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M Brandis

Publications and source records attributed to M Brandis.

At least 73 records · Page 4Linked to original sources
PubMed1997

A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1.

Juvenile nephronophthisis (NPH), an autosomal recessive cystic kidney disease, is the primary genetic cause of chronic renal failure in children. About two thirds of patients with NPH carry a large homozygous deletion at the gene locus NPH1 on 2q13. We here identify a novel gene. NPHP1, which extends over most of this common deletion. The 4.5-kb transcript encodes a protein with an SH3 domain, which is highly conserved throughout evolution. The 11-kb interval between the 3' end of NPHP1 and an inverted repeat containing the distal deletion breakpoint was found to contain the first exon of a second gene, MALL. In patients with a hemizygous deletion of the NPH1 region, additional point mutations were found in NPHP1 but not in MALL.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Hemolytic uremic syndromes in childhood.

The hemolytic uremic syndrome (HUS) comprises hemolytic anemia, acute renal failure, and thrombocytopenia. It is the most frequent cause of acute renal failure in childhood. Ninety percent of the patients have a diarrheal prodrome, and are referred to as having typical HUS. Approximately 10% exhibit the so-called atypical HUS. Typical HUS is caused by shigatoxin-producing Escherichia coli. The toxin, bound to the globotriosyl ceramide cell receptor and internalized, interferes with protein synthesis, predominantly of endothelial cells. The main target is the kidney, but nearly every organ system can be involved. The most common extrarenal involvement is damage to the central nervous system. The central event is probably an insult to the endothelial cell with consecutive loss of antithrombogenic properties. The von Willebrand factor, activation of platelets via platelet-activating factor, other growth factors (e.g., interleukins 1, 6, 8), nitric oxide, lipopolysaccharides, activated polymorphonucleated neutrophils, and the metabolites of the arachidonic acid cascade (e.g., prostaglandin I2) are believed to be involved in the pathogenic cascade. Controlled therapeutic trials with heparin, dipyridamole, aspirin, and urokinase have not been associated with improved outcome. Antibiotics have not yielded any benefit. Plasma infusions and plasma exchange appear to be efficacious, and are justified in cases of atypical HUS and thrombotic thrombocytopenic purpura. Binding of the toxin to the intestinal lumen, and thereby inhibition of enteral reabsorption, is under investigation.

Child↗
PubMed1997

Fatal sepsis caused by Corynebacterium amycolatum in a premature infant.

Corynebacterium amycolatum has not been reported as a cause of human infections up to now, but usually the bacterium is misidentified in clinical specimens as Corynebacterium xerosis. We report the first case of neonatal sepsis due to Corynebacterium amycolatum with a fatal outcome in a premature infant.

Corynebacterium↗
PubMed1996

Glomerulopathy associated with predominant fibronectin deposits: exclusion of the genes for fibronectin, villin and desmin as causative genes.

Glomerulopathy with predominant fibronectin deposits (GFD) is a newly recognized autosomal dominant renal disease that leads to albuminuria, microscopic hematuria, hypertension, renal tubular acidosis type IV, and end-stage renal disease in the second to fourth decade of life. Light microscopy documents extensive deposits in the subendothelial space, which on electron microscopy consist of non-oriented 12 x 125 nm fibers. Deposits are strongly immunoreactive for antibodies to fibronectin. We examined the hypothesis that a genetic defect in the gene for fibronectin is responsible for the disease. In a 197 member pedigree, 13 relatives developed end-stage renal failure from the disease. In 99 individuals haplotype analysis was performed using 6 microsatellite markers spanning a > 56 cM interval in chromosome region 2q34, where fibronectin, villin, and desmin map in close proximity. Haplotype analysis resulted in exclusion of the whole range of 78 cM covered by the markers examined. This result excludes fibronectin, villin, and desmin from being the causative genes for GFD in this large kindred.

Calcium-Binding Proteins↗
PubMed1996

Colonization and infection with Moraxella catarrhalis in childhood.

In a prospective clinical study, rates of isolation of Moraxella catarrhalis in nasopharyngeal aspirates from 122 children with respiratory tract infection and 72 healthy controls were compared. In the patient group, Moraxella catarrhalis and Streptococcus pneumoniae were the most frequently isolated pathogens (38% and 42%, respectively). Monocultures of each pathogen were equally distributed in patients and controls (41% and 42%), whereas mixed infections were found more frequently in the patient group (42% vs 14%; normal flora, 17% vs 44%). Moraxella catarrhalis appears to be a relevant respiratory pathogen. The isolation of two or more pathogens in nasopharyngeal aspirates seems to be as indicative of relevant infection as is monoculture.

Acute Disease↗
PubMed1996

Subureteral collagen injection versus antireflux surgery in primary vesico-ureteral reflux grade III.

UNLABELLED: Endoscopic subureteral collagen injection (SCIN) was performed in 24 girls and 5 boys (mean/range: 3.2/0.7-12.2 years) with primary grade III vesicoureteral reflux. Clinical outcome was compared to 20 girls and 6 boys treated by antireflux surgery (mean/range: 3.0/0.2-9.4 years). forty-one ureters were treated by endoscopy, 37 by surgery. Patients were followed for 12 months. SCIN was not associated with severe persistent complications. No reflux was detected immediately after SCIN. After 6 months recurrent grade II reflux was present in 1 (4%) surgically treated patient and in 12/29 (41%) patients treated by collagen injection. This corresponded to a recurrence rate of 1/37 (3%) of ureters following surgery and 15/41 (37%) following SCIN. 8/15 refluxing ureters after collagen showed decreased reflux grade (two grade I, six grade II). After 12 months 24/26 (92%) patients with antireflux surgery remained free of urinary tract infections as compared to 25/29 (86%) children following endoscopy. Following SCIN, 4/29 (14%) patients required secondary antireflux surgery because of recurrent urinary tract infections. CONCLUSION: On the basis of this study endoscopic SCIN appears to be safe in children. It is less effective than surgery with regard to elimination of primary grade II reflux. However, clinical success rate is comparable to surgery with regard to the frequency of recurrent urinary tract infections after the procedure. This may be due to the reduction of refluxing urine volume in those patients who showed recurrence of reflux after collagen injection.

Child↗
PubMed1996

Dyslipidaemia in a boy with recurrent abdominal pain, hypersalivation and decreased lipoprotein lipase activity.

UNLABELLED: An 8-year-old boy with frequently recurring pancreatitis-like abdominal pain, Fredrickson type V dyslipidaemia, and significantly decreased post-heparin plasma lipoprotein lipase (LPL) activity is described. In order to exclude familial LPL deficiency, the complete LPL coding gene sequence was analysed revealing compound heterozygosity for two mutations (Asp9Asn, Ser447Ter) which are not supposed to considerably impair lipolytic enzyme activity. However, until now the combination of both these mutations in one patient has not been observed. In addition to the common symptoms of LPL deficiency, a striking feature of unknown origin was hypersalivation. Treatment including a fat-restricted diet, omega-3 fatty acids, and nicotinic acid led to long symptoms-free intervals. Symptoms recurred however when the diet was not strictly adhered to. CONCLUSION: LPL deficiency is a rare cause of abdominal pain in childhood and deserves careful treatment in order to avoid pancreatitis. The presented patients is a unique compound heterozygote for two mutations which do not abolish lipolytic activity in the homozygote state. Identification of other individuals with this genotype is necessary to understand the phenotype in our patient.

Abdominal Pain↗
PubMed1996

Tamm-Horsfall protein as a marker of tubular maturation.

Tamm-Horsfall protein (THP), a glycoprotein with a molecular weight of 95 kilodaltons, is produced and secreted in the ascending loop of Henle. To evaluate the measurement of THP in the assessment of fetal renal development and function, we stained fetal kidney sections for THP and measured THP concentrations in 129 amniotic fluid samples from healthy pregnancies, together with other parameters such as transferrin, albumin, alpha 1- and beta 2-microglobulin. After the 16th week of gestation THP could be detected immunohistochemically in the distal tubular cells, but was not consistently detected by sandwich enzyme immunoassay until after the 20th week of gestation (detection limit 50 ng/ml). Between the 15th and 19th week of gestation THP was only detected occasionally, but after the 20th week of gestation the concentration increased significantly reaching levels of 0.4-4 mg/l at term. The THP concentration was lower in samples taken directly before birth than in the corresponding first urine after birth, indicating that THP is produced from the fetal kidney only and does not pass the placental barrier. This pattern was different from other proteins studied. Transferrin and albumin were significantly lower in the first urine voided, microglobulins remained unchanged, and the creatinine concentration increased. This indicates that maternal to fetal exchange or transport is likely for most of the other proteins. Measurement of THP concentrations, in addition to other proteins in the amniotic fluid, can improve fetal renal assessment, but because the range of THP concentrations is wide accurate predictions are still not possible.

Alpha-Globulins↗
PubMed1996

Primary treatment of propionic acidemia complicated by acute thiamine deficiency.

Propionic acidemia is often manifested during the neonatal period with vomiting, failure to thrive, lethargy, and hyperammonemic coma when catabolism is prolonged. Mild lactic acidosis frequently accompanies metabolic decompensation. We present two patients with propionic acidemia whose initial manifestation was complicated by severe lactic acidosis caused by thiamine deficiency, which resulted from an inadequate supply of, and an increased need for, thiamine during metabolic stress. To prevent acute thiamine deficiency, we propose early vitamin supplementation during treatment of any severe metabolic decompensation accompanied by insufficient food intake.

Acute Disease↗
PubMed1996

Elevated urinary excretion of endothelin in insulin-dependent diabetes mellitus: no influence of physical exercise.

The urinary excretion of endothelin was measured by radioimmunoassay in children with diabetes mellitus in metabolically stable condition before and after ergometric exercise. Apparently healthy children served as normal controls. The excretion of endothelin, calculated for 24h and the ratio of endothelin/creatinine in urine were also significantly higher in diabetic children compared to normal controls. Physical exercise had no influence on renal endothelin excretion. In diabetic children the volume of diuresis was higher compared to controls. Physical exercise had no influence on diuresis. In a previous study we found a positive correlation between diureses and endothelin excretion. Therefore, the increased endothelin excretion in the diabetic patients may be at least partially the consequence of the higher diuresis values. It cannot be excluded, however, that it may be a sign of altered renal function as well. Furthermore, the present study suggests that in patients with diabetes mellitus elevated sympathetic nerve activity as a result of physical activity does not influence renal endothelin production.

Adolescent↗
PubMed1996

Physical mapping of the gene for juvenile nephronophthisis (NPH1) by construction of a complete YAC contig of 7 Mb on chromosome 2q13.

Familial juvenile nephronophthisis (NPH) is an autosomal recessive cystic disease of the kidney that leads to end-stage renal failure in adolescence. NPH is the most common genetic cause of end-stage renal disease in children. A gene locus for nephronophthisis (NPH1) has been mapped by linkage analysis to chromosome 2q13. We report here the construction of a complete YAC contig in the minimum genetic region for NPH1 by STS content mapping using clones of the CEPH YAC libraries. A physical map of maximum distances between 32 STS markers was constructed, thereby defining the order of a total of 27 STS markers. Since D2S340 and D2S121 have previously been identified as flanking markers to the NPH1 gene, the new contig defines on a physical map the NPH1 minimum genetic region to a 6.4-Mb interval. As a novel assignment, expressed genes, some of which may be candidates for the disease, were localized to the NPH1 region. In addition, the known interstitial telomeric repeat on chromosome 2 was physically mapped to this region. This contig assembly provides the basis for closer definition of the NPH1 critical region through identification of more narrow flanking markers and for the construction of a transcriptional map of the region towards isolation of the NPH1 gene.

Base Sequence↗
PubMed1995

Refined genetic mapping of a gene for familial juvenile nephronophthisis (NPH1) and physical mapping of linked markers. APN Study Group.

We have recently assigned a gene for familial juvenile nephronophthisis (NPH1) to chromosome 2q between microsatellite markers at loci D2S135 and D2S110. Here we have extended and refined our previous linkage analysis by studying five additional NPH families and by testing five additional markers. By haplotype analysis in a large family yielding proof of linkage, D2S135 and D2S283 were defined with certainty as flanking the NPH1 critical region within a 14-cM interval. These data now allow cytogenetic assignment of the NPH1 critical region to 2q11.1-q21.1. Furthermore, haplotype analysis in 12 small families helped to define as flanking markers D2S293 and D2S363, which span an 8-cM interval. Multipoint linkage analysis by the location score method resulted in a maximum multipoint lod score of 10.30. The Zmax-1 support interval spans 6.9 cM and is flanked by marker loci D2S293 and D2S363. Since IL1A maps to this region and has been cytogenetically mapped to 2q13 in the literature, NPH1 can be assigned more closely to 2q13 or adjacent bands. Contigs of CEPH mega-YAC clones in the region were established by screening the clones with microsatellite markers, adding marker IL1A to the physical map as a novel assignment. We conclude that the NPH1 gene most probably localizes to an interval of 6.9 cM between marker loci D2S293 and D2S363 in the vicinity of 2q13. This contig mapping provides the basis for cloning of this interval and for isolation of the NPH1 gene.

Chromosome Mapping↗
PubMed1995

Pleuro-pulmonary blastoma: a case report and review of the literature.

Pleuro-pulmonary blastoma is a rare malignant lung tumor in children and distinct from ordinary pulmonary blastoma of adulthood. Combination chemotherapy plays an important role in the treatment of this tumor, but so far no attempt of high dose chemotherapy with subsequent bone marrow or blood stem cell transplantation has been published. The case is reported of a 2-year-old boy with pleuro-pulmonary blastoma who achieved partial remission with conventional chemotherapy and surgery. Subsequent administration of high dose melphalan, etoposide, and carboplatin, followed by autologous blood stem cell transplantation resulted in a 3-month disease-free interval but did not prevent eventual local recurrence, leading to death within a few weeks. Clinical presentation, pathology, management, and prognosis are discussed and the literature reviewed.

Child, Preschool↗
PubMed1995

Urinary excretion of adenosine deaminase binding protein in neonates treated with tobramycin.

The potential tubulotoxicity of tobramycin and cefotaxim were assessed in neonates by measuring the urinary level of adenosine deaminase binding protein (ABP) and urinary alpha 1-microglobulin and beta 2-microglobulin. In a prospective study, 33 neonates who received tobramycin and cefotaxim for suspected neonatal sepsis were compared with 48 untreated newborns during the first 10 days of life. The urinary concentrations of ABP and its excretion rates, corrected for body weight and body surface area, were significantly increased from the 1st day of treatment. Urinary alpha 1-microglobulin and beta 2-microglobulin were not elevated under tobramycin and cefotaxim during the first 2 days of treatment. We conclude that ABP may be a sensitive marker for the detection of proximal renal tubular injury during tobramycin and cefotaxim treatments of neonates. The increase in urinary ABP which occurs before an elevation of urinary alpha 1-microglobulin and beta 2-microglobulin may reflect earlier structural than functional alterations. However, since none of the treated infants had signs of electrolyte disorders or glomerular dysfunction, the clinical relevance of ABP measurement should be reevaluated.

Anti-Bacterial Agents↗