[Chondroblastoma of the Temporal Bone Removed Using a Middle Cranial Fossa Approach].

We report a case of chondroblastoma of the middle cranial fossa, probably arising from the (infra) mandibular fossa, and expanding to the attic and external auditory canal that was successfully removed using a middle cranial fossa approach. No recurrences occurred during an 8-year postoperative follow-up period. Initial biopsy findings suggested a pathological diagnosis of giant cell tumor that was later confirmed to be a chondroblastoma based on an immunohistochemical study of S-100. This case study suggests a profound understanding of the clinical features, histopathological characteristics, and possible treatment. of chondroblastoma.

A case of fibrillary glomerulonephritis associated with thrombotic microangiopathy and anti-glomerular basement membrane antibody.

We present the first report of a case of fibrillary glomerulonephritis (FGN) associated with thrombotic microangiopathy (TMA) and anti-glomerular basement membrane antibody (anti-GBM antibody). A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction. Laboratory data revealed normocytic-normochromic anemia with schistocytes in the peripheral smear, thrombocytopenia, increased serum lactate dehydrogenase, decreased serum haptoglobin, and negative results for both direct and indirect Coombs tests. Based on these results, we diagnosed TMA. Assays conducted several days later indicated a disintegrin-like and metalloprotease with a thrombospondin motif 13 (ADAMTS13) activity of 31.6%, and ADAMTS13 inhibitors were negative. We started plasma exchange using fresh frozen plasma and steroid pulse therapy. Anti-GBM antibody was found to be positive. Renal biopsy showed FGN. Blood pressure rose on the 46th hospital day, and mild convulsions developed. Based on magnetic resonance imaging of the head, the patient was diagnosed with reversible posterior leukoencephalopathy syndrome. Hypertension persisted despite administration of multiple antihypertensive agents, and the patient experienced a sudden generalized seizure. Computed tomography of the head showed multiple cerebral hemorrhages. However, his blood pressure subsequently decreased and the platelet count increased. TMA remitted following 36 plasma exchange sessions, but renal function was not restored, and maintenance hemodialysis was continued. The patient was discharged on the 119th day of hospitalization. In conclusion, it was shown that TMA, FGN and anti-GBM antibody were closely related.

Antenatal ultrasound visualization of left testis that then vanished after birth.

A 10-month-old infant was referred for disappearance of the left testis, which had been confirmed as present on antenatal ultrasound at 38 weeks of gestation, as well as at the newborn physical exam and the 4 month exam. The right testis was enlarged, whereas the left testis was palpated as a nubbin. The right testis measured on ultrasound was 1.6 × 0.8 × 1.0 cm; the testicular volume was 0.67 cm(3). The left nubbin was hyperechoic, and accurate measurement of testicular components was difficult. At the age of 1 year 8 months, with the diagnosis of left vanishing testis, inguinal exploration was undertaken to rule out intra-abdominal cryptorchidism. A fibrous nodule that connected to the spermatic vessels and the vas deferens was resected. Histopathology indicated a testicular remnant containing seminiferous tubules, hemosiderin deposits, calcification and marked fibrosis of the stroma, suggesting hemorrhagic infarction in utero.

The identification of a novel splicing mutation in C1qB in a Japanese family with C1q deficiency: a case report.

C1q deficiency is a rare disease that is associated with a high probability of developing systemic lupus erythematosus. We report a 4-year-old Japanese girl who presented with fever, facial erythema, joint pain, and oral ulceration. Complement deficiencies were suspected because of her persistent hypocomplementemia and normal levels of the complement proteins C3 and C4. We identified a novel homozygous splicing mutation in the C1qB gene, c.187 + 1G > T, which is the first mutation to be confirmed in a Japanese individual. Because treatment with steroids and immunosuppressive drugs was not effective, we commenced use of fresh frozen plasma to provide C1q supplements. Currently, the patient remains almost asymptomatic, and we are attempting to control the drug dosage and administration intervals of fresh frozen plasma.

A case of infantile systemic lupus erythematosus with severe lupus nephritis and EBV infection.

Infantile systemic lupus erythematosus (iSLE) is extremely rare. Patients with iSLE usually become severely unwell and have poor prognosis. Epstein-Barr virus (EBV) infection has been implicated in the development of SLE in both adults and children. Recently, we experienced a case of iSLE with severe lupus nephritis (LN) and EBV infection. A 14-month-old Japanese boy was diagnosed with iSLE according to the American Rheumatism Association criteria. Renal biopsy showed LN classified as International Society of Nephrology/Renal Pathology Society class IV-G (A), and liver biopsy showed lupus hepatitis. Steroid pulse treatment resulted in improvement of the levels of serological markers of SLE such as double-stranded DNA and complement, but his proteinuria worsened and he developed acute nephritic-nephrotic syndrome. Monthly intravenous cyclophosphamide (IVCY) therapy dramatically reduced his proteinuria and led to complete remission (urinary protein/creatinine ratio <0.1 mg/mg), with gradual improvement in levels of serological markers. EBV antibody titers and EBV polymerase chain reaction (PCR) of peripheral blood lymphocytes suggested that the onset of iSLE might have been associated with EBV infection. At his 2-year follow-up visit, he was healthy and remained in complete remission. We conclude that IVCY treatment might be well tolerated and effective in cases of iSLE. EBV infection might play an important role in the pathogenesis of iSLE.

TGFα shedding assay: an accurate and versatile method for detecting GPCR activation.

A single-format method to detect multiple G protein-coupled receptor (GPCR) signaling, especially Gα(12/13) signaling, presently has limited throughput and sensitivity. Here we report a transforming growth factor-α (TGFα) shedding assay, in which GPCR activation is measured as ectodomain shedding of a membrane-bound proform of alkaline phosphatase-tagged TGFα (AP-TGFα) and its release into conditioned medium. AP-TGFα shedding response occurred almost exclusively downstream of Gα(12/13) and Gα(q) signaling. Relying on chimeric Gα proteins and promiscuous Gα(16) protein, which can couple with Gα(s)- and Gα(i)-coupled GPCRs and induce Gα(q) signaling, we used the TGFα shedding assay to detect 104 GPCRs among 116 human GPCRs. We identified three orphan GPCRs (P2Y10, A630033H20 and GPR174) as Gα(12/13)-coupled lysophosphatidylserine receptors. Thus, the TGFα shedding assay is useful for studies of poorly characterized Gα(12/13)-coupled GPCRs and is a versatile platform for detecting GPCR activation including searching for ligands of orphan GPCRs.

Thomsen-Friedenreich antigen exposure as a cause of Streptococcus pyogenes-associated hemolytic-uremic syndrome.

Infection with Streptococcus pyogenes, a Group A beta-hemolytic streptococcus (GAS), is a rare cause of hemolyticuremic syndrome (HUS). Invasive infections with Streptococcus pneumoniae that produce neuraminidase are a well-recognized cause of HUS without diarrhea. The Thomsen- Friedenreich antigen (T antigen) plays a role in the pathophysiology of pneumococcal HUS. We describe the case of a 3-year-old boy with GAS-associated HUS and show how T-antigen exposure was implicated in this case. He had no diarrhea and cultures for blood, urine, and stool were negative. The urinary pneumococcal antigen was negative; his direct Coombs test was positive. Glomerular capillary loops, tubular epithelium on his renal biopsy specimen, and red blood cells in his blood smear showed positive fluorescence with anti-T lectin. Although the pathogenesis of GAS-associated HUS is not well understood, T-antigen exposure may be implicated in some cases with GAS-associated HUS.

Successful pregnancy in a patient suffering from recurrent mid-trimester miscarriage with C9 deficiency after receiving cervical cerclage followed by clindamycin and progesterone: a case report.

Complement component 9 (C9) deficiency is relatively common, especially in Japan. Here we present the case of a 27-year-old Japanese woman whose obstetric history involved three mid-trimester miscarriages (at 22 weeks', 18 weeks' and 21 weeks' gestation) and one early spontaneous miscarriage. Her fifth pregnancy was successfully managed by cervical cerclage at 13 weeks' gestation, followed by clindamycin administration (600 mg/day for 7 days) and progesterone injections (250 mg/week). She gave birth to a healthy 3326-g male infant at 40 weeks and 1 day gestation after natural onset of labor. After delivery, the serum complement components were analyzed. C9 protein and activity were undetectable in the patient's serum. We suggest that an immunologic disorder such as C9 deficiency should be considered as a potential complication of undiagnosed recurrent miscarriages.

GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position.

GPR34 is a G protein-coupled receptor belonging to the P2Y family. Here, we attempted to resolve conflicting reports about whether it is a functional lysophosphatidylserine (LysoPS) receptor. In HEK293 cells expressing human, mouse or rat GPR34 and Gα chimera between Gαq and Gαi1(Gq/i1), LysoPS quickly elevated intracellular Ca(2+) ion levels ([Ca(2+)](i)). LysoPS also stimulated alkaline phosphatase (AP)-tagged TGFα (AP-TGFα) release in GPR34-expressing HEK293 cells and induced the migration of CHO-K1 cells expressing GPR34. Other lysophospholipids did not induce these actions. Replacement of the serine residue of LysoPS abolished the reactivity of LysoPS with GPR34, indicating that GPR34 strictly recognizes the serine head group of LysoPS. Recombinant phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)) that deacylates fatty acid at the sn-1 position of PS and produces 2-acyl-LysoPS, but not catalytically inactive mutant PS-PLA(1), stimulated the release of AP-TGFα from GPR34-expressing cells. Consistent with the result, LysoPS was detected in the cells treated with wild-type PS-PLA(1) but not with the mutant PS-PLA(1). PS treated with PLA(1) was much more effective at stimulating AP-TGFα release than PS treated with PLA(2). In addition, migration-resistant 2-acyl-1-deoxy-LysoPS, a 2-acyl-LysoPS analogue, was much more potent than 1-acyl-2-deoxy-LysoPS. The present studies confirm that GPR34 is a cellular receptor for LysoPS, especially with a fatty acid at the sn-2 position.

Etanercept is safely used for treating psoriatic arthritis in a patient complicated with type 1 hereditary angioedema.

Hereditary angioedema (HAE) is a life-threatening disorder caused by deficiency or dysfunction of the C1 inhibitor protein. Patients with HAE are restricted in various medical treatments, which can induce an HAE attack. We herein report the first case of psoriatic arthritis (PSA) with type 1 HAE successfully treated with 25 mg of etanercept without HAE attack. Etanercept may represent a useful choice for treating patients with HAE accompanied by intractable PSA and rheumatoid arthritis (RA).

Cytologic detection of recurrence in extramammary Paget's disease of the vulva: a report of two cases.

BACKGROUND: Extramammary Paget's disease of the vulva (EMPDV) is a rare gynecologic malignancy. We examined two cases of EMPDV in which cytologic study led to early detection of disease recurrence. CASES: In case 1, a 71-year-old woman, recurrence was detected with malignant cells from the vaginal Papanicolaou smear a few months after radical surgery for endometrial cancer. An asymptomatic perineal erythematous lesion was identified and diagnosed as EMPDV by biopsy specimen. She underwent curative surgery, but during the follow-up period, malignant cells appeared again in her vaginal Papanicolaou smear, which led to early detection of the recurrent disease that was macroscopically invisible. In case 2, an 80-year-old woman presented with the complaint of perineal pruritus and was diagnosed with EMPDV. Twenty-two months after the curative primary surgery, bilateral groin lymphadenopathies appeared, and the cytologic specimen by fine needle aspiration biopsy from the lymph nodes led to early detection of the recurrence without her experiencing negative side effects such as severe pain. CONCLUSION: Cytologic examination is a simple but efficient diagnostic measure without major negative side effects, provided the procedures are applied adequately and performed correctly.

A case of dense deposit disease associated with a group A streptococcal infection without the involvement of C3NeF or complement factor H deficiency.

A 14-year-old girl presented with acute glomerulonephritis. Tests revealed hypocomplementemia and elevated Antistreptolysin-O titers, and renal biopsy revealed endocapillary and mesangial proliferative glomerulonephritis with double contours of the glomerular basement membrane (GBM). Despite methylprednisolone pulse therapy and the administration of oral prednisolone, overt proteinuria and hypocomplementemia persisted. A second renal biopsy 6 months later confirmed the initial diagnosis of dense deposit disease (DDD) based on electron-dense deposits in the GBM. C3 nephritic factor (C3NeF) and a deficiency of complement factor H (CFH) were not evident. A nephritis-associated plasmin receptor (NAPlr), nephritogenic group A streptococcal antigen, and the plasmin activity by in situ zymography were been in both the first and second biopsy specimens. The patient received combined immunomodulatory therapy with prednisolone and mizoribine, and the urinary protein decreased to a mild level at 27 months after disease onset. These findings suggest that persistent glomerular NAPlr deposition may be associated with the pathogenesis of DDD in some patients without the involvement of C3NeF or CFH mutation and that DDD patients of this type may respond to immunomodulatory treatment.

Correlation of the standardized uptake value in FDG-PET with the expression level of cell-cycle-related molecular biomarkers in resected non-small cell lung cancers.

PURPOSE: The aim of this study was to clarify the relationship between the maximum standardized uptake value (maxSUV) and the expression levels of cell-cycle-related molecular biomarkers. PATIENTS AND METHODS: Thirty consecutive patients with non-small cell lung cancer (NSCLC) were enrolled in the study. Histologically, the tumors included 23 adenocarcinomas and 7 squamous cell carcinomas. Protein expressions of Ki-67, proliferating cell nuclear antigen (PCNA), and p53 were examined by immunohistochemistry. RESULTS: The maxSUV was higher in poorly differentiated NSCLCs than in well-differentiated and moderately differentiated tumors (p <0.05). The Ki-67 labeling index was higher in squamous cell carcinomas than in adenocarcinomas (p <0.05), and also in poorly differentiated tumors than in well-differentiated and moderately differentiated tumors (p <0.01). A positive correlation was found between the maxSUV and Ki-67 expression level (r = 0.687, p <0.001). No correlation was found between maxSUV and PCNA expression (r = 0.214, p = 0.248) or between maxSUV and p53 expression (r = 0.357, p = 0.09). Among the molecular biomarkers, an association was found between the expression levels of Ki-67 and PCNA (r = 0.515, p <0.01). CONCLUSIONS: Immunohistochemical staining with Ki-67 in NSCLC correlates with maxSUV. Measurement of the maxSUV by PET is a simple and noninvasive method to determine the biological cancer cell proliferation potential.

Emerging lysophospholipid mediators, lysophosphatidylserine, lysophosphatidylthreonine, lysophosphatidylethanolamine and lysophosphatidylglycerol.

It is now widely accepted that lysophospholipids (LPLs), a product of the phospholipase A reaction, function as mediators through G-protein-coupled receptors. Notably, recent studies of lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) have revealed their essential roles in vivo. On the other hand, other LPLs such as lysophosphatidylserine (LPS), lysophosphatidylthreonine (LPT), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI) and lysophosphatidylglycerol (LPG) have been reported to show lipid mediator-like responses both in vivo (LPS and LPT) and in vitro (LPS, LPT, LPE and LPG), while very little is known about their receptor, synthetic enzyme and patho-physiological roles. In this review, we summarize the actions of these LPLs as lipid mediators including LPS, LPT, LPE and LPG.