Cell surface phenotype of in vitro proliferating lymphocytes in HTLV-I-associated myelopathy (HAM/TSP)

The in vitro proliferation of peripheral blood lymphocytes (PBLs) without any mitogenic stimulation is one of the hallmarks of human T lymphotropic virus type I (HTLV-I) infection. Recent evidence suggests a difference in the degree of the phenomenon between HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-I carriers (AC). In this article, we demonstrated several alterations in the features of the in vitro transformed lymphocytes between patients with HAM/TSP (n = 16) and AC (n = 8). The percentages of total CD8+ and CD8+CD28+ cells were significantly increased in the in vitro proliferating T lymphocytes derived from the patients with HAM/TSP when compared to those from AC. HAM/TSP was segregated from AC by the high degree of the proliferation of CD8+CD28+ cells. The expression of HTLV-I-specific antigens on the cultured PBLs was detected only in the subjects which showed low CD8+CD28+/CD4+ ratio of the in vitro proliferating lymphocytes. These findings suggest that this phenomenon distinguishes HAM/TSP from AC, not only in quantity but also in quality.     

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.     

Type 1 collagen as a potential niche component for CD133‐positive glioblastoma cells

Cancer stem cells are thought to be closely related to tumor progression and recurrence, making them attractive therapeutic targets. Stem cells of various tissues exist within niches maintaining their stemness. Glioblastoma stem cells (GSCs) are located at tumor capillaries and the perivascular niche, which are considered to have an important role in maintaining GSCs. There were some extracellular matrices (ECM) on the perivascular connective tissue, including type 1 collagen. We here evaluated whether type 1 collagen has a potential niche for GSCs. Imunohistochemical staining of type 1 collagen and CD133, one of the GSCs markers, on glioblastoma (GBM) tissues showed CD133‐positive cells were located in immediate proximity to type 1 collagen around tumor vessels. We cultured human GBM cell lines, U87MG and GBM cells obtained from fresh surgical tissues, T472 and T555, with serum‐containing medium (SCM) or serum‐free medium with some growth factors (SFM) and in non‐coated (Non‐coat) or type 1 collagen‐coated plates (Col). The RNA expression levels of CD133 and Nestin as stem cell markers in each condition were examined. The Col condition not only with SFM but SCM made GBM cells more enhanced in RNA expression of CD133, compared to Non‐coat/SCM. Semi‐quantitative measurement of CD133‐positive cells by immunocytochemistry showed a statistically significant increase of CD133‐positive cells in Col/SFM. In addition, T472 cell line cultured in the Col/SFM had capabilities of sphere formation and tumorigenesis. Type 1 collagen was found in the perivascular area and showed a possibility to maintain GSCs. These findings suggest that type 1 collagen could be one important niche component for CD133‐positive GSCs and maintain GSCs in adherent culture.     

Thyroid carcinoma and acute lymphoblastic leukemia in childhood

A 12-year-old boy with T-cell ALL was found to have occult papillary thyroid carcinoma at autopsy. This patient was treated with chemotherapy but no radiotherapy was utilized. Family history was not contributory. Because of short latent period (14 months) and no history of radiotherapy, an intrinsic factor might have played a major role in developing this second malignancy. Currently 11 solid tumors have been reported as second malignant neoplasms after ALL in childhood. Four (including this case) of 11 were thyroid carcinoma. Two of them did not receive any radiotherapy. Special interrelation between ALL and thyroid carcinoma may be considered. And this interrelation should be taken into account in following the patients with ALL in the future.     

Autoproliferative and self-reactive T-cell lines from patients with HTLV-I-associated myelopathy

In two patients with human T lymphotropic virus type 1 (HTLV-I)-associated myelopathy (HAM) and a non-HAM HTLV-I carrier, T-cell lines were generated and characterized from cerebrospinal fluid (CSF) lymphocytes and peripheral blood lymphocytes (PBL). In total, 62 T-cell lines were established using direct plating technique for expanding human T lymphocytes. Sixty three percent of the T-cell lines were CD4+, CDw29+ and HTLV-I gag+. CD8+T-cell lines were also established and they were gag-. Proliferation in the absence of additional antigens and exogenous interleukin 2 ("autoproliferation") was observed in 61% of the T-cell lines and significantly correlated with HTLV-I antigen (gag) expression. In addition, some T-cell lines from HAM patients exhibited proliferative response to self PBL, and the magnitude of their responses was diverse according to the phenotypes of stimulating cells. Therefore, the spontaneous lymphoproliferation observed in patients with HAM is generated by three components; HTLV-I-infected T cells and T cells reactive against HTLV-I and against self antigens. Since most gag+ T-cell lines produced lymphotoxin (LT)/tumor necrosis factor alpha (TNF alpha), it is suggested that those T cells are playing important roles in the pathogenesis of HAM.     

Chondroblastic osteosarcoma arising from the pleura: Report of a case

Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura.     

Case of Carney complex complicated with pituitary adenoma and Rathke cleft cyst

Carney complex is a rare autosomal-dominant, familial tumor syndrome first described in the mid 80's. This syndrome is multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous, and neural tumor, in addition to a variety of pigmented lesions of the skin and mucosa. We report the case of a 12-year-old female patient with Carney complex who manifested a high value of serum growth hormone (s-GH), cutaneous angiomyxomas and labial pigmented lesions. Magnetic resonance imaging (MRI) revealed a cystic pituitary tumor. We carried out removal of the pituitary tumor via the transsphenoidal approach. In addition to the pituitary adenoma, pathological examination revealed the presence of a Rathke cleft cyst. So far, approximately 500 cases of this disorder have been described, but there have been no cases similar to our case described here. Therefore, the present case seems to be the first case of Carney Complex complicated with pituitary adenoma and Rathke cleft cyst.     

Renal Actinomycosis Associated With A Duodenorenal Fistula Caused by Foreign Body

We are reporting a case of a rare renal actinomycosis in a 12-year-old mentally-retarded girl. Proteinuria and hemopyuria were pointed out one year before the operation by an annual medical check-up and IVP subsequently performed showed foreign bodies at the upper pole of the right kidney. The patient continued to have pyuria and right nephrectomy was performed. There was a fistula between the duodenum and the upper portion of the right kidney. Foreign bodies (two bobby pins) were found in the kidney. Subsequent pathologic examination of the resected kidney revealed an actinomycotic lesion.     

Frontofacial monobloc advancement using the Rigid External Distraction (RED-II) system

One-stage frontofacial monobloc advancement has been used to treat patients with craniofacial synostosis including Crouzon disease. Nishimoto et al. first applied a rigid external distraction system for two patients. However, precise surgical techniques and proper indication for this gradual distraction method have not yet been established. This report describes the advantages and detailed surgical methods of frontofacial monobloc advancement using a Rigid External Distraction (RED- II) System. Three patients with severe craniofacial synostosis including Crouzon disease and Treacher Collins syndrome were treated. The ages of patients were 9, 9, and 8 year old, respectively. The RED- II System was safely applied for these young children and cosmetic results were sufficient. No major postoperative complications occurred.     

Single-membrane–bounded peroxisome division revealed by isolation of dynamin-based machinery

Peroxisomes (microbodies) are ubiquitous single-membrane–bounded organelles and fulfill essential roles in the cellular metabolism. They are found in virtually all eukaryotic cells and basically multiply by division. However, the mechanochemical machinery involved in peroxisome division remains elusive. Here, we first identified the peroxisome-dividing (POD) machinery. We isolated the POD machinery from Cyanidioschyzon merolae, a unicellular red alga containing a single peroxisome. Peroxisomal division in C. merolae can be highly synchronized by light/dark cycles and the microtubule-disrupting agent oryzalin. By proteomic analysis based on the complete genome sequence of C. merolae, we identified a dynamin-related protein 3 (DRP3) ortholog, CmDnm1 (Dnm1), that predominantly accumulated with catalase in the dividing-peroxisome fraction. Immunofluorescence microscopy demonstrated that Dnm1 formed a ring at the division site of the peroxisome. The outlines of the isolated dynamin rings were dimly observed by phase-contrast microscopy and clearly stained for Dnm1. Electron microscopy revealed that the POD machinery was formed at the cytoplasmic side of the equator. Immunoelectron microscopy showed that the POD machinery consisted of an outer dynamin-based ring and an inner filamentous ring. Down-regulation of Dnm1 impaired peroxisomal division. Surprisingly, the same Dnm1 serially controlled peroxisomal division after mitochondrial division. Because genetic deficiencies of Dnm1 orthologs in multiperoxisomal organisms inhibited both mitochondrial and peroxisomal proliferation, it is thought that peroxisomal division by contraction of a dynamin-based machinery is universal among eukaryotes. These findings are useful for understanding the fundamental systems in eukaryotic cells.Peroxisomes are single-membrane–bounded organelles found in nearly all eukaryotic cells. In plant cells, peroxisomes are involved in a variety of metabolic pathways essential for development associated with photorespiration, lipid mobilization, and hormone biosynthesis (1, 2). In animals, abnormalities in peroxisome proliferation are associated with carcinogenesis, neurodegeneration, and cerebrohepatorenal syndrome (1, 3). Peroxisomes are thought to basically proliferate by division, although they do not contain DNA (1). Because the cells of multiperoxisomal organisms, such as yeasts, plants, and animals, contain irregularly shaped peroxisomes that divide randomly, their proliferation has been examined by analyzing peroxisome abundance and distribution (4, 5). Therefore, the division machinery (ring) that is essential for proliferation and plays a central role is unclear. Cyanidioschyzon merolae offers unique advantages for studying peroxisomal division, because each cell contains a minimal set of basic eukaryotic organelles, comprising one chloroplast, one mitochondrion, one cell nucleus, and one peroxisome, the divisions of which occur in that order and can be synchronized by light/dark cycles (6–9) (Fig. 1 A and B and Fig. S1). In C. merolae, peroxisomes do not form de novo from the endoplasmic reticulum in the peroxisomal division cycle but divide by binary fission (6, 7, 10). In addition, the complete sequence of the genome has enabled proteomic analyses (7, 11).Open in a separate windowFig. 1.Identification of Dnm1 from the dividing-peroxisome fraction. (A) Immunofluorescence and schematic images of mitochondrial and peroxisomal divisions of C. merolae. Peroxisomal (red) division occurred after mitochondrial (yellow) division. Chl, chloroplast; Mt, mitochondrion; Nu, nucleus; PC, phase-contrast image; Po, peroxisome. (B) Frequencies of dividing cell nuclei (Nu), dividing chloroplasts (Chl), dividing mitochondria (Mt), and dividing peroxisomes (Po) in non–oryzalin-treated cells (control) and oryzalin-treated cells (Orz+) at the indicated times after synchronization (n > 100). (C) Proteomic analysis of peroxisomal fractions in control and oryzalin-treated cells at 20 h after synchronization. The major bands specific to oryzalin-treated cells were identified as catalase (black arrowhead), Dnm1 (red arrowhead), and others. (D) Immunoblot analyses of Dnm1, catalase, mitochondria division protein (Mda1), porin, and chloroplast division protein (PDR1). Cell, whole cell; Mt/Chl, isolated mitochondria and chloroplast; Po, isolated peroxisomes. (Scale bars: 1 μm.)