Brain death in infants and children.
Explore the source record for details and available documents.
Brain Death↗
Biomedical subjects
K Sainio
Publications and source records attributed to K Sainio.
Neurotrophin 3 rescues neuronal precursors from apoptosis and promotes neuronal differentiation in the embryonic metanephric kidney.
We analyzed the developmental regulation and role of the neurotrophins during metanephric kidney morphogenesis. RNase protection assay revealed the presence of nerve growth factor, neurotrophin 3 (NT-3), and brain-derived neurotrophic factor mRNAs and the regulation of their expression during embryonic development of rat metanephros. NT-3 induced differentiation (neurite outgrowth) and survival (inhibition of apoptosis) of the neuronal precursors in cultured nephrogenic mesenchymes and neuronal differentiation in cultured whole kidneys, whereas NT-4/5, brain-derived neurotrophic factor, and nerve growth factor were without effect. The neurotrophins did not trigger tubular differentiation of isolated nephrogenic cells, which underwent apoptosis when cultured with or without the neurotrophins. NT-3 is thus an inducer of differentiation and a survival factor for renal neuronal cells, but none of the neurotrophins is a morphogen in kidney tubule induction.
Animals↗
Primary structure and expression of a novel human laminin alpha 4 chain.
The complete primary structure of a novel human laminin alpha 4 chain was derived from cDNA clones. The translation product contains a 24-residue signal peptide preceding the mature alpha 4 chain of 1792 residues. The domain structure is similar to that of the recently described alpha 3 chain [Ryan, Tizard, Van Devanter and Carter (1994) J. Biol. Chem. 269, 22779-22787]. Northern analysis of RNA from human fetal and adult tissues revealed developmental regulation of expression. In adult, strong expression was observed in heart as well as lung, ovary, small and large intestines, placenta and liver, whereas weak or no expression was detected in skeletal muscle, kidney, pancreas, testis, prostate or brain. In contrast, fetal lung and kidney revealed high expression. In situ hybridization analysis of human fetal and newborn tissues showed expression of the laminin in alpha 4 chain in certain mesenchymal cells in tissues such as smooth muscle and dermis.
Adult↗
Mismatch negativity indicates vowel discrimination in newborns.
The present study shows that an infrequent vowel ('deviant') presented among frequent vowels ('standard') elicits in sleeping human newborns a negativity in the auditory event-related potential (ERP) resembling the mismatch negativity (MMN) recorded in adults. Thus, the MMN appears to provide means to investigate brain mechanisms of vowel perception in infants.
Acoustic Stimulation↗
Activin disrupts epithelial branching morphogenesis in developing glandular organs of the mouse.
We report that activin profoundly alters epithelial branching morphogenesis of embryonic mouse salivary gland, pancreas and kidney rudiments in culture, indicating that it may play a role as a morphogen during mammalian organogenesis. In developing pancreas and salivary gland rudiments, activin causes severe disruption of normal lobulation patterns of the epithelium whereas follistatin, an activin-binding protein, counteracts the effect of activin. In the kidney, activin delays branching of the ureter bud and reduces the number of secondary branches. TGF-beta induces a pattern of aberrant branching in the ureter bud derived epithelium distinct from that seen for activin. Reverse-transcriptase polymerase chain reaction, Northern hybridization and in situ hybridization analyses indicate that these developing tissues express the mRNA transcripts for activin subunits, follistatin or activin receptors. Our results are suggestive of a potential role for the activin-follistatin system as an intrinsic regulator of epithelial branching morphogenesis during mammalian organogenesis.
Activin Receptors↗
The human laminin beta 2 chain (S-laminin): structure, expression in fetal tissues and chromosomal assignment of the LAMB2 gene.
The sequence of the human laminin beta 2 chain (previously s-laminin) was derived from cloned cDNAs. The complete translation product has 1798 amino acid residues, including a 32-residue signal peptide. The human chain lacks the tripeptide sequence LRE in domain I which is present in the rat polypeptide chain and has been shown to promote motor neuronal cell adhesion. The human gene (LAMB2) was localized to chromosome 3p21 using somatic cell hybrids and fluorescent in situ hybridization analysis. Northern and in situ hybridization analyses from numerous fetal tissues revealed that the beta 2 chain is generally widely expressed. beta 2, but not beta 1, was shown by in situ hybridization to be expressed in fetal brain and renal glomeruli. In fetal skin, beta 2 was expressed both in epidermal and dermal cells, while beta 1 was expressed only in the dermis. Expression of beta 2 in fetal liver was seen in hepatocytes, while no signals were observed for beta 1. In lung, both beta 1 and beta 2 were expressed in alveoli and bronchial smooth muscle cells, whereas only the beta 2 chain was expressed in bronchial epithelial cells. In striated muscle, however, the beta 1 chain, but not beta 2, was expressed. These results indicate different biological roles for the laminin beta 1 and beta 2 chains.
Amino Acid Sequence↗
The glomerular mesangium: studies of its developmental origin and markers in vivo and in vitro.
Cultured mesangial cells are widely used to explore their role in kidney glomerular functions, but methods to reliably identify these cells in vivo and in vitro are lacking. Furthermore, the proposed relationship of mesangial cells to e.g. fibroblasts and smooth muscle cells has not been systematically studied. Here we wanted to search for markers of practical use also in identifying cultured mesangial cells, and to apply these markers in a study of the origin of glomerular mesangium. No epitopes specific for only mesangial cells could be identified, and no evidence of their true relationship with neural or lymphocytic lineages could be found. Findings with the variety of markers used suggest that mesangial cells may be indistinguishable from smooth muscle cells and fibroblasts. A panel of antibodies, including those against Thy1.1, smooth muscle actin, desmin, cellular fibronectin and beta 1 integrin alpha 1 and alpha 5 chains, and Wistaria floribunda (WFA) and Ricinus communis (RCA I) lectins, were found useful for mesangial cell detection in vivo and in vitro. The origin of glomerular mesangial cells could not be conclusively determined, although the results indirectly suggest that mesangial cells together with endothelial cells migrate to the glomerulus from the outside.
Animals↗
Sensory neuropathy in infantile onset spinocerebellar ataxia (IOSCA).
Infantile onset spinocerebellar ataxia with sensory neuropathy is a new, inherited multisystem disorder discovered in 19 Finnish patients. In order to define the neuropathy of the disease, we measured sensory nerve action potentials and nerve conduction velocities in 18 patients, and recorded somatosensory evoked potentials (SEP) in 10 patients and performed a sural nerve biopsy in 13 patients. The fixed and teased nerve fascicles were examined by light and electron microscopy, and the whole transverse section of a nerve fascicle was photographed and enlarged for morphometric measurements. Our investigation revealed an early onset, rapidly progressive axonal neuropathy: the sensory action potentials were decreased after the age of 2 and a severe loss of mainly large myelinated fibers was found.
Adolescent↗
Antisense inhibition of low-affinity nerve growth factor receptor in kidney cultures: power and pitfalls.
1. Antisense inhibition of gene expression implies that the expression of the target protein is selectively inhibited at either the translational or the transcriptional level by complementary DNA or RNA constructs that are antiparallel to the target sequence. The antisense inhibition strategy provides means to study the roles of individual proteins and has, in spite of its limitations, gained a wide range of both therapeutic and experimental applications. 2. In developmental biology, protein expression has been selectively inhibited by the use of antisense gene transfection and by antisense deoxyoligonucleotides. The transfectability of embryonic tissues is variable, but in general fetal and embryonic cells take up foreign DNA relatively efficiently, in particular, short deoxyoligonucleotides that penetrate mesenchymal cells within a few hours without any manipulation. 3. We have now evaluated the advantages and pitfalls of antisense inhibition by deoxyoligonucleotides in organ culture and describe our experience from the inhibition of low-affinity nerve growth factor receptor expression in embryonic mouse and rat kidneys. 4. The expression of nerve growth factor receptor can be specifically inhibited by deoxyoligonucleotides, but the target sequence-dependent window of, in particular, phosphorothioate-modified oligonucleotides is quite narrow. The culture conditions affect the response to the oligonucleotides and their cellular incorporation is variable with respect to the cell type and stage of differentiation.
Animals↗
Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease.
We report the clinical findings in 19 Finnish patients, including six pairs of siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive clinical symptoms manifested between one and two years of age in previously healthy infants. The first manifestation of children at that age was clumsiness and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of deep tendon reflexes were discovered on clinical examination. By school age ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy developed by adolescence. In addition, an acute crisis with status epilepticus was a late manifestation. We found a marked decrease in sensory nerve condition velocities, a progressive loss of myelinated fibers in sural nerve specimen, and abnormal background activity in EEG with advancing age. The main finding in neuroradiological investigations was cerebellar atrophy. The occurrence of the disease in siblings and lack of manifestations in parents indicate recessive inheritance.
Adolescent↗
Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues.
The primary structure of the human laminin M chain was determined from cDNA clones isolated from human placental libraries. The clones covered a total of 6,942 bp, with 49-bp encoding a 5' end untranslated region and 6,893-bp coding for a translated sequence. The complete human laminin M chain contains a 22-residue signal peptide and 3,088 residues of the mature M chain. The M chain has a domain structure similar to that of the human and mouse A chains. The homology between the two human laminin heavy chains is highest in the short arm region and lowest in the long arm helical domain I + II. Northern blot analysis of human fetal tissues showed that the M chain was expressed in most tissues such as cardiac muscle, pancreas, lung, spleen, kidney, adrenal gland, skin, testis, meninges, choroid plexus, and some other regions of the brain, but not in liver, thymus, and bone. In situ hybridization localized the expression of the M chain gene to cells of mesenchymal origin. In contrast, expression of the A chain was observed only in kidney, testis, neuroretina and some region of brain as determined by Northern analyses. Epithelial and endothelial cells were negative for both M and A chain gene transcripts. The gene for the human M chain (LAMM) was localized to chromosome 6q22-->23.
Amino Acid Sequence↗
Neurotrophins and ciliary neurotrophic factor: their biology and pathology.
Neurotrophins (NTFs) and ciliary neurotrophic factor (CNTF) induce the differentiation of neuronal cells, rescue them from naturally occurring death, and trigger neuronal regeneration. The NTFs bind to two classes of cell surface receptors, whereas CNTF receptor is composed of three subunits. The functions of these polypeptide survival factors with trophic action on nerve cells have recently been approached by the targeted disruption of the CNTF, NTF and their receptor genes by the homologous recombination technique. The embryonic growth and morphogenesis of these gene 'knock-out' mice is normal, but they develop with defects in various subsets of the peripheral nervous system, and the homozygous mutant mice often die during the early postnatal period. Disturbances in the biology of NTFs and CNTF have recently been implicated in the pathogenesis of certain common neurodegenerative disorders, such as Parkinson's disease, motor neurone diseases, and Alzheimer's disease. Intensive research on their pharmaceutical perspective has, therefore, been provoked. All neurotrophins and CNTF can now be synthesized on a large scale as biologically active recombinant proteins, and several alternatives for their local applications to the target tissue have been presented. Their therapeutic potential is discussed.
Animals↗
Neuronal characteristics in embryonic renal stroma.
The metanephric mesenchyme is considered a homogeneous population of predetermined, but pluripotent cells with a nephrogenic bias. By an inductive stimulus, the mesenchyme is programmed to differentiate into the various epithelial phenotypes of the secretory nephron. A fraction of the mesenchymal cells, however, remains in the interstitium between the nephrons and differentiates into spindle-shaped, clear-cytoplasmic renal stroma. We have analyzed the molecular nature of these cells in order to discover the specific cell types that could be involved in the morphogenetic processes during kidney differentiation. In situ hybridization reveals neurofilament light protein mRNA, and immunohistology shows neurofilament light and medium proteins in the stromal cells around kidney tubules. By immunohistochemistry these peritubular stromal cells can be distinguished from the neuronal cells of the renal microganglion: the peritubular stromal cells are neurofilament-positive but L1 neural cell adhesion protein-negative, whereas the neuronal cells with axonal extension are both neurofilament-positive and L1 neural cell adhesion protein-positive. Proliferation index of the stromal cells was low as compared to tubular cells, as shown by bromodeoxyuridine incorporation.
Animals↗
Infantile neuronal ceroid-lipofuscinosis (INCL): diagnostic criteria.
Explore the source record for details and available documents.
Aging↗
Early juvenile neuronal ceroid-lipofuscinosis or variant Jansky-Bielschowsky disease: diagnostic criteria and nomenclature.
Explore the source record for details and available documents.
Aging↗
Transient ischemic cerebral lesions during induction chemotherapy for acute lymphoblastic leukemia.
Ninety children were treated for acute lymphoblastic leukemia or non-Hodgkin lymphoma during 1986 through 1992 in the Children's Hospital, University of Helsinki, in Finland. During induction chemotherapy, nine of the children had visual hallucinations progressing to confusion and seizure. The symptoms were often preceded by severe constipation and significantly elevated blood pressure. Neuroradiologic examinations showed bilateral cortical or subcortical white matter lesions. Despite the stroke like manifestations, the lesions were reversible. The triangular shape and location of the lesions in the watershed areas between the major cerebral arteries suggest vascular ischemia as the cause.
Adolescent↗
Epileptic seizures in aspartylglucosaminuria: a common disorder.
Aspartylglucosaminuria (AGU) is a lysosomal storage disorder with reduced life-span. An analysis of 121 Finnish patients showed that 22 to 78 adults (28%) and one of 43 children (2%) had epileptic seizures. Twelve patients had the onset of attacks after the age of 30 years. Eleven patients had generalized, nine partial and three unclassified seizures. The response to carbamazepine was good. The major interictal EEG abnormality was the attenuation of the amplitude found in 10/27 patients. The brain CT-scans showed diffuse atrophy in 8/11 patients.
Acetylglucosamine↗
A truncated laminin chain homologous to the B2 chain: structure, spatial expression, and chromosomal assignment.
We describe the identification of a novel laminin chain. Overlapping clones were isolated from a human fibrosarcoma HT1080 cell cDNA library spanning a total of 5,200 bp. A second set of clones contained an alternative 3' end sequence giving a total of 4,316 bp. The longer sequence contained an open reading frame for a 1,193-residue-long polypeptide. The alternative sequence was shortened at the carboxyl-terminal end coding for a 1,111-residue-long polypeptide. The amino acid sequence contained 21 amino acids of a putative signal peptide and 1,172 residues or alternatively 1,090 residues of a sequence with five distinct domains homologous to domains I-V in laminin chains. Comparison of the amino acid sequences showed that the novel laminin chain is homologous to the laminin B2 chain. However, the structure of the novel laminin chain isolated here differs significantly from that of the B2 chain in that it has no domain VI and domains V, IV, and III are shorter, resulting in a truncated laminin chain. The alternative sequence had a shortened domain I/II. In accordance with the current nomenclature, the chain characterized here is termed B2t. Calculation of possible chain interactions of laminin chains with the B2t chain domain I/II indicated that the B2t chain can replace the B2 chain in some laminin molecules. The gene for the laminin B2t chain (LAMB2T) was localized to chromosome 1q25-q31 in close proximity to the laminin B2 chain gene. Northern analysis showed that the B2t chain is expressed in several human fetal tissues but differently from the laminin B1 and B2 chains. By in situ hybridization expression of the B2t chain was localized to specific epithelial cells in skin, lung, and kidney as opposed to a general epithelial and endothelial cell expression of the laminin B2 chain in the same tissues.
Amino Acid Sequence↗