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M Schalling

Publications and source records attributed to M Schalling.

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

Polymorphic expression of multidrug resistance mRNA in lung parenchyma of nonpregnant and pregnant rats: a comparison to cystic fibrosis mRNA expression.

Multidrug resistance (MDR1b) and cystic fibrosis transmembrane conductance regulator (CFTR) proteins are members of the "ATP-binding cassette" superfamily of transporters. They are associated with chloride channel activities and ATP secretion and have complementary patterns of expression in several organs. In the rat uterus, CFTR expression is replaced by MDR1b expression during pregnancy. We have studied whether expression of MDR1b and CFTR also vary in the lung during pregnancy. No variations in MDR1b or CFTR mRNA levels during pregnancy were detected. However, there was an unusual degree of variation in MDR1b mRNA expression in lung parenchyma between animals in both the control group and the pregnant group. If present among humans, polymorphic expression of MDR1 in lung parenchyma may explain part of the differences in lung symptomatology observed in the CF patients carrying the same mutation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: altered processing of neuropeptide Y in the arcuate nucleus.

Neuropeptide Y is one of the most powerful neurochemical stimulants of food intake known. The neuronal substrate for this action is believed to be the neuropeptide Y-expressing cell population in the hypothalamic arcuate nucleus. In this study, mice homozygous for the anorexia mutation (anx) were investigated histochemically; anx is a recessive mutation that causes decreased food intake and starvation, leading to death 22 days after birth. We were interested to see whether any hypothalamic neurochemical abnormalities could be detected in this genetic model of starvation. By using immunohistochemistry and in situ hybridization, the hypothalamic distributions of neuropeptide Y, cholecystokinin, galanin, and serotonin, all messenger molecules postulated to be involved in the regulation of food intake and energy metabolism, were investigated. Immunoreactivities for somatostatin, the excitatory amino acid aspartate, and acetylcholinesterase were also studied. Neuropeptide Y-like immunoreactivity was increased markedly in arcuate cell bodies and decreased in terminals in the arcuate nucleus and other hypothalamic regions of anx/anx mice compared with normal litter mates. In situ hybridization for neuropeptide Y mRNA, however, showed no significant difference in gene expression in the arcuate nucleus. In addition, immunoreactivities for aspartate, acetylcholinesterase, and somatostatin in the arcuate nucleus were decreased in anx/anx mice. For cholecystokinin, galanin, and serotonin, no certain differences in hypothalamic immunoreactivity could be seen. These data suggest that a defect in neuropeptide Y-ergic signalling in the arcuate neurons may contribute to the failure to thrive in anx/anx mice.

Animals↗
PubMed1997

Effect of in vitro promoter methylation and CGG repeat expansion on FMR-1 expression.

Fragile X syndrome is associated with a CGG repeat expansion in the 5'-untranslated region of the FMR-1 gene. Within the FMR-1 promoter a CpG island is frequently methylated in fragile X patients. To identify the effect of methylation on FMR-1 expression, we transfected methylated and unmethylated constructs containing the FMR-1 promoter in front of the CAT gene (pFXCAT) into COS-1 cells. No difference between methylated and unmethylated DNA was observed initially, whereas reduced CAT mRNA levels were observed 48 h post-transfection of the methylated construct and increased CAT activity from unmethylated DNA was observed at 72 h. To determine the effect of a CGG repeat expansion on gene expression, we inserted >200 CGG repeats between the SV40 promoter and the CAT gene (pSV2CAT). A 3-fold reduction in CAT activity was observed 24-48 h post-transfection. To study the correlation between CGG repeat expansion and FMR-1 transcription, we inserted 200 CGG trinucleotide repeats into the pFXCAT construct. Only a slight difference in mRNA levels was found between cells transfected with pFX(CGG)200CAT or pFXCAT, but a complete lack of CAT activity was observed with introduction of the repeat. We conclude that a moderate size repeat markedly reduces translation. We propose that the presence of a repeat expansion per se is the major factor influencing FMR-1 function in fragile X syndrome.

Animals↗
PubMed1997

A high ratio of insulin-like growth factor II/insulin-like growth factor binding protein 2 messenger RNA as a marker for anaplasia in meningiomas.

Insulin-like growth factors (IGFs) I and II have been implicated as autocrine or paracrine growth promoters. These growth factors bind to specific receptors, and the response is modulated by interaction with IGF-binding proteins (IGFBPs). We observed a strong correlation between anaplastic/atypical histopathology and a high IGF-II/IGFBP-2 mRNA ratio in a set of 68 sporadic meningiomas. A strong correlation was also found between clinical outcome and IGF-II/IGFBP-2 ratio, whereas previously used histochemical markers were less correlated to outcome. We suggest that a high IGF-II/IGFBP-2 mRNA ratio may be a sign of biologically aggressive behavior in meningiomas that can influence treatment strategies. We propose that low IGFBP-2 levels in combination with increased levels of IGF-II would result in more free IGF-II and consequently greater stimulation of proliferation.

Adult↗
PubMed1997

Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression.

The role of expression and secretion of the ob gene product, leptin, for the regulation of plasma leptin levels has been investigated in vitro using abdominal subcutaneous adipose tissue of 20 obese, otherwise healthy, and 11 nonobese women. Body mass index (BMI, mean+/-SEM; kg/m2) in the two groups was 41+/-2 and 23+/-1, respectively. Fat cell volume was 815+/-55 pl in the obese and 320+/-46 pl in the nonobese group. In the obese group, plasma leptin concentrations and adipose leptin mRNA (relative to gamma actin) were increased five and two times, respectively. Moreover, adipose tissue secretion rates per gram lipid weight or per fat cell number were also increased two and seven times, respectively, in the obese group. There were strong linear correlations (r = 0.6-0.8) between plasma leptin, leptin secretion, and leptin mRNA. All of these leptin measurements correlated strongly with BMI and fat cell volume (r = 0.7- 0.9). About 60% of the variation in plasma leptin could be attributed to variations in leptin secretion rate, BMI, or fat cell volume. We conclude that elevated circulating levels of leptin in obese women above all result from accelerated secretion rates of the peptide from adipose tissue because of increased ob gene expression. However, leptin mRNA, leptin secretion, and circulating leptin levels are all more closely related to the stored amount of lipids in the fat cells of adipose tissue than they are to an arbitrary division into obese versus nonobese.

Actins↗
PubMed1997

MK-801 inhibits the cortical increase in IGF-1, IGFBP-2 and IGFBP-4 expression following trauma.

Cerebral contusions increase cortical expression of insulin-like growth factor 1 (IGF-1), IGF binding protein-2 (IGFBP-2) and IGFBP-4, mRNA levels increase at the contusion site (IGF-1, IGFBP-2 and -4) and along the ipsilateral cortex (IGFBP-2 and -4). Here we explore whether this upregulation is glutamate dependent. Rats were treated with the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or the non-NMDA antagonist CNQX before and after trauma, and analysed using quantitative in situ hybridization. The induction of IGF-1 expression was completely blocked by MK-801 or CNQX. IGFBP-2 mRNA levels remained high at the contusion site in the presence of either drug, but the increase was blocked in the cortex temporal to the impact by MK-801. The increase in IGFBP-4 mRNA was blocked by MK-801 but not by CNQX.

Animals↗
PubMed1997

Cystic fibrosis mRNA expression in rat brain: cerebral cortex and medial preoptic area.

Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression has been found in the medial preoptic area using in situ hybridization, addressing the possibility of CFTR regulation of sexual maturation and reproductive behaviour. CFTR mRNA has also been found in the cortical deep pyramidal layer V implying possible involvement of CFTR in 'motor' function and output control over bodily movements and secretion. CFTR production in the brain regions observed in this study implicate involvement of CFTR in cerebral control over motor/visceral and endocrine systems.

Animals↗
PubMed1997

Protein kinase C in the developing kidney: isoform expression and effects of ceramide and PKC inhibitors.

Protein kinase C (PKC) is a serine/threonine kinase recognized as a key enzyme in signal transduction mechanisms in various biological processes. During development, PKC is involved in the regulation of growth and differentiation. In mature tissue PKC is important for homeostatic functions. We studied PKC with regard to expression and effects on differentiation, growth and apoptosis in the developing kidney. Using in situ hybridization, we demonstrate age-dependent expression of PKC alpha, PKC delta, PKC zeta and PKC lambda during fetal and postnatal kidney development. The endogenous sphingolipid product ceramide, as well as specific PKC inhibitors, disturbed nephron formation and induced apoptosis in organ cultures of E13 kidneys. In primary cell cultures of proximal tubule cells, ceramide and the specific PKC inhibitors induced apoptosis. In conclusion, PKC alpha, PKC delta, PKC zeta and PKC lambda are expressed in an age-dependent pattern during kidney development. Inhibition of PKC disturbs nephron formation, inhibits growth and induces apoptosis in the developing kidney. The findings suggest that PKC plays an important role in regulating normal kidney growth and differentiation.

Animals↗
PubMed1997

Leptin gene is expressed in rat brown adipose tissue at birth.

The ob gene product leptin is secreted from adipose tissue. Leptin has dramatic effects on food intake and energy expenditure in rodents. Brown adipose tissue is the first form of adipose tissue to appear during development, and is present at birth in most species. The development of a leptin feedback system in early life and the relative role of the brown and white adipose tissues have not yet been revealed. We have investigated the expression of ob/leptin mRNA in brown adipose tissue around birth and with respect to feeding. Northern blotting analysis and in situ hybridization experiments demonstrated the presence of leptin mRNA in brown adipose tissue at 0, 18, and 24 h after birth. The leptin mRNA level was decreased at 8 h postpartum in fed animals and at 18 or 24 h in the absence of feeding. In addition, circulating leptin was detected in the plasma of newborn rats at 0, 10, or 24 h after birth, whereas it was not detectable in 10 h-old animals that did not suckle at their mother. The presence at birth of ob mRNA and circulating leptin, as well as the early effect of suckling on ob mRNA levels, suggests the precocious involvement of leptin in the control of food intake.

Adipose Tissue, Brown↗
PubMed1997

Oculopharyngeal muscular dystrophy (OPMD)--report and genetic studies of an Australian kindred.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant disease. Due to a founder effect, it is most commonly found in the French Canadian population. The gene has recently been mapped to chromosome 14q11.2-q13 in some of these families. Here we report an Australian kindred of German descent with OPMD. Linkage analysis supports its locus to chromosome 14q. Repeat expansion studies were also carried out, but a CAG trinucleotide repeat expansion detected did not cosegregate with the disease. We conclude that there is no evidence of genetic heterogeneity or involvement of repeat expansion in OPMD.

Australia↗
PubMed1997

Schizophrenia and neurotrophin-3 alleles.

Studies of brain anatomy and premorbid functioning indicate that schizophrenia may be of neurodevelopmental origin. In the neurotrophic factor neurotrophin-3 (NT-3) gene, the A3/147-bp allele in a dinucleotide repeat polymorphism located in the promoter region was found to be associated with schizophrenia in a Japanese study. Another NT-3 polymorphism (Glu63Gly) indicated an association with schizophrenic patients with a putative neurodevelopmental form of the disease. We examined Swedish schizophrenic patients (n = 109) and control subjects (n = 78) for the same two NT-3 polymorphisms, as well as a third silent exonic polymorphism (at Pro55). No significant difference was found between the two groups. However, in a meta-analysis including the present and previous studies of Caucasian subjects, the A3/147-bp allele frequency was found to be significantly higher in the schizophrenic patients. In the present study, carriers of the A3/147 bp allele tended to have an earlier age of onset and to display more extrapyramidal symptoms. In the silent exonic polymorphism (at Pro55), female schizophrenic patients had higher adenine and lower guanine allele frequencies than control female subjects. Together with previous studies, the results provide some support for an association between the NT-3 gene and certain forms of schizophrenia. This warrants further investigation of NT-3 and other neurotrophic factors with additional polymorphisms and larger patient samples.

Adult↗
PubMed1997

Increased leptin messenger RNA and serum leptin levels in children with Prader-Willi syndrome and nonsyndromal obesity.

To study the potential role of the ob gene pathway in childhood obesity, we have investigated leptin mRNA levels in s.c. adipose tissue obtained from nonobese prepubertal children (n = 20), obese nonsyndromal children (n = 6), and children with Prader-Willi syndrome (n = 6) by in situ hybridization histochemistry. We have also investigated the fasting serum leptin levels in such children. Compared with nonobese children, leptin mRNA expression was higher both in children with Prader-Willi syndrome and in children with nonsyndromal obesity (p < 0.01). Furthermore, the serum leptin levels were also significantly higher in both children with Prader-Willi syndrome and nonsyndromal obesity compared with the nonobese children (p < 0.001). However, no significant differences in adipose tissue leptin mRNA or serum leptin levels were observed between children with Prader-Willi syndrome and nonsyndromal obese children. As expected both fasting serum leptin levels and leptin mRNA expression levels correlated to body mass index (rs = 0.80 and 0.73, respectively, p < 0.005). No difference in leptin expression between Prader-Willi syndrome and nonsyndromal childhood obesity could be revealed in the present study. However, differences in the hypothalamic response to leptin between the two forms of obesity cannot be excluded.

Adipose Tissue↗
PubMed1997

Tumor-specific decreased expression of calcium sensing receptor messenger ribonucleic acid in sporadic primary hyperparathyroidism.

Secretion of PTH is regulated by extracellular calcium via calcium receptors (CaR) on the parathyroid cell surface. Recent studies have shown a decreased expression of CaR messenger RNA (mRNA) and CaR protein in pathological parathyroids. We studied the expression of CaR mRNA in pairs of adenoma and adenoma-associated normal gland from the same patients (n = 17) and in biopsies of normal parathyroid glands of normocalcemic subjects (n = 4) using in situ hybridization with oligonucleotide probes on frozen sections. No down-regulation of CaR mRNA caused by hypercalcemia could be demonstrated in the normal adenoma-associated parathyroids when compared with the normal parathyroids of normocalcemic subjects. In contrast, CaR mRNA in the adenomas was significantly reduced to 64% (median; range 41-98) of the corresponding normal adenoma-associated glands. No correlation was seen between CaR mRNA in the adenoma and preoperative serum calcium, PTH, or weight of the adenoma. Loss of heterozygosity studies were performed on adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated, excluding allelic loss as the cause for decreased CaR mRNA expression in the adenomas. It is concluded that the lowered levels of CaR mRNA in parathyroid adenomas may contribute to the increased set point of PTH secretion. In large adenomas the increased cell mass seems to be more important for the increased secretion of PTH.

Adenoma↗
PubMed1997

Delayed cytokine expression in rat brain following experimental contusion.

Proinflammatory cytokines mediate brain injury in experimental studies. This study was undertaken to analyze the production of proinflammatory cytokines in experimental contusion. A brain contusion causing delayed edema was mimicked experimentally in rats using a weight-drop model. Intracerebral expression of the cytokines interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF alpha), IL-6, and interferon-gamma (IFN gamma) was studied by in situ hybridization and immunohistochemistry. The animals were killed at 6 hours or 1, 2, 4, 6, 8, or 16 days postinjury. In the injured area, no messenger (m)RNA expression was seen during the first 2 days after the trauma. On Days 4 to 6 posttrauma, however, strong IL-1 beta, TNF alpha, and IL-6 mRNA expression was detected in mononuclear cells surrounding the contusion. Expression of IFN gamma was not detected. Immunohistochemical double labeling confirmed the in situ hybridization results and demonstrated that mononuclear phagocytes and astrocytes produced IL-1 beta and that mainly astrocytes produced TNF alpha. The findings showed, somewhat unexpectedly, a late peak of intracerebral cytokine production in the injured area and in the contralateral corpus callosum, allowing for both local and global effects on the brain. An unexpected difference in the cellular sources of TNF alpha and IL-1 beta was detected. The cytokine pattern differs from that seen in other central nervous system inflammatory diseases and trauma models, suggesting that the intracerebral immune response is not a uniform event. The dominance of late cytokine production indicates that many cytokine effects are late events in an experimental contusion: Different pathogenic mechanisms may thus be operative at different times after brain injury.

Animals↗
PubMed1996

PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.

A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.

Actins↗
PubMed1996

Increase of insulin-like growth factor (IGF)-1, IGF binding protein-2 and -4 mRNAs following cerebral contusion.

The insulin-like growth factor (IGF) system has a role in repair following hypoxic-ischemic injury in many tissues including the brain. To study the involvement of the IGF system following head trauma, we used a rat contusion model, which produces a focal lesion of the cerebral cortex. Molecules in the IGF system were analyzed using in situ hybridization at different times following impact. We observed a dramatic up-regulation of insulin-like growth factor binding protein-2 (IGFBP-2) mRNA in cortical areas adjacent to the injury 24 h after impact, with a peak 10-fold increase engaging most of the ipsilateral cortex 2 and 3 days post-contusion. Seven days after the contusion, IGFBP-2 expression was only moderately up-regulated and again concentrated around the injury. IGFBP-4 mRNA levels increased 4-fold ipsilateral to the site of injury, with retained pattern of cortical expression. IGFBP-3, IGFBP-5 and IGFBP-6 mRNA all displayed distinct expression patterns in the brain but no significant changes were observed following injury. In contrast, IGF-1 mRNA levels were very low prior to contusion, but increased markedly at the site of injury with a peak at day 3. We were unable to detect any changes in the type 1 IGF-receptor or IGF-2 mRNA following contusion. The neuropeptide cholecystokinin (CCK) mRNA was clearly up-regulated following contusion, with an even distribution over the ipsilateral cortex. The expression pattern of molecules in the IGF system post-contusion differs in part to changes observed following hypoxic-ischemia or ischemia alone, perhaps reflecting different regulatory mechanisms depending on the type of injury.

Animals↗