Biomedical subjects

T Manabe

Publications and source records attributed to T Manabe.

At least 271 records · Page 15Linked to original sources

PubMed1994

Release of adenosine by activation of NMDA receptors in the hippocampus.

Adenosine is present in the mammalian brain in large amounts and has potent effects on neuronal activity, but its role in neural signaling is poorly understood. The glutamate receptor agonist N-methyl-D-aspartate (NMDA) caused a presynaptic depression of excitatory synaptic transmission in the CA1 region of guinea pig hippocampal slices. This depression was blocked by an adenosine A1 receptor antagonist, which suggests that activation of the NMDA subtype of glutamate receptor raises the concentration of extracellular adenosine, which acts on presynaptic inhibitory A1 receptors. Strong tetanic stimulation caused a heterosynaptic inhibition that was blocked by both NMDA and A1 receptor antagonists. Enkephalin, which selectively inhibits interneurons, antagonized the heterosynaptic inhibition. These findings suggest that synaptically released glutamate activates NMDA receptors, which in turn releases adenosine, at least in part from interneurons, that acts at a distance to inhibit presynaptically the release of glutamate from excitatory synapses. Thus, interneurons may mediate a widespread purinergic presynaptic inhibition.

2-Amino-5-phosphonovalerate↗

PubMed1994

Long-term potentiation: evidence against an increase in transmitter release probability in the CA1 region of the hippocampus.

It is widely accepted that N-methyl-D-aspartate (NMDA)-receptor-dependent long-term potentiation (LTP) in the CA1 region of the hippocampus is triggered postsynaptically, but there is considerable debate as to the site at which the increase in synaptic strength is expressed. The irreversible open-channel blocking action of the NMDA receptor antagonist MK-801 has been used to test whether the probability of transmitter release (Pr) is increased during LTP. Although the rate of decline of the amplitude of the NMDA receptor-mediated excitatory postsynaptic current (EPSC) in the presence of MK-801 strongly depends on Pr, the rate of decline of the EPSC evoked at synapses expressing LTP is identical to that observed at synapses not expressing LTP. These findings are difficult to reconcile with models in which the expression of LTP is due to an increase in Pr.

Animals↗

PubMed1994

[Posterior proctomucosectomy and ileal pull-through reconstruction: a new restorative procedure after total proctocolectomy].

We reported a new method of restorative proctocolectomy using posterior approach and pull-through reconstruction. This method obviated transanal manipulation, a major factor causing damage to the internal sphincter, thus preventing fecal incontinence due to sphincter dysfunction. Also, temporary ileostomy was not necessary because the spout of an S-pouch was pulled down below the anal verge and its distal free end acted as a diverting stoma while the more proximal, healing zone (future anastomotic line) was kept from fecal contamination. This method was applied to a 32-year-old woman with familial polyposis coli and a 50-year-old woman with ulcerative colitis. Their bowel movements steadily decreased to three times and five times a day, respectively. There was no fecal leakage or perianal excoriation. The advantages as well as disadvantages of this method compared with the conventional techniques were discussed.

Adenomatous Polyposis Coli↗

PubMed1994

Expression of sialosyl-Tn antigen (monoclonal antibody MLS102 reactive) in normal tissues and malignant tumors of the digestive tract.

Oncogenic transformation is often associated with changes in the glycosylation state of malignant cells. We investigated the immunohistochemical localization of sialosyl-Tn antigen [O-linked NeuAc(alpha 2-->6)GAINAc] using a novel monoclonal antibody MLS102 in normal and malignant digestive-tract tissues. In normal tissues, weak MLS102 immunoreactivity was observed in the epithelium of the esophagus, stomach and colon. However, MLS102 immunoreactivity was strong in the goblet cells of the duodenum, but not in the Brunner glands. In carcinomas of the esophagus, stomach, colon, pancreas and biliary tract, positive staining was detected with a high frequency (80%-100%). In mucinous carcinomas and signet-ring cell carcinomas, malignant cells themselves and the mucins they secreted were strongly positive for sialosyl-Tn antigen. There was no significant correlation between the frequency of expression of sialosyl-Tn antigen and the degree of differentiation (grade). However, in the case of well-differentiated adenocarcinomas, sialosyl-Tn antigen was found mainly in the supranuclear areas (Golgi area), on the apical surface and in the adjacent cytoplasm. In poorly differentiated adenocarcinomas, the antigen was often detected in the whole plasma membrane and cytoplasm. Therefore, monoclonal antibody MLS102 may be useful in further elucidating the characteristics of digestive-tract cancers, and possibly in their treatment.

Antibodies, Monoclonal↗

PubMed1994

A rise in postsynaptic Ca2+ potentiates miniature excitatory postsynaptic currents and AMPA responses in hippocampal neurons.

We have investigated the site of expression of the potentiation of excitatory postsynaptic currents (EPSCs) induced by the activation of postsynaptic voltage-sensitive Ca2+ channels, by examining the effect of depolarizing pulses on miniature (m) EPSCs and responses to AMPA. Application of voltage pulses caused a approximately 2.5-fold increase in the mean amplitude of mEPSCs. This NMDA receptor-independent potentiation of mEPSC amplitudes was transient, returning to control values within 30-40 min. The potentiation was associated with a decrease in the number of small amplitude events and an increase in the number, as well as the maximum amplitude, of the larger events, with no apparent change in mEPSC kinetics. Accompanying the increase in mEPSC amplitudes, there was a 1.6-fold increase in the apparent frequency of events. Voltage pulse-induced potentiation was completely blocked by the inclusion of the Ca2+ chelator BAPTA in the recording pipette. Responses to repeated applications of AMPA were also potentiated following the application of voltage pulses, and the time course of this potentiation was similar to that observed with the mEPSCs. Our data indicate that rises in intracellular Ca2+ that occur independently of NMDA receptor activation can result in a potentiation of quantal size, which is due to an increase in the postsynaptic sensitivity of non-NMDA receptors.

Animals↗

PubMed1994

Assessment of the proliferative activity and radiosensitivity of human tumours using the cytokinesis-block micronucleus assay.

We established an in vitro cytokinesis-block micronucleus assay of human tumours for estimation of the proportion of cells undergoing mitosis (the dividing fraction, DF), the time for the number of nuclei to double and the radiosensitivity in terms of the micronucleus frequency, based on a concept described previously. Under certain conditions, the nuclear number doubling time (NNDT) was considered to represent the potential doubling time. Tumour specimens obtained at surgery were disaggregated into single-cell suspensions and were directly cultured in the presence of cytochalasin B with or without irradiation. At various intervals, the percentage of multinucleate cells (the plateau value represented the DF), the average number of nuclei per cell and the number of micronuclei in binucleate cells were determined. DF and NNDT values were obtained in 58 of the 73 tumours investigated, and the micronucleus frequency was obtained in 54 of these 58 tumours. The DF ranged from 4.1% to 71% and the NNDT ranged from 3.1 to 83 days. A DF > or = 20% was associated with a higher recurrence rate in patients undergoing curative operation. A correlation was found between the NNDT and the time to relapse in patients with recurrent disease. The average number of micronuclei per binucleate cell at 2 Gy of irradiation (after subtraction of the value at 0 Gy) ranged from 0.052 to 0.35. Tumours which produced more micronuclei after irradiation showed a better response to radiotherapy. This assay can be readily performed on human tumours and appears to have promise as a predictive assay for radiation therapy.

Adenocarcinoma↗

PubMed1994

ATP-dependent uptake of anti-neoplastic agents by acidic organelles.

Daunomycin, an anti-neoplastic agent, is known to be sequestered by acidic organelles in normal and multidrug-resistant cells [Willingham, M.C., Cornwell, M.M., Cardarelli, C.O., Gottesman, M.M., & Pastan, I. (1986) Cancer Res. 46, 5941-5946]. We studied the mechanism of accumulation of daunomycin into acidic organelles using chromaffin granule vesicles and proteoliposomes reconstituted with purified F-type H(+)-ATPase as model systems. Radiolabeled daunomycin was taken up by chromaffin vesicles upon addition of ATP. Its ATP-dependent uptake was stimulated about 1.4- to 1.8-fold by valinomycin plus K+, but was inhibited by ammonium chloride (10 mM) and nigericin plus K+. Quinidine (5 microM), verapamil (5 microM), or vanadate (0.5 mM), inhibitors of P-glycoprotein, had no effect on its uptake. Daunomycin was also taken up by liposomes reconstituted with F-type H(+)-ATPase. Furthermore, doxorubicin and vinblastine were taken up by these vesicles, whereas colchicine and rhodamine 123 were not. The accumulations of daunomycin and doxorubicin in acidic organelles of cultured cells were decreased by inhibiting vacuolar ATPase by addition of bafilomycin A1 or concanamycin A, or by increasing the internal pH by addition of nigericin. Melittin and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide dissipated the delta pH and inhibited accumulation of daunomycin in the membrane vesicles and acidic organelles in cultured cells. These results indicate that the delta pH established by vacuolar-type ATPase drives the uptake of daunomycin, doxorubicin or vinblastine into acidic organelles, and that no specific transporters are involved in their uptakes.

Adenosine Triphosphate↗

PubMed1994

Intramyocardial angiomyolipoma.

We report a case of cardiac angiomyolipoma in a 48-year-old woman who went to the hospital because of shortness of breath. Cardiac ultrasonography showed a right atrial mass, which was surgically removed. Pathologic examination revealed a 6-cm-diameter, dome-shaped mass composed of a mixture of blood vessels, smooth muscle, and fat. Because of its distinctive morphology and location, we diagnosed it as an intramyocardial angiomyolipoma. There was no evidence of tuberous sclerosis. Since excision of the mass, the patient has remained well without recurrence for 20 months. Angiomyolipomas usually develop in the kidney; extrarenal occurrence is rare. To date, no case of a cardiac angiomyolipoma has been reported in the English literature. The histogenesis of angiomyolipoma is uncertain, but it is most likely hamartomatous in nature.

Angiomyolipoma↗

PubMed1994

Immunohistochemical study of heparan sulfate proteoglycan in adenocarcinomas of the pancreas.

The prognosis for carcinoma of the pancreas is extremely poor. One of the characteristics of this tumor is its invasion of the surrounding tissues. Reduction of glycoprotein is considered to be conducive to invasion of the basement membrane by carcinoma cells. Heparan sulfate proteoglycan (HSPG), a kind of glycoprotein, is an important component of basement membrane. In this study, the relation between HSPG and carcinoma of the pancreas was examined by using the immunohistochemical method, and the survival rate of pancreatic adenocarcinoma was evaluated. We found that some carcinomas contained little or no HSPG. The poorer the differentiation of an adenocarcinoma of the pancreas, the lower was its content of HSPG. The level of HSPG was significantly different in carcinomatous and in noncarcinomatous cells. There was a close correlation among the content of HSPG, the degree of differentiation of carcinomas of the pancreas, and the survival time. HSPG seems to be useful in prognosis of adenocarcinoma of the pancreas.

Adenocarcinoma↗

PubMed1994

K-ras and p53 alterations in genomic DNA and transcripts of human pancreatic adenocarcinoma cell lines.

We analyzed 15 human pancreatic adenocarcinoma cell lines for alterations of the K-ras and the p53 genes and their transcripts. In 11 cell lines (73.3%), point mutations of the K-ras gene were found at codon 12 in exon 1. In 9 cell lines one allele was mutated and the other was wild type, and both the alleles were expressed into mRNA. In one cell line both alleles of codon 12 were mutated to TGT and GTT, respectively, but only TGT was transcribed into mRNA. Alterations in mRNA of the p53 gene were detected in 10 cell lines (66.7%). Analysis of the genomic sequence of the p53 gene revealed that the alterations consisted of 6 cases of base pair substitutions and 1 case of 1-bp deletion in evolutionarily conserved exons 5 to 8, 2 cases of splicing mutations in exon 4, and 1 case of novel deletion from exons 2 to 9. In 14 cell lines (93.3%), alterations were identified in the K-ras or p53 gene. Of these, 4 cell lines harbored K-ras mutations without p53 alteration, whereas 3 cell lines exhibited p53 alterations without K-ras mutation. Thus, it is suggested that activation of the K-ras gene and inactivation of the p53 gene are strongly and cooperatively associated with pancreatic carcinogenesis.

Adenocarcinoma↗

PubMed1994

Immortalization-susceptible elements and their binding factors mediate rejuvenation of regulation of the type I collagenase gene in simian virus 40 large T antigen-transformed immortal human fibroblasts.

Dramatic changes occur in expression of the type I collagenase gene during the process of immortalization in simian virus 40 large T antigen-transformed human fibroblasts (S. Imai and T. Takano, Biochem. Biophys. Res. Commun. 189:148-153, 1992). From transient transfection assays, it was determined that these changes involved the functions of two immortalization-susceptible cis-acting elements, ISE1 and ISE2, located in a 100-bp region about 1.7 kb upstream. The profiles of binding of an activator, Proserpine, to the enhancer ISE1 were similar in the extracts of young, senescent preimmortalized and immortalized cells. ISE2 contained both negative and positive regulatory elements located adjacent to each other. The positive regulatory element consisted of a tandem array of putative Ets family- and AP-1-binding sites. An activator, Pluto, interacted with this positive regulatory element and had an AP-1-related component as a complex. The binding activity of Pluto was predominantly detected only in the extract from senescent preimmortalized cells. In contrast, a repressor, Orpheus, which bound to the ATG-rich negative regulatory element of ISE2, was prominently detected in extracts from both young preimmortalized and immortalized cells and appeared to suppress transcription in an orientation-dependent manner. Thus, the interplay of Pluto and Orpheus was suggested to be crucial for regulation of the collagenase gene accompanying in vitro aging and immortalization. Proserpine seemed to interact with Pluto to mediate strong expression of the collagenase gene in cellular senescence. On the basis of these results, we propose a model for regulation of the collagenase gene during in vitro aging and immortalization.

Antigens, Viral, Tumor↗

PubMed1994

Pancreatic exocrine secretion in short-term pancreatic duct obstruction induced acute pancreatitis in rats: an in vivo and in vitro study.

We investigated digestive enzyme release following a short-term pancreatic duct obstruction in rats. An in vivo experiment demonstrated that a 6-hour pancreatic duct obstruction reduced digestive enzyme release evoked both by endogenously released cholecystokinin (CCK) due to pancreaticobiliary diversion and by exogenous administration of CCK8. In vitro experiments also showed that pancreatic duct obstruction reduced the maximal CCK8-evoked amylase secretion. Amylase secretion evoked by the calcium ionophore A23187 and by phorbol myristate acetate was also markedly decreased. These data suggest that pancreatic duct obstruction probably interferes with the secretory process downstream of hormone receptor binding, intracellular Ca2+ release and protein kinase C activation.

Acute Disease↗

PubMed1994

Platelet-activating factor involvement in the aggravation of acute pancreatitis in rabbits.

Platelet activating factor (PAF) was administered to anesthetized rabbits with cerulein-induced acute pancreatitis to investigate the role of PAF in the development of acute pancreatitis. In acute edematous pancreatitis, induced with cerulein 20 micrograms/kg/h i.v. for 5 h, blood flow in the gastroduodenal and superior mesenteric arteries (GDAF and SMAF) had decreased significantly by 30 min and the serum amylase and lipase levels were significantly increased in the early phase. In the cerulein+PAF group, in which PAF was injected 100 ng/kg/min i.v. for 20 min simultaneously with cerulein, GDAF and SMAF declined significantly to 52 +/- 4 and 47 +/- 3% (p < 0.05), serum amylase and lipase levels rose significantly to 1,110 +/- 150 and 1,370 +/- 190% (p < 0.01) at 300 min, much higher than in the cerulein group. Furthermore, scattered hemorrhages and more marked inflammatory cell infiltration were observed histologically. These findings suggest that PAF has an additive role in the aggravation of acute pancreatitis.

Acute Disease↗

PubMed1994

Synthesis and structure-activity relationships of antiallergic N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamides possessing both antihistaminic and anti slow-reacting substance (SRS) activities.

A series of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanamide derivatives were synthesized and tested for in vivo antianaphylactic activity and in vitro anti slow-reacting substance (SRS) activity. Among the compounds synthesized, N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2- thiazolyl]propanamide (7) was the best balanced compound (antianaphylactic activity, ED50 = 0.92 mg/kg p.o.; anti-SRS activity, IC50 = 0.89 microgram/ml). Regarding the biological activities of 7, we ascribe the antianaphylactic activity to its potent antihistaminic activity and the anti SRS activity to the inhibition of 5-lipoxygenase.

Amides↗

PubMed1994

Parachordoma of the buttock: an immunohistochemical case study and review.

We report a case of parachordoma occurring in the buttock of a 43-year-old man, and review 20 cases of parachordoma reported in the English literature. The tumor in our case was grossly 3 cm in dimension, solid, lobulated and grayish-white in color. Microscopically, the tumor consisted of epithelioid and spindle cells, and fibromyxoid stroma. The epithelioid cells were immunohistochemically positive for vimentin, S-100 protein, neuron-specific enolase, keratin, carcinoembryonic antigen and epithelial membrane antigen, and negative for HMB45. These findings are similar to those for chordoma rather than extraskeletal myxoid chrondrosarcoma. Although the etiopathogenesis of parachordoma remains obscure, Schwann cells or some other neuron-related cell origin are suspected.

Adult↗

PubMed1994

[A case of pulmonary alveolar proteinosis with high levels of tumor markers].

We report a case of pulmonary alveolar proteinosis (PAP) in which the serum levels of CEA, CA15-3, and TPA, as well as the whole lung lavage fluid levels of CEA, CA19-9, CA125, CA15-3, CA50, SLX, SCC, and TPA were high. The patient was a 39-year-old man who presented with exertional dyspnea, and nonsegmental bilateral reticular infiltration shadows in the middle and lower lung fields on the chest radiograph. A diagnosis of proteinosis was confirmed by histopathology of the transbronchial lung biopsy (TBLB) specimen, biochemical analysis of the phospholipids, and an electron microscopic study of lavage fluid. Whole lung lavages alleviated his symptoms, effaced the shadows on the chest radiographs and brought the blood gas values closer to normal. An immunohistochemical study of TBLB specimens showed that CEA, CA153, and SLX were positively stained in the alveolar epithelia. With repeated lavage, tumor markers (CEA, CA15-3, TPA) in the fluid decreased. These results suggest that the alveolar epithelia indeed produced these tumor marker molecules. In PAP, it is well recognized that CEA may be high in at least one of the following: serum, bronchoalveolar lavage fluid, and whole lung lavage fluid. To date, however, the site of production of such tumor markers had not been clearly demonstrated to be in the lung tissue. This case is interesting because there are few reports of PAP with high levels of tumor markers in the serum and whole lung lavage fluid, and because the tumor markers found in abnormally high amounts in this patient were produced by alveolar epithelia.

Adult↗

PubMed1994

Malignant localized fibrous tumor of the peritoneum arising in its benign counterpart.

We report a case of malignant localized fibrous tumor (LFT) of the peritoneum in a 78-year-old man. The tumor was pedunculated and the malignant area completely surrounded by its benign counterpart, forming "a nodule within a nodule" appearance. Histologically, the latter area showed typical features of a benign LFT, while the former fulfilled the criteria of a malignant LFT as defined by England et al.; i.e., one being rich in fibroblastic spindle cells with plump and atypical nuclei, hyalinized stroma and mitotic figures. Immunohistochemically, spindle cells in both portions of the tumor were positively stained for vimentin but completely negative for keratin (AE1/AE3), S-100 protein and desmin. There was a significant increase in proliferating cell nuclear antigen (PCNA)-positive cells in the malignant portion (80%) in comparison with the benign portion (45%). To date, we are not aware of any report on a malignant localized fibrous tumor in association with a benign counterpart. The unique association, therefore, prompted us to report our experience, and suggests the possibility of malignancy developing in the benign localized fibrous tumor.

Aged↗

PubMed1994

Mucin-producing pancreatic tumors: historical review of its nosological concept.

A brief historic outline of the problem of mucin-producing pancreatic tumors is presented. Based on the authors' observations, clinical aspects and pathomorphology of these tumors have been described. The authors propose their own classification of this tumor type which is based on the literature published so far. Their classification also takes into account the localization of lesions. Reference is made to the concept described by the term "mucinous ductetatic/cystic lesions" (MDCL) and it is also pointed out that mucinous carcinoma may develop on the background of MDCL. Since the appearance of the term "mucus secreting pancreatic cancer" or "mucin-producing pancreatic tumor", many similar and/or related conditions have been described especially in Japan under the same or different names. However, there seems to be some confusion about the concept of this condition not only among clinicians but also among pathologists. In addition, another entity, mucinous cystic neoplasms of the pancreas, was proposed and may have provided some overlap with the former conditions in its concept. Furthermore, definitions of these two conditions varied according to the authors. In this paper, therefore, we review and critically analyze cases of mucin-producing pancreatic tumor (MPPT) as well as mucinous cystic neoplasm (MCN) of the pancreas, and intend to classify them under a generic term, i.e. "mucinous ductectatic/cystic lesions (MDCL) of the pancreas".

Adenocarcinoma, Mucinous↗