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Biomedical subjects

J Jonsson

Publications and source records attributed to J Jonsson.

At least 37 records · Page 2Linked to original sources

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↗

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↗

Reference ranges for IgG, IgM and IgA in the serum of urban and rural Somalis.

In order to provide baseline data for an immuno-parasitological laboratory in Somalia, serum concentrations of IgG, IgM and IgA were determined in some key populations: healthy residents of Mogadishu (n = 157), inhabitants of the village of Daimo Samo (n = 276) and patients with malaria (n = 39) and visceral leishmaniasis (n = 26), both protozoan infections accompanied by hypergammaglobulinaemia and causing severe health problems in Somalia. Since the serum immunoglobulin concentrations in the Somali populations studied were not normally distributed, they were evaluated using medians and percentiles. Significantly higher values of IgG, IgM and IgA were demonstrated in healthy Mogadishu residents as compared to healthy Swedes. Daimo Samo villagers had significantly higher IgG and IgM values than healthy Mogadishu residents. Very high concentrations of IgG and IgM were demonstrated in sera from patients with visceral leishmaniasis. Somali patients with malaria also had marked hypergammaglobulinaemia, however, only in the IgG class. The high levels of IgG, IgM and IgA demonstrated in sera from Somalis, indicate the need for establishing local reference values and should be considered when introducing serological tests in tropical countries. Such methods are usually adopted to conditions in industrialized countries, where immunoglobulin contents of sera are lower.

Adolescent↗

Quantitative sequence-activity models (QSAM)--tools for sequence design.

Models have been developed that allow the biological activity of a DNA segment to be altered in a desired direction. Partial least squares projections to latent structures (PLS) was used to establish a quantitative model between a numerical description of 68 bp fragments of 25 E.coli promoters and their corresponding quantitative measure of in vivo strength. This quantitative sequence-activity model (QSAM) was used to generate two 68 bp fragments predicted to be more potent promoters than any of those on which the model originally was based. The optimized structures were experimentally verified to be strong promoters in vivo.

Base Composition↗

Amebiasis in Nicaragua: class specific serum antibody responses.

With the aid of the indirect hemagglutination (IHA) test and IgG ELISA the antibody profile against E. histolytica in León, Nicaragua was investigated in 562 sera from individuals belonging to various age groups. The highest reactivity was invariably recorded in the age group 6-15 years where 48% were seropositive. Several sera reactive by either one of IHA and IgG ELISA were negative by the other test. The main reason for this seems to be reactivity in different Ig classes. Treatment with 2-mercaptoethanol reduced the titre level in 63 of the 66 sera tested. Immunofluorescence using an anti-IgM conjugate showed that 26 of 43 sera contained specific IgM-antibodies, indicating that also unspecific reactions are involved in the IHA test. A comparison was made between class-specific reactivity in three population groups: healthy residents, healthy cyst carriers and patients with recent or acute liver abscess. No significant difference in the prevalence of reactions above the diagnostic significance level was recorded between cyst carriers and healthy residents. However, among the cyst carriers 33% had IgA and/or IgM antibodies but no demonstrable specific IgG. Most patients with recent and all with acute liver abscess reacted significantly above the diagnostic limit in all three tests.

Adolescent↗

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.

Amino Acid Sequence↗

A multivariate representation and analysis of DNA sequence data.

A new way to represent and analyze DNA sequence data is described. This approach complements methods currently used, in that it allows the systematic part of the variation between different sequences to be modeled. This can prove as informative as absence of variation (homology), which is the most widely used criterion for comparing sequence data. A multivariate sequence-activity model (SAM), for DNA-promoter sequences is presented, by which the relative promoter strength is modeled in terms of the primary DNA-sequence. The model is shown to have a good predictive capability. The coefficients from the model are interpreted, and used to design new structures predicted to be strong promoters in the system investigated. The approach described is also applicable to other kinds of sequence data, e.g. RNAs, proteins or peptides.

Base Sequence↗

A strategy for ranking environmentally occurring chemicals. Part VI. QSARs for the mutagenic effects of halogenated aliphatics.

A strategy for the systematic analysis and priority ranking of environmental chemicals has been applied to a class of 58 halogenated aliphatic hydrocarbons. A training set of ten compounds representing this class, was selected by statistical design. The training set compounds were then subjected to biological testing in the Salmonella typhimurium reverse mutation assay (Ames test). The measured biological data, recorded as dose-response curves, were analyzed to determine the mutagenic potency (slope of the initial portion) and the mutagen dose (MD 50) required to increase the number of revertants above the background by 50%. For each compound, four mutagenic potency estimates and four MD 50 values were determined, all originating from the tester strains TA 100 and TA 1535 with and without metabolic activation. The obtained responses were analyzed with multivariate techniques to give QSAR models relating the mutagenic potency data to the physico-chemical properties of the compounds. Finally, the derived QSARs were used to predict the mutagenic potencies and the MD 50S for the non-tested compounds in the class.

Chemical Phenomena↗

Peptide QSAR on substance P analogues, enkephalins and bradykinins containing L- and D-amino acids.

Peptide QSARs are constructed for substance P analogues, enkephalins (two examples) and bradykinins containing both L- and D-amino acids. As descriptors in the QSARs, the previously developed descriptors z1 (hydrophobicity), z2 (bulk) and z3 (electronic effect) are used together with a qualitative variable coding for variation in chirality. Two parametrizations of the peptide sequences are tested. In the first no chiral description is used at all, and in the second chirality is described by the qualitative variable. It is concluded that for the current series of peptides, the biological response to variation in amino acid sequence and chirality can be modelled.

Amino Acid Sequence↗

Renal transplantation at the Washington Hospital Center: experience with OKT3 and Minnesota antilymphoblast globulin for induction of immunosuppression.

These data demonstrate excellent long-term patient and graft survival rates when cytolytic induction therapy is combined with sequential addition of CsA. OKT3 and MAG produce virtually indistinguishable outcomes with low rates of rejection and DGF. The frequency of serious posttransplant complications, infection, rejection, and malignancy was low. Although both MAG and OKT3 are effective, each has its drawbacks. Problems associated with MAG therapy are leukopenia, thrombocytopenia, cumbersome administration, and difficulty monitoring the patient's specific level of induced immunosuppression. OKT3 is simpler to administer, easy to monitor, but first dose reactions may produce additional graft injury. Furthermore, OKT3 may not protect completely against all mechanisms of cellular rejection. In our patient population, the best results occurred when kidneys functioned immediately, when CsA was introduced promptly, and when there were several days of overlap, with MAG or OKT3, especially when OKT3 was used as the induction agent.

Adult↗

Antibodies against Entamoeba histolytica antigens in sera from individuals with amoebiasis of different localization.

The over-all contents and relative component composition of Entamoeba histolytica antigens in abscess fluids and in extracts of cultured amoebae, strain NIH 200, were studied by antigen-catching EIA, counterimmunoelectrophoresis (CIE) and immunoblotting techniques. The antigen contents of liver abscess fluid were determined semiquantitatively by the antigen-catching EIA in four cases. In CIE against a standard "diagnostic" extract of cultured amoebae, sera from cases of acute amoebic liver abscess gave 4-5 precipitation lines while sera from cases of intestinal amoebiasis gave at most 3 lines. In immunoblotting tests with the same antigen, intestinal cases gave blotting bands in the intermediate molecular weight range (25-99 kD) while acute abscess cases, in addition, gave bands in the high (100-175 kD) and low (= less than 25 kD) molecular weight range. These serological differences between clinical forms of amoebiasis were more definite when using amoeba abscess fluid as antigen. Amoeba antigens in high concentrations could be demonstrated in amoeba abscess fluids with all methods employed. In immunoblotting experiments abscess fluids generally gave stronger and more numerous bands with anti-amoeba antibody-containing sera than did the standard "diagnostic" antigen from cultured amoebae. Especially the abscess fluids gave with sera from acute abscess cases a number of prominent bands in the low molecular weight range (less than 25 kD). The experiments in this study were performed with crude amoebic extracts, which contained a multitudes of antigenic components and a still greater diversity of antigenically inert proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A case control study for major trauma in geriatric patients.

This study analyzed age as a univariate factor in survival in a national group of 46,613 major trauma patients and compared 180 elderly major trauma patients (greater than or equal to 65 years) to a similarly injured group of 3,918 younger patients (less than 65 years). In the national group, mortality rose sharply between age 45 (10%) and 55 (15%) and doubled at age 75 years (20%). This age-dependent survival decrement occurred at all Injury Severity Score values, for all mechanisms of injury, and for all body regions. In the comparison study, mortality in the elderly group was nearly double that of mortality in the younger group (27% vs. 14%). The older patients had a markedly higher complication death rate, especially for pulmonary (14/100 vs. 6.1/1100) and infectious complications (4.6/100 vs. 0.7/100). The median length of stay was twice as long for the older patients (14 days vs. 7 days). Cost data showed that the DRG prospective payment system grossly underestimated the cost of care for these patients (mean loss of $2,177.14 per patient). To minimize mortality and morbidity, triaging elderly trauma victims to trauma centers at a much lower threshold than similarly injured younger patients is recommended. The current DRG system should be altered to account for age-dependent morbidity. Further study is needed to determine whether more rigorous infection prophylaxis, immunomodulation, and pulmonary therapy will augment survival in elderly patients.

Adolescent↗