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Biomedical subjects

K Doi

Publications and source records attributed to K Doi.

At least 73 records · Page 4Linked to original sources
PubMed2001

C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization.

We recently reported that C-type natriuretic peptide (CNP) occurs in vascular endothelial cells and acts as a vascular-type natriuretic peptide. In the present study, we stimulated the cGMP cascade in proliferating smooth muscle cells (SMCs), in which particulate guanylate cyclase-B, the specific receptor for CNP, is predominantly expressed, by use of an adenovirus encoding rat CNP cDNA (Ad.CNP). In the Ad.CNP-treated cultured SMCs, CNP caused the growth inhibition of SMCs at G(1) phase with an early increase of p21(CIP1/WAF1) expression and subsequent upregulation of p16(INK4a). The expression of smooth muscle myosin heavy chain-2, which is the molecular marker of highly differentiated SMCs, was reinduced in the Ad.CNP-treated SMCs. The Ad.CNP-treated SMCs also reexpressed particulate guanylate cyclase-A, which shows high affinity to atrial and brain natriuretic peptide and is exclusively expressed in well-differentiated SMCs. CNP, which was overexpressed in rabbit femoral arteries in vivo at the time of balloon injury, significantly suppressed neointimal formation. Furthermore, an enhancement of the expression of smooth muscle myosin heavy chain-2 occurred in the residual neointima. In addition, early regeneration of endothelial cells was observed in the Ad.CNP-infected group. Thus, stimulation of cGMP cascade in proliferating dedifferentiated SMCs can induce growth inhibition and redifferentiation of SMCs with accelerated reendothelialization.

Adenoviridae↗
PubMed2001

Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans.

Ghrelin, an endogenous ligand for the GH secretagogue receptor, was isolated from rat stomach and is involved in a novel system for regulating GH release. Although previous studies in rodents suggest that ghrelin is also involved in energy homeostasis and that ghrelin secretion is influenced by feeding, little is known about plasma ghrelin in humans. To address this issue, we studied plasma ghrelin-like immunoreactivity levels and elucidated the source of circulating ghrelin and the effects of feeding state on plasma ghrelin-like immunoreactivity levels in humans. The plasma ghrelin-like immunoreactivity concentration in normal humans measured by a specific RIA was 166.0 +/- 10.1 fmol/ml. Northern blot analysis of various human tissues identified ghrelin mRNA found most abundantly in the stomach and plasma ghrelin-like immunoreactivity levels in totally gastrectomized patients were reduced to 35% of those in normal controls. Plasma ghrelin-like immunoreactivity levels were increased by 31% after 12-h fasting and reduced by 22% immediately after habitual feeding. In patients with anorexia nervosa, plasma ghrelin-like immunoreactivity levels were markedly elevated compared with those in normal controls (401.2 +/- 58.4 vs. 192.8 +/- 19.4 fmol/ml) and were negatively correlated with body mass indexes. We conclude that the stomach is a major source of circulating ghrelin and that plasma ghrelin-like immunoreactivity levels reflect acute and chronic feeding states in humans.

Adult↗
PubMed2001

Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase.

Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and cell contraction inactivated all three MAP kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)-cJun N-terminal kinase (JNK) and MKK3/6-p38 pathways). However, little is known about the molecular mechanisms that link the mechanical force to the MAP kinase cascades. To test whether Ras and Rap1 are possible components in the stretch-activated MAP kinase pathways, we examined if Ras and Rap1 were activated by cell stretching and if inhibition of their activity decreased the stretch-enhanced MAP kinase activity. Rap1 was activated by cell stretching and inactivated by cell contraction, whereas Ras was inactivated by cell stretching and activated by cell contraction. Rap1GapII and SPA-1, downregulators of Rap1 activity, decreased the stretch-enhanced p38 activity, whereas a dominant-negative mutant of Ras (RasN17) did not inhibit the stretch-initiated activation of MAP kinases. Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity. These results indicate that Rap1 is involved in transducing the stretch-initiated signal to the MKK3/6-p38 pathway, but not to the MEK1/2-ERK or the MKK4 (SEK1)/MKK7-JNK pathway. Thus, Rap1 plays a unique role in force-initiated signal transduction.

Animals↗
PubMed2001

Studies on the constituents of the leaves of Morus alba L.

Two novel prenylflavanes (1, 2) and a glycoside (3) of 1 were isolated along with six known compounds, isoquercitrin (4), astragalin (5), scopolin (6), skimmin (7), roseoside II (8) and benzyl D-glucopyranoside (9), from the leaves of Morus alba. The inhibitory activities of compounds 1, 2 and 3 on the oxidation of human low density lipoprotein (LDL) were investigated.

Antioxidants↗
PubMed2001

Isolation and characterization of enterocin SE-K4 produced by thermophilic enterococci, Enterococcus faecalis K-4.

Enterococcus sp. K-4, with a bacteriocin-like activity against E. faecium, was isolated from grass silage in Thailand. Morphological, physiological, and phylogenetic studies clearly identified strain K-4 as a strain of E. faecalis. Strain K-4 produced a maximal amount of bacteriocin at 43-45 degrees C. We purified, for the first time, the bacteriocin produced at high temperature by E. faecalis to homogeneity, using adsorption on cells of the producer strain and reversed-phase liquid chromatography. The bacteriocin, designated enterocin SE-K4, is a peptide of about 5 kDa as measured by SDS-PAGE, and Mass spectrometry analysis found the molecular mass of 5356.2, which is in good agreement. The amino acid sequencing of the N-terminal end of enterocin SE-K4 showed apparent sequence similarity to class IIa bacteriocins. Enterocin SE-K4 was active against E. faecium, E. faecalis, Bacillus subtilis, Clostridium beijerinckii, and Listeria monocytogenes. Enterocin SE-K4 is very heat stable.

Amino Acid Sequence↗
PubMed2001

A case of canine primitive neuroectodermal tumor (PNET).

A 2-year and 6 month-old, female, Golden Retriever showed circling behavior and seizure. By magnetic resonance imaging (MRI) examination, a mass was found on the surface of the left cerebral hemisphere, invading to the left temporal muscle. The skull bone between them was destroyed. The dog was euthanized and necropsied. Histologically, the mass contained a lot of undifferentiated anaplastic cells, forming Homer-Wright rosettes and pseudopalisading patterns. Thus, the case was diagnosed as primitive neuroectodermal tumor (PNET).

Animals↗
PubMed2001

Giant cell hepatitis in two young cats.

A very rare case of the liver lesion characterized by formation of multinucleated giant hepatocytes with inflammatory cell infiltration were observed in two young (1.5 years and 2 years old) cats bearing thymic malignant lymphoma. Histopathological features of this liver lesion were very similar to giant cell hepatitis (GCH) in human neonates and infants. Therefore, the lesion was diagnosed as feline GCH.

Animals↗
PubMed2001

Pneumocystis carinii pneumonia in a Cavalier King Charles Spaniel.

Pneumocystis carinii pneumonia was diagnosed by postmortem examination of a one-year-old Cavalier King Charles Spaniel with four-week history of dyspnea. Cytologic and histologic examination of lung tissues revealed numerous P. carinii trophozoites and cysts, and P. carinii specific DNA was detected by polymerase chain reaction. The dog showed hypogammagloblinemia and extremely low levels of serum IgG. It was considered that P. carinii pneumonia in this case was associated with an immunodeficient condition which has already been reported in Miniature Dachshunds.

Animals↗
PubMed2001

Esophageal adenosquamous carcinoma in a cat.

Esophageal carcinoma was observed in an eight-year-old, castrated male, Japanese domestic cat. Histologically, this neoplasm consisted of two different growth patterns, squamous cell carcinoma and adenocarcinoma. The results of immunohistochemical examination supported the fact that the two kinds of neoplastic cells have different characteristics. The tumor was, therefore, diagnosed as adenosquamous carcinoma. Esophageal tumors in the cat are very rare and, if any, neither adenocarcinoma nor adenosquamous carcinoma has been reported up to the present.

Animals↗
PubMed2001

Apoptotic cell death and cell proliferative activity in the rat fetal central nervous system from dams administered with ethylnitrosourea (ENU).

Ethylnitrosourea (ENU), a well known DNA alkylating agent, induces anomalies in the central nervous system (CNS), craniofacial tissues and male reproductive organs, and the enhancement of apoptosis is found in these tissues immediately after the administration of ENU (Katayama et al., 2000a). In this study, pregnant rats were treated with 60mg/kg of ENU at day 13 of gestation, and kinetics of apoptotic cells, mitotic cells and bromodeoxyuridine (BrdU)-positive cells in the fetal CNS were examined from 3 to 48 hours after the treatment (HAT). From 3 HAT, a significant increase in the number of apoptotic cells and a significant decrease in the number of mitotic cells were detected in the fetal CNS, and BrdU-positive cells significantly decreased in accordance with the increase in the number of apoptotic cells. The present results strongly suggest that both excess cell death by apoptosis and cell growth arrest indicated by decreased number of mitotic cells and BrdU-positive cells may have a close relation to the later occurrence of microencephaly following ENU-administration, and that ENU affects mainly S-phase cells and causes apoptosis.

Animals↗
PubMed2001

Restitutive response of Mini rat liver to injury induced by a single oral administration of thioacetamide.

Mini rats are a transgenic rat strain carrying antisense gene for rat growth hormone (GH), resulting in retarded growth and a lower blood GH level (136 +/- 42.0 ng/mL) compared with that of age-matched parental strain Wistar rats (329 +/- 337 ng/mL). Mini rats have been used by several investigators as a GH deficiency model. In this work, we gave a single oral administration of thioacetamide (TAA), a hepatotoxicant, to both Mini rats and Wistar rats to ascertain the influence of GH deficiency on liver response to chemically induced injury and subsequent regeneration. TAA administration caused liver injury in both strains, with a greater extent of injury in Mini rats. Proliferation of bile epithelial cells and so-called oval cells was prominent at Day 3 in Mini rats only, and this change correlated well with serum total bilirubin concentrations. Antibody against Ki-67 antigen revealed that cellular proliferation after TAA-induced liver injury was suppressed but prolonged in the Mini rat liver. Although hepatic stellate cells and Kupffer cells/macrophages were more abundant in the livers of TAA-treated Mini rats, the hepatic expression patterns of hepatocyte growth factor and transforming growth factor beta 1 were comparable to those of Wistar rats. Insulin-like growth factor-I gene expression was significantly reduced in the Mini rat liver. Our results imply that a lower GH level may exacerbate chemically induced liver injury, enhance infiltration/proliferation of non-parenchymal cells, suppress regeneration of hepatocytes, and induce proliferation of bile epithelial cells and oval cells when the liver is injured by TAA.

Administration, Oral↗
PubMed2001

[Efficacy of local ablation therapy for liver metastasis from colorectal cancer--radiofrequency ablation and microwave coagulation therapy].

We evaluated the efficacy of local ablation therapy in 40 patients with liver metastases from colorectal cancer. Radiofrequency ablation (RFA) and/or microwave coagulation therapy (MCT) were used. Ablation therapies were performed in percutaneous, endoscopic, and operative procedures. The regional recurrence rate at the therapeutic sites was 15% (median follow-up period of 2.5 years). The average surgical margin in the operative ablation group was 11 mm. The cumulative 5-year survival rates were 37% in the local ablation, 41% in the hepatic resection, and 5% in the regional chemotherapy groups. Major complications occurred in only two patients (one biliary fistula and one liver abscess). Together these observations indicate that local ablation therapy is a radical and safe locoregional therapy that provides adequate local control and contributes to long survival.

Catheter Ablation↗
PubMed2001

[A promising new treatment strategy for advanced hepatocellular carcinoma--"multi-ablation therapy" consisting of radio-frequency ablation (RFA), microwave coagulation therapy (MCT) and ethanol injection therapy (EIT)].

We introduce a new treatment strategy (multi-ablation therapy) for advanced hepatocellular carcinoma (HCC). The therapy consists of radio-frequency ablation (RFA), microwave coagulation therapy (MCT) and ethanol injection therapy (EIT). We assessed the efficacy of the therapy in 20 patients with advanced HCCs, including 10 patients with stage III and 10 patients with stage IV. The average tumor diameter was 3.6 cm (max: 6.6 cm) and the average tumor number was 3.6 (max: 11). RFA, MCT and EIT were performed in 20, 14 and 9 cases, respectively. A percutaneous, endoscopic and open approach was applied in 2, 11 and 7 cases, respectively. The average number of times treated on initial admission was 1.1. The response rate, calculated by the tumor necrosis effect, was 100%. The cumulative two-year recurrent rate in the treated sites was 33% and the 2-year cumulative survival rate was 90%. Complications were encountered in two patients (liver failure and pyothorax). Multi-ablation therapy provides an excellent prognosis for advanced HCC patients whose condition could not be controlled with conventional therapeutic modalities.

Carcinoma, Hepatocellular↗
PubMed2001

[Good response in case of hepatocellular carcinoma with portal tumor thrombs--a case report of interdisciplinary local therapy].

A 56-year-old male patient with chronic C type hepatitis had HCC which invaded right portal vein trunk (Vp3). In August 2000, we performed intrahepatic artery infusion chemotherapy with CDDP and 5-FU under subcutaneous interferon alpha treatment. In addition, we used chemoradiation therapy for portal tumor thrombus in HCC. As the result of such therapy, the size of HCC and portal tumor thrombus reduced and the level of PIVKA-II decreased. There were no side effects except fever due to interferon alpha treatment. In February 2001, we performed devascularization and RFA therapy for HCC in S7 of liver under laparoscope. The level of PIVKA-II was within the normal range. It is important to perform interdisciplinary therapy appropriate for the HCC status.

Antineoplastic Agents↗
PubMed2001

[Complete response (CR) in a case of advanced hepatocellular carcinoma by percutaneous multi-ablation therapy].

A 56-year-old male patient was diagnosed with hepatocellular carcinoma by abdominal ultrasonography. The tumor was located in segment 7-1 and was 7 cm in diameter. Two transcatheter arterial chemoembolizations (TACE) were not effective. The patient had experienced more than ten fractures because of fibrous dysplasia of the bone. Laparotomy was very risky, so we decided to perform multi-ablation therapy. This therapy consists of percutaneous radiofrequency ablation (RFA) and percutaneous ethanol injection therapy (PEIT). PEIT was applied to the lesion where extrahepatic the Glisson's capsule was near the tumor. After two sessions with these therapies, the tumor with the surrounding liver parenchyma turned necrotic. A complete response was obtained and the patient has been disease-free for 6 months. We conclude that our multi-ablation therapy is effective for patients with advanced hepatocellular carcinoma who have therapeutic limitations because of some preoperative complications.

Carcinoma, Hepatocellular↗
PubMed2001

Regional variations in the distributions of small intestinal intraepithelial lymphocytes (IELs) in BALB/c +/+, nu/+, and nu/nu mice.

Regional variations in intraepithelial lymphocytes (IELs) in the small intestine were examined in BALB/c +/+, nu/+, and nu/nu mice. The small intestine was obtained from 11- to 12-week-old mice and divided equally into three (proximal, middle, and distal) parts. The IELs were isolated from each part of the intestine, and the total numbers of IELs in nu/+ and nu/nu mice were about a fifth of those in +/+ mice. Regional variations in the distribution of the IEL alphabeta, but not the gammadelta T-cell subset were found by use of flow cytometry in +/+ and nu/+ mice. On the other hand, such differences were not found in nu/nu mice, suggesting that thymus-independent development of T cells is not different among regions. Different local expansion of thymus-dependent alphabeta T cells may cause the regional variations seen in the distribution of alphabeta T cell IELs in +/+ and nu/+ mice.

Animals↗
PubMed2000

A chromosomal locus encoding a phosphoserine phosphatase- and a truncated MinD-like protein affects differentiation in Streptomyces azureus ATCC14921.

We isolated BalA1, a representative transformant of thiostrepton-producing strain Streptomyces azureus ATCC14921, which carries an approximately 2.5-kb chromosomal DNA fragment on a high-copy-number plasmid. While strain BalA1 formed little aerial hyphae, its morphological defect was restored by cultivation with S. azureus, S. laurentii, etc. Strain BalA1 strongly inhibited the growth of Bacillus subtilis more than its parent strain, and also inhibited the development of its parent and some Streptomyces strains with thiostrepton resistance. Furthermore, it induced Streptomyces coelicolor A3(2) to produce undecylprodigiosin, at an early stage of growth. The 2.5-kb fragment contained two orfs, orf1 and truncated orf2. The deduced products were somewhat similar to phosphoserine phosphatase-like protein and the N-terminal region of MinD-like protein, respectively. The individual function of orf1 or the function of both orf1 and truncated orf2 seems to induce particular phenotypes or properties in strain BalA1.

Adenosine Triphosphatases↗