Late detection of supraclinoid carotid artery aneurysm after traumatic subarachnoid hemorrhage and occlusion of the ipsilateral cervical internal carotid artery.

BACKGROUND AND PURPOSE: We report the first case of traumatic aneurysm of the supraclinoid internal carotid artery (ICA), which we speculate may have developed or grown after traumatic occlusion of the ipsilateral cervical ICA. CASE DESCRIPTION: A 26-year-old man presented with severe traumatic subarachnoid hemorrhage (SAH) and occlusion of the right cervical ICA after a motor vehicle accident. Three-dimensional CT angiography on admission showed no aneurysm. However, cerebral angiography 3 weeks after the injury showed a large aneurysm of the right supraclinoid ICA. The aneurysm was trapped, and pathological examination showed that it was a traumatic aneurysm. CONCLUSIONS: In this case we cannot be sure that the aneurysm was not present on admission. In view of the significant SAH, a lesson of this case may be to suspect such an aneurysm early on and perform early diagnostic cerebral angiography.

Enhancement of diphtheria toxin-induced apoptosis in Vero cells by combination treatment with brefeldin A and okadaic acid.

In the present study, we compared the abilities of ricin and diphtheria toxin to induce apoptosis in Vero cells. The cytolysis and DNA fragmentation by ricin paralleled its protein synthesis inhibitory activity. However, unlike ricin, diphtheria toxin could induce neither cytolysis nor DNA fragmentation in Vero cells up to very high concentration, in spite of the fact that Vero cells were even more sensitive to protein synthesis inhibition by diphtheria toxin than ricin. Interestingly, coexistence of brefeldin A (BFA) and okadaic acid (OA) significantly enhanced diphtheria toxin-mediated cytolysis and DNA fragmentation without affecting the activity of protein synthesis inhibition. Ammonium chloride almost completely abolished the ability of diphtheria toxin to induce apoptosis in the presence of BFA and OA as well as the protein synthesis inhibitory activity. The mutant CRM 197, which does not catalyze the ADP ribosylation of elongation factor-2 (EF-2), failed to induce apoptosis in Vero cells even in the presence of BFA and OA. Thus, translocation of diphtheria toxin into the cytosol and subsequent enzymatic inactivation of EF-2 may be necessary steps to induce apoptosis. Taken together our results suggest that protein synthesis inhibition by toxins is not sufficient to induce apoptosis, and underlying mechanisms of apoptosis induction may be distinct between ricin and diphtheria toxin. Since a morphological change in the Golgi complex was observed in Vero cells treated with BFA and OA, modulation of the Golgi complex by these reagents may be partly responsible for enhanced apoptosis induction by diphtheria toxin.

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.

Essential role of polyamines in restoration of DNA synthesis after UV radiation and expression of UV resistance in Cockayne syndrome cells.

Activity of ornithine decarboxylase (ODC) in Cockayne syndrome (CS) cells which were characterized by a delay of the recovery of DNA synthesis after 254 nm ultraviolet light (UV) radiation was extremely inhibited by UV, followed by a progressive decrease of putrescine. When putrescine was added in the cultures, CS cells showed a rapid recovery in DNA synthesis and also an expression of UV-resistance as seen in normal cells. Thus, ODC induction system of CS cells is highly sensitive to UV. Considering current hot spots in DNA repair, our results probably reflect a defect of preferentially rapid repair in ODC gene of CS cells.

Characteristics of human hepatocellular carcinoma cell lines (Hep-KANO) derived from a non-hepatitic, non-cirrhotic hepatitis B virus carrier.

We have established two cell lines of hepatocellular carcinoma [Hep-KANO, clone 1 (CL-1) and clone 2 (CL-2)] from tissue obtained at autopsy of a hepatitis B virus (HBV) carrier without histological signs of hepatitis or liver cirrhosis. These cell lines differed considerably from each other in morphology, proliferation pattern, alpha-fetoprotein secretion, albumin synthesis, cytokine secretion, modal chromosome number and transplantability to nude mice. Histologic examinations also revealed differences between them. Amplification of N-myc, L-myc, H-ras, K-ras, N-ras, c-erb-B and c-erb-B-2 and rearrangement of p53 were not found in either of the cell lines. However, CL-1 and CL-2 showed an identical HBV-DNA integration pattern. A 4-fold amplification of c-myc was observed in CL-1, but not in CL-2. Hep-KANO cell lines, CL-1 and CL-2 may be useful in clarifying the question of whether hepatocarcinogenesis is directly caused by HBV infection.

Tenascin expression and postnatal development of the human prostate.

We investigated the distribution of tenascin during postnatal development of the human prostate. Monoclonal antibody specific to human tenascin was applied to paraffin sections by the avidin-biotin-complex method to examine its localization. Infantile prostates showed two distinct zones. The inner zone had sparse acini with fibromuscular bundles. The peripheral zone had similar acini and lighter stroma as compared with inner zone. Tenascin was found diffusely but weakly. The periglandular area occasionally showed immunoreactivity. The prostates from 9- to 13-year-old subjects had a morphology similar to that of the infantile gland. The difference was increased density of the acini. Immunoreactivity was low. In the prostates from 14- to 21-year-old subjects, the acini distribution was more crowded, and the epithelial lining had become taller in both zones. Tenascin distributed preferentially in the peripheral zone during this period. Simultaneously, the percent of glandular area in the peripheral zone rose abruptly. The dynamics of tenascin expression are closely associated with the development and maturation of the gland. The distribution of tenascin during the post-puberal period may suggest its participation in the preferential of prostatic carcinoma in the peripheral zone.

The frequency of latent prostatic carcinoma in young males: the Japanese experience.

Prostates obtained at autopsy from five different ethnic groups were serially step-sectioned and examined microscopically using identical techniques and diagnostic criteria. The groups consisted of African-American and white males from the United States of America, Japanese immigrants in Hawaii, and Japanese men in Japan. The prostates were collected between 1965 and 1979. The fifth group consisted of newly collected prostates from indigenous Japanese between 1982 and 1986. The frequency of latent prostatic carcinoma from men under 50 years of age was compared to each other and with those from men over 50 years of age. Latent carcinoma was not found in men between 30 and 39 years old in any groups except indigenous Japanese men (6%) who died from 1982 to 1986. The frequency of latent carcinoma in the patients in fifth decade varied from 0 to 20%. Latent tumor was not found in the African-Americans in the fifth decade. There was an age-dependent increase in prostate cancer in all groups. The Japanese prostates from 1982 to 1986 had a higher rate of latent cancer than the ones from 1965 to 1979 in each decade. International comparison of the latent prostatic carcinoma from the patients under 50 years of age showed similar tendency as those from over 50 years old, Japanese men had a marked increase in the frequency of latent prostate cancer from 1965-1979 to 1982-1986. These data suggest that the prevalence of prostate cancer may be increasing worldwide.

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.

Identification of a P-glycoprotein-related protein (mini-P-glycoprotein) which is overexpressed in multidrug resistant cells.

Drug resistant variant cell lines were selected in vitro for resistance to adriamycin or vincristine, P388/ADR and P388/VCR-600, respectively, from P388 murine leukemia cells. These cells were demonstrated by immunoblot studies with P-glycoprotein specific monoclonal antibody (C219) to overexpress not only P-glycoprotein but also approximately 65 kDa protein, and the expression levels were found to correlate with the degree of resistance. Furthermore, in Northern blot analysis with an MDR1 cDNA as a probe, an overexpressed transcript with the length of about 2.4 kilobases which might encode this previously uncharacterized protein was also detected in the multidrug resistant cell line. Thus, it is suggested that this protein might be associated with multidrug resistant phenotype and be related to P-glycoprotein.

Mucous gland metaplasia of the prostate.

Mucous gland metaplasia of the prostate was observed in 11 of the 1,236 autopsy cases. The cells were characterized by plump cytoplasmic mucin and tiny nuclei that were basally oriented. They resembled Cowper's gland (bulbourethral gland) epithelium. The lesion was located randomly within the glands and was very small; only one was larger than 1 mm2. The cytoplasmic mucin was periodic-acid Schiff positive and immunohistochemically negative for prostate-specific antigen. Lectin binding profiles were different from those of normal prostatic glandular epithelium and also from those of Cowper's gland. The importance of recognizing mucous metaplasia lies in its differentiation from other lesions, especially from low-grade carcinoma.

Wischnevsky's gastric lesions in accidental hypothermia.

We examine the pathogenesis of Wischnevsky's 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 degrees C); gastric lesions did not always reflect exposure temperatures. However, all victims exposed to temperatures greater than 10 degrees C had severe lesions. At temperatures less than 5 degrees 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 body's response to cold stress continues, or as result of a strong 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.

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. Immunoreactive 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.

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.

Disseminated mycobacterial infection in a hemophilia B patient with acquired immunodeficiency syndrome.

Disseminated mycobacterial infection was found at autopsy in a male patient with hemophilia B and acquired immunodeficiency syndrome (AIDS). In May 1986, 23 months before death, the patient had encephalitis for one month and in July he developed a fever, malaise and generalized lymphoadenopathy. Human immunosuppressive virus (HIV) was positive and the CD 4/8 ratio of lymphocyte surface markers was 0.1, but mycobacterium was not detected. In September 1986, he had severe dyspnea due to interstitial pneumonia and he was treated with high-dose methylprednisolone. He died after a 23-month course of fever, severe weight loss and terminal progressive deterioration, although he was treated with antibiotics, antifungal agents, gamma-globulin, steroid and a Azidothymidine.

Melorheostosis of the toe: a case report.

A case of melorheostosis in a 57-year-old Japanese woman is presented. This case is noteworthy because of its unusual radiographic features and local findings and its unusually long follow-up period of more than 29 years. Melorheostosis progresses very slowly over a long period of time, and can show bizarre features, simulating malignant tumor.

Latent prostatic carcinoma: pathological and epidemiological aspects.

In conclusion, a review of the epidemiology and pathology of latent prostatic cancer suggests this tumor to be the probable initial phase of a biological continuum that ends with metastatic cancer. Histological grade and tumor volume are highly correlated, as are histological grade and mitotic index. It has also been suggested that atypical intraductal hyperplasia is, in turn, a precursor of carcinoma. This concept gains support from the close association of the two conditions among younger (less than 60 years of age) patients and from their similar mitotic and labeling indices.

Trends in frequency of latent prostate carcinoma in Japan from 1965-1979 to 1982-1986.

By analyzing serial step-sections of whole prostate obtained at autopsy, we determined the chronologic change of the frequency of latent prostate tumor in Japan in two periods: 1965-1979 and 1982-1986. Methods of specimen preparation and examination were identical for both periods. The frequency with which latent prostate carcinoma was found in the 660 samples for 1982-1986 was 34.6% and was significantly higher than the 22.5% seen in the 576 observed for 1965-1979 (P less than .0001). This significant finding can be attributed to an increase in the frequency of latent infiltrative tumor (LIT). However, the increase in the frequency of noninfiltrative tumor (LNT) was less significant (P = .045). Both sets of specimens were subsequently combined and reanalyzed according to the year of birth of the decedents. The LIT has progressively increased in frequency in each age-specific category. By morphometry, we determined that the mean tumor volume decreased due to an increase in the number of smaller tumors during the study periods. Although the frequency of latent prostate carcinoma and the LIT:LNT in the samples obtained most recently were comparable to those of U.S. whites, cancer incidence and mortality rates remain lower in Japan. Apparently, the initial step in the induction of prostate carcinoma in indigenous Japanese is now similar to that in U.S. whites. The rates of clinical carcinoma in Japan are still low when compared with those in the United States and countries in Western Europe, but our findings may presage a time when these differences may be greatly reduced or nonexistent.