Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model

Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.     

Large cell carcinoma of the lung metastatic to nuchal muscle

Abstract Clinically apparent hematogenous skeletal muscle metastases from lung cancer are extremely rare. We present a 72-year-old man with a large cell lung carcinoma metastatic to nuchal muscle. Cervical computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a well-defined mass in the left splenius capitis muscle. A percutaneous needle biopsy was performed to establish a diagnosis. Localized skeletal muscle swelling may rarely prove to be metastases in patients with lung cancer, but should be investigated in the case of muscle swelling.     

Interchange trisomy 9 due to maternal t(6; 9) translocation

The occurrence of interchange trisomy due to a 3:1 malsegregation has been documented in only a few cases with trisomy 21. We describe the first case of interchange trisomy 9 due to a maternal t(6; 9) translocation. The patient, a boy neonate who died immediately after birth, had intra-uterine growth retardation, specific craniofacial features including microcephaly with a high forehead, low-set ears, upslanting short palpebral fissures, microphthalmia, bulbous nose and micrognathia, cryptorchidism, cystic kidney and various skeletal anomalies. His phenotype was consistent with that of the trisomy 9 syndrome. Cytogenetic analysis showed his karyotype of 47,XY,-6, + der(6), + der(9)t(6; 9)(q27;q21.1)mat. The present report indicates that a very rare interchange mode of a 3:1 segregation can give rise to a live birth with full trisomy 9 in female carriers with reciprocal translocations involving the proximal long arm of chromosome 9.     

Artificial Intelligence Trained by Deep Learning Can Improve Computed Tomography Diagnosis of Nontraumatic Subarachnoid Hemorrhage by Nonspecialists

Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease with a high mortality rate and is known as a disease that is hard to diagnose because it may be overlooked by noncontrast computed tomography (NCCT) examinations that are most frequently used for diagnosis. To create a system preventing this oversight of SAH, we trained artificial intelligence (AI) with NCCT images obtained from 419 patients with nontraumatic SAH and 338 healthy subjects and created an AI system capable of diagnosing the presence and location of SAH. Then, we conducted experiments in which five neurosurgery specialists, five nonspecialists, and the AI system interpreted NCCT images obtained from 135 patients with SAH and 196 normal subjects. The AI system was capable of performing a diagnosis of SAH with equal accuracy to that of five neurosurgery specialists, and the accuracy was higher than that of nonspecialists. Furthermore, the diagnostic accuracy of four out of five nonspecialists improved by interpreting NCCT images using the diagnostic results of the AI system as a reference, and the number of oversight cases was significantly reduced by the support of the AI system. This is the first report demonstrating that an AI system improved the diagnostic accuracy of SAH by nonspecialists.