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Biomedical subjects

M Watanabe

Publications and source records attributed to M Watanabe.

At least 235 records · Page 13Linked to original sources
PubMed2001

Resistant mechanisms of anthracyclines--pirarubicin might partly break through the P-glycoprotein-mediated drug-resistance of human breast cancer tissues.

Juliano and Ling initially reported the expression of a 170 kDa glycoprotein in the membrane of Chinese hamster ovarian cells in 1976, and named this glycoprotein P-glycoprotein (P-gp) based on its predicted role of causing "permeability" of the cell membrane. After much research on anthracycline-resistance, this P-gp was finally characterized as a multidrug-resistant protein coded by the mdr1 gene. Multidrug resistance associated protein (MRP) was initially cloned from H69AR, a human small cell-lung carcinoma cell line which is resistant to doxorubicin (DXR) but does not express P-gp. MRP also excretes substrates through the cell membrane using energy from ATP catabolism. The substrate of MRP is conjugated with glutathione before active efflux from cell membrane. Recently, membrane transporter proteins were re-categorized as members of "ATP-Binding Cassette transporter"(ABC-transporter) superfamily, as shown at http://www.med.rug.nl/mdl/humanabc.htm and http://www.gene.ucl.ac.uk/nomenclature/genefamily/abc.html. A total of ABC transporters have been defined, and MDR1 and multidrug resistance associated protein 1 (MRP1) were reclassified as ABCB1 and ABCC1, respectively. Their associated superfamilies include 11 and 13 other protein, in addition to ABCB and ABCC, respectively. Lung resistance-related protein (LRP) is not a member of the superfamily of ABC transporter proteins, because it shows nuclear membrane expression and transports substrate between nucleus and cytoplasm. LRP was initially cloned from a non-small cell lung carcinoma cell line, SW1573/2R120 which is resistant to DXR, vincristine, etoposide and gramicidin D and does not express P-gp. The mechanisms of resistance remains unclear, and why some resistant cell lines express P-gp and others express MRP and/or LRP is likewise unclear.

ATP-Binding Cassette Transporters↗
PubMed2001

Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy.

The purpose of this study was to clarify which myocardial histological findings associated with dilated cardiomyopathy (DCM) are reflected in quantitative 201Tl myocardial SPECT. We obtained studied SPECT images from 21 patients with DCM 10 minutes and 2 hours after they received an injection of 111 MBq 201Tl at rest. We calculated the percent coefficient of variation of myocardial 201Tl counts [%CV(TI)], the washout rate (WR), standard deviation of WR [SD(WR)], extent score (ES) and severity score (SS). We used image analysis to measure % fibrosis, % myocytes, the ratio of fibrous tissue to myocyte tissue (F/My), myocyte size and standard deviation of myocyte size [SD(My)] in left ventricular endomyocardial biopsy specimens. The %CV(Tl) was correlated with % fibrosis and F/My. The ES and SS also correlated with F/My. The correlation between SD(WR) and SD(My) was significant. The present findings suggest that %CV(Tl), ES and SS of rest 201Tl SPECT reflect myocardial fibrosis and that the standard deviation of washout reflects the distribution of myocyte size.

Biopsy↗
PubMed2001

Behavioral reactions reflecting differential reward expectations in monkeys.

Learning theory emphasizes the importance of expectations in the control of instrumental action. This study investigated the variation of behavioral reactions toward different rewards as an expression of differential expectations of outcomes in primates. We employed several versions of two basic behavioral paradigms, the spatial delayed response task and the delayed reaction task. These tasks are commonly used in neurobiological studies of working memory, movement preparation, and event expectation involving the frontal cortex and basal ganglia. An initial visual instruction stimulus indicated to the animal which one of several food or liquid rewards would be delivered after each correct behavioral response, or whether or not a reward could be obtained. We measured the reaction times of the operantly conditioned arm movement necessary for obtaining the reward, and the durations of anticipatory licking prior to liquid reward delivery as a Pavlovian conditioned response. The results showed that both measures varied depending on the reward predicted by the initial instruction. Arm movements were performed with significantly shorter reaction times for foods or liquids that were more preferred by the animal than for less preferred ones. Still larger differences were observed between rewarded and unrewarded trials. An interesting effect was found in unrewarded trials, in which reaction times were significantly shorter when a highly preferred reward was delivered in the alternative rewarded trials of the same trial block as compared to a less preferred reward. Anticipatory licks preceding the reward were significantly longer when highly preferred rather than less preferred rewards, or no rewards, were predicted. These results demonstrate that behavioral reactions preceding rewards may vary depending on the predicted future reward and suggest that monkeys differentially expect particular outcomes in the presently investigated tasks.

Animals↗
PubMed2001

Characterization of interglobular dentin and Tomes' granular layer in dog dentin using electron probe microanalysis in comparison with predentin.

The interglobular dentin (IG) and the Tomes' granular layer (TGL) as well as predentin are hypomineralized regions in dentin. Some previous studies proposed that the IG and the TGL are identical with difference only in size, whereas other suggested that they are distinct structures. In order to characterize their matrix components, the present study was designed to analyze the elements of calcium (Ca), phosphorus (P), and sulfur (S) in the IG and the TGL in comparison with predentin using the Electron Probe Microanalysis (EPMA). The TGL was highest in the concentration of both Ca and P among the hypomineralized regions followed by the IG and predentin, whereas predentin was the highest in the concentration of S followed by the IG and the TGL. Alcian blue staining suggested that the S elements identified with the EPMA are incorporated into the sulfated glycosaminoglycan chains of proteoglycans. The present study first demonstrated distinct characteristics of matrix components in the IG and the TGL, i.e., the IG is poorer in mineralization but much richer in a proteoglycan content than the TGL. The IG may originate from predentin because of their analogy, whereas the TGL may follow a different ontogeny.

Alcian Blue↗
PubMed2001

Stimulative effect of cadmium on prostaglandin E2 production in primary mouse osteoblastic cells.

We have reported that cadmium (Cd) stimulates bone resorption via prostaglandin E2 (PGE2), which is mainly produced in osteoblasts. Prostaglandin (PGs) is regulated by arachidonic acid (AA) release by phospholipase A2 (PLA2) and its conversion to PGs by cyclooxygenase (COX). In the present study, we investigated the possibility that Cd-induced PGE2 synthesis was mediated through PLA2 or COX or both using primary mouse osteoblastic cells in serum-free medium. Cd at 1 microM and above stimulated 14C-AA release from 14C-AA-prelabeled osteoblastic cells. PLA2 activity of cytosolic fraction in Cd-treated cells preferentially hydrolyzed AA at the Sn2 position of phospholipids and was inhibited by arachidonyltrifluoromethyl ketone (AACOCF3), an inhibitor of cytosolic PLA2 (cPLA2). Cd at 1 microM and above increased cPLA2 activity and the level of constitutive cPLA2 mRNA. Secretory PLA2 mRNA was not detected. On the other hand, Cd at 1 microM and above stimulated PGE2 production and its production was inhibited by an inhibitor of COX-2 (NS-398). Cd at 1 microM and above markedly stimulated COX-2 mRNA expression and slightly increased the level of COX-1 mRNA. An inhibitor of COX-1 (varelylsalicylic acid) did not affect Cd-induced PGE2 production. In addition, Cd-induced PGE2 synthesis was inhibited by AA-COCF3, On the other hand, IL-1 alpha, an inducer of COX-2, did not stimulated PGE2 production in present culture system. When IL-1 alpha- or Cd-treated cells were incubated with AA for 10 minutes, IL-1 alpha-treated cells as well as Cd-treated ones caused an increase in PGE2 production. This suggests that the mechanism of Cd-induced PGE2 production is different from that of IL-1 alpha, which may require an activation of cPLA2. From these results, it was found that Cd by itself stimulated PGE2 production by two successive steps that Cd increased cPLA2 activity and then COX-2 induction.

Animals↗
PubMed2001

"Schistotaxis" in cerebral blood flow on 99mTc-HMPAO single-photon emission computed tomography during a seizure following a stroke.

We describe a patient with seizures following a stroke in whom on ictal 99mTc-HMPAO single-photon emission computed tomography demonstrated cerebral blood flow "schistotaxis", i.e., focal hyperaemia corresponding to an epileptogenic focus together with an extensive hypoperfused area in the same hemisphere. This phenomenon may have been caused by haemodynamic alternation and a remote transneural effect during the seizures.

Aged↗
PubMed2001

Organochlorine pesticides, polychlorinated biphenyls, and butyltin compounds in blubber and livers of stranded California sea lions, elephant seals, and harbor seals from coastal California, USA.

Concentrations of polychlorinated biphenyls (PCBs), DDTs (p,p'-DDE, p,p'-DDD, p,p'-DDT), chlordanes (CHLs; cis-chlordane, cis-nonachlor, trans-nonachlor, and oxychlordane), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), tris(4-chlorophenyl)methane (TCPMe), tris(4-chlorophenyl)methanol (TCPMOH), and mono- (MBT), di-(DBT), and tri-butyltin (TBT) were determined in blubber and livers of 15 California sea lions (Zalophus californianus), 6 northern elephant seals (Mirounga augustirostris), and 10 harbor seals (Phoca vitulina) found stranded along the coasts of California, USA, during 1991-1997. Among the organochlorines analyzed, DDTs were predominant, followed in decreasing order by PCBs, CHLs, TCPMe, TCPMOH, HCHs, and HCB. The greatest concentrations of organochlorines were found in California sea lions. The highest DDT and PCB concentrations found in the blubber of California sea lions were 2,900 and 1,300 microg/g, lipid weight, respectively. Concentrations of TCPMe and TCPMOH in California sea lions were correlated significantly with DDT concentrations. Concentration ratios of various organochlorines in harbor seal livers were different from those in California sea lions and elephant seals, which suggested that the sources of exposure of harbor seals to organochlorines were different from those in the other two species. Concentrations of butyltin compounds in livers of pinniped species ranged from 2 to 99 ng/g, wet weight, which were less than those observed in cetaceans and in California sea otters.

Adipose Tissue↗
PubMed2001

The generation of anti-tumoral cells using dentritic cells from the peripheral bloood of patients with malignant brain tumors.

Dendritic cells (DCs) can be the principal initiators of antigen-specific immune responses. We analyzed the in vitro-responses against brain tumor cells using DCs from the peripheral blood of patients with brain tumors. Peripheral blood mononuclear cells (PBMC) were obtained from 19 patients with malignant brain tumors: 12 metastatic brain tumors of lung adenocarcinoma, 7 high-grade astrocytomas. PBMC were cultured with 100 ng/ml of GM-CSF and 10 ng/ml of IL-4 for 5 7 days in order to produce mature DCs. The autologous tumor lysate (5 mg/ml, containing 1 x 10(6) cells) was then added to the cultured DCs. Using the DCs generated by these treatments, we assessed the changes that occurred in their immune responses against brain tumor via 51Cr-release and lymphocyte proliferation assays. We found that the matured DCs displayed the typical surface phenotype of CD3+, CD45+, CD80+ and CD86+. After the pulsation treatment with tumor lysate, DCs were found to have strong cytotoxic T lymphocyte activity, showing 42.5+12.7% killing of autologous tumor cells. We also found an enhancement of allogeneic T cell proliferation after pulsing the DC with tumor lysate. These data support the efficacy of DC-based immunotherapy for patients with malignant brain tumors.

Adenocarcinoma↗
PubMed2001

Optimum treatment strategy for superficial esophageal cancer: endoscopic mucosal resection versus radical esophagectomy.

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.

Aged↗
PubMed2001

Effects of PR-350, a newly developed radiosensitizer, on dihydropyrimidine dehydrogenase activity and 5-fluorouracil pharmacokinetics.

This study was designed to investigate the effects of PR-350, a newly developed radiosensitizer, on dihydropyrimidine dehydrogenase (DPD) activity and 5-fluorouracil (5-FU) pharmacokinetics in 8-week-old male Sprague-Dawley rats. In an in vitro study with hepatic cytosol, DPD activity was dose-dependently reduced by PR-350 at 0.5, 1.0, and 2.0 mmol/l to 75.5%, 64.9%, and 61.5%, respectively, of the control values. In an ex vivo study, DPD activities in hepatic cytosols obtained from animals which had received PR-350 over 4 days (200 mg/kg per day) were not significantly different from those in animals which had not. In an in vivo study, none of the pharmacokinetic parameters obtained from the plasma concentration-time profile of 5-FU were significantly altered by single i.v. injections of PR-350 (50, 100, or 200 mg/kg). However, (E)-5-(2)-(bromovinyl)uracil (BVU), a DPD inhibitor, significantly increased the half-life and area under the curve of 5-FU to 238.1% and 323.2%, respectively, of the control values. Administration of PR-350 over 4 days (200 mg/kg per day) did not affect either of these parameters. The administration of PR-350 significantly reduced the clearance (73.5% of control) and volume of distribution (71.0% of control) of 5-FU, but the alterations were much less than those caused by BVU. These results suggest that the effect of PR-350 on 5-FU pharmacokinetics is much less than that of BVU and that the enhancement of 5-FU toxicity by PR-350 is less than we initially anticipated.

Animals↗
PubMed2001

Metachronous neurohypophysical immature teratoma occurring 10 years after total resection of pineal mature teratoma.

An 18-year-old boy presented with an immature neurohypophysial teratoma occurring 10 years after total resection of a mature pineal teratoma through an occipital transtentorial approach in 1989. Thorough histological examination had revealed a mature teratoma. He developed panhypopituitarism and diabetes insipidus in 1999. Magnetic resonance imaging revealed a suprasellar tumor occupying the third ventricle. This tumor was totally resected through a frontobasal approach. Histological examination revealed an immature teratoma. This tumor occurred in a different site from the initial tumor and was considered to be de novo and thus a so-called metachronous germ cell tumor. Patients with completely resected mature teratoma require extended follow-up, including periodic magnetic resonance imaging, because of the risk of such a metachronous germ cell tumor.

Adolescent↗
PubMed2001

Neuronal and glial advanced glycation end product [Nepsilon-(carboxymethyl)lysine]] in Alzheimer's disease brains.

The cellular distribution of an advanced glycation end product [Nepsilon-(carboxymethyl)lysine (CML)] in aged and Alzheimer's disease (AD) brains was assessed immunohistochemically. CML was localized in the cytoplasm of neurons, astrocytes, and microglia in both aged and AD brains. Glial deposition was far more marked in AD brains than in aged brains, and neuronal deposition was also increased. On electron microscopic immunohistochemistry, neuronal CML formed granular or linear deposits associated with lipofuscin, and glial deposits formed lines around the vacuoles. Neuronal and glial deposits were prominent throughout the cerebral cortex and hippocampus, but were sparse in the putamen, globus pallidus, substantia nigra, and cerebellum, with glial deposits being far more prominent in AD brains. The distribution of neuronal and glial deposits did not correspond with the distribution of AD pathology. The extent of CML deposits was inversely correlated with neurofibrillary tangle formation, particularly in the hippocampus. Most hippocampal pyramidal neurons with neurofibrillary tangles did not have CML, and most of the neurons with heavy CML deposits did not have neurofibrillary tangles. In the hippocampus, neuronal CML was prominent in the region where neuronal loss was mild. These observations suggest that CML deposition does not directly cause neurofibrillary tangle formation or neuronal loss in AD.

Aged↗
PubMed2001

Glomus tumors with cystic changes around the ankle.

Sizable glomus tumors with cystic changes in the ankle are extremely uncommon. This paper describes painless glomus tumors with cystic changes arising in the ankle of a 22-year-old woman. At the age of 14, a painless mass was noticed on the lateral side of the left ankle, and at age 21, another mass appeared on the medial side of the same ankle. Magnetic resonance imaging (MRI) and computed tomography (CT) scanning revealed 4.5 x 4.0 cm and 2.0 x 2.0 cm sized masses on the medial side and a 3.0 x 4.0 cm sized cystic mass on the lateral side of the ankle. The tumors were removed en bloc. Microscopically, the tumor consisted of perivascularly arranged cells with punched-out, round, and regular nuclei. Immunohistochemically, the tumor cells expressed SMA and HHF-35, indicating smooth muscle cell characters. The patient had no recurrence at 2 years after surgery.

Adult↗
PubMed2001

Comparative study of the molecular and functional expression of L-type Ca2+ channels and large-conductance, Ca2+-activated K+ channels in rabbit aorta and vas deferens smooth muscle.

The relationship between the density of ionic currents through major two channels, voltage-dependent L-type Ca2+ channels (L-type VDCC) and large-conductance, Ca2+-activated K+ channels (BKC), and the mRNA expression levels of alpha1C subunit of L-type VDCC (alpha1C) and alpha/beta subunits of BKC (alphaBK/betaBK) were compared in smooth muscle cells (SMC) of rabbit aorta and vas deferens using whole cell-voltage clamp and reverse transcription-polymerase chain reaction (RT-PCR) analyses. The density of the currents through VDCC (ICa) and BKC (IK,Ca) at +10 mV in aortic SMC was approximately one-seventh and one-sixth respectively of that in vas deferens. Whilst application of the Ca2+ channel agonist Bay K 8644 increased ICa by 75-90% in these SMC, the increase in IK,Ca was far greater in aorta than in vas deferens. The expression of the alpha1C transcript in vas deferens was approximately 3.5 times higher than that in aorta. In contrast, expression of alphaBK/betaBK was almost identical in both tissues, indicating the dissociation of IK,Ca density from the expression levels of BKC transcripts in aorta. The results were supported by Western blot and immunocytochemical analyses using subunit-specific antibodies. The lower Ca2+ influx through VDCC in aorta activates only a very limited fraction of BKC compared with that in vas deferens. The greater expression of BKC than of VDCC in aortic SMC contributes to a strong negative feed-back mechanism that minimizes membrane depolarization and acts as a safety margin to maintain low membrane excitability.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Intracellular calibration of the fluorescent Mg2+ indicator furaptra in rat ventricular myocytes.

Single ventricular myocytes enzymatically isolated from rat hearts were loaded with the Mg2+ indicator furaptra, and the relationship between the fluorescence ratio signal (R) and the intracellular free concentration of Mg2+ ([Mg2+]i) was studied in situ at 25 degrees C. After the application of ionophores (ionomycin, monensin, nigericin and valinomycin), an immediate change in furaptra R was noted, followed by a slow change in R that reached a steady level in 2-4 h. The direction of the early change in R that accompanied rigor contraction was independent of the extracellular Mg2+ concentration ([Mg2+]o), and was consistent with the breakdown of ATP and release of bound Mg2+. The intracellular calibration curve was constructed from the steady levels of R obtained at various [Mg2+]o between 0 and 47 mM. The dissociation constant of intracellular furaptra was estimated to be 5.3 mM, which was 44% higher than that determined in salt solutions (3.7 mM). The basal [Mg2+]i of rat ventricular myocytes calculated with the intracellular curve averaged 0.91 mM.

Adenosine Triphosphate↗
PubMed2001

Sequence comparisons among dispersed members of the Brassica S multigene family in an S9 genome.

Self-incompatibility (SI) systems prevent self-pollination and promote outbreeding. In Brassica, the SI genes SLG (for S-locus glycoprotein) and SRK (for S-receptor kinase) are members of the S multigene family, which share the SLG-like domain (S domain), which encodes a putative receptor. We have cloned members of the S multigene family from the S9 haplotype of B. campestris (syn. rapa). In addition, eight distinct genomic regions harboring 10 SLG/SRK-like genes were characterized in the present study. Sequence analysis revealed two novel SRK-like genes, BcRK3 and BcRK6 (for B. campestris receptor kinases 3 and 6, respectively). Other genes that were characterized included SFR2 (for S gene family receptor 2), SLR2 (for S locus related gene 2), and a pseudogene. Based on phylogenetic analysis of the nucleotide sequences of the S domain regions, SLG and SRK appear to be distinct from other members of the S multigene family. Linkage analysis showed that most members of the S multigene family are dispersed in the Brassica genome, and that SLR1 (S locus related gene 1) is not linked to the SLR2 in B. campestris.

Blotting, Southern↗