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H Imoto

Publications and source records attributed to H Imoto.

At least 19 recordsLinked to original sources
PubMed2006

The atypical antipsychotic clozapine impairs insulin secretion by inhibiting glucose metabolism and distal steps in rat pancreatic islets.

AIMS/HYPOTHESIS: Diabetogenic effects of some atypical antipsychotic drugs have been reported, although the mechanisms are not fully understood. We investigated the long-term effects of culturing isolated rat pancreatic islets with atypical antipsychotic clozapine. METHODS: Glucose- and non-glucose-stimulated insulin secretion, glucose metabolism and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in islets cultured with or without clozapine. RESULTS: Although acute incubation or 3-day culture with clozapine did not affect glucose-stimulated insulin secretion, clozapine suppressed glucose-stimulated insulin secretion by 53.2% at 1.0 micromol/l (therapeutic concentration) after 7 days of culture. Islet glucose oxidation and [Ca(2+)](i) elevation by high glucose were not affected after 3 days of culture, but clozapine significantly inhibited islet glucose oxidation, ATP production, and [Ca(2+)](i) elevation by high glucose after 7 days of culture. Moreover, 7 days of culture with clozapine inhibited insulin secretion stimulated by: (1) membrane depolarisation induced by high K(+); (2) protein kinase C activation; and (3) mastoparan at 16.7 mmol/l glucose under stringent Ca(2+)-free conditions. Elevation of [Ca(2+)](i) by high K(+)-induced membrane depolarisation was similar in control and clozapine-treated islets. Clozapine, a muscarinic blocker, acutely inhibited carbachol-induced insulin secretion, as did atropine, whereas after 7 days of culture atropine did not have the inhibitory effect shown by clozapine after 7 days. The impairment of glucose-stimulated insulin secretion recovered 3 days after the removal of clozapine treatment. CONCLUSIONS/INTERPRETATION: The present study demonstrated that the atypical antipsychotic drug clozapine directly impaired insulin secretion via multiple sites including glucose metabolism and the distal step in insulin exocytosis in a long-term culture condition. These mechanisms may be involved in the form of diabetes mellitus associated with atypical antipsychotic drugs.

Adenosine Triphosphate↗
PubMed2001

[Treatment and results of interstitial lung diseases in video assisted thoracoscopic lung biopsy].

In order to establish treatment of interstitial lung diseases in video assisted thoracoscopic lung biopsy, we retrospectively reviewed our experiences. The present study included 7 patients with a mean age of 46.4, range from 24 to 61, who were treated at our department from 1996 through 1999. They were 5 men and 2 women. The pathologic diagnosis was nonspecific interstitial pneumonia in 3 patients who responded to steroid therapy. Three other patients had usual interstitial pneumonia. One patient had lymphocytic interstitial pneumonia. No complications occurred. The results indicate that video assisted thoracoscopic lung biopsy is an effective and safe way to diagnose interstitial lung diseases.

Adult↗
PubMed2001

Prediction of pulmonary complications after a lobectomy in patients with non-small cell lung cancer.

BACKGROUND: Although the preoperative prediction of pulmonary complications after lung major surgery has been reported in various papers, it still remains unclear. METHODS: Eighty nine patients with stage I-IIIA non-small cell lung cancer (NSCLC) who underwent a complete resection at our institute from 1994-8 were evaluated for the feasibility of making a preoperative prediction of pulmonary complications. All had either a predicted postoperative forced vital capacity (FVC) of >800 ml/m(2) or forced expiratory volume in one second (FEV(1)) of >600 ml/m(2). RESULTS: Postoperative complications occurred in 37 patients (41.2%) but no patients died during the 30 day period after the operation. Pulmonary complications occurred in 20 patients (22.5%). Univariate analysis indicated that the factors significantly related to pulmonary complications were FVC <80%, serum lactate dehydrogenase (LDH) level > or =230 U/l, and arterial oxygen tension (PaO(2)) <10.6 kPa (80 mm Hg). In a multivariate analysis the three independent predictors of pulmonary complications were serum LDH > or =230 U/l (odds ratio (OR) 10.5, 95% CI 1.4 to 77.3), residual volume (RV)/total lung capacity (TLC) > or =30% (OR 6.0, 95% CI 1.1 to 33.7), and PaO(2) <10.6 kPa (OR 5.6, 95% CI 1.4 to 22.2). CONCLUSIONS: The above findings indicate that three factors (serum LDH levels of > or =230 U/l, RV/TLC > or =30%, and PaO(2) <10.6 kPa) may be associated with pulmonary complications in patients undergoing a lobectomy for NSCLC, even though the patient group was relatively small for statistical analysis of such a diverse subject as pulmonary complications.

Adult↗
PubMed2000

Discovery of novel, potent, and selective small-molecule CCR5 antagonists as anti-HIV-1 agents: synthesis and biological evaluation of anilide derivatives with a quaternary ammonium moiety.

The search for new small-molecule CCR5 antagonists by high-throughput screening (HTS) of the Takeda chemical library using [(125)I]RANTES and CHO/CCR5 cells led to the discovery of lead compounds (A, B) with a quaternary ammonium or phosphonium moiety, which were synthesized to investigate new MCP-1 receptor antagonists. A series of novel anilide derivatives 1 with a quaternary ammonium moiety were designed, synthesized, and tested for their CCR5 antagonistic activity. Through the optimization of lead compounds, we have found N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6, 7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetrahydr o-2 H-pyran-4-aminium chloride (1r, TAK-779) as a highly potent and selective nonpeptide CCR5 antagonist with a IC(50) value of 1.4 nM in the binding assay. Compound 1r also inhibited the replication of macrophage (M)-tropic HIV-1 (Ba-L strain) in both MAGI-CCR5 cells and PBMCs with EC(50) values of 1.2 and 3.7 nM, respectively. The synthesis and structure-activity relationships of 1r and its related compounds are detailed.

Amides↗
PubMed1999

Prognostic impact of telomerase activity in non-small cell lung cancers.

OBJECTIVE: To evaluate the clinical significance of telomerase activity, particularly in terms of prognostic impact, in non-small cell lung cancer (NSCLC). SUMMARY BACKGROUND DATA: Telomerase activity has been found in various tissues. The activation of telomerase is considered necessary for the immortalization of human tumor cells, including NSCLC. METHODS: The authors studied 103 NSCLC specimens using a polymerase chain reaction based on a telomeric repeat amplification protocol assay. RESULTS: Telomerase activity was detected in 85 (82.5%) of 103 NSCLC specimens but in none of the paired normal lung tissue specimens. More cases of positive telomerase activity were observed in the group with advanced disease and in the group with poorly differentiated tumors. Such factors as the mean age at surgery, sex, smoking, histologic type, and size of tumor extension did not correlate with the telomerase activity. The Kaplan-Meier survival curves in all patients with NSCLC demonstrated that patients with telomerase-positive tumors survived for a significantly shorter period than those with a telomerase-negative tumor (p = 0.0058). According to a multivariate analysis, telomerase activity was identified as an independent prognostic factor (RR = 8.62, p = 0.035). CONCLUSIONS: Telomerase activity was one of the most important prognostic factors in patients with NSCLC, and its potential prognostic implication was independent of tumor stage.

Adult↗
PubMed1998

Synthesis and biological activity of conformationally restricted analogues of milnacipran: (1S, 2R)-1-phenyl-2-[(R)-1-amino-2-propynyl]-N,N- diethylcyclopropanecarboxamide is a novel class of NMDA receptor channel blocker.

Conformationally restricted analogues of (+/-)-(Z)-2-aminomethyl-1-phenyl-N,N-diethylcyclopropanecarboxamide++ + [milnacipran, (+/-)-1] were designed on the basis of its characteristic cyclopropane structure and were synthesized enantioselectively to develop efficient NMDA receptor antagonists. Among these analogues, (1S,2R)-1-phenyl-2-[(R)-1-amino-2-propynyl]-N, N-diethylcyclopropanecarboxamide (2d) had one of the most potent affinities for the receptor, with a Ki value of 0.29 microM. The blockade of NMDA receptor channels expressed by Xenopus oocytes by 2d was investigated in detail, and 2d was identified as a new class of open channel blocker against this receptor.

Animals↗
PubMed1998

Percutaneous suction aspiration and drainage for pyogenic spondylitis.

STUDY DESIGN: Retrospective evaluation of results in 23 cases of early-stage pyogenic spondylitis treated with percutaneous suction aspiration and drainage. OBJECTIVES: To evaluate the efficacy of percutaneous suction aspiration and drainage as a treatment method for early-stage pyogenic spondylitis. SUMMARY OF BACKGROUND DATA: Traditional surgical treatment for pyogenic spondylitis has the disadvantage of increased morbidity caused by the extensive exposure required in the presence of infection. Recently, a few case reports have described minimally invasive treatment for pyogenic spondylitis in which percutaneous suction aspiration was used. However, the efficacy of this new treatment has not yet been evaluated. METHODS: All charts, radiographs, and bacteriologic and histologic findings were reviewed. All 23 patients who received the new treatment were observed clinically and radiographically, to evaluate the efficacy of the treatment. RESULTS: To date, all patients have been observed for more than 2 years. Twenty (87%) of the 23 patients have shown good results according to the evaluation. The causative organism was identified using tissue culturing in 12 (52%) of the 23 patients. The causative organism was Staphylococcus aureus in 8, and Staphylococcus epidermidis, Candida albicans, Pseudomonas aeruginosa, and Propionibacterium acnes in 1 each. Back pain as the major symptom in these patients was relieved within an average of 9.4 days after the operation. However, the patient in whom the spondylitis was caused by Candida albicans has received this new treatment twice without success. CONCLUSIONS: Evaluation of percutaneous suction aspiration with drainage shows that it is an effective treatment for early-stage pyogenic spondylitis.

Back Pain↗
PubMed1998

Vascular endothelial growth factor expression in non-small-cell lung cancer: prognostic significance in squamous cell carcinoma.

BACKGROUND: Recently, some studies have focused on the tumor angiogenesis and its prognostic value. We studied the expression of vascular endothelial growth factor, microvessel counts, and serum concentrations of vascular endothelial growth factor to investigate their association with clinicopathologic factors and prognosis in non-small-cell lung cancer. METHODS: The expression of vascular endothelial growth factor was determined by an immunohistochemical analysis from 91 paraffin specimens of completely resected non-small-cell lung cancers using anti-growth factor polyclonal antibody. Microvessel staining was performed by immunohistochemical analysis with anti-factor VIII-related antigen polyclonal antibody. Measurement of the serum concentrations of vascular endothelial growth factor used the sandwich enzyme-linked immunosorbent assay technique. RESULTS: Expression of vascular endothelial growth factor was detected in 48 of the 91 tumors. The positive ratio was significantly higher in patients with adenocarcinoma than in those with squamous cell carcinoma. The microvessel counts were significantly higher in the patients with nodal metastasis than in those without nodal metastasis. The serum concentrations of vascular endothelial growth factor were also significantly higher in the patients with T3-4 disease than in those with T1-2 disease. The microvessel counts were closely associated with expression of vascular endothelial growth factor. The prognosis of patients with a positive growth factor ratio was significantly worse than that of the patients with a negative ratio (p = 0.002), especially in squamous cell carcinoma. According to a multivariate analysis, only nodal status and expression of vascular endothelial growth factor were found to be independent prognostic factors. CONCLUSIONS: The expression of vascular endothelial growth factor was one of the most important prognostic factors in completely resected non-small-cell lung cancer, especially in squamous cell carcinoma.

Adult↗
PubMed1997

Prognostic value of the immunohistochemical detection of p16INK4 expression in nonsmall cell lung carcinoma.

BACKGROUND: The product of the p16INK4/CDKN2/MTS1 (p16) controls the transition from the G1 phase to the S-phase in the cell cycle by inhibiting the phosphorylation of the retinoblastoma gene product. A lack of p16 expression has been reported in various cancer cell lines and tumors; however, there have been only a few reports on the prognostic significance of p16 alteration. The authors studied p16 expression in nonsmall cell lung carcinoma (NSCLC) and also examined its correlation with clinicopathologic features and prognosis. METHODS: p16 expression was determined by immunohistochemical analysis of 115 paraffin specimens of primary NSCLC that were curatively resected. The immunohistochemical study was performed using the labeled streptavidin-biotin method with anti-p16 rabbit polyclonal antibody. RESULTS: Thirty-one of 115 NSCLC specimens (27%) showed negative p16 staining. The frequency of negative p16 expression was significantly higher in squamous cell carcinoma (39.5%) than in adenocarcinoma (20.3%) (P = 0.026). There were no statistically significant differences in the p16 status with respect to age, gender, smoking history, histologic differentiation, or stage of the disease. The Kaplan-Meier survival curves demonstrated that patients with negative p16 expression survived for a significantly shorter period of time than those with positive p16 expression (P = 0.043). p16 status was a significant prognostic factor, especially in patients with early stage disease (Stages I-II) (P = 0.039). CONCLUSIONS: A lack of p16INK4 expression in NSCLC was observed more frequently in squamous cell carcinoma than in adenocarcinoma, and also was found to be closely related to prognosis, especially in patients with early stage squamous cell carcinoma.

Adenocarcinoma↗
PubMed1997

Linkage map of Syrian hamster with restriction landmark genomic scanning.

We have constructed the linkage map with precise genetic analysis of the Syrian hamster, Mesocricetus auratus, according to the restriction landmark genomic scanning (RLGS) spot mapping method. Although only 3.2-6.6% of the total RLGS spots between the two strains, ACN and BIO 14.6, showed genetic variance, 572 loci were found to be polymorphic. Out of 569 RLGS loci and 3 other loci, 531 were mapped with the backcross (ACN x BIO 14.6) F1 x BIO 14.6. The cumulative map was 1111.6 cM, indicating that the spots/loci are located throughout the genome at 1.94 cM intervals on average. Thus, RLGS provides us with a rapid tool to construct the genetic map of any species, even if it has less genetic variation.

Animals↗
PubMed1996

Construction of high-resolution physical maps from yeast artificial chromosomes using restriction landmark genomic scanning (RLGS).

We have established a new system for chromosome-specific yeast artificial chromosome (YAC) contig construction using restriction landmark genomic scanning (RLGS-based YAC contig mapper). RLGS is a powerful tool for detecting more than 1000 restriction landmarks distributed on an entire genome in one procedure. In this system, RLGS is applied to sorted chromosomes to cover the target chromosome. Using these landmarks as guideposts, chromosome-specific YAC clones are then ordered. In this paper, we report the construction of a map for a human chromosome 21 YAC contig spanning q22.1 using this new approach. Applying RLGS to sorted chromosomes 21 enables detection of approximately 1400 spots (equivalent of 1050 PacI landmarks), covering the entire region of this chromosome. We constructed the 2.5-Mb YAC contig encompassing 21q22.1 with 66 spots (equivalent of 50 PacI landmarks). With this contig map, we could detect two deleted regions and chimerism in the YAC insert DNA. Our results demonstrated the usefulness of this approach for finding DNA alterations of YACs, such as deletions and chimerism.

Chimera↗
PubMed1996

Permeation of buprenorphine and its 3-alkyl-ester prodrugs through human skin.

PURPOSE: Homologous 3-alkyl-ester prodrugs (C2 to C4) of buprenorphine with decreased crystallinity have been synthesized and evaluated for transdermal delivery commensurate with opioid dependence treatment. METHODS: To assess the influence of derivatization on delivery, the permeation of the prodrugs through human skin was determined in vitro. Prodrug metabolism was measured in human blood and skin supernatant in vitro along with chemical hydrolysis controls. The prodrugs octanol/water partition coefficients were measured. RESULTS: Without exception, the prodrugs were completely hydrolyzed on passing through the skin and appeared as buprenorphine in the receptor compartment. However, using saturation conditions, in no instance did the buprenorphine flux through skin from a prodrug solution exceed the flux of buprenorphine base itself in vitro. Moreover, the flux of the acetyl ester, the least hydrophobic of the prodrugs, was not significantly elevated upon stripping the skin. Whether in blood or the skin supernatant, the prodrugs hydrolyzed in an apparent first-order fashion and rate constants and half-lives were calculated. CONCLUSIONS: We conclude from the results that the prodrugs' very high octanol/water partition coefficients (hydrophobicity) placed them in viable tissue layer controlled diffusion. Consequently, one does not derive the potential flux-increasing benefit of reducing crystallinity that was expected.

Administration, Cutaneous↗
PubMed1996

Transdermal prodrug concepts: permeation of buprenorphine and its alkyl esters through hairless mouse skin and influence of vehicles.

In vitro skin permeation of buprenorphine (BUP) and three of its alkyl ester prodrugs was evaluated using hairless mouse skin. The three esters selected were the acetyl ester (Ac-BUP), butyl ester (Bu-BUP), and isobutyl ester (Isb-BUP). These drugs were applied on the skin as saturated slurries in three vehicles commonly used to formulate agents for transdermal purposes: propylene glycol, polyethylene glycol 400 (PEG 400), and light mineral oil. Unique solubilities were found for each drug on each vehicle. Fluxes through hairless mouse skin were evaluated for each combination of drug and vehicle using Franz diffusion cells. From PEG 400 formulations, the skin fluxes of BUP, Ac-BUP, Bu-BUP, and Isb-BUP were 0.47 +/- 0.08, 1.64 +/- 0.31, 0.33 +/- 0.05, 0.75 +/- 0.20 micrograms/cm2/h, respectively. Thus, among the three potential prodrugs chosen, only Ac-BUP showed significantly higher skin flux than BUP. There were no inter-vehicle differences in the fluxes from saturated slurries between the vehicles. Moreover, all the esters were detected substantially in the form of regenerated parent drug (BUP) in the receptor compartment. Indeed, only Ac-BUP exited the skin in a measurably intact form, but the fraction escaping metabolism in transit was small (approximately 2%). However, based on drug dispositions in the skin, the regeneration of buprenorphine seems to depend on the alkyl chain length of the ester moiety. The molar percentages of regenerated parent drug in whole drug collected from the skin following the permeation experiments were: Ac-BUP, 9.2%; Bu-BUP, 40.7%; Isb-BUP, 9.6%, respectively. Thus, only Ac-BUP appears promising as a prodrug of buprenorphine, because it is not overly hydrophilic for skin permeation and is also highly metabolized to the parent compound while in the skin.

Analgesics, Opioid↗
PubMed1994

Antigenic alteration of an anomalous human luteinizing hormone caused by two chorionic gonadotropin-type amino-acid substitutions.

We analyzed the nucleotide sequence of the luteinizing hormone beta subunit (LH beta) in a patient with an anomalous LH. This anomalous LH showed abnormal immunogenicity, but normal bioactivity, suggesting that this variance of antigenicity was caused by amino acid substitution(s). In the anomalous LH, two single amino acid substitutions, Trp(TGG) to Arg(CGG) and Ile(ATC) to Thr(ACC), were found at the codon for the 8th and 15th residue of LH beta. These two substituted amino acid residues of the anomalous LH are identical to those of chorionic gonadotropin, but not to those of LH, although the rest of the region showed the normal sequence of human LH beta. Pedigree analysis by direct DNA sequencing revealed that the parents of the patient and the healthy sister were heterozygotes for the mutation and the patient and the healthy brother were homozygotes.

Abortion, Habitual↗
PubMed1994

Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method.

A new imprinted gene has been discovered in mice using the technique of restriction landmark genomic scanning (RLGS) with methylation sensitive enzymes. Eight out of 3,100 strain-specific NotI and BssHII spots were identified as imprinted in reciprocal F1 hybrids. Subsequently, we isolated a genomic clone for one locus on proximal chromosome 11 near the Glns locus, an imprinted region in uniparental disomic mice, and its corresponding cDNA clone. Expression of this transcript from the paternal allele was established using RT-PCR of reciprocal F1-hybrid mice. The amino-acid sequence deduced from the cDNA showed significant homology to the U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit.

Amino Acid Sequence↗
PubMed1994

Direct determination of NotI cleavage sites in the genomic DNA of adult mouse kidney and human trophoblast using whole-range restriction landmark genomic scanning.

Restriction landmark genomic scanning (RLGS) is a method for visualizing restriction landmarks, employing direct labeling of restriction sites of genomic DNA and high-resolution two-dimensional electrophoresis. We determined the conditions for both the first and second dimensions of RLGS that define all of the restriction fragments which carry the NotI landmark. Using this system, we determined the number of cleavable NotI sites of genomic DNA from the mouse kidney (C57BL/6) and from the human placenta. The mouse and human genomes were cleaved at 2,380 +/- 80 sites (4,760 +/- 160 spots) and 3,240 +/- 110 sites (6,480 +/- 220 spots), respectively with NotI.

Animals↗