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Biomedical subjects

K Sano

Publications and source records attributed to K Sano.

At least 451 records · Page 25Linked to original sources

Post-translational attainment of allelic exclusion of the T cell receptor alpha chain in a T cell clone.

Two in-frame rearranged mouse TCR alpha chain genes from a single CD4+ T cell clone, MS202, specific for self-class II MHC antigen were transfected into a TCR-negative T cell hybridoma together with a beta chain gene derived from the same T cell clone. Both alpha chain genes were efficiently transcribed and translated in the cytoplasm of host cells, but only one alpha chain (V alpha 5) was expressed on the cell surface in association with the partner beta chain (V beta 4). The other alpha chain gene (V alpha 4) was translated into a mature form of the alpha chain but was unable to make a pair with the beta chain, being prohibited from the surface expression. The supertransfection of the CD4 gene into the alpha beta transfectants did not alter the transcription and expression of both combinations of TCR alpha and beta genes. The original self-class II reactivity was, however, reconstituted only in the cells expressing V alpha 5 and V beta 4 genes supertransfected with CD4. These results indicate that the allelic exclusion of MS202 was achieved by a post-translational mechanism where the product of an in-frame rearranged alpha chain was unable to be expressed on the cell surface, allowing further rearrangement and expression of the other alpha chain gene. The self-class II reactivity of TCR was dependent on the co-expression of CD4 molecules.

Alleles↗

Prognostic implication of silver-binding nucleolar organizer regions (AgNORs) in oral squamous cell carcinoma.

Silver-binding nucleolar organizer regions (AgNORs) were counted in sections from formalin-fixed, paraffin-embedded tissue blocks of oral squamous cell carcinoma. Thirty-nine cases, that comprised poor prognostic group (n = 19) and good prognostic group (n = 20), were examined with respect to the relation between AgNOR counts and histologic grading, and correlation between AgNOR counts and prognosis. The pooled mean AgNOR counts were: Grade 1 carcinomas, 6.39 +/- 1.67 (mean +/- SD; n = 35); Grade 2, 9.74 +/- 1.72 (n = 3). Mean AgNOR count of Grade 3 was 6.19 +/- 2.37 (n = 1). The pooled mean AgNOR count in poor prognostic group was higher than that in good prognostic group. Five-year survival rate of the cases with high AgNOR counts (greater than or equal to 6.5) was significantly lower than that with low AgNOR counts (less than 6.5). High AgNOR counts are highly suggestive of poor prognosis in oral squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Lithium ion does not protect brain against transient ischemia in gerbils.

It has been proposed that lithium ion desensitizes neuronal receptors that function via the inositol phospholipid signaling mechanism. We examined the effects of lithium chloride on the morphologic outcome after 5 minutes of cerebral ischemia induced in gerbils by occluding both common carotid arteries under brief halothane anesthesia. In three treated groups of 10 gerbils each, 5 meq/kg i.p. lithium chloride was given 2 days, 1 day, and 2 hours before ischemia; 2 hours before ischemia; or immediately after the end of ischemia. Corresponding control groups of nine or 10 gerbils each received equivalent volumes of saline injected at comparable times. All gerbils were perfusion-fixed 1 week later, and neuronal density of the hippocampal CA1 pyramidal cells was determined. Lithium induced very mild intraischemic systemic hypothermia, but postischemic hyperthermia developed in both treated and control groups. Neuronal densities were equal in corresponding groups. The results indicate that our regimen of lithium administration provides no benefit in survival of hippocampal neurons, and intraischemic hypothermia of less than 0.8 degrees C is not protective. Other strategies to inactivate the signal transduction system that is specific for excitatory neurotransmission should be evaluated.

Animals↗

Thalamic atrophy following cerebral infarction in the territory of the middle cerebral artery.

We investigated shrinkage of the ipsilateral thalamus following infarction in the territory of the middle cerebral artery in 33 patients who were admitted less than or equal to 2 days after the stroke and who were followed by computed tomography for greater than 1 year with no recurrences. The thalamic area was measured on the computed tomograms, and the ratio of the ipsilateral area to the contralateral area was calculated. All values were compared with values from the initial computed tomogram taken less than or equal to 2 days after the stroke. The values of the ratio on follow-up computed tomograms decreased gradually in 15 patients. In these cases, the area of the ipsilateral thalamus was significantly reduced after 1 year (p less than 0.01) and marked atrophy was observed. These results demonstrate the significance of remote changes over a long period of time after focal cerebral infarction.

Atrophy↗

Effect of dexamethasone on pulmonary surfactant metabolism in hyperoxia-treated rat lungs.

We have examined the effect of dexamethasone on the metabolism of pulmonary surfactant in normal and hyperoxia-treated rats. The relative abundance of the surfactant-specific apoprotein A (SP-A) mRNA in lung tissues and the contents of disaturated phosphatidylcholine (DSPC) and SP-A were measured in bronchoalveolar lavage fluids and in lung tissues in 4-wk-old rats exposed to room air or greater than 90% oxygen for 7 d with or without simultaneous treatment with dexamethasone (0.5 mg/kg body wt for 7 d). The relative abundance of the SP-A mRNA was marginally increased by hyperoxia (1.3-fold over controls). Dexamethasone increased the relative abundance of the SP-A mRNA to a level comparable to that with hyperoxia treatment (1.5-fold over controls). In lavage fluids, the contents of DSPC and SP-A were increased by 4- and 6-fold over controls by hyperoxia, respectively, but they were increased only by 2-fold by dexamethasone. In lung tissues, the contents of DSPC and SP-A were increased by 3- and 2-fold over controls by hyperoxia, respectively. These values in lung tissues in the air-exposed rats were not significantly increased by dexamethasone. In hyperoxia-treated rats, dexamethasone did not significantly affect the relative abundance of the SP-A mRNA level and the contents of DSPC and SP-A in lavage fluids and lung tissues. These results indicate that mechanisms other than increased synthesis of SP-A are involved in hyperoxia-induced SP-A accumulation and that dexamethasone does not affect the abnormal accumulation of pulmonary surfactant induced by hyperoxia.

Animals↗

Pharmacokinetics of pirarubicin in pediatric patients.

The pharmacokinetics of pirarubicin and its active metabolite, doxorubicin, were studied after intravenous administration of pirarubicin (25-45 mg/m2) to ten pediatric patients. The concentration-time curves of pirarubicin in both blood and plasma showed representative biphasic patterns. Pirarubicin concentrations decreased rapidly from 0.5 to 2 h after administration and then decreased slowly until 24 h in all subjects. High concentrations of the metabolite, doxorubicin, were detected at 0.5 h after administration of pirarubicin which decreased gradually until 24 h. The area under the concentration-time curve from 0 to 24 h (AUC0-24) of pirarubicin and doxorubicin in blood were 3-4 times higher than those in plasma, suggesting that these drugs had a high affinity for blood cells. The AUC0-24 ratio of doxorubicin to pirarubicin in plasma was calculated to be 0.441. It might be indicated that not only pirarubicin but also doxorubicin are responsible for the therapeutic efficacy and the incidence of toxicity of pirarubicin. The pharmacokinetics of pirarubicin in pediatric patients was fundamentally similar to that of adults, but it was recognized that considerable interindividual variation in the disposition of pirarubicin and doxorubicin exists.

Adolescent↗

Metabolic fates of L-tryptophan in Saccharomyces uvarum (Saccharomyces carlsbergensis).

The metabolism of L-tryptophan by Saccharomyces uvarum (carlsbergensis) was investigated by simultaneous measuring of fluxes through kynureninase, through transaminases and into protein using L-[methylene-14C] and L-[side chain-2,3-3H]tryptophan. In yeasts cultivated in synthetic medium (S medium), the flux into protein was predominant, closely followed by the flux leading to 2-3H liberation. The proportion of L-tryptophan metabolized via the latter flux increased over 10-fold (75% of total tryptophan metabolized) as the concentration of L-tryptophan was raised from 5 x 10(-5) to 5 x 10(-4) M. L-Tryptophan metabolized via the kynureninase flux was less than 5% of total tryptophan metabolized. In yeast extract-polypepton-glucose medium (YPG medium), more tryptophan was incorporated into protein than in the S medium. Contribution of the kynureninase flux remained very low. Tryptophan metabolism via each flux changed depending on the growth phase. 2-3H liberation was shown to be primarily due to tryptophol synthesis by high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR), indole-3-acetic acid and kynurenic acid also contributing to 2-3H liberation but to a much lesser extent. 2-3H liberation increased dose-dependently at tryptophan concentration higher than 10(-5)M, while the kynureninase flux reached its plateau at 10(-5)M. Formation of tryptophol and indole-3-acetic acid via indole-3-pyruvic acid and indole-3-acetaldehyde with indole aldehyde as a by-product was confirmed using exogenous tryptophan metabolites with indole rings.

Biotransformation↗

Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses.

Nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma. To determine the etiological role of human papillomavirus in inverted papilloma, and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor, we retrospectively analyzed inverted papillomas from 26 patients, 7 of whom had squamous cell carcinoma. We used an immunohistochemical method and molecular pathologic techniques, or dot-blot hybridization of DNA extracted from paraffin-embedded tissues, in situ hybridization, and polymerase chain reaction. Human papillomavirus was detected in 5 of 26 patients (19%), 3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16. The latter 2 patients had inverted papillomas associated with squamous cell carcinoma. We speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas.

Adult↗

Application of bromodeoxyuridine immunohistochemistry to the rat temporomandibular joint.

To detect S-phase cells in the decalcified paraffin-embedded temporomandibular joint (TMJ) tissues of the rat, bromodeoxyuridine (BrdUrd) immunohistochemistry was performed. Percardiac perfusion of 10% EDTA-2Na Tris buffer accelerated the decalcification. The use of the monoclonal antibody to BrdUrd enabled the visualization of the distribution of S-phase cells. This method is practical in studying cell kinetics and the specific proliferation mode of the TMJ.

Animals↗

Metabolism of tryptophan to niacin in Saccharomyces uvarum.

In Saccharomyces uvarum, the effect of metabolic intermediates of the tryptophan-NAD pathway on the niacin-production was investigated. Exogenously added kynurenine and 3-hydroxyanthranilic acid raised the content of total niacin of the cells 2-fold as compared to the control cells, although anthranilic acid and tryptophan were less effective. Tryptophan was taken up into the cells faster than kynurenine, and the intracellular pool of tryptophan was larger than that of kynurenine. Of kynurenine (0.05 mM) added to the medium, 55% went through the transaminase flux (2-H liberation), 20% through the kynureninase flux, but none through the acetyl-CoA flux. As for tryptophan, only 2% went through the kynureninase flux. The products through the transaminase flux were identified as kynurenic acid (85%) and xanthurenic acid. 3-Hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and niacin were also detected. The metabolism of tryptophan via the kynureninase flux reached a plateau above 0.05 mM. The production of kynurenine and kynurenic acid gradually increased above 0.05 mM. Tryptophol was formed in parallel with the amount of tryptophan consumed, while the rate of niacin production increased after glucose and tryptophan were exhausted. Based on the data obtained, a possible regulatory mechanism of the tryptophan-NAD pathway was discussed.

Carbon Radioisotopes↗

Localized necrotizing arteritis. A report of two cases involving the gallbladder and pancreas.

We report two cases of localized necrotizing arteritis, one involving the gallbladder and one involving the pancreas. Both cases were found incidentally in surgically resected specimens. Vascular changes in both cases were similar to those seen in classic polyarteritis nodosa, involving medium-sized muscular arteries characterized by fibrinoid necrosis and panarterial and periarterial inflammations varying from active to resolving stages. Both patients had no constitutional symptoms or underlying serologic abnormalities suggestive of systemic angitis. To our knowledge, pancreas-limited arteritis has not previously been described. Whether these lesions represent an early manifestation of a systemic arteritides syndrome, a variant of polyarteritis nodosa, or a distinct entity should be prudently judged through a long-term follow-up.

Adult↗

[A case of renal cell carcinoma similar to rhabdoid tumor of kidney in an adult; trial of radiation and chemotherapy].

We report a case of sarcomatoid renal cell carcinoma in a 30-year-old woman. The pathological findings indicated renal cell carcinoma (solid sarcomatoid and pleomorphic type) similar to malignant rhabdoid tumor of kidney (MRTK). We treated her with combination chemotherapy (vincristine, adriamycin, cyclophosphamide and actinomycin D) and local irradiation after nephrectomy. The number of bone metastatic foci increased and brain metastasis occurred. However, irradiation was effective on each focus. She died 8 months after the operation caused by brain metastasis. We conclude that sarcomatoid renal cancer is highly malignant and chemotherapy-resistant, but radiation may be partially effective.

Adult↗

[Temporal profile of the superoxide dismutase and the ascorbic acid in focal cerebral ischemia].

It has been proposed that free radical reactions are involved in ischemic brain damage. Since irreversible pathological changes occurs very early phase of the focal ischemia and the ischemic brain edema reaches its peak at about 2 days of ischemia, the free radical reactions must take place before these changes. Superoxide dismutase is a famous enzyme that dismutase superoxide anion, which is believed to be one of the initiator of the free radical reactions. If superoxide anion plays a pivotal role in the genesis of pathological ischemic brain damage and edema, the activity of the enzyme may decrease in the early phase of ischemia. Ascorbic acid is also known to be a scavenger of superoxide anion, and brain tissue contains it in a high concentration. We investigated the changes in superoxide dismutase activity and concentration of reduced ascorbate in focal ischemia. Focal ischemia was produced in rats by permanent occlusion of the left middle cerebral artery. The animals were decapitated 30 minutes, 4, 24, and 48 hours after the operation. Middle cerebral artery territory of each cerebral hemisphere was homogenized and centrifuged with phosphate buffer. The supernatant was divided into two aliquots; one was dialyzed to remove ascorbate and the other was not. The SOD activity was measured by electron-spin-resonance (ESR) spin trapping method, and the ascorbic acid concentration was measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). Protein concentration was measured by Lowry's method. The enzyme activity was expressed as unit/mg protein, and the ascorbic acid concentration was expressed as microgram/g tissue. The SOD activity decreased markedly by dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Expression of smg p25A, a ras p21-like small GTP-binding protein, during postnatal development of rat cerebellum.

Changes in expression and localization of smg p25A, a ras p21-like small GTP-binding protein, in developing rat brain were analyzed in comparison with those of synaptophysin, a well-known synaptic vesicle-specific protein. The smg 25A mRNA was detected in whole brain of rat fetus at 14 days of gestation and its level was increased along with the age and reached the maximum level at postnatal day (P) 20. In postnatal cerebellum, the smg25A mRNA level was also increased age-dependently and the maximum level was observed at P30. Immunoblot analysis with an anti-smg p25A monoclonal antibody (MAb SG-11-7) and an anti-synaptophysin monoclonal antibody (SY 38) showed that expression of both smg p25A and synaptophysin was increased age-dependently in postnatal rat cerebellum. By immunofluorescent cytochemical study with the anti-smg p25A antibody, bright fluorescence was observed in the molecular layer of cerebellum and it was increased in accordance with the cerebellar development. In early postnatal cerebellum, the perikarya of Purkinje cells and the white matter were brightly stained with the antibody, but the fluorescence of these portions was faint in adult cerebellum. The anti-synaptophysin monoclonal antibody also stained the molecular layer of cerebellum but the perikarya of Purkinje cells and the white matter had only a weak immunoreactivity with the antibody irrespective of the age. These results indicate that smg p25A is predominantly present in the nerve terminals and that its amount is increased along with the development of postnatal rat cerebellum. Our results also suggest that smg p25A and synaptophysin have the different kinetics of synthesis, transport, and/or turnover in developing rat cerebellum.

Aging↗

Expression of the smg p25A (a ras p21-like GTP-binding protein) gene in human neuroblastoma cell lines and tumor tissues.

We have examined expression of the smg p25A (a ras p21-like GTP-binding protein) gene in neural crest-derived tumor cell lines and neuroblastoma tissues. The human neuroblastoma cell lines GOTO, IMR-32, NB-1, and SK-N-SH expressed the 1.6-kilobase smg-25A mRNA. SH-SY5Y and SH-IN, variant cell lines with a neuronal phenotype derived from SK-N-SH, expressed much more smg-25A mRNA than did SH-EP1, a variant line with an epithelium-like phenotype also derived from SK-N-SH. The primitive neuroectodermal tumor cell lines SK-N-MC and KU-SN and the Ewing's sarcoma cell lines RD-ES and SK-ES expressed the smg-25A mRNA to a much smaller extent than did neuroblastoma cell lines. Of 15 human neuroblastoma specimens tested, 13 expressed the smg-25A mRNA to various extents. When the relative ratio of the smg-25A mRNA level to the glyceraldehyde-3-phosphate dehydrogenase mRNA level was compared among neuroblastoma tumor tissues, the value was significantly higher in tumors histologically diagnosed as ganglioneuroblastoma. The smg-25A mRNA was not detected in the tissues of Hodgkin's lymphoma, Wilms' tumor, Ewing's sarcoma, or undifferentiated sarcoma of the liver. These results suggest that the smg-25A mRNA level is closely related to the neuronal differentiation state of tumors derived from the neural crest.

Blotting, Northern↗

Chronic maintenance of presynaptic terminals in gliotic hippocampus following ischemia.

Following brief cerebral ischemia, neurons are selectively damaged and die, whereas glial cells and blood vessels survive. This phenomenon of selective vulnerability is well illustrated in the hippocampal CA1 region. Five min of forebrain ischemia in the Mongolian gerbil produced selective neuronal necrosis in the hippocampal CA1 sector. After destruction and loss of CA1 neurons, a remarkable glial reaction (gliosis) was seen. The thickness of the CA1 subfield remained unchanged until 1 month after ischemia and then gradually shrank over several months. Ultrastructural observation of this region revealed persistent maintenance of presynaptic structures. Numerous presynaptic terminals containing synaptic vesicles were scattered throughout the gliotic scar tissue. These presynaptic terminals were apposed to degenerative structures which seemed most likely to be remnants of dendrites. In another group of animals, at one month following ischemic damage in the CA1 sector, the CA3 neurons were destroyed by kainic acid injection. In these animals, numerous degenerating presynaptic boutons were seen in the CA1 sector when fixed 4 days following kainate injection. These results indicate that even in gliotic tissue, presynaptic terminals can survive and maintain their structural characteristics although neuronal cell bodies are almost absent.

Animals↗