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Biomedical subjects

J Fohlman

Publications and source records attributed to J Fohlman.

At least 55 records · Page 3Linked to original sources
PubMed1985

High frequency of Coxsackie-B-virus-specific IgM in children developing type I diabetes during a period of high diabetes morbidity.

Twenty-four consecutive children with newly diagnosed insulin-dependent (type I) diabetes mellitus (IDDM) were investigated for a history of infectious disease. Thirteen of the 24 (54%) patients reported symptoms of acute infection within two months before diabetes was diagnosed. The mean age was 8.5 years and 15 (63%) of the patients were girls. No clear seasonal variation in onset was seen. Coxsackie B (CB)-virus-specific IgM responses were detected by reverse radioimmunoassay (RIA) in 16 of the 24 (67%) patients on the day of diagnosis of IDDM. The highest titre was usually recorded at that time, but with some the highest titre was found with a second serum obtained three to seven weeks after diagnosis. Thereafter the titres declined, and after six months IgM was detected only in a few patients. Thirteen patients displayed monotypic IgM responses, whereas three patients showed ditypic responses. Among the former, IgM was recorded against Coxsackie B4 (CB4) in four, B5 (CB5) in three, B1 (CB1) in two, B2 (CB2) in two, and B3 (CB3) in two patients. The ditypic responses were against CB2 and CB3, CB3 and CB4, and CB5. No CB-virus-specific IgM was detected in sera, found during the same period, from age-matched nondiabetic children without evidence of infection. In neutralisation (NT) tests, antibodies to the homotypic virus were found in 12 of the 16 diabetic patients showing CB-virus-specific at the time of diagnosis. A significant rise in NT titre was demonstrated in three of these patients. No significant clinical difference was noted between IgM positive and IgM negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1985

An incidence peak of juvenile diabetes. Relation to Coxsackie B virus immune response.

All new cases of insulin dependent diabetes mellitus (IDDM) in children below 15 years of age were recorded prospectively during a 21-year period 1964-1984 in a defined uptake area with a relatively constant child population. The total number of children recorded was 222-111 boys and 111 girls. The number of new cases varied between 4 cases in 1968 and 20 in 1984; in 1983 seventeen new cases were recorded. Specific IgM antibodies against Coxsackie B virus (CBV), types 1-5 were measured by a reverse radioimmunoassay (RIA) technique in 24 consecutive patients collected during the period March 1982-January 1984, some of whom represented the recent period of a very high incidence of diabetes. Sixteen patients (67%) exhibited CBV IgM responses, strongly suggesting a current or recent CBV infection. The titres declined during the first few months of diabetes and seemed to be absent after the first half-year period. Among age-matched non-diabetic children scheduled for elective procedures during the same period, no cases with CBV-IgM antibodies were detected. Only three of the 16 IgM-RIA-positive patients showed a significant rise in the neutralising antibody titre against the same Coxsackie B type. It is concluded that CBV may play a pathogenetic role in induction of IDDM, and possibly more frequently so during periods with a high incidence of diabetes, at least in children below 15 years of age.

Adolescent↗
PubMed1984

Molecular weight determinations of proteins by californium plasma desorption mass spectrometry.

The plasma desorption mass spectrometry method is used to determine the molecular weights of larger molecules than before, to determine the molecular weights of proteins and peptides in mixtures, and to monitor protein modification reactions. Proteins up to molecular weight 25,000 can now be studied with a mass spectrometric technique. Protein-peptide mixtures that could not be resolved with conventional techniques were successfully analyzed by this technique. The precision of the method is good enough to permit one to follow the different steps in the conversion of porcine insulin to human insulin.

Animals↗
PubMed1984

Californium-252 plasma desorption time of flight mass spectroscopy of proteins.

Fast heavy ions, i.e. fission fragments from a 252Cf-source, have been used to desorb and ionize peptides and proteins from a sample surface. Masses of the desorbed ions have been determined by the time-of-flight technique. The mass interval of the molecules studied is 1000-14 000 u. Quasi-molecular ions of higher masses than earlier reported have been observed. The results include the detection of quasi-molecular ions of proinsulins, cytochrome-C, ribonuclease and two phospholipases. The general features of mass spectra of proteins using this ionization method are described. Emphasis is put on the discussion of metastable ion decay, neutral components, multiply charged ions, isotopic broadening, and cluster ion formation. Also the precision which can be obtained with a straight time-of-flight mass spectrometer will be discussed. Future applications of the technique are outlined.

Animals↗
PubMed1983

The observation of quasi-molecular ions from a protein neurotoxin (MW 7821) using 127I-plasma desorption mass spectroscopy.

Fast heavy ions, i.e. 90 MeV 127I from the Uppsala tandem accelerator have been used to desorb and ionize molecules from a cobra venom neurotoxin. The protein is built up by 71 amino acid residues in a single polypeptide chain, tightly cross-linked by 5 disulfide bridges. The molecular weight as confirmed by protein sequence analysis is 7821. The ions were mass analyzed by the time-of-flight technique. This is to our knowledge the largest protein for which it has been possible to detect quasi-molecular ions by a mass spectrometric technique.

Amino Acid Sequence↗
PubMed1980

Biochemical comparison of HLA-DR molecules derived from autologous human T and B lymphoblasts.

Earlier findings that human activated T blasts display HLA-DR determinants have been confirmed. After phytohemagglutinin activation, Percoll gradient-purified blast cells were cultured for two weeks in mitogen-derived supernatants from human lymphocyte cultures. Using purified T blasts and internal labeling procedures, it was established that T blasts actively produced HLA-DR-like chains, as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Further, HLA-DR chains obtained from Epstein-Barr virus-transformed B cells and from T blasts of the same donor were compared. Two-dimensional gel electrophoretic comparisons indicated a striking homology between 29 kD and 35kD chains, obtained from the two different cell types. Peptide map analysis and preliminary amino acid sequence comparisons further supported this similarity. A more complete analysis would, however, be required to prove actual identity. The fact that human T blasts produce and display HLA-DR molecules very similar, if not identical, to those present on B cells must then be incorporated into models discussing major histocompatibility complex-restricted collaborations involving HLA-DR molecules.

Animals↗
PubMed1980

Complete amino acid sequence of pooled papain-solubilized HLA-A, -B, and -C antigens: relatedness to immunoglobulins and internal homologies.

Pooled, papain-solubilized HLA-A, -B, and -C antigens, derived from a large number of individuals and comprising several allelic forms, have been subjected to amino acid sequence determination. Despite the heterogeneity of the material, a main sequence representing all of the 273 amino acid residues could be established. The primary structure encompasses two immunoglobulin-like disulfide loops. The single carbohydrate moiety is attached to asparagine-86. Computer analyses demonstrated that the COOH-terminal one-third of the sequence, called H3, display statistically significant homology with members of the immunoglobulin family. The NH2-terminal two-thirds of the molecule, called H1 and H2, are not significantly homologous to any of the immunoglobulin sequences. However, H1 and H2 exhibit a distant relatedness to each other but no obvious similarity to the H3 region.

Amino Acid Sequence↗
PubMed1979

Amino acid sequence of a postsynaptic neurotoxin from the venom of the Australian tiger snake Notechis scutatus scutatus.

Although 60 percent of the protein in tiger snake (Notechis scutatus scutatus) venom consists of the basic per-synaptically neurotoxic and myotoxic phospholipases notexin and Notechis II-5 and other phospholipase homologs such as Notechis II-1, several post-synaptic "curaremimetic" neurotoxins are present in small amounts. The major one of these is a typical "long" neurotoxin containing 73 amino acids in a single peptide chain cross-linked by five disulfide bridges. The formula weight calculated from the amino acid sequence is 8,051. The LD50 for intravenous injection into mice is 125 micrograms/kg.

Amino Acid Sequence↗
PubMed1979

Amino acid sequence of an immunoglobulin-like HLA antigen heavy chain domain.

The classical human transplantation antigens, derived from the HLA-A, -B, and -C loci, are cell-surface-expressed glycoproteins. On the exterior of the cell the transplantation antigen heavy chain exposes two disulfide-containing domains and a glycosylated NH2-terminal extension. The disulfide-containing domain closest to the membrane has been isolated and its amino acid sequence has been determined. The HLA antigens used for the sequence analysis were derived from two and possibly three loci and comprised several allelic forms. The primary structure was remarkably invariant, and amino acid variations were observed only at three positions. Whether this suggests that the allelic variation of the HLA antigens is preferentially confined to other regions of the molecule or is a result of fortuitous selection of peptides remains to be established. The sequenced portion of the HLA antigen heavy chain is as homologous to beta 2-microglobulin and immunoglobulin light and heavy chains as are the latter to one another. This observation strengthens the notion that the transplantation antigens and the immunoglobulins are evolutionarily related.

Amino Acid Sequence↗
PubMed1979

Chemical modification of taipoxin and the consequences for phospholipase activity, pathophysiology, and inhibition of high-affinity choline uptake.

Treatment of taipoxin with p-bromophenacyl bromide resulted in modification of single histidine residues in the alpha and beta subunits. The modification decreased the neurotoxicity (lethality) 350-fold, but the inhibitory action on high-affinity choline transport was reduced only threefold. The phospholipase activity and Ca2+-association constants for taipoxin and its subunits were determined. A model for the neurotoxicity of taipoxin indicates the alpha subunit as the ultimate cause of the disruption of synaptic transmission.

Acetophenones↗