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Biomedical subjects

K Baczako

Publications and source records attributed to K Baczako.

At least 19 recordsLinked to original sources

Expression of retinoblastoma gene product in respiratory epithelium and sinonasal neoplasms: relationship with p16 and cyclin D1 expression.

Transition from G1 to S phase of the cell cycle is mediated by interactions between the Retinoblastoma gene product (pRb), p16, and cyclin D1. To determine the expression of these proteins in the sinonasal mucosa immunohistochemistry was carried out on archived tissue sections from 46 patients (37 men, 9 women, age range 17 to 82 years, median 55 years). Nuclear immunostaining for these proteins was assessed and the expression rates (percentages of immunoreactive nuclei) in normal respiratory epithelium, inverted sinonasal papillomas, cylindrical (oncocytic) sinonasal papillomas, and squamous cell carcinomas were compared. Normal respiratory epithelium showed significantly higher pRb expression in surface cells compared to basal cells (p < 0.05). In contrast, abundant pRb expression in surface and basal cells was detected in columnar differentiation in sinonasal papillomas and adjacent mucosa. Cuboidal and squamous metaplasia in inverted papillomas showed significantly reduced pRb expression in surface cells compared to columnar epithelium in inverted papillomas (p < 0.05, respectively). Expression of p16 was detected in all epithelial cell layers of normal respiratory epithelium, sinonasal papillomas, and adjacent mucosa. Cuboidal and squamous metaplasia in inverted papillomas showed increased p16 expression in surface cells compared to columnar epithelium in inverted papillomas (p < 0.05 between squamous metaplasia and columnar epithelium). Sinonasal squamous cell carcinomas showed the coexpression of pRb and p16. Expression rates of cyclin D1 higher than 10% were detected only in invasive carcinomas but not in carcinoma in situ, sinonasal papillomas or respiratory epithelium. Conclusively, pRb expression accompanies terminal differentiation in columnar surface cells. Expression of pRb in proliferating basal cells is present in sinonasal papillomas and adjacent mucosa but not in normal respiratory epithelium. Cuboidal and squamous metaplasia in inverted papillomas involves downregulation of pRb expression along with increased p16 expression in surface cells. Sinonasal squamous cell carcinomas coexpress pRb and p16. Overexpression of cyclin D1 in sinonasal lesions is confined to invasive squamous cell carcinomas.

Carcinoma, Squamous Cell↗

Cytokeratin expression and epithelial differentiation in Warthin's tumour and its metaplastic (infarcted) variant.

AIMS: Warthin's tumour is characterized by a bilayered columnar epithelium. Transformation into metaplastic (infarcted) Warthin's tumour includes squamous metaplasia of the epithelium along with regressive changes in the stroma. Misinterpretation of metaplastic Warthin's tumour for malignancy is a serious diagnostic pitfall. This study assesses the utility of cytokeratin expression in Warthin's tumour and its metaplastic variant. METHODS AND RESULTS: Twenty-six cases of Warthin's tumour, among them eight metaplastic Warthin's tumours, were investigated employing immunohistochemistry. Both Warthin's tumour and its metaplastic variant regularly expressed cytokeratins (CK) 7, 8, 18, and 19. Staining results with antibodies to CK10, 10/13, 1/2/10/11, and 20 were negative in all specimens. Immunoreactivity for CK 5/14 and 17 was restricted to basal cells in Warthin's tumour, but involved basal as well as surface cells in metaplastic Warthin's tumour. CONCLUSIONS: Warthin's tumour and its metaplastic (infarcted) variant both express CK 7, 8, 18, and 19, which are typical for columnar differentiation. Cytokeratins typical of squamous differentiation are absent from Warthin's tumour and its metaplastic variant, irrespective of the squamous morphology of the epithelium in metaplastic Warthin's tumour. The expression of CK 5/14 and 17, which are typical of regenerative cells, is restricted to basal cells in Warthin's tumour, but is expressed also in surface cells in metaplastic Warthin's tumour.

Adenolymphoma↗

Phospholipase A2 isoforms in acute pancreatitis.

OBJECTIVE: To assess phospholipase A2 isoforms during human and experimental acute necrotizing pancreatitis. Phospholipase A2 isoforms (group I, II, and IV) were examined in acute pancreatitis tissues in humans and rats to determine whether the exocrine pancreas itself is a source of these mediators. SUMMARY BACKGROUND DATA: Phospholipase A2 has important regulatory functions, especially in inflammation. METHODS: Using Northern blot analysis and immunohistochemistry, the expression and localization of phospholipase A2 isoforms were analyzed in pancreatic tissue obtained from 21 patients with acute necrotizing pancreatitis and in pancreatic tissues of rats with acute edematous and necrotizing pancreatitis. Rat samples were examined daily for 1 week. RESULTS: In human acute pancreatitis, phospholipase A2-I mRNA expression was 8.9-fold decreased. By contrast, phospholipase A2-II (7.8-fold) and phospholipase A2-IV (8.1-fold) mRNA levels were increased. By in situ hybridization, phospholipase A2-IV was found to be expressed in remaining acinar and ductal cells adjacent to the necrotic areas. Immunostaining revealed moderate to intense phospholipase A2-II immunoreactivity in remaining acinar and ductal cells next to the necrosis. In rat pancreatitis, phospholipase A2-II mRNA levels in the pancreas were unchanged in the early phase (8 hours) but markedly increased after 24 hours, with a fluctuating pattern until day 7. CONCLUSIONS: Enhanced expression of phospholipase A2-II and A2-IV isoenzymes in human and experimental acute pancreatitis suggests that these enzymes play a role in modulating the inflammatory reaction in the pancreas. Because phospholipase A2-II and A2-IV mRNA was strongly present in remaining viable pancreatic acinar and ductal cells, the pancreas itself seems to be at least partly a source and a regulator of phospholipase A2-II- and A2-IV-dependent inflammatory reactions in acute pancreatitis.

Adolescent↗

Patterns of p21(waf1/cip1) expression in non-papillomatous nasal mucosa, endophytic sinonasal papillomas, and associated carcinomas.

AIMS: To clarify p21(waf1/cip1) expression in sinonasal lesions. METHODS: Archived surgical specimens from 38 patients were investigated by means of immunohistochemistry. p21(waf1/cip1) staining was evaluated in the different layers of the epithelium. In addition, human papillomavirus (HPV) infection and p53 protein overexpression were assessed and correlated with p21(waf1/cip1) expression. RESULTS: p21(waf1/cip1) staining was negative in non-papillomatous nasal mucosa. HPV infection and p53 protein overexpression were not seen. Sixteen of 20 inverted papillomas showed p21(waf1/cip1) expression. HPV infection was found in 16 cases and p53 protein overexpression was present in 13 specimens. Expression of p21(waf1/cip1) was restricted to surface cells in five cases, but involved basal/parabasal cells in 11 specimens. Immunoreactivity for p21(waf1/cip1) in basal/parabasal cells colocalised with p53 protein overexpression. Enhanced expression rates for p21(waf1/cip1) were seen in transitional and squamous epithelium compared with columnar epithelium. p21(waf1/cip1) expression involved only surface cells in cylindrical cell papillomas. HPV infection and p53 protein overexpression were detected in all specimens. One of five squamous cell carcinomas showed p21(waf1/cip1) expression. HPV infection was seen in two cases, and all carcinomas showed p53 protein overexpression. CONCLUSIONS: Expression of p21(waf1/cip1) is associated with terminal differentiation in surface cells in inverted papillomas and cylindrical cell papillomas, but not in non-papillomatous nasal mucosa. Overexpression of p53 protein colocalises with p21(waf1/cip1) expression in basal/parabasal cells in inverted papillomas but not in cylindrical cell papillomas. Expression of p21(waf1/cip1) in squamous cell carcinomas involves a subset of tumours with p53 protein overexpression.

Adolescent↗

Coexpression of cytokeratins typical for columnar and squamous differentiation in sinonasal inverted papillomas.

Cytokeratin (CK) expression was studied in 22 sinonasal inverted papillomas. Columnar (respiratory) epithelium in inverted papillomas abundantly expressed CK7, CK8, CK18, and CK19. Immunoreactivity for CK5/14 and CK17 was found in basal and parabasal/suprabasal cells. Transitional (cuboidal) and squamous epithelium in inverted papillomas comparably expressed CK7, CK8, CK18, and CK19. In addition CK13 was found in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 involved all layers of the epithelium. In nonpapillomatous nasal mucosa adjacent to inverted papillomas, CK expression in columnar (respiratory) epithelium exactly matched the findings in inverted papillomas. Transitional (cuboidal) and squamous epithelium in nonpaillomatous mucosa were negative for CK7, CK8, CK18, and CK19. CK13 was expressed in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 was restricted to basal and parabasal/suprabasal cells. Conclusively, transitional (cuboidal) and squamous epithelium in inverted papillomas but not in the adjacent mucosa coexpress CKs typical for columnar and squamous differentiation.

Adult↗

Cytokeratin 19 expression in human gastrointestinal mucosa during human prenatal development and in gastrointestinal tumours: relation to cell proliferation.

Cytokeratin (CK) immunohistochemistry revealed changes in the CK19 immunoreactivity in human gastrointestinal epithelium during embryonic and fetal development. These changes were particularly marked in the jejunum and ileum. CK19 immunoreactivity was strong up to the 11th week of pregnancy, but was absent between weeks 12 and 17, and reappeared weakly from week 18 to week 24. This temporal pattern correlated with that of cell proliferation investigated by immunohistochemical detection of proliferating cell nuclear antigen. Marked CK expression was associated with a low proliferative rate and vice versa. To test whether these results were relevant to the assessment of intestinal metaplasia and the risk of malignant transformation with poor cell differentiation, adenomas and adenocarcinomas of the colon, intestinal metaplasia of the stomach, and two types of gastric carcinoma were also examined by CK19 immunohistochemistry. Substantial CK19 immunoreactivity was found in well-differentiated cancers and low-grade dysplasias with low cell proliferation, whereas only weak CK19 immunoreactivity was found in poorly differentiated carcinomas and high-grade dysplasias with a high proliferation rate.

Adenocarcinoma↗

Polyarteritis nodosa-like inflammatory vascular changes in the pancreas and mesentery of rats treated with streptozotocin and nicotinamide.

Pancreatic endocrine tumours and inflammatory vascular changes resembling those of human polyarteritis nodosa occurred simultaneously in male Holtzman rats after a single injection of streptozotocin and two injections of nicotinamide. The histomorphological appearance of the arterioles resembled that seen in vascular diseases of immunopathogenetic origin. The proximity of the vascular lesions to the hormone-producing tumour suggested that the tumour-related hormone production induced the development of the panarteritis. Streptozotocin-nicotinamide-induced vasculitis in rats was histologically similar to human polyarteritis nodosa. It may therefore provide a good animal model for the human disease.

Adenoma, Islet Cell↗

Structural changes in the gastric foveolar epithelium in Helicobacter pylori-positive gastritis revealed by keratin immunohistochemistry.

To clarify structural changes in the gastric foveolar epithelium in Helicobacter pylori (Hp)-positive gastritis, the expression rates of keratins 8, 18, 19, and 20 were assessed immunohistochemically in normal tissue and chronic gastritis. In normal tissue, keratin 8 was found in 100% of the cells. Staining for keratins 18 and 19 was abundantly positive. Keratin 20 was not expressed in the deep foveolae, but present in the upper foveolae and on the tips. No differences were found between the antrum and the body. In chronic gastritis, both Hp-positive and -negative, keratins 8, 18, and 19 were expressed comparably to normal tissue. Keratin 20 expression in the antrum was significantly lower in Hp-positive compared with Hp-negative gastritis (P < .05) and normal tissue (P < .05). In the body, staining for keratin 20 did not differ significantly between all groups. The difference in keratin 20 expression between the antrum and the body in Hp-positive gastritis was significant (P < .05). After successful eradication, staining for keratin 20 in the antrum normalized within 6 months (P < .05). These findings indicate structural changes in the gastric foveolar epithelium in Hp-positive gastritis. They predominantly include the antral region and show full reversibility after eradication.

Adult↗

Increased expression of transforming growth factor beta s after acute oedematous pancreatitis in rats suggests a role in pancreatic repair.

BACKGROUND: Transforming growth factor beta isoforms (TGF beta s) belong to a family of multifunctional regulators of cellular growth and differentiation. They are mitogenic and chemotactic for fibroblasts and are potent stimulators of extracellular matrix production (collagen) and deposition. Upregulation of TGF beta transcription has been reported for several in vivo systems during repair after injury. AIMS: To study the expression of the three mammalian isoforms of TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for fibroblast response in acute oedematous pancreatitis in rats. METHODS: Using northern blot analysis and immunohistochemistry, the expression and localisation of TGF beta isoforms, collagen, and amylase were analysed during the course of acute oedematous pancreatitis in rats, experimentally induced by intravenous caerulein infusion. RESULTS: Induction of acute pancreatitis resulted in a biphasic peak pattern of expression of TGF beta 1, beta 2, and beta 3 mRNA, with a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again from day 5 to day 7 (three-fold, 2.3-fold, 3.5-fold, respectively). The temporal changes in TGF beta mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a general indicator of acinar cell integrity, was slightly decreased after induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis tissue showed that increased expression of TGF beta s was mainly present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. CONCLUSION: Overexpression of TGF beta s after induction of acute pancreatitis suggests a role for these proteins in pancreatic repair and remodelling. The increased levels of TGF beta s may help suppress immune activation, and may contribute to the increase in the extracellular matrix including collagen and to the repair of the pancreatic parenchyma.

Acute Disease↗

Expression of cytokeratins typical for ductal and squamous differentiation in the human stomach: an immunohistochemical study of normal foveolar epithelium, Helicobacter pylori gastritis and intestinal metaplasia.

The expression of the cytokeratins (CK) 1, 5, 6, 7, 10, 13 and 14 was studied immunohistochemically in gastric biopsies from both the antrum and the body of 70 patients. Normal gastric foveolar epithelium (9 cases) Helicobacter pylori gastritis (23) and intestinal metaplasia (38) were examined. Positive staining results for CK 1, 5, 10 and 14 were not observed using the 34 beta E12 antibody. With antibodies to CK 5/6, 7 and 13 some, but not all cases, were immunoreactive. Predominantly positive staining included less than 10% of the cells and was always restricted to the tips and the juxtaluminal areas of the foveolae. No difference was seen between the antrum and the body. Comparing normal gastric mucosa with gastritis and intestinal metaplasia, cases positive for CK 5/6 were observed less frequently in intestinal metaplasia types II and II compared to the other groups. CK 7 was expressed exclusively in intestinal metaplasia. CK 13 was seen in all groups of specimens. Thus, cytokeratins typical for ductal structures (CK 7) and squamous epithelia (CK 5/6, CK 13) can be regarded as an inconstant, but not unusual observation in the gastric mucosa. Their expression may be controlled by both differentiation-related as well as environmental factors.

Adult↗

Hyperlipaemia intensifies the course of acute oedematous and acute necrotising pancreatitis in the rat.

BACKGROUND: Serum triglyceride concentrations higher than 10 to 20 mmol/l are probably a risk factor for developing acute pancreatitis in humans. AIMS: To therefore analyse the influence of hyperlipaemia on the course of acute oedematous and acute necrotising pancreatitis in rats. SUBJECTS: Male Wistar rats were used in all experiments. METHODS: Six different groups of animals were used: two groups without pancreatitis (controls), two with acute oedematous pancreatitis, and two with acute necrotising pancreatitis. One group from each pair was treated with Triton WR 1339, which induces endogenous hyperlipaemia. Blood samples were taken from all subjects to measure triglyceride, cholesterol, amylase, and lipase. Pancreatic tissue samples were taken and the degree of pancreatic damage was judged microscopically. RESULTS: In the control groups no significant changes occurred, either in serum enzyme activities or in histology. The hyperlipaemic subgroup of animals with acute oedematous pancreatitis developed significantly higher (p < 0.001) serum amylase activities and a greater degree of histological damage (p < 0.01) than the animals of the non-hyperlipaemic acute oedematous pancreatitis group. In the animals with necrotising pancreatitis, serum lipase activity and the histological degree of pancreatic damage were significantly higher in the hyperlipaemic animals than in the non-hyperlipaemic animals. CONCLUSION: This study shows that hyperlipaemia intensifies the course of acute oedematous and acute necrotising pancreatitis in rats.

Acute Disease↗

Immunohistochemical evaluation of keratin 20 expression in intestinal metaplasia types I to III.

AIMS: To investigate differences in expression of keratin 20, a cytoskeletal protein in gastrointestinal epithelial cells, in completely differentiated intestinal metaplasia (type I) and incomplete metaplasia (types II and III). METHODS: Gastric biopsy specimens from 66 patients with intestinal metaplasia were analysed immunohistochemically. Expression of keratin 20 was quantified as the percentage of immunoreactive cells on the tips, the upper, and deep foveolae. RESULTS: In all specimens keratin 20 was found on the tips and in the upper foveolae of intestinal metaplasia. Keratin 20 was not observed in the deep foveolae. No differences were seen between the antrum and the body. Expression patterns were comparable between types I and III. In type II, however, lower immunoreactivity was found. Both the differences between types I and II as well as between types II and III were significant (p < 0.05). CONCLUSIONS: Keratin 20 is expressed in metaplastic mucosa as a result of intestinal differentiation. Positive staining found exclusively in juxtaluminal cells occurs only in mature cells containing keratin 20. Lowered immunoreactivity in type II compared with types I and III indicates the different nature of type II intestinal metaplasia. Further studies are needed to shed light on the basic fundamental mechanism responsible for this.

Adult↗

[Helicobacter pylori eradication therapy with bismuth citrate/amoxycillin combination therapy].

The efficacy of a new combination preparation containing bismuth citrate and amoxicillin in one tablet was compared with the efficacy of bismuth citrate monotherapy in a randomised double-blind study on the eradication of Helicobacter pylori. The study involved 70 H. pylori positive (antrum biopsies showing a positive urease test) patients with non-ulcer dyspepsia and chronic gastritis. The treatment period was 14 days; 35 patients in group 1 received 2 tablets tid containing the bismuth citrate amoxicillin combination (BIAM tablet; 250 mg amoxicillin base and 120 mg bismuth); 35 patients in group 2 were treated with 2 tablets tid containing bismuth citrate (BI tablet; 120 mg bismuth). Total daily dose was therefore 1500 mg amoxicillin + 720 mg bismuth in group 1 patients resp. 720 mg bismuth in group 2 patients. 4 weeks after therapy H. pylori could not be histologically detected in the antrum of 22 patients (63%) in group 1 and 8 patients (24%) in group 2. Thus in group 1 (BIAM) a significantly higher eradication rate (p < 0.001) was shown than in group 2 (BI). Inflammation characterized by the infiltration of polymorphonuclear cells was significantly (p < 0.01) less pronounced in group 1 (BIAM) than in group 2 (BI) 4 weeks after the end of treatment. Gastrointestinal distress was quantified by evaluation of 13 different symptoms using a fourpoints scale at the beginning of the study and after 2 and 6 weeks. The sum of scores decreased by 81% in group 1 (BIAM) and 71% in group 2 (BI) after 6 weeks.

Adult↗

Lectin-binding properties of the antral and body surface mucosa in the human stomach--are the differences relevant for Helicobacter pylori affinity?

Biopsy specimens from histologically normal human gastric mucosa were examined histochemically with the use of lectins. Significant differences were found in the glycoconjugate patterns of the surface mucous cells between the body and the corresponding antrum. Two lectins (Ulex europaeus agglutinin I and Ricinus communis agglutinin I) specific for fucose and galactose residues stained the apical membrane and the intracellular (perinuclear) region of the antral mucosa more strongly than those of the body (P < 0.04). Body and antral biopsies from patients with Helicobacter pylori-positive chronic active gastritis were also studied, but the lectin patterns of Helicobacter pylori-infected body and antrum did not differ. On comparing these chronically infected gastric biopsies with normal antral mucosa, however, significant changes could be seen with the fucose-binding lectin as well as with two other lectins (succinylated concanavalin A and peanut agglutinin). These differences could have been induced directly by bacterial virulence factors or could be due to non-specific reactions to the inflammatory process.

Adult↗

[Endogenous prostaglandin synthesis and gastritis: lack of correlation with endoscopic findings, Helicobacter colonization and leukocytic infiltration of the mucosa].

We determined the capacity and the profile of prostaglandin synthesis in the antral mucosa of patients with erosive (n = 43) or non-erosive (n = 24) Type B gastritis in comparison with normal controls (n = 24). Prostaglandin synthesis was measured by the incorporation of 14C-labelled arachidonic acid into cyclooxygenase products in mucosal homogenate. There was no significant difference between controls and patients with antral gastritis. Furthermore, there was no correlation of the prostaglandin synthesis with helicobacter colonisation or with the degree of inflammation. In another group of 15 patients there was a 17% increased synthesizing capacity nearby the erosions, compared to a non-erosive area (p = 0.05). In these patients with chronic Type B gastritis the treatment with an antacid (Maalox 70, 4 x 10 ml) for 4 weeks did not affect the synthesizing capacity or the profile of mucosal prostaglandin synthesis.

Adult↗

The involvement of oxygen radicals in acute pancreatitis.

The purpose of this study was to assess the involvement of oxygen radicals in acute edematous and hemorrhagic pancreatitis. Acute pancreatitis was induced in rats by the CCK-analogue cerulein (5 micrograms/kg/h) and by retrograde injection of 5% sodium taurocholate for 30 min, 3.5 h, and 12 h. At the end of the infusion and observation time, serum enzymes, conjugated dienes, and malondialdehyde in the tissue were measured. Moreover, the tissue samples underwent light microscopical examination. In cerulein pancreatitis, an interstitial edema and intravascular margination of granulocytes in the pancreatic gland were observed after 3.5 h. After 12 h, the histological evaluation revealed a pronounced zymogen degranulation, extensive tissue necrosis and migration of granulocytes into the tissue. Parallelly, amylase and lipase increased by 15 and 35 times, respectively. In contrast, conjugated dienes and malondialdehyde increased in cerulein pancreatitis and reached their highest level after 3.5 h and decreased to normal levels after 12 h. The development of the histological damages and serum enzyme levels with sodium taurocholate pancreatitis was similar as compared to the cerulein pancreatitis, however, the development was faster and more traumatic. Already after 3.5 h an extensive zymogen degranulation and cell necrosis was observed. Concomitantly, the amylase and lipase levels increased by 90 and 30 times, respectively. Treatment with superoxide dismutase (100,000 U/kg/h) and catalase (400,000 U/kg/h) prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue edema and inflammatory response were not affected in both models of acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Involvement of neutrophils in postischaemic damage to the small intestine.

Haemorrhagic mucosal lesions are produced during intestinal ischaemia and after reperfusion probably mediated by oxygen radicals. Oxygen radicals react with cell membrane lipids and induce cell damage by peroxidation and induce accumulation of polymorphonuclear leucocytes in the tissue. The aim of the study was to elucidate the involvement of polymorphonuclear leucocytes in post-ischaemic intestinal damage. Intestinal ischaemia was induced in cats by partial occlusion of the superior mesenteric artery. Samples from the small intestine were excised before and at the end of the two hour hypotensive period as well as 10 minutes and 60 minutes after reperfusion. Conjugated dienes, myeloperoxidase, and the purine metabolites were determined in the samples. The tissue was also examined histologically. Seven cats were treated before reperfusion with a monoclonal antibody (IB4) which inhibits leucocyte adherence to endothelial cells and its subsequent activation. After reperfusion myeloperoxidase activity increased and the ischaemic mucosal lesions worsened significantly. IB4 treatment prevented an increase in post-hypotensive myeloperoxidase activity and attenuated the normally observed severe mucosal lesions. We conclude that the severe post-ischaemic lesions are induced by polymorphonuclear leucocytes. Such mucosal injury may be appreciably reduced by blocking leucocyte adherence with IB4.

Animals↗