Characterization of patients with systemic lupus erythematosus who meet the diagnostic criteria for TAFRO syndrome.

Purpose TAFRO syndrome is a novel disorder manifesting as fever, anasarca, thrombocytopenia, renal insufficiency and organomegaly, and its etiology has not been clarified. The aim of this study was to elucidate similarities and differences between systemic lupus erythematosus (SLE) and TAFRO syndrome. Methods We examined 46 consecutive patients diagnosed with SLE and determined whether they meet the proposed diagnostic criteria for TAFRO syndrome (2015 version). Results Of the 46 patients with SLE, four (8.7%) also met the TAFRO syndrome criteria (TAFRO-like group). All patients in the TAFRO-like group were males, and their mean age was significantly higher than that of the non-TAFRO group (67.5 ± 8.7 vs. 39.3 ± 18.1 years, p = 0.004). C-reactive protein and γ-glutamyl transpeptidase levels were significantly higher, and frequencies of anti-dsDNA and anti-Sm antibodies were significantly lower in the TAFRO-like than non-TAFRO group. Elder cases (onset age ≥ 50 years) met significantly more categories of the diagnostic criteria for TAFRO syndrome than did those with younger cases. Conclusions Several patients with SLE, especially elder cases, showed features similar to those of TAFRO syndrome. Although exclusion of SLE is needed in the diagnostic criteria for TAFRO syndrome, TAFRO syndrome-like SLE should be considered.

CT findings in 11 patients with TAFRO syndrome: a variant of multicentric Castleman's disease.

AIM: To assess detailed computed tomography (CT) findings in patients with the recently described thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome, in order to contribute to imaging interpretation in the challenging diagnosis of this disease. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived the need for informed consent. Eleven patients (six men, five women; mean age, 52.5 years) with confirmed TAFRO syndrome were included in this study. Chest-to-pelvis CT images were analysed for the presence of anasarca, organomegaly, bone lesions, and lung lesions. RESULTS: Anasarca was present in all patients and involved multiple cavities and tissues; pleural effusion and ascites were found in 100% of patients; pericardial effusion in 64%; periportal collar in 91%; gallbladder wall oedema in 78%; subcutaneous oedema in 91%; retroperitoneal oedema in 100%; and mesenteric oedema in 100%. Organomegaly involved multiple organs: hepatomegaly in 73%, splenomegaly in 82%, lymphadenopathy in 100%, and enlarged anterior mediastinum in 64% (solitary, well-circumscribed mass, 0%; infiltrative mass, 0%; non-mass-forming infiltrative lesion, 64%). Bone lesions were present in 91% patients and all bone lesions had ground-glass density with diffuse distribution. None of the patients had any lesions in their lungs. CONCLUSION: The present study revealed that the findings of anasarca, organomegaly, and diffuse bony ground-glass appearance were observed in detail on CT in patients with TAFRO syndrome. A "matted" appearance of the enlarged anterior mediastinum is the characteristic CT finding of TAFRO syndrome, and it is possible to diagnose TAFRO syndrome from the combination of several CT findings.

Impact of inflammation-based prognostic score on survival after curative thoracoscopic esophagectomy for esophageal cancer.

BACKGROUND: Despite recent improvements in early detection, progress in surgical techniques, and development of chemoradiation therapies, prognosis of esophageal cancer remains poor. The aim of the present study was to assess whether Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, has prognostic value independent of conventional clinicopathological criteria in patients undergoing curative resection for esophageal cancer, even in elderly patients. METHODS: We retrospectively reviewed the database of 141 consecutive patients with histologically verified esophageal squamous cell carcinoma who underwent potentially curative surgery in our institute, between January 2006 and December 2014. GPS and neutrophil lymphocyte ratio (NLR) were calculated. RESULTS: On multivariate analysis, TNM stage (p < 0.0001) and GPS (p = 0.041) were independently associated with worse prognosis in overall patients with esophageal cancer. Multivariate analysis evaluated the prognostic factors in two different patient groups: patients younger than 70 years (non-elderly) and those aged 70 years or more (elderly). Multivariate analysis demonstrated that TNM stage (p = 0.0003) was an only independent risk factor for a worse prognosis among non-elderly group. Meanwhile, multivariate analysis demonstrated that TNM stage (p = 0.001) and GPS (p = 0.043) were the independent risk factor for a worse prognosis among elderly group. CONCLUSION: The present study demonstrated that GPS is associated with prognosis and can be considered as an independent prognostic marker in patients who underwent esophagectomy. Moreover, the GPS has the advantage of being simple to measure, routinely available and well standardized. But the present study failed to confirm the NLR as a significant predictor of survival following resection for esophageal cancer.

Characterization of biogenic iron oxides collected by the newly designed liquid culture method using diffusion chambers.

We designed a new culture method for neutrophilic iron-oxidizing bacteria using liquid medium (i) to study the formation and mineralogical characteristics of biogenic iron oxides (BIOS) and (ii) to apply BIOS to various scientific and engineering applications. An iron-oxidizing bacterium, Mariprofundus ferrooxydans PV-1(T) (ATCC, BAA-1020), was cultured using a set of diffusion chambers to prepare a broad anoxic-oxic interface, upon which BIOS formation is typically observed in natural environments. Iron oxide precipitates were generated in parallel with bacterial growth. A scanning electron microscopy analysis indicated that the morphological features of the iron oxide precipitates in the medium (in vitro BIOS) were similar to those of BIOS collected from natural deep-sea hydrothermal environments in the Northwest Eifuku Seamount field in the northern Mariana Arc (in situ BIOS). Further chemical speciation of both the in vitro and in situ BIOS was examined with X-ray absorption fine structure (XAFS). A bulk XAFS analysis showed that the minerals in both BIOS were mainly ferrihydrite and oligomeric stages of amorphous iron oxyhydroxides with edge-sharing octahedral linkages. The amount of in vitro BIOS produced with the diffusion-chamber method was greater than those produced previously with other culture methods, such as gel-stabilized gradient and batch liquid culture methods. The larger yields of BIOS produced with the new culture method will allow us to clarify in the future the mineralization mechanisms during bacterial growth and to examine the physicochemical properties of BIOS, such as their adsorption to and coprecipitation with various elements and substances.

Isolated neurosarcoidosis in the medulla oblongata involving the fourth ventricle: a case report.

We report a 61-year-old woman with definite diagnosis of isolated neurosarcoidosis in the medulla oblongata involving the fourth ventricle. We could not recognize neurosarcoidosis as one of the differential diagnoses of the lesion before biopsy because the brainstem lesion location and periventricular lesion configuration were quite unusual.

Coupled regulation of interleukin-12 receptor beta-1 of CD8+ central memory and CCR7-negative memory T cells in an early alloimmunity in liver transplant recipients.

This study investigated how CD8(+) T cell subsets respond to allo- and infectious immunity after living donor liver transplantation (LDLT). Early alloimmunity: 56 recipients were classified into three types according to the post-transplant course; type I demonstrated uneventful post-transplant course, type II developed severe sepsis leading to multiple organ dysfunction syndrome or retransplantation and type III with acute rejection. In 23 type I recipients, the interleukin (IL)-12 receptor beta-1 (R beta 1)(+) cells of central memory T cells (Il-12R beta 1(+) T(CM)) were increased above the pretransplant level. In 16 type II recipients, IL-12R beta 1(+) T(CM) was decreased markedly below the pretransplant level on postoperative day (POD) 5. In 17 type III recipients, IL-12R beta 1(+) T(CM) was decreased for a more prolonged period until POD 10. Along with down-regulation of IL-12R beta 1(+) T(CM), the IL-12R beta 1(+) cells of CCR7-negative subsets (CNS) as well as perforin, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha decreased gradually, resulting in the down-regulation of effectors and cytotoxicity. The down-regulation of IL-12R beta 1(+) T(CM) was suggested to be due to the recruitment of alloantigen-primed T cells into the graft, and then their entry into the secondary lymphoid organ, resulting in graft destruction. Infectious immunity: immunocompetent memory T cells with the capacity to enhance effectors and cytotoxicity were generated in response to post-transplant infection along with both up-regulation of the IL-12R beta 1(+) T(CM) and an increase in the CNS showing the highest level of IL-12R beta 1(+) cells. In conclusion, this work demonstrated that the IL-12R beta 1(+) cells of T(CM) and CNS are regulated in a tightly coupled manner and that expression levels of IL-12R beta 1(+) T(CM) play a crucial role in controlling allo- and infectious immunity.

Two cases of recurrent IgA nephropathy following kidney transplantation.

Recurrence of immunoglobulin (Ig) A nephropathy following kidney transplantation has been described as occurring in 40% to 60% of cases. Although this type of recurrence was considered a benign condition for a long time, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We present 2 cases of recurrent IgA nephropathy following kidney transplantation. In case 1, renal function remained stable with a creatinine level of 1.2 mg/dL at 5 months after diagnosis and 61 months after transplantation. In case 2, the patient lost his graft and returned to regular hemodialysis at 36 months after diagnosis and 125 months after kidney transplantation.

[Aggressive NK cell leukemia/lymphoma: an autopsy case].

A 67-year-old man was admitted with erythematous skin papules, lymphadenopathy and liver dysfunction. The bone marrow was filled with atypical lymphoid cells, and a skin biopsy showed diffuse dermal infiltration of neoplastic cells, which were positive for CD2, CD8, CD56, TIA-1, Granzyme B and EBER (ISH), but negative for CD3, CD4, CD16 and CD57. Molecular analysis showed a germline configuration for T-cell receptor beta, gamma chain genes, and monoclonal integration of Epstein-Barr virus. The THP-COP regimen was not effective and the patient died of severe metabolic acidosis 2 months later. Autopsy revealed diffuse infiltration of neoplastic cells in almost all organs. Apoptosis of tumor cells and proliferation of hemophagocytic macrophages were remarkable. Neither angiocentricity nor necrosis was observed. The findings in this patient were indistinguishable from advanced-stage nasal-type NK cell lymphoma. However, the diagnosis of aggressive NK cell leukemia/lymphoma may be justified because of the marked involvement of the marrow at onset, fulminant clinical course and diffuse infiltration of tumor cells evident at autopsy.

Hydrogenobacter subterraneus sp. nov., an extremely thermophilic, heterotrophic bacterium unable to grow on hydrogen gas, from deep subsurface geothermal water.

A novel extreme thermophile was isolated from a water sample derived from a deep subsurface geothermal water pool at a depth of 1500 m in the Hacchoubaru geothermal plant in Oita Prefecture, Japan. The cells were found to be straight rods, each being motile by means of a polar flagellum. Growth was observed at temperatures between 60 and 85 degrees C (optimum 78 degrees C; 120 min doubling time) and between pH 5.5 and pH 9.0 (optimum 7.5). The isolate was a strictly aerobic heterotroph capable of utilizing a number of substrates such as yeast extract, peptone, tryptone, various carbohydrates, sugars, amino acids and organic acids. Elemental sulfur, thiosulfate, sulfide or cysteine-hydrochloride was required as an electron donor for growth. Hydrogen gas did not support growth. The G+C content of the genomic DNA was 44.7 mol%. Phylogenetic analysis based on 16S rDNA sequences and DNA-DNA hybridization analysis indicated that the isolate was closely related to members of the hydrogen-oxidizing, autotrophic and thermophilic genera Hydrogenobacter and Calderobacterium. However this isolate was differentiated from the previously described species of these genera on the basis of the physiological and molecular properties of the new isolate. The name Hydrogenobacter subterraneus sp. nov. is proposed; the type strain is HGP1T (= JCM 10560T = IFO 16485T).

Supratentorial astrocytomas and oligodendrogliomas treated in the MRI era.

BACKGROUND: There is at present no consensus on the policy for the treatment of patients with low-grade gliomas (LGGs). METHODS: This report is a retrospective multi-institutional study of 100 patients (ages 16-65 years) with astrocytoma (grade II), oligodendroglioma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma of the supratentorial areas which were treated with surgery and postoperative radiotherapy at five university hospitals in northern Japan between 1990 and 1997 when MRI was routinely used to determine the target volume. Most patients were irradiated with 50-60 Gy. The target volume usually covered the areas with T2 prolongation of MRI with a margin of 2 cm. RESULTS: The disease-specific 5-year survival rate was 87.4% for patients with oligodendroglioma and 75.3% for patients with astrocytoma. Survival for patients with astrocytoma in the MRI era appears to be improved compared with historical controls in the literature. Patients with astrocytoma aged 40 years and under had a significantly better disease-specific survival rate than those over 40 years (P < 0.05) and patients with oligodendroglioma and oligoastrocytoma showed a similar tendency. Patients with astrocytoma who had over 50% of their tumor removed had a significantly better survival rate than those who had less than 50% removed (P < 0.05). Chemotherapy appeared to improve the disease-specific survival rate of patients with oligodendroglioma but not that of patients with astrocytoma. CONCLUSION: Oligodendroglioma has a more protracted course of disease progression than astrocytoma. This particular feature and the sensitivity of LGGs to chemotherapy as well as their relevant prognostic factors, such as age, histopathology and amount of tumor removal, should be taken into account before any decision on treatment methods for LGGs is made.

Serum levels of soluble adhesion molecules in stem cell transplantation-related complications.

To assess the involvement of vascular endothelial cell activation and damage in stem cell transplantation (SCT)-related complications, such as acute and chronic GVHD and thrombotic microangiopathy (TMA), we investigated the changes in serum levels of soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) in SCT. The soluble form of intercellular adhesion molecule-1 (sICAM-1) was also analyzed. In patients with acute GVHD (grades II-IV), serum levels of sE-selectin and sICAM-1 increased around onset of GVHD (day 30). While the increase of sE-selectin levels was transient, sICAM-1 levels remained high until day 60. In patients with extensive chronic GVHD, sVCAM-1 as well as sE-selectin levels significantly increased. The appearance of clinical symptoms was preceded by elevations of sVCAM-1 and sE-selectin levels on day 60, and sICAM-1 levels on days 30 and 60. For the analysis of TMA, to exclude the influence of GVHD, serum levels were measured in auto-SCT patients. Around the onset of TMA, sVCAM-1 and sE-selectin levels significantly increased in patients with TMA without an increase of sICAM-1 levels. These findings support the notion that activation and injury of endothelium are commonly involved in the pathogenesis of acute and chronic GVHD and TMA.

Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia.

OBJECTIVE: To elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leukemia cell-associated T-cell anergy. MATERIALS AND METHODS: Leukemia cells of 30 patients with AML were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha. Cultured leukemia cells were evaluated for antigen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocytes, which were cocultured with leukemia blasts in the first MLC, were cultured with leukemia-derived dendritic cells in the second MLC. RESULTS: In cultures of leukemia cells from 21 of 30 patients examined, cells with stellate morphology and cell fractions with CD1a(+) and/or CD83(+) were present. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated antigen-presenting ability in leukemia-derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3, or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. The leukemic origin of dendritic cells was suggested by in situ hybridization. By coculture with CD80(-) leukemia blasts, the response of normal lymphocytes to leukemia-derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from a different individual as leukemia blasts. CONCLUSIONS: Escape of leukemia cells from anti-leukemia immunity may be associated with T-cell anergy caused by leukemia blasts. The results of the present study suggest that leukemia-derived dendritic cells can be applied efficiently in anti-leukemia immunotherapy.

Antisense therapy of influenza.

The liposomally encapsulated and the free antisense phosphorothioate oligonucleotides (S-ODNs) with four target sites (PB1, PB2, PA, and NP) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. On the other hand, the inhibitory effect of the liposomally encapsulated S-ODN targeted to PB1 was considerably decreased in comparison with those directed to the PB2 target sites. The liposomally encapsulated antisense phosphorothioate oligonucleotides exhibited higher inhibitory activities than the free oligonucleotides, and showed sequence-specific inhibition, whereas the free antisense phosphorothioate oligonucleotides were observed to inhibit viral absorption to MDCK cells. Therefore, the antiviral effects of S-ODN-PB2-AUG and PA-AUG were examined in a mouse model of influenza virus A infection. Balb/c mice exposed to the influenza virus A (A/PR/8/34) strain at dose of 100 LD(50)s were treated i.v. with various doses (5-40 mg/kg) of liposomally (Tfx-10) encapsulated PB2-AUG or PA-AUG before virus infection and 1 and 3 days postinfection. PB2-AUG oligomer treated i.v. significantly prolonged the mean survival time in days (MDS) and increased the survival rates with a dose-dependent manner. We demonstrate the first successful in vivo antiviral activity of antisense administered i.v. in experimental respiratory tract infections induced with influenza virus A.

22-Oxacalcitriol upregulates p21(WAF1/Cip1) in human parathyroid glands. A preliminary report.

In the era of 22-oxacalcitriol (OCT), newly synthesized 1 alpha,25-dihydroxyvitamin D(3) analogue, against secondary hyperparathyroidism, the indications of parathyroidectomy (PTx) has been restricted. Recent investigations on animal models have revealed the inhibitory effects on PTH secretion after OCT treatment, whereas there has been no evidence about human parathyroid glands. A 38-year-old man with a 19-year history of hemodialysis was performed PTx after the failure of OCT treatment. Expressions of proliferative nuclear cell antigen (PCNA), calcium-sensing receptor (CaSR), vitamin D receptor (VDR), p53 and p21(WAF1/Cip1) were analyzed by Western blotting and immunohistochemistry on resected parathyroid glands. We confirmed up-regulations of CaSR and VDR, which contribute the reduction of serum PTH, by OCT treatment. Concomitant up-regulation of p21(WAF1/Cip1) but not p53, especially in nodular hyperplasia, can be considered to induce cell cycle arrest of the parathyroid cells, but not cytocidal effect of OCT.

Delayed rupture of a pseudoaneurysm following pancreatoduodenectomy: report of a case.

We report herein the case of a 63-year-old man in whom delayed rupture of a pseudoaneurysm occurred 120 days following pancreatoduodenectomy. Color Doppler examination indicated a pseudoaneurysm originating from the ligated gastroduodenal artery. Transcatheter arterial embolization was done at the common hepatic artery, proximal and distal to the pseudoaneurysm, with microcoils. The patient had a minor elevation of liver enzymes, which subsequently returned to normal. Due to the absence of any postoperative complications such as pancreatic anastomotic leakage, we assumed that the pseudoaneurysm formation had been caused by a weakness in the arterial wall according to skeletonization resulting from lymphadenectomy and intraoperative radiation therapy. To our knowledge, this case represents the longest interval between pancreatoduodenectomy and rupture of a pseudoaneurysm ever to be reported in the literature.