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Biomedical subjects

C Hanck

Publications and source records attributed to C Hanck.

At least 19 recordsLinked to original sources
PubMed2005

A 93 year old man with the PRSS1 R122H mutation, low SPINK1 expression, and no pancreatitis: insights into phenotypic non-penetrance.

BACKGROUND: The cationic trypsinogen (PRSS1) R122H mutation causes autosomal dominant hereditary pancreatitis (HP) with multiple attacks of acute pancreatitis, but the penetrance, frequency, and severity of attacks are highly variable. HP twins study suggests that modifier genes influence severity but not penetrance. AIM: To investigate potential trypsin associated factors in subjects with the PRSS1 R122H mutation and phenotypic non-penetrance. METHODS: Two subjects from HP families (including a 93 year old subject with PRSS1 R122H without pancreatitis), one with chronic pancreatitis and one with a normal pancreas, were studied. Relative expression of: (a) the PRSS1 R122 and H122 alleles; and (b) the PRSS1 and SPINK1 genes in pancreatitis were determined using complementary methods. RESULTS: PRSS1 wild-type (R122) and mutant (H122) allele expression was equivalent in multiple (> 3) samples from the phenotypically affected and non-penetrant subjects with R122H genotypes using allele specific quantitative reverse transcription-polymerase chain reaction (RT-PCR) and intron spanning nested RT-PCR followed by cDNA sequencing. Compared with PRSS1 mRNA levels, SPINK1 mRNA levels were low in normal appearing tissue but markedly increased in samples with chronic inflammation, independent of PRSS1 genotype. CONCLUSION: Attacks of acute pancreatitis in HP subjects appear to be independent of the relative expression of the mutant PRSS1 H122 allele or SPINK1 gene expression. The marked increase in SPINK1 gene expression with inflammation is consistent with its regulation as an acute phase protein.

Aged, 80 and over↗
PubMed2004

[Diarrhea and weight loss in common variable immunodeficiency].

A 25-year-old male was hospitalized for diarrhea and weight loss. Since childhood he had experienced recurrent episodes of pneumonia and diarrhea. Physical and laboratory findings were compatible with malabsorption. On endoscopy, nodular lymphoid hyperplasia (NLH) of the small intestine was found. Common variable immunodeficiency syndrome (CVID) was suspected and diagnosis was established by demonstrating a significant reduction of plasma gamma-globulin levels. Immediately after starting immunoglobulin treatment diarrhea stopped, and both incidence and severity of pulmonary infections were significantly reduced, while recurrent gastrointestinal infections (notably lambliasis and Campylobacter infections) continued to occur and both bronchiectases and splenomegaly were progressive over years. This case report focuses on CVID as a potential underlying cause of diarrhea. The most important complications of the disease are presented. Therapeutical options are discussed in the light of recently published data.

Adult↗
PubMed2001

Gene expression of interleukin 18 in unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis.

BACKGROUND: Most patients with alcohol induced cirrhosis (AC) and chronic endotoxinaemia are not suffering from clinically evident systemic inflammatory reactions. This may be due to altered gene expression of cytokines, possibly related to endotoxin (for example, tolerance and sensitisation). Interleukin 18 (IL-18; interleukin gamma inducing factor) modulates local cytokine production in response to endotoxin (lipopolysaccharide (LPS)). AIM: To investigate the systemic immune response of patients with AC and to see if unstimulated peripheral blood mononuclear cells (PBMC) from patients with AC are activated and contribute to gene expression of IL-18. METHODS: Plasma levels of endotoxin (LPS) and serum levels of IL-18 were measured by enzyme linked immunoassay and the amoebocyte lysate test in 74 abstinent patients with different stages of AC (Child-Pugh stage A, n=18; B, n=22; C, n=34) and compared with healthy controls (n=43). Gene expression of IL-18 was assessed by semiquantitative reverse transcription-polymerase chain reaction in freshly isolated unstimulated PBMC of a subgroup of 14 patients with AC compared with five healthy controls. RESULTS: Gene expression of IL-18 specific mRNA in unstimulated PBMC was significantly enhanced in patients with advanced AC (Child-Pugh stage C) and correlated with plasma LPS and serum CD14 levels (Spearman rank correlation factors r=0.76 and r=0.72). Serum concentrations of IL-18 were also elevated compared with healthy controls (p<0.001) but correlation with serum levels of CD14 and plasma levels of LPS was much weaker compared with mRNA data (Spearman rank correlation factors r=0.47 and r=0.26). CONCLUSIONS: Our in vivo data suggest a presensitisation of "unstimulated" PBMC in the circulation of patients with AC by endotoxin. The term "unstimulated" may be inadequate in patients with AC. Further investigations are needed to define the exact mechanisms and localisation of sensitisation of PBMC in vivo.

Case-Control Studies↗
PubMed2000

Lipopolysaccharide/endotoxin induces IL-18 via CD14 in human peripheral blood mononuclear cells in vitro.

IL-18 shares activities with IL-12 in generating T-helper 1 cells and cytokine response. It mediates LPS/endotoxin lethality by IL-12 independent interferon-gamma synthesis and it induces bacteria-related organ failure. As peripheral blood mononuclear cells (PBMC) are potent producers of IL-18, we studied the regulation of IL-18 upon exposure to LPS and Staphylococcus aureus (SAC) in vitro. Freshly isolated PBMC constitutively expressed IL-18 mRNA. After unstimulated preincubation for 48 h, however, IL-18 transcripts were nearly not detectable by RT-PCR, but inducible by LPS or SAC (P<0.01). Both LPS and SAC were potent stimuli of IL-18 protein secretion (P<0.01). LPS-mediated IL-18 gene expression and secretion was CD14-dependent and significantly inhibited by co-incubation of PBMC with neutralizing CD14 antibody (P<0.01). We conclude that LPS-driven IL-18 is dependent on the expression of costimulatory factors and that IL-18 inhibition might attenuate IL-18-related toxic effects.

Adult↗
PubMed2000

Gene expression of TNF-receptors in peripheral blood mononuclear cells of patients with alcoholic cirrhosis.

BACKGROUND/AIMS: Elevated concentrations of tumor necrosis factor receptors have been detected in alcoholic cirrhosis, but it remains unknown whether or not peripheral blood mononuclear cells are a source of tumor necrosis factor receptors and reflect the clinical disease activity of patients with advanced alcoholic liver disease. METHODS: Twenty-two abstinent patients in different stages of alcohol-induced cirrhosis according to the criteria of the Child-Pugh classification (Child-Pugh stage A: 4, Child-Pugh stage B: 10, Child-Pugh stage C: 8) were compared with four healthy individuals. Semi-quantitative reverse transcriptase-polymerase chain reaction was used for the measurement of the expression of tumor necrosis factor-alpha, soluble tumor necrosis factor receptors-p55, -p75, interleukin-10 and inducible nitric oxide synthase in unstimulated peripheral blood mononuclear cells. RESULTS: Unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis demonstrate a stage-dependent enhanced RNA expression of tumor necrosis factor-alpha (healthy controls 0/4, Child-Pugh stage A 2/4, stage B 10/10, stage C 8/8; p<0.01). The mRNA expression of TNF-receptors-p55/-p75 is significantly higher in patients with severe alcoholic cirrhosis (Child-Pugh stage B or C patients) than healthy controls (p<0.05), while peripheral blood mononuclear cells from patients with Child-Pugh stage A show a similiar pattern of gene expression to healthy controls. No significant up-regulation of interleukin-10 was found. Inducible nitric oxide synthase was detectable in Child-Pugh stage C (p<0.05). CONCLUSIONS: Unstimulated peripheral blood mononuclear cells of patients with severe alcoholic cirrhosis (Child-Pugh stage B and C) demonstrate a systemic leukocyte activation and gene expression of tumor necrosis factor-alpha and tumor necrosis factor receptors-p55/-p75, which is correlated with the activity of the disease. Our data confirm previous studies that reported a correlation between plasma levels of pro-inflammatory cytokines and the severity of alcoholic cirrhosis. The role of interleukin-10 and inducible nitric oxide synthase in the pathogenesis of alcoholic cirrhosis remains to be fully elucidated.

Antigens, CD↗
PubMed2000

[Chronic abdominal pain and eosinophilia in a young African patient].

A 20-year-old African female was hospitalized several times for diffuse chronic abdominal pain. The following exclusions were made: Acute adnexitis (by laparoscopy), acute appendicitis (by appendectomy), gastric ulcerations (by esophagogastroduodenoscopy) as well as Crohn's disease and ulcerative colitis. However, once taking a closer microscopical look at the mucosa, that otherwise appeared colonoscopically to be normal, multiple eggs of schistosomiasis mansoni (S. mansoni) were found in the colon as well as the rectum. Thus, the diagnosis of an intestinal bilharziosis was finely established. In retrospect even the sample taken for the appendix could have indicated this diagnosis already earlier on. Both the antibodies (ELISA/IFAT) and the specific immunoglobulins (IgE) for S. mansoni proved significantly positive. Therapy of choice was a single oral dosage of praziquantel. Migration and tourism have considerably increased the range of tropical and infectious diseases that need to be included into differential diagnosis. This case report focuses on intestinal bilharziosis as a potential underlying cause of chronic abdominal pain in immigrants of endemically affected areas. Direct diagnosis is the most important diagnostic method. The adult worms are usually inaccessible, so the method of choice to assess both diagnosis and the degree of activity of a chronic infection is evidence of living eggs in the stool. Alternatively, in case of lack of direct evidence diagnosis can be established by endoscopy and rectal biopsy.

Abdominal Pain↗
PubMed1999

Immunological changes of mild acute pancreatitis in late-stage alcoholic chronic pancreatitis.

The exact immunological mechanisms underlying alcoholic chronic pancreatitis are unclear. To investigate the role of the tumor necrosis factor (TNF) receptor pathway the serum levels of TNF-alpha, soluble TNF receptors -p55/-p75, and CRP were determined by ELISA in 34 patients with late-stage alcoholic chronic pancreatitis and 28 controls. The disease activity (Balthazar scoring system) of acute pancreatitis on the background of late-stage chronic pancreatitis correlated with an increase of functionally active TNF receptor -p55/-p75 serum levels. Unstimulated peripheral blood mononuclear cells are one source of soluble TNF receptors and demonstrated a systemic leukocyte activation. The marked enhancement of soluble TNF receptors suggests that alcoholic chronic pancreatitis may be characterized by transient peaks of in situ TNF-alpha production preceding a long-lasting release of soluble TNF receptors. The data demonstrate immunological changes characteristic of acute pancreatitis in late-stage alcoholic chronic pancreatitis.

Acute Disease↗
PubMed1999

Cytokine gene expression in peripheral blood mononuclear cells reflects a systemic immune response in alcoholic chronic pancreatitis.

BACKGROUND: Recent data provide evidence of a systemic inflammatory response in severe acute pancreatitis; in contrast, the exact immune mechanisms underlying chronic pancreatitis remain unclear. METHODS: To investigate the immune response in the clinical features of chronic pancreatitis, we investigated the gene expression of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor (TNFR)-p55 and -p75 and inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cells (PBMC) of 18 patients with late-stage alcoholic chronic pancreatitis of different disease activity (Balthazar criteria). RESULTS: Semiquantitative reverse transcriptase-polymerase chain reaction revealed a significantly enhanced gene expression of TNF-alpha (P < 0.05), TNFR-p55 (P < 0.05) and TNFR-p75 (P < 0.01) in unstimulated PBMC of patients with advanced chronic pancreatitis (11/18 with calcifications) compared to healthy controls (n = 8). No significant difference was found between patients with mild acute pancreatitis and patients with an inactive quiescent pancreatitis. Moreover, no expression of inducible nitric oxide synthase was detectable. CONCLUSIONS: The enhanced gene expression of TNFR-p75, TNFR-p55 and TNF-alpha in unstimulated PBMC demonstrates an enhanced leucocyte activation in patients with late-stage chronic pancreatitis and suggests a pathogenetic role of the cytotoxic TNF-alpha pathway in the clinical features of alcoholic chronic pancreatitis. The pathogenetic role of nitric oxide in chronic pancreatitis remains to be fully elucidated.

Adult↗
PubMed1998

Induction of tumour necrosis factor (TNF) receptor type p55 and p75 in patients with chronic hepatitis C virus (HCV) infection.

There is evidence that TNF-alpha contributes to the pathogenesis of chronic viral hepatitis. The cellular effects of this cytokine are regulated by two specific receptors, and membranous shedding of these receptors reflects activation of the TNF system. We performed a study of TNF-alpha and functionally active soluble TNF-receptors (TNFR-p55 and -p75) in 105 patients with chronic HCV infection. In HCV RNA-positive patients a significant enhancement of TNF-alpha and both receptor types was observed compared with controls (TNF-alpha 83.8+/-91.7 pg/ml versus 18.8+/-8.4 pg/ml, P<0.001; TNFR-p55 1.4+/-0.4 ng/ml versus 0.9+/-0.2 ng/ml, P<0.0001; TNFR-p75 6.4+/-2.4 ng/ml versus 2.9+/-0.6 ng/ml, P<0.0001, respectively). The enhanced serum levels of TNF-alpha and TNFRs were reflected by a significant expression of TNFR-specific mRNA in peripheral mononuclear cells of HCV-infected patients (P<0.001). Serum aminotransferases correlated with soluble TNFR-p75 (P<0.001) but not with TNFR-p55 and TNF-alpha. We demonstrated an association of the degree of histological inflammation with both TNFRs (P<0.01). Furthermore, enhanced hepatocellular expression of TNF-alpha and TNFRs could be demonstrated by immunohistochemical staining in HCV-infected patients. Sixty-eight out of 105 patients were treated with interferon-alpha (IFN-alpha) (3x10(6)U x 3/week). Pretreatment levels of TNF-alpha and TNFRs did not differ between responders and non-responders. Our results demonstrate that TNF-alpha and TNFRs are enhanced in chronic HCV infection and reflect histological activity of the disease. This up-regulation of TNFRs might modify host response and potentially contribute to liver damage in chronic HCV infection.

Adult↗