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Biomedical subjects

A Zimmermann

Publications and source records attributed to A Zimmermann.

At least 109 records · Page 6Linked to original sources
PubMed1999

Regulatory peptide receptors in human hepatocellular carcinomas.

BACKGROUND: Overexpression of regulatory peptide receptors in selected human tumours is of diagnostic and therapeutic relevance. AIMS: To evaluate the expression of somatostatin, vasoactive intestinal peptide (VIP), substance P, cholecystokinin (CCK) A and B, and neurotensin receptors in hepatocellular carcinoma (HCC). METHODS: In vitro receptor autoradiography for the various peptide receptors using selective iodinated radioligands on tissue sections in 59 cases of HCC. RESULTS: 41% of HCC expressed somatostatin receptors; 47% expressed VIP receptors. VIP receptors were always identified in non-neoplastic liver tissue. Substance P receptors were only identified in 5% of HCC but in the majority of their peritumorous and intratumorous vessels. CCK-A and -B and neurotensin receptors were not detected in HCC. The somatostatin receptors showed high affinity for somatostatin and octreotide. The VIP receptors had high affinity for VIP, pituitary adenylate cyclase activating peptide (PACAP) 27, and a VIP1 selective analogue, suggesting the presence of VIP1/PACAP II type receptors. PACAP I receptors were identified in two cases. Substance P receptors were all of the NK1 subtype. The density of somatostatin receptors in HCC was low compared with the density found in liver metastases of neuroendocrine tumours. The VIP receptor density was always lower in HCC than in adjacent liver tissue. CONCLUSIONS: Somatostatin, VIP, and substance P may have a receptor mediated role in HCC. Substance P receptors may be involved in regulation of tumour associated blood flow; somatostatin receptors and VIP receptors may mediate tumour growth. Diagnostic and therapeutic evaluation of somatostatin and VIP analogues may be of interest in receptor positive HCC.

Adult↗
PubMed1999

Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer.

PURPOSE: The reasons for the high frequency of perineural invasion and the presence of pain in pancreatic cancer are still not clear. Nerve growth factor (NGF) and its high-affinity receptor TrkA are involved in stimulating epithelial cancer cell growth and perineural invasion, as well as in pain generation in chronic benign disorders. PATIENTS AND METHODS: NGF and TrkA were examined by Northern blot analysis, in situ hybridization, and immunohistochemistry in 27 normal and 37 pancreatic cancer tissue samples. The molecular findings were correlated with the degree of perineural invasion, pain, and histopathologic tumor characteristics. RESULTS: Northern blot analysis indicated that NGF and TrkA mRNA levels were increased 2.7-fold and 5.6-fold, respectively (P <.05 and P <.05), in pancreatic cancer tissues compared with the normal pancreas tissue. As shown by in situ hybridization and immunohistochemistry, NGF was strongly present in the cytoplasm of pancreatic cancer cells. TrkA was intensely present in the perineurium of pancreatic nerves but not in the cancer cells. There was no difference in NGF and TrkA expression between early (stages I and II) and advanced (stage III) tumor stages and between well-/moderately differentiated (grades 1 and 2) and poorly differentiated (grade 3) tumors. However, tumors with high NGF/TrkA expression levels exhibited more frequent perineural invasion (P <.01). Furthermore, increased NGF/TrkA expression levels were associated with a higher degree of pain (P <. 01). CONCLUSION: Enhanced expression of the NGF/TrkA system may influence perineural invasion and may contribute to the pain syndrome in human pancreatic cancer.

Adult↗
PubMed1999

Intrapancreatic accessory spleen. A rare cause of a pancreatic mass.

CONCLUSION: The clinical significance of intrapancreatic accessory spleens resides in the mimicry of pancreatic cancer. Radionuclide tests (Octreotide scan and Tc99m sulfur colloid scan) should be undertaken to distinguish these lesions from neuroendocrine tumors, hypervascular metastases and pancreatic carcinoma. If the tests are equivocal, diagnostic laparotomy or laparoscopy is recommended. BACKGROUND: Despite its relatively common occurrence, intrapancreatic ectopic splenic tissue is rarely detected owing to its asymptomatic nature. METHODS: We report a case of a clinically asymptomatic patient in which abdominal computed tomography (CT) scans revealed a mass of 1.5 cm in diameter in the distal pancreas. The tumor markers CA 19-9 and carcinoembryonic antigen (CEA) were slightly elevated, and pancreatic neoplasm was suspected. RESULTS: Left pancreatic resection and splenectomy were performed. The removed specimen disclosed the presence of an accessory spleen within the pancreatic tail.

Aged↗
PubMed1999

Cells with morphological and immunohistochemical features of hepatic stellate cells (Ito cells) form an extralittoral (extrasinusoidal) compartment in the cirrhotic rat liver.

Systematic studies on hepatic stellate cells and myofibroblasts have so far mainly focused on cells located in the perisinusoidal space of Disse, the so-called littoral compartment. Here, these cells play a key role for intralobular fibrogenesis and sinusoidal capillarization. However, advanced hepatic fibrosis and cirrhosis are characterized by portal tract fibrosis and septal fibrosis, thus involving cells outside the perisinusoidal space. To study the question as to whether hepatic stellate cells occur and are expanded in an extralittoral (extrasinusoidal) compartment in cirrhogenesis, we systematically analyzed the distribution and density of desminreactive stellate cells in a rat model of hepatic fibrosis. Fibrosis and remodeling of the liver were induced by bile duct ligation, and stellate cells were identified by single and double immunohistochemistry. We can show that desmin-reactive cells are reproducibly detectable in extralittoral compartments of the normal and fibrotic rat liver. Periductular extralittoral stellate cells are significantly more frequent in cirrhosis, indicating that extralittoral stellate cells expand in concert with proliferating ductules. The findings suggest that ductular proliferation thought to represent a pacemaker of hepatic remodeling is accompanied by a population of cells exhibiting the same phenotype as perisinusoidal stellate cells.

Animals↗
PubMed1999

Reduced expression of the metastasis suppressor gene KAI1 in advanced colon cancer and its metastases.

BACKGROUND: The expression of the KAI1 gene and its gene product were studied in metastatic and non-metastatic human colorectal cancer to evaluate its role in the metastatic process. METHODS: KAI1 mRNA and protein expression was examined in 36 primary colorectal carcinomas and 6 liver metastasis using Northern blot and Western blot analyses. Forty-six normal colonic tissue samples served as controls. The exact site of KAI1 expression was analyzed by in situ hybridization and by immunohistochemistry in primary tumors, in the corresponding normal tissues, in lymph node metastases and liver metastases. RESULTS: Densitometric analysis of Northern blots revealed overexpression of KAI1 mRNA in 87% of colonic cancer tissues in comparison with the corresponding normal colonic tissues. This increase was 9.1-fold in median (P < .001). KAI1 mRNA expression was strongly dependent on tumor stage. Colorectal cancer at stages II and III revealed significantly higher KAI1 mRNA levels than stage IV tumors (P < .03 and P < .015, respectively) or normal controls. In addition, liver metastases showed reduced KAI1 mRNA expression when compared with their corresponding primary tumor. In situ hybridization confirmed the stage-dependent expression results obtained by Northern blots, in which the KAI1 mRNA signal was exhibited almost exclusively in the epithelial cells. Lymph node and liver metastases were largely devoid of KAI1 mRNA. Western blot analysis showed a highly significant increase of KAI1 protein level in stage II cancers in comparison with the normal colon (P < .001) but also in comparison with the more advanced tumor stages III and IV (P < .03) and P < .02, respectively), when metastases were already present. In accordance, KAI1 immunostaining decreased successively with the advance of the tumor stage and was absent in lymph node and liver metastases. CONCLUSIONS: These data demonstrate that the KAI1 mRNA expression and the KAI1 protein level increase in an earlier tumor stage of colorectal cancer, decrease in advanced stages, and are lost in metastases. The loss of KAI1 might favor the ability of colorectal cancer cells to metastasize.

Adult↗
PubMed1998

[Severe hepatocellular damage after administration of paracetamol and chlorzoxazone in therapeutic dosage].

A 64 year old patient developed severe hepatocellular damage with jaundice and coagulopathy during ingestion of a combination of paracetamol and chlorzoxazone in therapeutic dosage. The risk factors for the development of liver cell necrosis following ingestion of paracetamol in therapeutic dosage are discussed. In particular in patients with risk factors (e.g. alcoholics and patients with heart failure) paracetamol-induced liver failure has to be considered in the presence of high transaminases, even when paracetamol was ingested in therapeutic dosage. Chlorzoxazone itself rarely can induce an idiosyncratic hepatocellular damage.

Acetaminophen↗
PubMed1998

Reduced KAI1 expression in pancreatic cancer is associated with lymph node and distant metastases.

KAI1 belongs to a structurally distinct family of membrane glycoproteins, which function via cell-cell and cell-extracellular matrix interactions, thereby potentially influencing the ability of cancer cells to invade tissues and to metastasize into lymph nodes and distant organs. In the present study, we examined KAI1 expression in lymph node and liver metastases in comparison with primary pancreatic cancer to evaluate its influence on metastasis. KAI1 mRNA analysis was performed by Northern blot analysis and in situ hybridization. In addition, the respective protein was studied by immunostaining. Fourteen primary pancreatic cancer samples in which no lymph node metastases were present and 25 primary pancreatic cancer samples in which lymph node metastases were present at the time of tumor resection were included. In 20 of these cases, primary pancreatic cancer tissues and corresponding lymph node metastases from the same patient were studied. Furthermore, 11 liver metastases were available for KAI1 analysis. Increased steady-state levels of KAI1 mRNA were found in 33/39 (85%) primary pancreatic cancers in comparison with normal controls. Statistical analysis of KAI1 mRNA levels and clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher in non-metastasized tumors compared with tumors in which lymph node or distant metastases were present. In lymph node metastases KAI1 mRNA expression was lower than in the corresponding primary tumors: In 14 of 20 lymph node metastases no KAI1 mRNA expression and in 6 of 20 lymph node metastases only weak KAI1 mRNA levels were present in some cancer cells. Cancer cells of distant metastases were devoid of or exhibited low KAI1 mRNA levels compared with those of primary pancreatic cancers. A similar pattern was observed by immunostaining. These data support the hypothesis that KAI1 gene expression might influence the metastatic ability of pancreatic cancer cells in vivo. Reduction of KAI1 appears to promote cancer cell spread in lymph nodes and distant organs.

Adult↗
PubMed1998

Activation of the serine proteinase system in chronic kidney rejection.

BACKGROUND: Activation of the serine proteinase system is an important mechanism that contributes to tissue remodeling. In the present study, we analyzed the expression of urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), and plasminogen activator inhibitor type 1 (PAI-1) in samples of chronically rejected human kidneys. METHODS: Using Northern blot analysis, immunohistochemistry, and a uPA activity assay, specimens from 10 chronically rejected kidneys and 10 normal kidney samples were analyzed. RESULTS: By Northern blot analysis, the expression of uPAR and PAI-1 mRNA was 2.9-fold (P<0.05) and 2.3-fold (P<0.05) increased in chronically rejected kidney samples, respectively, compared with normal controls. In contrast, uPA mRNA levels in chronically rejected kidneys were comparable to those in the normal controls. Immunohistochemical analysis in normal kidneys showed weak immunostaining of uPA, moderate to intense uPAR and PAI-1 immunostaining in proximal tubules, and moderate immunostaining in distal tubules, but no signal in the glomeruli or cortical vessels. A similar staining pattern was found in the distal and proximal tubules in rejected kidney tissue samples. However, in the rejected kidneys, the number of tubules was markedly reduced. In addition, within the glomeruli of rejected kidney samples, there was positive immunostaining for uPA, uPAR, and PAI-1 in the mesangial cells, but negative staining in most of the endothelial cells, whereas the normal kidneys revealed no immunoreactivity in these structures. CONCLUSION: The demonstrated up-regulation of uPA/uPAR/PAI-1 in chronic renal rejection is consistent with the plasminogen/plasmin system contributing to tissue remodeling in this disorder. These factors might activate latent transforming growth factor-betas, which have been reported to be enhanced in this disorder, contributing to the generation of the extracellular matrix.

Aged↗
PubMed1998

Effects of tilmicosin on acute undifferentiated respiratory tract disease in newly arrived feedlot cattle.

OBJECTIVES: To evaluate effects of tilmicosin when used in fever-based and metaphylactic treatment programs to attenuate acute undifferentiated bovine respiratory disease (BRD) in cattle that recently arrived at feedlots, and to evaluate the effects of tilmicosin for the treatment of BRD. DESIGN: Randomized-block controlled study. ANIMALS: 1,639 calves from livestock auctions. PROCEDURES: Cattle were assigned to 3 groups. Cattle in the nonmedicated (control) group were not given antibiotics during processing. Cattle in the fever-based treatment group were given tilmicosin (10 mg/kg [4.5 mg/lb] of body weight, s.c.) during processing when their rectal temperature was > or = 40 C (104 F). All cattle in the metaphylactic treatment group were given tilmicosin (10 mg/kg, s.c.) during processing. Calves with BRD were treated with tilmicosin (10 mg/kg, s.c.). RESULTS: Morbidity rates in the metaphylactic (30.4%) and fever-based (44.7%) treatment groups were less than that for the nonmedicated group (54.8%). Mortality rate for the metaphylactic group during the first 28 days (1.1%) and during the entire study (1.7%) was less than that for the nonmedicated group (3.3 and 4.6%, respectively). Differences were not observed in therapeutic response rates among calves with BRD that were treated. CLINICAL IMPLICATIONS: Fever-based and metaphylactic treatment programs that used tilmicosin decreased the prevalence of BRD and improved growth of calves. Metaphylactic treatment decreased the number of fatalities caused by BRD in high-risk calves. Fever-based treatment was less effective than metaphylactic treatment for decreasing the prevalence of BRD in newly arrived cattle.

Acute Disease↗
PubMed1998

[Central lung embolism in chronic interstitial pneumopathy].

An 80 year old patient with known interstitial pneumopathy of unknown etiology was hospitalized because of acute onset and rapid deterioration of dyspnea at rest within days. A foregoing neurologic investigation including CT and EEG because of prior syncopes and cramp attacks had not revealed pathologic findings. Thorax X-ray at admission showed homogenous loss of transparency on the left side, calcified basal plaques on both sides and prominent central pulmonary vessels with jumping caliber. A punctate of the leftsided pleural effusion revealed lymphocytic exsudate, normal pH, low glucose and an elevated LDH. The patient died shortly after a collapse at a bowel visit and pulmonary embolism was suspected in accordance to results from arterial blood gas analysis, ECG and chest X-ray. Neurologic symptoms could be explained by recurrent pulmonary embolism. Pleural plaques together with the punctate suggested a malignant etiology. A mesothelioma was taken into consideration, although there were no anamnestic reports on an exposition to asbestos. Autopsy revealed almost complete central embolism of the left pulmonary artery with acute cor pulmonale thus confirming the clinical suspicion. The embolus showed components of different ages of origin. Besides bronchitic and emphysematous alteration histology of the pulmonary tissue revealed interstitial and septal fibrosis with focal tissue consolidation. In one giant cell a typical asbestos body was found (in 1 out of 10 sections). In spite of missing information on an exposition to asbestos an abnormally high exposition must be taken into consideration because of the finding of an asbestos particle in relation to the amount of tissue studied. Apart from interstitial fibrosis asbestos may also cause consolidation of pulmonary tissue. Histology of plaquelike lesions revealed mesothelioma of fibrous type. This finding supports the suspicion that a major part of the pulmonary lesions was due to exposition to asbestos.

Aged↗
PubMed1998

Growth pattern and NGF-dependent survival of dorsal root ganglia neurons of distinct glyco-phenotype.

Cell-surface glyco-phenotypes of dorsal root ganglia (DRG) neurons were specified with monoclonal antibodies (mABs) D1 and E1. D1 demarcated sensory afferents in skin but not muscle target. More than 90% of the drg neurons supported by nerve growth factor (NGF) in vitro were D1 positive (D1+). A fraction of these D1+ neurons, those of small to intermediate soma size, coexpressed a PNGase-sensitive glycoepitope E1, defined by mAB E1. In situ and in vitro, E1+/D1+ and E1-/D1+ neurons and nerve fibers were affiliated. After separation of the two glyco-phenotypes, NGF-dependent survival of E1-/D1+ neurons was no longer observed. Two interrelated concepts emerge from these findings: (a) NGFs survival functions for cutaneous sensory neurons are in part indirect and appear to be based on interneuronal cooperation for survival; and (b) interneuronal survival dependencies are likely to be a decisive factor governing nerve fiber assemblages.

Afferent Pathways↗
PubMed1998

KAI1 is unchanged in metastatic and nonmetastatic esophageal and gastric cancers.

Down-regulation of KAI1 mRNA expression has been shown to be associated with the formation of metastases or disease progression in pancreatic cancer. Whether KAI1 possesses similar characteristics in other malignancies of the gastrointestinal tract is not known. Here, we compared the patterns of KAI1 mRNA expression in 41 esophageal cancers and 35 stomach cancers to assess whether KAI1 might also be of biological relevance in the metastatic ability of these tumors. By Northern blot analysis, KAI1 mRNA levels ranged widely in both normal and cancerous esophageal and gastric tissue samples, with no statistical differences. No association between KAI1 mRNA expression and tumor stage or tumor differentiation was seen in these tumors. In addition, KAI1 mRNA expression was similar in primary esophageal and gastric cancer samples with or without metastases. By in situ hybridization, KAI1 mRNA expression was evident in the cytoplasm of most squamous epithelial cells in the normal esophagus and in nonmucosal epithelial cells of the normal stomach. The staining intensity in the esophageal and gastric cancer cells was similar to that in the normal controls. This differential pattern of KAI1 mRNA expression in esophageal and gastric cancers in comparison to pancreatic cancer indicates that KAI1 seems to influence the potential of gastrointestinal cancer cells to metastasize differently. In esophageal and gastric cancers, the formation of metastases is not dependent on the reduction of KAI1 in the cancer cells.

Adult↗
PubMed1998

KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma.

Down-regulation of KAI1 expression has been shown to be associated with formation of metastases or disease progression in prostate and pancreatic cancer. In the present study we analyzed the expression pattern of KAI1 in metastatic and nonmetastatic hepatocellular carcinomas (HCCs) in comparison with normal livers to evaluate whether alteration of KAI1 also facilitates the metastatic ability in this malignancy. Thirty-nine primary HCCs and 10 normal liver tissue samples were studied for KAI1 messenger RNA (mRNA) expression with use of Northern blot analysis and in situ hybridization. By Northern blot analysis, moderate to strong KAI1 mRNA expression was present in normal liver samples. In contrast, KAI1 mRNA expression in tissue samples of primary HCCs was markedly decreased compared with normal controls. The normal/tumor ratio of KAI1 mRNA expression was 2.6:1 (P <.01). Primary HCCs that gave rise to metastasis showed significantly lower KAI1 mRNA levels than nonmetastasized HCCs (P <. 05). As seen by in situ hybridization, moderate to strong cytoplasmic KAI1 mRNA staining was present in almost all normal hepatocytes. Bile ducts, blood vessels, and connective tissue showed no or only faint KAI1 mRNA expression in the normal liver samples. In nonmetastatic HCCs, the cancer cells exhibited in situ hybridization signals that were similar to the normal controls. In contrast, most of the primary HCC cells in samples with metastases showed only faint or moderate KAI1 mRNA expression predominantly in the perinuclear regions. When KAI1 mRNA expression of primary hepatocellular cancer cells was compared with metastasized cancer cells in lymph nodes, with intrahepatic satellite metastasis, or with peritoneal metastasis in the same patients, significantly lower (P <.01) KAI1 mRNA levels were present in the metastasized HCC cells. Reduced KAI1 mRNA in HCC cells seems to influence their metastatic ability and thereby enhances the malignant potential of HCC.

Aged↗
PubMed1998

Ureaplasma urealyticum colonization and bronchopulmonary dysplasia: a comparative prospective multicentre study.

UNLABELLED: To determine the role of tracheal colonization at birth with Ureaplasma urealyticum and other pathogenic bacteria with regard to the development of bronchopulmonary dysplasia (BPD), 97 premature infants with very low birth weight (< 1500 g) were followed prospectively over 30 days in a multicentre study. Of those infants, 35 were colonized with Ureaplasma urealyticum (group Ia), 22 with other pathogenic bacteria (group Ib) and 40 infants with sterile tracheal aspirates served as controls (group II). Colonization with Ureaplasma urealyticum or with pathogenic bacteria independently increased the risk of developing BPD as compared to the controls (OR 2.55; 95% CI [1.11, 5.87]). Among Ureaplasma urealyticum and bacterial colonized infants, duration of mechanical ventilation and oxygen requirement were significantly longer than among controls (P < 0.05); during the interval of 11 to 35 days of life, every additional day of ventilation significantly increased the risk of BPD (OR 1.22; CI [1.12, 1.32]). The rate of oxygen supplementation, which was similar in both groups during the first 2 weeks of life, was significantly higher among the colonized infants at day 21 (0.38+/-0.18 and 0.39+/-0.16 vs 0.31+/-0.13, P < 0.05) and at day 28 (0.38+/-0.21 and 0.34+/-0.15 vs 0.28+/-0.12, P < 0.05). For infants still ventilated at age of 28 days, Ureaplasma urealytricum and bacterial colonization were associated with a significant higher risk for BPD than for uncolonized controls (OR 5.53; [1.27, 24.02]. Association of Ureaplasma urealyticum and of bacterial colonization and BPD was not weakened after adjustments were made in a multivariate analysis for other significant risk factors. CONCLUSION: Ureaplasma urealyticum colonization is as an important risk factor in the development of bronchopulmonary dysplasia as bacterial colonization even after treatment with surfactant.

Bronchopulmonary Dysplasia↗
PubMed1998

Increased expression of erbB3 in colorectal cancer is associated with concomitant increase in the level of erbB2.

ErbB3 is a transmembrane signaling molecule that shares close structural homology with epidermal growth factor receptor (EGFR), erbB2, and erbB4. They have all been implicated in cell transformation and tumor pathogenesis, but very little is known about the role of erbB3 in normal colon and colorectal cancer. Therefore, in the current study, we determined whether erbB3 is found in normal human colon and whether its expression is altered in colorectal cancer. Because of some evidence that erbB3 might interact with erbB2 and EGFR, respectively, by heterodimerization, we also included erbB2 and EGFR analysis with special regard to coexpression. The study was performed on 35 patients operated on for colorectal carcinoma. The normal human colon showed weak erbB3 and erbB2 immunostaining, predominantly in surface epithelial cells. EGFR immunoreactivity in normal colon varied from weak to strong. In contrast, in 31 of 35 (89%) and in 29 of 35 (83%) colonic cancers, moderate to strong immunoreactivity for erbB3 and erbB2, respectively, was present in most epithelial cancer cells. A concomitant erbB3 and erbB2 immunostaining advantage could be found in 77% of cancerous tissues in comparison with the normal colon. No difference in EGFR immunostaining was evident between normal colon and cancer. Northern blot analysis showed an increase in erbB3 and erbB2 mRNA levels in 64% of cancers in comparison with normal colon samples. By densitometry, 2.3-fold and a 1.5-fold significant increases in erbB3 and erbB2 mRNA levels, respectively, were calculated in the cancerous tissues. Eighty-five percent of cancers with erbB3 mRNA overexpression showed an increase in erbB2 mRNA. Southern blot analysis did not indicate any gene amplification or rearrangement responsible for erbB2 or erbB3 overexpression. EGFR, however, was decreased in cancer on mRNA level. These findings indicate that erbB2 and erbB3, but not EGFR, may contribute to tumor growth and disease progression in colon cancer. The correlation between increased erbB2 and erbB3 expression in both Northern blots and immunohistochemical analysis suggests a co-overexpression of erbB2 and erbB3 and might support the hypothesis that these two growth factor receptors act together by heterodimer formation.

Adenocarcinoma↗
PubMed1998

Apoptosis inhibiting factor Bcl-xL might be the crucial member of the Bcl-2 gene family in colorectal cancer.

Since the role of the Bcl-2 gene family has been only poorly investigated in colorectal cancer, we have examined the expression of the apoptosis blockers Bcl-xL and Bcl-2, as well as the proapoptotic factors Bax and Bak. Northern blot analysis and immunohistochemistry were performed on normal and cancerous colonic tissue from 12 patients. In colorectal cancer, Bcl-xL immunoreaction was stronger than in normal controls, and 83% of the cancers had increased Bcl-xL mRNA expression. The median densitometric Bcl-xL values were 3.4-fold higher in carcinomas (P<0.005). In contrast to the normal colon, colorectal carcinomas often lack any Bcl-2 immunostaining, and Bcl-2 mRNA was not detectable by Northern blots either. Bax was not obviously altered in colorectal cancer, either at the protein level or at the mRNA level compared to the normal control colon. Bak mRNA expression exhibited a wide variation in carcinomas, but was somewhat decreased in comparison to the controls. Of these members of the Bcl-2 gene family, Bcl-xL seems to play a major role in colorectal tumorigenesis and disease progression. An agonistic effect might have caused the tendency for reduced Bak expression. The Bcl-2/Bax regulation system of cell homeostasis seems to be of lesser importance.

Aged↗
PubMed1998

Liver iron and fibrosis during long-term treatment with deferiprone in Swiss thalassaemic patients.

Serum ferritin levels, hepatic histology and iron concentration were studied in a 'veteran' group of seven Swiss beta-thalassaemic patients after 93-99 months of treatment with the oral iron chelator deferiprone (L1), and another four patients who had received 54-82 months of L1 therapy. Despite continuous compliance, unexplained resurgence of serum ferritin levels occurred in 4/7 patients of the 'veteran' group after 4-5 years on L1. In three of these a concomitant increase of liver iron was also observed. Hepatic histology revealed significantly higher degrees of fibrosis in 6/11 hepatitis C (HC)-positive patients (fibrosis scores 1-5, mean 3.0) than in the HC-negative group (fibrosis score 0-2, mean 0.8). Two HC-negative patients had no detectable fibrosis after 98 and 93 months on deferiprone. Therefore the hepatic pathology in these patients cannot definitely be attributed as a side-effect of deferiprone. Chronic active hepatitis C and the accumulation of iron are the major causative factors to be considered.

Adolescent↗