NEMO mutation as a cause of familial occurrence of Behçet's disease in female patients.

Behçet's disease is a chronic, relapsing, multisystem inflammatory disease of unknown etiology. Nuclear factor κB (NF-κB) essential modulator (NEMO) that is required for the activation of NF-κB plays an important role in inflammation. To investigate the role of NEMO in the pathogenesis of Behçet's disease, we analyzed NEMO gene and its expression pattern in tissues in a family with Behçet's disease. We found a heterozygous mutation (1217A> T, D406V) in a 6-year-old girl and her mother. Skewed X-chromosome inactivation was not observed in the peripheral blood mononuclear cells as well as in oral and intestinal mucosa of the patients. Accordingly, there was a significant proportion of peripheral blood monocytes that did not produce sufficient intracellular tumor necrosis factor-α with the stimulation of lipopolysaccharide. Heterozygous NEMO mutation is a cause of familial occurrence of Behçet's disease in female patients.

Mutated SEA-D227A-conjugated antibodies greatly enhance antitumor activity against MUC1-expressing bile duct carcinoma.

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we have directed our attention to superantigens (SAgs), the most potent known activators of T lymphocytes. In our previous study, staphylococcal enterotoxin A (SEA) was conjugated chemically with MUSE11 mAb, which recognizes the MUC1 cancer-associated antigen, and shown to enhance the specific cytotoxic activity of T-LAK cells against MUC1-expressing BDC cells (TFK-1) in vitro and in vivo. However, it is probable that SEA might cause side-effects because of nonspecific binding to class II positive cells. In order to overcome these, we generated mutated SEA (mSEA) by changing Asp at position 227 of native SEA to Ala, which has reduced affinity to MHC class II molecules, but retains the potential for T cell activation. When mSEA-D227A was administered to rabbits to examine effects on blood pressure, 500 times more mSEA-D227A was tolerated than native SEA. This prompted us to construct a mSEA-D227A-conjugated mAb, reactive with MUC1. It augmented the antitumor activity of T-LAK cells significantly, and furthermore, mSEA-D227A could be conjugated to two bispecific antibodies, BsAb (anti-MUC1 x anti-CD3) and BsAb (anti-MUC1 x anti-CD28), which in combination had greater enhancing effects than mSEA-D227A-conjugated anti-MUC1 mAb, and combination of unconjugated BsAbs. These findings indicate a utility of mSEA-D227A-conjugated antibodies for targeted cancer immunotherapy.

Specific targeting immunotherapy of cancer with bispecific antibodies.

In order to enhance cell mediated cytotoxicity, bispecific antibodies (BsAbs), molecules combining two or more antibodies with different antigenic specificities, have been developed as new agents for immunotherapy. Our recent studies revealed that simultaneous administration of two kinds of BsAbs (anti-tumor x anti-CD3 plus anti-tumor x anti-CD28) together with lymphokine activated killer cells with a T cell phenotype (T-LAK cells) inhibited growth of human xenotransplanted tumors in severe combined immunodeficient (SCID) mice, while single BsAb was without effect. Three kinds of BsAbs (anti-tumor x anti-CD3, anti-tumor x anti-CD28, anti-tumor x anti-CD2) showed the highest cytotoxicity against tumor cells when given simultaneously with T-LAK cells or peripheral blood mononuclear cells in vitro and in vivo. BsAbs can be preserved for immediate application, while cytotoxic T lymphocytes (CTLs) must be made-to-order, and are time-consuming to prepare. Tumor associated antigens, such as MAGE antigens, SART antigens, MUC1 antigen, c-erbB 2 antigen or cancer/testis antigens can be served to target antigens for BsAb production. By conjugation with antibodies to effector cells (anti-CD3, anti-CD28, anti-CD16, anti-CD64, anti-CD89 or anti-CD2), many kinds of BsAbs can be produced to cover most types of cancers from different organs. Therefore this strategy might be ubiquitously applicable to most malignancies.

Influence of biliary drainage catheter on bile duct wall thickness as measured by intraductal ultrasonography.

OBJECTIVE: To determine the influence of biliary drainage catheter placement on bile duct wall thickness, we performed intraductal ultrasonography (IDUS) in patients before and after biliary drainage. METHODS: Patients underwent IDUS before and after either short-term (n = 9, 6 to 8 days) or long-term (n = 9, 14 to 35 days) biliary drainage using a thin (2.0 mm diameter), 20 MHz probe inserted by means of a transpapillary route or a percutaneous tract. The bile duct wall thickness (mean +/- standard deviation) was retrospectively measured at the upper portion of the common hepatic duct. RESULTS: The bile duct wall thickness increased from 0.8+/-0.4 mm (predrainage) to 2.0+/-1.6 mm (post-drainage) in the long-term group (p < 0.001) but was not significantly increased in the short-term group. CONCLUSIONS: The bile duct wall thickness as measured on IDUS appears to be increased after placement of biliary drainage catheters.

Diagnosing extrahepatic bile duct stones using intraductal ultrasonography: a case series.

BACKGROUND AND STUDY AIMS: Intraductal ultrasonography (IDUS), a new ultrasonographic diagnostic procedure, was used to assess the presence of extrahepatic bile duct stones. PATIENTS AND METHODS: The IDUS apparatus consisted of a 6-French high-frequency (20 MHz) probe. Prior to clinical application, in-vitro studies were conducted in a water tank. Clinically, IDUS was successful in 31 patients after endoscopic retrograde cholangiography. Interpretations of IDUS images were evaluated in comparison with cholangiographic and fluoroscopic findings. RESULTS: Experimental testing demonstrated that stones or fragments were typically visualized as strong, high-echo images with acoustic shadowing; air bubbles were seen as fan-shaped high-echo areas or comet-shaped high-echo areas; and sludge was visualized as soft, easily changing, high-echo structures. Extrahepatic bile duct stones were visualized by IDUS in 30 of 31 patients (96.8%), while fluoroscopy and cholangiography identified 19 (61.3%) and 25 (80.6%), respectively. Accurate differentiation between stones and air bubbles was also possible. CONCLUSION: IDUS could be a useful modality in the diagnosis of extrahepatic bile duct stones.

Central distribution of sensory fibers in the facial nerve: an anatomical and immunohistochemical study.

Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injection into the facial nerve of the cat resulted in retrograde labeling in the geniculate and jugular ganglia ipsilaterally. Labeled fibers were found to enter into the brain stem through the intermediate and vagal nerves. These fibers ascended or descended into the dorsal portion of the spinal trigeminal tract and were distributed to the principal sensory nucleus of the trigeminal nerve, marginal layer of the interpolar part of the spinal trigeminal nucleus, nucleus of the solitary tract and ventrolateral portion of the cuneate nucleus. It was of particular interest in the present study that the intensive labeling was present in the medial portion of laminae I-IV of the upper cervical spinal cord. The immunohistochemical study revealed a lot of substance P-immunoreactive neurons in the geniculate and jugular ganglia, and heavy accumulation of immunoreactive fibers in laminae I-II of the upper cervical spinal cord.

Limitations of intraductal ultrasonography in differentiating between bile duct cancer in stage T1 and stage T2: in-vitro and in-vivo studies.

BACKGROUND AND STUDY AIMS: We investigated whether intraductal ultrasonography (IDUS) could distinguish between stage T1 and T2 bile duct cancer. MATERIALS AND METHODS: In-vitro study. Resected bile duct specimens (n = 8) were immersed in a water tank and were pierced with straight pins to clarify the normal layer structure. Ultrasonosgraphic images (20MHz) of the positions of pin echoes were compared to the positions of pin holes as seen on histologic analysis of the specimens. In-vivo study. A thin-caliber high-frequency (6 Fr, 20 MHz) ultrasonic probe was inserted into the bile duct via a transhepatic route or a transpapillary route in 26 patients with bile duct cancer who underwent surgical resection. RESULTS: In-vitro study. The inner hypoechoic layer on the IDUS image corresponded not only to the fibromuscular layer but also to a part of fibrous layer of the perimuscular loose connective tissue on histologic analysis, especially in the cases with moderate to severe bile duct wall fibrosis. The outer hyperechoic layer corresponded to the subserosal fat tissue. In-vivo study. In four of six patients with tumor limited to the inside hypoechoic layer on IDUS images, the histologic findings showed tumor invasion to the fibrous layer of the perimuscular loose connective tissue. Due to this limitation, accuracy of IDUS in T-staging was only 20/26 (77 %). CONCLUSIONS: IDUS cannot reliably distinguish bile duct cancer in stage T1 from that in stage T2.

Articulating subtype differences in self and relational experience among alcoholic men using structural analysis of social behavior.

L. Benjamin's (1984) structural analysis of social behavior (SASB) system was used as the organizing framework within which to characterize the phenomenology of self and other relationship experience among subtypes of alcoholic men. Within the context of a community-based study of psychopathology, groups of antisocial alcoholic (AAL), nonantisocial alcoholic (NAAL), and nonalcoholic (control) men completed ratings of their introject (self-concept) and spousal experience. Group differences in demography and psychopathology provided strong support for subtype variations among alcoholic men that could not be attributed to global differences in adaptive functioning. SASB data showed consistency in circumplex ordering across the groups in ratings of self-experience and in ratings of the spousal relationship. AAL men were the most self-neglecting, blaming, and least trusting, and control men were the most relationally connected, with NAAL men falling in between. Despite the importance of the subtyping distinction, in some areas, alcoholism, regardless of subtype, was the core differentiating factor.

Assessment of the course and variations of the hepatic artery in bile duct cancer by intraductal ultrasonography.

BACKGROUND: We evaluated the course and variations of the hepatic artery in bile duct cancer using intraductal ultrasonography (IDUS). METHODS: IDUS was used to demonstrate the course of the hepatic artery preoperatively in 20 patients with extrahepatic bile duct cancer, and the image was compared with angiographic and surgical findings. RESULTS: IDUS was able to assess tumor invasion to the main branch of the right hepatic artery in all cases. However, it demonstrated only three cases in the left hepatic artery and four cases in the proper hepatic artery. When the hepatic artery indicated re-entry or bifurcation on the IDUS image, the proximal portion of re-entry or bifurcation was established as the proper hepatic artery, but when it showed neither re-entry nor bifurcation it was established as the right hepatic artery. CONCLUSIONS: IDUS demonstrated the main branch of the right hepatic artery in all cases, but was not useful for demonstration of the left and proper hepatic arteries. Correct assessment of re-entry and bifurcation was essential on IDUS images for making the distinction between the right hepatic artery and the proper hepatic artery.

Assessment of pancreatic parenchymal invasion by bile duct cancer using intraductal ultrasonography.

BACKGROUND AND STUDY AIMS: This study was performed to clarify the diagnostic accuracy of intraductal ultrasonography (IDUS) in assessing pancreatic parenchymal invasion by bile duct cancer. PATIENTS AND METHODS: Preoperative assessment of pancreatic parenchymal invasion was carried out by IDUS via a percutaneous tract or a transpapillary route in 18 patients with extrahepatic bile duct cancer. Various probes with diameters of 1.4, 2.0, 2.4, 2.6 and 3.2 mm, and frequencies of 7.5, 15, 20 and 30 MHz were used. All patients underwent angiography and endoscopic ultrasonography (EUS). In the first six cases, IDUS and EUS images were analyzed retrospectively without knowledge of the operative outcome or the results of other imaging tests. In the subsequent 12 cases, the IDUS und EUS images were prospectively reviewed prior to surgery. The diagnostic accuracy of IDUS was compared with angiography and EUS by means of a histopathological examination of the resected specimens. RESULTS: The accuracy of IDUS, EUS, and angiography in assessing pancreatic parenchymal invasion was 100%, 78% and 61%, respectively. However, IDUS could not assess pancreatic capsular invasion. The accuracy of IDUS in assessing horizontal tumor extension to the intrapancreatic bile duct and to the hepatic side was 83% and 72%, respectively. CONCLUSIONS: IDUS proved useful for assessing the extension of cancer invasion to the pancreatic parenchyma, but not to the pancreatic capsule or mucosal surface.

[Coronary artery bypass grafting surgery without cardiopulmonary bypass in a patient with calcified aorta].

Coronary artery bypass surgery in a 67-year-old male with severe calcified ascending aorta was performed without cardiopulmonary bypass under beating heart, utilizing the left internal thoracic artery graft. No neurological complication was observed and postoperative angiogram showed good graft patency. We think coronary revascularization without cardiopulmonary bypass can be one of the safe and reliable methods to avoid complications associated with aortic cross clamping and aortic cannulation with severely calcified aorta.

Assessment of portal vein invasion by bile duct cancer using intraductal ultrasonography.

BACKGROUND AND STUDY AIMS: We recently reported on the contribution of intraductal ultrasonography (IDUS) to the regional staging of bile duct cancer, and we present here the first detailed study of the value of IDUS in assessing the portal vein invasion by bile duct cancer. PATIENTS AND METHODS: Preoperative assessment of portal vein invasion was performed by IDUS via a percutaneous tract or via transpapillary route in 18 patients with extrahepatic bile duct cancer. Various probes, with diameters of 1.4, 2.0, 2.4, 2.6, and 3.2 mm, and frequencies of 7.5, 15, 20, and 30 MHz, were used. All patients additionally underwent endoscopic ultrasonography (EUS) and angiography. In the first six cases, the IDUS and EUS images were analyzed retrospectively without the knowledge of operative results or the other imaging tests. In the remaining 12 cases, IDUS and EUS images were prospectively reviewed prior to surgery, without knowledge of the angiographic findings. The gold standard for the results of IDUS, EUS and angiography was the histopathological findings in 17 resected tumors, and the intraoperative findings in one patient who did not undergo resective surgery. RESULTS: IDUS was able to demonstrate the portal vein in all cases. Its accuracy in diagnosing portal vein invasion was 100% for all locations. EUS was useful in assessing portal vein invasion at the middle and distal bile duct (the accuracy was 91%), but was not useful in assessing invasion at the proximal bile duct (the accuracy was 57%). CONCLUSIONS: IDUS proved useful for assessing the extension of cancer invasion into the portal vein, even in proximal bile duct tumors.

Assessment of hepatic artery invasion by bile duct cancer using intraductal ultrasonography.

BACKGROUND AND STUDY AIMS: This study was performed to clarify the diagnostic accuracy of intraductal ultrasonography (IDUS) in assessing hepatic artery invasion by bile duct cancer. PATIENTS AND METHODS: Preoperative assessment of hepatic artery invasion was performed by IDUS via a percutaneous tract or the transpapillary route in a total of 22 patients with extrahepatic bile duct cancer. The probes used had a diameter of 1.4, 2.0, 2.4, 2.6, and 3.2 mm, and frequencies of 7.5, 15, 20, and 30 MHz. In the first six cases, IDUS images were analyzed retrospectively with no knowledge of the operative results or of the other imaging tests. In the following 16 cases, the IDUS images were prospectively reviewed prior to surgery without knowledge of the angiographic findings. The diagnostic accuracy of IDUS was compared with angiography in all cases, with the histopathological results in 20 resected cases, and with the intraoperative findings in two cases with only surgical exploration. RESULTS: IDUS was able to demonstrate the right hepatic artery in all cases, and its accuracy in diagnosing right hepatic invasion was 100%. However, IDUS was able to visualize the proper hepatic artery in only four cases (18%), and the left hepatic artery in only three cases (14%), respectively. IDUS could not visualize the area outside of the hepatoduodenal ligament, because of its low penetration depth. CONCLUSIONS: IDUS proved useful for assessing the extension of bile duct cancer invasion into the right hepatic artery. However, IDUS did not sufficiently demonstrate the proper hepatic artery and the left hepatic artery for diagnosing vascular involvement.

Midbrain paralemniscal projections to the facial nucleus: an anatomical and immunohistochemical study.

Serial 30 microns-thick sections through the midbrain tegmentum were stained with cresyl violet. The PL was found to be situated along the medial edge of the lateral lemniscus. The PL consisted of small- (10-15 microns) and medium-sized neurons (25-35 microns), and was the most prominent at the caudal level of the superior colliculus. In order to confirm the existence of the inhibitory paralemniscal-facial pathway, a combined HRP and immunohistochemical technique was use in the rat. This experiment revealed that 10.9% of the total number of GABA immunoreactive PL neurons also labeled with HRP after HRP injection was made in the medial part of the facial nucleus (FN). Electron microscopic observations were carried out on the medial part of the facial nucleus (FN) after kainic acid injection was made into the contralateral PL in the cat. The majority of degenerating PL fibers were ranged from 0.5 to 3.1 microns in diameter and made synaptic contacts with somata, proximal dendrites and dendritic profiles. These fibers, containing either round or pleomorphic vesicles, formed asymmetrical or symmetrical synapses. It was of particular interest in the present study that 40.7% of the total number of degenerating fibers make synaptic contacts with large dendrites more than 3.0 microns in diameter.

[Vein patch angioplasty for coronary revascularization to ischemic heart disease: report of two cases].

Two cases of vein patch angioplasty for ischemic heart disease were presented. The first case (59-year-old female) admitted to our hospital because of posterolateral infarction. Preoperative coronary angiogram (CAG) showed stenosis of 4-PD of RCA, proximal LAD and distal LCX. The second case (62-year-old male) admitted for operation of abdominal aortic aneurysm. Preoperative CAG showed stenosis of proximal RCA and mid LAD. Stenosis of 4-PD and proximal RCA was relieved by patch angioplasty using saphenous vein graft and coronary artery bypass to LAD was performed by left internal thoracic artery graft. Both cases showed successful enlargement of RCA stenosis and good graft patency at the postoperative CAG. Vein patch angioplasty is thought to be an alternative method for coronary revascularization to ischemic heart disease.

Preoperative staging of extrahepatic bile duct cancer with intraductal ultrasonography.

OBJECTIVE: To evaluate the tumor extension of extrahepatic bile duct cancer by means of intraductal ultrasonography (IDUS). METHODS: IDUS preoperatively assessed the tumor extensions in 25 patients with extrahepatic bile duct cancer. The diagnostic accuracy of IDUS was investigated by comparison with other diagnostic imaging modalities in all cases and with histopathological findings of resected specimens in 18 cases. RESULTS: IDUS proved useful in assessing the extension of cancer invasion to the pancreas parenchyma, portal vein, and right hepatic artery. The limitation of the degree of accuracy, based on the group staging criteria, was 68%. IDUS could not assess tumor invasion to the perimuscular loose connective tissue. Therefore, it could not distinguish stage II from stage I. IDUS could not sufficiently assess epicholedochal lymph node metastases (differential diagnosis between stages II and III) and could not demonstrate distant metastases (differential diagnosis between stages IVA and IVB) because of the inevitable attenuation of the echo itself. IDUS could assess cases of stage IVA correctly in 8/8 (100%) cases. The combination of PTC/ERC and IDUS could assess the horizontal extension correctly in 13/18 (72%) cases. The combination of PTC/ERC, percutaneous transhepatic cholangioscopy (PTCS), and IDUS assessed the horizontal extension in 14/15 (93%) cases. CONCLUSION: 1) IDUS, with a high-frequency probe, was very useful for assessing tumor infiltration in the hepatoduodenal ligament. 2) IDUS could not assess tumor extension outside of the hepatoduodenal ligament, but conventional ultrasonography and angiography could compensate for it. 3) The combination of PTC/ERC, PTCS, and IDUS could assess horizontal extension correctly.

A case of chronic pancreatitis with pseudocysts complicated by infection and obstructive jaundice.

We report a case of chronic pancreatitis with pseudocysts complicated by infection and obstructive jaundice. A 49-yr-old male was admitted with the complaints of fever and jaundice. Laboratory findings included high biliary tract enzyme values and normal serum amylase value. Ultrasonography and computed tomographic scan demonstrated a cyst, 4 cm in diameter, in the pancreas head. Cholangiography revealed a long, tapered obstruction of the common bile duct which was apparently compressed by the cyst. Although the jaundice improved after percutaneous transhepatic biliary drainage, fever continued, and the cyst was aspirated. Bacteriological examination of the contents revealed infection. The symptoms disappeared rapidly and the cyst decreased in size soon after aspiration. The stenosis of the common bile duct showed improvement for several weeks but then regressed. In a patient with secondary pancreatic infection or obstructive jaundice following pancreatic disease, distinguishing the condition is an important aspect of accurate diagnosis and therapy.

A case of anomalous arrangement of the pancreaticobiliary ductal system demonstrated by intraductal ultrasonography.

A 55-yr-old female was hospitalized with epigastric pain. Conventional ultrasonography revealed marked dilation of the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography showed fusiform dilation of the CBD. The common channel of the pancreatic duct and choledochus was 20 mm long. A diagnosis of congenital choledochal dilation accompanied by anomalous arrangement of the pancreaticobiliary ductal system (AAPBDS) was made. Intraductal ultrasonography (IDUS) was performed. IDUS demonstrated the union of the pancreatic duct and choledochus within the pancreatic parenchyma. This meant that the union existed outside the duodenal wall, confirming the diagnosis of AAPBDS. Although endoscopic retrograde cholangiopancreatography alone could show the maljunction in this case, simultaneous IDUS will be useful in making an accurate diagnosis of AAPBDS.

[Assessment of tumor extent in extrahepatic bile duct cancers--utility of intraductal ultrasonography].

Intraductal ultrasonography (IDUS) were performed in patients with extrahepatic bile duct cancer and compared to other diagnostic modalities and to resected specimens. Endoscopic ultrasonography (EUS) is a non-invasive diagnostic method useful for screening patients with bile duct cancers and determining whether they are resectable or not. While, EUS was not useful for the differential diagnosis of advanced and early tumors, and less useful in case of bile duct tumors located at the hilus hepatitis. IDUS proved useful without blind spot even in case of bile duct cancers at the hilus hepatis. IDUS was especially useful for the differential diagnosis of advanced and early tumors. IDUS is the very accurate diagnostic modality which make up for EUS and essential to determine the appropriate operation plan.