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Biomedical subjects

T Mori

Publications and source records attributed to T Mori.

At least 127 records · Page 7Linked to original sources
PubMed2001

Reduced cortical injury and edema in tissue plasminogen activator knockout mice after brain trauma.

Tissue plasminogen activator (tPA) may play a deleterious role after brain injury. Here, we compared the response to traumatic brain injury in tPA knockout (KO) and wildtype (WT) mice after controlled cortical impact. At 6 h after trauma, blood-brain barrier permeability was equally increased in all mice. However, by 24 h specific gravity measurements of brain edema were significantly worse in WT mice than in KO mice. At 1 and 2 days post-trauma, mice showed deficits in rotarod performance, but by day 7 all mice recovered motor function and there were no differences between WT and KO mice. At 7 days, cortical lesion volumes were significantly reduced in KO mice compared with WT mice. However, there were no significant differences in CA3 hippocampal neuron survival. These data suggest that tPA amplifies cortical brain damage and edema in this mouse model of traumatic brain injury.

Animals↗
PubMed2001

Topical formulations and wound healing applications of chitosan.

Chitosan is being used as a wound-healing accelerator in veterinary medicine. To our knowledge, chitosan enhances the functions of inflammatory cells such as polymorphonuclear leukocytes (PMN) (phagocytosis, production of osteopontin and leukotriene B4), macrophages (phagocytosis, production of interleukin (IL)-1, transforming growth factor beta 1 and platelet derived growth factor), and fibroblasts (production of IL-8). As a result, chitosan promotes granulation and organization, therefore chitosan is beneficial for the large open wounds of animals. However, there are some reported complications of chitosan application. Firstly, chitosan causes lethal pneumonia in dogs which are given a high dose of chitosan. In spite of application of chitosan to various species, this finding is observed only in dogs. Secondly, intratumor injection of chitosan on mice bearing tumor increases the rate of metastasis and tumor growth. Therefore, it is important to consider these effects of chitosan, prior to drug delivery.

Administration, Topical↗
PubMed2001

Prevention of neonatal estrogen imprinting by vitamin A as indicated by estrogen receptor expression in the mouse vagina.

Treatment of female mice with estrogen during the neonatal period induces estrogen-independent persistent proliferation and cornification of the vaginal epithelium when the animals become adults. However, the occurrence of such irreversible vaginal changes is blocked by concurrent retinol acetate (RA) treatment. This study aimed to determine the expression pattern of estrogen receptor (ER) alpha and beta in the vaginas of ovariectomized 35-day-old mice treated neonatally with 17beta-estradiol (E(2)) and/or RA. The amounts of ERalpha and ERbeta mRNA molecules in the vaginal RNA samples were determined by competitive reverse transcription/polymerase chain reaction. The levels of both mRNAs were lower in ovariectomized mice that had been treated neonatally with E(2) but not in those treated with E(2) plus RA. Neonatal E(2) treatment caused a decrease in the percentage of ERalpha-immunoreactive cells in the vaginal stroma during adulthood, and concurrent RA treatment inhibited the decrease. The amount of each ER mRNA was also measured in the vaginas of mature mice treated with E(2) and RA; no inhibitory activity of RA was seen in the mature mice. Our studies indicate that, in mouse vagina, the irreversible effects of neonatal imprinting by estrogen might be prevented by the simultaneous administration of vitamin A through the inhibition of a decrease of the number of ER-expressing cells.

Age Factors↗
PubMed2001

Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia.

Deleterious processes of extracellular proteolysis may contribute to the progression of tissue damage after acute brain injury. We recently showed that matrix metalloproteinase-9 (MMP-9) knock-out mice were protected against ischemic and traumatic brain injury. In this study, we examined the mechanisms involved by focusing on relevant MMP-9 substrates in blood-brain barrier, matrix, and white matter. MMP-9 knock-out and wild-type mice were subjected to transient focal ischemia. MMP-9 levels increased after ischemia in wild-type brain, with expression primarily present in vascular endothelium. Western blots showed that the blood-brain barrier-associated protein and MMP-9 substrate zonae occludens-1 was degraded after ischemia, but this was reduced in knock-out mice. There were no detectable changes in another blood-brain barrier-associated protein, occludin. Correspondingly, blood-brain barrier disruption assessed via Evans Blue leakage was significantly attenuated in MMP-9 knock-out mice compared with wild types. In white matter, ischemic degradation of the MMP-9 substrate myelin basic protein was significantly reduced in knock-out mice compared with wild types, whereas there was no degradation of other myelin proteins that are not MMP substrates (proteolipid protein and DM20). There were no detectable changes in the ubiquitous structural protein actin or the extracellular matrix protein laminin. Finally, 24 hr lesion volumes were significantly reduced in knock-out mice compared with wild types. These data demonstrate that the protective effects of MMP-9 gene knock-out after transient focal ischemia may be mediated by reduced proteolytic degradation of critical blood-brain barrier and white matter components.

Actins↗
PubMed2001

Alterations of repeated sequences in 5' upstream and coding regions in colorectal tumors from patients with hereditary nonpolyposis colorectal cancer and Turcot syndrome.

One of the characteristics of tumors from patients with germline mutations of DNA mismatch repair genes is instability at microsatellite regions (MSI). We analysed alterations at repeated sequences of coding regions, as well as those of 5' upstream regions, in 29 MSI-High colorectal tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and Turcot syndrome. We found that repeated sequences in 5' upstream regions were altered in these tumors, at considerable frequencies. The (A)10 repeat in the promoter region (position -178 to approximately -169) of the GAPDH gene was altered in 17% of the tumors. The (A)10(TA)9 in the 5' upstream region (position -318 to approximately -291) of the mitochondrial isoleucyl tRNA synthetase gene (IleRS-A), coded in nuclear DNA, was altered in 59% of the tumors, whereas (A)9 in the 5' upstream region (position -859 to approximately -851) of cytoplasmic isoleucyl tRNA synthetase gene (IleRS-B) was not altered. Alteration at repeated sequences in the coding regions were 72% at TGFbetaRII(A)10, 24% at IGFIIR(G)8, 45% at BAX(G)8, 55% at E2F4(CAG)13, 66% at caspase-5 (A)10, 31% at MBD4(A)10, 55% at hMSH3(A)8 and 34% at hMSH6(C)8. The number of altered genes increased with the advancement of carcinoma according to Dukes categories: mean numbers of altered genes within these 10 genes were 2.6 for Dukes A, 4.7 for Dukes B and 7.8 for Dukes C. The mean number for adenomas was 2.0. These results suggest that the MSI phenotype also causes alteration of 5' upstream regions which may affect apoptosis and some mitochondrial functions in HNPCC and Turcot tumors, and that accumulation of altered genes with repeated sequences is associated with the progression of HNPCC and Turcot colorectal tumors.

Adenoma↗
PubMed2001

Promotion of radiation-induced formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by nitro 5-deazaflavin derivatives.

6-Nitro- and 8-nitro-5-deazaflavin derivatives have been found to enhance prominently the radiation-induced formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) at the expense of formation of 2,6-diamino-4-hydroxy-5-formamidopyrimidine nucleosides (FapydGuo) both in deaerated and in N(2)O saturated aqueous 2'-deoxyguanosine solutions. The radiosensitizing capacity of a 9-nitro-5-deazflavin derivative was observed only in the N(2)O saturated aqueous solutions.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Observation of spin-orbit splitting in lambda single-particle states.

The spin-orbit splitting of Lambda single-particle states in (13)(Lambda)C was measured. The 13C(K-,pi(-))(13)(Lambda)C reaction was used to excite both the 1/2(-) and 3/2(-) states simultaneously, which have predominantly 12C(0(+)) x p(Lambda) configuration. gamma rays from the states to the ground state were measured in coincidence with the pi(-)'s, by which ls splitting was found to be 152+/-54(stat)+/-36(syst) keV. The value is 20-30 times smaller than exhibited by the ls splitting in the nuclear shell model. This value gives us new insight into the YN interaction.

Journal Article↗
PubMed2001

Transcriptional dysregulation of the p73L / p63 / p51 / p40 / KET gene in human squamous cell carcinomas: expression of Delta Np73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51.

We have recently identified a second p53 -related p73L gene, also referred to as p63 / p51 / p40 / KET gene, which encodes the 2 major isoforms p73L and p51 resulting from different exon usage at their amino terminal regions. Although p73L and p51 are suspected to play oncogenic and tumour suppressive roles in mammalian cells, respectively, no evidence of linkage between the expression of these isoforms and human cancers has been reported so far. In this study, we first investigated the expression profile of p51 and p73L in various human tumour cell lines and found that a novel isoform, termed DeltaNp73L, was predominantly expressed in squamous cell carcinomas. The expression profile of DeltaNp73L/p73L/p51 in primary human skin cancer specimens showed that the expression of p51 was frequently lost (62%) but was detected in all normal skin samples. In p51-expressing skin cancers, DeltaNp73L expression was associated at a high frequency (75%) though it was not detected in normal skin tissues. Transient co-transfection data indicate the possibility that DeltaNp73L can inhibit p53-, and more preferentially, p51-mediated transactivation. These data suggest that the loss of expression of p51 and/or the expression of DeltaNp73L might contribute to the pathogenesis of human squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed2001

Dynamics for reaction of an ion pair in aqueous solution: reactivity of carboxylate anions in bimolecular carbocation-nucleophile addition and unimolecular ion pair collapse.

[reaction: see text]. The sum of the rate constants for solvolysis and 18O-scrambling of 4-MeC6H4(13)CH(Me)18OC(O)C6F5 in 50/50 (v/v) trifluoroethanol/water, k(solv) + k(iso) = 1.22 x 10(-5) s(-1), is larger than k(solv) = 1.06 x 10(-5) s(-1) for solvolysis of the unlabeled ester. This shows that the ion pair intermediate undergoes significant internal return. The data give k(-1) = 7 x 10(9) s(-1) for internal return by unimolecular collapse of the ion pair, which is significantly larger than k(Nu) = 5 x 10(8) M(-1) x s(-1) for bimolecular nucleophilic addition of carboxylate anions to 4-MeC6H4CH(Me)+.

Anions↗
PubMed2001

Carbon dioxide degassing by advective flow from Usu volcano, Japan.

Magmatic carbon dioxide (CO2) degassing has been documented before the 31 March 2000 eruption of Usu volcano, Hokkaido, Japan. Six months before the eruption, an increase in CO2 flux was detected on the summit caldera, from 120 (September 1998) to 340 metric tons per day (September 1999), followed by a sudden decrease to 39 metric tons per day in June 2000, 3 months after the eruption. The change in CO2 flux and seismic observations suggests that before the eruption, advective processes controlled gas migration toward the surface. The decrease in flux after the eruption at the summit caldera could be due to a rapid release of CO2 during the eruption from ascending dacitic dikes spreading away from the magma chamber beneath the caldera.

Journal Article↗
PubMed2001

Novel androgen-dependent promoters direct expression of the C4b-binding protein alpha-chain gene in epididymis.

C4b-binding protein (C4BP) is a large plasma protein composed of seven alpha-chains and one beta-chain and is involved in the fluid phase regulation of the classical pathway of the complement system. Complement inhibitory activity is located in the alpha-chain, and its mRNA has been detected only in liver to date. Here, we have isolated cDNA clones encoding the alpha-chain of guinea pig C4BP (C4BP alpha) and have demonstrated significant C4BP alpha mRNA expression in epididymis as well as liver. The level of C4BP alpha transcripts increased in the epididymis after birth, while it remained constant in the liver. C4BP alpha mRNA was also detected in the normal murine epididymis at a significant level, but it decreased drastically after castration, suggesting that epididymal expression of the C4BP alpha gene is regulated by androgen. Gene analysis of guinea pig C4BP alpha indicated that liver and epididymis C4BP alpha mRNA share the coding region and 3'-untranslated region, but are transcribed from independent promoters on a single-copy gene. Two novel epididymis-specific promoters were identified in the region corresponding to the first intron of liver transcripts. The binding motif for hepatocyte NF-1 occurs in the promoter used for transcription of liver C4BP alpha, whereas androgen-responsive elements occur in both promoters used in the epididymis. These findings present a novel link between complement regulators and reproduction. Furthermore, variation in the 5'-untranslated regions, arising from alternative splicing of the newly identified exons, is demonstrable in the guinea pig C4BP alpha transcripts.

3' Untranslated Regions↗
PubMed2001

Genetic variation in angiotensin-converting enzyme does not prevent development of cardiac hypertrophy or upregulation of angiotensin II in response to aortocaval fistula.

BACKGROUND: Experimental and clinical evidence suggests that angiotensin II may be an important mediator of cardiac hypertrophy in response to hemodynamic stress. We investigated the effect of genetic variation in angiotensin-converting enzyme (ACE) on the development of cardiac hypertrophy and left ventricular (LV) dysfunction in response to volume overload. METHODS AND RESULTS: Male heterozygous ACE knockout (1/0) and wild-type (1/1) mice were studied 4 weeks after the creation of an aortocaval fistula (ACF). The LV weight/body weight ratio increased 74% in ACF versus sham-operated control mice but did not differ between genotypes. Echocardiographic circumferential stress versus rate-corrected velocity of circumferential shortening curves demonstrated depressed LV function in ACF versus sham-operated mice but no difference between genotypes. LV ACE activity was higher in 1/1 versus 1/0 mice and in ACF versus sham-operated mice, and it increased significantly more in the 1/1 versus the 1/0 mice after ACF (P<0.001 for effect of genotype, ACF/sham operation, and interaction term). LV angiotensin II was higher in ACF versus sham-operated mice but did not differ between genotypes, despite 3-fold higher LV ACE activity in ACF 1/1 versus ACF 1/0 mice. CONCLUSIONS: ACE underexpression does not prevent cardiac hypertrophy or LV dysfunction in response to volume overload. LV angiotensin II is unaffected by ACE genotype, both at baseline and after volume overload, indicating that the heart can maintain angiotensin II levels across a broad range of genetic ACE variation under both physiological and pathophysiological conditions.

Angiotensin II↗
PubMed2001

Sequence-specific affinity precipitation of oligonucleotide using poly(N-isopropylacrylamide)-oligonucleotide conjugate.

In this study we develop a sequence-specific precipitation separation system of oligonucleotide (ODN) using a conjugate between poly(N-isopropylacrylamide) (PNIPAM) and ODN. PNIPAM is known as a thermoresponsive polymer and dehydrates to precipitate above its phase transition temperature in an aqueous milieu. The principal advantage of this separation system using the conjugate is that the hybridization reaction between the conjugate and oligonucleotide is conducted in homogeneous solution. The conjugate was prepared by copolymerization between N-isopropylacrylamide and a vinyl-derivatized (dT)(8). The obtained conjugate efficiently precipitated (dA)(8) from solution when the solution contained more than 1.5 M NaCl. The conjugate containing 3 nmol of (dT)(8) residue was able to precipitate 1.4 nmol of (dA)(8), suggesting that the (dT)(8) residue of the conjugate formed a triple helix with (dA)(8). From an equimolar mixture of (dA)(8) and its one point mutant, the conjugate selectively precipitated (dA)(8): the highest selectivity was obtained for the isolation of (dA)(8) from the mixture consisting of (dA)(4)dT(dA)(3) and (dA)(8). When the conjugate was applied for the precipitation of five oligo(dA)s having different chain lengths, the longer oligo(dA)s tended to be precipitated by the conjugate more efficiently than the shorter ones. The conjugate could be used repeatedly for precipitation of (dA)(8) without showing any loss in precipitation efficiency.

Acrylic Resins↗
PubMed2001

Effects of conditioned medium on activities of PAL, CHS, DAHP synthase (DS-Co and DS-Mn) and anthocyanin production in suspension cultures of Fragaria ananassa.

A conditioned medium (CM) prepared from cell suspension cultures of strawberry stimulated anthocyanin synthesis. The effect was significantly (P<0.05) greater than that of synthetic medium (SM), with macronutrient concentrations, carbohydrate concentrations and pH adjusted to those of CM. The activity of 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase (EC 4.1.2.15) (DS-Mn, DS-Co), phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) and chalcone synthase (CHS, EC 2.3.1.74) were monitored in the CM- and SM-cultured cells. PAL and CHS activities were found to increase significantly (P<0.05) in the CM-cultured cells. CHS transcript levels were higher in the CM-cultured cells compared to transcript abundance in SM-cultured cells. There was no significant difference in the DS-Mn and DS-Co activities of cells grown in conditioned or synthetic media.

Journal Article↗
PubMed2001

Activation of the caspase cascade during Stx1-induced apoptosis in Burkitt's lymphoma cells.

Shiga toxin 1 (Stx1) produced by Escherichia coli has been reported to induce apoptosis in many different cell types, including Burkitt's lymphoma (BL) cells. Since it has been established that the caspases play essential roles as the effector molecules in the apoptotic process in most cases, we examined the kinetics of caspase activation during the process of Stx1-mediated apoptosis of BL cells. Using Ramos BL cells that are highly sensitive to Stx1-mediated cytotoxicity, we observed that multiple caspases, including caspase-3, -7, and -8 were promptly activated following Stx1 treatment, as indicated by both the procaspase cleavages and enhancement of cleavage of the tetrapeptide substrates of the caspases. In addition, the inhibition assay revealed that caspase-8 is located upstream of both caspase-3 and -7, suggesting that Stx1-mediated apoptosis utilizes a similar caspase cascade to that involved in Fas-mediated apoptosis. Neither anti-Fas mAb nor TNF-alpha, however, affected the Stx1-mediated apoptosis of Ramos cells. Although the precise mechanism of Stx1-mediated activation of caspase-8 is still unclear, we have demonstrated that crosslinkage of CD77, a functional receptor for Stx1, with specific antibody is sufficient to induce activation of caspase-8. Our findings should provide new insight into the understanding of the molecular basis of Stx1-mediated cell injury.

Antibodies, Monoclonal↗
PubMed2001

A lipid-coated lipase as an efficient hydrolytic catalyst in the two-phase aqueous-organic system.

A lipid-coated lipase has been known to be soluble in organic solvents and act as an efficient esterification catalyst in the dry organic solvent. It was also found to act as an efficient hydrolytic catalyst for lipophilic esters in the two-phase aqueous-organic system. Both the lipid-coated lipase and substrates are solubilized in the organic phase and the hydrolysis occurs with water molecules from the aqueous phase. Therefore, the reaction was 40-100 times faster than that of the native lipase, in which the enzyme and substrate exist separately in the aqueous and organic phase, respectively, and the reaction proceeded at the interface. The hydrolysis rates for the lipid-coated lipase were not affected by the aqueous pH and agitation speed of the two-phase. Enzymatic activity of the lipid-coated lipase was compared with that of the poly(ethylene glycol)-grafted lipase. Michaelis-Menten kinetics in the two-phase reactions was also studied.

Alcohols↗