Biomedical subjects

E Adachi

Publications and source records attributed to E Adachi.

At least 55 records · Page 3Linked to original sources

PubMed1997

Basement-membrane stromal relationships: interactions between collagen fibrils and the lamina densa.

Collagens, the most abundant molecules in the extracellular space, predominantly form either fibrillar or sheet-like structures-the two major supramolecular conformations that maintain tissue integrity. In connective tissues, other than cartilage, collagen fibrils are mainly composed of collagens I, III, and V at different molecular ratios, exhibiting a D-periodic banding pattern, with diameters ranging from 30 to 150 nm, that can form a coarse network in the extracellular matrix in comparison with a fine meshwork of lamina densa. The lamina densa represents a stable sheet-like meshwork composed of collagen IV, laminin, nidogen, and perlecan compartmentalizing tissue from one another. We hypothesize that the interactions between collagen fibrils and the lamina densa are crucial for maintaining tissue-tissue interactions. A detailed analysis of these interactions forms the basis of this review article. Here, we demonstrate that there is a direct connection between collagen fibrils and the lamina densa and propose that collagen V may play a crucial role in this connection. Collagen V might also be involved in regulation of collagen fibril diameter and anchoring of epithelia to underlying connective tissues.

Animals↗

PubMed1997

Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of beta-dystroglycan in the outer plexiform layer of the retina.

Dp260 is a C-terminal isoform of dystrophin and is expressed specifically in the retina. Abnormal electroretinograms (ERG) in some Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients are likely linked to a disruption of Dp260. To clarify the importance of Dp260 in the retina, we examined dystrophin exon 52 knock-out mice, whose expression of Dp260 is impaired. We also confirmed the localization of Dp260 in the outer plexiform layer (OPL) of the retina. Disruption of Dp260 causes a change in the localization of beta-dystroglycan, which is normally found in the OPL of the retina. This suggests a requirement for Dp260 for normal formation of the dystrophin-dystroglycan complex in the retina. Dp71, also expressed in the retina, was, however, not detected in the OPL. The difference in localization of Dp260 and Dp71 implies that the two isoforms have different functions. The dystrophin exon 52 knock-out mice had a prolonged implicit time of the b-wave in ERG, although no significant change was observed in amplitude. These ERG findings differed from those of DMD and BMD patients, especially with regard to amplitude of the b-wave, but make it clear that Dp260 is required for normal electrophysiology.

Animals↗

PubMed1997

Isolated collagen IV retains the potential to form an 18-nm sided polygonal meshwork of the lamina densa.

Polygonal meshworks were revealed in the aggregates reconstituted from isolated collagen IV as well as in the lamina densa of mouse pancreas by the quick-freezing and deep-etching technique. Collagen IV solution with acetic acid from the bovine lens capsules and that isolated from the pepsin-solubilized fraction of human placenta reconstituted polygonal meshworks, which were dimensionally similar to the meshwork seen in the lamina densa of mouse pancreas. The average lengths between branching points in the lamina densa, and the meshworks of collagen IV derived from the bovine lens capsules and from the human placenta were 20.1 +/- 7.7 nm (mode = 18 nm), 21.6 +/- 11.3 nm (mode = 14 nm), and 21.6 +/- 9.0 nm (mode = 18 nm), respectively. These observations suggest that collagen IV can, in the absence of other macromolecules including laminins, comprise a skeletal meshwork similar in dimensions to that of the lamina densa.

Animals↗

PubMed1996

Factors correlated with portal venous invasion by hepatocellular carcinoma: univariate and multivariate analyses of 232 resected cases without preoperative treatments.

BACKGROUND: The postoperative intrahepatic recurrence of hepatocellular carcinoma (HCC) is high. It is difficult to distinguish whether the recurrence is metastatic or new primary lesion. To determine the malignant potential of HCC itself, we analyzed the risk factors associated with portal venous invasion since this is direct evidence of tumor invasiveness. METHODS: Two hundred and thirty-two patients who underwent curative hepatectomy for HCC without preoperative treatments were included in this study, because preoperative treatment caused the tumor to undergo a variety of histologic change. We analyzed the risk factors linked to portal venous invasion by both univariate and multivariate analyses. RESULTS: In an univariate analysis, tumors larger than 3 cm, high histologic grade (III or IV), the presence of fibrous capsule, necrosis, mitotic rate of more than 4/10 high power fields, peliotic change, presence of tumor giant cells, high platelet count, low level of indocyanine green retention rate at 15 minutes, and the absence of cirrhosis were significantly correlated with portal venous invasion. In multiple stepwise logistic regression analysis, tumors larger than 3 cm, high histologic grades, and the presence of fibrous capsule were strong predictors of portal venous invasion by HCC. CONCLUSIONS: Because the blood vessels of the fibrous capsule were frequently invaded by cancer cells, it may have been possible to prevent postoperative metastatic recurrence if HCC were resected before becoming large enough to have a fibrous capsule.

Adult↗

PubMed1996

Spindle cell hepatocellular carcinoma. A clinicopathologic and immunohistochemical analysis of 15 cases.

BACKGROUND: Spindle cell hepatocellular carcinoma (SpHCC) has rarely been reported, and its clinicopathologic characteristics, histogenesis, and prognosis after hepatic resection have yet to be clarified. METHODS: Fifteen cases of SpHCC, including 13 surgically resected patients and 2 autopsy cases, were studied clinicopathologically and immunohistochemically. RESULTS: In 13 resected patients, all except 1 were male and the serum alpha-fetoprotein (AFP) was positive in 6 (46%). Portal venous invasion and intrahepatic metastases were frequent. In an immunohistochemical analysis of 13 SpHCC tumors, cytokeratin CAM 5.2 and AFP were positive in 8 (62%) tumors and 3 (23%) tumors in both ordinary HCC and spindle cell components, respectively. The spindle cell components, but not ordinary HCC components, revealed a positive reaction for vimentin in 8 (62%) tumors, S-100 protein and HAM-56 in 3 (23%) tumors, HHF-35 in 2 (15%) tumors, and alpha-smooth muscle actin, desmin, and KP-1 in 1 (8%) tumor, respectively. p53 overexpression was found in two SpHCC tumors. The survival curve after hepatic resection in the 13 patients with SpHCC was significantly worse than that of the 371 patients with Stage II-IV ordinary HCC (P < 0.001). CONCLUSIONS: These results suggest that SpHCC represents a sarcomatous transformation of HCC. The spindle cell components revealed an immunohistochemical expression of several markers of mesenchymal cells. In addition, poor survival after hepatic resection was documented.

Adult↗

PubMed1996

Gelation of the lens capsule type IV collagen solution at a neutral pH.

It is known that the type IV collagen extracted from EHS tumor assembles under a physiological condition, but not in a gel form. The EHS type IV collagen requires the other basement membrane components, laminin1, heparansulfate proteoglycan, and/or nidogen for gelation. On the other hand, Muraoka et al. reported that the bovine lens capsule type IV collagen alone gelated under a unique and unexpected condition of 2 M guanidine-HCl and 50 mM dithiothreitol, a condition which is thought to be dissociative for most biological macromolecules, including extracellular matrix [Muraoka, M. et al. (1996) J. Biochem. 119, 167-172]. The present report shows that the bovine lens capsule type IV collagen formed a gel under physiological conditions of pH and ionic environment, though the apparent rigidity of the gel was weaker than that of the gel formed in 2 M guanidine-HCl and dithiothreitol. The rigidity depended greatly on the incubation temperature and NaCl concentration of the type IV collagen solution, as observed in terms of the contractility of gel volume under centrifugal force. the gel formed in 150 mM NaCl and 20 mM phosphate, pH 7.3, at 28 degrees C contracted to 20% of the original volume on centrifugation of 1,800 x g for 10 min, while the gel formed at 4 degrees C, where type I collagen did not gelate at all, retained 90% of the original volume at the same centrifugal force. NaCl concentration was another important factor influencing the mechanical properties of type IV collagen gel. The gel formed at 150 mM showed maximal rigidity in the range of 0 to 300 mM in terms of the contractility on centrifugation. An image of a Pt/C replica of the gelated type IV collagen reconstituted at 4 or 28 degrees C in 20 mM phosphate, pH 7.3, containing 150 mM NaCl showed fine meshworks consisting of rather homogeneous pore sizes, resembling the skeletal structure of basal lamina. Since the condition where the type IV collagen alone formed gels was physiological in terms of ionic strength and pH, the aggregate structure and gel properties might reflect the in vivo type IV collagen supramolecular structure and the property.

Animals↗

PubMed1996

Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma.

To assess the characteristics of intrahepatic metastatic lesions (IML) in hepatocellular carcinoma (HCC), we analysed both the histological features and proliferative activities of 15 resected cases of HCC accompanied by IML. The histological features of the IML were essentially the same as those observed in the main nodules in 12 (80%) of 15 cases. In 13 (87%) of 15 cases, the labelling index of proliferating cell nuclear antigen (PCNA) in the IML was either higher than or the same as in the main nodules. In 10 (77%) of 13 cases, the MIB-1 labelling index in the IML was either higher than or the same as in the main nodules. The results indicate that the histological features of the IML are essentially the same as those of the main nodules, while the proliferative activities in the IML were generally higher than those in the main nodules. Such characteristics may thus provide a clue to help distinguish intrahepatic metastasis from the multicentric occurrence of HCC.

Aged↗

PubMed1996

[Clinical and electrophysiological studies on posterior retinitis pigmentosa].

On the basis of fundus appearance and angiographic fundus pictures, 48 cases of posterior retinitis pigmentosa were divided into pericentral type (20 cases), perimacular type (21 cases), and macular type (7 cases). We compared the 3 groups clinically and electrophysiologically. Visual acuity and visual field were progressively deteriorated in half of the cases of pericentral type two years after the initial visit. The waveform of flash electroretinogram (ERG) was negative in the pericentral type, subnormal in the perimacular type, and normal in the macular type. These ERG findings suggest that the rod function was more severely damaged in the pericentral type than in the other types. Contrary to the ERG findings, the pattern-evoked cortical potential was normal in the pericentral type, and we assumed there is less damage of the foveal function in the pericentral type.

Adolescent↗

PubMed1996

Localization of human placental glucose transporter 1 during pregnancy. An immunohistochemical study.

To elucidate the potential roles of glucose transporter 1 (GLUT1) in human placenta during pregnancy, we examined the localization of GLUT1 in human placenta at various stages by immunohistochemistry with an anti-GLUT1 antibody by use of both light and electron microscopy. Specific staining for GLUT1 was localized on the apical brush border and along the basal plasma membrane of the syncytiotrophoblasts. The staining at the apical side was more intense than that at the basal side during the early stages of gestation. In later gestational stages, however, the staining pattern at the apical side became blurred and the staining intensity at the basal side increased. The cytotrophoblasts, seen embedded in the basal part of the syncytiotrophoblasts, seemed to show immunoreactivity for GLUT1 along the plasma membranes at the light-microscopic level. However, immuno-electron microscopic analysis with either pre- or post-embedding methods revealed that specific staining for GLUT1 was hardly observed on the cytotrophoblasts, but the cytotrophoblasts were often surrounded by immunoreactive processes of syncytiotrophoblasts. The blood capillaries and erythrocytes in the stroma of placental villi were always immunoreactive for GLUT1 throughout pregnancy. These findings suggest that GLUT1 may play a vital role in human pregnancy.

Capillaries↗

PubMed1996

The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver.

We performed immunohistochemical studies on 90 surgically resected liver tumors, including 30 tumors each from hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and metastatic colorectal adenocarcinoma (MCA), using monoclonal antibodies against cytokeratin (CK) 7, CK 19, and CK 20 to examine the differences in the CK expressions in primary and metastatic carcinomas of the liver. We also investigated the usefulness of such expression in the differential diagnosis in addition to existing markers such as alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9. For CK 7, all except for one (97%) of the CCs were diffusely positive, whereas only two (7%) HCCs and one (3%) MCAs were diffusely positive. For CK 19, 23 (77%) CCs and 19 (64%) MCAs were diffusely positive, whereas no HCCs were positive. For CK 20, 22 (74%) MCAs were diffusely positive, whereas no HCC and three (10%) CCs were diffusely positive. The findings concerning the expression of immunohistochemical CK are therefore considered to be useful in addition to the diagnostic criteria when making a differential diagnosis of primary and metastatic carcinomas of the liver.

Adenocarcinoma↗

PubMed1995

Small hepatocellular carcinoma of single nodular type: a specific reference to its surrounding cancerous area undetected radiologically and macroscopically.

A total of 128 surgically resected small hepatocellular carcinomas, measuring less than or equal to 3 cm in diameter, were studied by both macroscopic and histologic examinations. In 95 single nodular-type tumors of the 128 lesions, eight tumors were associated with the cancerous areas of well differentiated hepatocellular carcinoma around the nodule. These surrounding cancerous areas went undetected by both the preoperative radiological examinations and the gross findings of resected specimens. Based on the immunohistochemical findings, the labeling index, both of the proliferating cell nuclear antigen (PCNA) and of the Ki-67 in the surrounding cancerous areas, were lower than that of the main nodules but higher than in the nontumorous liver parenchyma in seven of eight cases. These results suggest that the main nodule was generated from the surrounding cancerous area, supporting the hypothesis of a stepwise progression of HCC. Even if the tumor seems to be a small and single nodular type, it is recommended that its surrounding areas should be closely examined and the surgical cutting margin should be made more than 1.0 cm away from the main nodule at hepatic resection.

Carcinoma, Hepatocellular↗

PubMed1995

Changes of compound action potentials in retrograde axonal degeneration of rat optic nerve.

Electrophysiological recordings of compound action potentials (CAPs) were made from the optic nerve (ON) following unilateral optic tract (OT) transection in adult rats. In response to optic chiasm stimulation CAPs recorded from the ON ipsilateral to the transected OT, i.e., the ON of control side, revealed three positive waves, termed n1, n2, and n3 components, corresponding to fast-, intermediate-, and slow-conducting fibers. Two weeks after OT transection, CAPs recorded from the ON contralateral to the transected OT, i.e., the ON of cut side, were generally smaller in amplitude than those recorded from the ON of control side. The degree of amplitude reduction was different among three components; n3 component was severely reduced and n2 component was moderately reduced, whereas n1 component relatively persisted. These tendencies were more marked in CAPs recorded at 4 weeks after OT transection; n3 component disappeared, whereas n1 and n2 components decreased in amplitude with elongation of latency. Cross sections of the ON after unilateral OT transection were examined electron microscopically, in which significant decrease in fiber density, demyelination, and distorted fibers were verified in the cut side. The present study suggests that slower-conducting ON fibers, that is, smaller-diameter ON fibers are initially and remarkably thrown into retrograde degeneration, while larger-diameter ON fibers are relatively resistant to axotomy.

Action Potentials↗

PubMed1995

Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma.

BACKGROUND/AIMS: Postoperative intrahepatic recurrence of human hepatocellular carcinoma is high. Recently, the relationship between proliferating cell activity in the cirrhotic liver and occurrence or recurrence of hepatocellular carcinoma has been reported. METHODS: One hundred two resected cases of small hepatocellular carcinoma of < 3 cm in diameter without venous invasion or intrahepatic metastasis were examined to ascertain the factors affecting postoperative intrahepatic recurrence. RESULTS: Cumulative intrahepatic recurrence rates at 1, 3, and 5 years after surgery were 12.0%, 57.2%, and 67.6%, respectively. The log-rank test indicated that serum albumin levels of < 3.7 g/dL, alanine aminotransferase levels of more than 54 IU/L, active inflammation in the nontumorous portion, and high proliferating cell nuclear antigen labeling index in the nontumorous portion (> 23.2%) were significant risk factors for recurrence. Tumor factors, including tumor size, histological grade, or alpha-fetoprotein level, were not significant risk factors. Cox's proportional hazard model identified that serum albumin level and alanine aminotransferase level were independently associated with intrahepatic recurrence after hepatectomy. CONCLUSIONS: This study suggests that the principal cause linked to either a recurrence or a second new growth of hepatocellular carcinoma in the remnant liver after hepatectomy was the state of the underlying liver parenchyma as well as other tumor factors per se.

Adult↗

PubMed1995

Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features.

We herein evaluated 36 cases of combined hepatocellular and cholangiocarcinoma (cHCC-CC) (including 29 surgically resected and seven autopsy cases) by the immunohistochemical methods of anticytokeratin antibodies 7 and 19, and then analyzed the clinicopathologic features by comparing cHCC-CC with ordinary hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The results indicated that even if mucin production could not be confirmed, nine cases with HCC areas that showed a histological resemblance to CC also showed immunohistological biliary differentiation. Therefore, we advocate that these HCC with biliary differentiation based on an immunohistochemical analysis should thus be included in the criteria of cHCC-CC in broad terms. Regardless of the extent of mucin production, the cHCC-CCs as indicated by an immunohistochemical analysis are considered to have a similar background to that of ordinary HCCs regarding such factors as the average age, male:female ratio, hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) positivity, alpha-fetoprotein level, and the presence of cirrhosis. However, cHCC-CCs tend to metastasize to many organs and the lymph nodes, and, as a result, have a poor prognosis.

Bile Duct Neoplasms↗

PubMed1995

Condensation of collagen fibrils to the direct vicinity of fibroblasts as a cause of gel contraction.

Fibroblasts were cultured within FITC-prelabeled type I collagen. Cells initially round in shape protruded processes, and began to collect the fibrils into their vicinity. Repeated protrusion and withdrawal of cell processes was observed. Consequently, condensed fluorescence was observed on the elongated bipolar cells stained with rhodamine-phalloidin. Concomitantly with these events, the gel began to contract in overall size, with an increase of fluorescence intensity. Scanning electron micrographs of the contracted gel showed a disproportional distribution of collagen fibrils: a highly condensed region surrounding cell bodies and a moderately condensed region. A major portion of condensed fibrils may have been derived from reconstituted collagen fibrils, since fibroblasts within collagen gel synthesized little collagen. When the gel adhered to glass tightly, so that overall contraction was prevented, the fluorescence in a range of scores of micrometers from the cells disappeared owing to depletion of fibrils by the cells. The combined spaces with null fluorescence in total under repressed contraction corresponded well to the reduction in volume due to gel contraction. It seems likely that the fibril condensation onto the cells causes the overall gel contraction.

Actins↗

PubMed1995

[Intra-bile duct growth of hepatocellular carcinoma: value of biliary dilatation on CT].

In order to evaluate the usefulness of CT in demonstrating biliary invasion by hepatocellular carcinoma, 191 surgically proved cases were studied. Among 191 CT scans performed before surgery, six (3%) showed biliary dilatation. Pathological biliary invasion was found in eight cases (4%). Of these eight cases, four cases (50%) showed biliary dilatation on CT. In six cases with biliary dilatation on CT, pathological biliary invasion was revealed in four cases (67%). In two cases, the large (> or = 6cm) encapsulated tumors located in the hepatic hilum dilated the intrahepatic bile duct without intraductal tumor growth. We concluded that biliary dilatation on CT cannot be a sign of biliary invasion by hepatocellular carcinoma.

Adult↗

PubMed1995

The clinical significance of p53 gene mutation in hepatocellular carcinomas from Japan.

To clarify the clinical significance of the mutation of p53 gene in hepatocellular carcinoma (HCC), 90 resected specimens from Japanese patients were assayed using a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. p53 mutations were detected in 25 cases (27.8%) at exons 4, 5, 6, 7, and 8, and the most frequent region of the mutation was at exons 5 and 7. No statistically significant correlation was observed between the p53 mutations and the clinical features except for the preoperative alpha-fetoprotein (AFP) level (P < .05). According to the pathological features, prognostic factors, such as size of the tumor, vascular invasion, fibrous capsule infiltration, and intrahepatic metastasis, showed no relationship to the existence of the mutation. However, p53 mutations were significantly associated with the degree of differentiation of HCC; that is, the mutation was found in 19 cases of 53 poorly differentiated HCCs (35.9%) and 2 of 3 cases of anaplastic HCCs (66.7%). The presence of p53 mutations was associated with a shortened cancer-free survival (P < .001, by log rank test) and a shortened survival (P < .05). A multivariate analysis by the Cox regression analysis showed that the p53 mutations were an unfavorable prognostic factor related to recurrence (P < .005), which is especially significant within the first postoperative year. These results suggest that the mutations of p53 gene of HCC might be an independent prognostic predictor to help in the selection of candidates who should undergo more intensive postoperative treatment.

Adult↗

PubMed1995

[Chemoradiation therapy with low-dose carboplatin for squamous cell carcinoma of the esophagus].

Twenty-three patients with squamous cell carcinoma of the esophagus were treated with low-dose carboplatin and radiation therapy. Patients received 1.6 Gy-fractions daily; the total dose was 50-70 Gy for 14 unresectable cases, and 30-40 Gy for 8 resectable cases as preoperative irradiation. Carboplatin (30 mg/m2/day) was administered intravenously just before the irradiation; total dose was 1,100-2,000 mg for the unresectable cases, and 750-1,200 mg for the resectable cases. The response rate of the unresectable tumors was 86% (CR 5, PR 7, and NC 2). Three of the five CR patients were alive without recurrence for more than 2 years. The response rate of the resectable tumors was 75%. Although major toxicity was bone marrow suppression, there were no serious complications. These results suggest that this regimen is effective for patients with squamous cell carcinoma of the esophagus.

Aged↗