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Biomedical subjects

H Mori

Publications and source records attributed to H Mori.

At least 235 records · Page 13Linked to original sources
PubMed2000

Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor-beta in mesangial cells.

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell proliferation, differentiation, and production of extracellular matrix proteins in various types of cells including mesangial cells. Although TGF-beta has been also known as an important player in the pathogenesis of various fibrotic diseases including glomerulosclerosis, signal-transduction cascades of TGF-beta have remained to be clarified. However, emerging evidence indicates that TGF-beta can activate various signal transduction cascades such as Smad proteins and mitogen-activated protein kinases (MAPKs) in many types of cells. Here, we examine the role of MAPKs in TGF-beta-induced gene expression of extracellular matrix proteins in mesangial cells. TGF-beta increases extracellular signal-regulated kinase (ERK) activity, one of the MAPKs, and the expression of fibronectin mRNA and protein in rat mesangial cells. Furthermore, PD98059, a specific inhibitor of MAPK/ERK kinase (MEK), can inhibit this TGF-beta-induced fibronectin expression. These data suggest that MAPKs play an important role in TGF-beta-mediated extracellular matrix production in mesangial cells.

Animals↗
PubMed2000

Acute renal failure after a sea anemone sting.

A 27-year-old man suffering from severe swelling and pain in his right arm was referred to our hospital. He showed signs of acute renal failure (ARF) with severe dermatitis of his right arm. Three days before being admitted, he accidentally touched some kind of marine organism with his right hand while snorkeling in the Sulu Sea around Cebu Island. Within a few minutes, he was experiencing severe pain in his right hand. Then his right hand gradually became swollen. The marine creature responsible for this injury was thought to have been a sea anemone, which is a type of coelenterate. Histologic findings of a renal biopsy indicated that acute tubular necrosis (ATN) had caused ARF in this patient's case. Supportive therapies improved renal function of this patient, and steroid pulse therapy attenuated the severe skin discoloration. The ATN was thought to have been caused by the poison from a sea anemone because there were no other conceivable reasons for the patient's condition. This is the first time that a marine envenomation case has been reported in which the sting of a sea anemone has caused ATN without the failure of any other organs.

Acute Kidney Injury↗
PubMed2000

Effects of Fas-mediated liver cell apoptosis on diethylnitrosamine-induced hepatocarcinogenesis in mice.

The present study was designed to investigate the effect of Fas-mediated liver cell apoptosis, induced by a hamster monoclonal antibody against mouse Fas antigen, on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. DEN (10 microg g(-1), intraperitoneally (i.p.)) was given to 15-day-old male C3H/HeJ mice. Three weeks after DEN treatment, Fas-mediated liver cell apoptosis induced by anti-Fas antibody resulted in a biphasic effect on induction of liver cell tumours, depending on dosage and time of antibody administration. Single or multiple treatment with high dose anti-Fas antibody (5 microg animal(-1)), induced gross liver cell damage and decreased the incidence of liver cell tumours in DEN-treated mice. In contrast, five treatments with low dose anti-Fas antibody (2 microg animal(-1)), induced dispersed localized liver cell damage and promoted the number of large-sized liver cell adenomas and hepatocellular carcinomas. These findings suggest that high dose anti-Fas antibody has a marked effect on the clearance of DEN-initiated liver cells, whereas repeated administration of low dose anti-Fas antibody promotes hepatocarcinogenesis. It is concluded that Fas-mediated liver cell apoptosis has a biphasic effect on hepatocarcinogenesis.

Adenoma↗
PubMed2000

Amelioration of microvascular myocardial ischemia by gene transfer of vascular endothelial growth factor in rabbits.

OBJECTIVES: Restoration of coronary blood flow by angiogenesis may offer a new approach to intractable ischemic heart disease. In the present study, we investigated the angiogenic effects of gene transfer of vascular endothelial growth factor 165 on microvascular myocardial ischemia. METHODS: A rabbit model of microvascular myocardial ischemia was created by plugging coronary microvessels with microspheres (15 microm in diameter, 2.8 x 10(5)/kg, n = 29). Gene transfer was performed by semi-selective intracoronary injection of recombinant adenovirus expressing vascular endothelial growth factor 165 forty minutes after microsphere injection (n = 9). RESULTS: Microsphere injection reduced myocardial perfusion (78% +/- 9% of baseline tissue flow) and diminished myocardial contraction (61% +/- 12% of the baseline ejection fraction) and cardiac performance (elevated left ventricular end-diastolic pressure and decreased systemic flow) in the acute phase. At 17 +/- 3 days, gene transfer of vascular endothelial growth factor 165 had had the following effects: (1) promoted coronary angiogenesis as evidenced by myocardial flow above the baseline (121% +/- 24%), (2) increased vascular density revealed by synchrotron radiation microangiography and histologic analysis, (3) ameliorated the degree of myocardial ischemia as evidenced by myocardial lactate content and the extent of histologic necrosis, and (4) restored heart function as evidenced by increased ejection fraction (95% +/- 10%), reduced left ventricular end-diastolic pressure, and restored body weight. CONCLUSIONS: In vivo vascular endothelial growth factor 165 gene transfer promoted angiogenesis and was an effective approach to treating microvascular myocardial ischemia.

Adenoviridae↗
PubMed2000

Spontaneous disappearance and reappearance of a ruptured cerebral aneurysm: one case found in a group of 33 consecutive patients with subarachnoid hemorrhage who underwent repeat angiography.

The spontaneous disappearance and reappearance of a ruptured cerebral aneurysm is generally assumed to be a rare phenomenon although the actual incidence is unknown. Among 39 consecutive cases of acute subarachnoid hemorrhage (SAH), 33 were studied by three-dimensional computed tomographic angiography (CTA) within 6 h after the onset of SAH, followed by digital subtraction angiography (DSA) within 24 h after the ictus. Of those patients, one, a 58-year-old woman, had a saccular aneurysm at the distal anterior cerebral artery; the aneurysm was clearly demonstrated by CTA 2.5 h after the SAH onset, but was not shown by a subsequent DSA performed 8.5 h after the ictus. A follow-up DSA detected the neck of aneurysm on day 11, and the whole aneurysm was visualized on day 19. The observations in this particular case suggest that the spontaneous disappearance of a ruptured cerebral aneurysm may occur during the ultra-early stage of SAH and that reappearance may follow during the next few weeks. The patient did not suffer complications such as vasospasm or systemic hypotension nor was she treated with antifibrinolytic agents. The aneurysmal shape and the surrounding clot are considered as putative factors possibly related to the intermittent appearance of the aneurysm.

Aneurysm, Ruptured↗
PubMed2000

Differential expression of beta-catenin in human glioblastoma multiforme and normal brain tissue.

Angiogenesis is considered to play an important role in the development of malignant brain tumors, especially glioblastoma multiforme (GBM). Abnormal vascular construction with a glomeruloid appearance is characteristic of GBM. beta-catenin is known as one of the adhesive molecules associated not only with cell adhesion and cell polarity, but also with carcinogenesis. We postulated the relevance of beta-catenin to vigorous endothelial proliferation in human GBM because the vascular cells (VCs) are apt to lose their cell polarity. The object of this study is to compare the immunohistochemical localization of beta-catenin in VCs between GBMs and normal brain tissues. Immunohistochemical analysis of beta-catenin for VCs in 32 GBMs and 10 normal brain tissues was performed. beta-catenin was found concentrated in the areas of vascular cell-cell junction and internal surface of the vascular lumen in all normal brains. In contrast, beta-catenin, in proliferating VCs in GBMs, was stained homogeneously and intensely in the cytoplasms of 26 cases (81.3%), in which nuclear staining of beta-catenin was also recognized in four cases (12.5%). In conclusion, the intracellular localization of beta-catenin in VCs of GBMs was found to be different from that of normal brain tissues. The changes of expression of beta-catenin may be associated with the angiogenesis or transformation of the VCs in human GBM.

Brain↗
PubMed2000

Length recognition at the N-terminal tail for the initiation of FtsH-mediated proteolysis.

FtsH-mediated proteolysis against membrane proteins is processive, and presumably involves dislocation of the substrate into the cytosol where the enzymatic domains of FtsH reside. To study how such a mode of proteolysis is initiated, we manipulated N-terminal cytosolic tails of three membrane proteins. YccA, a natural substrate of FtsH was found to require the N-terminal tail of 20 amino acid residues or longer to be degraded by FtsH in vivo. Three unrelated sequences of this segment conferred the FtsH sensitivity to YccA. An artificially constructed TM9-PhoA protein, derived from SecY, as well as the SecE protein, were sensitized to FtsH by addition of extra amino acid sequences to their N-terminal cytosolic tails. Thus, FtsH recognizes a cytosolic region of sufficient length (approximately 20 amino acids) to initiate the processive proteolysis against membrane proteins. Such a region is typically at the N-terminus and can be diverse in amino acid sequences.

Amino Acid Sequence↗
PubMed2000

Two distinct action mechanisms of immunophilin-ligand complexes for the blockade of T-cell activation.

The immunosuppressive effects of cyclosporin A (CsA) and FK506 are mediated through binding to immunophilins. Here we show that FK506-FKBP complex suppresses the activation of JNK and p38 pathways at a level upstream of mitogen-activated protein kinase (MAPK) kinase kinase (MAPKK-K) besides the calcineurin-NFAT pathway. A238L, a viral gene product that binds to immunophilin, also blocks activation of both pathways. In contrast, direct inhibitors of calcineurin, Cabin 1 and FR901725, suppress the activation of NFAT but not the JNK or p38 pathway. We further demonstrate that co-expression of a constitutively active NFAT and a constitutively active MEKK1 renders the interleukin-2 promoter in Jurkat T lymphocytes resistant to CsA and FK506, whereas Jurkat cells expressing a constitutively active NFAT alone are still sensitive to CsA or FK506. Therefore, CsA and FK506 exert their immunosuppressive effects through targeting both the calcineurin-dependent NFAT pathway and calcineurin-independent activation pathway for JNK and p38.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Characterization of a mutant form of SecA that alleviates a SecY defect at low temperature and shows a synthetic defect with SecY alteration at high temperature.

The secY205 mutant is cold-sensitive for protein export, with an in vitro defect in supporting ATP- and preprotein-dependent insertion of SecA into the membrane. We characterized SecA81 with a Gly516 to Asp substitution near the minor ATP-binding region, which suppresses the secY205 defect at low temperature and exhibits an allele-specific synthetic defect with the same SecY alteration at 42 degrees C. The overproduced SecA81 aggregated in vivo at temperatures above 37 degrees C. Purified SecA81 exhibited markedly enhanced intrinsic and membrane ATPase activities at 30 degrees C, while it was totally inactive at 42 degrees C. The trypsin digestion patterns indicated that SecA81 has some disorder in the central region of SecA, which encompasses residues 421-575. This conformational abnormality may result in unregulated ATPase at low temperature as well as the thermosensitivity of the mutant protein. In the presence of both proOmpA and the wild-type membrane vesicles, however, the thermosensitivity was alleviated, and SecA81 was able to catalyze significant levels of proOmpA-stimulated ATP hydrolysis as well as proOmpA translocation at 42 degrees C. While SecA81 was able to overcome the SecY205 defect at low temperature, the SecY205 membrane vesicles could not significantly support the translocation ATPase or the proOmpA translocation activity of SecA81 at 42 degrees C. The inactivated SecA81 molecules seemed to jam the translocase since it interfered with translocase functions at 42 degrees C. Based on these results, we propose that under preprotein-translocating conditions, the SecYEG channel can stabilize and activate SecA, and that this aspect is defective for the SecA81-SecY205 combination. The data also suggest that the conformation of the central region of SecA is important for the regulation of ATP hydrolysis and for the productive interaction of SecA with SecY.

ATP-Binding Cassette Transporters↗
PubMed2000

Male flower-specific expression of genes for polygalacturonase, pectin methylesterase and beta-1,3-glucanase in a dioecious willow (Salix gilgiana Seemen).

We isolated cDNA clones (pSgPG1 through pSgPG4, pSgPME1 and pSgGN1) for the polygalacturonases (PGs), pectin methylesterase (PME) and beta-1,3-glucanase (GN) that are expressed specifically in male flowers of the dioecious willow (Salix gilgiana Seemen). The structural characteristics of the deduced proteins, designated SgPGs, SgPME1 and SgGN1, respectively, suggest that these enzymes function in pollens or anthers. The four SgPGs were more than 91.9% homologous to one another at the amino acid level, indicating that their genes are members of a single family. Although the expression of the SgPGs, SgPME1 and SgGN1 was specific to male catkins (inflorescences), these genes were found in the genomes of both male and female plants. The expression of the transcripts of SgPGs, SgPME1 and SgGN1 was regulated developmentally in male reproductive organs. Maximal expression of SgPGs and SgPME1 was detected when male flowers were fully open and mature, while maximal expression of SgGN1 occurred at an earlier time. In situ hybridization revealed that the expression of SgPGs and SgPME1 was restricted to mature pollen grains after microspore mitosis. These results suggest that the pollen-specific or anther-specific expression of genes for PGs, PME and GN occurs in a dioecious plant, willow, just as it does in monoecious plants, and that the expression of these genes is related to the developmental stage of pollen grains during male gametogenesis.

Amino Acid Sequence↗
PubMed2000

Two novel transcripts expressed in pea dormant axillary buds.

To elucidate the molecular mechanism of apical dominance, the expression patterns of genes that are preferentially expressed in dormant axillary buds of pea (Pisum sativum L. cv. Alaska) seedlings were investigated. We isolated two cDNA clones, cPsAD1 and cPsAD2 whose corresponding genes were named PsAD1 and PsAD2, from a cDNA library of dormant axillary buds using the differential display method. The deduced amino acid sequence of PsAD1 contains 87 residues and is rich in glycine residues in the amino terminal region. A search of the protein databases failed to find any sequences similar to PsAD1 protein except for the glycine-rich region. Northern blot analyses showed that PsAD1 mRNA mainly accumulated in dormant axillary buds and that its amount rapidly decreased after decapitation of the terminal bud. In situ hybridization analyses indicated that PsAD1 mRNA was localized in the apical meristem, procambia, and leaf primordia in dormant axillary buds that were competent to grow out but whose growth was temporarily suspended. That is, the expression of the PsAD1 gene is closely associated with the dormancy of axillary buds. The deduced amino acid sequence of PsAD2 contains 98 amino acid residues and is not similar to those of previously characterized proteins. PsAD2 mRNA accumulated in dormant axillary buds, roots, mature leaflets and elongated stems, suggesting that PsAD2 is involved in not only the dormancy of axillary buds but also the non-growing state in various tissues.

Amino Acid Sequence↗
PubMed2000

Acropetal disappearance of PsAD1 protein in pea axillary buds after the release of apical dominance.

We recently isolated PsAD1 cDNA from pea (Pisum sativum L. cv. Alaska) seedlings, whose mRNA abundantly accumulated in dormant axillary buds and disappeared after decapitation [Madoka and Mori (2000) Plant Cell Physiol. 41: 274]. To further elucidate the function of PsAD1, we investigated the temporal and spatial distribution patterns of PsAD1 protein using Western blot and immunocytochemical analyses. Western blot analyses showed that accumulation patterns of PsAD1 protein in axillary buds after decapitation and in response to IAA and 6-benzyladenine were the same as those of PsAD1 mRNA. Immunocytochemical analyses showed that (1) PsAD1 proteins were localized in the procambia, leaf primordia, apical meristem, and secondary axillary buds in the dormant axillary bud, and this distribution was the same as that of PsAD1 mRNA, (2) PsAD1 proteins acropetally disappeared after decapitation, and (3) the growth of axillary buds occurred in the same manner. These acropetal changes occur in a manner similar to the way in which the procambium differentiates into vascular tissue. These results suggest that PsAD1 plays some role in the inhibition of growth and differentiation, or in the maintenance of the dormant state in axillary buds.

Amino Acid Sequence↗
PubMed2000

Isolation of a novel 190 kDa protein from tobacco BY-2 cells: possible involvement in the interaction between actin filaments and microtubules.

Interaction between actin filaments (AFs) and microtubules (MTs) has been reported in various plant cells, and the presence of a factor(s) connecting these two cytoskeletal networks has been suggested, but its molecular entity has not been elucidated yet. We obtained a fraction containing MT-binding polypeptides, which induced bundling of AFs and of MTs. A 190 kDa polypeptide which associated with AFs was selectively isolated from the fraction. This polypeptide was thought to have an ability to bind to both AFs and MTs. We raised a monoclonal antibody against the 190 kDa polypeptide. Immunostaining demonstrated the association of the 190 kDa polypeptide with AF bundles and with MT bundles formed in vitro. Immunocytochemical studies throughout the cell cycle revealed that the 190 kDa polypeptide was localized in the nucleus before nuclear envelope breakdown, and in the spindle and the phragmoplast during cell division. After the re-formation of the nuclear envelope, the 190 kDa polypeptide was sequestered to the daughter nuclei. Using the antibody, we succeeded in cloning a cDNA encoding the 190 kDa polypeptide.

Actin Cytoskeleton↗
PubMed2000

Antitumor activity of 2-amino-4,4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one against Meth A tumor transplanted into BALB/c mice.

We examined the in vivo effect of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3- one (Phx) on Meth A carcinoma cells transplanted into BALB/c mice, in terms of both antitumor activity and side effects. Phx, which was synthesized by the reaction of 2-amino-5-methylphenol with bovine hemolysates, was administered i.p. at doses of 1 and 5 mg/kg to BALB/c mice transplanted with Meth A tumor cells. Phx exerted a strong antitumor activity to Meth A tumor growing in the mice as 5-fluorouracil (5-FU) did. The antitumor activity of Phx at the dose of 5 mg/kg was comparable to that of 5-FU at the dose of 7.8 mg/kg. In contrast, unlike 5-FU, Phx did not cause leukopenia while showing a strong antitumor activity. The compound also produced little changes in body weight and no wasting of mice developed. These results show that Phx has strong anti-tumor activity, but exerts lower side effects and suggest that Phx is available for therapeutic purposes in the future.

Animals↗
PubMed2000

Three-dimensional reconstructed images after rotational angiography in the evaluation of intracranial aneurysms: surgical correlation.

OBJECTIVE: To evaluate the diagnostic accuracy of three-dimensional reconstructed images from rotational digital subtraction angiography in the surgical treatment of intracranial aneurysms. METHODS: Twenty-two patients with 34 intracranial aneurysms underwent biplane angiography (40 degrees per s, 4.5 degrees per image, 8.8 frames per s). Three-dimensional (3-D) reconstructed images were obtained at a separate Advantage 3.1 workstation (General Electric, Milwaukee, WI) after the rotational images were transferred. The available visualization techniques included maximum intensity projection, shaded surface display, and virtual endoluminal view. All images were evaluated in correlation with intrasurgical visual data recorded on digital videotapes. RESULTS: 3-D reconstructed images correlated well with surgical findings. The shape of the aneurysms, their neck size, and their relationships to the parent vessels and other branches were depicted clearly, especially compared with images obtained by two-dimensional conventional digital subtraction angiography and magnetic resonance angiography. CONCLUSION: 3-D digital subtraction angiography enables the surgeon to understand the 3-D structure of lesions and is very useful in planning the surgical treatment of cerebral aneurysms.

Angiography, Digital Subtraction↗
PubMed2000

Reduction of vesicular acetylcholine transporter in beta-amyloid protein-infused rats with memory impairment.

The aim of this study was to investigate spatial memory and quantitative acetylcholine transporter autoradiography using a high-sensitivity imaging plate system in rats treated with beta-amyloid protein, a model of Alzheimer's disease. An eight-arm radial maze was used to evaluate spatial memory. The performance of the eight-arm radial maze task was impaired in beta-amyloid protein-treated rats. In the parietal cortex, [3H]-vesamicol binding to the vesicular acetylcholine transporter was significantly lower in beta-amyloid protein-treated rats than in vehicle-treated rats, and was significantly correlated with the mean number of correct selections in the maze task of the first 5 days in the post-operative state. These results indicate that the reduction in [3H]-vesamicol binding to vesicular acetylcholine transporter is related to memory impairment induced by beta-amyloid protein. Beta-amyloid protein-infused rats with spatial memory impairment may be useful for the development of new radiolabelled vesamicol analogues for the objective evaluation of Alzheimer's disease.

Alzheimer Disease↗