Biomedical subjects

T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 469 records · Page 26Linked to original sources

PubMed1999

The effects of kallidinogenase on choroidal blood flow in a hypertensive rabbit model.

PURPOSE: The purpose of the present study was to investigate the effects of kallidinogenase on chorioretinal circulatory disorder, on the basis of chorioretinal blood flow and fundus findings, in a renal hypertensive rabbit model. METHODS: In a renal hypertensive rabbit model produced according to Goldblatt's method, chorioretinal blood flow was continuously measured by noncontact laser Doppler flowmetry (LDF). Ophthalmography was conducted before and 30 minutes after drug administration. RESULTS: Measurement by LDF revealed 16% reduction in chorioretinal blood flow in the hypertension group compared with the control group. The administration of kallidinogenase dose-dependently increased chorioretinal blood flow in both groups, the hypertension group being more sensitive to kallidinogenase than the control group. In contrast, none of the controls (vinpocetine and DL-alpha-tocopherol nicotinate) exerted effects on chorioretinal blood flow in the hypertension group. Fundus examination demonstrated narrowing of the choroidal arterioles following an increase in blood pressure, and expansion of the arterioles following the administration of kallidinogenase. CONCLUSION: Kallidinogenase was shown to improve ophthalmic circulation by increasing chorioretinal blood flow in renal hypertensive rabbits.

Animals↗

PubMed1999

A novel water-soluble vitamin E derivative protects against experimental colitis in rats.

This study was designed to investigate the effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on experimental colitis in rats. Colitis was induced in male Wistar rats weighing 200 grams using an enema of trinitrobenzene sulfonic acid (TNBS) dissolved in 50% ethanol; 1 ml of TMG dissolved in physiological saline (0.2 mg/ml, 2 mg/ml, 20 mg/ml) was injected intraperitoneally every day for 1 week after the enema. The damage score, wet weight of the colon, and increase in body weight were estimated 1 week after the enema of TNBS. Thiobarbituric acid-reactive substances (TBA-RS), an index of lipid peroxidation, and the level of alpha-tocopherol or TMG in the colonic mucosa were measured 1 week after the induction of colitis. As a result, increase in body weight was inhibited by the induction of colitis, although the inhibition was reduced in the group treated with TMG. The damage score, wet weight and TBA-RS were increased significantly in the colitis group; however, they were inhibited by the administration of TMG. The alpha-tocopherol level in the colonic mucosa was reduced by the induction of colitis, wheres TMG could not be detected in the colonic mucosa of rats treated with TMG. These results suggest that TMG is effective for the treatment of colitis in rats induced by TNBS.

Animals↗

PubMed1999

Number and anatomical extent of lymph node metastases in gastric cancer: analysis using intra-lymph node injection of activated carbon particles (CH40).

BACKGROUND: The long-term survival of 200 patients with gastric cancer who underwent radical gastrectomy was analyzed with respect to the number and anatomical extent of lymph node metastasis. All of the patients received intra-lymph node injection of fine activated carbon particle solution (CH40) during surgery. METHODS: The average number of resected lymph nodes increased in line with the anatomical level of lymph node dissection; 32.5 per patient in D1, 42.3 in D2, 3 and 66.3 in D4. The percentage of blackened lymph nodes without metastasis (42.4%) was slightly higher than that of lymph nodes containing metastasis (37.2%), but the difference was not statistically significant. Of the 200 patients, 61 (30.5%) had microscopic evidence of metastatic lymph node involvement. Twenty-two patients had between one and three metastatic lymph nodes, 19 had between four and nine and 20 patients had more than nine. The 5-year survival rate was 93.1% in patients without lymph node metastasis, 71.9% in patients with 1-8 metastatic nodes, 36.1% in patients with 4-9 nodes and 19.2% in patients with > 9 nodes. RESULTS: The 5-year survival rate according to the anatomical extent of metastatic lymph nodes was 93.1% in n0, 63.1% in n1, 37.9% in n2, 27.8% in n3 and 0% in n4. The number of metastatic lymph nodes and also their anatomical extent were identified as independent prognostic factors for survival by multivariate analysis. CONCLUSION: The number and anatomical extent of metastatic lymph nodes have similar impacts on prognosis in gastric cancer.

Adult↗

PubMed1999

Inhibitory effects of of L-2'-deoxyguanosine 5'-triphosphate (L-dGTP) and L-2'-deoxythymidine 5'-triphosphate (L-dTTP) on human telomerase.

Telomerase, which synthesizes telomeric DNA in eukaryotic cells, is classified as a reverse transcriptase. To clarify the recognition of 2'-deoxyribonucleoside 5'-triphosphate (dNTP) chirality by telomerase, we studied the inhibitory effects of L-dGTP on HeLa cell telomerase activity using a quantitative 'stretch PCR' assay. L-dGTP had a weakly inhibitory effect (IC50 = 200 microM) in the presence of 10 microM dGTP. This effect was less obvious when the concentration of dGTP was higher. L-dTTP had a similar inhibitory effect. These findings suggest that telomerase may bind to L-dGTP and L-dTTP, and that the ability of telomerase to bind to dGTP or dTTP is changed.

Base Sequence↗

PubMed1999

Participation of cofilin in opsonized zymosan-triggered activation of neutrophil-like HL-60 cells through rapid dephosphorylation and translocation to plasma membranes.

We studied the roles of cofilin, an actin-binding phosphoprotein, in superoxide production of neutrophil-like HL-60 cells triggered by opsonized zymosan (OZ). OZ caused dephosphorylation of cofilin as well as a transient increase of F-actin. Both reactions were complete within 30 s. Okadaic acid (OA) magnified the OZ-triggered O2--production 3.3-fold at 1 microM, but inhibited it completely at 5 microM. We used these critical concentrations to study the effects of OA on changes in phosphorylation and intracellular localization of cofilin. The OZ-induced dephosphorylation of cofilin was inhibited by 5 microM OA but not by 1 microM OA. Subcellular fractionation and immunoblotting revealed that 1 microM OA increased cofilin on the phagosomal membranous fraction but 5 microM OA decreased it. At 1 microM, OA increased translocation of p47phox to membranes, which may explain in part the enhancing effect of 1 microM OA. Confocal laser scanning microscopy showed that: (i) Cofilin diffused throughout the cytosol of resting cells, but accumulated at the plasma membranes forming phagocytic vesicles in activated cells. (ii) At 1 microM, OA had little effect on the OZ-evoked translocation of cofilin, whereas 5 microM OA suppressed it completely. (iii) OA alone, which could not trigger the phagocytic respiratory burst, did not cause any change in the distribution of cofilin at such concentrations. Furthermore, in a superoxide-producing cell-free system employing membranous and cytosolic fractions, affinity-purified anti-cofilin antibody showed an enhancing effect. These results suggest that cofilin participates in the superoxide production of the OZ-activated phagocytes through dephosphorylation and translocation. The roles of cofilin in the activated leukocytes will be discussed.

Actin Depolymerizing Factors↗

PubMed1999

Two mRNA species encoding calcium-dependent protein kinases are differentially expressed in sexual organs of Marchantia polymorpha through alternative splicing.

In plants, calcium-dependent calmodulin-independent protein kinases (CDPKs) are the predominant calcium-regulated protein kinases and their genes are encoded by a multigene family. A CDPK gene was cloned from a liverwort, Marchantia polymorpha, which showed a high level of sequence similarities to other higher plant CDPK genes. The liverwort CDPK gene consisted of 9 exons and 8 introns. The 6th and 7th exons (Exon 6A and Exon 6B) were almost identical except for 4-amino acid substitutions, both of which coded for EF-hands in the calcium-binding domain. RT-PCR analysis revealed that two species of mature mRNA containing either Exon 6A or Exon 6B were generated from a single CDPK gene by mutually exclusive alternative splicing. Both histidine-tagged fusion proteins derived from cDNAs containing either Exon 6A or Exon 6B exhibited calcium-dependent protein kinase activity in vitro. Preferential accumulation of the mature mRNA with Exon 6A detected in male sexual organ implies possible sexual control of the ratio between the two CDPK isozymes through alternative splicing. Functions and evolution of CDPKs are discussed based on the structure and expression of the liverwort CDPK gene.

Alternative Splicing↗

PubMed1999

The spinal antinociceptive effects of a novel competitive AMPA receptor antagonist, YM872, on thermal or formalin-induced pain in rats.

UNLABELLED: Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonists have spinally mediated analgesic effects on acute nociception; however, their current formulations are not water-soluble and have toxic side effects. A new competitive AMPA antagonist, YM872 (2,3-dioxo-7-[1H-imidazol-1-yl]-6-nitro-1,2,3,4-tetrahydro-1-quinoxal inyl acetic acid) is water-soluble and may have fewer side effects. The purpose of this study was to investigate the analgesic effects of YM872 on both acute thermal and irritant-induced pain. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters and were tested for their tail withdrawal response by the tail flick test and for their paw flinches by formalin injection after the intrathecal administration of YM872. The tail flick latency increased dose-dependently with a 50% effective dose (ED50) value of 1.0 microg. The number of flinches in both Phase 1 and Phase 2 of the formalin test decreased with increasing dose of YM872. ED50 values were 0.24 microg in Phase 1 and 0.21 microg in Phase 2. YM872 10 and 30 microg induced motor disturbance and flaccidity. In rats, the intrathecal administration of YM872 had analgesic effects on both acute thermal and formalin-induced nociceptions. Transient motor disturbance and flaccidity occurred only with large doses. YM872 may have potential in the clinical management of both acute and chronic pain. IMPLICATIONS: A novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM872, may have an analgesic effect on both acute and chronic pain when administered intrathecally.

Analgesics, Non-Narcotic↗

PubMed1999

The systemically administered competitive AMPA receptor antagonist, YM872, has analgesic effects on thermal or formalin-induced pain in rats.

UNLABELLED: A new competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, (2,3-dioxo-7-[1H-imidazol-1-yl]-6-nitro-1,2,3,4-tetrahydro-1-quinoxal inyl) acetic acid (YM872) has analgesic effects on acute thermal- and formalin-induced nociception by intrathecal administration. The purpose of this study was to determine the analgesic effects of systemically administered YM872 in both acute thermal- and irritant-induced pain. Sprague-Dawley rats were tested for tail withdrawal response by the tail flick test and for paw flinches by formalin injection after intraperitoneal administration of YM872. The tail flick latency increased dose-dependently with a 50% effective dose value of 156.3 microg. The number of flinches in both first and second phases of the formalin test decreased with increasing the dose of YM872. The 50% effective dose values were 1.0 microg in the first phase and 38.7 microg in the second phase. Transiently, intraperitoneal administration of 1 and 10 mg of YM872 induced motor disturbance and 10 mg induced loss of pinna reflex. We conclude that intraperitoneal administration of YM872 had analgesic effects on both acute thermal- and formalin-induced nociceptions in rats. Transient motor disturbance and loss of pinna reflex occurred only with large doses. IMPLICATIONS: Intraperitoneally administered YM872, a new alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, had analgesic effects on thermal- and formalin-induced pain in rats. Larger doses induced transient motor disturbance and loss of pinna reflex mediated in the brain.

Analgesics, Non-Narcotic↗

PubMed1999

Analgesic interaction between intrathecal midazolam and glutamate receptor antagonists on thermal-induced pain in rats.

BACKGROUND: Two major neurotransmitters, gamma-aminobutyric acid (GABA) and the excitatory amino acid, glutamate, may be involved in nociception in the spinal cord. GABA and glutamate receptors may operate in concert to modify signals in the central nervous system. The purpose of this study was to investigate the spinal analgesic interaction between midazolam, a benzodiazepine-GABA(A) receptor agonist, and two glutamate receptor antagonists on acute thermal nociception. METHODS: Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters and were tested for their tail withdrawal response by the tail flick test after intrathecal administration of saline, midazolam (1-100 microg), AP-5 (1-30 microg), or YM872 (0.3-30 microg). AP-5 is an N-methyl-D-aspartate (NMDA) receptor antagonist and YM872 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist. The combination of midazolam and the other two agents were also tested by isobolographic analyses. Motor disturbance and behavioral changes were observed. RESULTS: Dose-dependent increases in the tail flick latency were observed with midazolam, AP-5, and YM872 with 50% effective dose values of 1.57+/-0.34 (SEM) microg, 5.54+/-0.19 microg, and 1.0+/-0.22 microg, respectively. A potent synergy in analgesia with decreased behavioral changes and motor disturbance was obtained when combining midazolam with AP-5 or YM872. CONCLUSIONS: Spinally administered midazolam and an NMDA- or an AMPA-receptor antagonist exhibited potent synergistic analgesia on acute thermal nociception in rats. Side effects, shown by behavioral changes and motor disturbance, decreased with the combination of the agents. These results point out an important direction for the study of acute nociception.

2-Amino-5-phosphonovalerate↗

PubMed1999

Spatial cognitive performance after chronic focal cerebral ischemia in rats.

The authors investigated the impairment of spatial cognitive performance in rats with chronic focal cerebral ischemia using the Morris maze, and examined the correlation between this deficit and other behavioral changes, such as step-through latency in passive avoidance task and neurologic score, or pathologic changes. The authors focused on the relationship between the damaged brain region and the affected spatial learning behavior. In the Morris maze task at 8 weeks after the middle cerebral artery (MCA) occlusion, escape latency, swimming path length, and percent time spent in goal quadrant of MCA-occluded rats were impaired, which correlated with shrinkage of the cortex involving parietal cortex, but not caudate-putamen (CP). Middle cerebral artery-occluded rats were also impaired in the percent time spent in the outermost annulus and in turning ratio, which significantly correlated with shrinkage of CP, but not cortex. Middle cerebral artery-occluded rats showed two typical search patterns; one was almost the same as that of sham-operated and intact rats, and the other was round shaped and had less turning behavior. Both subgroups of MCA-occluded rats divided by turning ratio had significantly impaired spatial cognitive performance, which indicates that the changes of search pattern did not affect cognitive performance in the Morris maze. The neurologic deficits recovered gradually after MCA occlusion, which correlated with shrinkage of cortex and CP. The step-through latency in passive avoidance task of the MCA-occluded rats was impaired, but did not correlate with shrinkage of cortex or CP. These results suggest that the long-term spatial cognitive deficit of MCA-occluded rats is in part associated with damage to the cortex involving parietal cortex, and that the change of search strategies is associated with damage to CP. These findings support the idea that different brain regions contribute differently to cognitive performance, search strategies, avoidance task, and neurologic performance, and may be useful for estimating the related region of functional disorder in the clinical situation.

Analysis of Variance↗

PubMed1999

Elastofibroma dorsi: CT, MRI, and pathologic findings.

We report two cases of elastofibroma dorsi and discuss the CT and MR findings and histopathology of these tumors. Increased awareness of the characteristic MR patterns should lead to reduced misdiagnosis of such lesions as malignant and prevent unnecessary wide excision.

Female↗

PubMed1999

Spontaneous spiral formation in two-dimensional oscillatory media.

Computational studies of pattern formation in a modified Oregonator model of the Belousov-Zhabotinsky reaction is described. Initially inactive two-dimensional reaction media with an immobilized catalyst is connected to a reservoir of fresh reactants through a set of discrete points distributed randomly over the interphase surface. It is shown that the diffusion of reactants combined with oscillatory reaction kinetics can give rise to spontaneous spiral formation and phase waves.

Journal Article↗

PubMed1999

Crystallization and preliminary x-ray study of two crystal forms of Klebsiella oxytoca diol dehydratase-cyanocobalamin complex.

Two crystal forms of Klebsiella oxytoca diol dehydratase complexed with cyanocobalamin have been obtained and preliminary crystallographic experiments have been performed. The crystals belong to two different space groups, depending on the crystallization conditions. One crystal (form I) belongs to space group P212121 with unit-cell parameters a = 76.2, b = 122.3, c = 209. 6 A, and diffracts to 2.2 A resolution using an X-ray beam from a synchrotron radiation source. The other crystal (form II) belongs to space group P21 with unit-cell parameters a = 75.4, b = 132.7, c = 298.8 A, beta = 91.9 degrees, and diffracts to 3.0 A resolution. For the purpose of structure determination, a heavy-atom derivative search was carried out and some mercuric derivatives were found to be promising. Structure analysis by the multiple isomorphous replacement method is now under way.

Bacterial Proteins↗

PubMed1999

Squamous cell carcinoma in a renal transplant recipient with linear porokeratosis.

A 40-year-old man developed squamous cell carcinoma on a perianal lesion of linear porokeratosis after renal transplantation. The tumor metastasized to the left inguinal lymph node 25 months after the primary tumor was excised. p53 overexpression was observed in the tumor cells, but not in the porokeratotic lesion. Interestingly, continuous subcutaneous infusion of peplomycin for the lymph node metastasis significantly improved the warty lesions of porokeratosis. In this patient, immunosuppressive agents might have accelerated the development of carcinoma on a skin area with malignant potential.

Adult↗

PubMed1999

Conservation of putative promoter sequences located upstream of chlamydial major sigma factor gene, sigA among Chlamydia spp.

A highly conserved 40-nucleotide sequence was identified. Two completely conserved sequences, TAGATT and TAAACT, separated by 17 nucleotides resemble the consensus sequence recognized by the Escherichia coli major sigma factor and sequence found in other chlamydial promoters. In addition, the adenine-rich sequence present in many chlamydial promoters was also conserved upstream of the putative -35 element. These findings suggest that the conserved sequence may play a role in the regulatory function at the transcriptional level. Multiple ATG codons were found at the 5'-terminal region of the chlamydial sigA ORFs except for Chlamydia pneumoniae, although the putative Shine-Dargarno sequence was absent.

Bacterial Outer Membrane Proteins↗

PubMed1999

Human immunodeficiency virus type 1 Vpr modifies cell proliferation via multiple pathways.

Vpr, one of the accessory molecules of HIV-1, has been demonstrated to arrest the cell cycle at the G2 phase. This Vpr-mediated cell cycle arrest is implicated to have an important role in the viral life cycle. In the present study, we quantitate the extent of Vpr-mediated cell cycle arrest with the use of a bicistronic vector consisting of a vpr gene and a green fluorescence protein sequence. Using this system, we examined the effect of several Vprs on cell cycle progression and growth of cells from different species quantitatively. We found that Vpr from the T-cell line-adapted HIV-1SF2 strain (Vpr2) could not significantly induce G2 arrest in HeLa cells but was able to induce it in 293T cells. However, strong inhibition of cell proliferation in HeLa cells as well as in 293T cells was observed by Vpr2. This ability of Vpr2 to inhibit cell proliferation without G2 arrest was also observed when expressed in monkey cell line. Analyses of chimeric Vprs revealed that this species-non-specific growth inhibitory activity of Vpr was not mediated solely by the C-terminal region of Vpr. These results indicated that the growth inhibitory activity of Vpr is independent of its G2 arresting activity. In addition, the species-non-specific nature of this activity suggests that Vpr has a novel mechanism to retard cell proliferation by influencing basic cellular functions.

Adaptation, Biological↗

PubMed1999

Characterization of the Coxiella burnetti sucB gene encoding an immunogenic dihydrolipoamide succinyltransferase.

The Coxiella burnetii sucB gene encoding the dihydrolipoamide succinyltransferase (E2o) enzyme was cloned by immunological screening of a lambda EMBL3 genomic library prepared from strain Nine Mile DNA and sequenced. The homology of the cloned gene product to the counterpart in Escherichia coli was 54.3%, but the homology of the N-terminal region was only 42%. The gene was expressed in E. coli as an independent unit from its own promoter, producing an immunoreactive protein of about 50 kDa on SDS-PAGE which reacted with antisera from laboratory animals and sera from human patients with acute Q fever. The study results suggest that the C. burnetii E2o enzyme may serve as a potential target antigen for diagnostic assays for Q fever.

Acyltransferases↗

PubMed1999

Multiple K-ras mutations in hyperplasia and carcinoma in cases of human pancreatic carcinoma.

Mucous cell hyperplasia (MCH) has been considered an important precursor of pancreatic ductal carcinoma based on histological and molecular research, although various K-ras mutations rates are seen among cases with pancreatic carcinoma, chronic pancreatitis and normal pancreas, with a wide range of histological characters. To investigate the premalignant potential of MCH and the multicentricity of pancreatic carcinoma, we analyzed K-ras mutation at codon 12 in carcinoma foci of 82 cases of surgically-resected pancreatic carcinoma [67 solid-type carcinomas (SCs) and 15 ductectatic-type carcinomas (DCs)], as well as in both MCH and carcinoma foci in 42 cases (30 SCs and 12 DCs), using an enriched polymerase chain reaction (PCR)-enzyme linked mini-sequence assay (ELMA). K-ras mutation was recognized in 85% (57/67) of SCs and 73% (11/15) of DCs, and multiple K-ras mutations in 12% (8/67) of SCs and in 20% (3/15) of DCs. Multiple K-ras mutations were also recognized in MCHs in 47% (14/30) of SCs and in 42% (5/12) of DCs. Moreover, the same sequence at K-ras codon 12 in MCH and carcinoma was identified in 76% (32/42) of carcinoma cases and it was more frequently recognized in hyperplasias with histological atypia (51%, 37 of 72 foci) than those without atypia (24%, 16 of 68 foci) (P<0.0007). These results further support the idea of multicentric carcinogenesis and premalignant potential of atypical hyperplasia in the human pancreas, although about half of the hyperplasias around carcinomas were not thought to be direct precursors.

Adult↗