Failure of inactivated influenza A vaccine to protect healthy children aged 6−24 months

BACKGROUND: The efficacy of inactivated influenza vaccine in healthy infants and children younger than 24 months has not been confirmed. The aim of the present study was to determine the prophylactic effect of inactivated influenza vaccine against influenza A in healthy children aged 6-24 months. METHODS: Healthy infants and young children (6-24 months old) were immunized by subcutaneous injection of inactivated influenza vaccine before influenza seasons. Age matched children were randomly assigned as the control. These children were followed up from January to April in each year (2000, 2001 and 2002). The attack rates of influenza A infection was compared and statistically assessed. RESULTS: The attack rate of influenza A virus infection in the vaccine group and the control group were 14.8% (n = 27) vs 12.5% (n = 32) in 2000 (P = 0.526); 2.8% (n = 72) vs 7.2% (n = 69) in 2001 (P = 0.203); and 3.4% (n = 52) vs 8.9% (n = 56) in 2002 (P = 0.205). The attack rates of influenza A between the two groups were not significantly different. CONCLUSIONS: Inactivated influenza vaccine did not reduce the attack rate of influenza A infection in 6-24 month old children.     

The critical roles of serum/glucocorticoid-regulated kinase 3 (SGK3) in the hair follicle morphogenesis and homeostasis: the allelic difference provides novel insights into hair follicle biology

Mutation in the serum/glucocorticoid regulated kinase 3 (Sgk3, also known as Sgkl or Cisk) gene causes both defective hair follicle development and altered hair cycle in mice. We examined Sgk3-mutant YPC mice (YPC-Sgk3(ypc)/Sgk3(ypc)) and found expression of SGK3 protein with altered function. In the hair follicles of YPC mice, the aberrant differentiation and poor proliferation of hair matrix keratinocytes during the period of postnatal hair follicle development resulted in a complete lack of hair medulla and weak hair. Surprisingly, the length of postnatal hair follicle development and anagen term was shown to be dramatically shortened. Also, phosphorylation of GSK3beta at Ser9 and the nuclear accumulation of beta-catenin were reduced in the developing YPC hair follicle, suggesting that phosphorylation of GSK3beta and WNT-beta-catenin pathway takes part in the SGK3-dependent regulation of hair follicle development. Moreover, the above-mentioned features, especially the hair-cycling pattern, differ from those in other Sgk3-null mutant strains, suggesting that the various patterns of dysfunction in the SGK3 protein may result in phenotypic variation. Our results indicate that SGK3 is a very important and characteristic molecule that plays a critical role in both hair follicle morphogenesis and hair cycling.     

Intraoperative radiation therapy for advanced neuroblastoma: the problem of securing the IORT field

The purpose of this study is to evaluate the efficacy of intraoperative radiation therapy (IORT) and the problem of securing the IORT field in advanced pediatric neuroblastoma. Between 1996 and 2005, 12 children received IORT for advanced pediatric neuroblastoma patients. Electron beam energies ranged from 10 to 12 MeV and median dose was 10 Gy (8-12 Gy). All of them had surgery with IORT against the primary tumor site and the abdominal aorta surroundings. A gross total resection (GTR) was achieved in 10 patients and subtotal resection (STR) was two patients. All of 12 patients were classified as high risk. Nine patients were alive 17-120 (mean 48 months) after diagnosis. Local tumor control was achieved in 100% of patients, of whom one experienced local recurrence outside the IORT field. At the operation, it was difficult to secure the IORT field because of the angle of the radiation cylinder in three patients. One of the three of these patients experienced local recurrence outside of the IORT field in the upper side of superior mesenteric artery and two of three patients had an external beam radiation after surgery, and there was no local recurrence. One patient had a postoperative ileus, and one patient had transient diarrhea and hydronephrosis. For advanced neuroblastoma patients, IORT produced excellent local control after surgery. However, there is a problem of securing the IORT field. For local control, it is necessary to add an external beam radiation after IORT when it is difficult to secure the IORT field.     

Detection of genetic alterations in advanced prostate cancer by comparative genomic hybridization

In this study, we examined nine cases of advanced Japanese prostate cancer by comparative genomic hybridization (CGH) to detect chromosomal imbalances across the entire genome and to identify several new regions likely to contain genes important to the development and progression of this disease. These cases had been previously examined for numerical chromosomal aberrations by fluorescence in situ hybridization (FISH). By CGH, the following regions were found to be over-represented (gains), with fluorescence ratio values higher than the threshold: 4p, 6p, 8q, 11q, 12q, 15q, 16p, 17q, 20, and 21 (>4 cases); underrepresentation (losses) involved: 1q, 4q, 5q, 6q, 13q, 14q, and 22 (>4 cases). The shortest regions of overlap (SRO) of gains were noted at 8q24.1 through q24.3, 12q23, and 17q23 through q24 (>5 cases). The SRO of losses were seen at 5q14 through q21, 6q16.1 through q21, 13q21.3 through q22, and 14q21 (>5 cases). Notably, the gain of chromosomes 8 and 12 by CGH was in agreement with the FISH data, suggesting that the gain of chromosomes 8 and 12 may play an important role in prostate carcinogenesis. The genes on the SRO regions were also discussed in relation to oncogenes and bone metastases.     

Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice

Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells. Accordingly, these mice show impaired bacterial clearance in response to acute septic peritonitis and are highly susceptible to infection by the intestinal nematode Strongyloides venezuelensis. Systemic anaphylactic shock responses, however, are intact. We found that although reconstitution of PI3Kminus sign/minus sign mice with bone marrow--derived mast cells (BMMCs) restored anti-bacterial immunity, only T helper type 2 (TH2)-conditioned BMMCs, not "standard" BMMCs, were able to restore anti-nematode immunity. This finding highlights the importance of the TH2 response in the control of nematode infection. Thus, PI3K likely plays an essential role in host immune responses by regulating both the development and induction of mast cells.     

Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters

To delineate more precisely the somatic von Hippel-Lindau disease (VHL) gene alteration as well as to elucidate its etiologic role in renal tumorigenesis, we examined a total of 240 sporadic renal cell carcinomas (RCCs) for somatic VHL gene alterations by DNA-SSCP followed by sequencing, methylation-specific PCR assay, microsatellite LOH study, and Southern blot analysis. Intragenic mutation of the VHL gene was found exclusively in clear-cell or variant-type RCCs at a frequency of 51% (104/202). Hypermethylation of the VHL promoter region was detected in an additional 11 clear-cell RCCs. Microsatellite analysis demonstrated that LOH of the VHL locus was found in 140/155 (90%) informative clear-cell RCCs. The VHL gene therefore seems to be inactivated in a two-hit manner by intragenic mutation or hypermethylation plus allelic loss in clear-cell RCC. Genomic rearrangement of the VHL gene detected by Southern analysis was not found (0/216 cases); this is in contrast to germ lines in which Southern aberrations consisted of 7-19% of the mutations. Clinicopathologic data demonstrated that VHL mutation/LOH did not vary according to tumor progression in clear-cell RCC, including tumor diameter, stage, grading, distant metastasis, and lymph node metastasis. Interestingly, VHL mutation was significantly less frequent in RCCs occurring in younger (< or = 55 years) than that in older (> or = 56 years) patients. These data suggested that the inactivation of the VHL tumor-suppressor gene is a specific genetic change in clear-cell RCC, and that it may occur at an early or first step in the clear-cell tumorigenic pathway rather than as a late event.     

Genetic changes in localized prostate cancer of Japanese patients shown by comparative genomic hybridization

To search for additional amplification and deletion sites that may serve as a starting point for the discovery of new oncogenes or tumor suppressor genes, 30 Japanese localized prostate cancers were analyzed by comparative genomic hybridization (CGH) in this study. CGH was used to search for changes in DNA sequence copy-number in a series of 30 primary prostate adenocarcinomas, consisting of 22 cases of pT2N0 (organ confined; without capsular invasion) and 8 cases of pT3N0 (with capsular invasion), removed by radical prostatectomy. CGH revealed that the shortest regions of overlap (SRO) of gains in pT2N0 were at 8q22.2 approximately q24.2, 11q13.1 approximately q14.1, and 12q23 approximately q24.2, whereas the SRO of losses were seen at 8p23.3 approximately p22, 13q21.2 approximately p22, and 18q21 approximately q22. The SRO of gains in pT3N0 were noted at 5q32 approximately q34, 8q22.3 approximately q24.1, 11q14.1 approximately q22.3, and 12q22 approximately q24.2, whereas the SRO of losses were seen at 18q21.2 approximately q23. These results suggest that gains or losses of DNA in these regions are important for prostate cancer progression. The detection of the SRO may serve as a starting point to discover novel oncogenes and tumor suppressor genes involved in prostate cancer progression.     

Change in intrathoracic pressure in rats with spontaneous and controlled ventilation during microgravity by parabolic flight

We previously reported that the intrathoracic pressure (ITP) decreases and the transmural pressure of the aortic wall (TMP) increases during 4.5 s of microgravity (muG) induced by free drop. To examine the ITP response to a longer period of muG in the absence of the respiratory rate (RR) decrease, i.e., bradypnea, which occurs at the onset of muG, we measured the aortic blood pressure at the diaphragma level (AP) and ITP. We then calculated the TMP at the aortic arch level during 20 s of muG induced by parabolic flight in anesthetized rats (n = 7) with either spontaneous ventilation (SPN-V) or controlled ventilation (CONT-V). In the SPN-V group, the bradypnea was observed in all rats after the onset of the muG (RR change -13.9 +/- 2.9/min). The ITP during muG (-9.3 +/- 0.9 mmHg) was significantly lower than that during 1 G (-7.7 +/- 0.9 mmHg), and the TMP was significantly increased during muG (112 +/- 6 mmHg) compared to 1 G (103 +/- 5 mmHg). Similar changes in ITP and TMP were observed in the CONT-V group: During muG and 1G, respectively, the ITP was -8.4 +/- 0.6 mmHg and -5.9 +/- 0.7 mmHg, and the TMP was 112 +/- 6 mmHg and 101 +/- 6 mmHg, whereas no change in RR was observed because of the controlled ventilation. These results show that the ITP decreases and the TMP increases during muG, and they are not affected by a disturbance of respiratory rhythm.     

Effects among healthy subjects of the duration of regularly practicing a guided imagery program

Background  

We examined a large number of healthy adults in the general community who had individually participated in a guided imagery (GI) program daily and for various durations, to examine the psychophysiological effects of a GI program within a healthy group.