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Biomedical subjects

Y Takano

Publications and source records attributed to Y Takano.

At least 307 records · Page 17Linked to original sources
PubMed1993

Apoptosis induced by microtubule disrupting drugs in cultured human lymphoma cells. Inhibitory effects of phorbol ester and zinc sulphate.

The effects of the microtubule disrupting drugs (MDD) vinblastine, vincristine and colchicine on a human lymphoma cell line, BM 13674, were investigated. Twelve hours after administration of vinblastine (10(-3) mg/ml), vincristine (10(-2) mg/ml) or colchicine (10(-2) mg/ml), cell death with the characteristic morphology of apoptosis was observed in 71.6%, 82.2% and 76.9% of the cells respectively. The mode of death was confirmed as apoptotic by the occurrence of internucleosomal DNA cleavage, which was demonstrated by agarose gel electrophoresis. For the purpose of casting light on the mechanism involved, inhibition tests were performed on apoptosis induced by one of these drugs, vinblastine, using a phorbol ester (PDBu), zinc sulphate and cycloheximide. PDBu, an activator of protein kinase C, and zinc sulphate, a putative inhibitor of the endonuclease were thought to be responsible for internucleosomal DNA cleavage; both markedly reduced the induction of apoptosis. The protein synthesis inhibitor cycloheximide, on the other hand, had no inhibitory effect. Moreover, cycloheximide treatment per se enhanced apoptosis. This suggests that new protein synthesis is not required for the execution of vinblastine-induced apoptosis. Such a finding is in accord with recent reports suggesting that the "death program" within many cell types may be primed but unable to proceed due to concomitant production of specific "apoptotic inhibitors". It is suggested that phorbol esters prevent vinblastine-induced apoptosis in the BM 13674 cells by activating one or more of these specific "apoptotic inhibitors", possibly by means of PKC-mediated phosphorylation.

Apoptosis↗
PubMed1993

An immunohistochemical and molecular biological study of c-erbB-2 amplification and prognostic relevance in gallbladder cancer.

Forty-three cases of gallbladder cancer were investigated for c-erbB-2 gene amplification and c-erbB-2 protein over-expression using a combined polymerase chain reaction (PCR) and immunohistochemical approach. Thirty out of 43 cases (69.6%) demonstrated c-erbB-2 gene amplification, the positive rates being 50% and 77.4% for twelve early cancers and thirty-one advanced cancers, respectively (P < 0.05). However, there was no statistically significant correlation between c-erbB-2 gene amplification and histologic grade of differentiation or lymph node metastasis. Fourteen out of 43 cases (32.6%) showed positive immunoreactivity reflecting c-erbB-2 protein over-expression but again no statistically significant correlation was found with grade of differentiation, invasion or lymph node metastasis. Neither the c-erbB-2 gene nor the protein revealed any close relation to prognosis. In contrast, histopathologic findings for histologic grade of differentiation, invasion grade and lymph node metastasis showed good correlations to prognosis and between themselves. In conclusion, while c-erbB-2 gene and protein in gallbladder cancers might be related to invasiveness, they are not applicable as predictive factors for prognosis.

Base Sequence↗
PubMed1993

Protection by sterols against the cytotoxicity of syringomycin in the yeast Saccharomyces cerevisiae.

A brief exposure (ca 20 min) of the yeast Saccharomyces cerevisiae to the phytotoxin syringomycin was sufficient to kill the cell. The protective effect of sterols against this cytotoxicity of syringomycin was investigated. Syringomycin was much more toxic to growing cells than to stationary-phase cells. The cytotoxicity of syringomycin was reduced in an environment containing sterols. Cytotoxicity of syringomycin at 3 micrograms ml-1 (ca 2.5 microM) was completely abolished by the simultaneous presence of 10 microM-cholesterol in the medium. Cholesterol acetate had no protective effect. Ergosterol, sitosterol and stigmasterol also protected against syringomycin, but they were less effective than cholesterol. The protective effect of sterols against the action of syringomycin is consistent with our hypothesis that membrane ergosterol is a critical component for syringomycin-binding as suggested by recent genetic studies.

Bacterial Proteins↗
PubMed1993

Comparative immunohistochemical studies of p53 and proliferating cell nuclear antigen expression and argyrophilic nucleolar organizer regions in pancreatic duct cell carcinomas.

Thirty-eight cases of pancreatic duct cell carcinoma were examined for p53 expression and proliferating cell nuclear antigen (PCNA) by enhanced immunohistochemistry, as well as for changes in numbers of argyrophilic nucleolar organizer regions (AgNORs). Fifteen cases (39.5%) showed p53 overexpression, which tended to increase in proportion to the histopathological grading of malignancy. However, tumor stage and lymph node status were not correlated to p53 overexpression. PCNA labeling index (LI) increased with both histologically malignant grading and pathological stage, but was not correlated with lymph node status. The expression of p53 and PCNA thus did not necessarily reflect the degree of malignant development. In contrast, AgNOR number showed statistically significant correlations with these three indicators of malignancy. A comparative analysis of p53, PCNA LI and AgNOR number showed overexpression of p53 to be correlated to PCNA LI and essentially unrelated to AgNOR number. The present results thus indicate a close relation between p53 and PCNA, while AgNORs appear to be regulated separately from either of them.

Adult↗
PubMed1993

Pathologic analyses of non-overt necrotizing type Kikuchi and Fujimoto's disease.

Twenty-eight cases of non-overt necrotizing type Kikuchi-Fujimoto disease (KF disease, histiocytic necrotizing lymphadenitis) were investigated clinicopathologically, immunohistochemically and electron microscopically in order to analyze the nature of this disease. In addition, investigations to detect the presence of Epstein-Barr virus (EBV) using the polymerase chain reaction (PCR) and in situ hybridization (ISH) were also performed as a high incidence of positive serum immunoreactivity to EBV had been revealed in the cases examined. The clinical features were an equal male to female ratio, mean age of 26 years, mild leukopenia and about 40% association with fever over 38 degrees C. The major particular pathologic features were: (i) varying amounts of nuclear debris in the pathologic areas, identified as apoptosis by electron microscopy; (ii) presence of medium to large sized transformed lymphocytes (immunoblasts), a very small number of them positive for both UCHL1 and L26, and plasmacytoid cells, some of them positive for UCHL1; and (iii) characteristically shaped histiocytes predominant in the pathologic areas, with irregular nuclei and strongly positive for anti-lysozyme and anti-alpha 1-antitrypsin antibodies. Investigations with PCR and ISH revealed a complete absence of EBV in these cases despite excellent results for positive controls. It was therefore considered that EBV was not a causative virus for KF disease.

Adolescent↗
PubMed1993

Human hepatic infarction: histopathological and postmortem angiological studies.

Twenty hepatic infarction cases selected from 5420 consecutive autopsy cases were investigated to clarify the pathogenetic aspects of this disease. Additional postmortem angiological studies of 24 normal human livers obtained at autopsy were also further performed to analyse the effects of blocking vascular structures on lesion development. Seventeen of the 20 cases (85%) were clinically associated with systemic circulatory insufficiency, especially hepato- and/or renal failure. Histopathologically, there was a significantly closer relationship between the location of infarcted regions and portal vein thrombosis than with either hepatic vein thrombosis or hepatic arterial damage. The borders between infarcted regions and surviving hepatic parenchyma were located around central veins, corresponding with the microcirculatory periphery of the portal venous system. Postmortem angiographic studies revealed that hepatic lobuli mainly consist of portal vein branches. Moreover, postmortem embolization studies of six normal livers using glass beads and barium-gelatin injection showed that physical occlusion of portal vein branches produced defects in broad areas of the hepatic parenchyma. Therefore, it is suggested that the development of hepatic infarction principally depends on disturbances of the portal venous system. In addition, systemic circulatory insufficiency, which reduces the intrahepatic blood flow, probably contributes greatly to the development of hepatic infarction.

Adult↗
PubMed1993

Pharmacological profiles of muscarinic receptors in the longitudinal smooth muscle of guinea pig ileum.

We have examined the pharmacological subtypes of muscarinic receptors mediating phosphoinositide hydrolysis and contraction in the longitudinal smooth muscle of guinea pig ileum with the use of muscarinic antagonists. Carbachol increased the formation of 3H-inositol phosphates (IPs) in a dose-dependent manner in both ileal smooth muscle and the frontal cortex of rats. The rank order of muscarinic antagonists for inhibition of IP formation induced by carbachol was 4-DAMP = atropine > pirenzepine > AF-DX 116 in guinea pig ileal smooth muscle. In ileal smooth muscle, the inhibition by the M1 antagonist pirenzepine was about 15 times less than that by atropine. However, in the rat frontal cortex, the inhibition by pirenzepine was only about 3 times less than that by atropine. The inhibitory effect of the M2 antagonist AF-DX 116 was weak in both ileal muscle and the frontal cortex. The M3 antagonist 4-DAMP strongly inhibited carbachol-induced IP formation in ileal smooth muscle. The rank order of muscarinic antagonists for inhibition of contraction induced by 10(-7) M carbachol was atropine > or = 4-DAMP > pirenzepine > AF-DX 116. These results suggest that both IP formation and the contractile response induced by muscarinic agonists are mediated through the muscarinic M3 subtype in guinea pig ileum.

Animals↗
PubMed1993

Histochemical localization and X-ray microanalysis of calcium in the rat submandibular gland: demonstration of possible sites for microlith induction.

Rapidly frozen and freeze-substituted submandibular glands of young female rats were embedded in Epon and processed for histochemical demonstration of calcium with the glyoxal bis (2-hydroxyanil) (GBHA) staining method. GBHA staining of thick Epon sections revealed discrete calcium reactions of moderate intensity in practically every secretory granule but not in other compartments of the acinar cells. The saliva in the excretory duct was also reactive with GBHA and showed a drastic decrease in staining intensity toward the distal segments of excretory ducts with larger diameters. In addition, the duct saliva contained numerous tiny particles that were highly GBHA reactive. Stromal cells and cells lining the excretory duct were totally free of reactions. In the acinar cells, X-ray analysis detected distinct peaks for calcium in secretory granules and smaller ones in the Golgi apparatus, while they were undetectable in the rough surfaced endoplasmic reticulum (RER), implicating post-RER calcium loading in the secretory pathway. Electron-dense deposits in the duct saliva showed distinct peaks both for calcium and phosphorus, though these appeared in the acinar secretory granules and other cytoplasmic regions lacked phosphorus. Our observations thus demonstrated physiological calcium in the intra- as well as extracellular compartments of the submandibular gland, and further confirmed drastic changes in chemical composition along the synthetic and secretory pathways of the saliva, by both histochemical and X-ray microanalytical methods. GBHA staining of calcium combined with X-ray microanalysis is useful for an evaluation of the physiology and histo-pathological changes of the salivary glands associated with initial phases of microliths as well as sialoliths formation.

Aminophenols↗
PubMed1993

Postnatal development of periodontal innervation in rat incisors: an immunohistochemical study using protein gene product 9.5 antibody.

The postnatal development of innervation in the lingual periodontal ligament of rat incisors was investigated by immunohistochemistry using an antibody against protein gene product 9.5 (PGP 9.5), a neuron-specific protein. Immunostaining with the antibody enabled the clear demonstration of chronological alteration in the distribution and maturation of nerve terminals after birth. At 1 day after birth, thick nerve fibers showing PGP 9.5-immunoreactivity first appeared in the loose connective tissue corresponding to the future periodontal ligament, without forming an apparent terminal structure. At 4 days, two portions became distinguishable in the lingual periodontal ligament: alveolus- and tooth-related parts being comparable to those in the adult ligament. The immunoreactive nerve fibers increased in density and appeared to extend more incisally. Those restricted to the alveolus-related part showed ramifications with a small number of expanded or bulbous portions, and terminated among the periodontal fibers. Characteristic dendritic and expanded terminals, similar to Ruffini endings in the adult ligaments, began to occur in the lingual periodontal ligament at 7 days after birth and gradually increased in number until day 11 when the incisal edges emerged in the oral cavity. At approximately 15 days after birth, nerve endings possessing morphological features similar to Ruffini endings in adult rats were recognizable in the entire length of the periodontal ligament. After the eruption of first molars, the periodontal Ruffini endings drastically increased in number, and by the time the occlusion between the first molars was established, became identical in distribution and density to those seen in the lingual periodontal ligament of adult rat incisors. These findings suggest that the mechanical stimuli due to tooth eruption and occlusion might be a prerequisite for the final differentiation and maturation of the periodontal Ruffini endings.

Aging↗
PubMed1993

Sinusoidal vessels in the periodontal ligament of hamster incisors: their distribution, structure and possible function.

Vascular architecture in the periodontal ligament of hamster incisors was investigated by use of vascular casts under a scanning electron microscope (SEM). In addition to ordinary nutrient blood vessels, anastomosing vessels of large caliber developed, surrounding the incisor. From their characteristic configuration, these vessels were regarded as "sinusoids". The plexus of sinusoidal vessels was connected with capillaries in the papillary layer of the enamel organ at the labial periodontal ligament, and with veins penetrating into the alveolar bone on the lingual side. Transmission electron microscopic (TEM) observation showed that the sinusoidal wall was composed of only a thin layer of endothelial cells, lacking a smooth muscular element, and surrounded by densely arranged collagen fibers. Although the frequent association of Ruffini-type nerve endings with sinusoidal vessels was noted, neither direct contact nor specialized structures between these was recognizable. A possible function of the periodontal sinusoids is discussed on the basis of their distribution and ultrastructural evidence.

Animals↗
PubMed1993

Integrin VLA-5 negative primary plasma cell leukemia.

We present a case of primary plasma cell leukemia with Bence Jones proteinuria. After combination chemotherapy, leukemic cells and the urinary levels Bence Jones protein were decreased. Small lytic bone lesions were detected only in the skull. Typical plasma cells were rarely seen in peripheral blood on the hyperleukocytic phase, however they were increased in the advanced stages. The most important diagnostic sign was persistent expression of CD38 antigen on leukemic cells throughout the entire course of the illness and these leukemic cells expressed very late antigen-4 (VLA-4) but not VLA-5.

ADP-ribosyl Cyclase↗
PubMed1993

[Blood level monitoring of FK506 on kidney transplant recipients].

Blood level monitoring of FK506 was performed on 6 kidney transplant recipients. Reproducibility was evaluated on trough and AUC levels in both whole blood and plasma samples. Reproducibility was almost the same degree on both trough and AUC levels and in both whole blood and plasma samples. Trough and AUC levels in whole blood and AUC in plasma were low at the onset of rejection episodes, whereas those were high at the onset of adverse effects by FK506 such as hyperglycemia, hyperkalemia and neurological symptoms. Frequent trough level monitoring is useful to detect kidney transplant rejection and adverse effects by FK506.

Graft Rejection↗
PubMed1993

[A case of lung cancer producing CA19-9 and amylase].

We report a case of lung cancer producing CA19-9 and amylase. A 58-year-old woman was admitted with dry cough and right chest pain. Chest X-ray and CT showed a mass shadow in the right lung field and right pleural effusion. Histological examination of a lung specimen obtained by TBLB and cytological examination of pleural effusion showed adenocarcinoma. The diagnosis of lung adenocarcinoma was made. CA19-9 values in serum and pleural effusion were very high. Amylase value was high in pleural effusion, but that in serum was normal. The amylase isozyme pattern was salivary-type. No abnormality was detected on abdominal CT and ultrasonography. In spite of treatment of the pleural effusion, the patient's condition gradually deteriorated and she died of respiratory failure. Histological examination of lung specimens obtained at necropsy showed moderately differentiated papillary type adenocarcinoma. Immunohistochemically, the tumor cells stained positively for both CA19-9 and amylase. We conclude that the lung cancer produced both CA19-9 and amylase.

Adenocarcinoma, Papillary↗
PubMed1993

Chronic spinal infusion of dexmedetomidine, ST-91 and clonidine: spinal alpha 2 adrenoceptor subtypes and intrinsic activity.

The antinociceptive effect (hot plate test) and behavioral changes produced by the continuous 7-day i.t. infusion of alpha 2 adrenoceptor agonists dexmedetomidine (10 and 3 nmol/hr), clonidine (100 and 30 nmol/hr) and 2-(2,6-diethylphenylamino)-2-imidazoline (ST-91) (30 and 10 nmol/hr) were examined in rats. The highest doses of each agonist produced an equivalent increase in hot plate latency on day 1 of infusion. These effects diminished to near base line by 5 to 7 days. In separate groups, i.t. dose-response curves were obtained with dexmedetomidine, clonidine and ST-91 in groups of rats which had received a 7-day infusion of saline or the equianalgesic concentrations of dexmedetomidine (10 nmol/hr) or ST-91 (30 nmol/hr). Dose-response curves in drug-infused animals showed a right shift as compared to the vehicle-infused rats. Calculation of the ratio of the ED50 values (tolerance ratio: drug vs. control) in animals receiving the continuous infusion of dexmedetomidine vs. saline indicated: 8- (6-12), 36- (19-54) and 1.0- (0.6-1.5) (ratio with 95% Cl) fold rightward shifts of dexmedetomidine, clonidine and ST-91 dose-response curves, respectively. Chronic infusion of ST-91 resulted in 62- (36-127), 22- (13-46) and 0.9- (0.7-1.1) fold rightward shift of the ST-91, clonidine and dexmedetomidine dose-response curves, respectively. Previously, we have shown that dexmedetomidine and clonidine act upon spinal alpha 2 adrenoceptor, which appeared distinguishable from that acted upon by ST-91.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗