Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce cell cycle progression through the synthesis of c-Myc protein by internal ribosome entry site-mediated translation via phosphatidylinositol 3-kinase pathway in human factor-dependent leukemic cells

To investigate the roles of c-myc during hematopoietic proliferation induced by growth factors, we used factor-dependent human leukemic cell lines (MO7e and F36P) in which proliferation, cell cycle progression, and c-Myc expression were strictly regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). In these cell lines, both c-myc mRNA and c-Myc protein stability were not affected by GM-CSF and IL-3, suggesting a regulation of c-Myc protein at the translational level. However, rapamycin, an inhibitor of cap-dependent translation, did not block c-myc induction by GM-CSF and IL-3. Thus, we studied the cap-independent translation, the internal ribosome entry site (IRES), during c-Myc protein synthesis using dicistronic reporter gene plasmids and found that GM-CSF and IL-3 activated c-myc IRES to initiate translation. c-myc IRES activation, c-Myc protein expression, and cell cycle progression were all blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In another factor-dependent cell line, UT7, we observed the cell cycle progression and up-regulation of c-Myc protein, c-myc mRNA, and c-myc IRES simultaneously, which were all inhibited by LY294002. Results indicate that hematopoietic growth factors induce cell cycle progression via IRES-mediated translation of c-myc though the PI3K pathway in human factor-dependent leukemic cells.     

A case of thoracic esophageal cancer with an unusual type of duplicated inferior vena cava

We describe here a thoracic esophageal cancer with an unusual type of duplicated inferior vena cava. A 58-year-old man was referred to our hospital because a tumor in his lower esophagus had been identified by endoscopy and radiology. Computed tomography scans showed an unusual type of duplicated inferior vena cava characterized by both common iliac veins flowing back into the left-sided inferior vena cava, which drained into the azygos vein, whereas the right-sided one had no drainage. Esophagectomy was performed 3 weeks later after preoperative chemotherapy. Because the patient could have developed thrombosis of the left-sided inferior vena cava and severe hypotension caused by decreased venous return to the heart if the azygos vein had been severed, the azygos vein was preserved. Thus, when performing surgery for thoracic esophageal cancer, the surgeon should check for a duplicated inferior vena cava and preserve the azygos vein if necessary.     

Rapid Identification and Subtyping of Helicobacter cinaedi Strains by Intact-Cell Mass Spectrometry Profiling with the Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

Helicobacter cinaedi infection is recognized as an increasingly important emerging disease in humans. Although H. cinaedi-like strains have been isolated from a variety of animals, it is difficult to identify particular isolates due to their unusual phenotypic profiles and the limited number of biochemical tests for detecting helicobacters. Moreover, analyses of the 16S rRNA gene sequences are also limited due to the high levels of similarity among closely related helicobacters. This study was conducted to evaluate intact-cell mass spectrometry (ICMS) profiling using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) as a tool for the identification of H. cinaedi. A total of 68 strains of H. cinaedi isolated from humans, dogs, a cat, and hamsters were examined in addition to other Helicobacter species. The major ICMS profiles of H. cinaedi were identical and differed from those of Helicobacter bilis, which show >98% sequence similarity at the 16S rRNA sequence level. A phyloproteomic analysis of the H. cinaedi strains examined in this work revealed that human isolates formed a single cluster that was distinct from that of the animal isolates, with the exception of two strains from dogs. These phyloproteomic results agreed with those of the phylogenetic analysis based on the nucleotide sequences of the hsp60 gene. Because they formed a distinct cluster in both analyses, our data suggest that animal strains may not be a major source of infection in humans. In conclusion, the ICMS profiles obtained using a MALDI-TOF MS approach may be useful for the identification and subtyping of H. cinaedi.     

Infection-immunity liaison: Pathogen-driven autoimmune-mimicry (PDAIM)

Autoimmunity causes pathological conditions resulting in autoimmune diseases (ADs). Although autoimmunity is a mystery, immunological dogma suggests that autoreactive cell reactivation (ACR) breaks self-tolerance and induces autoimmunity. Thus, ACR is a royal pathway for ADs. Cumulative evidence implicates environmental factors as secondary triggers of ADs in the genetically susceptible hosts. Infection is the most likely trigger. Although several mechanisms have been proposed to explain how infectious agents trigger ADs, ACR is assumed to be an essential pathway.     

PLATELET KINETICS AFTER TRANSFUSION

A kinetics model is proposed for platelet disposition after transfusion of platelets. In this model, transfusion of platelets and production of endogenous platelets contribute to an increase in the number of platelets in patients, and the life span and age of each platelet contribute to a decrease. The time course of the number of platelets after transfusion of platelets is theoretically described by this model to be a straight line followed by a concave curve. When the platelets have a life span without any variation, a linear pattern is observed in spite of their different ages at the transfusion. This model with a constant life span was applied to three patients receiving platelet transfusion, and the model parameters were calculated by curve fitting the observed platelet levels to the model using the nonlinear least-squares method. As a result, the life span, distribution volume per body weight, and endogenous platelet level (averages for three patients) were calculated as 6·29 d, 0·137 L kg⁻¹, and 1·40×10⁴ counts μL⁻¹, respectively. The calculated platelet levels in individual patients were compared with the observed ones during the next transfusions, and the relative and absolute differences between calculated and observed values were 2·0±15.3% and −0·075±0·443×10⁴ counts μL⁻¹ (mean±SD, 15 observed points for three patients), respectively. These case studies suggest that the model could be clinically useful for individual platelet transfusion.     

A rare case of metastatic renal cell carcinoma resembling a nerve sheath tumor of the cauda equina.

We present a rare case of solitary metastasis to the cauda equina from the kidney. The patient was a 68-year-old man with a two-year history of low back pain. His past medical history revealed a renal cell carcinoma diagnosed seven years earlier. His lumbosacral MR imaging showed a well-demarcated, intradural extramedullary mass at the L3 level. He underwent an L2-4 laminectomy. The operative findings of the tumor quite resembled that of a nerve sheath tumor. It did not infiltrate into the subarachnoid space and involved only one spinal nerve. Pathology of the tumor was a metastasis of the renal cell carcinoma. Only 10 cases with such a metastasis to the cauda equina have been reported in the English literature. We added the 11th and reviewed the literature with reference to tumor pathologies, clinical findings and route of metastasis to the cauda equina.     

Japanese guidelines for atopic dermatitis 2017

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is an inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.The basics of treatment discussed in this guideline are based on the “Guidelines for the Treatment of Atopic Dermatitis 2008” prepared by the Health and Labour Sciences Research and the “Guidelines for the Management of Atopic Dermatitis 2015 (ADGL2015)” prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the “Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2016” together with those for other allergic diseases.     

The treatment outcomes of synchronous and metachronous esophageal squamous cell carcinoma and head and neck squamous cell carcinoma

Background

The treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC) and head and neck squamous cell carcinoma (HNSCC) have been poorly documented.

Patients and methods

We investigated 50 patients with synchronous and metachronous ESCC and HNSCC. We focused on the treatment results of 20 patients with synchronous ESCC and HNSCC who received simultaneous chemoradiotherapy (CRT).

Results

There were 34 patients (68.0?%) with stage 0?CI ESCC and 40 patients (80.0?%) with stage II?CIV HNSCC. A total of 13 (26.0?%) patients underwent endoscopic mucosal resection and 28 (56.0?%) underwent CRT for ESCC, and 35 (70.0?%) of the patients with HNSCC were treated with CRT. The 5-year overall survival rates of the 50 patients with synchronous and metachronous ESCC and HNSCC was 57.8?%. For the 20 patients with synchronous ESCC and HNSCC who received simultaneous CRT, the CRT was completed in 19 (95.0?%) patients. Although grade 3?C4 adverse events were observed in five (25.0?%) patients, there were no therapy-related deaths. Complete responses (CRs) of both ESCC and HNSCC were observed in ten (50.0?%) patients. The 5-year overall survival rate of the 20 patients was 60.0?%. CRs of both ESCC and HNSCC were obtained in seven (58.3?%) patients by using a cisplatin/5-FU regimen (n?=?12), and in the other three (37.5?%) patients by a platinum-based monotherapy regimen (n?=?8).

Conclusion

The surveillance of double cancer and the use of radical treatment contributed to the favorable outcome of the patients with ESCC and HNSCC. The optimal chemotherapy regimen for simultaneous CRT remains to be determined.