Search PubMed⌕ Search

Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 235 records · Page 13Linked to original sources

Involvement of tetrodoxin-sensitive sodium channels in rat growth hormone secretion induced by pituitary adenylate cyclase-activating polypeptide (PACAP).

Both pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and growth hormone-releasing hormone (GRH) stimulated growth hormone (GH) release from perfused rat anterior pituitary cells. Tetrodotoxin (TTX) blunted the GH release induced by PACAP-38 but not by GRH. Mefenamic acid, a blocker of non-selective cation channels, unaffected GH release elicited by PACAP-38 and GRH. These results suggest an involvement of TTX-sensitive Na+ channels but not Ca2+-activated nonselective cation channels in PACAP-38-induced GH secretion, and that post-receptor mechanisms for PACAP-38 are different from those activated by GRH.

Animals↗

Impaired induction of the CD28-responsive complex in granulocyte colony-stimulating factor mobilized CD4 T cells.

Use of the CD28/B7 costimulatory signal for T-cell activation was analyzed in granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (G-PBMCs) and in peripheral blood mononuclear cells obtained before administration of G-CSF (preG-PBMCs). CTLA4Ig inhibition of OKT3-stimulated proliferation was significantly lower in G-PBMCs compared with preG-PBMCs (39.9% +/- 5.6% and 72.2% +/- 5.4%, respectively; P < .001). Furthermore, as shown in electrophoretic mobility-shift assays, the inducible level of the T-cell transcription factor CD28 responsive complex (CD28RC) was suppressed in CD4 cells derived from G-PBMC. However, depletion of CD14 cells from G-PBMCs restored CD28RC induction to normal levels. Taken together, these findings suggest that the large number of CD14 monocytes in G-PBMCs may limit T-cell responsiveness by suppressing the induction of the CD28RC.

Abatacept↗

Noradrenaline release in the rat subfornical organ area to blood pressure changes.

To verify whether noradrenergic inputs to the subfornical organ (SFO) are involved in the control system of arterial pressure, we investigated the effects of blood pressure changes on noradrealine (NA) release in the SFO and its surrounding sites using microdialysis techniques in rats. Hemorrhage (5 or 10 ml/kg) significantly increased the NA concentration in the region of the SFO, but did not cause significant changes in the sites away from the SFO. An elevation in arterial pressure following intravenous administration of the alpha-agonist metaraminol slightly decreased the NA level in the region of the SFO. These results imply that the noradrenergic neural inputs to the SFO area may be involved in the control of cardiovascular function.

Adrenergic alpha-Agonists↗

Neurons induce the activation of microglial cells in vitro.

Although microglial cells are well known to become activated in the pathological brain, mechanisms underlying the microglial activation are not fully understood. In the present study, with an aim to elucidate whether neurons are involved in the microglial activation, we compared the morphology and the superoxide anion (O2-)-generating activity of rat microglial cells in pure culture with those of cells cocultured with rat primary cortical neurons. Microglial cells in pure culture in serum-free Eagle's minimum essential medium on poly-L-lysine-coated coverslips displayed ramified morphology and suppressed activity of O2- generation. In contrast, microglial cells in neuron-microglia coculture under the same conditions as those for the pure culture displayed ameboid shape and upregulated activity of O2- generation. Electron microscopic observation revealed that microglial cells in coculture were more abundant in Golgi apparatus and secretory granules than those in pure culture and that some of microglial cells in the vicinity of neurites exhibited membrane specialization reminiscent of a junctional apparatus with high electron density between a microglial soma and a neurite. Microglial cells in coculture tended to tie neurites in bundles by extending processes. Medium conditioned by neurons significantly enhanced O2- generation by microglia, but microglial cells in contact with or in close apposition to cocultured neurons were much more intensely activated than those remote from the neurons. Furthermore, the membrane fraction of cortical neurons activated microglial cells, and this effect was abolished by treating the neuronal membrane with trypsin or neuraminidase. In conclusion, neuronal-microglial contact may be necessary to mediate microglial activation. The present findings suggest that the contact of microglia with damaged neurons in the brain is a plausible cause to activate microglia in the neuropathological processes.

Animals↗

Minimally invasive needlescopic cholecystectomy.

We utilized a mini-sized grasper and retractor measuring 2.5 mm in diameter and a new mini-sized laparoscope measuring 3 mm in diameter to perform a laparoscopic cholecystectomy. A 10/12-mm trocar was inserted as the first trocar for the laparoscope and specimen extraction. Under a direct laparoscopic view, the mini-sized grasper and retractor were inserted and the laparoscopic procedures were performed mainly through the 5-mm trocar placed on the left upper quadrant as the working port. These procedures were successfully performed on five patients with a comparable operation time to that of a conventional laparoscopic cholecystectomy, but appeared to be more minimally invasive.

Cholecystectomy, Laparoscopic↗

Gastric emptying after pylorus-preserving gastrectomy in comparison with conventional subtotal gastrectomy for early gastric carcinoma.

It is well known that surgical intervention on the stomach will greatly alter gastric function and gastric emptying. In this study, we evaluated the difference in postoperative gastric remnant emptying following pylorus-preserving gastrectomy (PPG) and conventional subtotal gastrectomy (CDG) using sulfamethizole capsule food. The subjects comprised 18 patients who underwent PPG and 23 who underwent CDG for early gastric carcinoma. While delayed gastric emptying was observed early after PPG, 1 year after PPG it was markedly accelerated compared with that measured in the early postoperative period. However, it was slower than that in the CDG patients. On the other hand, rapid gastric emptying was observed early after CDG and did not change with time. These findings stress that although PPG results in stasis in the early postoperative period, it seems to prevent unduly rapid emptying.

Anti-Infective Agents↗

Preparation of a conjugate of mitomycin C and anti-neural cell adhesion molecule monoclonal antibody for specific chemotherapy against biliary tract carcinoma.

To develop a specific chemotherapy modality for the perineural invasion of neural cell adhesion molecule (NCAM) positive biliary tract cancer, an anticancer drug, mitomycin C (MMC), was covalently bound to anti-NCAM monoclonal antibody (anti-NCAM MoAb) to form a conjugate using the cyanogen bromide method. The substitution ratio of the conjugate determined spectrophotometrically was 3.5 (MMC mol/immunoglobulin G mol). The cytotoxic activity of the conjugate, which was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test in the growth inhibition of the neuroblastoma cell line with NCAM expression, was maintained at 65.8% to 94.5% compared with the same concentration of MMC solution. The binding activity of the conjugate to the NCAM-positive bile duct cancer was examined by immunohistochemical staining and proved to be the same level as that of free anti-NCAM MoAb. The conjugate prepared in this study therefore appeared to be a potentially useful tool for immunotargeting specific chemotherapy against biliary tract cancer with NCAM expression.

Antibiotics, Antineoplastic↗

Mapping attractor fields in face space: the atypicality bias in face recognition.

A familiar face can be recognized across many changes in the stimulus input. In this research, the many-to-one mapping of face stimuli to a single face memory is referred to as a face memory's 'attractor field'. According to the attractor field approach, a face memory will be activated by any stimuli falling within the boundaries of its attractor field. It was predicted that by virtue of its location in a multi-dimensional face space, the attractor field of an atypical face will be larger than the attractor field of a typical face. To test this prediction, subjects make likeness judgments to morphed faces that contained a 50/50 contribution from an atypical and a typical parent face. The main result of four experiments was that the morph face was judged to bear a stronger resemblance to the atypical face parent than the typical face parent. The computational basis of the atypicality bias was demonstrated in a neural network simulation where morph inputs of atypical and typical representations elicited stronger activation of atypical output units than of typical output units. Together, the behavioral and simulation evidence supports the view that the attractor fields of atypical faces span over a broader region of face space that the attractor fields of typical faces.

Face↗

Quantitative analysis of alpha-fetoprotein mRNA in circulating peripheral blood of patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas.

In conjunction with strategies introduced in recent years to identify cancer micrometastasis through amplification of cancer-associated mRNA, we developed a highly sensitive system to detect alpha-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients. The aim of the present study was to make our original system quantitative. Peripheral venous blood from patients with hepatocellular carcinoma and alpha-fetoprotein-producing gastric carcinoma was subjected to reverse transcription followed by our original three-step polymerase chain reaction co-amplifying both the original sequence and our synthetic competitor. We succeeded in modifying our system for quantitative analysis, and investigated the perioperative change, the postoperative change and the change after chemotherapy in order to illustrate the possible application of this method. The quantitative analysis of alpha-fetoprotein mRNA present in the peripheral blood represents a useful tool for analyzing the relationship of surgery to recurrence, the effect of chemotherapy, and to predict impending recurrence in patients with hepatocellular and alpha-fetoprotein-producing gastric carcinomas.

Carcinoma, Hepatocellular↗

Training 'greeble' experts: a framework for studying expert object recognition processes.

Twelve participants were trained to be experts at identifying a set of 'Greebles', novel objects that, like faces, all share a common spatial configuration. Tests comparing expert with novice performance revealed: (1) a surprising mix of generalizability and specificity in expert object recognition processes; and (2) that expertise is a multi-faceted phenomenon, neither adequately described by a single term nor adequately assessed by a single task. Greeble recognition by a simple neural-network model is also evaluated, and the model is found to account surprisingly well for both generalization and individuation using a single set of processes and representations.

Computer Simulation↗

Responses of raphe nucleus projecting subfornical organ neurons to angiotensin II in rats.

The subfornical organ (SFO) is an important central site of action of circulating angiotensin II (ANG II). Although neuroanatomical tracing studies have identified the efferent pathways from the SFO to the midbrain raphe nucleus (RN), the functional role of the pathways is unknown. The present study was carried out to examine the responses of SFO neurons projecting to the dorsal RN (DRN) to microiontophoretic application or intracarotid injection of ANG II in male rats under urethane anesthesia. Twenty-three neurons in the SFO were antidromically identified by electrical stimulation of the midbrain DRN. Of these identified units, 13 were excited by ANG II applied iontophoretically, while 10 were unresponsive. ANG II-induced excitation was prevented by the ANG II antagonist saralasin (Sar) applied iontophoretically. The activity of seven out of 10 units that displayed this excitation to iontophoretically applied ANG II was also enhanced by intracarotid injection of ANG II. These results suggest that SFO neurons projecting to the DRN may monitor the circulating level of ANG II and carry the information to the DRN.

Angiotensin II↗

Effect of coronary bypass grafting onto the site of old myocardial infarction and the recovery of cardiac function.

This study investigated whether or not revascularization to the site of old myocardial infarction can bring beneficial effects on postoperative cardiac function. Thirty-two patients without a history of old myocardial infarction and 71 with a history of old myocardial infarction were included. The mean number of grafts bypassed were 2.7 and 2.8, and the mean duration of aortic clamping was 99 min and 105 min in non-old myocardial infarction and old myocardial infarction patients, respectively. All the patients underwent simple coronary artery bypass grafting electively. The left ventricular stroke work index in non-old myocardial infarction and old myocardial infarction were 40.8 g-m/m2 and 38.9 g-m/m2 preoperatively, and this was recovered to 41.4 g-m/m2 and 38.7 g-m/m2, respectively, at 24 hours after reperfusion (NS). Subgroups of old myocardial infarctions had high ejection fractions of more than 50% (49) and low ejection fractions of less than 50% (22). The left ventricular stroke work index in high and low ejection fractions was 39.7 g-m/m2 and 36.7 g-m/m2 preoperatively (NS). Recovery rates in both high and low ejection fractions were reduced to 74.2% and 84.3% at 3 h after reperfusion (P < 0.001 and P < 0.05 versus preoperative value), but were increased in the low ejection fraction by up to 102.7% and 108.5% at 6 and 12 h after reperfusion, while still remaining reduced in the high ejection fraction at 88.8% and 88.2%, respectively (P < 0.01). At 24 h after reperfusion, left ventricular stroke work index in the low ejection fraction was improved to 44.3 g-m/m2 or 130% of the preoperative value, and the high ejection fraction was 37.5 g-m/m2 or 100% (NS). This showed that a chief cause of reduced cardiac function in the low ejection fraction was mainly reversible myocardial damage or hibernation. Preoperative mean left ventricular ejection fractions in non-old myocardial infarctions and old myocardial infarctions were 73.1% and 55.9%, and these returned to 73.7% (NS) and 61.8% (P < 0.001) at 1 month post-coronary artery bypass grafting. A similar trend towards a significant improvement was shown in both end-diastolic volume indices and end-systolic volume indices of patients with an old myocardial infarction (P < 0.001). Regional wall motion according to AHA classification in patients with old myocardial infarctions was estimated from biplane left ventriculogram as normal, reduced, none, dyskinetic and aneurysmal, and scored as 0, 1, 2, 3 and 4, respectively. Summated scores in old myocardial infarctions was improved from 5.2 to 4.1 after coronary artery bypass grafting (P < 0.05). There was a significant improvement of summated scores from 8.17 to 6.28 in the low ejection fraction (P < 0.05); however, this was not reflected in the high ejection fraction (3.76 to 3.0; NS). The regional wall motion in the old myocardial infarctions that were heart bypassed to the left anterior ascending artery (n = 67) or to the circumflex artery (n = 40) were significantly improved at regions 2 (P < 0.05), 3 (P < 0.05) and 7 (P < 0.05), and that bypassed to right coronary artery (n = 50) was also improved at regions 3 (P < 0.05), 5 (P < 0.05) and 7 (P < 0.001). This shows that augmentation of regional blood flow by coronary artery bypass grafting will contribute to awakening the hibernated myocardium even in the old myocardial infarction.

Case-Control Studies↗

Cytokeratin 20 mRNA in peripheral venous blood of colorectal carcinoma patients.

A highly sensitive system was previously developed by us to detect the presence of colorectal carcinoma cells in blood in the form of cytokeratin 20 (CK20) mRNA. In the present study, we used an improved version of this system to analyse the peripheral blood of 28 patients with colorectal carcinoma, five patients with non-cancerous intestinal diseases and six normal controls for the presence or absence of CK20 mRNA and to investigate the relationship between the mRNA results and prognosis. All eight patients with recurrence were positive for CK20 mRNA, as were four patients in the Dukes' C stage with either distant metastasis or dissemination. Five of the nine patients in the Dukes' C stage with neither distant metastasis nor dissemination were positive, and three of these developed recurrence within 11 months after the analysis. Only one of the seven patients in the Dukes' A or B stage was positive, and none showed recurrence during the 1-19 months of observation. None of the five patients without carcinomas or of the six normal controls was positive. Although the follow-up period is limited and the recurrences were all local at present, these results suggest that the presence of CK20 mRNA in circulation may be a useful indicator for the screening of advanced colorectal carcinoma patients with a high risk of recurrence.

Adult↗

Bone marrow infarction due to acute graft-versus-host disease in an acute lymphoblastic leukemia patient after unrelated bone marrow transplantation.

We report a case of bone marrow infarction in a 20-year-old woman with acute lymphocytic leukemia (ALL) who underwent unrelated bone marrow transplantation (BMT). Hematopoietic engraftment occurred on day 9 and, thereafter, the patient developed acute dermal and hepatic graft-versus-host disease (GVHD). She also experienced severe arthralgia in her knee joints on day 21. Immunosuppressive therapy with prednisolone (PSL) for acute GVHD was given, and the arthralgia improved rapidly, correlating with the improvement in dermal and hepatic GVHD. Based on the laboratory findings and analysis of magnetic resonance images, she was diagnosed as having bone marrow infarction. The cause of the bone marrow infarction was thought to be acute GVHD-related microangiopathy.

Adult↗

Epidermal growth factor protects neuronal cells in vivo and in vitro against transient forebrain ischemia- and free radical-induced injuries.

Epidermal growth factor (EGF) has been considered to be a candidate for neurotrophic factors on the basis of the results of several in vitro studies. However, the in vivo effect of EGF on ischemic neurons as well as its mechanism of action have not been fully understood. In the present in vivo study using a gerbil ischemia-model, we examined the effects of EGF on ischemia-induced learning disability and hippocampal CA1 neuron damage. Cerebroventricular infusion of EGF (24 or 120 ng/d) for 7 days to gerbils starting 2 hours before or immediately after transient forebrain ischemia caused a significant prolongation of response latency time in a passive avoidance task in comparison with the response latency of vehicle-treated ischemic animals. Subsequent histologic examinations showed that EGF effectively prevented delayed neuronal death of CA1 neurons in the stratum pyramidale and preserved synapses intact within the strata moleculare, radiatum, and oriens of the hippocampal CA1 region. In situ detection of DNA fragmentation (TUNEL staining) revealed that ischemic animals infused with EGF contained fewer TUNEL-positive neurons in the hippocampal CA1 field than those infused with vehicle alone at the seventh day after ischemia. In primary hippocampal cultures, EGF (0.048 to 6.0 ng/mL) extended the survival of cultured neurons, facilitated neurite outgrowth, and prevented neuronal damage caused by the hydroxyl radical-producing agent FeSO4 and by the peroxynitrite-producing agent 3-morpholinosydnonimine in a dose-dependent manner. Moreover, EGF significantly attenuated FeSO4-induced lipid peroxidation of cultured neurons. These findings suggest that EGF has a neuroprotective effect on ischemic hippocampal neurons in vivo possibly through inhibition of free radical neurotoxicity and lipid peroxidation.

Animals↗

Prolyl hydroxylase and tissue inhibitor of metalloproteinase in pure pancreatic juice in patients with chronic pancreatitis.

Prolyl hydroxylase is a key enzyme in collagen synthesis, and tissue inhibitor of metalloproteinase (TIMP) is known to suppress collagenolytic enzymes. To see whether the levels of these two enzymes in serum and human pure pancreatic juice (PPJ) are good indicators of pancreatic fibrosis in chronic pancreatitis (CP), we examined 15 controls, 14 alcoholics without evident pancreatic diseases (7 current drinkers and 7 former drinkers), and 19 patients with CP. Levels of the two enzymes were determined by a sandwich enzyme immunoassay method. TIMP-1 levels in PPJ were significantly higher in patients with CP than in controls and alcoholics, with overlap in only a few exceptional patients. A significant inverse correlation between TIMP-1 and bicarbonate output in PPJ was observed. Prolyl hydroxylase levels in PPJ, in contrast, were significantly higher in current drinkers than in patients with CP, controls, and former drinkers, with overlap in only a few exceptional patients with relapsing CP. Identical results were obtained even when the enzyme levels were expressed as nanograms per milligram of protein. Serum levels of prolyl hydroxylase and TIMP-1 showed no significant differences among controls, current alcoholics, former alcoholics, and patients with CP. These results indicate that the raised level of TIMP-1 in PPJ, unlike that of prolyl hydroxylase, is a good indicator of pancreatic fibrosis in CP.

Adult↗

Bone marrow dysplasia with basophilic cells in a patient with angiocentric lymphoma.

We report a 46-year-old man suffering from angiocentric lymphoma of the skin. On admission, he had atypical cells rich in basophilic granules in the bone marrow and peripheral blood, in addition to skin eruptions and bone marrow dysplasia. Immediately after diagnosis, the patient was treated with multidrug combination chemotherapy. At first, the chemotherapy markedly relieved the skin eruption and bone marrow dysplasia, and atypical cells in the bone marrow and peripheral blood disappeared rapidly. However, the disease gradually became resistant to chemotherapy, resulting in a gradual deterioration of the skin eruption and bone marrow dysplasia, and reappearance of atypical cells. The levels of serum cytokines such as interleukin-4 and interleukin-6, and of soluble interleukin-2 receptor correlated well with the disease states. These results suggest that the lymphoma cells directly or indirectly induce the production of these cytokines and that a dysregulated cytokine network, which might be caused by lymphoma cells, induces an increase in atypical cells.

Bone Marrow↗

[The change of localization on cytokeratin of uterine cervix and the relationship to the pattern of invasion in cervical cancer].

An immunohistochemical study of 63 cases of uterine cervical cancer was undertaken. It was confirmed that the biological character of the cancer cells derived from the reserve cells changed over the course of invasion. Squamous cell carcinoma had positive keratin antibodies such as CK 10/13 (DE-K 13), CK 14 (NCL-LL 002) and CK 7 (OV-TL 12/30). In invasive squamous cell carcinoma, CK 14 positive cells were piled up and tended to be stained positive by PCNA and laminin. There were two types of staining, one of which revealed CK 14 strongly positive, and the other weakly positive. The first type differed from the second in depth and localization. The cells on the margin of a cluster of cancer cells were stained positive with CK 14 as in normal basal cells. The results obtained suggested: 1) squamous cell carcinoma has not only the character of normal squamous cells, but also that of the cells derived from the cervical glands. 2) cancer cells may develop in accordance with the character of basal cells, and the patterns of invasion change according to the character of basal cells in cancer tissue.

Biomarkers, Tumor↗