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Biomedical subjects

Hiroshi Hashimoto

Publications and source records attributed to Hiroshi Hashimoto.

At least 91 records · Page 5Linked to original sources

A case report of the efficacy of apheresis for refractory autoimmune thrombocytopenia in a patient with systemic lupus erythematosus associated hemolytic anemia.

Autoantibodies against platelets are found in patients with autoimmune thrombocytopenic purpura (AITP) as well as in thrombocytopenia associated with systemic lupus erythematosus (SLE). The high titer of platelet associated immunoglobulin G (PA IgG) suggests the presence of antibodies against platelets. Platelet associated antibodies are thought to play a major role in the pathogenesis of autoimmune thrombocytopenia. There is a possibility that double filtration plasmapheresis (DFPP) is effective in removing the antibodies against platelets from the peripheral blood. It is suggested that DFPP may reinforce the efforts of the conventional treatment, especially high-dose intravenous immunoglobulin therapy (IVIg). DFPP was performed for severe thrombocytopenia on a SLE patient with high PA IgG value, refractory to the conventional therapy including corticosteroid therapy and IVIg. The patient underwent three sessions of DFPP combined with IVIg and the corticosteroid therapy immediately before the initiation of IVIg. The severe thrombocytopenia improved drastically after the combination treatment, accompanied with the decrease of the PA IgG titer. It was suggested that DFPP combined with corticosteroid and IVIg was effective for severe autoimmune thrombocytopenia on SLE patients refractory to the conventional therapies.

Adult↗

Double filtration plasmapheresis for the treatment of a rheumatoid arthritis patient with extremely high level of c-reactive protein.

A 68-year-old-male who was diagnosed as having rheumatoid arthritis (RA) 7 years previously was admitted the Chiba Social Insurance Hospital due to general fatigue, spiking fever, and appetite loss. Blood tests showed extremely high levels of C-reactive protein (CRP, 318.5 mg/dL), and hypergammapathy (IgG 3228 mg/dL, IgA 905 mg/dL, IgM 2537 mg/dL) and high titers of rheumatoid factor (RAPA 40960X). He was diagnosed as having RA with vasculitis, according to interstitial pneumonitis, cutaneous nodules and polyneuropathy. Prednisolone (30 mg/day) was prescribed, however, myeloperoxidase-antineutrophil cytoplasmic antibody proved to be positive (86EU) and cyclophosphamide (50 mg/day) was added one week later. Additionally, IgM K-chain M-protein was revealed and the differentiation between auto-immune and hematologic diseases was required for further drug prescriptions. Therefore, double filtration plasmapheresis (DFPP) was initiated weekly. Hematologic diseases were negated and the hypergammapathy was improved. C-reactive protein and MPO-ANCA decreased to the normal level after three sessions (IgG 1064 mg/dL, IgA 331 mg/dL, IgM 94 mg/dL, CRP 0.04 mg/dL) and the patients symptoms improved. Prednisolone was tapered and he was discharged. It was suggested that the case presented here was quite rare, having an extremely high level of CRP which was successfully managed by DFPP.

Aged↗

[Paravesical granuloma after inguinal herniorrhaphy].

Paravesical granuloma is a rare complication after inguinal herniorrhaphy. We report a case of this rare disease and review 27 previously reported cases. A 70-year-old male presented with hematopyuria. He had undergone right inguinal herniorrhaphy five years earlier. On presentation, the right inguinal area was wet with exudate. Cystoscopy revealed edematous mucosa on the right side of the bladder dome, but transurethral bladder biopsy demonstrated no malignancy. CT identified a 2-cm diameter mass with heterogeneous appearance on the right side of the bladder dome. Treatment with antibiotics proved ineffective and en bloc excision of the tumor with partial cystectomy was performed. Symptoms subsequently resolved completely. Histopathologically, the tumor represented inflammatory granuloma, and a mesh thought to be a remnant from the previous herniorrhaphy was found in the central portion of the tumor. Paravesical granuloma should be considered for patients with continuous hematopyuria and a history of inguinal herniorrhaphy.

Aged↗

[A case of late recurrence of germ cell tumor].

A 19-year-old male was admitted to our hospital because of retroperitoneal tumor and metastases in the lung and liver. He underwent chemotherapy followed by retroperitoneal lymph node dissection and pathologic examination revealed mostly necrotic tissue with a small amount of teratomatous tissue. Two years later, a hyper echoic lesion was found in the left testis, and left high orchiectomy was performed. The resected specimen appeared to be a burned-out testicular tumor. Ten years later, CT scan detected lymph node swelling in the retroperitoneum, and excision of the tumor was performed. Pathologic examination revealed well-differentiated adenocarcinoma. Since no primary adenocarcinoma was found, this case was considered late relapse of a germ cell tumor.

Adenocarcinoma↗

Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus (FK506) in patients with active rheumatoid arthritis (RA) exhibiting resistance to disease modifying antirheumatic drug (DMARD) therapy, and to determine the optimal dosage. METHODS: A total of 212 patients with DMARD-resistant RA were enrolled in this double blind, multicenter, randomized, placebo controlled study and allocated to 3 groups. Patients were administered tacrolimus at a dosage of 1.5 mg/day (68 patients) or 3 mg/day (70 patients), or placebo (74 patients), for 16 weeks. They were allowed to continue taking prednisolone (< or = 5 mg/day) and/or one nonsteroidal antiinflammatory drug (NSAID) during the study. Clinical assessment was based on the American College of Rheumatology (ACR) 20% criteria. RESULTS: ACR 20% response rates were higher in both tacrolimus groups (3 mg: 48.3%; 1.5 mg: 24.6%) than in the placebo group (14.1%), with the rate in the 3 mg group significantly higher. There were no significant differences between the tacrolimus groups and placebo group in the incidence of adverse events. The main adverse events in the tacrolimus groups, especially in the 3 mg group, were renal function abnormalities and gastrointestinal symptoms. However, no significant differences were observed among the 3 groups in the incidence of any adverse event except decrease in serum Mg level. CONCLUSION: Our findings demonstrate excellent dose-dependent efficacy of tacrolimus in patients with DMARD-resistant RA and strongly suggest the usefulness of tacrolimus for treatment of RA. The optimal dosage appears to be 3 mg/day in terms of efficacy and safety.

Adult↗

Autoimmune response to proteasome activator 28alpha in patients with connective tissue diseases.

OBJECTIVE: To determine the autoimmune response against proteasome activator 28alpha (PA28alpha) in patients with various connective tissue diseases, and to compare the immunoreactivity between anti-PA28alpha and anti-Ki antibodies. METHODS: Serum samples were obtained from 219 patients with various connective tissue diseases. cDNA encoding full-length human PA28alpha and Ki were produced by polymerase chain reaction. Antigens were expressed as glutathione S-transferase (GST) fusion proteins. The immunoreactivity of serum for PA28alpha and Ki was studied by Western blotting. An inhibition test was performed by ELISA using purified Ki antigen. RESULTS: Anti-PA28alpha> antibody was detected in serum from 23% of patients with systemic lupus erythematosus (SLE) and 24% with Sjögren's syndrome (SS). These rates were significantly higher than those for the other rheumatic diseases. Since both PA28alpha and Ki are elements of the PA28 complex and their amino acid sequences share 40.2% homology, immunoreactivity to PA28alpha was studied further. Among 27 anti-Ki positive serum samples, 13 samples (48%) also reacted with PA28alpha, suggesting a relationship between anti-PA28alpha and anti-Ki antibodies. To investigate whether this finding was due to the presence of cross-reacting epitopes for PA28alpha and Ki antigens, an inhibition test was performed by ELISA. The reactivity to purified Ki antigen was not inhibited by preincubation with recombinant PA28alpha. CONCLUSION: Detection of anti-PA28alpha antibody was significantly higher in serum from patients with SLE and SS. The relationship between anti-PA28alpha and Ki antibodies suggests the importance of an antigen-driven system in the induction of an autoimmune response to PA28 complex.

Antibody Specificity↗

[Postoperative hypoglycemia after resection of pheochromocytoma: a case report].

We report a case of severe hypoglycemia following resection of pheochromocytoma. A 39-year-old male was admitted to our hospital with a chief complaint of palpitation. Blood pressure and fasting blood glucose were within the normal range. Computed tomography and magnetic resonance imaging revealed a right adrenal tumor (7.5 x 5 x 7 cm) and 131I-MIBG scintigraphy showed marked tumor uptake of isotope. As plasma and urinary catecholamine levels were very high, a clinical diagnosis of pheochromocytoma was established. Doxazosin and propranolol were administered for 43 days prior to adrenalectomy. During intensive care monitoring 2 hours postoperatively, the patient became drowsy and began to sweat. Although blood pressure remained stable, severe hypoglycemia (38 mg/dl) and hyperinsulinism (63.67 microU/ml) were confirmed. Infusion of 50% glucose improved these symptoms and plasma glucose level and insulin secretion normalized within 15 days of surgery. We also reviewed 25 cases of hypoglycemia after resection of pheochromocytoma. We recommend close monitoring of blood glucose for at least 6 hours after adrenalectomy for pheochromocytoma.

Adrenal Gland Neoplasms↗

Autoimmune response to proteins of proliferating cell nuclear antigen multiprotein complexes in patients with connective tissue diseases.

OBJECTIVE: To analyze the autoimmune response to the proliferating cell nuclear antigen (PCNA) multiprotein complex in patients with connective tissue diseases (CTD). METHODS: The PCNA complex was purified by affinity chromatography using anti-PCNA monoclonal antibodies. Then 196 serum samples from patients with systemic lupus erythematosus (SLE) and 82 from patients with other CTD were tested for reactivity with the complex by immunoblotting. RESULTS: Of 196 SLE sera, 61 (31%) reacted with at least one component of the PCNA complex, and most reactive sera contained autoantibodies to several components of the complex. Autoantibodies to PCNA complex were less common in patients with other CTD, and most of their sera reacted only with one or a few proteins in the complex. Two out of 20 scleroderma sera reactive with 100, 85, and 70 kDa proteins in the PCNA complex also had autoantibodies to topoisomerase I (topo I) antibodies, which is an element of the complex. These findings suggest that the autoimmune response to the PCNA complex was specific for SLE. Anti-PCNA complex antibodies were associated with an increased serum level of PCNA detected by ELISA. The spreading of the autoimmune response to the elements of the complex was observed in parallel with the increased serum PCNA level when a series of sera from a lupus patient were tested longitudinally. In addition, anti-PCNA complex antibodies were significantly correlated with lupus erythematosus cells. CONCLUSION: The "antigen-drive" system may play a crucial role in inducing the autoimmune response to the PCNA complex in patients with SLE.

Autoimmunity↗

[Tumor enucleation for pelvic schwannoma: a case report].

A 36-year-old man with a complaint of pollakisuria visited our hospital. A non-displaceable, palm-sized tumor was palpable in the lower abdomen. Laboratory data were normal except for slightly high serum S100 protein. Intravenous pyelography revealed hydronephrosis on the right side and deviation of the bladder to the left. Computed tomogaphy revealed a heterogenous tumor in the pelvis with a cystic lesion and calcification. The tumor was 16 x 12 x 11 cm in size and in contact with the sacrum. The tumor was extirpated following diagnosis as a benign schwannoma by needle biopsy. The pelvic cavity was occupied by the tumor rigidly adhered to the sacrum. Although serious complications, such as bleeding and nerve injury were apprehended, we incised the tumor capsule and enucleated the contents as much as possible. The histopathological diagnosis of the resected specimen was benign schwannoma, type Antoni A. In the last 10 years, 37 cases of pelvic schwannoma have been reported in the Japanese literature. In most of them, surgical extirpation was difficult to perform because of adhesion to the sacrum. If the tumor is confirmed benign from histopathologic findings preoperatively, tumor enucleation may become a therapeutic option.

Adult↗

Crystallization and preliminary X-ray crystallographic analysis of human peptidylarginine deiminase V.

Human peptidylarginine deiminase V (PAD V) is a post-translational enzyme that catalyzes the conversion of arginine residues in protein into citrulline residues in the presence of calcium ion. Crystals of PAD V have been grown at 293 K using polyethylene glycol monomethylether as a precipitant. Crystals diffracted beyond 2.7 A resolution at 100 K at the SPring-8 synchrotron-radiation source. The crystal belongs to space group C2, with unit-cell parameters a = 144.6, b = 60.4, c = 113.4 A, beta = 123.6 degrees. The asymmetric unit contains one molecule, with a V(M) of 2.56 A(3) Da(-1) and a solvent content of 56.1%. A full set of X-ray diffraction data was collected to 2.8 A resolution with a completeness of 97.5%. Heavy-atom derivatives have been successfully prepared and structure analysis is in progress.

Crystallization↗

Churg-Strauss syndrome (CSS) in a patient receiving pranlukast.

Pranlukast is a cysteinyl leukotriene receptor I antagonist (LTRAs) approved for treatment of asthma in Japan since 1995. Compared to other LTRAs, such as zafilukast and montelukast, only few cases with Churg-Strauss syndrome (CSS) have been reported in association with treatment with pranlukast. We describe a 17-year-old Japanese male patient who developed CSS with a 13 month history of mild asthma receiving pranlukast for 11 months without systemic and/or inhaled corticosteroid administration prior to development of CSS. From the aspect of temporal relationship between treatment with pranlukast and development of CSS, a direct induction of CSS by pranlukast is suggested in our case.

Adolescent↗

Acute acalculous cholecystitis induced by mesenteric inflammatory veno-occlusive disease (MIVOD) in systemic lupus erythematosus.

A 43-year-old woman with systemic lupus erythematosus (SLE) was treated for lupus pleurisy. During the course of her illness, she abruptly suffered severe right hypochondriac pain and high-grade fever. Abdominal ultrasonography revealed a thickening of the gallbladder wall without cholelithiasis, and she was diagnosed with acute acalculous cholecystitis (AAC). Laparoscopic cholecystostomy was performed. Pathological examination revealed lymphocytic venulitis without arteritis. Antiphospholipid antibodies were not demonstrated during the course of illness. From these findings, the cause of AAC was revealed as a mesenteric inflammatory veno-occlusive disease (MIVOD), which is a novel venopathy mainly affecting the mesenteric vein and/or its branches, causing serious ischemic complications. MIVOD should be considered as a possible cause of AAC.

Acalculous Cholecystitis↗

Clinical and epidemiologic analysis of giant cell (temporal) arteritis from a nationwide survey in 1998 in Japan: the first government-supported nationwide survey.

OBJECTIVE: To elucidate epidemiologic and clinical manifestations of Japanese patients with giant cell arteritis (GCA), the first nationwide survey for GCA was conducted in 1998 in Japan. METHODS: The first questionnaire on GCA for patients treated in 1997 was sent to 10,717 medical departments in Japan. A total of 177 patients were reported. Among the 177 patients, 66 GCA patients with detailed clinical and epidemiologic features on second survey were analyzed. RESULTS: Prevalence in patients 50 years of age and older in 1997 was 1.47 per 100,000 population in Japan. The average age at onset was 71.5 years old. The male:female ratio was 1:1.7. The association with permanent and complete visual loss (6.5%), jaw claudication (15.2%), and polymyalgia rheumatica (PMR) (30.3%) were low in frequency compared with those reported from other countries. All patients were treated with corticosteroids. Only 3 (4.5%) patients were reported as deceased due to other causes. CONCLUSION: The prevalence of GCA in Japan was revealed to be extremely low compared with other countries. Clinical findings of permanent and complete visual loss, jaw claudication, and PMR were infrequent among Japanese patients with GCA.

Aged↗

The crystal structure of the novel calcium-binding protein AtCBL2 from Arabidopsis thaliana.

Arabidopsis thaliana calcineurin B-like protein (AtCBL2) is a member of a recently identified family of calcineurin B-like calcium-binding proteins in A. thaliana. The crystal structure of AtCBL2 has been determined at 2.1 A resolution. The protein forms a compact alpha-helical structure with two pairs of EF-hand motifs. The structure is similar in overall folding topology to the structures of calcineurin B and neuronal calcium sensor 1, but differs significantly in local conformation. The two calcium ions are coordinated in the first and fourth EF-hand motifs, whereas the second and third EF-hand motifs are maintained in the open form by internal hydrogen bonding without coordination of calcium ions. Both a possible site and a possible mechanism for the target binding to AtCBL2 are discussed based on the three-dimensional structure.

Amino Acid Motifs↗

Crystallization and preliminary X-ray characterization of a novel calcium-binding protein AtCBL2 from Arabidopsis thaliana.

A new family of calcineurin B-like calcium-binding proteins has recently been identified in Arabidopsis thaliana. AtCBL2, a member of this family, has been crystallized in the presence of calcium ions using polyethylene glycol as a precipitant at 293 K. The crystals belong to space group C222(1), with unit-cell parameters a = 83.9, b = 118.1, c = 49.1 A. The asymmetric unit contains one molecule, with a V(M) of 2.36 A(3) Da(-1) and a solvent content of 48%. Native diffraction data to 2.1 A resolution have been collected using synchrotron radiation at SPring-8.

Arabidopsis↗

Dermatofibrosarcoma protuberans of breast.

We describe the case of a 57-year-old woman with a tumor of the breast suspected of being a dermatofibrosarcoma protuberans (DFSP). To confirm the diagnosis, molecular studies were performed on fixed tumor and revealed the presence of the fusion product of the COL1A1-PDGFB genes characteristic of DFSP.

Breast Neoplasms↗