Biomedical subjects

Isao Narama

Publications and source records attributed to Isao Narama.

10 recordsLinked to original sources

PubMed2006

Induction of squamous cell carcinoma of forestomach in diabetic rats by single alloxan treatment.

Male rats of WBN/Kob strain are one of the diabetic model animals and develop long-lasting diabetic symptoms and some complications from about 40 weeks of age without any treatment. A single intravenous dose of alloxan, a non-genotoxic diabetogenic chemical, frequently induced proliferative lesions of squamous epithelium in tongue, esophagus and forestomach of male and female WBN/Kob rats, and hastened the onset and acceleration of diabetic conditions. Histopathologically, proliferative changes of squamous cell of forestomach varied with the severity of hyperplasia in alloxan-treated rats (100% of 31 males and 94.1% of 17 females) and progressed to SCC in approximately 20% of all rats. Metastasis to regional lymph nodes was also observed in two cases. Proliferative changes were most severe in the forestomach and were constantly accompanied with chronic suppurative inflammation of the mucosal epithelium with infection of filamentous fungi and/or bacterial colonies. In contrast, forestomach of the spontaneously diabetic male rats showed only slight hyperplasia of the mucosal epithelium confined to the limiting ridge in approximately 30% of the cases. All non-diabetic female rats showed neither proliferative changes nor the inflammatory process in the mucosa. Immunohistochemically, COX-2 and iNOS were positive in these chronic suppurative inflammatory lesions accompanied by proliferative squamous epithelium. From these results, it is suggested that chronic inflammatory processes play an important role in the pathogenesis of alloxan-induced SCC. An experimental system of alloxan-induced SCC might serve as a suitable model for the study of the inflammation-related promotion of carcinogenesis.

Alloxan↗

PubMed2006

Pigment epithelium-derived factor inhibits advanced glycation end product-induced retinal vascular hyperpermeability by blocking reactive oxygen species-mediated vascular endothelial growth factor expression.

Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis, suggesting that loss of PEDF contributes to proliferative diabetic retinopathy. However, the role of PEDF against retinal vascular hyperpermeability remains to be elucidated. We investigated here whether and how PEDF could inhibit the advanced glycation end product (AGE) signaling to vascular hyperpermeability. Intravenous administration of AGEs to normal rats not only increased retinal vascular permeability by stimulating vascular endothelial growth factor (VEGF) expression but also decreased retinal PEDF levels. Simultaneous treatments with PEDF inhibited the AGE-elicited VEGF-mediated permeability by down-regulating mRNA levels of p22(phox) and gp91(phox), membrane components of NADPH oxidase, and subsequently decreasing retinal levels of an oxidative stress marker, 8-hydroxydeoxyguanosine. PEDF also inhibited the AGE-induced vascular hyperpermeability evaluated by transendothelial electrical resistance by suppressing VEGF expression. Furthermore, PEDF decreased reactive oxygen species (ROS) generation in AGE-exposed endothelial cells by suppressing NADPH oxidase activity via down-regulation of mRNA levels of p22(PHOX) and gp91(PHOX). This led to blockade of the AGE-elicited Ras activation and NF-kappaB-dependent VEGF gene induction in endothelial cells. These results indicate that the central mechanism for PEDF inhibition of the AGE signaling to vascular permeability is by suppression of NADPH oxidase-mediated ROS generation and subsequent VEGF expression. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy.

Adult↗

PubMed2006

A newly established mutant strain with mild-type ocular coloboma (retinochoroidal coloboma without microphthalmia) in albino mice.

BACKGROUND: A complicated malformation of the fundus accompanied by typical ocular coloboma was detected in albino fatty liver Shionogi (FLS) mice. We elucidated a new type of 3-dimensional anomalous structure inside the eye in this mouse strain. METHODS: The fundi of FLS mice aged 1, 3, 5, and 20 weeks were observed intensively, both macroscopically and by light microscopy. For the prenatal study, coronal serial sections of eyes of FLS embryos were examined by light microscopy on gestation day (GD) 15.0. RESULTS: The frequency of ocular coloboma was almost 70% in FLS mice, and the inheritance mode of this anomaly is suggested to be autosomal recessive with incomplete penetrance. Stereoscopic observation and light microscopy revealed that the mice had characteristic fundus features at any age during the postnatal period. Following ectopic ciliary epithelia, the surface of the retina protruded like a roof, and on the opposite side of the "roof," a translucent membrane without retinal tissue and choroidal tissue was also consistently detected in the inferior part of the fundus. On GD 15.0, the inner layer and the outer layer were not normally fused at the optic fissure, where a part of the outer layer was absent and the irregular fold of the inner layer was conspicuous in the colobomatous eye of the FLS embryo. CONCLUSIONS: The characteristics of the ocular coloboma in FLS mice are thought to be similar to a mild-type malformation in humans. These ocular defects seem to be situated along the failed fetal optic fissure.

Albinism↗

PubMed2006

Pulmonary intravascular hemangiosarcoma in a cat.

A 9-year-old, castrated male Japanese domestic cat presented with a complaint of exertional dyspnea. Based on the radiographic findings, presumptive diagnosis of aspiration pneumonia or primary diffuse pulmonary neoplasia in the right middle lobe was made. Histologically, the pulmonary lesion was characterized by diffuse thickening of alveolar wall with the proliferation of apparently atypical irregular-shaped cells. Immunohistochemical staining using anti-human factor VIII-related antigen antiserum showed positive reaction in the cytoplasm of the atypical cells. According to the findings, the lesion was diagnosed as pulmonary intravascular hemangiosarcoma.

Animals↗

PubMed2005

Diffuse global granulomatous glomerulonephritis in a pig.

Diffuse global granulomatous glomerulonephritis with unique morphological characters was detected in a pig. The structure of the basement membrane of glomerular tufts was destroyed in almost all glomeruli. Various inflammatory cells consisted mainly of macrophages infiltrated severely into the glomerular tuft and the Bowman's space of and extended to the periglomerular interstitium. Periarteritis with fibrinoid necrosis was occasionally seen in the arterioles and small arteries running through the renal parenchyma and pelvis. In the present case, the results of either the immunohistochemical reactions to the antigens against PRRSV or PCV-2 or Ziel-Neelsen staining for acid-fast bacilli were negative and no pathogenic bacteria were cultured.

Animals↗

PubMed2004

Characterization of spontaneous dermatitis in beige rats with IgE hyperproduction.

BACKGROUND: Atopic dermatitis (AD) is a common skin disease characterized by chronic recurrent eczematous lesions, but its exact etiology and mechanism are unclear. We found that beige rats (DAbg/bg), a mutant model of Chediak-Higashi syndrome, develop skin lesions characterized by pruritus, excoriation, erosion and alopecia. We describe the beige rat and examine its possible usefulness as an AD model. METHODS: Beige rats of 4, 8, 13, 16, 26 and 52 weeks were used. Histological analysis of the skin was performed. Plasma IgE and cytokines were measured. Th1 and Th2 cytokines and RANTES mRNA expression of skin and lymph nodes were evaluated. Passive cutaneous anaphylaxis (PCA) reactions were examined, and maximization tests were conducted. RESULTS: Skin lesions begin to develop with increases in serum IgE levels and the expression of IL-4 mRNA in the lymph node and skin. Histologically, skin lesions are characterized by acanthosis, ulceration and inflammatory cell infiltration in the dermis. Inflammatory cells consist of CD3+, CD4+, ED1+, ED2+ and I-A+ mononuclear cells, eosinophils, degranulated mast cells and neutrophils accompanying interleukin (IL)-4, interferon (IFN)-gamma and RANTES mRNA expressions of the skin. Inflammatory cells are reduced during chronification with decreased expressions of IL-4, IFN-gamma and RANTES mRNA. In addition, the rats show a high sensitivity to PCA reactions and maximization tests. CONCLUSIONS: Our results show that some of the skin lesions of beige rats are morphologically similar to human AD, being characterized by inflammatory cell composition in the acute phase, and increased IgE and RANTES levels. However, the inflammatory process and cytokine expression pattern are different from those in human AD.

Animals↗

PubMed2004

Effect of iron lactate overloading on adenine nucleotide levels and adenosine 3'-monophosphate forming enzyme in rat liver and spleen.

To elucidate the pathophysiological significance of adenosine 3'-monophosphate (3'-AMP) forming enzyme in rats, the effect of iron lactate overloading on the enzyme activities and adenine nucleotide levels in the liver and spleen was examined. Sprague-Dawley rats were fed a diet supplemented with 0%, 0.625% or 5.0% of iron lactate for 4 weeks. Iron deposition was found in periportal hepatocytes, Kupffer cells and macrophages of red pulp of the spleen. No significant changes in hematological parameters were detected. Although serum alkaline phosphatase and inorganic phosphorus levels elevated slightly in the 5.0% group, activities of alanine aminotransferase and aspartate aminotransferase, and levels of serum urea nitrogen and creatinine were not changed significantly. The ATP levels in the liver and spleen of iron fed groups were significantly decreased, but adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP) levels were within control levels. On the other hand, the levels of ATP, ADP and AMP in the erythrocytes without mitochondria were not suppressed by the iron lactate overloading. Free activity of 3'-AMP forming enzyme, one of ribonucleases (RNase), was not changed in the liver of iron-overloaded rat, and total amount of 3'-AMP and adenosine formed after the treatment of the crude enzyme(s) with p-chloromercuribenzensulfonic acid, a SH blocker of RNase inhibitors, was decreased dose-dependently. On the contrary, free activity of 3'-AMP forming enzyme was enhanced dose-dependently in the spleen of iron-overloaded rat but the total activity was not changed. However, the free and total 3'-AMP forming enzyme activities in the liver and spleen of iron-overloaded rats became equal at the dosage of 5.0% of iron lactate. The results obtained suggested that iron loading might induce significant decrease in hepatic and splenic ATP levels via malfunction of their mitochondria and might lead dissociation of RNase-RNase inhibitor complex to activate 3'-AMP forming enzyme in both tissues.

Adenine Nucleotides↗

PubMed2003

Preparation of 9-hydroxy grayanotoxin derivatives and their acute toxicity in mice.

Novel 9alpha and 9beta-hydroxy grayanotoxin II derivatives were prepared by photo-sensitized oxygenation of iso-grayanotoxin II and oxidation of grayanotoxin II tetraacetate with selenium dioxide respectively. The lethal dosage of 9alpha and 9beta-hydroxy grayanotoxin II were lower than that of grayanotoxin II. In addition, the lethal dosage of 9beta-hydroxy-dihydro grayanotoxin II was higher than that of dihydro grayanotoxin II.

Animals↗

PubMed2003

Deformed liver with prominent proliferation of bile ducts in a pig.

A deformed liver characterized by remarkable ductular proliferation was encountered in a 6-month-old pig and examined histopathologically. The most conspicuous histopathologic change was a mild to severe ductular proliferation in the interlobular areas without any degenerative changes of cholangiolar epithelial cells or hepatocytes. Fibrotic changes and reconstruction of the lobule were not found. Morphological evidence of intrahepatic and extrahepatic cholestasis was lacking. Other characteristics were deformity with displacement of the gall bladder, irregular shape and size of lobules, and structural abnormality of large-sized vessels. The severe ductular proliferation was considered to be due to structural malformations of the excretion channel of bile.

Animals↗

PubMedDate not supplied

Iron lactate-induced osteomalacia in association with osteoblast dynamics.

Osteomalacia was induced in rats fed a diet containing 50,000 ppm (5%) iron lactate for 13 weeks. The histopathology and histomorphometrical dynamics of osteoblasts under this condition were examined. Bone histomorphometry of the proximal tibial metaphysis revealed that the osteoblast surface, osteoid volume, osteoid surface and labeled surface ratio, which are the parameters of bone formation had increased. The blood chemistry revealed the greatest elevation in the osteocalcin level; however, the parathyroid hormone (PTH) secretion and inorganic phosphorus level were very low. From the serum biochemical, histopathological and histomorphometrical findings, the bone lesion in iron lactate-overloaded rats was considered to be similar to low turnover osteomalacia showing decreased trabeculae in secondary spongiosa and increased lamellar osteoid. Furthermore, an iron-positive reaction was detected at the interface between osteoid and mineralized bone. In the bone lesions induced by chronic iron overload, osteoblast recruitment exceeded that of mineralization or, alternatively, the iron within osteoblasts along the trabecular bone suppressed the remodeling and led to an increase in osteoid thickness.

Administration, Oral↗