The involvement of the neuronal Golgi apparatus and trans-Golgi network in the human olivary hypertrophy

We studied the Golgi apparatus (GA) and trans-Golgi network (TGN) in the human olivary hypertrophy by immunohistological methods with organelle specific antibodies against the medial cisternae of the organelle (MG160) and the trans-Golgi network (TGN46). The GA and TGN of enlarged neurons in the inferior olivary nuclei in the early stages after central tract lesions lost the normal network-like configuration, and they were reduced to numerous small disconnected granules (fragmentation). In chronic stages after lesions, the GA and TGN of vacuolated or enlarged neurons showed a variety of morphological profiles, such as normal-looking patterns, fragmentation, reduction in number, and aggregation around nuclei or at a distance in the cytoplasm. In patients with multiple system atrophy, the GA and TGN of the neurons in the inferior olivary nuclei showed almost similar findings to those seen in the chronic stages after brainstem lesions. These results suggest that the GA and TGN are affected in degenerating neurons by anterograde transneuronal mechanisms.     

Surgical treatments for 7 pituitary adenomas in multiple endocrine neoplasia type 1

We analyzed 7 pituitary adenomas in patients with multiple endocrine neoplasia type 1 (MEN1). Their incidence was 1.6% among 450 patients with pituitary adenomas which had been treated surgically in our department between 1978 and 1999. The age, gender, symptoms, type of hormone secretion, pathological and operative findings in the MEN1 patients were not apparently different from those in the non-MEN1 patients. Incidence of non-functioning pituitary adenomas, however, was more frequently encountered in our series than that in previous reports among Caucasian people. One patient who had 5 previous operations for the MEN tumors died following postoperative subarachnoid hemorrhage. Four of the seven patients presented initial symptoms related to pituitary adenomas and increased serum Ca level was retrospectively recognized in three of the four at the time of treatment for the pituitary adenomas.     

Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed.Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2′-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-¹⁰B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-¹⁰B (BPA), the tumors were irradiated with neutrons, or those without ¹⁰B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency).Results: Without ¹⁰B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With ¹⁰B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons.Conclusion: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.     

Regression of a presumed meningioma with the antiestrogen agent mepitiostane. Case report

This 68-year-old woman underwent a distal gastrectomy for gastric cancer in August 1994. A presumed meningioma of the falx was found incidentally on a staging examination of the gastric cancer, but the meningioma was not treated with surgery. Instead, after gastrectomy the patient received tegafur as adjuvant chemotherapy until February 1996, when she was readmitted to the hospital because of loss of appetite and emaciation but with no recurrence of the gastric cancer. A computerized tomography scan obtained during this second admission showed no change in the meningioma. To improve her general condition, tegafur was discontinued and she was started on a course of the antiestrogen agent mepitiostane. Administration of mepitiostane for approximately 2 years resulted in a marked regression (73%) of the meningioma. This is the first reported case of a presumed meningioma that regressed as a result of use of the antiestrogen agent mepitiostane.     

Characterization of mouse Ire1 alpha: cloning, mRNA localization in the brain and functional analysis in a neural cell line

In yeast, an endoplasmic reticulum (ER)-associated protein, Ire1p, is believed to initiate the unfolded protein response (UPR), that is responsible for protein folding in the ER under stressed conditions. Two mammalian homologs of Ire1p have been identified, Ire1 alpha and Ire1 beta. We have previously reported that familial Alzheimer's disease linked presenilin-1 variants downregulate the signaling pathway of the UPR by affecting the phosphorylation of Ire1 alpha. In the present study, we cloned the mouse homolog of Ire1 alpha for generating genetically modified mice. Ire1 alpha was ubiquitously expressed in all mouse tissues examined, and was expressed preferentially in neuronal cells in mouse brain. This led us to investigate the effects of the downregulation of the UPR on the survival of neuronal cells under conditions of ER stress. Morphological and biochemical studies using a dominant-negative form of mouse Ire1 alpha have revealed that cell death caused by ER stress can be attributed to apoptosis, and that the downregulation of the UPR enhances the apoptotic process in the mouse neuroblastoma cell line, Neuro2a. Our results indicate that genetically modified mice such as transgenic mice with a dominant-negative form of Ire1 alpha might provide further understanding of the pathogenic mechanisms of Alzheimer's disease and other neurodegenerative disorders.     

Mini mid-line skin incision--a more cosmetic challenge for surgery of funnel chest: report of a case

We performed a operation using a mini mid-line skin incision for ten-year-old male with funnel chest. The skin incision was made from the level of nipple to the lower end of the xiphoid process. He had sternal elevation as corrective surgery. There was no complication and he discharged at 11th day after surgery. We believe our method is more appropriate in fulfilling the cosmetic needs for the patient of funnel chest.