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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 253 records · Page 14Linked to original sources

Increase in three alpha,beta-dicarbonyl compound levels in human uremic plasma: specific in vivo determination of intermediates in advanced Maillard reaction.

Methylglyoxal (MGO), glypxal (GO) and 3-deoxyglucosone (3-DG) are reactive alpha,beta-dicarbonyl intermediates in advanced Maillard reaction, which form advanced glycation and oxidation end products (AGEs) by reaction with both lysine and arginine residues in protein. We measured these three dicarbonyl compound levels in human plasma to estimate the relationship between accumulation of alpha, beta-dicarbonyl compounds and AGE formation reactions in uremia and diabetes in human plasma by a highly selective and specific assay, electrospray ionization liquid chromatography mass spectrometry (ESI/LC/MS). We show that 3-DG and MGO levels are significantly higher in uremia and diabetes compared with age-matched healthy controls. Only the GO level in uremic plasma is significantly higher compared to diabetes and healthy controls. In both diabetic and uremic patients, these dicarbonyl compounds promote AGE accumulation in vivo, and especially in uremic patients, increased accumulation of GO could result from accelerating oxidative stress.

2-Naphthylamine↗

Morphological characterization of relationship between gap junctions and gonadotropin releasing hormone nerve terminals in the rat median eminence.

The present study aimed to reveal possible morphological relationships between gonadotropin-releasing hormone (GnRH) nerve terminals and gap junctions in the median eminence. Coronal brain sections from castrated male rats were dual immunostained with GnRH and either connexin 26, 32, or 43, and examined by confocal laser microscopy. Connexin 43-immunoreactive puncta were distributed between GnRH-immunoreactive fibers, and some of them were colocalized with GnRH-immunoreactivities. Dual immunostaining with connexin 43 and glial fibrillary acidic protein revealed that most of the puncta were located in astrocytes. At the immunoelectron microscopic level, connexin 43-immunoreactivities were mainly located on the plasma membranes of glial-like processes. Few connexin 26- or connexin 32-immunoreactivities were found in the median eminence. The present results indicate the possibility that gap junctions play a role in the GnRH release at the median eminence.

Animals↗

Topography of the secondary somatosensory cortex in humans: a magnetoencephalo-graphic study.

The topography of the secondary somatosensory cortex (SII) responses to somatosensory stimulation applied to various parts of the body of normal volunteers was analyzed using magnetoencephalography (MEG). Although there were large inter-individual differences, the following orders of a location of equivalent current dipoles (ECDs) were found; (1) Anterior-posterior direction: lower lip-upper lip-thumb-middle finger-foot, (2) Medial-lateral direction: foot-middle finger-thumb-upper lip-lower lip, and (3) Lower-upper direction: lower lip-upper-lip-thumb-middle finger-foot. In general, these findings are similar to those obtained in studies of monkeys. However, the differentiation was not as clear as that seen in the homunculus in the primary somatosensory cortex (SI). The auditory cortex is located at a site more posterior, lateral and lower than the SII.

Adult↗

Steroid sulfatase expression is an independent predictor of recurrence in human breast cancer.

Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present study, we have measured STS mRNA levels in 97 breast cancers by reverse transcription-PCR using a fluorescent primer in the presence of an internal standard RNA and evaluated its association with disease-free and overall survival. The median value was 728.0 amol/ng RNA (range, 0-11,778 amol/ng RNA). Levels were significantly higher in tumors demonstrating lymph node metastasis than in those without nodal involvement (P = 0.033) and in patients who experienced a recurrence during the follow-up period (mean, 40.8 months; median, 39 months) compared with those with no evidence of further disease (mean, 49.2 months; median, 48 months; P = 0.029). No significant associations were found between STS mRNA expression and age, menopausal status, tumor size, histological grade, estrogen receptor status, or postoperative adjuvant therapy. High levels of STS mRNA proved to be a significant predictor of reduced relapse-free survival as a continuous variable (log STS mRNA; P = 0.028). As a dichotomous variable with an optimized cutoff point of 1,240 amol/ng RNA, expression was also associated with a significantly shorter relapse-free survival rate (P = 0.002), but no significant correlation was found between the STS mRNA level and overall survival. Expression was found to be an independent factor for predicting relapse-free survival on multivariate analysis. The results thus support a putative role of STS in breast cancer growth and metastasis.

Adult↗

A pedigree with a novel presenilin 1 mutation at a residue that is not conserved in presenilin 2.

OBJECTIVE: To disclose a novel mutation of the presenilin 1 (PS1) gene responsible for early-onset Alzheimer disease and to clarify genotype-phenotype correlation that should help to establish the function of this protein. BACKGROUND: The PS1 and presenilin 2 (PS2) genes carry missense mutations in families with Alzheimer disease. The PS1 and PS2 proteins have similar structures, and all presently known mutations are in nucleotides coding for amino acids that are conserved between the 2 presenilins. METHODS: Sequence and restriction fragment length polymorphism analyses of PS1 gene of DNA from a pedigree with early-onset Alzheimer disease. RESULTS: Sequence analysis disclosed a novel PS1 mutation in a pedigree of Japanese origin with early-onset Alzheimer disease. This mutation, which is predicted to cause a missense substitution of lysine for glutamic acid, occurred at codon 123 of PS1 that was not a conserved residue in PS2. The 2 patients of this pedigree shared an early clinical phenotype consisting of later-onset, progressive aphasia, but preserved visuospatial ability, which was indistinguishable from those of other PS1-associated Alzheimer disease cases. CONCLUSION: These results demonstrate that a missense mutation in a region not conserved between PS1 and PS2 can cause Alzheimer disease.

Age of Onset↗

Expression of vascular endothelial growth factor in exuberant tracheal granulation tissue in children.

Prolonged tracheotomy and endotracheal intubation often induce symptoms of airway obstruction and delay decannulation and extubation. Bronchoscopic examination of patients undergoing these treatments usually shows the presence of exuberant (pseudopapillary or nodular) granulation tissue occupying the airway lumen. An immunohistochemical analysis was undertaken of vascular endothelial growth factor (VEGF) expression in exuberant tracheal granulation tissue (n=17) obtained from children treated with prolonged tracheotomy or endotracheal intubation. Increased levels of VEGF protein and mRNA were expressed mainly by tracheal epithelial cells that migrated to cover the granulation tissue and partly by pericapillary macrophages in this tissue, whereas normal tracheal epithelium did not express VEGF. The VEGF expression level correlated significantly with the severity of the exuberant granulation tissue response (p=0.0018). As VEGF induces angiogenesis and vascular permeability, characteristics of granulation tissue, and plays a pivotal role in granulation tissue development, enhanced VEGF expression may be involved in the development of exuberant tracheal granulation tissue.

Adolescent↗

Diffusion- and perfusion-weighted MR imaging of transient focal cerebral ischaemia in mice.

Temporary focal ischaemia was induced in wild-type C57Black/6 mice by thread occlusion of the middle cerebral artery (MCA). Recirculation was started after 60 min and maintained for 24 h, after which the mouse brain was frozen in situ. Development of the cerebral infarct was monitored by diffusion-, perfusion- and T(2)-weighted magnetic resonance imaging (MRI) during ischaemia, during the early reperfusion period of 90 min, and at 24 h after reperfusion. Ischaemia caused a marked reduction of the perfusion signal intensity and of the apparent diffusion coefficient (ADC) of tissue water in the ipsilateral MCA territory. In sham-operated control animals ADC remained unchanged. Hemispheric lesion volume after 1 h MCA occlusion was 53 +/- 6% (n = 6), as defined by an ADC decrease of more than 20%. Recirculation reduced hemispheric lesion volume to only 27 +/- 13%, while there was a trend towards secondary lesion growth at 24 h. Post-ischaemic recovery of perfusion was slow, heterogeneous and incomplete. A region-of-interest analysis showed only partial and transient recovery of the ADC, particularly in the dorsolateral cortex and lateral caudate putamen, which may be explained by inadequate reperfusion in these regions. Detailed MRI studies of cerebral ischaemia and reperfusion may now also be performed in the transgenic mice.

Animals↗

Regional metabolic disturbances and cerebrovascular anatomy after permanent middle cerebral artery occlusion in C57black/6 and SV129 mice.

C57Black/6 and SV129 mice are widely used for the production of transgenic mutants in molecular stroke research but the ischemic susceptibility of these strains is influenced by differences in vascular anatomy and the responsiveness to excitotoxins and vasodilatory stimuli. To differentiate between these opposing effects on infarct size, the vascular territory of the two strains was correlated with the hemodynamic, metabolic, and morphological consequences of permanent middle cerebral artery (MCA) occlusion. The vascular anatomy was studied by latex infusion, brain infarction by vital staining, the size of the ischemic penumbra by imaging of ATP and protein synthesis, and blood flow by laser-Doppler flowmetry. In C57Black/6 mice the MCA-supplied vascular territory and the size of brain infarcts were significantly larger than in SV129 mice but the size of the penumbra and the residual blood flow in the center of the MCA-supplying territory were similar in both strains. These findings suggest that differences in infarct size in C57Black/6 and SV129 mice are determined mainly by the vascular anatomy and not by differences in collateral vascular responsiveness or excitotoxicity.

Adenosine Triphosphate↗

Ratio of branched chain amino acid to tyrosine after hepatectomy.

The roles of branched chain amino acids (BCAAs) and the tyrosine (Tyr) profile after liver resection were investigated using an inexpensive enzymatic method that was recently developed to quantify their concentrations. The preoperative BCAAs-to-Tyr ratio (BTR) was significantly correlated with the preoperative indocyanin green clearance ratio. The BTR decreased immediately after surgery in all patients, but it was significantly lower in those who had undergone major hepatectomies. After the infusion of BCAA-enriched amino acid solution, the BTR increased substantially, being significantly higher in patients who had not suffered an elevation in total bilirubin after liver resection. These findings indicate that this new enzymatic method to quantify the concentration of BCAAs and Tyr is useful to control the infusion of amino acids and to study the role of amino acid metabolization during the perioperative period.

Amino Acids, Branched-Chain↗

Desmoid tumor of the chest wall following chest surgery: report of a case.

Desmoid tumors of the chest wall following chest surgery are a rare occurrence. A case of this disease is reported herein together with a review of the literature. A 74-year-old man, who had previously undergone a right lower lobectomy for squamous cell carcinoma of the lung, was referred to our hospital with an abnormal shadow on his chest X-ray. The tumor, located in the right lateral chest wall, was successfully resected by an aggressive, wide extirpation, and a final diagnosis of a desmoid tumor originating in the chest wall was made. When following up patients after surgery for lung cancer, the possibility of desmoid tumors developing in the incised chest wall should therefore be kept in mind.

Aged↗

Intussusception of a mucocele of the appendix secondary to an obstruction by endometriosis: report of a case.

We treated a patient with a complete invagination of the cecum which contained a mucocele of the appendix secondary to an obstruction by endometriosis. Preoperatively, a barium enema showed a crab's claw-like area without filling in the oral side of the transverse colon. An emergency laparotomy was performed and revealed a mucocele of the appendix to have induced appendicecal invagination; however, no colonic invagination was observed. An appendicecal resection was thus done. Pathologically, the resected specimen was a mucosal hyperplasia with mucin-secreting lesions of the appendix. The theories regarding the pathogenesis of appendicecal mucocele are reviewed and discussed.

Adult↗

Variable expression of heparan sulfate epitopes in crescents of human glomerulonephritis.

Crescentic glomerulonephritis leads to a rapid loss of renal function. Although glomerular crescents are rich in extracellular matrix (ECM), the composition and genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major ECM molecule and has polymeric structure of great variability. Recent findings that alterations in HS epitopes are associated with renal pathology prompted us to hypothesize that specific HS epitopes might be expressed in the evolution of crescents. We reviewed clinical records of 724 patients who underwent renal biopsy and found 21 patients with rapidly progressive glomerulonephritis. Immunohistochemistry was performed using monoclonal antibodies (mAbs) against well-defined HS epitopes. One mAb was directed against unsaturated uronic acid residues generated during the selective removal of HS by heparitinase (a), and a further two different mAbs against N-sulfate-enriched and O-sulfate-poor portions of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular crescents but not to fibrous crescents, the periglomerular areas and noncrescentic intraglomerular areas. We concluded there are regional differences in HS epitope expression, although HS are ubiquitous components of glomerular ECM. N-sulfate-enriched and O-sulfate-poor portions of HS might play a role in crescent formation.

Animals↗

Neuroendocrine carcinoma of the sigmoid colon: report of a case.

Neuroendocrine carcinoma of the colon is a rare entity; however, this type of tumor is known for its aggressive progression and poor prognosis. A case of a 56-year-old Japanese male is presented in this report. A huge, child's head-sized tumor was found to have grown extraluminally on the sigmoid colon with multiple liver metastases. The tumor measured 16.5 x 15 x 8.2 cm in size and weighed 1 300 g. The patient died of hepatic failure due to massive liver metastases 6 months after operation. The pathological findings including an electron microscopic analysis were correlated with those of neuroendocrine carcinoma. We reviewed the English literature, and analyzed 94 cases of neuroendocrine carcinoma which had been reported previously. The nomenclature and definition of this disease still remains somewhat unclear, and not a small population of this disease may thus have been misdiagnosed and treated as other less aggressive entities. The necessity to make an accurate differential diagnosis in such cases is thus emphasized.

Carcinoma, Neuroendocrine↗

Tumor necrosis factor-alpha and interleukin-1beta increase the Fas-mediated apoptosis of human osteoblasts.

Our recent work demonstrated functional Fas expression on human osteoblasts, and the histologic examination of the periarticular osteoporosis region in patients with rheumatoid arthritis (RA) showed apoptosis in osteoblasts. High concentrations of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6--which are thought to increase bone resorption--have been determined in RA synovium. We investigated the effect of these cytokines on the Fas-mediated apoptosis of human osteoblasts. The human osteoblastic cell line MG63 and human primary osteoblast-like cells from bone biopsy specimens were used as human osteoblasts. Fas expression on these cells was examined by flow cytometry, and Fas-mediated apoptosis induced by anti-Fas immunoglobulin M (IgM) was determined by a chromium 51 release assay, the presence of cells with hypodiploid DNA, staining with Hoechst 33258 dye, and the detection of DNA fragmentation on agarose gel electrophoresis. The proliferation of osteoblasts was analyzed by a tritiated thymidine incorporation assay. Spontaneous apoptosis was not found on cultured osteoblasts. The apoptosis of human osteoblasts was not induced by TNF-alpha, IL-1beta, or IL-6 alone in the absence of anti-Fas IgM. In addition, proliferation of the cells was not affected by these cytokines. Fas was constitutively expressed on unstimulated osteoblasts, and treatment of these cells with IL-1beta or TNF-alpha significantly augmented Fas expression. Human osteoblasts were committed to apoptosis with anti-Fas IgM, and the treatment of both IL-1beta and TNF-alpha markedly increased Fas-mediated apoptosis. TNF-alpha augmented both Fas expression and Fas-mediated apoptosis more efficiently than did IL-1beta. In addition, an additive effect on both Fas expression and Fas-mediated apoptosis was demonstrated when TNF-alpha and IL-1beta were added to osteoblasts. IL-6 influenced neither Fas expression nor the Fas-mediated apoptosis of osteoblasts. Furthermore, no synergistic effect of IL-6 with IL-1beta or TNF-alpha was observed. IL-1beta, TNF-alpha, or IL-6 did not change Bcl-2 expression. Our results suggest that IL-1beta and TNF-alpha regulate osteoblast cell number by up-regulating the Fas-mediated apoptosis of osteoblasts, one of the putative mechanisms inducing periarticular osteoporosis in patients with RA.

Apoptosis↗

Use of a Palmaz stent for tracheomalacia: case report of an infant with esophageal atresia.

A male infant with congenital cardiac anomalies and esophageal atresia with tracheoesophageal fistula (EA-TEF) showed intractable respiratory symptoms after delayed primary repair of EA-TEF. Computed tomography demonstrated that the trachea was compressed by the enlarged aorta. Artificial ventilation was necessary even after aortopexy performed at 2 months of age. At 140 days of age, an expandable metallic stent (Palmaz stent) was inserted through a rigid bronchoscope into the trachea underfluoroscopic control. His respiratory status improved dramatically, and he was extubated in 18 hours. Although the follow-up period has been 9 months, the short-term result is satisfactory. The expandable metallic stent placement should be considered in patients with EA-TEF who show intractable respiratory symptoms caused by tracheomalacia.

Esophageal Atresia↗