Hidetoshi Okabe

MRI findings in intramuscular lipomas

Abstract Objective. To investigate the spectrum of magnetic resonance (MR) findings of intramuscular lipoma. Design and patients. A retrospective review of 17 consecutive cases of intramuscular lipoma examined with MR imaging was undertaken. Features assessed included the size and margin of the mass; the homogeneity of the contents, including the presence or absence of intermingled muscle fibers; whether the mass was uninodular or multinodular; and the presence of linear structures between and within the tumor nodules. Three well-differentiated liposarcomas and one dedifferentiated liposarcoma associated with lipoma-like components were also studied to allow a comparison of the benign and malignant lesions. Results. The diameter of the intramuscular lipomas varied from less than 3 cm to more than 10 cm. Ten of the intramuscular lipomas were homogeneous but the remaining seven were inhomogeneous with intermingled muscle fibers within the mass. The intramuscular lipomas were well defined in 12 cases, and infiltrative in five. In one case the margin of the lesion showed prominent infiltration of the surrounding muscle tissue. Of the 17 cases of intramuscular lipoma, 15 were composed of a single nodule, whereas three of four cases of liposarcoma were composed of multinodular masses. Conclusion. The MR findings of intramuscular lipoma varied from a small, single and homogeneous mass identical to ordinary (superficial) lipoma, to a large, inhomogeneous lesion with an infiltrative margin. The presence of infiltrative margins and intermingled muscle fibers in intramuscular lipoma indicates a benign lesion rather than malignancy. In addition, uninodularity of the mass is helpful in differentiating intramuscular lipoma from well-differentiated liposarcoma.

Oxidative stress increases MICA and MICB gene expression in the human colon carcinoma cell line (CaCo-2)

The human major histocompatibility complex class I chain-related A gene (MICA) and the MICB gene are newly identified members of the major histocompatibility complex class I chain-related gene family. We demonstrate here that oxidative stress, induced by H(2)O(2), promoted MICA (2.2-fold) and MICB (3.8-fold) gene expression using the human colon carcinoma cell line (CaCo-2) and semi-quantitative RT-PCR.

Significance of MIB-1 staining indices in meningiomas: comparison of two counting methods.

The authors evaluated the predictability of MIB-1 immunohistochemistry for growth and recurrences of meningiomas using two different counting methods: 1) in the area of the highest MIB-1 labeling (HL method) and (2) in randomly selected fields (RS method). The MIB-1 staining indices (SIs) determined by the HL method were approximately twice as high as those by the RS method, and the correlation coefficient between them was high (R = 0.86) in 139 meningiomas when transformed logarithmically. The differences in SIs in histologic grades were significant with either method. Tumor doubling time (Td) was calculated in 22 meningiomas from serial radiologic examinations. The RS method yielded a slightly higher correlation coefficient between log Td and log SI than the HL method. When the authors examined the predictability of recurrence in 112 totally removed meningiomas, the RS method distinguished the recurrent group more definitively. Several benign meningiomas with low SIs by the RS method exhibited focal accumulation of MIB-1-positive cells. Although they were assigned high MIB-1 values by the HL method, these meningiomas did not recur, and therefore obscured the prognostic importance of the MIB-1 value with the HL method. Focal accumulation of MIB-1-positive cells in meningiomas is not likely to correlate with their biologic aggressiveness.

Truncating mutations of RB1CC1 in human breast cancer.

The protein RB1CC1 (retinoblastoma 1 (RB1)-inducible coiled-coil 1) has been identified as a key regulator of the tumor-suppressor gene RB1 (ref. 1). RB1CC1 is localized in the nucleus and has been proposed to be a transcription factor because of its nuclear localization signal, leucine zipper motif and coiled-coil structure. The gene RB1CC1 is localized to a region of chromosome 8q11 (ref. 2) containing several loci of putative tumor-suppressor genes; however, its role in human cancers remains to be determined. Here we report that 20% (7 of 35) of primary breast cancers examined contained mutations in RB1CC1, including nine large interstitial deletions predicted to yield markedly truncated RB1CC1 proteins. Wildtype RB1CC1 and RB1 were absent or significantly less abundant than normal in the seven cancers with mutations in RB1CC1, but were abundant in cancers without such mutations. In all seven cancers, both RB1CC1 alleles were inactivated; two showed compound heterozygous deletions. Thus, RB1CC1 is frequently mutated in breast cancer and shows characteristics of a classical tumor-suppressor gene.

Multiple IgG4‐related sclerosing lesions in the maxillary sinus, parotid gland and nasal septum

IgG4‐related sclerosing disease is recognized as a distinct clinicopathological entity. It is well known that this disease can occur in the salivary, lacrimal and pituitary glands, in the head and neck region. The nasal cavity is an extremely rare site of involvement of IgG4‐related sclerosing disease. Herein is reported a case of multiple IgG4‐related sclerosing lesions in the maxillary sinus, parotid gland and nasal septum. A 73‐year‐old Japanese man presented with nasal obstruction and tumors of the right maxillary sinus and parotid gland were detected, after which resections of these tumors were performed. One year after the last surgery, he noted swelling of the nasal septum, and the tumor was resected. These three tumors had similar histopathology, such as conspicuous fibrosclerotic changes with dense lymphoplasmacytic infiltration and occasional obliterative phlebitis. Immunohistochemistry indicated abundant IgG4‐positive plasma cell infiltration and high ratios of IgG4‐positive/IgG‐positive plasma cells (>70%) in all three lesions. The diagnosis of multiple IgG4‐related sclerosing lesions was made. The present case suggests that IgG4‐related sclerosing lesion can occur in the maxillary sinus and nasal septum, and represents an extension of the spectrum of IgG4‐related sclerosing disease.

Identification of RB1CC1, a novel human gene that can induce RB1 in various human cells.

Multidrug resistance to anti-cancer agents (MDR) is a major barrier to successful cancer treatment. Current knowledge about genes that contribute to MDR is limited, however, and its mechanisms remain unclear. To identify genes involved in MDR, we performed differential display analysis and isolated a novel human gene, RB1CC1 (RBI-inducible Coiled-Coil 1). The 6.6-kb RB1CC1 cDNA encodes a putative 1594-amino-acid protein that contains a nuclear localization signal, a leucine zipper motif and a coiled-coil structure. Western blot analysis and immunocytochemical staining with anti-RB1CC1 antibody showed that endogenously expressed RB1CC1 protein localized to the nucleus. In MDR variants of human osteosarcoma cells, RB1CC1 expression increased in response to doxorubicin-induced cytotoxic stress and remained elevated for the duration of drug treatment. RB1CC1 expression levels correlated closely with those of RB1 (retinoblastoma 1 ) in cancer cell lines as well as in various normal human tissues. Moreover, introduction of wild-type RB1CC1 significantly induced RB1 expression in human leukemic cells. These data suggest that RB1CC1 may be a key regulator of RB1 gene expression.

Combined Effect of Hydrogen Peroxide Induced Oxidative Stress and IL-1α on IL-8 Production in CaCo-2 Cells (a Human Colon Carcinoma Cell Line) and Normal Intestinal Epithelial Cells

Oxidative stress, IL-1α, and IL-8 are known to contribute to mucosal inflammation of the gastrointestinal tract. We examined the IL-8 response after brief exposure to hydrogen peroxide induced oxidative stress in CaCo-2 cells (a human colon carcinoma cell line) and in human intestinal epithelial cells. In addition, we examined whether exposure to oxidative stress, followed by IL-1α, could modulate IL-8 production. A transient up-regulation of IL-8 mRNA expression was observed after hydrogen peroxide treatment. Hydrogen peroxide induced oxidative stress was also observed to promote IL-8 secretion. Exposure to hydrogen peroxide, followed by IL-1α, enhanced IL-8 production over that achieved with IL-1α alone. Thus, oxidative stress and IL-1α were observed to cooperatively enhance IL-8 production.

IgG4-related inflammatory aneurysm of the aortic arch

IgG4‐related sclerosing disease can occur in the cardiovascular system and some inflammatory abdominal aortic aneurysms have been shown to belong to IgG4‐related sclerosing disease. Herein is reported a case of IgG4‐related inflammatory aortic aneurysm of the aortic arch. A 71‐year‐old Japanese man was found to have an aneurysm of the aortic arch with maximum dimension of 5.5 cm. The surgically resected aneurysm wall had conspicuous fibrosclerotic changes, dense lymphoplasmacytic infiltration and occasional obliterative phlebitis in the adventitia; the thickness of the adventitia was 6.5 mm. Immunohistochemistry indicated numerous IgG4‐positive plasma cell infiltrates; 84% of the IgG‐bearing cells were IgG4 positive. The diagnosis of IgG4‐related inflammatory aortic aneurysm of the aortic arch was made. Although previously reported IgG4‐related inflammatory aortic aneurysms were confined to the abdominal aorta, the present case report demonstrates that IgG4‐related inflammatory aortic aneurysm can occur in the aortic arch, thereby extending the spectrum of IgG4‐related periaortitis. Further studies are needed to clarify the spectrum of IgG4‐related sclerosing disease in the cardiovascular system.

RB1CC1 insufficiency causes neuronal atrophy through mTOR signaling alteration and involved in the pathology of Alzheimer's diseases.

RB1-inducible Coiled-Coil 1 (RB1CC1) has been shown to be a novel tumor suppressor regulating RB1 expression. Neuronal abundance of RB1CC1 is reported to contribute to the non-proliferating enlarged cell phenotype through the maintenance of RB1 and mTOR. To clarify whether RB1CC1 insufficiency is involved in neuronal atrophy and Alzheimers pathology, we investigated modifications of RB1CC1 as a possible cause of atrophy or death through the disturbance of mTOR signaling in Neuro-2a neuroblastoma cells. We also evaluated the correlation between RB1CC1 and mTOR signaling in a series of Alzheimers brain tissues. Though RB1CC1 introduction enhanced neurite growth, RNAi-mediated knockdown of RB1CC1 or rapamycin treatment caused neurite atrophy and apoptosis due to mTOR signaling reduction in the differentiated Neuro-2a cells. Both TSC1 and RB1CC1 were equally functional and maintained mTOR signaling, indicated by phospho-S6 (Ser240/244) expression in 69% of Alzheimers (9/13 cases) and 100% of normal brains (6/6 cases). However, scanty RB1CC1 expression, less than TSC1, caused phospho-S6 disappearance in 31% of Alzheimers tissues (4/13 cases). These findings suggest that RB1CC1 insufficiency may result in mTOR signaling repression through unbalanced TSC1 abundance and may induce neuronal atrophy. These observations may have implications for the pathogenesis of Alzheimers disease.

Expression of macrophage inflammatory protein‐1α (MIP‐1α) in human endometrium throughout the menstrual cycle

Objective To investigate the distribution and the role of macrophage inflammatory protein‐la (MIP‐ 1α) in human endometrium during cyclic changes.