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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 901 records · Page 50Linked to original sources

Increased population of nonhormone-producing cells suggests the presence of dysfunctional growth hormone cells in the anterior pituitary gland of the spontaneous dwarf rat.

Anterior pituitary gland of the spontaneous dwarf rat (SDR) with isolated growth hormone (GH) deficiency was studied using immunocytochemistry, cell count and in situ hybridization. The standard immunocytochemistry of five anterior pituitary hormones [adrenocorticotropic hormone (ACTH), luteinizing hormone, thyroid-stimulating hormone, prolactin (PRL) and GH] and S-100 protein failed to detect any cytological difference between normal rats and SDRs, except for the size of different types of cells which were smaller in SDR than in normal rats, and GH cells which were undetectable in the SDR. The cell count study again showed lack of immunoreactive GH cells in the SDR. The population of PRL cells was significantly reduced in the SDR by 40% in male and 30% in female when compared to those of the control. The population of ACTH cells was larger in the male SDR. The population of the immunonegative cells was calculated by subtracting the sum of the percentages of immunopositive cells from 100, and it was found to be remarkably increased in the SDR. The population of immunonegative cells was about 55% in both male and female SDRs, whereas it was calculated to be 18.7% (male) or 10.2% (female) in the control rats. In situ hybridization study using GH cRNA indicated the presence of a considerable number of cells which express GH mRNA in the SDR as well as in the control rats. These results taken as a whole suggest the presence of a number of dysfunctional GH cells in the SDR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Role of gastric mucosal prostaglandin E2 in the inhibitory action of secretin and somatostatin on gastric acid secretion in the rat.

We investigated the effect of indomethacin on secretin- and somatostatin-induced inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 microgram/kg.h) in anesthetized rats. Intravenous administration of a prostaglandin synthesis inhibitor, indomethacin (2 mg/kg + 1 mg/kg.h), completely abolished the inhibition of gastric acid secretion induced by intravenous infusion of secretion (0.05 CU/kg.h). The inhibitory effect of intravenous infusion of somatostatin (Sandostatin; 0.2 micrograms/kg.h). The inhibitory the gastric acid was not significantly changed by indomethacin. Secretin significantly increased the gastric mucosal content of prostaglandin E2, and the increase was completely blocked by indomethacin. Somatostatin, however, had no significant effect on gastric mucosal prostaglandin E2. The results suggest that endogenous prostaglandin is involved in the mechanism of inhibition of gastric acid secretion by secretin, but not by somatostatin.

Animals↗

Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes.

The present study was conducted to examine the effect of activin A on growth of rat hepatocytes. EGF induced a 10-fold increase in DNA synthesis as assessed by [3H]thymidine incorporation in cultured hepatocytes. When activin A was added together with EGF, DNA synthesis induced by EGF was markedly inhibited. Inhibition was detected at a concentration of 10(-10) M, and 5 x 10(-9) M activin A almost completely blocked EGF-mediated DNA synthesis. Similarly, activin A completely blocked DNA synthesis induced by hepatocyte growth factor/scatter factor. Activin A was capable of inhibiting EGF-mediated DNA synthesis, even when added 36 h after the addition of EGF. With the same time interval, TGF-beta also blocked EGF-induced DNA synthesis. Although both activin A and TGF-beta inhibited growth of hepatocytes in a similar manner, either activin A or TGF-beta did not compete with each other in their binding when assessed by competitive binding using an iodinated ligand. When hepatocytes were incubated with EGF, release of bioactivity of activin A into culture medium was detected after 48 h or later. Activity of activin A was released from parenchymal cells but not from nonparenchymal cells. mRNA for beta A subunit of activin was detected only slightly in unstimulated hepatocytes, but markedly increased at 48 h after the addition of EGF. To determine whether endogenously produced activin A affects DNA synthesis, we examined the effect of follistatin, an activin-binding protein that blocks the action of activin A. An addition of follistatin significantly enhanced EGF-induced DNA synthesis. Finally, in partial hepatectomized rat, expression of mRNA for beta A subunit in liver was markedly increased 24 h after the partial hepatectomy. These results indicate that activin A inhibits initiation of DNA synthesis in hepatocytes by acting on its own receptor and that activin A acts as an autocrine inhibitor of DNA synthesis in rat hepatocytes.

Activins↗

Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis.

Upregulation of integrin adhesive receptors has been implicated in various pathological conditions. We examined expression and function of integrin adhesive receptors on peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE), particularly those with the complication of vasculitis, and found that VLA-4 and LFA-1 expression was increased in SLE patients with vasculitis, while LFA-1 but not VLA-4 expression was increased in those without vasculitis. These results suggested a role of VLA-4 in the pathogenesis of vasculitis in SLE. Functional studies further demonstrated that adhesion to cytokine-activated human umbilical cord vein endothelial cells and to the CS-1 alternatively spliced domain of fibronectin was significantly increased in SLE patients with vasculitis. Analysis of the functional epitopes on the alpha 4 chain demonstrated that antigen densities of all the functional epitopes were increased in those with vasculitis, indicating that the increased expression of VLA-4 resulted from the increased number of VLA-4 molecules, and was not secondary to an increase in one particular functional epitope. Immunoprecipitation studies further support these results. Interestingly, high molecular weight bands associated with VLA-4 were observed in about half of the SLE patients with vasculitis. These results introduce a possibility that upregulation of integrin adhesive receptors has a potential role in the pathogenesis of vasculitis in SLE.

Adolescent↗

Existence of activin-A in A- and D-cells of rat pancreatic islet.

Activin-A, a member of the transforming growth factor-beta supergene family, stimulates insulin secretion in rat pancreatic islets and causes glycogenolysis in isolated rat hepatocytes. These observations prompted us to determine whether activin-A existed in rat pancreas by using an immunocytochemical method. Cells in pancreatic islets were stained by antibody against activin-A, whereas no immunoreactivity was observed in exocrine pancreas. Cells localized in the mantle of the islets were densely stained by the antibody. Immunoelectron microscopic study showed that activin-A existed in secretory granules in both A- and D-cells. Furthermore, studies using a double labeling method revealed that activin-A coexisted with glucagon in secretory granules in A-cells and with somatostatin in D-cells. Antibody against inhibin-A weakly stained cells in both the core and mantle of the islets only when the rat was pretreated with colchicine. Subtypes of activin subunit in islets were identified to be beta A by a reverse transcription-polymerase chain reaction method. In addition, mRNA for inhibin alpha-subunit was expressed in islets. However, mRNA for these inhibin subunits was not detected in exocrine pancreas. To further examine the action of activin-A on insulin secretion, we examined the effect of activin-A in a flow-through perifusion system. Activin-A induced a biphasic insulin secretory response in the presence of 2.8 mM glucose, and a low concentration of activin-A, which does not stimulate insulin secretion by itself, markedly enhanced glucose-mediated insulin secretion at concentrations above 2.8 mM glucose. Inhibin-A did not affect insulin secretion. These results suggest the existence of activin-A in A- and D-cells of rat pancreatic islets and raise the possibility that activin-A acts as a physiological regulator of carbohydrate metabolism.

Activins↗

Processing of mutated proinsulin with tetrabasic cleavage sites to mature insulin reflects the expression of furin in nonendocrine cell lines.

Furin is a mammalian propeptide-processing endoprotease in nonendocrine cells and has been demonstrated to be present in virtually all nonendocrine cells, including fibroblasts, epithelial cells, and hepatocytes. Furin cleaves the concensus processing site -Arg-4-X-3-Lys/Arg-2-Arg-1 decreases X+1-. Some subunit-containing precursor proteins, including an insulin receptor precursor, possess an additional basic residue at position -3, thus forming a tetrabasic processing site. This implies that a tetrabasic processing site must be easily cleavable in nonendocrine cells. We created a mutant proinsulin DNA with a peptide structure comprised of B- and A-chains linked to the C-peptide by a pair of tetrabasic residues, in the following order: B-chain-Arg-Arg-Lys-Arg-C peptide-Arg-Arg-Lys-Arg-A-chain. The native proinsulin structure was B-chain-Arg-Arg-C-peptide-Lys-Arg-A-chain. Both the native and mutant proinsulins were expressed in the following four cell lines: a monkey kidney-derived cell line (COS-7), a Chinese hamster ovary-derived cell line (CHO), a human liver cancer-derived cell line (HepG2), and a mouse fibroblast-like cell line (NIH3T3). We used these cell lines because they contain different quantities of furin mRNA, ranking as follows: NIH3T3 > HepG2 > COS > CHO. When mutant insulin was expressed in these cells, the conversion of proinsulin to mature insulin was approximately 85% in NIH3T3, 70% in HepG2, 60% in COS, and 50% in CHO. The conversion correlated well with the furin expression in each cell line as measured by the density of its Northern blot band. Moreover, in CHO, the cell line with the lowest furin expression, coexpression of mutant proinsulin with furin resulted in complete conversion of proinsulin to mature insulin.

3T3 Cells↗

Distinct effects of clinically used anthracycline antibiotics on ras oncogene-expressed cells.

Doxorubicin, pirarubicin, and FAD-104, but not aclarubicin or MX 2, flattened the morphology of NIH3T3 cells that had been transformed by human H-ras and K-ras. The effect appeared on almost all cells, as early as 2 d following exposure to the antibiotics at concentrations inhibiting cell growth by 50% or more. The morphological alteration accompanied other normal cell phenotypes, such as the restoration of actin stress fibers, anchorage dependence of cell growth and an increase in nucleoside diphosphate (NDP) kinase activity. NIH3T3 cells transformed by src and other tumor cell lines responded less prominently, if at all.

3T3 Cells↗

The prognostic significance of exercise-induced silent ST-segment depression in patients after myocardial infarction.

To evaluate the prognostic value of exercise-induced silent ST-segment depression, 157 patients who had suffered myocardial infarction underwent symptom-limited exercise testing and coronary angiography. Patients were divided into 3 groups according to the presence or absence of ischemic ST-segment depression and angina during exercise testing. Group A patients had ST-segment depression without angina. Group B patients had both ST-segment depression and angina. Group C patients had neither ST-segment depression nor angina. All patients were followed without coronary artery bypass graft or percutaneous transluminal coronary angioplasty for an average of 36 months and the frequency of coronary events (cardiac death, recurrent myocardial infarction and unstable angina pectoris) was compared. Group A patients had less severe coronary artery disease, greater coronary reserve during exercise and exercised longer than group B. However, the prognosis of group A was similar to group B, and was worse than group C. Using the Cox proportional hazards model, ischemic ST-segment depression was the most useful index for predicting future coronary events among the baseline values, coronary angiographic and exercise testing variables. However, angina during exercise testing was not an independent predictor. Thus, post-infarction patients showing exercise-induced ST-segment depression should be treated carefully regardless of the presence or absence of angina.

Adult↗

Dissociation of cyclic GMP level from relaxation of the distal, but not the proximal colon of rats.

The role of cyclic GMP (cGMP) in nonadrenergic, noncholinergic (NANC) relaxation of the longitudinal muscle of rat proximal and distal colon was examined. Electrical field stimulation (EFS) of preparations of longitudinal muscle from the proximal region significantly increased the cGMP content. Nitro-L-arginine inhibited this increase, and L-arginine reversed the inhibitory effect of nitro-L-arginine. Exogenously added nitric oxide (NO) and atrial natriuretic peptide (ANP) also increased the cGMP content of preparations of the proximal colon and induced muscle relaxation. From these and our previous findings suggesting an essential role of NO in NANC inhibition in the proximal colon, we conclude that the mechanism of NANC inhibition in the proximal region of rat colon involves NO and a cGMP generating system. In contrast, although exogenously added NO and ANP increased the cGMP content in the distal colon to the same extent as in the proximal colon, they did not induce any muscle relaxation. Vasoactive intestinal peptide (VIP), the most likely candidate as a NANC neurotransmitter in rat distal colon, did not increase the cGMP content in this region. Furthermore, no participation of NO in the NANC inhibitory response was observed in the distal region, but EFS increased the cGMP content significantly. Thus we conclude that relaxation of longitudinal smooth muscle in the distal portion of rat colon is not associated with a change in the cGMP content.

Animals↗

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↗

Cytomegalovirus mononucleosis with mixed cryoglobulinemia presenting transient pseudothrombocytopenia.

A 61-year-old man was admitted to our hospital because of fever and general malaise. We diagnosed his condition as cytomegalovirus (CMV) mononucleosis by hematological testing. His platelet count was decreased in spite of collection with several anticoagulants at room temperature (20 degrees C); no decrease was observed at 37 degrees C. Mixed cryoglobulinemia, monoclonal IgM and polyclonal IgG, which acted as anti-platelet antibodies in cold condition, were found in the patient's serum. With the resolution of CMV infection, the cryoglobulins disappeared and the platelet count returned to normal without platelet agglutination. This is the first report of transient pseudothrombocytopenia in CMV mononucleosis with mixed cryoglobulinemia.

Antigens, Human Platelet↗

Duodenal stromal tumor with neural differentiation.

A 49-year-old woman was admitted to our hospital for detailed evaluation of an abdominal mass. Ultrasonography and computed tomography revealed two tumors, one a submucosal lesion of the duodenal second portion and the other a left adrenal tumor. Angiography showed that the tumors were hypervascular. Both tumors were removed surgically and examined histologically using hematoxylin-eosin staining. The duodenal tumor (10 x 6 x 5 cm) was initially diagnosed as a schwannoma, but immunohistochemical studies showed that it was S-100 protein negative and neuron-specific enolase positive. Therefore, this tumor was identified as a stromal tumor with neural differentiation. The left adrenal tumor was a nonfunctioning adenoma.

Adenoma↗

Postnatal development of visual evoked potentials in Japanese black calves.

The visual evoked potential (VEP) was recorded in six Japanese Black calves from 1 to 10 weeks after birth. The VEP waveform recorded at the 1st week was consisted of three positive and three negative peaks. The VEP showed little postnatal changes except for the shortening of the peak latencies of P1 and N3 and the increase of the peak-to-peak amplitudes of P1-N1 and P2-N2 (significant between the 1st and 10th week of age). The visual function associated with generation of the flash VEP is suggested to have almost developed at birth in the calf. The postnatal measurement of the VEP would be useful for evaluating the neurologic disorders of the visual system in young calves.

Aging↗

Auditory information in playing tennis.

Three experienced tennis players used earplugs to deprive them of auditory information when playing tennis matches. They lost more games in the auditory-deprived condition than in the condition without earplugs. Their ability in receiving the service decreased although ability to deliver the service did not. These observations suggest that multisensory information is used in an adaptive manner when playing tennis.

Adult↗

Effects of dibutyryl cyclic AMP and papaverine on intrahepatocytic bile acid transport. Role of vesicle transport.

The secondary messenger cyclic AMP plays an important role in regulating biliary excretory function by stimulating the transcytotic vesicle transport system, whereas papaverine exerts an inhibitory effect on this system. We therefore investigated their effects on bile acid-induced cytotoxicity and intrahepatocytic content of bile acid in primary cultured rat hepatocytes. Simultaneous addition of 1 mM dibutyryl cyclic AMP (DBcAMP), an analogue of cAMP, with 1 mM taurochenodeoxycholic acid (TCDCA) significantly decreased the release of lactate dehydrogenase (LDH) as compared with the case with 1 mM TCDCA alone (7.1 +/- 0.13% of total versus 10.7 +/- 0.3%). In contrast, 0.1 mM papaverine approximately doubled the amount of LDH (22.0 +/- 0.6% of total versus 10.7 +/- 0.3%; P < 0.01). The intracellular content of TCDCA 180 min after the administration of 1 mM TCDCA alone was 20.8 +/- 0.7 nmol/mg protein, that after simultaneous administration of 1 mM DBcAMP, 16.2 +/- 1.0 nmol/mg protein, and that after the simultaneous administration of 0.1 mM papaverine, 38.5 +/- 1.9 nmol/mg protein. A clear correlation between the release of LDH from hepatocytes and the intracellular content of TCDCA was thus observed. When given together with 1 mM taurocholic acid (TCA) or 1 mM tauroursodeoxycholic acid (TUDCA), papaverine exerted little effect on cytotoxicity or intrahepatocytic bile acid content. When cells were bathed in a medium free of bile acid after pretreatment with 1 mM TCDCA and 1 mM DBcAMP, additional exposure to DBcAMP for 30 min significantly stimulated reduction of intracellular TCDCA content (30.2 +/- 0.4% of total versus 44.0 +/- 1.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Natural history and URSO dissolution therapy of gallbladder stones in the elderly].

To determine how to treat silent gallstones in the elderly, 1771 autopsied cases 65 years of age or older were studied retrospectively, and 121 cases with asymptomatic gallbladder stones were followed for over 3 years. Of these, 47 cases treated with ursodeoxycholic acid (UDC) for over 3 years were investigated to determine the efficacy of UDC therapy. In the autopsied cases, the incidence of gallbladder stones was 16%, and increased with age. The ratio of males to females was 1:1.2. Only 3.2% of people with silent gallstones developed symptoms. Autopsy studies showed that the majority of people with gallstones died of unrelated causes such as benign respiratory and circulatory diseases. Only 1.8% of patients with gallstones died of acute cholecystitis or gallbladder carcinoma. UDC treatment was effective in 55.9% of patients with radiolucent stones. The percentage of patients requiring surgery due to becoming symptomatic was much lower (6.4%) in UDC-treated patients. The visualization of the gallbladder on cholecystogram improved in cases treated with UDC. These results indicate that elderly patients with silent gallstones generally develop neither symptoms nor carcinoma. Therefore, follow-up management by ultrasonography and cholecystography can be allowed. We also emphasized that a satisfactory response was obtained with long term UDC therapy.

Administration, Oral↗