Five FGF receptors with distinct expression patterns.
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Animals↗
Biomedical subjects
H Hirvonen
Publications and source records attributed to H Hirvonen.
Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues.
Genetic subtypes of alpha 2-adrenergic receptors (AR) may mediate distinct physiological functions, and undergo differential cell type-specific regulation. Thus, these distinct receptor subtypes are possible targets for the development of subtype-selective drugs. We have analyzed the tissue distribution of two human alpha 2-adrenoceptor subtype gene mRNAs, alpha 2-C4 and alpha 2-C10, in normal human fetal and adult tissues. Both receptor subtype mRNAs were abundantly expressed in fetal brain and choroid plexus. In non-neural fetal tissues, alpha 2-C10 mRNA was detected in spleen, kidney, adrenal gland, and skin, while alpha 2-C4 transcripts were observed only in kidney and skin. Most regions of the adult brain also expressed both subtypes, but with marked quantitative differences. For example, cerebral cortex contained predominantly alpha 2-C10 mRNA, whereas the caudate nucleus expressed mostly alpha 2-C4 mRNA. In adult peripheral tissues, alpha 2-C10 mRNA expression was most abundant in spleen and renal cortex, and expression of alpha 2-C4 mRNA was strongest in renal cortex and medulla. These different expression patterns provide evidence for the differential regulation of the two alpha 2-adrenergic receptor genes and warrant further investigation with techniques capable of improved anatomical resolution. Regional differences in receptor subtype expression may be valuable for the development of new, subtype-selective pharmacological agents with more targeted actions compared to currently used alpha 2-adrenoceptor agonists and antagonists.
Animals↗
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↗
Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.
Based on the map location of the aniridia (AN) locus in human chromosomal band 11p13, we have cloned a candidate AN cDNA (D11S812E) that is completely or partially deleted in two patients with AN. The less than 70 kb smallest region of overlap between the two deletions encompasses the 3' coding region of the cDNA. This cDNA, which spans over 50 kb of genomic DNA, detects a 2.7 kb message specifically within all tissues affected in AN. The predicted polypeptide product possesses a paired domain, a homeodomain, and a serine/threonine-rich carboxy-terminal domain, structural motifs characteristic of certain transcription factors. The concordance between expression and pathology, map location, structure, and predicted function argues that the cDNA corresponds to the AN gene.
Amino Acid Sequence↗
Expression of L-myc and N-myc proto-oncogenes in human leukemias and leukemia cell lines.
The myc proto-oncogenes encode nuclear phosphoproteins, which are believed to participate in the control of cell proliferation and differentiation. Deregulated expression of c-myc has been implicated in several human hematopoietic malignancies. We have studied the expression and mRNA processing of human L-myc, N-myc, and c-myc genes in a panel of human leukemias, leukemia cell lines, and normal hematopoietic cells. L-myc mRNA was expressed in three acute myeloid leukemias (AML) studied and in several myeloid leukemia cell lines. Only low expression levels were observed in adult bone marrow and in fetal spleen and thymus. The K562 and Dami leukemia cell lines showed a unique pattern of L-myc mRNA processing, with approximately 40% of L-myc mRNA lacking exon III and intron I. N-myc was expressed in five of six AML cases studied, in one of nine acute lymphocytic leukemia (ALL) cases, and in several leukemia cell lines, while c-myc mRNA was detected in all leukemias and leukemia cell lines studied. Coexpression of all three myc genes was observed in Dami and MOLT-4 cell lines and in two AMLs, and either L-myc or N-myc was coexpressed with c-myc in several other cases. These results show that in addition to c-myc, the L-myc and N-myc genes are expressed in some human leukemias and leukemia cell lines, and suggest a lack of mutually exclusive cross-regulation of the myc genes in human leukemia cells.
Blotting, Northern↗
FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern.
We have previously identified two novel members of the fibroblast growth factor receptor (FGFR) gene family expressed in K562 erythroleukemia cells. Here we report cDNA cloning and analysis of one of these genes, named FGFR-4. The deduced amino acid sequence of FGFR-4 is 55% identical with both previously characterized FGFRs, flg and bek, and has the structural characteristics of a FGFR family member including three immunoglobulin-like domains in its extracellular part. Antibodies raised against the carboxy terminus of FGFR-4 detected 95 and 110 kd glycoproteins with a protein backbone of 88 kd in COS cells transfected with a FGFR-4 cDNA expression vector. The FGFR-4 protein expressed in COS cells could also be affinity-labeled with radioiodinated acidic FGF. Furthermore, ligand binding experiments demonstrated that FGFR-4 binds acidic FGF with high affinity but does not bind basic FGF. FGFR-4 is expressed as a 3.0 kb mRNA in the adrenal, lung, kidney, liver, pancreas, intestine, striated muscle and spleen tissues of human fetuses. The expression pattern of FGFR-4 is distinct from that of flg and bek and the yet additional member of the same gene family, FGFR-3, which we have also cloned from the K562 leukemia cells. Our results suggest that FGFR-4 along with other fibroblast growth factor receptors performs cell lineage and tissue-specific functions.
Amino Acid Sequence↗
cyl encodes a putative cytoplasmic tyrosine kinase lacking the conserved tyrosine autophosphorylation site (Y416src).
We have isolated a cDNA encoding a novel tyrosine kinase family member, named cyl (consensus tyrosine-lacking kinase), from the K562 human leukemia cell line. The deduced cyl protein lacks signal and transmembrane sequences but contains features of known cytoplasmic tyrosine kinases, including amino-terminal SH3 and SH2 domains. However, having very short amino and carboxy termini, cyl does not seem to belong to any of the previously characterized subfamilies of cytoplasmic tyrosine kinases. Furthermore, cyl lacks the highly conserved tyrosine autophosphorylation site (Y416src) in the tyrosine kinase catalytic domain. The cyl gene is located on human chromosome 15. It is expressed ubiquitously as two independently regulated mRNA species of 2.6 and 3.4 kb in human leukemia cell lines and fetal tissues.
Adrenal Glands↗
Genomic variation of herpes simplex virus type 2 isolates analysed by hybridization after electroblotting from polyacrylamide gels.
Genomic variation of herpes simplex virus type 2 (HSV-2) strains was analysed by polyacrylamide gradient gel electrophoresis and subsequent hybridization to cloned HSV-2 sequences. Two probes were used, one from the L-segment and one from the S-segment of the HSV-2 genome. The probes did not contain a-repeat sequences. Hybridization to the specific sequences in individual DNA fragments obtained by use of the frequently cleaving restriction endonuclease Alu I revealed variations in the genome not detectable by analysing the fragment size only. The use of 35S-labelled deoxynucleotide in the radioactive labelling of the probe further improved the resolution of the method.
DNA, Viral↗
Expression of the myc proto-oncogenes in developing human fetal brain.
We have analysed c-myc, N-myc and L-myc gene expression in developing human fetal brain by Northern hybridization, RNAase protection and in situ hybridization. The unique zonal organization of the developing fetal brain allows a particularly good assessment of the coupling of myc gene expression to cell proliferation and differentiation in vivo. By Northern and in situ hybridization, L-myc as well as c-myc and N-myc transcripts in the brain were found in the post-mitotic cortical and intermediate layers, as well as in the mitotically active layers containing the neuroepithelial precursor cells. Consistent results were also obtained for L-myc using RNAase protection analysis. Both the 3.6 and 3.8kb forms of the L-myc mRNA, resulting from alternative splicing of intron I, were detected in layers of neuroectodermal origin, but not in the meninges or choroid plexus. We also extended L-myc expression and splicing analyses to other developing human fetal tissues. L-myc mRNA was expressed in several other fetal tissues, particularly in fetal skin. Predominantly intron I containing L-myc mRNA was observed in fetal striated and cardiac muscle. Thus, L-myc is expressed in a wider spectrum of developing tissues than previously known. Our findings also, show that L-myc as well as N-myc and c-myc expression is uncoupled from cell division in developing brain.
Blotting, Northern↗
The N-myc proto-oncogene and IGF-II growth factor mRNAs are expressed by distinct cells in human fetal kidney and brain.
We studied the expression of the N-myc proto-oncogene and the insulin-like growth factor-II (IGF-II) gene in human fetuses of 16-19 gestational wk. Both genes have specific roles in the growth and differentiation of embryonic tissues, such as the kidney and neural tissue. Since continued expression of N-myc and IGF-II mRNAs is also a characteristic feature of Wilms' tumor, a childhood neoplasm of probable fetal kidney origin, we were particularly interested in the possibility that their expression might be linked or coordinately regulated in the developing kidney. Expression of N-myc mRNA was observed in the brain and in the kidney by Northern hybridization analysis. In in situ hybridization of the kidney, N-myc autoradiographic grains were primarily located over epithelially differentiating mesenchyme while most of the mesenchymal stromal cells showed only a background signal with the N-myc probe. N-myc mRNA was detectable throughout the developing brain with a slight accentuation in the intermediate zone cells in between the subependymal and cortical layers. Thus, even postmitotic neuroepithelial cells of the fetal cerebrum expressed N-myc mRNA. In Northern hybridization, IGF-II mRNA signal was abundant in the kidney but much weaker, though definite, in the brain. The regional distribution of IGF-II mRNA in the kidney was largely complementary to that of N-myc. IGF-II autoradiographic grains were located predominantly over the stromal and blastemal cells with a relative lack of hybridization over the epithelial structures. In the brain, IGF-II mRNA was about two- to threefold more abundant in the subependymal and intermediate layers than in the cortical plate and ependymal zone, respectively. The fetal expression patterns of the N-myc and IGF-II mRNAs are reflected by the types of tumors known to express the corresponding genes during postnatal life such as Wilms' tumor. However, the apparent coexpression of the IGF-II and N-myc genes in immature kidneys occurs largely in distinct cell types.
Autoradiography↗
Expression of mRNAs coding for the alpha 1 chain of type XIII collagen in human fetal tissues: comparison with expression of mRNAs for collagen types I, II, and III.
This paper describes the topographic distribution of the multiple mRNAs coding for a novel human short-chain collagen, the alpha 1 chain of type XIII collagen. To identify the tissues and cells expressing these mRNAs, human fetal tissues of 15-19 gestational wk were studied by Northern and in situ hybridizations. The distribution pattern of the type XIII collagen mRNAs was compared with that of fibrillar collagen types I, II, and III using specific human cDNA probes for each collagen type. Northern hybridization showed the bone, cartilage, intestine, skin, and striated muscle to contain mRNAs for type XIII collagen. An intense in situ hybridization signal was obtained with the type XIII collagen cDNAs in the epidermis, hair follicles, and nail root cells of the skin, whereas the fibrillar collagen mRNAs were detected in the dermis. Cells in the intestinal mucosal layer also appeared to contain high levels of alpha 1(XIII) collagen mRNAs, but contained none of the fibrillar collagen mRNAs. In the bone and striated muscle, alpha 1(XIII) collagen mRNAs were detected in the mesenchymal cells forming the reticulin fibers of the bone marrow and endomycium. The hybridization signal obtained with the alpha 1(XIII) collagen cDNA probe in cartilaginous areas of the growth plates was similar, but less intense, to that obtained with the type II collagen probe. A clear hybridization signal was also detected at the (pre)articular surfaces and at the margins of the epiphyses, whereas it was weaker in the resting chondrocytes in the middle of the epiphyses. The brain, heart, kidney, liver, lung, placenta, spleen, testis, tendon, and thymus did not appear to contain alpha 1(XIII) collagen mRNAs.
Blotting, Northern↗
Enhanced expression of TGF-beta and c-fos mRNAs in the growth plates of developing human long bones.
The expression of mRNAs for type I and type II procollagens, transforming growth factor-beta (TGF-beta) and c-fos was studied in developing human long bones by Northern blotting and in situ hybridization. The cells producing bone and cartilage matrix were identified by hybridizations using cDNA probes for types I and II collagen, respectively. Northern blotting revealed that the highest levels of TGF-beta mRNA were associated with the growth plates. By in situ hybridization, this mRNA was localized predominantly in the osteoblasts and osteoclasts of the developing bone, in periosteal fibroblasts and in individual bone marrow cells. These findings are consistent with the view that TGF-beta may have a role in stimulation of type I collagen production and bone formation. Only a low level of TGF-beta mRNA was detected in cartilage where type II collagen mRNA is abundant. In Northern hybridization, the highest levels of c-fos mRNA were detected in epiphyseal cartilage. In situ hybridization revealed two cell types with high levels of c-fos expression: the chondrocytes bordering the joint space and the osteoclasts of developing bone. These differential expression patterns suggest specific roles for TGF-beta and c-fos in osseochondral development.
Bone Development↗
[Efficiency of the blood cell separator Haemonetic 30 in the separation of platelets from single donors].
By means of the Haemonetic 30 separator we were able to collect 4.1 +/- 0.94 X 10(11) (X +/- 1 SD) platelets in 57 procedures consisting of 5-6 cycles. The platelet yield was significantly influenced by the blood volume processed and by initial platelet counts in donors. Augmenting platelet collection volume in the red colored part of the buffy-coat from 10-20 ml did not increase the yield. Transfusion of collected platelets into 27 non-sensitized patients showed normal recovery of 43% at one hour and shortening of bleeding time from over 30 min to a mean of 5 min 20 sec in 12 patients tested. Autotransfusion of 51Cr-labeled platelets into 8 healthy donors revealed identical recoveries (42 +/- 12%) and a normal survival time (9.2 +/- 0.7 days).
Cell Separation↗
[Allophlogisty in several psoriasis patients].
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Anthralin↗