperpigmented skin. By successive column chromatography on TSK 2000SW, Mono Q, and octadecyl-NPR, the PIMSF was purified to homogeneity with a single band of apparent molecular mass of 7.9 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The specific bioactivity of PIMSF increased by 5,195-fold over the original skin homogenate. In cultured guinea pig melanocytes, this purified PIMSF had the potential of activating an intracellular signal transduction system such as inositol 1,4,5-trisphosphate formation and intracellular calcium levels through a pertussis toxin-sensitive G protein-coupled receptor. PIMSF consistently caused a rapid translocation of cytosolic protein kinase C (PKC) to membrane-bound PKC within 5 min of treatment with a return to the basal level after 120 min. The stimulating effects of PIMSF on proliferation and melanization of cultured guinea pig melanocytes were abolished completely by a PKC down-regulating agent (phorbol 12,13-dibutyrate). PIMSF was similar in molecular mass to rat growth-related oncogene alpha (GRO-alpha; molecular mass of 7.9 kDa) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had immunocross-reactivity with GRO-alpha upon Western immune blotting analysis. Further, the stimulatory effect of purified PIMSF on DNA synthesis of cultured guinea pig melanocytes was suppressed markedly by the addition of anti-rat GRO-alpha antibody, implying that the PIMSF is apparently identical to GRO-alpha. These findings suggest that PAN allergy provides a new mechanism of hyperpigmentation in which biological factors such as the GRO-alpha superfamily generated within allergy-induced skin stimulate melanocytes through activation of the PKC-related signal transduction pathway.

Allergens↗
PubMed1998

Unique appendages associated with spores of Bacillus cereus isolates.

Electron microscopic observations revealed the presence of a new type of large appendage on the spores of two Bacillus cereus strains isolated from phylloplanes. The appendages were thin and sword-like in shape, having the sizes of 1.5 to 2.8 microns in length and 0.03 to 0.6 micron in width. There were no core or sheath structures in these appendages. The number of appendages on a spore ranged from three to more than twenty, radiating from the swelling on one end of the exosporium. These appendages gave a unique octopus- or jellyfish-like feature to the spores.

Bacillus cereus↗
PubMed1998

A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: implication for immunotherapy of human hepatocellular carcinoma.

Although treatment for hepatocellular carcinoma (HCC) has recently improved, most patients still relapse and die from this disease. The development of new therapeutic and preventive strategies for HCC is, therefore, required. A novel mutant protein (mutein) of human tumor necrosis factor alfa (TNF-alpha mutein F4614, 1SSSRGDSD... 29V ... 155L) was developed to decrease several adverse effects of TNF-alpha. F4614 is known to lack hypotensive effects of human TNF-alpha without losing its anti-tumor effect in mice transplanted with Meth-A sarcoma. Our study investigated the anti-tumor effects of F4614 against hepatoma cells in vitro and in vivo. F4614 significantly inhibited growth of all four tumor cells in vitro. A murine hepatoma cell line, MH134, when incubated in the presence of F4614, exhibited upregulation of surface major histocompatibility complex (MHC) class-I, intercellular adhesion molecule-1 (ICAM-1) and B7-1 molecules, and a decreased proportion of cells in the G2/M phase of the cell cycle. In addition, F4614 induced apoptosis in a significant number of MH134 cells. TNF-alpha and F4614 (5 microg/mouse daily for 5 days) showed similar anti-tumor activities in syngeneic MH134-bearing mice and heterogeneic PLC/PRF/5-bearing athymic nude mice. Intratumoral injection of F4614 or TNF-alpha was more effective than intravenous injection. Immunohistochemical analysis of the tumors treated by F4614 revealed that tumors were surrounded with a large number of Mac-1+ cells and a small number of CD4+ and CD8+ T cells; that suggests that intratumoral injection of F4614 elicited host immunoreactions. Thus, F4614 may be a new strategy for immunotherapy of HCC.

Animals↗
PubMed1998

The offset cortical potential: an electrical correlate of movement inhibition in man.

Nine normal subjects were asked to make either a brisk isometric pinch of a force transducer held between the forefinger and thumb, or to hold a pinch for approximately 15 s and then release the force suddenly without any overt antagonist contraction. EEG activity was averaged about the onset or offset of EMG activity, and movements were made in the subjects' own time. All subjects found the task simple. The EEG activity preceding offset of contraction (offset cortical potential) was significantly smaller in lateral leads than that seen before onset of contraction. Midline activation was similar in both tasks. We suggest that in the onset task, motor cortex activity related to the act to be performed contributes substantially to the EEG potentials in lateral leads. This activity is absent in the offset task which requires only withdrawal of tonic input to motor cortex. Midline activity, common to both onset and offset tasks, could reflect timing, attentional, or other processes. The results are discussed in relation to previous data from an isotonic relaxation task.

Adult↗
PubMed1998

Effect of interleukin-8 on production of tumor-associated substances and autocrine growth of human liver and pancreatic cancer cells.

We have previously reported that human liver cancer cell lines produce interleukin-8 (IL-8) at high levels. Those tumor cells appeared to express two kinds of IL-8 receptor on their surface. In order to analyze the role of IL-8 on the biological characteristics of those tumor cells, we suppressed IL-8 production from human liver (HuH-7 and HuCC-T1) and pancreatic cancer cell lines (HuP-T4) by treatment with IL-8 antisense oligonucleotides. Suppression of IL-8 production resulted not only in inhibition of cell growth, but also in an increase in the concentrations of some tumor-associated substances such as carbohydrate antigen 19-9 (CA19-9) in the medium. These data indicate that IL-8 produced by human liver and pancreatic tumors may act as an autocrine growth factor and may control the production of some tumor-associated substances. Furthermore, surface expression of sialyl-Lewis(a), which is a ligand for ELAM-1 on human umbilical vein endothelial cells (HUVEC), HuCC-T1 and HuP-T4 cells was decreased and the attachment of these tumor cells to HUVEC was inhibited by treatment with IL-8 antisense oligonucleotide. Since the soluble form of CA19-9 (sialyl-Lewis(a)) was shown to inhibit the tumor cell binding to HUVEC, the decrease in release of CA19-9 into the medium and increase in the expression of sialyl-Lewis(a) on the cell surface may suggest that IL-8 production from the tumor cells enhances metastatic potential by augmenting the binding activity of the tumor cells to HUVEC. These data demonstrate that a cytokine produced by tumor cells may function as an autocrine growth factor and affect tumor cell dissemination.

Antigens, CD↗
PubMed1998

Ultrastructural and permeability features of microvessels in the olfactory bulbs of SAM mice.

The ultrastructural features of microvessels showing increased permeability to intravenously injected horseradish peroxidase (HRP) were examined in the olfactory bulbs of senescence-accelerated prone mice (SAMP8), which showed age-related deficits in learning and memory, and senescence-accelerated resistant mice (SAMR1), which did not show the age-related deficits. HRP was visualized with tetramethyl benzidine (TMB) and diaminobenzidine (DAB) for light and electron microscopic examination, respectively. In the olfactory bulbs of 13-month-old SAMP8 mice, the staining reaction with TMB for HRP appeared in the neuropil of central area (granule cell layer and subependymal layer), in the pia mater and in the vascular wall. Some vessels located in the central area showed several changes observed at the ultrastructural level. The cytoplasm of the endothelial cells, especially in the arterioles, was segmentally thickened and contained numerous vesicles and vacuoles, some of which were HRP positive. The endothelial cell surface was occasionally undulated with microvillous protrusions. Membranous inclusions within the basal lamina, suggesting the cellular (presumably pericytal) degeneration, were frequently observed, especially in venules. The collagen deposits were occasionally observed in the subendothelial space of some vessels. Perivascular cells with vacuolated inclusions or lipid-like droplets were present around some vessels in the central area of the olfactory bulbs of aged SAMP8 mice. On the other hand, in the microvessels located in the areas negative for HRP-TMB reaction, except the vessel walls, the cytoplasm of the endothelial cells with smooth luminal surface was flattened and some vesicles located there contained HRP-DAB reaction product. Weak staining reaction with TMB for HRP appeared also in the central area of the olfactory bulbs of 3-month-old SAMP8 mice and 3- and 13-month-old SAMR1 mice. The cytoplasm of the endothelial cells in the olfactory bulbs of these mice was focally thickened and contained some cytoplasmic vesicles. Occasionally, the endothelial cell surface was moderately undulated with few microvillous protrusions. Membranous inclusions within the basal lamina were not observed in these animals. These findings indicate that the endothelial cells and pericytes in some vessels located in the central area of the olfactory bulb of aged SAMP8 mice, which show staining reaction with TMB for HRP, are ultrastructurally changed, suggesting their altered functions.

Age Factors↗
PubMed1998

Hybrid-type stabilizer for off-pump direct coronary artery bypass grafting.

We have developed a mechanical stabilizer for use in off-pump direct coronary artery bypass grafting. We consider it an improvement on the sucker-type stabilizer, although it uses the mechanisms of the compressor-type. Our hybrid stabilizer effectively immobilizes the local heart surface with light compression and low evacuation. We believe that its use will eliminate the need for further immobilization and thus reduce cardiac invasiveness.

Anastomosis, Surgical↗