Cell biological basis for combination radiotherapy using heavy-ion beams and high-energy X-rays.

We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray.     

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.     

Profiling of proteins phosphorylated or dephosphorylated during hyperactivation via activation on hamster spermatozoa

Background and Aims  It has been widely accepted that sperm hyperactivation is regulated by protein phosphorylations. But, the sperm hyperactivation phosphorylation pathway is not well understood yet because several different proteins have been detected in other studies. In order to understand the phosphorylation pathway that regulates hyperactivation, we established how to extract sperm protein completely and detected proteins that were phosphorylated during hyperactivation. Methods  Protein phosphorylation of hamster spermatozoa was detected by western blotting using antiphospho-amino acid monoclonal antibodies or the SELDI ProteinChip system with IMAC-Ga(III). Results  We detected 75 protein/peptide phosphoryations using the method established in the present study. Tyrosine phosphorylations occurred during hyperactivation. Serine or threonine phosphorylations occurred for 30 min. Furthermore, four of the serine or threonine phosphorations were phosphorylated by A-kinase. As for peptides, 15 peptides were dephosphorylated for 30 min. Other peptides were phosphorylated during hyperactivation. Conclusions  Because most of the proteins detected in the present study have been described previously, we could detect comprehensive protein phosphorylations. Moreover, we also detected many novel phosphopeptides. Although we did not understand the role of peptide, it was likely that motility was basically regulated by serine/threonine phosphorylations and hyperactivation was mainly regulated by tyrosine phosphorylations. (Reprod Med Biol 2006; 5: 123–135)     

Three-dimensional analysis of benign paroxysmal positional nystagmus in a patient with anterior semicircular canal variant.

OBJECTIVE: To show the positional nystagmus in a patient who had suffered from benign paroxysmal positional vertigo (BPPV) that was thought to be caused by involvement of the anterior semicircular canal (ASCC) (A-BPPV). STUDY DESIGN: Retrospective case report. SETTING: City hospital. PATIENT: The present study reports a rare case of A-BPPV in a 41-year-old woman. CASE REPORT: The patient is 41-year-old woman who developed a positional vertigo after playing volleyball on March 22, 2005 and consulted our hospital the next day. When left Dix-Hallpike maneuver was performed, she showed a positional nystagmus of which fast phase direction of the torsional component was clockwise while that of the vertical component was downward. We plotted the slow phase eye velocity of the positional nystagmus during the left Dix-Hallpike maneuver on three-dimensional coordinates that showed the axis of the positional nystagmus to be perpendicular to the plane of the right ASCC. CONCLUSION: These results suggested that the patient was suffering from A-BPPV.     

Third nerve palsy and serous retinal detachment with preeclampsia.

Visual disturbances occur more frequently during preeclampsia than during pregnancy in general, but visual disturbances due to cranial nerve palsy are rare. We present the case of a 35-year-old preeclamptic woman with left third nerve palsy and left serous retinal detachment. The patient complained of visual disturbance and double vision soon after cesarean section. Left third nerve palsy and left serous retinal detachment were diagnosed by urgent ophthalmologic evaluation. Aneurysm and organic brain lesion were ruled out by diagnostic imaging. By 2 months postpartum, the visual disturbance had improved spontaneously.     

Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence.

PURPOSE: To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection. PATIENTS AND METHODS: We sequenced exons 18-21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer. Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen (CEA) levels. RESULTS: EGFR mutations were found in 33 patients (56%). Of these mutations, 17 were deletions around codons 746-750 and 15 were point mutations (12 at codon 858, three at other codons), and one was an insertion. EGFR mutations were significantly more prevalent in females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor shrinkage and/or CEA decrease to less than half of the baseline level in 26 patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect was not assessable in nine patients. Female, never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was effective in 24 of 29 patients with EGFR mutations, compared with two of 21 patients without mutations (P < .0001). Of note, del746-750 might be superior to L858R mutations for prediction of gefitinib response. Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment (P = .0053). CONCLUSION: EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.     

Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma.

PURPOSE: In the present study, we investigated the degree of protein expression and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell lines and freshly isolated tumors, and trastuzumab-mediated biological activity, in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2-expressing esophageal SCC cell lines. EXPERIMENTAL DESIGN: Ten different SCC cell lines with various levels of HER-2 status evaluated by flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization were evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated by trastuzumab. RESULTS: Trastuzumab induced ADCC against HER-2-expressing esophageal SCC and the activities reflected the degree of HER-2 expression analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against transforming growth factor-beta-producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-beta. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2-expressing esophageal SCC. CONCLUSION: HER-2-expressing esophageal SCC cells could be killed by trastuzumab-mediated ADCC and the activity reflected the degree of HER-2 expression detected by flow cytometry.     

Hyperlipidemia as a risk factor for Trousseau syndrome-related cerebral infarction in patients with advanced gastrointestinal cancer

Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome-related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58–75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome-related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome-related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785-27.513). Trousseau syndrome-related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.     

T‐cell‐rich HLA‐haploidentical hematopoietic stem cell transplantation for relapsed/refractory pediatric Philadelphia chromosome‐positive acute lymphoblastic leukemia without posttransplant tyrosine kinase inhibitor therapy

Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph‐ALL). However, the prognosis of cases of relapsed or refractory Ph‐ALL remains poor. Here, we aimed to assess the efficacy of T‐cell‐rich HLA‐haploidentical hematopoietic stem cell transplantation (TCR‐haplo‐HSCT) in eight patients with relapsed or refractory pediatric Ph‐ALL. Transplant‐related mortality was observed in two patients. All patients discontinued TKI after receiving TCR‐haplo‐HSCT. The 3‐year probability of overall survival and event‐free survival was 75.0 and 62.5%, respectively. These results indicate the efficacy of TCR‐haplo‐HSCT for relapsed/refractory pediatric Ph‐ALL.     

The relationship between intraocular pressure and refractive error adjusting for age and central corneal thickness

PURPOSE: To investigate the relationship between intraocular pressure (IOP) and refractive errors after adjusting for age, central corneal thickness (CCT), and other related factors. METHODS: IOP, CCT and refractive errors were measured in the right eyes of 1855 subjects, aged 40-82 years, in a cross-sectional study design. Subjects were divided into groups by refractive status: hyperopia, emmetropia, mild myopia, moderate myopia, or high myopia. With adjustments for age, CCT, blood pressure, obesity, education, hypertension, diabetes, and smoking status, IOP was estimated for each refractive status using a general linear model. RESULTS: IOP increased with advancing degrees of myopia, even after adjustment for age, CCT, and other related factors (p = 0.011). Estimated IOP of moderate myopia was significantly higher than that of emmetropia (p = 0.022). CONCLUSIONS: Our results confirm the positive association between IOP and increasing degrees of myopia. This finding would support the hypothesis that the relationship between glaucoma and myopia might be pressure mediated.