Itsuo Kusano

Tenascin in tissue perturbation repair.

Tenascin is an extracellular matrix glycoprotein consisting of six disulfide‐linked subunits with molecular masses of 190‐250 kDa. The cDNAs of chicken, mouse and human tenascins were cloned and their amino acid sequences were determined. Molecular analysis of the tenascin gene revealed that it contains a region homologous to the fibrinogen gene, and repetitive sequences of the type III fibronectin and epidermal growth factor genes. Several isoforms of the tenascin gene as splicing variants have also been found. Culture studies have shown that tenascin has multiple functions including cell attachment and detachment, promotion and inhibition of neural crest cell migration, cell growth stimulation and hemagglutination. Immunohistochemistry of a variety of tissues, both normal and abnormal, from various animals has shown that the distribution of tenascin is characteristic, and spatially and chronologically restricted. lmmunoreactive tenascin was demonstrated in the dense mesenchyme present around growing epithelia during embryogenesis and oncogenesis. Besides its oncofetal expression, tenascin was also found in many tissues with inflammation such as healing wounds, regenerating tissue and irritated tissue. These findings suggest that tenascin probably functions as a homeostatic factor in the repair of tissue perturbation. Acta Pathol Jpn 41: 247‐258, 1991.

Rupture of a benign mediastinal teratoma into the right pleural cavity

A 27-year-old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid. The activity of the amylase is thought to be the most likely cause of the rupture. High levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors.

Demonstration of MDR1 P-glycoprotein isoform expression in benign and malignant human prostate cells by isoform-specific monoclonal antibodies

Prostate cancers are resistant to many anticancer agents at the time of presentation. P-glycoprotein (P-gp) is believed to mediate multidrug resistance phenotype. To elucidate the possible role of P-gp in such an intrinsic drug resistance of prostate cancers, its expression was examined immunohisochemically using two P-gp isoform-specific monoclonal antibodies (mAbs) with the paraffin embedded prostate samples derived from five nonmalignant and 30 untreated prostate cancer patients. In all of five normal prostate tissues, P-gp was consistently detected with both mAbs in the epithelial cells, especially at their apical site, and the level of expression was higher in the inner zone than in outer zone. On the other hand, tumor cells expressed P-gp heterogeneously in distribution and intensity; in 25 of 30 malignant cases P-gp expression was clearly demonstrated, whereas its expression was only faintly detected in other cases. However, the staining intensities for P-gp in prostate cancer cells were generally lower than in normal prostate epithelial cells. Thus, not only normal prostate epithelial cells but prostate cancer cells express at least MDR1 P-gp isoform. These results suggest that P-gp expression might play some role in intrinsic drug resistance of prostate cancer cells to many cytotoxic drugs as well as in relative resistance of the inner zone cells to the prostate carcinogenesis.

Wischnevsky's gastric lesions in accidental hypothermia.

We examine the pathogenesis of Wischnevskys lesions. These gastric lesions were found in 15 of 17 deaths due to accidental hypothermia. Deaths occurred at various minimum temperatures (-2.4–20.4 °C): gastric lesions did not always reflect exposure temperatures. However, all victims exposed to temperatures > 10°C had severe lesions. At temperatures < 5°C, on the other hand, severe gastric lesions were seen in victims younger (43.2 years old) than those with mild lesions (61.0 years old). These findings suggest that gastric lesions develop by exposure to temperatures at which the bodys response to short-term stress. Histopathologic examination demonstrated a characteristic finding of cystic dilatation of the capillaries, presumably due to massive reperfusion after functional collapse of the microcirculation in the gastric mucosa.

Cardiac rupture due to severe fatty infiltration in the right ventricular wall.

An extremely rare case of sudden death caused by cardiac rupture due to severe fatty infiltration in the right ventricular myocardium is presented. The patient, a 74-year-old woman, had no history of chest trauma, hypertension, or pulmonary disease. The autopsy showed a small tear in the right ventricle and cardiac tamponade, but no coronary artery lesion. In the right ventricular myocardium, muscle fibers were definitely atrophic or absent, with massive fatty replacement. Fatty infiltration of the myocardium, if severe, can be a cause of serious cardiac dysfunction or, occasionally, sudden death.

A case of allergic liver injury induced by tegafur.

A 51-year-old woman constitutionally susceptible to allergy presented with acute allergic liver injury. She was taking tegafur for treatment of carcinoma of the uterus. The acute liver injury appeared 3 weeks after the first drug administration. She had marked elevation of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT), moderate jaundice, and eosinophilia. The virus markers revealed hepatitis B surface antigen (HBsAg) (-) antibody to hepatitis B surface antigen (HBsAb) (+), and immunoglobulin M HA antibody (IgM HA Ab) (-). The laparoscopic and histologic findings were compatible with drug-induced liver injury. Further, the results of the lymphocyte stimulation test (LST) and challenge test by tegafur were positive. From the above findings, the liver injury was diagnosed to be an allergic reaction induced by tegafur. The hepatic function returned to normal about 20 days after tegafur administration was suspended. Allergic liver injury induced by tegafur is very rare. We report the case with a short review of the literature.

Case report 862

* This paper was presented at the 18th Annual Meeting of the Skeletal Society, San Diego, Calif., 1991 complain of left shoulder pain again, and came to Mie University Hospital. X-rays revealed a soap-bubble-like expansile change in the left humeral head (Fig. 1A). Laboratory findings were all within normal limits. En bloc resection of the lesion was performed on November 21, 1968 (Fig. 1B), and she remained disease-free for 13 years thereafter. At the beginning of September 1981 she returned to our hospital because shoulder pain on the opposite side. She had moderate tenderness in the right shoulder joint but the range of motion was normal. X-rays showed a eccentric, purely osteolytic lesion without any periosteal reaction in the right humeral head (Fig. 2A). No abnormality was found in the blood chemistry. She underwent curettage of the lesion, cryosurgery with liquid nitrogen and bone grafting on September 24, 1981. After surgery, she did well until the beginning of March 1983, when X-rays showed a new osteolytic lesion beneath the previously curetted area of the right humeral head (Fig. 2B). Curettage and bone grafting was performed again on April 28, 1983. In March of the next year the tumor relapsed again (Fig. 2C); no other lesions were found in the entire skeleton and or in either lung. On April 16, 1984, en bloc resection of the lesion was performed. Since then, the patient has been tumor-free up to now (Fig. 3).

DNA synthesis and hypersensitivity to ultraviolet radiation in Cockayne's syndrome cells

Abstract The present study deals with ultraviolet-light (uv) sensitivity and DNA repair as well as semiconservative DNA synthesis in Cockaynes syndrome (CS) cells in vitro . Homozygous CS cell lines were found to be more uv sensitive in colony-forming ability than normal human fibroblast cell lines. There was no difference in either excision repair or postreplication repair following uv irradiation when comparing CS cells with normal cells. Semiconservative DNA synthesis of both CS cells and normal cells was depressed to the same extent by uv irradiation. The subsequent recovery of CS cell lines, however, was reduced. This reduction in recovery appears to be caused by inhibition of replicon initiation following uv irradiation. These processes in the heterozygous CS cell line were indistinguishable from those of normal cells. These findings support the hypothesis that uv-induced chromatin alteration in no relation to well-known DNA repair processes persists longer in CS cells than in normal cells. This condition results in inhibition of replicon initiation.