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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 235 records · Page 13Linked to original sources

Effect of the angiotensin-converting enzyme inhibitor enalapril on post-transplant erythrocytosis.

Post-transplant erythrocytosis (PTE) is increasingly recognized as a complication of kidney transplantation. In this study we report the effect of the angiotesin-converting enzyme (ACE) inhibitor enalapril on hematocrit (Ht) and erythropoietin in four patients with PTE. Four renal allograft recipients with Ht greater than 51% were studied. Treatment was initiated with enalapril administered orally at a dose of 2.5 mg/day. All the patients had an increase of hemoglobin (Hb) (17.7 +/- 0.64 g/dl), Ht (54.5 +/- 1.29%) and red blood cell count (RBC) (584 +/- 19.2 x 10(4)/microliter). All patients responded to enalapril in 8 weeks with a significant decrease of Hb, Ht, and RBC. In one patient, the downward trend was more rapid and sustained, and treatment had to be discontinued to prevent the development of anemia. Serum erythropoietin showed normal in all four patients and remained unchanged during the study, even after discontinuation of enalapril treatment. Serum creatinine remained relatively stable throughout the study. These results suggest that PTE may not be dependent upon circulating erythropoietin and that enalapril treatment may be an effective treatment of PTE without renal dysfunction.

Adult↗

Assessment of hair cell death using the dye extrusion method.

We examined the usefulness of the dye extrusion method for assessing cochlear hair cell death in guinea pigs. Unilateral temporal bones were incubated in sterile Dulbecco modified Eagle's medium for 1-6 h and then perfused with PBS/0.3% trypan blue to determine hair cell viability. Cells with nuclei stained with trypan blue were assumed to have died. The contralateral temporal bones of each animal were incubated with the same medium for 1-6 h and examined by transmission electron microscopy (TEM). This method revealed that hair cell viability under these conditions was maintained for at most 3 h. After incubation for more than 3 h, hair cell injury began and increased. After 6 h incubation, TEM revealed apoptotic death of outer hair cells. The results with this method agreed with the TEM findings. The dye extrusion method is simple, easy and useful for screening hair cell death in the cochlea under pathological conditions.

Animals↗

Cleavage product from the NO donor NOC-5 and inner ear hair cell damage.

Nitric oxide (NO) is a neurotoxic gas which causes neuronal cell death. NO ototoxicity has also been reported, 1-Hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5), NO donor, was used for studying NO. In this in vitro study, we examined whether NOC-5 and the cleavage products arising from it after production of No have ototoxic effects on the cochlea. The temporal bones of 55 guinea pigs were dissected and incubated in Dulbecco Modified Eagle's Medium (DMEM) with low glucose and 10% foetal bovine serum (FBS) perfused with various concentrations (100, 50, 10, 1 mM, 100 microM) of NOC-5 (pH 7.4) or the same concentrations of N-isopropyl 1-3 propanildiamine (R-NH2). Hair cell death was assessed using trypan blue staining. With NOC-5, percentages of outer hair cell death were 99.2, 98.0, 45.2, 40.5, and 20%, respectively, and percentages of inner hair cell death were 69.3, 70.2, 22.5. 11.1 and 0%, respectively. With R-NH2, percentages of outer hair cell death were 90.3, 81.1, 29.8, 21.0 and 19.3%, respectively, and percentages of inner hair cell death were 61.4, 48.1, 10.2, 5.4 and 0%, respectively. Ultramicroscopic examination showed that hair cell death was necrotic. Although NOC-5 is useful for study of NO, its cleavage products are also ototoxic.

Animals↗

Induction of macrophage exudation in the inner ear by OK432 treatment.

OK432, a heat- and penicillin-treated lyophilized powder of a low virulent Su strain of Streptococcus pyogenes, was injected into the perilymphatic space of guinea pigs in order to determine the kinetics of exudation of inflammatory cells into the cochlea over a 7-day period. OK432 induced exudation of many neutrophils and Asialo GM1-positive cells into the scala tympani. The numbers of these cells peaked on the first day after OK432 treatment, and then gradually decreased. Four days after treatment very few of either of these types of cells were observed in the scala tympani. Asialo GM1-positive cells were confirmed to be activated macrophages. In ears treated with physiological saline or with the additive included in OK432 in control studies, no notable changes in the inner ear were recognized. These findings suggest that the inner ear can undergo induction of macrophage rapidly exudation by OK432 treatment as has previously been observed for other organs.

Animals↗

Surgical treatment of cancer extending from the retromolar fossa to the masticator space.

Cancer extending from the retromolar fossa to the masticator space with neck metastasis (T4N2M0, Stage IV) was surgically removed en bloc by maxillectomy using a mandibular swing technique. This approach allowed a wide surgical view and was useful as handling the external and internal pterygoid muscles and upper neck dissection could be combined. Though there have been several surgical approaches to the masticator space, in the case of tumors which are commonly malignant there, this approach is useful and satisfactory.

Carcinoma, Squamous Cell↗

Study of tuberculosis in the field of otorhinolaryngology in the past 10 years.

Over the 10 years from 1988 to 1997, a total of 18 cases of tuberculosis of the head and neck (8 of the cervical lymph node, 5 of the larynx, 2 of the salivary glands, and 1 each of the hypopharynx, tongue and middle ear) were diagnosed in our department. Four cases were diagnosed in 1996 and 8 in 1997, indicating a rapid increase over these 2 years. Definitive diagnosis was based on histopathological examination in 14 cases, detection of M. tuberculosis in 1 case and exclusion diagnosis, mainly using the tuberculin skin test, in 3 cases. The length of time from the first examination to obtaining a definitive diagnosis was 14.2 +/- 6.5 days in five subjects in whom tuberculosis was suspected from the beginning or in whom tuberculosis was suggested by the physician in making a differential diagnosis, 25.3 +/- 17.2 days in the group in whom malignant tumour was suspected and 64.3 +/- 57.3 days in other cases. Although no significant difference was found (p = 0.077), the length of time until diagnosis tended to be shorter in the cases that were suspected of having tuberculosis from the beginning. Family history and past history of tuberculosis, contact with a tuberculous patient and abnormal findings at chest X-ray were examined as background factors, and some of these were present in nine out of the 18 cases. In the five cases diagnosed in the early stage, some of the background factors were found in four cases. However, no significant difference in the time until definitive diagnosis was found between the groups with or without background factors in all cases (p = 0.675). These results suggest the importance of considering tuberculosis when performing differential diagnoses.

Adolescent↗

Apoptotic cell death in Kikuchi's disease: a TEM study.

The pathogenesis of Kikuchi's disease (Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis) remains unclear. However, some previous studies have suggested that a disorder in cellular immunity is responsible for this disease, and apoptotic cell death appears to be the principal finding in the histogenesis of this disease. In the present study, a lymph node from a female patient with Kikuchi's disease was examined by transmission electron microscopy (TEM). TEM revealed specific morphological features of apoptotic cells, such as nuclear chromatin condensation and fragmentation along the nuclear membrane with intact organelles, and the presence of histiocytes phagocytosing karyorrhectic debris (apoptotic bodies) in areas affected by Kikuchi's disease. Although neither the role nor the trigger of apoptosis in Kikuchi's disease has been clearly determined, our findings show that apoptotic cell death clearly plays a role in the pathogenesis of Kikuchi's disease.

Adult↗

[Two cases of cerebral aneurysm detected after recanalization of the middle cerebral artery].

Two cases of aneurysm incidentally detected after recanalization of middle cerebral artery (MCA) occlusion are reported. Patient 1 was a 62-year-old male with sudden onset of left hemiparesis. We performed emergent intravascular surgery. The initial cerebral angiography revealed occlusion at the M1 portion of the right MCA. After partial recanalization with a microcatheter, carotid angiography revealed a right M1-M2 junction aneurysm. Due to the risk of aneurysmal rupture, the thrombolytic procedure was stopped. Follow up angiography after 1 month revealed complete recanalization of the right MCA and a persistent aneurysm. Patient 2 was a 65-year-old male with left hemiparesis. The initial cerebral angiography revealed occlusion at the M1 portion of the right MCA. After 1 month follow-up cerebral angiography revealed spontaneous recanalization of the right MCA and an incidental aneurysm at the M1-M2 junction. Neck clipping of the aneurysm was performed. When using a microcatheter or microballoon catheter to treat arterial occlusion, surgeons should consider the possibility of a rupture of a hidden aneurysm.

Aged↗

[Autoantibodies to heparin polysaccharides bind to vascular endothelial cells].

Heparan sulfate, a glycosaminoglycan component of vascular endothelial proteoglycans, provides the anticoagulant functions associated with heparin on the endothelial cell surface. We have demonstrated the presence of spontaneous occurring antibodies to heparin polysaccharides (HPS) in humans. Elevation of serum anti-HPS antibodies were closely associated with the prevalence of thrombosis or fetal loss in patients with autoimmune disease. Affinity purified anti-HPS antibodies inhibited heparin dependent formation of thrombin-antithrombin III complexes. In order to further analyze these autoantibodies, a murine IgG monoclonal anti-HPS antibody, designated H16, was generated. H16 mAb specifically bound to heparin, heparan sulfate and human umbilical vascular endothelial cells (HUVEC). The binding of H16 mAb to HUVEC was specifically inhibited by heparin. Further, H16 mAb inhibited the binding of antithrombin III to heparin in a dose dependent manner. These results indicate that this mAb could recognize antithrombin III-binding sites on vascular endothelial heparan sulfate, leading to procoagulant states through the inhibition of heparin/heparan sulfate dependent anticoagulant process.

Abortion, Spontaneous↗

Light-induced resetting of a mammalian circadian clock is associated with rapid induction of the mPer1 transcript.

To understand how light might entrain a mammalian circadian clock, we examined the effects of light on mPer1, a sequence homolog of Drosophila per, that exhibits robust rhythmic expression in the SCN. mPer1 is rapidly induced by short duration exposure to light at levels sufficient to reset the clock, and dose-response curves reveal that mPer1 induction shows both reciprocity and a strong correlation with phase shifting of the overt rhythm. Thus, in both the phasing of dark expression and the response to light mPer1 is most similar to the Neurospora clock gene frq. Within the SCN there appears to be localization of the induction phenomenon, consistent with the localization of both light-sensitive and light-insensitive oscillators in this circadian center.

Animals↗

Immunohistochemical analysis of progesterone receptor and Ki-67 labeling index in astrocytic tumors.

BACKGROUND: Intracranial tumors such as meningiomas express steroid hormone receptors but little is known regarding progesterone receptor (PR) in astrocytic tumors. The authors evaluated expression of PR in 86 astrocytic tumors in relation to tumor proliferative potential. METHODS: Paraffin embedded tumor sections were stained with polyclonal antiprogesterone antibody by the peroxidase-antiperoxidase method and with monoclonal MIB-1-Ki-67 antibody by avidin-biotin complex immunohistochemistry. RESULTS: Sixty-three of the 86 astrocytic tumors (73%) showed positive PR immunoreactivity. PR expression was observed in 4 of 9 pilocytic astrocytomas, 13 of 24 Grade 2 astrocytomas, 15 of 20 anaplastic astrocytomas, and 31 of 33 glioblastomas. In addition to the tumor cells, cells of microvascular endothelial proliferation and the smooth muscle of tumor vessel walls were frequently PR positive. Glioblastomas had a significantly higher percentage of PR positive cells compared with anaplastic (P < 0.0008) and low grade (P < 0.0001) astrocytomas. Patients with PR positive astrocytomas were of an older age than patients with PR negative astrocytomas (48.71 +/- 21.95 years vs. 37.09 +/- 24.69 years; P < 0.04). The mean Ki-67 labeling index (LI) was significantly higher in the high grade (3-4) astrocytomas compared with low grade (1-2) astrocytomas (P < 0.0001). PR positive astrocytic tumors had higher Ki-67 LI than PR negative tumors. PR expression was not correlated with tumor recurrence and patient survival. CONCLUSIONS: The current study suggests that PR in the astrocytic tumors correlates with histologic grade and PR may participate in the growth of these tumors and tumor angiogenesis. The measurement of PR in these tumors may indirectly represent tumor growth potential.

Adolescent↗

Concurrent blockade of beta-adrenergic and muscarinic receptors suppresses synergistically long-term potentiation of population spikes in the rat hippocampal CA1 region.

The muscarinic acetylcholine receptor antagonist scopolamine, but not the beta-adrenoceptor antagonist propranolol or atenolol, suppressed tetanus-induced long-term potentiation (LTP) of population spikes in the rat hippocampal CA1 region. When scopolamine was coapplied with propranolol or atenolol, a synergistic effect in preventing LTP generation was observed. On the other hand, the coapplication of scopolamine and atenolol failed to affect tetanus-induced LTP of field EPSP. These findings suggest that cooperative mechanisms via muscarinic and beta-adrenergic receptor activation might contribute to LTP induction in terms of the EPSP-spike potentiation, i.e., an increase in the excitability of hippocampal CA1 pyramidal cells after tetanic stimulation, but are independent of the tetanus-evoked potentiation of a synaptic component.

Acetylcholine↗

Purification and characterization of the protein kinase encoded by the UL13 gene of herpes simplex virus type 2.

The proteins encoded by the UL13 genes of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) have been predicted to be protein kinases. To identify the UL13 gene product, we have raised a rabbit polyclonal antiserum against a His.Tag-HSV-1 UL13 fusion protein. The antibody specifically reacted with the 60-kDa UL13 fusion protein expressed in Escherichia coli and also recognized 56- to 57-kDa late proteins in nuclear fractions of HSV-1- and HSV-2-infected cells. On the other hand, novel casein kinase activity was induced at the late stage of infection when Vero cells were infected with HSV-1 and HSV-2. The induction of the activity was most prominent in the nuclear fractions of HSV-2-infected cells and therefore we purified the protein kinase (PK) from the nuclear extracts by successive column chromatography (phosphocellulose, DEAE-cellulose, and hydroxyapatite) using casein as an exogenous substrate. The final preparation of the enzyme contained a single major protein with an apparent molecular weight of 56 kDa which was specifically reacted with the UL13 antiserum. The PK activity was optimal in the absence of NaCl and at relatively high pH. Acidic proteins such as casein and phosvitin were efficiently phosphorylated by the PK. A basic protein, protamine, which is the best substrate for the HSV-2 US3 PK, was not detectably phosphorylated but histone was a relatively good substrate for the UL13 PK. Phosphoamino acid analysis revealed that the PK phosphorylated serine and threonine but not tyrosine. Moreover the enzyme was found to be highly resistant to heparin, a potent inhibitor of casein kinase II (CK II) and also resistant to CK I-7, a synthetic inhibitor of CK I, but very sensitive to a bioflavonoid quercetin. These results indicate that the HSV-2 UL13 PK had unique catalytic properties different from those of cellular CK I, CK II, and the viral PK encoded by the US3 gene. We have also determined the complete nucleotide sequence of the HSV-2 UL13 gene. The overall amino acid homology between the HSV-2 and HSV-1 UL13 PKs was 85.9% and the homology was highly conserved in the C-terminal region.

Amino Acid Sequence↗

Effect of the chimeric soluble granulocyte colony-stimulating factor receptor on the proliferation of leukemic blast cells from patients with acute myeloblastic leukemia.

The biological roles of the soluble granulocyte colony-stimulating factor (G-CSF) receptor, which arises as a result of alternative RNA splicing, are as yet unknown. In this study, we examined the in vitro effect of a chimeric protein composed of the extracellular region of a murine G-CSF receptor and the human IgG1 Fc region because a human natural soluble G-CSF receptor was not available. First, we found that this chimeric soluble G-CSF receptor could inhibit the biological activity of G-CSF on normal bone marrow colony formation. Because G-CSF also plays an important role in the proliferation of leukemic blast cells, we next examined the effect of the soluble G-CSF receptor on leukemic blast colony formation in 10 acute myeloblastic leukemia cases. Although G-CSF stimulated the proliferation of leukemic progenitor cells to form leukemic blast colonies, the chimeric soluble G-CSF receptor completely inhibited this stimulatory effect. Furthermore, the chimeric soluble G-CSF receptor also inhibited spontaneous leukemic blast colony formation in two cases. Because a high concentration of G-CSF was observed in the supernatants of leukemic blast cells from these two cases, it seems likely that the soluble G-CSF receptor cut off the autocrine growth mechanism of leukemic blast cells mediated by G-CSF. These findings suggest the possibility that the soluble G-CSF receptor could be used in a clinical application for acute myeloblastic leukemia patients in the future.

Animals↗

Decreased level of light-induced Fos expression in the suprachiasmatic nucleus of diabetic rats.

We assessed light-induced Fos-immunoreactive cells in the suprachiasmatic nucleus of diabetic rats. The number of Fos-immunoreactive cells significantly decreased in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats as compared with control Long-Evans Tokushima Otsuka (LETO) rats. In contrast there was no decrease in the number of Fos-immunoreactive cells in young OLETF rats which have not yet developed diabetes. Two months after the administration of streptozotocin (STZ) to Wistar rats, the number of Fos-immunoreactive cells significantly decreased, although 1 week after the administration of STZ, the number had not yet changed in these STZ-induced diabetic rats. These results suggest that chronic diabetic (hyperglycemic) conditions may affect the light entraining responses in the suprachiasmatic nucleus (SCN).

Animals↗

The involvement of calmodulin and Ca2+/calmodulin-dependent protein kinase II in the circadian rhythms controlled by the suprachiasmatic nucleus.

We investigated the involvement of calmodulin and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the photic entrainment of circadian rhythms using calmodulin inhibitors such as calmidazolium (CMZ) and trifluoperazine (TFP), and a CaMKII inhibitor, KN-62, in rats. Fos expression in the suprachiasmatic nucleus (SCN) of rats induced by photic stimulation (300 lux, 1 h) during the early subjective night of the rats was inhibited by treatment with CMZ (10 mg/kg i.p.) or TFP (20 mg/kg i.p.) 30 min before photic stimulation. With respect to the neuronal firing rate in the rat SCN slice, KN-62 and CMZ application during the early subjective night attenuated the glutamate (10 microM)-induced phase shift. The present results suggest that calmodulin and CaMKII are involved in the photic entrainment mechanism in the rodent SCN.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗