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L Kenner

Publications and source records attributed to L Kenner.

At least 19 recordsLinked to original sources
PubMed2005

mRNA expression patterns indicate CD30 mediated activation of different apoptosis pathways in anaplastic large cell lymphoma but not in Hodgkin's lymphoma.

One of the main functions of the tumor necrosis factor receptor (TNFR) family is induction of apoptosis. CD30, a member of the TNFR superfamily is overexpressed in highly proliferating tumors such as anaplastic large cell lymphoma (ALCL) and Hodgkin's lymphoma (HL). CD30 stimulation leads to apoptosis and growth arrest in cultured ALCL, but not in Hodgkin-Reed-Sternberg cells. To identify changes in the transcriptional program responsible for these opposing effects, we performed gene expression analysis in CD30-stimulated ALCL (Karpas 299) and HL (KM-H2) cell lines using cDNA microarrays. Selected genes were validated by real-time PCR. Hierarchical clustering was applied to the whole dataset and separated the cell lines clearly with respect to their origin. In HL, there were only minor CD30-specific alterations, whereas ALCL unequivocally showed a pronounced CD30-specific transcriptional response. Ninety-three genes (6.6% of total) were deregulated by more than a factor of two after CD30 stimulation in ALCL cells. The majority of genes identified are involved in cell cycle regulation and apoptosis. mRNA expression patterns further indicate that in contrast to HL, CD30 stimulation in ALCL induces cell death via the CD95-CD95 ligand (CD95L) pathway and the TNF-R1/TNF-R2 crosstalk. These data provide a detailed view on the transcriptional changes upon CD30 stimulation and may explain the observed functional differences of HL and ALCL.

Apoptosis↗
PubMed2002

[Primary high-grade B-cell lymphoma of the CNS. Case report and review of the literature].

We report the case of a 69-year-old patient referred to our clinic because of mania. When examined by neuroradiological imaging, there were lesions seen appearing and disappearing in different regions of the brain during a period of 2 months. Differential diagnosis of these changing lesions, progressive severe illness, and the role of glucocorticoid therapy concerning these lesions are discussed. The diagnosis of primary CNS lymphoma of the B-cell type could not made sure until autopsy.

Aged↗
PubMed2001

Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases.

Reduced hepatobiliary transporter expression could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice. Because little is known about alterations of hepatobiliary transport systems in human cholestatic liver diseases, it was the aim of this study to investigate such potential changes. Hepatic mRNA levels in hepatobiliary transport systems for bile salts (NTCP, BSEP), organic anions (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR3), and aminophospholipids (FIC1) were determined in 37 human liver biopsies and control livers by competitive reverse-transcription polymerase chain reaction (RT-PCR). Transporter tissue distribution was investigated by immunofluorescence microscopy. In patients with inflammation-induced icteric cholestasis (mainly cholestatic alcoholic hepatitis), mRNA levels of NTCP, OATP2, and BSEP were reduced by 41% (P <.001), 49% (P <.005), and 34% (P <.05) compared with controls, respectively. In addition, NTCP and BSEP immunostaining was reduced. MRP2 mRNA levels remained unchanged, but canalicular immunolabeling for MRP2 was also decreased. mRNA expression of MRP3, MDR1, MDR3, and FIC1 remained unchanged. In contrast to the alterations of transporter expression in inflammation-induced icteric cholestasis, transporter expression did not change in anicteric cholestasis caused by primary biliary cirrhosis (PBC) stages I and II. In conclusion, reduced expression of hepatobiliary transport systems for bile salts and other organic anions may contribute to inflammation-induced cholestasis in humans. Reduction of transporter gene expression can occur at the mRNA level as observed for NTCP, OATP2, and BSEP. However, reduced MRP2 immunostaining in the presence of conserved MRP2 mRNA levels suggests an additional role for posttranscriptional/posttranslational mechanisms.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Compactotomy in Huntington's chorea.

Advances in neuroradiological and neurosurgical techniques have lead to a growing interest in functional neurosurgical interventions for medically intractable movement disorders. The majority of these procedures are performed in patients with hypokinetic movement disorders, especially Parkinson's disease. However, relatively few interventions were done in hyperkinetic disorders such as Huntington's disease (HD), mainly owing to the lack of an adequate target nucleus. We have recently described the case of a reversible chorea in a genetically confirmed HD patient. We subsequently identified a marked bilateral degeneration of the substantia nigra as the probable reason for choreatic cessation. We therefore suggest that primary striatal atrophy causing hyperkinesia and secondary substantia nigra atrophy favouring hypokinesia were balanced in this patient, thus resulting in a close-to-physiologic GABAergic basal ganglia output. We postulate that deep brain stimulation of the substantia nigra pars compacta may ameliorate hyperkinesia in choreatic movement disorders, thus representing the first effective therapy in Huntington's chorea. Several lines of evidence in recent neurophysiological research support our hypothesis and are discussed below.

Humans↗
PubMed2000

The tumor-associated shift in immunoglobulin G1/G2 is expressed at the messenger RNA level of peripheral blood B lymphocytes in patients with gynecologic malignancies.

BACKGROUND: Previously, it could be demonstrated that human patients with malignant diseases of various tissues exhibited characteristic and highly significant changes in the serum patterns of immunoglobulin (Ig)G subclasses, consisting of a decrease in IgG1 and an increase in IgG2 relative to total IgG. The aim of the current study was to determine whether this phenomenon was detectable at the level of IgG-producing B lymphocytes. METHODS: Using a competitive reverse transcriptase polymerase chain reaction specific to IgG1 and IgG2, the gene expression of these 2 IgG subclasses in peripheral B cells from 10 patients with carcinomas of various sites within the female reproductive tract and 10 healthy controls was quantitatively determined, in parallel with the concentrations of the respective serum proteins. RESULTS: Absolute levels of IgG subclass messenger ribonucleic acid (mRNA) showed a slight but not significant decrease in IgG1 and an increase in IgG2 in patients with gynecologic malignancies. However, the ratio of IgG1 to IgG2 expression showed a highly significant (P < 0.001) decrease in tumor patients compared with healthy controls, and corresponded to the change in the ratio of IgG1 to IgG2 serum proteins. CONCLUSIONS: These data suggest that the shifts in the serum patterns of IgG1 and IgG2 observed in patients with gynecologic malignancies are due to irregular biosynthesis of these IgG subclasses at the B-cell level.

B-Lymphocytes↗
PubMed2000

Association of the vitamin D receptor genotype BB with low bone density in hyperthyroidism.

Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases. In several conditions such as low calcium intake, an influence of vitamin D receptor (VDR) polymorphisms on BMD has been suggested. In the present study, we investigated the relationship of Bsm I and Fok I polymorphisms of the VDR gene and BMD in patients with hyperthyroidism, a disease that often results in low BMD. Bsm I and Fok I genotypes were determined in 76 postmenopausal hyperthyroid patients and 62 healthy postmenopausal women as controls. Patients and controls were matched for age, time since menopause, and lifestyle factors and were free of estrogen medication. BMD evaluation included axial dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (PQCT). Low BMD was defined as -2.5 STD below the young adult mean value. Biochemical parameters investigated were thyroid hormones, osteocalcin, and 25-(OH)-vitamin D3 as well as routine laboratory data. Low BMD was found in 61% of hyperthyroid patients and in only 23% of euthyroid controls. In the group of hyperthyroid patients with low bone density, the BB genotype (VDR Bsm I polymorphisms) was significantly more frequent (39%) than in controls (13%; p = 0.003) and hyperthyroid patients with normal BMD (6%; p = 0.013). The odds ratio (OR) for low BMD in patients with BB genotype was 5.7 (95% CI, 1.7-19.1; p < 0.005) as compared with the Bb and bb genotypes and 5.5 (95% CI, 2.3-13.2; p < 0.0001) for hyperthyroidism alone. The cumulative risk for low BMD in patients with hyperthyroidism and BB genotype was 31.4 (95% CI, 3.9-256; p < 0.0003). VDR Fok I genotypes showed no significant relationship with BMD or other general or bone-specific parameters. Thus, hyperthyroidism and the genetic background of a BB genotype may promote synergistically the development of low BMD in hyperthyroid patients. Screening for the BB genotype in these patients therefore could help to identify those with particularly high risk for the development of low BMD and allow early treatment.

Absorptiometry, Photon↗
PubMed1999

Altered microtubule-associated tau messenger RNA isoform expression in livers of griseofulvin- and 3,5-diethoxycarbonyl-1, 4-dihydrocollidine-treated mice.

Tau proteins belong to the family of microtubule-associated proteins (MAPs), which so far have been mostly detected in neuronal cells. Different domains on the protein serve different functions. By alternative splicing, several mRNAs and tau isoforms are created from one gene, which contain these functionally important domains to various degrees, and thus differ in their microtubule-related properties. In the present article, several novel observations are reported. Tau mRNA and proteins have been identified and further characterized in mouse liver. It is shown on the basis of mRNA determinations that at least three tau isoforms differing particularly with respect to their amino-terminal domains are present in mouse liver. The major and predominant isoform (isoform 1) lacks portions encoded by exons 2 and 3, which are responsible for cross-talk of microtubules with their environment ("projection domain"). Moreover, mRNA encoding tau protein with four repeats of the microtubule binding domain predominate in embryonal as well as adult mouse liver in contrast to brain, in which a shift from the predominant three-repeat isoform to the four-repeat isoform characterizes the transition from the embryonic to the adult stage. Intoxication with griseofulvin (GF) or 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) significantly affects in a reversible manner the levels of tau mRNA as well as isoform ratios in mouse liver, but not in mouse brain. Tau mRNAs are significantly increased in intoxicated mouse livers. Moreover, a shift to isoform 1 lacking exons 2 and 3 occurs. However, the increase in liver tau protein was less than expected from increased mRNA levels, which could be the result of translational or posttranslational regulation. The consequences on microtubular function are as yet unclear, but impairment can be expected because the overexpressed tau mRNA isoform lacks the domain that mediates interaction of microtubules with their environment. On the other hand, the ratio of polymerized (microtubules) to nonpolymerized tubulin remained unaffected.

Animals↗
PubMed1999

ABL amplification in a patient with lymphoid blast crisis of chronic myelogenous leukaemia.

Although chronic phase myelogenous leukaemia (CML) is characterised by the Philadelphia (Ph) chromosome leading to a fusion of the BCR and ABL genes, additional genetic alterations involved in blast crisis are poorly understood. We report an at least 15-fold amplification of the ABL oncogene in a 29-year-old male patient with a variant Ph-positive t(19;22)(p13;q11.2) CML who presented in lymphoid blast crisis. Our finding suggests that an amplification of the ABL oncogene might play a part in the appearance of an aggressive phenotype in some cases of CML.

Adult↗
PubMed1998

Venous thrombosis in a replanted finger with underlying factor V Leiden mutation.

Resistance to activated protein C (APC resistance) was described recently as a cause for thrombophilia. APC inactivates coagulation co-factors Va and VIIIa. A single base-pair mutation changing Arg506 to Gln at the APC cleavage site of the factor V gene leads to a factor V Leiden variant, which is the most frequent cause of APC resistance. Recently, its role in peripheral venous thrombosis during pregnancy was described. We here report a case with thrombosis of the venous anastomoses after finger replantation with resistance to activated protein C associated with factor V Leiden mutation.

Adult↗
PubMed1996

Acute Budd-Chiari syndrome with fulminant hepatic failure in a pregnant woman with factor V Leiden mutation.

Budd-Chiari syndrome during pregnancy has rarely been reported. This report presents a case of acute hepatic failure in a 20-year-old pregnant woman attributable to Budd-Chiari syndrome with underlying resistance to activated protein C caused by factor V Leiden mutation. The patient delivered a healthy girl by cesarean section in the 31st week of pregnancy. Acute hepatic failure in the 6th week postpartum was successfully treated by emergency liver transplantation, and the patient and her child were doing well at 8-month follow-up. Liver transplantation was lifesaving; normal factor V production by the transplant corrected the underlying coagulopathy. In this patient, latent thrombophilia attributable to activated protein C resistance was apparently aggravated by the hypercoagulable state of pregnancy leading to acute Budd-Chiari syndrome. Activated protein C resistance should be sought as an etiologic factor in patients with Budd-Chiari syndrome.

Adult↗
PubMed1995

[Expanded diagnostic possibilities for diagnosis and differential diagnosis of autoimmune hepatopathies using polymerase chain reaction (PCR)].

This is a report on a case of autoimmunehepatopathy with misleading virus serology: A 34-year old female patient presented with abdominal signs of hepatopathy at Graz University School of Medicine. Hepatitis-C virus (HCV) serology was strongly positive indicating virus contact. The cellular activation was elevated, additionally increased ds-DNA-titer and mitochondrial antibody titres including the subfraction M2 were increased. In view of the differential diagnosis and therapeutic consequences molecular biology was used for additional information and a PCR carried out. The latter excluded infection with HCV confirming a false positive virus serology. The patient was treated with ursodesoxycholic acid, steroids and enzymes. She improved and showed no viral exposure. We conclude, that molecular biology represents an essential tool for the diagnosis of some selected critical cases of autoimmune-diseases such as autoimmune hepatopathy with false positive virus serology, if the underlying etiopathogenesis is not clear.

Adult↗
PubMed1995

Alcoholic liver disease: molecular-pathologic aspects.

Mallory bodies (MBs) are characteristic morphologic features of alcoholic hepatitis but are also associated with non-alcoholic liver diseases including long lasting cholestasis, metabolic and neoplastic disorders. MBs contain in addition to keratins non-keratin components, including microtubule-associated (tau protein) and other not yet characterized proteins in an aggregated form. Aggregation of these components in the cell is promoted by posttranslational modifications, such as partial proteolysis, phosphorylation and cross-linking, and may result in functional and structural disturbances of the cell depending on the physiologic function of the components involved. Several enzymes responsible for these modifications are Ca(++)-dependent. Thus, disturbance of Ca(++)-homeostasis may play an essential role in the pathogenesis of MBs. In some structural aspects MBs closely resemble inclusions associated with degenerative disorders of the central nervous system, including Alzheimer's and Parkinson's disease. Studies on the pathogenesis of MBs, therefore, not only shed light on a peculiar type of liver cell injury but may also assist in the understanding of other chronic degenerative diseases, particularly those of the central nervous system.

Alzheimer Disease↗
PubMed1994

cDNA cloning of the human peroxisomal enoyl-CoA hydratase: 3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme and localization to chromosome 3q26.3-3q28: a free left Alu Arm is inserted in the 3' noncoding region.

Enoyl-CoA hydratase:3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme is one of the four enzymes of the peroxisomal beta-oxidation pathway. Here, we report the full-length human cDNA sequence and the localization of the corresponding gene on chromosome 3q26.3-3q28. The cDNA sequence spans 3779 nucleotides with an open reading frame of 2169 nucleotides. The tripeptide SKL at the carboxy terminus, known to serve as a peroxisomal targeting signal, is present. DNA sequence comparison of the coding region showed an 80% homology between human and rat bifunctional enzyme cDNA. The 3' noncoding sequence contains 117 nucleotides homologous to an Alu repeat. Based on sequence comparison, we propose that these nucleotides are a free left Alu arm with 86% homology to the Alu-J family. RNA analysis shows one band with highest intensity in liver and kidney. This cDNA will allow in-depth studies of molecular defects in patients with defective peroxisomal bifunctional enzyme. Moreover, it will also provide a means for studying the regulation of peroxisomal beta-oxidation in humans.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1994

Expression of three- and four-repeat tau isoforms in mouse liver.

Tau protein is a member of the family of microtubule-associated proteins, which support microtubule polymerization and stability. Under pathological conditions, tau is a major constituent of neurofibrillary tangles in nerve cells of patients with Alzheimer's disease. Neurofibrillary tangles share some morphological, biochemical and immunological properties with cytoplasmic inclusions associated with other diseases, such as Mallory bodies in the livers of patients with alcoholic hepatitis and in corresponding mouse models. Recently a Mallory body component was identified that in molecular mass and isoelectric point resembles the abnormally phosphorylated tau of neurofibrillary tangles. There has been, however, so far no report describing the occurrence of tau in normal liver. We now demonstrate the expression of two tau isoforms containing three and four repeats, respectively, of the microtubule-binding domains in normal mouse liver and kidney. This finding provides evidence for a physiological role of tau in the liver and, consequently, the basis for the involvement of tau in pathological situations.

Animals↗