PubMed Health⌕ Search

Biomedical subjects

F Shimamoto

Publications and source records attributed to F Shimamoto.

At least 19 recordsLinked to original sources

Quantitative measurement of hepatic portal perfusion by multidetector row CT with compensation for respiratory misregistration.

Our purpose was to determine whether hepatic portal perfusion assessed by multidetector row CT using compensation for respiratory misregistration can predict the severity of chronic liver disease. We carried out dynamic CT in 43 patients (chronic hepatitis: n=9; cirrhosis: n=24; normal liver: n=10). In this series, 20 patients had liver tumours. The CT protocol was designed to avoid respiratory artefacts and included two interscan breathing periods during the study. To compensate for respiratory misregistration, image sets in the same z-axis position were acquired from four-slice data on each scan, and the portal perfusion calculations were made according to the maximum slope method. Portal perfusion was compared with and without compensation for respiratory misregistration, and the different types of hepatic disease. In the liver tumour patients in particular, portal perfusion was compared with the degree of hepatic fibrosis in the liver sections. Portal perfusion in the patients without compensation for respiratory misregistration (1.10 ml min(-1)ml(-1)) was higher than that of those with compensation (0.99 ml min(-1)ml(-1); p=0.036). Hepatic portal perfusion of patients with chronic hepatitis (0.97 ml min(-1)ml(-1)) and liver cirrhosis (0.88 ml min(-1)ml(-1)) was less than that of patients with normal liver (1.32 ml min(-1)ml(-1); p=0.03, 0.001). Moderate correlation was seen between portal perfusion and the percentage of fibrosis in patients with liver tumours (r=0.55). Hepatic portal perfusion obtained by multidetector row dynamic CT using compensation for respiratory misregistration has the potential to improve non-invasive assessment of the degree of chronic liver disease.

Aged↗

Necessity of multiple gastric biopsies from different sites for detection of clarithromycin-resistant Helicobacter pylori strains.

BACKGROUND: It has been reported that approximately 10% of patients infected with Helicobacter pylori have both clarithromycin-susceptible and clathromycin-resistant strains. However, there have been no reports indicating whether only one gastric biopsy is sufficient to detect clarithromycin-resistant strains. METHODS: Sixty-five H. pylori-infected patients were selected for this study, and 40 of them were given clarithromycin-based eradication therapy. Four gastric biopsies, 2 from the antrum and 2 from the corpus, were obtained from each of the 65 patients. Susceptibility of H. pylori strains to clarithromycin was examined by detecting mutations of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: The clarithromycin-resistant strains were detected in 16 of the 65 (25%) patients. Only 5 of the 16 (31%) patients had the resistant strains in both the antrum and corpus. When only 1 or the other biopsy from the antrum was used, the resistant strains were detected in 8 (50%) or 9 (56%) of the 16 patients. CONCLUSIONS: These data indicate that multiple gastric biopsies from both the antrum and the corpus should be used to detect clarithromycin-resistant H. pylori strains.

Adult↗

Human telomerase reverse transcriptase, p53 and Ki-67 expression and apoptosis in colorectal serrated adenoma.

BACKGROUND: Serrated adenoma (SA) has recently been proposed as a distinct histological lesion of the colorectum. However, no definite histopathologic criteria for SA have been established, and its histogenesis and natural history remain unclear. METHODS: We analysed 25 hyperplastic polyps (HPs), 26 low-grade SAs (LG-SAs), 32 high-grade SAs (HG-SAs), 18 low-grade tubular adenomas (LG-TAs), 16 high-grade TAs (HG-TAs) and 20 carcinoma in situ (CIS). To clarify molecular features of SA, we used in situ hybridization to examine the expression of human telomerase reverse transcriptase (hTERT), immunohistochemistry to examine the expressions of p53 and Ki-67, and in situ DNA nick end labeling to detect apoptotic cells. RESULTS: The incidence of hTERT expression was 1 (4.0%) of 25 for HP, 12 (46.2%) of 26 for LG-SA, 18 (56.3%) of 32 for HG-SA, 6 (33.3%) of 18 for LG-TA, 7 (43.8%) of 16 for HG-TA, 12 (80.0%) of 15 for CIS, respectively. The incidence of hTERT expression in SA was significantly higher than that in HP. Seventeen (29%) of the 58 SAs were regarded as positive for p53 protein, but none of the HPs showed p53 immunoreactivity. Ki-67 labeling index in SA, TA and CIS was significantly higher than that in HP. The apoptototic index was not significantly different between HP, SA, TA and CIS. In HG-SA, the incidence of hTERT expression in p53-positive lesions was significantly higher than that in p53-negative lesions. CONCLUSIONS: These results suggest that hTERT and p53 expression increase in the early stages of carcinogenesis in SA and that SA has a malignant transformation similar to that of TA. It may be useful to investigate hTERT and p53 expression for differential diagnosis of SA from HP.

Adenoma↗

Microsatellite instability is a genetic marker for the development of multiple gastric cancers.

Multiple gastric cancers are found in 5-15% of all patients with gastric cancer. However, no molecular markers have yet been shown to be clinically useful for predicting which patient will or will not have multiple gastric cancers. Recently, microsatellite instability (MSI) has been identified as a molecular marker for multiple colorectal cancers. To elucidate whether MSI could be used as a molecular marker for multiple gastric cancers, we examined MSI in 38 patients with a single gastric cancer, in 26 patients with synchronous multiple gastric cancers and in 14 patients with metachronous multiple gastric cancers. In the patients with synchronous multiple gastric cancers, 1 of the larger tumors was examined. In the patients with metachronous multiple gastric cancers, the first gastric cancer was examined. Five microsatellite loci, including D17S855, D18S58, D18S61, BAT25 and BAT40, were examined with microsatellite assay. MSI was divided into low frequency of MSI (MSI-L) and high frequency of MSI (MSI-H) by the number of affected loci. MSI-L was detected in 3 of the 38 (8%) patients with a single gastric cancer, in 7 of the 26 (27%) patients with synchronous multiple gastric cancers and in 6 of the 14 (43%) patients with metachronous multiple gastric cancers. MSI-H was detected only in 1 of the 38 (3%) patients with a single gastric cancer. The frequency of MSI-L was significantly higher in patients with multiple gastric cancers, both synchronous and metachronous, than in those with a single gastric cancer (p < 0.05 and p < 0.01, respectively). Patients with MSI(+) gastric cancer developed a significantly higher frequency of secondary gastric cancer, when compared with patients with MSI(-) gastric cancer (p < 0.05). These data suggest that MSI may play an important role in the development of multiple gastric cancers, and it may be used clinically as a molecular marker for the prediction of multiple gastric cancers.

Colorectal Neoplasms↗

Angiogenesis at the site of deepest penetration predicts lymph node metastasis of submucosal colorectal cancer.

PURPOSE: Intratumor microvessel count has been reported as a useful prognostic factor in patients with cancer of various organs. This study was undertaken to clarify the relation between microvessel count and lymph node metastasis in submucosal colorectal cancer. METHODS: Microvessel count was estimated in 254 invasive tumors that had been resected from patients with submucosal colorectal cancer. Immunohistochemistry with antibodies against CD34 was performed on archival specimens, and microvessel counts were estimated based on the average count of three fields (original magnification, x400) in the most vascular area at the site of deepest submucosal penetration. RESULTS: Microvessel count ranged from 10 to 98, with a median of 40. Lesions with high microvessel counts (> or =40) had a significantly higher incidence of lymph node metastasis than those with low microvessel counts (<40; 21.8 percent vs. 6.2 percent). None of the 79 lesions with low microvessel counts and submucosal invasion up to a depth of 1,500 microm had metastasized to the lymph nodes. In multivariate analysis, microvessel count was an independent risk factor for lymph node metastasis in submucosal colorectal cancer (P = 0.0026). CONCLUSION: Microvessel count at the site of deepest submucosal penetration can be one of the most useful predictors for lymph node metastasis. Analysis that combines microvessel count and depth of submucosal invasion may predict the occurrence of lesions without lymph node metastasis.

Adenocarcinoma↗

B-cell monoclonality in Helicobacter pylori-associated chronic atrophic gastritis.

B-cell monoclonality has been reported not only in gastric lymphoma, but also in 1.3-21% of Helicobacter pylori-associated chronic gastritis (Hp-CG) cases. The aim of this study was to determine the significance of B-cell monoclonality in Hp-CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The density of Hp, polymorphonuclear neutrophil activity, chronic inflammation, glandular atrophy, and intestinal metaplasia (IM) were scored according to the updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy chain gene rearrangement using polymerase chain reaction amplification. B-cell monoclonality was detected in 6% of informative samples. B-cell monoclonality was found in 18% of the samples from Hp-CG patients with marked glandular atrophy but in none of the samples from Hp-CG patients with none to moderate glandular atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG patients with marked IM, in 11% of the samples from Hp-CG patients with moderate IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell monoclonality was significantly more frequent in Hp-CG patients with marked glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was also more significantly frequent in Hp-CG patients with moderate or marked IM than in Hp-CG patients without IM (P < 0.05). Of 35 Hp-CG patients, 26 (74%) had identical B-cell populations in the antrum and the corpus, and all were polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B-cell populations in at least one gastric biopsy specimen. There were no patients with monoclonal B-cell populations in both the antrum and the corpus. These data suggest that glandular atrophy and IM in gastric biopsy specimens may be markers for gastric mucosa-associated lymphoid tissue (MALT) lymphoma-genesis and that multiple gastric biopsy specimens from both the antrum and the corpus may be needed to assess the risk of gastric MALT lymphoma.

B-Lymphocytes↗

Cathepsin D expression as a possible predictor of lymph node metastasis in submucosal colorectal cancer.

The aim of this study was to clarify the usefulness of cathepsin D expression as a predictor of lymph node metastasis in submucosal colorectal cancer (CRC). Cathepsin D expression was examined immunohistochemically in cancer and stromal cells located at the deepest portion of 254 invasive tumours that had been resected from patients with submucosal CRC. In cancer cells, the expression was classified according to differences in intracellular localisation: polarity positive, apical type (PA); polarity positive, basal type (PB); polarity negative (PN); or no expression (NE). Lesions with PN or NE expression showed a significantly higher incidence of lymph node metastasis than those with PA or PB expression. Alternatively, lesions with positive expression in stromal cells showed a significantly higher incidence of lymph node metastasis than that of those with negative expression. None of the lesions with PA or PB expression and negative expression in stromal cells had metastasised to the lymph node. In conclusion, analysis combining cathepsin D expression in cancer and stromal cells may be a quite useful predictor for lymph node metastasis and may broaden the indications for curative endoscopic treatment of submucosal CRC.

Analysis of Variance↗

Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: a comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component.

BACKGROUND AND AIMS: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). METHODS: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. RESULTS: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. CONCLUSIONS: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.

Adult↗

Clinicopathologic features and endoscopic treatment of superficially spreading colorectal neoplasms larger than 20 mm.

BACKGROUND: A colorectal neoplasm that spreads superficially over the mucosa is known as a laterally spreading tumor. The clinicopathologic features of these large lesions and the efficacy and safety of endoscopic mucosal resection (EMR) were studied retrospectively. METHODS: Surgically or endoscopically resected laterally spreading tumors larger than 20 mm in diameter were studied. Lesions were divided into 2 macroscopic subtypes: F-type, composed of superficially spreading lesions with a flat and smooth surface, and G-type, composed of superficially spreading aggregates of nodules that form relatively flat, broad-based lesions with granulonodular and uneven surfaces. RESULTS: Thirty-three lesions were of the F-type and 87 the G-type. G-type (mean +/- SD, 35.3 +/- 11.4 mm) lesions were significantly larger (p < 0.01) than F-type (26.0 +/- 7.2 mm) lesions. F-type lesions had a significantly higher frequency of invasive cancer (27.2%) than G-types (10.3%)(p < 0.05). Of the 120 lesions, 81 (67.5%) were resected endoscopically. Patients with 78 of these lesions were followed postoperatively for 60.8 +/- 20.1 months. The rate of local recurrence of endoscopically treated tumors as determined at colonoscopy was 7.4% (6/78). These lesions were completely resected endoscopically. Distant metastases were not detected. Thirteen (16.0%) patients had local bleeding after EMR that was stopped endoscopically. Microperforation of the colonic wall as a result of EMR was diagnosed in 1 (1.2%) of 81 cases. CONCLUSIONS: Laterally spreading tumors larger than 20 mm, especially those of the G-type, have a low rate of invasion despite their relatively large size. The F-type lesion has a higher malignant potential than the G-type. EMR is an effective and safe treatment for the large laterally spreading tumor.

Adenoma↗

Clinical significance of human erythrocyte glucose transporter 1 expression at the deepest invasive site of advanced colorectal carcinoma.

OBJECTIVE: Malignant cells exhibit increased glucose uptake and utilization in vitro and in vivo. This process is thought to be mediated by the glucose transporter (Glut) family. The aim of this study was to elucidate the clinical significance of Glut1 expression at the site of deepest invasion as a predictor of the invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). METHODS: One hundred and fifty-two patients who had undergone surgical resection for advanced CRC were entered in this study. Histologic subclassifications at the deepest invasive site included well-differentiated (W), moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp), poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression was examined immunohistochemically with a labeled streptavidin-biotin kit using anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67 expression was also examined. All immunoreactivity was analyzed at the deepest invasive site, central portion and superficial part. The immunohistochemical expression of Glut1 was defined as positive if distinct staining of the membrane or cytoplasm was observed in at least 30% of tumor cells. RESULTS: Glut1 expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive site. The incidence of Glut1 expression at the deepest invasive site correlated significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%), depth of invasion (invasion of muscularis propria/invasion of subserosa or subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs. presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke's stage (Duke's <D, 32% vs. Duke's D, 51%). In the central portion and superficial part, there were no significant differences between Glut1, Ki-67 expression and clinicopathological findings. Glut1 expression at the deepest invasive site correlated significantly with the Ki-67 labeling index. In cases of curative surgery, patients with Glut1-positive lesions at the deepest invasive site showed a significantly poorer prognosis than those with Glut1-negative lesions. Multivariate analysis with logistic regression for 5-year survival in patients who had undergone curative surgery showed that lymph node metastasis and Glut1 expression were significant risk factors. CONCLUSION: These results indicate that Glut1 expression at the deepest site of tumor invasion can be a useful predictor of a high malignant potential and poor prognosis in advanced CRC.

Adenocarcinoma↗

Helicobacter pylori eradication therapy for high-grade mucosa-associated lymphoid tissue lymphomas of the stomach with analysis of p53 and K-ras alteration and microsatellite instability.

Recent studies have shown that 70-80% of low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress in response to eradication of Helicobacter pylori (H. pylori). However, there are no reports on whether gastric high-grade MALT lymphomas regress after H. pylori eradication. We performed H. pylori eradication therapy in 4 patients with stage I, high-grade MALT lymphoma after obtaining their informed consent. H. pylori infection was observed in all 4 patients. The patients were treated with proton-pump inhibitor-based eradication therapy for 1 or 2 weeks, and then underwent endoscopic examination and biopsy sampling. H. pylori eradication was achieved in all 4 patients. Six months after eradication treatment, 2 patients showed complete regression of the lymphoma and 2 patients showed no change. The 2 patients with non-responding lymphoma were then treated with an additional chemotherapy (CHOP regimen), whereupon the tumors completely regressed. These patients, followed-up at least 18 months after eradication treatment, showed no recurrence. We also examined genetic alteration of the p53 and K-ras genes and microsatellite instability in these high-grade MALT lymphomas. One patient with a tumor that showed no change after H. pylori eradication, had a loss of heterozygosity of the p53 gene. No other genetic alterations were detected among the patients. Our results indicate that the eradication of H. pylori may be effective not only for patients with low-grade MALT lymphoma but also for patients with high-grade MALT lymphoma. The treatment may be efficacious as a first-line therapy for patients with high-grade MALT lymphoma. However, our sample size was limited and further studies are needed to clarify the issue.

Aged↗

MUC1 and cathepsin D expression in early colorectal carcinoma showing V type pit pattern.

The relation between MUC1, cathepsin D expression, and histologic features in early colorectal carcinomas (CRCs) with V type pit pattern was examined in 78 patients. We classified V type pit pattern into two grades (VA, VN) and we subclassified the VN type pit pattern into three subtypes (Grade A, B, and C) according to the degree of appearance of VN type pit pattern. At the tumor surface, the status of desmoplastic reaction and pit disorder or destruction were subclassified histologically into three grades (-, +, ++). MUC1 and cathepsin D expression were examined immunohistochemically at a superficial level and at the deepest part of the tumor invasion. MUC1 expression showed a significant correlation with high grade carcinoma, desmoplastic reaction (+) levels in VA type pit pattern (P<0.05), and high grade carcinoma, sm2 and sm3 lesions, desmoplastic reaction (+) and (++) levels, pit disorder or destruction (+) and (++) levels in VN type pit pattern (P<0.05). Cathepsin D expression had a significant correlation with m and sm1 lesions and desmoplastic reaction (-) levels in VN type pit pattern (P<0.05). In VA type pit pattern, a significant correlation between cathepsin D expression and histologic findings was absent. The incidence of MUC1 expression in VN.Grade B and C type pit pattern was significantly higher than that in VA and VN.Grade A type pit pattern (P<0.05). The incidence of cathepsin D expression in VA, VN.Grade A and B type pit pattern was significantly higher than that in VN.Grade C type pit pattern (P<0.05). MUC1 expression (+) or (++) levels at the deepest part of a tumor was identical to that (+) or (++) levels at the superficial part except for one case. Cathepsin D expression at the deepest part of a tumor differed from that at the superficial part. Desmoplastic reaction may be related to MUC1 and cathepsin D expression; however, pit disorder or destruction may be related to only MUC1 expression in V type pit pattern. MUC1 expression at the superficial part of a tumor may be related to expression at the deepest part; however, cathepsin D expression at the superficial part may not be related to expression at the deepest part in submucosal CRCs with V type lesions.

Cathepsin D↗

Epithelial-myoepithelial carcinoma of the parotid gland with adenoid cystic carcinoma-like features: a case report with immunohistochemical study.

A 69-year-old japanese female with epithelial myoepithelial carcinoma (EMC) in the parotid gland is reported. The tumor, 3.5 x 4.0 x 1.5 cm in size, was located in the left parotid gland. Histopathological examination of the surgically removed tumor revealed that it was composed of double-layered, tubule-like structures formed by inner eosinophilic ductal cells and outer clear cells, as well as solid clear cell nests. The unique histological finding of this tumor was that it had a cribriform-like arrangement of myoepithelial cells resembling an adenoid cystic carcinoma. On the other hand, the typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of low molecular weight cytokeratins, CAM 5.2 and EMA in the ductal part, and smooth muscle actin, S-100 protein, and vimentin in the myoepithelial component.

Aged↗

Telomere reduction in human liver tissues with age and chronic inflammation.

Telomere shortening in human liver with aging and chronic inflammation was examined by hybridization protection assay using telomere and Alu probes. The reduction rate of telomere repeats in normal liver (23 samples from patients 17-81 years old) was 120 bp per year, which is in good agreement with the reported reduction rate in fibroblasts of 50-150 bp at each cell division and replacement rate of human liver cells, once a year. Mean telomere repeat length shortened to about 10 kbp in normal livers from 80-year-old individuals. The number of telomere repeats in chronic hepatitis (26 samples) and liver cirrhosis (11 samples) was significantly lower than that in normal liver of the same age (P < 0. 01). Telomere length in all these chronic liver disease samples, other than two exceptions, was not reduced shorter than 5 kbp, which was assumed to give a limit of proliferation (Hayflick's limit) to untransformed cells.

Adolescent↗

Precancerous hepatic nodules had significant levels of telomerase activity determined by sensitive quantitation using a hybridization protection assay.

BACKGROUND: Telomeric repeat amplification protocol using internal telomerase assay standard (ITAS) (conventional TRAP) has detected telomerase activity in various malignant tumors. With conventional TRAP, it is difficult to differentiate quantitatively low levels of telomerase activity between well-differentiated hepatocellular carcinomas (HCCs) and dysplastic nodules because of quantitative limitation. To apply a telomerase assay for differential diagnosis, we used a hybridization protection assay combined with TRAP (TRAP/HPA). This combination had better sensitivity and wider linearity than conventional TRAP. METHODS: TRAP/HPA was applied for quantitative measurement of telomerase activity in various hepatic tissues. Telomerase activity was evaluated in 10 precancerous hepatic nodules, 17 well-differentiated HCCs, 19 moderately differentiated HCCs, 5 poorly differentiated HCCs, 22 nontumorous chronic hepatic disease samples, and 2 normal liver tissues. RESULTS: Telomerase activity in HCCs tended to increase according to the malignant transformation. The average relative telomerase activity in 0.6 microg protein, which was expressed as cell equivalent activity of MKN-1, a gastric carcinoma cell line, was 8.5 in precancerous hepatic nodules, 87 in well-differentiated HCCs, 265 in moderately differentiated HCCs, 447 in poorly differentiated HCCs, and 0.4 in nontumorous hepatic tissues, including chronic liver diseases. CONCLUSIONS: TRAP/HPA was sensitive enough to distinguish the telomerase activity in precancerous hepatic nodules from that in other lesions. Telomerase activity in precancerous hepatic nodules was higher than that in nontumorous hepatic tissues. However, the activity in precancerous hepatic nodules was lower than that in well-differentiated HCCs, although statistically not significant. The authors suggest that precancerous hepatic nodules with telomerase activity above the diagnostic cutoff level (twice the highest activity in nontumorous hepatic tissues, or the 2 cell equivalent activity of MKN-1) should be treated as malignancy.

DNA Primers↗

Progression of primary biliary cirrhosis after proctocolectomy for ulcerative colitis.

We report a case of progression of primary biliary cirrhosis (PBC) after proctocolectomy for ulcerative colitis. A 43-year-old woman underwent a total proctocolectomy after being diagnosed with ulcerative colitis. In the course of the preoperative investigation, liver function test results were within the normal range. Four months after the proctocolectomy, the patient showed a high level of alkaline phosphatase (2398 IU/l) and a positive anti-mitochondrial antibody titer (>1:160). There were no associated symptoms. A liver biopsy demonstrated expansion of all portal areas by infiltrates of lymphocytes and histiocytes. These appearances indicated chronic biliary disease and were compatible with PBC. The association of PBC and ulcerative colitis is rare. However, a review of the recent literature suggests that PBC and ulcerative colitis may be associated; this combination should be kept in mind.

Adult↗

Expression of telomerase component genes in hepatocellular carcinomas.

The aim of the study was to clarify the role of telomerase component genes in hepatocarcinogenesis and to examine both the relationship between the expression of telomerase component genes and histological differentiation in hepatocellular carcinoma (HCC) and the relationship between expression levels of telomerase component genes and telomerase activity in HCCs. Telomerase is a ribonucleoprotein enzyme composed of a template RNA and several proteins. Recently, three such telomerase component genes have been identified: human telomerase reverse transcriptase (hTERT); human telomerase RNA component (hTERC); and telomerase-associated protein 1 (TEP1). The expression of these components was evaluated in 34 HCCs and 24 non-cancerous liver tissues by reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of hTERT mRNA was detected in most HCCs, but not in the non-cancerous tissues (P<0.01). Expression of hTERC was detected in both HCCs and non-cancerous tissues, but the expression level in HCCs was higher than that in non-cancerous tissues (P<0.01) and tended to increase as histological differentiation became less marked. The expression level of hTERT mRNA correlated with relative telomerase activity (P<0.01). These results suggest that telomerase reactivation during hepatocarcinogenesis might be regulated by only hTERT and an increase in telomerase activity level in tumour progression might be regulated by both hTERT and hTERC.

Adult↗

Growth characteristics of rectal carcinoid tumors.

PURPOSE: Tissue growth depends on both cell proliferation and cell death. This study was designed to examine the growth characteristics of rectal carcinoid tumors. METHODS: Fifty rectal carcinoid tumors were studied clinicopathologically and experimentally. Expression of Ki-67, TGF-alpha, p53, and bcl-2 was examined immunohistochemically, and apoptotic cells were identified by the in situ DNA nick end labeling method. EGF receptor expression was examined by a colorimetric in situ mRNA hybridization technique. RESULTS: The median Ki-67 labeling index (LI) in all lesions was 0.62 +/- 0.59%. Ki-67 LI was significantly (p < 0.01) higher in lesions larger than 5 mm than in lesions smaller than 5 mm. TGF-alpha was expressed more frequently (p < 0.01) in lesions larger than 5 mm (100%) than in lesions smaller than 5 mm (65.2%). Ki-67 LI was significantly (p < 0. 05) higher in lesions with TGF-alpha expression than in lesions without TGF-alpha expression. The in situ hybridization revealed EGF receptor expression in all 46 lesions with intact mRNA (100%), and coexpression of TGF-alpha and EGF receptor was found in 39 of the 46 (84.8%) lesions. The median apoptotic index (AI) in all lesions was 0.15 +/- 0.12%. AI has increased with tumor size and was significantly (p < 0.05) higher in lesions with a higher Ki-67 LI than in lesions with a lower Ki-67 LI. p53 protein was detected in only 1 patient who had liver metastases, and the gene mutation was confirmed by polymerase chain reaction and single-strand conformation polymorphism analysis. bcl-2 expression was absent in all lesions. CONCLUSIONS: The Ki-67 LI indicated a low cellular proliferative activity in rectal carcinoid tumors. AI was very low, and was significantly correlated with proliferative rate. Inhibition of apoptosis by mutated p53 or bcl-2 may not have occurred in most of these tumors. TGF-alpha/EGF receptor autocrine mechanisms may play a possible role in tumor growth, and the cellular proliferative activity may increase as tumors grow larger.

Apoptosis↗