Serum Levels Of Interleukin-2 Receptor Research Articles

Safety Analysis of Apatinib Combined with Chemotherapy in the Treatment of Advanced Gastric Carcinoma: A Randomised Controlled Trial.

Objective To study the safety of apatinib combined with chemotherapy in the treatment of advanced gastric carcinoma (GCA). Methods 74 patients with advanced GCA treated in the oncology department of Weifang People's Hospital (January 2019–January 2020) were enrolled in this study and equally split into study group (SG) and reference group (RG) according to the odd and even admission numbers. RG underwent chemotherapy alone, while SG received apatinib combined with chemotherapy. The clinical indicators of serum matrix metalloproteinase 9 (MMP-9), serum interleukin-2 receptor (SIL-2R), and immune cell level were detected in the two groups before and after treatment to analyze the therapeutic effect of different treatment methods on patients with advanced gastric carcinoma. Results No obvious differences in gender ratio, average age, average BMI, pathological staging, pathological types, organ metastasis types, and residence were observed between the two groups (P > 0.05). The short-term follow-up results showed that the disease control rate (DCR) in SG was markedly higher compared with RG (P < 0.05). The MMP-9 and SIL-2R levels in both groups after treatment decreased (P < 0.05), and the levels in SG after treatment were notably lower compared with RG (P < 0.001). Compared with RG, CD3+, CD4+, and CD4+/CD8+ levels in SG after treatment were notably higher (P < 0.001), while the CD8+ level was notably lower (P < 0.001). The median progression-free survival (MPFS) and overall survival (OS) in SG were markedly higher compared with RG (P < 0.001). The GQOLI-74 scores in both groups after treatment increased (P < 0.001), and the GQOLI-74 score in SG after treatment was markedly higher compared with RG (P < 0.001). The total incidence of adverse reactions was lower in SG than in RG (P < 0.05). Conclusion Apatinib combined with chemotherapy is superior to chemotherapy alone in effectively improving treatment outcomes in patients with advanced GCA.

Serum levels of soluble interleukin-2 receptor (sIL-2R) and cancer antigen 125 (CA 125) in dogs diagnosed with cutaneous lymphoma

Serum levels of soluble interleukin-2 receptor (sIL-2R) and cancer antigen 125 (CA 125) in dogs diagnosed with cutaneous lymphoma

Clinical Significance of Interleukin-2 Receptor, Interleukin-8 Expression Levels in the Diagnosis of Infection in Patients with Hematological Malignancies

To investigate the clinical value of expression level of interleukin-2 receptor (IL-2R) and interleukin-8 (IL-8) in the fever patients with hematological malignancies. A total of 121 inpatients in the First Affiliated Hospital of Anhui Medical University from April 2018 to October 2019 were enrolled in this study. The patients were separated into infection group (61 cases) and non-infection group (60 cases). In the meantime, 40 healthy people without fever or infection in the hospital for physical examination were set as matched group. C-reactive protein (CRP), procalcitonin (PCT), and cytokines were detected in all the patients with fever after admission and infection control. While, blood samples were taken from healthy people during physical examination. The expression levels of IL-2R in infection group were higher than those in the control group (P<0.001), and the level of serum IL-2R in infection group was also higher than that in the non-infection group (P<0.05). Based on Spearman analysis, in patients with malignant hematologic disease, serum IL-2R level was positively correlated with CRP (r=0.557, P<0.001) and IL-8 (r=0.479, P<0.001), and IL-8 level was positively correlated with CRP (r=0.318, P<0.001). Compared with the non-infection group, the area under the curve (AUC) for the level of CRP, PCT, and IL-2R of the infection group was 0.714 (95%CI: 0.623-0.806), 0.765 (95%CI: 0.680-0.851), and 0.761 (95%CI: 0.686-0.836), the sensitivity was 0.705, 0.852, and 0.705, and the specificity was 0.717, 0.70, and 0.60, respectively. While, AUC of CRP+PCT, CRP+IL-2R, PCT+IL-2R, and CRP+PCT+IL-2R was 0.789 (95%CI: 0.712-0.866), 0.702 (95%CI: 0.623-0.782), 0.757 (95%CI: 0.677-0.838), and 0.789 (95%CI: 0.712-0.866), the sensitivity was 0.738, 0.934, 0.705, and 0.738, and the specificity was 0.840, 0.470, 0.810, and 0.840, respectively. CRP, PCT, IL-2R, and IL-8 are useful parameters for diagnosis of the infectious fever in patients with hematological malignancies, which provides the basis of initial diagnosis and rational use of antibioties for clinician.

Hypercalcemia After Cosmetic Oil Injections: Unraveling Etiology, Pathogenesis, and Severity.

Intramuscular injections of paraffin oil can cause foreign body granuloma formation and hypercalcemia. Macrophages with the ability to produce high levels of 1,25(OH)2 D3 may induce the mineral disturbance, but no major series of patients have been published to date. Here, medical history, physical evaluation, biochemical, and urinary analysis for calcium homeostasis were obtained from 88 males, who 6 years previously had injected paraffin or synthol oil into skeletal muscle. Moreover, granuloma tissue from three men was cultured for 48 hours ex vivo to determine 1,25(OH)2 D3 production supported by qPCR and immunohistochemistry of vitamin D metabolism and immune cell populations after treatment with 14 different drugs. The 88 men were stratified into men with hypercalcemia (34%), whereas normocalcemic men were separated into men with either normal (42%) or suppressed parathyroid hormone (PTH) (24%). All men had high calcium excretion, and nephrolithiasis was found in 48% of hypercalcemic men, 22% of normocalcemic men with normal PTH, and 47% of normocalcemic men with suppressed PTH. Risk factors for developing hypercalcemia were oil volume injected, injection of heated oil, high serum interleukin-2 receptor levels, and high urine calcium. High 1,25(OH)2 D3 /25OHD ratio, calcium excretion, and low PTH was associated with nephrolithiasis. The vitamin D activating enzyme CYP27B1 was markedly expressed in granuloma tissue, and 1,25(OH)2 D3 was released in concentrations corresponding to 40% to 50% of the production by human kidney specimens. Dexamethasone, ketoconazole, and ciclosporin significantly suppressed granulomatous production of 1,25(OH)2 D3 . In conclusion, this study shows that injection of large oil volumes alters calcium homeostasis and increases the risk of nephrolithiasis. Hypercalciuria is an early sign of disease, and high granulomatous 1,25(OH)2 D3 production is part of the cause. Prospective clinical trials are needed to determine if ciclosporin, ketoconazole, or other drugs can be used as prednisolone-sparing treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).

Mucosa-associated lymphoid tissue (MALT) lymphoma developing in ectopic mediastinal thyroid tissue: a case report

BackgroundNormally located in the neck, ectopic mediastinal thyroid tissue consists of very rare ectopic thyroid tissue that does not connect to the thyroid gland. A patient with mucosa-associated lymphoid tissue (MALT) lymphoma that has developed in mediastinal thyroid tissue, to our best knowledge, has not been previously reported.Case presentationA 67-year-old woman presented with a superior mediastinal mass that was revealed by chest computed tomography (CT), an optional examination she hoped, during a medical checkup. Contrast-enhanced CT scan performed in our hospital for close examination confirmed the presence of a 2 × 1.3 cm poorly enhanced mass anterior to the trachea during the arterial phase. Magnetic resonance imaging depicted low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. I-131 meta-iodobenzylguanidine did not accumulate in the mass. Serum levels of interleukin-2 receptor, catecholamine, and anti-acetylcholine receptor antibody were within the normal range. The mass was resected through a transverse neck incision for the diagnosis and treatment. The histopathological diagnosis of the specimen was ectopic mediastinal thyroid tissue associated with MALT lymphoma and chronic thyroiditis. Immunoglobulin heavy chain class switch recombination was identified. Fine-needle aspiration biopsy of the cervical thyroid showed chronic thyroiditis but not lymphoma. The patient’s postoperative thyroid function was normal. To date, the patient’s recovery has been uneventful, and she is being monitored without further treatment.ConclusionWe treated the patient with MALT lymphoma that developed in ectopic mediastinal thyroid tissue. This novel case illustrates a new differential diagnosis associated with ectopic mediastinal thyroid tissue.

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

BackgroundHemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13).Case presentationAn 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13.ConclusionsIt is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay.

The significance of serum levels of soluble interleukin-2 receptor in patients undergoing maintenance hemodialysis

Background Elevated serum levels of sIL-2R are commonly observed in patients undergoing maintenance hemodialysis (MHD). However, the clinical implications in these subjects are unclear. This study is aimed to assess the significance of elevated sIL-2R levels in MHD patients. Methods A total of 382 MHD patients were followed-up from September 2016 to December 2019. Patients were divided into two groups: high sIL-2R, with sIL-2R levels ≥2-fold of the upper limit of normal (710 U/ml); and low sIL-2R, with sIL-2R levels < 2-fold the upper limit of normal. The relationships between sIL-2R levels and other clinical parameters, as well as patient prognosis were both assessed. Results The median concentration of sIL-2R was 1268 U/mL. A total of 372 (97.38%) patients exhibited sIL-2R levels higher than the upper limit of the normal range. Multiple linear regression analysis revealed that monocyte count (β = 0.1571, p = 0.01), and β2-MG (β = 0.2635, p < 0.0001), hemoglobin (β = −0.1610, p = 0.001), SCr (β = −0.3471, p < 0.0001), and HDL-C (β = −0.1091, p = 0.029) levels were independent factors influencing serum concentrations of sIL-2R. High sIL-2R was significantly correlated with non-cardiovascular-related mortality (OR 2.97 [95% CI 1.59–5.56; p = 0.001), of which 39 (82.98%) were attributed to infection and/or cancer. Conclusions Elevated sIL-2R is prevalent in MHD patients and related with several unfavorable parameters. sIL-2R appears to have no ability to predict cardiovascular mortality, which accounts for approximately one-half of all deaths. However, sIL-2R may be beneficial in predicting noncardiovascular mortality.

Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma

AbstractCyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). The deregulation of CDK9/P-TEFb has important implications for many cancer types. BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase 1 studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL). As a result of CDK9 inhibition and subsequent inhibition of phosphorylation at serine 2 of the RNAPII CTD, BAY 1143572 decreased c-Myc and Mcl-1 levels in ATL-derived or human T-cell lymphotropic virus type-1 (HTLV-1)–transformed lines and primary ATL cells tested, leading to their growth inhibition and apoptosis. Median inhibitory concentrations for BAY 1143572 in ATL-derived or HTLV-1–transformed lines (n = 8), primary ATL cells (n = 11), and CD4+ cells from healthy volunteers (n = 5) were 0.535, 0.30, and 0.36 μM, respectively. Next, NOG mice were used as recipients of tumor cells from an ATL patient. BAY 1143572–treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both). BAY 1143572–treated ATL-bearing mice demonstrated significantly prolonged survival compared with untreated ATL-bearing mice (n = 7 for both). Collectively, this study indicates that BAY 1143572 showed strong potential as a novel treatment of ATL.

Correlation of spleen metabolism assessed by 18F-FDG PET with serum interleukin-2 receptor levels and other biomarkers in patients with untreated sarcoidosis.

The objective of our study was to assess the possible relationship between splenic F-18-fluorodeoxyglucose (18F-FDG) uptake and other established biochemical markers of sarcoidosis activity. Thirty treatment-naive sarcoidosis patients were prospectively enrolled in this study. They underwent biochemical laboratory tests, including serum interleukin-2 receptor (sIL-2R), serum C-reactive protein, serum angiotensin-I converting enzyme, and 24-h urine calcium levels, and a whole-body combined 18F-FDG PET/computed tomography (PET/CT) scan as a part of an ongoing study at our institute. These biomarkers were statistically compared in these patients. A statistically significant linear dependence was detected between sIL-2R and log-transformed spleen-average standard uptake value (SUV avg) (R2=0.488, P<0.0001) and log-transformed spleen-maximum standard uptake value (SUV max) (R2=0.490, P<0.0001). sIL-2R levels and splenic size correlated linearly (Pearson's r=0.373, P=0.042). Multivariate linear regression analysis revealed that this correlation remained significant after age and sex adjustment (β=0.001, SE=0.001, P=0.024). No statistically significant associations were detected between (a) any two serum biomarkers or (b) between spleen-SUV measurements and any serum biomarker other than sIL-2R. Our analysis revealed an association between sIL-2R levels and spleen 18F-FDG uptake and size, whereas all other serum biomarkers were not significantly associated with each other or with PET 18F-FDG uptake. Our results suggest that splenic inflammation may be related to the systemic inflammatory response in sarcoidosis that may be associated with elevated sIL-2R levels.

Abstract 146: Third Intravenous Immunoglobulin Is An Effective Option For Kawasaki disease Patients Resistant To Cyclosporin A

Background: About 10-20% of patients with Kawasaki Disease (KD) who fail to respond to IVIG, show a high prevalence of CAL. The new guideline (2012) has proposed several options for second- and third-line therapy for patients resistant to IVIG. However, there are still no definite treatment options for refractory KD. We have reported that cyclosporin A (CsA) is a well tolerated, safe and promising option for patients resistant to IVIG. However, certain subgroups of such patients may also be resistant to CsA. In this study, we examined if a third course IVIG might be effective for patients resistant to CsA. Patients and Methods: Between April 2008 and May 2014, 42 Japanese patients who met the diagnostic criteria for KD and received CsA treatment were enrolled as study subjects. All patients were resistant to both initial (2 g/kg for 24 hours) and additional IVIG, and were then administered CsA orally (Neoral[[Unable to Display Character: &amp;#9415;]], oral solution, Novartis Pharma Co. Ltd., Tokyo, Japan). The initial dose of CsA was 4mg/kg/day, and it was divided into two equal daily doses every 12 hours. The dose of CsA was adjusted to between 4 and 8 mg/kg/day to maintain a trough level of 60-200 ng/ml by reference to clinical and laboratory data such as body temperature and C-reactive protein level. After the start of CsA treatment, if patients remained febrile for more than 5 days, or if fever returned after an afebrile period within 5 days, CsA treatment was judged to be ineffective, and the patients were then given a third course of IVIG. We analyzed some laboratory data between CsA effective group and CsA resistant group. Results: CsA treatment was judged to be ineffective in 14 of 42 (33%) patients. Eleven of those 14 patients received a third IVIG, and then, 8 (72.7%) patients of them became afebrile within 24hours. The other three patients became afebrile after a fourth IVIG. The serum levels of AST and soluble interleukin-2 receptor before the start of CsA treatment were significantly lower in CsA effective group than in CsA resistant group. Conclusion: A third course of IVIG is an effective option for KD patients who are resistant to CsA .

Evidence of Abnormal Epidermal Nerve Fiber Density in Fibromyalgia: Clinical and Immunologic Implications

A subset of patients with fibromyalgia (FM) exhibit a large fiber demyelinating peripheral polyneuropathy akin to that seen in chronic inflammatory demyelinating polyneuropathy (CIDP). It has been suggested that this demyelinating process is likely to be immune mediated. Because it is known that similar large fiber neuropathic lesions may be associated with a cutaneous small fiber neuropathy, we sought to determine the prevalence of small fiber neuropathy, as measured by epidermal nerve fiber density (ENFD), in a series of patients with FM and clinically healthy control subjects. Forty-one consecutive patients with FM and 47 control subjects underwent a 3-mm punch skin biopsy at the proximal thigh and distal leg near the ankle, for analysis of the ENFD. Patients with FM who had clinical evidence of a disorder known to be associated with small fiber neuropathy were excluded. The patients with FM also underwent pinwheel testing and vibratory testing for hypesthesia and serologic testing for a series of cytokine, circulating immune complex, and complement measurements. All patients with FM had evidence of stocking hypesthesia. The ENFD of patients with FM was lower than that of control subjects at both the calf (mean ± SD 5.8 ± 2.8 versus 7.4 ± 1.9; P = 0.0002) and thigh (9.3 ± 3.2 versus 11.3 ± 2.0; P = 0.0007). There was an inverse correlation between calf ENFD and age at the time of skin biopsy in patients with FM (r = -0.29, P = 0.03) but not in control subjects; however, analysis of covariance showed that this relationship could not be explained by aging alone. Serologic evaluation showed an inverse correlation between calf ENFD in patients with FM and the interleukin-2 receptor (IL-2R) level (r = -0.28, P = 0.04). However, an inverse correlation between thigh ENFD and serum IL-2R levels did not reach significance (P = 0.08). Analysis of thigh-to-calf ENFD ratios suggested that the ENFD decline in FM is affected by both a diffuse and a length-dependent process. The calf and thigh ENFD in patients with FM is significantly diminished compared with that in control subjects. Advancing age alone cannot explain this finding. Calf ENFD was inversely correlated, although weakly, with serum levels of IL-2R. These findings suggest that small fiber neuropathy is likely to contribute to the pain symptoms of FM; that pain in this disorder arises, in part, from a peripheral immune-mediated process; and that measurement of ENFD may be a useful clinical tool in FM.

Tandem triplication of the BCL2 gene in CD5-positive intravascular large B cell lymphoma with bone marrow involvement

Dear Editor, Intravascular large B cell lymphoma (IVLBCL) is a rare subtype of diffuse large B cell lymphoma (DLBCL) characterized by the selective growth of lymphoma cells within the lumina of vessels [1]. Cytogenetically, the majority of IVLBCL cases demonstrated complex karyotypes with multiple numerical and structural changes, and the most frequent duplicated regions were shown to be the 11q13→qter region and all of chromosome 18 [2, 3]. On the other hand, triplications of chromosome segments other than 1q have been rarely found in hematological malignancies [4–8]. Here, we describe an unusual case of IVLBCL with a tandem triplication of the BCL2 gene at 18q21. An 82 year-old female was admitted because of fever. Computed tomography scans revealed hepatosplenomegaly without lymphadenopathy. Peripheral blood (PB) examination showed hemoglobin 105 g/L, platelets 52×10/L, and leukocytes 10.1× 10/Lwith 15% abnormal lymphocytes. Serum levels of lactate dehydrogenase (LDH) and soluble interleukin-2 receptor were 6,382 IU/L (normal range, 115~217) and 8,429 U/mL (124~ 466), respectively. Bone marrow (BM) was normocellular with 42.4 % abnormal lymphocytes positive for CD5, CD19, CD20, and HLA-DR (Fig. 1a). Pathological examination of the BM revealed a focal and sinusoidal growth pattern of large lymphoid cells, indicating a diagnosis of IVLBCL (Fig. 1b). Immunohistochemistry demonstrated that they were positive for CD5, CD20, BCL2, and MUM1, but negative for CD10 and BCL6 (Fig. 1c, d). The patient received R-CHOP therapy and achieved hematological complete remission. However, 12 months later, she relapsed and died of progressive disease. G banding and spectral karyotyping of BM cells showed 47,XX,del (2)(q?),+del(3)(p?),der(10)t(10;20)(q24;?), dup(17)(q21q23),dup(18)(q11.2q23) [20] (Fig. 1e). Unexpectedly, fluorescence in situ hybridization (FISH) detected three BCL2 signals on the dup(18)(q11.2q23), indicating a tandem triplication of BCL2 (Fig. 1f). Namely, the short 18q fragment containing BCL2 attached to the dup(18). FISH on interphase nuclei confirmed four BCL2 signals. According to the Mitelman Database, nine cases of hematological malignancies with duplication/triplication of 18q (duplication, eight; triplication, one) in the stem-lines have been described [4, 9, 10]. All cases were diagnosed with B lymphoid malignancies. The duplicated regions in two cases of acute lymphoblastic leukemia did not contain 18q21, whereas those in seven cases of B cell lymphomas (DLBCL, four; IVLBCL, one; Burkitt lymphoma, one; mantle cell lymphoma, one) retained 18q21. Thus, duplication/triplication of 18q including 18q21 seems to be specifically associated with B cell lymphomas and suggests the significance of BCL2 in their pathogenesis. Among these, one case with trp(18)(?q21q23) exhibited a tandem triplication of BCL2 [2]. This 62-year-old male was diagnosed as having IVLBCL with BM/PB involvement, thrombocytopenia (34×10/L), and high LDH (2,266 U/L). Lymphoma cells were positive for K. Yamamoto (*) :A. Okamura :K. Yakushijin :H. Matsuoka : H. Minami Division of Medical Oncology/Hematology, Department of Medicine, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan e-mail: kyamamo@med.kobe-u.ac.jp

Multiple Cerebral Infarctions and Intracranial Vessel Abnormalities

Several months before being admitted to the hospital, a 65-yearold woman noted relapsing fevers, night sweats, fatigue, and a 16-kg weight loss. In the weeks before her hospital admission, she developed subacute cognitivedeteriorationand progressive headaches. On presentation she has difficulties initiating speech (nonfluent aphasia) and responds slowly and inconsistently to questions. Otherwise, her physical examination is unremarkable. Laboratory studies reveal an elevated erythrocyte sedimentation rate (ESR) (135mm/h), anemia (hemoglobin level, 9.5 g/dL), and high serum levels of soluble interleukin2 receptor (sIL2R) (36 551pg/mL), lactatedehydrogenase (LDH) (448 U/L), and β2-microglobulin (3.1 mg/L), with normal renal function, liver enzyme levels, and serum immunological andmicrobiological findings. Analysis of the cerebrospinal fluid (CSF) demonstrates amildly increased leukocyte count (11 × 10/L) and total protein concentration (0.10g/dL).Magnetic resonance imagingof the brain shows multiple infarctions, and digital subtraction angiography of the intracranialvesselsdemonstratesabnormalitiessuggestiveofvasculitis (Figure 1). An electrocardiogram, computed tomography scans of the chest and abdomen, 18-fluorodeoxyglucose positron emission tomography, transesophagealechocardiography, inspectionof theskin, and ophthalmologic evaluation are unremarkable. Quiz at jama.com A B Brain magnetic resonance imaging (MRI) Digital subtraction angiography

Validation of the japanese version of the sarcoidosis health questionnaire: A cross-sectional study

BackgroundAlthough impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ.FindingsThe SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement.ConclusionsThe Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.

Progressive external ophthalmoplegia as initial manifestation of sporadic late-onset nemaline myopathy

Sporadic late-onset nemaline myopathy (SLONM) is a rare disease and typically presents in patients older than 40 years with slowly progressive weakness in a limb-girdle distribution and unremarkable family history [1, 2]. Serum creatine kinase is usually normal, and electromyography may show myopathic changes. Nemaline rods in affected muscle fibers are considered the histopathological hallmark of nemaline myopathy and are mainly found within the sarcoplasm, inside of myonuclei, or both [3]. Ocular involvement has never been described in a patient with SLONM. We report a patient with SLONM suffering from prominent involvement of external ocular muscles. A 60-year-old female patient was reexamined for a chronic progressive oculopharyngeal syndrome that was present for 6 years. Initial symptoms were double vision and ptosis, followed by weakness of eye-closure. Two years after the onset of symptoms, she presented an exclusive picture of external ophthalmoplegia. During the following years she was unable to open or close her eyes voluntarily, lost her ability to whistle or smile, developed a hoarse voice and swallowing difficulties. There was no diurnal variation of symptoms, or fatigability. Family history for neuromuscular diseases was unremarkable. On examination she had complete bilateral ptosis and palsy of extraocular muscles, while pupillar size and pupillar reactions to light and accommodation were normal. She had a myopathic face with atrophy of masseter and temporalis muscles, severe bilateral facial palsy, and severe dysphonia. Strength was MRC grade 4 for neck flexion, head rotation, and neck extension. Further neurological examination was normal, notably fundoscopy and proximal and distal limb strength. Laboratory examinations provided normal values for standard parameters, serum creatine kinase, a comprehensive panel of autoimmune antibodies, including antibodies against acetylcholine receptor or muscle-specific kinase, anti-HIV 1/2 antibodies, and p24 antigen. Serum ACE, soluble Interleukin-2 receptor levels, serum and urine calcium levels, and repeated imaging studies ruled out sarcoidosis. Protein electrophoresis and immunofixation did not show any paraprotein, findings that rule out an association with HIV, sarcoidosis, or monoclonal gammopathy, as described in some patients in the literature [4–7]. MRI revealed symmetric atrophy of ocular muscles and fatty degeneration of pterygoideus medialis and masseter muscles, no signs of edema or contrast enhancement. Thorough neuromuscular transmission studies as well as spinal cord and brain imaging were unremarkable. No other organs were involved. Muscle biopsy of the sternocleidomastoideus revealed numerous rods, which appeared to be O. Wengert A. Meisel Department of Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany

Abstract 4524: Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: in vitro and in vivo effects of a novel Bcl-2 family inhibitor, ABT-737

Abstract Adult T-cell lymphoma/leukemia (ATLL) is a T-cell malignancy caused by the human T-lymphotrophic virus type I (HTLV-I), and its therapeutic outcome still remains extremely poor. Therefore, novel therapeutic strategies are needed to improve treatment outcomes. In this study, we elucidated the therapeutic potential of targeting the anti-apoptotic Bcl-2 family proteins for the treatment of ATLL using ABT-737 (Abbott Laboratories, Abbott Park, IL, USA), a small molecule inhibitor of Bcl-2, Bcl-XL and Bcl-w. We first validated the rationale of this study by immunohistochemically assessing the expression of Bcl-2 family proteins in 25 lymph-node specimens derived from ATLL patients. The Bcl-2 and/or Bcl-XL proteins were expressed in 80% of specimens. We next examined the cytotoxicity of ABT-737 against three ATLL cell lines by the Colorimetric method. ABT-737 significantly inhibited growth of MT-1, MT-2 and HuT 102 cells with concentrations of 50 percent inhibition of 2.4, 0.23 and 0.008μM at 72 h, respectively. We then tried to clarify the mechanism of growth inhibition induced with ABT-737 using MT-1 and MT-2 cells. ABT-737 induced apoptosis in both cells with cleavage of caspases 9 and 3, and PARP. ABT-737 also induced apoptosis in fresh tumor cells derived from patients with ATLL. We also tested if ABT-737 enhances the cytotoxicity induced by conventional chemotherapeutic agents or novel agents. The interactions between them were evaluated using the Chou-Talalay method. ABT-737 synergistically enhanced the cytotoxicity and apoptosis induced by doxorubicin, vincristine or etoposide and bortezomib or suberolyanilide hydroxamic acid, which are current key drugs and promising candidates for the treatment of ATLL, respectively. Finally, we investigated the growth inhibition of ABT-737 in ATLL-xenografted mice. The mean tumor volume and weight, and mean serum level of soluble interleukin-2 receptor α at day 21 of the treated mice with ABT-737 (100mg/kg/day) were significantly lower than those of vehicle-treated mice. Moreover, massive induction of apoptosis was observed in tumors treated with ABT-737 by the TUNEL assay. These results suggest that the use of ABT-737, either alone, or in combination with other conventional cytotoxic and novel drugs, represents a promising novel targeted approach to overcome drug resistance and to improve patient outcome in ATLL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4524.

Multiple Sclerosis: Relationships Between Cytokines, MRI Lesion Burden, Visual Evoked Potentials and Disability Scores

Aim: The aim of this study was to investigate the relationships between the disability (EDSS) scores, magnetic resonance imaging (MRI) lesion burden, the visual evoked potential (VEP) latencies and the cytokine levels in patients with multiple sclerosis (MS) that previously not studied. Method: Study group consisted of 40 MS patients with either relapsing-remitting (RR) (n=29) or secondary progressive course (n=11) and control group comprised 35 matched healthy subjects. Student’s t test, Mann-Whitney U, Chi-squared and correlation analyses were used for statistical analyses. Result: In patient group EDSS scores varied from 1.5 to 8.5, all had abnormal MRI T2 plaque burden and 65.0% had abnormal VEP latencies. Serum levels of tumor necrosis factor-alpha (TNF-а) and interleukin-2 receptor (IL-2R) were significantly higher in patients compared to controls (P 0.05). The total EDSS scores significantly correlated with the T2 plaque counts (r=0.637, P 0.05). Conclusion: Our data indicate that despite clinical stability, immunological activity is not interrrupted in MS and the production of different cytokines were not uniformly affected by the immunomodulator medication. New therapeutic strategies correcting cytokine balance may be useful in MS.

Solitary intradural extramedullary lymphoma of the cervical spine

The authors report on the case of a 64-year-old man with solitary intradural extramedullary non-Hodgkin lymphoma of the cervical spine. The lesion mimicked the appearance of meningioma on MR imaging. Positron emission tomography showed increased accumulation of fluorine-18-labeled fluorodeoxyglucose only in the cervical lesion. Serum levels of C-reactive protein and soluble interleukin-2 receptor were mildly elevated. At surgery, the intradural tumor in the subarachnoid space was totally extirpated. Based on histopathological findings, diffuse, large B-cell type non-Hodgkin lymphoma was diagnosed. Postoperatively, the patient was treated with 2 courses of chemotherapy by intrathecal injection of methotrexate, cytarabine, and prednisolone and 4 courses of intravenous rituximab, an antibody binding to CD20 on the surface of B cells. All preoperative symptoms completely resolved after surgery. Two years postoperatively, the patient was faring well with no evidence of local recurrence or new lesions at any other site. To the best of the authors' knowledge, this case is the first reported instance of solitary intradural extramedullary non-Hodgkin lymphoma of the cervical spine.

Diffuse chronic leptomeningitis with seropositive rheumatoid arthritis: report of a case successfully treated as rheumatoid leptomeningitis

A case of biopsy-confirmed chronic leptomeningitis complicating rheumatoid arthritis in a 53-year old female is reported. Her symptoms included weight loss, severe depression, and pyrexia. Magnetic resonance imaging was useful in diagnosis. Intravenous methylprednisolone was prescribed (1 g/day for 3 days), followed by prednisolone (initial dose of 30 mg daily), and this treatment was effective. Her IgG-index, serum levels of soluble interleukin-2 receptor and ferritin, and cerebrospinal level of interleukin-6 paralleled her clinical course.

Elevated serum levels of soluble interleukin-2 receptor in chronic eosinophilic leukemia/hypereosinophilic syndrome with FIP1L1-PDGFRα fusion gene

Elevated serum levels of soluble interleukin-2 receptor in chronic eosinophilic leukemia/hypereosinophilic syndrome with FIP1L1-PDGFRα fusion gene