Role of macrophage migration inhibitory factor in otitis media with effusion in adults

Otitis media with effusion (OME) is one of the most common ear diseases. Bacterial endotoxins and several inflammatory cytokines appear to be involved in the pathogenesis of OME in children; however, little is known of the immunological aspects of the onset of OME in adults. We sought to determine the presence of macrophage migration inhibitory factor (MIF) as well as interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), and endotoxin in middle ear effusions (MEEs) from adult patients with OME. In addition, the levels of MIF in MEEs from adults and children were compared. MEE was obtained from 95 adults and 11 children. The levels of MIF, IL-1beta, TNF-alpha, and RANTES were determined by enzyme-linked immunosorbent assay, and the concentrations of endotoxin and total protein were determined by the Endospec assay and bicinchoninic acid assay, respectively. MIF was detected in 97.9% of the MEEs from adults, while endotoxin, IL-1beta, TNF-alpha, and RANTES were detected in 96.8, 12.6, 5.3, and 43.9%, respectively. In addition, the level of MIF was significantly higher than those of endotoxin, IL-1beta, and TNF-alpha. A positive correlation between the levels of MIF and endotoxin was observed. MIF and endotoxin were detected in 81.8 and 72.7%, respectively, of the MEEs from the children. The level of MIF was significantly higher in the children, and conversely that of endotoxin was significantly higher in the adults. These results suggest that the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults.     

Clonality analysis of different histological components in combined small cell and non-small cell carcinoma of the lung

Combined small cell and non-small cell carcinoma is relatively rare in the lung. Examination of the clonal relationship of different components in this type of tumor may give a clue to the rarity. We retrieved 6 such tumors; all 6 had small cell carcinoma and adenocarcinoma components, and 3 had an additional squamous cell carcinoma component. We examined the point mutations in the p53 gene and allelic loss (ie, the loss of heterozygosity [LOH] pattern) of chromosome 3p in each component. p53 mutations were detected in the small cell carcinoma component of 5 tumors and in the non-small cell carcinoma components of 2 tumors. In 1 case, the squamous cell carcinoma component had a p53 mutation locus identical to that in the small cell carcinoma component, but in the other case, the adenocarcinoma component had a different mutation than that in the small cell carcinoma component. Chromosome 3p LOH loci in the squamous cell carcinoma component were present in the small cell carcinoma component in all 3 cases, but some LOH loci were not identical in the small cell carcinoma and adenocarcinoma components in 3 cases. These results suggest that the small cell and squamous cell carcinoma components of combined small cell lung carcinomas have an intimate clonal relationship. On the other hand, the adenocarcinoma component often may be derived from a separate clone or, more likely, undergo a progressive process separate from the squamous cell-small cell carcinoma beginning in a very early stage, that is, before the appearance of p53 and chromosome 3p abnormalities. This tumorigenesis process may explain the relative rarity of combined small cell and non-small cell carcinoma, which occurs primarily in the peripheral lung, an infrequent site of squamous cell carcinoma.     

Visual checkerboard-evoked potentials from upper and lower retinal halves,and variation of check size

Human visually evoked potentials were studied with checkerboard reversal stimulation of the upper and lower halves of the visual field, using different check sizes and field diameters. Although attenuation of the overall amplitude was seen in the potentials with stimulation of the upper visual half-field, the steady-state response amplitude vs spatial frequency curves for upper and lower half-field stimulation were similar. Decrease of field size reduced the amplitude but did not change the shape of the amplitude vs spatial frequency curve with its peak of 14 min of arc check size. Dissimilar characteristics of half-field responses were seen with 2/sec reversal: stimulation of the lower visual half-field evoked wave forms with a positive component of 102 (112) msec peak latency, which was delayed by 21.5 (24) msec when the upper half-field was stimulated, using 56 (14) min checks.     

Impact of Tdap vaccine during pregnancy on the incidence of pertussis in children under one year in Brazil – A time series analysis

Pertussis is a globally distributed infectious disease that is a significant cause of morbidity and mortality, especially in infants who are too young to be immunized. This disease is common in childhood, and when it occurs during the first few months of life, it leads to hospitalization and, sometimes, death. Brazil has adopted the strategy of maternal immunization against pertussis in late 2014. This study aims to analyze public data on the disease to determine whether there was an impact on the disease burden following the introduction of the vaccine Tdap in pregnant women and its magnitude. We performed a time-series analysis of the incidence of pertussis between October 2010 and January 2019. We stratified the population of interest into three groups: infants aged less than two months old, infants aged two to six months, and infants aged six months to one year, according to Brazil's vaccination schedule. We found a protective effect of maternal vaccination in all age groups, more prominent on the first group. Before the intervention, infants under two months had a higher risk of getting pertussis in comparison with infants two to six months old (HR 1.15, CI 95%: 1.11–1.19). After the intervention, age under two months is a protective factor compared with two to six months (HR 0.90, CI 95%: 0.82–0.98). The pertussis incidence reduced in all age groups and all Brazil's Regions.     

PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.     

Combining the Tumor Contact Length and Apparent Diffusion Coefficient Better Predicts Extraprostatic Extension of Prostate Cancer with Capsular Abutment: A 3 Tesla MR Imaging Study

Purpose: To assess the diagnostic performance of the tumor contact length (TCL) and apparent diffusion coefficient (ADC) for predicting extraprostatic extension (EPE) of prostate cancer with capsular abutment (CA).Methods: Ninety-three patients with biopsy-proven prostate cancer underwent 3-Tesla MRI, including diffusion-weighted imaging (b value = 0, 2000 s/mm²) and radical prostatectomy. Two experienced radiologists, blinded to the clinicopathological data, retrospectively assessed the presence of CA on T2-weighted imaging (T2WI). TCL on T2WI and ADC values were measured on detecting CA in prostate cancer. We used the receiver operating characteristic curves to assess the diagnostic performance of TCL and ADC values for predicting EPE.Results: CA was present in 58 prostate cancers among 93 patients. The cut-off value for TCL was 6.9 mm, which yielded an area under the curve (AUC) of 0.75. This corresponded to a sensitivity, specificity, and accuracy of 84.2%, 61.5%, and 69.0%, respectively. The cut-off value for ADC was 0.63 × 10^–3 mm²/s, which yielded an AUC of 0.76. This, in turn, corresponded to a sensitivity, specificity, and accuracy of 84.2%, 59.0%, and 67.2%, respectively. The combined cut-off value of TCL and ADC yielded an AUC of 0.82. The specificity (84.6%) and accuracy (81.0%) of the combined value were superior to their individual values (P < 0.05).Conclusion: A combination of TCL and ADC values provided high specificity and accuracy for detecting EPE of prostatic cancer with CA.     

Improvement of embryonic development and production of offspring by transferring meiosis-II chromosomes of senescent mouse oocytes into cytoplasts of young mouse oocytes

Purpose  The effects of reciprocal transplantation of meiosis-II chromosomes between senescent and young mouse oocytes were evaluated based on pre- and post-implantation development ability of resultant embryos. Methods  Karyoplasts including meiosis-II chromosomes of oocytes from senescent Rockefeller mouse/Ms-Rb(6, 15) females (10 to 12 months, age-related infertile mice) were transferred into cytoplasts of oocytes from young F₁ females (3 to 5 months). Reconstructed oocytes were fertilized in vitro, and then the resultant embryos were cultured in vitro and transferred to recipient mice. Results  The reconstructed oocytes that consisted of aged-karyoplasts and young-cytoplasts showed significantly improved embryonic development (from 23.2% to 30.0%) and development to term (from 6.3% to 27.1%, P < 0.05) as compared with the oocytes reconstructed from young-karyoplasts and aged-cytoplasts. Conclusions  The present study showed successful rejuvenation for age-related infertility using transplantation of meiosis-II chromosomes in animal experimental models. Capsule Transplantation of meiosis-II chromosomes of senescent mouse oocytes into cytoplasts of young mouse oocytes improves subsequent embryonic and fetal development until birth.     

Usefulness of directly observed therapy (DOT) during hospitalization as DOTS in Japanese style

Many patients with smear positive tuberculosis were hospitalized during the initial phase of chemotherapy but DOT was not applied to patients with tuberculosis in Japan. We tried randomized clinical study to evaluate the usefulness of DOT during admission. 135 culture positive TB patients were administered by DOT and 124 culture positive TB patients were self-administered during admission. There was no significant difference between 2 groups in the clinical background factors, treatment and the incidence of adverse reactions. Treatment completion rate was 94.1% in DOT group and 87.9% in non-DOT group. Default rate was significantly lower in DOT group (4.4%) than in non-DOT group (11.3%). We concluded that "DOT during admission" was useful to improve the outcome of chemotherapy for tuberculosis and it is preferable to apply DOT throughout treatment course for patients with tuberculosis in Japan.     

Efficient protective activity of a planar catechin analogue against radiation-induced apoptosis in rat thymocytes

About two thirds of biological damage due to low linear energy transfer (LET) radiation, such as X-rays and the plateau region of heavy-ion beams, is known to be caused by the hydroxyl radical (˙OH), the most powerful reactive oxygen species (ROS), generated via ionisation and excitation of water molecules. Thus, compounds having an efficient scavenging activity against ROS are expected to exhibit a radioprotective activity. A planar catechin analogue, where an isopropyl fragment was introduced into the catechol ring of (+)-catechin, showed an efficient protective effect against X-ray induced apoptosis in rat thymocytes compared to (+)-catechin. The planar catechin scavenged 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH˙) solubilised in water by β-cyclodextrin about 10-fold faster than (+)-catechin in phosphate buffer (0.1 M, pH 7.4) at 298 K. Furthermore, the experimental log P value of the planar catechin (1.22) is reported to be significantly larger than that of (+)-catechin (0.44). The higher radical-scavenging activity and lipophilicity of the planar catechin than those of (+)-catechin may contribute in part to the higher protective activity against X-ray-induced apoptosis in rat thymocytes.

A planar catechin analogue showed a significant higher protective activity against X-ray induced apoptosis in rat thymocytes than (+)-catechin.