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J Jonsson

Publications and source records attributed to J Jonsson.

At least 19 recordsLinked to original sources
PubMed1999

Identification and characterization of a highly conserved protein absent in the Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E) contiguous gene deletion syndrome (AMME).

We recently described a novel contiguous gene deletion syndrome (AMME) in Xq22.3 that includes Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E). While the Alport syndrome is due to deletion of the COL4A5 gene, no other genes are known in the region with the exception of our recent finding of the FACL4 gene. In our effort to isolate additional genes from the deleted region, we have identified the gene named AMMECR1 (Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis chromosomal region gene 1). RACE experiments and screening of cDNA libraries enabled us to obtain the entire ORF of the gene (1002 bp) followed by about 2 kb of 3'UTR. AMMECR1 is composed of six exons, shows a ubiquitous 6.5-kb transcript, and codes for a protein with a molecular mass of 35.5 kDa. Sequence analysis revealed that this gene is conserved in several species ranging from Caenorhabditis elegans and yeast to micro-organisms. Exon 2 of AMMECR1 encodes a domain consisting of six amino acids identically conserved throughout the course of evolution and whose function is as yet unknown. Analysis of the predicted protein product using ExPAsy tools raises the possibility that the gene may code for a regulatory factor potentially involved in the development of AMME contiguous gene deletion syndrome.

Amino Acid Sequence↗
PubMed1998

New chemical descriptors relevant for the design of biologically active peptides. A multivariate characterization of 87 amino acids.

In this study 87 amino acids (AA.s) have been characterized by 26 physicochemical descriptor variables. These descriptor variables include experimentally determined retention values in seven thin-layer chromatography (TLC) systems, three nuclear magnetic resonance (NMR) shift variables, and 16 calculated variables, namely six semiempirical molecular orbital indices, total, polar, and nonpolar surface area, van der Waals volume of the side chain, log P, molecular weight, and four indicator variables describing hydrogen bond donor and acceptor properties, and side chain charge. In the present study, the data from a previous characterization of 55 AA.s from our laboratory have been extended with data for 32 additional AA.s and 14 new descriptor variables. The new 32 AA.s were selected to represent both intermediate and more extreme physicochemical properties, compared to the 20 coded AA.s. The new extended and updated principal property scales, the z-scales, were calculated and aligned to previously reported z(old)-scales. The appropriateness of the extended z-scales were validated by the use in quantitative sequence-activity modeling (QSAM) of 89 elastase substrate analogues and in a QSAM of 29 neurotensin analogues.

Amino Acids↗
PubMed1998

beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes.

To study the late beta-cell-specific function of the homeodomain protein IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted specifically in beta cells. These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression. We also provide evidence that IPF1/PDX1 regulates the expression of Glut2 in a dosage-dependent manner suggesting that lowered IPF1/PDX1 activity may contribute to the development of type II diabetes by causing impaired expression of both Glut2 and insulin.

Amyloid↗
PubMed1998

Incidence of opiates, amphetamines, and cocaine in hair and blood in fatal cases of heroin overdose.

The purpose of the present study was to investigate the occurrence in hair, of some drugs of abuse in deaths caused by heroin overdose, in comparison to findings in blood. Blood, urine and hair samples were obtained during routine post mortem examinations. Samples were analysed for amphetamines, opiates, and cocaine. Immunometric drug screening was performed in urine and positive results confirmed with gas chromatography-mass spectrometry (GC-MS) of blood samples. All hair samples were analyzed with GC-MS. Hair samples were either incubated with methanol for determination of opiates and cocaine, or dissolved in sodium hydroxide for determination of amphetamines. All 19 blood samples were positive for morphine (0.04-0.4 microgram g-1) and ten were also positive for 6-acetylmorphine (0.003-0.02 microgram g-1). Thirteen of the hair samples were positive for 6-acetylmorphine and seven of which were positive also for morphine. Concentrations ranged from 0.3-7.4 and 0.3-1.3 (ng mg-), respectively. Amphetamine was found in three blood samples (0.04-1.2 micrograms g-1) and in eleven hair samples (0.4-18.3 ng mg-). Cocaine was determined in one blood sample (0.03 microgram g-1) and two hair samples (0.7-6.5 ng mg-). Out of the nineteen cases studied, eight showed chronic multi drug use on the basis of the results of hair analysis. In six subjects no opiates could be detected in hair, suggesting; "first" or occasional intake of heroin, which could be a contributing factor to the overdose death, because of lack of tolerance. We conclude that analysis of hair can be a useful complement to analysis of more conventional autopsy material, especially when investigating overdose deaths and previous histories of drug use and abuse.

Adult↗
PubMed1998

Effects of tacrolimus on hyperlipidemia after successful renal transplantation: a Southeastern Organ Procurement Foundation multicenter clinical study.

BACKGROUND: Tacrolimus has been shown to have a less adverse effect on the lipid profiles of transplant patients when the drug is started as induction therapy. In order to determine the effect tacrolimus has on lipid profiles in stable cyclosporine-treated renal transplant patients with established hyperlipidemia, a randomized prospective study was undertaken by the Southeastern Organ Procurement Foundation. METHODS: Patients of the 13 transplant centers, with cholesterol of 240 mg/dl or greater, who were at least 1 year posttransplant with stable renal function, were randomly assigned to remain on cyclosporine (control) or converted to tacrolimus. Patients converted to tacrolimus were maintained at a level of 5-15 ng/ml, and control patients remained at their previous levels of cyclosporine. Concurrent immunosuppressants were not changed. Levels of total cholesterol, triglycerides, total high-density lipoprotein, low-density lipoprotein (LDL), very-low-density lipoprotein, and apoproteins A and B were monitored before conversion and at months 1, 3, and 6. Renal function and glucose control were evaluated at the beginning and end of the study (month 6). RESULTS: A total of 65 patients were enrolled; 12 patients failed to complete the study. None were removed as a result of acute rejection or graft failure. Fifty-three patients were available for analysis (27 in the tacrolimus group and 26 controls). Demographics were not different between groups. In patients converted to tacrolimus treatment, there was a -55 mg/dl (-16%) (P=0.0031) change in cholesterol, a -48 mg/dl (-25%) (P=0.0014) change in LDL cholesterol, and a -36 mg/dl (-23%) (P=0.034) change in apolipoprotein B. There was no change in renal function, glycemic control, or incidence of new onset diabetes mellitus in the tacrolimus group. CONCLUSION: Conversion from cyclosporine to tacrolimus can be safely done after successful transplantation. Introduction of tacrolimus to a stable renal patient does not effect renal function or glycemic control. Tacrolimus can lower cholesterol, LDL, and apolipoprotein B. Conversion to tacrolimus from cyclosporine should be considered in the treatment of posttransplant hyperlipidemia.

Adult↗
PubMed1998

On the Singlet Spectrum of ZrS.

Three electronic transitions in the singlet manifold of the zirconium sulphide (ZrS) molecule have been rotationally analyzed. They are the B1Pi-X1Sigma+, C1Sigma+-X1Sigma+, and E1Sigma+-X1Sigma+ systems with (0,0) band heads at 924.60, 731.51, and 494.47 nm, respectively. The ground state X1Sigma+ has an equilibrium bond distance of 2.15661(4) Å. Perturbations in the B1Pi and C1Sigma+ states are discussed. Copyright 1998 Academic Press.

Journal Article↗
PubMed1996

Detection of circulating donor deoxyribonucleic acid by microsatellite analysis in a liver transplant recipient.

The diagnosis of graft-versus-host disease following liver transplantation may be delayed because the clinical and pathological features are nonspecific. We report the use of microsatellites to support a diagnosis of GVHD in a patient who developed fever and a skin rash 28 days after liver transplantation. The pattern of microsatellite alleles amplified from the peripheral blood on day 51 posttransplant indicated that recipient and donor DNA were present in approximately equal proportions. Microsatellite typing is a simple and rapid method to identify high levels of circulating donor DNA to support a diagnosis of GVHD following liver transplantation.

Alleles↗
PubMed1996

Pancreatic-duodenal homeobox 1 -role in gastric endocrine patterning.

The gastrointestinal tract is subdivided into regions with different roles in digestion and absorption. How this patterning is established is unknown. We now report that the pancreatic-duodenal homeobox 1 gene (pdx1) is also expressed in cells of the distal stomach. Positive cells include subpopulations of the three main endocrine (gastrin, somatostatin and serotonin) cell types of this region. Pdx1 deficient mice were virtually devoid of gastrin cells, had normal numbers of somatostatin cells and increased numbers of serotonin cells. Pdx1 is thus important for development of the gastrin cells of the antropyloric mucosa of the stomach and probably acts by controlling the fate of gastrin/serotonin precursor cells.

Animals↗
PubMed1996

The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice.

We have previously shown that mice carrying a null mutation in the homeobox gene ipf1, now renamed to pdx1, selectively lack a pancreas. To elucidate the level at which PDX1 is required during the development of the pancreas, we have in this study analyzed the early stages of pancreas ontogeny in PDX-/- mice. These analyses have revealed that the early inductive events leading to the formation of the pancreatic buds and the appearance of the early insulin and glucagon cells occur in the PDX1-deficient embryos. However, the subsequent morphogenesis of the pancreatic epithelium and the progression of differentiation of the endocrine cells are arrested in the pdx1-/- embryos. In contrast, the pancreatic mesenchyme grows and develops, both morphologically and functionally, independently of the epithelium. We also show that the pancreatic epithelium in the pdx1 mutants is unable to respond to the mesenchymal-derived signal(s) which normally promote pancreatic morphogenesis. Together these data provide evidence that PDX-1 acts cell autonomously and that the lack of a pancreas in the pdx1-/- mice is due to a defect in the pancreatic epithelium.

Animals↗
PubMed1996

A convenient derivatization method for the determination of amphetamine and related drugs in urine.

The most commonly abused CNS stimulant in Sweden is amphetamine followed by phenmetrazine. Methamphetamine and phentermine are rarely seen but still of interest. This paper describes a rapid and sensitive method for the analysis of amphetamine, methamphetamine, phentermine, and phenmetrazine in urine using gas chromatography with nitrogen sensitive detection (GC-NPD). The method also qualitatively determines ephedrine and norephedrine. The derivatization was carried out at room temperature with methyl chloroformate to form the corresponding carbamates. Other chloroformate analogues were also tested. Because methyl chloroformate is relatively stable in the presence of water the extraction and derivatization were combined in one step. A concentration step was not necessary to achieve sufficient sensitivity. The recovery was more than 83% for all analytes. The LOQ was 0.05, 0.03, 0.07 and 0.01 (microgram/mL urine) for amphetamine, methamphetamine, phentermine and phenmetrazine respectively. The cut-off was set at 0.2 microgram/mL. The within-day and between-day relative standard deviation (RSD) for amphetamine were 2.2% (n = 9) and 4.7% (n = 5) respectively. There was a good quantitative correlation (r2 = 0.995) between GC-NPD using chloroformate derivatives and gas chromatography-mass spectrometry (GC-MS) using trifluoroacetic anhydride (TFA) as derivatizing agent for the determination of amphetamine in authentic samples.

Amphetamines↗
PubMed1995

Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia.

Extracellular superoxide dismutase (EC-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a secreted Cu- and Zn-containing tetrameric glycoprotein, the bulk of which is bound to heparan sulfate proteoglycans in the interstitium of tissues. To test the function of EC-SOD in vivo, mice carrying a targeted disruption of the EC-SOD gene were generated. The EC-SOD null mutant mice develop normally and remain healthy until at least 14 months of age. No compensatory induction of other SOD isoenzymes or other antioxidant enzymes was observed. When stressed by exposure to > 99% oxygen, the EC-SOD null mutant mice display a considerable reduction in survival time compared to wild-type mice and an earlier onset of severe lung edema. These findings suggest that while under normal physiological conditions other antioxidant systems may substitute for the loss of EC-SOD; when the animal is stressed these systems are unable to provide adequate protection.

Animals↗
PubMed1995

Visceral leishmaniasis in Somalia. Circulating antibodies as measured by DAT, immunofluorescence and ELISA.

Sera from patients with visceral leishmaniasis (VL) (n = 26), healthy residents of Mogadishu (n = 157), inhabitants of a village in an endemic area (n = 276) and healthy Swedes (n = 60) were examined using the direct agglutination test (DAT), immunofluorescence (IF) and ELISA for antibodies against Leishmania donovani. The study was carried out in order to provide baseline data for antibody responses in visceral leishmaniasis as existing in Somalia and to explore which one of these methods would be most suitable for diagnosis of clinical cases as well as for epidemiological population studies in Somalia. All patients had high levels of circulating antibodies, however, lower values were recorded in the early stages of the disease. High reactivity in ELISA was seen first after one year. All three tests distinguished well between sera from VL patients and healthy controls. Approximately 10% of the sera from villagers were reactive above the cut-off levels in the three tests. DAT is the simplest to perform and does not require much equipment. ELISA can be made simple and economic if performed in one serum dilution and read visually. IF requires more expensive and specialized equipment and is not suitable for large scale examination of sera. A complete evaluation of the three tests should also include the analysis of sera from various stages and manifestations of the disease.

Adolescent↗
PubMed1995

IPF1, a homeodomain protein with a dual function in pancreas development.

Insulin promoter factor 1 (IPF1), is a homeodomain protein which, in the adult mouse pancreas, is selectively expressed in beta-cells, and which binds to, and transactivates, the insulin promoter via the P1 element. In mouse embryos, IPF1 expression is initiated when the foregut endoderm commits to a pancreatic fate, i.e. prior to both morphogenesis and hormone specific gene expression. At later stages of development the expression is restricted to the dorsal and ventral walls of the primitive foregut at the positions where the pancreases will form. Mice homozygous for a targeted mutation in the Ipf1 gene selectively lack the pancreas. The mutant pups develop to term and are born alive, but die after a few days. The gastrointestinal tract with its associated organs show no obvious malformations. No pancreatic tissue and no ectopic expression of insulin or pancreatic amylase could be detected in this region in mutant neonates or embryos. These findings demonstrate that IPF1 is needed for the formation of the pancreas, and suggest that IPF1 acts to determine the fate of common pancreatic precursor cells and/or to regulate their propagation. The lack of a pancreas in the Ipf1-deficient mutants, the pattern of IPF1 expression and its ability to stimulate insulin gene transcription, strongly suggest that IPF1 functions both in the early specification of the primitive gut to a pancreatic fate and in the maturation of the pancreatic beta-cell.

Aging↗
PubMed1994

Insulin-promoter-factor 1 is required for pancreas development in mice.

The mammalian pancreas is a mixed exocrine and endocrine gland that, in most species, arises from ventral and dorsal buds which subsequently merge to form the pancreas. In both mouse and rat the first histological sign of morphogenesis of the dorsal pancreas is a dorsal evagination of the duodenum at the level of the liver at around the 22-25-somite stage, and shortly thereafter a ventral evagination appears as a derivative of the liver diverticulum. Low levels of insulin gene transcripts are already present and restricted to the dorsal foregut endoderm at 20 somites, suggesting that pancreas- or insulin gene-specific transcriptional factors are present in this region before the onset of morphogenesis. Insulin-promoter-factor 1 (IPF1) is a homeodomain protein which, in the adult mouse pancreas, is selectively expressed in the beta-cells and binds to and transactivates the insulin promoter. In mouse embryos, IPF1 expression is restricted to the developing pancreatic anlagen and is initiated when the foregut endoderm is committed to a pancreatic fate. We now show that mice homozygous for a targeted mutation in the Ipf1 gene selectively lack a pancreas. The mutant pups survive fetal development but die within a few days after birth. The gastrointestinal part and all other internal organs were normal in appearance. No pancreatic tissue and no ectopic expression of insulin or pancreatic amylase could be detected in mutant embryos and neonates. These findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/or to regulate their propagation.

Animals↗
PubMed1994

Similar regulatory mechanisms despite differences in membrane lipid composition in Acholeplasma laidlawii strains A-EF22 and B-PG9. A multivariate data analysis.

Mycoplasmas are small, cell wall-deficient bacteria. The metabolic regulation of the lipid composition in the membrane of the species Acholeplasma laidlawii, strains A-EF22 and B-JU, is governed mainly by the balance between the potential formation of lamellar and nonlamellar phase structures. However, the regulatory features have not been consistently observed in the B-PG9 strain. A comparison has been performed between the membrane lipid composition for strains A-EF22 and B-PG9, simultaneously changing eight experimental conditions known to affect the regulation and packing properties of the A-EF22 lipids. Multiple regression and partial least-square discriminant analyses of many variables showed: (i) quantitative differences in membrane lipid and protein composition, and in membrane protein molecular masses of the two strains; (ii) different molar fractions of the major polar lipids monoglucosyldiacylglycerol (nonlamellar) and diglucosyldiacylglycerol (lamellar), which were caused by differences in lipid acyl chain length and unsaturation inherent in the strains and by the type of growth medium used; and (iii) similar regulatory mechanisms for changes in the lipid composition under most conditions, responding to the experimentally varied bilayer and nonbilayer properties of the lipid matrix. These regulatory principles are probably valid in other bacteria as well.

Acholeplasma laidlawii↗