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Biomedical subjects

K Uematsu

Publications and source records attributed to K Uematsu.

At least 37 records · Page 2Linked to original sources

What patients can survive disease free after complete resection for hepatocellular carcinoma?: A multivariate analysis.

BACKGROUND: Although there have been extensive studies to determine risk factors affecting survival after resection for hepatocellular carcinoma (HCC), we still do not know which patients can survive disease free after curative resection. This study was undertaken to determine independent risk factors affecting the length of disease-free survival. METHODS: 171 patients, who survived disease free more than 1 year after curative resection, were divided into four groups according to the disease-free period: Group I (n = 96) for the patients with intrahepatic recurrence between 1 and 3 postoperative years, Group II(n = 27) for those between 3 and 5 years, Group III (n = 40) for those between 5 and 10 years and Group IV (n = 8) for those without recurrence within 10 years. The 37 variables (host factors, tumor factors, non-tumor liver factors, surgical factors) were compared among the four groups. Activity of hepatitis and hepatic fibrosis was scored by the Histological Activity Index (HAI). In a multivariate study, possible prognostic variables with a statistical difference in the disease-free survival rate among each category were preliminarily selected from the 37 variables and the independent variables were finally selected using a proportional hazard analysis. RESULTS: The patients' age, indocyanine green retention rate, microscopic tumor capsular invasion and portal invasion, cell differentiation, extent of hepatectomy, aggressiveness of chronic hepatitis and inflammatory activity assessed by HAI score were significantly different among the four groups. In the multivariate analysis, the following variables were selected as the independent determinants favorable for achieving a longer disease-free period: younger age, lower indocyanine green retention rate, solitary HCC with expansive growth, no microscopic portal invasion and lower activity of co-existing hepatitis. CONCLUSIONS: The importance of inflammatory activity in addition to aging, hepatic reserve and tumor characteristics was confirmed as a risk factor for recurrence by multivariate analysis. To achieve better disease-free survival, not only early detection but also suppression of co-existing hepatitis is necessary.

Aged↗

Novel toluene elimination system in a toluene-tolerant microorganism.

In studies of Pseudomonas putida IH-2000, a toluene-tolerant microorganism, membrane vesicles (MVs) were found to be released from the outer membrane when toluene was added to the culture. These MVs were found to be composed of phospholipids, lipopolysaccharides (LPS), and very low amounts of outer membrane proteins. The MVs also contained a higher concentration of toluene molecules (0.172 +/- 0. 012 mol/mol of lipid) than that found in the cell membrane. In contrast to the wild-type strain, the toluene-sensitive mutant strain 32, which differs from the parent strain in LPS and outer membrane proteins, did not release MVs from the outer membrane. The toluene molecules adhering to the outer membrane are eliminated by the shedding of MVs, and this system appears to serve as an important part of the toluene tolerance system of IH-2000.

Bacterial Outer Membrane Proteins↗

[Microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung].

A 67-year-old man who had worked as an aluminum grinder had been given a diagnosis of pneumoconiosis. Ten years later, he was admitted with fever, dyspnea on exertion, and numbness. Chest roentgenograms showed linear-reticular shadows in both lower lung fields. ELISA-based tests were positive for perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA). Renal biopsy specimens disclosed crescentic glomerulonephritis and angiitis of small arteries. Our diagnosis was microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung. The results of high-energy dispersion X-ray microanalysis indicated that the patient's lungs contained aluminum. His general condition improved with the administration of corticosteroid and immunosuppressive agents, and his chief symptoms disappeared.

Aged↗

[Mechanism of resistance to growth inhibition by transforming growth factor-beta 1 (TGF-beta 1) in primary lung cancer and new molecular targets in therapy].

Transforming Growth Factor-beta 1 (TGF-beta 1) regulates the proliferation of normal epithelial cells, and resistance to TGF-beta 1 growth inhibition is a common feature of human cancers including lung cancer. In order to understand the mechanism of resistance to growth inhibition by TGF-beta 1 and to reverse the regulation of proliferation in lung cancer, we determined the genomic structure of the genes involved in the signal transduction pathway of TGF-beta 1 and performed an initial mutation survey of the complete coding region of the genes in lung cancer and cell lines with the resistance to growth inhibition by TGF-beta 1. First, a mutation analysis of the TGF-beta type II receptor (TGF-beta RII) was performed. Point mutations of the gene were detected in several colon cancers and an adenocarcinoma of the lung in the poly-A sequence. No mutations of Smad 2, 3, 4, 5 and TGF-beta type I receptor (TGF-beta IR) genes were detected in a series of the tumors we tested, although several mutations of Smad 2 and 4 were previously reported. Frequent alterations of the p15 gene and reduced expression of p21 we already reported from our previous studies. We also determined the genomic structure of the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R), which is involved in activating TGF-beta 1, and performed an initial mutation survey of the complete coding sequences of the gene. A point mutation at exon 40 was found in one lung adenocarcinoma cell line. In summary, alterations in the many genes involved in the signal transduction of TGF-beta 1 were found and may mediate the loss of TGF-beta 1 responsiveness in lung cancer. The molecular targets for the regulation of the proliferation of lung cancer are thought to be p15, p21 and the transcriptional regulators.

Cell Division↗

Naturally occurring somatic motoneuron death in a teleost angelfish, Pterophyllum scalare.

Naturally occurring somatic motoneuron death in a teleost angelfish, Pterophyllum scalare, was investigated histochemically and electron microscopically. The number of motor axons in the ventral root, which corresponds to the motoneuron number in spinal hemisegment, was rapidly increased beyond the adult value within 3 days after hatching, and then decreased to reach the adult value within a few weeks. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) histochemistry, which detects fragmented nuclear DNA characteristic to apoptotic cells, showed that the apoptotic cells are located in the motor column of the cord in the larvae at specific developmental stages. Electron microscopic observations of the spinal cells further confirmed the motoneuron apoptosis. The present data suggest that the massive death of somatic motoneurons at certain ontogenic stages which has been known to occur in higher vertebrates also takes place in fish.

Animals↗

Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene/partial hepatectomy model.

Oval cells that develop in the rat 2-acetylaminofluorene/partial hepatectomy (AAF/PH) model express the c-kit receptor tyrosine kinase (KIT) and its ligand, stem cell factor (SCF). We investigated the role of the SCF/KIT system in the development of oval cells using Ws/Ws rats, whose c-kit kinase activity was severely impaired owing to a small deletion in the kinase domain. On days 7, 9, and 13 after PH in the AAF/PH model, the development of oval cells was remarkably suppressed in Ws/Ws rats when compared with that of the control normal (+/+) rats. However, oval cells that developed in Ws/Ws rats expressed marker proteins of oval cells, such as alpha-fetoprotein (AFP), cytokeratin-19 (CK-19), and flt-3 receptor tyrosine kinase, similar to those of +/+ rats. Furthermore, labeling with [3H]-thymidine and immunostaining of Ki-67 showed that the proliferative activity of oval cells that developed in Ws/Ws rats was comparable with that of +/+ rats. The present results indicate that the signal transduction of the SCF/KIT system plays a crucial role in the development of oval cells, at least, in the rat AAF/PH model, and suggest that KIT-mediated signal transduction plays only a small role in determining the phenotype and in the proliferative activity of oval cells.

2-Acetylaminofluorene↗

Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis.

The PTEN/MMAC1 gene located at 10q23, has been proposed to be a tumor suppressor gene. To determine the involvement of alteration of the PTEN/MMAC1 gene in carcinogenesis and the progression of primary lung cancers, we analyzed tumor samples of primary and distant metastatic sites and normal lung tissue samples of 30 patients with advanced lung cancer with distant metastasis. The tissues were analyzed for allelic deletion and mutational inactivation of PTEN/MMAC1 by loss of heterozygosity (LOH) analysis, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), and direct sequence analysis. LOH of the PTEN/MMAC1 locus was common in each histologic type of primary lung cancer. In this study, the overall allelic deletion rate was 33.3% (7/21). Allelic loss at the primary site and that at the metastatic site of each patient, were identical; in most cases, it seemed that the allelic loss had occurred before metastasis. Sequence analysis of the PTEN/MMAC1 gene revealed a G to C substitution located 8 bp upstream of the coding region of exon 1 and which seems to be a polymorphism, in 4 of the 30 cases. Somatic mutations of the PTEN/MMAC1 gene were not identified in any of the tumors at the primary and metastatic sites. These data indicate that point mutations in the PTEN/MMAC1 gene are probably not an important factor in tumorigenesis and the progression of a major subset of lung cancers. Due to frequent allelic loss at the PTEN/MMAC1 locus occurring at a stage earlier than the metastatic process, alternative mechanisms in which the remaining allele is inactivated such as methylation or homozygous deletion of a small region of the gene that can not be detected by the usual analysis, or alteration of other important tumor suppressor genes lying close to the PTEN/MMAC1 gene on 10q23, may be involved in the tumorigenesis of lung cancers of all histologic subtypes.

Alleles↗

Posthatching development of spinal motoneurons in the angelfish Pterophyllum scalare.

We investigated the posthatching developmental sequence of spinal motoneurons innervating the axial muscles in the teleost angelfish, Pterophyllum scalare, by means of retrograde labeling with horseradish peroxidase. Two discrete types of spinal motoneurons, primary-type motoneurons and secondary motoneurons were labeled in a temporally different sequence during the course of larval development. These two types of motoneurons were morphologically distinguishable from one other. Primary-type motoneurons are generated by day 1 posthatching and do not increase in number over the observed period (to day 12 posthatching). In contrast, the secondary motoneurons increase in number through posthatching day 3. Differentiation of the spinal motoneurons appears to be nearly complete a few days before the onset of free swimming. In addition, the data suggest that the differentiation of secondary motoneurons precedes the development of the red muscle that is to be innervated by the motoneurons.

Animals↗

Lead poisoning in wild waterfowl in Japan.

We collected 430 harvested ducks (Anas sp. and Aythya sp.) from nine prefectures in Japan between 1994 and 1997. Fifteen (4%) of 363 birds harvested during and after hunting seasons had one lead pellet each in the proventriculus and gizzard. In addition, 32 (34%) of 93 swans (Cygnus sp.) and two of 14 geese (Anser sp.) found dead from various wetlands had lesions consistent with lead poisoning. One to nine swans suspected of having toxicosis from ingestion of lead shot were found dead each year. Twenty-seven (84%) of the 32 lead-exposured swans were found in Hokkaido Prefecture. We concluded that lead poisoning is still a serious threat to waterfowl in Japan and that there is considerable need for environmental improvement concerning this problem.

Animals↗

[Diagnosis of ulcerative colitis and the biopsy method].

The biopsy specimen should be oriented flat on a ground glass slide or on a piece of filter paper so that the submucosa is on the slide and the mucosa uppermost to allow proper histopathological interpretation. It is important to perform the biopsy based on a full knowledge of features of inflammatory diseases of the large intestine. Biopsies should be taken from apparently normal and abnormal mucosa. It is necessary to observe the mucosa of the colon carefully for any mass lesions to find dysplasia or cancer complicating the ulcerative colitis. Any suspicious areas should be liberally biopsied. Biopsies should also be performed at random, because of possible existence of dysplasia or cancer which is not visible at endoscopy. This occurs especially in the rectum; biopsies can also be performed after inversion of the endoscope.

Biopsy↗

Comparison of pathologic changes in Helicobacter pylori-infected Mongolian gerbils and humans.

Helicobacter pylori has been recognized as a pathogen causing gastroduodenal disease, with adequate evidence to prove this relation in clinical research. Available animal models, however, were inadequate until 1995, when a new animal model of H. pylori infection was established using Mongolian gerbils. In this study we compared pathological changes in seven H. pylori-infected Mongolian gerbils with ulcers to five patients with gastric ulcer who underwent operation. All of the animals showed positive reactions for both H. pylori culture and serum anti-H. pylori antibody titer. All human subjects had H. pylori on the mucosal surface. Thus, inflammatory cell infiltration in the pyloric gland area was observed throughout almost all layers in the animals. In contrast, inflammation was observed in the surface layer of the mucosa in the pyloric gland area in the human subjects. Lymph follicle formation was observed more often in humans than in the animals. Inflammation of the fundic gland area in both groups was weaker than of the pyloric gland area and was observed within the mucosa. Histological changes observed in both groups were chronic active gastritis, lymph follicles, and intestinal metaplasia in the stomach. H. pylori-associated gastritis in humans is characterized by erosion, inflammation with neutrophil infiltration, lymph follicles, intestinal metaplasia, and atrophy. These findings are similar to those in this animal model. Thus, H. pylori infection might participate in the pathogenesis of gastroduodenal mucosal damage. In conclusion, the Mongolian gerbil is a good animal model for H. pylori-associated gastric diseases, and it might be useful for investigating the pathogenesis of H. pylori infection.

Adult↗

Pathologic changes in the glandular stomach and duodenum in an H. pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model following Hirayama's method to investigate gastric diseases associated with H. pylori infection. We orally administered the culture broth of H. pylori ATCC 43504 to 8-week-old male Mongolian gerbils. After this, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks some of them were sacrificed for histopathologic examination and H. pylori culture. H. pylori colonization in the glandular stomach was seen in all the infected gerbils but only a few H. pylori were detected histologically. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. In addition, we found intestinal metaplasia and gastric ulcers from 12 and 24 weeks, respectively. There was mild to moderate inflammation in the duodenum but no ulcerative lesions or gastric metaplasia were observed. Some histologic findings were similar to those in humans, but inflammation occurred mainly in the deep mucosa and submucosa. This is a good animal model for H. pylori-associated gastric diseases but not for duodenal ulcers or gastric metaplasia. It might be useful for investigating the pathogenesis of H. pylori infection in the stomach.

Animals↗

Endovascular papillary angioendothelioma (Dabska tumor) in an elderly woman.

A patient with endovascular papillary angioendothelioma with a low grade of malignancy showing papillary proliferation of endothelioid cells is presented. The patient, an 83-year-old woman, underwent resection of a tumor of the neck. At operation a 9 x 7 cm cystic tumor containing yellow transparent liquid with clots was found in the subcutaneous tissue. Histological studies showed endothelioid cells with spindle-shaped nuclei proliferated in layers around the fibrovascular cores, which showed the characteristic appearance of papillary proliferation. These cells were immunohistochemically positive for CD31, CD34 and factor VIII-related antigen. Based on these observations, the tumor was considered to be an endovascular papillary angioendothelioma (Dabska tumor). Dabska tumor is a vascular tumor with a low grade of malignancy and usually occurs in infants and young children. About 13 cases of Dabska tumor have been reported. The occurrence of a Dabska tumor in an aged patient is considered to be rare.

Aged↗

Preventive effect of erythromycin on experimental bleomycin-induced acute lung injury in rats.

BACKGROUND: Erythromycin has been reported to have an inhibitory effect on chronic inflammatory airway disease and chronic infiltration of neutrophils into the airway. Bleomycin (BLM) often induces interstitial lung fibrosis following acute lung injury. A study was undertaken to investigate the effects of erythromycin (EM) on experimental bleomycin-induced acute lung injury in rats. METHODS: Bleomycin-induced lung injury was assessed by light microscopic examination, measurement of neutrophil elastase activity and of the interleukin 8 (IL-8) content in bronchoalveolar lavage (BAL) fluid. The potential inhibitory effect of erythromycin was assessed by overall comparison of erythromycin untreated (BLM alone), concurrently treated (BLM + EM), and pretreated (BLM + pre-EM) groups. RESULTS: The neutrophil count and concentration of neutrophil-derived elastase in BAL fluid were significantly different in the three groups. The morphological changes of lung injury were also less extensive in rats pretreated with erythromycin. However, these protective effects were not marked in the group concurrently treated with erythromycin. Moreover, the concentration of IL-8 in the BAL fluid tended to be less in the erythromycin treated groups; however, there were no significant differences between the bleomycin-treated groups. CONCLUSION: Erythromycin exhibits a prophylactic effect on acute lung injury induced by intratracheal administration of bleomycin, which is possibly associated with a downregulation of neutrophil-derived elastase.

Animals↗

Adrenal hemorrhage associated with Klebsiella oxytoca bacteremia.

Septic adrenal hemorrhage is classically caused by meningococcemia. An autopsied case is presented of a 45-year-old man with adrenal hemorrhage due to Klebsiella oxytoca bacteremia following placement of a central venous catheter. He died 5 hours after developing disseminated intravascular coagulation (DIC). The bacterial entry site may have been the catheter. The cause of death was considered to be pulmonary edema due to bacteremia rather than adrenal insufficiency due to hemorrhage. Septic adrenal hemorrhage should be recognized as a subtype of sepsis rather than adrenal insufficiency, and may be caused in conditions of severe sepsis with DIC, independent of the microorganic variety.

Adrenal Gland Diseases↗

[Pagetoid spread of intratubular germ cell neoplasia into rete testis forming tumor-like mass].

Intratubular germ cell neoplasia (ITGCN) is the preinvasive phase of testicular germ cell tumors. ITGCN can spread into the rete testis in a pagetoid manner, but there are very few published data about this phenomenon. Furthermore, the tumor-like mass formed by ITGCN with pagetoid spread into the rete testis has not been documented to date, and the present case is the first to be reported. A tumor-like mass was found close to the superior pole of the left testis in a 39-year-old male and was unrelated to the epididymis. Three other nodules of seminoma surrounded by fibroconnective tissue existed next to the mass. Histological sections revealed ITGCN which was characterized by the presence of large and polygonal germ cells exhibiting clear cytoplasm with distinct cell borders. The cytoplasm was rich in glycogen and the cell membrane was immunohistochemically positive for placental alkaline phosphatase. The nuclei had less coarse chromatin than that of seminoma. ITGCN cells spread in between the lining epithelium of the rete and the basement membrane. This characteristic spread was consistent with pagetoid spread into the rete testis.

Adult↗