Non-glycosylated G protein with CpG ODN provides robust protection against respiratory syncytial virus without inducing eosinophilia

IntroductionRespiratory syncytial virus (RSV) vaccines targeting the fusion glycoprotein (F protein) are highly effective clinically in preventing RSV challenges. The attachment glycoprotein (G protein) is a potentially effective vaccine antigen candidate, as it is important for cell adhesion during infection. However, vaccine-associated enhanced diseases in mice, such as eosinophilic lung inflammation following RSV challenge, are a concern with G protein vaccines. This study aimed to design an effective G protein vaccine with enhanced safety and efficacy by evaluating the efficacy and adverse reactions of vaccines composed of different recombinant G proteins and adjuvants in mice.MethodsMice were subcutaneously immunized with glycosylated G protein expressed in mammalian cells (mG), non-glycosylated G protein expressed in Escherichia coli (eG), or F protein with or without aluminum salts (alum), CpG oligodeoxynucleotide (CpG ODN), or AddaVax. After vaccination, the levels of G-specific antibody and T-cell responses were measured. The immunized mice were challenged with RSV and examined for the viral load in the lungs and nasal turbinates, lung-infiltrating cells, and lung pathology.ResultsmG with any adjuvant was ineffective at inducing G-specific antibodies and had difficulty achieving both protection against RSV challenge and eosinophilia suppression. In particular, mG+CpG ODN induced G-specific T helper 1 (Th1) cells but only a few G-specific antibodies and did not protect against RSV challenge. However, eG+CpG ODN induced high levels of G-specific antibodies and Th1 cells and protected against RSV challenge without inducing pulmonary inflammation. Moreover, the combination vaccine of eG+F+CpG ODN showed greater protection against upper respiratory tract RSV challenge than using each single antigen vaccine alone.DiscussionThese results indicate that the efficacy of recombinant G protein vaccines can be enhanced without inducing adverse reactions by using appropriate antigens and adjuvants, and their efficacy is further enhanced in the combination vaccine with F protein. These data provide valuable information for the clinical application of G protein vaccines

The Uteroglobin Gene G38A Polymorphism Is Not Associated with Kawasaki Disease

This study analyzed the genomic DNA extracted from 170 patients with Kawasaki disease as well as their clinical and laboratory parametersto determine whether uteroglobin gene polymorphism, which may be associated with the morbidity rate and severity of IgA nephropathy, is involvedin the pathogenesis of Kawasaki disease, which is another type of vasculitic syndrome in childhood. The uteroglobin genotype at position38 was determined by Sau96I digestion of PCR products. The uteroglobin genotype and allele frequency in Kawasaki disease patientswere compared with those of published control data reported by three independent studies on Japanese individuals. The clinical parametersinvestigated were age at onset, gender, duration of fever, white blood cell count, C-reactive protein, aspartate aminotransferase, alanineaminotransferase and total protein. No significant difference associated with the uteroglobin genotype was observed in the clinical parameters.The genotypic and allele frequencies at position 38 of the uteroglobin gene did not differ significantly in the three studies of Japanese healthycontrols and the present study. The logistic regression analysis demonstrated that no clinical parameter was associated with the progressionto coronary artery lesions except for the duration of fever (odds ratio = 1.7; 95% confidential interval = 1.42-2.05). In conclusion, the presentstudy failed to prove an association of uteroglobin gene polymorphism with the morbidity rate or the severity of Kawasaki disease, but suggestedthe existence of a factor contributing to the onset of Kawasaki disease and progression to coronary artery lesions in Kawasaki diseasepatients

Some Factors Concerning the Distribution of Bronchial Glands

It is well known that the secretion from bronchial glands play an important role to make the airway clean up against sticky bronchial secret. The aim of the present study was to evaluate the relationship between the functional modality of bronchial glands and occurrence of postoperative pulmonary complication due to difficulty of expectoration. However, the noteworthy development of bronchial glands was proved histologically with a distribution index (DI) in each circumstances of either the elderly more than 40 of age or existing inflammation of bronchial trees. Based on histochemical examination by means of PAS stain, the almost same attitudes in regard to magnitude of secretion were not necessarily documented even among bronchial glands with marked development. It was of note that the intimate correlation between secretory behavior of bronchial glands and development of bronchial glands was not certified in the series of this study and that secretory function of bronchial glands did not compatible with pronounced distribution and marked development of them. As a result of this study, the preventive role of bronchial glands from occurrence of postoperative pulmonary complication has not been substantiated by morphological and biochemical study

Clinical Evaluation of Immune Response in Patients with Lung Cancer

In patients with lung cancer, the immune response was observed with an analysis of various factors which mostly related to its prognosis. Its response was extremly depressed in the course of following surgery in advanced cases of stage III and IVas well as in unresectable cases for lung cancer, compared with those of stage I and II . Furthermore, it showed that the high levels of immune response were seen in those of long term survivors given OK-432 during follow-up period. It was obvious from this study that the use of OK-432 was suitable for activation of the immune reaction against host as one of the immunopotentiators. Meanwhile, from the immunological mechanism of view, the hyperactivity of immune response enable the patient to be free from recurrence of cancer for a long term following surgery, in contrast the low level of the immune response showed to be poor prognosis owing to early appearance of recurrence. Furthermore, the effectiveness in use of OK-432 was clinically presented in patients with malignant pleural effusion, which showed direct cytocidal action of OK-432 given intrapleurally with a 10 or 14 days interval

Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: An analysis of Japan Multinational Trial Organisation LC00-03

We examined the impact of pretreatment neutrophil count on survival in patients with advanced non-small-cell lung cancer (NSCLC). A total of 388 chemo-naive patients with stage IIIB or IV NSCLC from a randomised controlled trial were evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte and monocyte counts and neutrophil-lymphocyte ratio on survival were examined using the proportional hazards regression model to estimate hazard ratios after adjustment for covariates. The optimal cut-off value was determined by proportional hazards regression analysis with the minimum P-value approach and shrinkage procedure. After adjustment for prognostic factors, the pretreatment elevated neutrophil count was statistically significantly associated with short overall (P = 0.0008) and progression-free survival (P = 0.024), whereas no association was found between prognosis and lymphocyte or monocyte count. The cut-off value selected for neutrophil count was 4500 mm-3 (corrected hazard ratio, 1.67; 95% confidence interval (CI), 1.09-2.54). The median survival time was 19.3 months (95%CI, 16.5-21.4) for the low-neutrophil group (≥4500 mm-3, n = 204) and was 10.2 months (95%CI, 8.0-12.3) for the high-neutrophil group (≥4500 mm-3, n = 184). We confirmed that pretreatment elevated neutrophil count is an independent prognostic factor in patients with advanced NSCLC receiving modern chemotherapy. Neutrophil count is easily measured at low cost, and it may be a useful indicator of patient prognosis

The Kidneys and Aldosterone/Mineralocorticoid Receptor System in Salt-Sensitive Hypertension

Strong evidence supports the ability of the aldosterone/mineralocorticoid receptor (MR) system to dominate long-term blood pressure control. It is also increasingly recognized as an important mediator of cardiovascular and renal diseases, particularly in the presence of excessive salt intake. In a subgroup of individuals with metabolic syndrome, adipocyte-derived aldosterone-releasing factors cause inappropriate secretion of aldosterone in the adrenal glands during salt loading, resulting in the development of salt-induced hypertension and cardiac and renal damage. On the other hand, emerging data reveal that aldosterone is not a sole regulator of MR activity. We have identified the signaling crosstalk between MR and small GTPase Rac1 as a novel pathway to facilitate MR signaling. Such a local control system for MR can also be relevant to the pathogenesis of salt-sensitive hypertension, and future studies will clarify the detailed mechanism for the intricate regulation of the aldosterone/MR cascade

An Experimental Evaluation of Tracheal Blood Flow with Special Referrence to Operative Procedure of Tracheal Mobilization

Based on the study with special referrence to blood flow in the trachea, the factors influential on the operative procedure of tracheal mobilization were carefully evaluated to ensure optimal surgical results. It has already been assumed with an aid of microangiographic technique that the main trancheal blood flow comprise two routes, namely, adventitial and submucosal layers. The amount of blood flow in the trachea divided into individual two layers were measured by hydrogen clearance test with wire electrodes placed in either adventitial or submucosal layer. When employed the procedure of extensive mobilization of the trachea, the level of tracheal blood flow reduced in adventitial layer rather lthan in submucosal layer. Blood flow in submucosal layer, however, remain closely near the normal level, which is thought to compensate a decreased blood supply in the tracheal adventitia. Meanwhile, when proposed an excessive tension of more than 800g at the site of anastomosis, a decrease in submucosal blood flow has become manifest despite of a slight decrease in adventitial blood flow simultaneously. Greater emphasis has been focused upo