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Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 73 records · Page 4Linked to original sources

The three-dimensional architecture of retinal blood vessels in KK mice, with special reference to the smooth muscle cells and pericytes.

In the present study, the three-dimensional architecture of retinal vasculature was studied in KK mice, by combined use of resin injection, chemical treatment and scanning electron microscopy (SEM). In particular, Mercox/methylmethacrylate resin-injected eye tissues were subjected in sequence to NaClO immersion, ultrasonication and HCl treatment. The present technological innovation made possible SEM visualization of deeper retinal vasculature. In KK mice, the tunica media of stem arterioles and of first and second order branches consisted of a single layer of spindle-shaped smooth muscle cells provided with spine-like cytoplasmic processes. In addition, there occurred small triangular smooth muscle cells provided with slender cytoplasmic processes. The processes, giving off tiny secondary processes, overlapped with each other, thus forming assemblages around branching sites. Such a structure was particularly prominent for those branching sites where parent arterioles gave rise to their branches in a side arm-like pattern. The third (and occasionally fourth) order branches were surrounded by atypical smooth muscle cells, with considerable dimension of endothelial surface remaining uncovered. Capillary pericytes consisted of fusiform cell bodies and slender cytoplasmic processes. Smooth muscle cells of retinal venules differed from those of arterioles. They were stellate in shape, exhibiting several cytoplasmic processes.

Animals↗

Differential dosimetry in a neutron-proton mixed field with low-pressure proportional counters.

For a mixed radiation field of neutrons and protons, radiation events were discriminated between photons, neutrons, and protons using a thin plastic scintillator. Distributions of lineal energy were measured with low-pressure proportional counters (LPPCs). To estimate the distribution of lineal energy for ICRU muscle, measurements were carried out using A-150-walled, graphite-walled, ZrO2-walled, and Zr-walled counters. Data were corrected for different atomic compositions between the A-150 plastic and ICRU muscle.

Energy Transfer↗

Value of lipiodol computed tomography and digital subtraction angiography in the era of helical biphasic computed tomography as preoperative assessment of hepatocellular carcinoma.

OBJECTIVE: To compare the diagnostic accuracies of Lipiodol computed tomography (CT) and helical biphasic CT as preoperative imaging modalities for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Lipiodol CT after digital subtraction angiography has long been used as a highly sensitive imaging modality for HCC. The recent advent of helical CT has allowed scanning the entire liver during both the arterial and portal venous phase of contrast enhancement. METHODS: The authors analyzed data from 164 patients who underwent hepatic resection for HCC to calculate the sensitivity and specificity of these modalities. Findings of intraoperative ultrasonography followed by histologic confirmation were set as the gold standard. RESULTS: Although sensitivity decreased with both modalities as tumors became small and well differentiated, helical CT showed a higher sensitivity than Lipiodol CT in detecting well-differentiated HCC nodules smaller than 2 cm. In contrast, Lipiodol CT was superior to helical CT for the detection of small but moderately to poorly differentiated nodules. The overall sensitivity of helical CT was higher than that of Lipiodol CT. These findings suggest that helical CT is superior in delineating early HCC, whereas Lipiodol CT is specific to the detection of intrahepatic metastases. In terms of specificity, helical CT was superior to Lipiodol CT. CONCLUSIONS: Helical CT and Lipiodol CT are complementary modalities. At present, helical biphasic CT does not obviate the need for invasive techniques such as angiography and Lipiodol CT as preoperative examinations for HCC.

Adult↗

Sole expression of laminin gamma 2 chain in invading tumor cells and its association with stromal fibrosis in lung adenocarcinomas.

Laminin-5 (LN-5), an important basement membrane (BM) protein consisting of laminin alpha3, beta3 and gamma 2 chains, has been suggested to be involved in tumor cell invasion and tissue repair. In this study, the distribution of the LN-5 subunits in atypical adenomatous hyperplasia (AAH) and different types of adenocarcinomas of the lung was examined by immunohistochemical analysis. In AAH and non-sclerosing, well-differentiated adenocarcinomas, the LN gamma 2 chain was frequently detected along with the continuous BMs. These BMs were also positive for both LN alpha3 and beta3 chains, suggesting that LN-5 had been deposited. In contrast, the cytoplasmic staining for the LN gamma 2 chain was frequently observed in tumor cells of sclerosing, well-differentiated adenocarcinomas, as well as of moderately and poorly differentiated adenocarcinomas, without any evidence of co-expression of the LN alpha3 and beta3 chains. This staining pattern of the LN gamma 2 chain was prominent in carcinoma cells invading into interstitial stroma and was associated with the formation of a central scar in the tumor tissues. These results suggest that the LN gamma 2 chain monomer could be an important indicator of progression of lung adenocarcinoma.

Adenocarcinoma↗

A study of factors influencing prognosis after resection of hepatic metastases from colorectal and gastric carcinoma.

OBJECTIVE: The aim of this study is to determine the absolute contraindication for hepatic resection for colorectal metastases and investigate the value of hepatectomy for gastric metastases by comparing it with the results of colorectal metastases performed with the same criteria. METHODS: A retrospective cohort study was conducted in patients undergoing hepatic resection for metastatic colorectal (n = 64) and gastric (n = 17) carcinomas. Common predictive factors for both metastases were analyzed by the stratified Cox proportional hazard model. In this model, the different baseline hazard was set for each disease, whereas the risk of each covariate was assumed to be equal in both gastric and colorectal metastases. RESULTS: Overall 1-, 2-, and 5-yr survival rates after hepatectomy for colorectal and gastric metastases were 90%, 73%, 42%, and 47%, 22%, 0%, respectively. Factors controlling prognosis were as follows: age > or = 60, extrahepatic metastases, serosal invasion, grade of lymph node metastases, tumor cell differentiation of the primary lesion(s), carcinoembryonic antigen level, tumor-exposed surgical margin, and blood transfusion. In particular, presence of extrahepatic metastases showed the markedly high-risk ratio among these eight variables. CONCLUSIONS: Hepatectomy, if possible, is indicated in patients with hepatic metastases from colorectal carcinoma if there are no extrahepatic metastases and if the primary disease is controlled. It is indicated only in carefully selected patients with metastases from gastric carcinoma.

Adult↗

Pancreatic islet regeneration by ephedrine in mice with streptozotocin-induced diabetes.

In this experiment, we investigated the effects of crude Ephedrae herba, alkaloid extract of Ephedrae herba and 1-ephedrine, a major alkaloid component, on diabetic mice induced by streptozotocin (STZ). The alkaloid extract and 1-ephedrine showed suppression on the hyperglycemia. The suppression by Ephedrae herba of hyperglycemia may therefore be due to 1-ephedrine. Furthermore, we found that Ephedrae herba, alkaloid and 1-ephedrine promoted the regeneration of pancreas islets following atrophy induced by STZ. It is therefore suggested that Ephedrae herba may regenerate atrophied pancreatic islets, restore the secretion of insulin, and thus correct hyperglycemia.

Animals↗

Interaction of poly(2-acrylamido 2-methylpropane sulfonate)-grafted polystyrene beads with cationic complement proteins.

Influence of various biomaterials on the complement system in serum has been intensively studied by many research groups, since activation of the complement pathway in vivo has been known to give rise to some pathological conditions, such as inflammation and anaphylaxis. Much effort has been devoted to develop new materials that do not activate or deteriorate the complement system. The present work is aimed at revealing the mode of reactions of anionic poly(2-acrylamido 2-methylpropane sulfonate) grafted on polystyrene bead (PAMPS-g-bead) with serum complement. Complement activity assay, determination of complement proteins levels, and immunoblot analysis were carried out for sera pretreated with PAMPS-g-beads. The results clearly showed that, when PAMPS-g-beads were incubated with serum, those beads adsorbed several complement proteins, i.e. C1q, factor D, factor P, C6, and C8, but the generation of activation fragments of complement components was not observed. Especially, factor D was most effectively removed from serum, resulting in potential inhibition of the alternative pathway. A larger amount of PAMPS-g-beads was needed to decrease the serum CH50 level. That may be caused by removal of C6. Although some polyanions, such as dextran sulfate, were reported to activate the complement system, the obtained results indicate that the PAMPS-g-bead is not an activator of the complement pathway, but acts as an adsorbent of complement components. One possible clinical application of the PAMPS-g-beads is adsorption of serum factor D by extracorporeal treatment of patients with renal failure with a high level of factor D, because the increased quantity of factor D in serum may cause consistent activation of the alternative pathway.

Biocompatible Materials↗

Tubulointerstitial injury of Thy-1 nephritis in uninephrectomized stroke-prone spontaneously hypertensive rats.

Thy-1 nephritis was induced in stroke-prone spontaneously hypertensive rats (SHR-SP) with unilateral nephrectomy (UNX) and normotensive same genetic strain Wistar-Kyoto (WKY) rats with UNX to evaluate whether the tubulointerstitial injury in Thy-1 nephritis is accelerated by long-term systemic and intraglomerular hypertension. SHR-SP that underwent UNX at twelve weeks of age were randomly assigned to receive monoclonal anti-thy 1.1 antibody (group SP), and normal saline (group SC). Age-matched normotensive WKY rats served as controls and were given the same dose of monoclonal anti-thy 1.1 antibody after UNX (group WK). In all groups, the blood pressure and renal function were assessed, and morphologic changes of tubulointerstitium were examined by using immunohistochemistry and light microscopy twelve weeks after Thy-1 nephritis induction (in groups SP and WK) and UNX alone (in group SC). In all groups, histological findings, the degree of monocyte/macrophage infiltration, interstitial expression of alpha-smooth muscle actin (alpha-SMA), which is a marker for myofibroblasts, and the degree of tubular cell proliferation were examined. In addition, assessments of blood pressure, serum creatinine and BUN levels, and the degree of proteinuria were made. In parallel to glomerular structural damage, interstitial fibrosis with predominant monocyte/macrophage influx, increased interstitial expression of alpha-SMA and tubular cell proliferation were observed in group SP. A significant increase in serum creatinine and proteinuria were also present in this group. In contrast, the changes observed in group SC were not so evident or extensive as in group SP. The level of proteinuria was lower than that in group SP. No evident tubulointerstitial changes were found in group WK. The results showed that tubulointerstitial injury was prominently progressed in the hypertensive model with Thy-1 nephritis. This suggests that sustained systemic and glomerular hypertension is not only ultimately responsible for the progression of immunologically mediated glomerular injury, but is also responsible for subsequent tubulointerstitial changes. Migration and proliferation of myofibroblasts and intense influx of monocytes/macrophages may contribute to the development of tubulointerstitial fibrosis.

Animals↗

No alteration in serum leptin levels during acute endotoxemia in sheep.

To determine the role of leptin in endotoxin-induced anorexia in ruminants, circulating leptin levels were measured during acute experimental endotoxemia in sheep. Injection of bacterial lipopolysaccharide (450 ng/kg, i.v.) induced anorexia accompanied with fever and increases in serum levels of cortisol, insulin and glucose which are known to stimulate leptin secretion in rodent and human, while it did not affect serum leptin levels at all. These results indicate that serum leptin levels in sheep during acute endotoxemia are differentially regulated from those in rodent and human, and that leptin might not be involved in the endotoxin-induced anorexia in sheep.

Acute Disease↗

Significance of proneural basic helix-loop-helix transcription factors in neuroendocrine differentiation of fetal lung epithelial cells and lung carcinoma cells.

In this brief review article, we describe how cell fate determination by which the airway epithelial cells become neuroendocrine or non-neuroendocrine is regulated by a network of basic helix-loop-helix transcription (bHLH) factors in a similar manner to neuronal differentiation, and how this system could work to determine cell differentiation of human lung carcinomas. Immunohistochemical studies reveal that mammalina achaete-scute complex homologue (Mash)1 is expressed in pulmonary neuroendocrine cells (PNEC), while hairy and Enhancer of split (Hes)1 is expressed in pulmonary non-neuroendocrine cells (non-PNEC). Studies using gene-deficient mice for the bHLH factors revealed that in Mash1 homozygous null mice no PNEC are detected, while PNEC increase markedly in Hes1 homozygous null mice. These observations suggest that Mash1 is an essential positive factor for neuroendocrine differentiation of lung epithelium, and that Hes1 is one of the repressive factors for neuroendocrine differentiation. Moreover, immunohistochemical studies revealed that Notch receptors are detected in non-PNEC, and thus the Notch signalling pathway could play a role in the determination of airway epithelial cell differentiation. In human lung carcinomas, a similar bHLH network should operate to determine cell differentiation phenotypes. Generally, expression of the human homologue of Mash1 (HASH1) is detected in small cell carcinoma and carcinoids, while Hes1 seems to be expressed mainly in non-small cell carcinoma. Thus, proneuronal bHLH factors may play roles in cell fate determination of the airway epithelial system, and may regulate human airway epithelial cells in diseased conditions.

Animals↗

Hemolytic uremic syndrome with intracranial hemorrhage following mitomycin C administration.

A 50-year-old woman treated for breast cancer with mitomycin C developed severe hypertension, followed by deep coma 3 days later. Computed tomography of the brain showed frontoparietal intracranial hemorrhage accompanied by subarachnoid hemorrhage. The patient was diagnosed additionally with hemolytic uremic syndrome (HUS) based on hemolytic anemia with schistocytosis, thrombocytopenia, and acute renal failure. The patient underwent hemodialysis and plasmapheresis with no improvement. We present the pathologic findings of the general vessels, which has been reported rarely. This case represents the first reported intracranial hemorrhage in HUS following mitomycin C administration. We emphasize the need to control blood pressure in patients with HUS.

Alkylating Agents↗

Identification of hepatic venous territories in liver resection by using color Doppler ultrasonography: report of two cases.

OBJECTIVE: Resection of the hepatic vein because of the proximity of tumors may result in increased congestion in the noncancerous parenchyma, which in turn may lead to functional hepatic volume loss and postoperative hepatic failure, especially in a case of low hepatic reserve. However, to our knowledge, no technique for estimating the extent of dependent hepatic venous territories before hepatic resection has been established. We examined the possibility of using color Doppler ultrasonography for this purpose. METHODS: A color Doppler system and a linear array transducer equipped with multiple Doppler frequencies ranging from 7 to 13 MHz were used intraoperatively. Two patients with hepatocellular carcinomas were examined. By tracking entire branches of the targeted vessel, from the trunk to the terminal branches extending to the liver surface, it was possible for the boundaries of the dependent areas to be projected and marked on the liver surface with either ink or electrocautery. RESULTS: In both cases, this method was effective for either minimizing the congestive area or preserving the hepatic mass that was being drained via aberrant routes. CONCLUSIONS: Identification of hepatic venous territories by means of color Doppler ultrasonography may provide new information about intrahepatic blood circulation and may increase the safety and curability of hepatic resection.

Aged↗

Tissue distribution of CD6 and CD6 ligand in cattle: expression of the CD6 ligand (CD166) in the autonomic nervous system of cattle and the human.

We studied the tissue distribution of CD6(+) lymphocytes and cells expressing the CD6 ligand (also known as activated leukocyte cell adhesion molecule CD166) in calves by immunohistochemistry using an anti-bovine CD6 monoclonal antibody (mAb), a human CD6 (huCD6)-immunoglobulin G1 fusion protein (huCD6-Ig), and an anti-human CD166 (anti-huCD166) mAb. The huCD6-Ig and anti-huCD166 mAb bound to the sympathetic and parasympathetic nerve fibers but not to myelinated nerve fibers in the spinal nerve. Studies with human tissue using the anti-huCD166 mAb yielded identical patterns of labeling. Dense accumulations of CD6(+) lymphocytes were present in areas of the thymuses and spleens of calves, in areas innervated by huCD6-Ig(+) nerves. The cDNAs encoding the bovine CD166 and CD6 were isolated from the sympathetic ganglion and spleen, respectively. Predicted amino acid residues that are important for human and mouse CD6-CD166 binding were also conserved in bovine CD6 and CD166. Bovine CD166 transcripts were detected by reverse transcriptase-PCR in all the tissues that bound huCD6-Ig. These results show that the bovine orthologue of CD166 was constitutively expressed in the autonomic nervous systems of cattle and suggest that CD6(+) lymphocytes adhere to CD166(+) autonomic nerve terminals via CD6.

Activated-Leukocyte Cell Adhesion Molecule↗

A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes.

Endothelin (ET)-1(1-31) is a novel 31-amino acid-length peptide derived from big ET-1 by chymase or other chymotrypsin-type proteases and is a major ET derivative in human neutrophils. In this study, we revealed that ET-1(1-31), but not big ET, exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mediator, although the effects were less potent than those of formyl-methionyl-leucyl-phenylalanine or interleukin-8. However, the chemotactic effects of ET-1(1-31) were much greater than those of the 21-amino acid ET-1, ET-1(1-21). Checkerboard analyses revealed that the effects are chemotactic rather than chemokinetic. The effects of ET-1(1-31) are not mediated by interleukin-8 or monocyte chemoattractant protein-1. The chemotactic effects and an increase in intracellular-free Ca(2)(+) caused by ET-1(1-31) were significantly inhibited by BQ123, an ET(A) receptor antagonist, but not by BQ788, an ET(B) receptor antagonist, suggesting that ET-1(1-31) mediates chemotaxis through an ET(A) or ET(A)-like receptor.

Calcium↗

Brain interleukin-1 is involved in blood interleukin-6 response to immobilization stress in rats.

Interleukin (IL)-6, a cytokine for host defense responses to infection and inflammation, is known to be induced by non-invasive physical or psychological stress, too. To test possible involvement of brain IL-1 in the stress-induced IL-6 production, IL-1 mRNA expression in the hypothalamus, in parallel with blood IL-6 level, was examined in rats subjected to restriction of their movement (immobilization stress). When rats were immobilized, the hypothalamic IL-1 beta mRNA level was increased in 1 hr, followed by progressive rises in the serum IL-6 level. The immobilization-induced rise in serum IL-6 was mimicked by intracerebroventricular (icv) administration of IL-1 beta under normal conditions, whereas it was attenuated by icv injection of an IL-1 receptor antagonist. These results indicate that IL-1 in the hypothalamus plays a pivotal mediating role in the stress-induced peripheral IL-6 production.

Animals↗

Increased concentrations of protein gene product 9.5 in the synovial fluid from horses with osteoarthritis.

Our previous study established protein gene product 9.5 (PGP 9.5), a ubiquitin C-terminal hydrolase, as a specific cytochemical marker of synovial lining cells (type B synoviocytes) in the horse joint. The present study aimed to detect PGP 9.5 in the synovial fluid and shows that PGP 9.5 is a valuable marker of osteoarthritis in the horse. Immunohistochemical staining confirmed rich and consistent localization of PGP 9.5 immunoreactivity in the cytoplasm of synovial lining cells in the normal horse joint. Western blot analysis of synovial fluid from normal joints could detect a significant band corresponding to that contained in the brain and synovial membrane extracts. When 60 synovial fluid samples from normal and abnormal joints were assayed with an enzyme-linked immunosorbent assay (ELISA) system, the concentration of PGP 9.5 tended to be elevated in osteochondrosis dissecance, inflammatory arthropathy and intra-articular fracture, among which a statistically significant elevation was recognizable between the intra-articular fracture and the control. Thus, this study demonstrated the possibility that PGP 9.5, derived from synovial lining cells, may be a new biochemical marker for arthritic disorders of the horse.

Animals↗