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Biomedical subjects

G Friman

Publications and source records attributed to G Friman.

At least 73 records · Page 4Linked to original sources
PubMed1992

The possible role of Coxsackie A and echo viruses in the pathogenesis of type I diabetes mellitus studied by IgM analysis.

IgM antibodies to Coxsackie B virus (CBV) have recently been observed in the serum of a relatively high proportion of children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). In the present study, 108 IDDM patients below the age of 15 years, diagnosed during the period 1976 to 1985, were investigated at the onset of their disease by mu-antibody-capture radioimmunoassay (RIA) of IgM against seven different enterovirus antigens, namely virions of CBV serotypes 1-5 (CBV 1-5) and procapsids of CBV 3 and CBV 5. As has been shown the RIAs with virions give type-specific or narrow type-specific reactions, whereas procapsids react with IgM against both homotypic and heterotypic enteroviruses. The annual frequency of IgM against virions varied between 15 and 76% (mean 38%). IgM against CBV3 and CBV2 predominated, but IgM against the other serotypes was also observed. When procapsids were used as antigen, the frequency of IgM varied between 11 and 86% (mean 63%). With virions and procapsids, the corresponding variation was 44-100% (mean 70%). The total number of patients exhibiting virion-IgM was 41, whereas procapsid-IgM alone [indicating an infection with Coxsackie A virus (CAV) and/or echo virus (EV)] was detected in 36 patients. For 2 of the years, samples of serum from control groups were included. These showed a significantly lower frequency of IgM in both the virion and the procapsid RIAs. It is concluded that not only infection with CBV but also that with other enteroviruses, such as CAV and/or EV, may be involved in the pathogenesis of IDDM in children.

Adolescent↗
PubMed1992

Altered distribution of 109cadmium in mice during viral infection.

The distribution of the toxic heavy metal cadmium (Cd) was studied in Coxsackie virus B3 (CB3)-infected Balb/c mice by whole-body autoradiography and gamma-counting. The distribution of 109Cd was studied 4 days post CB3-inoculation and 10 min after intravenous injection of 0.21 microgram of Cd/kg body weight. Whole-body autoradiography results showed that the distribution of 109Cd is greatly changed during this viral infection. This newly discovered distribution was mainly visible as a greatly increased accumulation in the renal and adrenal cortices. After impulse counting of selected organs it was found that the normal accumulation of 109Cd in the kidneys (184,354 +/- 30,961 c.p.m.) was increased by 47% (P less than 0.05) during CB3 infection (270,503 +/- 54,780 c.p.m.). In contrast to healthy animals, some infected mice showed accumulation of 109Cd in the spleen. These results show for the first time that an invading micro-organism can change the distribution of an environmental pollutant.

Adrenal Cortex↗
PubMed1991

Does exercise stress alter susceptibility to bacterial infections?

Swimming was used for evaluating alterations in performance capacity and as a means for studying the influence of exercise stress on susceptibility to Streptococcus pneumoniae and Francisella tularensis infections in two strains of rats, i.e. Fisher-Dunning (FD) and Sprague-Dawley (SD). The performance capacity was reduced by both diseases and was correlated to the dose of the given micro-organism. FD rats, however, were more susceptible to the infection and showed a greater deterioration than SD rats. The effects of exercise stress on disease lethality varied with the time that it was performed. Strenuous exercise immediately before infection drastically reduced susceptibility to either of the bacteria, while a similar bout of exercise performed after infection increased disease-related mortality in both diseases.

Animals↗
PubMed1991

Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats.

The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection.

Animals↗
PubMed1991

Effects of training on metabolic responses and performance capacity in Streptococcus pneumoniae infected rats.

These experiments were designed to study whether endurance training prior to Streptococcus pneumoniae infection in rats (N = 15 in each group) alters lethality, performance capacity, and related energy metabolism. A 5-d.wk-1, 4-wk-long pre-infection training program with gradually increasing swim time caused no protection from lethality (48% at 72 h post-inoculation), but performance capacity increased by 68% (P less than 0.01). The catabolic responses as evidenced by changes in insulin and glucagon levels were less pronounced. Mobilization of free fatty acids increased twofold (P less than 0.01), and improved ketonemic adaptation (47%, P less than 0.01) occurred with concomitant saved carcass, liver, and skeletal muscle glycogen contents (P less than 0.01). This shift from carbohydrate toward fat metabolism during exercise as a result of training was also reflected by 21% lower (P less than 0.01) blood lactate levels. It was concluded that the improved metabolic status, characterizing the trained as compared with the untrained host, is partly preserved during ongoing acute gram-positive bacterial infection.

Animals↗
PubMed1990

Vaccination of Balb/c mice against enteroviral mediated myocarditis.

A non-virulent strain of Coxsackie B3 (CB3) virus was used to produce a subunit vaccine. It contains the capsid proteins VP1, 2, 3 and probably 4 and can be made RNA-free. It is based on the ISCOM technology ensuring non-toxic properties and good adjuvant effect. Vaccinated animals at doses above 16 ng were completely protected from mortality when challenged with a myocarditic strain of CB3. Histologically no inflammatory lesions were found in the heart. This was corroborated using immune histological techniques with monoclonal antibodies against lymphocyte subsets. Even at a dose of 0.16 ng a delayed mortality was observed. Neutralizing antibody titres rose to 512, thus ensuring a circulating level well above that considered protective. It is suggested that vaccination might be a possible way of prophylaxis for myocarditis and even dilated cardiomyopathy, the latter presently being the chief cause of heart transplantation. By persistence or triggering of autoimmune phenomena Coxsackie virus is incriminated as the first step in pathogenesis.

Animals↗
PubMed1990

Detection of Staphylococcus aureus infection by enzyme-linked immunosorbent assay and immunoblotting, using high molecular weight staphylococcal proteins.

Two high molecular weight staphylococcal proteins, fibronectin-binding protein and a Mr 200,000 protein, were investigated as antigens for serodiagnosis of staphylococcal infections. Sera from patients with staphylococcal infections and from controls were subjected to immunoblot analysis with staphylococcal lysate proteins to identify staphylococcal antigens to which patients with staphylococcal infections specifically exhibited antibodies. One such protein was found in the Mr 200,000 region. This protein was purified and used as antigen in ELISA and compared with other antigens, namely fibronectin-binding protein(s) (FNBP, Mr 185,000), alpha-toxin and teichoic acid. Sera from patients with staphylococcal infections contained antibodies to the high molecular weight proteins in higher titers than sera from patients with non-staphylococcal infections or healthy subjects. Based on their amino-acid compositions and different abilities to bind fibronectin it was concluded that the Mr 200,000 protein and FNBP were not identical.

Adolescent↗
PubMed1990

A qualitative and quantitative method for in situ characterization of the inflammatory response in experimental myocarditis.

Coxsackie virus B3 causes myocarditis in Balb/c inbred mice. In this model mortality is about 60% on day 7 and 95% on day 12 after inoculation. Significant inflammatory infiltrates appear on day 7. Recent research has focused on the immune response to explain the ensuing tissue damage. Thus we were interested in mapping cellular interaction and time course to understand the development of a possible autoimmune attack. By a newly developed immunohistochemical staining technique single lymphocytes could be visualized and different lymphocyte subpopulations enumerated. Stained cells were easily detectable and readily distinguishable from non-stained cells. Before day 7 Th cells could only occassionally be seen. The number of pan T lymphocytes increased almost 10-fold from day 7 to 12. The T helper/T killer ratio did not change significantly but indicated a predominant increase in Tk-cells. The B cell population also increased, roughly about ten times. The number of class II positive cells was constant. No expression of Il-2 receptor was found. In preliminary studies, exercise and methylprednisolone treatment tended to influence the expression of class II antigens. Cyclophosphamide and cyclosporine A reduced the number of inflammatory cells more than 10-fold. No clear concurrent reduction in mortality was observed.

Animals↗
PubMed1990

Total and net muscle protein breakdown in infection determined by amino acid effluxes.

The present investigation was undertaken to study whether, in human infection of varying severity, peripheral 3-methylhistidine efflux and urinary excretion are associated with net protein degradation and to estimate the protein synthesis rate from the combined effluxes of 3-methylhistidine, tyrosine, and phenylalanine. Quadruplicate femoral arteriovenous differences of 3-methylhistidine, tyrosine, and phenylalanine were multiplied by leg plasma flow in 15 infected patients. Leg effluxes for 3-methylhistidine, tyrosine, and phenylalanine were -0.074 +/- 0.011, -2.57 +/- 0.43, and -3.17 +/- 0.44 mumol/min, respectively. There was a significant linear relationship (P less than 0.01) between the effluxes of tyrosine and phenylalanine and the efflux and urinary excretion of 3-methylhistidine. A significant release of tyrosine and phenylalanine was observed in patients studied at the 3-methylhistidine level seen in normal healthy subjects. It is concluded that in infection 1) there is an increased breakdown of skeletal muscle protein and a reduced rate of protein synthesis, with the latter being relatively more important in patients with mild disease; and 2) urinary 3-methylhistidine excretion is associated with net skeletal muscle protein degradation for the patient group studied.

Abdomen↗
PubMed1990

Cardiovascular lipid accumulation with Coxsackie B virus infection in mice.

The authors used a myocarditic coxsackievirus B3 infection in Balb/c mice to investigate cardiovascular lipid accumulation and whether a cholesterol-enriched diet influences the development of the myocardial inflammatory reaction. It was found that, seven days after CB3 infection, the accumulation of 14C-cholesterol increased by 75% (P less than 0.001) in the heart and by 92% (P less than 0.001) in the aorta. This infection also caused extensive inflammatory lesions (4.5% of tissue section area) and lipid accumulation in the myocardium seven days after inoculation. Seven weeks on a 1% cholesterol-enriched diet did not affect the myocardial area damaged (3.9%), the lethality, or immune cell activity (T, B, and natural killer [NK] cells). The response pattern of myocardial lymphocyte subpopulations was studied with an immune histochemical staining technique. The number of Mac 2+ (macrophages), class II expressing cells, or the T cytotoxic, suppressor/T helper cell ratio was not changed by the cholesterol diet. The number of class II cells tended to increase (38%) with cholesterol and was positively correlated (P less than 0.001) with the Mac 2 expression regardless of the cholesterol diet. Although moderate diet-induced hypercholesterolemia did not alter host response to viral infection, these results support the idea that virus and immune cells may cooperate and play a role in arterial and myocardial lipid accumulation, possibly acting as initiating factors for atherosclerosis.

Animals↗
PubMed1989

Effects of the immunomodulator LS 2616 on lymphocyte subpopulations in murine Coxsackievirus B3 myocarditis.

Quinoline-3-carboxamide (LS 2616) is a broadly acting immunostimulator with anti-inflammatory effects in Coxsackie virus B3-induced myocarditis in female BALB/c mice. This infection caused extensive inflammatory and necrotic lesions in the myocardium 7 days after inoculation (6.8% of tissue section area). The damaged area was reduced (to 3.7% (p less than 0.05] and the lethality decreased when LS 2616 was administered over 14 days, starting 7 days before the inoculation. The response pattern of lymphocyte subsets in situ in myocardial inflammatory lesions was elucidated by a newly developed immune histochemical staining technique. LS 2616 increased the number of class II-expressing cells 3-fold (p less than 0.01) and the CTL, Ts:Th cell ratio by 55% (p less than 0.05), whereas Lyt-1+ and TIB+ cells were unaffected. After 7 days of LS 2616 treatment, spleen lymphocyte activity tended to increase (T cells by 21% (NS) and B cells by 60% (p less than 0.05), respectively). The activity of NK cells increased by 51% (p less than 0.01). LS 2616 may thus have potential in therapy of human inflammatory disorders, such as myocarditis.

Adjuvants, Immunologic↗
PubMed1989

The Swedish childhood diabetes study III: IgM against coxsackie B viruses in newly diagnosed type 1 (insulin-dependent) diabetic children--no evidence of increased antibody frequency.

Sera from essentially all Swedish children aged 0-14 years with Type 1 (insulin-dependent) diabetes mellitus with onset during an autumn period (October-December 1985) and a late spring period (May-June 1986) were selected. In all, 98 patients were analysed for IgM antibodies against coxsackie B virus serotypes 1 through 5 by a mu-antibody capture radio immunoassay technique. Sera from 94 referent children matched for age, sex and residential area, collected during the same period, were also analysed. During the autumn period, 10 out of 67 (15%) diabetic children were IgM positive while 14 out of 75 (19%) of the healthy referent children demonstrated positivity. During the late spring period only one out of 31 (3%) children with diabetes and two out of 19 (10%) referent children were IgM positive. In the diabetic patients, five were coxsackie B2 positive while coxsackie B1, 3, 4 and 5 were represented by one to three patients each. Eight referent children were coxsackie B4 positive, six were B3 positive and two B2 positive, while no referent children were positive against coxsackie B1 and 5. During these two periods in late 1985 and early 1986 these data demonstrate no evidence of increased antibody frequency against coxsackie B virus 1 through 5 at the onset of childhood diabetes in Sweden.

Adolescent↗
PubMed1989

Exercise in coxsackie B3 myocarditis: effects on heart lymphocyte subpopulations and the inflammatory reaction.

To investigate whether exercise in coxsackie B3 virus infection is detrimental to the myocardium, Balb/c mice were inoculated with the virus and exercised to exhaustion on a motor-driven treadmill up to 48 hours after the inoculation. This infection evokes myocarditis. The inflammatory and necrotic lesions in the ventricular myocardium 7 days after the inoculation covered 4.32% of the tissue section area in the nonexercised group. Exercise at 0 hours did not affect this myocardial damage (4.77%), whereas exercise at 48 hours after the inoculation increased the lesion to 7.85% (p less than 0.05). Lethality was not influenced by exercise. The response pattern of myocardial lymphocyte subpopulations was studied with an immune histochemical staining technique. The number of T cytotoxic, T suppressor cells increased threefold (p less than 0.01), and the T cytotoxic, suppressor/T helper cell ratio increased twofold (p less than 0.01) with exercise at 48 hours but was unchanged with exercise at 0 hours. The number of class II expressing cells decreased with exercise at 48 hours (p less than 0.05) and was negatively correlated (p less than 0.01) with the size of the inflammatory reaction. The development of myocardial inflammatory and necrotic lesions seems to be dependent on the presence and cooperation of class II expressing cells and T killer cells. Furthermore, failure to restrict physical activity in the acute phase of this infection may well contribute to the progression of the disease.

Animals↗
PubMed1989

Splanchnic and peripheral release of 3-methylhistidine in relation to its urinary excretion in human infection.

The present investigation was undertaken in order to determine the release of 3-methylhistidine (3MH) from the splanchnic region and from the leg, and the contributions these make to the increase in urinary 3MH excretion in infection. Thirteen febrile patients with infection were investigated. After an overnight fast, hepatic vein, femoral vein, and radial artery catheterizations were performed. Splanchnic and leg blood flows were determined by dye dilution technique. Plasma 3MH was analyzed by a modified HPLC method. The release of 3MH from the leg was 0.064 +/- 0.007 mumol/min (+/- SE) and from the splanchnic region 0.012 +/- 0.013 mumol/min. These releases of 3MH constitute 27% +/- 2% and 8% +/- 6% of the individual urinary excretions, respectively. With increasing degree of catabolism, measured as individual 3MH increase above baseline excretion or as the 3MH to creatinine ratio (3MH:Cr), the relative contribution to urinary excretion from the leg was increased (individual increase, P = 0.08; 3MH:Cr, P less than 0.01). Since this contribution was not decreased in the more catabolic patients, as would have been expected if the increase in urinary 3MH originated elsewhere, it is concluded that skeletal muscle is the source, and these results thus validate the use of urinary 3MH excretion as a marker of myofibrillar protein catabolism in infected patients.

Adult↗
PubMed1989

Evaluation of urinary 3-methylhistidine excretion in infection by measurements of 1-methylhistidine and the creatinine ratios.

When 3-methylhistidine (3MH) excretion is used as an indicator of myofibrillar protein catabolism, there are restricting factors, such as meat intake, incorrect 24-h urine collections, and a large interindividual variation in basal excretion. 1-Methylhistidine (1MH) was previously suggested as an indicator of meat intake. We studied the basal urinary excretion of 1MH and whether this was influenced by infection and we compared the use of 3MH vs the 3MH:creatinine ratio (3MH:Cr) in detecting changes during infection. The basal excretion of 1MH was 84.9 mumol/24 h and its creatinine molar ratio (1MH:Cr) was 7.4 x 10(-3) with no change during infection. Because 1MH:Cr was significantly increased in 4 of 14 patients, their 3MH values were considered influenced by meat intake and thus discarded. Among the remaining 10 patients, 9 showed a significant individual increase in 3MH:Cr during infection compared with only 4 in 3MH. This was due to a higher precision in 3MH:Cr despite the concomitant significant increase in urinary creatinine excretion.

Adolescent↗
PubMed1989

Exchange of 3-methylhistidine in the splanchnic region in human infection.

This investigation was undertaken to determine the splanchnic exchange of 3-methylhistidine (3MH) in infection. Hepatic vein, femoral vein, and radial artery catheterizations were performed in 12 febrile patients with infections of varying severity. Differences in arteriovenous 3MH, analyzed by high-performance liquid chromatography, were multiplied by the plasma flows, determined by a dye dilution technique. The mean splanchnic efflux was 0.062 +/- 0.180 mumol/min (mean +/- SD) with uptake occurring in five patients. The splanchnic uptake was significantly (p less than 0.001) correlated with the urinary 3MH excretion and the peripheral release from the leg. It is concluded that in human infection, splanchnic 3MH release is low and in patients with high rates of myofibrillar catabolism there may even be an uptake. The urinary 3MH excretion is still a marker of myofibrillar protein breakdown because it correlates well with the release from the leg, regardless of whether the patient has a splanchnic uptake or a release.

Chromatography, High Pressure Liquid↗