PubMed Health⌕ Search

Biomedical subjects

N Uesugi

Publications and source records attributed to N Uesugi.

At least 19 recordsLinked to original sources
PubMed1999

Clinical and morphometrical interrelationships in patients with overt nephropathy induced by non-insulin-dependent diabetes mellitus. A light- and electron-microscopy study.

To clarify the relationships between clinical and renal structural findings in non-insulin-dependent diabetes mellitus (NIDDM), we studied 19 renal biopsy specimens from patients with overt diabetic nephropathy induced by NIDDM. By a conventional biopsy examination using light, immunofluorescent and electron microscopy, we excluded patients with any non-diabetic renal diseases which may have caused urinary abnormalities. Using standard stereological methods, the glomerular filtration surface area per nephron (S-Filt/neph), mesangial volume per glomerulus (V-Mes/glom), mesangial matrix volume per glomerulus (V-MM/glom) and the width of the glomerular basement membrane (GBM) were measured in nonoccluded glomeruli. The hyaline change in the arteriole was analyzed semiquantitatively using light microscopy as an index of arteriolar hyalinosis. Light-microscopic findings demonstrated minimal lesions in 4 cases, focal and/or segmental sclerotic lesions in 4 cases, and diffuse mesangial expansion in 11 cases (with and without nodular lesions in 9 and 2 cases, respectively). Mean glomerular volume of an open glomerulus in diabetic patients was 1.6 times the reference value obtained from nondiabetic patients with mild proteinuria and/or hematuria and normal renal function. Clinical parameters, including the duration of diabetes, urinary protein excretion and creatinine clearance were all related to S-Filt/neph, V-Mes/glom, V-MM/glom and the width of the GBM. In addition, V-MM/glom, the width of the GBM and the index of arteriolar hyalinosis were closely interrelated. Based on these findings, diabetic renal changes, including an increase in the mesangial matrix, thickening of the GBM and arteriolar hyalinosis, appeared to progress in parallel, and may reflect various clinical manifestations in patients with overt diabetic nephropathy induced by NIDDM without nondiabetic renal lesions.

Adult↗
PubMed1999

Possible induction of renal dysfunction in patients with lecithin:cholesterol acyltransferase deficiency by oxidized phosphatidylcholine in glomeruli.

To clarify the causes of renal dysfunction in familial lecithin:cholesterol acyltransferase (LCAT) deficiency, kidney samples from 4 patients with LCAT deficiency (3 homozygotes and 1 heterozygote) were examined immunohistochemically. All of the patients exhibited corneal opacities, anemia, renal dysfunction, deficiencies in plasma high density lipoprotein and LCAT activity and mass, and an increase in the ratio of plasma unesterified cholesterol to esterified cholesterol. Renal lesions began with the deposition of lipidlike structures in the glomerular basement membrane, and these structures accumulated in the mesangium and capillary subendothelium. By electron microscopy, 2 types of distinctive structure were found in glomerular lesions: vacuole structures and cross-striated, membranelike structures. The plasma oxidized phosphatidylcholine (oxPC) -modified low density lipoprotein (LDL) levels in LCAT-deficient subjects were significantly (P<0.01) higher than those in controls (1.30+/-0.82 versus 0.42+/-0.32 ng/5 microg LDL, respectively), and a significant (P<0.01) difference was observed even after adjustment for confounding factors by an analysis of covariance. The patient with the highest plasma oxPC-modified LDL had the most membranelike structures in the glomeruli and showed the greatest renal deterioration from a young age. In glomerular lesions, although there was an abundance of apoB and apoE, oil red O-positive lipids, macrophages, apoA1, and malondialdehyde were scarce. OxPC was found extracellularly in glomerular lesions, and although its distribution differed from that of apolipoproteins, it was quite similar to that of phospholipids. In conclusion, these results indicate that oxPC in plasma and glomeruli is distinctive for patients with LCAT deficiency. Therefore, oxPC may be a factor in the deterioration of kidneys in patients with familial LCAT deficiency.

Adult↗
PubMed1998

Appearance of cross linked proteins in human atheroma and rat pre-fibrotic liver detected by a new monoclonal antibody.

A new monoclonal antibody against malondialdehyde (MDA)-treated low density lipoprotein (LDL) was raised using homogenate of human atheroma as immunogen. This antibody, DLH2, was obtained by selecting the clones which did not react to native LDL but did react to copper-induced oxidized LDL (OxLDL). DLH2 showed a greater reactivity to MDA-LDL than to OxLDL. When LDL was treated with various aldehyde containing reagents, treatment of LDL with glutaraldehyde or MDA greatly increased the reactivity to the antibody, while LDL treated with 2,4-hexadienal or 4-hydroxynonenal was not reactive. Among many proteins tested, high density lipoprotein, bovine serum albumin and hemoglobin showed significant reactivity to DLH2 after they were treated with MDA or glutaraldehyde. When low density and high density lipoproteins treated with MDA were subjected to immunoblot analysis, newly formed products larger than the original apolipoproteins were detected with the antibody, suggesting that this antibody recognizes aggregated proteins with divalent short chain cross linkers. The antigenic materials were shown by immunohistochemical analysis to be present in foamy macrophages in human atheromatous lesions. DLH2 antigen did not colocalize either with apolipoprotein B. Furthermore, we found a massive accumulation of the antigenic material in Kupffer cells in the liver of rats treated with alcohol and carbonyl iron, a model of hepatic fibrosis due to oxidative stress. These results suggest the presence of cross linked proteins in damaged tissues.

Animals↗
PubMed1998

Genetic changes in primary colorectal cancer by comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a powerful new technique for the molecular cytogenetic analysis of cancer. In this method, at first the cancer DNA and normal DNA are labeled with biotin and digoxigenin, respectively, and then the labeled DNAs are applied onto normal lymphocyte metaphase preparations in hybridization. After hybridization, they are stained with FITC and rhodamine, respectively, so chromosomal gains and losses in cancer are thus detected by using a green:red ratio. In this study, we analyzed the abnormal chromosomes in nine cases with human primary colon cancer. A gain in chromosomes 11p, 12q, 16p, 20p, and 20q were observed, while a loss of 18q and 22q were discovered. CGH may thus provide us with important information for analyzing the genes in colon cancer.

Chromosome Aberrations↗
PubMed1998

Correlation of histologic morphology and tumor stage with molecular genetic analysis using microdissection in gastric carcinomas.

Precise correlation of histomorphology with the results of molecular genetic analysis is difficult in gastric cancer tissue composed of intestinal and diffuse types. A novel microdissection procedure was applied to correlate p53 and APC allelic loss with histologic type and tumor stage (mucosal vs. invasive cancer) in formalin-fixed, paraffin-embedded specimens of 25 gastric cancers. In addition, mucosal and invasive lesions were dissected from each of 11 invasive gastric cancers to study progression, and allelic loss of the p53 and APC genes was assessed. The p53 gene underwent loss of heterozygosity (LOH) in 4 of 4 informative cases of intestinal-type gastric cancer with mucosal lesions associated with invasion. By contrast, no p53 LOH was found among 6 informative cases with mucosal cancer. LOH of the APC gene in both intestinal and diffuse types of cancer was detected in 4 of 7 and 5 of 6 informative cases, respectively. These data suggest that allelic deletion of the p53 gene in intestinal-type gastric carcinoma predicts the invasive potential of mucosal cancer, and that inactivation of the APC gene plays a role in the genetic tumorigenesis of both intestinal and diffuse types of gastric cancer. Microdissection can correlate genetic alterations with histologic morphology in gastric cancer.

Adenocarcinoma↗
PubMed1998

Glomerular score as a prognosticator in IgA nephropathy: its usefulness and limitation.

Glomerular sclerosis, mesangial hypercellularity, extracapillary lesions, interstitial fibrosis, and vascular sclerosis have been reported to be the significant pathologic prognosticators in IgA nephropathy (IgAN). We developed our own scoring for the following main glomerular changes in 248 patients with IgAN: 1) glomerular hypercellularity (mesangial and endocapillary), 2) segmental lesions such as tuft adhesion, crescent and segmental sclerosis, 3) global glomerular sclerosis. Indices of each lesion were semiquantitatively determined. The sum of these three indices was defined to be a glomerular score. We found that a glomerular score significantly related to the outcome of patients with IgAN in univariate life table analysis. We also semiquantitatively determined total score including tubulo-interstitial and vascular lesions as well as glomerular score and compared the predictive power as a prognosticator between glomerular score and total score. Using Cox's proportional Hazard model and log-likelihood ratio test, we confirmed that predictive power of glomerular score was better than that of total score. Furthermore, we assessed the reproducibility of glomerular score using Kappa statistics. Three pathologists read 100 biopsies which were randomly selected from the materials and all pathologists read them twice. A value of Kappa between the first and second observation of pathologist A, B and C was 0.68, 0.71 and 0.60, respectively. Values of Kappa between Pathologist A and B were ranging from 0.45 to 0.47, those between Pathologist A and C from 0.30 to 0.36, and finally those between Pathologist B and C were ranging from 0.12 to 0.23. Therefore, intra-observer reproducibility was nearly excellent. And inter-observer reproducibility between Pathologist A and B was satisfactory. However, inter-observer reproducibility between Pathologist A and C and between B and C was not satisfactory. We feel our scoring system is very convenient and easy to be understood as a prognosticator in patients with IgAN. It, however, should be used by one pathologist because of excellent intra-observer reproducibility and rather unsatisfactory inter-observer reproducibility.

Female↗
PubMed1997

Lobular form idiopathic glomerulonephritis with massive subendothelial and paramesangial immune deposits, a three-year follow-up case.

We report a patient with unusual glomerulonephritis. A 24-year-old Japanese female was hospitalized in October 1995 because of nephrotic syndrome. Lobular form glomerulonephritis with mesangial proliferation associated with massive wide-spread accumulation of slightly eosinophilic, periodic acid Schiff-positive amorphous materials in the luminal side of the capillary walls and paramesangial area was observed in the renal biopsy specimen. Immunofluorescent study revealed massive strong staining for IgM and C4 along the capillary walls and in the mesangium. Deposits of IgA, IgG, C3 and fibrinogen were also observed. Electron microscopy showed normal thickness of the capillary basement membrane and a large amount of subendothelial and paramesangial electron dense, finely granular deposits without fibrils or tubular structures. There were no clinical or laboratory findings of systemic diseases, such as systemic lupus erythematosus and cryoglobulinemia. Therefore, we believed that this case involved an unusual idiopathic glomerular disease with massive subendothelial and paramesangial immune deposits. Glomerulonephritis in this patient appeared to be resistant to treatment with corticosteroids and that this glomerulopathy may be a progressive disease as shown during the 3-year observation. Furthermore, our patient had idiopathic hyperprolactinemia and subclinical hypothyroidism. However, the relationship between glomerulonephritis and endocrinopathy in our patient is unknown.

Adult↗
PubMed1996

Common deleted region on the long arm of chromosome 5 in esophageal carcinoma.

BACKGROUND & AIMS: The existence of an unknown tumor-suppressor gene on 5q for esophageal carcinoma other than the APC gene has been suggested. The location of the putative tumor-suppressor gene on 5q, distinct from the APC gene, was examined. METHODS: Sixty-one primary esophageal carcinomas were examined for nine microsatellite loci by the polymerase chain reaction followed by polyacrylamide gel electorophoresis. Loss of heterozygosity at the APC gene locus also was examined by the polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: Thirty-five of 61 esophageal carcinomas (57%) showed loss of heterozygosity at single or multiple loci on 5q, and the smallest common deleted region was identified at 5q31.1, the location of the IRF-1 gene locus. All tumors showing loss of heterozygosity at the APC gene locus showed complete or large interstitial deletions on 5q. CONCLUSIONS: Deletion at the APC gene locus may just be the result of large deletions on 5q and may not be important in esophageal carcinogenesis, and the IRF-1 gene or other gene(s) on 5q31.1 may be the true target of frequent deletions on 5q that may play an important role in the pathogenesis of the majority of esophageal carcinomas.

Carcinoma↗
PubMed1995

Monosomy of chromosome 18 detected by fluorescence in situ hybridization in colorectal tumors.

BACKGROUND: At least two different evolutional pathways of colorectal cancer, namely the adenoma-carcinoma sequence and de novo carcinogenesis, have been indicated. However, whether there is a difference between them in affected chromosomes and genes has not yet been elucidated. Chromosomal examination is expected to provide a clue to an answer to this question. In this study, the relation of aberrations in chromosome 18 to type of colorectal cancer was examined. METHODS: Numeric aberrations in chromosome 18 were investigated in 71 colorectal tumors by means of fluorescence in situ hybridization, using an alphoid satellite DNA probe specific for the pericentromeric region on chromosome 18. RESULTS: The loss of one chromosome 18 was found in 33% (6 of 18) of patients with early cancer, excluding those with cancer in an adenoma. The loss was frequent in early colorectal carcinomas without foci of adenoma (four of six patients, 67%), whereas monosomy 18 was not significant in those with foci of adenoma except for patients with a hereditary background. Specimens exhibiting monosomy 18 were macroscopically classified as flat lesions, but the converse was not true. No adenoma showed monosomy 18. It was encountered in 44% of nine cancers with invasion to the muscularis propria. However, no significant subpopulation of monosomy 18 was present in cancers penetrating through the serosa or adventitia in which polysomic populations were often identified alternatively. Furthermore, tetrasomy for this chromosome was exclusive in these advanced cancers. CONCLUSIONS: The loss of chromosome 18 is closely related to colorectal cancers without foci of adenoma.

Adenoma↗
PubMed1995

Oxidized low density lipoprotein stimulates collagen production in cultured arterial smooth muscle cells.

We examined the interactive effect of oxidized low density lipoprotein (LDL) and ascorbic acid on collagen production in cultured smooth muscle cells (SMCs). Porcine aortic SMCs were incubated with 50-200 micrograms/ml of human LDL with/without 5 microM Cu2+ for 24 h. Collagen production was assayed by successive salt precipitation at acidic and neutral pH after pepsin digestion of 3H-proline-labeled collagenous protein. Oxidation of LDL was evaluated by electrophoresis and by the level of thiobarbituric acid reactive substances (TBARS). Ascorbic acid reduced the oxidation of LDL + Cu2+ (53% reduction). In the presence of ascorbic acid, no differences were noted in collagen production between LDL and LDL + Cu2+. Without ascorbic acid, collagen production with LDL + Cu2+ was increased dose-dependently up to 6-fold with 150 micrograms/ml LDL, while no such effects were observed at any doses of native LDL. The addition of butylated hydroxytoluene to LDL + Cu2+ strongly suppressed oxidation (88% reduction), and significantly reduced collagen production close to that seen with native LDL. These results indicate that oxidized LDL stimulates collagen production in SMCs, while native LDL does not. Therefore, oxidized LDL may play a direct role in stimulating collagen production in SMCs, which could lead to collagenosis in atherosclerosis.

Animals↗
PubMed1995

Intratumoral regional heterogeneity of DNA ploidy patterns in colorectal carcinomas.

There is no agreement on the evaluation of intratumoral DNA ploidy heterogeneity, and its clinical significance remains controversial. We categorized intratumoral ploidy heterogeneity in an effort to avoid confusion and misunderstanding among investigators. We classified the heterogeneity into 3 major types (Types A, B and C) and a combined type (Type D), based on the intratumoral distribution profiles of DNA aneuploid lines identified by flow cytometry in 52 cases of colorectal cancer with intratumoral DNA ploidy heterogeneity selected from a consecutive series. Every carcinoma examined in this study fell into one of the 4 categories: Twenty-six tumors (50%) were classified as Type A, 6 (11%) as Type B, 2 (3%) as Type C, and 18 (36%) as Type D. We discussed the mechanisms of DNA ploidy heterogeneity evolution within a tumor, and also proposed a pathway to these types of DNA ploidy heterogeneity as an aid to understanding the relationship between tumor progression and DNA ploidy changes.

Carcinoma↗
PubMed1995

[A case of so-called carcinosarcoma of the esophagus].

So-called carcinosarcoma of the esophagus is rare malignant tumors composed of carcinoma and sarcomataous components. We described a case of so-called carcinosarcoma and reviewed some literature. A 67-year-old man visited our hospital because of difficulty in swallowing, general fatigue, and sore throat. Barium swallow esophagogram showed a large polypoid lesion in the middle, lower thoracic esophagus. Endoscopy also demonstrated a pedunculated polypoid tumor. Histological examination of the biopsy specimen revealed malignant findings. Thoracic esophagectomy with cervical, thoracic, abdominal dissection was performed. A polypoid tumor, 10.5 x 5.2 x 3.5 cm in size, was removed. In the polypoid lesion, spindle-shaped cells made interlacing bundles similar to sarcoma and surrounded nests of squamous cell carcinoma. Near the pedicle, squamous cell carcinoma invaded muscularis mocosae. And lymph node metastasis was detected. Epitherial membrane antigen (EMA) was detected in some parts of the polypoid lesion. So according to Guide Lines for Clinical and Pathological Studies on Carcinoma of the Esophagus, this case was diagnosed as so called carcinosarcoma.

Aged↗
PubMed1994

Identification of S-phase cells with PC10 antibody to proliferating cell nuclear antigen (PCNA) by flow cytometric analysis.

We estimated the expression of proliferating cell nuclear antigen (PCNA) in HeLa S3 cells by flow cytometry with monoclonal antibody (MAb) PC10. HeLa cells were fixed with six different fixation procedures: 15-min and 30-min acetone, 15-min acetone followed by 15-min methanol (acetone/methanol), 30-min methanol, 15-min methanol followed by 15-min acetone (methanol/acetone), and a mixture of acetone and methanol. The fixed cells were applied to MAb PC10 against PCNA and then treated with FITC. With five fixation procedures except for acetone/methanol, PCNA was expressed in almost all cells with similar shapes and different FITC intensity levels on PCNA/DNA bivariate cytograms, whereas acetone/methanol fixation allowed PCNA detection in S-phase cells with a cytogram that showed a horseshoe-like pattern with a peak level at mid-S-phase. Flow cytometric dual parameter analysis of PCNA/BrdU was carried out in HeLa cells to confirm detection of PCNA in S-phase cells with acetone/methanol fixation. The population of cells stained for both parameters, i.e., S-phase cells, was obviously discriminated from that of the non-S-phase cell in PCNA/BrdU bivariate cytograms. These results strongly suggest that PCNA used with acetone/methanol fixation would be equal to BrdU as an S-phase marker.

Antibodies, Monoclonal↗