Accumulation of a soluble form of human nectin-2 is required for exerting the resistance against herpes simplex virus type 2 infection in transfected cells.

Cell entry of herpes simplex virus type 2 (HSV-2) requires the interaction of viral glycoprotein D (gD) with the receptor nectin-1 and herpesvirus entry mediator (HVEM). In addition, it is known that nectin-2 is also functional as a receptor for HSV-2, although the binding to the gD is weak. To examine an antiviral potential of a soluble form of human nectin-2 (hNectin-2Ig), transfected Vero cells expressing the entire ectodomain of nectin-2 fused to the Fc portion of human IgG were established. Specific binding of hNectin-2Ig to HSV-2 gD was confirmed by ELISA. Competitive ELISA demonstrated that accumulation of hNectin-2Ig in transfected cells increased significantly in a cell culture time dependent manner. Viral growth of several HSV-2 strains was significantly inhibited in the transfected cells that were cultured for 72 hr compared with control Vero cells, but not in cells that were cultured for 24 hr. These results indicate that accumulation of a soluble form of nectin-2 is required for exerting the resistance against HSV-2 infection.

Techniques to facilitate ERCP with a conventional endoscope in patients with previous pancreatoduodenectomy.

There is little guidance on the performance of endoscopic retrograde cholangiopancreatography (ERCP) in patients with previous pancreatoduodenectomy. We reviewed techniques for ERCP with a conventional endoscope and assessed its value in 10 patients with previous pancreatoduodenectomy (15 ERCPs). After exploration of the surgical reconstruction, we used a front-viewing endoscope, and we used a small firm pillow under the abdomen and hand compression for preventing loop formation. Successful insertion to the ductal anastomoses and biliary cannulation were achieved in 13 / 15 procedures (87 %). In 6 procedures where we attempted pancreatic cannulation, we could not identify the pancreatojejunostomy, but after spraying contrast around the suspected location of the ductal anastomosis we obtained a pancreatogram in 4 / 6 procedures (67 %). Endoscopic biliary interventions were successful in 6 / 7 procedures (86 %). No complications were encountered. Use of appropriate techniques makes ERCP with a conventional endoscope feasible, effective, and safe in patients with previous pancreatoduodenectomy. Endoscopic therapy can be performed successfully in the bile duct, but has limited value regarding the pancreatic duct.

Diurnal variation of hemodynamic indices in non-dipper hypertensive patients.

The purpose of this study was to elucidate the underlying mechanisms of blunted nocturnal blood pressure reduction in non-dipper hypertensive patients. We studied the diurnal variations in systemic hemodynamic indices and baroreflex sensitivity. In 45 subjects with essential hypertension (24 men; mean age, 49+/-1 years), intra-arterial pressure was monitored telemetrically. Non-dippers were defined as those with a nocturnal reduction of systolic blood pressure of less than 10% of daytime systolic blood pressure. Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. Baroreflex sensitivity was calculated as deltapulse interval/deltasystolic blood pressure on spontaneous variations. The mean values of the hemodynamic parameters were calculated every 30 min. Twenty-six subjects were classified as non-dippers. Daytime blood pressure was not significantly different between dippers (149+/-4/87+/-3 mmHg) and non-dippers (147+/-3/82+/-2 mmHg), while the nighttime blood pressure was significantly reduced in dippers (131+/-3/77+/-2 mmHg) but not in non-dippers (145+/-3/80+/-2 mmHg). Nocturnal decreases in both cardiac index and stroke index were smaller in non-dippers (-12.0+/-1.2% and 1.5+/-1.0%) than in dippers (-17.5+/-1.4% and -2.2+/-1.1%). Baroreflex sensitivity significantly increased at nighttime both in dippers (6.5+/-0.6 to 8.0+/-0.7 ms/mmHg) and in non-dippers (5.1+/-0.3 to 6.4+/-0.4 ms/mmHg). Neither daytime nor nighttime baroreflex sensitivity was significantly different between the groups. We conclude that the hemodynamics of non-dipper essential hypertension are characterized by an inadequate nocturnal decrease in cardiac index and stroke index, suggestive of relative volume expansion or malsuppressed sympathetic activity.

Colonisation and transmission of Clostridium difficile in healthy individuals examined by PCR ribotyping and pulsed-field gel electrophoresis.

Healthy adults who had not been exposed to antimicrobial agents for the preceding 4 weeks were examined for intestinal carriage of Clostridium difficile. The 1234 individuals examined were composed of seven groups: three classes of university students, hospital workers at two hospitals, employees of a company and self-defence force personnel at a local station. Overall, 94 (7.6%) individuals were positive for C. difficile by faecal culture but carriage rates among the study groups ranged from 4.2% to 15.3%. Typing by PCR ribotyping and pulsed-field gel electrophoresis demonstrated clusters of carriers colonised by a single type in each of three groups, indicating that cross-transmission of C. difficile can occur in community settings. Follow-up culture was performed on 38 C. difficile-positive individuals and C. difficile was isolated again from 12 (32%) of them 5-7 months after the initial culture; six (50%) of these 12 individuals had a new strain on repeat culture. Two or more family members were C. difficile-positive in five of 22 families examined. C. difficile with an identical type was isolated from persons within a family in only one family. These results suggest that intestinal carriage by healthy adults may play a role as a reservoir for community-acquired C. difficile-associated diarrhoea, but that cross-transmission of C. difficile does not occur frequently among family members at home.

Effect of atenolol or enalapril on diurnal changes of blood pressure in Japanese mild to moderate hypertensives: a double-blind, randomised, crossover trial.

This randomised, double-blind, crossover study compared enalapril 5 mg, and atenolol 50 mg, each dosed once daily for 4 weeks, and investigated casual and diurnal BP changes using 24 hour ambulatory BP monitoring. Both atenolol and enalapril satisfactorily lowered BP during the day and no excessive falls occurred at night. The tendency for BP to increase during the day and decrease at night was maintained during both active periods. Pulse rate was reduced only by atenolol throughout 24 hours. The BP increase observed 2 hours after rising in the morning was suppressed by atenolol but not by enalapril. Both drugs reduced the rates of systolic (greater than or equal to 160 mmHg) and diastolic (greater than or equal to 95 mmHg) BP increases to half of those during placebo. The frequency with which diastolic BP increased above these limits was less during the atenolol period. The difference in BP between a hospital casual reading and the mean 24 hour ambulatory reading was reduced only by atenolol. Furthermore, only atenolol suppressed the BP and pulse rate increases on exercise.

Alcohol sclerotherapy of hepatic cysts: its effect in relation to ethanol concentration.

While ultrasonically guided percutaneous aspiration and ethanol injection therapy has proved useful for non-neoplastic giant hepatic cysts that cause symptoms, the optimum quantity of ethanol injected into hepatic cysts has not been established. In eight patients with non-neoplastic giant hepatic cysts who were treated by ethanol injection, ethanol concentration in cystic fluid after treatment was estimated. Ethanol concentrations ranged from 5.9 to 47.6%. Hepatic cyst regressed almost completely in five cases; in all of which, the estimated ethanol concentrations were more than 40%. Our results suggest that it is desirable to drain cystic fluid as much as possible and to inject ethanol as little as possible, so that the estimated ethanol concentration in the cyst exceeds 40% for maximal effect and minimal side effects.

Pseudotumorous pancreatitis associated with ulcerative colitis.

Pancreatitis is believed to be one of the uncommon extraintestinal manifestations of ulcerative colitis (UC). A 66-year-old woman who had been treated for UC for eight months was admitted to our hospital because of epigastralgia. Laboratory examinations revealed elevated pancreatic enzymes. Because differentiation of pseudotumorous pancreatitis from pancreatic cancer was difficult by the imaging findings, she underwent a distal pancreatectomy. Histologically, the tumorous lesion was composed of fibrosis with lymphocytic infiltration. We concluded that this case was pseudotumorous pancreatitis as an extraintestinal manifestation of UC.

Acute liver injury that followed food-dependent exercise-induced anaphylaxis.

We describe an unusual case of acute liver injury that followed food-dependent exercise-induced anaphylaxis (FDEIAn). A 45-year-old man who experienced anaphylactic shock induced by postprandial exercise and took alcohol that night was admitted the following day to our hospital because of general fatigue. Laboratory examinations revealed elevated hepatic enzymes (aspartate aminotransferase (AST) 6,110 IU, alanine aminotransferase (ALT) 4,178 IU). He had two similar episodes in the past. We speculated that acute liver injury in this case might be induced by interaction of anaphylactic shock and alcohol.

Clinical features of serologically non-B non-C chronic liver disease.

BACKGROUND/AIMS: To clarify the clinical features of serologically non-B non-C chronic liver disease (SNBNCLD). MATERIAL AND METHODS: Two hundred-eleven Japanese patients hospitalized for clinical manifestations associated with non-alcoholic chronic liver disease were tested by hepatitis B surface antigen (HBsAg) by reversed passive hemagglutination (RPHA) and the second generation hepatitis C antibody (HCVAb) by passive hemagglutination (PHA). RESULTS: Twenty-two patients (10.4%, 15 men and 7 women) were diagnosed as having SNBNCLD, evaluated clinically and compared with other close etiologies. Their clinical manifestations and severity of liver disease were similar to those of other etiologies. The average age was higher than hepatitis B (p < 0.001), primary biliary cirrhosis (PBC, p < 0.05), autoimmune hepatitis (AIH, p < 0.05) and hepatitis C. None of them had a history of blood transfusion before the onset. Concomitance of hepatoma was seen in 40.9%, being uncommon compared with hepatitis B (p < 0.01) and hepatitis C (p < 0.005). No significant difference of the survival rate was shown compared to other etiologies. HBsAb was more frequent (36.4%) than in hepatitis C (p < 0.05), and disappearance of HBsAg was seen in two hepatitis B patients during the follow-up period. CONCLUSION: Our data suggest that SNBNCLD is unique and important clinical entity associated with previous hepatitis B.

Diffuse intrahepatic recurrence after resection of hepatocellular carcinoma.

BACKGROUND/AIMS: An early diffuse type in the pattern of the postoperative intrahepatic recurrence of hepatocellular carcinoma has been recognized. The purpose of this study was to elucidate risk factors for diffuse recurrence of hepatocellular carcinoma. METHODOLOGY: The subjects involved in the present study were 114 patients with hepatocellular carcinomas resected in Tenri Hospital during the past 12 years. Univariate analysis was used for retrospective determination of the factors related to diffuse recurrences after surgery in 10 cases among 114 patients. RESULTS: The risk factors linked to diffuse recurrence were microscopical portal infiltration (P < 0.01), elevated alpha-fetoprotein (more than 1000 ng/mL) (P < 0.05), the absence of preoperative transcatheter arterial embolization (P < 0.01), and two or more segmentectomies of the liver (P < 0.01). Six of 10 patients with microscopical portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL) had diffuse recurrence (P < 0.01). Six of 8 patients with two or more segmentectomies without preoperative TAE had diffuse recurrence (P < 0.01). CONCLUSIONS: When patients with the diagnosis of operable hepatocellular carcinoma have portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL), two or more segmentectomies of the liver without preoperative transcatheter arterial embolization should be avoided.

Replacement of internal protein genes, with the exception of the matrix, in equine 1 viruses by equine 2 influenza virus genes during evolution in nature.

To establish the evolutionary association between the equine 1 H7 HA and M genes, phylogenetic analyses of the six internal gene segments of equine 1 influenza viruses (H7N7 subtype) were performed using partial nucleotide sequences. The results demonstrated that five internal genes (PBI, PB2, PA, NP and NS) of equine 1 viruses isolated after 1964 were replaced by those of equine 2 H3N8 viruses. However, the M gene was maintained during the evolution of these equine 1 viruses. These findings suggest a functional association between equine H7 HA and M gene products, most likely M2 protein.

Potentially virulent Newcastle disease viruses are maintained in migratory waterfowl populations.

Forty-seven Newcastle disease virus (NDV) strains isolated from fecal samples of waterfowls in Alaska and Siberia from 1991 to 1996 were analyzed for their virulence. None of the viruses formed plaques on MDBK cells in the absence of trypsin. Of these, 29 strains showed virulent character by the mean death time with the minimum lethal dose in chicken embryos comparable to velogenic NDV strains. Of the 29 strains, 11 were sequenced for their fusion protein (F) gene. The results showed that 5 of them contained a pair of dibasic amino acids at the cleavage site of the F, which is of a virulent type. The present results suggest that potentially virulent strains of NDV are maintained in migratory waterfowl populations in nature, and that some of those may be transmitted to domestic poultry and acquire pathogenicity during passages in chicken population.

Acquisition of pathogenicity of a Newcastle disease virus isolated from a Japanese quail by intracerebral passage in chickens.

Newcastle disease virus (NDV) was isolated from a Japanese quail (Cotornix cotornix japonica). The effect of intracerebral and intranasal passages of the NDV in chickens on the pathogenicity was studied. Pathogenicity of the viruses of different passage levels was compared with that of the original isolate by the mean death time with the minimum lethal dose in chicken embryos, intracerebral pathogenicity index in day-old chicks, intravenous pathogenicity index with 6-week-old chickens and the mortality rates of chickens and quails inoculated intravenously or intranasally. The original isolate from the quail did not kill chickens but only embryos and some one-day-old chicks, exhibiting a mesogenic character. Pathogenicity of the virus of the 10th intranasal passage was not different from that of the original isolate. The viruses passaged intracerebrally, on the other hand, killed chickens of all ages by either route of inoculation, showing a velogenic property. Virus recovery from the blood and the brain was positive only in the chickens infected with brain-passaged viruses by any route of inoculation. Virus titers in the tissues of chickens infected with the brain-passaged viruses were higher than those with the original isolate and the virus of the 10th intranasal passage. These results indicate that the enhanced pathogenicity of the mesogenic NDV isolate from the quail for chickens was induced by acquiring the properties of neurotropism and pantropism through intracerebral passage in chickens.

[Long-term effect of transcatheter arterial embolization therapy for renal angiomyolipoma].

We report a case of a 21-year-old man with a right renal angiomyolipoma who has been observed for 20 months after successful treatment with selective transcatheter arterial embolization (TAE). In May 1993, he was transferred to our hospital for the treatment of an abdominal mass. Examination revealed a solid and fat-containing right renal tumor on computed tomography (CT) and magnetic resonance imaging (MRI), hypervascular staining with multiple peripheral microaneurysms on renal angiogram, indicating an angiomyolipoma (AML). He did not have any signs of tuberous sclerosis. Because he complained of abdominal pain and the tumor was 9 cm in diameter, TAE of the tumor using polyvinyl alcohol foam was performed to prevent life-threatening hemorrhage. Renal angiogram after TAE demonstrated a complete shut-down of blood supply to the tumor and CT scan, 6 and 20 months after TAE, demonstrated a decrease in size to 4.5 cm in diameter, showing a favorable long-term effect of treatment. He has been symptom-free for 20 months. TAE appears to be a safe and effective treatment for AML, preventing tumor growth and thus possibly hemorrhage or rupture of the tumor over the long -term.

[Effects of cyclosporin A on the diurnal variation of blood pressure in patients with nephrotic syndrome].

We investigated the hemodynamic, renal, and hormonal effects of cyclosporin A (CyA) treatment (6 mg/kg per day) for 4 weeks in 12 patients with nephrotic syndrome (8 women: 4 men, aged 36-66 years, 3 cases of focal glomerular sclerosis: 9 cases of membranous nephropathy). To evaluate the effects of CyA on the diurnal variation of blood pressure (BP), 24-h non-invasive BP monitoring was performed using model ABPM-630 (Nihon Colin, Tokyo, Japan) before and during CyA treatment. As indices of hemodynamics, intra-arterial pressure was monitored and cardiac output was measured by the dye-dilution technique using a cuvette at 0 and 4 weeks after treatment. CyA ameliorated urinary protein excretion and hypoproteinemia from 3.5 +/- 0.9 to 2.2 +/- 0.7 g/day, and serum protein concentration from 4.9 +/- 0.2 to 5.5 +/- 0.2 g/dl after 4 weeks' treatment. Endogenous creatinine clearance, 24-h urinary sodium excretion, and plasma renin activity decreased significantly at 1 week. CyA treatment raised casual BP from 122 +/- 4/75 +/- 2 to 140 +/- 5/87 +/- 3 mmHg after 1 week and to 146 +/- 4/90 +/- 2 mmHg after 4 weeks. Before treatment 24-h ambulatory BP monitoring showed BP reduction at night (116 +/- 5/68 +/- 3 mmHg) compared to the daytime (124 +/- 5/75 +/- 2 mmHg). The diurnal variation of BP disappeared during CyA treatment; mean daytime and nighttime pressures were 135 +/- 4/81 +/- 2, 132 +/- 5/80 +/- 3 mmHg at 1 week and 139 +/- 5/83 +/- 3, 131 +/- 6/80 +/- 3 mmHg at 4 weeks, respectively. On hemodynamic study; a 4-week treatment with CyA increased mean arterial pressure from 91 +/- 3 to 104 +/- 3 mmHg, total peripheral resistance index from 2.1 +/- 0.1 to 2.5 +/- 0.1 x 10(3) dyne.sec.cm-5.m2, and unchanged heart rate and cardiac index. Serum Mg concentration decreased from 2.1 +/- 0.1 to 1.7 +/- 0.1 mg/dl. These results suggest that CyA-induced hypertension is characterized by the loss of nocturnal decline in blood pressure, which is accompanied by volume retention after 1 week and systemic vasoconstriction after 4 weeks.

[Endosonographic diagnosis of metastatic tumors in the recto-uterine or recto-vesical space by transrectal scan].

A 6-year experience of transrectal ultrasonography (TRUS) in 75 patients with advanced gastrointestinal cancers was reviewed regarding the diagnostic yield of metastatic extrarectal tumors. A diagnostic capability of TRUS (a sensitivity of 82.9%, a specificity of 97.5% and an accuracy of 90.7%) was statistically superior to that of digital rectal examination (a sensitivity of 62.9%, a specificity of 75% and an accuracy of 69.3%). However, TRUS could hardly correctly diagnose a miliary type of extrarectal tumors in contrast to nodular and thickened types. TRUS also had an advantage over conventional ultrasonography in detecting a small amount of ascites with a sensitivity of 75%, a specificity of 93% and an accuracy of 86.6%. Patients with positive signs of extrarectal tumors or ascites on TRUS survived significantly shorter than those with negative signs. TRUS renders a convenient means in the objective diagnosis of peritoneal carcinomatosis, and predicts patient's prognosis.

[Prognostic factors and the significance of gastrectomy in gastric lymphoma].

Fifty cases of primary gastric lymphoma treated at Tenri Hospital between 1975 and 1992 were reviewed retrospectively. Histopathologically they were classified according to the Working Formulation into three groups: low grade 3 cases, intermediate grade 42 of which 34 were diffuse large cell and high grade 5. Their clinical stages according to the Ann Arbor staging system were as follows; Stage I 15 cases, Stage II 17, Stage III 5 and Stage IV 13. Twelve variables were tested by univariate analysis for prognosis. Significant prognostic factors were clinical stage, tumor depth to the gastric wall, regional lymph node involvement, macroscopic finding of tumor shape and surgical resectability. Important variables were tested by using a multiple regression, the 5 most significant variable being curative surgical resection. The year survival after curative resection was 93.8% and 25.2% for other patients (p < 0.001). In the patients with Stage II-disease, the greater the 'N-number' of regional lymph node involvement according to the General Rules for the Gastric Cancer Study was, the lower the survival rate was due to the difficulty for curative resection (p < 0.05). The same curative resection is necessary for gastric lymphoma as for gastric cancer. In the patients with Stage III or IV disease, higher survival rate was achieved in the gastrectomy group than the others. In conclusion, an aggressive surgical intervention is warranted in the treatment of gastric lymphoma of any stage.

Acetyl-L-carnitine normalizes the impaired long-term potentiation and spine density in a rat model of global ischemia.

As a consequence of an ischemic episode, energy production is disturbed, leading to neuronal cell death. Despite intensive research, the quest for promising neuroprotective drugs has largely failed, not only because of ineffectiveness, but also because of serious side-effects and dosing difficulties. Acetyl-l-carnitine (ALC) is an essential nutrient which plays a key role in energy metabolism by transporting fatty acids into mitochondria for ß-oxidation. It is an endogenous compound and can be used at high dose without toxicity in research into ischemia. Its neuroprotective properties have been reported in many studies, but its potential action on long-term potentiation (LTP) and dendritic spine density has not been described to date. The aim of the present study was an evaluation of the possible protective effect of ALC after ischemic insults inflicted on hippocampal synaptic plasticity in a 2-vessel occlusion (2VO) model in rats. For electrophysiological measurements, LTP was tested on hippocampal slices. The Golgi-Cox staining technique was used to determine spine density. 2VO resulted in a decreased, unstable LTP and a significant loss of dendritic spines. ALC administered after 2VO was not protective, but as pretreatment prior to 2VO it restored LTP nearly to the control level. This finding paralleled the histological analysis: ALC pretreatment resulted in the reappearance of dendritic spines on the CA1 pyramidal cells. Our data demonstrate that ALC administration can restore hippocampal function and spine density. ALC probably acts by enhancing the aerobic metabolic pathway, which is inhibited during and following ischemic attacks.