Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer

Although estrogen is known to play a crucial role in the pathogenesis of breast cancer, the molecular mechanisms underlying the action of estrogen remain elusive. In the present study, we focused on keratinocyte growth factor (KGF) and its receptor (KGFR) in the pathogenesis of breast cancer, as a growth factor mediating estrogen action, since significant roles of KGF were demonstrated in various steroid hormone-dependent tissues. First, using paraffin-embedded specimens from 42 breast cancer patients, we examined expression patterns of KGF and KGFR by both immunohistochemistry using newly generated antibodies and nonradioactive in situ hybridization with T-T dimerized synthetic oligonucleotide probes. We next compared the results with the expression of estrogen receptor (ER) alpha and beta, proliferative activity and apoptotic frequency (TUNEL staining). Also, the similar approaches were taken to analyze the expression and role of KGF in ER-positive (MCF7, ZR-75-1) and ER-negative (SK-BR-3, MDA-MB-231) human breast cancer cell lines in vitro. In the surgical specimens, KGF was expressed in cancer cells as well as stromal cells in 19/42 cases (45%), while KGFR was found in cancer cells in 24/42 cases (57%). The distribution of protein and mRNA in the analysis of both KGF and KGFR expression generally coincided. Moreover, KGF expression was closely associated with the expression of ER alpha, and the coexpression of KGF and KGFR significantly correlated with lower TUNEL index, but not with proliferative activity. In accordance with the in vivo findings, KGF expression was detected only in ER alpha-positive MCF7 and ZR-75-1 cells in vitro. And more importantly, we found the inhibitory effect of KGF upon the induction of apoptosis by anticancer drugs in MCF7 cells. Collectively, our results indicate that ER alpha may be involved in KGF expression, and that KGF may play antiapoptotic roles, rather than mitogenic, in human breast cancer.     

Cleveland clinic CorAide blood pump circulatory support without anticoagulation

The Cleveland Clinic CorAide left ventricular assist system consists of a permanently implantable centrifugal pump in which the rotating assembly is completely suspended and noncontacting. A series of chronic animal in vivo studies were conducted to evaluate the biologic effects of CorAide circulatory support without the use of anticoagulation therapy. The CorAide pump was implanted in six calves (five calves for 21 to 32 days and one calf for 95 days). The first five calves received intravenous heparin during the early postoperative periods (2-7 days). Heparin administration was then discontinued and no other anticoagulant drugs were used for the duration of the experiments. The last calf did not receive any anticoagulant except for a bolus dose of heparin (200 U/kg) during surgery. Hemodynamics were stable in all six calves, with a mean pump flow of 5.6+/-1.2 L/min and mean arterial pressure of 100+/-4 mm Hg. The blood pump surfaces were clean of thrombus in all six calves. Significant findings at autopsy were limited to one case of renal infarction. There was no incidence of mechanical failure, bleeding, or device infection. The CorAide pump can be safely run with minimal or no anticoagulant therapy.     

Sustained interleukin-6 signalling leads to the development of lymphoid organ-like structures in the lung

A variety of pathological changes are seen in lymphoproliferative disorders of the lung but the histogenesis of these abnormalities is not yet fully understood. We previously showed that adenovirus vector-mediated transient expression of both the human interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes, but not the IL-6 gene alone, in the rat lung induced lymphocytic alveolitis. In the present study, we explored the lung pathology of human IL-6 and IL-6R double transgenic mice to elucidate the effects of prolonged IL-6 signalling on the lung. The transgenic animals developed mononuclear cell accumulation in peribronchovascular regions, but little infiltration into alveolar spaces. Immunohistochemical analysis revealed that the cellular accumulations contained not only mixtures of inflammatory cells but also lymphoid tissue-like structures. As the expression of CXCL13/BLC, the indispensable chemokine for lymphoid organogenesis, was recognized in the B cell follicles of the pulmonary lesions, we speculate that this chemokine plays an inductive role in the development of the lymphoid tissue-like structures. These structures were distinguished from bronchus-associated lymphoid tissues (BALTs) by their location and by the lack of lymphoepithelium, which is a characteristic of BALT. These findings imply that IL-6 signalling may play a role in the pathogenesis of lymphoproliferative disorders of the lung.     

Validation of ECRHS Questionnaire in Japanese to use for nation-wide prevalence study of adult asthma]

PURPOSE: To enable international comparison of prevalence in asthma, we translated and evaluated ECRHS Questionnaire, which is introduced in GINA. Considering COPD prevalence in elder people, we added two questions to the ECRHS Questionnaire. METHOD: The Japanese edition of ECRHS Questionnaire was responded by 366 patients who were diagnosed asthma without COPD, 61 patients who were diagnosed COPD without asthma, and 137 healthy persons who were not diagnosed asthma or COPD. We analyzed the answers of the each group and evaluated the validity of the questionnaire to use for the nation-wide prevalence study of adult asthma in future. RESULTS: The question of 'Wheezing at any time in the last 12 months' had the highest Youden's index and validity to pick up asthma patients. The questions of 'Waking up with a feeling of tightness in chest at any time in the last 12 months' and 'Waking up by an attack of shortness of breath at any time in the last 12 month' had the highest specificity to pick up asthma patients. Most of the questions which were related asthma were able to be answered by asthma patients properly, but some questions were improperly answered by patients and healthy persons in elderly. The results in this study showed the less recognition of their diseases in elderly patients than younger patients and the limitation of the study with written questionnaire for elderly people. Not a few COPD patients complained wheezing or whistling in the chests as same as asthma patients in this study. CONCLUSION: We concluded that we had almost enough reliability in the Japanese edition of the ECRHS questionnaire for screening survey of asthma prevalence in Japan.     

Direct evidence for preferential multiplication ofBabesia gibsoni in young erythrocytes

To clarify the effect of the age of host erythrocytes on the multiplication ofBabesia parasites,B. gibsoni was cultured together with reticulocytes, immature erythrocytes, or mature erythrocytes from dogs. Parasitemia reached peak levels (34.1%±15.8%) at cultivation day 8 in immature-erythrocyte culture, whereas the highest parasitemia attained in mature-cell culture was only 3.6%±2.2% at day 5. These results clearly demonstrate thatB. gibsoni parasites preferentially invade and multiply in young erythrocytes rather than in mature cells.     

F-waves of the facial muscles in healthy control subjects and in patients with peripheral facial nerve disturbance

F-waves were recorded from the mentalis muscles with surface electrodes following stimulation of the marginal mandibular branch of the facial nerve in healthy control subjects during wakefulness, non-REM (rapid eye movement) sleep and voluntary contraction and in patients with Bell's palsy and acoustic neurinoma. The F-wave of the facial muscles results from the backfiring of antidromically activated alpha motoneurons in the facial motonucleus. Therefore, first, the F-waves were not easily elicited in patients with any disturbance in the proximal segment of the facial nerve (Bell's palsy and acoustic neurinoma). Second, the F-waves were affected by excitability of the facial motonucleus; the F-waves were inhibited significantly during sleep and enhanced significantly during voluntary contraction compared with those at rest during wakefulness. When the stimulation strength was set submaximum for M-waves, F-waves were elicited but H-waves, which have lower threshold than M-waves, were not elicited in the facial muscles, unlike the case of the extremities. Measurement of the F-waves of facial muscles is a new method for estimating excitability of the facial motonucleus unless there is any disturbance of the proximal segment. Fundamental characteristics of the facial F-waves were shown in the present study and measuring facial F-waves is clinically applicable for investigation of both excitability of the facial motonucleus and facial peripheral nerve disturbance.     

NECROSIS OF PORTAL TUMOR EMBOLUS OF HEPATOCELLULAR CARCINOMA BY LIPIODOL TRANSCATHETER CHEMO-EMBOLIZATION. A Case Report

We describe a case of hepatocellular carcinoma in which a tumor embolus in the portal vein and 3 of 4 intrahepatic metastases were necrosed completely by Lipiodol transcatheter chemo-embolization (Lipiodol-TCE). Tumor emboli in the portal vein and intrahepatic metastases usually cannot be necrosed by conventional transcatheter chemo-embolization alone, because small nodules such as intrahepatic metastases and tumor emboli in the portal vein are supplied blood from the portal vein. However, in this case, Lipiodol-TCE was effective against tumor emboli in the portal vein and intrahepatic metastases. ACTA PATHOL JPN 38: 1363-1367, 1988.     

CARCINOID TUMOR OF THE MIDDLE EAR: An Immunohistochemical and Electron Microscopic Study Report of a Case

A primary tumor of the middle ear was examined histologically, histochemi-cally, immunohistochemically and ultrastructurally. Neuroendocrine cell differentiation, a carcinoid feature, was demonstrated by the presence of numerous argyrophil granules, as well as positive serotonin, glicentin, glucagon, and human pancreatic polypeptide (hPP) granules in some of the Grimelium-positive cells. Chromogranin A was also detected in the cells, but much less frequently than Grimelius-positive staining. Neither neuron-specific enolase (NSE) nor epithelial membrane antigen (EMA) was demonstrated in the tumor. Mucin was demonstrated only intraluminally. Electron microscopy revealed many typical neurosecretory granules in tumor cells, but no apical mucin granules. The tumor appeared to be benign, and there has been no sign of recurrence during a postoperative period of one year. ACTA PATHOL JPN38: 1453–1460, 1988.