Unaltered oxygen tension in rat pancreatic islets despite dissociation of insulin release and islet blood flow

The present study investigated the importance of a tightly regulated islet blood flow for an optimal oxygenation of the islet tissue during different demands for insulin release. Glucose and/or a non-specific nitric oxide synthase inhibitor (L-NNA) were infused intravenously in non-pretreated or vagotomized rats and the animals were subjected to measurements of islet blood flow, oxygen tension and serum insulin concentrations. Islet blood flow was measured using a non-radioactive microsphere technique, tissue oxygen tension was recorded with Clark microelectrodes and insulin concentrations were determined by enzyme-linked immunosorbent assay technique. Administration of L-NNA (0.3 mg kg(-1) min(-1)) for 10 min halved basal islet blood flow, but did not affect serum insulin concentrations. Glucose administration (10 mg kg(-1) min(-1)) induced a marked increase in islet blood flow, which could be prevented by vagotomy or L-NNA. The serum insulin concentrations increased in all glucose-infused animals. The islet tissue oxygen tension remained similar in all animals despite these interventions. Reasons other than oxygenation of the islet tissue must explain the normally existing tight regulation of islet blood flow.     

Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice.

DBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus formation without T cell infiltration and only limited MHC class II expression. Specific pathogen-free DBA/1 mice from different sources developed the same disease. Analyses of inbred mouse strains with various genetic backgrounds and F1 hybrids revealed that the disease is genetically dependent of DBA/1 recessive genes. However, F1 hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/1 mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing effects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development of arthritis is dependent on hormonal and behavioural mediated effects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristane-induced arthritis. We conclude that the spontaneously developing arthritis in the normal DBA/1 strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis.     

Immunoglobulin E in the feces of children and adolescents from some tropical and subtropical countries

Eighteen of 27 individuals, aged from 6 months to 19 years (mean 5 years, 7 months), from countries in the tropics or the subtropics had either intestinal parasitic infestations or intestinal enteropathogenic bacterial infections or both. Fourteen of those with intestinal pathogens had detectable concentrations of IgE in their fecal extracts, ranging from less than 0.5 to 420 IU/ml extract (mean 33 IU/ml). This rate of occurrence was significantly higher than the number of IgE-positive fecal extracts in a group of 54 healthy nonallergic Norwegian children (p less than 0.001), but did not differ from that of a group of 40 allergic children (p greater than 0.20). The individuals with intestinal helminthic infection had the highest fecal IgE concentrations. Of the 9 individuals who did not have any demonstrable intestinal pathogen, low concentrations of IgE could be detected in feces from only 2, which did not differ from the rate in the healthy Norwegian controls. The concentrations of IgE in the feces of the subjects from tropical/subtropical regions correlated linearly with the corresponding serum concentrations of IgE (r = 0.69; p less than 0.001). The results indicate that the combined load of intestinal pathogens, including helminths, protozoa, and enteropathogenic bacteria, may stimulate IgE production in the gut.     

The Effect of 6-Aminonicotinamide Blockade of the Pentose Phosphate Pathway on Catecholamines in the Rat Adrenal Medulla,Superior Cervical Ganglion,Hypothalamus and Synaptosome Fractions

The effect on tissue catecholamines of blockade of the pentose phosphate pathway with 6-aminonicotinamide (6-AN) was studied in the rat. 6-AN at 35–50 mg kg^-1 persistently lowered the adrenaline content in the adrenal gland to less than 10% of control values and caused a 50% loss of noradrenaline, which recovered. When the amine turnover rate was increased by a preceding period of drum stress, 6-AN also consistently depressed noradrenaline in the gland. 6-AN was without significant effect on the noradrenaline concentration in heart tissue, hypothalamus and superior cervical ganglion and did not affect the uptake or release of catecholamines in vitro. The possibility is discussed that 6-AN interferes with the biosynthesis of catecholamines, when it blocks the pentose phosphate pathway, by decreasing the supply of reducing equivalents in the form of NADPH which are necessary for the tetrahydropteridine cofactors of tyrosine hydroxylase.     

Effect of hyperthyroidism on fibre-type composition, fibre area, glycogen content and enzyme activity in human skeletal muscle

Seven hyperthyroid patients were studied by repeated muscle biopsies (vastus lateralis) before and after a period of medical treatment which averaged 10 months. The biopsies were analysed with regard to fibre-type composition, fibre area, capillary density, glycogen content and enzyme activities representing the glycolytic capacity (hexokinase, 6-phosphofructokinase), oxidative capacity (oxoglutarate dehydrogenase, citrate synthase) and Ca2+- and Mg2+-stimulated ATPase in muscle. In the pretreatment biopsy (hyperthyroid state), there was a significantly lower proportion of type I fibres (30% vs. 41%), a higher capillary density (23%), lower glycogen content (33%), and higher hexokinase activity (32%) compared with the post-treatment biopsy. No significant changes in the activity of the remaining enzymes were observed. The present study indicates that hyperthyroidism induces a transformation from type I to type II fibres in human skeletal muscle. The increase in hexokinase activity probably reflects a higher glucose utilization by skeletal muscle in order to compensate partially for the reduced glycogen content.     

On the significance of the respiratory exchange ratio after different diets during exercise in man

Total respiratory exchange ratio (R) was compared to the respiratory exchange ratio over the legs (RQL) during exercise after different diets, to evaluate if R (which represents a mean for the whole body) can be used to estimate the relative proportions of fat and carbohydrate oxidation in exercising muscle. One important prerequisite for this is a steady state acid base balance, 7 subjects were studied at rest and during the later part of a 25 min exercise (65% of Vo2 max) on two occasions, the first preceded by a fat rich diet and the second by a carbohydrate rich diet. Oxygen uptake, R and arterial-femoral venous differences for [O2], [CO2], PCO2 and pH and arterial concentrations for lactate and beta-hydroxybutyrate were measured. Respiratory exchange ratio over the exercising legs (RQL) and ventilation/oxygen uptake were calculated. Arterial pH, PCO2, lactate and beta-hydroxybutyrate as well as specific ventilation attained steady levels during the later part of exercise after both diets. Although arterial lactate and beta-hydroxybutyrate differed between the diets, the arterial pH and specific ventilation were the same. Both R and RQL were higher after the carbohydrate than after the fat diet and there was no systematic difference between R and RQL. Therefore, it seems likely that R estimates the proportion of fat and carbohydrate oxidation in skeletal muscle during submaximal exercise after extreme diets.     

Analysis of the relationship between viral infection and autoimmune disease

The clinical association between viral infection and onset or exacerbation of autoimmune disorders remains poorly understood. Here, we examine the relative roles of molecular mimicry and nonspecific inflammatory stimuli in progression from infection to autoimmune disease. Murine herpes virus 1 (HSV-1 KOS) infection triggers T cell-dependent autoimmune reactions to corneal tissue. We generated an HSV-1 KOS point mutant containing a single amino acid exchange within the putative mimicry epitope as well as mice expressing a TCR transgene specific for the self-peptide mimic to allow dissection of two pathogenic mechanisms in disease induction. These experiments indicate that viral mimicry is essential for disease induction after low-level viral infection of animals containing limited numbers of autoreactive T cells, while innate immune mechanisms become sufficient to provoke disease in animals containing relatively high numbers of autoreactive T cells.     

Identification of a new HLA-DPB1 allele,HLA-DPB1*9001

During routine typing of a potential bone marrow donor, a new HLA DPB1 allele was identified. The new allele, officially named HLA DPB1*9001, differs from HLA DPB1*01011 in the second hypervariable region, where a single nucleotide substitution in position 191 changes the codon 35 from TAC to TTC with a predicted amino acid change from Tyr to Phe.     

Kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the hprt gene of Chinese hamster ovary cells

The kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone(MX) in the protein coding region of the hprt gene of Chinesehamster ovary (CHO) cells were determined by direct sequencingof polymerase chain reaction (PCR)-amplified cDNA. Primary mutationswere found in 15 of 19 of the mutants: 11 were G:CT:A transversions,two were A:TT:A transversions and two were deletions of singleG:C base pairs (-1 frameshifts). The remaining four mutantshad large alterations in the cDNA that were explained by mRNAsplicing errors. A group of control mutants had more diversehprt cDNA alterations than MX-induced mutants. Transversionsyielding an A:T base pair were the predominant type of MX-inducedmutations, in agreement with previous findings in bacteria.This specificity may be explained by the ‘A rule’,that DNA polymerases preferentially insert, adenine nucleotidesopposite non-instructional lesions.