Honeycomb-like tubular structure in axoplasm

Summary A honeycomb-like tubular array was observed in heavily myelinated axons. It was observed in the cerebellum of an apparently normal rat and a chimpanzee with Kurulike symptoms. It was also found in the cerebral cortex of a mouse that had had a intracerebral tumor implant. A common underlying etiology could not be found. It is suggested, however, that this structure represents a specific axonal response to perhaps a variety of as yet unknown conditions.This work was done during the tenur of United States Public Health Service, National Cancer Institute, Special Fellowship Award No. IF3-CA-31, 147-Ol.     

Catecholaminergic neurons in the parabrachial nucleus of normal individuals and patients with idiopathic parkinson's disease

The parabrachial nucleus is believed to play a role in autonomic regulation. We have used the Fontana-Masson ammoniacal silver nitrate method and a tyrosine hydroxylase–immunostaining technique to demonstrate the presence of neuromelanin-containing catecholaminergic neurons in the parabrachial nucleus of normal individuals. In addition, we also show that there is a significant reduction of these catecholaminergic neurons and presence of Lewy bodies in the parabrachial nucleus of patients with idiopathic Parkinson's disease. These findings may be related to the several autonomic disturbances that may occur in idiopathic Parkinson's disease.     

Induction of IL-1 beta-converting enzyme-independent apoptosis by IL-2 in human T cell lines

Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-OmI expressing endogenously three subunits, i.e. alpha, beta and gamma chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous alpha and gamma chains and exogenous beta chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1 beta-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant beta chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor beta chain, which are essential but not critical for IL-2- mediated cell growth respectively. Collectively, IL-2 functions not only on growth promotion and prevention of apoptosis but also on induction of apoptosis, which may be implicated in physiological regulation of immune reactions by controlling growth and activation of T cells.      

Some effects of intracerebral lead implantation in the rat

Pellets of lead acetate were implanted into the forebrains of adult rats which were sacrificed at intervals between 4 days and 4 weeks thereafter. Parenchymal necrosis and a number of reactive changes including edema and macrophage invasion were observed. Lead deposits were found in the extracellular spaces and within macrophages but only to a slight extent within glial or meningeal cells. Vascular changes were quite remarkable and included proliferation and the appearance of fenestrated blood vessels as well as some with tubular bodies and striking increases in the number of pinocytotic vesicles.     

Prognostic significance of combined expression of MUC1 and adhesion molecules in advanced gastric cancer

The objective of the present study was to evaluate the combination of MUC1 and the status of adhesion molecules in advanced gastric cancers as a possible predictor of patient survival. Two hundred and two paraffin-embedded specimens of gastric carcinoma were examined by immunohistochemical staining using monoclonal antibodies against MUC1 mucin, E-cadherin and beta-catenin. The expression of MUC1 was considered positive if at least 10% of the neoplastic cells were stained. E-cadherin and beta-catenin were classified into four groups. Only a membranous pattern, which was stained as strongly as normal epithelial cells, was judged as normal. The absent pattern (loss of staining), cytoplasmic pattern (cytoplasmic staining with loss of membranous expression), and heterogeneous pattern (cytoplasmic staining with preservation of membranous expression) were considered abnormal. There was a significant relationship between MUC1-positive expression and abnormal expression of E-cadherin (P=0.017). The cancer with abnormal E-cadherin expression or MUC1-positive expression increased, indicating that the cancer invasion was deep. Survival analysis of the outcome revealed that the survival time for those with abnormal E-cadherin/MUC1-positive expression was shorter than for those with other expression patterns. Multivariate analysis revealed that patients with abnormal E-cadherin/MUC1-positive expression had a poorer prognosis with significance (P<0.0001). In conclusion, abnormal E-cadherin/MUC1-positive expression pattern in advanced gastric cancer is an independent unfavorable prognostic marker.     

A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in patients with gastric carcinoma

In order to determine the in vivo characteristics of huA33, an open label dose escalation biopsy-based phase I clinical trial and radioimmunolocalization study were conducted with a complement determinant region-grafted humanized monoclonal antibody against the A33 antigen in patients with gastric carcinoma. Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0 mg/m(2)). Patients with locally advanced (UICC-TNM [International Union Against Cancer-tumor, node, metastasis] stage over 2 but resectable at clinical diagnosis) gastric carcinoma received a single infusion of (131)I-huA33 1 week prior to surgery. Adverse events were monitored, and imaging studies with gamma camera plus ex vivo scintigraphy of the resected specimen, biodistribution study by dosimetry analysis of the biopsied and resected tissues, and immunohistochemical analysis were carried out and evaluated. No dose-limiting toxicity was observed during the trial. Therefore, the maximum tolerated dose was not reached. Although cancer tissues with + intensity and <25% extent by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%) extent by frozen and paraffin sections in the biopsied specimen showed positive ex vivo tumor images and positive antigen expression in resected gastric cancer specimens, and the biodistribution analysis showed tumor uptake of (131)I-huA33. In conclusion, humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that expressed A33 antigen strongly. These excellent targeting characteristics of huA33 indicate potential for targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting.     

Fine structure of intercellular junctions and blood vessels in medulloblastomas

Summary Six medulloblastomas were studied by electron microscopy. Two features were found which seem to be constant and essential characteristics of medulloblastoma. First, cell junctions are abundant between tumor cells. These are mostly desmosome-like but other, closer junctions, were also seen. Second, the capillary endothelia contain frequent tubular bodies and other inclusions which may be related to them.     

Matrilsin expression is a useful marker of submucosal invasion and lymph node metastasis in early stage signet ring cell carcinoma of the stomach

BACKGROUND: Matrilysin (MMP-7) is considered to play an important role in tumor progression and metastasis. The aim of this study was to examine the MMP-7 expression of early-stage undifferentiated gastric carcinoma, and to investigate differences between gastric signet ring cell (SIG) and other undifferentiated carcinomas (non-SIG). METHODS: Immunohistochemical staining of MMP-7 was performed using specimens from 150 patients with early-stage gastric undifferentiated carcinomas (76 SIG, 74 non-SIG). RESULTS: SIG had a larger proportion of mucosal-confined carcinoma and a lower rate of lymphatic invasion than non-SIG (P < 0.05). The incidence of the positive expression of MMP-7 in submucosal SIG was significantly higher than that of mucosal SIG (P < 0.01). In contrast, MMP-7 expression was frequently found in mucosal non-SIG, suggesting an apparent difference in the invasiveness between mucosal SIG and non-SIG. The larger the size of the mucosal SIG, the more frequently MMP-7 positive expression was demonstrated (P < 0.05). There was a significant correlation between MMP-7 positive expression and lymph node metastasis of early SIG (P < 0.05). CONCLUSION: Early SIG revealed less invasiveness than non-SIG in terms of clinicopathologic features and MMP-7 expression. Preoperative estimation of the MMP-7 expression might be useful as a predictor of submucosal invasion and lymph node metastasis in early SIG.