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Objective To analyze the clinical and endocrine characteristics of patients with primary adrenal lymphoma. Patients We retrospectively reviewed the cases of five patients with primary adrenal lymphoma who were treated in our hospital between April 2004 and March 2015. We investigated the characteristics of the clinical and pathological findings, treatment, prognosis and complications of adrenal insufficiency. Results Adrenal insufficiency, which was confirmed by the laboratory data at the initial presentation, was observed in two cases. One case was complicated by relative adrenal insufficiency during a course of chemotherapy. The plasma adrenaline and urinary adrenaline levels were decreased in four cases and three cases, respectively. Diffusion MRI was radiologically diagnostic. In all of the cases, the patients were pathologically diagnosed with diffuse large-B cell lymphoma and were treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like chemotherapy. Two patients received central nervous system prophylaxis with high-dose methotrexate. Four of the patients survived and one patient died during the follow-up period. Conclusion The early detection of adrenal insufficiency and the administration of an appropriate dose of hydrocortisone are necessary during the course of chemotherapy as well as at the initial manifestation. The exclusion of adrenal dysfunction prior to invasive diagnostic procedures, such as CT-guided needle biopsy, is also critical.

Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) affecting B-cells or T-cells, respectively. The serum level of soluble interleukin-2 receptor (sIL-2R) is known to reflect the immune activity and tumour volume in aggressive NHL; however, the release of sIL-2R in LBL has not been extensively studied. Further, the relationship between sIL-2R release and the expression level of IL-2R α subunit (CD25) remains unknown. In the present study, we examined the serum level of sIL-2R in 23 patients with T lymphoblactic lymphoma (T-LBL) and compared these with the levels in 20 patient with T acute lymphoblastic leukaemia (T-ALL), 40 patients with diffuse large B-cell lymphoma (DLBCL) and 40 patients with peripheral T-cell lymphoma (PTCL), not otherwise specified. The release of sIL-2R into the serum in patients with T-LBL was significantly lower than that for T-ALL, DLBCL and PTCL (p

We have reported previously that duodenal follicular lymphoma (FL) is distinct from nodal FL and showed more resemblance to mucosa-associated lymphoid tissue lymphoma, and that FL frequently involved the duodenal second portion. In the present study, we examined duodenal FLs and gastric/colonic FLs to clarify the clinicopathological and immunological differences between the tumor types. We analyzed 8 samples of gastric FL, 17 of duodenal ones, and 5 of colonic/rectal ones, and characterized them by immunohistochemistry, immunogenotyping, and histology. Gastric and colonic FLs presented in submucosal to subserosal areas, whereas duodenal ones presented in the mucosal to submucosal layers. Immunohistochemical analysis revealed that duodenal FLs exhibited the following phenotypes: CD10 (+), B-cell lymphoma 2 (BCL-2) (+), BCL-6 (+), activation-induced cytidine deaminase (AID) (-), BACH2 (+), CD27 (+), MUM-1 (-), Blimp-1 (-), and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes: CD10 (+), BCL-2 (+), BCL-6 (+), AID (+), BACH2 (+), CD27 (-), MUM-1 (-), Blimp-1 (-), and a dense CD21 network (nodal pattern). Expression of AID and CD27 in lymphoma cells and the CD21 network pattern were considerably different between duodenal FLs and gastric/colonic ones. Moreover, in situ hybridization revealed that, in the duodenal FLs, BACH2 was expressed at the periphery of the tumor follicle and tumor villi. The number of immunoglobulin heavy-chain variable domains VH4 and VH5 were higher in duodenal follicular lymphomoas than in gastric FLs. The lymphoma cells of duodenal FLs are different from those of gastric/colonic FLs, and duodenal FL is distinct even within the gastrointestinal tract. Somatic hypermutation in immunoglobulin genes and CD27 expression are hallmarks of memory B cells. We suggest that duodenal FL cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation.

We have introduced S1–S2 paradigm (task S) as well as oddball paradigm (task O) visual event-related potentials (ERPs) under different interstimulus intervals (ISIs) in Parkinson's disease (PD). ERP measurements were correlated with motor disability, WAIS-R, and regional cerebral blood flow (rCBF). The ‘group’ influence was characterized by longer latency for P300, N200, and reaction time and decreased P300 amplitude in PD. Both P300 latency and reaction time during task O showed significantly longer latency in longer ISI condition. Our results revealed ‘ISI’ influence on ERPs during task S and significant correlation between ERPs and rCBF in task S.

To study the human brain activity correlated with illusory perception, we chose a physically flat plane figure which looks like a convex figure. We studied visual evoked potential (VEP) changes, which reflect perceptual properties of illusory perception. We defined two paradigms, an illusory paradigm (IP) and a control paradigm (CP). Two stimuli, A and B, were randomly presented in the IP, while stimuli C and D were randomly presented in the CP. Stimulus A was the only figure which looked like a convex figure. A three-way analysis of variance was applied to the VEP components in each paradigm, with three factors: figures, electrodes, and sessions. Different configuration patterns between the two paradigms explained different grand mean VEP waveforms between the two paradigms; a greater N1 for the CP, a greater P1 for the IP, and marked attenuation of the N3 and P3 components for the IP. Significant main effects of figures only for the IP were found on P1 and P1N2 amplitude and P2 latency, which are assumed to reflect perceptual properties of stereoscopical illusory perception.

To expand the applications of poly(ethylene glycol) (PEG)-protein conjugates for clinical use, we have developed a novel method for dual and site-specific incorporations of PEG derivatives into proteins using a substrate peptide (AQQIVM, named TG2) and transglutaminase (TGase). In our previous studies, TG2 was shown to be a special peptide with two adjacent Gln substrates for guinea pig liver transglutaminase (G-TGase). We have now constructed a chimeric protein (named rTG2-IL-2) of human interleukin-2 (IL-2), in which TG2 was fused to the N-terminus of IL-2. For the G-TGase-catalyzed reaction, rTG2-IL-2 was dually and site-specifically modified with alkylamine derivatives of PEG (PEG10, average M(r) 10 kDa) at both the Gln2 and Gln3 residues in the appended tag. To demonstrate the effectiveness of the G-TGase-catalyzed PEG-incorporation, we have compared the characteristics and the biological properties of PEG10-rTG2-IL-2 species with two PEG10 molecules attached to rTG2-IL-2 [(PEG10)(2)-rTG2-IL-2] with that of (PEG10)(2)-rhIL-2(R), in which PEG10 was randomly incorporated into rhIL-2 by a general procedure using a N-hydroxysuccinimidyl ester of PEG (PEG10-COOSu) (M(r) 10 kDa). (PEG10)(2)-rTG2-IL-2 was found to be superior in its in vitro bioactivities and equivalent in its pharmacokinetic profiles to (PEG10)(2)-rhIL-2(R). Unlike most previous methods, this approach can place dual PEG chains at designed sites on chimeric proteins without decreasing their bioactivities. Thus, TGase-catalyzed PEG-incorporation would improve the therapeutic utility of PEG-protein conjugates.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) consists of a heterogeneous group of lymphomas. Patients. generally show an aggressive clinical course and very poor outcome. Although the 2008 World Health Organization classification of PTCL-NOS includes 3 variants, low-grade lymphoma is not Included. Of 277 PTCL-NOS cases recorded in our consultation files, we examined the clinicopathologic characteristics of 10 patients with T-cell lymphomas composed of small-sized cells with slight nuclear atypia. Eight patients showed extranodal involvement (5 patients, spleen; 3 patients, thyroid), and 5 patients were at clinical stage I or II. Histologically, all samples presented diffuse infiltrate of small lymphoid cells, with few mitotic figures. Immunohistologically, all samples were positive for CD3, and CD:20 Was detected in 5 samples. All samples showed a low Ki-67 labeling index (mean, 1.05%), and 7 samples were positive for central memory T-cell markers. Clonal T-cell receptor gamma chain and/or alpha-beta chain gene rearrangements were detected in all 10 patients. Five patients received chemotherapy, whereas for 3 patients, treatment consisted only of observation following surgical resection of the spleen or thyroid. Nine patients were alive at a median follow-up time of 19.5 months, whereas 1 patient died of an unrelated disease. The present study strongly indicates that T-cell lymphoma with small-sized lymphoma cells and a low Ki-67 labeling index is a distinct variant. Recognition of this novel lymphoma subtype, which should not be defined merely as PTCL-NOS, should be seriously considered.

Immunoglobulin (Ig) G4-related disease has been recently described. This disease affects various organs, including lymph nodes. We describe the case of a 52-year-old Japanese man with IgG4-related lymphadenopathy with inflammatory pseudotumor (IPT)-like features. Five years ago, the patient noticed a painless mass in the mandible but did not consult a doctor. Recently, he noted that the mass had increased in size and consulted an oral surgeon in the hospital. Excisional biopsy was performed for diagnosis. Histopathological examination revealed that most of the enlarged lymph node was occupied by the hyalinized tissue. A few residual lymphoid follicles with hyperplastic germinal centers and infiltration of plasma cells and eosinophils were observed. Most of the plasma cells expressed IgG4, and the ratio of IgG4-positive cells to IgG-positive cells was 57.1%. These findings were consistent with IgG4-related lymphadenopathy. In conclusion, pathologists should consider IgG4-related lymphadenopathy when diagnosing a lesion with IPT-like features.

A guinea pig liver transglutaminase (G-TGase)-mediated procedure for the site-specific modification of chimeric proteins was recently reported. Here, an alternative method with advantages over the recent approach is described. This protocol utilizes a microbial transglutaminase (M-TGase) instead of the G-TGase as the catalyst. M-TGase, which has rather broad structural requirements as compared to the G-TGase, tends to catalyze an acyl transfer reaction between the gamma-carboxamide group of a intact protein-bound glutamine residue and various primary amines. To demonstrate the applicability of the M-TGase-catalyzed protein modification in a drug delivery system, we have utilized recombinant human interleukin 2 (rhIL-2) as the target protein and two synthetic alkylamine derivatives of poly(ethyleneglycol) (PEG12; MW 12 kDa) and galactose-terminated triantennary glycosides ((Gal)(3))) as the modifiers. For the M-TGase-catalyzed reaction with PEG12 and (Gal)(3), 1 mol of alkylamine was incorporated per mole of rhIL-2, respectively. Peptide mapping of (Gal)(3)-modified rhIL-2 ((Gal)(3)-rhIL-2) by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) suggested that the Gln74 residue in rhIL-2 was site specifically modified with (Gal)(3). The PEG12-rhIL-2 and (Gal)(3)-rhIL-2 conjugates retained full bioactivity relative to the unmodified rhIL-2. In pharmacokinetic studies, PEG12-rhIL-2 was eliminated more slowly from the circulation than rhIL-2, whereas (Gal)(3)-rhIL-2 accumulated in the liver via hepatic asialoglycoprotein receptor binding. The results of this study expand the applicability of the TGase-catalyzed methodology for the preparation of protein conjugates for clinical use.