Erythropoietin-producing cerebellar tumour.
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Adult↗
Biomedical subjects
Yuji Ohtsuki
Publications and source records attributed to Yuji Ohtsuki.
Distribution of tumor-infiltrating dendritic cells in human non-small cell lung carcinoma in relation to apoptosis.
Host defense mechanisms play important roles in suppressing the development and growth of tumors. It is known that S-100 protein-positive immature dendritic cells (S100DC), as antigen presenting cells (APC), and macrophages have roles in the immune responses to tumor growth. Mediators such as nitric oxide are also important in the surveillance against cancer. We examined the distribution of S100DC and CD68-positive macrophages (CD68MØ) immunohistochemically to compare the condition of apoptotic tumor cells in 69 patients with human non-small cell lung carcinoma. The expression of inducible nitric oxide synthases (iNOS) in tumors was also studied. Unlike macrophages, S100DC were distributed predominantly in cancer nests. In the areas with infiltration of 'many' S100DC (i.e. more than 10 DC/HPF), we found two distinct patterns of tumor infiltration: scattered and aggregated infiltration of DC in tumor nests. In areas of scattered S100DC distribution, only a few apoptotic tumor cells could be detected. However, in the areas of DC aggregations, apoptotic tumor cells were significantly more abundant (P = 0.0491). In contrast to S100DC, the distribution and density of CD68MØ were associated with iNOS expression of tumor cells (P < 0.0001), but not with distribution of apoptotic tumor cells. These findings reveal differences in the in vivo condition between S100DC and CD68MØ in tumors, and suggest there is a relationship between tumor-infiltrating S100DC aggregation and apoptosis in in vivo non-small cell lung cancers.
Adult↗
Lipoma-like tumor mass probably arising in the retroperitoneal heterotopic pancreas: a previously undescribed lesion.
Heterotopic pancreatic tissue is found in several locations of the body. However, to the best of our knowledge, there have been no reports on heterotopic pancreas in the retroperitoneum. A case of retroperitoneal lipoma-like large tumor mass probably arising in the heterotopic pancreas is reported. A 45-year-old Japanese woman was admitted to hospital because of back pain. Imaging modalities showed an abnormal mass in the retroperitoneum separate from the surrounding organs, including the pancreas and kidney. Histologically, the mass consisted of mature adipose tissue and scattered ductal and acinar elements. Although there was no islet tissue in this fatty mass, the epithelial elements suggested heterotopic pancreatic tissue in origin. The present case is very unusual; however, heterotopic pancreas should be considered in the differential diagnosis of retroperitoneal tumors.
Biomarkers, Tumor↗
Molecular polymerase chain reaction diagnosis of pulmonary mucormycosis caused by Cunninghamella bertholletiae.
OBJECTIVE: Mucormycosis is an uncommon but frequently fatal infection caused by strains of mucorales in immunocompromised hosts. In this study, we report a case of pulmonary mucormycosis associated with acute lymphocytic leukaemia caused by Cunninghamella bertholletiae, a rare pathogen. METHODOLOGY: Retrospective analysis of the stored serum, sputum, and necropsy lung tissue samples from this patient, enabled subspecies identification by means of panfungal polymerase chain reaction (PCR), direct DNA sequencing of the PCR products, and homology search with nucleotide basic local alignment search tool. RESULTS: The development of a reliable diagnostic blood test for angio-invasive fungal infections such as mucormycosis is desirable, because the sensitivity of culture for these fungi is extremely low. CONCLUSION: Panfungal PCR on serial serum samples might be useful for the diagnosis of pulmonary mucormycosis.
Cunninghamella↗
Infrequent alteration in the p53R2 gene in human transitional cell carcinoma of the urinary tract.
OBJECTIVE: Functional defects in DNA repair have been shown to be associated with genomic instability followed by cancer. Recently, p53R2 [p53-inducible ribonucleotide reductase (RR) small subunit 2 homologous] was identified as a novel RR gene which is directly regulated by p53 protein in the G1 and G2 phases of the cell cycle supplying nucleotides to repair damaged DNA. METHODS: We performed genetic analyses of p53R2 to determine whether p53R2 alterations play significant roles in urothelial tumorigenesis. Genomic DNA from 108 primary transitional cell carcinomas (TCCs; 81 of the urinary bladder and 27 of the renal pelvis or ureter) was analyzed for mutation in the p53R2 gene by direct sequencing. We focused on three domains of the p53R2 gene: one RR small subunit signature involving codons 120-146 (region 1) and two putative nuclear localization signal sequences, involving codons 149-155 (region 2) and codons 163-169 (region 3). In addition, a p53-binding site of 20 nucleotides in intron 1 of p53R2 was also analyzed. RESULTS: One renal pelvic TCC (0.9%: 1/108) had a single-base substitution in p53R2 with a G to T transversion resulting in the amino acid substitution Glu136 --> Asp. This base substitution was localized within the domain of exon 4 encoding the RR small subunit signature, and causes an amino acid substitution in one of the most highly conserved regions of p53R2, in which human R2 and yeast RNR2 and RNR4 proteins are highly homologous. CONCLUSION: This finding provides the in vivo evidence for the infrequent involvement of alterations in p53R2 inhuman urothelial TCCs.
Aged↗
Prognostic significance of serine 392 phosphorylation in overexpressed p53 protein in human esophageal squamous cell carcinoma.
OBJECTIVE: Posttranscriptional modification involving phosphorylation of wild-type p53 has been considered to play a role in the stabilization of p53. Little is known, however, about the role of phosphorylation of mutant p53 overexpressed in tumors. The aim of this study is to determine the phosphorylation state of p53 in tumors and its contribution to tumor development. METHODS: Using immunohistochemical techniques, we examined the phosphorylation of Ser392 and 15 sites in p53 overexpressed in 137 esophageal squamous cell carcinomas (ESCCs). The relationships between the phosphorylation and the expression of cell cycle regulators, Ki-67 labeling index (LI), apoptotic index, clinicopathological factors, and patient prognosis were tested statistically. RESULTS: Of the 137 samples examined, staining for Ser392 phosphospecific p53 antibody was detected in 53 (38.7%) cases, corresponding to 58.9% of 90 p53-positive cases, whereas only 3 (2.2%) were positive for Ser15 phosphospecific p53 antibody. A significant correlation was identified between Ser392 phosphorylation and high levels of Ki-67 LI (p = 0.0271), lymphatic invasion (p = 0.0246), and poorer prognosis for patients with stage II and III advanced tumors (p = 0.0136). Using multivariate analysis, Ser392 phosphorylation was recognized as an independent prognostic factor (p = 0.0136). CONCLUSIONS: These findings suggest that p53 protein overexpressed in ESCCs is frequently phosphorylated at Ser392, and that the Ser392 phosphorylation might contribute to tumor progression of ESCCs.
Adult↗
Three cases of non-specific interstitial pneumonia associated with primary lung cancer.
NSIP associated with primary lung cancer has been rarely reported. In the present report, three cases of histologically proven non-specific interstitial pneumonia (NSIP) associated with primary lung cancer are described. Importantly, in our 3 cases, interstitial pneumonia which is histologically proven to be NSIP was observed diffusely in both lungs. NSIP in these 3 cases responded to steroid therapy. However, 2 patients died from primary lung cancer and 1 patient died from progression of the interstitial pneumonia. Although the association between lung cancer and NSIP has been rarely documented, this combination was considered to be one of the paraneoplastic phenomena. The possible association between primary lung cancer and NSIP is discussed.
Adenocarcinoma↗
Circulating macroglobulinemia cells.
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Humans↗
[Sjögren's syndrome with solitary nodular pulmonary amyloidosis].
We describe a case of limited pulmonary amyloidosis with Sjögren syndrome. A 58-yr-old woman was referred to our hospital because of an abnormal chest radiograph (solitary small nodule) that was examined to investigate the cause of a persistent cough. A chest CT revealed a solitary small nodule in the left lower lung field. The specimens obtained by thoracoscopic surgery showed AL (kappa) amyloid deposits with lymphoplasmacytic infiltrate. Immunofixation of the serum and concentrated urine failed to demonstrate monoclonal immunoglobulins, and no amyloid deposits in the stomach were detected. She was subsequently diagnosed as having primary Sjögren's syndrome. Nodular pulmonary amyloidosis with Sjögren syndrome is very rare condition, and most cases present multiple nodules. As far as is known, this is the first report of a solitary nodule in pulmonary amyloidosis with Sjögren syndrome.
Amyloidosis↗
Fibroblast growth factor receptor 3 protein expression in urothelial carcinoma of the urinary bladder, exhibiting no association with low-grade and/or non-invasive lesions.
Activating mutations of fibroblast growth factor receptor 3 (FGFR3), found in autosomal dominant human skeletal dysplasia, were reported to be involved in tumorigenesis and correlate with low-grade and superficial lesions of urothelial carcinoma. FGFR3 protein expression was immunohistochemically investigated in 126 cases of urothelial carcinoma of the urinary bladder to evaluate the role of this receptor in tumor behavior. p53 expression and the proliferating activity of tumor cells, assessed by Ki-67 expression, were also analyzed in parallel. Cytoplasmic and/or membrane immunostaining for FGFR3 was observed in 62 (49.2%) cases, including 20 (15.9%) cases of intense staining and 42 (33.3%) of moderate staining. p53 expression and Ki-67 labeling index (LI) were significantly correlated with high tumor grade (p=0.0093 and <0.0001, respectively) and invasion (p=0.0041 and <0.0001, respectively). Although there were two groups of interesting cases: low-grade and non-invasive tumors negative for p53 but positive for FGFR3, and high-grade and invasive tumors positive for p53 but negative for FGFR3, no statistically significant relationship was found between FGFR3 expression and tumor grade, invasion, p53 expression or Ki-67 LI. These results suggest that FGFR3 protein expression in bladder cancer is unlikely to affect tumor behavior as a unique single factor.
Biomarkers, Tumor↗
Phosphorylation state of tumor-suppressor gene p53 product overexpressed in skin tumors.
Post-transcriptional modification of p53 by phosphorylation has been proposed as an important mechanism of p53 stabilization and functional regulation. However, little is known about the phosphorylation state of mutant p53 protein overexpressed in human tumors. We evaluated immunohistochemically the p53 phosphorylation state of Ser392 and Ser15 sites in 44 actinic keratoses (AKs), 62 squamous cell carcinomas (SCCs), 23 Bowen's disease (BDs) and 43 basal cell carcinomas (BCCs). The mean labeling index (LI) of phospho-Ser392-p53 was significantly higher than that of phospho-Ser15-p53 in all cases. Phospho-Ser392-p53 protein was frequently overexpressed in not only SCCs but also AKs and BDs, revealing no significant difference in the immunoreactivity among them. In BCCs, phospho-Ser392-p53 immunoreactivity was significantly lower than that in BDs, and phospho-Ser15-p53 immunoreactivity was significantly lower than that in SCCs. Ser15 phosphorylation was significantly correlated with a high level of Ki-67 LI in BCCs. These results suggest that p53 overexpressed in skin tumors is more frequently phosphorylated at Ser392 residue than Ser15, and that the Ser392 phosphorylation is more likely to occur early in the pathogenesis of SCC. Moreover, the decreased level of the phosphorylation might be characteristic of BCC, but the Ser15 phosphorylation seems to have an influence on BCC development.
Bowen's Disease↗
Overexpression of carbonic anhydrase-related protein VIII in human colorectal cancer.
Carbonic anhydrase-related protein (CA-RP) VIII, which is a member of the CA gene family, has been shown to have no catalytic CA activity and its biological function is still unknown. Recently, overexpression of CAs IX and XII has been reported in certain types of malignancy. To investigate a potential role for CA-RP VIII in human colorectal epithelial carcinogenesis, colorectal tissue specimens from surgically resected adenocarcinomas (n = 60) and endoscopically polypectomized adenomas (n = 13) were analysed by immunohistochemistry using monoclonal antibodies to CA-RP VIII and Ki-67 antigen. Less than 5% of epithelial cells in normal colonic mucosae (n = 73) were CA-RP VIII-positive and these were localized to the deep part of the cryptal epithelium. Increased expression of CA-RP VIII was observed in 78% of colorectal carcinomas. An intense signal was frequently observed at the tumour invasion front and its distribution was completely different from that of Ki-67 antigen. Colorectal adenomas also showed significant immunopositivity for CA-RP VIII, but its expression level was much lower than in adenocarcinomas. These findings suggest that CA-RP VIII plays a role in the process of invasion in colorectal cancer.
Adenocarcinoma↗
Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma.
In the present study, we cloned and characterized a novel actin-binding molecule, designated skeletrophin, from aggregated neuroblastoma cells. The putative amino acid sequence of human skeletrophin cDNA contained a cysteine-rich zinc-finger motif which was also found in dystrophin and five ankyrin repeats. Northern blot analysis revealed that the 3.2-kb skeletrophin mRNA was expressed in normal skeletal muscle, and to a lesser extent in heart, brain, and kidney. Specific antibody was prepared to human skeletrophin peptide, and a single protein band with an approximate molecular weight of 70 kd was detected in tissue extracts by immunoblotting using the antibody. To better understand the biological properties of skeletrophin, we used a yeast two-hybrid system to screen for molecules interacting with skeletrophin and found that skeletrophin bound to actin monomer. Co-immunoprecipitation experiments also demonstrated that skeletrophin was able to bind to actin monomer. Fluorescence in situ hybridization mapped the skeletrophin gene on human chromosome 1p36.2-36.3, in which putative tumor suppressor genes for malignant melanoma have been postulated to exist. We therefore immunohistochemically stained benign nevi and malignant melanoma tissues. Notably, 23 of 25 benign nevi expressed skeletrophin in cytoplasm, but 18 of 38 cases of primary skin melanoma appeared to lack skeletrophin expression. Treatment with a demethylating agent, 5'-aza-2-deoxycytidine, restored skeletrophin expression in cultured Mewo melanoma cells. The present findings suggest that skeletrophin may be a novel actin-binding cytoskeleton-related molecule, expression of which is silenced in a considerable number of melanoma specimens.
Actins↗
Megakaryoblastic leukemia cell line MOLM-16 derived from minimally differentiated acute leukemia with myeloid/NK precursor phenotype.
The megakaryoblastic leukemia cell line MOLM-16 was established at relapse from the peripheral blood of a 77-year-old Japanese woman with minimally differentiated acute myeloid leukemia (AML-M0). Immunophenotyping of the fresh leukemic cells revealed a myeloid/NK precursor phenotype being positive for CD7, CD13, CD33, CD34, and CD56. In addition, megakaryocyte-associated antigens CD41 and CD61 were found to be positive. The established cell line designated MOLM-16 was proliferatively responsive to the treatment with various cytokines including EPO, GM-CSF, IL-3, PIXY-321, and TPO. MOLM-16 revealed characteristics of the megakaryocytic lineage in terms of immunophenotyping being positive for CD9, CD31, CD36, CD41, CD61, CD62P, CD63, CD110, CD151, thrombospondin, von Willebrand factor (vWf), and fibrinogen. Electron microscopic analysis showed positivity for ultrastructural platelet peroxidase in the nuclear envelope. The karyotype analysis of MOLM-16 revealed various numerical and structural abnormalities including t(6;8)(q21;q24.3), t(9;18)(q13;q21) and marker chromosomes. The extensive immunological, cytogenetic and functional characterization of MOLM-16 suggests that this cell line may represent a scientifically significant in vitro model which could facilitate the evaluation of megakaryocytic differentiation.
Aged↗
Pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex.
It has been argued whether bronchiectasis is truly caused by MAC infection or just a predisposed condition in which MAC colonizes. Our present study was designed to evaluate the pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex (MAC) lung infection and to demonstrate MAC in the lesion of bronchiectases. A retrospective study was performed in nine cases with positive cultures for MAC in whom lung resections were performed. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. In addition, MAC were cultured from all nine lung specimens. Pathological findings of bronchiectases were evaluated in these nine patients. Destruction of bronchial cartilage and smooth muscles layer, obstruction of airway by granulomas, and ulceration of bronchial mucosa were frequently observed. Our present study demonstrates that destruction of fundamental bronchial structure due to extensive granuloma formation throughout the airways was likely the main cause of bronchiectases in MAC infection.
Adult↗
Aberrant cytokeratin expression and high susceptibility to apoptosis in autoimmune hepatitis.
Immunopathological differences between autoimmune hepatitis (AIH) and chronic hepatitis C (CH-C) have not been well investigated. Therefore, we immunohistochemically examined the expression of various cytokeratins (CKs) not only in liver tissues of AIH but also in those of CH-C at the active stage. Furthermore, to evaluate the immune surveillance system and the susceptibility to apoptosis, immunohistochemical staining of human leukocyte antigen (HLA)-DRalpha, cathepsin D, B cell leukemia-2 (bcl-2), bcl-2-associated X protein (bax) and caspase 3 was also performed. Heterogeneous expression of CK 8 and CK 18 was observed in hepatocytes of AIH, while homogeneous expression was observed in hepatocytes of CH-C. Aberrant expression of CK 7 and CK 19 was observed in hepatocytes of AIH, while it was not in hepatocytes of CH-C. Expression of HLA-DRalpha was observed in hepatocytes of AIH but not in those of CH-C. Furthermore, expression of cathepsin D, bax and caspase 3 was much stronger in hepatocytes of AIH than in those of CH-C. These results indicate that cytoskeletal alterations of hepatocytes in AIH may increase the susceptibility to apoptosis and induce hepatocyte destruction.
Journal Article↗
Inflammatory pseudotumor of the liver: report of a case diagnosed by needle biopsy.
We report a case of a 76-year-old man with inflammatory pseudotumor, xanthogranuloma type of the liver. The patient showed clinical manifestations of a liver abscess. Abdominal sonography and computed tomography revealed an additional tumor-like lesion adjoining the liver abscess. Following treatment with antibiotics for 20 days, the liver abscess disappeared, but there was no change in the size and shape of the tumor-like lesion. Histological analysis of a specimen obtained from the tumor-like lesion by needle biopsy revealed an infiltration of abundant foamy histiocytes with massive fibrosis. Without any treatment, the tumor-like lesion gradually diminished in 5 months. In previous literatures, most cases with xanthogranuloma of the liver underwent hepatectomy or diagnostic laparotomy. The findings presented herein suggest that in cases of an atypical solid mass in the liver accompanied by a clinical inflammatory process, inflammatory pseudotumor should be considered, and, if the disease is suspected, liver needle biopsy is recommended to prevent an unnecessary surgical operation.
Journal Article↗
High molecular weight vimentin complex is formed after proteolytic digestion of vimentin by caspase-3: detection by sera of patients with interstitial pneumonia.
In a previous study, we demonstrated anti-vimentin antibodies in sera of patients with interstitial pneumonia. We hypothesized that antibodies in sera might detect vimentin fragments formed during the process of apoptosis. To prove this, recombinant human vimentin was digested by recombinant human caspase-3 or caspase-8. Then, Western blotting using several commercially available antibodies against human vimentin or patients' sera which had anti-vimentin autoantibodies, was performed. As a result, after recombinant human vimentin was digested by caspase-3 or caspase-8, several vimentin fragments were formed and detected by 2 kinds of monoclonal anti-vimentin antibodies (clone 3B4 and clone V9) as well as by polyclonal sheep anti-human vimentin antibody. It was demonstrated that high molecular weight vimentin was formed after the digestion of vimentin by caspase-3, which was only detected by patients' sera. The high molecular weight vimentin was not formed after digestion of vimentin by caspase-8. Our present results show that high molecular weight vimentin was formed after the digestion of vimentin by caspase-3. In addition, it is suggested that this high molecular weight vimentin acted as an autoantigen to form anti-vimentin autoantibody in vivo.
Animals↗