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Biomedical subjects

Shogo Katsuda

Publications and source records attributed to Shogo Katsuda.

At least 19 recordsLinked to original sources

Intrahepatic sarcomatoid cholangiocarcinoma of round cell variant: a case report and immunohistochemical studies.

Sarcomatoid transformation was observed in 4.5% of autopsied cases of intrahepatic cholangiocarcinoma. Here, we report a case of intrahepatic sarcomatoid cholangiocarcinoma with round cell feature, extremely rare variant. An 87-year-old man was incidentally found to have a tumor in the left lobe of the liver by abdominal computed tomography scans. The patient was clinically diagnosed to have intrahepatic cholangiocarcinoma and received palliative care without specific treatment. He died of hepatic insufficiency 3 months after the diagnosis. The autopsied liver specimens showed a reddish gray tumor of 4.0x2.8 cm in size. Histologically, the tumor was centrally hemorrhagic and necrotic and was composed of tubular adenocarcinoma and a round cell component, which has an eccentrically located nucleus and eosinophilic cytoplasm without mucin production. Immunohistochemically, the adenocarcinoma cells expressed cytokeratin 19 and beta-catenin in their cytoplasm, with E-cadherin and CD44s at the plasma membrane. In the round cells, cytokeratin 19 and vimentin was detected in their cytoplasm and CD44s at the plasma membrane. E-cadherin immunoreactivity was weakly present in their cytoplasm and beta-catenin was negative. Loss or reduction of the E-cadherin and beta-catenin expressions and overexpression of CD44s in the round cells are suggested to be contributed to the high propensity for lymphatic permeation and poor prognosis.

Aged↗

Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type: immunohistochemical studies and mutation analysis of the p53 gene.

Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type fulfilling the 1999 WHO criteria is rare. Here, we report a case of this type of tumor determined entirely by histological examinations. A 57-year-old man was incidentally found to have a demarcated 3cm mass in his lower lobe of the right lung. The tumor was composed of tall columnar cells containing cytoplasmic mucins, cuboidal cells without mucins, and intermediate cell types with lepidic growth patterns. Tumor cells were distributed within a region of 2cm in diameter, and no stromal, vascular, or pleural invasion was observed. Immunohistochemically, both the mucinous and nonmucinous components were positive for cytokeratin 7, TTF-1, and E-cadherin, and negative for cytokeratin 20, consistent with the results for nonmucinous bronchioloalveolar carcinoma. No mutations were detected in exons 5-8 of the p53 gene. The present tumor was composed mainly of morphologically mucinous bronchioloalveolar carcinoma, but presented different immunohistochemical profiles of ordinary mucinous bronchioloalveolar carcinoma. This case suggests that the mucinous component in bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type has characters dissimilar to conventional mucinous bronchioloalveolar carcinoma, and is probably derived from the nonmucinous component.

Adenocarcinoma, Bronchiolo-Alveolar↗

Specific removal of beta1-adrenoceptor autoantibodies by immunoabsorption in rabbits with autoimmune cardiomyopathy improved cardiac structure and function.

Growing evidence suggests that the beta1-adrenoceptor-directed autoimmune mechanism may play an important role in the pathogenesis of idiopathic dilated cardiomyopathy. The aim of this study is to further study the effect of specific immunoabsorption of anti-beta1-adrenoceptor autoantibodies on cardiac structure and function in autoimmune cardiomyopathy in rabbits. Twenty-four male rabbits were divided into 2 groups: (1) one immunized with beta1-adrenoceptor peptide (beta1 group, n=16), and (2) the other receiving saline injection as a control (control group, n=8). Immunization was performed once a month for 8 months. A high concentration of anti-beta1-adrenoceptor autoantibodies was exhibited throughout the immunization period. Rabbits in the beta1 group showed increased left ventricular end-diastolic diameter (LVDd), decreased left ventricular ejection fraction (LVEF) and increased LV mass/body weight ratio after the 8th month. Immunoabsorption with beta1-adrenoceptor peptide column was able to remove up to 35% of anti-beta1-adrenoceptor autoantibodies in 2 h, resulting in decreased LVDd and increased LVEF 3 months after. Specific removal of anti-beta1-adrenoceptor autoantibodies improved cardiac structure and function in experimental autoimmune cardiomyopathy. These results suggest that anti-beta1-adrenoceptor autoantibodies are of pathogenic importance in the induction of cardiomyopathy, and that specific immunoabsorption as an emerging therapy may be considered when anti-beta1-adrenoceptor autoantibodies are pathophysiologically involved.

Amino Acid Sequence↗

Expression of ADAMTS-4 (aggrecanase-1) and possible involvement in regression of lumbar disc herniation.

STUDY DESIGN: Examination of ADAMTS-4 expression, and cellular lineages, distribution, and numbers of ADAMTS-4 (aggrecanase-1) expressing cells in herniated lumbar intervertebral discs. OBJECTIVE: To determine the expression of ADAMTS-4, a metalloproteinase capable of digesting aggrecan, and its role in herniated lumbar intervertebral disc degradation. SUMMARY OF BACKGROUND DATA: Matrix metalloproteinases degrade extracellular matrix of herniated discs, but the mechanism of aggrecan degradation, the major component of intervertebral discs, is poorly understood. METHODS: Surgically resected herniated lumbar intervertebral discs from 22 patients were subclassified into protrusion, subligamentous extrusion, transligamentous extrusion, and sequestration types. Reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry were used to evaluate ADAMTS-4 messenger ribonucleic acid and protein expression. RESULTS: Expression of ADAMTS-4 messenger ribonucleic acid and protein was shown in the samples of herniated lumbar intervertebral discs. Immunohistochemical staining showed that ADAMTS-4 was mainly localized in CD68-positive mononuclear cells in granulation and adjacent disc tissues. ADAMTS-4 positive cell counts were significantly higher in transligamentous extrusion and sequestration than protrusion and subligamentous extrusion types. Alcian blue staining showed a decrease of proteoglycan in transligamentous extrusion and sequestration cases. CONCLUSIONS: Macrophages infiltrating granulation and adjacent disc tissues express ADAMTS-4, suggesting its involvement in herniated disc regression.

ADAM Proteins↗

Transfer of immune components from rabbit autoimmune cardiomyopathy into severe combined immunodeficiency (SCID) mice induces cardiomyopathic changes.

BACKGROUND: Growing evidence suggests that autoimmune mechanism plays an important role in the pathogenesis of cardiomyopathy. The purpose of this study was to investigate whether passive transfer of IgG and/or lymphocytes from rabbits with autoimmune cardiomyopathy is able to reproduce cardiomyopathic changes in severe combined immunodeficiency (SCID) mice. METHODS AND RESULTS: SCID mice were injected intraperitoneally with IgG and/or peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1-adrenoceptor peptide and M2-muscarinic receptor peptide (beta1+M2 group) or rabbits with adjuvant (N group). Thirty five SCID mice were divided into seven groups; N-IgG, N-PBL, N-IgG & PBL, (beta1+M2)-IgG, (beta1+M2)-PBL, (beta1+M2)-IgG & PBL and control groups. Heart weight in three (beta1+M2) groups were significantly increased. All mice in three (beta1+M2) groups showed high titer of rabbit anti-beta1 adrenoceptor autoantibodies, and 4 mice in the (beta1+M2)-PBL group and 3 mice in the (beta1+M2)-IgG & PBL group showed a significant increase in titer of rabbit anti-M2-muscarinic receptor autoantibodies. Focal infiltration of inflammatory cells in the myocardium was observed in the (beta1+M2)-IgG & PBL group. In the (beta1+M2)-PBL group and (beta1+M2)-IgG & PBL group, cardiomyocyte diameters were significantly increased. Some myocytes of the (beta1+M2)-IgG & PBL group exhibited intracellular edema, clumps of Z-band and increased numbers of mitochondria by using electron microscopy. CONCLUSION: Transfer of IgG and PBL from rabbits immunized with combined beta1 and M2 peptides was able to reproduce the early stage of cardiomyopathic changes in SCID mice.

Amino Acid Sequence↗

Microvessel density: correlation with 18F-FDG uptake and prognostic impact in lung adenocarcinomas.

UNLABELLED: Although researched for many years, the prognostic value of tumor angiogenesis reflected by microvessel density (MVD) is still controversial, and there have been no previous reports regarding the correlation with 18F-FDG uptake in lung adenocarcinomas. Therefore, in the present study, we investigated the correlation between MVD determined with different endothelial cell antibodies and 18F-FDG uptake and compared the prognostic impact of those factors in lung adenocarcinomas. METHODS: Forty-four patients with 45 lung adenocarcinomas underwent 18F-FDG PET before surgery. Consecutive paraffin-embedded sections obtained from each resected tumor were immunostained for CD31 (a panendothelial cell marker), CD105 (a proliferation-related endothelial cell marker), and CD34/alpha-SMA (for double labeling of endothelial cells and mural cells). Four high-power fields in the area with the highest MVD were selected for analysis. Computer-assisted image analysis was used to assess MVD. RESULTS: MVD staining results for panendothelial cell markers can be classified into 3 microvessel patterns: diffuse, alveolar, and mixed. The highly ordered alveolar pattern is believed to represent preexisting alveolar vessels trapped in lung adenocarcinomas and may have no significant meaning for the aggressiveness of tumors. Preexisting alveolar cells also do not contribute to 18F-FDG uptake. CD105 staining of MVD (CD105-MVD) showed a significantly positive correlation with 18F-FDG uptake (P < 0.0001), whereas CD31 staining of MVD (CD31-MVD) showed a marginally negative correlation with it (P = 0.057). Although CD105-MVD correlated negatively with prognosis, patients with low CD105-MVD, compared with those with high or moderate CD105-MVD, had a much better prognosis in both disease-free and overall survival analyses (P = 0.017 and P = 0.013, respectively). Patients with low CD31-MVD had the worst prognosis (P = 0.032 for disease-free survival analysis and P = 0.179 for overall survival analysis). CONCLUSION: There is no positive correlation between 18F-FDG uptake and MVD determined with panendothelial cell markers (CD31 and CD34); in contrast, there is a marginally negative correlation between them. MVD determined with CD105, which is a proliferation-related endothelial cell marker, reflects active angiogenesis, correlates positively with 18F-FDG uptake, and is a better indicator of prognosis in lung adenocarcinomas.

Adenocarcinoma↗

Papillary thyroid carcinoma with anaplastic transformation showing a rhabdoid phenotype solely in the cervical lymph node metastasis.

We describe a rare case of anaplastically transformed papillary thyroid carcinoma with a rhabdoid phenotype appearing solely in a metastatic focus. A 77-year-old man presented with a rapidly enlarging, painful right lateral cervical mass. CT scan revealed a tumor in the right upper pole of the thyroid gland and a right lateral cervical mass. Examination of surgically resected specimens disclosed that the thyroid tumor was a well-differentiated papillary carcinoma (2.0 cm in diameter), and the right lateral cervical mass was an anaplastic carcinoma (2.4 cm in diameter) showing a rhabdoid phenotype with scant amounts of a papillary carcinoma component in the periphery, considered to be transformed through the metastasis of the papillary thyroid carcinoma in a cervical lymph node. The rhabdoid cells had eccentric nuclei with conspicuous nucleoli and spherical hyaline cytoplasmic inclusions, which are immunoreactive for vimentin and sarcomeric actin. Ultrastructurally, these had globular aggregation of thin and intermediate filaments. Nuclear immunoreactivity for INI1 indicated that the tumor had no INI1 abnormalities, suggesting a secondary rhabdoid tumor. Recurrence developed in the right cervical and mediastinal lymph nodes, and the patient died of disease 6 months after surgery. A rhabdoid phenotype is a pathological hallmark indicating the aggressive nature not only in the neck region, but also in other organs.

Aged↗

Hepatocellular carcinoma and nonalcoholic steatohepatitis developing during long-term administration of valproic acid.

We report a case of hepatocellular carcinoma (HCC) arising in nonalcoholic steatohepatitis (NASH). The patient, a 64-year-old man, was incidentally found to have multiple tumors in the liver when admitted for pneumonia. He had been obese, had been receiving a standard dose of valproic acid since clipping surgery for subarachnoid hemorrhage 17 years previously, and had not consumed any alcohol since the surgery. Laboratory data revealed moderate hyperlipidemia and no evidence of diabetes mellitus, hepatitis B or C infection. The patient died of hepatic insufficiency, and an autopsy was performed. A tumor, a maximum of 13 cm in diameter, grossly occupied the entire left lobe and one third of the right lobe of the liver. Histologically, moderately differentiated HCC was found with foci of poorly differentiated HCC. The non-tumorous area showed NASH with moderate bridging fibrosis, without interface hepatitis, hemochromatosis, or copper accumulation. In this patient, obesity, hyperlipidemia, and long-term treatment with valproic acid could have all been associated with induction of NASH. The present case suggests that HCC could develop in non-cirrhotic NASH liver, and that chronic inflammation in itself could be an important risk factor in the development of HCC.

Anticonvulsants↗

Adenoid cystic carcinoma of the maxillary sinus with gradual histologic transformation to high-grade adenocarcinoma: a comparative report with dedifferentiated carcinoma.

We report a unique case of adenoid cystic carcinoma (ACC) of the maxillary sinus, with gradual histologic transformation from lower-grade ACC (cribriform and tubular types) to high-grade adenocarcinoma (HGA) showing a sequential histologic spectrum via solid-type ACC. A 74-year-old man presented with swelling and mild pain of the right cheek. CT scan showed a mass measuring approximately 4 cm, with marked bone destruction in the right maxillary sinus. A surgically resected specimen revealed that the tumor was comprised of three different components: HGA and solid-type ACC in the central portion and lower-grade ACC in the periphery. The tumor was discriminated from a dedifferentiated carcinoma or hybrid tumor. Autopsy specimens also demonstrated both solid-type ACC and HGA components in the lung and spleen. Immunohistochemically, positive staining of p53 protein was detected on both solid-type ACC and HGA cells, but cyclin D1 and HER2/neu was only seen in HGA cells. Solid-type ACC cells were immunoreactive for CD117 (c-kit), but lower-grade ACC and HGA cells were negative. This case suggests that the overexpression of CD117, p53 protein, cyclin D1, and HER2/neu might be involved in the progression from lower-grade ACC to solid-type ACC and HGA.

Actins↗

Pleomorphic adenoma (benign mixed tumor) of the breast: a case report and review of the literature.

We report a case of pleomorphic adenoma (benign mixed tumor) of the breast, which is an extremely rare location for this tumor. Examination of a 55-year-old woman unexpectedly revealed a mass measuring 0.8 cm in diameter in the subareolar region of the right breast. Excisional biopsy was performed, and the tumor histologically showed pleomorphic adenoma composed of duct epithelial cells, myoepithelial cells, and a myxochondroid matrix. Immunohistochemically, duct epithelial cells were positive for the estrogen receptor, but negative for the progesterone receptor. The nuclei of the spindle and myoepithelial cells were immunoreactive for HMGI-C and HMGI(Y) proteins, indicating a histogenesis similar to pleomorphic adenoma of the salivary glands. Interphase fluorescence in situ hybridization performed on paraffin-embedded tissue sections with 12q15 probes and a 6p21 probe demonstrated no chromosomal rearrangement. Sixty-nine cases of this type of tumor arising in the breast have been described previously. Using imaging procedures, the tumor has occasionally been misdiagnosed as malignant clinically and even pathologically in frozen section diagnosis. Careful diagnosis based on paraffin sections is required to avoid unnecessary aggressive surgery, and pathologists should include pleomorphic adenoma in the differential diagnosis of a demarcated, juxtaareolar, small hard mass.

Adenoma, Pleomorphic↗

Berry splenic artery aneurysm rupture in association with segmental arterial mediolysis and portal hypertension.

A rare case of berry splenic artery aneurysm (SAA) rupture associated with segmental arterial mediolysis (SAM) and portal hypertension is reported. A 66-year-old woman, diagnosed as having liver cirrhosis and portal hypertension 6 years earlier, suddenly developed a lancinating pain in the upper abdomen and lost consciousness. She recovered consciousness while being transferred to hospital by ambulance. During the investigations, her level of consciousness suddenly deteriorated. Ultrasonography showed a massive intraperitoneal hemorrhage, and she died 5(1/2) h after admission. On gross examination at autopsy it was not possible to find the rupture point of the vessel because the pancreas was embedded in a massive hematoma. However, careful dissection of the pancreatic tail after fixation revealed a berry aneurysm measuring 0.8 cm in diameter in a branch adjacent to the bifurcation in the distal third of the main splenic artery. Microscopic examination detected a rupture of the aneurysm. The histology of the arterial wall proximal to the aneurysm showed typical SAM. In general, berry SAA caused by SAM is rare and unlikely to rupture. The SAA in the present case likely occurred and ruptured due to the combination of SAM and portal hypertension.

Aged↗

Large cell calcifying Sertoli cell tumor of the testis: comparative immunohistochemical study with Leydig cell tumor.

Large cell calcifying Sertoli cell tumor is a rare type of testicular tumor. Reported herein is a Japanese patient with this tumor not associated with Carney's complex. An 11-year-old boy was admitted to hospital because of left testicular enlargement, and radical orchiectomy was performed. Macroscopically, the tumor was well circumscribed and had a maximum diameter of approximately 2 cm. The cut surface showed a yellow-white solid mass. Histologically, the tumor was composed of large neoplastic cells with abundant eosinophilic cytoplasm with a tubular, trabecular, and solid arrangement and loose myxoid stroma with irregularly shaped calcification. Immunohistochemically, the tumor cells were positive for vimentin, S-100 protein, calretinin, inhibin-alpha, melan-A, and CD10, and type IV collagen and laminin were observed in the extracellular matrix around the tumor cells. The distributions of melan-A, CD10, and mitochondria were characteristically patchy; in contrast, they were diffusely distributed in the cytoplasm in a control case of Leydig cell tumor. The differences in immunostaining patterns for melan-A, CD10, and mitochondria as well as positivity for S-100 protein-beta might be useful diagnostic hallmarks of large cell calcifying Sertoli cell tumor for discrimination from Leydig cell tumor.

Antigens, Neoplasm↗

Apoptosis and its related genes in renal epithelial cells of the stone-forming rat.

Experimental hyperoxaluria and calcium oxalate (CaOx) crystals are associated with renal epithelial injury and cell death. A recent study has demonstrated an oxalate-induced increase in cellular apoptosis in vitro, and speculates that this phenomenon may contribute to stone formation. We investigated the incidence of apoptotic cells and the expression of apoptosis related genes in the kidneys of stone-forming rats. Male Wistar rats were administrated ethylene glycol in drinking water and force fed with 1alpha-OH-D3. Apoptosis was detected as a ladder of fragmented DNA in agarose gels of electrophoresed genomic DNA. Apoptotic cells were localized by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The expression of apoptosis-related genes was analyzed by both reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. While no labeling was detected in the controls or on the first day of administration by the TUNEL method, labeling began to be detected in the renal tubular epithelium of the outer medulla at day 3, and the number of labeled cells increased progressively during the observation period. A ladder of DNA fragments was demonstrated in the kidneys of rats after 2 weeks. Immunohistochemical studies revealed the expression of Fas ligand (Fas L), Bax and interleukin-1 beta converting enzyme (ICE) in the renal tubular epithelium of the descending limb of loop of Henle and the distal convoluted tubules. mRNA of the ICE, c-myc, p53 and Fas L genes was also upregulated in the kidneys of the stone-forming rats.

Animals↗

Phorbol myristate induces apoptosis of taxol-resistant sarcoma cells in vitro.

Taxol was found to induce polyploidization and apoptosis in cultured methylcholanthrene-induced sarcoma cells (Meth-A cells), but some of the cells in G1 phase were not affected. We refer to these cells as taxol-resistant cells. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) regulator, was used to test the taxol-resistant cells. Many of the taxol-resistant cells disappeared after treatment with taxol in the presence of PMA. To explore the mechanism of this effect, we employed flow cytometry to determine levels of p53, p21, bcl-2 and caspase proteins in the taxol-resistant cells, and found that the expression of the bcl-2 protein was markedly decreased and the expression of the caspase protein markedly increased after treatment with taxol in the presence of PMA. These findings suggest that PMA enhances the sensitivity of taxol-resistant cells to taxol, and taxol treatment in the presence of PMA induces the apoptosis of taxol-resistant cells by inhibiting the expression of the bcl-2 protein and increasing the expression of the caspase protein.

Animals↗

Oxidative stress and vascular permeability in steroid-induced osteonecrosis model.

We focused on the role of oxidative stress in the pathogenesis of steroid-induced osteonecrosis (ON) and the possibility of preventing this condition by antioxidant administration. Methylprednisolone 4 mg/kg was injected only once into Japanese white rabbits. The involvement of oxidative stress and the presence/absence of bone circulatory impairment were investigated in groups of 10 rabbits killed at 3, 5, and 14 days each and in 10 rabbits administered the antioxidant glutathione. Reduced blood glutathione and lipid peroxide levels were determined biochemically, and the presence/absence of advanced glycation end-product expression was determined immunohistochemically. Vascular permeability in bone was confirmed by finding albumin leakage into the stroma. These blood biochemical and immunohistochemical studies clarified that the oxidative stress in this model developed 3-5 days after steroid administration. Elevated vascular permeability was observed in the 5- and 14-day groups. Hence, circulatory disturbance in bone was noted 5 days after steroid administration, coinciding with the onset of oxidative stress. The rate of ON development, which was 70% in the steroid-alone 14-day group, was significantly reduced to 0% in the steroid + antioxidant group. These results suggest the involvement of oxidative stress and vascular permeability in this steroid-induced ON model and the possibility of its prevention by suppression of oxidative stress.

Animals↗

High mobility group I-C protein in astrocytoma and glioblastoma.

High mobility group I-C (HMGI-C) protein is a non-histone DNA-binding factor that organizes active chromatin. This protein is expressed during the limited phase of embryonic development and may regulate the expression of genes critical for embryonic cell growth and differentiation. As embryonic mechanisms are also known to play a role in the development of some neoplasms, we investigated human brain tumors for the expression of HMGI-C to determine its role in the differentiation of glial cell tumors. Immunohistochemical analysis revealed HMGI-C in all of the low-grade astrocytomas, in 2 of 3 anaplastic astrocytomas (grade 3), but in only one of 8 glioblastomas. The results were confirmed at the mRNA level by nested reverse-transcription polymerase chain reaction analyses. Loss of HMGI-C was also demonstrated in a case of glioblastoma transformed from the low-grade astrocytoma strongly expressing HMGI-C protein. These results suggest that HMGI-C may be involved in the differentiation of glial tumor cells, and that loss of HMGI-C expression may contribute to the transformation of low-grade astrocytoma into glioblastoma.

Astrocytoma↗

Amiodarone minimizes experimental autoimmune myocarditis in rats.

Amiodarone, a promising drug for the treatment of tachyarrythmias, was recently found to have immunomodulatory effects in vitro. We hypothesized that amiodarone would affect the immune system in vivo and examined the effect of amiodarone on myocarditis in rats. We induced experimental autoimmune myocarditis in rats by cardiac myosin immunization and treated the animals with an intraperitoneal injection of amiodarone at 25 mg/kg/every other day, 10 times after the induction of experimental autoimmune myocarditis. In the treated group, both microscopic and macroscopic examinations showed reduced heart weights, a mild and localized infiltration of inflammatory cells and fibrosis in the myocardium, and a mild congestion in the liver and lungs as compared with the control group. The phenotypic distribution of lymphocytes in peripheral blood showed a significant decrease in the CD4/CD8a ratio in the treated group, but not in the control group. The proportion of mast cells involved in inflammatory cell infiltration was lower in the treated group than the control group. In vitro, amiodarone inhibited the proliferation of mast cells by arresting them in the G2 phase of the cell cycle. These results indicated that amiodarone minimized the progression of experimental autoimmune myocarditis, suggesting a potential therapeutic role for amiodarone treatment in patients suffering from myocarditis, especially myocarditis complicated by cardiac arrhythmias. One possible mechanism by which amiodarone minimizes the progression of experimental autoimmune myocarditis may be to affect the immune system via the immunomodulatory effects on T cell and mast cell functions.

Amiodarone↗