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Biomedical subjects

M Higashiyama

Publications and source records attributed to M Higashiyama.

At least 145 records · Page 8Linked to original sources

Extramammary Paget's disease of the bronchial epithelium.

We report the first case, to our knowledge, of extramammary Paget's disease of the bronchial epithelium. The tumor displayed Paget's cells scattered within the bronchial epithelium in most of the lesion, but infiltrating into the bronchial submucosa and pulmonary parenchyma with microglandular and papillary patterns in some area. In addition to the histologic findings of coexistence with adenocarcinomatous components, in situ involvement into bronchial glands and ducts by Paget's cells was observed, suggesting that extramammary Paget's disease of the bronchial epithelium may be a variant of pulmonary adenocarcinoma, which is associated with bronchial glands.

Aged↗

[Skeletal alterations associated with long-term etretinate therapy].

Radiographic skeletal examinations were performed in sixteen adult patients who had received etretinate therapy for various keratinizing disorders (psoriasis vulgaris 13, pustular psoriasis 2, pustulosis palmoplantaris 1) over periods ranging from 0.7 to 4.5 years. The total dose of etretinate ranged from 5.1 to 36.5 g. In these patients, the frequency and the degree of skeletal alterations including hyperostosis, calcification of ligaments and periosteal thickening was found to be higher than that in age- and -sex matched, nontreated controls. Furthermore, almost all of these patients were asymptomatic and revealed no abnormalities in laboratory data, including levels of serum calcium, inorganic phosphate and alkaline phosphatase. It is necessary for patients who are undergoing long-term etretinate therapy to be examined regularly for such skeletal abnormalities.

Adult↗

Surgical management of lung metastases. Usefulness of resection with the neodymium:yttrium-aluminum-garnet laser with median sternotomy.

Between May 1969 and September 1989, 677 metastatic lesions were resected during 107 operations in 100 patients with pulmonary metastases from various primary sites at the Center for Adult Diseases, Osaka, Japan. Of those patients, 65 underwent conventional lateral thoracotomy, and 35 patients had median sternotomy. No significant difference existed in actuarial survival after the first operation to remove the metastases between the two patients groups. Furthermore, local excision of 418 lesions was performed in 25 patients with the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Of those, 18 patients had undergone a one-stage operation for bilateral lesions through a median sternotomy approach. Although our study was not randomized, survival of the 25 patients treated with the Nd:YAG laser tends to be longer than survival of the 75 patients for whom the Nd:YAG laser was not used. We concluded that aggressive excision and evaporation of multiple lung metastases with the Nd:YAG laser under median sternotomy is a safe and promising variation in technique and that this approach will expand the scope of surgical indications for metastatic lung tumors. For a clearer demonstration of the influence of differences in surgical techniques on long-term survival it is necessary to conduct randomized prospective studies of the surgical techniques.

Adolescent↗

[Clinicopathological study of small adenocarcinoma of the lung].

Until December, 1987, a total of 55 cases of small primary adenocarcinoma of the lung (2 cm or less in diameter) were surgically treated in our department. Resected specimens were classified into three groups; 18 advanced cases (Stage III, IV), 22 early cases (Stage I) without recurrence, and 10 early cases (Stage I) with recurrence after surgery. Histopathologically, in advanced cases, lymphatic invasion, mitosis and cellular atypia were more frequently noted than in early cases. Fibrotic scar, which meant long-term existence of cancer, and vessel invasion were more frequently found in early cases with recurrence than in early cases without recurrence. The postoperative survival was largely dependent on distant metastasis via vessel invasion in advanced cases as well as early cases with recurrence. Mediatinal recurrence often occurred even in early cases with marked lymphatic invasion.

Adenocarcinoma↗

Expression of pancreatic secretory trypsin inhibitor gene in human colorectal tumor.

Expression of pancreatic secretory trypsin inhibitor (PSTI) gene was examined by Northern blotting analyses in 31 human colorectal tumors that included two benign adenomas and 26 adenocarcinomas. Among the total of 28 cases which proved to be adequate for mRNA analyses, all but one showed the expression of PSTI at various levels. In contrast, PSTI expression was not detected in two malignant lymphomas of the rectum. The level of PSTI expression was not correlated with the patient's age, sex, tumor location or size, stage of differentiation, lymph node metastasis, or progression stage. Some colorectal adenocarcinomas were also shown to express genes that can hybridize with human trypsinogen cDNA probe. It looks as though in these tumors, a protease(s) and its inhibitor are produced simultaneously as part of a cellular self-defense mechanism.

Adenocarcinoma↗

The effect of heparin on multiple organ failure and disseminated intravascular coagulation in a sepsis model.

In order to elucidate a possible role of hypercoagulability leading to disseminated intravascular coagulation (DIC) in the pathogenesis of multiple organ failure (MOF), unfractionated heparin and the related agents were administered to septic rabbits which manifest DIC and MOF. Administration of heparin resulted in prevention of thrombocytopenia, leukopenia and elevation of plasma bilirubin and creatinine. The morphological hepatic damage was also ameliorated by heparin. Similar favorable effects were obtained by the administration of low molecular weight heparin. Dextran sulfate prevented the hepatic damage to some extent without improvement on other parameters. No significant effect was observed by the administration of a synthetic thrombin inhibitor (MD805). These results indicate that the favorable effect of heparin is due to its anticoagulant property, especially anti-Xa activity. Thereby, it is concluded that the hypercoagulable state leading to DIC is a prerequisite for the occurrence of MOF in sepsis.

Animals↗

Expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer.

We examined the expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer by immunohistochemical staining using an anti-PSTI antiserum, an in situ hybridisation technique utilising sulphonated PSTI cDNA probe, and a Northern blot hybridisation method, using a 32P-labelled PSTI cDNA probe. Immunohistochemically, PSTI was detected in 80 of 95 (84%) colorectal cancer cases. Analyses with in situ hybridisation as well as Northern blot hybridisation demonstrated PSTI mRNAs in immunohistochemically positive cases, showing PSTI could be produced in colorectal cancerous cells. Histologically well or moderately differentiated adenocarcinoma showed higher incidence of PSTI immunoreactivity than the other types. Furthermore, the intensity of the immunohistochemical staining for PSTI increased the more cases advanced, particularly in regard to depth of invasion and tumour size. Thus, PSTI expression is widespread in colorectal cancer, and occurs more commonly in advanced cases. Considering the suggestion that PSTI is a growth-stimulating factor as an well as inhibitor to proteolytic proteinase, the present findings may indicate that PSTI expressed in colorectal cancerous cells may play a role possibly closely associated with tumour development.

Adult↗

Immunohistochemical study on pancreatic secretory trypsin inhibitor (PSTI) in gastric carcinomas.

The expression of pancreatic secretory trypsin inhibitor (PSTI) was studied immunohistochemically in 106 cases of gastric carcinoma. Of the 45 intestinal-type carcinomas, 34 cases (76%) expressed PSTI: 15 (63%) of 24 early carcinomas and 19 (90%) of 21 advanced carcinomas, the incidence being significantly different (P less than 0.05). Furthermore, in the intestinal-type carcinomas, a significant correlation was observed between PSTI expression and clinical stage or nodal involvement. On the other hand, of the 61 diffuse-type carcinomas, including 27 early and 34 advanced carcinomas, 54 cases (89%) were positive for PSTI; a high incidence of the PSTI expression was observed in both early and advanced carcinomas, being 93% and 85%, respectively. Moreover, PSTI-positive cells were localized in more than half of the early diffuse-type gastric carcinomas at the invading zone of the surrounding tissues. The incidence of PSTI expression in advanced scirrhous-type carcinomas (100%) was significantly higher than that (76%) in medullary-type ones (P less than 0.05). Thus, the present findings, together with the previous reports that PSTI stimulates 3H-thymidine incorporation into DNA in human fibroblasts, suggest that the PSTI expressed in gastric carcinomas may possibly possess a biologic function responsible for the tumor growth and progression and for the stromal proliferation of fibrous tissues.

Adenocarcinoma↗

Growth-inhibitory effects of 1,25-dihydroxyvitamin D3 on normal and psoriatic keratinocytes.

The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the growth and DNA synthesis of cultured human keratinocytes obtained from involved and uninvolved psoriatic epidermis and normal epidermis were studied. Treatment with 10(-8) M and 10(-7) M of 1,25(OH)2D3 inhibited cell growth as follows: 58.5 +/- 19.3% and 21.3 +/- 13.6% in normal keratinocytes (n = 6); 43.8 +/- 22.8% and 17.8 +/- 12.3% in psoriatic uninvolved keratinocytes (n = 4); 51.7 +/- 18.2% and 13.2 +/- 6.4% in psoriatic involved keratinocytes (n = 6). Inhibition was virtually complete at 10(-6) M. DNA synthesis was also inhibited by 10(-8) M, 10(-7) M and 10(-6) M of 1,25(OH)2D3 as follows: 70.0 +/- 8.3%, 59.0 +/- 6.8% and 16.7 +/- 4.0%, respectively, in normal keratinocytes (n = 3); 78.5 +/- 13.5%, 51.5 +/- 25.5% and 24.5 +/- 21.5%, respectively, in psoriatic uninvolved keratinocytes (n = 2); and 69.3 +/- 14.5%, 41.3 +/- 19.1% and 14.8 +/- 11.2%, respectively, in psoriatic involved keratinocytes (n = 4). These results indicate that 1,25(OH)2D3 functions as a growth inhibitor for cultured human keratinocytes derived from both normal and psoriatic skin.

Calcitriol↗

[Problems concerning the diagnosis and treatment of multiple primary carcinoma of the lung].

Data on 44 patients with multiple primary carcinoma of the lung are presented. Twenty had metachronous tumors, and 24 had synchronous tumors. Twenty-one patients had undergone complete resection for both tumors, and 14 had undergone resection for only one of two tumors. The remaining 9 patients underwent no operation and were treated with photodynamic, radiation and/or chemotherapy. Long-term survival of more than 3 years was achieved for 11 patients, nine of whom had synchronous lesions. Furthermore, they included 3 patients who underwent nonsurgical therapy for both lesions. On the other hand, the prognosis after resection of the second tumor in patients with metachronous lesions was poor. This was thought to be the result of failure to diagnose the second lesion due to incomplete long-term follow-up. We conclude that careful attention to the operative indications is necessary for patients with multiple lesions, particularly lesions such as early squamous cell carcinomas.

Adenocarcinoma↗

Sepsis model with reproducible manifestations of multiple organ failure (MOF) and disseminated intravascular coagulation (DIC).

A new reproducible animal model of sepsis was established to investigate interrelationship between disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). Sepsis was induced by injecting fecal suspension into bile duct of rabbits, in which the amount of endotoxin in circulating blood was gradually increased and manifestations of sepsis were confirmed. During 9 hours' observation period, an occurrence of hypercoagulable state leading to DIC was evidenced by the abnormal hemostaseological parameters. Simultaneously the elevation of plasma bilirubin and creatinine levels was observed, indicating the presence of liver and kidney failure, which was confirmed by the histological examination. Thereby, the present sepsis model complicates DIC and MOF with high reproducibility, which is relevant to sepsis seen in clinical patients.

Animals↗

A novel type of human alpha-amylase produced in lung carcinoid tumor.

A novel type of alpha-amylase was detected in a lung carcinoid tissue after surveying the cDNA library constructed from this tumor mRNA. Nucleotide sequence analysis showed that the amylase expressed in this carcinoid tumor has 13 and 6 amino acid substitutions when compared with salivary amylase (Amy1) and pancreatic amylase (Amy2), respectively. The nucleotide sequence homologies of cDNAs between this carcinoid amylase and amy1, amy2 are 97.5% and 98.2%, respectively. The nucleotide sequence comparison strongly suggests that this new amylase is the product of the amy3 gene that has been detected in human genome [Emi et al., Gene 62 (1988) 229-235]

Amino Acid Sequence↗

A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient.

A human hybridoma clone (A4-33) was established by fusion of human lymphoblastoid cells, HO-323, with lymphocytes of axillary lymph nodes obtained from a breast cancer patient. This clone has been stable, producing IgM for over 24 months. Enzyme-linked immunosorbent assay (ELISA) showed that monoclonal antibody A4-33 reacted strongly to MCF-7, and weakly to PANC-1 and HT-29, but not to other human malignant cell lines. The reactivity of A4-33 to MCF-7 was markedly reduced by treatment with periodate, but not affected or enhanced by neuraminidase or trypsin. Immunoperoxidase staining of normal human tissue sections showed that A4-33 reacted to acinar and ductal cells of the mammary gland and to ductal epithelial cells of the salivary gland, sweat gland, pancreas and bile duct. With malignant tumor sections, A4-33 reacted to breast cancer, pancreatic cancer and parotid cancer. These results suggested that A4-33 recognized the antigen which commonly exists on ductal epithelial cells of the exocrine gland.

Antibodies, Monoclonal↗

Evaluation of dot-immunobinding assay for carcinoembryonic antigen determination in nipple discharge as an adjunct in the diagnosis of early breast cancer. Research Group for Carcinoembryonic Antigen in Nipple Discharge.

We have previously reported carcinoembryonic antigen (CEA) measurement in nipple discharge to be a useful adjunct in the diagnosis of non-palpable breast cancer. As an extension, a dot-immunobinding assay was developed to screen a large number of patients with nipple discharge for non-palpable breast cancer. The principle is as follows. CEA bound to a solid phase monoclonal anti-CEA antibody is detected by a second monoclonal anti-CEA antibody conjugated with horseradish peroxidase. The use of tetramethylbenzidine as a chromogen results in a stable color reaction that can be semiquantitively analyzed by the naked eye. The CEA levels determined by this dot assay correlated well with CEA levels determined using the former Elmotec assay. To determine whether or not the method could also be feasible in the detection of non-palpable breast cancer, a collaborative study from 12 Japanese institutes was organized. The CEA levels in nipple discharges from 155 patients were assayed. Thirteen of 30 patients with palpable breast cancer and 22 of 30 patients with non-palpable breast cancer exhibited CEA values higher than 400 ng/ml, a cut-off value determined using 89 benign controls. The specificity (91%) and sensitivity (73%) of this test were higher than those of mammography or cytology. The incidence of elevated CEA levels in nipple discharge correlated significantly with the incidence of intratumoral antigen expression. Thus, the system could prove useful in screening for early breast cancer.

Body Fluids↗

Tetrodotoxin in two species of ribbon worm (Nemertini), Lineus fuscoviridis and Tubulanus punctatus.

Extracts of two species of ribbon worm, Lineus fuscoviridis and Tubulanus punctatus, had lethal potencies in mice from 15-503 MU/g of worm and from less than 10-540 MU/g, respectively. The toxins were partially purified by ultrafiltration and column chromatography using Bio-Gel P-2 and Bio-Rex 70 (H+ form). Thin-layer chromatographic, high performance liquid chromatographic and gas chromatography-mass spectrometric analyses revealed the presence of tetrodotoxin and anhydrotetrodotoxin plus some unidentified compounds.

Animals↗

Use of sulfonated probes for in situ detection of amylase mRNA in formalin-fixed paraffin sections of human pancreas and submaxillary gland.

A sulfonated probe and its applicability to in situ hybridization is described and discussed. The DNA probes were modified by introducing an antigenic sulfone group into the cytidine residues of the denatured DNA (Budowsky EI, Sverdlov ED, Monastyrkaya GS: New method of selective and rapid modification of the cytidine residues. FEBS Lett 25:201, 1972). Hybridization of the sulfonated DNA with the target nucleic acid sequences was confirmed by an avidin-biotin peroxidase complex method using a monoclonal antibody specific to sulfonated DNA. The detection limit of this system was estimated to be about 1.25 pg of actual target sequences by dot blot hybridization analysis. When the sulfonated probes of human amylase cDNA were applied to in situ hybridization immunohistochemistry on formalin-fixed paraffin sections of the human pancreas and submaxillary gland, hybridization signals were clearly localized in the cytoplasm of the acinar cells of the pancreas, and in the serous cells of the submaxillary gland. Suitable probe lengths for in situ hybridization immunohistochemistry were between 100 and 800 bases. The in situ hybridization technique utilizing a sulfonated DNA probe is sensitive, simple, and easy to perform and applicable to studies of cell biology.

Amylases↗