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Biomedical subjects

Hiroshi Hashimoto

Publications and source records attributed to Hiroshi Hashimoto.

At least 109 records · Page 6Linked to original sources

De novo germinoma in the brain in association with Klinefelter's syndrome: case report and review of the literature.

BACKGROUND: There are no previous reports about de novo germ cell tumors without any past history of germ cell tumor. We describe a case of de novo cerebral germinoma in association with Klinefelter's syndrome. CASE DESCRIPTION: A boy had undergone growth hormone therapy for dwarfism because of hypopituitarism from 10 to 17 years old. The result of karyotyping at the age of 13 was 47,XXY. Magnetic resonance images (MRI) of the brain at the age of 17 years showed no lesions. Two years later, at the age of 19, the patient noticed onset of mild right hemiparesis. MR imaging revealed the existence of a brain tumor in the left temporal lobe and hypothalamus. The patient underwent an operation and the histologic diagnosis of the lesion was germinoma. After postoperative chemotherapy and radiation therapy, the lesion disappeared and the patient was discharged uneventfully. CONCLUSIONS: To the best of the authors' knowledge, this is the first reported case of a germ cell tumor to be de novo without any past history of other germ cell tumor and the seventh case in which it occurred in association with Klinefelter's syndrome.

Adult↗

Immune abnormalities induced by human endogenous retroviral peptides: with reference to the pathogenesis of systemic lupus erythematosus.

P15E is a specific sequence among the envelope gene (env)-encoded transmembrane proteins of exogenous and endogenous retroviruses. A synthetic peptide (CKS- 17) that shows homology to this p15E region in several species of retrovirus is known to induce immune abnormalities. In this study, we examined the effect of a synthetic peptide derived from a region of human endogenous retrovirus (HERV) clone 4-1 (lambda4 - 1) similar to sequences of CKS-17 on the induction of systemic lupus erythematosus (SLE)-related immune abnormalities. Our results indicated that this peptide could induce T-cell activation and anergy in normal peripheral blood mononuclear cells, and the peptide could also promote the production of interleukins IL-6 and IL-16. These phenomena are representative immune abnormalities observed in SLE patients. Thus, our findings support the possibility that HERV acts as a pathogen in human SLE.

Cells, Cultured↗

Multiple spindle cell lipomas of the tongue: report of a case.

Spindle cell lipoma (SCL) is a relatively uncommon benign lipomatous tumor characterized by a mixture of mature adipocytes and bland spindle cells on a fibromyxoid background. These lipomas usually arise as solitary nodules in the subcutaneous tissue of the posterior neck, shoulder and back in adult men. Multiple SCLs account for 0.5% to 3% of all SCLs. In the literature, there have been 15 cases of intraoral SCL, including 6 cases of SCL in the tongue. We report a case of multiple SCLs on the bilateral margins of the tongue of a 75-year-old Japanese man. The tumors were removed surgically, and they exhibited the classic histopathological features of SCL, being well-circumscribed masses composed of a mixture of adipocytes and fibroblast-like spindle cells within a fibromyxoid stroma. Immunohistochemical analysis revealed that the spindle cells were strongly positive for CD 34 and bcl-2. To our knowledge, this is the first report of a case of multiple SCLs of the tongue.

Adipocytes↗

Intranasal pericytic tumors (glomus tumor and sinonasal hemangiopericytoma-like tumor): report of two cases with review of the literature.

An intranasal glomus tumor and a sinonasal hemangiopericytoma-like tumor are reported. Both patients were elderly women suffering from nasal bleeding, and presented with a polypoid mass arising in the nasal septum. Microscopically, the glomus tumor displayed a proliferation of uniform rounded or cuboidal epithelioid cells arranged in sheets and interrupted by a rich vasculature with a characteristic configuration mimicking the normal glomus bodies, while the sinonasal hemangiopericytoma-like tumor featured a perivascular proliferation of spindle- to oval-shaped cells that were arranged in short fascicles. Both tumors shared immunohistochemical features supporting their myoid differentiation by the expression of vimentin, alpha-smooth muscle actin and muscle-specific actin, albeit with no immunoreaction to desmin. Both the intranasal glomus tumor and sinonasal hemangiopericytoma-like tumor are characterized by a perivascular growth pattern and myoid differentiation, having a close relation to the 'perivascular myomas', which was recently designated.

Aged↗

Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype.

Inflammatory myofibroblastic tumor (IMT), synonymously referred to as inflammatory pseudotumor, is a distinctive mesenchymal lesion composed of spindle cells displaying morphological features of myofibroblasts admixed with considerable numbers of inflammatory cells. Recent genetic and molecular studies have shown that a subset of IMT is characterized by the expression of altered anaplastic lymphoma kinase (ALK) protein mostly resulting from rearrangements of the ALK gene such as TPM3-ALK, TPM4-ALK and CLTC-ALK fusion genes. We analyzed the ALK status in nine cases of IMT arising in various anatomical locations. Six cases showed immunohistochemical expression of the ALK protein, and two ALK-positive lesions examined by reverse transcription-polymerase chain reaction and a subsequent sequencing analysis harbored the TPM4-ALK fusion gene. Of note, the majority of ALK-positive tumor cells in four of the six lesions lacked the coexpression of myogenic markers including alpha-smooth muscle actin, a cytoskeletal protein indicating myofibroblastic differentiation, whereas a substantial number of tumor cells in the remaining two cases coexpressed ALK and alpha-smooth muscle actin and/or desmin. In an ultrastructural study of the lesion with predominant ALK-positive/actin-negative cells, spindle cells failed to demonstrate features of myofibroblasts such as intracytoplasmic bundles of thin filaments and dense bodies. The current findings suggest that ALK-positive cells in IMT are not always myofibroblastic but might be immature primitive mesenchymal cells.

Adult↗

Expression of estrogen receptors alpha and beta in soft tissue sarcomas: Immunohistochemical and molecular analysis.

Sex hormones can regulate differentiation and growth of mesenchymal cells and their neoplastic counterparts. This study aims to investigate the expression status of estrogen receptors (ER), ER alpha and ER beta, in a variety of soft tissue sarcomas. One hundred and twenty soft tissue sarcomas were immunohistochemically examined for the expression of ER alpha and ER beta proteins. Fifty-six tumors were further analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and 30 tumors were further analyzed by in situ hybridization (ISH) assay for their gene expression. The expression level of ER proteins was assessed in correlation with clinicopathological parameters such as patients' age, gender, and tumor Ki-67 labeling index. Forty-five (37.5%) tumors expressed ER alpha protein and 52 (43.3%) tumors expressed ER beta protein at variable levels. Both receptors were expressed with relatively high frequencies in several types of tumors (e.g. dermatofibrosarcoma protuberance, well-differentiated liposarcoma, myxoid liposarcoma, and myxoid malignant fibrous histiocytoma). A positive correlation was seen between the expression levels of ER alpha and ER beta in the current series. Thirty-one of the 42 informative cases examined by RT-PCR and 15 of the 16 informative tumors examined by ISH showed compatible results with those by immunohistochemistry. Neither gender nor age had a significant influence on the ER expression status. No significant correlation between the expression level of either type of ER and the tumor proliferation activity was identified. The results indicate that both ER isoforms are frequently expressed in certain subsets of soft tissue sarcomas, but their expression levels seem unrelated to the tumor proliferation activity.

Adult↗

Primary poorly differentiated monophasic synovial sarcoma of the lung. A case report with immunohistochemical and genetic studies.

We describe a case of a poorly differentiated monophasic synovial sarcoma arising in the lung of a 50-year-old man. The tumor, which was located in the right upper lobe, was lobulated, relatively well-circumscribed, and whitish to yellowish in color. Microscopically, it was composed exclusively of ovoid to polygonal or short spindle cells, with a high nuclear to cytoplasmic ratio and relatively scant cytoplasm, arranged in solid sheets or in a hemangiopericytomatous pattern with intervening wiry collagen fibers. At the periphery of the tumor, entrapped benign alveolar epithelium produced a pseudo-biphasic appearance. In some areas, an abundance of keloidal collagen imparted a close resemblance to a solitary fibrous tumor, making it difficult to establish the diagnosis on the initial needle biopsy, although the malignant nature of the tumor was suggested because of nuclear anaplasia. Immunohistochemically, the tumor was positive for cytokeratin AE1/AE3, CAM5.2, EMA, vimentin, bcl-2 protein, calretinin, and CD34. The reverse transcriptase-polymerase chain reaction (RT-PCR), using RNA extracted from fresh-frozen tissue, demonstrated SYT/SSX-1 fusion transcripts, confirming the diagnosis of synovial sarcoma. Microscopic examination demonstrated metastatic deposits in hilar lymph nodes. This case indicates that a primary pulmonary synovial sarcoma, particularly in its poorly differentiated form, is a diagnostically challenging and highly aggressive neoplasm typically found at an advanced stage.

Biomarkers, Tumor↗

Array-based analysis on tobacco plastid transcripts: preparation of a genomic microarray containing all genes and all intergenic regions.

The plastid genome of higher plants includes about 120 genes. We adopted genomic array technologies to the tobacco plastid genome. A microarray was constructed, consisting of 220 DNA fragments that cover the whole genome sequence. Each DNA fragment corresponds to a single known gene or an intergenic region. We evaluated reliability of this microarray by comparing the plastid RNA level in light- or dark-grown tobacco seedlings. The transcripts encoding photosynthetic subunits increased significantly in light-grown tissues as expected. Furthermore, we found unexpected signals in several intergenic regions, suggesting the existence of novel transcripts in tobacco plastids.

DNA, Plant↗

Microtubule-associated protein-2 and class III beta-tubulin are expressed in extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma of uncertain histogenetic origin. Because recent reports have indicated neural-neuroendocrine differentiation in some extraskeletal myxoid chondrosarcomas, we investigated 25 tumors for expressions of microtubule-associated protein-2 and Class III beta-tubulin, which are major components of microtubules and specifically localized in neurons and their derivatives. Immunohistochemical expression of microtubule-associated protein-2 and Class III beta-tubulin was studied in extraskeletal myxoid chondrosarcomas using formalin-fixed, paraffin-embedded tissues. Cytoplasmic expressions of microtubule-associated protein-2 and Class III beta-tubulin were detected in 21 (84%) and 13 (52%) of the 25 extraskeletal myxoid chondrosarcomas, respectively, although the number of positively stained tumor cells varied. Expression of the Class III beta-tubulin gene was also assessed in two immunohistochemically positive cases by in situ hybridization using an oligonucleotide probe specific for its transcript, and both cases showed expression of Class III beta-tubulin transcript. Another case was examined with immunoelectron microscopy, and immunogold particles for Class III beta-tubulin were localized to microtubular aggregates. Our data indicate that microtubules in extraskeletal myxoid chondrosarcoma are similar to those found in neurons, further supporting the concept that neural-neuroendocrine differentiation occurs in a significant number of extraskeletal myxoid chondrosarcoma.

Chondrosarcoma↗

Adaptive scan sequence for real-time ultrasound 3-D imaging.

An adaptive scan sequence is proposed for real-time ultrasound three-dimensional (3-D) imaging. Generally, the refresh rate of 3-D imaging is limited by the view window, resolution and sound speed in the human body. If the object is transformed or moved during the data set acquisition, the 3-D image will be distorted. To realize a high refresh rate for 3-D imaging, a reduction of the number of transmissions is required. Using a small number of transmissions results in a small view window or low resolution. In this paper, we propose a method to adaptively modify the spatial and temporal beam density according to the local motion of the object. We present 3-D images of a phantom with high frame rate, high resolution and wide view-angle window, significantly reducing the size of the full real scan raw data set.

Image Processing, Computer-Assisted↗

[The comparison in double immunodiffusion and western blotting methods of anti-SS-A/B antibodies in patients with Sjögren's syndrome].

OBJECTIVE: To investigate the autoimmune responses against SS-A/B antigens by double immunodiffusion (DID) and western blotting (WB) in primary and secondary Sjögren's syndrome (SS). PATIENTS: Forty-nine patients with primary SS (PSS), 28 patients with secondary SS (SSS) and control group that couldn't be diagnosed as SS were included in this study. RESULTS: In DID analysis, Anti-SS-A antibody was detected in 69% of PSS and 86% of SSS, and anti-SS-B antibody was found in 22% of PSS and 39% of SSS. No significant difference could be demonstrated between PSS and SSS concerning anti-SS-A/B antibodies. Conversely, WB studies disclosed evidences that 18% of PSS and no SSS reacted only with the 52 kD protein, and there was significantly increased in PSS. Sera reacting with the 60 kD antigen were found in 37% of PSS, 71% of SSS, and 75% of SSS with SLE, 63% of SSS with RA. The ratio of SSS, and SSS with SLE were particularly significantly higher than PSS. CONCLUSION: Our results revealed data that there are the difference of reactivity against SS-A/B antigens in WB between PSS and SSS.

Antibodies, Antinuclear↗

Differential diagnosis of benign peripheral lipoma from well-differentiated liposarcoma on MR imaging: is comparison of margins and internal characteristics useful?

OBJECTIVE: Our objective was to evaluate the reliability of MR imaging in distinguishing between benign lipoma and well-differentiated liposarcoma. MATERIALS AND METHODS: The MR images of 35 pathologically proven benign lipomas in 35 patients and 23 well-differentiated liposarcomas in 17 patients were retrospectively reviewed. T1-, T2-, and fat-suppressed T1-weighted images were obtained after administration of gadopentetate dimeglumine. Margins and internal characteristics revealed on the MR images and the degree of contrast enhancement of septa were evaluated. These MR imaging findings were compared for well-differentiated liposarcomas and benign lipomas. RESULTS: Completely irregular margins were recognized only in benign lipomas with a pathologic diagnosis of infiltrating lipoma. All tumors without a recognizable nonadipose component were benign lipomas (p < 0.05). As for the well-differentiated liposarcomas, thick septa and nodular or patchy nonadipose components were present more frequently in deep and retroperitoneal lesions than in subcutaneous lesions (p < 0.01). No cases showed only thin septa in the deep lesions of well-differentiated liposarcoma, and all cases showed thick septa or nodular or patchy nonadipose components. The septa in well-differentiated liposarcomas enhanced more strongly than did those in benign lipomas. The septa showed no enhancement relative to muscle in 11 of 19 benign lipomas, whereas the septa showed moderate or marked enhancement in all well-differentiated liposarcomas (p < 0.01). CONCLUSION: Careful assessment of margins and internal characteristics on MR imaging can be a useful aid in further distinguishing between biologically different benign lipoma and well-differentiated liposarcoma.

Adult↗

[Pulmonary rhabdomyosarcoma generated during treatment of testicular tumor].

A 23-year-old male was admitted to our hospital for the management of pulmonary metastases. He had undergone right high orchiectomy, chemotherapy with four courses of PEB regimen (cisplatin, etoposide, bleomycin) and retroperitoneal lymph node dissection the previous year. The pathological findings showed mixed germ cell tumor (seminoma, yolk sac tumor, embryonal carcinoma) in the testis and mature teratoma in the draining lymph node. Two courses of salvage chemotherapy using a VIP regimen (etoposide, ifosfamide, cisplatin) were performed after diagnosis of pulmonary metastases, but had no affect on tumor size. Video-assisted excision of pulmonary metastases was then performed, giving a pathological diagnosis of rhabdomyosarcoma in all three resected tumors. The operation was followed by three courses of CYVADIC (cyclophosphamide, vincristine, adriamycin, dacarbazin) chemotherapy and oral cyclophosphamide, as a small residual tumor was suspected. These chemotherapeutic interventions have appeared effective, with no apparent recurrence of lesions at present, one year after the excision of pulmonary metastases.

Adult↗

Clinical significance of antibodies to TS1-RNA in patients with mixed connective tissue disease.

OBJECTIVE: To investigate the clinical significance of anti-TS1-RNA antibodies in patients with mixed connective tissue disease (MCTD). METHODS: Anti-TS1-RNA antibodies were detected by immunoprecipitation using 32P-UTP labeled TS1-RNA as the antigen source. In total, 104 patients with MCTD, 30 with Sjögren's syndrome, 30 with systemic lupus erythematosus (SLE), 25 with systemic sclerosis, 23 with polymyositis or dermatomyositis, and 10 with rheumatoid arthritis were examined. Specificity of anti-TS1-RNA antibodies was analyzed by immunoprecipitation using HeLa cell extracts. RESULTS: The frequency of anti-TS1-RNA antibodies was 31.7% in patients with MCTD, significantly higher than in SLE (p < 0.05). In anti-TS1-RNA positive patients, the incidence of hypertension and proteinuria and the frequency of anti-Sm and anti-dsDNA antibodies associated with SLE were higher than those of anti-TS1-RNA negative patients. Clinical features of SS such as sicca complex, the serum level of IgA, and anti-SSA antibodies were also elevated. The frequency of anti-TS1-RNA antibodies was significantly higher in SLE patients with anti-U1-RNP antibodies (p < 0.01); however, anti-TS1-RNA positive sera did not precipitate the specific RNA including U1 RNA in immunoprecipitation using HeLa cell extracts. In longitudinal studies, the level of anti-TS1-RNA antibodies changed in parallel with disease activity. CONCLUSION: We found that the level of anti-TS1-RNA antibodies was possibly correlated with the disease activity of lupus-like clinical features in patients with MCTD.

Adult↗

Relationships between autoantibody responses to deletion mutants of Ki antigen and clinical manifestations of lupus.

OBJECTIVE: To determine the relationships between subtypes of anti-Ki antibodies and clinical manifestations of systemic lupus erythematosus. METHODS: The cDNA encoding full-length bovine Ki antigens or N- or C-terminal fragments were produced by polymerase chain reaction, and the fragments of Ki antigen were expressed as GST fusion proteins. Immunoreactivities of anti-Ki antibodies were tested by Western blotting. RESULTS: Of 60 sera reactive with full-length Ki antigen (KiF), 21 sera recognized only KiF. KiC5, a fragment containing the last 69 C-terminal amino acids, was recognized by 23 sera. Since no significant difference was observed in prevalence of reactivities between fragments from KiC2 to KiC5, a domain within the last 69 C-terminal amino acids was suggested to be the most common antigenic domain expressed among the GST fusion proteins. All 11 sera reacting with a fragment containing the initial 81 N-terminal amino acids also recognized all other fragments. A domain homologous to SV40 nuclear localization signal was required for N-terminal recognition by 8 sera. Reactivity to the last 69 C-terminal amino acids and the initial 81 N-terminal amino acids showed specificities to systemic lupus erythematosus without and with Sjögren's syndrome, respectively. Sicca was significantly more prevalent in patients whose sera reacted with both N- and C-terminal fragments, while prevalence of anti-SSA/Ro antibody was low. CONCLUSION: Ki antigen contains multiple epitopes recognized by autoimmune sera. Autoantibody profiles revealed distinctive immune responses, associated with certain clinical subtypes.

Autoantibodies↗

[Two cases of vesical nephrogenic adenoma].

Case 1: A 52-year-old man receiving regular treatment for quadriplegia due to Friedreich disease visited our hospital with the chief complaint of macroscopic hematuria. He had undergone cystostomy 12 years ago due to neurogenic bladder. The computed tomography and cystoscopic examination revealed a bladder tumor with a few bladder stones. Transurethral resection of bladder tumor (TUR-Bt) was performed after bladder stone removal in May 2000. The pathological diagnosis showed nephrogenic adenoma. Case 2: A 54-year-old man had been treated with bladder tumor by TUR-Bt in Nov. 1995. The pathological diagnosis showed transitional cell carcinoma, G3, pT2 and intravesical instillation therapy using THP was performed. The bladder tumor had recurred twice and the instillation therapy had been exchanged to BCG since Nov. 1997. A small bladder tumor was observed in Jan. 2001, and from the biopsy specimen it was diagnosed as nephrogenic adenoma. Forty-six cases of urothelial nephrogenic adenoma including our cases have been reported in Japan. Chronic stimulation such as bladder stone and infection is thought to induce nephrogenic adenoma. BCG instillation therapy is believed to be an initiation factors for nephrogenic adenoma.

Adenoma↗

[Retroperitoneal germ cell tumor with testicular calcification indicating tiny testicular origin: consideration of the origin of retroperitoneal germ cell tumors: report of two cases].

Two cases of germ cell neoplasm retrospectively considered to have been of testicular origin are reported. Case 1. A 19-year-old male with brain, liver and retroperitoneal tumors was diagnosed with yolk sac tumor by retroperitoneal tumor biopsy. After multidisciplinary treatment, a region of calcification was detected in the left testis on scrotal sonography and left high inguinal orchiectomy was performed. Case 2. A 57-year-old male with neck, lung and retroperitoneal tumors was diagnosed with yolk sac tumor by supraclavicular biopsy. From initial examination, scrotal sonography revealed a small calcified lesion in the right testis. After chemotherapy, high inguinal orchiectomy and retroperitoneal lymphadenectomy were simultaneously performed. Pathologic evaluation of these testicular specimens revealed calcification and a fibrous scar in correspondence with the clinical diagnosis. These changes were considered as scars of the primary testicular tumor due to burned-out tumor or the result of reaction to chemotherapy. Since a primary tumor of testicular origin may exist in the extragonadal germ cell tumor, it is important to examine the intrascrotal contents in detail in the case of so-called extragonadal germ cell tumors with palpably normal testes. In such cases, there are two possible conditions, an occult testicular tumor and a burned-out testicular tumor. We briefly reviewed 42 such cases in the Japanese literature. It appears that there are very few true extragonadal germ cell tumors, and that the possibility of primary testicular origin metastasizing from viable occult testicular tumor or burned-out testicular tumor with spontaneous regression is high in retroperitoneal germ cell tumors.

Adult↗