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T Otani

Publications and source records attributed to T Otani.

At least 145 records · Page 8Linked to original sources

Effects of the enediyne C-1027 on intracellular DNA targets.

We examined DNA damage induced by the enediyne-containing antitumor antibiotic C-1027 in intracellular nuclear and mitochondrial DNA targets using the episome-containing cell line 935.1. Strand-scission activity of the C-1027 holoantibiotic was measured by the topological forms conversion assay in episomal and mitochondrial DNA, as well as in cell-free plasmid DNA. Genomic DNA damage was quantitated by filter elution analysis. Comparisons were made to the well-characterized enediyne neocarzinostatin. From these studies, mixed single- and double-strand breaks were observed not only in cell-free, plasmid DNA but also in intracellular episomal, mitochondrial, and genomic DNA at low nanomolar concentrations. C-1027 cleaved DNA 285-fold more efficiently in cells than in a cell-free environment, and displayed preference for intracellular DNA species in the following rank order: episome > mitochondrial DNA >> genomic. NCS also damaged the non-histone-associated mitochondrial DNA, but not the episome. Cleavage of the 935.1 cell episome by C-1027 occurred at specific sites including the BPV origin of replication and E6/E7 open reading frame regions, as well as the MMTV LTR promoter region.

Aminoglycosides↗

Patellar tracking measurement in the normal knee.

Eleven fresh frozen cadaveric knee specimens were mounted in a knee kinematics test device, and normal patellar movements were evaluated with use of an external device for direct measurement of patellar movements. The effects of four different measurement conditions were assessed through alteration of one condition and determination of its effect on patellar kinematics with the use of six specimens. The four conditions included (a) change of the measuring axis from an axis parallel to the central axis of the femur (femoral axis) to one parallel to the central axis of the tibia (tibial axis), (b) rotation of the femoral axis internally 6 degrees, (c) change of the direction of the quadriceps force from parallel to the mechanical line of the lower extremity to a direction parallel to the femoral shaft, and (d) increase of the magnitude of the quadriceps force from 111 to 500 N. During knee flexion, the patella shifted laterally after a slight initial medial shift, tilted laterally from midflexion to 90 degrees, and gradually rotated medially. The patellar shift relative to the tibial axis appeared to be more medial than the shift measured relative to the femoral axis; the discrepancy was caused by the valgus position of the tibia relative to the femur. Changing the rotational angle of the femoral axis artificially changed the patellar position. Varying the direction of the quadriceps within the narrow range and increasing the quadriceps force did not affect patellar movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Differential distribution of mRNA for the alpha- and beta-subunits of chorionic gonadotrophin in the implantation stage blastocyst of the marmoset monkey.

We studied the expression of mRNA encoding the alpha- and beta-subunits of marmoset chorionic gonadotrophin (mCG) in implantation stage blastocysts and in a trophoblastic cell line derived from such blastocysts. In this investigation in situ hybridization was carried out using digoxygenin-labelled riboprobes to localize the subunit transcripts. The trophoblastic cell line, known to secrete bioactive mCG, was used as a positive control. Marmoset uterine embryos were cultured to hatched blastocysts and following growth on Matrigel or plastic were processed for in situ hybridization at developmental stages ranging from 13-15 days post-conception. In serial sections mCG-beta mRNA was detected mainly in polar trophoblast. The mRNA for mCG-alpha was expressed more uniformly in polar and mural trophoblast. Transcripts for the beta-subunit were not expressed, or present as weak signals, in the inner cell mass (ICM) and endoderm. However, low levels of mRNA for mCG-alpha were detected in the ICM and visceral endoderm. We have concluded that mRNA for mCG-beta was primarily localized to patches of syncytiotrophoblast at the embryonic pole and sparsely distributed in mural trophoblast, while the transcripts for mCG-alpha were distributed more uniformly in differentiating cytotrophoblast and syncytium, and at much lower levels in ICM and early endoderm.

Animals↗

Metabolic regulation and microangiopathy in a cohort of Japanese IDDM-patients.

In Caucasian patients with insulin-dependent diabetes mellitus (IDDM) proliferative diabetic retinopathy (PDR) and persistent proteinuria (PP) are associated, and major risk factors for development of microangiopathy have been identified. The aim of the present study was to evaluate whether these risk factors are also relevant and whether an association exists between the microangiopathic complications in Japanese IDDM-patients. A clinic-based cohort of 324 Japanese IDDM-patients was followed (a mean follow-up of 7 years). Annual examination for development of PDR and PP was performed. Fifty-eight patients developed PDR and 24 developed PP. Development of PDR was associated to high HbA1c-levels, i.e., the 4th quartile (RR 7.9, P < 0.0001), background retinopathy at admission (RR 9.9, P < 0.0001), high age at diabetes onset (RR 2.9, P < 0.0001) and female gender (RR 1.7, P < 0.05). Development of PP was associated to high HbA1c-levels (RR 2.8, P < 0.001) and background background retinopathy at admission (RR 7.9, P < 0.0001). The risk of developing PP was 9 times higher in patients developing PDR than in patients not developing PDR (P < 0.0001). The effect of metabolic control in our cohort was similar to that found in the DCCT and SDIS studies. In conclusion, development of PP is closely associated with PDR, also in Japanese IDDM-patients. The effect of metabolic control is the same as in Caucasian patients. Development of malignant angiopathy in IDDM-patients is not confined to Caucasian IDDM-patients, and the incidence rates are comparable to those found in Caucasian IDDM.

Adolescent↗

Role of epidermal growth factor (EGF) and its receptor in the development of the human placenta.

To elucidate the role of EGF in human placental development, effects of EGF on the proliferation and differentiation of trophoblasts were investigated. Explants of trophoblastic tissues obtained from 4-5 week or 6-12 week placentas were, respectively, cultured with or without EGF, in the presence or absence of triiodo-L-thyronine (T3) in a serum-free condition. The proliferative activity was examined by immunocytochemical staining with an antibody Ki-67, and the differentiated function was assessed by the ability to secrete human chorionic gonadotrophin (hCG) and human placental lactogen (hPL). In 4-5 week placentas, EGF and EGF receptor were localized in cytotrophoblast (C-cell), and EGF augmented the proliferation of C-cell without affecting the ability to secrete hCG and hPL. In contrast, in 6-12 week placentas, EGF and EGF receptor were localized in syncytiotrophoblast (S-cell), and EGF stimulated the secretion of hCG and hPL without affecting the proliferation of C-cell. In situ hybridization with c-erb B probe revealed that c-erb B mRNA is expressed in the S-cell after 6 weeks' gestation. Column chromatography of the serum-free media obtained by 5-day culture of early placental tissues resulted in the elution of immunoreactive EGF. The addition of T3 (10(-8) mol L(-1)) resulted in increased secretion of immunoreactive EGF by placental explants. These findings suggest that EGF acts as an autocrine factor in regulating early placental growth and function in synergy with thyroid hormone.

Epidermal Growth Factor↗

Interventional trial for colorectal cancer prevention in Osaka: an introduction to the protocol.

We established a protocol for an interventional randomized controlled trial for prevention of colorectal cancer by attaching special importance to feasibility. The subjects were patients with multiple colorectal tumors. Two regimens were formulated for prevention of colorectal cancer. One was dietary guidance alone (Regimen I), and the other was dietary guidance plus eating wheat bran biscuits (Regimen II). The main end points of the trial were examinations for recurrence of colorectal tumors after 2 and 4 years. The target number of patients was 200 in total, i.e. 100 for each group. During the 18 months from the beginning of recruiting of subjects (up to November 1994), 28 (97%) of the 29 patients recruited for Regimen I and 32 (97%) of the 33 patients recruited for Regimen II agreed to participate in the trial. The trial progressing well.

Aged↗

TOC-39, a novel parenteral broad-spectrum cephalosporin with excellent activity against methicillin-resistant Staphylococcus aureus.

TOC-39, a new parenteral cephalosporin, is a hydroxyimino-type cephem antibiotic with vinylthio-pyridyl moiety at the 3 position. TOC-39 was evaluated for antibacterial activity against various clinically isolated strains. TOC-39 had excellent activity, stronger than that of methicillin, oxacillin, the cephalosporins tested, imipenem, gentamicin, minocycline, tobramycin, ofloxacin, and ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) and had an MIC comparable to that of vancomycin (the MICs of TOC-39 and vancomycin for 90% of the strains tested were 3.13 and 1.56 micrograms/ml, respectively). Against Enterococcus faecalis strains, which are resistant to cephalosporins, TOC-39 was twice as active as ampicillin. Against methicillin-susceptible S. aureus, coagulase-negative Staphylococcus spp., and Streptococcus pneumoniae, TOC-39 was twice as active as or more active than cefotiam, ceftazidime, flomoxef, and cefpirome. Against Streptococcus pyogenes, TOC-39 was superior to cefotiam, ceftazidime, and flomoxef and was similar to cefpirome. In addition, the activity of TOC-39 was equal to or greater than that of cefotiam, ceftazidime, flomoxef, and cefpirome against Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii. In terms of bactericidal effect against MRSA, TOC-39 was superior to vancomycin. No mutant resistant to TOC-39 or vancomycin was obtained from susceptible MRSA strains. In murine systemic infection models, TOC-39 showed potent activity against S. aureus and E. coli. Against highly MRSA, the activity of TOC-39 was comparable to that of vancomycin.

Animals↗

[A case of patent urachus].

A case of congenital patent urachus is reported. A 12-month-old boy was referred to our outpatient clinic with the complaint of watery discharge from the navel. A cystography revealed the communication between the dome of the urinary bladder and the umbilicus. Excretion from the umbilicus of indigocarmine solution instilled into the urinary bladder was recognized. There were no complicated abnormalities in other organs. The patient underwent radical operation. Herein, we collected 164 cases of urachal disorders reported in Japan and reviewed the incidence, clinical symptoms, diagnosis and treatment. The classifications of the disease were briefly discussed.

Humans↗

Reaming technique of the femoral diaphysis in cementless total hip arthroplasty.

Distal fixation enhances initial torsional stability of cementless femoral components in primary and revision total hip arthroplasty. Surgical technique affects the quality of distal fixation, and too aggressive a technique can cause femoral fracture during insertion of the stem. Thirty-five adult human cadaveric femoral specimens were implanted with either a standard or long femoral stem. Control specimens were reamed 0.5 mm less than the diameter of the distal cylindrical portion of the stem and were broached line to line proximally. The proximal femur was removed from the remaining specimens to allow assessment of distal fixation. The controls outperformed the distal-only fixation groups in all testing modes, illustrating that proximal and distal fixation work in concert to resist torsional load. The average failure torque in underreamed specimens with only distal fixation was 23.6 Nm for standard length stem specimens and 41.3 Nm for long stem specimens, whereas the average failure torque for specimens with only distal fixation prepared by a line-to-line reaming technique was only 6 Nm. The estimated length of tight distal fit should be 10 to 40 mm to obtain sufficient initial torsional stability of the stem and still avoid intraoperative femoral fracture.

Adult↗

[Expression of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor messenger RNA in human endometrium and endometrial carcinoma].

To study the regulation of c-erbB, EFG and TGF-alpha in endometrium, we examined the expression of their mRNA in 5 normal endometrial and 5 endometrial carcinoma tissues by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR). By Northern blot with 10 micrograms of total RNA, c-erbB mRNA was not detected in the normal endometrium, but it was detected in 3 samples of endometrial carcinoma tissues. On the other hand RT-PCR identified c-erbB mRNA in all the normal endometrium and endometrial carcinoma tissues by amplifying cDNA derived from c-erbB mRNA. EGF mRNA was detected by RT-PCR in normal endometrium except in the early follicular phase. It was detected in all cases of endometrial carcinoma tissues. TGF-alpha mRNA was also detected in all the normal and endometrial carcinoma tissues by RT-PCR. Our study suggests that an autocrine/paracrine mechanism of EGF may regulate the endometrial cycle. Because some endometrial carcinoma tissues express the c-erbB mRNA much more than normal endometrium, disruption of the autocrine/paracrine mechanism may trigger subsequent endometrial carcinogenesis.

Adenocarcinoma↗

[Two cases of priapism cured by transcatheter embolization of internal pudendal arteries].

We report here two cases of priapism. One of these cases was suspected to be drug induced and high and low flow mixed type. The patient had taken the drugs, alpha-blocker for hypertension and dysuria by BPH for a long time. He was treated by a caveno-glandular shunt. After surgery, detumescence was obtained for some time, but erection appeared again soon. Transcatheter embolization of the internal pudendal arteries was then performed, and detumescence became permanent. The other case was an idiopathic and high flow type. Detumescence was achieved soon by transcatheter embolization of the internal pudendal arteries only, then he experienced morning erection imperfectly on the 9th day after this treatment. The management of priapism as reported to date is also reviewed.

Aged↗

Enhancement of platelet recovery in X-irradiated guinea pigs by romurtide, a synthetic muramyl dipeptide derivative.

The response of megakaryocytes and platelets to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in normal and irradiated guinea pigs. Romurtide was administered subcutaneously in a single dose or daily doses at levels of 1 to 100 micrograms/animal/day to normal animals to assess the dose response. Subsequently, dosage at 100 micrograms/animal/d for 8 consecutive days was initiated in separate groups of animals immediately after 1 Gy total body x-irradiation. In normal animals, a significant dose-dependent increase in the platelet count was noted, and a prolonged thrombocytopoiesis was detectable from 7 through 15 days after the initiation of romurtide administered for 8 days at a dose of 100 micrograms/animal/d. A significant increase in the white blood cell (WBC) count was also observed during days 1 through 11 after beginning romurtide treatment. In the irradiated animals, the treatment with romurtide increased platelet counts during the recovery phase of thrombocytopenia, thus apparently decreasing the time required for recovery to a normal platelet level. Before the rapid recovery of platelet counts by romurtide treatment, a marked increase in the number of megakaryocytes was noted as early as 7 days after irradiation. This increase was accompanied by an accelerated shift of the size distribution of megakaryocytes toward larger size class. Thus, the mean megakaryocyte size was significantly greater in guinea pigs receiving romurtide than in controls. Preceding the increase in the number of megakaryocytes, the serum interleukin-6 levels were found to be approximately 5 times greater than those in control animals. Treatment with romurtide diminished the WBC count nadir, resulting in significantly higher WBC count levels than in controls. Elevation of the plasma fibrinogen level was observed in the treated animals, and normalized gradually after discontinuation of romurtide treatment. These results indicate a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

Acetylmuramyl-Alanyl-Isoglutamine↗

Development of proliferative retinopathy in Japanese patients with IDDM: Tokyo Women's Medical College Epidemiologic Study.

We studied the development of proliferative diabetic retinopathy (PDR) in Japanese insulin-dependent diabetes mellitus (IDDM). Subjects were 373 patients who were diagnosed as IDDM between 1951 and 1984, before the age of 30 years, and had no PDR at the first visit to the Diabetes Center. Development of PDR was analyzed by Kaplan-Meier's life-table method in relation to the duration of IDDM. The cumulative incidence of PDR was 20% at 15 years of duration of IDDM, 40% at 19 years, and 70% at 29 years. Female patients (n = 233) developed PDR significantly faster than males (n = 140) (P < 0.002). In both sexes, patients with onset of IDDM at 0-8 years showed significantly slower development than patients with the onset at 9-17 (P < 0.0001) and 18-29 years (P < 0.001). Impact of femaleness on the development was the greatest in patients with age at onset of IDDM at 9-17 years (P < 0.005). Analysis according to the calendar year at onset of IDDM and diabetes duration at the first visit to the Diabetes Center did not show any significant influence on the development of PDR. In conclusion, sex and age at onset of IDDM may be associated with increased risk for the development of PDR in relation to the duration of diabetes in Japanese IDDM.

Adolescent↗

Ejaculation obtained by intracavernous papaverine in a cervical spinal cord injury patient resulting in pregnancy and childbirth. Case report.

A 28 year old male sustained a cervical spinal cord injury (C5, complete) from a traffic accident and was impotent. He started intracavernous injection therapy, by his partner, of papaverine hydrochloride for impotence, restoring ejaculation. His partner had a successful pregnancy after normal sexual intercourse, and delivered a mature female child weighing 3330 g. To our knowledge this is a rare case of a patient with a complete spinal cord injury fathering a child by the above technique.

Adult↗