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Biomedical subjects

T Naitoh

Publications and source records attributed to T Naitoh.

At least 55 records · Page 3Linked to original sources

[A patient with lung metastasis of medulloblastoma].

A 15-year-old boy had metastasis to the spinal cord and then to the lung after an operation to remove a primary medulloblastoma. A medulloblastoma developed at the age of 10 years. The tumor was completely resected and the brain and spinal cord were irradiated. At the age of 13 years, metastasis to the sacral spinal cord developed and was treated with radiotherapy and intramedullary injection of methotrexate. At the age of 15 years, metastasis to the lung developed and was treated with chemotherapy (CBDCA, VP-16) followed by radiotherapy. Three months after the end of that therapy, the disease recurred but another course of radiotherapy and chemotherapy (VCR) was successful. Chemotherapy and radiotherapy were effective against metastatic lesions of medulloblastoma. With improvement in the survival rate among patients with medulloblastoma, we can expect incidence of extraneural metastases to increase. In addition to recurrence of the primary lesion and intramedullary dissemination, these metastatic lesions also require attention.

Adolescent↗

Metamorphic shortening of the alimentary tract in anuran larvae (Rana catesbeiana).

BACKGROUND: The premetamorphic alimentary tract in anurans can be more than 10 times a tadpole's body length but then dramatically shortens to a third or less of that length by the end of metamorphosis. Although there have been many studies on histological changes in the anuran gut with metamorphosis, the broader question of where the major shortening occurs has not been previously addressed. This topic is investigated here. METHODS: We began our study by labeling intestinal coils in situ in preserved Rana catesbeiana tadpoles and then uncoiling their intestines, locating, and measuring the labeled points. This allowed us to map the coiled gut of the tadpole, such that the distance along the oral-anal axis could be determined by simply counting coils. We next implanted markers into the intestinal coils of live R. catesbeiana tadpoles at five known locations along the oral-anal axis, established from the prior mapping. The tadpoles were then induced to metamorphose by immersion in thyroid hormone. After the gut had shortened to a third of its premetamorphic length, the positions of the implanted markers were determined through dissection. RESULTS: Relative distances between the marked points did not change when the gut shortened. CONCLUSIONS: The results indicate that during metamorphosis the intestine shortens uniformly along its length and not preferentially from one region or another. Although metamorphosis was artificially induced, the shortening that we observed matches that occurring during natural metamorphosis.

Animals↗

Transferrin is not involved in initial uptake process of iron in rat duodenal mucosa. Ultrastructural study by x-ray energy spectrometry.

The role of transferrin in iron absorption by the duodenal mucosa in rats with iron deficiency and controls was evaluated immunohistochemically. Ferric iron was administered to each rat using a metallic gastric tube. Transferrin was stained by an immunoperoxidase method and iron with Prussian blue in the same duodenal sections and observed by light microscopy. The localization of transferrin differed from that of ferric iron both in rats with iron deficiency and in controls. In iron-deficient rats, transferrin was weakly stained after iron administration but was strongly stained after saline administration. In contrast, in controls, transferrin was weakly stained after saline administration but was strongly stained after iron administration. By electron microscopy, x-ray energy spectrometric analysis of the transferrin-positive areas showed no iron peak. In iron-deficient rats, accumulation of electron-dense transferrin-negative microgranules was observed in some of the duodenal columnar epithelium. X-ray energy spectrometric analysis of this area revealed iron, indicating iron absorption. These results suggest that mucosal transferrin does not act as a shuttle protein in iron absorption via the rat duodenal columnar epithelium, and the function of this protein may be to inform the absorptive cells of the iron status of the body as observed in other organs.

Animals↗

Interpretation of extravascular thermal volume of the lung in patients with chronic pulmonary diseases.

To understand the significance of measured extravascular thermal volume of the lung (ETVL) in chronic pulmonary diseases, we measured ETVL using the double-indicator dilution technique in 17 emphysematous patients and 15 patients with pulmonary fibrosis. The level of ETVL in emphysema is significantly correlated with parameters reflecting the severity of the disease, including FEV1.0% (r = 0.54, p < 0.05), DLCO/VA (r = 0.54, p < 0.05), PaO2 (r = 0.61, p < 0.01), and mean pulmonary artery pressure (r = -0.61, p < 0.01). In pulmonary fibrosis, a significant inverse correlation was found between ETVL and PaO2 (r = -0.64, p < 0.02), DLCO/VA (r = -0.58, p < 0.05), and %VC (r = -0.61, p < 0.02). The mean level of ETVL in both groups of patients was lower than previously reported normal values. These results suggest that ETVL may reflect the decrease in pulmonary vasculature in emphysematous patients, while it may signify a decrease of pulmonary vasculature and increased volume of pulmonary interstitial tissue surrounding the pulmonary vasculature in pulmonary fibrosis. We conclude that ETVL may represent a good estimate of the condition of the pulmonary vasculature and interstitial tissue volume in patients with chronic pulmonary diseases.

Aged↗

The structure-activity relationship between synthetic butylidenephthalide derivatives regarding the competence and progression of inhibition in primary cultures proliferation of mouse aorta smooth muscle cells.

The inhibitory effects of synthetic butylidenephthalide (BP) derivatives on 10% fetal bovine serum-stimulated proliferation were assayed by measuring the proliferative cell number at an interval of 12 h in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the anti-proliferation effect were in the order BP-42 (4,5-dihydroxy BP) > BP-92 (4,5-dihydroxy butylphthalide) > BP-97 (6,7-dihydroxy-3-(3-bromo-1-octenyl)-phthalide) > BP-82 (6,7-dihydroxy BP) > BP-86 (5,6-dihydroxy BP) > BP-87 (4,5,6-trihydroxy BP) > BP-85 (4,7-dihydroxy BP) > BP-84 (5,7-dihydroxy BP) > BP-4C3 (4-methoxy propylphthalide) > BP-7 (4-hydroxy BP) > BP-40 (4,5-dimethoxy butylphthalide) > BP-5C3 (4-hydroxy propylphthalide). We divided these anti-proliferative effects into anti-competence and anti-progression effects by using a convenient assay. BP-42 had the greatest potency in used phthalides for competence inhibition of the SMC proliferation. BP-92 had small potency for competence inhibition. BP-97 had greater potency for competence inhibition than BP-82. These results demonstrated that the anti-proliferative effect of BP-42 was greatest in used phthalides in primary cultures of vascular SMC. The 4,5-dihydroxy group and 3-butylidene or 3-(3-bromo-1-octenyl) group in these synthetic BP derivatives contributed to the anti-competence effect on SMC. BP-42 may become a prototype of an anti-atherosclerotic drug.

Animals↗

Amphibian amplexus in microgravity.

We report here on the amplectic behavior of the Japanese treefrog (Hyla japonica) in microgravity. Treefrogs were exposed to 35 cycles of altered gravity, including approximately 1.5 sec of G < 0.1 every 3 min and 15 sec, on the FreeFall "G.0" ride at Space World amusement park in Kitakyushu, Japan. During this period a pair of frogs spontaneously entered and maintained amplexus for 1 hr 20 min, before being removed from the ride. In freefall, the pair extended their hindlimbs in the characteristic posture of treefrogs in microgravity. This is the first report of a vertebrate entering and sustaining a copulatory or amplectic posture under gravitational extremes, including true freefall. These observations bode well for the potential of anurans to breed in microgravity and to be used for biological research in space.

Animals↗

Behavior of Japanese tree frogs under microgravity on MIR and in parabolic flight.

Japanese tree frogs (Hyla japonica) were flown to the space station MIR and spent eight days in orbit during December, 1990. Under microgravity, their postures and behaviors were observed and recorded. On the MIR, floating frogs stretched four legs out, bent their bodies backward and expanded their abdomens. Frogs on a surface often bent their neck backward and walked backwards. This behavior was observed on parabolic flights and resembles the retching behavior of sick frogs on land--a possible indicator of motion sickness. Observations on MIR were carried out twice to investigate the frog's adaptation to space. The frequency of failure in landing after a jump decreased in the second observation period. After the frogs returned to earth, readaptation processes were observed. The frogs behaved normally as early as 2.5 hours after landing.

Adaptation, Physiological↗

Diabetic GK rat plasma but not normal Wistar rat plasma induces insulin-stimulated DNA synthesis in primary cultured smooth muscle cells in GK rat aorta.

We investigated the effect of diabetic plasma on insulin-stimulated DNA synthesis in primary cultured aortic smooth muscle cells (SMC) of the GK rat, a model of non-insulin-dependent diabetes mellitus, and compared it with that of Wistar normal rat plasma. We measured the incorporation of 3H-thymidine into cultured SMC. The diabetic plasma (3%) of GK rat, but neither the plasma (3%) of Wistar normal rat nor the plasma (3%) (not containing both insulin-like growth factor-I (IGF-I) and corticosterone) of Wistar hypophysectomized rat induced insulin-stimulated DNA synthesis in GK rat SMC. The responsiveness of SMC to insulin, not to IGF-I, was decreased remarkably by the diabetic state. The diabetic plasma of GK rat remarkably enhanced and the plasma of Wistar hypophysectomized rat weakly enhanced insulin-stimulated DNA synthesis in Wistar normal rat SMC. Corticosterone (20 nM) increased insulin-stimulated DNA synthesis in GK rat SMC but decreased it in Wistar normal rat SMC, using the plasma of Wistar hypophysectomized rat. Corticosterone levels were lower in GK rat plasma than in normal Wistar rat plasma. These results demonstrate that the enhancement of insulin-stimulated DNA synthesis in diabetic SMC by the diabetic plasma of GK rat may be due to neither IGF-I nor corticosterone but due to other factors.

Animals↗

Application of pharmacokinetic studies to a novel antidepressant, E2011.

1. The original drug tested here, (5R)-3-[2-(3-cyanopropyl)benzothiazol-6-yl]-5-methoxymethyl-2-oxaz olidinone (ER-4539), exhibited strong MAO-A inhibitory activity in vitro, but its bioavailability in rat was very low. After ER-4539 was administered orally to dog, a metabolite was found in plasma. 2. The metabolite was isolated by hplc after incubation with dog liver microsomal preparations. Its structure, determined by ms and nmr analysis, was alpha-hydroxy-ER-4539. The configuration of the alpha-hydroxy metabolite was (S), determined in comparison with the authentic sample of (R) and (S) by hplc. The isolated metabolite had potent MAO-A inhibitory action in vitro, indicating that it would have antidepressant action. 3. (5R)-3-[2-((1S)-3-Cyano-1-hydroxypropyl)benzothiazol-6-yl]-5- methoxymethyl-2-oxazolidinone (E2011), the synthesized metabolite, has been improved in regard to biopharmaceutical characteristics in rat and dog.

Animals↗

[Clinical usefulness of serum assay of EIA-CYFRA 21-1 in lung cancer].

Enzyme immunoassay CYFRA 21-1, a novel lung tumor marker presented in serum (upper limit of normal values: 3.5 ng/ml) was measured in 84 patients with lung cancer and 141 patients with benign respiratory diseases. The positive rate for CYFRA 21-1 in primary lung cancer was 70.3% and the false positive rate in respiratory diseases was 24.1%. In respect to the histological types of lung cancer, CYFRA 21-1 was elevated in 85.0% of squamous cell carcinoma and in 64.8% of other cell types of primary lung cancer. Elevated CYFRA 21-1 levels were found in 40% of Stage I-II, in 80.0% of Stage IIIA-B, and in 73.5% of Stage IV. The overall diagnostic efficiency was 53.4% for CYFRA 21-1 and 44.5% for CEA, respectively. Receiver operating characteristic (ROC) curve analysis suggested that CYFRA 21-1 test has an advantage over CEA. From the results of this study, CYFRA 21-1 was more efficient than CEA as primary diagnostic marker in lung cancer.

Biomarkers, Tumor↗

Motion sickness in amphibians.

We explored the question of whether amphibians get motion sickness by exposing anurans (frogs) and urodeles (salamanders) to the provocative stimulus of parabolic aircraft flight. Animals were fed before flight, and the presence of vomitus in their containers after flight was used to indicate motion-induced emesis. None of the species that we studied vomited during the 8 to 10 parabolas of each flight. However, at least one specimen from each of the anuran species Rana rugosa, Rana nigromaculata, Hyla japonica, and Rhacophorus schlegelii vomited in a period of 0.5 to 42 h after flight. Some specimens of R. nigromaculata, H. japonica, and R. schlegelii were also observed retching without emesis either during or shortly after exposure to parabolic flight. We were unable to induce either emesis or retching behavior in the aquatic from Xenopus laevis. Among the urodeles studied we saw no signs of motion sickness in either adult or larval Cynops pyrrhogaster, but at least one larval Hynobius nebulosus vomited shortly after parabolic flight. The amphibian species that exhibited the most motion sickness were the same ones that showed the greatest amount of tumbling during the microgravity phases of their parabolic flights. The most distinctive difference between motion sickness in amphibians and mammals that vomit, including man, is the long delay between a provocative stimulus and emesis proper in the amphibians. The retching behavior we induced in the frogs was identical to that described previously for frogs treated with emetic drugs. H. japonica, exposed to extended periods of microgravity on the MIR Space Station, flattened their bellies against the substrate and dorsiflexed their heads in a manner reminiscent of drug-induced nausea. In light of our current observations of retching behavior in motion sick H. japonica, we suggest that the previously observed behavior of three frogs on the MIR Space Station was a manifestation of motion sickness.

Animals↗

Chemical structure-activity of cnidium rhizome-derived phthalides for the competence inhibition of proliferation in primary cultures of mouse aorta smooth muscle cells.

Inhibitory effects of cnidium rhizome-derived phthalides on competence and progression phases of fetal bovine serum (10%)-induced proliferation were compared in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the competence inhibition were in the order of senkyunolide L ((Z)-6-hydroxy-7-chloro-6,7-dihydroligustilide) > senkyunolide H ((Z)-6,7-dihydroxy-6,7-dihydroligustilide) > senkyunolide J ((3S)-(E)-6,7-dihydroxy-3,6,7,8-tetrahydroligustilide) > senkyunolide I ((E)-6,7-dihydroxy-6,7-dihydroligustilide) > ligustilide = senkyunolide A ((3S)-3,8-dihydroligustilide) > butylidenephthalide. The order of their potencies for the progression inhibition was parallel with that for the competence inhibition. Senkyunolide L is considered to have been formed during the extraction of cnidium. These results demonstrate that the (Z)-6,7-dihydroxy isomer of the dihydroligustilide derivatives is essential for the anti-competent effect on proliferation of the SMC in primary culture. Senkyunolide H in cnidium rhizome may be a prototype for a new anti-atherosclerotic drug.

4-Butyrolactone↗

[A case of obstructive sleep apnea syndrome with increased lung water during sleep].

A 22-year-old man was admitted to the department of plastic surgery in our university with diagnosis of ankylosis and microgeniea. His complaints were snoring and somnolence in the daytime, so we performed a Respigraph (Chest) that showed obstructive apnea during sleep. We diagnosed obstructive sleep apnea syndrome. So we observed pulmonary circulation and measured lung water using the double indicator dilution method (Nihon Koden, MTV-1100) during sleep. During the period of apnea, arterial oxygen pressure and mixed venous saturation decreased, reversely, mean pulmonary arterial pressure rose, lung water (ETV) and central blood volume increased. We considered that the increase of lung water during sleep apnea is caused by hemodynamic change due to hypoxia and increase of venous return. After operation, the value of blood gas assay and apnea index were improved.

Adult↗

Metamorphic changes in the vagal innervation to the alimentary tract in the green frog, Rana clamitans (Ranidae).

The alimentary tract of typical anurans shortens extensively at metamorphosis, when the microphagous tadpole transforms into a macrophagous frog. We used methylene blue vital stain and Sihler stain, in conjunction with microdissection, to map the distribution of the gastric branch of the vagus nerve in green frogs (Rana clamitans) before and after metamorphosis. After metamorphosis, terminal divisions of the gastric branch can be observed on the tunica musculosa extending as far as the pylorus. In the tadpole, the gastric branch ends abruptly on the esophagus. The premetamorphic pattern of innervation is consistent with the absence of digestive activity in the foregut before metamorphosis. Preliminary experiments, involving stimulation of the gastric branch of the vagus in the tadpoles, confirm the anatomical observation of the absence of vagal innervation before metamorphosis.

Animals↗

Diabetic state-induced modification of insulin-stimulated, glucose uptake into and kinase activity in, the diaphragm muscle of genetically diabetic KK-CAy mice.

The effect of insulin on glucose and 2-deoxyglucose uptake into isolated diaphragm was investigated in genetically diabetic KK-CAy mice, and in part in alloxan-treated mice. Concentration-response curves of insulin for glucose uptake (8.3 mM in vitro) for 1 h were shifted to the left in two kinds of diabetic model mice. Insulin-stimulated glucose uptake was biphasic; it was high 1 week, and returned to the normal level 4 weeks, after alloxan injection despite high blood glucose levels. Insulin-stimulated glucose uptake was the same at higher glucose levels (25 mM) as at 8.3 mM glucose for 1 h, despite an increase in basal glucose uptake (without insulin) in KK-CAy mice. Insulin-receptor kinase activity in diabetic KK-CAy mouse diaphragm also changed biphasically as the glucose concentration increased: an increase at 8.3 mM, but no increase at 16.7 mM or 25.0 mM glucose for 3 h-pretreatment including 1 h-insulin treatment. These results suggest that although the initial state of diabetes enhances insulin action, the prolonged hyperglycemia rather suppressed the insulin action in vivo.

Animals↗

Suppression by high glucose concentration of insulin receptor up-regulation in diaphragm and flexor digitorum brevis muscles from diabetic KK-CAy and streptozotocin-diabetic mice.

The specific binding of insulin to diaphragm and flexor digitorum brevis (FDB) muscles isolated from diabetic KK-CAy and streptozotocin (STZ)-diabetic ddY mice was investigated under high glucose concentration in vitro. For high-affinity insulin receptor under 2.8 mM glucose, amounts of the receptor and values of dissociation constant (Kd) were greater in both diabetic muscles than in the corresponding normal control muscles, respectively. High glucose concentration up to 16.7 mM reduced both the up-regulation of the receptor and the decrease in the affinity by the diabetic state. These studies strongly suggest that high glucose level in the diabetic state in vivo may suppress the up-regulation of high-affinity insulin receptor in both models of diabetic mice.

Animals↗

Platelet-derived growth factor (PDGF) accelerates induction of competence, and heparin does not inhibit PDGF-induced competence in primary cultured smooth muscle cells of rat aorta.

The time-dependent effect of platelet-derived growth factor (PDGF) on cell proliferation was investigated to clarify whether PDGF accelerates the rate of proliferation or its start in primary cultured smooth muscle cells (SMC) of rat aorta. In synchronized SMC at the G0 phase, 1, 10 and 100 ng/ml PDGF started DNA synthesis at 24, 15-18 and 12 hr, respectively, after stimulation by 3% fetal bovine serum (FBS) or hypophysectomized rat plasma (deficient in insulin-like growth factor-I (IGF-I)). Heparin (1, 10 or 100 micrograms/ml) decreased only the rate of DNA synthesis stimulated by PDGF in synchronized SMC. DNA synthesis in non-synchronized cells stimulated by PDGF with FBS was determined up to 10 days in culture. The stimulation with 1% FBS plus 30 ng/ml PDGF potentiated the DNA synthesis which was saturated with stimulation by 10% FBS alone, suggesting that prolonged treatment of PDGF transforms SMC. These results demonstrated that PDGF concentration-dependently accelerated the induction of competence independently of IGF-I, and heparin did not inhibit PDGF-induced competence but inhibited progression in primary cultured SMC of rat aorta.

Animals↗