Release of granule proteins from human eosinophils stimulated with mast-cell mediators

Background It has been suggested that mast cells and eosinophils are major effector cells in the pathogenesis of allergic diseases. However, the interaction of these cells has not been thoroughly elucidated. We examined eosinophil cationic protein (ECP) release and cytosolic free calcium concentration ([Ca²⁺]) in human eosinophils induced by the major mast-cell mediators including cytokines. Methods Eosinophils from healthy donors were stimulated with the major mast-cell mediators for 20 min after preincubation with cytochalasin B for 10 min. ECP in supernatants was measured by radioimmunoassay. Moreover, t o examine changes of [Ca²⁺]i in eosinophils, Fura-2-loaded eosinophils were monitored for fluorescence changes after stimulus addition. Results Of the tested mediators (prostaglandin [PG]D₂, leukotriene (LT)B₄, platelet-activating factor (PAF), histamine, LTQ, and eosinophil chemotactic factor of anaphylaxis [ECF-A]), LTB₄ and PAF induced ECP release from eosinophils. Any cytokines produced by human mast cells, i.e., interleukin (IL)-4, IL-5, IL-8, tumor necrosis factor (TNF), or granulocyte-macrophage colony-stimulating factor (GM-CSF), did not induce ECP release in our system. ECP release triggered with LTB₄ and PAF occurred at concentrations of 10^?8-10^?6 M concentration-dependently. LTB4 and PAF also elicited a rise in [Ca²⁺]_i in eosinophils. Neither PGDj, histamine, nor LTC₄ induced ECP release, although they increased cytosolic calcium in eosinophils. Conclusions Of mast-cell mediators, LTB₄ and PAF induced eosinophil degranulation. The contribution of LTB4 and PAF from mast cells to eosinophil degranulation may be important in the pathogenesis of allergic inflammatory diseases.     

Changing incidence of anal sphincter tears in four Nordic countries through the last decades

Objectives

Anal sphincter rupture is a serious complication of a vaginal delivery. A considerable number of women suffer permanent anal incontinence after this type of injury. The incidence of sphincter tears is believed to have increased over several decades in Denmark, Norway, Sweden and Finland, but there seem to be significant differences in the incidence rates among these countries. The aim of this study is to compare frequency of anal sphincter tears among the four Nordic countries, and to discuss the possible reasons for the development.

Study design

Ecological register study. Anal sphincter ruptures are registered as third and fourth degree perineal tears in the national birth and hospital registries in the Nordic countries. Data from these registries were sampled from Denmark, Finland, Norway and Sweden. The incidences of anal sphincter ruptures were calculated as percentages of all vaginal deliveries and caesarean sections were excluded. The test of relative proportions, Chi-square and linear regression modelling were used to study the difference between countries and time trends.

Results

The frequency of anal sphincter rupture was significantly higher in three countries, Denmark 3.6%, Norway 4.1% and Sweden 4.2%, compared to Finland 0.6%. The trend was clearly increasing from the early 1970s in all countries.

Conclusions

There is a significant difference in the Nordic countries in the incidence of anal sphincter tears and a significant increment in the incidence over three decades. Our hypothesis is that change in the routines during labour may be one reason for this increment. Higher episiotomy frequency in Finland may be one contributing reason. We assume that there has been a change in the conduct of labour during the last decades, and protecting the perineum may have lost its importance in the three Nordic countries, while the classic method of protecting perineum is still in use in Finland.     

HIV-1 in Ethiopia: Phylogenetic divergence from other HIV-1 strains

Phylogenetic tree analysis was performed on selected polymerase chain reaction (PCR)-amplified and sequenced regions of the gag and env reading frames of several Ethiopian and Swedish human immunodeficiency virus type 1 (HIV-1) strains. These regions are considered to be conserved parts of the HIV-1 genome and correspond to the p7 of the core (gag) and part of the carboxy terminal of the gp41 protein of env respectively. Comparisons were made with all available HIV-1 sequences.The tree analysis showed that gag sequences from nine and env sequences from four Ethiopian strains all grouped together in separate branches distinct from all other sequenced European, North American, and African HIV-1 isolates. Thus, the Ethiopian strains seem to represent a highly divergent group of HIV-1, which might have developed during a relatively early stage of HIV-1 evolution.     

Effect of vertical positioning on organ dose, image noise and contrast in pediatric chest CT—phantom study

Background

CT optimization has a special importance in children. Smaller body size accentuates the importance of patient positioning affecting both radiation dose and image quality.

Objective

To determine the effect of vertical positioning on organ dose, image noise and contrast in pediatric chest CT examination.

Materials and methods

Chest scans of a pediatric 5-year anthropomorphic phantom were performed in different vertical positions (?6 cm to +5.4 cm) with a 64-slice CT scanner. Organ doses were measured with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Image noise and contrast were determined from the CT number histograms corresponding to different tissues.

Results

Significant changes in organ doses resulting from vertical positioning were observed, especially in radiosensitive anterior organs. The breast dose increased up to 16% and the thyroid dose up to 24% in lower positions. The noise was increased up to 45% relative to the centre position in the highest and lowest vertical positions, with a particular increase observed on the anterior and posterior sides, respectively. Off-centering also affected measured image contrast.

Conclusion

Vertical off-centering markedly affects organ doses and measured image-quality parameters in pediatric chest CT examination. Special attention should be given to correct patient centering when preparing patients for CT scans, especially when imaging children.     

Grading score system: A method for evaluation of the degree of senescence in Senescence Accelerated Mouse (SAM)

For evaluation of the degree of senescence in SAM-P, accelerated senescence prone mouse, formerly called SAM or prone series or P-series, consisting of SAM-P/1, SAM-P/2, SAM-P/3 and SAM-P/4 corresponding to P-1, P-2, P-3 and P-4 series, respectively, in the previous reports, and in SAM-R, accelerated senescence resistant mouse, formerly called resistant series or R-series, consisting of SAM-R/1, SAM-R/2 and SAM-R/3 corresponding to R-1, R-2 and R-3 series, respectively, in the previous reports, the grading score system was adopted. The items to be examined in this system include 11 categories selected from the clinical signs and gross lesions considered to be associated with the aging process. The degree of the senescence in each category was graded from 0 to 4 according to the detailed criteria devised in our laboratory. After 8 months of age each mouse was examined every 4 months, and some of the mice were examined after 2 months of age.In almost all categories, the grading score and incidence began to increase from 4 or 6 months of age and continued to increase with advancing age in both SAM-P and SAM-R. The increase, however, was more marked in SAM-P than in SAM-R. The slow but steady increase in the SAM-R levelled out at 24 months of age and was comparable to that of 12 months of age in SAM-P. In both SAM-P/1 at 8 months of age and SAM-R/2 at 12 months of age, there was a significant reverse correlation between total score of this grading score system and length of residual life after examination.Systematic and extensive studies using the grading score system showed that if the validity of the system is, based on “irreversibility” and “universality” of the changes in     

Impact of histological subtype on survival of patients with surgically-treated stage IA2-IIB cervical cancer: Adenocarcinoma versus squamous cell carcinoma

Objectives

To evaluate the significance of adenocarcinoma (AC) compared with squamous cell carcinoma (SCC) with regard to the survival of surgically-treated early stage cervical cancer patients.

Methods

We retrospectively reviewed the medical records of 520 patients with FIGO stage IA2-IIB cervical cancer who were treated with radical hysterectomy with or without adjuvant radiotherapy between January 1998 and December 2008. The patients were classified according to (i) pathological risk factors (low-, intermediate-, or high-risk group) and (ii) adjuvant radiotherapy (concurrent chemoradiotherapy [CCRT group] or radiotherapy alone [RT group]). Survival outcomes were examined by Kaplan-Meier method and compared with Log-rank test. Multivariate analysis for disease-specific survival (DSS) was performed using Cox proportional hazards regression model to investigate the prognostic significance of histological subtype.

Results

AC histology was associated with significantly decreased DSS compared with SCC histology in the intermediate- and high-risk groups (hazard ratio: 3.06 and 2.88, respectively, both P < 0.05) while there was no survival difference in the low-risk group (P = 0.1). Among patients who received any types of adjuvant radiotherapy, DSS of AC histology patients were significantly poorer than SCC histology. Multivariate analysis demonstrated AC histology to be an independent predictor of decreased DSS in both CCRT and RT groups. Moreover, pelvic nodal metastasis significantly predicted the poor survival of patients with AC histology who received CCRT in multivariate analysis

Conclusions

Adenocarcinoma is an independent prognostic indicator of poor survival in early stage cervical cancer patients with intermediate- and high-risk factors, regardless of the type of adjuvant radiotherapy after radical hysterectomy.     

Leiomyosarcoma of the sacral bone in a patient with a past history of resection of uterine leiomyoma

We report here a case of leiomyosarcoma in the sacrum with a differential diagnosis of metastasizing leimyoma of uterus, since the patient had a past history of resection of uterine leimyoma 19 years ago. The sacral tumor was an osteolytic lesion, 8x6 cm in size on radiological examination. Microscopically, tumor cells consisted of spindle shaped cells with moderate cellular atypia. The tumor cells invaded into the surrounding muscle tissue. Immunohistochemistry revealed that the tumor cells were positive for alpha-SMA and vimentin, and they were enclosed by type IV collagen, suggesting the presence of the basement membrane. The labeling index of Ki-67 in the tumor cells was 25%. Re-examination of leiomyomas of uterus resected 19 years ago showed that they were typical leiomyomas, showing well-circumscribed tumors, composed of well-differentiated smooth muscle cells without nuclear atypia. The presence of radiological and pathological findings of malignancy of the sacral tumor excluded the possibility of metastasizing leiomyoma, suggesting that the sacral tumor was another primary tumor.     

The neuronal regulation of fracture healing: Effects of sciatic nerve resection in rat tibia

The effect of sciatic nerve resection on tibial fracture healing was studied in rats 25 days post-trauma. To prevent differences in loading between sham-operated and nerve-resected animals the fractured limbs were cast-immobilized. On radiograms 8 of 11 fractures in the sham-operated animals showed very little callus formation in contrast to only 1 of 8 fractures in the group with nerve resection. Measured by single-photon absorptiometry, animals with sciatic nerve resection had a higher bone mineral content than the sham-operated animals. However, the mechanical strength in three-point cantilever bending was not better in the nerve-resected rats, implying a defective organization of the large callus. These results suggest neural regulation plays a role in the type of fracture healing, primary or secondary, and in the amount and quality of the callus.