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Biomedical subjects

Y Ohtsuki

Publications and source records attributed to Y Ohtsuki.

At least 91 records · Page 5Linked to original sources
PubMed1999

Elevated serum and BAL cytokeratin 19 fragment in pulmonary fibrosis and acute interstitial pneumonia.

Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, it was hypothesized that CK19 may be increased in the serum and epithelial lining fluid of the respiratory tract from patients with pulmonary fibrosis. CK19 was measured in the serum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis and the correlation between CK19 levels and clinical parameters evaluated. Nineteen patients diagnosed with idiopathic pulmonary fibrosis (IPF), eight with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), seven patients with acute interstitial pneumonia (AIP), and 10 normal smokers as a control group were studied. CK19 levels in sera of patients with IPF and patients with PF-CVD were significantly increased compared to those of normal smokers. CK19 levels in sera of patients with AIP were significantly increased compared to those of other groups. CK19 values in the BALF of patients with pulmonary fibrosis were significantly elevated compared to those of normal smokers. CK19 values in sera charged according to the progression or improvement of the acute lung injury. Immunohistochemical study using pulmonary tissues obtained from patients with AIP demonstrated that the hyaline membrane and proliferating type II pneumocytes were stained by anti-human cytokeratin 19 antibody. These data demonstrated that the measurement of cytokeratin 19 fragment is a useful parameter to evaluate the activity of lung epithelial cell damage and repair.

Acute Disease↗
PubMed1999

Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia.

The aim of this study was to investigate whether idiopathic pulmonary fibrosis (IPF) can be distinguished from rheumatoid arthritis (RA)-associated interstitial pneumonia (RA-IP) by means of quantitatively assessing myofibroblasts and S-100 protein positive dendritic cells. Seven patients with IPF and twelve with RA, in whom the pathological findings were consistent with usual interstitial pneumonia (UIP) were studied. Antibodies to vimentin, alpha-smooth muscle actin (alpha-SMA) and S-100 protein were used for immunohistochemical studies performed using the streptavidin/biotin/peroxidase complex method, applied to dewaxed sections from each case. In fibrosis of RA-IP, appearance of both vimentin- and alpha-SMA-positive cells, namely myofibroblasts, was widely observed, together with the pathological patterns of honeycombing, UIP and bronchiolitis obliterans-organizing pneumonia (BOOP). Fibrosis, in cases of chronic IPF, was found to be characterized mainly by vimentin-positive but alpha-SMA-negative fibroblasts. Pulmonary tissues from RA-IP patients especially when associated with a BOOP pattern, contained many cells positive for S-100 protein. However, such cells were generally hard to find in cases of IPF. These findings suggests that idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia can be differentiated from each other, to some extent, based on the appearance of myofibroblasts and the presence of S-100-positive dendritic cells.

Actins↗
PubMed1999

Comparison of deregulated expression of cyclin D1 and cyclin E with that of cyclin-dependent kinase 4 (CDK4) and CDK2 in human oesophageal squamous cell carcinoma.

The expressions of cyclin D1, cyclin E, cyclin-dependent kinase 4 (CDK4), and CDK2 were immunohistochemically examined in 90 patients with human oesophageal squamous cell carcinoma (SCC) to determine their relationship to the tumour behaviour and patient prognosis. Nuclear immunostaining of cyclin D1 and cyclin E was observed in 28 (31.1%) and 27 tumours (30.0%) respectively. Thirty-nine tumours (43.3%) and 31 tumours (34.4%) exhibited both cytoplasmic and nuclear positivity for CDK4 and CDK2 respectively. Of 28 cyclin D1-positive and 27 cyclin E-positive tumours, CDK4 was overexpressed in 12 (42.8%) tumours and CDK2 in seven (25.9%) tumours respectively. There was no significant relationship in immunopositivity between cyclin D1 and CDK4 or between cyclin E and CDK2. Simultaneous immunoreactivity for both cyclin D1 and CDK4 was significantly associated with venous invasion (P < 0.05). In a univariate analysis, the prognosis of patients with tumours that were both cyclin D1- and CDK4-positive was significantly poorer than that of patients with cyclin D1-negative tumours (P < 0.05). In a multivariate analysis, both cyclin D1 and CDK4 immunoreactivities (P < 0.01) and tumour stage (P < 0.001) were recognized as independent risk factors. In this analysis, the hazard ratio for cyclin D1-positive and CDK4-negative cases compared with cyclin D1-negative cases was significant (hazard ratio = 3.128, 95% confidence interval = 1.418-6.899, P = 0.0047). No significant prognostic relevance was detected in both cyclin E and CDK2 immunoreactivity. Our in vivo findings suggest that in human oesophageal SCC, cyclin D1 and cyclin E and their functional partners, CDK4 and CDK2, often exhibit dysregulated overexpression in many cases, and that tumours with simultaneous expression of cyclin D1 and CDK4 are frequently associated with venous invasion and have a worse prognosis, statistically. Moreover, overexpression of cyclin D1 alone may also contribute to tumour progression independent of CDK4 overexpression.

Aged↗
PubMed1999

Detection of large molecular weight cytokeratin 8 as carrier protein of CA19-9 in non-small-cell lung cancer cell lines.

It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19-9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC.

Adenocarcinoma↗
PubMed1999

Pigmented squamous cell carcinoma of the scrotum associated with a lentigo.

Only 13 cases of pigmented squamous cell carcinoma (SCC) have been reported in the English language literature, with most frequent development in the oral cavity and conjunctiva. However, no case of pigmented SCC of the scrotum has been reported. We report here a case of pigmented SCC that arose primarily in the scrotum of a 70-year-old man. Light microscopically, this tumour exhibited the typical features of a pigmented SCC, including not only keratinization and intercellular bridges but also colonization by plump dendritic melanocytes with marked pigmentation. These features were clearly confirmed by immunohistochemistry, including strong positivity of tumour cells for high-molecular-weight cytokeratin and of colonizing melanocytes for HMB-45. The tumour was associated with a lentiginous lesion and partly involved it. Melanocytes entrapped from the lentigo might therefore have been activated during enlargement of this tumour, resulting in melanocyte colonization. Fourteen cases of pigmented SCC, including ours, are clinicopathologically reviewed.

Aged↗
PubMed1999

An immunohistochemical study on a case of granulocyte-colony stimulating factor-producing gall-bladder carcinoma.

Primary gall-bladder carcinoma producing granulocyte-colony stimulating factor (GCSF) is extremely rare. Only four cases, histologically investigated, have been reported to date in the English literature. We report a case of a 48-year-old female with primary gall-bladder carcinoma, associating with leukocytosis (15 700/mm3) and a high level of serum GCSF (54.0 pg/mL). The tumor was, histologically, a poorly differentiated adenocarcinoma with marked interspersed neutrophils invading into the primary tumor itself and the right lobe of the liver. Tumor cells distinctly showed positive immunoreaction in the cytoplasm with anti-GCSF antibody, and in the nucleus for anti-p53 antibody. After surgery, the leukocytosis and serum level of GCSF began to decrease. These findings confirmed the present case of GCSF-producing gall-bladder carcinoma, exhibiting leukocytosis. A total of five cases, including our case, reported as a GCSF-producing gall-bladder carcinoma were clinicopathologically reviewed.

Adenocarcinoma↗
PubMed1999

p53 mutations in tumor and non-tumor tissues of thorotrast recipients: a model for cellular selection during radiation carcinogenesis in the liver.

Concerns over cancer development from exposure to environmental sources of densely ionizing, high linear energy transfer (LET) radiation, such as alpha-particles from radon, is a current public health issue. The study of tumors attributable to high LET irradiation would greatly augment our insights into the biological mechanisms of carcinogenesis. Chronic low-dose-rate internal exposure to alpha-radiation from thorium dioxide deposits following intravascular administration of the radiographic contrast agent Thorotrast is known to markedly increase the risk of cancer development, especially that of hepatic angiosarcomas and cholangiocarcinomas. Although the mechanism is hypothesized to be via cellular damage, DNA being a major target, wrought by the high LET alpha-particles, the specific genes and the actual sequence of events involved in the process of transforming a normal cell into a malignant one are largely unknown. To shed some light on the molecular mechanisms of cancer development during a lifetime exposure to alpha-radiation, we analyzed the most commonly affected tumor suppressor gene in humans, p53, in 20 Thorotrast recipients who developed cancer, mostly of hepatic bile duct and blood vessel origin. Of the 20 cases, 19 were found to harbor p53 point mutations. Moreover, the accompanying non-tumor tissues from these patients also had p53 mutations, albeit at lower frequency. The distribution pattern of the point mutations was significantly different between the non-tumor and tumor tissues, with most mutations in malignant tissues located in the highly conserved domains of the p53 gene. Our results support the idea that p53 mutations are important in the genesis of Thorotrast-induced tumors but that these point mutations are a secondary outcome of genomic instability induced by the irradiation. Additionally, non-tumor cells harboring p53 mutations may gain some survival advantage in situ but mutations in the domains responsible for the formation of structural elements critical in binding DNA may be necessary for a cell to reach full malignancy.

Aged↗
PubMed1999

Detection of anti-ADAM 10 antibody in serum of a patient with pulmonary fibrosis associated with dermatomyositis.

OBJECTIVES: It has been suggested that the humoral immune system plays a part in the pathogenesis of pulmonary fibrosis. Although circulating autoantibodies to lung protein(s) have been suggested, few lung proteins have been characterised. The purpose of this study is to determine the antigen recognised by serum of a patient with pulmonary fibrosis associated with dermatomyositis. METHODS: To accomplish this, anti-small airway epithelial cell (SAEC) antibody in a patient's serum was evaluated using a western immunoblot. RESULTS: An autoantibody against SAEC was found, and the antigen had a molecular weight of 62 kDa. Using the patient's serum, clones from the normal lung cDNA library were screened and demonstrated that anti-SAEC antibody in the patient's serum was against ADAM (A disintegrin and metalloprotease) 10. CONCLUSION: This is the first report that demonstrates the existence of anti-ADAM 10 antibody in a patient with pulmonary fibrosis associated with dermatomyositis.

ADAM Proteins↗
PubMed1999

Pathological and radiological changes in resected lung specimens in Mycobacterium avium intracellulare complex disease.

The present study was designed to evaluate the pathological and immunohistochemical findings of Mycobacterium avium intracellulare complex (MAC) lung infection. A retrospective study was performed in five cases with positive cultures for MAC in whom lung resections were performed between January 1989 and December 1996. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria defined by the American Thoracic Society. In addition, MAC was cultured from all of the five lung specimens. Pathological and immunohistochemical findings as well as chest computed tomography (CT) findings were evaluated in these five patients. Pathological findings of bronchiectasis, bronchiolitis, centrilobular lesion, consolidation, cavity wall and nodules were demonstrated, respectively, in relation to chest CT findings. Extensive granuloma formation throughout the airways was clearly demonstrated. Immunohistochemical staining demonstrated: 1) epithelioid cells and giant cells; 2) myofibroblasts extensively infiltrating the cavity wall; and 3) B-cells detected in aggregates in the vicinity of the epithelioid granulomas. This study identified pathological and immunohistochemical characteristics of Mycobacterium avium complex infection relative to chest computed tomography findings and allowed the conclusion that bronchiectasis and bronchiolitis were definitely caused by Mycobacterium avium complex infection.

Adult↗
PubMed1999

Sequential changes of hepatocyte growth factor in the serum and enhanced c-Met expression in the myocardium in acute myocardial infarction.

A 68-year-old male with acute myocardial infarction (AMI) was admitted to the hospital with chest pain that had started 1 day earlier. The serum levels (ng/ml) of hepatocyte growth factor (HGF) were 1.06, 1.22, 1.05, 0.72 and 0.64 on days 2, 3, 4, 5 and 6 postinfarction, respectively. He died suddenly due to cardiopulmonary arrest on day 6. At autopsy, approximately 400 ml of bloody pericardial fluid, caused by rupture of the left ventricle, was detected and the c-Met expression in the myocardium was immunohistochemically found to be most intense in the border zone of the infarcted and non-infarcted region. Although there was no c-Met expression in the infarcted myocardium, it was increased in the myocardial cells surrounding the blood vessels. This is the first report to show sequential changes of HGF in the serum, as well as c-Met expression in the myocardium, in a patient with AMI.

Aged↗
PubMed1999

Application of an in situ PCR hybridization method to detection of human T-lymphotropic virus type I-infected cells in the lung.

We applied an in situ polymerase chain reaction (PCR) hybridization method in order to detect human T-lymphotropic virus type I-infected cells in routinely-processed paraffin sections of the lung from 13 autopsied patients with adult T-cell leukemia (ATL). Previously reported protocol resulted in somewhat non-specific staining in our sections. Therefore, we used a hot start PCR method using specialized commercially-available polymerase in order to increase the specificity. Of 6 patients with ATL cell invasion into the lungs, 4 exhibited strong positive staining of almost all invading ATL cells. In contrast, 7 patients without ATL cell invasion into the lungs did not demonstrate any significant reactivity. Since the method described here is a relatively simple hot start method and does not yield false-positives, it may allow us to determine whether human T-lymphotropic virus type I (HTLV-I) associated disorders are related to lymphocytes integrating the HTLV-I genome.

Adult↗
PubMed1999

In situ detection of Aspergillus 18S ribosomal RNA in invasive pulmonary aspergillosis.

OBJECTS: We attempted to evaluate the usefulness of in situ hybridization (ISH) in the specific diagnosis of Aspergillus pulmonary infection. METHODS: We used an ISH technique using a multiple digoxigenin-incorporating probe, which was constructed by means of the polymerase chain reaction (PCR) from the 18S ribosomal RNA of Aspergillus fumigatus. MATERIALS: We studied twelve formalin-fixed, paraffin-embedded lung tissue sections from autopsy-confirmed invasive pulmonary aspergillosis (IPA) (5 acute myelocytic leukemias, 2 acute lymphocytic leukemias, 2 chronic myelocytic leukemias, 1 adult T-cell leukemia, 1 non-Hodgkin's lymphoma and 1 chronic obstructive pulmonary disease.), and 18 sections from other pulmonary infections as control. RESULTS: ISH using the probe and a low-viscosity hybridization buffer solution (LV) positively stained hyphal elements in 12 of 12 autopsy lung tissue specimens from subjects with IPA, while ISH using the probe and a high viscosity hybridization buffer solution (HV) positively stained the hyphal elements in 6 of 12. Specifically, ISH (LV) demonstrates hyphal elements of Aspergillus spp. in the center of Aspergillus abscess. While, ISH (HV) can detect hyphal elements located in the periphery of a suppurative abscess as well as those in the blood vessel. Conversely, ISH did not show positive results for any of the autopsy tissue specimens from subjects with other fungal pneumonia infections (Candida n=5, Mucor n=2, Cryptococcus n=2, and Pseudallescheria n=1), Pneumocystis carinii pneumonia (n=5), and cytomegalovirus pneumonia (n=3). Dual staining by means of ISH and immunohistochemistry (IHC) using anti-neutrophil elastase (NE) and anti-CD68 monoclonal antibodies showed that NE positive cells were localized at the edge of the radial growth of the organism, but CD68 positive cells were located around the center of the abscess. The accumulation of NE positive cells was rarely seen in half of the cases (6/12). In contrast, CD68 positive cells were routinely present in the center of the abscess (12/12). CONCLUSION: ISH in conjunction with IHC is a useful tool for differentiating Aspergillus spp. from other fungal genera in tissue sections from patients with IPA and may have a certain role in the evaluation of the interactions between organisms and recruiting inflammatory cells.

Adult↗
PubMed1999

Immunohistochemical study of a patient with diffuse pulmonary corpora amylacea detected by open lung biopsy.

The chest radiographs of an asymptomatic 58-year-old Japanese man with pulmonary corpora amylacea (PCA) revealed bilateral patchy and nodular infiltrates. Lung specimens obtained by open lung biopsy were histochemically and immunohistochemically analyzed. In all sections of dissected lung tissue, hematoxylin and eosin staining revealed homogeneous eosinophilic acellular round bodies (50-100 microm in diameter) containing granular black pigments in the alveolar spaces. Some round bodies were surrounded and phagocytized by alveolar macrophages. The laminated round bodies stained positively with PAS and Congo red. In addition, many of the rounded bodies contained particles which stained positively with Berlin blue. Immunohistochemical staining for epithelial membrane antigen (EMA) as well as PE-10 was distinctively positive. This is a very rare case of diffuse PCA found by open lung biopsy. Immunohistochemical examination suggested that PCA consisted of pulmonary surfactant protein and epithelial membrane antigen.

Biopsy↗
PubMed1999

Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage.

Expressions of p53 protein and epidermal growth factor receptor (EGFR) were immunohistochemically investigated in 111 patients with papillary thyroid carcinomas (PTC) in order to evaluate their co-expression in relation to lymph node metastases (LNM), tumor size and clinicopathologic stage. In PTC, positive staining for p53 in dewaxed sections was present in nuclei or cytoplasm, or in both, whereas surface linear or cytoplasmic staining for EGFR was observed with varying degrees of extent and intensity. Positive reaction (more than 10% of tumor cells positive) was observed in 65 cases (58. 5%) for p53, and in 87 cases (78.4%) for EGFR. A significant correlation was found between p53 protein and EGFR overexpressions (p<0.01). Notably, p53-positive cases always exhibited positive staining for EGFR. Forty-four patients (39.6%) exhibited concomitant LNM, most of whom had both p53 and EGFR expression in primary foci. Statistical analysis revealed that co-expression of p53 protein and EGFR was significantly correlated with LNM, tumor size and clinicopathologic stage, but no correlation was found between their co-expression and age or sex. Our findings suggest that overexpression of p53 protein or EGFR in PTC tends to be associated with a high frequency of LNM, increased tumor size and advanced clinicopathologic stage, and that co-expression of both p53 protein and EGFR may predispose to growth and progression of PTC. Our findings also suggest that p53 protein and EGFR expressions may be clinicopathologic and prognostic indicators of PTC.

Adolescent↗
PubMed1999

Dermatofibrosarcoma protuberans harboring t(9;22)(q32;q12.2).

More than 20 cases of dermatofibrosarcoma protuberans (DFSP) exhibiting chromosomal abnormalities have been reported. Approximately three fourths of these tumors have harbored supernumerary ring chromosomes, which have been suggested to be specific for this tumor. However, a small number of DFSPs with translocations such as t(2;17), t(X;7), and t(17;22) have recently been reported. We report a DFSP arising in a 23-year-old woman which unexpectedly exhibited the balanced translocation, t(9;22)(q32;q12.2) as the only anomaly with G-band technique. Dual-color fluorescence in situ hybridization (FISH) confirmed these cytogenetic findings. Similar to that previously reported for DFSPs with translocations, the present tumor also lacked ring chromosomes.

Adult↗