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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 613 records · Page 34Linked to original sources

Parainfluenza virus type 1 infects olfactory neurons and establishes long-term persistence in the nerve tissue.

A mouse model of Sendai virus infection was adopted to examine the in vivo neurovirulence of parainfluenza viruses. A nested polymerase chain reaction detected the Sendai virus nucleoprotein gene in the olfactory bulbs of intranasally infected mice for at least 168 days post-infection (p.i.) and virus-specific messenger RNAs for 28 days p.i. Viral proteins were histochemically detected in some olfactory neurons for 7 days p.i. They were also found in glomeruli of the olfactory bulbs but not in the mitral cells and the tufted cells. No virus was detected in the whole brain not including the olfactory bulbs. When mice were inoculated with UV-inactivated virus, the viral RNA was present in the olfactory bulbs for a short period of 14 days, with no demonstrable viraemia. These results demonstrate that the parainfluenza virus directly accesses the central nervous system via olfactory neurons and establishes long-term persistence in the nerve tissue.

Animals↗

Expression of CD44 variant exons 8-10 in colorectal cancer and its relationship to metastasis.

Splice variants of CD44 are overexpressed in human lung, breast, and colon carcinoma cell lines. This study was conducted to clarify the association between the expression of CD44 variant exons 8-10 and metastatic potential in human colorectal cancer. We found that the expression of a CD44 splice variant containing exons v8-10 was increased in all of 60 colorectal cancer specimens examined compared with matched normal colerectal mucosa, as determined by Northern blotting. Expression of CD44 variant exons 8-10 did not significantly correlate with histological type, depth of tumor invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the level of CD44 variant exon 8-10 expression was significantly higher in carcinomas associated with liver metastasis than in those without liver metastasis. In addition, expression of CD44 variant exons 8-10 in the liver metastases was more intense than that in the primary colorectal cancers. These findings indicated that this domain of the CD44 glycoprotein encoded by exons v8-10 may play an important role in tumor hematogenous metastasis of human colorectal cancer.

Blotting, Northern↗

Expression of CD44 variant exons 8-10 in gastric cancer.

The expression of CD44 variant containing variant exons 8-10 product (CD44v8-10) was studied by western blot analysis and immunohistochemistry in gastric cancers using a monoclonal antibody, 44-1V. On western blots, a single band of 130 kD was recognized in stomach cancer cell lines. CD44v8-10 expression, with reactivity localized in the cell membrane, was found in 65 (33.5%) of the 194 advanced gastric cancers. There was no correlation between CD44v8-10 immunoreactivity and serosal, lymphatic, or lymph node invasion. However, there was significant correlation with CD44v8-10 immunoreactivity and venous invasion. CD44v8-10-positive cancers were more frequently associated with hematogenous metastasis than those which were immunonegative. There was an inverse association between CD44v8-10 immunoreactivity and peritoneal dissemination, especially in diffuse type adenocarcinomas. These observations indicate that CD44v8-10 may play a role in the metastasis of gastric cancer.

Adenocarcinoma↗

Expression of endogenous retroviruses, ERV3 and lambda 4-1, in synovial tissues from patients with rheumatoid arthritis.

We addressed the question of whether or not expression of human endogenous retroviruses (ERV), ERV3 and lambda 4-1, is related to the pathogenesis of rheumatoid arthritis (RA). In genomic Southern hybridization, there were no significant differences between RA patients and healthy volunteers with regard to frequencies of restriction fragment length polymorphism (RFLP) patterns, for either ERV3 or lambda 4-1. By Northern blot analysis using fresh synovial tissues, cultured synovial cells, and peripheral blood mononuclear cells (PBMC) from patients with RA, we noted two molecular species of ERV3 mRNAs of 3.5 kb and 9.0 kb sizes, and one single molecular species of lambda 4-1 mRNAs of 4.2 kb size. The expression was detected not only in RA patients but also in synovial cells from osteoarthritis (OA) as a non-RA control and PBMC from healthy volunteers, and was not related to RA activities or treatments. Although ERV3 and lambda 4-1 expression may not be directly associated with the pathogenic pathway of RA, the possibility exists that human ERV may have a causative role in autoimmune diseases, including RA. We also examined the effect of cytokines on the transcriptional regulation of ERV3. Although the level of ERV3 expression in cultured synovial cells did not change with IL-1 beta treatment, the level for cultured proximal tubular epithelial cells (hKEC) was up-regulated.

Arthritis, Rheumatoid↗

Regional difference of endogenous ATP release in the pulmonary artery of rabbits.

1. The release of adenyl purines such as ATP, ADP, AMP and adenosine, from the pulmonary artery trunk (PAT), extrapulmonary artery (EPA) and intrapulmonary artery (IPA) were compared. 2. The amount of basal overflow of adenyl purines from the PAT was significantly smaller than those from EPA and IPA. There was no significant difference between the amount of the overflow from EPA and PAT. 3. Methoxamine, an alpha 1-adrenoceptor agonist, significantly increased the overflow of adenine nucleotides from the PAT, EPA and IPA, but did not increase those of adenosine. Methoxamine-induced release of adenyl purines from IPA was significantly larger than those from EPA and PAT. 4. These results suggest that an alpha 1-adrenoceptor-mediated mechanism for ATP-release is not homogeneously distributed in the pulmonary artery and a larger amount of ATP may be released in the peripheral part of the artery.

Adenosine↗

Shortening of the hippocampal formation in first-episode schizophrenic patients.

Shortening of hippocampal formation (HF) in chronic schizophrenic patients have been demonstrated in our previous study. The purpose of the present study is to test if shortening of the HF occurs in schizophrenic patients suffering their initial psychotic episode. We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 20 first-episode schizophrenic patients, 21 chronic schizophrenic patients, and 25 healthy subjects. Both groups of schizophrenic patients demonstrated significant shortening of the HF compared with normal controls (first-episode schizophrenia, 5.3%; chronic schizophrenia, 8.0%). However, the HF length was not significantly different between the first-episode and chronic schizophrenic patients. No significant correlation was seen between the HF length and the duration of illness in chronic schizophrenic patients. These results suggest that the HF shortening observed in schizophrenic patients may be genetic and/or developmental in origin.

Acute Disease↗

Experimental osteodystrophy of chronic renal failure induced by aluminum- and ferric-nitrilotriacetate in Wistar rats.

The aluminum (AI) and iron (Fe) chelate complexes of nitrilotriacetate (NTA) cause renal insufficiency when they are administered intraperitoneally to rats. Their effects on bone metabolism were studied in 4 week old Wistar rats. Daily intraperitoneal administration of AI-NTA (3mg AI/kg for 11 weeks) induced osteomalacia, impaired bone growth, decreased bone mineral density, lower serum PTH levels than normal as well as renal insufficiency. Al staining showed diffuse deposition in the trabecula and a strong linear band of aluminum deposited at the mineralization front and along the cement line. The osteoid seen markedly within the trabecula was probably the decalcified portion of the bone, the calcium apatite of which was defectively fabricated because of diffuse Al deposition in the trabecula. Al deposition along the cement line would make it much more susceptible to external shear stress than normal. Although daily intraperitoneal administration of Fe-NTA (6 mg Fe/kg for 11 weeks) caused impaired bone growth, decreased bone mineral content and renal insufficiency, the osteoid volume did not increase. Fe staining showed that Fe was deposited diffusely in the cytoplasm of osteoblasts. The results of this study demonstrated that during renal insufficiency, different minerals exhibit different modes of action on bone metabolism, and that Al-NTA is useful for experimental animal models of Al-induced osteomalacia in renal insufficiency.

Animals↗

Automated measurement of reticulated platelets in estimating thrombopoiesis.

We described a fully automated measurement of reticulated platelets using a fluorescent dye, auramine O, and a reticulocyte counter, the R-3000, equipped with special software. Reproducibility and linearity were shown to be good. In the normal subjects studied (n = 60), the mean value for reticulated platelets was 0.98% +/- 0.41% and the mean absolute count was 2.12 +/- 0.69 x 10(9)/l. The absolute count for reticulated platelets was significantly lower (p < 0.05) in patients with reduced thrombopoiesis as seen in acute myeloblastic leukemia, aplastic anemia or chemotherapy-induced thrombocytopenia and it was elevated (p < 0.05) in essential thrombocythemia and in chronic myelocytic leukemia with thrombocytosis. All 20 patients with chronic idiopathic thrombocytopenic purpura had a high percentage of reticulated platelets. The percentage of reticulated platelets was significantly increased (p < 0.05) in patients with impaired thrombopoiesis despite the reduction in the absolute count. In 2 leukemic patients, an apparent rise was noticed in the percentage of reticulated platelets which preceded by several days a progressive increase in the platelet count at the recovery phase of thrombocytopenia. The results suggest that an automated measurement of reticulated platelets can be applied to routine laboratories for clinical use.

Adolescent↗

Mucosal ulceration in isolated amphibian stomachs in vitro. Roles of nutrient HC03- and endogenous prostaglandins.

We examined the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on mucosal ulceration in isolated bullfrog stomachs and investigated the roles of endogenous prostaglandins (PGs) and nutrient HCO3- in the mucosal protection in vitro. Gastric sacs were prepared by separation from the muscle layer and incubation for 1-8 h in HCO3--Ringer's solution gassed with 95% 02/5% CO2 or PO3(-)4-Ringer's solution gassed with 100% 02 in the presence of histamine (1 x 10(-4) M). Under these conditions, multiple ulcers developed in the mucosa only when the gastric sacs were incubated in HCO3--free nutrient solution; both the number and severity of ulcers increased with time and reached a maximum after 6 h of incubation. Luminal pH was decreased because of stimulation of acid secretion by histamine, irrespective of whether the mucosa was bathed in Ringer's solution with or without HCO3-, while gastric potential difference was reduced only in the mucosa bathed in HCO3--free nutrient solution. 16,16-Dimethyl PGE2 added to the nutrient side significantly reduced the number of ulcers developed in the mucosa bathed in HCO3--free nutrient solution. In contrast, indomethacin and aspirin, but not salicylate, caused ulceration even in the mucosa bathed in HCO3--nutrient solution. Histamine-induced acid secretion was reduced by 16,16-dimethyl PGE2 but not affected by these NSAIDs. In conclusion, ulceration of the isolated gastric mucosa in the presence of acid depends upon either a deficiency of endogenous PGs or a lack of nutrient HCO3-/CO2.

16,16-Dimethylprostaglandin E2↗

Surface antigens on eosinophils in bronchial asthma and eosinophilic pneumonia.

Surface antigens on peripheral blood eosinophils from 23 patients with bronchial asthma, 6 with eosinophilic pneumonia and 8 controls were examined using a new direct method. Peripheral blood eosinophils in bronchial asthma and eosinophilic pneumonia showed higher complexity and/or granularity than those from controls. The percentage expression of HLA DR, CD4 and CD45RO on peripheral blood eosinophils from patients with bronchial asthma were increased compared with those from patients with eosinophilic pneumonia and from the controls. These results suggest that peripheral blood eosinophils in bronchial asthma may play a role in immunoregulation via the expression of human leukocyte antigens, such as HLA-DR, CD4 and CD45RO, that interact with lymphocytes, and may function as antigen-presenting cells. Furthermore this study suggests that there may be different phenotypes of eosinophils with differing surface antigens and intercellular reactions between eosinophils and lymphocytes.

Adult↗

Rat kidney thromboxane receptor: molecular cloning, signal transduction, and intrarenal expression localization.

Thromboxane (TX) plays important roles in control of renal hemodynamics and water and electrolyte metabolism, and is involved in the pathophysiology of many renal diseases. The aim of the present study is to isolate a rat kidney cDNA encoding functional TX receptor, and to reveal its intrarenal expression localization. A clone (rTXR2) was isolated from a rat kidney cDNA library by a homology screening approach. rTXR2 was shown to encode the amino acid sequence containing seven transmembrane spanning domains representing rat (r) TX receptor. The membrane from COS-7 cells transiently transfected with rTXR2 cDNA was shown to be specifically bound by a thromboxane receptor antagonist, SQ29548. Either in Xenopus oocyte expression or in transfected COS-7 cells, rTX receptor was shown to be linked with Ca2+ messenger system. TX receptor-mediated increase in cytosolic Ca2+ was also observed in cultured glomerular mesangial cells. In situ hybridization showed that rTX receptor mRNA was detected in renal glomeruli, smooth muscle cells in renal arterioles, and transitional cell epithelium of renal pelvis. Reverse transcription linked to PCR applied to microdissected nephron segments indicated the presence of rTX receptor mRNA exclusively in the glomerulus. In conclusion, we have cloned a functional rat kidney TX receptor, which is expressed specifically in renal glomerulus, arterial smooth muscle cells, and transitional cell epithelium of renal pelvis. The present study will provide important insights into the etiology and pathophysiology of renal diseases with relation to TX metabolism.

Amino Acid Sequence↗

Immunohistochemical localization of thromboxane receptor and thromboxane synthase in rat testis.

The cellular localization of thromboxane A2 receptor (TXR) and thromboxane synthase (TXS) in rat testes was examined with an antibody against the carboxyl-terminal tail of rat TXR and anti-porcine lung TXS antibody. By light microscopy immunoreactivity for TXR was shown to be present in spermatids, whereas spermatogonia, spermatocytes, and spermatozoa lacked the immunoreactivity. Immunoelectron microscopic analysis revealed that immunostainable TXR was present in acrosomes of spermatids. In contrast, immunoreactivity for TXS was present in all stages of spermatogenic cells; spermatogonia, spermatocytes, spermatids, and spermatozoa. TX system may possibly contribute to the formation of acrosomes or have some unrecognized functions in an autocrine/paracrine fashion.

Amino Acid Sequence↗

Pharmacological activity of chemically modified subfragment from human serum IgG. XIV. Inhibitory effect of carboxamide-methylated light chain (G1L) on tyrosine phosphorylation and tumor necrosis factor-alpha production from murine macrophages stimulated by lipopolysaccharide.

Carboxamide-methylated light chain (G1L) from human serum IgG inhibited the secretion of tumor necrosis factor (TNF-alpha), one of the inflammatory cytokines, from adherent splenocytes and thioglycolate-induced peritoneal macrophages. The inhibition of TNF-alpha secretion by G1L was associated with disappearance of tyrosine phosphorylation on about 40 kDa protein when thioglycolate-induced peritoneal macrophages were stimulated with lipopolysaccharide (LPS). It is possible that this G1L anti-inflammatory activity occurs through the blockage of the phosphorylation of about 40 kDa protein.

Animals↗

Angiotensin II type-1 receptor antagonist as well as angiotensin converying enzyme inhibitor attenuates the development of heart failure in aortocaval fistula rats.

OBJECTIVES: We investigated the effect of chronic administration of an angiotensin II type-1 receptor antagonist in the development of heart failure due to volume overload in rats. METHODS: Aortocaval fistula (AVF), a model of volume overloaded heart failure, was induced in rats by our newly developed technique using a simple and rapid 18-gauge needle multipuncture. After 3 weeks of oral administration of an angiotensin II receptor antagonist TCV-116, 1 mg/kg per day, we evaluated the hemodynamics, heart weight, and degree of left ventricular dilatation. We also compared the effect of TCV-116 with that of an angiotensin-converting enzyme inhibitor delapril, 1 g/L in drinking water. RESULTS: AVF heart failure produced by our technique exhibited significant increases in the left ventricular end-diastolic pressure (LVEDP) (12 = 1 vs 4 +/- 1 mmHg, p < 0.05), right atrial pressure (RAP) (5.0 +/- 0.6 vs 1.0 +/- 0.4 mmHg, p < 0.05), right ventricular systolic pressure (RVSP) (58 +/- 6 vs 33 +/- 1 mmHg, p < 0.05), left ventricular weight (LVW) (3.00 +/- 0.13 vs 2.09 +/- 0.04 g/kg BW, p < 0.05), right ventricular weight (RVW) (0.93 +/- 0.05 vs 0.59 +/- 0.01 g/kg BW, p < 0.05), and left ventricular end-diastolic volume index (LVEDVI) (2.55 +/- 0.14 vs 0.80 +/- 0.12 ml/kg BW, p < 0.05) as compared with these values in sham-operated rats. There were no differences in shunt ratio between untreated and TCV-116- and delapril-treated AVF groups. TCV-116 improved these hemodynamics, as did delapril (TCV-116 vs delapril: LVEDP 8 +/- 1 vs 8 +/- 1, RAP: 3.8 +/- 0.6 vs 2.3 +/- 1.4, RASP: 50 +/- 2 vs 46 +/- 3, LVW: 2.53 +/- 0.11 vs 2.52 +/- 0.15, RVW: 0.80 +/- 0.04 vs 0.77 +/- 0.06, LVEDVI: 1.67 +/- 0.15 vs 1.70 +/- 0.17). CONCLUSION: These results suggest that AVF rats with volume overload produced by a new multipuncture method exhibit both right- and left-side heart failure. Angiotensin II type-1 receptor antagonist as well as angiotensin converting enzyme inhibitor attenuate the development of this type of heart failure in rats.

Analysis of Variance↗

[Pharmacological study on the dry distillation tar of delipidated soybean (Glyteer) (5): Antimicrobial activity].

Glyteer (GL) possessed a broad antimicrobial spectra against bacteria and fungi. The antimicrobial activity of GL was bactericidal action, but not bacteriostatic action. GL was more effective against fungi than bacteria. GL ointment also showed antimicrobial activity equal to that of GL. Furthermore, GL had an effect on methicillin-resistant Staphylococcus aureus (MRSA). Resistance to GL was not induced in broth cultures of Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, and Trichophyton mentagrophytes. These results suggest that GL applied externally exerts a potent effect as an anti-microbial drug for dermopathy with various microbialpathogens.

Bacteria↗

Role of the sympathetic nervous system in gastric functional changes induced by thyrotropin-releasing hormone in rats.

We determined the changes in gastric functions and systemic blood pressure in response to thyrotropin-releasing hormone (TRH) simultaneously in anesthetized rats and examined the role of the sympathetic nervous system in these changes. TRH injected i.c. increased gastric acid secretion, contraction and mucosal blood flow, and produced hemorrhagic lesions in the glandular stomach. These responses to TRH were almost completely inhibited by bilateral cervical vagotomy or atropine. The increased gastric acid secretion and contraction in response to TRH were significantly augmented by pretreatment with yohimbine but not with prazosin. Bilateral adrenalectomy also potentiated the gastric acid secretory and contractile responses to TRH. Neither prazosin, yohimbine nor adrenalectomy had any appreciable effect on the increased gastric mucosal blood flow induced by TRH. TRH-induced gastric mucosal lesions were significantly aggravated by yohimbine and adrenalectomy. In vagotomized rats, TRH significantly suppressed the gastric functional changes induced by electrical stimulation of the vagus nerves. These data suggest that while gastric functional changes and mucosal lesions induced by TRH mainly occur through stimulation of the vagus nerves, these responses are extensively modified by the sympathetic nervous system including the adrenal glands.

Adrenergic Fibers↗

Desensitization of capsaicin-sensitive sensory neurons in rat stomachs on chronic treatment with sodium taurocholate.

We examined the effects of chronic treatment with 10 mM sodium taurocholate (TC) on gastric functions, capsaicin-sensitive afferent neurons and the gastric mucosa in male rats. Stomachs were mounted in Lucite chambers, and then the transmucosal potential difference (PD), luminal pH and gastric mucosal blood flow (GMBF) in response to TC or capsaicin was determined. In normal animals, 10 mM TC caused a reduction in PD, and increases in luminal pH and GMBF. Capsaicin (1 mg/ml) produced an apparent increase in GMBF without any change in PD or luminal pH. After 4- or 12-week treatment with TC, the basal PD was significantly reduced, and the luminal pH tended to increase. The increase in GMBF in response to TC or capsaicin was profoundly suppressed in TC-pretreated animals. The calcitonin gene-related peptide release in response to capsaicin was significantly reduced after 4 weeks treatment with TC. There were no microscopical changes in the oxyntic mucosa until 4 weeks after TC treatment except for exfoliation of surface cells. However, an increase in inflammatory cell infiltration was observed 12 weeks later. We conclude that chronic treatment with TC causes desensitization of capsaicin-sensitive afferent neurons and reduces GMBF, which may result in the production of gastritis.

Animals↗

Effect of prolonged beta-adrenergic blockade induced by atenolol on left ventricular remodeling after acute myocardial infarction in the rat.

Beta-adrenergic receptor blockade reduces the mortality rate after acute myocardial infarction (AMI) in humans. However, the effects of beta blockade on left ventricular remodeling remain unknown. Therefore, in the present study we investigated the effect of prolonged beta-adrenergic receptor blockade with atenolol on left ventricular remodeling following AMI in rats. Myocardial infarction (MI) was produced in Wistar-Kyoto rats by ligating the coronary artery. Four groups of rats were studied: sham-operated (n = 10); atenolol (1 g/l in drinking water) treated sham-operated (n = 8); untreated MI (n = 11); atenolol treated MI (n = 10). Hemodynamic measurements were made about 3 weeks after the operation. Infarct size was similar in treated and untreated MI rats (31.2 +/- 2.5% cf. 33.5 +/- 2.0%). MI rats were characterized by increases in left ventricular end-diastolic pressure (LVEDP), right atrial pressure (RAP), right ventricular systolic pressure (RVSP), and left ventricular end-diastolic volume index (LVEDVI), as compared with sham-operated rats. In sham-operated rats, prolonged beta-adrenergic receptor blockade produced only a reduced HR. Atenolol-treated MI rats had a significantly higher LVEDP, RAP and LVEDVI than did rats with untreated MI. Prolonged beta-adrenergic receptor blockade with atenolol appeared to promote left ventricular remodeling after AMI. Thus, the treatment of AMI with beta-adrenergic receptor blockade in the clinical setting should be evaluated with respect to ventricular remodeling during prolonged therapy.

Animals↗