Assessment of proliferating cell nuclear antigen immunostaining in parotid tumors

We evaluated the prognostic value of immunostaining proliferating cell nuclear antigen (PCNA) by using a monoclonal antibody (PC10) in patients with parotid tumors. Twenty-seven cases were studied. Immunohistochemical studies were carried out on paraffin-embedded tissues from the patients, and the PCNA index was calculated as the percentage of positively staining tumor cells. The PCNA index ranged from 0.1 to 65.3%. We divided the 27 lesions into three groups histologically: group A with benign pleomorphic tumors (11 cases), group B with low-grade malignant tumors (5 cases), and group C with high-grade malignant tumors (11 cases). The mean PCNA index was 0.7% in group A, 2.0% in group B, and 23.1% in group C. The clinical data revealed a significantly higher local tumor recurrence and mortality rate in group C than in groups A and B. We conclude that PCNA may be used as an important indicator for determining clinical prognosis in parotid tumors. Received: 26 July 1997 / Accepted: 28 October 1997     

CSF phosphorylated tau protein and mild cognitive impairment: a prospective study

Cerebrospinal fluid (CSF) tau protein phosphorylated at both Thr231 and Ser235 sites (CSF/phospho-tau(231-235)) and total tau (CSF/total-tau) were quantified by sandwich ELISA in 20 patients with mild cognitive impairment (MCI) who eventually developed AD on follow-up as well as seven memory complainers with no objective memory loss. 13/20 (65%) of the MCI patients had high CSF/total-tau and detectable levels of CSF/phospho-tau(231-235), whereas these markers were low and under a detectable level in all of the memory complainers. Although either a total-tau, phospho-tau measurement or a combination of these can help in predicting if MCI will develop AD, our results suggest that the pathogenic steps of AD may be at the stage that finally leads to an accumulation of abnormally phosphorylated tau and neuron death, at least in some brain areas, when MCI patients present with the earliest detectable clinical symptoms of dementia.     

Depression of long term potentiation in gerbil hippocampus following postischemic hypothermia

To investigate the mechanism of chronic cell death following postischemic hypothermia, the change of N-methyl- -aspartate receptor (NMDAR) were examined by immunohistochemistry of NMDAR1 and long-term potentiation (LTP) in the CA1 subfield of the gerbil hippocampus. At 1 week following postischemic hypothermia (32°C×4 h), all CA1 neurons survived; however, immunoreactivity of NMDAR1 increased in neuronal perikarya whereas decreased in dendrites in the CA1 neurons. The abnormality was still observed in remaining CA1 neurons at 1 month after hypothermia. LTP was also significantly depressed at 1 week after hypothermia. These results suggest that some abnormalities in the glutamate receptor may be caused by ischemia; such abnormality would persist in spite of hypothermia treatment, resulting in the depression of LTP.     

Veno-venous bypass to prevent myocardial ischemia during right heart bypass operation in PA, IVS, and RV dependent coronary circulation

There is a risk of myocardial ischemia in patients with pulmonary atresia and intact ventricular septum associated with right ventricle dependent coronary circulation, especially during open heart operation. Cardiopulmonary bypass unloads the right ventricle, and thereby reduces the coronary perfusion pressure in an area that is wholly or partly dependent on the right ventricle. We present a veno-venous bypass technique to keep the right ventricle beating and ejecting to supply the oxygenated blood into the right ventricle dependent myocardium and consequently to prevent myocardial ischemia during right heart bypass operation.     

Midline exposure of the thoracoabdominal aorta

Extended aortic replacement from the aortic arch to the descending thoracic or thoracoabdominal aorta has been performed through a left thoracotomy or a thoracoabdominal incision combined with or without a median sternotomy. However, a left thoracotomy incision may be unfavorable when dense adhesion of the lung is anticipated. We report a redo patient who underwent simultaneous replacements of the aortic arch and the thoracoabdominal aorta through a midline incision without entering the left pleural cavity.     

Label‐free multiphoton excitation imaging as a promising diagnostic tool for breast cancer

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two‐dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging‐based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near‐infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label‐free MPM imaging is a promising method for the real‐time automatic diagnosis of breast cancer.     

Hepatoma-derived growth factor as a prognostic marker in completely resected non-small-cell lung cancer

Hepatoma-derived growth factor (HDGF), unrelated to hepatocyte growth factor, is a heparin-binding protein originally purified from human hepatoma HuH-7 cells. HDGF exhibits mitogenic activities for certain hepatoma cells, fibroblasts and vascular smooth muscle cells, and angiogenic activities through nuclear targeting. Recently, HDGF was found to be a mitogen for lung epithelial cells in vitro and in vivo. This suggests that HDGF may play a critical role in the development and progression of lung cancer. We investigated, immunohistochemically, the relationship between HDGF expression and clinicopathological variables, and the prognostic significance of HDGF in 102 patients with completely resected non-small-cell lung cancer (NSCLC: 70 adenocarcinomas and 32 squamous cell carcinomas). To address the mechanism of action of HDGF, we evaluated the contribution of HDGF to tumor cell proliferation and intratumor angiogenesis using anti-Ki-67 and anti-CD31 antibodies, respectively. HDGF expression was strongly detected in the nucleus of cancer cells; the HDGF-labeling index (LI) was 20-95% (median 64.5%). There was no significant association between HDGF-expression level and clinicopathological variables. Patients with NSCLC showing a high HDGF-LI (> or =65%) had significantly worse overall and disease-free survivals than those with NSCLC showing a low HDGF-LI. Multivariate analysis revealed that HDGF is a significant independent prognostic factor, more powerful than pathological stage. Moreover, HDGF expression correlated with Ki-67-LI and intratumor microvessel density. We consider HDGF as a useful prognostic marker for patients with completely resected NSCLC and it may play a critical role in the pathobiology of lung cancer through its mitogenic and angiogenic activities.