Biomedical subjects

T Yazaki

Publications and source records attributed to T Yazaki.

At least 19 recordsLinked to original sources

PubMed2000

Intravesical and intravenous therapy of human bladder cancer by the herpes vector G207.

G207, a conditionally replicating herpes vector, efficiently kills human bladder cancer cells in vitro. To evaluate the therapeutic potential of G207, we have established three in vivo models similar to the clinical situation. In vivo, G207 was intraneoplastically, intravesically, or intravenously inoculated in nude mice. Intraneoplastic inoculation into subcutaneous tumor caused significant tumor growth inhibition. Intravesical inoculation of G207 also caused decreased tumor growth in an orthotopic human bladder cancer model. Furthermore, multiple intravenous inoculation markedly inhibited subcutaneous tumor growth. These results suggest that intravesical therapy with G207 is effective for localized bladder tumor, especially for carcinoma in situ (CIS), and intravenous therapy with G207 is promising for invasive or metastasized bladder tumor.

Animals↗

PubMed2000

Expression of L1 and TAG-1 in the corticospinal, callosal, and hippocampal commissural neurons in the developing rat telencephalon as revealed by retrograde and in situ hybridization double labeling.

In the telencephalon, the corticospinal (CS), callosal, and hippocampal commissural neurons are the major types of neurons that have axons crossing the midline of the brain. To understand the mechanisms involved in crossing the midline structure and to examine whether the expression patterns of L1 and TAG-1 in the commissural neurons are similar to those in the spinal cord, we investigated L1 and TAG-1 expression in these neurons in rats by using a double-labeling technique involving retrograde labeling and in situ hybridization. Expression of L1 messenger RNA was detected in the retrogradely labeled CS projection neurons by 1,1;-dioctadecyl-3,3, 3;,3;-tetramethylindocarbocyanine perchlorate (DiI) injection into the pons at embryonic day (E) 19, but expression of TAG-1 messenger RNA was not detected in these neurons. Also, after their axons crossed the pyramidal decussation, continued expression of L1 but no expression of TAG-1 in the CS projection neurons was shown by an additional double-labeling experiment involving DiI injection into the spinal cord at postnatal day (P) 1. An immunohistochemical study showed that L1 was continuously present in each level of the CS tract at E21 and P3, but TAG-1 immunoreactivity was not found in any level at any stage. Finally, we examined the expression of L1 and TAG-1 messenger RNAs in the callosal and hippocampal commissure neurons after their axons had crossed the midline by using the double-labeling technique. In both cases, hybridization signals of the L1 and TAG-1 messenger RNAs were observed in the retrogradely labeled neurons at P3. These results suggest that the roles of L1 and TAG-1 in the formation of the commissures in the forebrain are different from their roles in the spinal cord.

Animals↗

PubMed2000

Antitumoral effects of defective herpes simplex virus-mediated transfer of tissue inhibitor of metalloproteinases-2 gene in malignant glioma U87 in vitro: consequences for anti-cancer gene therapy.

We set up experiments to evaluate the effects of defective herpes simplex virus (HSV)-mediated in vitro gene transfer of tissue inhibitor of metalloproteinases-2 (TIMP-2) in malignant glioma cells. Intrinsic TIMPs are known to be inhibitors of the strong invasive activities of matrix metalloproteinases in malignant gliomas. The defective HSV vectors dvSRaTIMP2 was engineered to express human TIMP-2 (hTIMP-2) with a combination of replication-competent HSV mutant, temperature-sensitive HSV-tsK, and amplicon plasmid-containing hTIMP-2. The hTIMP-2 gene was driven by the simian virus 40 promoter. The helper virus (HSV-tsK) was thermosensitive; consequently, this vector could proliferate only at 31.5 degrees C. After infection of U87 human glioblastoma cells with the vector in vitro, expression of TIMP-2 was confirmed by reverse zymography. The U87 cells infected in vitro either with dvSRaTIMP2 or HSV-tsK were efficiently destroyed under replication-permissive conditions (at 31.5 degrees C) and significantly lowered under replication-nonpermissive conditions (at 37 degrees C). The invasive activity of U87 was clearly inhibited by dvSRaTIMP2 infection at both 31.5 degrees C and 37 degrees C. Our studies suggest that TIMP-2 expressing the defective HSV vector is possibly useful for the treatment of malignant brain tumors.

Animals↗

PubMed2000

Oncolytic viral therapy for human prostate cancer by conditionally replicating herpes simplex virus 1 vector G207.

Over the last few years, a conditionally replicating herpes simplex virus 1 (HSV-1) vector, G207 has been used for the treatment of several malignant tumors. In this article we evaluate the anti-tumoral effect of G207 against prostate cancer in vitro and in vivo. The susceptibility of the human prostate cancer cell lines, DU145 and PC3 to G207 at a multiplicity of infection (MOI) of 0.1 was examined. In addition, the growth characteristics of G207 were assessed. Athymic mice with s.c. tumors were inoculated in vivo intraneoplastically with 1 x 10(7) plaque-forming units (PFU) of G207. For the pathological analyses, s.c. tumors were stained with X-gal. DU145 and PC3 were efficiently destroyed by G207 within 7 days. The viral yields of G207 increased time-dependently. In vivo, the intraneoplastic inoculation of G207 induced a significant inhibition of the tumor growth. The mean tumor growth ratio was significantly inhibited in the G207-treated tumors (DU145, P < 0.0001; PC3, P < 0.001 versus controls). In a pathological study, many lacZ-positive cells were diffusely present in the G207-treated tumors. G207 showed a significant antitumoral effect against human prostate cancer cell lines, and thus may be considered a useful agent for the treatment of prostate cancer.

Animals↗

PubMed1999

Ureteropyeloscopy in the diagnosis of patients with upper tract hematuria: an initial clinical study.

BACKGROUND: To study the usefulness and safety of ureteropyeloscopy in the diagnosis of upper tract hematuria of unknown etiology by standard diagnostic methods. METHODS: Fifteen patients with upper tract hematuria of unknown etiology were the subjects of the present study. Prior to ureteropyeloscopy, they underwent standard diagnostic methods, including cystourethroscopy, excretory urography and computed tomography scan. The upper tract (ureter, renal pelvis and calyces) was inspected systematically with a flexible ureteropyeloscope under epidural anesthesia. A biopsy specimen was obtained when neoplasm of a suspicious lesion was seen. Bleeding and hemangiomatous lesions were fulgurated at the time of ureteropyeloscopy. RESULTS: Unilateral gross hematuria was seen in 12 patients. Imaging studies revealed a filling defect in four patients, ureteral stenosis in one patient and nutcracker phenomenon in one patient. Urine cytology was positive in three patients and suspicious in four patients. Results of ureteropyeloscopy were papillary tumor in three patients, whitish encrustation in one patient, redness of the renal pelvis in one patient, bleeding from the renal calyx in two patients, hemangiomatous lesion in one patient, ureteral stenosis in two patients and no abnormalities in five patients. Biopsies were performed in five patients. The pathology results were transitional cell carcinoma in four patients and no abnormality in one patient. Although a ureteral stent catheter was placed in one patient, no serious complications were encountered during or after the procedures. CONCLUSIONS: Ureteropyeloscopy was useful and relatively safe. This endoscopic examination can differentiate insignificant lesions from significant lesions by visual inspection of the lesions, in addition, pathological diagnosis by biopsy specimen can also be performed if deemed necessary. Ureteropyeloscopy is recommended in the diagnosis of upper tract hematuria of unknown etiology.

Adult↗

PubMed1999

Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation of intracerebral injection in nonhuman primates.

This study examined the safety of intracerebral inoculation of G207, an attenuated, replication-competent herpes simplex virus type 1 (HSV-1) recombinant, in nonhuman primates. Sixteen New World owl monkeys (Aotus nancymae [karyotype 1, formerly believed to be A. trivirgatus]), known for their exquisite susceptibility to HSV-1 infection, were evaluated. Thirteen underwent intracerebral inoculation with G207 at doses of 10(7) or 10(9) PFU, two were vehicle inoculated, and one served as an infected wild-type control and received 10(3) PFU of HSV-1 strain F. HSV-1 strain F caused rapid mortality and symptoms consistent with HSV encephalitis, including fever, hemiparesis, meningitis, and hemorrhage in the basal ganglia. One year after G207 inoculation, seven of the animals were alive and exhibited no evidence of clinical complications. Three deaths resulted from nonneurologic causes unrelated to HSV infection, and three animals were sacrificed for histopathologic examination. Two animals were reinoculated with G207 (10(7) PFU) at the same stereotactic coordinates 1 year after the initial G207 inoculation. These animals were alive and healthy 2 years after the second inoculation. Cerebral magnetic resonance imaging studies performed both before and after G207 inoculation failed to reveal radiographic evidence of HSV-related sequelae. Despite the lack of outwardly observable HSV pathology, measurable increases in serum anti-HSV titers were detected. Histopathological examination of multiple organ tissues found no evidence of HSV-induced histopathology or dissemination. We conclude that intracerebral inoculation of up to 10(9) PFU of G207, well above the efficacious dose in mouse tumor studies, is safe and therefore appropriate for human clinical trials.

Animals↗

PubMed1999

Bilateral emphysematous pyelonephritis with autosomal-dominant polycystic kidney disease successfully treated by conservative method.

Emphysematous pyelonephritis (EPN) is an uncommon and potentially life-threatening necrotizing inflammation of the renal parenchyma. EPN associated with autosomal dominant polycystic kidney disease (ADPCK) is extremely rare. We report such a case of bilateral EPN with ADPCK that was successfully treated with conservative methods. To our knowledge, our case is only the second to document bilateral EPN occurring with ADPCK and the first one to be treated successfully with conservative methods.

Anti-Bacterial Agents↗

PubMed1998

Characterization of the subsite structure of the beta-glucosidase from Aspergillus niger, an aspect of the mechanism of carbohydrate recognition.

Steady-state kinetics on the reaction catalyzed by the beta-glucosidase of Aspergillus niger were carried out to evaluate the kinetic parameters, Km and ko, for phenyl beta-D-glucosides. The ko/Km values, which may relate to productive binding at subsites, were found to correlate with the substituent constant pi (hydrophobicity), suggesting that subsite 2 has a hydrophobic character. A "hydrophobic-driven" mechanism is considered to contribute to the productive E-S complex for recognition of the substrate.

Aspergillus niger↗

PubMed1998

Developmental changes in the NGF content in the brain of young, growing, low-birth-weight rats.

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla oblongata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.

Animals↗

PubMed1998

Protective effect of ceftriaxone against the nephrotoxicity of isepamicin administered once daily in rats.

The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was investigated. For 14 d, Wistar rats were administered either ceftriaxone 100 mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as compared with the control animals which received saline (p<0.01). However, the increase in NAG level was markedly less when isepamicin was administered in combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine NAG activity. Serum creatinine levels were significantly higher in animals treated with isepamicin alone than in control animals (p<0.01) or animals receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the renal intracortical accumulation of isepamicin (p<0.01). Histopathologically, ceftriaxone induced very few cellular alterations and considerably reduced the manifestation of typical signs of isepamicin nephrotoxicity. This investigation demonstrates that ceftriaxone protects animals against isepamicin-induced nephrotoxicity.

Animals↗

PubMed1998

[Imaging studies of excretory urography and computed tomography scan for patients suffering from renal colic].

Renal colic mainly due to urolithiasis is one of the most common morbid conditions in urology and commonly seen in the urology emergency clinic. Imaging studies were performed to evaluate the upper urinary tract of 29 patients suffering from renal colic in the 2 years between November, 1994 and October, 1996. After intramuscular injection of the analgesic (pentazocine, 15 mg), all 29 patients were examined by excretory urography (IVP) at the time of the first visit. In some patients abdominal plain computed tomography (CT) scan was performed consecutively even when extravasation of the contrast medium was not seen. Spontaneous peripelvic extravasation was seen in 14 patients (11 males and 3 females) with urolithiasis; 7 of them were diagnosed by IVP, 5 by IVP plus CT scan and 2 with CT scan only. IVP imaging study followed by plain abdominal CT scan is useful even when the contrast medium is not extravasated on IVP in patients suffering from renal colic.

Adult↗

PubMed1998

[A clinical study of superficial bladder cancer with grade 3 components].

A retrospective study was done on 33 patients treated for superficial bladder cancer, pTa and pT1, with grade 3 components between 1986 and 1995. All patients had undergone transurethral resection of the tumor (TUR-Bt), which was followed by total cystectomy in 7 patients. Three patients died of pulmonary diseases or heart attack and 6 patients subsequently died of bladder cancer. The 2-year and 5-year disease-specific survival rates of these patients were 83% and 75%, respectively, and the mean duration of follow-up was 50 months. Comparison of the disease-specific survival rates for several factors revealed that the configuration and size of the tumors were significantly predictable factors for prognosis. In well-selected patients with grade 3 superficial bladder cancer, bladder preservation seems to be possible by TUR with or without adjuvant therapies. Hence further studies on a larger series are needed to elucidate more feasible and reliable prognostic factors to avoid unnecessary cystectomy and improve the quality of life of the patients.

Adult↗

PubMed1998

[Clinical studies on the quality of life in patients with ileal conduit].

Between August, 1985 and December. 1995 ileal conduit was performed in 36 cases of bladder cancer (30 males, 6 females). A survey based on a questionnaire was carried out on 15 patients to assess their quality of life (QOL) after the surgery. The questionnaire dealt with the working situation, appetite, sleep, defecation, bathing, travel, general health condition, satisfaction, sexual life and erection. Although only 64.0% of the patients returned to work, appetite, hours of sleep and bathing frequency showed only a slight decrease. We performed total cystectomy without using the nerve sparing method. After the operation, three patients could have an erection and enjoy sexual life. Because the ileal conduit resulted in few complications and only a slight reduction in QOL, it was considered an appropriate operation.

Activities of Daily Living↗

PubMed1997

Multiple isoforms of neuregulin are expressed in developing rat dorsal root ganglia.

Accumulating evidence suggests that neuregulin (NRG) plays special roles in the development of the mammalian nervous system. We have already identified NRG as a survival factor for Schwann cells during development. In this report, we have studied all possible NRG isoforms and expression of NRG in the developing rat dorsal root ganglia (DRG) and compared them with those of brain and spinal cord. Neural NRG isoforms comprise common immunoglobulin and epidermal growth factor domains. Various different transcripts were characterized, which arose by alternative splicing in several regions: N-terminal (exon 1 or 2), spacer (exon 5), juxtamembrane (exon 9 or 10), and cytoplasmic (exon 12, 13, or 14) domains. At least 13 novel isoforms among 16 splice variants were identified. The transmembrane isoforms of NRG are dominant forms in developing rat DRG. The mRNA expression of NRG isoforms in DRG is similar to that in spinal cord, while in brain the expression is much less. The mRNA in DRG was found at similar levels from birth to postnatal day 7 of the premyelinating stage, and it decreased afterward. Our results suggest that several NRGs, including isoforms not reported before, play a role as survival factors for Schwann cells in the premyelinating stage.

Aging↗

PubMed1997

Subsite structure of the beta-glucosidase from Aspergillus niger, evaluated by steady-state kinetics with cello-oligosaccharides as substrates.

The beta-glucosidase from a commercially available preparation from Aspergillus niger was highly purified. The Michaelis constant Km and the molar activity K0 for cello-oligosaccharide substrates Gn (n = 2-6) were obtained by steady-state kinetic analysis on the beta-glucosidase-catalyzed hydrolysis at 25 degrees C and pH 5.0. Stoichiometric production of Gn-1 by the beta-glucosidase reaction for Gn was confirmed by HPLC techniques. Based on Km and K0 for Gn, subsite affinities (Ai, i = 1-6) were estimated as follows (kcal/mol): A1 = 1.3, A2 = 5.2, A3 = 0.65, A4 = -0.10, A5 = -0.65, and A6 = -0.26, of which A1-A3 are much higher than those of the beta-glucosidase of Candida wickerhamii. The subsite structure is quite similar to that of the alpha-glucosidase of A. niger, whereas the dependence of k0 on n is highly characteristic for beta-glucosidase, and decreases with n, suggesting some interaction between the particular subsites.

Aspergillus niger↗

PubMed1997

Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.

Adult↗

PubMed1996

Expression of L1 in primary astrocytes via a defective herpes simplex virus vector promotes neurite outgrowth and neural cell migration.

The neural cell adhesion molecule L1 is a transmembrane glycoprotein of approximately 200 kDa molecular weight that is a member of the immunoglobulin super family. Multiple functions of L1 have been reported, including cell-cell interactions, neurite elongation, axonal fasciculation, cell migration, and myelination. L1 plays important roles in neural development and axonal regeneration in the peripheral nervous system (PNS), however, in the adult it is only present on neurons in the central nervous system (CNS). In the present study we have used defective herpes simplex virus (HSV) vectors to express full-length human or rat L1 in cultured primary rat cortical astrocytes. Rat cerebellar granule cells, a rather homogeneous population of neurons, co-cultured on a substrate layer of L1-expressing astrocytes demonstrated increased migration and neurite extension compared with neurons co-cultured on lacZ-expressing astrocytes of uninfected astrocytes. There was no detectable difference between human and rat L1. Because this vector system can be used to confer phenotypic changes in primary nervous system cells it will be useful for in vitro and in vivo studies of neural regenerative sprouting and plasticity in the CNS.

Animals↗

PubMed1996

Yearly variation of spontaneous somatic mutation frequency in the stamen hairs of Tradescantia clone KU 9 grown outdoors, which showed a significant increase after the Chernobyl accident.

Scoring of spontaneous somatic pink mutation frequency in the stamen hairs of Tradescantia clone KU 9, a heterozygote for flower color (blue/pink; the blue color being dominant), was carried out for 11 years on plants grown outdoors, during the period of May 11-31 (for 3 weeks) in every year from 1982 to 1992. Weekly and yearly variations of the spontaneous mutation frequency were observed, and such variations could mostly be correlated to the difference in temperature. That is, the mutation frequency was generally higher in the weeks and years when the temperature was relatively low, showing the strongest negative correlation with the average minimum temperature. The variations were also correlated to the diurnal temperature difference, the mutation frequency being higher with larger diurnal temperature difference in general. However, the mutation frequency observed in 1986 was exceptionally higher than that expected from the temperature for this year, and was very significantly higher than for other years. The scoring of mutation frequency was thus continued in 1986 for an additional 4 weeks (June 1-28), and it was confirmed that such higher mutation frequencies lasted for 6 weeks in total. The exceptionally high mutation frequency seemed to be related to the radioactive fallout which occurred in early to mid May of 1986, even in Japan, after the serious nuclear reactor accident at Chernobyl, and also to the biological concentrations of radioactive nuclides which subsequently occurred, although it was difficult to conclude this definitely. The mutation frequency in 1987 was second highest, and was also significantly higher than the lowest mutation frequency observed in 1990.

Climate↗