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Biomedical subjects

T Otani

Publications and source records attributed to T Otani.

At least 109 records · Page 6Linked to original sources

Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis.

The pathological activation of zymogens within the pancreatic acinar cell plays a role in acute pancreatitis. To identify the processing site where activation occurs, antibodies to the trypsinogen activation peptide (TAP) were used in immunofluorescence studies using frozen sections from rat pancreas. Saline controls or animals receiving caerulein in amounts producing physiological levels of pancreatic stimulation demonstrated little or no TAP immunoreactivity. However, after caerulein hyperstimulation (5 micrograms. kg-1. h-1) for 30 min and the induction of pancreatitis, TAP immunoreactivity appeared in a vesicular, supranuclear compartment that demonstrated no overlap with zymogen granules. The number of vesicles and their size increased with time. After 60 min of hyperstimulation with caerulein, most of the TAP reactivity was localized within vacuoles >/=1 micrometer that demonstrated immunoreactivity for the granule membrane protein GRAMP-92, a marker for lysosomes and recycling endosomes. Pretreatment with the protease inhibitor FUT-175 blocked the appearance of TAP after hyperstimulation. These studies provide evidence that caerulein hyperstimulation stimulates trypsinogen processing to trypsin in distinct acinar cell compartments in a time-dependent manner.

Acute Disease↗

A randomized study of short-versus long-term intravesical epirubicin instillation for superficial bladder cancer. Nagoya University Urological Oncology Group.

OBJECTIVE: A prospective randomized study was undertaken to determine whether prophylactic maintenance instillation of epirubicin following induction treatment is beneficial in patients with superficial bladder cancer. PATIENTS AND METHODS: One hundred and forty-eight patients with resectable superficial bladder cancer (Ta-1, single, multiple, primary or recurrent with, however, no recurrence during the last year) were enrolled in this study. In both arms, epirubicin (40 mg/ml in normal saline) was administered six times within 4 weeks after a transurethral resection of the bladder tumor(s). In arm A, the patients received 11 additional monthly instillations of epirubicin. RESULTS: Of the 148 patients, 138 (93.2%) were eligible and followed for an average of 29.6 months. 93 (67.4%) had a solitary tumor. No significant difference in the recurrence-free curve was observed between the two arms (p = 0.62). The recurrence rate per year was 0.16 in arm A and 0.17 in arm B. Toxicity included vesical irritability in 10 (7.2%) and hematuria in 1 patient. No significant difference in the frequency or degree of toxicity was observed between the two arms. CONCLUSION: These data suggest that maintenance instillation of epirubicin does not reduce superficial bladder cancer recurrence.

Administration, Intravesical↗

Effect of increased physical activity on bone mineral density in postmenopausal osteoporotic women.

The effect of increased physical activity on bone mineral density (BMD) of the lumbar vertebrae was examined in postmenopausal osteoporotic women. Thirty-five postmenopausal women, aged 53-77 years, whose BMD in the lumbar vertebrae (L2-L4) measured by dual energy x-ray absorptiometry (Norland XR-26) was below (> 30%) the young adult mean, were divided into two groups: a control group of 20 women and an exercise group of 15 women. The physical exercise consisted of daily outdoor walking and gymnastic training performed for 12 months. During the study period, all subjects were treated with calcium lactate, 2.0 g, and 1 alpha-hydroxyvitamin D3, 1 microgram, daily. Initial L2-L4 BMD was 0.611 +/- 0.045 (mean +/- SEM) g/cm2 in the control group and 0.606 +/- 0.066 g/cm2 in the exercise group (NS). In the control group, the BMD changes were -0.54 +/- 0.58% (mean +/- SEM) at 6 months and +1.00 +/- 1.29% at 12 months, compared to the baseline (P = 0.3424, by oneway ANOVA). In the exercise group, however, the changes were +1.78 +/- 0.90% and +4.48 +/- 0.93%, respectively (P = 0.0305, by two-way ANOVA). These data suggest that increased physical activity consisting of daily outdoor walking and gymnastic training can be useful in increasing lumbar BMD in postmenopausal osteoporotic women on calcium and vitamin D3 supplementation.

Aged↗

High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients. Risk analysis.

OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30 years) can develop diabetic end-stage renal failure (ESRF) in their thirties, this study was performed to elucidate the incidence and determinants for the development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence of diabetic nephropathy and its relationship to baseline characteristics and long-term metabolic control were determined in 426 early-onset Japanese NIDDM patients who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41 developed diabetic nephropathy manifested by persistent proteinuria (incidence rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean HbA1c (measured by a high-performance chromatography method that is standardized and comparable to the one used in the Diabetes Control and Complications Trial study) was around 7% or less, few developed nephropathy. The incidence of nephropathy increased with increasing mean HbA1c level in a dose-dependent manner (chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control. CONCLUSIONS: The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.

Adult↗

[Vesicoureteral reflux and urinary incontinence in myelodysplastic patients: a comparison between those who had anti-reflux surgery alone and those who were treated by anti-reflux surgery combined with bladder augmentation with or without sling operation].

BACKGROUND: Vesicoureteral reflux and urinary incontinence are frequently observed among myelodysplastic patients. Since the conservative therapy is not always effective to improve these pathologies, surgical intervention is necessary for some of the patients. METHODS: Thirty-eight myelodysplastic patients were divided into 2 groups: Group A comprised 17 patients who had been operated by anti-reflux surgery (crossover method) alone and Group B 21 patients who had undergone anti-reflux surgery (Orikasa's method) and augmentation enterocystoplasty with or without sling operation. Cessation rate of reflux, bladder capacity, bladder compliance and operative complications were analyzed in the 2 groups. A questionnaire was sent to the patient asking to answer frequency of clean intermittent catheterization (CIC), severity of urinary incontinence, satisfaction rate for operation and so on. Mean followed-up periods were 11.7 (5.3-13.6) years for Group A and 3.7 (0.6-6.9) years for Group B, respectively. RESULTS: Reflux was successfully eradicated in 19 of 24 ureters (79%) of Group A and in 25 of 29 ureters (86%) of Group B, which was not significantly different. In Group A, bladder capacity and compliance slightly improved. The latter, however, remained less than 10 ml/cmH2 O. Bladder capacity and compliance of Group B increased more than twice the original value with statistical significance. Operative complication in Group A was ureteral obstruction in 1 patient, which eventually necessitated peritoneal dialysis. In Group B revision of ventriculoperitoneal shunt was necessary in 4 patients, incomplete ileus was conservatively treated in 3, and a bladder stone was formed in 1. The patients assessed that frequency of pyelonephritis was less in Group B compared to Group A. Other subjective parameters, however, such as frequency of CIC, severity of urinary incontinence, postoperative changes in the amount of urinary incontinence, and satisfaction rate for operation, were not different between the 2 groups. COMMENTS: Though operation-related complications occurred more frequently in those of Group B, these patients enjoyed significant improvement in bladder capacity and bladder compliance. We conclude when the conservative therapy fails to cure and improve vesicoureteral reflux and urinary incontinence, surgical interventions including anti-reflux surgery and augmentation cystoplasty with or without sling operation are recommended as a treatment option.

Adolescent↗

MJ347-81F4 A & B, novel antibiotics from Amycolatopsis sp.: taxonomic characteristics, fermentation, and antimicrobial activity.

Strain MJ347-81F4 has been found to produce two new cyclic thiazolyl peptide antibiotics, components A and B. Taxonomic studies including morphological and physiological characteristics and chemical analysis of whole cells of the producing strain revealed this microorganism to belong to genus Amycolatopsis, and so we designated the strain Amycolatopsis sp. MJ347-81F4. After 10 to 12 days of fermentation, most of the antibacterial activity was present mainly in the mycelial cake and reached its maximum level. In comparison with reference compounds, A as the major component showed excellent in vitro activity against gram-positive bacteria including highly methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis with MICs in the range of concentration of 0.006 to to approximately 0.1 microg/ml. The results on the antimicrobial activity against thiazolyl peptide-resistant mutants of Bacillus subtilis NRRL B-558 indicated that the possible molecular target of MJ347-81F4 component A might be the 50S subunits of the ribosome, the inactivation of which would inhibit protein synthesis.

Anti-Bacterial Agents↗

[Circadian rhythm of parasympathetic nervous function in asthmatic children].

We examined the circadian rhythm of parasympathetic nervous function in asthmatic children. The subjects were 80 patients with asthma (mild 54 patients, moderate 15 patients and severe 11 patients) and 90 individuals in healthy children. All the patients underwent 24-electrocardiography in normal condition. We measured the %RR50 for hour and analyzed the rhythm using the single cosine fitting method, comparing the values of the Amplitude, the MESOR and the Acrophase in terms of the therapy and also the severity of asthma. Circadian rhythm disappeared in 9 of the 80 asthmatic children and was observed in all the individuals in the healthy children. The value of MESOR was lower in the asthmatic children than in the healthy children. There was no significant difference between the different severity or therapies in each group. In some asthmatic children, the circadian rhythm of parasympathetic nervous function disappeared, the parasympathetic nervous function was low in remission. It is suggested that the disorder of biologic rhythm is related to the pathogenesis of asthma.

Asthma↗

[A cooperative study on concomitant with low-dose divided administration of cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study Group].

For patients with unresectable gastric cancer registered between July 1994 and September 1995, the following dosage regimen was examined: a drip infusion of cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300 mg/m2/day for 21 days. The whole cycle was repeated again after 2-week withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect to histological classification, there was no difference in appearance of the effect between the moderately differentiated type at 62.5% and the low-differentiated type at 42.9%. The cases which became resectable after the administration included those in which the tumor disappeared completely in the resected specimens. As adverse reactions encountered in the cases above Grade 3, anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10, 5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin, leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively, while renal or liver dysfunction did not occur. This dosage regimen was considered useful for unresectable advanced gastric cancer, although myelosuppression should be watched carefully.

Adult↗

Romurtide, a synthetic muramyl dipeptide derivative, promotes megakaryocytopoiesis through stimulation of cytokine production in nonhuman primates with myelosuppression.

The response of megakaryocytes and cytokines to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in monkeys with myelosuppression by carboplatin-treatment. Romurtide increased the number of megakaryocytes and promoted the shift of megakaryocytes towards high ploidy class indicative of the promotion of the proliferation and maturation of megakaryocytes. The serum levels of interleukin-6, stem cell factor, and erythropoietin elevated significantly before the enhanced response of megakaryocytes induced by romurtide was observed. Romurtide also enhanced production of colony-stimulating factors (CSFs), such as granulocyte-CSF, macrophage-CSF, and granulocyte-macrophage CSF by monkey mononuclear cells. The stimulating effect of romurtide on the production of those cytokines and CSFs is likely to be responsible for the subsequent promotion of the proliferation and maturation of marrow megakaryocytes.

Acetylmuramyl-Alanyl-Isoglutamine↗

In vitro study using leukemia cell line panel to demonstrate rapid thymic T cell death due to contact with HIV-1 carrier cell clones.

A rapid (within 1 h) and profound cytotoxic cell death of immature TdT+CD4+CD8+ and/or TdT+CD4+ thymic T cell type leukemia cell lines, and of normal thymocyte populations rich in TdT+CD4+CD8+ cells was induced by contact with some human immunodeficiency virus type-1 (HIV-1) carrier T cell clones. This cytotoxic reaction, without requiring a complete viral replication cycle in the thymic T cells, did not occur in any mature CD4+CD8+ and/or CD4+ T cells which are otherwise permissive for virus infection. Although it was not an antigen-specific cytotoxic reaction, the rapid and profound thymic T cell destruction was shown, at the individual clonal level, to be triggered specifically by the binding of CD4 molecules on thymic T cells with gp120/gp160 on HIV-1 carrier clones. The present study suggesting direct elimination of immature T cells by contact with some HIV-1-infected T cells, may provide a novel insight into the mechanism responsible for the mature CD4+ T cell depletion in HIV-1 infection.

Antigens, CD↗

Distribution of a synthetic protease inhibitor in rat pancreatic acini after supramaximal secretagogue stimulation.

Protease inhibitors may have a beneficial effect in acute pancreatitis. The effects of E3123, a new low molecular weight protease inhibitor, on the ultrastructure of isolated pancreatic acini were examined using transmission electron microscopy. Acini supramaximally stimulated with cerulein (10(-8) M) formed large cytoplasmic vacuoles similar to those generated in the cerulein-induced in vivo model of pancreatitis. Pretreatment of isolated acini with E3123 significantly reduced the size and number of vacuoles associated with cerulein treatment. The distribution of 3H-E3123 in acinar cells was examined using a pulse-chase protocol and electron microscopic autoradiography. Cellular levels of 3H-E3123 increased about 30-fold in acinar cells treated with cerulein (10(-8) M) compared to unstimulated controls. In cerulein-treated acini examined after a 5-min chase, 47.4% of the autoradiographic grains were associated with the rough endoplasmic reticulum and 13.2% were associated with zymogen granules. After 30 min of incubation, the grains associated with the endoplasmic reticulum decreased to 18.5% but increased to 26.3% over zymogen granules. Thus, E3123 is taken up by the acinar cell and follows a cellular itinerary similar to that of newly synthesized secretory proteins. One potential conclusion from these studies is that the ability of E3123 to reduce the formation of vacuoles in supra-maximally stimulated acini may be due to its inhibition of proteases within the secretory pathway.

Amylases↗

Interferon-alpha and -gamma differentially reduce rapid immature T-cell death by contact with HIV-1 carrier cell clones in vitro.

The non-antigen specific rapid cytotoxic (CT) death of immature TdT+CD4+CD8+ T cells due to contact with HIV-1 carrier T-cell clones we have found recently is a novel phenomenon. The effects of interferons (IFN) on this CT reaction were studied in vitro. Treatment of the HIV-1 carrier clones, referred to as "effectors," with IFN-alpha but not IFN-gamma, or of the susceptible immature TdT+CD4+CD8+ T cells, referred to as "targets," with IFN-gamma but not IFN-alpha, for 24 hr prior to CT testing was found to reduce the CT reaction. Simultaneously, a down-regulated CD8 expression and an up-regulated antigen expression of both major histocompatibility antigen complex class I (MHC-I) and HIV-1 gp120/gp160 in the IFN-alpha treated effector (gp120+CD8+ HPB-ALL/HIV), and/or simultaneously up-regulated antigen expression of both CD8 and MHC-I in the IFN-gamma treated target (CD4+CD8+ HPB-ALL) were found to be associated with reduced CT reaction. However, altered antigen expression in the IFN-gamma treated effectors or IFN-alpha treated targets did not affect the ultimate degree of CT reaction. This study thus suggests a possible therapeutic efficacy of IFN by reducing the direct elimination of the T-cell precursors in HIV-1 infection.

Anti-HIV Agents↗

Ultrasonic wave propagation in bovine cancellous bone.

The acoustic properties of bovine cancellous (spongy) bone have been experimentally studied in vitro by the pulse transmission technique. Fast and slow longitudinal waves have been clearly identified when the acoustic wave propagates parallel to the direction of the trabeculae. Propagation speeds and attenuation of the fast and slow waves were observed in the frequency range of 0.5-5 MHz. Theoretical discussion is given to Biot's theory and the propagation of sound waves in fluid-saturated porous media.

Animals↗

Early gamma interferon responses in lethal and nonlethal murine blood-stage malaria.

This study was undertaken to explore early differences in cytokine production during nonlethal and lethal blood-stage murine malaria infections. Cytokine analysis of spleens during these infections showed that the principal difference between two nonlethal and two lethal Plasmodium species was the production of gamma interferon 24 h after infection with nonlethal parasites. In contrast, no increases in interleukin-4 production were observed in the first 24 h and tumor necrosis factor alpha levels increased equally in both nonlethal and lethal infections. During the later phase of infection with nonlethal parasites, both gamma interferon and interleukin-4 levels increased markedly a few days before parasite clearance. Early increases in gamma interferon production in nonlethal infections of Plasmodium yoelii and Plasmodium chabaudi were dose related and increased significantly with the size of the inoculum. Studies with the nonlethal P. yoelii suggest that the early gamma interferon response is mediated by T cells and natural killer cells, as it was reduced in athymic mice and in mice depleted of their natural killer cells by treatment with specific antiserum. Infecting mice with increasing numbers of lethal P. yoelii and Plasmodium berghei parasites did not increase the amount of gamma interferon, interleukin-4, and tumor necrosis factor alpha produced in a dose-dependent fashion. We conclude that one consequence of the early production of gamma interferon and tumor necrosis factor-alpha, particularly after nonlethal P. yoelii infection, may be to adjust the balance of T-helper cell subset activation, and probably that of other immune responses, so as to enhance the mechanisms that are essential for elimination of the parasites. This suggests that a successful vaccine should contain antigens capable of inducing such responses.

Animals↗

Increased serum concentrations of type IV collagen and laminin associated with granulosa cell tumour of the ovary.

A 65 year old woman presented with an ovarian mass. Ultrasonography and computed tomography findings, and an increased serum oestrogen concentration were suggestive of an oestrogen producing ovarian tumour. The tumour was removed surgically and weighed 460 g. The pathological diagnosis was adult-type granulosa cell tumour. Strong immunohistochemical staining specific for type IV collagen and laminin was observed, and these components were localised to the pericellular region of the granulosa cells. The serum concentrations of these basement membrane components (measured by radioimmunoassay) were very high before surgery, but decreased rapidly thereafter. Serial measurement of type IV collagen and laminin, in conjunction with other tumour markers and oestrogen concentrations, might be helpful in evaluating prognosis of ovarian granulosa cell tumours, in detecting metastatic or recurrent lesions and in monitoring response to treatment.

Aged↗