Search PubMed⌕ Search

Biomedical subjects

T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 235 records · Page 13Linked to original sources
PubMed2001

[Minimally invasive treatment of colorectal cancer].

It may be widely interpreted that minimally invasive treatment of colorectal cancer includes endoscopic mucosal resection, transanal endoscopic microsurgery (TEM), laparoscopic surgery and open reduction-surgery as well as adjuvant treatments such as chemotherapy, radiotherapy and thermotherapy. With the development of medical technology and instruments, we have now a wide and new range of choices for each cancer stage of patients. However, it is not yet clear that minimally invasive treatment necessarily leads to better results in survival and recurrent rates of the patients, as compared with conventional surgery. We should therefore take into full consideration the lingering problems in selecting the new therapies. In this paper, we show the strong and weak points of laparoscopic surgery, TEM, right hemi-colectomy preserving Bauhin's valve and adjuvant radiotherapy for lower rectal cancer, and discuss ongoing problems.

Colectomy↗
PubMed2001

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). III. Secular changes in susceptibility].

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined and the results were compared with those obtained between 1991 and 1998. Comparison was made by classifying strains isolated from patients into those with uncomplicated UTIs and those with complicated UTIs (including with or without indwelling catheter). About E. faecalis, increase of low sensitive strains noted in the former year showed a decreasing tendency, however, one strain each with MIC of 4 micrograms/ml to vancomycin (VCM) was detected in patients with both uncomplicated and complicated UTIs. As for S. aureus, many sensitive strains to cephems, imipenem (IPM) and VCM were noted, and each MIC50 was better than that in the former years. S. aureus strains showing low susceptibility to arbekacin (ABK) were detected in patients with complicated UTIs in this year as well as in the former year, and one strain each with MIC of 16 micrograms/ml and 32 micrograms/ml was detected. Susceptibilities of E. coli were effective to all drugs except for penicillins and minocycline (MINO). Decrease of low sensitive strains was also noted in all drugs except for quinolones. Each MIC90 of ciprofloxacin (CPFX) and sparfloxacin (SPFX) in patients with complicated UTIs against E. coli was 3 degrees classes lower than that in patients with uncomplicated UTIs. As for Klebsiella pneumoniae, decrease of low sensitive strains to cephems was noted in patients with uncomplicated UTIs in 1998. In 1999, low sensitive strains decreased also in patients with complicated UTIs, and few were detected. Susceptibilities of K. pneumoniae to quinolones were effective as compared with those in the former years with the MIC80s of 0.125 microgram/ml or below without detection of low sensitive strains. One low sensitive strain of K. pneumoniae with MIC of 8 micrograms/ml was detected for gentamicin (GM). Susceptibilities of P. aeruginosa to carbapenems were notable. The MIC90 of meropenem (MEPM) and IPM was 4 micrograms/ml each which was 2 degrees better than that in 1998. Resistant P. aeruginosa strains to other drugs except for monobactams decreased in 1999.

Anti-Bacterial Agents↗
PubMed2001

[Effect of monoclonal antibody-neocarzinostatin conjugate for gastric cancer with peritoneal dissemination--comparison between early and late administration].

A7-NCS, which is a conjugate of the monoclonal antibody A7 against a human colonic cancer and the anticancer agent neocarzinostatin (NCS), reacts with human gastric cancers at a high rate. The anticancer effect of A7-NCS is stronger than that of free NCS. Nude mice models of peritoneal dissemination were established simply by intra-peritoneal inoculation of the antigen-positive human gastric cancer cell line MKN45. Using these models, the anticancer effect of A7-NCS against the peritoneal dissemination of gastric cancer was examined. The murine peritoneal dissemination models were divided into three groups. The anticancer effect of the group injected intra-peritoneally with A7-NCS 2 days after cancer inoculation was compared with that injected 18 days after inoculation. The anticancer effect in the 18-day group was inferior to that in the 2-day group, but was superior to that in the non-treated group. To get a better result in the 18-day group, which is in the advanced stage of peritoneal dissemination, repeated injection and the dose of A7-NCS should be examined.

Animals↗
PubMed2001

[Clinical trial of thermoradiotherapy and internal iliac arterial infusion of 5-FU for unresectable pelvic tumor].

Clinically, unresectable pelvic tumor is difficult to treat because the patients have poor prognosis and often suffer from severe pain and edema of the lower limbs due to the tumor invasion of the pelvic bone and the sciatic nerve. To improve QOL of such patients, we performed thermoradiotherapy (RTHT) or internal iliac arterial infusion of 5-FU (IIAI) for 7 patients who developed unresectable pelvic tumors which relapsed after surgery for 6 colorectal cancers and one leiomyosarcoma of the uterus. The mean tumor diameter was 10.2 cm and an evaluation by computed tomography revealed 2 of 6 tumors had a partial response (PR) and 3 no change (NC). Each of the 4 patients who had been ill in bed recovered to the point of being able to walk with a cane or wheel themselves in a wheelchair after the therapy.

Aged↗
PubMed2001

[A case of brainstem encephalitis associated with Epstein-Barr virus infection: differentiation of acute disseminated encephalomyelitis and Bickerstaff's brainstem encephalitis].

A 28-year-old woman initially suffered high fever and headache (day 1). Aseptic meningitis was diagnosed on day 3. Limb ataxia, however, appeared on day 7, and external ophthalmoplegia and drowsiness were recognized on day 8. Urinary disturbance and orthostatic hypotension appeared on day 13. Cerebrospinal fluid showed moderately high cell counts(mononuclear cells, 51/microliter; polynuclear cells, 9/microliter). MRI T2-weighted images showed high intensity lesions in the pons and mesencephalon. No serum anti-GQ1b IgG antibody was detected on day 4. Epstein-Barr virus (EBV) viral capsid antigen-IgG antibody was positive, and EBV determined nuclear antigen antibody was seroconverted. EBV-DNA was detected in the CSF by PCR. These findings indicate prior infection by EBV. After intravenous dexamethasone therapy, these symptoms rapidly disappeared. Our patient showed external ophthalmoplegia, ataxia, and disturbance of consciousness, which are the cardinal signs in Bickerstaff's brainstem encephalitis. The time course of her neurological symptoms, the presence of meningitis, and the MRI findings, however, indicated the pathogenesis of acute disseminated encephalomyelitis rather than Bickerstaff's brainstem encephalitis. We diagnosed this patient as a brainstem encephalitis associated with EBV infection.

Adult↗
PubMed2001

[The advantages and disadvantages of administering anti-cancer chemotherapy at home].

We analyzed the effectiveness of anti-cancer chemotherapy administered at home. Continuous hepatic arterial infusion (HAI) of 5-FU (250 mg/day) for unresectable liver metastases of colorectal cancer (129 cases) and systemic administration of 5-FU and CDDP (FP therapy) as a palliative treatment or for recurrent cases of colorectal cancer (145 cases) were evaluated. The response rate for HAI was 59.7%, and 50% survival according to the outcome of HAI was CR: 765 days PR: 607 days NC: 233 days and PD: 146 days. The residual life span of patients who showed CR or PR was significantly prolonged. The occurrence of complications from HAI was 15.1%. On the other hand, the response rate was 19.3%, and 50% survival was 292 days. The one-year survival rate was 38.7%. The mean duration of this chemotherapy and the mean stay at home were 188.2 days and 237.8 days, respectively. The mean rate of home stays was 68.6%. The group of performance status (PS) 0 or improving PS accounted for 74.5% of all cases. Those with a PS grade 3 or 4 accounted for only 1-4% of the patients. Finally, both chemotherapies could be continued at the outpatient clinic or at home.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Studies on quality and safety control of drugs for human use from transgenic animals/clone animals].

Recently the pharmaceuticals, which were produced using transgenic animals, have been developed, and will be submitted for registration in nearly future in Japan as well as in USA and EU. In addition, clone animals are also thought to be useful for the productions of the pharmaceuticals. This study has been, therefore, undertaken to establish the technical requirement for registration of the pharmaceuticals. They should be evaluated from the following standpoints: 1) Transgene construct and its characterization; 2) Creation and characterization of the transgenic founder animal; 3) Establishment of a reliable and continuous source of transgenic founder animals; 4) Generation and selection of the production animals; 5) Maintenance of transgenic animals; 6) Recovery and purification of products from transgenic animals; 7) Characterization of products; 8) Process validation/evaluation and in-process test; 9) Specification of products; 10) Stability of products; 11) Preclinical safety evaluation and clinical evaluation. Cloning technology by nuclear transfer of a transformed somatic cell has been already applied to the creation of the transgenic founder animal for the production of pharmaceuticals. The pharmaceuticals produced using the clone animals could be evaluated from almost the same standpoints. However, the flexible evaluation will be also needed depending on the development of the technology.

Animals↗
PubMed2001

[Sensory extinction phenomenon of double simultaneous stimulation: the analysis of consecutive stroke series with acute and unilateral lesions].

We evaluated consecutive stroke patients with an acute, unilateral lesion, in order to elucidate the anatomical correlates and the clinical course of sensory extinction phenomenon as well as its relation with unilateral spatial neglect (USN) and anosognosia for hemiplegia (AHP). Subjects consisted of 76 patients with right cerebral hemispheric lesions (RHL) and 43 with left cerebral hemispheric lesions (LHL). Twelve of 76 patients with RHL and 18 of 43 patients with LHL were excluded from this study, because of consciousness disturbance, aphasia, severe sensory disturbance, hemianopia, or severe dementia. All of the patients included in this study had an ischemic or hemorrhagic stroke, who admitted to our hospital within 24 hours after the onset of stroke. We repeatedly examined the patients to detect the presence of sensory extinction phenomenon, USN, and AHP from their acute to chronic stage. The incidence of extinction phenomenon in RHL was 33% (11/19 with cortical lesions and 10/45 with deep-seated lesions). When we excluded the patients with a lacunar stroke or TIA, 10 of 13 patients with subcortical lesions had sensory extinction phenomenon. Nineteen of 21 patients with RHL who showed sensory extinction phenomenon also accompanied USN, and twelve had associated AHP. The sensory extinction phenomenon disappeared within 20 days in 6 of 10 patients with subcortical lesions and 3 of 11 with cortical lesions. In contrast, three of 25 (12%) patients with LHL showed extinction phenomenon, the incidence being much rarer than the lesion in the right. Of these, two had USN and one had AHP together. All the deficits disappeared within 20 days after the onset of stroke in patients with LHL. Our studies may show that subcortical lesions present with extinction phenomenon more frequently than cortical lesions, although the phenomenon caused by the subcortical lesions of often disappear in a few weeks.

Aged↗
PubMed2000

Activation of p42/44 and p38 mitogen-activated protein kinases by extracellular calcium-sensing receptor agonists induces mitogenic responses in the mouse osteoblastic MC3T3-E1 cell line.

Recently, substantial evidence has accumulated that the G-protein-coupled, extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) is expressed in bone marrow-derived cells, including osteoblasts, stromal cells, monocytes-macrophages, and osteoclast precursor cells. Our previous studies have shown that the mouse osteoblastic MC3T3-E1 cell line also expresses the CaR and exhibits mitogenic responses when exposed to various CaR agonists. In this study, in order to understand the signaling pathway(s) mediating this response, we studied the effects of CaR agonists on the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK) (Erk1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK) in MC3T3-E1 cells. Raising the level of Ca(2+)(o) (4.5 mM) or addition of the polycationic CaR agonists, gadolinium (Gd(3+)) (25 microM), neomycin (300 microM) or spermine (1 mM), each stimulated phosphorylation of both p42/44 and p38 MAPKs, but not JNK, as assessed using phospho-specific antibodies to the respective MAPKs. Furthermore, phosphorylation of p42/44 and p38 MAPK were markedly inhibited by their selective and potent inhibitors, PD98059 (50 microM) and SB203580 (10 microM), respectively. Finally, the two inhibitors suppressed [(3)H]thymidine incorporation into DNA in MC3T3-E1 cells at a normal level of Ca(2+)(o) (1.8 mM) as well as when stimulated by high (4.5 mM) Ca(2+)(o), Gd(3+), or neomycin. Thus, in mouse osteoblastic MC3T3-E1 cells, both the p42/44 and p38 MAPK cascades play pivotal roles in CaR-stimulated mitogenic responses.

3T3 Cells↗
PubMed2000

Recognition of 2'-deoxy-l-ribonucleoside 5'-triphosphates by human telomerase.

Telomerase is classified as one of the reverse transcriptases (RTs). To clarify whether l-enantiomers of natural 2'-deoxyribonucleoside 5'-triphosphates (dNTPs) are recognized by human telomerase, a quantitative telomerase assay based on the "stretch PCR" method was developed and used for kinetic analysis of the inhibitory effects of these compounds on the enzyme. Among the four l-enantiomers of dNTPs, l-dTTP and l-dGTP inhibited telomerase activity and the others showed slight or no inhibitory effect. Lineweaver-Burk plot analysis showed that the inhibition modes of l-dTTP and l-dGTP were partially competitive (mixed type) and competitive with the corresponding substrate dNTP, respectively. However, the K(i) values of l-dTTP and l-dGTP (21 and 15 microM) were several times larger than the K(m) values (3-6 microM). These results suggest that the active site of telomerase is not able to discriminate strictly the chirality of dNTPs, although it is more discriminatory than HIV-1 RT.

Deoxyadenine Nucleotides↗
PubMed2000

Pharmacological profile of YM-31636, a novel 5-HT3 receptor agonist, in vitro.

We investigated the in vitro pharmacological profile of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate). In cloned human 5-HT3A receptors, YM-31636 had a pKi value of 9.67 vs. ramosetron and pKi values for other 5-HT3 receptor agonists were less than 7. YM-31636 showed very low affinities for other receptors. YM-31636 induced contraction of isolated guinea pig distal colon. The intrinsic activity was approximately 0.90 compared with 5-hydroxytryptamine's (5-HT) 1.0, and the potency was 26 times greater than that of 5-HT. YM-31636 increased short-circuit current (Isc) in the isolated guinea pig distal colon. In this case, the relative intrinsic activity was approximately 0.19. In isolated guinea pig right atrium, YM-31636 induced tachycardia with the relative intrinsic activity of approximately 0.23. All these effects of YM-31636 were antagonized by ramosetron, a selective 5-HT3 receptor antagonist. These results suggest that YM-31636 is a potent and selective 5-HT3 receptor agonist, preferentially acting on the contraction of the colon.

Acetylcholine↗
PubMed2000

Dehydroaltenusin, a mammalian DNA polymerase alpha inhibitor.

Dehydroaltenusin was found to be an inhibitor of mammalian DNA polymerase alpha (pol alpha) in vitro. Surprisingly, among the polymerases and DNA metabolic enzymes tested, dehydroaltenusin inhibited only mammalian pol alpha. Dehydroaltenusin did not influence the activities of the other replicative DNA polymerases, such as delta and epsilon; it also showed no effect even on the pol alpha activity from another vertebrate (fish) or plant species. The inhibitory effect of dehydroaltenusin on mammalian pol alpha was dose-dependent, and 50% inhibition was observed at a concentration of 0.5 microm. Dehydroaltenusin-induced inhibition of mammalian pol alpha activity was competitive with the template-primer and non-competitive with the dNTP substrate. BIAcore analysis demonstrated that dehydroaltenusin bound to the core domain of the largest subunit, p180, of mouse pol alpha, which has catalytic activity, but did not bind to the smallest subunit or the DNA primase p46 of mouse pol alpha. These results suggest that the dehydroaltenusin molecule competes with the template-primer molecule on its binding site of the catalytic domain of mammalian pol alpha, binds to the site, and simultaneously disturbs dNTP substrate incorporation into the template-primer.

Animals↗
PubMed2000

The biochemical mode of inhibition of DNA polymerase beta by alpha-rubromycin.

Quinone antibiotics, alpha- and beta-rubromycin, were originally found as inhibitors of retroviral reverse transcriptase. We investigated the effects of these agents on DNA metabolic enzymes including DNA and RNA polymerases as retroviral reverse transcriptase is a kind of the polymerase. As expected, we found that alpha- and beta-rubromycin strongly inhibited not only the retroviral reverse transcriptase activity, but the activities of the mammalian DNA polymerases, telomerase and terminal deoxynucleotidyl transferase in vitro. These agents should therefore be classified as DNA polymerase inhibitors. The Ki values of alpha-rubromycin against nucleotide substrate were 0.66 and 0.17 microM for DNA polymerase alpha and beta (pol. alpha and beta), respectively, and those of beta-rubromycin was 2.40 and 10.5 microM, respectively. Alpha-rubromycin strongly inhibited the pol. beta activity, and showed the strongest pol. beta inhibitory effect reported to date. At least on pol. beta, alpha-rubromycin was suggested to bind to the active region competing with the nucleotide substrate, and subsequently inhibit the catalytic activity. alpha-Rubromycin directly competed with the nucleotide substrate, and indirectly but simultaneously and non-competitively disturbed the template-DNA interaction with pol. beta.

Animals↗
PubMed2000

Suppression of the expression of the CYP2B1/2 gene by retinoic acids.

The effects of 5alpha-androsten-3alpha-ol (ASE), and retinoic acids (RAs) and their precursors on the phenobarbital (PB)-mediated induction of CYP2B1 and 2B2 were examined in cultured rat hepatocytes. Two isomers of RA, 9-cis- and all-trans-RA, suppressed markedly the effect of PB on CYP2B1/2 expression, while ASE had no suppressive effect. The effect of 9-cis-RA appeared at a lower concentration than the all-trans-isomer, indicating the dominant action of the former isomer. Suppression with 9-cis-retinal was also observed, but all-trans-retinol and -retinal were without effect. These results suggest that: (1) ASE, an inverse agonist for the constitutive androstane receptor (CAR), does not play a major role in the suppression of the CYP2B; (2) 9-cis-RA suppresses CYP2B induction by reducing ligand-free retinoid X-receptors (RXR) available for dimerization with the CAR; and (3) enzymes responsible for RA formation play an important role in the mechanism governing CYP2B regulation.

Androstenols↗