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Y Horiguchi

Publications and source records attributed to Y Horiguchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.

Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.

Animals↗
PubMed2000

Transthoracic ultrasonic visualisation of coronary aneurysm, stenosis, and occlusion in Kawasaki disease.

OBJECTIVE: To determine the sensitivity and specificity of our transthoracic echocardiographic technique using high frequency (7.5 MHz) transducers for identification of the presence and type of coronary artery disease in patients with Kawasaki disease. DESIGN: The results of the prospective echocardiographic study in each of seven segments of the four major coronary arteries were compared with the selective coronary angiograms. SETTING: Kitasato University Hospital. SUBJECTS: 60 patients with Kawasaki disease, ranging in age from 8.0 months to 22 years (median, 6.0 years). RESULTS: Adequate echocardiographic images were obtained in 397 (95%) of 420 coronary segments. Coronary angiography showed the presence of coronary aneurysms in 87 segments and stenosis or occlusion in 28. The overall sensitivity and specificity of cross sectional echocardiography for correctly identifying coronary aneurysms were 95% and 99%, respectively; for correctly identifying coronary stenosis or occlusion the values were 85% and 98% for the right coronary artery, and 80% and 97% for the left anterior descending coronary artery. Agreement on the presence or absence of coronary aneurysms and obstructive lesions on echocardiograms between the two observers was 1.0 and 0.98, respectively. CONCLUSIONS: Echocardiography may provide a non-invasive means of identifying the presence and type of coronary artery disease in patients with Kawasaki disease.

Adolescent↗
PubMed2000

Synthesis of methoxy-2-quinolones via pummerer-type cyclization of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides.

The thionium ions 10 generated by Pummerer reaction of N-aryl-N-methyl-3-(phenylsulfinyl)propionamides 4 caused not only an electrophilic cyclization reaction producing 2-quinolones 8, but also the formation of the vinyl sulfides 5 and 6 in favor of the latter reaction. On the other hand, the treatment of the vinyl sulfides 5 and 6 with p-toluenesulfonic acid induced cyclization to afford the 2-quinolones 8 in excellent to moderate yields, depending on the electronic properties of the aromatic ring, thus providing a convenient method for the synthesis of methoxy-2-quinolones.

Acetic Anhydrides↗
PubMed2000

Long-term follow-up of periodontitis in a patient with Chédiak-Higashi syndrome. A case report.

Chediak-Higashi syndrome (CHS) is an extremely rare hereditary disease characterized by leukocyte dysfunction. We report on a 21-year-old woman who presented at the age 9 years with CHS and serious periodontal tissue destruction around erupted teeth. The patient had received systemic, radiographic, immunological, microbial, and clinical periodontal examinations since childhood. The chemotactic activity of neutrophils in the Boyden chamber assay was 22% of the control, and leukocyte bactericidal activity was one-third of the control. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia were isolated from periodontal pockets. Periodontal treatment including oral hygiene was provided, followed by professional tooth cleaning from the age of 12 to 21 years. However, the mobility of teeth and the inflammation of periodontal tissue progressed. This CHS patient presented with periodontal disease of extremely early onset, which was resistant to periodontal treatment.

Actinobacillus Infections↗
PubMed2000

Serum interleukin 6 as a prognostic factor in patients with prostate cancer.

The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.

Aged↗
PubMed2000

Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is dependent on the sequence and order: a liposome-mediated gene therapy treatment for bladder cancer.

We have developed a novel liposome-mediated immunogene therapy using interleukin 2 (IL-2) and B7.1 in a murine bladder cancer model. A carcinogen-induced murine bladder cancer cell line, MBT-2, was transfected with cationic liposome 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleolylphosphatidylethanolamine and IL-2 plasmid. The optimized transfection condition generated IL-2 levels of 245-305 ng/10(6) cells/24 h, 100-fold higher than the levels seen with retrovirus transfection. Ninety percent of the peak level of IL-2 production was maintained for up to 11 days after transfection. Animal studies were conducted in C3H/HeJ female mice with 2 x 10(4) MBT-2 cells implanted orthotopically on day 0. Multiple vaccination schedules were performed with i.p. injection of 5 x 10(6) IL-2 and/or B7.1 gene-modified cell preparations. The greatest impact on survival was observed with the day 5, 10, and 15 regimen. Control animals receiving retrovirally gene-modified MBT-2/IL-2 cell preparations had a median survival of 29 days. Animals receiving the IL-2 liposomally gene-modified cell preparation alone had a median survival of 46 days. Seventy-five percent of animals receiving IL-2 followed by B7.1 gene-modified tumor vaccines were the only group to show complete tumor-free survival at day 60. All of these surviving animals rejected the parental MBT-2 tumor rechallenge and survived at day 120 with a high CTL response. In conclusion, liposome-mediated transfection demonstrates a clear advantage as compared with the retroviral system in the MBT-2 model. Multi-agent as opposed to single-agent cytokine gene-modified tumor vaccines were beneficial. These "targeted" sequential vaccinations using IL-2 followed by B7.1 gene-modified tumor cells significantly increased a systemic immune response that translated into increased survival.

Animals↗
PubMed1999

Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier.

Claudins, comprising a multigene family, constitute tight junction (TJ) strands. Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half. We examined the effects of the COOH-terminal half fragment of CPE (C-CPE) on TJs in L transfectants expressing claudin-1 to -4 (C1L to C4L, respectively), and in MDCK I cells expressing claudin-1 and -4. C-CPE bound to claudin-3 and -4 with high affinity, but not to claudin-1 or -2. In the presence of C-CPE, reconstituted TJ strands in C3L cells gradually disintegrated and disappeared from their cell surface. In MDCK I cells incubated with C-CPE, claudin-4 was selectively removed from TJs with its concomitant degradation. At 4 h after incubation with C-CPE, TJ strands were disintegrated, and the number of TJ strands and the complexity of their network were markedly decreased. In good agreement with the time course of these morphological changes, the TJ barrier (TER and paracellular flux) of MDCK I cells was downregulated by C-CPE in a dose-dependent manner. These findings provided evidence for the direct involvement of claudins in the barrier functions of TJs.

Animals↗
PubMed1999

Strip biopsy of superficial bladder tumors using an electrosurgical snare.

BACKGROUND/METHODS: Transurethral strip biopsy of bladder tumors using an electrosurgical snare was tested to determine whether or not this technique provides any advantage to the histologic examination of bladder cancers and to the management of superficial bladder tumors as a routine treatment. RESULTS/DISCUSSION: Our research results confirm that the strip biopsy technique can be applied as an alternative transurethral management procedure for treatment of superficial bladder tumors. Moreover, the results demonstrate that the procedure can also provide significantly greater histologic diagnostic advantages for bladder cancers than are possible through cold cup biopsy or transurethral resection.

Biopsy↗
PubMed1999

Cytotoxic necrotizing factor type 2 produced by pathogenic Escherichia coli deamidates a gln residue in the conserved G-3 domain of the rho family and preferentially inhibits the GTPase activity of RhoA and rac1.

Cytotoxic necrotizing factor types 1 and 2 (CNF1 and -2) produced by pathogenic Escherichia coli strains have 90% conserved residues over 1,014-amino-acid sequences. Both CNFs are able to provoke a remarkable increase in F-actin structures in cultured cells and covalently modify the RhoA small GTPases. In this study, we demonstrated that CNF2 reduced RhoA GTPase activity in the presence and absence of P122(RhoGAP). Subsequently, peptide mapping and amino acid sequencing of CNF2-modified FLAG-RhoA produced in E. coli revealed that CNF2 deamidates Q63 of RhoA-like CNF1. In vitro incubation of the C-terminal domain of CNF2 with FLAG-RhoA resulted also in deamidation of the FLAG-RhoA, suggesting that this region contains the enzymatic domain of CNF2. An oligopeptide antibody (anti-E63) which specifically recognized the altered G-3 domain of the Rho family reacted with glutathione S-transferase (GST)-RhoA and GST-Rac1 but not with GST-Cdc42 when coexpressed with CNF2. In addition, CNF2 selectively induced accumulation of GTP form of FLAG-RhoA and FLAG-Rac1 but not of FLAG-Cdc42 in Cos-7 cells. Taken together, these results indicate that CNF2 preferentially deamidates RhoA Q63 and Rac1 Q61 and constitutively activates these small GTPases in cultured cells. In contrast, anti-E63 reacted with GST-RhoA and GST-Cdc42 but not with GST-Rac1 when coexpressed with CNF1. These results indicate that CNF2 and CNF1 share the same catalytic activity but have distinct substrate specificities, which may reflect their differences in toxic activity in vivo.

Amino Acid Sequence↗
PubMed1999

Identification of functional domains of Bordetella dermonecrotizing toxin.

Bordetella dermonecrotizing toxin (DNT) stimulates the assembly of actin stress fibers and focal adhesions by deamidating Gln63 of the small GTPase Rho. To clarify the functional and structural organization of DNT, we cloned and sequenced the DNT gene and examined the functions of various DNT mutants. Our analyses of the nucleotide and amino acid sequences revealed that the start codon of the DNT gene is a GTG triplet located 39 bp upstream of the reported putative initiation ATG codon; consequently, DNT contains an additional 13 amino acids at its N-terminal end. All of the N-terminally truncated mutants were found to modify Rho. The shortest fragment of DNT possessing the Rho modification activity consists of amino acids from Ile1176 to the C-terminal end. This fragment overlaps the region homologous to Escherichia coli cytotoxic necrotizing factors (CNFs), which show activity similar to that of DNT. The introduction of a mutation at Cys1305 located in the highly conserved region between CNFs and DNT eliminated the activity, indicating that this domain is the catalytic center of DNT. The N-terminal fragment (1 to 531) of DNT failed to modify Rho but reduced the DNT-induced polynucleation in MC3T3-E1 cells when simultaneously added with the holotoxin, suggesting competitive inhibition in the receptor-binding or internalizing step. Our finding that DNT consists of an N-terminal receptor-binding and/or internalizing domain and a C-terminal catalytically active domain may facilitate analysis of the overall action of the toxin on the mammalian target cells.

Amino Acid Sequence↗
PubMed1999

Human herpesvirus 6 open reading frame U83 encodes a functional chemokine.

Some viruses including herpesviruses have undergone evolution to benefit viral infection and propagation by pirating and modifying host genes such as chemokine genes. Human herpesvirus 6 (HHV-6), acutely or persistently infects mononuclear cells in vitro. DNA sequence analysis of HHV-6 has revealed that the putative protein encoded by an open reading frame (ORF) of the U83 gene in HHV-6 variant B resembled a human chemokine. We have cloned the U83 gene and analyzed the biological function of this gene. The U83 gene contained an ORF encoding a 113-amino-acid peptide, starting at the first methionine and containing a possible signal peptide and the typical cysteine residues characteristic of the chemokines. Reverse transcription-PCR analysis of mRNA and immunofluorescent-antibody testing of infected cells both indicated that the encoded protein was a late protein. The ORF U83 gene fused to the Fc gene was expressed as a fusion protein in COS-7 cells by transfection, and the fusion protein was purified from the supernatant of transfected cells to test its biological function. The purified protein was capable of inducing transient calcium mobilization in THP-1 cells and of chemotactically activating THP-1 cells. These findings suggested that the U83 protein might play an important role in HHV-6 propagation in vivo by activating and trafficking mononuclear cells to sites of viral replication, thus aiding the development of superbly efficient virus production mechanisms.

Amino Acid Sequence↗
PubMed1999

A prospective multicenter trial evaluating diagnostic validity of multivariate analysis and individual serum marker in differential diagnosis of pancreatic cancer from benign pancreatic diseases.

CONCLUSION: A multivariate analysis of CAMPAS-PX2 can increase its diagnostic accuracy in differential diagnosis of pancreatic cancer from benign pancreatic or extrapancreatic disease, when compared with CA19-9 alone. However, the improvement in diagnostic accuracy is still not satisfactory in spite of an elaborate combination of serum markers in diagnosis for pancreatic cancer. Optimal combination of a sensitive serum marker and another diagnostic modality, such as ultrasonography, can be a practical way to improve important diagnostic and cost-effectiveness in diagnosis for pancreatic cancer. BACKGROUND: No specific biological test has yet been developed for diagnosis of pancreatic cancer, although increasing numbers of tumor markers become available. For improvement in the diagnostic and cost effectiveness, it is important to select optimal combination of several serum markers relatively independent of each other. METHODS: A new model of discriminant function, computer-aided multivariate and pattern analysis system for pancreatic cancer examination 2 (CAMPAS-PX2), was developed based on the data of the 23 serum tumor markers from the first prospective trial (1) to differentiate between pancreatic cancer and benign pancreatobiliary disease by logistic regression analysis using a stepwise selection method. In 243 patients suspected of having pancreatic pancreatic cancer by a multicenter prospective study, the diagnostic value of the multivariate analysis, CAMPAS-PX2, was compared with the 23 markers. RESULTS: Pancreatic cancer was subsequently identified in 27 patients. Positive in disease, negative in health, and area under receiver operating characteristic curve were significantly higher by CAMPAS-PX2 (89, 87, 91%) than by CA 19-9 (78, 82, 84%), the most sensitive marker among the 23 markers.

Biomarkers, Tumor↗
PubMed1999

Sex-related differences in plasminogen activator and plasminogen activator inhibiting activities in young and aged rats.

The purpose of this study was to determine whether aging influences the sex-related differences in fibrinolytic activity in rats. We measured plasminogen activator (PA) activity and plasminogen activator inhibiting (PAI) activity in 5-, 12-, 45-, and 60-week-old male and female rats. We also examined the effects of gonadectomy and sex hormone-treatments in adult male and female rats. The increase in age did not influence the PA activity in the male or female rats. However, the PA activity was higher in the female rats than in the males in all four age groups. Orchidectomy caused a significant increase in PA activity in the male rats. Estradiol treatment induced a significant increase of PA activity in ovariectomized female rats. Testosterone treatment resulted in a decrease of PA activity in orchiectomized male rats. The increase in age had an effect on PAI activity; the activity level in the 45- and 60-week-olds was stronger than that in the 12-week-old rats. The PAI activity was not significantly different between the normal rats of each sex. Gonadectomy did not influence the PAI activity in male or female rats, and testosterone and estradiol treatments also did not affect PAI activity in gonadectomized male and female rats. We found that the increase in age induced a decrease in the fibrinolytic system in the rats, and that there were sex-related differences in the fibrinolytic system in even 60-week-old rats.

Aging↗
PubMed1998

Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene.

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast-derived cell lines. We have mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplication and divergence occurred 22 million years ago.

Antigens, Surface↗
PubMed1998

Synthesis and evaluation of artificial taxoids with antitumor and multi-drug resistance reversing activities.

Artificial taxoids were synthesized and subjected to evaluation of their ability of multi-drug resistance reversing and antitumor activities. While the taxoid 4 could not increase cellular accumulation of vincristine in multi-drug resistant tumor cells, the C4-hydroxy analog 15 showed significant effect. However, these compounds showed weak activities on growth inhibition of cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Prospective echocardiographic analysis of progressive obstruction of the proximal pulmonary artery in congenital heart disease and obstructed pulmonary flow.

BACKGROUND: It is uncertain whether proximal pulmonary artery (PA) obstruction exists soon after birth and whether its progress relates directly to postnatal ductal constriction in congenital heart disease and obstructed pulmonary flow. METHODS: Serial morphometric analyses of the PA branches by echocardiogram were performed in 28 patients (mean age at initial study 2.5 days) until severe constriction of the ductus occurred (mean age 47 days). These patients were divided into 2 groups by subsequent angiographic or postmortem confirmation; 10 with proximal PA obstruction (group 1) and 18 without obstruction (group 2). RESULTS: At the time of initial examination, the mean indexed diameter of the proximal PA on the side of the ductus arteriosus in group 1 was significantly smaller than that on the contralateral side (5.2+/-0.7 versus 9.0+/-0.7 mm/BSA0.5, P < .001) or that in group 2 (8.0+/-0.4 mm/BSA0.5, P < .001). In group 1, 8 patients had a proximal PA index on the ductal side < or = 5.5 mm/BSA0.5, which was less than those of any group 2 patients. After severe constriction of the ductus, the proximal PA index on the ductal side further decreased only in group 1 (P < .01). CONCLUSIONS: These data indicate that unilateral obstructive lesion of branch PA is present shortly after birth and its progression relates directly to ductal constriction. Neonates with branch PA obstruction can be identified on their initial echocardiogram as having a proximal PA index on the ductal side < or = 5.5 mm/BSA0.5.

Arterial Occlusive Diseases↗