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Biomedical subjects

B Landin

Publications and source records attributed to B Landin.

At least 19 recordsLinked to original sources
PubMed2006

Erythropoiesis in the Rps19 disrupted mouse: Analysis of erythropoietin response and biochemical markers for Diamond-Blackfan anemia.

The human ribosomal protein S19 gene (RPS19) is mutated in approximately 20% of patients with Diamond-Blackfan anemia (DBA), a congenital disease with a specific defect in erythropoiesis. The clinical expression of DBA is highly variable, and subclinical phenotypes may be revealed by elevated erythrocyte deaminase (eADA) activity only. In mice, complete loss of Rps19 results in early embryonic lethality whereas Rps19+/- mice are viable and without major abnormalities including the hematopoietic system. We have performed a detailed analysis of the Rps19+/- mice. We estimated the Rps19 levels in hematopoietic tissues and we analyzed erythrocyte deaminase activity and globin isoforms which are used as markers for DBA. The effect of a disrupted Rps19 allele on a different genetic background was investigated as well as the response to erythropoietin (EPO). From our results, we argue that the loss of one Rps19 allele in mice is fully compensated for at the transcriptional level with preservation of erythropoiesis.

Anemia, Diamond-Blackfan↗
PubMed2000

Electrospray tandem mass spectrometry in the rapid identification of alpha-chain haemoglobin variants.

The potential use of electrospray tandem mass spectrometry in the rapid characterisation of haemoglobin variants found in the Swedish population has been assessed. Analysis times of the order of 5 -10 min were routinely achieved, and identification of variants using mass spectrometry as the sole analytical technique was possible. However, additional information, readily available from isoelectric focusing experiments, made identification simpler and more secure. In the present communication we report on the identification of the alpha-chain variants, Hb Russ, Hb Le Lamentin and Hb Q-Iran. The identifications were confirmed by the use of nucleotide sequencing techniques.

Genetic Variation↗
PubMed1996

Two different mutations in codon 97 of the beta-globin gene cause Hb Malmö in Sweden.

An abnormal hemoglobin with increased oxygen affinity, Hb Malmö [alpha 2 beta 297(FG4)His-->Gln], was found to cause erythrocytosis in two apparently unrelated Swedish families. Direct nucleotide sequencing of amplified DNA demonstrated a CAC-->CAA substitution in one family and a CAC-->CAG substitution in the other. Both mutations resulted in a His-->Gln substitution in codon 97. This finding prompted us to examine the possible point mutations underlying the different hemoglobin variants reported in the literature.

Adult↗
PubMed1996

Bioavailability of cyclosporine in rats after intragastric administration: a comparative study of the L2-phase and two other lipid-based vehicles.

The purpose of this study was to evaluate formulations based on surface active dietary lipids only as oral vehicles for cyclosporine. The absolute bioavailability of cyclosporine from two new lipid vehicles was determined in rats after intragastric administration and compared to that of Sandimmun oral solution, which contains non-ionic surface active substances in addition to dietary lipids. In the new vehicles, cyclosporine was dissolved in two different mixtures of glycerides from long-chained fatty acids. One mixture forms an L2-phase, an oil with very low interfacial tension towards water, and was administered both as the oily L2-phase and as a predispersed emulsion formulation. The other mixture forms a liquid crystalline phase and was administered only as an aqueous dispersion. The mean bioavailability of cyclosporine from Sandimmun was 8% while it was 34% from the L2-phase, 38% from the predispersed L2-phase and 27% from the dispersed liquid crystalline phase. The coefficients of variation in area under the blood concentration curve after administration of the two formulations based on the L2-phase were quite low (31% for the L2-phase and 24% for the predispersed L2-phase) and comparable to that after intravenous administration (24%), while the dispersed liquid crystalline phase gave a higher variability (91%), comparable to that of Sandimmun oral solution (101%). The low variabilities found with the two L2-phase vehicles suggest that this formulation is "self-emulsifying' in the gastrointestinal tract. Since the L2-phase is based on dietary lipids only, it is expected to be well tolerated and could prove to be a good vehicle for long-term clinical use of oral cyclosporine.

Administration, Oral↗
PubMed1995

Initiation codon mutation (ATG --> ATA) of the beta-globin gene causing beta-thalassemia in a Swedish family.

An initiation codon mutation ATG-->ATA of the beta-globin gene was found in seven members of three generations of a family living in northern Sweden. This mutation, which has not previously been described, changes the initiation codon for methionine into a codon for isoleucine and will then result in a beta zero-thalassemic phenotype. The affected family members all present hematological findings typical for beta-thalassemic trait, with slight anemia, marked microcytosis, and increased levels of Hb A2.

Adolescent↗
PubMed1994

Haemoglobin Köln as de novo mutations in Sweden: diagnosis by PCR and specific enzymatic cleavage.

Three independent cases of chronic haemolytic anaemia in Sweden have recently been demonstrated to be due to the unstable haemoglobin variant Hb Köln. The patients, all of whom have partially compensated chronic haemolytic anaemia, presented with aggravated haemolysis during acute infections in childhood. In one case, acute B19 parvovirus infection induced an aplastic crisis. The substitutions all seem to have occurred as de novo mutations. Diagnosis was based on haemoglobin instability testing and isoelectric focusing of haemoglobin dimers. The final identification procedure for the substitutions included extraction of DNA from whole blood, polymerase chain reaction (PCR) amplification of parts of the beta-globin gene and nucleotide sequencing of the resulting material, or studies of restriction length polymorphisms (RFLPs) using the restriction endonucleases Mae II or Nla III. The use of PCR-RFLP is recommended as a valuable tool for diagnosing Hb Köln.

Adult↗
PubMed1994

Hb Trollhättan [beta 20(B2)Val-->Glu]--a new haemoglobin variant with increased oxygen affinity causing erythrocytosis.

Erythrocytosis is sometimes caused by the presence of haemoglobin (Hb) variants with increased oxygen affinity. Here we describe a beta-globin variant found by isoelectric focusing (IEF) of Hb from a 23-year-old Swedish male with moderate erythrocytosis. Amplification of DNA corresponding to the beta-globin gene and subsequent nucleotide sequencing revealed heterozygosity for a GTG-->GAG mutation at codon 20, thus suggesting a Val-->Glu substitution, which was confirmed at the protein level. This mutation occurs at the same position as Hb Olympia [beta 20(B2)Val-->Met], another variant associated with erythrocytosis due to increased oxygen affinity. The novel variant, Hb Trollhättan [beta 20(B2)Val-->Glu], which was also associated with increased oxygen affinity, was shown to be present in three generations of the patient's family.

Adult↗
PubMed1993

Unstable haemoglobin causing haemolytic anaemia: de novo mutation in Sweden identified by PCR.

A 38-year-old Swedish woman was investigated because of mild anaemia resistant to iron therapy. Mild haemolytic disease was found by routine blood tests. Neither HPLC (HbA1c quantification) nor Hb-electrofocusing revealed any major abnormal fraction, although in vitro testing of haemoglobin instability indicated the presence of unstable haemoglobin. PCR was used to amplify coding regions of the beta globin gene. Direct nucleotide sequencing of this material revealed heterozygosity for a substitution corresponding to the haemoglobin variant alpha 2 beta 2 135(H13)Ala-->Pro. This clearly unstable variant, named Hb Altdorf, has earlier been described only in a family of Italian descent. Examination of beta globin genes from six family members of the proposita by PCR followed by specific cleavage with the restriction enzyme Ban I, revealed the mutation in her two children but not in her parents or siblings. This case demonstrates that haemoglobin variants can not be ruled out as a cause of haematological disease even if the parents lack symptoms and standard tests, such as HPLC and electrophoresis/electrofocusing, do not reveal major abnormalities.

Adult↗
PubMed1993

Rare beta chain hemoglobin variants found in Swedish patients during HBA1c analysis.

Here we report the occurrence of five different beta chain hemoglobin variants not previously described in Sweden. The variants were found during quantification of HbA1c using ion exchange high performance liquid chromatography (HPLC) or isoelectrofocusing. Samples were examined either at protein level by separation of globin chains on C8 reversed phase HPLC, digestion with trypsin or lysylendopeptidase and separation of peptides by C18 reversed phase HPLC, or at DNA level by direct nucleotide sequencing of double-stranded DNA fragments amplified from exon 1 + 2 of the beta-globin gene. The variants were: Hb Raleigh [beta 1 (NA1)Val-->Ac-Ala], Hb J-Baltimore [beta 16(A13)Gly-->Asp], Hb Tacoma [beta 30(B12)Arg-->Ser], Hb K-Ibadan [beta 46(CD5)Gly-->Glu], and Hb Fukuyama [beta 77(EF1)His-->Tyr]. Hb Tacoma, Hb K-Ibadan, and Hb Fukuyama were slightly unstable in the isopropanol test, but no signs of hemolysis were found in the patients who all had normal hematological findings.

Adolescent↗
PubMed1993

Hb Karlskoga or alpha 2 beta (2)21(B3) Asp-->His: a new slow-moving variant found in Sweden.

An abnormal variant comprising approximately 39% of total hemoglobin was found in a 48-year-old Swedish woman. The variant was eluted from ion exchange high performance liquid chromatography (HPLC) used for routine quantification of Hb A1c at a position similar to Hb S. Amplification of beta-globin exons and nucleotide sequencing revealed heterozygosity for a GAT-->CAT mutation in codon 21, corresponding to the amino acid substitution Asp-->His at position 21. This mutation was confirmed by amino acid composition and peptide sequence determinations. Substitutions in this position are not likely to affect the function of the hemoglobin molecule and the hemoglobin variant, for which the name Hb Karlskoga is proposed, was not associated with any overt hematological abnormalities.

Amino Acid Sequence↗