Molecular pathways in bone marrow homing: dominant role of alpha(4)beta(1) over beta(2)-integrins and selectins

The specific retention of intravenously administered hemopoietic cells within bone marrow is a complex multistep process. Despite recent insights, the molecular mechanics governing this process remain largely undefined. This study explored the influence of beta(2)-integrins on the homing to bone marrow and repopulation kinetics of progenitor cells. Both antifunctional antibodies and genetically deficient cells were used. In addition, triple selectin-deficient mice were used as recipients of either deficient (selectin or beta(2)) or normal cells in homing experiments. The homing patterns of either beta(2) null or selectin null cells into normal or selectin-deficient recipients were similar to those of normal cells given to normal recipients. Furthermore, spleen colony-forming units and the early bone marrow repopulating activity for the first 2 weeks after transplantation were not significantly different from those of control cells. These data are in contrast to the importance of beta(2)-integrin and selectins in the adhesion/migration cascade of mature leukocytes. The special bone marrow flow hemodynamics may account for these differences. Although early deaths after transplantation can be seen in recipients deficient in CD18 and selectin, these are attributed to septic complications rather than homing defects. However, when beta(2)- or selectin-null donor cells are treated with anti-alpha(4) antibodies before their transplantation to normal or selectin-deficient recipients, a dramatic inhibition of homing (>90%) was found. The data suggest that the alpha(4)beta(1)/vascular cell adhesion molecule-1 pathway alone is capable of providing effective capture of cells within the bone marrow, but if its function is compromised, the synergistic contribution of other pathways, that is, beta(2)-integrins or selectins, is uncovered.     

Autoantibody against erythrocyte protein 4.1 in a patient with autoimmune hemolytic anemia

We observed the presence of a new autoantibody, anti-erythrocyte protein 4.1, in a patient with autoimmune hemolytic anemia (AIHA). Western blotting analysis revealed that IgG from the patient's plasma reacted with erythrocyte protein 4.1. However, among other patients with hemolytic diseases (six having AIHA and three each having either hereditary spherocytosis, elliptocytosis, or lead poisoning) as well as among control subjects, no antibody activity to protein 4.1 was observed. In addition to the anti-protein 4.1 antibody, two different kinds of anti-erythrocyte antibodies were detected by conventional serological studies in this patient. One of them was an anti-Ena-like antibody in the eluate from the patient's erythrocytes, while another was the anti-S-specific antibody in the plasma. An elution study and an absorption study using S antigen-positive erythrocytes demonstrated that the anti-protein 4.1 antibody differed from both the anti-Ena-like antibody and the anti-S antibody. Familial analysis of the patient revealed the same antibody in her brother, who did not have hemolytic anemia. These results demonstrate that anti-protein 4.1 antibody is considered to be included in the spectrum of anti-cytoskeleton autoantibodies, which have been observed in patients having increased cell lysis as well as in healthy subjects.     

Usefulness of gradient tree boosting for predicting histological subtype and EGFR mutation status of non-small cell lung cancer on 18 F FDG-PET/CT

To develop and evaluate a radiomics approach for classifying histological subtypes and epidermal growth factor receptor (EGFR) mutation status in lung cancer on PET/CT images. PET/CT images of lung cancer patients were obtained from public databases and used to establish two datasets, respectively to classify histological subtypes (156 adenocarcinomas and 32 squamous cell carcinomas) and EGFR mutation status (38 mutant and 100 wild-type samples). Seven types of imaging features were obtained from PET/CT images of lung cancer. Two types of machine learning algorithms were used to predict histological subtypes and EGFR mutation status: random forest (RF) and gradient tree boosting (XGB). The classifiers used either a single type or multiple types of imaging features. In the latter case, the optimal combination of the seven types of imaging features was selected by Bayesian optimization. Receiver operating characteristic analysis, area under the curve (AUC), and tenfold cross validation were used to assess the performance of the approach. In the classification of histological subtypes, the AUC values of the various classifiers were as follows: RF, single type: 0.759; XGB, single type: 0.760; RF, multiple types: 0.720; XGB, multiple types: 0.843. In the classification of EGFR mutation status, the AUC values were: RF, single type: 0.625; XGB, single type: 0.617; RF, multiple types: 0.577; XGB, multiple types: 0.659. The radiomics approach to PET/CT images, together with XGB and Bayesian optimization, is useful for classifying histological subtypes and EGFR mutation status in lung cancer.     

Improvement of region of interest extraction and scanning method of computer-aided diagnosis system for osteoporosis using panoramic radiographs

Objectives

Patients undergoing osteoporosis treatment benefit greatly from early detection. We previously developed a computer-aided diagnosis (CAD) system to identify osteoporosis using panoramic radiographs. However, the region of interest (ROI) was relatively small, and the method to select suitable ROIs was labor-intensive. This study aimed to expand the ROI and perform semi-automatized extraction of ROIs. The diagnostic performance and operating time were also assessed.

Methods

We used panoramic radiographs and skeletal bone mineral density data of 200 postmenopausal women. Using the reference point that we defined by averaging 100 panoramic images as the lower mandibular border under the mental foramen, a 400?×?100-pixel ROI was automatically extracted and divided into four 100?×?100-pixel blocks. Valid blocks were analyzed using program 1, which examined each block separately, and program 2, which divided the blocks into smaller segments and performed scans/analyses across blocks. Diagnostic performance was evaluated using another set of 100 panoramic images.

Results

Most ROIs (97.0%) were correctly extracted. The operation time decreased to 51.4% for program 1 and to 69.3% for program 2. The sensitivity, specificity, and accuracy for identifying osteoporosis were 84.0, 68.0, and 72.0% for program 1 and 92.0, 62.7, and 70.0% for program 2, respectively. Compared with the previous conventional system, program 2 recorded a slightly higher sensitivity, although it occasionally also elicited false positives.

Conclusions

Patients at risk for osteoporosis can be identified more rapidly using this new CAD system, which may contribute to earlier detection and intervention and improved medical care.

     

Conventional X-ray versus CT in diagnosis of chronic sinusitis in children]

The interpretation of conventional radiographic views for sinusitis in children has given rise to considerable controversy. Thirty-three children (66 sides of sinuses) aged from 4 to 15 years who were suspected of having chronic sinusitis were studied to determine the accuracy of conventional X-ray examination, comparing the results with those of CT. Coronal CT was taken after conventional X-ray examination (Waters and occipito-frontal views), and the time interval between these two examinations was 0 to 14 days (average 5.1 days). The rate of correspondence in diagnosis of sinus pathology between conventional X-ray views and CT was 74.3% in the maxillary sinus and 40.9% in the ethmoid. The rate of overestimation with conventional X-ray views was 24.2% in the maxillary sinus and 56.1% in the ethmoid, while that of underestimation was 1.5% and 3.0% in the maxillary and the ethmoid sinus respectively. The incidence of false positives according to conventional X-ray views was 8.0% in the maxillary sinus and 33.3% in the ethmoid. Our results indicate that Waters view is sufficient to diagnose maxillary sinus pathology in children. However, additional radiologic examinations, such as CT, are necessary in investigating the pathologic conditions of the ethmoid sinus, since diagnostic significance of occipito-frontal view for ethmoid pathology is doubtful in children. A routine preoperative CT is recommended, which allows a detailed evaluation of pathologic changes and anatomical relations of the ethmoid before embarking a surgical intervention for the ethmoid sinus in children.     

Effects of oral caffeine intubation on bones in protein-energy malnourished newborn rats

Lactating dams with 8 suckling pups were fed either a 6% or a 20% protein diet from the birth of the pups to day 15. The pups were divided into caffeine and noncaffeine groups. Every other day between days 3 and 13, pups were either intubated with caffeine (1 mg/100 mg) dissolved in 0.1 ml physiological saline solution, or 0.1 ml saline solution as a control. On day 15, mandible and long bone weights, DNA, protein and calcium contents, collagen synthesis and 45Ca uptake in these bones of the pups were studied. Nutritional factors exercised consistent effects on all the studied parameters, but there was no difference in effects attributable to caffeine intubation, except the increased collagen synthesis in the long bones of the group with 6% protein diet with caffeine as compared to noncaffeine members of the same dietary group. We concluded that the direct administration of a relatively small amount of caffeine to newborns causes minor effects on bone development under certain nutritional conditions.     

Prenatal protein-energy malnutrition alters various biochemical components of the membranous bones in fetal rats

The effects of prenatal protein-energy malnutrition on the biochemical parameters of the membranous bone were studied using fetal rats. Timed pregnant rats were fed a protein-deficient diet as an experimental group from day 13 of gestation, whereas control dams were fed a normal protein diet. By day 15, radioactive Na2SO4 was injected. On day 22, all fetuses were delivered by cesarean section. The hexosamine content per milligram dry tissue, and the protein and hexosamine contents per guanidine-HCl extract were greater in the mandibles but less in the calvaria of the malnourished group than in those of the controls. Calcium content per gram dry tissue was lower in both bones of the malnourished group. 35S-sulfate uptake per milligram dry tissue or milligram proteoglycan was greater in the malnourished group than in the controls in both bones. The mandible in the malnourished group had less lower-weight molecular proteoglycan subunits in the dissociative condition. Protein-energy malnutrition affects the mandible and calvaria in different ways, although both bones originate from membranous bone. Insufficient degradation of proteoglycan could be the reason for the delay of mineralization in the malnourished bones.