Induction of insulin-like growth factor 2 expression in a mesenchymal cell line co-cultured with an ameloblast cell line

Various growth factors have been implicated in the regulation of cell proliferation and differentiation during tooth development. It has been unclear if insulin-like growth factors (IGFs) participate in the epithelium–mesenchyme interactions of tooth development. We previously produced three-dimensional sandwich co-culture systems (SW) containing a collagen membrane that induce the differentiation of epithelial cells. In the present study, we used the SW system to analyze the expression of IGFs and IGFRs. We demonstrate that IGF2 expression in mesenchymal cells was increased by SW. IGF1R transduces a signal; however, IGF2R does not transduce a signal. Recombinant IGF2 induces IGF1R and IGF2R expression in epithelial cells. IGF1R expression is increased by SW; however, IGF2R expression did not increase by SW. Thus, IGF2 signaling works effectively in SW. These results suggest that IGF signaling acts through the collagen membrane on the interaction between the epithelium and mesenchyme. In SW, other cytokines may be suppressed to induce IGF2R induction. Our results suggest that IGF2 may play a role in tooth differentiation

Rationale and Design of a Prospective, Multicentre, Stop Tyrosine Kinase Inhibitor Trial of Paediatric Patients with Chronic Myeloid Leukaemia with Sustained Complete Molecular Response (STKI-14)

Chronic myeloid leukaemia (CML) is a relatively rare disease in children, accounting for 2–3% of all paediatric leukaemia cases. Generally, children with CML can avoid hematopoietic stem cell transplantation and achieve molecular responses with tyrosine kinase inhibitors (TKI). However, CML stem cells are thought to survive in many patients, even after TKI treatment. Many aspects of the toxic effects of prolonged exposure to TKIs during childhood remain unclear, particularly those regarding growth impairment. This lack of clarity underscores the importance of the present clinical trial, which aims to clarify the feasibility of treatment-free remission (TFR) in children following TKI treatment. We aim to examine the long-term out-comes and complications of TKIs before and after cessation to better understand the unknown complications that could arise in adulthood. This trial targets patients who were diagnosed with CML at an age younger than 20 years, were in the chronic or accelerated phase at initial diagnosis and remained in complete molecular remission for at least 2 years after TKI administration. We will examine the utility of TKI cessation and assess the treatment results of patients who resumed TKI therapy after losing a major molecular response. We will also investigate factors related to the feasibility of a TFR after TKI cessation

シンキ ケツユウビョウ A カンジャ ニ タイ スル ダイ 8 インシ セイザイ オ モチイ タ キンキュウ タイオウ : 2 ニュウジ レイ ホウコク

確定診断前に凝固第VIII因子(F VIII)製剤の緊急投与を要した重症型血友病A の2 乳児例を報告する.症例1 は10 か月男児.反復する嘔吐を主訴に入院した.左上肢に腫張を伴う筋肉内出血と硬膜外血腫を認めた.症例2 は10 か月男児.止血困難な口唇裂傷後の出血を主訴に来院し,重度の貧血を認めた.2 例ともプロトロンビン時間(PT)正常,活性化プロトロンビン時間(APTT)の著明な延長より,血友病を強く疑った.いずれも重篤な出血を認めたため,凝固因子活性値による確定診断を待たず,緊急でF VIII製剤の投与を試みた.投与後2 例ともAPTT は改善し,出血症状も改善した.後日2 例ともにF VIII活性が1%未満と判明し,重症型血友病A と確定診断された.The cause of hemophilia A and B involves loss of factor VIII( FVIII) and factor IX( FIX), respectively. The hereditary form of this hemorrhagic disease is X-linked recessive. It is well established that the critical region for hemophilia A is localized on Xq28 and for hemophilia B on Xq27.1- 27.2. The initial symptom is bleeding in the mucous membranes often accompanied by intramuscular and intraarticular hemorrhage. The hemorrhages in the joints cause joint contracture as a sequela. The diagnosis of hemophilia is based on a normal bleeding and prothrombin time(PT)and prolonged activated partial thromboplastin time (APTT). We report here two infants of the severe typical from of hemophilia A who were treated with sufficient needed dosage of recombinant factor VIII before a final diagnosis was made. Case 1 was a 10-month-old boy. He was hospitalized for recurrent vomiting. He had intramuscular bleeding with swelling of the left shoulder and upper extremity. A head CT showed multiple epidural hematomas. Case 2 was a 10-month-old boy. He was sent to our hospital because of a lip laceration that did not stop bleeding, and he had severe anemia. We made the diagnosis of hemophilia A based on both their normal laboratory finding of PT and on the finding of extended APTT. Before confirming the decision diagnosis of hemophilia, we intravenously injected recombinant FVIII immediately, because of the severe hemorrhagic symptoms. After the therapy, both the APTT and hemorrhagic symptoms improved. These two cases were later confirmed as a severe infantile form of hemophilia A with less than 1 % factor VIII activity

Fluctuations in C-Reactive Protein in a Hepatoblastoma Patient with Thrombocytosis

We observed the changes in serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) in a patient with hepatoblastoma exhibiting thrombocytosis. The concomitant changes of IL-6 and CRP concentrations after the initiation of chemotherapy, in the absence of infection, suggested that the IL-6, which is synthesized in hepatoblastoma cells and induces thrombocytosis, also stimulated CRP production in the present case. IL-6 is thought to play an important role in thrombocytosis in hepatoblastoma