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Biomedical subjects

P Rieger

Publications and source records attributed to P Rieger.

At least 19 recordsLinked to original sources
PubMed2001

Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.

We report a Turkish family with parental consanguinity and at risk for sialidosis type II, an inherited autosomal recessive disorder caused by lysosomal alpha-N-acetyl-neuraminidase (sialidase, NEU1) deficiency. The proband was a premature male infant that presented with hydrops, hepatomegaly, respiratory distress syndrome, and anemia and that died of respiratory insufficiency 2 months after birth despite intensive care. An abnormally increased [14C]methylamine incorporation and an isolated deficiency of lysosomal alpha-N-acetyl-neuraminidase were found in cultured skin fibroblasts. A previous pregnancy of the mother terminated in a spontaneous abortion in the 13th week of gestation. A successive pregnancy showed hydrops fetalis, and an enzymatic assay of cultured amniotic fluid cells indicated a deficiency of alpha-N-acetyl-neuraminidase. Following pregnancy termination at 20 weeks gestation, light microscopy of fetal tissues revealed classic vacuolation not only in liver, bone marrow, brain, and kidney, but also in endocrine organs such as the thyroid gland, adrenal gland, hypophysis, and testes, and in the thymus. DNA analysis of the family showed that both the proband and the third sibling had a novel homozygous nonsense point mutation at nucleotide 87 in exon 1 of the alpha-N-acetyl-neuraminidase (neu1) gene causing a substitution of tryptophan at codon 29 by a termination codon (W29X). DNA sequencing of polymerase chain reaction products identified the parents as heterozygous carriers. To detect neu1 mRNA expression, a real-time reverse transcription/polymerase chain reaction was performed, and similar rates of neu1 mRNA expression were found in the fibroblasts of the fetus, the 2nd sibling, and in controls. The very early termination codon with complete loss of neuraminidase activity is probably the molecular basis of the unusually severe vacuolation pattern in this form of congenital sialidosis.

Abnormalities, Multiple↗
PubMed2001

Possible mechanism of regression of myocardial hypertrophy.

Structure of the myocardium was studied in rabbits with renovascular hypertension during the development of myocardial hypertrophy and its regression under the effect of beta-adrenoceptor antagonist lopressor. Myocardial hypertrophy was associated with ultrastructural changes in cardiomyocytes, while lopressor therapy led to their regression and normalization of cardiomyocyte ultrastructure. Regression of hypertrophic changes was accompanied by a marked increase in the number of extracellular nuclei, which indicated enhanced apoptosis of cardiomyocytes.

Adrenergic beta-Antagonists↗
PubMed2001

Regulation of type 1 pili expression as exemplified by Escherichia coli strain m17.

Studies of E. coli strain M17 colibacterin and its derivatives showed that fimH gene regulates morphological characteristics of type 1 fimbria and cell piliation on the whole. Gene fimH has a negative effect and decreased the percentage of piliated cells in the population and piliation of individual cells, which does not agree with its role of a positive regulator.

Adhesins, Bacterial↗
PubMed2000

Tropism of human cytomegalovirus for endothelial cells is determined by a post-entry step dependent on efficient translocation to the nucleus.

Marked interstrain differences in the endothelial cell (EC) tropism of human cytomegalovirus (HCMV) isolates have been described. This study aimed to define the step during the replicative cycle of HCMV that determines this phenotype. The infection efficiency of various HCMV strains in EC versus fibroblasts was quantified by immunodetection of immediate early (IE), early and late viral antigens. Adsorption and penetration were analysed by radiolabelled virus binding assays and competitive HCMV-DNA-PCR. The translocation of penetrated viral DNA to the nucleus of infected cells was quantified by competitive HCMV-DNA-PCR in pure nuclear fractions. The intracytoplasmic translocation of capsids that had penetrated was followed by immunostaining of virus particles on a single particle level; this was correlated with the initiation of viral gene expression by simultaneous immunostaining of viral IE antigens. The infectivity of nonendotheliotropic HCMV strains in EC was found to be 100-1000-fold lower when compared to endotheliotropic strains. The manifestation of this phenotype at the level of IE gene expression indicated the importance of initial replication events. Surprisingly, no interstrain differences were detected during virus entry. However, dramatic interstrain differences were found regarding the nuclear translocation of penetrated viral DNA. With nonendotheliotropic strains, the content of viral DNA in the cell nucleus was 100-1000-fold lower in EC when compared to endotheliotropic strains, thereby reflecting the strain differences in IE gene expression. Simultaneous staining of viral particles and viral IE antigen revealed that interstrain differences in the transport of penetrated capsids towards the nucleus of endothelial cells determine the EC tropism of HCMV.

Active Transport, Cell Nucleus↗
PubMed1998

Human trophoblast cells are permissive to the complete replicative cycle of human cytomegalovirus.

Human trophoblast cells were permissively infected by human cytomegalovirus. The kinetics of viral immediate-early, early, and late gene expression was clearly delayed compared to that in fibroblasts. Productive infection was unequivocally proven by the detection of virion particles, infectious virus in trophoblast culture supernatant, and cell-to-cell spread of cytomegalovirus from infected trophoblasts to uninfected fibroblasts. These observations indicate that infected trophoblasts may be involved in maternofetal transmission of human cytomegalovirus.

Antigens, Viral↗
PubMed1998

Visualization of enteroviral replication in myocardial tissue by ultrastructural in situ hybridization: identification of target cells and cytopathic effects.

In humans as well as in various murine models, enteroviruses are capable of inducing a severe acute and chronic myocarditis, which is characterized by myocytotoxic alterations and interstitial mononuclear infiltrates. With regard to the pathogenesis of enteroviral myocarditis, coxsackievirus B3 (CVB3)-infected immunocompetent A.CA/SnJ (H-2f) mice were used as a model to trace viral plus- and minus-strand RNA during acute and chronic organ infection by ultrastructural in situ hybridization techniques. For electron microscopic detection of enteroviral RNA in myocardial tissue, a pre-embedding hybridization technique was developed and optimized for excellent conservation of structural integrity and RNA retention. Herein, we demonstrate how the virus gains access to the myocardium during viremia involving infection of the capillary endothelial cells. In myocytes, viral replication was found to be closely associated with the generation of vesicular regions and lysis of myofibrils, resulting in complete destruction of the internal architecture of the cell. In the course of acute infection, the direct cell-to-cell spread of the virus from one myocyte to the other was found to be related with filaments of the cytoskeleton. The observation of prominent cytopathic alterations in close spatial association with viral replication before the development of the reactive cellular immune response strongly implies that the loss of host cell integrity is a direct consequence of acute viral replication. In addition to myocytes, non-heart muscle cells were found to be infected during acute as well as chronic disease. Viral replication observed in myocardial fibroblasts and immune cells such as B lymphocytes proved to be associated with minor cytopathic effects. The technique of electron microscopic in situ hybridization established for the detection of viral RNA within myocardial tissue provides a powerful tool for the elucidation of molecular and structural interrelationships in organ pathology.

Animals↗
PubMed1997

CADASIL: skin biopsy allows diagnosis in early stages.

OBJECTIVES: Our aim was to investigate the diagnostic impact of skin biopsies in CADASIL patients. MATERIALS AND METHODS: Eight consenting CADASIL patients belonging to a German-Caucasian kindred were assessed clinically, genetically, by MRI and skin biopsy. Skin biopsy results were compared to 5 patients suffering from sporadic leucoencephalopathies (control group). RESULTS: Six CADASIL patients presented with symptoms ranging from migraine to severe tetraparesis with dementia. Two clinically unaffected patients had abnormal MRIs. On MRI 7 patients showed various degrees of leucoencephalopathy. One 22-year-old woman with migraine had a normal MRI. Granular, electron dense, osmiophilic material (GEM) was found in skin biopsies of all 8 patients including the 22-year-old woman with migraine and a normal MRI. As shown by genetic linkage analysis she was carrying the disease haplotype. GEM was not found in the control group. CONCLUSION: Our findings substantiate the impact of skin biopsies in defining the carrier status in CADASIL families.

Adult↗
PubMed1994

Phase II radioimmunotherapy trial with 131I-CC49 in colorectal cancer.

BACKGROUND: Radiolabeled CC49, a second generation high affinity monoclonal antibody (MoAb) reactive with tumor-associated glycoprotein 72 (TAG72) has undergone previous Phase I testing in patients with colon cancer. Based on this report, the authors treated 15 refractory metastatic colon cancer patients with 131I-CC49 to determine its overall toxicity and the response to therapy of patients treated with it. METHODS: Patients received 75 mCi/m2 131I-CC49 (20 mg MoAb) intravenously for a period of 30-60 minutes. Whole body retention was derived from the measured dose-rate of I-131 monitored daily at 1 m using an ion chamber. Two whole-body and static-gamma camera images were taken of patients on days 4 and 7 after the infusion. RESULTS: Nonhematologic toxicity (Grade 1-2) consisted of nausea (two patients), arthralgias (three patients), transient fever and chills (two patients), and transient blood pressure changes (two patients). At 4-5 weeks posttreatment, reversible Grade 3-4 thrombocytopenia was observed in 7 of 15 patients, and reversible Grade 3-4 granulocytopenia was observed in 6 of 15 patients. Twelve of 13 patients tested developed human anti-mouse antibody (range, 161 to > 20,000 ng/ml) at 6-8 weeks postinfusion. Mean +/- SD whole-body half-life (whole-body retention) of 131I-CC49 was 57.3 +/- 13.4 hours. Tumors were seen in all patients. In two of three patients treated a second time, an increased whole body clearance rate correlated with elevated human anti-mouse antibody, reduced uptake in tumor, and enhanced uptake in the thyroid. Estimated tumor doses ranged from 19-667 rads. Red marrow dose estimated from whole body retention ranged from 60 to 117 rads and correlated with decreases in platelet count. No objective tumor responses (i.e., partial or complete) were observed. CONCLUSIONS: Despite minimal toxicity and favorable tumor uptake, efficacy has been limited at this dose and schedule.

Animals↗
PubMed1994

Investigation of the coxsackievirus B3 nonstructural proteins 2B, 2C, and 3AB: generation of specific polyclonal antisera and detection of replicating virus in infected tissue.

The coxsackievirus B3 (CVB3) nonstructural proteins 2B and 3AB were synthesized as beta-galactosidase fusion proteins in E. coli in order to generate specific polyclonal antisera. 2B and 3AB fusion proteins were purified by preparative SDS-polyacrylamide gel electrophoresis and inoculated into rabbits. Protein 2C-specific antiserum was produced using synthetic oligopeptides which were defined by computer based amino acid sequence analysis. Specificity of the generated antisera was analysed by immunoblotting, immunofluorescence, immunohistochemistry and immunoelectron microscopy. All antisera allowed specific detection of the viral proteins 2B, 2C, and 3AB in CVB3-infected cells as well as in myocardial and pancreatic tissue of CVB3-infected mice. In addition, the CVB3 2C-specific antiserum was shown to be highly cross-reactive with the analogous protein of other picornaviruses, including cardiotropic enterovirus serotypes such as coxsackievirus A9, coxsackievirus B (types 1-5), and echovirus 11. Moreover, the immunological detection of nonstructural proteins enables diagnosis of replicating virus in infected tissue. These results demonstrate that the generated antisera are valuable tools for diagnostic approaches. Furthermore, they may help to elucidate the role of the nonstructural proteins 2B, 2C, and 3AB in enteroviral replication and pathogenesis.

Animals↗
PubMed1991

Natural history of Coxsackievirus B3-induced myocarditis in ACA/Sn mice: viral persistence demonstrated by quantitative in situ hybridization histochemistry.

Enteroviruses are considered to be the major aetiological agents of myocarditis in humans. Recent in situ hybridization studies on endomyocardial biopsies and autopsy hearts indicate that enterovirus RNA can be detected (pattern of persistent infection) not only in acute myocarditis (pattern of acute infection), but also in chronic dilated cardiomyopathy. Our experimental studies on murine coxsackievirus B3 myocarditis provided evidence that persistent infection may also occur in mice. Quantitative in situ hybridization and immunohistochemistry as well as electron microscopical in situ hybridization experiments were performed on ACA/SnJ mice 3-30 days after infection. The pattern of acute infection (days 3-9 p.i.) is characterized by rapid progression of myocardial lesions, an increasing number of inflammatory cells and a high number of infected myocytes. Hallmarks of the persistent pattern (days 15-30 p.i.) are reduced inflammation, reduced numbers of persistently infected cells and a slow progression of myocardial lesions. Infection is primarily restricted to degenerated, atrophic myocytes and to fibroblasts.

Animals↗
PubMed1987

[Protective reaction of the myocardium in poisoning].

Intensive synthesis of collagen-like substance was revealed in the rabbit myocardium during experimental diphtheria intoxication. It was more marked in the right ventricle 24 hours after the injection of diphtheria toxin. Since similar changes (the substance was mainly formed around blood vessels) have been observed in other cases of toxic myocardial alterations (i.e. ethanol intoxication, injection of pharmacological agents, etc.), it can be assumed that it is a standard protective reaction of the altered heart to the penetration of toxic agents from the blood into the myocardial tissue.

Animals↗
PubMed1986

[Neuroradiologic aspects of aneurysm-induced subarachnoid hemorrhage and its complications].

The distribution of aneurysms in 129 patients with subarachnoidal haemorrhage (SAH) (ACA 42%, MCA 27%, ICA 21%, vertebral and basilar artery 10%) differs from the result of large statistics, where aneurysms of the ICA represent the most frequent group. The difference is considered as a consequence of the small statistical group. No differences were found with respect to complications from SAH (angiospasm 24%, infarction 14%, hydrocephalus 18%, second haemorrhage 23%, mortality 20%). The validity of CT and angiography in search for SAH and aneurysm and temporal aspects, correlated with the examination, are discussed.

Cerebral Angiography↗
PubMed1983

Fenestration and duplicate origin of the left vertebral artery in angiography. Report of three cases.

Three cases are shown; 2 of angiographically proven distal fenestration of the left vertebral artery and one of duplicate origin. Both anomalies are classified as of inhibitory type. Their incidence in the literature is reviewed. Underlined is the fact that variations of this nature frequently occur in combination with other inhibitory malformations particularly in the vascular and skeletal systems.

Adult↗
PubMed1981

Thalamic bleeding: diagnosis, course and prognosis.

Isolated thalamic bleeding without involvement of the internal capsule or other neighboring structures is extremely rare. Thalamic hemorrhage often leads to bleeding into the ventricular system. The extent of the bleeding is not a valid criterion for prognosis. The chance of survival was found to be poorest in initially comatose patients. CT is eminently suitable for determining the size and position of the hemorrhage and also for the followup of thalamic bleeding. No significant correlation was found between the clinical and CT outcome.

Adolescent↗