Tadashi Uyama

A Study of the Electrical Bio-impedance of Tumors

A new system of impedance measurement over a frequency range of 0 to 200 kHz was developed by a three-electrode method. In this study, the electrical impedances of various tumors were measured in vivo in 54 patients with breast disease (31 breast cancers, 13 fibroadenomas, and 10 fibrocystic diseases) and 57 patients with pulmonary disease (44 lung cancers, 5 metastatic pulmonary tumors, 4 pulmonary tuberculoses, and 4 organized pneumonias). On the basis of those impedance measurements and the equivalent circuits in vivo, we calculated the extracellular resistance (Re), intracellular fluid resistance (Ri), and cell membrane capacitance (Cm) in tissues, all of which were compared among the various diseases. It was found that Re and Ri were significantly higher in breast cancers than in benign tumors and normal breast tissues and that Cm was significantly lower in breast cancers than in other tissues. On the other hand, Re and Ri were significantly higher, and Cm was significantly lower, in normal lung tissues than in pulmonary masses. Re and Ri were significantly higher, and Cm was significantly lower, in malignant tumors than in organized pneumonias. The results showed that these parameters (Re, Ri, and Cm) exhibit significant differences among various tissues and tumors, suggesting possible applications in tumor diagnosis.

LATE AIRWAY CHANGES CAUSED BY CHRONIC REJECTION IN RAT LUNG ALLOGRAFTS

Airway disease after lung or heart-lung transplantation is one of late major complications, affecting the prognosis of the transplants. Little is known about the causes of airway changes. We performed rat lung transplantation and investigated the late airway changes of the long-term surviving lung grafts: allografts, BN to Lewis; isografts, BN to BN rat. All recipients were treated with CsA. We found airway changes, i.e., mucosal ulceration, granulation, submucosal fibrosis, which was located in the large airways, in four of five allografted lungs. The lung isografts showed no pathological abnormalities. Immunopathological studies disclosed the localized expression of MHC class II antigens on the bronchial epithelium of the large airways where recipient type dendritic cells accumulated in the submucosa and CD4 positive predominant lymphocytes infiltrated. These findings support the idea that the late airway changes in lung transplants are caused by immunologically mediated chronic rejection.

A dose‐response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients

Mutations of the p53 tumor suppressor gene are frequent in lung cancers. It is suggested that p53 mutations are associated with smoking‐induced lung carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse transcription‐polymerase chain reaction‐single strand conformation polymorphism (RT‐PCR‐SSCP) to ascertain the association between p53 mutations and smoking. Twenty‐five (47%) of 53 lung cancers carried p53 mutations. A discriminant analysis showed that the Brinkman index (0.156) and gender (0.140) significantly influenced p53 mutations. Furthermore, there was a dose‐response relationship between the quantity of cigarettes consumed and the frequency of p53 mutations in lung cancer patients (P < 0.001). In patients with adenocarcinoma, the frequency of p53 mutations correlated with the amount of the tobacco smoked (P < 0.05). We suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

High frequency of p53 protein expression in thymic carcinoma but not in thymoma

Thymic epithelial tumours are broadly classified into thymomas and thymic carcinomas. Although both tumours occasionally show invasive growth, they exhibit different clinical and biological findings. The oncogene and anti-oncogene in thymic epithelial tumours have not been evaluated fully. We investigated the expression of p53 protein by immunohistochemical analysis using the anti-p53 polyclonal antibody (CM-1) in 17 thymomas and 19 thymic carcinomas. We also examined p53 gene (exon 5-8) mutation in 18 thymic carcinomas by using polymerase chain reaction-single-strand conformation polymorphism methods and direct sequencing. Of the thymoma cases, only one invasive thymoma showed focal nuclear staining. Fourteen of the 19 thymic carcinomas (74%) showed nuclear staining. Point mutations of the p53 gene were recognized in only 2 of the 18 thymic carcinomas (11%). One was the mutation C to T transition in the first letter of codon 222 in exon 6, which results in the amino acid substitution from proline to serine. Another was a silent mutation. p53 protein accumulation is highly frequent in thymic carcinomas but not in thymomas, and gene mutation is uncommon in thymic carcinomas.

Relationship between prognostic score and thyrotropin receptor (TSH-R) in papillary thyroid carcinoma: immunohistochemical detection of TSH-R

We have demonstrated the expression of thyrotropin receptor (TSH-R) in thyroid neoplasms (13 adenomas, 21 papillary carcinomas, two follicular carcinomas) and adjacent normal thyroid using the monoclonal antibody against human TSH-R and have also demonstrated a relationship between prognostic scores and the expression of TSH-R. Among the adenomas, eight showed an intensity similar to that of normal thyroid and five showed a higher intensity than normal. Two tumours exhibited heterogeneous distribution of TSH-R. Among the papillary carcinomas, seven showed similar intensity to normal tissue and four showed higher intensity and ten showed weaker intensity. Eight tumours showed heterogeneous distribution of the stain. Among the follicular carcinomas, one showed similar intensity to normal tissue and the other exhibited weaker intensity. Both cases showed homogeneous distribution of TSH-R. The adenomas never showed a weaker intensity than normal thyroid, but various intensities of TSH-R occurred in differentiated carcinomas. There was no significant relationship between the clinical data and the signal intensity in the adenomas. Among the papillary carcinomas, however, the group with weaker intensity had significantly poorer prognostic scores than the other two groups. Thus, we assume that low TSH-R may be expressed by the clinically high-risk group of patients with papillary thyroid carcinoma.

Pleuropulmonary Blastoma: Fluorescence In Situ Hybridization Analysis Indicating Trisomy 2

We report a case of pleuropulmonary blastoma occurring in the right upper lobe and pleura of a 29-month-old boy. Histologically, the tumor was composed of undifferentiated mesenchymal cells with occasional rhabdomyoblastic and chondroid differentiation. Immunohistochemical analysis showed vimentin immunoreactivity in most of the tumor cells, myoglobin, desmin, and actin in the rhabdoid cells, and S-100 protein in the chondroid cells. Fluorescence in situ hybridization (FISH) analysis showed trisomy 2 and normal chromosomal copy numbers for chromosomes 7, 12, 17, 18, and X in the majority of the tumor cell nuclei. The identification of trisomy 2 in the current pleuropulmonary blastoma confirms a previous cytogenetic finding of chromosome 2 abnormality with cultured metaphase cells of a similar case, indicating that the acquisition of an additional chromosome 2 copy in pleuropulmonary blastoma is a nonrandom chromosomal alteration and that pleuropulmonary blastoma is cytogenetically distinct from pulmonary blastoma in which chromosome 2 is bisomic. It is also suggested that pleuropulmonary blastoma may have an intimate tumorigenetic relationship with embryonal rhabdomyosarcoma.

Extrathymic malignancy in patients with myasthenia gravis

The presence of extrathymic malignancies was investigated in 296 thymectomised myasthenia gravis (MG) cases. In 5 of the 296 cases, extrathymic malignant tumours were observed. 4 of the 5 cases had thymomatous MG. 3 cases had malignant fibrous histiocytoma. Extrathymic malignancies were observed more frequently in thymomatous MG than in non-thymomatous MG. 59 cases (60 tumours), including our 5 cases, who had MG and extrathymic malignant tumours were compiled from the literature. In the 60 extrathymic malignancies, leukaemia and reticulo-endothelial sarcoma were the most frequent types.

Pulmonary varices: A case report and review of the literature

A case of a 47-year-old woman with pulmonary varix is reported herein. Saccular dilatation of the inferior pulmonary vein resembled a pulmonary perihilar mass which could not be palpated at the time of thoracotomy. Aneurysmal dilatation of the pulmonary vein, otherwise known as pulmonary varix, is rare. Only 71 such cases, including 17 cases in Japan, have been reported. Pulmonary varices may be classified into three types, namely: saccular type, tortuous type and confluent type. Most of the varices seen in patients with valvular disease have been of the confluent type (62 per cent), however tortuous type varices have also been seen in some cases (19 per cent). Pulmonary venous hypertension may be one of the major causes of confluent type pulmonary varices as regression of pulmonary varices after mitral valve replacement has been reported. None of the saccular type cases, however, were accompanied by valvular disease. This indicates that local factors may also be an important cause of saccular type varices.

Value of mass screening for thyroid cancer.

Abstract. This study aims to clarify the presently uncertain value of mass screening for thyroid cancer, which has been performed by physical examination along with mass screening for breast cancer in Zentsuji, Japan since 1983. Among 18,619 subjects, 36 individuals with thyroid cancer (0.19%) were found. The detection rate was 0.40% at the initial screening and 0.10% during subsequent periodic screening. All thyroid cancers were confirmed histologically as well differentiated carcinoma. The tumor size in the mass-screening group (14 ± 6 mm) was significantly smaller than in patients presenting at an outpatient clinic during the same period (19 ± 13 mm) (p < 0.05). The incidence of nodal metastases in the mass-screening group (38%) was significantly lower than in the outpatient group (68%) (p < 0.05). Thus mass screening seemed to find thyroid cancers in a relatively early stage. Mass screening for thyroid cancer was economic in this instance because it was performed together with screening for other cancers, such as breast cancer. Thyroid cancer screening required less than one additional minute per subject. The ultimate aim of mass screening is to reduce mortality. No improvement in prognosis from enforced mass screening for thyroid cancer was detected in this study. It cannot be demonstrated that there is sufficient value of mass screening for thyroid cancer to perform it independently despite early cancer detection.

Mutations in the P53 tumour suppressor gene in primary lung cancer in Japan

The reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis and sequencing were used to examine p53 gene alterations in 18 surgical specimens of primary lung cancers obtained in Japan. Somatic mutations resulting in amino acid changes were found in eight of the 18 cases (44%). Seven missense mutations were located in amino acid-conserved domains or their vicinities (codons 110 to 307). Most mutations were found at G-C pairs, suggesting that specific carcinogens are involved in the etiology of lung cancer. The p53 mutations showed a significant association with a history of smoking (P = 0.0294). We suggest that the p53 mutations may be associated with smoking-induced lung carcinogenesis.