Measurement of ion species in high current ECR H⁺/D⁺ ion source for IFMIF (International Fusion Materials Irradiation Facility).

Ion species ratio of high current positive hydrogen/deuterium ion beams extracted from an electron-cyclotron-resonance ion source for International Fusion Materials Irradiation Facility accelerator was measured by the Doppler shift Balmer-α line spectroscopy. The proton (H(+)) ratio at the middle of the low energy beam transport reached 80% at the hydrogen ion beam extraction of 100 keV/160 mA and the deuteron (D(+)) ratio reached 75% at the deuterium ion beam extraction of 100 keV/113 mA. It is found that the H(+) ratio measured by the spectroscopy gives lower than that derived from the phase-space diagram measured by an Allison scanner type emittance monitor. The H(+)/D(+) ratio estimated by the emittance monitor was more than 90% at those extraction currents.

Operation and commissioning of IFMIF (International Fusion Materials Irradiation Facility) LIPAc injector.

The objective of linear IFMIF prototype accelerator is to demonstrate 125 mA/CW deuterium ion beam acceleration up to 9 MeV. The injector has been developed in CEA Saclay and already demonstrated 140 mA/100 keV deuterium beam [R. Gobin et al., Rev. Sci. Instrum. 85, 02A918 (2014)]. The injector was disassembled and delivered to the International Fusion Energy Research Center in Rokkasho, Japan. After reassembling the injector, commissioning has started in 2014. Up to now, 100 keV/120 mA/CW hydrogen and 100 keV/90 mA/CW deuterium ion beams have been produced stably from a 10 mm diameter extraction aperture with a low beam emittance of 0.21 π mm mrad (rms, normalized). Neutron production by D-D reaction up to 2.4 × 10(9) n/s has been observed in the deuterium operation.

New technique of laparoscopic colectomy with the LAP DISC and a 5-mm flexible scope.

PURPOSE: We devised a new method for the safe introduction of the first trocar and induction of pneumoperitoneum for laparoscopic excision of the large intestine. METHODS: With this method, a small laparotomy is first conducted according to the size of the exposed affected intestinal tract or tumor size, prior to the application of a LAP DISC (LD) to the wound and introduction of a 12-mm trocar for the establishment of pneumoperitoneum. The method is advantageous in that organ injury and vessel injury are avoided when the small laparotomy is conducted first, and prompt transition to a conventional laparotomy is possible. The diaphragm of the iris bulb can be controlled in a non-stepwise manner. In addition, trocars, the stapler, and other instruments, can be inserted under the pneumoperitoneum. Furthermore, the use of a 5-mm flexible scope allows surgical maneuvers, except for application of LD, to be conducted via 5-mm trocars. In addition, the 5-mm scope can be inserted through any trocar, allowing multidirectional avoidance of dead space and intraperitoneal observation. When only 5-mm trocars are used, it is not necessary for the sites of trocar puncture to be closed by sutures, and this minimizes the risk of adhesions and port-site herniation. The method is also considered to be excellent from the point of view of esthetics. RESULTS: We employed this surgical approach in 50 patients with colorectal cancer at our hospital. None of the patients developed any traumatic complications associated with the insertion of trocars, and none of the patients, even those with a past history of abdominal operation, required conversion to conventional laparotomy. CONCLUSIONS: Based on these results, this method involving a small laparotomy prior to the application of an LD and introduction of a 12-mm trocar for establishing pneumoperitoneum, with the efficient use of a 5-mm flexible camera, is considered to be safe and useful for laparoscopic excision of the large intestine.

Long latency response in soleus muscle evoked by magnetic stimulation at the foramen magnum.

We performed magnetic stimulation at the level of foramen magnum in healthy subjects to evaluate the long latency response in lower limb muscle. Subjects assumed an upright stance and we recorded electromyographic activities in soleus muscle. A late response at the onset latency of approximately 40 ms was elicited. The late response wasn't induced in other lower limb muscles; anterior tibial muscle, quadriceps femoris muscle, and biceps femoris muscle. Additionally, magnetic stimulation to foot motor cortex, basal occiput and cervical nerve roots did not evoke the response with latency of 40 ms. These results reveal the late response in soleus muscle that has not been previously reported. We speculate that it is involved with the long-loop reflex.

Efficacy of imatinib mesylate (STI571) treatment for a patient with rheumatoid arthritis developing chronic myelogenous leukemia.

We report on an 80-year-old man with rheumatoid arthritis (RA) who presented with chronic myelogenous leukemia (CML). Five years after the onset of RA, the CML diagnosis was made. The patient was treated for CML with 300 mg of imatinib mesylate (STI; signal transduction inhibitor 571) for 8 weeks. Laboratory tests showed that the C-reactive protein level, percentage of cells exhibiting the Philadelphia chromosome (Ph1), WBC count, and Lansbury index for RA all dropped respectively from 7.5 mg/dl to 1.0 mg/dl, 74.9% to 1%, 25, 100/microl to 9900/microl, and 51% to 14%. Administration of imatinib mesylate is felt to be effective in treating not only CML but also RA in the active stage.

Transcranial magnetic stimulation over the cerebellum evokes late potential in the soleus muscle.

Transcranial magnetic stimulation (TMS) with a double cone coil placed over the left lateral side of the basal occiput was able to elicit late electromyographic (EMG) responses at the bilateral soleus muscles (SOL) averaged over 30 stimulation events, with a mean latency of approximately 100 ms. These EMG responses were detected using a low frequency bandpass filter with 0.05 Hz magnetic stimulation on ten healthy subjects in standing posture. As magnetic stimulation over the left basal occiput with a double cone coil can stimulate cerebellar structure, this late response seems to be conducted from the cerebellar structure to the SOL via an as yet unknown descending pathway. Here, we report new late EMG responses in relation to cerebellum or cerebellum related structures.

Three-dimensional reconstruction of colorectal tumors from serial tissue sections by computer graphics: a preliminary study.

BACKGROUND/AIMS: We present herein the three-dimensional reconstruction of colorectal tumors, with particular reference to growth pattern into each layer of the colorectal wall, and measurement of tumor volume and surface area. METHODOLOGY: Conventional tissue section images of colorectal tumors were analyzed using a computer graphics analysis program. The two-dimensional extent of invasion by each tumor into each layer of intestinal wall were determined from the images of each section. Based on data from multiple sections, tumor and surrounding normal tissue layers were reconstructed three-dimensionally, and volume and surface area of the tumors were determined. RESULTS: Using this technique, three-dimensional morphology of tumor and tumor progression into colorectal wall could be determined. Volume and surface area of the colon tumor were 4871 mm3 and 1741 mm2, respectively. Volume and surface area of the rectal tumor were 1090 mm3 and 877 mm2, respectively. CONCLUSIONS: This technique may provide a new approach for pathological analysis of colorectal carcinoma.

[A case of biloma caused by early complications of hepatic artery infusion chemotherapy].

We report a 70-year-old male who had biloma as an early complication of hepatic artery infusion chemotherapy. The patient had a history of subtotal gastrectomy for a advanced gastric cancer. Two years after the primary operation on the stomach, a solitary metastatic liver tumor was indicated by follow-up abdominal CT, and a segmental hepatectomy was performed. Soon after the hepatectomy, intraarterial catheter placement was performed via the left subclavian artery for preventive chemotherapy. Infusion chemotherapy of 10.5 g 5-FU and 75 mg CDDP was administered for a month, during which time the patient had liver dysfunction, fever, tenderness, and abdominal fullness. Abdominal CT revealed a large low density mass at a lateral segment of the liver which could not be seen on the previous CT image. Also, extravasation of contrast media was identified by angiography via the reservoir catheter. Using an interventional technique, percutaneous transhepatic drainage for biloma and extubation of the reservoir catheter were performed. The present case is thought to be of an early and rare complication of hepatic artery infusion chemotherapy. The etiology is discussed herein.

Expression of connexin 32 and 43 in developing rat submandibular salivary glands.

The expression of the gap-junction proteins connexin 32 and 43 in the developing rat submandibular gland was determined using reverse transcription-polymerase chain reaction and immunohistochemistry. Sprague-Dawley rats from the 17th gestational day through to the 28th postnatal day were used. Connexin 43 gene expression was detected on the 17th gestational day. Connexin 32 gene expression was also detected on the 17th gestational day but less intensely. Immunolabelling for connexin 43 was also found in the developing submandibular gland from the 17th gestational day. Prenatally the most immunoreactive areas for connexin 43 were located in the periphery of terminal tubules, but some staining was discernible between the cells in terminal buds. In the postnatal period, reactive areas were located at both the periphery of acinus-like structures and around the intercalated duct. This is consistent with the known association of connexin 43 with myoepithelial cells. Connexin 32 immunostaining was first detected in the developing submandibular glands on the 18th day of prenatal development. Positive staining was present on the lateral side of the proacinar and mature acinar cells. The number of immunoreactive areas per cell increased during early development followed by a significant decrease perinatally. During postnatal development the density of areas again showed a pattern of increase. These results suggest that connexin 43 is associated with growth and differentiation in the pre- and perinatal periods and also with the contractile function of myoepithelial cells in the postnatal period of the developing submandibular gland. It is also implied that the number of connexin 32-positive areas may correspond to an increase or decrease in the number of proacinar and mature acinar cells.

Melanoma antigen recognition by tumour-infiltrating T lymphocytes (TIL): effect of differential expression of melan-A/MART-1.

We have isolated, from an individual patient with metastatic melanoma, a series of eight TIL clones capable of lysing autologous melanoma cell targets. Six of the eight clones expressed TCRAV2S1 and lysed targets expressing HLA-A2 and the Melan-A/MART-1 peptide: AAGIGILTV. Polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis showed that the Melan-A/MART-1-specific clones were predominant in the bulk culture prior to cloning. However, the tumour progressed in vivo even in the presence of these tumour cell-lytic clones. Using the anti-Melan-A/MART-1 MoAb (A-103), we noted that Melan-A/MART-1 expression on three melanoma cell lines varied considerably during in vitro culture, in the absence of T cell immunoselection, relative to cell density. Tumour cells which spontaneously decreased Melan-A/MART-1 expression were less susceptible to specific TIL lysis. Melan-A/MART-1 expression and susceptibility to lysis increased in cells cultured at lower density. These data suggest that modulation of tumour antigen may account for tumour progression in the presence of tumour cell-lytic T lymphocytes. The observations suggest a possible explanation for the common finding of Melan-A/MART-1-specific lytic TIL in clinically progressing melanomas, as well as a possible pathway for therapeutic intervention.

A case of adenocarcinoma of the small intestine in a Japanese patient with Crohn disease: a report with immunohistochemical and oncogenic analyses.

We report a rare case of Crohn disease accompanied by a small-bowel carcinoma that developed in a 54-year-old Japanese man. The ulcerating tumor, which histologically proved to be a poorly differentiated adenocarcinoma and dysplasia surrounding the carcinoma, was located in the diseased ileum. The Ki-67 immunoreactive epithelial cells were increased in regenerative mucosa as compared with values for normal mucosa. The Ki-67- and p53-positive cells were increased in dysplasia and carcinoma as compared with values for regenerative or normal mucosa. In contrast, the p21(WAF1/CIP1) immunoreactive cells were decreased in this order. Intense DCC (deleted in colorectal cancer) expression was constantly shown among normal, regenerative, dysplastic and cancerous tissues. No bcl-2 expression and c-Ki-ras mutations were apparent. In conclusion, enhanced epithelial cell proliferation, p53 overexpression, and decrease of p21(WAF1/CIP1) expression may predispose the small-bowel mucosa to dysplasia and carcinoma development in Crohn disease.

Connexins in the developing salivary glands.

Freeze-fracture and immunohistochemistry were used to elucidate the ultrastructure of gap junctions and the expression of connexins (gap junction structural proteins) Cx32 and Cx43 in the developing rat submandibular glands. Developing rat submandibular glands were examined from the 17th gestational day to the 14th day after birth. Gap junctions could be observed as clusters of particles 9-12 nm in diameter during the gestational days. The junctions were very small and consisted of about 20 particles in a relatively regular arrangement with a wide center-to-center spacing of 15-18 nm on the PF face. Fluorescence spots reacting positively to Cx43 were found between glandular cells from the 17th gestational day. Very few spots positive to Cx32 could be detected during gestation, their numbers increasing after birth. The possibility that Cx32 may have a role in the establishment of secretory regulation and that Cx43 is associated before birth with glandular growth and differentiation is discussed.

Expression of beta-catenin in normal breast tissue and breast carcinoma: a comparative study with epithelial cadherin and alpha-catenin.

Expression of beta-catenin was investigated in normal breast tissue and 66 breast carcinomas in conjunction with expression of epithelial cadherin (E-CD) and alpha-catenin. In normal mammary ducts and acini, intense beta-catenin immunoreactivity was present at the basolateral surfaces of luminal epithelium and weak immunoreactivity was observed at the lateral borders of myoepithelial cells. No beta-catenin was revealed at the myoepithelial basal surface. The intercellular expression of beta-catenin, as well as of E-CD and alpha-catenin, was also observed in carcinoma tissues with varying staining intensity. Almost all of 10 intraductal carcinomas and approximately 70% of 41 invasive ductal carcinomas expressed the three molecules at the same level as in normal glands, whereas approximately 80% of 13 invasive lobular carcinomas showed severe deficiency of them. Two lobular carcinomas in situ showed complete absence of all of the proteins. Some of these findings were confirmed biochemically by immunoblotting analysis. In invasive ductal carcinomas, alpha-catenin was reduced more frequently in diffuse than in solid type tumours, whereas the level of expression of beta-catenin and E-CD was unchanged between them. No correlation was present between reduced expression of the adhesion molecules and lymph node metastasis.

Expression of epithelial cadherin and alpha- and beta-catenins in nontumoral livers and hepatocellular carcinomas.

Expression of the cell adhesion molecule, epithelial cadherin (E-CD) and its binding proteins, alpha- and beta-catenins, in normal liver, chronic liver diseases, and hepatocellular carcinomas (HCCs) was investigated immunohistologically. In normal liver, weak immunostaining of E-CD and catenins was observed at the lateral membranes of the hepatocytes, whereas at the interlobular bile duct epithelia, they stained strongly. No immunoreactions were seen in sinusoidal Kupffer cells. Similar results were observed in the majority of livers from chronic hepatitis and cirrhosis sufferers; however, hepatocytes undergoing regeneration and rosette formation, as well as Hering canals and proliferating ductules, showed markedly increased molecular expression. Analysis of 66 HCC lesions revealed that the majority (64.3-96.6%) of thin trabecular- and pseudoglandular-type tumors preserved or overexpressed E-CD and catenins, whereas thick trabecular-type HCCs frequently showed low E-CD and alpha-catenin expression (56.5-65.2% reduction), suggesting that the thick trabecular histology represented diffuse tumor cell growth. Likewise, the E-CD and catenin expression levels correlated with the HCC cell differentiation grades. These collective results indicate that intercellular adhesion mediated by the E-CD-catenin system plays a role in morphological changes in nonmalignant and malignant hepatic diseases.

Decreased L-selectin expression in CD34-positive cells from patients with chronic myelocytic leukaemia.

Abnormal adhesive interaction between bone marrow stroma and progenitors, one of the causes of unregulated proliferation in chronic myelocytic leukaemia (CML), may be caused by some alterations in adhesion molecules on CML progenitors. We investigated the expression of adhesion molecules (CD44, VLA-5, VLA-4, LFA-1, ICAM-1, L-selectin and c-kit) on bone marrow CD34++ cells from 16 CML patients by three-colour flow cytometry. The mean percentage of cells expressing L-selectin in the CD34++CD38+(or)++ fraction from untreated CML patients was significantly lower, and that in the CD34++CD38- fraction tended to be lower than that from normal controls. Among 11 CML patients treated with interferon-alpha (IFN-alpha), the mean percentage of the cells expressing L-selectin in the CD34++CD38- fraction from three patients with a low percentage of Ph1(+) cells in bone marrow was significantly higher than that from five patients with a high percentage of Ph1(+) cells. In addition, L-selectin expression rate was inversely correlated to the percentage of Ph1(+) cells. There was no significant difference between the untreated patients and normal controls with regard to the expression rates of the other adhesion molecules in each CD34++ fraction except LFA-1. These data suggest that decreased L-selectin expression in CML CD34++ cells reflects one of the features of malignant CML progenitors.

[Experience and problems with home parenteral nutrition for patients with peritonitis carcinomatosa].

Since 1987, we have been using home parenteral nutrition (HPN) for patients with peritonitis carcinomatosa, who had undergone surgery for cancer of the digestive tract and who could not take food orally. We have been inserted catheterization for HPN in 90 patients. Nine of them underwent the treatment as training, but HPN was possible in the remaining 81 patients (90%). The patients in whom the treatment failed to be transferred to HPN showed worsening of their general condition during hospitalization, because the period of training was long. As a result, they could not be discharge. We considered that the timing of transfer to HPN was inappropriate. The largest number of patients, 57, had undergone surgery for cancer of the stomach and esophagus, which was the underlying disease. The mean period of HPN was 108.2 days. According to the underlying disease, the period was longest, 115.7 days, for cancer of the stomach and esophagus, followed by 93.8 days for colorectal cancer. The performed rate of HPN for 60, 90, 180 and 270 days were 56.7, 36.0, 17.9 and 6.5%, respectively, with the one-year cumulative rate of 3.3%. HPN for terminal stage of cancer is an effective treatment for patients with peritonitis carcinomatosa, and it allowed improvement in the quality of life. Cooperation with various medical staff members is also necessary and a hospital system should be established for safe and smooth achievement of the treatment method.

[Effect of prophylactic intra-arterial infusion of anticancer drugs on post hepatic resection for hepatic metastasis of colorectal cancer].

Prophylactic intra-arterial infusion of anticancer drug on post hepatic resection for hepatic metastasis of colorectal carcinoma were performed 8 cases. In our cases consisted of 8 patients of mean age of 54.3 years (male 3 cases and female 5 cases, synchronous metastasis 4 cases and metachronous 4 cases). All patients were received intra-arterial bolus injection of MMC (4-8 mg/body) at day 1 and continuous infusion of 5-FU (250-750 mg/body) for 7 days on admission. After discharged, patients were received bolus injection of 5-FU (250-750 mg/body) for once a week. Side effect of this treatment was not appeared and all of them obtained very good QOL. There were no recurrence sign of residual liver and this procedure was very useful method for post hepatic resection for hepatic metastasis of colorectal cancer.

Immunotherapy for Stewart-Treves syndrome. Usefulness of intrapleural administration of tumor-infiltrating lymphocytes against massive pleural effusion caused by metastatic angiosarcoma.

We describe a 56-year-old woman with Stewart-Treves syndrome who had severe dyspnea from a pleural effusion caused by metastatic angiosarcoma in the right lung. Tumor-infiltrating lymphocytes (TIL) in the pleural effusion were cultured and expanded in vitro in the continuous presence of recombinant interleukin 2 with periodic stimulation by CD3 antibody. The expanded TIL were administered intrapleurally seven times at 1- to 4-week intervals in combination with intravenous infusion of recombinant interleukin 2. A panel of T-cell clones was also obtained from TIL. Immunotherapy dramatically improved the patient's dyspnea and pleural effusion. A CD4+ T-cell clone and a CD8+ T-cell clone established from TIL had specific cytotoxicity to the tumor cells.