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Biomedical subjects

G Asano

Publications and source records attributed to G Asano.

At least 73 records · Page 4Linked to original sources

Immunohistochemical and ultrastructural studies of basal cells, Clara cells and bronchiolar cuboidal cells in normal human airways.

Immunohistochemical studies were made of the distribution of various cytokeratins (CK), Clara cell secretory protein (CC10), surfactant protein A (SP-A) and type VII collagen in normal human airways. Electron microscopic studies were made to identify hemidesmosomes and anchoring fibrils on the basal surfaces of the epithelial cells. CK19 was detected in all epithelial cells, and CK17 in all basal cells. CK14 was coexpressed in a few basal cells, and this coexpression was decreased in the distal airways. Two types of basal cells were recognized. One type, found mainly in large airways, was characterized by abundant intermediate filaments and well-developed hemidesmosomes and anchoring fibrils. The second type contained few intermediate filaments and poorly developed hemidesmosomes and anchoring fibrils. Reactivity for type VII collagen was found along the basement membrane throughout the airways, but not in the alveoli. Clara cells were reactive for CC10 and CK17, but not for CK14 and SP-A. The bronchiolar cuboidal cells in the respiratory bronchioles were positive only for CK19. Surfactant protein A was present only in type II alveolar epithelial cells. Thus, two types of basal cells are present in airways, and the bronchiolar cuboidal cells appear distinct from these basal cells, Clara cells and type II alveolar epithelial cells.

Adult↗

A case report of renal cell tumor in a 45-year-old female mimicking lower portion nephrogenesis.

This report describes a renal tumor with an unusual histology in a 45-year-old woman. The tumor was white in color, different from usual renal cell carcinoma, and mainly consisted of variously shaped tubules formed by flat or cuboid cells within marked edematous stroma. Elaborated branching or tubules arranged in a papillary pattern with focal spindle-shaped cell proliferation were characteristic features. Immunohistochemical staining expressed diffusely positive for vimentin and S-100 protein, partially positive for cytokeratin and epithelial membrane antigen and negative for Leu-M1, Leu-7, CD34 and markers for muscle cells. Ultrastructural studies of the tumor cells showed adenocarcinoma-like characteristics. According to these histological, immunohistochemical and electron microscopy findings, it is suggested that this tumor be designated as unclassified renal cell carcinoma with histology mimicking lower-nephron nephrogenesis.

Biomarkers, Tumor↗

Nitric oxide production and energy state in the heart after endotoxin administration.

To evaluate nitric oxide (NO) production and the energy state of the heart after endotoxin administration, Wistar rats were injected i.p. with 10 mg/kg Escherichia coli lipopolysaccharide (endotoxin). Morphologic changes, plasma nitrite concentration, expression of inducible NO synthase (iNOS), and cardiac energy state, as reflected by several metabolites, were observed chronologically 0 (control), 4, 6 and 8 h after endotoxin administration. Electrocardiography (ECG) demonstrated arrhythmia after endotoxin administration. Biochemically, NO production increased in blood and iNOS increased in the heart. The amount of myocardial beta-ATP measured by 31P magnetic resonance spectroscopy (31P-MRS) increased transiently and then decreased. This transient increase might be a hyperdynamic response to endotoxin administration. At 4 and 6 h after endotoxin administration, pH measured by 31P-MRS was slightly decreased, but this decline was not statistically significant. On the other hand, the amount of lactate in heart samples increased in the 1H magnetic resonance spectra (1H-MRS). Ultrastructurally, in cardiovascular tissue, intracytoplasmic organelles were observed to be injured in blood vessels and cardiomyocytes associated with mast cell infiltration. These results suggest significant metabolic and morphologic abnormalities in the heart after endotoxin administration.

Animals↗

[The change of localization on cytokeratin of uterine cervix and the relationship to the pattern of invasion in cervical cancer].

An immunohistochemical study of 63 cases of uterine cervical cancer was undertaken. It was confirmed that the biological character of the cancer cells derived from the reserve cells changed over the course of invasion. Squamous cell carcinoma had positive keratin antibodies such as CK 10/13 (DE-K 13), CK 14 (NCL-LL 002) and CK 7 (OV-TL 12/30). In invasive squamous cell carcinoma, CK 14 positive cells were piled up and tended to be stained positive by PCNA and laminin. There were two types of staining, one of which revealed CK 14 strongly positive, and the other weakly positive. The first type differed from the second in depth and localization. The cells on the margin of a cluster of cancer cells were stained positive with CK 14 as in normal basal cells. The results obtained suggested: 1) squamous cell carcinoma has not only the character of normal squamous cells, but also that of the cells derived from the cervical glands. 2) cancer cells may develop in accordance with the character of basal cells, and the patterns of invasion change according to the character of basal cells in cancer tissue.

Biomarkers, Tumor↗

Effects of serum of streptozotocin-induced diabetic rats on vascular smooth muscle cell growth in vitro.

This study was undertaken to biochemically and immunohistochemically clarify the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), fibroblast growth factor receptor (bFGFR), insulin-like growth factor-I receptor (IGF-IR) and vascular smooth muscle cell (VSMC) growth by using Streptozotocin (STZ) treated rat serum. At 12, 16, 24 weeks after STZ administration, blood sera were collected from STZ treated rats. STZ treated rat sera promoted much more vascular smooth muscle cel proliferation than control sera. IGF-I was increased in the sera of STZ treated rats. Also according to western blot analysis, the protein synthesis of bFGFR and IGF-IR in the VSMCs was increased in STZ treated rat sera. Immunohistochemically, bFGF, IGF-I and their receptors were much more localized in VSMCs in STZ treated rat sera than in control sera. These results suggest that the growth factors and their receptors produced in VSMCs in STZ treated rat serum may contribute to the proliferation of VSMCs in autocrine and paracrine patterns.

Animals↗

Rapid diagnosis at the outpatient clinic for breast tumors by fine needle aspiration cytology. The utility.

The aim of this study was to emphasize the utility and prove the accuracy of rapid diagnosis at the outpatient clinic for breast tumors by fine needle aspiration cytology [FNAC]. Rapid diagnosis for breast tumors by FNAC is performed on the same day just after mammography and echonography are carried out at our hospital and the result reported to the patients while they are waiting at the outpatient clinic. We evaluated FNAC by rapid diagnosis at the outpatient clinic for 1,786 breast tumors during the last ten years. The cases of no judgement (Class 0) were 11%, negative cases (Class I & II) 72%, suspicious cases (Class III) 7%, and positive cases (Class IV & V) 10%. We experienced only 4 false negative cases and 0 false positive cases among 1,198 cases during the last 5 years, whereas there were 8 false negative cases and 2 false positive cases among 588 cases during the first 5 years. Two false positive cases in the the first 5 years were judged as Class IV, but definitive surgery [mastectomy] was not performed because rapid diagnosis during the operation by frozen section confirmed no malignancy. As a result, all the cases in which mastectomies were performed up to now were confirmed malignant. We emphasize that rapid diagnosis at the outpatient clinic for breast tumors by FNAC is very useful for early detection and treatment and it is very important to consider the histological type of breast tumors by FNAC to prevent misjudgement.

Adult↗

Immunohistochemical and morphometric evaluations of coronary atherosclerotic plaques associated with myocardial infarction and diabetes mellitus.

Immunohistochemical and morphometrical studies were performed to elucidate the specificity of atherosclerosis in the descending branch (the segments 5 and 6) of the left coronary artery associated with acute myocardial infarction (AMI) in the anterior wall of the heart and non-insulin-dependent diabetes mellitus (NIDDM). The NIDDM without AMI group showed diffuse intimal thickening with smooth muscle cells, combined with much more intense immunostaining of tenascin than the non diabetic groups. The AMI without NIDDM group showed atheromatous thickening with decreased smooth muscle cells, a large number of macrophage and TUNEL-positive cells compared with the groups without AMI. However, the AMI with NIDDM group revealed atherosclerotic lesion with decreased smooth muscle cells, increased macrophages and TUNEL positive cells associated with the increased localization of tenascin and TGF-beta1 compared with the control. These findings suggest that the specificity of coronary atherosclerosis in diabetic patients may be the extensive atherosclerotic changes associated with increased tenascin. In AMI with NIDDM, increased TGF beta1 may induce apoptosis in the atheroma and coronary dysfunction, contributing to the development of acute myocardial infarction.

Actins↗

[The role of the heat shock protein in human breast cancer].

OBJECTIVE: To study the role of heat shock proteins (HSP) in the cell cycle and various processes of carcinogenesis. METHODS: Immunohistochemical SP methods, electron microscopy, in situ hybridization and RT-PCR were used to evaluate the expression of HSP, mainly HSP90, ubiquitin and HSP70 in breast cancer tissues. RESULTS: HSP90 mRNA was expressed at much higher levels in cancerous tissue than in non-cancerous tissues. In addition, a close relation between HSP90 mRNA expression and proliferating cell nuclear antigen labelling index (PCNA L. I.) was observed in cancerous tissue. These findings suggest that increased expression of HPS90 isoform may play a role in cell proliferation. On the other hand, HSP90 mRNA was expressed in the more poorly differentiated carcinomas of the breast. The intracellular localization of HSP70 was consistent with that of ubiquitin. The PCNA L. I. was significantly higher in specimens showing HSP70 in nucleus. HSP73 mRNA, a member of HSP70 family, was also expressed at higher levels in cancerous tissues associated with a high PCNA L. I. than in non-cancerous tissues. CONCLUSION: These results suggest that HSP90 may play a role in cancer cell proliferation and that HSP90 may contribute to cell differentiation and structural constitution. In addition, HSP70, especially HSP73, is related to ubiquetin and seems to be a marker for cancer proliferation.

Breast Neoplasms↗

Deposition of advanced glycation end products (AGE) and expression of the receptor for AGE in cardiovascular tissue of the diabetic rat.

Advanced glycation end products (AGE) in tissues are important for the central pathological features of diabetic complication. Although AGE bind to several cell-surface sites, resulting in altered cellular functions, receptor for AGE (RAGE) appears to have a central role. We examined AGE accumulation and RAGE expression in the aorta and heart of rats with streptozotocin (STZ)-induced diabetes, 0, 4, 8, 12, 16 and 24 weeks after STZ administration. Early atherosclerotic findings in the intima and medial thinning were observed in the aorta after 16 weeks of STZ-Induced diabetes. Immunohistochemistry and microscope spectrophotometry showed that AGE deposition increased significantly in the aorta and vessels of the myocardium, depending on the period of hyperglycaemia. RAGE was expressed in the endothelial cells and vascular smooth muscle cells of all animals. The number of smooth muscle cells with RAGE immunoreactivity increased until 12 weeks after STZ injection, and then decreased in rats with diabetes between 16 and 24 weeks. On the other hand, total RAGE mRNA levels in the aorta and heart continued to increase with the duration of hyperglycaemia. Furthermore, AGE-BSA induced RAGE mRNA expression of human umbilical vein endothelial cells in vitro. Taken together, the AGE accumulation might initiate diabetic macroangiopathy through RAGE, and the increase of RAGE expression by endothelial cells could be a reason that diabetes mellitus accelerates atherosclerosis rapidly.

Animals↗

Production of macrophage colony-stimulating factor by murine liver in vivo.

In previous reports, the authors demonstrated that M-CSF was produced by primary-cultured non-parenchymal (NPLC) and parenchymal (PLC) liver cells. In order to clarify the biological role of M-CSF produced by the liver, macrophage colony-stimulating factor (M-CSF)-producing cells in vivo were investigated using reverse transcriptase polymerase chain reaction (RT-PCR), dot blot analysis, in situ hybridization and immunohistochemistry. M-CSF mRNA was constantly identified by RT-PCR in the liver, NPLC and PLC, before and after partial hepatectomy. Dot blot analysis showed that fluctuations of M-CSF mRNA level after partial hepatectomy were not statistically significant. In situ hybridization revealed that M-CSF mRNA was expressed mainly in NPLC and vascular endothelial cells (VEC). In addition, a small number of PLC also expressed M-CSF mRNA. Neither the distribution nor the frequency of M-CSF mRNA positive cells in regenerative livers differed significantly from normal livers. M-CSF immunoreactivity was present in NPLC and VEC at all the times before and after partial hepatectomy, while PLC exhibited M-CSF immunostaining 0.5 days after partial hepatectomy. As normal liver expressed M-CSF mRNA to the same degree as regenerative liver, hepatic M-CSF mRNA production in vivo may be related to the physiological function of the liver. However, transient expression of M-CSF protein in PLC at an early stage after partial hepatectomy may be associated with liver regeneration.

Animals↗

Gastrointestinal autonomic nerve tumors: immunohistochemical and ultrastructural studies in cases of gastrointestinal stromal tumor.

The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor with a morphological feature resembling the cell processes of the enteric plexus, and was originally termed a plexoma or plexosarcoma. Light microscopic studies show the GAN tumor most often consists of spindle-shaped cells indistinguishable from a smooth muscle tumor or Schwann cell tumor. Immunohistochemical and ultrastructural examinations of 18 cases of gastrointestinal stromal tumor (GIST) were performed. During ultrastructural examination, all of the 12 cases which were immunohistochemically positive for S-100 protein or neuron-specific enolase (NSE) showed synapse-like structures containing dense core neurosecretory granules measuring 100-200 nm, and 40-60 nm endocytoplasmic vesicles. These results suggest that most GIST of neurogenic origin are tumors derived from the myenteric nerve plexus.

Adult↗

Purification and partial characterization of a novel human platelet aggregation factor in the extracellular products of Streptococcus mitis, strain Nm-65.

A human blood platelet aggregation factor was purified from the extracellular products (ECP) of Streptococcus mitis, strain Nm-65 by sequential chromatography on DEAE-Sepharose CL-6B, hydroxyapatite and Superdex 75 columns. The purified factor (S. mitis-derived human platelet aggregation factor, Sm-hPAF) gave a single band with a molecular weight of 66 kDa on SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Sm-hPAF showed a peak absorption at 278 nm and an isoelectric point of around 8.5. Chemical analyses revealed that Sm-hPAF contained no sugars and that its first 15 amino-terminal amino acid residues were H-DEQGNRPVETENIAR. Platelet aggregation activity of Sm-hPAF was abolished by heating at 45 degrees C for 10 min. Platelet aggregation by Sm-hPAF was accompanied by a release of prostaglandin E2 (PGE2) in a dose-dependent manner. The platelet aggregation was not inhibited by either prostaglandin E1 (PGE1) or Gly-Arg-Gly-Asp-Ser (GRGDS), that inhibit the platelet aggregation induced by collagen. Twenty (77%) platelet rich-plasma (PRP) specimens derived from 26 healthy volunteers were aggregated by Sm-hPAF, but the remaining 6 (23%) were not reactive. A preliminary study suggested the presence of an inhibitory factor against Sm-hPAF in the plasma from a non-reactive donor.

Adult↗

[Laminin-dependent growth arrest of human hepatic carcinoma cell line, HuH-7, in association with expression of p21/WAF-1 protein].

Laminin-overlay to the culture of a human hepatocellular carcinoma cell line, HuH-7, resulted in changes in the cell behavior; suppression of the cell growth, conversion of the cell morphology, and the elevated secretion of cellular AFP in the culture medium, implying that the cells had undergone apparent differentiation in vitro. Together with the behavioral changes, the cells showed positive immunohistochemical staining of the anti-p 21/WAF 1 antibody over the cell nucleus and the amount of p 21/WAF-1 proteins was increased in the cells. p53 protein was detected both in the control cells and the cells with the laminin overlay. These findings indicate that the laminin-dependent changes in the cell behavior are closely associated with the activation of the cyclin-dependent kinase inhibitor, p 21/WAF-1, and that? is uncoupled with the p 53 expression.

Carcinoma, Hepatocellular↗

[Predisposition of subclones of pancreatic carcinoma cells, AsPC-1, to changes in functional and histopathological features of xenograft tumors with response to extracellular matrix].

We cloned two characteristics subclones from a human pancreatic carcinoma cell line, AsPC-1, according to their distinctive cell shapes; one an epithelial morphology and designated as "Beto-1" and the other a fibroblastic morphology and designated as "Fib-1". Fib-1 grew faster than Beto-1, but the growth rate of the cells on plastics was as high as that of the cells on the extracellular matrix extracts, matrigel. The pancreatic tumor-marker proteins, alpha-amylase, insulin, CEA, POA, PP, and AFP, but not CA 19-9, were positive in both subclones. Type IV collagen, fibronectin, and laminin, were all positive in both subclones; furthermore, the integrin adhesion receptor molecules, alpha 2 beta 1-subunit, alpha 5-subunit, and alpha 6-subunit, were also positive. The intercellular adhesion molecules, E-cadherin and ICAM-1, were detected in Beto-1 and Fib-1, respectively. Although both subclonal cells attached to type IV collagen, fibronectin, and laminin in a concentration-dependent manner. Beto-1 adhered most strongly to type IV collagen and Fib-1 attached most strongly to fibronectin. Beto-1 showed morphological differentiation on matrigel and in the tumor xenografts. Further, there was more fibroblast infiltration and type IV collagen production in Beto-1 tumor tissues, and more lymphocyte and neutrophil infiltration in tumors of Fib-1 which expressed ICAM-1 proteins. This study indicated that the histological diversity observed in the pancreatic carcinoma was evolved from the composition of the tumor cells which express the specific adhesion receptors.

Animals↗

Morphological characteristics and clinical significance of nerve distribution in pancreatic cancers.

Macroscopic and immunohistochemical observations were made to clarify the innervation of normal pancreatic tissues, and the clinicopathological and electron-microscopic findings of 33 cases of pancreatic cancer were obtained. The results showed that the innervation of both the head and the body of the pancreas mainly consisted of nerve fibers separated from the right celiac neuroganglion and the right half of the superior mesenteric arterial plexus. The pancreas was full of nerve fibers ending at acinar lobules, among which the adrenergic nerves commonly control the walls of blood vessels. Pancreatic cancer tends to be accompanied by invasion and metastasis along intra or extra-pancreatic nerves, and we found that the positive rates for invasion and metastasis were 73.33% and 60.00%, respectively. The follow-up study revealed that the nerve-invasion group had worse prognosis than the non-invasion group (P < 0.05). The approaches of the invasions of the nerves were as follows: (1) through the vessels of the perineurium; (2) through the perineurium; and (3) through the synaptic membrane of nerve endings. The invasion were a continuous process, often resulting in the destruction or even the disappearance of the normal structure of the nerve fibers. The above results suggest that there are plentiful vegetative nerves inside or outside the pancreas and that pancreatic cancers have a tendency of invading and metastasizing along or around nerves.

Adult↗