Energy of the

The low-lying isomeric state of ^{229}Th provides unique opportunities for high-resolution laser spectroscopy of the atomic nucleus. We determine the energy of this isomeric state by taking the absolute energy difference between the excitation energy required to populate the 29.2-keV state from the ground state and the energy emitted in its decay to the isomeric excited state. A transition-edge sensor microcalorimeter was used to measure the absolute energy of the 29.2-keV γ ray. Together with the cross-band transition energy (29.2 keV→ground) and the branching ratio of the 29.2-keV state measured in a recent study, the isomer energy was determined to be 8.30±0.92 eV. Our result is in agreement with the latest measurements based on different experimental techniques, which further confirms that the isomeric state of ^{229}Th is in the laser-accessible vacuum ultraviolet range.

MIB-1 index is unlikely to predict relapse-free survival in patients who underwent R0-esophagectomy for esophageal squamous cell carcinoma.

MIB-1 is a cell proliferation marker and has previously been investigated as a diagnostic or prognostic indicator of malignancy. Previous studies have investigated MIB-1 index and clinicopathological factors in relation to prognosis of patients with esophageal cancer, with conflicting results. The aim of this study is to assess the prognostic significance of MIB-1 index in patients with thoracic esophageal squamous cell carcinoma. A total of 78 patients who underwent R0-esophagectomy for thoracic esophageal squamous cell carcinoma were enrolled in this study. Preoperatively, 29 patients underwent chemotherapy, six underwent chemoradiotherapy, and the remaining did not undergo any preoperative therapy. The MIB-1 labeling index was reported by counting 500 tumor cells in the hot spots of nuclear labeling. Correlations between MIB-1 index, clinicopathological factors, and relapse-free survival (RFS) were investigated. The mean MIB-1 index was 39.3 ± 21.0 (range: 0-91.3). There was no significant correlation between clinicopathological factors and MIB-1 index in the study patients, irrespective of whether they underwent preoperative therapy. Univariate analysis revealed no significant association between MIB-1 index and RFS. However, depth of tumor invasion, lymph node metastasis and stage, all showed a significant correlation to RFS. Multivariate analysis of RFS revealed that stage was the only significant factor. Conversely, MIB-1 index was not significantly related to RFS (p = 0.41). In conclusion, MIB-1 index is unlikely to be a significant prognostic indicator for esophageal cancer.

Complete, long-lasting protection against lethal infectious bursal disease virus challenge by a single vaccination with an avian herpesvirus vector expressing VP2 antigens.

Marek's disease herpesvirus is a vaccine vector of great promise for chickens; however, complete protection against foreign infectious diseases has not been achieved. In this study, two herpesvirus of turkey recombinants (rHVTs) expressing large amounts of infectious bursal disease virus (IBDV) VP2 antigen under the control of a human cytomegalovirus (CMV) promoter or CMV/beta-actin chimera promoter (Pec promoter) (rHVT-cmvVP2 and rHVT-pecVP2) were constructed. rHVT-pecVP2, which expressed the VP2 antigen approximately four times more than did rHVT-cmvVP2 in vitro, induced complete protection against a lethal IBDV challenge in chickens, whereas rHVT-cmvVP2 induced 58% protection. All of the chickens vaccinated with rHVT-pecVP2 had a protective level of antibodies to the VP2 antigen at the time of challenge, whereas only 42 and 67% of chickens vaccinated with rHVT-cmvVP2 or the conventional live IBDV vaccine, respectively, had the antibodies. The antibody level of chickens vaccinated with rHVT-pecVP2 increased for 16 weeks, and the peak antibody level persisted throughout the experiment. The serum antibody titer at 30 weeks of age was about 20 or 65 times higher than that of chickens vaccinated with rHVT-cmvVP2 or the conventional live vaccine, respectively. rHVT-pecVP2, isolated consistently for 30 weeks from the vaccinated chickens, expressed the VP2 antigen after cultivation, and neither nucleotide mutations nor deletion in the VP2 gene was found. These results demonstrate that the amount of VP2 antigen expressed in the HVT vector was correlated with the vaccine efficacy against lethal IBDV challenge, and complete protective immunity that is likely to persist for the life of the chickens was induced.

Gizzard erosion in broiler chicks by group I avian adenovirus.

Incidences of mortality without any clinical signs occurred in growing chicks in a broiler flock. Five 17-day-old dead broilers with gizzard erosions were investigated pathologically. Macroscopically, the gizzards were found to be dilated with bloody fluids. The koilin layer of the gizzards showed multifocal black patches (erosions). Histologically, there was necrosis of the koilin layer, degeneration and depletion of the gizzard glandular epithelium with intranuclear inclusion bodies, and hyperplasia of the macrophages in the lamina propria. An immunohistochemical analysis revealed intranuclear inclusion bodies in the degenerating gizzard glandular epithelial cells that stained positively for group I avian adenovirus antigen. Ultrastructurally, numerous viral particles (an average of 72 nm in diameter, from 63 to 88 nm) were in the intranuclear inclusions of glandular epithelium. This study suggests that the gizzard erosions may have been caused by group I avian adenovirus. In addition, the degeneration and depletion of gizzard glands secreting koilin substances, by adenovirus, may induce a reduction of koilin substances, which may then cause gizzard erosion (focal loss of the koilin layer).

Identification of a genetic determinant of pathogenicity in chicken anaemia virus.

The molecular basis of pathogenicity of the chicken anaemia virus (CAV) needs to be clarified in order to develop a safe, live virus vaccine. In this study, several high- and low-pathogenic infectious DNA clones were obtained from field virus samples after 12 or 38 passages in MDCC-MSB1 cells. The high-pathogenic clones induced a low haematocrit, low weight gain and high mortality. Nucleotide sequence analyses identified one amino acid, at residue 394 of the VP1 capsid protein, as a major determinant of pathogenicity. To determine the role of this amino acid in pathogenicity, chimeric infectious DNA clones and point-mutated clones were used for chicken pathogenicity tests. These analyses clearly demonstrated that residue 394 of VP1 was crucial for the pathogenicity of CAV; all of the cloned viruses with glutamine at this position were highly pathogenic, whereas those with histidine had low pathogenicity. Low-pathogenic CAV, based on an infectious DNA clone, is a candidate for a genetically homogeneous and stable CAV live vaccine.

Clinicopathological features of superficial spreading and nonspreading squamous cell carcinoma of the esophagus.

OBJECTIVES: Superficially spreading carcinoma of the esophagus, consisting mainly of intraepithelial carcinoma, is not as rare as was previously thought. Despite the surgical significance of this entity, no general definition has been established, and the clinical features of this disease remain to be clarified. METHODS: A total of 54 patients with superficial carcinoma of the esophagus (defined as carcinoma limited to the epithelium or superficially invading the lamina propria or submucosa) were classified into two groups according to the longitudinal extent of the lesion. A total of 13 patients with superficially spreading carcinoma (defined as a superficial carcinoma measuring >5 cm and consisting mainly of intraepithelial carcinoma) were compared to 41 patients with nonspreading esophageal carcinoma. RESULTS: One patient with superficially spreading carcinoma had a positive resection margin because of multiple cancerous lesions. The only significant difference in the clinical and pathological features of the two groups was a higher prevalence of associated multiple cancerous lesions in patients with the superficially spreading type. CONCLUSIONS: Superficially spreading carcinoma of the esophagus is often associated with multiple cancerous lesions. For endoscopists and esophageal surgeons, it is important to define the proximal extent of intraepithelial cancer and the presence of multiple cancerous lesions to perform curative resection.

Types of lumbar herniated disc and clinical course.

STUDY DESIGN: A retrospective study of different types of herniated discs and duration of symptoms in patients with lumbar disc herniation, and a trial of longer conservative treatment to reduce the number of operations. OBJECTIVE: To determine whether noncontained and contained herniated discs have different clinical courses and to evaluate the results of the clinical trial of longer and vigorous conservative treatment. SUMMARY OF BACKGROUND DATA: The possibility of a difference in clinical features between contained and noncontained disc herniation has been suggested previously. METHODS: In the first study, the medical history and intraoperative findings of 156 patients who had undergone herniotomy were reviewed. In the second study, conservative treatment of at least 2 months' duration was recommended for all patients with lumbar disc herniation. RESULTS: In the first study, patients with noncontained disc herniation had a shorter preoperative clinical course than those with contained disc herniation. It was rare for noncontained herniation to require surgery 4 months or more after the onset of symptoms. In the second study, the authors' protocol reduced the number of herniotomies required, especially the number of operations for the patients with noncontained disc herniation. CONCLUSIONS: The authors believe that patients with noncontained lumbar disc herniation can be treated without surgery, if these patients can tolerate the symptoms for the first 2 months.

Bilirubin impairs bactericidal activity of neutrophils through an antioxidant mechanism in vitro.

BACKGROUND: Liver failure accompanied by hyperbilirubinemia after major hepatic resection is profoundly associated with septic complications. Although the immune dysfunction in cholestasis has been intensively investigated, the contribution of increased serum bilirubin to the impaired resistance to bacterial infection remains to be elucidated. Because bilirubin possesses an antioxidant activity, we hypothesized that bilirubin may scavenge reactive oxygen species (ROS) produced by neutrophils and consequently impair neutrophil bacterial killing. To address this, we evaluated the effects of bilirubin on the bactericidal activity of ROS or of neutrophils in vitro. MATERIALS AND METHODS: The antioxidant activity of bilirubin was determined using an ROS-sensitive fluorophore, dichlorofluorescin diacetate (DCFH-DA). Bilirubin concentration in the buffer solution was monitored spectorophotometrically after incubation with ROS. The effect of bilirubin on killing of Escherichia coli by ROS or by isolated human neutrophils was determined by counting the viable E. coli after incubation on nutrient agar. RESULTS: The bilirubin concentration in the buffer solution was decreased by the addition of hydrogen peroxide, especially in the presence of peroxidase or ferrous iron. DCFH-DA oxidation by ROS or activated neutrophils was inhibited by bilirubin in a dose-dependent manner. The bactericidal activity of ROS or of isolated neutrophils was significantly attenuated by bilirubin. CONCLUSIONS: Bilirubin impairs bactericidal activity of neutrophils through scavenging ROS. Increased levels of serum bilirubin may well be responsible for the impaired bacterial clearance in patients with hyperbilirubinemia.

Five-year survivors after aggressive surgery for stage IV gallbladder cancer.

PURPOSE: To describe 5-year survivors after radical surgery for stage IV gallbladder cancer and to determine the characteristics leading to potential long-term survival. METHODS: Of 59 patients undergoing radical resection for stage IV disease between 1979 and 1994, 6 patients who have survived for more than 5 years were followed up. RESULTS: Three patients had developed obstructive jaundice due to involvement of the hepatic hilum, but the other three had not. The jaundiced patients had remarkable tumor spread over the bile duct and right hepatic artery within the hepatoduodenal ligament. However, the proper and left hepatic arteries and the portal trunk and its left branch were free from tumor involvement. The nonjaundiced patients had N1 or N2 lymph node metastasis. However, none underwent bile duct resection or pancreatoduodenectomy to establish radical lymphadenectomy. CONCLUSIONS: Selected patients with stage IV gallbladder cancer may be candidates for 5-year survival when the primary tumor is fairly localized even if it forms a large mass and involves neighboring organs including the hepatic duct, lymph node metastasis is limited to N1 and N2 except for the celiac and superior mesenteric nodes and is less infiltrative, and distant metastasis including that in the paraaortic area is absent.

Mucosal dysplasia in the bile duct after choledochoduodenostomy: a case report.

A 60-year-old woman who had undergone cholecystectomy, choledocholithotomy and choledochoduodenostomy 21 years previously for cholecystolithiasis and choledocholithiasis, presented with nausea and vomiting. With a preoperative diagnosis of recurrent common bile duct stones, the extrahepatic bile duct was excised and choledochojejunostomy was performed. Histologic examination of the resected specimen disclosed chronic cholangitis, papillary epithelial hyperplasia, and mild dysplasia. Choledochoduodenostomy predisposes to reflux of duodenal contents, resulting in chronic mechanical and chemical irritation likely to induce histopathologic alterations in the bile duct mucosa. Since bile duct dysplasia induced by chronic inflammation may be a precursor of cancer, indication for choledochoduodenostomy should be specific and limited, and careful long-term follow-up is mandatory.

[Extended liver resection for hilar cholangiocarcinoma].

Liver resection for hilar cholangiocarcinoma should be designed for individual patients, based on both precise diagnosis of cancer extent and accurate evaluation of hepatic functional reserve. Therefore we have developed various types of hepatic segmentectomy. Combined caudate lobectomy is essential in every patient with separated hepatic confluence. So-called extensive hepatectomy, resection of 50% or more of the hepatic mass, includes right lobectomy and right or left trisegmentectomy. Right lobectomy with caudate lobectomy is indicated when the progression of cancer is predominant in the right anterior and posterior segmental bile ducts. The plane of liver transection is along the Cantlie line, and the left hepatic duct is divided just at the right side of the umbilical portion of the left portal vein. Right trisegmentectomy with caudate lobectomy is performed in carcinoma which involves the right hepatic ducts in continuity with the left medial segmental bile duct. The umbilical portion of the left portal vein is freed from the umbilical plate by dividing the small portal branches arising from the cranial side of the umbilical portion. Then the left lateral segmental bile ducts are exposed and divided at the left side of the umbilical portion of the left portal vein. Left trisegmentectomy with caudate lobectomy is suitable for carcinoma which involves the left intrahepatic bile duct in continuity with the right anterior segmental bile duct. Liver transection is advanced along the right portal fissure. The right posterior segmental bile duct is usually divided distal to the confluence of the inferior and superior branches.

Induction of hydropericardium in one-day-old specific-pathogen-free chicks by adenoviruses from inclusion body hepatitis.

The pathogenicities of inclusion body hepatitis (IBH) and hydropericardium syndrome (HPS) strains of adenovirus for specific-pathogen-free (SPF) chicks were compared. One-day-old SPF chicks inoculated intramuscularly with the DPI-2 (serotype 2), S-PL1 (serotype 2), TR630 (serotype 8), and Saga97 (serotype 8) strains from IBH and with the LVP-1 strain (serotype 4) from HPS exhibited the mortality, liver enlargement, and hydropericardium characteristic of gross change found in HPS. The chicks inoculated with the IBH and HPS strains exhibited similar histologic and immunohistochemical changes. Neither mortality nor pathologic changes occurred in 3-wk-old SPF chicks inoculated with IBH strains, although HPS strain induced HPS lesions in them. This study indicates that IBH strains of adenovirus can also reproduce HPS lesions and mortality in 1-day-old SPF chicks and that IBH and HPS strains may have similar pathogenicities except for their different virulence for older chickens.

Lesions of bone and bone marrow in myeloid leukosis occurring naturally in adult broiler breeders.

Lesions of bone and bone marrow in myeloid leukosis (ML) occurring naturally in adult broiler breeders were investigated pathologically. During gross examination, nodules and protrusions were commonly observed on the surface of the sternum, ribs, vertebrae, and synsacrum. The bone marrow of all the bones of the body was pale in color. Histologically, granulated myelocytes proliferated in the bone marrow of various bones and in the periosteum of the sternum, ribs, vertebrae, and synsacrum. The first proliferation of tumor cells occurred in the bone marrow of epiphysis. The myelocytes invaded through haversian and Volkmann's canals from the bone marrow to periosteal areas. Hematopoiesis was suppressed by marked proliferation of tumor cells in the bone marrow of the whole bone. Atrophy was also seen in the bones, including medullary bones of the chickens suffering from ML. Proliferation of myelocytes was seen in the bone marrow and periosteum of ossified cartilaginous rings of the trachea and larynx. Marked proliferation of myelocytes was seen in the dura mater of spinal cords, and it subsequently depressed the spinal cords. Bone formation with cartilage was seen in the periosteum of the sternum having marked proliferation of myelocytes in the bone marrow and periosteum. Ultrastructurally, tumor cells showed large nuclei and cytoplasm with large round electron-dense lysosomes. The virus particles were rarely detected in the cytoplasm of tumor cells. The polymerase chain reaction test of tumor samples showed positive for subgroup J avian leukosis virus. This study indicates that the myelocytes can invade through the compact bones to the periosteum in the sternum, ribs, vertebrae, synsarcum, and ossified cartilage of trachea and larynx having thinner compact bones. In addition, the periosteal osteogenesis with cartilage in the sternum may be reactive change against the bone atrophy because of the marked proliferation of myelocytes.

Persistent infection with chicken anaemia virus and some effects of highly virulent infectious bursal disease virus infection on its persistency.

Chicken anaemia virus (CAV) infectivity and the effect of highly virulent infectious bursal disease virus (hv IBDV) infection on CAV's infectivity were examined in chickens inoculated with CAV or inoculated dually with CAV and hv IBDV. Five chickens inoculated dually with hv IBDV at 35 days old and then with CAV at 40 days old exhibited no clinical signs of disease, but showed atrophic bursae of Fabricius when necropsied 4 weeks later. Upon examining the chickens at 7 days postinoculation (dpi) with CAV, it was found that hv IBDV infection had inhibited production of virus neutralising (VN) antibody to CAV, and that it was possible to recover CAV from plasma of these chickens. Although VN antibody to CAV appeared after 14 dpi, CAV was recovered from blood cells (BC s) at high titres ranging from 10(2.5)to 10(5.5)TCID(50)/0.1 ml, 7 to 28 dpi in IBDV -induced immunosuppressed chickens. In addition, CAV was sporadically recovered, using rectal swabs, from the dually inoculated chickens at low titers, ranging from 10(1.0)to 10(2. 0)TCID(50)/0.1 ml). In contrast, although CAV was recovered from BC s in most of the chickens inoculated with CAV alone, the titers were lower (10(1.0)to 10(2.5)TCID(50)/0.1 ml). No CAV was detected from the rectal swabs of these chickens. The results of virus recovery were confirmed by polymerase chain reaction. This study first examined the persistency of CAV in BC s and the effective enhancement of primary CAV infection as a result of immunosuppression caused by hv IBDV infection.

Pathologic study of specific-pathogen-free chicks and hens inoculated with adenovirus isolated from hydropericardium syndrome.

The mortality and pathology caused by serotype 4 adenovirus, isolated from chickens with hydropericardium syndrome (HPS) in Japan, was investigated in specific-pathogen-free (SPF) chickens. One-day-old to 15-mo-old SPF chickens were inoculated intramuscularly, orally, and intranasally with liver homogenates from HPS chickens or isolated serotype 4 adenovirus. There were no clinical signs before death. The mortality rate in all groups of 1-day-old chicks was 100%, irrespective of the inoculum or inoculation route. Four-week-old chickens inoculated with liver homogenate also had a 100% mortality rate. Five-week-old chickens inoculated with cell culture of HPS adenovirus had a 40% mortality rate. The mortality rates of 7-mo-old hens inoculated with liver homogenates intramuscularly and orally were 75% and 25%, respectively. In 15-mo-old hens inoculated with liver homogenates intramuscularly, the mortality rate was 70%. Gross lesions were hydropericardium and swelling and congestion of the liver with occasional petechial hemorrhages. Histologically, the liver had diffuse or multifocal hepatic necrosis and hemorrhage with intranuclear inclusion bodies noted within hepatocytes. In the spleen, macrophages containing erythrocytes and yellow pigment were prominent in the red pulp. In the lung, a moderate diffuse macrophage infiltration was noted throughout the lung parenchyma, and these macrophages contained yellow pigment. In the pancreas of the chicks inoculated at 1 day old, there was multifocal necrosis of glands with intranuclear inclusion bodies. Intranuclear inclusion bodies were seen also in the gizzard, proventriculus, duodenum, cecum, kidney, and lung of the chicks inoculated at 1 day old. Immunohistochemically, the intranuclear inclusion bodies of various organs showed positive reactions against group I avian adenovirus. Adenovirus was recovered from the liver of chickens with HPS. This study indicates that HPS adenovirus is able to reproduce HPS lesions and mortality in SPF chicks and even adult chickens and that it is a highly pathogenic strain.

[Treatment of recurrent cancer after surgery for biliary malignancies].

Our strategy for recurrent tumor after surgical resection for biliary malignancies, especially for hilar cholangiocarcinoma, is described. One hundred and thirty-three patients with hilar cholangiocarcinoma underwent curative resection in our department until November, 1998, and recurrent carcinomas have been pointed out in 73 patients (54.9%). The site of recurrence was peritoneum (21 cases), liver (16 cases), pre-caval and retro-duodenal space (15 cases), hepatic hilum (11 cases), lymph node (9 cases), bone (6 cases), sinus tract of percutaneous transhepatic biliary drainage (PTBD) (5 cases) and so on. Surgical resection was applied to recurrent carcinomas after careful evaluation, and 9 patients underwent surgical resection of the recurrent tumor: sinus tract of PTBD in the abdominal and/or chest wall (4 cases), lymph node (2 cases), liver (1 case), hepaticojejunostomy (1 case) and duodenum (1 case). There were three hospital death patients. Other six patients survived for 16 months on an average (11-20 months) after surgery for recurrent tumor. PTBD for recurrent cancer at the hepatic hilum and gastrojejunostomy for local recurrence around the duodenum improved quality of life of patients. Radiation therapy for bone metastasis or local recurrence at the hepatic hilum was sometimes very effective. Effect of systemic or transarterial chemotherapy is still unknown.