Radioimaging of human glioma xenografts with 123I labeled monoclonal antibody G-22 against glioma-associated antigen

Summary Monoclonal antibody (MCA) G-22 is directed against a human glioma-associated surface antigen. Its availability for the radioimmunodetection of human glioma was analyzed by utilizing the xenografts in athymic mice. Nude mice with subcutaneous grafts of U251-MG or U251-SP glioma received intravenous administration of ¹²³I or ¹³¹I labeled F(ab)2 fragment or whole immunoglobulin. Results of radioimaging revealed that ¹²³I-labeled antibody was better than the ¹³¹I-labeled. It was also noted that administration of ¹²³I-labeled F(ab)2 fragment of G-22 MCA enabled the imaging of human glioma xenografts weighing 80–650 mg after 48 hours. When biodistribution of ¹²³I MCA was compared between G-22 and control antibodies, the percentages of dose/g in tumors were 5.228–1.799 at 30 hours and 4.112–1.132 at 48 hours with G-22 and they were 4.164–1.248 and 0.314–0.142 with control. The tumor/blood ratio until 72 hours after injection was constantly above 1 with G-22 and less than 1 with control antibody. These results indicate the potential usefulness of G-22 MCA for the radioimmunodetection of human gliomas.     

Detection of α S1-casein in vomit from bottle-fed babies by enzyme-linked immunosorbent assay

Summary This study describes a sensitive enzyme-linked immunosorbent assay (ELISA) using rabbit anti-bovine S1-casein antibody for the detection of commercial milk and milk-containing vomit. The antibody does not react with other human body fluids such as breast milk. The stability of S1-casein antigenic activity was examined after storage at different temperatures and enzyme digestion. There was no decrease after storage for one year at room temperature but 40% of the activity was lost after 6 months at 37°C. Enzyme digestion (6 hours, 37°C) resulted in 65 70% loss of activity but the antibody reacted with the peptide fragments of S1-casein. Vomit samples from 3 normal infants were tested by ELISA, and a S 1-casein could be detected in 1 cm² stain.     

Immediate surgery reduces mortality in deeply comatose patients with spontaneous cerebellar hemorrhage

Cerebellar hemorrhage is regarded as a neurosurgical emergency. However, patients with deteriorating consciousness are very likely to die irrespective of the choice of therapy, and it is not clear if surgical intervention can benefit patients in a deeply comatose state. We reviewed 20 patients with a Glasgow Coma Scale score of 3 at admission to ascertain the salvage rate and determine the prognostic factors. Four patients who were managed conservatively died within 2 days. Sixteen patients underwent decompressive suboccipital craniectomy and hematoma evacuation. At discharge, three patients were moderately disabled, three were severely disabled, four were persistently vegetative, and six had died. The overall mortality was 50%. The mean interval between the onset of symptoms and the operation was 1.67 +/- 0.29 hours in patients with favorable outcome, and significantly longer at 2.42 +/- 0.49 hours in patients with an unfavorable outcome (p = 0.025). Immediate evacuation of the hematoma reduces morbidity and mortality even in deeply comatose patients, especially if the time interval between the onset and surgery is within 2 hours.     

A Comparison of Visual Field and Optic Disc Appearance Depending on the Peak Intraocular Pressure in Patients with Normal-tension Glaucoma

Purpose To review the outcome of surgery for strabismus due to ethmoid sinus surgery.Cases and Methods The series comprised 13 cases, 1 of inferior rectus paresis, 1 of superior oblique paresis, 6 of medial rectus paresis, and 5 of medial rectus muscle palsy due to third nerve palsy. In the cases of paresis of the rectus muscle, resection of the rectus muscles was mainly performed. In the cases of palsy of the rectus muscle, transposition of the extraocular muscle with simultaneous recession of the lateral rectus muscle was performed. The major aim of surgery was to bring both eyes into alignment and to eliminate diplopia in the primary position.Results The mean preoperative horizontal deviation of 18.1 degrees of exotropia in the paresis cases was reduced to 1.4 degrees of exotropia after surgery. The mean preoperative vertical deviation of 3.8 degrees of hypertropia was reduced to 1.4 degrees of hypertropia postoperatively. The mean preoperative horizontal deviation of 35.6 degrees of exotropia in the palsy cases was reduced to 9.4 degrees of exotropia after surgery. The mean preoperative vertical deviation of 2.0 degrees of hypertropia was increased to 2.6 degrees of hypertropia postoperatively. Postoperatively, diplopia was absent in 11 cases with a slightly compensatory head posture.Conclusions Surgery for strabismus due to sinus surgery induces improvements in eye position and diplopia. Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc 107:425–432, 2003)     

Serial changes in N-isopropyl-p[125I]-iodoamphetamine in mouse lung observed with a confocal laser scanning microscope

Serial changes in N-isopropyl-p[125I]-iodoamphetamine (125I-IMP) in mouse lungs were observed with a confocal laser scanning microscope. Male mice were intravenously injected with 125I-IMP and subjected to autoradiographic procedures 20 minutes, and 3 and 24 hours after injection. Differential interference contrast (DIC) images and confocal images were obtained with a confocal laser scanning microscope, and superimposed images were evaluated. Large numbers of silver grains were observed in the interstitium, bronchioles, and alveolar sacs 20 minutes after the injection, and lamellar distribution of the grains was observed on the ciliary surface. The numbers of silver grains in the interstitium and bronchioles had decreased 3 hours after the injection of 125I-IMP, but the numbers of silver grains in the alveolar spaces had not. Although small numbers of silver grains remained in both the bronchioles and alveolar sacs 24 hours after the injection, most of them had washed out. Confocal laser scanning microscopy is considered to be a useful procedure for studying the distribution of radioisotopes by microautoradiography, because it allows clear autoradiographs to be obtained in which tissues and silver grains are perfectly matched and all silver grains are in focus.     

PAX5 alterations in an infant case of KMT2A‐rearranged leukemia with lineage switch

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A‐rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A‐MLLT3‐rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A‐MLLT3‐rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre‐post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia.     

The clinical relevance of unfolded protein response signaling in breast cancer

Protein homeostasis regulated by the Endoplasmic Reticulum (ER) is a recognized process involved in cancer progression. ER stress activates the Unfolded Protein Response (UPR) and has been implicated in a variety of cancers. Given the role of the UPR activation in carcinogenesis, we hypothesized that UPR activation could be associated with pathological progression, higher clinical stage, and worse survival in breast cancer. A total of 4,416 breast cancer patients from multiple independent cohorts were analyzed. We defined the UPR pathway score by the degree of enrichment by Gene Set Variant Analysis and median was used to divide high vs. low score groups in each cohort. High UPR breast cancer significantly enriched not only cell proliferation-related but also other pro-cancerous gene sets consistently in both METABIC and {"type":"entrez-geo","attrs":{"text":"GSE96058","term_id":"96058"}}GSE96058 cohort. Majority of UPR pathway score high cells in the bulk tumor were tumor cells compared to other cells, including stromal, T-, B-, and myeloid-cells (P<0.001). UPR score was significantly associated with advanced stage, high grade, and triple negative breast cancer (TNBC) (all P<0.001). High UPR breast cancer was associated with worse patient survival in both cohorts (all P<0.001). Among breast cancer subtype, ER-positive/HER2-negative breast cancer with high UPR was significantly associated with worse survival, but neither HER-positive nor TNBC. High UPR ER-positive/HER2-negative breast cancer was infiltrated with high level of Th1 and Th2 cells, M1 macrophage, and plasma cells. On the other hand, they were significantly infiltrated with high level of several types of stromal cells in tumor microenvironment (all P<0.001). Finally, high UPR metastatic breast cancer was also associated with worse patient survival (P=0.041). UPR signaling is associated with cancer aggressiveness, and worse survival, especially ER-positive/HER2-negative breast cancer subtype.