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Biomedical subjects

B Meister

Publications and source records attributed to B Meister.

At least 73 records · Page 4Linked to original sources
PubMed1995

Altered expression after expansion of a v-erbA transgene in transgenic mice.

Repetitive DNA is known to undergo size variations based on an increase or decrease in the number of monomer units. We describe here the spontaneous expansion of an experimentally introduced tandem array of repeats in a transgenic mouse consisting of the human beta-actin promoter fused to the viral oncogene v-erbA and an SV40 polyadenylation signal (hAP/v-erbA). The expansion of the transgene was identified during routine screening of transgenic offspring for heterozygosity or homozygosity in one founder line. The control heterozygote genome consisted of the hAP/v-erbA transgene organized as a tandem array approximately five monomer units at a single chromosomal locus. The number of units increased to 20-21 copies, and germline transmission of the expanded units was stable for at least two generations. The majority of animals carrying the expanded monomer units retained their RNA expression patterns; however, some of these animals had drastically reduced expression levels. We discuss the possibility that expansion of repeated units may provide a mechanism by which the expression of a deleterious transgene is reduced.

Actins↗
PubMed1995

Fulminant hepatic failure in a child as a potential adverse effect of trimethoprim-sulphamethoxazole.

UNLABELLED: Trimethoprim-sulphamethoxazole (TMP-SMZ) is considered a safe drug for treatment of infectious bacterial diseases in children. Side-effects are rare and generally take the form of a hypersensitivity reaction to the sulphamethoxazole component of the drug. Hepatic injury usually presents as a transient elevation of liver enzymes, which is of little clinical relevance. Fulminant liver failure due to TMP-SMZ has been reported in only six adults and never in children. We here report a 5-year-old girl who developed fulminant liver failure 3 weeks after her third exposure to TMP-SMZ. After a biphasic clinical course she underwent successful liver transplantation. CONCLUSION: Trimethoprim-Sulphamethoxazole may cause fulminant liver failure in children. The disease can run a biphasic clinical course and liver transplantation must be considered as the therapeutic option for these patients.

Biopsy↗
PubMed1995

Increased expression of serotonin transporter messenger RNA in raphe neurons of the aged rat.

The action of serotonin (5-hydroxytryptamine; 5HT) in the nervous system is terminated by reuptake of the neurotransmitter into the presynaptic nerve terminal via a plasma membrane-bound transporter protein. Recently, cDNAs encoding serotonin transporter protein were cloned. Using in situ hybridization we have studied the expression of serotonin transporter mRNA in the bulbospinal 5HT system of adult (2-3 months) and aged (30 months) rats. In adult rats, serotonin transporter mRNA labelled neurons were detected in the nucleus raphe obscurus, pallidus and magnus. In all aged rats, the optical density of the serotonin transporter mRNA labelling of individual cell profiles was increased by 20-30% (P < 0.001) when compared with adult rats. Five of the six aged rats studied had various degrees of hindlimb motor dysfunctions. In rats with the most pronounced signs of hindlimb motor dysfunction the number of labelled neurons was increased by 25-75% (P < 0.01) when compared with young adult rats. It is concluded that an increased serotonin transporter gene expression is present in the bulbospinal 5HT system of aged animals.

Aging↗
PubMed1995

Expression of protein kinase C isoforms in renal tissue.

PKC plays a central role for the regulation of renal function. PKC consists of a family of isoenzymes. By employing Northern blot techniques we have demonstrated that mRNA transcripts for the classical Ca(2+)-dependent, diacylglycerol-activated isoform alpha, the novel, Ca(2+)-independent isoform delta and the atypical isoform zeta are abundantly expressed in the rat kidney. The novel PKC-epsilon was weakly expressed. The classical PKCs beta I, beta II and gamma could not be detected. The mRNA expression of PKC-delta and -zeta increased with age. The intrarenal localization of PKC-alpha, -delta and -zeta isoforms were studied in the adult kidney using in situ hybridization. In the cortex, the PKC-alpha isoform showed the strongest hybridization signal. PKC alpha, delta and zeta were all distributed in the outer medulla. The PKC-alpha probe detected particularly strong signal in the outer stripe of the outer medulla. Western blot confirmed the presence of the PKC-alpha, -delta and -zeta enzymes in renal tissue. The results show cell-specific and developmentally-dependent expression of three types of PKC isoforms with different responses to diacylglycerol and calcium. The developmental increase of both PKC-delta and PKC-zeta suggests a specific role for these isoforms for the functional regulation of the mature kidney.

Animals↗
PubMed1995

Laminin and neuropeptide Y are increased by synapsin transfection in cultured NG108-15 neuroblastoma/glioma hybrid cells.

We have investigated the presence and expression of laminin and neuropeptide Y (NPY) in several NG108-15 cell lines transfected with synapsin Ib, IIa, or IIb. The content of laminin, a basal membrane glycoprotein that promotes adhesion and induces neurite out-growth and neuronal differentiation, was increased in all transfected cell lines examined. In cells that were chemically differentiated with prostaglandin E1 plus 3-isobutyl-1-methylxanthine, laminin levels were increased even further. The content of NPY, suggested to be a neurotransmitter/neuromodulator in peripheral sympathetic neurons as well as in central neurons, was also increased in all transfected cell lines examined. Immunohistochemical analysis combined with confocal laser microscopy showed that NPY staining was granular and very often enriched in neuritic varicosities. The distribution and the staining pattern of NPY were consistent with storage of NPY in large dense-cored vesicles. The results indicate that, in differentiated neurons, the synapsins increase the levels of a neuropeptide transmitter stored in large dense-cored vesicles and of an extracellular matrix protein associated with neuronal maturation.

Glioma↗
PubMed1995

Protein phosphatase-1 in the kidney: evidence for a role in the regulation of medullary Na(+)-K(+)-ATPase.

Previous studies of hormonal regulation of renal Na(+)-K(+)-ATPase have indicated that the activity of the sodium pump is regulated by phosphorylation-dephosphorylation reactions. Here we report that okadaic acid (OA) and calyculin A (CL-A), inhibitors of protein phosphatase (PP)-1 and PP-2A, inhibited Na(+)-K(+)-ATPase activity in cells from the rat thick ascending limb (TAL) of loop of Henle in a dose-dependent manner. CL-A was 10-fold more potent than OA. On the basis of the inhibitory constant values of CL-A and OA for PP-1 and PP-2A, it is concluded that the tubular effect is mainly due to inhibition of PP-1. In situ hybridization studies with oligonucleotide probes revealed very strong PP-1 alpha and PP-1 gamma 1 mRNA labeling in the outer stripe of the outer medulla, strong labeling in the inner stripe of the outer medulla, and weak labeling in the inner medulla. Very weak labeling was demonstrated in the outer cortex. PP-1 beta mRNA labeling was very strong in the inner stripe of the outer medulla, whereas the outer stripe had weaker labeling, and the inner medulla had weak labeling. PP-1 alpha, PP-1 beta, and PP-1 gamma 1 mRNA were also demonstrated in the transitional epithelium of the ureter. The abundance of the PP-1 alpha and PP-1 gamma isoforms as measured by immunoblotting was very high in tissue from the outer medulla, which also has a high abundance of the endogenous dopamine-regulated PP-1 inhibitor, DARPP-32.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Identification of synaptic proteins and their isoform mRNAs in compartments of pancreatic endocrine cells.

Several proteins that are of importance for membrane trafficking in the nerve terminal have recently been characterized. We have used Western blot and immunohistochemistry to show that synaptotagmin, synaptobrevin/VAMP (vesicle-associated membrane protein), SNAP-25 (synaptosomal-associated protein of 25 kDa), and syntaxin proteins are present in cells of the islets of Langerhans in the endocrine pancreas. Synaptotagmin-like immunoreactivity (-LI) was localized to granules within the cytoplasm of a few endocrine cells located in the periphery of the islets, identified as somatostatin-containing cells, and in many nerve fibers within the islets. VAMP-LI was seen in granules of virtually all pancreatic islet cells and also in nerve fibers. SNAP-25-LI and syntaxin-LI were predominantly present in the plasma membrane of the endocrine cells, including insulin-producing beta cells. In situ hybridization, using isoform-specific oligonucleotide probes, detected VAMP-2, cellubrevin, SNAP-25, syntaxin 1A, 4, and 5, and munc-18 mRNAs in isolated pancreatic islets and in insulin-producing cells. The results show the presence of several synaptic proteins at protein and mRNA levels in pancreatic islet cells, suggesting that they may have specific roles in the molecular regulation of exocytosis also in insulin-secreting cells.

Animals↗
PubMed1994

Thyroid abnormalities and hepatocellular carcinoma in mice transgenic for v-erbA.

The v-erbA oncogene consists of an avian retroviral gag gene fused to a mutated thyroid hormone receptor. To define better its role as an oncogene in mammals and its ability to function as a dominant negative transcription factor, transgenic mice expressing v-erbA ubiquitously were generated. The effects of v-erbA are pleiotropic, tissue-specific and dose dependent. Mice have breeding disorders, abnormal behavior, reduced adipose tissue, hypothyroidism with inappropriate TSH response, and enlarged seminal vesicles. This provides an animal model consistent with the proposal that v-ErbA functions as a dominant negative receptor by transcriptional interference or squelching of normal receptors or associated proteins. Finally, male animals develop hepatocellular carcinoma, demonstrating that v-erbA can promote neoplasia in mammals.

Adipose Tissue↗
PubMed1994

Multiple neuropeptide immunoreactivities in a renin-producing human paraganglioma.

BACKGROUND: A case of a renin-producing paraganglioma of adrenal origin with metastases to the retroperitoneal area, paravaginal area, and the ovary is reported with immunohistochemical findings indicating expression of multiple neuropeptide immunoreactivities. The patient was 23 years old at the time of diagnosis, and died from metastatic spread of the tumor 7 years later. METHODS: Tumor tissue was examined by light microscopy, indirect immunohistochemistry, and electron microscopy. RESULTS: The tumor tissue investigated contained several cells exhibiting opioid peptide-like immunoreactivities (i.e., enkephalin and dynorphin-like immunoreactivity [LI]). A lower number of cells displayed neuropeptide Y-, galanin-, somatostatin-, neurotensin-, substance P-, peptide histidine-isoleucine-, cholecystokinin-, renin-, and calbindin-LI. CONCLUSION: To the authors' knowledge, galanin, dynorphin, peptide histidine-isoleucine, cholecystokinin, and calbindin have not been reported previously to occur in paraganglioma, and renin has been reported to occur very rarely. A review of recent literature suggest that enkephalin-, neuropeptide Y-, and somatostatin-like immunoreactivities may be useful as diagnostic markers for paragangliomas.

Adrenal Gland Neoplasms↗
PubMed1994

Segment-specific expression of messenger RNA encoding for a glutamate transporter by renal tubule cells.

Transport of the amino acid glutamate across plasma membranes of neurons, glial cells and epithelial cells of the small intestine and kidney is carried out via specific transport proteins. Recently, a high-affinity Na(+)-dependent glutamate transporter was cloned from rabbit small intestine. We have designed oligonucleotide probes to sequences of rabbit glutamate transporter mRNA and used these for in situ hybridization histochemistry in order to define the cellular localization of glutamate transporter mRNA in the rabbit kidney. Strong hybridization with the probes to glutamate transporter mRNA was demonstrated in the outer stripe of the outer medulla, with tubular rays radiating into the cortex. In emulsion-dipped and hematoxylin-eosin counterstained sections, it could be seen that cells expressing glutamate transporter mRNA were localized in the outer stripe of the outer medulla, coinciding with the S3 segment of proximal tubules. The results show that glutamate transporter mRNA is expressed in proximal tubule cells of the rabbit kidney, suggesting that Na(+)-dependent uptake of glutamate occurs primarily within this nephron segment.

Amino Acid Transport System X-AG↗
PubMed1994

Methotrexate osteopathy in infants with tumors of the central nervous system.

Methotrexate osteopathy, previously reported as a complication of maintenance-therapy for acute lymphoblastic leukemia, is characterized by osteopenia, particularly involving the lower extremities, thick, dense provisional zones of calcification, growth arrest lines, and corner fractures resembling scurvy. In attempts to postpone radiotherapy in infants under three years of age, the multicentric German therapy protocol for childhood central nervous system tumors (HIT-89 protocol) has employed high cumulative methotrexate doses. Here we describe osteopathy in three patients as a toxic side effect after administration of cumulative methotrexate doses of 20 g/m2, 80 g/m2 and 135 g/m2. The high prevalence of this adverse effect in infants with tumors of the central nervous system may be attributed to the long-term therapy with high cumulative methotrexate-doses. Both factors may favor intracellular accumulation of methotrexate and formation of methotrexate-polyglutamates and may be responsible for bone toxicity. Apparently the susceptibility of the rapidly growing skeletal structures of infants under three years of age to this toxic side effect of methotrexate is remarkably high.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Hexokinase I messenger RNA in the rat central nervous system.

Hexokinase I (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is the first enzyme required in the metabolism of glucose in the central nervous system and plays a major role in regulation of the cerebral glycolytic rate. The distribution of hexokinase I mRNA was examined throughout the central nervous system of the rat by use of oligonucleotide probes and in situ hybridization histochemistry. In the rhinencephalon, strong hexokinase I mRNA labeling was demonstrated in the glomerular, mitral, internal granular, and internal plexiform layers, whereas the olfactory nerve, external plexiform, and subependymal layers and ependyma were devoid of labeling. Within the telencephalon, strong labeling was present in all layers (with the exception of the molecular layer) of the cerebral cortex, in the septum, in CA1-4 and dentate gyrus of the hippocampus, and in several amygdaloid nuclei. There was only weak labeling in the nucleus accumbens and caudate putamen. In the diencephalon, there was in general a strong labeling in the epithalamus, in several thalamic nuclei, including the anteriodorsal, anterioventral, anteriomedial, reticular, paravetricular, intermediodorsal, anteriomedial, interanteriomedial, rhomboid, reuniens, and parafascicular thalamic nuclei. Several hypothalamic regions, including the subfornical organ, the medial preoptic area, the suprachiasmatic, supraoptic, paraventricular, dorsomedial, ventromedial nuclei, and the zona incerta, were strongly labeled. In the mesencephalon, there was particularly strong labeling in the pars compacta and reticulata of the substantia nigra, central gray, and red nucleus, in the Darkschewitsch nucleus, and in the medial accessory oculomotor nucleus. In the rhombencephalon, there was strong hybridization in all raphe nuclei, pontine, tegmental, lateral parabrachial, olivary nuclei, and several cranial motor nuclei. All neurons of the locus ceruleus were heavily labeled. Very strong labeling was present in Purkinje and granular cells of the cerebellar cortex. Neurons of the medulla oblongata area postrema, nucleus tractus solitarius, reticular nucleus, nucleus cuneatus and several motor nuclei were strongly labeled. In the spinal cord, labeled cells were present in all laminae, and also neurons of the dorsal root ganglion were heavily labeled. Hexokinase I mRNA was also demonstrated in the epithelium lining the the choroid plexus. In the E15 fetus, very strong labeling was seen in the liver, heart, and trigeminal ganglion, with less intense labeling in in the brain and other tissues having more moderate labeling. Administration of 2% saline as drinking water resulted in a marked increase in hexokinase I mRNA in the magnocellular neurons of the supraoptics and paraventricular nuclei. In summary, the results show extensive neuronal distribution of hexokinase I mRNA with regional differences in the expression pattern.

Animals↗
PubMed1994

Coexisting NPY and NE synergistically regulate renal tubular Na+, K(+)-ATPase activity.

The sympathetic renal nerves are of central importance for the regulation of sodium balance. Sodium excretion decreases following renal nerve activation and increases following denervation. These effects have been attributed to norepinephrine (NE) acting on alpha-adrenergic receptors. In the present study, using isolated permeabilized rat renal proximal convoluted tubule (PCT) cells, neuropeptide Y (NPY) was shown to stimulate Na+, K(+)-ATPase activity. This 36-amino acid peptide is a messenger molecule in the sympathetic nervous system which is co-stored with NE and dopamine-beta-hydroxylase (DBH), the NE synthesizing enzyme in the renal nerves. The effect is likely to be mediated via the NPY Y2 receptor, a pertussis toxin (PTX)-sensitive G-protein, and calcium. It is partially antagonized by alpha-adrenergic antagonists, and enhanced by the subthreshold doses of alpha-adrenergic agonists. Our results suggest an important role for this peptide in the regulation of the sodium balance in the kidney.

Animals↗
PubMed1994

Cholecystokinin B receptor gene expression in hypothalamic neurosecretory neurons after experimental manipulations.

Magnocellular neurons of the supraoptic (SON) and paraventricular (PVN) nuclei projecting to the neurohypophysis produce, in addition to the classical hormones vasopressin and oxytocin, a large number of other peptides, one of which is cholecystokinin (CCK). Binding sites for CCK have been identified in the posterior pituitary. Recently the cDNAs for CCKA and CCKB receptors were isolated and characterized, and CCKA and CCKB receptor mRNAs were localized in the SON and PVN. We have used complementary oligonucleotides and in situ hybridization histochemistry to study CCKB receptor mRNA in hypothalamic neurons. Changes in the expression of CCKB receptor mRNA in the SON and PVN were analysed in salt-loaded as well as in hypophysectomized animals. Levels of CCKB receptor mRNA in the PVN and SON increased markedly in salt-loaded animals as compared to controls. An increase in CCKB receptor mRNA levels was seen in the SON and PVN after 3 days of salt loading, with high levels continuing through 5 and 7 days. At 14 days, the levels of CCKB receptor mRNA in the PVN were significantly lower as compared to 7 days. Hypophysectomy 5 days prior to sacrifice, resulting in a nerve lesion in the neurohypophysial pathway and removal of the anterior pituitary hormones, induced a significant increase in CCKB receptor mRNA levels in neurons of the PVN. The increase in CCKB receptor mRNA labelling after salt loading was mainly observed in the ventrolateral part of the PVN and in the dorsolateral part of the SON, corresponding to oxytocin-containing neurons, whereas the increase after hypophysectomy was mainly seen in the central part of the PVN and in the ventral part of the SON, corresponding to vasopressin-containing neurons. The results suggest that the synthesis of CCKB receptors in magnocellular neurons is increased upon osmotic challenge and hypophysectomy.

Animals↗
PubMed1994

Identification of CD34+ cord blood cells and their subpopulations in preterm and term neonates using three-color flow cytometry.

Three-color flow cytometry was used to identify CD34+ cord blood (CB) hematopoietic progenitors of preterm (n = 13) and term (n = 18) neonates. The frequency of CD34+ CB cells gated on the lymphocyte fraction in term neonates is about half the frequency of preterm neonates (mean 1.84 +/- 0.8 vs. 3.49 +/- 1.8, p < 0.005). The difference of absolute CD34+ cells between the 2 groups did not reach statistical significance (premature 169 +/- 161 vs. mature 108 +/- 62.6 x 10(6) cells/l). The proportion of myeloid lineage-committed CD34+ cells coexpressing the CD33 antigen in preterm neonates does not significantly differ from that found in term neonates. However, in preterm neonates a higher fraction of erythroid lineage-committed CD34+ cells coexpresses the CD71 antigen as compared with term neonates (mean 28.7 +/- 14.1 vs. 11.4 +/- 5.7, p < 0.001). The positive correlation between gestational age and the ratio of myeloid/erythroid lineage-specific progenitor cells (r = 0.61, n = 31, p < 0.0005) suggests gestational changes in lineage commitment of CD34+ cells.

Antigens, CD↗