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Biomedical subjects

K Böker

Publications and source records attributed to K Böker.

At least 19 recordsLinked to original sources
PubMed2001

Autoimmune hepatitis associated with coagulation disorders and immunethyreopathy.

We present the case of a 42-year-old female patient with the diagnoses of autoimmune hepatitis type I and autoimmune thyroiditis. Furthermore this patient had an unusual combination of coagulation disorders with homozygous Factor V Leiden mutation (APC resistance) and presence of antiphospholipid antibodies, leading to deep vein thromboses and miscarriages. Only few cases with the combination of autoimmune hepatitis and antiphospholipid antibodies have been described and almost all of them had become symptomatic with the antiphospholipid syndrome. As both autoimmune phenomenons furthermore share similar HLA-patterns, their coincidence is probably not as uncommon as the limited number of case reports suggests. Therefore attention in patients with autoimmune hepatitis should be focused on thrombophilia.

Activated Protein C Resistance↗
PubMed2001

Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease.

Hepatitis C virus (HCV) infection becomes chronic in more than 70% of patients, leading to end stage liver disease in about 20-30% of these patients. Apart from the virus itself, host factors that modulate the immune response are likely to be involved in determining the outcome of HCV infection. Studies on the association of human leucocyte antigens (HLAs) and HCV infection have shown inconsistent results. Selection of patient subgroups may be crucial. However, any association relevant to HCV disease progression will become evident, especially in those patients with end stage liver disease. Therefore, we analysed the phenotype frequencies of HLA antigens in two groups of 69 and 39 patients with HCV induced liver cirrhosis who had received a transplant or were awaiting liver transplantation. The first group was typed serologically and compared with 331 blood and liver donors. The second group, prospectively HLA typed by a polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) procedure for HLA-DRB and DQB alleles, was compared with another 170 PCR-SSO typed and randomly selected blood donors. Decreased frequencies for HLA-DR5 and HLA-DQ3 were found in one group of patients with HCV induced liver cirrhosis compared with the control groups. In the second analysis comparing 39 patients with end stage liver cirrhosis with blood donors, we confirmed the significant decrease in HLA-DRB1*11 and HLA-DQB1*03, which corresponded to serological HLA-DR5 and HLA-DQ3 antigens, respectively. Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03 alleles is associated with a reduced risk for the development of HCV induced end stage liver disease.

Alleles↗
PubMed1999

Mutation analysis in patients with Wilson disease: identification of 4 novel mutations. Mutation in brief no. 250. Online.

In order to obtain novel mutations in the recently discovered Wilson disease gene, we screened 5 unrelated German individuals for mutations in the 21 exons and their flanking intronic sequences. We detected 9 mutations affecting the Wilson disease gene. Four of those, designated 802-808delTGTAAGT, 2008-2013delTATATG, Cys985Thr, and Ile1148Thr have not yet been reported. One patient had a homozygous mutation whereas the remaining four subjects were compound heterozygous. Therefore these data confirm, that mutations causing Wilson disease are frequently found in affected subjects and they are very heterogenous.

Adenosine Triphosphatases↗
PubMed1999

Familial Amyloidotic Polyneuropathy: domino liver transplantation.

BACKGROUND/AIMS: The primary cause of Familial Amyloidotic Polyneuropathy is a variant transthyretin gene on chromosome 18. Progressive polyneuropathy followed by fatal cardiac and renal failure commonly manifest during middle age. Within 10 years after onset of clinical symptoms, affected individuals usually die due to malnutrition or heart failure. Currently, liver transplantation is the only available therapeutic option. METHODS: We performed liver transplantation in two patients with Familial Amyloidotic Polyneuropathy carrying the transthyretin-30 mutant. Two patients aged more than 50 years received the two explanted amyloidotic livers. This procedure is called Domino liver transplantation. We report the outcome in the studied subjects and analyze the metabolic consequences of this procedure. RESULTS: We determined the serum half-life of transthyretin-30 as 2.25 days using daily monitoring of transthyretin-30 levels. An affected amyloidotic patient had an increased serum concentration of lipoprotein(a) of 78 mg/dl before transplantation. The tumor patient, who received the organ from this affected patient, developed an almost identical serum concentration of lipoprotein(a) after liver transplantation, confirming the liver as the primary site of synthesis of this lipoprotein. CONCLUSION: Once Domino liver transplantation has been performed, the impact of the liver-dependent metabolism of specific proteins of interest can be studied.

Adult↗
PubMed1999

Malabsorption with progressive weight loss and multiple intestinal ulcers in a patient with T-cell lymphoma.

We describe a 52-year-old woman who presented with severe diarrhea, nausea, intermittent abdominal pain and weight loss of 18 kg within ten months. Jejunal and duodenal ulcers were detected by endoscopy and multiple biopsies revealed villous atrophy of the jejunum. However, neither gliadin nor endomysium antibodies were detected and no clinical and histological improvement was achieved after gluten withdrawal. Despite strong clinical suspicion for intestinal lymphoma many unrevealing biopsies were done. The patient developed intermittent septic fever and diagnostic laparotomy revealed jejunal perforation. Partial jejunal resection was performed and histology confirmed the diagnosis of an intestinal T-cell lymphoma without celiac disease. Malabsorption and all intestinal ulcers disappeared during the course of chemotherapy (six cycles CHOP) and the patient recovered remarkably.

Biopsy↗
PubMed1998

Two-step procedure in Budd-Chiari syndrome with severe intrahepatic vena cava stenosis: vena cava stenting and portocaval shunt.

Budd-Chiari syndrome is characterized by hepatic venous outflow obstruction, which often leads to death as a result of portal hypertension and liver failure. Venous decompressive shunt surgery and liver transplantation represent efficient surgical treatments of Budd-Chiari syndrome. In the case presented here, severe intrahepatic compression of the inferior vena cava (IVC) was caused by the hypertrophic caudate lobe. A mere portocaval shunt was not feasible because of a large pressure gradient across the intrahepatic stenosis. A two-step procedure with preoperative radiological dilation and stenting of the intrahepatic IVC followed by a portocaval shunt was successfully performed. Consequently, liver transplantation and its subsequent immunosuppression could be avoided.

Adult↗
PubMed1997

[Therapy of persistent bleeding esophageal varices using intrahepatic portosystemic stent shunt and immediate liver transplantation].

A 41-year-old patient with liver cirrhosis due to autoimmune hepatitis received an emergency transjugular portosystemic stent shunt for uncontrolled acute variceal hemorrhage. Because of markedly impaired liver function, liver transplantation was considered to be indicated and was performed on the following day. Intraoperatively, one of the intrahepatic metal stents migrated unnoticed into the pulmonary artery. The postoperative course was uncomplicated and the displaced stent was left in situ. Eighteen months after the transplantation the patient is well with normal liver function and no pulmonary problems.

Adult↗
PubMed1997

Hepatitis B associated liver failure following bone marrow transplantation.

BACKGROUND: Several cases have been reported showing clearance of HBsAg in chronic hepatitis B carriers due to adoptive transfer of immunity by an hepatitis B immunised bone marrow. CASE REPORT: We report on a 27-year-old man with chronic myelocytic leukemia and asymptomatic chronic hepatitis B who received allogeneic bone marrow transplantation (BMT). The donor was his HLA identical brother with natural immunity against hepatitis B. Before BMT the donor had received an additional dose of recombinant hepatitis B vaccine. Twenty days after BMT alanine aminotransferase levels increased and graft versus host disease of the skin was observed. Elevation of liver enzymes was initially attributed to graft versus host disease of the liver and the patient received high doses of steroids in addition to standard immunosuppression. Alanine aminotransferase levels increased up to a maximum on day 52 while the HBV DNA level peaked on day 38 after BMT. A liver biopsy showed reactivation of hepatitis B and treatment with steroids was tapered down. Although alanine aminotransferase and HBV DNA levels decreased, liver function deteriorated. The patient died 130 days after BMT due to liver failure. CONCLUSION: This report indicates that disturbance of the balance between HBV replication and immune control after BMT may result in fatal reactivation of hepatitis B. Careful monitoring, including HBV DNA level and early liver biopsy, of patients with chronic hepatitis B undergoing BMT as well as determination of the HBV immune status of the BMT donor is suggested and necessary.

Adoptive Transfer↗
PubMed1997

Fatal clinical course of ornithine transcarbamylase deficiency in an adult heterozygous female patient.

Ornithine transcarbamylase (OTC) deficiency is an X-linked inherited disease and the most common inborn error in urea synthesis in humans. In adult heterozygous patients, partial OTC deficiency can be responsible for life-threatening hyperammonemic coma, with a frequency of 15 %. We report the clinical course of a heterozygous female patient and discuss the therapeutic options, including hemodialysis and continuous arteriovenous hemofiltration for reduction of ammonia levels as well as liver transplantation as a definitive therapy.

Adult↗
PubMed1996

Association between fulminant hepatic failure and a strain of GBV virus C.

BACKGROUND: The GB virus C (GBV-C) and the hepatitis G virus (HGV) have been detected in patients with acute indeterminant hepatitis and post-transfusion hepatitis. However, the role of the new hepatitis viruses in the aetiology of fulminant hepatitis is little understood. We investigated the presence of GBV-C/HGV in patients with fulminant hepatic failure. METHODS: Serum samples from 22 German patients with fulminant hepatic failure and 106 symptom-free blood donors (controls) were studied for presence of GBV-C RNA by seminested reverse transcriptase PCR. Primer sequences were derived from the published gene sequences of the conserved NS3 region of the GBV-C prototype and the published isolates. Nucleotide and amino acid sequences of GBV-C-positive isolates, the control RNA, and the published HGV and GBV-C prototype sequences were compared by multiple sequence alignment. We also compared the GBV-C sequences of virus-positive patients who had fulminant hepatic failure with those of 19 patients with chronic hepatitis from our centre. In addition, we searched databases and published papers for further GBV-C helicase sequences in patients with non-fulminant hepatitis. FINDINGS: GBV-C RNA was detected in 11 (50%) of the 22 patients with fulminant hepatic failure and in five (4.7%) of 106 control-group blood donors. Among the patients with fulminant hepatic failure, six of seven with fulminant hepatitis B and five of ten with fulminant non-A-E hepatitis were positive for GBV-C RNA. Analysis of nucleic acid sequences showed six mutations at defined positions in all 11 patients with fulminant hepatic failure who were positive for GBV-C. None of these mutations were found in the five GBV-C-positive control-group blood donors. Of the six nucleotide changes, four caused no amino acid changes, whereas two mutations at position 100 (G to T) and 102 (T to C) led to an alanine to serine change in the predicted translation product. However, comparison with GBV-C sequences of patients with non-fulminant hepatitis showed that this amino acid mutation was not specific for fulminant hepatic failure. The sequence-motif containing the six nucleotide mutations detected in all patients with fulminant hepatic failure was found in only two of 19 German patients with chronic hepatitis from our centre, and in only one of 88 GBV-C sequences from non-fulminant patients reported by others. INTERPRETATION: The frequency of GBV-C RNA is higher in fulminant hepatic failure than in any other group of patients with hepatitis, particularly in patients with fulminant hepatitis B or fulminant non-A-E hepatitis. A specific strain of GBV-C may occur in serum of German patients with fulminant hepatic failure.

Adult↗
PubMed1996

3-D coculture of hepatic sinusoidal cells with primary hepatocytes-design of an organotypical model.

Models for cocultures of parenchymal (PC) and nonparenchymal cells (NPC) of the liver relied on mixing the cells in a two-dimensional configuration or on establishing spheroidal aggregates. In vivo hepatic nonparenchymal cells, such as endothelial cells and Kupffer cells, are separated from parenchymal cells by extracellular matrix (ECM). Due to their location outside of the space of Disse they can form a barrier toward the sinusoid. Hepatocytes are attached to ECM of the space of Disse via two opposing sinusoidal surfaces. No three-dimensional coculture model reflecting this specific microenvironment of the liver cell plates in vivo has been available to date. We designed a three-dimensional model by positioning NPC on top of PC enclosed as a monolayer within a collagen sandwich. A gas-permeable membrane support can be used to allow the supply of oxygen to the resulting cell plate also from underneath the cell layers. Morphological analysis was performed by inverse and cross-sectional studies by light microscopy, scanning, and transmission electron microscopy of the coculture model. Cuboidal hepatocytes formed confluent layers below the NPC layer. They regularly expressed bile canaliculi at intercellular contact zones. Both sinusoidal surfaces expressed microprojections. Characteristic NPC including endothelial cells, Kupffer cells, and Ito cells completely covered the second matrix layer within a week. Kupffer cells were located on top of endothelial cells. Ito cells were intermingled and could be identified by their intracytoplasmic lipid droplets. LPS stimulation of cocultures resulted in a depression of albumin secretion. Phase I and phase II metabolites of the cytochrome P-450 1A1 substrate ethoxyresorufin were generated independently from the presence of cocultured NPC. This study describes the development of a novel three-dimensional coculture model, which intends to mimic more closely the microenvironment of the hepatic sinusoid by respecting the specific plate structure of the liver parenchyma. The model could serve as a complex tool to study potential collaborations between PC and NPC of the liver.

Albumins↗
PubMed1996

Development, stability, and clinical correlations of allogeneic microchimerism after solid organ transplantation.

To assess the development, stability, and clinical relevance of donor-type microchimerism, skin and blood were analyzed in heart (n = 53) and liver (n = 18) transplant recipients by nested polymerase chain reaction. Microchimerism was detectable in 40 (75%) and 13 (72%) patients after heart and liver transplantation, respectively. In heart transplantation, chimerism-positive patients showed a lower frequency of acute rejection as compared with negative patients, although this was only of borderline statistical significance. Repeated intraindividual analyses demonstrated variable patterns of microchimerism over time, but changes did not correlate to the clinical state. In liver transplantation, chimeric state showed no clear correlation with the patients' immunological situation. Our results demonstrate that peripheral microchimerism frequently develops after different types of organ transplantation and represents a dynamic process but without diagnostic value to predict the immunological risk for individual patients.

Base Sequence↗
PubMed1996

The creatinine approach to estimate skeletal muscle mass in patients with cirrhosis.

The creatinine-method to estimate muscle mass is frequently used in clinical studies, although the validity of this approach is uncertain in patients with cirrhosis. In this study 102 patients with cirrhosis differing in cause, clinical state, liver, and renal function were investigated to determine whether reduced liver or renal function may explain in part the low levels of urinary creatinine excretion frequently observed in these patients. Muscle mass assessed by 24-hour urinary creatinine excretion was compared with anthropometrically obtained muscle mass calculated from arm muscle area (AMA), and with body cell mass (BCM) estimated by bioelectrical impedance analysis and total body potassium counting. In cirrhosis, the 24-hour urinary creatinine excretion was 10.4% and AMA was 19% lower than predicted values. The differences between the results obtained by different methods did not show any relation to parameters of liver function (ICG-t1/2, caffeine-t1/2, MEGX-test, cholinesterase) or the severity of liver disease (i.e., Child-Pugh score). In contrast, renal function was strongly correlated with the differences between creatinine- and anthropometric-muscle mass (r = .64, P < .001). At the same time, patients with normal renal function (62% of the whole population) had significantly higher creatinine (29.1 +/- 8.5 vs. 15.8 +/- 6 kg, P < .001) and anthropometric-muscle mass (22.4 +/- 6 vs. 17.9 +/- 5.3 kg; P < .01) than patients with reduced renal function (38% of the patients). In addition, significantly higher differences between measured and predicted values of urinary creatinine excretion (-0.389 +/- 0.33 vs. 0.06 +/- 0.31 g/24 h; P < .001) and of AMA (13.2 +/- 12 vs. 7.2 +/- 12 cm2; P < .03) were found in the subgroup with impaired renal function. In conclusion, renal dysfunction but not reduced liver function systematically affects the urinary creatinine method for the estimation of skeletal muscle mass in cirrhosis.

Adult↗
PubMed1996

[Indications for liver transplantation in severe amanita phalloides mushroom poisoning].

The clinical course of 12 patients with mushroom poisoning was evaluated in order to define the parameters considered to be relevant to the indication for liver transplantation. Eight patients recovered under conservative therapy; one patient died due to pre-existing, concomitant cardiopulmonary disease. In three patients transplantations had to be performed because of severe liver failure. On admission, the transplanted patients had a decreased Quick's test score and factor V value (< 10%). The peak of liver enzymes, serum bilirubin, serum creatinine, partial thromboplastin time and azotemia were not of any prognostic value. Main indications for liver transplantation were a very low initial Quick's test score and factor V value (both < 10%) and their inadequate response under substitution therapy. The development of encephalopathy and renal failure were further parameters indicating poor prognosis.

Adolescent↗
PubMed1995

Ultrastructural and functional differentiation of hepatocytes under long-term culture conditions.

BACKGROUND: Studies on hepatocytes grown in different culture systems have shown that these cells rapidly dedifferentiate on a single support with liquid medium on top (single gel technique). However, in systems sandwiching them between two layers of extracellular matrix (double gel technique), the cells are able to regain and maintain typical light microscopical appearance and function. Their ultrastructural morphology is as yet unknown. METHODS: Isolated, adult rat hepatocytes were grown in both systems, and their fine structure (thin section electron microscopy) and the functional ability of albumin production (immunoassay) were studied and compared in both culture systems after 2, 7, and 14 days. RESULTS: The hepatocytes in conventional single gel culture did not completely regain their normal morphology and rapidly underwent progressive dedifferentiation. This was characterized by loss of cell polarization in terms of obliteration of the bile canaliculi-like intercellular expansions, loss of cell membrane differentiations, and reduction of organelles. Cytoskeletal components gradually increased, building up large filamentous zones underneath the plasma membrane. In double gel culture, the hepatocytes reachieved and maintained intact morphology and polarity over at least 14 days. The bile canaliculi were formed, preserved, or even enlarged and were associated with dense peribiliary bodies and Golgi fields. The plasma membrane facing both collagen layers bore numerous cytoplasmic microprojections like the sinusoidal surfaces of the hepatocytes in situ. Cell organelles, glycogen particles, and lipid droplets were always present. CONCLUSIONS: The hepatocyte is a cell type in which ultrastructural and functional differentiation are strongly interdependent. For these cells, the morphological microenvironment (i.e. the bipolar position of the extracellular matrix) may be as important or even more decisive for maintenance of normal cell differentiation than modifications of the composition of the matrix itself or addition of other cell types, as focused in other studies.

Albumins↗
PubMed1995

An organotypical in vitro model of the liver parenchyma for uptake studies of diagnostic MR receptor agents.

Testing of receptor-specific MR contrast agents targeted to the liver is hampered by a shortage of viable in vitro models with in vivo-like hepatocellular morphology. Coated pits are ultrastructural signs of an active receptor mediated endocytosis in hepatocytes. Expression of coated pits by matrix overlaid hepatocytes was studied by transmission electron microscopy. Binding of a rhodaminated asialoglycoprotein receptor agent (MION-ASF-rh) was assessed by fluorescence microscopy. Fluorescence of cells exposed to MION-ASF-rh with D(+)-galactose reduced fluorescent light emission to a level of 58% of MION-ASF-rh-induced fluorescence. After preincubation with the hepatotoxin CCl4 a dose-dependent decrease in fluorescent light emission resulted. Hepatocytes maintained a homogeneous cell surface expression, with microprojections, coated pits, and vesicles on both sinusoidal surfaces. Matrix overlaid primary hepatocytes constitute a viable, morphologically and functionally differentiated model. This model can be used to study receptor binding, uptake, and blockage of diagnostic magnetopharmaceuticals under controlled conditions.

Animals↗
PubMed1995

Circulating and tissue guanylin immunoreactivity in intestinal secretory diarrhoea.

Guanylin is a recently discovered peptide hormone that activates intestinal guanylate cyclase (GC-C) and thereby stimulates intestinal chloride secretion. Immunohistochemistry showed its presence in enterochromaffin (EC) cells of the gut. In vitro studies suggested that guanylin plays an important role in the endogenous modulation of intestinal salt and water secretion. In the present study the concentration of circulating immunoreactive (IR)-guanylin in plasma of patients with intestinal diarrhoea due to chronic bowel inflammation and patients with carcinoid tumours were measured with a specific radioimmunoassay. In 22 patients with Crohn's disease and eight patients with ulcerative colitis, plasma concentrations of IR-guanylin were 44 +/- 3 and 42 +/- 4 fmol mL-1, respectively. Levels were not different from that in 44 healthy volunteers suggesting that the circulating hormone is not involved in diarrhoea of these patients. In 17 patients with symptomatic carcinoid tumors the median concentration of circulating IR-guanylin was significantly enhanced (94 +/- 16 fmol mL-1, range 37-312 fmol mL-1). Immunohistochemistry revealed the presence of immunoreactive guanylin in carcinoid tissues, suggesting that these tumours co-release guanylin along with their usual resident hormone, serotonin. Enhanced local secretion of guanylin may play a causal role in diarrhoea of these patients and its elevation in plasma may be of diagnostic value in this type of endocrine tumours.

Adult↗