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N Uesugi

Publications and source records attributed to N Uesugi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Microsatellite instability in gallbladder carcinoma: two independent genetic pathways of gallbladder carcinogenesis.

Although the genetic basis for gallbladder carcinogenesis has not been clarified, considerable evidence has shown that genetic alterations play an important role in the development and progression of human cancers. In this study, we analyzed 30 gallbladder carcinomas to investigate the role of genetic alterations in their tumorigenesis, and to study correlations with their clinicopathological features. Tissue samples were obtained from 30 patients with gallbladder carcinoma (11 men and 19 women; mean age, 62 years; age range, 38-80 years). Genomic DNAs were extracted from fresh tumor tissue. We examined loss of heterozygosity (LOH) in the p53, APC, DCC, RB, and NM23-H1 gene regions by polymerase chain reaction (PCR)-LOH assay using an automated fluorescent DNA sequencer employing four microsatellite markers (p53, APC, DCC, NM23-H1). Five additional microsatellite markers were used for the determination of microsatellite instability (MSI). LOH was found at p53 in 9 of 15 informative cases (60%), at DCC in 10 of 22 (45%), at APC in 5 of 15 (33%), at RB in 1 of 8 (13%), and at NM23-H1 in 1 of 15 (7%). MSI was observed in 5 of 30 cases (17%) in at least one chromosomal loci of these nine microsatellite markers. None of the patients with MSI-positive tumors showed lymph node metastasis, and there was an inverse correlation between MSI and the presence of LOH in gallbladder carcinoma. These results suggest that there are two independent genetic pathways in gallbladder carcinogenesis; that is, an MSI pathway and an LOH pathway.

Adult↗
PubMed2000

Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma.

BACKGROUND & AIMS: Microsatellite instability (MSI) in mitochondrial DNA (mtDNA) is observed in some colorectal carcinomas. We attempted to determine if mitochondrial MSI (mtMSI) and mutations occur in gastric carcinomas and if the mtMSI phenotype underlies specific clinicopathologic profiles. METHODS: Sixty-two gastric carcinomas (34 intestinal and 28 diffuse types) were investigated. Coding mutations in 8 different mitochondrial genes, mtMSI in a noncoding (C)n tract, and p53 gene mutations were examined by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. MSI in nuclear DNA (nMSI) and loss of the p53 gene were examined using microsatellite markers. RESULTS: Ten of 62 (16%) carcinomas showed the mtMSI phenotype. Mitochondrial gene mutation was detected in 5 carcinomas, 4 of which also showed the mtMSI phenotype. There was a positive correlation between mtMSI and nMSI status. In intestinal carcinomas, mtMSI, nMSI, and p53 gene alterations were frequently detected from early to advanced stages. In diffuse carcinomas, both kinds of MSI were found in only advanced (subserosal or serosal invasion) carcinomas. Six of 7 carcinomas with the nMSI phenotype and all 5 carcinomas with mitochondrial coding mutations had a considerable intestinal-type tumor cell component. CONCLUSIONS: Mitochondrial gene mutations, which are associated with the mtMSI phenotype, may play a specific role in the tumorigenesis of intestinal-type gastric carcinomas.

Cell Nucleus↗
PubMed2000

Use of crypt isolation to determine loss of heterozygosity of multiple tumor suppressor genes in colorectal carcinoma.

Analysis of loss of heterozygosity (LOH) is very important in the study of tumor suppressor genes. However, accurate LOH analysis of tumor suppressor genes is difficult because of dilution by contaminating non-tumor DNA. Thus, enrichment of tumor DNA is required to accurately determine LOH of the tumor. We developed a new application of the fluorescent polymerase chain reaction by coupling it with crypt isolation to accurately assess the incidence of LOH of tumor suppressor genes in 45 colorectal carcinomas. LOH was observed at p53 in 26 of 37 tumors (70.3%), at APC in 13 of 35 (37.1%), at DCC in 16 of 25 (64.0%), at NF-2 in 5 of 23 (21.7%), and at nm23 H-1 in 7 of 30 (23.3%). We could clearly determine LOH of these genes because the crypt isolation technique was used. Although the incidence of LOH at each of these loci, as determined by using this technique, was similar to that obtained in previous studies using conventional methods, this method provides a simpler, more accurate way to assess LOH. In addition, the morphology of the samples can be analyzed before genetic analysis.

Adenocarcinoma, Mucinous↗
PubMed2000

Esophageal squamous cell carcinoma characterized by extensive chondroid differentiation.

A rare case of carcinoma characterized by extensive chondroid elements at a site of primary esophageal and metastatic lesion is reported. The patient was a 67-year-old man complaining of dysphagia due to an ulcerative lesion at the lower middle esophagus. He underwent irradiation treatment prior to surgery. Histologically, the tumor consisted of both carcinomatous and chondroid elements and had invaded deeply into the esophageal wall. The carcinomatous cells had gradually become chondroid cells embedded within an extensive extracellular matrix. In addition, the metastatic lesion showed findings similar to those of the primary lesion. Immunohistochemistry revealed that both carcinomatous and chondroid elements were immunostained with cytokeratin and epithelial membrane antigen, suggesting an epithelial nature to the chondroid cells. Conversely, only chondroid cells were positively stained for S-100 protein. Furthermore, bone morphogenetic proteins (BMP) were positive for chondroid cells and their surrounding carcinomatous cells. Given the apparent transition between carcinomatous and chondroid cells based on microscopy and immunohistochemical findings in the present case, we concluded that the chondroid cells were derived from carcinomatous cells. In addition, our findings suggest that BMP produced by carcinomatous cells lead to chondroid differentiation of the carcinoma cells.

Aged↗
PubMed2000

Allelic losses of 17p, 5q, and 18q loci in diploid and aneuploid populations of multiploid colorectal carcinomas.

17p, 5q, and 18q allelic losses are involved in the pathogenesis and progression of colorectal carcinoma, and DNA aneuploidy in this type of cancer is thought to result from alterations of these chromosomal loci. However, genetic differences between diploid and aneuploid populations of multiploid carcinoma, defined as the coexistence of diploid and aneuploid populations in the same area, remain unclear. The differences in 17p, 5q, and 18q allelic losses between the diploid and aneuploid populations in 24 sporadic DNA multiploid colorectal carcinomas were analyzed by use of crypt isolation coupled with DNA cytometric sorting and polymerase chain reaction assay. 17p Allelic loss was observed in 7 of 22 diploid populations excluding 1 case of microsatellite instability but was found in 21 of 23 aneuploid populations. Although 5q allelic loss was detected in only 3 of 22 diploid populations, 13 of 22 aneuploid populations had 5q allelic loss. Losses of the 18q allele were frequently found in aneuploid populations (15 of 20), although no 18q allelic loss was detected in corresponding diploid populations. 17p Allelic losses may play an important role in the progression from a diploid status to an aneuploid status in a specific subset of colorectal cancer. However, 18q or 5q allelic losses do not appear to precede nor to facilitate the aneuploid clonal divergence of cancer cells. Multiploidy is a useful model to study genetic alterations between diploid and aneuploid populations.

Adult↗
PubMed2000

Glycoxidative modification of AA amyloid deposits in renal tissue.

BACKGROUND: N(epsilon)-carboxymethyllysine (CML) is a product of the oxidative modification of glycated proteins, which damages proteins with ageing, diabetes, uraemia and Alzheimer's disease. In contrast, pyrraline is one of the advanced glycation end products, which is independent of oxidative processes. CML has been identified in beta-amyloid of Alzheimer's disease and beta(2)-microglobulin-associated amyloid. We investigated whether CML and pyrraline are formed in AA and AL amyloid of the kidney. METHOD: Renal specimens from 19 cases of AA amyloidosis and 14 cases of AL amyloidosis were investigated for immunolocalization of CML, pyrraline, collagen type IV and laminin in amyloid deposits. Renal biopsies of 10 age-matched cases with thin basement membrane disease and normal renal function were used as controls. The fractional areas of amyloid, CML, laminin and collagen IV in glomeruli and interstitium (%amyloid, %CML, %laminin and %collagen, respectively) were calculated using the point counting method. The correlation between these parameters was evaluated using Spearman's rank correlation test. RESULTS: CML colocalized with AA amyloid, but not AL amyloid, except in two cases of the latter with a long history of nephropathy exceeding 14 years. In contrast, pyrraline was not observed in either type of amyloid. Mean %CML in AA amyloid was significantly higher than %collagen and %laminin in glomeruli and interstitium, indicating that AA amyloid is modified by CML independent of colocalized extracellular matrix. %CML significantly correlated with %amyloid both in glomeruli and interstitium in AA amyloidosis. AL amyloid cases with a long history of nephropathy showed positive staining for CML in glomeruli and interstitium but no staining for collagen IV and laminin in amyloid deposits. CONCLUSION: CML modification may occur in amyloid deposits of AA amyloidosis, independent of extracellular matrix components. Glycoxidative modification may have a functional link to AA amyloid deposition in renal tissues.

Adult↗
PubMed2000

Possible involvement of altered RGD sequence in reduced adhesive and spreading activities of advanced glycation end product-modified fibronectin to vascular smooth muscle cells.

Although fibronectin (FN) modified by advanced glycation end products (AGEs) has been shown to contribute to the development of diabetic vascular complications through its reduced adhesive activity to vascular cells, little is known about changes in the cell binding domain of AGE-modified FN. Here we examined the mechanism of reduced adhesive and spreading activities of AGE-modified FN to vascular smooth muscle cells (SMCs), particularly the contribution of modification of Arg-Gly-Asp (RGD) sequence. Incubation with glucose caused not only the formation of N(epsilon) -carboxymethyllysine and pentosidine, but also polymerization of FN in a dose- and time-dependent manner. AGE-modified FN had significantly low adhesive and spreading activities to cultured SMCs. On the other hand, multimeric FN formed by disulfide bonds did not show any effect on either cell adhesion or spreading. The adhesive activity of type I collagen, one of the RGD sequence-containing proteins, to SMCs also decreased by AGE-modification. The inhibitory effect of AGE-modification on cell adhesion was significantly greater in type I collagen than in FN. Although the extent of AGE-modification of type I collagen was indistinguishable from that of FN, AGE-modification decreased the arginine content of type I collagen by 69.5% and of FN by 30.6%, compared with their non-glycated forms. The addition of RGD peptides caused a decrease in adhesion of SMCs to non-glycated FN, but not to AGE-modified FN. Modification of RGD sequence with glyoxal eliminated its inhibitory effect on cell adhesion. Our results suggest that a marked decrease in adhesive and spreading activities of AGE-modified FN to SMCs might largely be due to a modification of its RGD sequence by AGE, thus suggesting a potential link between AGE modification of FN and the pathogenesis of diabetic angiopathy.

Amino Acids↗
PubMed2000

Causal relationship between conformational change and inhibition of domain functions of glycoxidative fibronectin.

Glycoxidative modification of various body proteins, including fibronectin (FN), has been shown to change their structural and functional properties, and be implicated in pathogenesis of diabetic complications. Little is known about the role of secondary structure of glycoxidative FN (gFN) in its domain functions. gFN was prepared by incubation with 25 and 200 mM glucose in 0.2 M sodium phosphate buffer at 37 degrees C on a shaking plate under aerobic and sterile conditions for various time intervals up to 49 days, being defined as gFN25 and gFN200, respectively. Unmodified FN (uFN) was prepared by incubation in 0.2 M sodium phosphate buffer without any glucose at 4 degrees C for 49 days. The extent of glycoxidative modification was examined using a noncompetitive enzyme-linked immunosorbent assay with an antibody against N(epsilon) -(carboxymethyl)lysine (CML), one of the major glycoxidation products. The binding activities of uFN and gFN to collagen, gelatin and heparin were determined by a solid phase enzyme immunoassay or heparin-affinity HPLC. Cell attachment was estimated by the extent of adhesion of FITC-labeled smooth muscle cells to uFN or gFN. Conformational change in gFN was detected by SDS-polyacrylamide gel electrophoresis and spectroscopy (circular dichroism). CML was detected in gFN25 and gFN200 after 49 and 21 days of incubation, respectively. Levels of CML were about six-fold higher in gFN200 than in gFN25 after 49 days. Both gFN25 and gFN200 showed a significant decrease in the ability of binding to collagen and gelatin after 7 days of incubation. The binding activity for heparin was significantly decreased in both gFN25 and gFN200 after one day. Cell attachment activity was reduced to 89% and 76% of the unmodified form in both gFN25 and gFN200 after 49 days, respectively. High molecular weight materials were found in gFN25 and gFN200 after 21 and 7 days, respectively. CD spectrum showed that gFN25 had lost its native conformation after 3 days of incubation, depending upon the concentration and incubation interval of the applied glucose. These in vitro results suggest that the loss of native conformation may reduce the domain functions of gFN, including binding activity to macromolecular ligands and cell attachment, and may play a major role in the pathogenesis of diabetic complications.

Cell Adhesion↗
PubMed2000

A unique method for mutation analysis of tumor suppressor genes in colorectal carcinomas using a crypt isolation technique.

BACKGROUND: Contamination of nontumor tissue makes genetic analysis difficult. For this reason, it is important to obtain pure tumor tissue to ensure accurate genetic analysis. OBJECTIVE: To accurately assess the incidence of mutation of tumor suppressor genes (p53: exon 5-8; APC: mutated cluster region; NF-2 gene: all exons) in 45 colorectal carcinomas. METHODS: We developed an application of the polymerase chain reaction-single-strand conformation polymorphism and DNA sequence by coupling them with crypt isolation. RESULTS: Mutations of p53 and APC genes were found in 24 and 22 of 45 colorectal carcinomas, respectively. No mutation of the NF-2 gene was observed in this cancer. Single-strand conformation polymorphism using a crypt isolation technique showed a clear migrating band and no false-positive data. CONCLUSIONS: The crypt isolation technique is a useful method for accurately analyzing genetic alterations. Furthermore, our proposed method confirmed the morphological findings obtained before the genetic analysis.

Adenocarcinoma↗
PubMed2000

[SIRS in surgical stress].

It has been suggested that SIRS are triggered by superfluous pro-inflammatory cytokine production, and that organ injury is caused by uncontrolled inflammatory responses. However, the results of clinical studies, on the usefulness of specific cytokine antagonists and anti-TNF antibodies for the treatment of septic shock, have been unsatisfactory. The reason for this might have been that when uncontrolled inflammatory reactions progressed locally, anti-inflammatory reactions were elevated in the circulated blood by way of CARS, thus the timing of administration and pharmacokinetics did not match clinical course. Recent research has shown that SIRS is always accompanied by CARS, and since it seems to do the amplitude of SIRS and CARS to each other so that there may be a deep valley, if there is a high mountain. We introduce the recent knowledge which indicates that SIRS is a preliminary alert for not only organ dysfunction but also immunosuppression after severe injury or major surgery.

Cytokines↗
PubMed1999

Role of DNA aneuploidy, overexpression of p53 gene product, and cellular proliferation in the progression of gastric cancer.

DNA aneuploidy, p53 overexpression, and high cell proliferation frequently occur in gastric cancer. However, little is known about the time of their appearance throughout cancer progression. Therefore, the objective of the present study was to determine when such abnormalities occur during gastric cancer progression. We classified the gastric cancers examined into intestinal (n = 65) and diffuse (n = 34) types. DNA ploidy was examined using flow cytometry and expression of MIB-1 and p53 immunoreactivity were studied using the avidin-biotin complex method in three stages of gastric cancer (mucosal, submucosal, deeply invasive cancer, i.e., advanced cancer). The incidence of DNA aneuploidy in intestinal-type mucosal cancers (15/27, 55.6%) was lower than that of submucosal invasive cancers (14/16, 87.5%) or advanced cancers (19/22, 86.4%), while a low incidence of DNA aneuploidy was observed in each diffuse-type cancer group (mucosal, 1/12, 8.3%; submucosal invasive, 3/9, 33.3%; advanced, 8/14, 57.1%). Although overexpression of the p53 gene in intestinal-type cancer was found in early stage, that in diffuse-type cancer was observed in advanced stage. Among the intestinal-type mucosal cancers, the MIB-1 percent positive was higher in aneuploid tumors than diploid ones. DNA aneuploidy and overexpression of the p53 gene may play an important role in the early tumorigenesis of intestinal-type gastric cancer and in the late event of tumorigenesis of diffuse-type gastric cancer.

Aged↗
PubMed1999

Problems in neoadjuvant chemoradiotherapy preceding surgery for advanced squamous cell carcinoma of the thoracic esophagus.

The adverse effect of neoadjuvant chemoradiotherapy on the postoperative course in esophageal cancer was studied in 9 patients undergoing neoadjuvant chemoradiotherapy preceding surgery for thoracic esophageal carcinoma possibly involving adjacent organs (neoadjuvant group), and 13 patients undergoing surgery without neoadjuvant therapy for same disease (control group). The two groups were compared for volume of intraoperative hemorrhage, surgical duration, frequency of postoperative morbidity, and for postoperative changes in blood platelet counts, and serum thrombopoietin and interleukin-6 levels. Mean intraoperative blood loss was 1121 g (580-1,662 g) in the neoadjuvant group and 546.5 g (274.7-778.3 g) in controls group (Student's T test: p < 0.01). No significant difference was seen found between the two groups in the degree of postoperative deterioration in cardiopulmonary function or in interleukin-6 levels. Blood platelet counts decreased in both groups until postoperative day 7, but recovery on postoperative day 14 was significantly depressed in the neoadjuvant group compared to controls. Serum thrombopoietin levels were higher in the neoadjuvant group than in controls (Mann-Whitney U-test: p < 0.05). We found that neoadjuvant chemoradiotherapy induces latent postoperative myelosuppression and may lead to intractable infection.

Aged↗
PubMed1999

Analysis of subclonal expansion of colorectal carcinomas by flow cytometry.

DNA heterogeneity of colorectal carcinomas has been investigated by flow cytometry, most studies have focused on the clinical usefulness of DNA ploidy analysis. Since cancers consist of predominant subclones with proliferative advantage due to clonal expansion, we attempted to analyse the clonal expansion of colorectal carcinomas within a tumour by measuring DNA ploidy. The DNA ploidy and heterogeneity of multiple fresh samples obtained from 164 colorectal adenocarcinomas were analysed by flow cytometry. Each tumour was divided into an average of six specimens, which were analysed separately. For 146 of the tumours (89%) at least one DNA aneuploid population was found within the cancer tissue examined. DNA multiploidy was detected in 26 cases (17.8%) among the cancers with aneuploidy. Based on the DNA index (DI), hypertriploid aneuploidy (1.7<DI<1.8) was found most frequently in the aneuploid colorectal cancers examined. DNA ploidy heterogeneity was seen in 75 (51.4%) of the DNA aneuploid tumours. There were only 3 cases with more than three subclones including a diploid line. The present results indicate that colorectal carcinomas consist of a few dominant subclones and have a DNA content (hypertriploid aneuploid) that confers a proliferative advantage.

Adenocarcinoma↗
PubMed1999

Usefulness of proliferative activity, DNA ploidy pattern and p53 products as diagnostic adjuncts in colorectal adenomas and intramucosal carcinomas.

Although numerous studies have assessed the biologic parameters of tumors, measurement of these parameters has had, to date, little impact on histologic diagnosis. Furthermore, analysis of a single parameter is insufficient to evaluate tumor malignant potential. In the present study, cell proliferation, DNA ploidy and p53 product were analyzed to objectify the tumor malignant potential in colorectal adenomas and intramucosal carcinomas. Sixty-one adenomas and 49 intramucosal carcinomas were studied using immunohistochemical analysis of Ki-67 and p53, silver-staining nucleolar organizer region (AgNOR) stain and DNA ploidy in fresh samples. Intramucosal carcinoma exhibited a greater Ki-67-positive rate and AgNOR count than the adenomas, although these parameters varied widely among samples. The incidence of aneuploidy and p53 over-expression in colorectal intramucosal carcinomas was significantly higher than in colorectal adenomas. These results indicate that DNA aneuploidy and p53 accumulation are the most reliable parameters for distinguishing benign and malignant lesions.

Adenocarcinoma↗
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↗
PubMed1999

[Clinicopathological and morphometrical analysis of 5 cases from 4 families of fibronectin glomerulopathy].

Fibronectin glomerulopathy (FNG) is an inherited disease, characterized by massive fibronectin (FN) deposits in the glomeruli. We semiquantitatively analyzed glomerular lesions and their progression in 5 cases with FNG from 4 different families: a 4 year-old male, a 19 year-old female, a 27 year-old male, a 58 year-old male (the father of the former case) and a 75 year-old male. All subjects showed a 201 times higher value of mean glomerular-tuft area (GA) and a 2.0 times higher mean number of mesangial cells (No. of MC) relative to control (p < 0.001). Strong positive correlations were observed between GA and the No. of MC (r = 0.86, p < 0.001). The younger cases showed markedly higher value of GA and No. of MC than the older cases. Mean individual capillary luminal area was decreased in all but one case and the mean total capillary luminal area, which is roughly estimated as the glomerular filtration area, was less changed compared with the control. The number of capillary loops tended to increase, indicating elongation of the capillary loops. The fractional area of FN (%FN), collagen IV (%Coll. IV) and laminin (%Lam) were high in all cases except for the first Bx in the 27 year-old case. The %FN strongly correlated with %Coll. IV and %Lam (r = 0.86, r = 0.69, p < 0.001, respectively). Serial biopsy (Bx) with a 10 year-interval was examined in the 27 year-old case and his father: GA and No. of MC were increased 1.4 and 1.9 times in the son, compared with his first Bx (p < 0.001, respectively), while no change was observed in the father. The %FN, %Coll. IV and %Lam were significantly increased in their second Bx (p < 0.001). These results suggest that 1) enlargement of the glomeruli in FNG is caused by intraglomerular accumulation of FN, Coll. IV and Lam and proliferated mesangial cells, 2) there is a strong influence from the aging factor, and 3) compensatory elongation of the loops (increase in the capillary luminal area) may maintain the glomerular filtration.

Adult↗