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Biomedical subjects

K Shibuya

Publications and source records attributed to K Shibuya.

At least 163 records · Page 9Linked to original sources
PubMed1995

Induction of metallothionein synthesis in transplanted murine tumors by X irradiation.

Although recent studies have shown that radiation can induce metallothionein (MT) synthesis in normal tissues, the induction of tumor MT synthesis by irradiation has not been reported. We examined the accumulation of MT in the Meth-A tumor (mouse fibrosarcoma cells) transplanted into mice exposed to whole-body X irradiation. In the present study, the MT content in the tumor cells was increased by X irradiation in a dose-dependent manner. The MT level induced in the tumor cells by X irradiation was elevated not only after a single exposure but also after repeated exposures. Several studies have shown that MT is one of the important cellular factors in resistance to various anticancer drugs and ionizing radiation. Thus our results suggest that the radiation-induced MT in the tumor cells may have to be taken into consideration when designing protocols for radio- and chemotherapy.

Animals↗
PubMed1995

[Primary varicella pneumonia with respiratory failure].

Varicella pneumonia is a rare but serious and occasionally fatal complication of infection with varicellazoster. A 40-year-old man was admitted to our hospital with fever, eruptions, dyspnea, and severe hypoxemia. A chest X-ray film showed diffuse nodular infiltrative shadows in both lung fields. Transbronchial lung biopsy was done, and examination of the specimen revealed an organizing exudative reaction in the alveolar spaces, as well as interstitial inflammation. Primary varicella pneumonia was diagnosed on the basis of family history, typical eruptions, high titer of antibody against varicellazoster virus, and pathological findings. The patient was treated with methylprednisolone, antibiotics, acyclovir, and immunoglobulin. The skin eruptions and disturbances of gas exchange and diffusion resolved in about one week, but the infiltrative shadows on chest X-ray films remained for more than eight weeks.

Acute Disease↗
PubMed1994

Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2.

Interleukin-2 is an autocrine growth factor for T cells which also activates other cells including B cells and natural killer cells. The subunits of the interleukin-2 receptor (IL-2R) lack intrinsic enzymatic activity, but protein tyrosine phosphorylation is a critical event following ligand binding and src family kinases, such as Lck, are known to be activated by IL-2 (refs 5-9). However, IL-2 signalling can occur in the absence of receptor interaction with Lck, suggesting that other protein tyrosine kinases might be important. Here we report that a new member of the Janus family of kinases (Jak-3) is coupled to the IL-2R in human peripheral blood T cells and natural killer cells.

Cell Line↗
PubMed1994

Biological behaviour and morphological characteristics of a transplantable tumour (MM-KMY) derived from a malignant meningioma in an F344 rat.

A subcutaneously transplantable meningeal tumour (MM-KMY) was derived from a spontaneous malignant meningioma which developed in the cerebellar meninges of a female F344 rat. MM-KMY was subjected to 25 serial passages in syngeneic male and female rats. The transplants grew in 8 weeks into a nodule with an average diameter of 5.7 cm and average weight of 125.2 g. MM-KMY possessed large cysts containing fluid and necrotic tissue. Metastases frequently occurred in the lungs of MM-KMY-bearing rats. Histologically, both the original tumour and MM-KMY consisted of round to fusiform neoplastic cells of varying size, with nuclear pleomorphism. Mitotic figures occurred frequently. MM-KMY cells were positive for vimentin. Ultrastructurally, the cells showed desmosome-like structures, interdigitating processes and cytoplasmic intermediate filaments, suggesting an arachnoid cell origin. Abnormal accumulations of hyaline droplets in renal tubular epithelial cells were frequently observed in MM-KMY-bearing rats, suggesting overload of low molecular proteins in the renal tubules. The droplets gave a faint immunoreaction for lysozyme. The relation between the appearance of renal tubular hyaline droplets and the growth of MM-KMY remains to be determined. MM-KMY may prove useful for studying the biological behaviour and morphogenesis of meningeal tumours.

Animals↗
PubMed1994

Morphology of spontaneous Harderian gland tumors in aged B6C3F1 mice.

Spontaneous Harderian gland tumors in B6C3F1 mice were found in 18 (3.1%) (one male had bilateral tumors) of 589 males and 18 (3.0%) of 609 females. The tumor-bearing mice ranged in age from 73 to 109 weeks. These tumors comprised 32 adenomas (86.5%), four adenocarcinomas (10.8%) and one pleomorphic tumor (2.7%); the adenomas were classified, based on the growth patterns, into 17 papillary, nine cystic papillary, five acinar and one cystic types. Two adenocarcinomas grew papillary and invaded surrounding tissues, and the other two grew acinously. The pleomorphic tumor consisted of pleomorphic cells some of which had a keratin-positive epithelial feature and acini lined by atypical epithelial cells.

Adenocarcinoma↗
PubMed1993

Enrichment of interleukin-2-responsive natural killer progenitors in human bone marrow.

Natural killer (NK) cells can be cultured in interleukin-2 (IL-2)-containing medium from selected human bone marrow (BM) cells obtained after the elimination of mature T and NK cells. To isolate and characterize IL-2-responsive NK progenitors in the selected BM cells, we investigated the expression of IL-2 receptors (IL-2R) on these cells. Neither CD25 (IL-2R alpha) nor IL-2R beta antigen was observed on the selected BM cells before culture. However, CD25+ cells without detectable levels of IL-2R beta antigen appeared 24 hours after culture in IL-2-containing medium. Cells were sorted from each fraction of the selected BM cells 24 hours after culture after staining with anti-CD33, anti-CD34, and anti-CD25 monoclonal antibodies. The generation of NK cells (CD3- CD56+ cells) and NK activity were observed only from the CD33-/CD34-/CD25+ cell fraction after culture in IL-2-containing medium. The frequency of IL-2-responsive NK progenitors relative to the fraction was 1/231 (95% confidence range, 1/156 to 1/289), which corresponded to the frequency relative to the total number of selected BM cells when the frequency relative to the CD33-/CD34-/CD25+ cell-fraction was converted according to the percentage of these cells in the total number of selected BM cells. These results indicated that IL-2-responsive NK progenitors were enriched in the CD33-/CD34-/CD25+ cell fraction.

Bone Marrow↗
PubMed1993

Biological behaviour and morphological characteristics of a transplantable tumour derived from a uterine smooth muscle tumour in the F344 rat.

A subcutaneously transplantable tumour (SMT-Y) was established from a smooth muscle tumour arising from the uterus of a female F344 rat. SMT-Y was serially passaged by subcutaneous implantation into syngeneic female rats up to the 15th generation, but transplantation failed in males. The rat with the primary uterine tumour also had mononuclear cell leukaemia (MCL), and MCL cells grew concurrently in implanted rats. At passage five, MCL cells were eliminated from transplants by implanting the central part of an SMT-Y nodule, consisting only of neoplastic smooth muscle cells. SMT-Y at passages six to 15 was examined biologically and morphologically. The primary tumour and SMT-Y tumours consisted mainly of interlacing fascicles of elongated and fusiform neoplastic smooth muscle cells with abundant cytoplasm. Occasional cells showed nuclear atypia. Mitosis counts per 10 high-power microscopic fields in the primary tumour and SMT-Y ranged from 11 to 36. Neoplastic cells reacted positively for desmin, muscle actin and myosin, but not for myoglobin. Electron microscopy revealed cytoplasmic myofilaments with oval dense bodies. These findings suggested a smooth muscle origin of SMT-Y and it was regarded as a leiomyosarcoma by the criteria for human uterine smooth muscle tumours. Despite the malignant histological features, SMT-Y grew slowly into a large nodule, with an average diameter of 5 cm and average weight of 81 g, 24 weeks after transplantation. Neither invasive tumour growth nor metastases were observed in SMT-Y-bearing rats.

Animals↗
PubMed1993

Induction of Fc gamma R-III (CD16) expression on neutrophils affected by paroxysmal nocturnal haemoglobinuria by administration of granulocyte colony-stimulating factor.

The inducibility of glycosyl-phosphatidylinositol (GPI)-anchored proteins on affected paroxysmal nocturnal haemoglobinuria (PNH) neutrophils (PMN) after both in vitro and in vivo stimulation was investigated. Fc gamma R-III (CD16), decay-accelerating factor (DAF/CD55) and 20 kD homologous restriction factor (HRF20/CD59) were demonstrated to be concurrently deficient on unstimulated defective PNH PMN. Upon in vitro stimulation with either N-formyl-methionyl-leucyl-phenylalanine (fMLP), zymosan-activated serum (ZAS), or recombinant human granulocyte colony-stimulation factor (G-CSF), neither CD16 nor CD55 expression was induced on defective PNH PMN. G-CSF was administered to two patients with PNH when their conditions were complicated by bacterial infections, or to prevent infections associated with the extraction of teeth or cataract surgery. CD16 expression was induced on the defective PNH PMN in both cases during the administration of G-CSF, but the expression of CD55 and CD59 was not. CD16, induced on the defective PNH PMN during the administration of G-CSF, was phosphatidylinositol-specific phospholipase C (PIPLC)-sensitive, implying that it had GPI-linkage to the membranes. The patients treated with G-CSF recovered from infection or evaded infection. These observations suggest that a deficiency of GPI-anchored proteins is not always seen in defective PNH blood cells, at least under certain stimulation conditions.

Antigens, CD↗
PubMed1993

Multicystic peritoneal mesothelioma in a Fischer-344 rat.

A spontaneous multicystic peritoneal mesothelioma was detected in a 108-wk-old male Fischer-344/DuCrj rat. Grossly, a tumor containing numerous, semi-transparent, variously sized, thin-walled cysts was found on the splenic serosal surface. Microscopically, each cyst was surrounded by variable amounts of loose connective tissue. The luminal and free surfaces of the cysts were covered by a single layer of flattened or cuboidal mesothelial cells. No metastases were detected in any of the other organs. Diagnosis was supported by immunohistochemistry and ultrastructural features.

Aging↗
PubMed1993

Synthesis and antiarrhythmic activity of disubstituted phenylpyridine derivative.

A series of disubstituted phenylpyridine derivatives was synthesized and their antiarrhythmic effects against chloroform-induced ventricular arrhythmias in mice were examined. Among them, 2- and 3-[2-(3-aminobutyramido)-4-(2,2,2-trifluroethoxy)phenyl]pyri dines (23h, 24h) and 3-[2-(3-aminobutyramido)-4-ethoxyphenyl]pyridine (24i) showed potent antiarrhythmic activity. They had approximately twice the potency of mexiletine (III). Compound 24i was selected from this series as a candidate for further development; it was found to have a class I B electrophysiological character and to show a slow kinetic rate-dependent block (RDB) of the sodium channel in cardiac muscle.

Animals↗
PubMed1993

Unilateral atrophy of the optic nerve associated with retrograde and anterograde degenerations in the visual pathways in Slc: Wistar rats.

Unilateral degenerative atrophy of the optic nerve (ON) occurred in 6 of 80 male and 4 of 80 female Slc: Wistar rats. Two of these cases completely lost the intracranial portion of the unilateral ON and the remainder had the small ON. The optic disc and ON were located histologically in the posterior pole of the eyeball of 2 rats with no intracranial ON. ON lesions in all cases were characterized by a reduced number of axons with a small number of myelinated axons and marked astrogliosis. There were also swelling, fragmentation and spheroid formation of axons, as well as thickening of the connective tissue sheaths and vessel walls in the ON. One side of the optic chiasma and optic tract contralateral to the affected ON reduced in volume, became degenerated and were accompanied by gliosis. Focal or diffuse degeneration of the retina was observed in the eyeballs with affected ON. Retinal ganglion cells decreased in the number showing chromatolysis. These retinae became thin and developed degeneration of both inner and outer portions with sclerotic changes in the retinal vessels. The ophthalmic and ciliary arteries in the eyeballs with affected ON often developed proliferative or occlusive endoarteritis, suggesting that retinal lesions may have resulted not only from axonal degeneration in the ON but also from ischemia. Histologic lesions suggestive of transneuronal degeneration were found in the contralateral lateral geniculate body and rostral colliculus. Based on the data presented, it was presumed that a primary lesion may have been induced in the ON by a circulatory disturbance and followed by retrograde and anterograde degenerations in the visual pathways.

Animals↗
PubMed1993

Deficiency of glycosyl phosphatidylinositol-anchored proteins in polymorphonuclear leukocytes from patients with paroxysmal nocturnal hemoglobinuria with low-grade hemolysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder characterized by the deficiency of glycosyl phosphatidylinositol (GPI)-anchored proteins in blood cell membranes. We experienced a patient with PNH whose grade of hemolysis was reduced during the course of the disease. An analysis of the expression of GPI-anchored proteins on blood cells revealed typical PNH defects in polymorphonuclear leukocytes (PMN), but not in red blood cells (RBC). Accordingly, we investigated the expression of CD59 on RBC and of CD59 and CD16 on PMN in PNH patients, using immunofluorocytometry. We examined the cells of 8 PNH patients with different grades of hemolysis. PNH-affected PMN deficient in CD16 and CD59 were clearly demonstrated in every patient, including those with low-grade hemolysis. We conclude that demonstration of PNH-affected PMN deficient in GPI-anchored proteins has diagnostic values even in PNH patients with low-grade hemolysis.

Aged↗
PubMed1993

Preparation and characterization of porous apatite ceramics coated with beta-tricalcium phosphate.

Hydroxyapatite (Ca10(PO4)6(OH)2; HA) is one of the most biocompatible materials with bones, and porous HA is promising bone substitute materials for clinical applications. While there are reports that beta-tricalcium phosphate (Ca3(PO4)2; TCP) has higher resorbability than HA when the material is implanted in a bone defect. In the present study, porous HA coated with beta-TCP was prepared by our unique method. The porous HA of about 60% porosity with interconnecting pore structure was soaked in diammonium hydrogen phosphate solution, and then the HA was sintered at 900 degrees C for 3 h. beta-TCP was revealed by X-ray diffractometry on the surface of porous HA. It was possible to control the content of surface-formed beta-TCP arbitrary by varying the concentration of the solution. The obtained HA coated with 33 wt% beta-TCP (33TCP) had about 60% open porosity with the pore size from 150 to 400 microns. The average compressive strength of this porous ceramics was 17.5 MPa. Surface coated HA with beta-TCP deprived of the brittleness in handling. The weight of HA implanted into muscles was increased obviously at 4 weeks because of formation of carbonate hydroxyapatite on the surface of HA. The weight of 33TCP was scarcely changed up to 12 weeks, but the weight tended to increase at 24 weeks. The carbonate hydroxyapatite was not formed on 33TCP at 4 weeks, but formed on it at 24 weeks. Therefore beta-TCP coated porous HA behaved like beta-TCP initially after implantation, and then behaved like HA.

Animals↗
PubMed1993

Technetium-99m(V)dimercaptosuccinic acid uptake in intra-abdominal massive deposit of amyloid protein.

Technetium-99m(V)dimercaptosuccinic acid (DMSA) scintigraphy was performed in two patients with pathologically confirmed primary amyloidosis. Both patients had tumor-like deposits of AL-type amyloid in the abdomen. Marked uptake of the tracer by the amyloid deposits was noted. Technetium-99m-(V)DMSA scintigraphy appears to be useful in detecting the distribution of amyloid deposits and in determining the appropriate site for biopsy.

Abdomen↗
PubMed1992

Decay-accelerating factor functions as a signal transducing molecule for human monocytes.

Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol-anchored membrane protein that protects cells from damage by autologous complement activation. Of the four mAb against DAF prepared in our laboratory, 1C6 completely blocked DAF function, whereas 5B2 partially blocked it. Using these mAb, we investigated whether human monocytes were activated via DAF molecules. When monocytes were incubated with 1C6 alone, glucose was consumed in significant amounts and phagocytosis of latex beads was enhanced, indicating that the monocytes had been activated. However, 1C6 did not enhance the production of monokines, TNF-alpha, and IL-1 alpha and -beta. The F(ab')2 fragment of 1C6 also activated monocytes, whereas 5B2 and the Fab fragment of 1C6 could not. To further examine monocyte activation, these cells were treated with phosphatidylinositol-specific phospholipase C. Increased glucose consumption and enhanced phagocytic activity by 1C6 were considerably reduced in monocytes treated with phosphatidylinositol-specific phospholipase C. In addition, we found that 1C6 stimulated the generation of inositol trisphosphate. These results demonstrate that the signal transmitted via the DAF molecule is capable of stimulating monocytes.

Antibodies, Monoclonal↗
PubMed1992

Morphological characteristics of a transplantable nephroblastoma (NB-Y) in F344 rats and the relation of tumour growth to hyper-reninaemia in NB-Y-bearing rats.

A transplantable tumour, designated NB-Y, was established from a spontaneous nephroblastoma in an F344 rat. NB-Y was serially passaged in syngeneic rats by subcutaneous implantation up to the 49th generation. The transplants grew into nodules with an average diameter of 5 cm and average weight of 92.9 g 4 weeks after implantation. The primary tumour and NB-Y consisted mainly of sheets or clusters of undifferentiated blastemal cells, which reacted immunohistochemically for vimentin but not for keratin. Renin-containing cells were observed in the small blood vessel walls within the primary tumour, but neoplastic cells of both primary tumour and NB-Y failed to stain for renin. Plasma renin activity was significantly higher (40.7 ng per ml per h) in transplanted rats 4 weeks after implantation compared with non-transplanted controls (28.0 ng per ml per h). Hyperplastic juxtaglomerular cells were often observed in rats bearing NB-Y. Sinusoidal dilatation was present in the liver, adrenal glands, pituitary gland and bone marrow of recipients, suggesting abnormal blood flow provoked via the renin-angiotensin system. The present study revealed the development of hyper-reninaemia in NB-Y-bearing rats, but its pathogenesis remains unknown.

Anemia↗
PubMed1992

Clinical experience in using a new type of nasal prong for administration of N-CPAP.

Nasal continuous positive airway pressure (N-CPAP) has been used in infants with decreased lung compliance for increasing the functional residual capacity (FRC), decreasing the work of breathing and improving the PaO2/PAO2 (arterial-alveolar PO2 ratio) without intubation. However, the currently available nasal prongs for administration of N-CPAP have presented some problems in fixation, and lesions to the nasal septum or nostrils might be induced by aggressive pressure intended to fix them. We would therefore like to report our experience in using a new type of nasal prong for administration of N-CPAP therapy. The nasal prongs we used were provided by Dr. Wung of Columbia University in New York, who first designed them, and have been used safely, effectively and without any complications.

Apnea↗