Immunological equivalence between mouse brain-derived and Vero cell-derived Japanese encephalitis vaccines

The persistent spread via animal reservoirs urges expanding vaccination programs against pathogens like the Japanese encephalitis virus, JEV. The JEV is spreads to new areas by domestic as well as by wild animals. Although there is a safe and efficient vaccine on the market, this is derived from infected mouse brains, why today's situation requires overcoming the potential risk caused by using animal tissues. To meet this demand we have developed a Vero cell-derived JEV vaccine, using the same virus strain as in the established one. A phase III clinical study of the new vaccine has recently been completed with positive outcome. Like the established mouse brain-derived vaccine, the Vero cell-derived one is a formalin inactivated whole virus vaccine. We here demonstrate the very good agreement in immunological tests between the two antigens. The study includes analyses with two neutralizing monoclonal antibodies that blocks cell entry at a late stage in infection, assumedly interfering with fusion-related refolding in the virus fusion protein. It is obvious that the formalin inactivation treatment, with both virus preparations, retains these essential vaccine epitopes.     

A Case Report of Severe Visceral β2‐Microglobulin‐derived Amyloidosis Without Obvious Joint Symptoms or Radiological Findings in a Chronic Hemodialyzed Patient With Systemic Lupus Erythematosus

Beta‐2‐microglobulin‐derived amyloidosis (Aβ2M amyloidosis) is a critical complication for patients undergoing long‐term renal replacement therapy. Osteoarticular lesions, rather than visceral organs, are susceptible to this type of amyloidosis, and the visceral form seems to occur at a relatively late stage. Herein, we report a case of severe visceral Aβ2M amyloidosis without obvious joint symptoms or radiological findings in a chronic hemodialyzed patient who had received long‐term treatment with glucocorticoid steroids for systemic lupus erythematosus. It should be noted that prominent visceral Aβ2M amyloidosis can develop without any osteoarticular symptoms or radiological abnormalities in dialyzed patients undergoing prolonged glucocorticoid therapy.     

Benign Schwannoma of the Esophagus Removed by Enucleation: Report of a Case

(Received for publication on Sept. 18, 1998; accepted on July 13, 1999)     

A case of mesothelial cyst at the inguinal region

A 54-year-old man presented with the left inguinal swelling. The operation was performed with diagnosis of the hydrocele of spermatic cord. A tumor was 3.0 cm x 2.5 cm in size, cystic with yellowish serous fluid. After the operation, this tumor is diagnosed as mesothelial cyst through the histopathologic examination. This is a rare case, however it is worth to consider that there is a possibility to be a mesothelial cyst when the tumor has been found at the inguinal region.     

Anti-ribosomal P antibodies are associated with nephritis, vascular thrombosis and lymphocytopenia in patients with systemic lupus erythematosus

In the present study, anti-ribosomal P antibody in sera of patients with systemic lupus erythematosus was assayed using an enzyme-linked immunosorbent assay, and its association with clinical symptoms of the patients was analyzed. The presence of anti-ribosomal P antibody was associated with increased frequency of lupus nephritis in the presence of anti-DNA antibody, and was associated with increased frequency of vascular thrombosis in the presence of anti-beta2 glycoprotein I antibody and/or lupus anticoagulant. The level of anti-ribosomal P antibody correlated inversely with the peripheral lymphocyte counts.     

Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine

The safety and effectiveness of a Vero cell-derived inactivated Japanese encephalitis (JE) vaccine were compared with those of a current JE vaccine in non-clinical studies and a phase I clinical trial. The single-dose toxicity study showed no toxicity of either the current JE vaccine or the investigational Vero cell-derived JE vaccine. In a local irritation study, the degree of irritation caused by both vaccines was determined to be the same as that induced by normal saline. To investigate genotoxicity, a chromosomal aberration test was conducted and the results were negative. Both JE vaccines were administered to a group of 30 subjects who were seronegative (neutralizing antibody titer <10(1)) for JEV virus (Beijing-1 Strain). Each subject was subcutaneously inoculated twice at an interval of 1-4 weeks, followed by an additional booster inoculation 4-8 weeks later, and clinical reactions and serological responses were subsequently investigated. Adverse drug reactions of local reaction, headache and malaise were mild, occurring at a rate of 6.7 and 20.0% after administration of the Vero cell-derived JE vaccine and the current JE vaccine, respectively. The seroconversion rate after three doses of both JE vaccines was 100%, while the geometric mean titer for the Vero cell-derived and current JE vaccines was 10(2.35) and 10(2.03), respectively. These results suggest that the safety and effectiveness of the Vero cell-derived inactivated JE vaccine are equal to those of the currently available conventional vaccine in humans, and that the Vero cell-derived vaccine could be a useful second-generation JE vaccine.     

H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts

IL-12 is considered to be one of the most important cytokines in anti-cancer therapy. We have demonstrated that substances derived from Basidiomycetes, such as active hexose-correlated compound (AHCC) and PSK induce the production of IL-12. In this study, the MHC dependency of IL-12 production induced by various mycelial extracts, PSK, AHCC and IL-X, was examined. During tumor-bearing, higher serum IL-12 levels were observed in H-2a and H-2b mice as compared to H-2d mice. Concerning the effect of genetic background of mice on response to mycelial extracts, AHCC administration enhanced the serum IL-12 level in H-2b mice but not in H-2d mice, while PSK administration increased the serum IL-12 level in H-2d mice but not in H-2b mice. IL-X, components derived from the same Basidiomycetes, also enhanced the serum IL-12 level in H-2b mice in the early stage of tumor like AHCC, and maintained serum IL-12 at a level higher than the normal value accompanying tumor growth, whereas AHCC did not restore the lowered serum IL-12 level accompanying tumor growth. These results showed that AHCC or IL-X is effective in a genetically Th1-dominant individual whereas PSK is effective in a genetically Th2-dominant individual or Th2-dominant status in advanced cancer patients. So we propose that the suitable combinations of various mycelial extracts may be effective methods of endogenous IL-12 induction for cancer patients of all stages, which is important as a cancer therapy that is relatively free from adverse reactions and which emphasizes the QOL in individual patients.     

Effects of stress of postnatal development on corticosterone,serotonin and behavioral changes

Stressful events early in life are associated with later psychiatric disorders. We focused on developmental stage and evaluated changes in the corticosterone and serotonergic systems as well as in later anxiety-related behavioral tests. Stressed male Wistar rats were divided into two groups: stressed from postnatal day 11 (PND 11) to 15 and stressed from PND 16 to 20. The rats were exposed to an elevated open platform. Stress increased corticosterone in both experimental groups. In the hypothalamus, amygdala and hippocampus, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) increased in the rats stressed from PND 11 to 15, and decreased in the rats stressed from PND 16 to 20. In a later behavioral test, rats stressed from PND 11 to 15 traveled shorter distances and tended to spend less time in the center than control rats following restraint stress. There were no significant changes in 5-HT and 5-HIAA in hypothalamus, amygdala and hippocampus after restraint stress in adults. These findings indicate that stress reactions and later effects are different depending on the developmental stage during which the rats were stressed. Stress during the PND 11–15 period may enhance later anxiety-related behaviors without altering 5-HT and 5-HIAA content.     

A case of rapidly progressive interstitial pneumonia with anti-pL-12-antibodies successfully treated by pulse methylprednisolone and cyclophosphamide

A 51-year old man with severe acute respiratory failure was referred to our hospital. He presented with cyanotic digits, high fever and dyspnea. The chest radiograph and chest CT scan showed diffuse ground-glass-opacities and reticular shadows in both lung fields. We diagnosed acute interstitial pneumonia. The pulmonary infiltration seen on chest radiograph diminished gradually after pulse methylprednisolone and cyclophosphamide therapy. Later, we screened his sera for antibodies to anti-aminoacyl tRNA synthetase to diagnose anti-aminoacyl tRNA synthetase syndrome because anti-PL-12 antibodies were positive. This case has been followed but no myositis or recurrence of interstitial pneumonia has been recognized.