Biomedical subjects

Yuh Fukuda

Publications and source records attributed to Yuh Fukuda.

At least 19 recordsLinked to original sources

PubMed2006

Extracellular matrix metalloproteinase inducer in interstitial pneumonias.

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycosylated transmembrane protein that induces matrix metalloproteinases (MMPs), is minimally expressed in the normal adult lung. We previously reported that it is up-regulated in murine bleomycin-induced lung injury. In this study, we determined the expression of EMMPRIN and its association with MMP-2, MMP-7, and MMP-9 in interstitial pneumonias (IPs). We performed immunohistochemistry for EMMPRIN and MMPs on lung tissue from 22 subjects with various IPs. We did bronchoalveolar lavage (BAL) on 9 of these subjects and 13 others with IPs to measure the soluble EMMPRIN in BAL fluid. For comparison, immunohistochemistry or BAL was done on 14 subjects without IPs. The staining intensity for each protein was scored from 0 to 3 in various epithelial cell types. Soluble EMMPRIN in BAL fluid was measured by an enzyme-linked immunosorbent assay. Extracellular matrix metalloproteinase inducer was prominent in abnormal epithelial cells. It was more prominent in hyperplastic type II cells, compared with epithelium in alveolar bronchiolization. It was also elevated in BAL fluid from the subjects with IPs. Matrix metalloproteinases were expressed in cells expressing EMMPRIN, although the profile of MMPs varied among the different abnormal epithelial cell types with MMP-2 and MMP-7 in hyperplastic type II cells and MMP-7 and MMP-9 in cells showing squamous metaplasia and cells comprising bronchiolization. These results suggest a role of EMMPRIN in reepithelialization in IPs.

Basigin↗

PubMed2006

Cyclooxygenase-2 expression correlates with membrane-type-1 matrix metalloproteinase expression in colorectal cancer tissue.

PURPOSE: Elevated expression of cyclooxygenase-2 has been found in colorectal cancer. One of the mechanisms through which cyclooxygenase-2 affects tumorigenesis is through its overexpression, which leads to increased invasiveness of cancer cells. A crucial step in this pathway is thought to be the induction of membrane-type-1 matrix metalloproteinase, which activates matrix metalloproteinase-2. However, to date there have been few clinicopathologic studies concerning cyclooxygenase-2-mediated invasiveness in human colorectal cancer tissues. METHODS: We performed immunohistochemical analysis of the respective antigens on colorectal cancer specimens obtained by surgical resections from 96 patients with colorectal cancer. RESULTS: Cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression was positive exclusively in cancer cells in 88 cases (92 percent) and 23 cases (24 percent), respectively. All 23 cases expressing membrane-type-1 matrix metalloproteinase also expressed cyclooxygenase-2. Matrix metalloproteinase-2 expression was positive in cancer cells in 20 cases (21 percent) and stromal cells in 52 cases (54 percent). Expression of matrix metalloproteinase-2 in cancer cells correlated with lymphatic invasion and local recurrence. Statistically, a significant correlation was found between cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression, and membrane-type-1 matrix metalloproteinase and matrix metalloproteinase-2 expression in cancer cells. There was no association between cyclooxygenase-2 expression and matrix metalloproteinase-2 expression. However, immunostaining of serial sections revealed that in the majority of cases examined, nearly 100 percent of cancer cells expressing matrix metalloproteinase-2 also coexpressed cyclooxygenase-2. CONCLUSIONS: This study indicates strong association between both cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression, and membrane-type-1 matrix metalloproteinase and matrix metalloproteinase-2 in colorectal cancer. These results support our thesis of a direct correlation between cyclooxygenase-2 and membrane-type-1 matrix metalloproteinase expression--with consequent association between cyclooxygenase-2 and matrix metalloproteinase-2 activation, and tumor invasiveness andrecurrence in certain cases of colorectal cancer.

Adult↗

PubMed2006

[A case of multicentric Castleman disease showing diffuse cystic change in the lung].

A 31-year-old woman was admitted to our hospital because of progressive dyspnea and chest X-ray abnormality. She was given a diagnosis of bronchial asthma 3 years previously. She had received medical treatment, but her dyspnea did not improve. Chest CT showed multiple thin-walled cysts and centrilobular nodules throughout both lungs. Video-assisted thoracoscopic lung biopsy revealed remarkable plasmacytic infiltration in the bronchioles and its surrounding interstitium. Small cystic lesions were detected and with remarkable mural plasmacytic infiltration. The immunohistochemistry showed infiltrated plasmacytes with polyconal characteristics. Her biochemical examinations showed polyclonal hyperimmunoglobulinemia and a high range of serum IL-6. In addition, CT scans showed multiple mediastinal and intraperitoneal lymphadenopathy. From these examinations, she was given a diagnosis of multicentric Castleman disease (MCD) with pulmonary involvement showing diffuse cystic change. This case showed an unusual pattern of MCD with pulmonary involvement. However, we suggest that MCD also should be considered as a differential diagnosis in cases with diffuse lung cystic changes.

Adult↗

PubMed2005

Epimorphin expression in interstitial pneumonia.

Epimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP), and lungs with usual interstitial pneumonia (UIP); we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling.

Cells, Cultured↗

PubMed2005

Primitive neuroectodermal tumor/Ewing's sarcoma with long-term follow-up.

We have reported a case of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/EWS) in a 32-year-old female who had had no symptoms until the tumor was detected in a general examination after she gave birth. Chest X-ray showed a well-defined, rounded mass in the left lower lung field. Computed tomographic scan of the chest revealed a distinct mass adjacent to the anterolateral thoracic wall. The macroscopic findings had shown a well-capsulated tumor with a stalk emanating from the thoracic wall. PNET/EWS was histologically diagnosed. The tumor was composed of atypical, small round cells. It stained positively with antibodies to the MIC2 gene product. Postoperative adjuvant radiotherapy of 50 Gy was performed. Adjuvant chemotherapies were not performed. Four years later, a small recurrent nodule in the left lung was surgically resected. Since her initial diagnosis, the patient has survived for seven years; in the three years since her second surgery, she has had no other recurrence or metastasis.

Adult↗

PubMed2005

Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue.

Recently, three different prostaglandin E2 synthases have been identified: microsomal prostaglandin E synthase (mPGES)-1, cytosolic PGES (cPGES), and mPGES-2; however, their role and connection to cyclooxygenase (COX)-2 in the gastric ulcer repair process remain unknown. Therefore, we examined mPGES-1, cPGES, and mPGES-2 expression and localization in the stomach in vitro and in vivo. Tissues were obtained from Helicobacter pylori (H. pylori)-infected patients and consisted of surgical resections of gastric ulcers, or biopsies of gastric ulcers or gastritis. mPGES-1 mRNA and protein expression levels were examined by real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. mPGES-1, cPGES, and mPGES-2 localization were analyzed immunohistochemically. Induction of PGES expression in response to interleukin (IL)-1beta was examined in vitro in the cultured human gastric fibroblast line Hs262.St. Real-time PCR analysis of mPGES-1 mRNA expression in biopsy samples showed significantly higher expression levels in open than in closed gastric ulcer tissue. Western blot analysis showed mPGES-1 protein expression limited to open ulcer tissue, while mPGES-2 and cPGES immunoreactivities were seen in both open and closed ulcer tissue. Immunohistochemical analysis showed strong mPGES-1 expression in fibroblasts and macrophages of the ulcer bed, paralleling COX-2 expression. cPGES and mPGES-2 expression levels were seen in both fibroblasts of the ulcer bed and in epithelial cells. Furthermore, stronger cPGES and mPGES-2 immunoreactivities were seen in scattered mast cell-like cells and neuroendocrine-like cells, respectively. Induction of mPGES-1 expression in response to IL-1beta was seen in cultured gastric fibroblasts in vitro, and double immunostaining showed mPGES-1 coexpression with COX-2 in fibroblasts of the ulcer bed in vivo. In conclusion, mPGES-1, cPGES, and mPGES-2 are all expressed in gastric ulcer tissue, but only mPGES-1 parallels COX-2 expression in mesenchymal and inflammatory cells of the ulcer bed, suggesting a key role for this enzyme in the ulcer repair process.

Adult↗

PubMed2005

Clinicopathological differences between acute and chronic eosinophilic pneumonia.

OBJECTIVE: Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). Furthermore, there are no reports describing the clinicopathological differences between the various forms of eosinophilic pneumonias. METHODOLOGY: The histological findings in acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) were examined and the clinical and radiological features were contrasted with them. RESULTS: Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases, while air space consolidation was seen in all CEP cases. Histologically, interstitial oedema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, although the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls. CONCLUSIONS: An essential histological difference between AEP and CEP is the severity of basal lamina damage and the amount of subsequent intraluminal fibrosis. In AEP particularly, these findings explain the radiographical findings, as well as the rapid and complete improvement noted in such cases.

Acute Disease↗

PubMed2005

Spurt bleeding from a calcificated gastrointestinal stromal tumor in the stomach.

Calcifications within primary gastrointestinal tumors are rare. Gastrointestinal stromal tumor (GIST) is an unusual nonepithelial tumor that develops in the gastrointestinal tract. In this paper we describe a case of spurt bleeding from a calcificated GIST in the stomach successfully treated by partial gastric resection. A 77-year-old man was admitted for chest discomfort and loss of consciousness. Endoscopic examination revealed spurt bleeding from the top of the submucosal tumor. No other lesions or points of bleeding were found in the stomach. Emergency partial gastrectomy was performed, and the stomach was closed. The cut surface of the tumor had a firm, solid, whitish-gray parenchyma with patchy calcification. Microscopic observation revealed a profusion of spindle-shaped tumor cells with calcification growing from the gastric muscular propria to the submucosa. The cells exhibited low mitotic activity and no prominent signs of nuclear atypia. Immunohistochemical staining of the tumor demonstrated positive reactivity for CD34, KIT, and vimentin, but negative reactivity for alpha-smooth muscle actin, desmin, and S-100 protein. Tumor cells positive for Mib-1 were rare. The diagnosis of the tumor was established as GIST.

Aged↗

PubMed2005

Histopathological study of tissue reaction to pacemaker electrodes implanted in the endocardium.

Limited information is available about histopathological reactions to the implanted endocardial electrodes of pacemakers (PM). Gross anatomic and histologic studies of tissue reactions to PM electrodes were made in thirteen autopsy cases (nine men and four women, ages 25 approximately 89 years, mean age 71.8) who died two months to twenty-one years after PM implantation. Nine of them had complete atrioventricular (AV) block, three had sick sinus syndrome, and one had bradycardia-tachycardia syndrome. The direct causes of death were not related to their PM. The tip with projecting tines was implanted in the right ventricle in all patients. At the contact area between the electrode and the endocardium, no tissue reaction was observed in one patient with a history of over sixteen years of PM implantation. However, cardiomyocytes under the tip had been replaced by fibrotic tissue in many other patients. In two patients in particular where the electrode had been implanted at the apex of each right ventricle, all cardiomyocytes had disappeared and only fibrotic tissue and adipose tissue were observed under the tip. These findings suggest that mechanical stress caused by attaching the tip tightly damages cardiomyocytes and brings about changes in the pacing thresholds. In three patients, a space was seen between the tip and the endocardium. A fibrous sheath covering the electrode extended to the tip and formed a thick fibrous cap. This non-excitable fibrous cap acted as a virtual electrode and possibly affected the elevation of the threshold in these patients. In four patients, extensive myocardial fibrosis due to disease, e. g. previous myocardial infarction, dilated cardiomyopathy, amyloidosis, or sarcoidosis, was found in the area surrounding the tip and also might affect the elevation of the threshold. We concluded that elevation of pacing thresholds after PM implantation is not due to reactive endocardial thickening. The space between the tip and the endocardium is occupied by a fibrous sheath, and an overly tight attachment damages cardiomyocytes causing replacement fibrosis. Thus, it is not desirable in some patients to insert the electrodes into the apex, where the myocardium is thin. To avoid the elevation of thresholds, development of further devices is necessary to allow electrode fixation to the endocardium with a more suitable pressure level.

Adult↗

PubMed2005

Resection of liver metastases from an alpha-fetoprotein-producing gastric cancer.

We describe successful resection of rapidly enlarging liver metastases from an alpha-fetoprotein-producing gastric cancer, as these usually carry a dismal prognosis. A 68-year-old woman underwent distal gastrectomy for an alpha-fetoprotein-producing gastric cancer without liver metastasis. The tumor was a moderately differentiated tubular adenocarcinoma with invasion of the muscularis propria. Venous and lymphatic invasion were noted, as was metastasis to lymph nodes along the greater curvature. Serum alpha-fetoprotein was 331 ng/mL before gastrectomy, decreasing to 18.6 ng/mL by postoperative day 28. At 2 months after operation, computed tomography detected no metastasis, but at 4 months alpha-fetoprotein increased to 2,190 ng/mL, and at 5 months liver tumors were detected by ultrasonography and computed tomography. Serum alpha-fetoprotein increased to 5,673 ng/mL, and serum PIVKA2 concentration was 18 mAU/ml just before operation. Extended left hepatectomy was performed. The resected specimen of segment 4 contained two well-defined tumors, measuring 5 x 4 cm and 2 x 2 cm, while that of segment 5 contained a similar-appearing tumor measuring 2 x 2 cm. The resected tumors had the same histologic appearance as the previously removed gastric cancer. The tumor cells were immunohistochemically reactive for alpha-fetoprotein. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. Serum alpha-fetoprotein decreased to 20 ng/mL by postoperative day 15, and to 5 ng/mL by 2 months after operation. For 5 months since operation, no recurrence has become evident, and serum alpha-fetoprotein has remained within the normal range.

Adenocarcinoma↗

PubMed2004

Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue.

In vitro studies suggest that cyclooxygenase-2 (COX-2) induces angiogenesis by stimulating angiogenic growth factors while inhibiting apoptosis in cancer cell lines. A series of 107 gastric adenocarcinoma cases that had undergone gastrectomy was studied to determine the correlation between COX-2 expression, angiogenesis, and apoptosis in human gastric cancer tissue. COX-2, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and Bcl-2 were stained by single and dual immunoassaying methods. Microvessel density was determined by immunostaining for CD34. Apoptosis was evaluated with the TUNEL assay. COX-2 expression was positive exclusively in cancer cells in 46 cases (43%). COX-2 expression significantly correlated with VEGF and PDGF expression. Dual staining for COX-2 and VEGF showed that colocalization of these proteins was most frequent at the advancing edge of cancer cells. Microvessel density was higher in COX-2-and VEGF-positive cases than in COX-2- and VEGF-negative cases. In addition, COX-2 expression correlated with Bcl-2 expression. The apoptotic index was lower in COX-2-positive cancer cells than in COX-2-negative cases. Multivariate analysis revealed that coexpression of COX-2 and VEGF, age, lymph node status, and serosal invasion were independent prognostic factors for overall survival in gastric cancer patients. Therefore, these data suggest that COX-2 contributes to gastric cancer development by promoting angiogenesis and inhibiting apoptosis.

Adenocarcinoma↗

PubMed2004

Vascular endothelial growth factor165 resolves glomerular inflammation and accelerates glomerular capillary repair in rat anti-glomerular basement membrane glomerulonephritis.

Vascular endothelial growth factor (VEGF) is essential for maintenance of the glomerular capillary network. The present study investigated the effects of VEGF in rats with progressive crescentic glomerulonephritis (GN). Necrotizing and crescentic GN was induced in rats by injection of anti-rat glomerular basement membrane (GBM) antibody. The alterations of glomerular capillaries and glomerular VEGF expression were assessed. In addition, the effects of continuous VEGF165 administration (10 microg/100 g per d) on glomerular capillaries, glomerular inflammation, and the course of crescentic GN were examined. The appropriate timing of VEGF administration in progressive GN also was evaluated. In anti-GBM GN, necrotizing and crescentic glomerular lesions occurred by day 7, and newly formed necrotizing lesions reoccurred by week 3. Expression of VEGF was markedly reduced in necrotizing and crescentic lesions. Capillary repair was impaired after capillary destruction in necrotizing and crescentic glomeruli, which rapidly progressed to sclerotic glomeruli with chronic renal failure. In contrast, in the rats that received VEGF165 administration from day 7, the necrotizing and crescentic lesions recovered and renal function significantly improved in week 4. This was evident by proliferating endothelial cells and glomerular capillary repair. In addition, VEGF administration decreased intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 expression in glomeruli (particularly on endothelial cells), reduced glomerular infiltrating CD8-postive and ED-1-positive cells, and inhibited the newly formed necrotizing lesions. VEGF administration was apparently effective against both the inflammatory and necrotizing glomerular lesions. These results suggest that VEGF administration resolves glomerular inflammation and accelerates glomerular recovery in the progressive necrotizing and crescentic GN. The therapeutic application of VEGF may be clinically useful for severe GN accompanied by extensive glomerular inflammation and endothelial injury.

Animals↗

PubMed2004

Mechanism of transepithelial elimination of elastic fibers in keratoacanthoma.

Transepithelial elimination of elastic fibers is frequently seen in keratoacanthoma. However, the mechanism underlying this elastic fiber transport is not yet fully understood. We investigated the process by comparing the related features of 27 cases of keratoacanthoma, eight cases of squamous cell carcinoma and 11 cases of seborrheic keratosis (control). Microscopically, transepithelial elimination of elastic fibers was specifically observed in keratoacanthomas. Elastic fibers were surrounded by keratoacanthoma cell membrane and were ultrastructurally associated with hemidesmosomes and the basement membrane. Collagen fibrils were also observed within small, membrane-delineated vesicles within cells in the lower layers of the tumor. Also noted was strong expression of matrix metalloproteinase-1, which was detected by immunohistochemical analysis and in situ hybridization. Western blotting showed significantly stronger labeling of matrix metalloproteinase-1 in samples of keratoacanthoma than in normal epidermis. In contrast, squamous cell carcinomas and seborrheic keratosis exhibited none of the aforementioned characteristics. We propose that keratoacanthoma cells entrap, lift and eliminate elastic fibers as they proliferate and keratinize toward the epidermal surface, while simultaneously phagocytosing collagen fibrils. In that regard, matrix metalloproteinase-1 appears to play a key role in the degradation of collagen fibrils.

Adult↗

PubMed2004

Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa.

OBJECTIVES: One of the counter-effects of Helicobacter pylori eradication therapy is subsequent obesity. Ghrelin is a recently discovered growth hormone releasing peptide. This endogenous secretagogue increases appetite and facilitates fat storage. The majority of circulating ghrelin is produced in the gastric mucosa. Therefore, we aimed at investigating changes in ghrelin immunoreactivity in gastric mucosa tissues of patients infected with H. pylori. METHODS: Sixty-one patients with H. pylori infection (25 cases each of duodenal and gastric ulcer, and 11 cases of gastritis) and 22 healthy controls without H. pylori infection were included in the study. H. pylori-infected patients received standard proton pump-based triple therapy followed by histological examination and (13)C-urea breath test to confirm H. pylori eradication. H. pylori was eradicated in 50 out of 61 patients. Biopsy specimens were obtained from antrum and corpus before and 3 months following eradication. Ghrelin expression was evaluated immunohistochemically with an anti-ghrelin antibody, and the number of ghrelin-positive cells determined per 1 mm(2) of the lamina propria mucosa. RESULTS: There was no relationship between ghrelin immunoreactivity and body weight or body mass index for healthy controls. The number of ghrelin-positive cells was significantly lower for H. pylori-infected patients than for healthy controls. However, the ghrelin-positive cell number increased significantly following H. pylori eradication without significant change in severity of atrophy. CONCLUSIONS: These data indicated that H. pylori infection affected ghrelin expression. After H. pylori eradication, gastric tissue ghrelin concentration increased significantly. This could lead to the increased appetite and weight gain seen following H. pylori eradication.

Adult↗

PubMed2003

Immunohistochemical study of the expression of drug-resistant proteins in large cell neuroendocrine carcinoma of the lung.

OBJECTIVES: In 1999, the World Health Organization categorized pulmonary large cell neuroendocrine carcinoma as a variant of large cell carcinoma. However, an optimal treatment for large cell neuroendocrine carcinoma has not been established yet. Recently, multimodality therapy combining both surgery and adjuvant chemotherapy has been reported as a useful treatment for large cell neuroendocrine carcinoma, but the effect of chemotherapy on it has not yet been fully investigated. Thus, we evaluated immunohistochemical data of the expression of drug-resistant proteins in large cell neuroendocrine carcinoma. METHODS: We identified 10 large cell neuroendocrine carcinomas (1.2%) out of 850 primary lung cancers that had been surgically resected. We examined the immunohistochemical staining of three drug-resistant proteins, namely, P-glycoprotein, metallothionein and glutathione S-transferase-pi to compare large cell neuroendocrine carcinoma with other histological types of lung cancer. RESULTS: The mean tumor cell positivity rates for P-glycoprotein, metallothionein and glutathione S-transferase-pi in large cell neuroendocrine carcinoma were 0%, 2.4 +/- 3.6% and 35.0 +/- 37.5%, respectively. The positivity rates for P-glycoprotein and glutathione S-transferase-pi were significantly lower than those in adenocarcinoma (P = 0.0003, P = 0.0009). The positivity rate for glutathione S-transferase-pi was also lower than that in squamous cell carcinoma (P = 0.0387). These drug-resistant proteins showed similar expression pattern in both large cell neuroendocrine carcinoma and small cell carcinoma except glutathione S-transferase-pi. CONCLUSION: Immunohistochemical expression of drug-resistant proteins in large cell neuroendocrine carcinoma was lower than that in adenocarcinoma and squamous cell carcinoma, and differences exist in drug-resistance between large cell neuroendocrine carcinoma and small cell carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Hepatocyte growth factor-stimulating endothelial cell growth and accelerating glomerular capillary repair in experimental progressive glomerulonephritis.

Hepatocyte growth factor (HGF) is one of the major growth factors that stimulate the growth and the migration of vascular endothelial cells. In this study, we examined the beneficial effects of HGF for glomerular repair in an experimental progressive glomerulonephritis (GN) model prepared by injecting both anti-Thy-1.1 antibody (day 0) and habu-snake venom (day 1) in rats. The rats received continuous intraperitoneal administration of recombinant human HGF (80 microg/100 g/day) or vehicle control at an early stage (day 2 to day 9), after severe glomerular injury. The vehicle-infused control rats initially showed severe mesangiolysis with large ballooning (day 2), followed by the prominent proliferation of mesangial cells with minimal capillary regeneration (day 5 to week 2), and global sclerosis with chronic renal failure (week 4 to week 8). Although mesangiolysis with large ballooning and mesangial cell proliferation were also observed in the HGF-infused rats, glomerular capillary regeneration with marked endothelial cell proliferation occurred during HGF administration from day 2 to day 9. Subsequently, the glomerulus was repaired with the development of the capillary network and the reduction of mesangial hypercellularity from week 2 to week 4, and almost all of the glomeruli showed a normal structure by week 8. The HGF-treated rats showed significantly better renal functions (Cr: 0.3 +/- 0.1 vs. 3.5 +/- 1.1 mg/dl in control, p < 0.001), less proteinuria (21.2 +/- 8.0 mg/day vs. 421.4 +/- 45.1 mg/day in control, p < 0.001) and less glomerular sclerosis at week 8 than the vehicle-infused rats. We conclude that HGF accelerated glomerular repair through the growth of capillary endothelial cells and capillary regeneration in experimental progressive GN. Administering HGF is a logical and efficient strategy for treating progressive GN with severe capillary destruction.

Animals↗

PubMed2003

Prognostic suggestion in the evaluation of solid component in poorly differentiated adenocarcinoma of the lung.

UNLABELLED: Pulmonary adenocarcinoma composed of pure or predominant solid components is reported to be a highly malignant tumor. However, the existence of solid components and its connection with biological behavior have not been well documented. To answer this question, we histologically subclassified poorly differentiated adenocarcinoma (P/D Ad Ca) into solid type and non-solid type, and compared the biological behavioral characteristics. MATERIAL AND METHODS: All histological specimens of surgically resected primary lung carcinoma diagnosed as P/D Ca or large cell carcinoma in Nippon Medical School Hospital were re-evaluated according to the 1999 WHO manual. The cases re-evaluated as P/D Ad Ca were further divided into solid type and non-solid type according to our original definition: the solid type contains solid components where a glandular structure is not recognized in more than one high-power field, while in the non-solid type, a small glandular structure is observed in every high-power field. The differences in the occurrence of lymph node metastasis were assessed by Fisher's exact test. RESULTS: Among 109 cases satisfying both histological and clinical investigation, 45 cases were re-evaluated as P/D Ad Ca; solid type (n=22), and non-solid type (n=23). Lymph node metastases occurred at a higher rate in the solid type than in the non-solid type (p<0.01). CONCLUSION: Patients with solid type Ad Ca have reached a more advanced stage than patients having non-solid type due to high metastatic rate to lymph nodes. These results suggest that we should not overlook solid components even if the solid components are the focal lesion. This sub-typing alerts clinicians to survey metastases, and may contribute to therapeutic strategies in the future.

Adenocarcinoma↗

PubMed2003

[Comparative study on the sclerotic changes of cardiac valve and blood vessel].

BACKGROUND: Recently, there is an increase in number of surgical treatments for the aortic stenosis caused by valvular sclerosis with aging. Whether valvular sclerosis are related to aortic atherosclerosis, the prevention therapy of arteriosclerosis may benefit the clinical treatment of the valvular dysfunction due to aging. MATERIALS AND METHODS: Gross, histological and immunohistochemical studies were made on 159 autopsy cases (97 men, 62 women, mean age 65.1 years old). The degree of sclerotic change in aortic valve (AV), mitral valve (MV), aorta (Ao) and coronary artery (CA) was classified by gross examination to none, mild, moderate, and severe, scored as 0 to 3, respectively. The data were statistically analyzed by the correlation test. To observe the expression of bone related proteins in valve calcification, indirect immunostaining procedures were applied with antibodies to osteocalcin, osteopontin and osteonectin. RESULTS: Grossly, there was a significant correlation in sclerotic change between Ao and AV, Ao and MV, AV and MV, CA and AV, and CA and MV, respectively (p<0.01). Also, the degree of sclerotic change in each tissue was correlated with patients'age. However, the grade of sclerotic change of each tissue was variant in each case. On gross observation, all valvular sclerosis showed yellowish thickening and/or calcification. Microscopically, hyalinous change of the fibrosa was observed in the yellowish lesion of the valves. Accumulations of foamy macrophages were found focally at the surface area of the fibrosa, but no atheromatous change was observed in the valves. Calcified deposits, if present, were found in the fibrous valvular ring or fibrosa with hyalinous degeneration. In MV, calcification was usually localized in the fibrous ring. However, in AV, valvular calcification extended diffusely in the fibrosa and caused stenosis in some cases. These lesions were similar to calcified area in the intima with fibrous thickening of Ao and/or CA, but were different from atheromatous lesion of these tissues. Immunohistochemically, calcified areas of valves showed stronger reaction for osteocalcin than that of vessels. CONCLUSION: Among sclerotic change of cardiac valves and arteriosclerosis, statistical correlations were found, but pathological features were different. Main causes of these differences are thought to be 1) not only the shear stress, but also intramural pressure and mechanical stress with opening and closing may interfere the sclerotic change of cardiac valves, and 2) mechanism of valvular sclerosis may be different from arteriosclerosis because medial smooth muscle cells are absent in the valves.

Adolescent↗