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Biomedical subjects

Y Nagata

Publications and source records attributed to Y Nagata.

At least 253 records · Page 14Linked to original sources

Bone marrow stromal cells produce thrombopoietin and stimulate megakaryocyte growth and maturation but suppress proplatelet formation.

Production of blood cells is regulated by the interplay of various cytokines and bone marrow stromal cells. Recently, a ligand for the orphan receptor Mpl was identified as thrombopoietin (TPO), which specifically regulates megakaryocyte differentiation, and it was reported to be expressed mainly in liver and kidney. As it was found that thrombopoietin is also produced in bone marrow stromal cells, we studied further the roles of bone marrow stromal cells on megakaryocytopoiesis and platelet formation. The stromal cells stimulated growth and maturation of bone-marrow-derived megakaryocytes in the presence of thrombopoietin, and also supported growth of BaF3 cells expressing exogenous Mpl without thrombopoietin. Thrombopoietin induces drastic morphological change of megakaryocytes in bone marrow cells in vitro, ie, the formation of lengthy beaded cytoplasmic processes (proplatelet formation). However, when the purified megakaryocytes were cocultured with the stromal cells with or without thrombopoietin, most of the megakaryocytes adhered to the stromal cells and remained unchanged, while free megakaryocytes induced proplatelet formation. These observations indicated that the stromal cells in a hematopoietic microenvironment in bone marrow secrete thrombopoietin and stimulate proliferation and maturation of megakaryocytes, but the interaction of megakaryocytes with the stromal cells may suppress proplatelet formation.

Animals↗

A rare case of serous cystadenoma of the pancreas presenting with left-sided portal hypertension.

We herein report the case of a 63-year-old woman with a serous cystadenoma of the pancreas presenting with left-sided portal hypertension secondary to isolated splenic vein occlusion. She was admitted to our hospital for sudden hematemesis. Emergency upper gastrointestinal endoscopy revealed hemorrhagic erosive gastritis and isolated varices in the gastric fundus. An abdominal angiographic study disclosed a large hypervascular tumor of the pancreatic tail which caused isolated splenic vein occlusion by tumor compression and formed large hepatopetal collaterals via the gastric varices. The patient underwent tumor resection with splenectomy and, as a result, the gastric varices disappeared and the postoperative course was uneventful. Left-sided portal hypertension secondary to splenic vein occlusion is an uncommon complication mostly associated with pancreatitis and pancreatic carcinoma. Although benign pancreatic neoplasms only rarely cause such a condition, the possibility of gastrointestinal bleeding due to this condition should be carefully taken into consideration when treating pancreatic disease.

Angiography↗

Mechanistic analysis of high antitumor effect of intradermal administration of lipopolysaccharide from Pantoea Agglomerans.

Lipopolysaccharide from Pantoea Agglomerans (LPSp) has a remarkably high antitumor activity even against poorly immunogeneic tumors when given by intradermal injection combined with cyclophosphamide (CY). We have extended this study to gain an insight into the mechanism of this antitumor effect, and especially into the induction of cell mediated immunity. In immunohistological studies, extensive necrosis and marked infiltration of the inflammatory cells at the tumor were observed after intradermal injection of LPSp combined with CY, but not after CY alone or after no treatment. The cells around the tumors were mostly neutrophils and macro phages (Mac 1+); T cells (CD4+, CD8+) were also present. The serum levels of cytokines, induced after intradermal injection of LPSp, were determined and compared with intravenous administration of LPSp or recombinant TNF-SAM2. TNF-alpha, IL-1, IL-6 and GM-CSF were measured by ELISA as a marker of cytokine induction. The peak level of TNF-alpha induced by intradermal injection of LPSp was about 5000 pg ml-1, which was considered relatively small since this level was observed even in clinical trial. There seems to be a longer period of release of TNF-alpha after an intradermal injection than after an intravenous injection. This may produce the remarkably high antitumor effect of the intradermal injection. The antitumor effect of intradermal administration combined with CY was evaluated in nude mice to clarify the role of T cells in high antitumor activity. In this experiment, antitumor activity was found to be much less in BALB/c nu/nu mice without regression, while complete regression was frequently observed in syngeneic mice, showing the crucial role of T cells in this treatment. These observations suggest that intradermal administration of LPSp in combination with CY continuously releases and induces not only extensive necrosis of the tumor but also cell mediated antitumor immunity, which may be indispensable for complete regression of the tumor. Clinical application of this treatment for advanced cancer patients is in progress.

Animals↗

Relationship between sonographic endometrial thickness and progestin-induced withdrawal bleeding.

OBJECTIVE: To determine whether the response to the progestin challenge test can be predicted from the endometrial thickness measured sonographically. METHODS: Progestin challenge tests were performed on 44 women with secondary amenorrhea, each of whom also had her endometrial thickness measured by transvaginal ultrasonography and her serum estradiol (E2) levels determined. The relationships between the response to the challenge test, endometrial thickness, and serum E2 levels were studied, as well as whether the presence or absence of withdrawal bleeding could be predicted from the endometrial thickness and serum E2 levels. RESULTS: The endometrium was significantly thicker in 32 women who had withdrawal bleeding (10.3 +/-4.1 mm) than in the 12 who did not bleed (5.0 +/- 1.3 mm) (P < .001). The serum E2 level was also significantly higher in the positive group: 45.3 +/- 19.4 versus 18.6 +/- 8.0 pg/mL (P < .001). Endometrial thickness of 6.0 mm or more predicted the occurrence of withdrawal bleeding with an accuracy of 95.5%. Endometrial thickness was superior to the serum E2 level in predicting withdrawal bleeding. CONCLUSION: Progestin-induced withdrawal bleeding can be predicted from the endometrial thickness measured sonographically.

Adult↗

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control.

PURPOSE: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). MATERIALS AND METHODS: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60-66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72-74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for > 2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. RESULTS: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42-49 days was significantly higher than that of tumors with an OTT of > 49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). CONCLUSIONS: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.

Adult↗

Induction of tissue transglutaminase in rat superior cervical sympathetic ganglia following in vitro stimulation of retinoic acid.

The addition of retinoic acid (RA, 50 nM) to Dulbecco's modifed Eagle's medium containing 1.0 percent bovine serum albumin and 50 mu g/l of gentamicin markedly increased the activity of a Ca(2+) -dependent tissue transglutaminase (TGase) (ca. 3.2-fold), which stabilizes newly formed protein assemblies at the sites of synapses, in isolated rat superior cervical sympathetic ganglia (SCG), which is abundant in synapses, following in vitro aerobic incubation for 3 h at 37 degrees C. An isomer of RA, 13-cis-RA (50 nM), showed the same tendency but rather lesser magnitude (ca. 1.7-fold) in ganglionic TGase activation. Also, retinal (50 nM), a precursor of RA, had a little effect on TGase stimulation (ca. 1.5-fold) in SCG. The RA-induced enhancement of ganglionic TGase activity was completely eliminated in the presence of either actinomycin D (1.0 mu g/ml), a depressant of molecular transcriptional activity, or a potent inhibitor of protein synthesis, cycloheximide (10 mu g/ml). Kinetic analyses show that the stimulation of ganglionic TGase activity evoked by RA addition was associated with only an increase in V max value (ca. 3.3-fold) without change in Km value. Thus, the enzyme protein of TGase might be synthesized de novo in the ganglia in response to RA. The RA-induced activation effect of ganglionic TGase almost disappeared (ca. 1.3-fold) 1 week following denervation, by which time preganglionic cholinergic nerve terminals were degradated. In axotomized SCG, where sympathetic neurons were degenerated and reactive proliferation of glial cells was in progress, the RA-evoked increase in ganglionic TGase activity was attenuated (ca. 1.3-fold). These findings imply that some retinoids, especially RA effectively participate in the cholinergic potentiation of synaptic activity.

Animals↗

Setting standards for the levels of endotoxin in the embryo culture media of human in vitro fertilization and embryo transfer.

OBJECTIVE: To clarify the optimum set standards for the levels of endotoxin in a culture medium for human IVF-ET programs. DESIGN: Retrospective and randomized study. SETTING: One hundred patients underwent 163 cycles of IVF-ET at Fukuoka University Hospital. INTERVENTIONS: Measurements for endotoxin were performed using the Limulus Amoebocyte Lysate test. The negative group was administered media with < 1 pg/mL of endotoxin and the positive group was given media with > or = 1 pg/mL of endotoxin. MAIN OUTCOME MEASURES: Human embryo development, clinical outcomes, and pregnancy outcomes were evaluated in each group and also the levels of endotoxin. RESULTS: The rates of clinical pregnancy (26.1%) and the live birth rates (20.7%) in the negative media were significantly higher than those in the positive media (9.9% and 5.6%, respectively). Rates of embryo development were decreased and a gestational sac and fetal heart beat were not detected in media with > 2 pg/mL of endotoxin. CONCLUSION: The set standard for the level of endotoxin in a medium should be < 1 pg/mL to obtain the best outcome. The allowable levels of endotoxin in a medium should be < or = 2 pg/mL in human IVF.

Adult↗

Protection of scallop sarcoplasmic reticulum ATPase from thermal inactivation by removal of calcium from high-affinity binding sites on the enzyme.

Sarcoplasmic reticulum (SR) vesicles were isolated from scallop muscle by the method of Abe et al. (J. Biochem. 112, 822-827, 1992) and their thermolability was examined in the presence and absence of Ca2+. When SR was preincubated at 38 degrees C in the presence of 0.1 mM Ca2+, Ca2+ transport activity decreased as a function of time with a half-inhibition time of about 5 min. Activities of the Ca(2+)-dependent ATPase, phosphoenzyme (EP) formation and E2 to E1 transition were decreased by the heat treatment in parallel with the Ca2+ transport activity. In contrast, when SR was preincubated at 38 degrees C in the presence of 2-5 mM EGTA, all of these activities, except for the Ca2+ transport, were markedly protected from the heat inactivation. The uncoupling between Ca2+ transport and the ATPase reaction did not lead to a rise in the Ca2+ permeability of SR membrane. Plots of the ATPase activity or steady-state level of EP against pCa in the thermal incubation medium revealed a typical sigmoidal curve with a half-inhibition concentration and Hill number of about 0.5 microM and 1.80, respectively. These results suggest that 2 mol of Ca2+ must be removed from the high-affinity Ca2+ binding sites on the ATPase to stabilize the Ca(2+)-ATPase against heat inactivation. The protection from heat inactivation disappeared if SR was preincubated at 38 degrees C after having been solubilized with a nonionic detergent, but returned when the detergent was removed to reconstitute the SR membrane. These results suggest that the protection of ATPase from thermal inactivation in EGTA may require a membrane structure in which the ATPase molecules exist in an appropriate arrangement.

Adenosine Triphosphate↗

Clinical usefulness of determining the rate of thermal clearance within heated tumors.

Between June 1987 and June 1988, 28 patients (28 tumors) with liver, retroperitoneal, intrapelvic, or superficial tumors were treated with hyperthermia combined with radiotherapy and/or chemotherapy. Hyperthermia was administered once or twice a week for 30-60 min per session, up to a total of 2-11 sessions, with an 8-MHz RF capacitive heating device. Blood flow in the tumors was evaluated from the rate of thermal clearance (TCR) using the bio-heat transfer equation. The TCR was measured in the middle of the first heating session and at the end of the last heating session by turning off the output power of the heating device. For 9 patients, contrast-enhanced CT scans were taken and CT numbers at the centers of tumors were measured before and after the entire course of hyperthermia. Changes in TCR were closely related to average tumor center temperature, changes in CT number, and tumor response. When smaller and more superficial tumors were treated by hyperthermia combined with radiotherapy and/or chemotherapy that consisted of many heating sessions and during which a high average tumor center temperature was achieved, a better tumor response was obtained. The better the tumor response, the higher the local control rate became. The cause-specific survival rate of patients who achieved good tumor responses was higher than that of patients who showed poor tumor responses. Changes in TCR and CT number in heated tumors were useful and important indicators of tumor response to hyperthermia.

Adolescent↗

Metastatic testicular choriocarcinoma of the skin. Report and review of the literature.

Choriocarcinoma is a malignant growth of trophoblastic cells characterized by secretion of human chorionic gonadotropin. Choriocarcinoma usually arises from fetal trophoblasts and rarely arises from germ cells in the testis or ovary or derives from dedifferentiation of other carcinomas. Skin metastasis of choriocarcinoma is rare: only seven cases have been reported in the English and Japanese literature. We report the case of a 22-year-old Japanese man with pure choriocarcinoma of the testis who developed skin metastases that presented as multiple reddish nodules. Microscopic examination of both the primary lesion of the testis and the cutaneous metastasis demonstrated the typical histologic features of pure choriocarcinoma. The patient died 3 months after the initial onset of skin metastasis. Review of the literature indicates that skin metastasis of choriocarcinoma usually occurs as a nodular lesion with the histologically typical feature of the primary disease and signals of poor prognosis.

Adult↗

Assessment of cerebral fat embolism by magnetic resonance imaging in the acute stage.

The authors assessed the characteristic appearance of magnetic resonance imaging (MRI) of cerebral fat embolism in three patients. The MRI features in the acute stage were characterized by widespread, spotty lesions in the white matter, which appeared hyperintense on T2-weighted images and iso- or hypointense on T1-weighted images. The relation between clinical features and MRI findings are discussed.

Acute Disease↗

Evaluation of angiogenic inhibitors with an in vivo quantitative angiogenesis method using agarose microencapsulation and mouse hemoglobin enzyme-linked immunosorbent assay.

In the present work, using a previously reported in vivo quantitative tumor-angiogenesis model, we attempted to ascertain whether this animal model is suitable for practical use in monitoring inhibitors of tumor angiogenesis. Mouse sarcoma-180 cells, human A431 cells or rat C6 cells microencapsulated in agarose beads were implanted s.c. into C57BL/6 mice. The level of blood vessel induction at the agarose pellet site was evaluated using mouse hemoglobin enzyme-linked immunosorbent assay on day 10 after implantation. Hydrocortisone, tetrahydro-S, medroxyprogesterone acetate, pentosan polysulfate and suramin inhibited blood vessel growth in our in vivo tumor-angiogenesis assay system, and heparin enhanced the antiangiogenic effects of hydrocortisone and tetrahydro-S. These results are almost entirely consistent with those observed in common assay systems, and suggest that this method may be useful for the identification and quantitative evaluation of inhibitors of tumor angiogenesis.

Animals↗

Effects of weight loss on bone mineral density in rats.

OBJECTIVE: To evaluate the effects of weight loss on bone mineral density (BMD). METHODS: Eight-week-old female rats were divided into 4 groups: Those in Group A received a restricted diet for 4 weeks; those in Group B received a restricted diet and were treated with estrogen; those in Group C were castrated; and those in Group D underwent sham operations. The rat's body weight (BW) and vaginal smears were checked, and their femoral BMD was measured. RESULTS: The BW and BMD at 12 weeks were lower in Groups A and B than in Groups C and D; thereafter, however, these values increased for Groups A and B, but were still lower than those in Group D even at 20 weeks. In Group C, the BMD did not decrease, but it was significantly lower than that in Group D at 16 and 20 weeks. Group A showed continuous diestrus 2 weeks after dietary restriction began, but recovered to a 4-day cycle 2 weeks after the initiation of free food consumption. CONCLUSION: Weight loss had a greater effect on BMD than hypoestrogenism.

Animals↗

The relation between body-fat distribution and lipid metabolism in postmenopausal women.

OBJECTIVE: To evaluate the relationship between body-fat distribution and lipid metabolism in postmenopausal women. METHODS: Fifty-four women (mean: 61.8 +/- 7.8 years old) showing hyperlipidemia and 63 controls were enrolled in this study. Their baseline characteristics and body-fat indices, as measured by DEXA, were compared. The correlations between the serum-lipid levels and the variables were evaluated. RESULTS: The amount of upper-half-body fat and the body-fat ratio were significantly higher in the hyperlipidemia group. In single-regression analysis, there were low levels of correlation between the serum TC levels and the amount of upper-half-body fat and the upper-body fat ratio. There was a low level of correlation between the serum TG level and the amount of upper-half-body fat, the upper-lower-half-body-fat ratios, and the upper-half-body-fat ratio. After adjusting for variables, the serum TC and TG levels best correlated with the amount of upper-half-body-fat (r = 0.458, r = 457, respectively). CONCLUSION: In postmenopausal women, lipid metabolism is reflected in the amount of upper-half-body fat, irrespective of age and the body-mass index (BMI).

Adipose Tissue↗

A novel developmental stage-specific lectin of the basidiomycete Pleurotus cornucopiae.

A novel lectin was isolated from mycelia of the basidiomycete Pleurotus cornucopiae grown on solid medium. The lectin was purified to homogeneity by mucin-Sepharose affinity chromatography. The molecular mass of the lectin was 40 kDa under reducing conditions, but the subunits were polymerized through disulfide bridges under physiological conditions. Hemagglutinating activity of this lectin was completely inhibited by 2-mercaptoethanol, indicating that the multimer is active. The activity was also inhibited by EDTA, and restored by CaCl2. N-Acetyl-D-galactosamine was the most potent hapten inhibitor. N-terminal amino acid sequence analysis revealed that the mycelial lectin was different from the fruit body lectin of this organism. The mycelial lectin appeared prior to fruit body formation and disappeared during the formation of fruit bodies. The lectin was localized on the surface of solid-medium-grown mycelia, and only dikaryotic, and not monokaryotic, mycelia produced the lectin. These results suggest that the appearance of this lectin is associated with fruit body formation.

Amino Acid Sequence↗

Development of an MR simulator: experimental verification of geometric distortion and clinical application.

PURPOSE: To evaluate the geometric distortion on magnetic resonance (MR) images obtained with a permanent magnet system and determine the usefulness of MR imaging-assisted x-ray simulation in radiation therapy treatment planning (RTTP). MATERIALS AND METHODS: The authors measured the distortion on MR images of grid-pattern phantoms. MR imaging-assisted x-ray simulation was performed with skin markers in 14 patients with bone tumors. Treatment planning had already been performed with a conventional system. RESULTS: On phantom images, most of the positional displacements within a 120-mm radius from the center of the static magnetic field were less than 2 mm; larger displacements were observed in the peripheral region of the images. MR imaging was useful in the RTTP of all patients. The original radiation field was modified after MR examination in six patients. CONCLUSION: The amount of image distortion within the practical area is acceptable for RTTP. MR imaging-assisted x-ray simulation is useful for patients with bone tumors and warrants further investigation.

Aged↗

A high linoleate and a high alpha-linolenate diet induced changes in learning behavior of rats. Effects of a shift in diets and reversal of training stimuli.

Rats fed from weaning on semi-purified diets supplemented either with linoleate-rich safflower oil (S) or alpha-linolenate-rich perilla oil (P) were mated. Half of the progeny were weaned to the original diet of the dams (SS and PP), the other two groups were shifted to diets enriched in the other fatty acid (SP and PS). Brightness-discrimination learning ability was tested daily for 30 d beginning at 11 weeks of age, with a bright light as the positive stimulus. The learning performance was inferior in the group fed the safflower diet through two generations (SS) as compared with groups fed the perilla diet through two generations (PP) or for which the diets were shifted at weaning (PS and SP). The docosahexaenoate content of brain phospholipids was significantly less in the SS group compared with the three other groups. After 30 d of the learning test, the effect of shifting the stimulus was tested for another 30 d, this time using a dim light as the positive stimulus. The learning performance was superior in the PP group to the SS group throughout the latter 30 sessions, the difference being even more obvious than during the first 30 d. These results indicate that the decrease in the discrimination-learning ability induced by alpha-linolenate deficiency is a relatively reversible process; both the docosahexaenoate content in brain and the learning performance were restored by supplementing alpha-linolenate after the weaning.

Animals↗