PubMed Health⌕ Search

Biomedical subjects

Yuji Ohtsuki

Publications and source records attributed to Yuji Ohtsuki.

At least 73 records · Page 4Linked to original sources

Association between inducible nitric oxide synthase expression and p53 status in human esophageal squamous cell carcinoma.

Nitric oxide (NO) produced by the NO synthase (NOS), a family of enzymes such as inducible NOS (iNOS), has been suggested to play an important role in tumor bioloty. We immunohistochemically examined iNOS and p53 protein expression in 105 patients with esophageal squamous cell carcinoma (ESCC). Direct sequence analysis for the p53 gene was performed in 51 of 105 tumors. In total, 56 of 105 (53.3%) tumors exhibited intracytoplasmic staining for anti-iNOS antibody, including 17 (16.2%) cases of homogeneous and intense immunostaining (++) and 39 (37.1%) of heterogeneous staining (+). Of 62 p53 protein-positive tumors, 40 (63.5%) were positive for iNOS, and of 43 p53 protein-negative tumors, 27 (62.8%) were negative for iNOS. Of 34 iNOS-positive tumors, 23 (67.6%) carried a p53 gene mutation, and of 17 iNOS-negative tumors, 12 (70.6%) had wild-type p53 gene. There was a significant relationship between iNOS immunoreactivity and p53 protein overexpression (p = 0.0058) as well as p53 mutation frequency (p = 0.0163). No association was found between iNOS immunoreactivity and p53 mutation type, any clinicopathological factor and patient prognosis. Our in vivo findings suggest that iNOS activity might be associated with p53 alteration and contribute to tumorigenesis in ESCC.

Adult↗

Myofibroblasts proliferation of idiopathic and collagen vascular disorders associated nonspecific interstitial pneumonia.

Nonspecific interstitial pneumonia (NSIP) has been recognized as a separate histological classification of interstitial lung disease. Similar features are found not only in idiopathic NSIP, but also in NSIP associated with collagen vascular disorder (CVD-NSIP). We examined the clinical symptoms, laboratory findings, and prognosis of 13 cases of idiopathic NSIP and 11 cases of CVD-NSIP. Immunohistochemical staining was performed using the streptavidin/biotin/peroxidase method with anti-alpha-smooth muscle actin antibody. No differences in the distribution of clinical features, laboratory findings, and prognosis were observed between idiopathic NSIP and CVD-NSIP. In immunohistochemical staining of the fibrosing areas, myofibroblasts were observed in 7 of 13 idiopathic NSIP cases, but in 10 of 11 CVD-NSIP cases. With regards to intra-alveolar organization, myofibroblasts were observed in all 10 CVD-NSIP cases, but they were observed in only 2 of 9 idiopathic NSIP cases. We found a significantly higher myofibroblast proliferation in the intra-alveolar organization of CVD-NSIP compared to idiopathic NSIP. Clinically, idiopathic NSIP and CVD-NSIP are similar, but are pathologically different.

Aged↗

Early-phase neutrophilia in cigarette smoke-induced acute eosinophilic pneumonia.

Although cigarette smoking is a recognized cause of acute eosinophilic pneumonia (AEP), and an increase in eosinophils in the lung is a common occurrence in AEP, early-phase neutrophilia in AEP is not well understood. We describe three cases of cigarette smoke (menthol type)-induced AEP with neutrophilia in the lungs or blood. Increased in-vitro production of the neutrophil chemoattractant interleukin (IL)-8 by human bronchial epithelial cells (HBECs) was correlated with neutrophilia. We suggest that IL-8 released from HBECs is involved in neutrophilia in the lung in AEP, and is newly recognized as an important factor in the early phase of AEP development.

Acute Disease↗

Immunohistochemical characterisation of pulmonary hyaline membrane in various types of interstitial pneumonia.

AIMS: Hyaline membrane (HM) in diffuse alveolar damage (DAD) pattern is frequently detected in the acute stage of interstitial pneumonia (IP). To determine the exact nature of HM, we investigated immunohistochemically 25 cases of HM-containing IP. METHODS: The cases examined using various kinds of antibodies were four cases associated with rheumatoid arthritis, five with usual interstitial pneumonia, two with dermatomyositis, five with viral infection, one case with progressive systemic sclerosis and eight cases caused by other agents. RESULTS: HM mostly reacted with antibodies to PE10 (SP-A), Factor VIII, KL-6 and EMA and, interestingly, stained for AE1/AE3, CK19, and Hup-1 in some cases, but was negative for PTAH staining. However, the immunoreactivities of HM varied even within the same disease or section. CONCLUSIONS: The immunohistochemical heterogeneity of HM suggests that HM may be formed by different mechanisms in various types of IP. Our findings also suggest that the main components of HM are derived from alveolar epithelial cells and their proteins, some including cytoplasmic element of CK19, and also from serum factors, but not fibrin. The immunohistochemical characteristics of HM in DAD pattern will aid understanding of the significance of HM formation in IP.

Adult↗

[A case of pulmonary Langerhans' cell histiocytosis].

A 42-yr-old woman was referred to our hospital because of multiple small nodules in a chest radiograph. She had no symptoms such as dyspnea, cough or sputum. A chest CT revealed many centrilobular small nodules and thin-walled cysts with predominance in the peripheral area of the lungs. The specimens obtained by thoracoscopic surgery showed granulomas with scattered eosinophils and numerous Langerhans' cells. The Langerhans' cells were positive for both S-100 protein and CD1a. These findings are compatible with pulmonary Langerhans' cell histiocytosis (LCH). Since the granulomas showed no fibrotic changes, the LCH may have been in its early stages. However, there were clusters of lymphocytes and macrophages around the terminal and respiratory bronchioles, and cystic lesions without cellular infiltrates, in the specimens. The former histologic findings suggested respiratory bronchiolitis causing interstitial lung disease and the latter are indistinguishable from centrilobular emphysema. Therefore, these smoking-related diseases may have been superimposed on the LCH in this patient.

Adult↗

cDNA cloning and developmental expression of murine carbonic anhydrase-related proteins VIII, X, and XI.

To help understand the biological functions of carbonic anhydrase-related proteins (CA-RPs VIII, X, and XI), we obtained cDNA clones of murine CA-RPs X and XI and studied the tissue distribution of all three CA-RPs and their developmental expression in the murine embryonic brain. The amino acid sequences of murine CA-RPs are highly conserved with their human homologues, indicating a fundamental biological role of CA-RPs. Among a panel of vital organs, the strongest mRNA expression of all three CA-RPs was consistently observed in the brain. Immunohistochemical analysis revealed the expression of all three CA-RPs in the neural cell body and neurites. CA-RP X was also observed in the myelin sheath, as demonstrated using the shiverer demyelinated mouse. In murine embryos, CA-RP VIII and X messages first appeared in the middle of the gestation period, while the CA-RP XI message was seen at an early gestational stage and expressed to a lesser extent as gestation progressed. All CA-RPs were expressed in the neuroprogenitor cells in the subventricular area and subsequently detected in the neural cells migrating to the cortex. Although the exact function of CA-RPs is still undefined, these findings suggest an important role of CA-RPs in the CNS.

Animals↗

Expression of carbonic anhydrase-related protein CA-RP VIII in non-small cell lung cancer.

Carbonic anhydrase-related protein (CA-RP VIII) lacks a Zn-binding motif which is essential for carbonic anhydrase activity. Therefore, CA-RP VIII is believed to have a no catalytic activity and a new biological property. In the present study, CA-RP VIII expression in non-tumorous lung and non-small cell lung carcinomas was investigated. Little or no expression of CA-RP VIII was observed in human lungs by Northern-blot analysis. Reverse-transcription polymerase chain reaction analysis demonstrated CA-RP VIII mRNA in developing human lungs and, to a lesser extent, in normal lungs. Subsequent immunohistochemical staining revealed that CA-RP VIII was expressed in the pulmonary epithelium in developing lungs; however, CA-RP VIII expression was restricted in bronchial ciliated cells in adult lungs. Neither bronchial gland nor squamous metaplasia of interstitial pneumonia expressed CA-RP VIII. In contrast, CA-RP VIII was strongly expressed in almost all archival lung cancer specimens, which included 24 squamous cell carcinomas, 25 adenocarcinomas, and 6 adenosquamous cell carcinomas. Cancer cells at the front of tumor progression expressed CA-RP VIII in particular abundance. The present findings suggest that CA-RP VIII may play a role in non-small lung cell carcinomas.

Animals↗

A case of salivary gland-type mixed tumor of the lung differentiating toward type II alveolar epithelial cells in glandular components with a literature review.

Salivary gland-type mixed tumor primarily arising in the lung is extremely rare. We report here a case of this type of tumor that occurred in the periphery of S4 of the right middle lobe in a 74-year-old man. Light-microscopically, this lung tumor, 15x9mm in size, exhibited almost the same features as those of mixed tumor of the salivary gland intermingled with chondromyxoid stroma, glandular component, solid growth pattern of myoepithelial components and well-developed cartilage formation, exhibiting a sharp margin. Immunohistochemical study revealed that the glandular components in the tumor was positive for thyroid transcription factor-1, TTF-1, a marker of epithelial cells of the thyroid as well as the lung. Furthermore, surface lining cells of the glandular components and luminal contents were positive for surfactant apoprotein A, PE-10, used as a marker of type II alveolar epithelial cells. These findings clearly demonstrate for the first time that glandular epithelial cells in the present salivary gland-type mixed tumor exhibited differentiation toward type II alveolar epithelial cells.

Aged↗

Downregulation of expression of a novel cadherin molecule, T-cadherin, in basal cell carcinoma of the skin.

T-cadherin appears to act as a tumor-suppressor factor in various cancers. Downregulation of T-cadherin is caused by a combination of allelic loss and hypermethylation of the T-cadherin promoter region and is related to cancer invasion. To elucidate the molecular mechanism of invasiveness of basal cell carcinoma of the skin, T-cadherin expression was investigated in archival pathological tissue sections made up of normal counterparts of skin and various types of basal cell carcinoma. Immunohistochemical staining showed that T-cadherin was not expressed in 38 of 51 (75%) basal cell carcinoma specimens, whereas normal counterparts of the skin appeared to express abundant T-cadherin. Loss of heterozygosity in intron 1 of the T-cadherin gene was found in four of 20 informative cases that did not express T-cadherin. Aberrant methylation of the T-cadherin promoter region also was found in six of 25 basal cell carcinomas by methylation-specific polymerase chain reaction. In contrast, no structural alternations were found in two loss of heterozygosity-positive basal cell carcinomas on sequence analysis. These findings indicated that T-cadherin expression was downregulated by a combination of allelic loss and aberrant methylation in basal cell carcinoma of the skin. Loss of T-cadherin expression might be related to the biological behavior of basal cell carcinoma. In addition, results of the present study suggested that downregulation of T-cadherin in various cancers might be related to tumor invasiveness rather than metastasis, because basal cell carcinoma of the skin principally lacks metastatic activity.

Amino Acid Sequence↗

Frequent phosphorylation at serine 392 in overexpressed p53 protein due to missense mutation in carcinoma of the urinary tract.

Post-transcriptional modification of p53 by phosphorylation has been proposed to be an important mechanism of p53 stabilization and functional regulation. Phosphorylation of p53 Ser392, in particular, activates specific DNA binding functions by stabilizing p53 tetramer formation. This study evaluated the relationship between p53 Ser392 phosphorylation and various types of p53 missense mutation detected in urothelial transitional cell carcinomas (TCCs), with stratification of the mutations according to the functional domains elucidated by the crystal structure of the p53 protein. Of 41 TCCs with missense mutations, 26 (63.4%) exhibited immunopositivity with Ser392 phospho-specific p53 antibody. In comparison to structural mutations, the missense mutations at exon 7 (p=0.0307) or located in regions that affect direct DNA binding ability (p = 0.0273) were significantly associated with Ser392 immunopositivity. No statistically significant relationship was found between Ser392 immunoreactivity and other different types of p53 mutation. The prevalence of cases exhibiting Ser392-positive immunostaining was higher for high-grade (p <0.0001) and advanced-stage TCCs (p =0.0119) than for TCCs with wild-type p53. No significant relationship was found between Ser392 immunoreactivity and apoptotic index in urothelial TCCs. These in vivo findings indicate that Ser392 phosphorylation frequently occurs in mutant form p53 in TCCs. Because mutant form p53 can act dominant-negatively by heterooligomerization with wild-type p53, these findings also suggest that Ser392 phosphorylation might activate tetramer formation to promote the dominant-negative effects of mutant form p53, and thereby contribute to proliferation of aggressive TCCs.

Aged↗

Typical nemaline bodies presenting in a patient with polymyositis.

A 66-year-old woman presented with a progressive myopathy affecting the proximal limbs and unusual pathological findings of nemaline bodies on muscle biopsy. Histological examination demonstrated that the bodies were mainly located in the subsarcolemmal region of atrophic fibers, exhibited strong immunoreactivity with antibodies to both alpha-actinin and m-actin, and had a typical lattice-like appearance at higher magnification on electron microscopy. These findings were the same as those for nemaline myopathy. The patient responded to steroid therapy, but relapse occurred after steroid was discontinued. Given the clinical criteria of polymyositis, we believe that the occurrence of nemaline bodies in our patient should be interpreted primarily as an epiphenomenon of primary myopathy.

Actinin↗

Expression of T-cadherin in Basal keratinocytes of skin.

T-cadherin is a unique member of the cadherin superfamily that shares the ectodomain organization with classical cadherins, but lacks both transmembrane and cytoplasmic regions and is instead anchored to the plasma membrane through a glycosyl-phosphatidylinositol (GPI) moiety. The function of T-cadherin has not been revealed yet. The special structure of T-cadherin might endow this molecule with specific intracellular targeting properties and functions that are distinct from classical cadherins. T-cadherin was originally cloned from chicken embryo brain and then was also found in mouse and human nervous and cardiovascular systems; however, T-cadherin in the keratinocytes and skin tissue is still an unknown area that remains to be explored. To test whether the unusual truncated T-cadherin is expressed in keratinocytes, we performed the reverse transcriptase-polymerase chain reaction of T-cadherin, as well as several classical cadherins (E-, P-, and N-cadherin), on the mouse keratinocyte cell line Pam212, fibroblast NIH3T3, and melanoma cell B16. The result indicated that mouse keratinocytes expressed the mRNA of truncated T-cadherin apart from classical cadherins, E-, and P-cadherin. To confirm the expression of T-cadherin in mouse keratinocytes, immunocytochemistry staining was carried out on Pam212 cells by using rabbit anti-T-cadherin antibody and rat antimouse E- and P-cadherin antibody. The result of immunofluorescence staining proved that T-cadherin was expressed in mouse keratinocytes. In order to analyze the distribution patterns of T-cadherin and classical cadherins on the keratinocytes, 3D scanning was performed by using a confocal microscope. From the Z-sections and XZ-sections, it was clearly demonstrated that T-cadherin was distributed diffusely on the whole cell surface, while E- and P-cadherin were concentrated on the cell-cell contacts. To examine the expression and the localization of T-cadherin on skin tissue, the frozen sections of the mouse back skin were immunohistochemically labeled by using anti-T-cadherin antibody. It was found that T-cadherin was intensively expressed only on the basal cell layer of the mouse skin. Apart from mouse keratinocytes and mouse skin, we further examined the expression of T-cadherin in human keratinocytes and human skin by western blot, immunocytochemistry, and immunohistochemistry staining. The same results were achieved with human samples. In this study, we found and verified that T-cadherin was expressed on the mouse and human keratinocytes and specifically localized on the basal cell layer of skin. The nature of T-cadherin function and its mechanism of localization at the basal cell layer of skin are important issues to be addressed concerning this unique member of the cadherin family and its physiologic and pathologic roles in the skin.

3T3 Cells↗

Evaluation of the clonality of multilobar bronchioloalveolar carcinoma of the lung: case report.

A case of multilobar bronchioloalveolar carcinoma (BAC) is reported. To investigate the clonality of BAC, immunohistochemical staining as well as genetic analysis were performed. To investigate point mutations of the p53 gene, we used the polymerase chain reaction and fluorescence-based single strand conformation polymorphism analysis method. The BAC tissues of the right upper lobe, right lower lobe, and the other lobes were considered to be multiclonal. This case suggests that multilobar BAC might occur with multiclonality.

Adenocarcinoma, Bronchiolo-Alveolar↗

Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma.

We previously reported that T-cadherin (CDH13, H-cadherin), a unique cadherin molecule, was expressed on the basal cell layer in normal murine and human epidermis. In the present study, T-cadherin expression in archival human skin specimens comprising a spectrum of human squamous cell neoplasia was investigated. T-cadherin expression was observed in both normal epidermal basal cells and adnexal epithelial cells of formalin-fixed and paraffin-embedded tissue sections. Western immunoblotting also revealed that mature T-cadherin protein was expressed in cultured human skin tissue equivalent. Atypical keratinocytes in 27 of 53 specimens of actinic keratosis and 23 of 30 specimens of Bowen's disease expressed T-cadherin. In contrast, T-cadherin was focally expressed in 6 of 56 invasive cutaneous squamous cell carcinomas. To explore the molecular mechanism of down-regulation of T-cadherin expression in invasive squamous cell carcinoma, loss of heterozygosity, genetic alternations, and methylation status in the 5' region of the T-cadherin gene were investigated. Loss of heterozygosity at intron 1 of the T-cadherin gene was observed in 8 of 28 informative cases of invasive squamous cell carcinoma. Although no structural genomic alternations were found by sequence analysis, aberrant promoter methylation of the T-cadherin gene was found in 12 of 28 invasive squamous cell carcinomas. T-cadherin expression was restored in cultured A431 cells, in which aberrant methylation was found by treatment with the demethylating agent 5'-aza-2-deoxycytidine. These findings suggest that a combination of deletion and aberrant methylation of the T-cadherin gene may play a role in loss of gene expression in a considerable number of invasive cutaneous squamous cell carcinomas.

Cadherins↗

Immunohistochemical distribution of epithelioid cell, myofibroblast, and transforming growth factor-beta1 in the granuloma caused by Mycobacterium avium intracellulare complex pulmonary infection.

The present study was designed to evaluate the distribution of epithelioid cells, myofibroblasts, and TGF-beta1 in the formation of granuloma caused by Mycobacterium avium intracellulare complex (MAC) lung infection. A retrospective study was performed for 9 cases of positive MAC culture in which lung resections were performed between January 1989 and August 1999. Resected lung specimens were evaluated histologically and immunohistochemically for CD68 (stain for monocytes and macrophages, and epithelioid cells) and alpha-smooth muscle actin as well as vimentin (stain for myofibroblasts), and TGF-beta1 was performed. When granuloma was initially formed, no myofibroblasts were found, but as caseous necrosis appeared, the thin epithelioid cell layer was detected and the outer myofibroblast layer gradually became thick. In the cavitary wall, the layer of epithelioid cells and multinucleated giant cells surrounded necrosis, and was associated with the outer layer of myofibroblasts. In addition, the anti-TGF-beta1 antibody stained the cytoplasm of epithelioid cells and multinucleated giant cells, preceding the advent of myofibroblasts. In summary, our present study evaluated distributions of epithelioid cells, myofibroblasts, and TGF-beta along with the morphogenesis of granuloma, and clearly demonstrated the immunohistochemical difference between granuloma with caseous necrosis and granulomas without caseous necrosis.

Actins↗

Multiple eccrine spiradenomas on the hand, forearm and head.

The first case of multifocal eccrine spiradenomas on the hand, forearm and scalp is described. This case is unusual in that the tumors located on the little finger included the nail matrix and occurred in a linear/zosteriform distribution, resulting in a nail deformity. The nodules on the forearm and scalp were in a random distribution. Histologically, each tumor was highly cellular and composed of two cell types: small darkly staining basaloid cells and larger, pale cells. Ultrastructural observations often showed an intracellular lumen with numerous microvilli in larger pale-staining cells.

Adenoma, Sweat Gland↗

The distribution and number of Leu-7 (CD57) positive cells in lung tissue from patients with pulmonary fibrosis.

Leu-7 positive lymphocytes, including natural killer cells, play an important role in the immune system's surveillance function to prevent the development of cancer. The incidence of lung cancer is significantly high in patients with end-stage pulmonary fibrosis. We hypothesized that the number of Leu-7 positive cells may be decreased in areas of severe pulmonary fibrosis. To demonstrate this, Leu-7 positive cells were immunohistochemically stained in 41 lung specimens obtained from patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders. The number of Leu-7 positive cells was evaluated according to the pathological findings. In pathologically normal lung, Leu-7 positive cells were mostly found within the capillaries of the septa and rarely in the alveolar space or the stroma. The number of Leu-7 positive cells was 0.69 +/- 0.15 in areas of advanced fibrosis (n = 41), 2.39 +/- 0.60 in areas that had newly developeing fibrosis (n = 41), 1.14 +/- 0.57 in bronchiolitis obliterans organizing pneumonia (n = 9), and 1.35 +/- 0.87 in diffuse alveolar damage (DAD) (n = 11). The number of Leu-7 positive cells in areas of newly developing fibrosis (2.39 +/- 0.60) was significantly higher than that in areas of established fibrosis (0.69 +/- 0.15, P < 0.05). Our present study demonstrates a significant decrease in the number of Leu-7 positive cells in areas of advanced fibrosis. This evidence may partly explain the high incidence of lung cancer associated with pulmonary fibrosis.

Aged↗