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Biomedical subjects

K Kiehne

Publications and source records attributed to K Kiehne.

At least 19 recordsLinked to original sources
PubMed2002

Unusual course of colonic tattooing with India ink.

We here report the successful but unusual course of colonic tattooing in a patient with a carcinoma in situ in a polyp. A 70-year-old woman was admitted for persistent diarrhea, occult fecal blood, and anemia. During colonoscopy, a pedunculated large polyp in the sigmoid colon occluding the lumen was removed successfully. Histopathological examination revealed a carcinoma in situ with a resection of the peduncle in sano. At the second sigmoidoscopy, the polypectomy site was marked with India ink to facilitate the recovery of the polypectomy site in follow-up endoscopies. Three months later, the India ink had spread in the submucosal layer and a segment measuring 15 cm was colored dark blue. At the original polypectomy site, an uncolored flat mucosal proliferation was found above the dark colonic wall. After mucosectomy, the tissue was classified as hyperplastic. Six weeks later, a second control sigmoidoscopy did not show any suspicious mucosal alterations.

Adenoma, Villous↗
PubMed2001

Mechanisms of lectin (phytohemagglutinin)-induced growth in small intestinal epithelial cells.

BACKGROUND/AIMS: The lectin phytohemagglutinin is a mitogen for intestinal epithelial cells in vivo. The mechanisms of action are unknown and were therefore analyzed in vitro. METHODS: Human (Intestine-407) and rat (IEC-6; IEC-18) intestinal epithelial cell lines were stimulated with phytohemagglutinin. Proliferation was assayed by (3)H-thymidine incorporation, activation of mitogen-activated protein kinase (MAPK) by Western blotting, and induction of c-fos mRNA expression by semiquantitative polymerase chain reaction. Control experiments were performed with phenyl-N-acetyl-alpha-D-galactosaminide or the tyrosine kinase inhibitor tyrphostin A25. RESULTS: Phytohemagglutinin (0.1 microg/ml) significantly stimulated proliferation in all three cell lines after 48-72 h. MAPK activation was detected after 15-30 min, and an induction of c-fos mRNA expression after 15- 30 min of stimulation. Mitogenic effects were blocked by preincubation with phenyl-N-acetyl-alpha-D-galactosaminide or tyrphostin A25. CONCLUSION: Phytohemagglutinin stimulated proliferation, MAPK activation and induction of c-fos mRNA expression. The lectin may contribute to intestinal mucosal growth and regeneration thereby preventing gut atrophy.

Animals↗
PubMed2000

High complication rate of bile duct stents in patients with chronic alcoholic pancreatitis due to noncompliance.

BACKGROUND AND STUDY AIMS: Biliary obstruction in chronic pancreatitis is frequently treated by endoscopic insertion of a plastic stent into the common bile duct, a therapy regarded as having a low complication rate. The aim of this study is to analyze the frequency and severity of complications caused by biliary stents in patients with chronic alcoholic pancreatitis. PATIENTS AND METHODS: We retrospectively analyzed all our patients with chronic pancreatitis (n = 14) who were provided with a plastic stent for biliary stenosis between June 1993 and December 1997. Stent exchanges were followed until December 1998. RESULTS: Stent insertion was performed without early complications and was successful in each patient. Only two patients were admitted after 3-4 months at the scheduled dates for stent exchange, both without complications. In one of these patients, the bile duct stenosis was reopened after two stent exchanges over a total period of 8 months. Most of our patients (n=12) did not come at the arranged dates for stent exchange. They were repeatedly admitted (mean 2.9 times/patient, range 1-5) as emergency cases with severe complications of biliary obstruction, such as cholangitis or biliary sepsis. Reopening of the bile duct stenosis was not achieved in these patients. CONCLUSIONS: We associate the high rate of complications with the noncompliance of our patients, who were all alcoholics. The high incidence of late complications in noncompliant patients is a limitation of biliary stenting, and appears to be potentially harmful.

Adult↗
PubMed2000

C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and in pancreatic cancer cells.

BACKGROUND: Activation of the receptor c-met stimulates motility, mitosis, morphogenesis, processes involved in organ regeneration, or progression of malignancies. In the present study we investigated the expression of c-met protein in the regenerating pancreas and characterized the influence of cytokines on c-met expression. METHODS: Acute pancreatitis was induced in rats by cerulein injection. Rat acini and rat and human pancreatic cancer cells were stimulated with interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta1 (TGF-beta1). C-met expression was analyzed by means of Western blotting and localization in pancreatic tissue by immunohistochemistry. RESULTS: C-met protein expression was significantly upregulated in the regenerating pancreas and localized in areas of regenerating tissue. Stimulation with cytokines resulted in a two- to threefold increase of c-met expression in vitro. CONCLUSION: Enhanced c-met expression after acute pancreatitis suggests that HGF/met has an important role in pancreatic regeneration, which is probably mediated by cytokines. This regulatory mechanism is also of importance in pancreatic cancer.

Acute Disease↗
PubMed2000

Functional expression of HGF and its receptor in human colorectal cancer.

BACKGROUND: Hepatocyte growth factor (HGF) stimulates proliferation, migration and morphogenesis of epithelial cells by specific binding to its receptor c-met. Overexpression of HGF or c-met has been reported for human gastric or pancreatic cancer. In colorectal cancer overexpression of c-met but not HGF has been shown. However, elevated HGF serum levels have been detected in colorectal cancer patients. Therefore, the present study was performed to investigate expression patterns of both c-met and HGF in colorectal cancers and metastasis in comparison to normal mucosa. Furthermore, the mitogenic actions of HGF on colorectal cancer cells were studied in vitro. METHODS: Expression of c-met and HGF were analyzed by RT-PCR and Western blotting and localized in the tissues utilizing immunohistochemistry. Mitogenic effects of HGF were determined in four human colon cancer cell lines by (3)H-thymidine incorporation studies. RESULTS: C-met and HGF mRNA were detectable in 60% of the normal specimen, but in the majority of cancer samples, and in just 33% of the liver metastasis. In cancer samples a coexpression of c-met and HGF was detected in 77% of the specimens. The extent of protein expression of receptor and ligand correlated with the mRNA expression. Moreover, c-met protein expression was increased 2- to 3-fold in colorectal cancers. C-met was detected in cells of epithelial origin, whereas HGF was expressed by mesenchymal cells. In vitro, HGF significantly stimulated cell growth in all four cell lines. CONCLUSION: Overexpression of c-met protein in colorectal cancers is combined with an expression of HGF in the majority of cases suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues.

Adenocarcinoma↗
PubMed1997

Thyroid autoantibodies and thyroid dysfunction during treatment with interferon-alpha for chronic hepatitis C.

Interferon-alpha (2a or 2b) is increasingly used for treatment of chronic hepatitis C virus (HCV) infection. Recent reports suggested a correlation between increases in thyroid autoantibodies and the development of thyroid dysfunction during interferon-alpha therapy. In this study, we analyzed thyroid hormones and antithyroid antibodies at monthly intervals in 53 patients who received interferon alpha for chronic active hepatitis C infection. Of five patients with initially elevated levels of antithyroid peroxydase antibodies (anti-TPO), the antibodies increased further in two of them. Ten patients, who started interferon therapy with normal antibody levels, developed elevated anti-TPO antibodies for limited times during treatment. Levels of anti-TPO antibodies showed a marked fluctuation, and only three patients had increased anti-TPO antibodies persisting for longer than 3 mo. Antithyroglobulin antibodies appeared in four patients, all of whom were also positive for anti-TPO antibodies. No changes in TRAB levels were observed. All of these patients with elevated antithyroid antibodies remained in an euthyroid state. One patient with normal antithyroid antibodies developed thyroiditis with severe thyrotoxicosis after 9 wk of interferon therapy. These findings suggest that the induction of antithyroid antibodies during treatment with interferon-alpha does not indicate clinical relevant thyroid dysfunction. Routine measurement of antithyroid antibodies during interferon-alpha therapy does not seem to be mandatory.

Adult↗
PubMed1997

c-met expression in pancreatic cancer and effects of hepatocyte growth factor on pancreatic cancer cell growth.

Hepatocyte growth factor (HGF) is a widely expressed growth factor secreted by cells of mesenchymal origin, which has been shown to be involved in growth processes of multiple cell types. The HGF receptor, the product of the c-met protooncogene, is expressed mainly by epithelial cells. Increased expression of the HGF receptor has been observed in various tumors. To investigate the expression of the HGF receptor in the pancreas, we analyzed rat and human normal tissue and pancreatic carcinoma by Western blot analysis. We observed weak expression of c-met reactivity in normal pancreas but markedly enhanced expression in both rat and human pancreatic cancer. To test the possibility that HGF could act as a growth factor on pancreatic carcinoma, the effects of HGF on DNA synthesis in a rat and two human pancreatic carcinoma cell lines were analyzed. HGF induced dose-dependent [3H]thymidine incorporation, reaching 320, 210, and 180% above unstimulated controls in AR4-2J, PancTu-1, and 818/4 cells, respectively. The activation of signal transduction pathways by HGF was further analyzed in AR4-2J cells. After stimulation, a rapid and intense increase in receptor tyrosine phosphorylation was detected. Furthermore, HGF induced a time- and dose-dependent induction of c-fos expression. The addition of tyrphostin, a specific tyrosine kinase inhibitor, prevented c-fos induction and inhibited HGF-induced [3H]thymidine incorporation. In summary, our results demonstrate strongly increased HGF receptor expression in pancreatic carcinoma and support the assumption that HGF could act as a growth promoting factor on this cancer via stimulation of tyrosine kinases.

Animals↗
PubMed1996

[Chronic granulomatous chorioretinitis in tuberculosis].

BACKGROUND: Though the incidence of tuberculosis decreased substantially during the second half of the century, a steady increase of new cases has been observed within the last decade. Among other reasons, the growing number of immunodeficient patients (e.g. HIV, therapy with immunosuppressive agents) and migration from underdeveloped to industrial countries contribute to this finding. PATIENT: A 57-year-old male patient presented with a history of chronic bilateral chorioretinitis of unknown origin. During the last months a marked decrease in visual acuity of the left eye was noted. Prior diagnostic attempts had not led to a specific diagnosis. Notable was the history of long-term systemic corticosteroid therapy for chronic obstructive lung disease. Funduscopy of the right eye revealed a choroidal granuloma with adjacent serous retinal detachment. Both eyes showed multiple dot-like lesions in the retinal pigment epithelium of the posterior pole. Finally the diagnosis could be made by isolating Mycobacterium tuberculosis from sputum samples and gastric aspirate. Within a few weeks after starting tuberculostatic therapy the ocular symptoms regressed and the visual acuity improved significantly. DISCUSSION: Securing the diagnosis of tuberculous uveitis is often difficult. The differential diagnosis includes other granulomatous ocular inflammations. The detection of Mycobacterium tuberculosis and the clinical course make the diagnosis most likely. CONCLUSION: Tuberculosis should always be included in the differential diagnosis as a possible etiology for uveitis, particularly in those cases taking a chronic course. Despite the recent emergence of drug-resistant strains in most cases tuberculosis is a well curable disease.

Chorioretinitis↗
PubMed1995

Down-regulation of bradykinin receptors and bradykinin-induced Ca2+ mobilization, tyrosine phosphorylation, and DNA synthesis by autocrine factors, tumor necrosis factor alpha, and interferon beta in Swiss 3T3 cells.

Preincubation of quiescent Swiss 3T3 cells in fresh synthetic medium caused a reduction of the lag period prior to bradykinin-stimulated DNA synthesis as well as a leftward shift in the dose-response curve (half-maximum effect at 2 nM and 8 nM for preincubated cells and control cells, respectively). These enhancing effects were selective for bradykinin since vasopressin-stimulated DNA synthesis was not affected by preincubation in synthetic medium. Preincubation in synthetic medium also caused a marked enhancement (five- to sixfold increase) of bradykinin-induced Ca2+ mobilization from intracellular stores. This enhancement was time-dependent, peaked after 12 h of preincubation, and was prevented by inhibition of RNA or protein synthesis. Furthermore, preincubation in synthetic medium did not enhance the Ca2+ mobilization by bombesin, vasopressin, or PDGF. Additionally, bradykinin-induced tyrosine phosphorylation was also enhanced by prior incubation in fresh medium. Scatchard analysis of [3H]bradykinin binding revealed a doubling of the number of bradykinin receptors without any significant change of affinity after preincubation, thus providing an explanation for the increased cellular responsiveness to bradykinin. This enhancement of responsiveness to bradykinin was caused by the removal of an inhibitory factor present in conditioned medium which is produced by the cells and accumulates gradually in the medium. Addition of tumor necrosis factor alpha or interferon beta to synthetic medium substituted for conditioned medium in preventing the increase in responsiveness to bradykinin. These findings demonstrate a novel mechanism that regulates cellular sensitivity to bradykinin via an autocrine factor(s).

3T3 Cells↗
PubMed1994

Synergistic stimulation of DNA synthesis by bradykinin and vasopressin in Swiss 3T3 cells.

Vasopressin and bradykinin bind to receptors coupled to GTP-binding proteins and rapidly induce polyphosphoinositide breakdown leading to Ca2+ mobilization and activation of protein kinase C. Both peptides are known to induce mitogenesis in the presence of growth factors that act through receptors with intrinsic tyrosine kinase activity. Surprisingly, addition of a combination of vasopressin and bradykinin to Swiss 3T3 cells synergistically stimulates DNA synthesis in the absence of any other growth factors. This effect is induced at nanomolar concentrations of the peptides and could be inhibited by addition of specific receptor antagonists or broad spectrum neuropeptide antagonists. Bradykinin, which stimulates transient activation of protein kinase C, induces DNA synthesis in synergy with substances that cause long-term activation of protein kinase C, like vasopressin or phorbol 12,13-dibutyrate. Down-regulation of protein kinase C inhibited the induction of mitogenesis by the combination of vasopressin and bradykinin, thus demonstrating the importance of long-term activation of this enzyme for DNA synthesis. Analysis of tyrosine phosphorylated proteins of M(r) = 110,000-130,000 and M(r) = 70,000-80,000 revealed a biphasic response after stimulation with bradykinin, whereas the response induced by vasopressin declined after the initial maximum. The combination of bradykinin with vasopressin caused an enhanced and prolonged increase in tyrosine phosphorylation of these proteins as compared with the individual peptides. Inhibition of tyrosine phosphorylation by tyrphostin was paralleled by inhibition of DNA synthesis. Together, these results demonstrate synergistic stimulation of DNA synthesis by bradykinin and vasopressin via prolonged stimulation of multiple signaling pathways and imply that the interactive effects of Ca(2+)-mobilizing peptides on mitogenesis may be more general than previously thought.

3T3 Cells↗
PubMed1992

The influence of alpha- and beta-galactose residues and sialic acid O-acetyl groups of rat erythrocytes on the interaction with peritoneal macrophages.

The significance of glycoconjugates on the surface of rat erythrocytes was studied in the interaction of these cells with homologous peritoneal macrophages. The erythrocytes exposing terminal alpha-galactose and thus of B blood group specificity, as well as sialic acid are not bound by the macrophages. beta-Galactose residues exposed by sialidase induced strong binding and additional alpha-galactosidase treatment enhanced the binding. beta-Galactose exposed on glycolipids after pronase and alpha-galactosidase treatment induced no binding. An intact protein core of the glycoproteins on the erythrocyte surface was necessary for interaction with macrophages. Partial de-O-acetylation of sialic acids prior to sialidase treatment stimulated subsequent binding of the erythrocytes.

Acetylation↗
PubMed1991

Cell-specific expression of plant histone H2A genes.

Histone H2A is a component of eukaryotic chromatin whose expression has not been studied in plants. We isolated and characterized a tomato and a pea cDNA encoding histone H2A. We found that in tomato H2A is encoded by a small gene family and that both the pea and the tomato mRNAs are polyadenylated. Tomato H2A has 82% amino acid residue identity to pea H2A, 83% to wheat, and 65% to human and yeast H2A. Plant H2As differ from fungal and animal H2As in their amino-terminal and carboxy-terminal regions. Carboxy-terminal plant H2A regions contain the motif SPKK, a peptide implicated in binding of A/T-rich DNA regions. By using RNA gel blot analysis, we determined that the steady-state mRNA level of these genes was abundant in apices and early developing fruit and very low in mature tissues. In situ RNA hybridization showed strong spatial regulation because the mRNA was abundant in some cells and not detectable in others. In tomato shoot tips, H2A-expressing cells were distributed irregularly in or near meristems. In tomato or pea root tips, expressing cells were concentrated near the apex, and their distribution was consistent with that expected of cycling cells. Other H2A transcripts were found in nondividing cortical cells that are known to undergo endoduplication during the late maturation phase of primary development.

Amino Acid Sequence↗