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  • 1
    ISSN: 1432-0533
    Keywords: Chronic manganese poisoning ; Pallidal lesion ; Distribution of manganese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An autopsy case of a 52-year-old man suffering from chronic manganese poisoning (CMP) is reported with determination of the manganese distribution in the brain. The patient had been working in a manganese ore crushing plant since 1965. In 1967 he began to complain of difficulties in walking and diminished libido. Later, he developed various neuro-psychiatric symptoms including euphoria, emotional incontinence, masked face, monotonous speech, “cock-walk”, increased muscle tone, weakness of upper and lower extremities, tremor of the eye lids, and exaggeration of knee jerks. The major neuro-pathological change was degeneration of the basal ganglia, in which the pallidum was severely affected. The pallidum discolsed a loss and degeneration of nerve cells, which was especially marked in the medial segment, a prominent decrease of myelinated fibers, and moderate astrocytic proliferation. The substantia nigra was intact. Distribution of manganese in the brain of the present case of CMP was determined using flameless atomic absorption spectrometry and compared with control cases and also a case of Parkinson's disease (PD). There was no significant difference between the control cases and the case of PD in average concentration of manganese and its ditribution in the brain. The present case of CMP showed no elevation in average concentration of manganese in the brain. However, there were some changes in its distribution. Thus, the continuance of neurological disorders in CMP is not linked to an elevated manganese concentration itself in the brain. CMP appears to be different from PD in neuropathology and manganese behavior in brain.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims:  Early gastric carcinomas have two characteristic growth types, superficial spreading (SUP) and penetrating (PEN). Higher mucosal apoptotic activity and lower p21WAF1/CIP1 expression and submucosal low proliferative activity have been shown in the former, compared with the latter. In order to cast light on whether angiogenesis contributes to these growth patterns, the present immunohistochemical study was performed with cancer tissues.Methods and results:  Of a total of 807 early gastric carcinomas, 30 PEN and 33 SUP type submucosal invasive carcinoma cases were immunohistochemically compared. CD34 positivity, microvascular density (MVD), and expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), but not cyclooxygenase 2 (COX-2) were higher in cancer cells in both mucosal and submucosal layers in PEN than in SUP (P 〈 0.05). Submucosal MVD in PEN type was greater (P 〈 0.01) in cases with high than with low Ki67 labelling. Significant correlations were shown between MVD and VEGF, iNOS and COX-2, and VEGF and iNOS expression in the PEN type, but only a weak correlation between iNOS and COX-2 expression was evident with the SUP type.Conclusions:  Increased MVD in PEN type has an intimate causal relationship to angiogenic factors, high VEGF and iNOS expression. The SUP type, in contrast, has characteristics of low angiogenesis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Expression of cell cycle regulatory proteins in the multistep process of oesophageal carcinogenesis: stepwise over-expression of cyclin E and p53, reduction of p21WAF1/CIP1 and dysregulation of cyclin D1 and p27KIP1 Aims: Cell cycle regulatory proteins were analysed by immunohistochemistry in order to clarify how their expression changes with the degree of atypia as oesophageal surface squamous epithelium progresses from normal mucosa, through reactive change, low-grade dysplasia, and high-grade dysplasia to mucosal invasive carcinoma. Methods and results: Immunostaining for cyclin D1, cyclin E, p21, p27, p53 and Ki67 proteins was performed using 22 normal mucosa, 17 reactive change, 22 low-grade dysplasia, 15 high-grade dysplasia and 22 mucosal invasive carcinoma specimens. Normal mucosa, low-grade dysplasia and high-grade dysplasia samples were taken from patients without any oesophageal invasive carcinoma by endoscopic biopsy or endoscopic mucosal resection, and reactive change and mucosal invasive carcinoma were obtained from oesophagectomy material. Stepwise over-expression of cyclin E (P 〈 0.0001) and p53 (P 〈 0.0001), reduction of p21 (P=0.0189) and dysregulation of cyclin D1 and p27 were observed in the multistep process of oesophageal carcinogenesis. Significant differences in expression of p27 (P 〈 0.0001), p53 (P=0.0299) and Ki67 (P=0.0101) were observed between reactive change and low-grade dysplasia. Furthermore, expression of cyclin D1, cyclin E, p27 and p53 in mucosal invasive carcinoma were significantly different from those in high-grade dysplasia (P=0.0079, P=0.0237, P=0.0042 and P= 0.0299, respectively). Conclusions: Cell cycle regulatory proteins, cyclin E, p53 and p21 show stepwise over-expression or reduction with progression of oesophageal carcinogenesis, correlating with the increased cell proliferation observed with Ki67 labelling. We conclude that immunohistochemical analysis for p27, p53 and Ki67 is practically useful for the discrimination between low-grade dysplasia and reactive change. Cyclin D1, cyclin E, p27 and p53 help to distinguish high-grade dysplasia from mucosal invasive carcinoma.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Although p27Kip1(p27) is a cyclin-dependent kinase inhibitor and a contribution to tumorigenesis has been hypothesized, the possible role in tumours arising in the nasal and paranasal sinus regions is still unknown.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsSeventy-six sinonasal tumours, including 28 inverted papillomas (IPs) and 48 squamous cell carcinomas (SCCs), were immunohistochemically investigated, along with 46 exophytic papillomas (EPs) of upper respiratory tract and 34 samples of normal paranasal sinus epithelium. The results were also compared with expression of p21WAF1 (p21) and p53, cell proliferation assessed in terms of Ki67 labelling indices (LIs), and human papillomavirus (HPV) infection. The average p27 scores decreased from normal through to malignant lesions, while Ki67 LI scores showed a stepwise increase, the inverse correlation between scores for all categories being significant (r = − 0.639, P 〈 0.0001). In the SCCs, p27 expression was significantly higher in keratinizing than nonkeratinizing type tumours (P 〈 0.05), while there was no association with p21 and p53 expression. Although HPV DNAs for type 16 and 18 were detected in two (7.4%) of 27 EPs, six (35.8%) of 28 IPs, and nine (28.1%) of 32 SCCs, no relation with p27 scores was evident.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionLoss of p27 expression correlates with increased cell proliferation in sinonasal tumours. Moreover, the expression appears to be associated with keratinization in SCCs of the paranasal sinus. These findings indicate that p27 expression may be a useful marker for the dysregulation of cell kinetics in these tumours.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: AimsTo investigate the histogenetic relationship between gastric epithelial neoplasms we studied differences in expression of mucin carbohydrate antigens and mucin core protein, in normal and metaplastic gastric mucosa, and in gastric adenomas and superficial adenocarcinomas.Methods and resultsWe generated four monoclonal antibodies, including HGM72/75 against human gastric mucin and HCM14/21 against human colonic mucin, and investigated immunoreactivities of these antibodies and MUC2 protein expression in normal and metaplastic gastric mucosa, adenomas (15 samples) and superficial adenocarcinomas (intestinal-type, 77; diffuse-type, 59 samples). HGM72 reacted with mucous neck cells of the fundic glands and with pyloric glandular cells whereas HGM75 stained foveolar cells and metaplastic goblet cells. Weak binding of HCM14/21 and strong staining with MUC2 were found in metaplastic goblet cells. Binding of HGM75, HCM14, MUC2, but not HGM72 was high in adenomas. An equivalent staining with HGM72 and HGM75 with low expression of MUC2 and HCM14 was shown in intestinal-type carcinomas while the diffuse-type demonstrated more strong reactivity with HGM75 than with HGM72, MUC2 and HCM14. Little binding of HCM21 was observed in any specimens.ConclusionsThis study demonstrates that adenomas predominantly have a intestinal phenotype, but both types of adenocarcinomas retain some cells with a gastric phenotype during the early steps of neoplastic development.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis.Aim : To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach.Methods : Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3–5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed.Results : After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group.Conclusions : Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims : The causal relationship of H. pylori gastric colonization with gastric cancer development has not as yet been fully elucidated. The prevalence of H. pylori infection increases with age in the asymptomatic population in Japan, and reaches a high plateau in those older than 40 years. The objective of this study was to assess the link between H. pylori and gastric carcinomas in patients younger than 40 years. Methods and results : Detection of H. pylori and assessment of background mucosa based on the Sydney system was performed histopathologically for 40 Japanese gastric cancer cases younger than 40 years and compared with 40 age- and sex-matched controls. H. pylori infection in gastric mucosa was detected significantly more frequently (P 〈 0.001) in patients with cancer (29/40; 72.5%) than in controls (11/40; 27.5%). Additionally, by histopathological comparison between intestinal (18 cases) and diffuse (70 cases) types of young gastric cancer patients, mucosal atrophy and intestinal metaplasia were found to coexist with acute and chronic inflammation in the background mucosa of both intestinal and diffuse types, being significantly more prevalent than in young controls. Conclusions : As well as the high prevalence of H. pylori in young subjects with gastric cancer, it is clear that persistent infection induces mucosal damage, resulting in atrophy and intestinal metaplasia. Thus, acute/chronic gastritis could play an essential role in the early development of neoplasia in the stomach.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 392 (1982), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2307
    Keywords: Oesophageal squamous cell carcinoma ; Apoptosis ; Cell growth ; p53 Protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess cell death and cellular proliferation activity, the apoptosis index, the Ki67 proliferative index and overexpression of p53 protein were evaluated in 69 oesophageal squamous cell carcinomas (ESCC), all surgically resected from Japanese patients. Apoptosis was examined by Gavrieli's method in histological sections, and proved to be significantly related to keratinization and ESCC progression. Overall labelling indices were 15.68±4.04 (positive/1,000 nuclei) and 6.79±0.64 respectively, in keratinizing and nonkeratinizing types. The apoptosis labelling index increased, especially in keratinizing lesions, from 4.50±0.59 with cancer invasion to mucosa through 11.46±2.70 with involvement of the submucosa up to 21.18±3.72 in cases of penetration to the muscularis propria or adventitia. The relationship between apoptosis, Ki67 scores and p53 expression was determined in identical cancer nests on serial sections. An inverse correlation was shown between the apoptosis score and the Ki67 score in both keratinizing and nonkeratinizing types. There was no significant correlation between apoptosis score and p53 expression, either overall or separately in keratinizing or nonkeratinizing types of ESCC. Our results suggest that a mechanism of induction of apoptosis similar to that operating in normal epidermis acts in keratinizing ESCC, and that as tumour volume increases, single cell death becomes more frequent.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 122 (1996), S. 427-432 
    ISSN: 1432-1335
    Keywords: Bcl-2 ; p53 ; DCC ; LOH ; Gastric carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to clarify the association betweenbcl-2 protein (Bcl-2) expression and genetic alteration, we investigatedp53 andDCC (deleted in the colon carcinoma gene locus) gene abnormalities in Bcl-2-positive and-negative gastric carcinomas using a polymerase chain reaction/loss of heterozygosity (LOH) assay. Bcl-2 immunoreactivity was found in 25 of 178 (14%) gastric carcinoma cases. With these 25 positive cases, the proportion 18/87 (20.6%) of the total in early stages demonstrating invasion of the mucosa and/or submucosa was significantly greater (P=0.013) than the 7/91 (7.7%) found for advanced tumors exhibiting invasion into or through the muscularis propria. However, there was no statistically significant variation between the proportions for differentiated (17/98 cases, 17.3%) and undifferentiated (8/80 cases, 10%) lesions. Sixteen Bcl-2-positive cases (9 cases were not studied because of insufficient specimen material to allow extraction of DNA) and 31 cases randomly selected from a Bcl-2-negative group were analyzed for the presence ofp53-LOH or DCC-LOH and forp53 by immunohistochemistry. The minority of the Bcl-2-positive group hadp53-LOH and were immunopositive for p53 (P=0.033,P=0.028 respectively), while no association was found in the Bcl-2-negative category. In contrast, there was no correlation at all between Bcl-2 expression and DCC-LOH although the number of informative cases analyzed was too small to allow definite conclusions. These results indicate that Bcl-2 may be predominantly expressed at an early stage in gastric carcinomas, possibly in negative association withp53 gene abnormalities.
    Type of Medium: Electronic Resource
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