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Biomedical subjects

T Otani

Publications and source records attributed to T Otani.

At least 127 records · Page 7Linked to original sources

Existence of early-onset NIDDM Japanese demonstrating severe diabetic complications.

OBJECTIVE: To identify the clinical characteristics of early-onset NIDDM patients with severe diabetic complications. RESEARCH DESIGN AND METHODS: The clinical cases of a large number of diabetic patients who visited a diabetes center within the period 1970-1990 were reviewed. Of a total of 16,842 diabetic patients, 1,065 (6.3%) had early-onset NIDDM (diabetes diagnosed before 30 years of age). These 1,065 patients were divided into two groups, those who developed proliferative retinopathy before the age of 35 (n = 135) and those who did not (n = 930). Development of proliferative retinopathy, nephropathy, renal failure, blindness, and atherosclerotic vascular disease were compared between the two groups. RESULTS: The subgroup of 135 patients was characterized by poor glycemic control, often requiring insulin therapy and a higher familial prevalence of diabetes, and contained a greater proportion of women than the subgroup of 930 patients. Of the 135 patients, 99 (67%) developed proliferative retinopathy before the first visit. The 135 patients developed severe progressive complications in contrast to the 930 patients. A total of 81 patients (60%) developed diabetic nephropathy at a mean age of 31 years, 31 (23%) developed renal failure requiring dialysis at a mean age of 35 years, 32 (24%) became blind at a mean age of 32 years, and 14 (10%) developed atherosclerotic vascular disease at a mean age of 36 years. CONCLUSIONS: Some Japanese early-onset NIDDM patients develop severe diabetic complications in their youth. Most of them had no symptoms nor regular treatment regarding diabetes until they were noticed to have developed severe diabetic complications. Although the relevant prevalence and the pathogenetic mechanism underlying the rapid onset of the complications remain to be determined, prolonged inadequate treatment of and familial predisposition to diabetes may be contributing factors. Careful diabetes care in the twenties, not only for IDDM but also for NIDDM patients, is warranted.

Adult↗

A new anthracycline antibiotic, IT-62-B, converts the morphology of ras-transformed cells back to normal: taxonomy, fermentation, isolation, structure elucidation and biological characterization.

A new antibiotic, IT-62-B was isolated from the culture broth of Streptomyces sp. IT-62 by extraction with acetone and then with ethyl acetate, followed by conventional column chromatography using silica gel, Sephadex LH-20 and silica ODS. Its structure (C39H47NO15, MW 769) was determined by 1H, 13C NMR, MS, IR and UV spectrometric techniques to be a new member of the baumycin-group anthracyclines. It showed moderate activity against Gram-positive bacteria and had antitumor activity against various tumor cell lines. Further, antibiotic IT-62-B converted the morphology of ras-transformed NIH3T3 cells and T-cells back to normal at concentrations inhibiting cell growth by 30% or more.

Animals↗

Inhibition of anchorage-independent growth of tumor cells by IT-62-B, a new anthracycline.

IT-62-B, a new anthracycline isolated from fermentation broths of Streptomyces sp. IT-62, reversed certain tumor cell phenotypes in vitro including some of human origin. The observed normal phenotypes were anchorage dependence of cell growth, flattened cell morphology and restoration of actin stress fibers. The extent of the anchorage dependence of cell growth induced by IT-62-B was generally greater than that by doxorubicin or pirarubicin. The cell-flattening effect of IT-62-B on cells of T24 (human bladder), but not on C-33A (human cervix), accompanied inhibition of fos gene expression. T24 cells, once flattened by IT-62-B, retained their flat morphology even in drug-free, fresh medium and eventually died in several days. IT-62-B, unlike doxorubicin, only slightly inhibited the topoisomerase II reaction in vitro and DNA synthesis in isolated cell nuclei.

Actins↗

[A case of uretero-aortic fistula].

We report a case of uretero-aortic fistula. A 69-year-old man with rectal cancer underwent a pelvic exenteration and a double--barreled cutaneous ureterostomy in the right lower abdomen. Stomal stenosis necessitated continuous indwelling of double J stents in the two ureters. Two years postoperatively, massive bleeding occurred during exchange of double J catheters. Occlusive ureterogram demonstrated a uretero-aortic fistula at the crosspoint between the left ureter and the aorta. The surgical repair consisted of closure of the aortic fistula, ligation of the left ureter proximal to the fistula and percutaneous left nephrostomy.

Aged↗

Acquired cytotoxic activity of CD8+ HIV-1IIIB carrier immature T cell clones specific to CD4+CD8+ (parental) human T cell clones and normal thymocytes.

By infecting human leukemia cell lines in vitro with HIV-1IIIB' a number of HIV-1 carrier clones were generated. Among them, 5 of 13 CD8+ HIV-1 carrier T cell clones were shown to acquire a rapid cytotoxic activity (within 1 hour) specific to TdT+CD4+CD8+ immature T cells including normal thymocytes. This novel cytotoxic reaction, without requiring virus infection and indicating a rapid T cell precursor elimination during active lymphopoiesis, suggests a mechanism responsible for mature CD4+ T cell depletion in HIV-1 infected individuals.

Antigens, CD↗

Radiographic changes in the patella after total knee arthroplasty without resurfacing the patella. Comparison of osteoarthrosis and rheumatoid arthritis.

The necessity of patellar resurfacing has aroused considerable controversy. Between 1986 and 1996, we have routinely performed 208 primary total knee arthroplasties (TKAs) without resurfacing the patella. However, we have occasionally observed gradual postoperative patellar deterioration which caused peripatellar pain. This study observed the radiographic changes in the patella after TKA without resurfacing the patella to assess the effect of the changes on the clinical results. Sixty out of 208 TKAs were assessed in this study. The original diagnoses were osteoarthrosis (OA) in 17 joints and rheumatoid arthritis (RA) in 43 joints. Fourteen patients (23.3%) complained of postoperative peripatellar pain: 2 of the 17 patients with OA (11.8%) and 12 of the 43 with RA (27.9%). Lateral tilt of the patella slightly decreased with time, but lateral shift increased slightly. Patellar length and width increased throughout the follow-up period. The thickness of the patella, especially in the RA cases, significantly (Mann-Whitney, p < 0.05) decreased with time. According to these radiographic findings, as time passed the thickness of the patella decreased, its length and width increased, and the patella as a whole became flattened. On examining the effect of this flattening on postoperative pain, it was found that about 70% of those patients whose patellar thickness had decreased to 80% or less complained of peripatellar pain. In the case of the OA patients, however, there was no statistically significant correlation between patellar flattening and pain. It is concluded that patellar resurfacing should be considered for the patient with rheumatoid arthritis. Because patellar flattening did not develop in many patients with OA and few of them complained of peripatellar pain, patellar resurfacing should not be performed routinely.

Activities of Daily Living↗

Oral application of romurtide, a synthetic muramyl dipeptide derivative, stimulates nonspecific resistance to microbial infections and hematopoiesis in mice.

Romurtide given orally enhanced the nonspecific resistance against microbial infections and hematopoiesis up to the levels achieved by subcutaneous (s.c.) injection of the compound in mice. Oral romurtide conferred protection and, in consequence, enhanced therapeutic efficacy of antibiotics against systemic infections in mice. The leukocytosis followed by the elevations of colony stimulating activity in serum and the colony forming unit of granulocyte-macrophage (c.f.u.-GM) in femoral bone marrow was observed as successive event in mice treated orally with romurtide. To obtain a comparable potency to s.c. injection of the compound at a dose of 0.1 mg per mouse, oral application required doses of 3 and 10 mg per mouse for stimulating the nonspecific resistance to infection and hematopoiesis, respectively.

Acetylmuramyl-Alanyl-Isoglutamine↗

Romurtide, a synthetic muramyl dipeptide derivative, accelerates peripheral platelet recovery in nonhuman primate chemotherapy model.

We investigated the therapeutic effects of romurtide, a synthetic muramyl dipeptide derivative, on experimental thrombocytopenia induced by carboplatin in cynomolgus monkeys. A prolonged thrombocytopenia due to a severe myelosuppression was induced by carboplatin. Romurtide given subcutaneously elevated significantly the peripheral platelet counts during both early initiation and later recovery phase of thrombocytopenia, thereby shortening the time required for recovery to a normal platelet level and the duration of thrombocytopenia. An oral administration of romurtide was also found to have a similar therapeutic efficacy to subcutaneous administration. These results demonstrated a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

Acetylmuramyl-Alanyl-Isoglutamine↗

Effect of medial displacement of the tibial tubercle on patellar position after rotational malposition of the femoral component in total knee arthroplasty.

A large Q angle induced by technical error such as an internally rotated femoral component causes patellar failure after total knee arthroplasty. The effect of medial displacement of the tibial tubercle to decrease the Q angle for patellar tracking was studied by evaluating the patellar position relative to the patellar groove on the femoral component in cadaver specimens. A 5 degrees internally rotated femoral component caused the patella to shift medially about 5 mm, and also caused the tibia to rotate internally about 3 degrees at full extension. With a 5 degrees externally rotated femoral component, normal patellar tracking occurred. The distance of medial displacement was determined so that the patellar tendon was parallel to the longitudinal axis of the tibia at full extension. This allowed the quadriceps tendon, the patella, and the patellar tendon to form a straight line. The average distance of medial transposition of the tibial tubercle was 9.32 mm. Medialization of the tibial tubercle caused the patella to shift about 2 mm medially from the patellar groove. The transfer also caused an external rotation of the tibia (2 degrees-5 degrees). Medial transfer of the tibial tubercle changes patellar kinematics and corrects the tendency toward lateral patellar dislocation caused by internally rotating the femoral component; however, it also creates minor patellar and tibial kinematic changes that may have a clinical effect.

Biomechanical Phenomena↗

[Photodynamic therapy for gastric cancer].

In this article, we first present our clinical data on PDT for the treatment of gastric cancer and make a comparison between a continuous wave laser and a pulsed laser. The reasons for PDT failure in certain cases are also discussed. In the fifteen years from 1981 to 1995, we have treated a total of 76 gastric cancer lesions (73 cases), which was consist of 69 early gastric cancer lesions (66 cases) and seven advanced gastric cancer lesions (seven cases) by PDT. From 1981 to 1990, we used an argon dye laser (ADL, Models 171-08 and 375-03, Spectra-Physics, Mountain View, Calif., US) as an excitation light source for PDT with HpD (Photofrin I), DHE (Photofrin II) or PHE (freeze-dried Photofrin II). From analysis of the results in terms of the depth of cancer invasion in these 44 lesions (41 cases), the rate of cure for mucosal carcinomas was 57% (13/23), that of submucosal carcinomas was 53% (10/19), and that of carcinomas invading more than the muscularis propria was 0% (0/2). These data can be interpreted to indicate that the ADL laser beam could not penetrate and supply sufficient energy to activate HpD not only in the submoucosal layer but also in the mucosal layer. In 1990, therefore, we investigated an excimer dye laser (EDL, Hamamatsu Photonics, Hamamatsu, Japan), because its pulsed beam with extremely high peak power was expected to be more efficient at exciting HpD than continuous wave lasers such as ADL and high frequency pulsed lasers such as cooper vapor dye laser (Cu VDL). From 1990 to 1995, twenty-seven early gastric cancer lesions (27 cases) and five advanced gastric cancer lesions (five cases) were treated by PDT with EDL and PHE. Of these 32 lesions, the rate of cure for mucosal carcinomas was 100% (15/15), that of submucosal carcinomas was 75% (9/12), and that of carcinomas invading more than the muscularis propria was 20% (1/5). For the purpose of determining how much energy was required for a complete cure in early gastric cancer, and to compare the efficacy of ADL and EDL, the relation between the response (cure or no cure) and irradiated energy intensity (dose: J/cm 2) was evaluated by the depth of cancer invasion and kind of laser used in PDT. A smaller EDL dose was more effective than ADL in terms of photodynamic action.

Adenocarcinoma↗

[Serum prostate specific antigen for the early detection of prostate cancer in outpatients of internal medicine].

Screening was performed on 102 patients aged 60 years or older who visited the Outpatient Department of Internal Medicine in Tane General Hospital between June 1994 and May 1995. Of those screened, 36 patients (35.3%) had elevated prostate specific antigen (PSA) values, and 20 of them visited the Urological Department, and underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for further screening. Of the 16 patients who underwent ultrasound guided biopsies of the prostate, 7 patients were found to have prostate cancer. Therefore, the cancer detection rate was 6.9%, which was about 4 times higher than that of mass-screening examinations previously reported in the Japanese literature. These findings suggested that the screening using PSA in outpatients of Internal Medicine may be useful for the early detection of prostate cancer.

Aged↗

[Choroidal vascular lesions in serous retinal detachment viewed with indocyanine green angiography].

In serous retinal detachment due to damaged retinal pigment epithelium (RPE), fluorescein angiography shows dye leakage into the subretinal space from the choroid. We performed indocyanine green (ICG) angiography in 110 eyes with serous retinal detachment comprising 71 eyes with central serous chorioretinopathy (CSC), 19 with bullous retinal detachment, 18 with Harada's disease, and 2 with toxemia of pregnancy. Choroidal tissue staining was present around the site of subretinal leakage in late-phase ICG angiograms from 63 eyes with CSC and 18 with bullous retinal detachment. ICG angiography also showed leakage from choroidal vessels in 16 eyes with Harada's disease and 2 with toxemia of pregnancy. As a common feature, ICG angiography showed choroidal vascular hyperpermeability in various types of serous retinal detachment. Choroidal circulation was delayed in Harada's disease and toxemia of pregnancy. Choroidal hypoperfusion and hyperpermeability of choroidal vessels probably contribute to the damage of RPE, and choroidal vascular hyperpermeability probably provides fluid pressure to move fluid into the subretinal space from the choroid.

Adult↗

Preliminary X-ray diffraction study of a new crystal form of C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C-1027 from Streptomyces globisporus.

A new crystal form of C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C-1027 isolated from Streptomyces globisporus was obtained by the vapor-diffusion procedure using lithium sulfate as a precipitant. In the present crystallization, it is noteworthy that large-sized single crystals successfully grew from very small droplets (less than 1.01 micro l). The present crystals belong to the trigonal system, space group P3(1)21 or P3(2)21 with cell dimensions of a = b = 62.6 and c = 54.2 A. Assuming that the asymmetric unit contains one molecule, the V(m) value is calculated as 2.9 A(3) Da(-1). A total of 3654 independent reflections from two native crystals was obtained up to 2.5 A resolution with synchrotron radiation, the merging R factor being 0.097.

Journal Article↗

Effects of the DNA-damaging enediyne C-1027 on intracellular SV40 and genomic DNA in green monkey kidney BSC-1 cells.

This study describes the selective ability of C-1027 to induce limited double-strand damage in a viral DNA target. The effect of the cellular environment on C-1027 activity was examined by assaying the extent, as well as the specificity, of damage to simian virus 40 (SV40) DNA in lytically infected mammalian BSC-1 cells and in purified SV40 DNA preparations. C-1027 damage to intracellular SV40 DNA was quantitated by topological forms conversion analysis. A gradual decrease in intracellular supercoiled form I accompanied by an increase in form III was observed with C-1027 concentrations from 2 to 100 nM, with a 50% reduction in form I observed at 50 nM. Damage to purified SV40 DNA also was most pronounced between 10 and 100 nM C-1027. When concentrations were expressed as r values (drug/DNA molar ratio), the amount of C-1027 necessary to effect a 50% reduction in form I was lower for intracellular (r = 0.002) than for purified SV40 DNA (r = 0.0035). Double-strand damage was more likely to occur with C-1027 treatment of intracellular compared to purified SV40 DNA. However, with both purified and intracellular DNA, restriction enzyme digestion analysis revealed double-strand damage at a number of specific sites throughout the genome, particularly within the early region of the SV40 genome (e.g., within the coding sequence for large T-antigen). No significant damage was observed in either the origin (ORI) or the termination (TER) regions of SV40 replication. The extent of C-1027 damage to uninfected BSC-1 cell DNA was also quantitated using pulsed-field gel electrophoresis. At 0.1 nM (r = 2.8 x 10(-5), where incorporation of [3H]thymidine was reduced by 80%, 600 rad equiv of damage was detected in uninfected BSC-1 cells. At C-1027 r values from 1 x 10(-4) to 40 x 10(-4), double-strand breaks were from 80- to 40-fold more frequent in SV40 than in BSC-1 cell genomic DNA. By contrast, 50-fold more drug was necessary to inhibit intracellular SV40 DNA accumulation compared to [3H]thymidine incorporation into uninfected BSC-1 cells. Thus, SV40 DNA synthesis appeared to be less sensitive to C-1027-induced lesions than replication in uninfected BSC-1 cells.

Aminoglycosides↗