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Biomedical subjects

M Brandis

Publications and source records attributed to M Brandis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enterohemorrhagic Escherichia coli infections: following transmission routes.

Infections with enterohemorrhagic Escherichia coli (EHEC) are the major cause of hemolytic-uremic syndrome (HUS), the most-common cause of acute renal failure in childhood. The mortality rate of HUS (0%-5% in most recent series and 10%-30% in individual reports) and residual chronic renal sequelae (in up to 50% of patients in long-term follow-up studies) emphasize the seriousness of HUS for public health. Several studies have described possible sources of EHEC infection. However, in the majority of cases the pathogen cannot be identified in food or animals and the routes of transmission remain unclear. In this review article the hypothesized routes of transmission are summarized. The medical data bases "Medline" and "Current contents" were screened for the years January 1966 through November 1998. The difficulties in following the chain of EHEC infection are discussed. A precise evaluation of the environmental aspects of the patient is a precondition for further analysis.

Escherichia coli Infections↗
PubMed2000

Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes.

The flavonoid genistein has been shown to activate a Cl(-) conductance in various cell types expressing CFTR. We examined if similar effects can be observed when genistein is applied to native ex vivo tissues from human respiratory tract and rectum. We further compared the effects when genistein was applied to oocytes of Xenopus laevis expressing CFTR. In oocytes, both wtCFTR and DeltaF508-CFTR were activated by genistein while both cyclic AMP (K(v)LQT1) and Ca(2+) (SK4) activated K(+) channels were inhibited at high concentrations of genistein. Biopsies from nasal polyps and rectal mucosa were obtained from normal individuals (non-CF) and CF patients and in the presence of amiloride (10 micromol l(-1); mucosal side) the effects of genistein were assessed using a perfused Ussing chamber. In non-CF airway epithelia, genistein (50 micromol l(-1); mucosal side) increased lumen negative I(sc) but had no additional effects on tissues pre-stimulated with IBMX and forskolin (100 micromol l(-1) and 1 micromol l(-1); both sides). In non-CF rectal biopsies, in the presence of amiloride (10 micromol l(-1); mucosal side) and indomethacin (10 micromol l(-1); basolateral side), genistein increased lumen negative I(sc) and enabled cholinergic (carbachol; CCH, 100 micromol l(-1); basolateral side) stimulation of Cl(-) secretion indicating activation of luminal CFTR Cl(-) channels. However, after stimulation with IBMX/forskolin, genistein induced opposite effects and significantly inhibited CCH activated I(sc). In CF airway and intestinal tissues genistein failed to induce Cl(-) secretion. Thus, genistein is able to activate luminal CFTR Cl(-) conductance in non-CF tissues and mutant CFTR in oocytes. However, additional inhibitory effects on basolateral K(+) conductance and missing effects in native CF tissues do not support the use for pharmacological intervention in CF.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X-linked lymphoproliferative disease without evidence for Epstein-Barr virus infection.

We present two male siblings suffering from recurrent manifestations of B-cell non-Hodgkin's lymphoma (NHL) and recurrent infections of the lower respiratory tract associated with bronchiectasis. Immunodeficiency could not be demonstrated by any laboratory investigation. In both patients, lymphomas developed without evidence for Epstein-Barr virus (EBV) infection, i.e. no antibody response to EBV-specific antigens, negative EBV-PCR (polymerase chain reaction) in peripheral blood cells, and absence of latent membrane protein (LMP) and EBV-encoded RNA (EBER) in lymphoma cells. Molecular analysis of the SH2D1A, the gene for X-linked lymphoproliferative disease (XLP) led to the identification of a deletion in the first exon in both patients. Therefore, we postulate that the genetic defect and the following dysregulation of the B-/T-cell interaction rendered these patients susceptible to the early onset of B-cell NHL and that EBV infection is not an obligate prerequisite.

Child, Preschool↗
PubMed2000

Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree.

Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene.

Adolescent↗
PubMed2000

Portal vein and bone involvement in disseminated cat-scratch disease: report of 2 cases.

Cat-scratch disease (CSD) is a common cause of regional lymphadenopathy. We describe 2 children with an unusual presentation of disseminated CSD, the first one presenting with persistent fever, multilocular abscesses in liver and spleen as well as osteolytic lesions in the lumbar spine and the second one with portal vein thrombosis and severe ascites.

Bone and Bones↗
PubMed2000

Defective cholinergic Cl(-) secretion and detection of K(+) secretion in rectal biopsies from cystic fibrosis patients.

Rectal biopsies from cystic fibrosis (CF) patients show defective cAMP-activated Cl(-) secretion and an inverse response of the short-circuit current (I(sc)) toward stimulation with carbachol (CCh). Alternative Cl(-) channels are found in airway epithelia and have been attributed to residual Cl(-) secretion in CF colon. The aim of the present study was to investigate ion conductances causing reversed I(sc) upon cholinergic stimulation. Furthermore, the putative role of an alternative Ca(2+)-dependent Cl(-) conductance in human distal colon was examined. Cholinergic ion secretion was assessed in the absence and presence of cAMP-dependent stimulation. Transepithelial voltage and I(sc) were measured in rectal biopsies from non-CF and CF individuals by means of a perfused micro-Ussing chamber. Under baseline conditions, CCh induced a positive I(sc) in CF rectal biopsies but caused a negative I(sc) in non-CF subjects. The CCh-induced negative I(sc) in non-CF biopsies was gradually reversed to a positive response by incubating the biopsies in indomethacin. The positive I(sc) was significantly enhanced in CF and was caused by activation of a luminal K(+) conductance, as shown by the use of the K(+) channel blockers Ba(2+) and tetraethylammonium. Moreover, a cAMP-dependent luminal K(+) conductance was detected in CF individuals. We conclude that the cystic fibrosis transmembrane conductance regulator is the predominant Cl(-) channel in human distal colon. Unlike human airways, no evidence was found for an alternative Cl(-) conductance in native tissues from CF patients. Furthermore, we demonstrated that both Ca(2+)- and cAMP-dependent K(+) secretion are present in human distal colon, which are unmasked in rectal biopsies from CF patients.

Adolescent↗
PubMed2000

Role of K(V)LQT1 in cyclic adenosine monophosphate-mediated Cl(-) secretion in human airway epithelia.

Ion transport defects underlying cystic fibrosis (CF) lung disease are characterized by impaired cyclic adenosine monophosphate (cAMP)-dependent Cl(-) conductance. Activation of Cl(-) secretion in airways depends on simultaneous activation of luminal Cl(-) channels and basolateral K(+) channels. We determined the role of basolateral K(+) conductance in cAMP- dependent Cl(-) secretion in native human airway epithelium obtained from non-CF and CF patients. CF tissues showed typical alterations of short-circuit currents with enhanced amiloride-sensitive Na(+) conductance and defective cAMP-mediated Cl(-) conductance. In non-CF tissues, Cl(-) secretion was significantly inhibited by the chromanol 293B (10 micromol/liter), a specific inhibitor of K(V)LQT1 K(+) channels. Inhibition was increased after cAMP-dependent stimulation. Similar effects were obtained with Ba(2+) (5 mmol/liter). In patch-clamp experiments with a human bronchial epithelial cell line, stimulation with forskolin (10 micromol/liter) simultaneously activated Cl(-) and K(+) conductance. The K(+) conductance was reversibly inhibited by Ba(2+) and 293B. Analysis of reverse-transcribed messenger RNA from non-CF and CF airways showed expression of human K(V)LQT1. We conclude that the K(+) channel K(V)LQT1 is important in maintaining cAMP-dependent Cl(-) secretion in human airways. Activation of K(V)LQT1 in CF airways in parallel with stimulation of residual CF transmembrane conductance regulator Cl(-) channel activity or alternative Cl(-) channels could help to circumvent the secretory defect.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene.

Reduced mucociliary clearance in primary ciliary dyskinesia (PCD) causes recurrent infections of the upper and lower respiratory tract. The disease is usually inherited as an autosomal recessive trait. To identify a gene locus for PCD, we studied a large consanguineous family of Arabic origin. Direct examination of the respiratory cilia revealed ciliary akinesia. Electron microscopic examination of cilia showed absence of the outer dynein arms. Two of four affected individuals exhibited a situs inversus, typical for Kartagener syndrome, due to randomization of the left/right body axis. A total genome scan with 340 highly polymorphic microsatellites was performed. We localized a new gene locus for PCD to a region of homozygosity by descent on chromosome 5p15-p14 with a parametric multipoint logarithm of odds ratio (LOD) score of Zmax = 3.51 flanked by markers D5S2095 and D5S502 within an interval of 20 centimorgans sex-averaged genetic distance. Applying a polymerase chain reaction-based approach, we identified a 1.5-kb partial complementary DNA of DNAH5 encoding a Chlamydomonas-related axonemal heavy dynein chain within the critical disease interval of this new PCD locus. On the basis of the Chlamydomonas model for PCD, this gene represents an excellent candidate for PCD.

Amino Acid Sequence↗
PubMed2000

Inhibition of amiloride-sensitive epithelial Na(+) absorption by extracellular nucleotides in human normal and cystic fibrosis airways.

Cystic fibrosis (CF) airway epithelia are characterized by enhanced Na(+) absorption probably due to a lack of downregulation of epithelial Na(+) channels by mutant CF transmembrane conductance regulator. Extracellular nucleotides adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) have been shown to activate alternative Ca(2+)-dependent Cl(-) channels in normal and CF respiratory epithelia. Recent studies suggest additional modulation of Na(+) absorption by extracellular nucleotides. In this study we examined the role of mucosal ATP and UTP in regulating Na(+) transport in native human upper airway tissues from patients with 16 patients with CF and 32 non-CF control subjects. To that end, transepithelial voltage and equivalent short-circuit current (I(SC)) were assessed by means of a perfused micro-Ussing chamber. Mucosal ATP and UTP caused an initial increase in lumen-negative I(SC) that was followed by a sustained decrease of I(sc) in both non-CF and CF tissues. The amiloride-sensitive portion of I(SC) was inhibited significantly in normal and CF tissues in the presence of either ATP or UTP. Both basal Na(+) transport and nucleotide-dependent inhibition of amiloride-sensitive I(SC) were significantly enhanced in CF airways compared with non-CF. Nucleotide-mediated inhibition of Na(+) absorption was attenuated by pretreatment with the Ca(2+)-adenosine triphosphatase inhibitor cyclopiazonic acid but not by inhibition of protein kinase C with bisindolylmaleimide. These data demonstrate sustained inhibition of Na(+) transport in non-CF and CF airways by mucosal ATP and UTP and suggest that this effect is mediated by an increase of intracellular Ca(2+). Because ATP and UTP inhibit Na(+) absorption and stimulate Cl(-) secretion simultaneously, extracellular nucleotides could have a dual therapeutic effect, counteracting the ion transport defect in CF lung disease.

Absorption↗
PubMed1999

Lack of correlation between CFTR expression, CFTR Cl- currents, amiloride-sensitive Na+ conductance, and cystic fibrosis phenotype.

Cystic fibrosis (CF) is characterized by defective Cl- and enhanced Na+ conductance, both due to malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in airway epithelial cells. In the present study we examined whether expression of CFTR mRNA (CFTR messenger ribonucleic acid) is different in airway epithelia derived from either CF patients or healthy volunteers. Moreover, we tried to correlate differences in epithelial Cl- and Na+ conductance with the level of CFTR mRNA expression and studied whether these properties correlate to the clinical phenotype of CF patients. To that end, CFTR mRNA was determined by means of quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and cyclic adenosine monophosphate (cAMP)-activated Cl- and epithelial Na+ conductances were examined in airway epithelial cells using microelectrode techniques. Complementary in vitro data were obtained from cultured CF and non-CF airway epithelial cell lines. Genotype and Shwachman score were assessed for each patient. We found variable levels of CFTR mRNA expression in airway cells of both CF patients and healthy volunteers. As expected, epithelial Na+ conductance was enhanced and CFTR Cl- conductance was absent in airway cells from CF patients. However, CFTR mRNA expression did not correlate with either electrophysiological properties or Shwachman scores obtained from CF patients. In addition, CFTR mRNA expression did not correlate to Cl- conductance in cultured CF and non-CF airway epithelial cells. These results indicate a lack of correlation between levels of CFTR mRNA and CFTR function, and that only small amounts of CFTR are required for expression of the CFTR Cl- conductance.

Amiloride↗
PubMed1999

Haemophagocytosis in early congenital syphilis.

UNLABELLED: A previously healthy male infant developed hepatosplenomegaly, severe anaemia and thrombocytopenia 5 weeks after birth. Marked haemophagocytosis was present in the bone marrow. A typical maculopapular rash suggested early congenital syphilis. The diagnosis was confirmed by serology and by the presence of untreated syphilis in both parents. CONCLUSION: Syphilis needs to be excluded in infants suspected of haemophagocytic lymphohistiocytosis.

Biopsy, Needle↗
PubMed1999

Low prevalence of the immunoglobulin-A-binding beta antigen of the C protein among Streptococcus agalactiae isolates causing neonatal sepsis.

Streptococcus agalactiae (Group B streptococcus, GBS) is the most important pathogen causing neonatal sepsis. The role of bacterial proteins contributing to pathogenicity in GBS infections has not yet been clearly determined, but the C protein complex has been suggested to be involved in both virulence and protective immunity. The aim of this study was to assess the prevalence of GBS strains bearing the gene encoding for the beta antigen of the C protein among clinical isolates from 68 neonates with sepsis, 45 newborns colonized without clinical signs of infection, and 50 isolates from pregnant women. The prevalence of the beta antigen gene in all three groups was low (24% vs. 19% vs. 22%) [corrected], and the differences between groups were not statistically significant. Clinical characteristics and cytokine plasma levels did not differ between septic patients with beta antigen-positive and -negative strains. The beta-antigen gene was not found among serotype III isolates, which accounted for roughly half of all the strains isolated. Thus, polymerase chain reaction (PCR) analysis based on the beta antigen gene seems not helpful for distinguishing invasive from colonizing GBS strains. A vaccine based on peptide antigens from the beta antigen of the C protein would most probably not provide protection against the majority of GBS isolates. When analyzing the PCR products of the C protein beta antigen gene by DNA sequencing, a genetic heterogeneity was observed, revealing small repetitive genetic elements within the amplified fragment, an observation that should be studied further.

Antigens, Bacterial↗
PubMed1999

Hepatopathy in two infants with short-bowel syndrome and cytomegalovirus infection.

In children with short-bowel syndrome and the need for long-term parenteral nutrition, hepatic dysfunction is a multifactorial phenomenon that has not been completely understood. Alterations in gut motility lead to intraluminal stasis which is thought to be a major etiologic factor for bacterial overgrowth and subsequent cholestasis, especially when the ileocecal valve is absent. We report on two infants with short-bowel syndrome caused by gastroschisis and intestinal atresia. The intestinal lengths after resection were 18 and 55 cm. Long-term parenteral nutrition (PN) was obligatory due to intestinal shortness in the first patient and dilatation of the preatretic bowel segment with ineffective peristalsis in the second patient. Despite multiple trials of enteral nutrition and medical therapy for gut decontamination and stimulation of bowel motility, hepatopathy developed in both patients in a similar period of time and to about the same degree. At the age of 4 and 6 weeks, respectively, increasing bilirubin values were measured. Deterioration of liver function and thrombocytopenia at the age of 3 to 4 months led to the diagnosis of acute cytomegalovirus (CMV) infection. Treatment with ganciclovir followed. Both patients died of acute liver failure at the age of 7 and 9 months, respectively. Additional hepatic injury secondary to CMV infection might have contributed to the rapid deterioration of liver disease. Screening for further hepatotoxic factors, especially infectious etiologies, is therefore recommended in children with short-bowel syndrome. Liver transplantation should be considered early in cases of progressive hepatic dysfunction.

Cytomegalovirus Infections↗
PubMed1999

CFTR-mediated inhibition of epithelial Na+ conductance in human colon is defective in cystic fibrosis.

Cystic fibrosis (CF) patients show characteristic defects in epithelial ion transport, such as failure in cAMP-dependent Cl- secretion. Because the cystic fibrosis transmembrane conductance regulator (CFTR) also functions as a downregulator of epithelial Na+ channels (ENaC), enhanced Na+ conductance was found in the airways of CF patients. Here, we examined whether enhanced epithelial Na+ conductance is also present in the colonic epithelium of CF patients and examined the underlying mechanisms. Thus transepithelial voltages were measured, and equivalent short-circuit currents (I(sc-eq)) were determined by means of a novel type of Ussing chamber. Non-CF tissues demonstrated cAMP-dependent Cl- secretion that was absent in biopsies of CF patients. Correspondingly, Isc-eq was inhibited in non-CF but not in CF epithelia when synthesis of endogenous prostaglandins was blocked by indomethacin. In the presence of indomethacin, a larger portion of amiloride-sensitive Isc-eq was detected in CF tissues, suggesting enhanced ENaC conductance in colonic mucosa of CF patients. Increase of intracellular cAMP by forskolin and IBMX inhibited amiloride-sensitive ENaC currents in non-CF tissues but not in CF biopsies. Therefore, enhanced epithelial Na+ conductance is present in the CF colon and is probably due to missing downregulation by CFTR.

Adolescent↗
PubMed1999

Focal dermal hypoplasia (Goltz-Gorlin syndrome) associated with obstructive papillomatosis of the larynx and hypopharynx.

A 14-year-old girl with focal dermal hypoplasia (Goltz-Gorlin-syndrome) presented with dysphagia, hoarseness, inspiratory stridor, intermittent dry cough and a 10% weight loss. Endoscopy showed that these symptoms were caused by papillomatosis of the hypopharynx and the larynx. The papillomatous masses were resected subtotally by endoscopic laser treatment. Residual papillomas were left in the subglottic space but tracheotomy could be avoided. Complete clinical recovery with adequate weight gain as well as, resolution of dyspnoe and dysphagia resulted after the intervention. Histological examination did not show morphological signs of human papilloma virus as an etiological agent.

Adolescent↗