Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Two cases of mesenteric panniculitis]

Two patients with mesenteric panniculitis are presented. In the first patient, a provisional diagnosis of ileus was made, based on the clinical features and imaging data. Laparotomic findings showed that the ileum was bound tightly by a fibrous strip and dilated, with thickened and swollen mesentery. Incision of the fibrous strip was performed, and the clinical symptoms were improved. The second patient was strongly suspected to have mesenteric panniculitis, from characteristic features on abdominal computed tomography and barium enema. Conservative therapy was effective in this case. We emphasize the variety of clinical courses in mesenteric panniculitis, requiring selection of the most suitable treatment.     

Allergic Predisposition Among Infants with Bronchiolitis

Allergic predisposition among infants with bronchiolitis was examined. The number of infants with serum IgE exceeding mean +1 SD was 31/70 (44.3%). The rate of positive radioallergosorbent test (RAST) scores of 1 or more to mites, egg white, or milk was 31/71 (43.7%) and that of scores over 2 was 11/71 (15.5%). Eosinophils and/or mast cells were found in their nasal smears on several occasions. These results indicated that allergic predisposition may be observed among infants with bronchiolitis.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Endocrine and hemodynamic responses to total body hyperthermia in humans

We investigated effects of total body hyperthermia (TBH) on endocrine and hemodynamic responses. A total of five treatments were performed in five patients with gastric cancer under neuroleptanesthesia with morphine followed by 0.2 to 0.4% enflurane. TBH was extracorporeally induced with veno-venous shunt incorporating with heat exchanger to keep their temperature between 41.5 degrees C and 42.0 degrees C for three hours. The patients were administered angiotensin to maintain tumor blood flow. Lactated Ringer's solution was administered at the rate of 10 to 15 ml.kg-1.hr-1 for five hours. Plasma cortisol levels decreased significantly to about one third of the control value after heating and the levels recovered to the control value after cooling. Plasma norepinephrine level increased significantly to about 7 to 9 times the control value following TBH, but this hormonal response was insufficient to reveal marked direct hemodynamic effects. The magnitude of fall in SVR was more significant in spite of the administration of angiotensin. Cardiac index increased significantly to about 2.0 to 2.6 fold of control value, but mean arterial blood pressure (MAP) decreased significantly to about two thirds to four fifths of the control value. Morphine relieved the hormonal response in ACTH and cortisol strongly, but morphine suppressed hemodynamics by decreasing SVR. Neither norepinephrine released from sympathetic nerve endings nor even 50 to 200 ng.kg-1.min-1 of angiotensin administered failed to restore SVR or MAP during hyperthermia.     

“Chain-link” combined tissue transfer for the reconstruction of the mandible

We describe a procedure for “chain-link” combined tissue transfer connecting the vascular pedicle of a deep circumflex iliac flap with that of a forearm flap after wide resection of the mandible. Combination of these flaps facilitated the reconstruction of the defect in both intra- and extraoral soft tissue and the mandibular bone. This method is useful when cervical recipient blood vessels are limited due to the wide resection of the primary tumor and radical neck dissection.     

Bleeding from foveolar hyperplasia developing on a gastrointestinal stromal tumor of the stomach

A 52‐year‐old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia.     

Lidocaine Increases Intracellular Sodium Concentration through Voltage-dependent Sodium Channels in an Identified Lymnaea Neuron

Background: The local anesthetic lidocaine affects neuronal excitability in the central nervous system; however, the mechanisms of such action remain unclear. The intracellular sodium concentration ([Na+]i) and sodium currents (INa) are related to membrane potential and excitability. Using an identifiable respiratory pacemaker neuron from Lymnaea stagnalis, the authors sought to determine whether lidocaine changes [Na+]i and membrane potential and whether INa is related to these changes.

Methods: Intracellular recording and sodium imaging were used simultaneously to measure membrane potentials and [Na+]i, respectively. Measurements for [Na+]i were made in normal, high-Na+, and Na+-free salines, with membrane hyperpolarization, and with tetrodotoxin pretreatment trials. Furthermore, changes of INa were measured by whole cell patch clamp configuration.

Results: Lidocaine increased [Na+]i in a dose-dependent manner concurrent with a depolarization of the membrane potential. In the presence of high-Na+ saline, [Na+]i increased and the membrane potential was depolarized; the addition of lidocaine further increased [Na+]i, and the membrane potential was further depolarized. In Na+-free saline or in the presence of tetrodotoxin, lidocaine did not change [Na+]i. Similarly, hyperpolarization of the membrane by current injections also prevented the lidocaine-induced increase of [Na+]i. In the patch clamp configuration, membrane depolarization by lidocaine led to an inward sodium influx. A persistent reduction in membrane potential, resulting from lidocaine, brings the cell within the window current of INa where sodium channel activation occurs.     

Detailed Analysis of Mucosal Restoration of the Small Intestine After the Cavitary Two-Layer Cold Storage Method

Small bowel transplantation (SBT) is associated with a high incidence of infectious complications because of ischemia/reperfusion (I/R) mucosal injury concomitant with potent immunosuppression. In this study, we evaluated whether the cavitary two-layer method (cTLM) could reduce I/R injury and allow early mucosal restoration, particularly after prolonged preservation and transplantation. Canine heterotopic segmental SBT was performed immediately without preservation (group 1), after 24-h preservation in UW solution (group 2) or by the cTLM (group 3). The graft samples were taken 1 h after reperfusion and on days 1, 4 and 7. We assessed graft mucosa with detailed microscopic and electromicroscopic analyses. In Group 3, histological injury and cell apoptosis after transplantation were significantly alleviated and rapidly recovered to a similar level of group 1. The mucosal restoration was morphologically completed within 4 days. In contrast, in group 2, more pronounced mucosal injury and delayed recovery were noted. Crypt cell proliferation activity was well maintained in groups 1 and 3 throughout the experimental period. Our ultrastructural analysis suggested that mitochondrial integrity achieved by the cTLM was a basal mechanism under the prompt mucosal restoration. The cTLM could reduce I/R injury, facilitate mucosal regeneration and restore the nearly normal structure early after SBT.