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Biomedical subjects

H Persson

Publications and source records attributed to H Persson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Markedly improved skeletal muscle function with local muscle training in patients with chronic heart failure.

BACKGROUND: Reduced heart pump function and skeletal muscle abnormalities are considered important determinants for the low physical exercise capacity in chronic heart failure. Because of reduced ventricular function, traditional physical rehabilitation may cause underperfusion and low local work intensity, thereby producing suboptimal conditions for skeletal muscle training. HYPOTHESIS: The study was undertaken to determine the effects of local exercise training, designed as one- or two-legged knee extensor training, on exercise capacity in patients with moderate chronic heart failure. Because such exercise models use only about one quarter to half the muscle mass used in cycle ergometer training, the influence of a restricted circulatory capacity should therefore be limited. Further, we aimed to determine whether or not chronic heart failure skeletal musculature abnormalities are counteracted with such training. METHODS: Fourteen patients with chronic heart failure [age 58 +/- 3 years, ejection fraction (EF) 28 +/- 4%] were randomized to two different training protocols three times a week for 8 weeks and compared with a nontraining control group (n = 7, age 62 +/- 3, EF 27 +/- 3%). Group 2L (n = 7) underwent simultaneous two-legged knee extensor training (about 4 kg working muscle) for 15 min at 65-75% of VO2 max of the two-legged kick. Group 1L (n = 7) trained each leg at a time for 15 min of continuous one-legged dynamic knee extensor work with the same training load per muscle mass, that is, at 35% of VO2 max of the two-legged kick (about 2 kg working muscle). Peak VO2 of two-legged knee extensor exercise (l/min), two-legged endurance (W), and strength (Nm) were determined before and after the training period. The activity of citrate synthase (CS) was estimated in tissue samples from the quadriceps femoris muscle. RESULTS: Peak VO2 did not change with training. Two-legged knee extensor endurance exercise capacity increased by an average of 40-50% (p < 0.01) in all training patients in both the 2L and 1L groups, while no change was observed in the control group. Depressed skeletal muscle CS activity increased by 25-35% in both training groups (p < 0.01). Strength increased by 16% in the 2L group after training (p < 0.05), while no change was seen in the 1L and control groups. CONCLUSIONS: Skeletal muscle changes in stable moderate chronic heart failure are not entirely irreversible. A major factor contributing to these changes and to exercise limitation is deconditioning. Local muscle training is efficient and can at least partially improve skeletal muscle function in these patients. Different degrees of local activation, that is, one- or two-legged knee extensor exercise, do not seem to differ in terms of their effect on exercise capacity. Depressed skeletal muscle oxidative capacity adapts to such physical training with increased activity to an extent not different from that for healthy volunteers.

Adaptation, Physiological↗
PubMed1996

Presence of sulphatide (3'-sulphogalactosylceramide) in pericytes in the choroid layer of the eye: sharing of this glycolipid autoantigen with islets of Langerhans.

The aim of the study was to investigate the distribution in the eye of sulphatide, an acid glycolipid which has previously been demonstrated in islets of Langerhans, nervous tissue and in kidney glomeruli of diabetic patients, and against which antibodies have been found in patients with newly diagnosed insulin-dependent diabetes mellitus. A specific monoclonal antibody, Sulph I, was used for detection of sulphatide by thin-layer chromatography, and light and electron microscope immunohistochemistry. A distinct, patchy staining was found in the choroid layer and the ciliary processes. The antigen was confirmed to be sulphatide and its concentration in human eyes was 30 nmol sulphatide/g wet tissue. By electron microscopy, anti-sulphatide choroid labelling was demonstrated in pericytes and in smooth muscle cells surrounding vessels. No Sulph I-negative pericytes were seen. Double labelling with Sulph I and anti-smooth muscle actin revealed that only pericytes in the eye contained sulphatide and not those in heart, lung, liver, adrenal, spleen, lymph node, thymus, or pancreatic tissue. Thus, sharing of the autoantigen sulphatide has been demonstrated between islets of Langerhans and pericytes in the choroid layer of the eye.

Aged↗
PubMed1996

Development and clinical application of immunoassays for European adder (Vipera berus berus) venom and antivenom.

An ovine affinity purified Fab antivenom was used in a clinical trial in Sweden to treat European adder (Vipera berus berus) envenoming. Immunoassays were developed to measure V. b. berus venom and antivenom concentrations in clinical samples to help assess the efficacy of treatment. A radioimmunoassay (RIA) was developed, optimized and validated to measure plasma levels of V. b. berus venom and compared with a conventional ELISA. Both showed a similar variation of zero binding in biological samples and the results obtained correlated closely. However, the ELISA was quicker and more sensitive (0.8 compared with 2 micrograms/litre). Before administration of antivenom, V. b. berus venom concentrations in plasma ranged from 10 to 53 micrograms/litre; 12 hr after the Fab infusion, no patient had measurable levels. However, two patients had low venom levels 24 hr after treatment. ELISA and RIA were also developed, optimized and used to measure concentrations of free Fab in plasma. There was a biexponential fall of Fab concentration with a fast distribution phase (t 1/2 = 0.9 hr) and a slower elimination phase (t 1/2 = 18 hr). The amount of Fab excreted in urine was low.

Animals↗
PubMed1996

Effects of beta receptor antagonists on left ventricular function in patients with clinical evidence of heart failure after myocardial infarction. A double-blind comparison of metoprolol and xamoterol. Echocardiographic results from the Metoprolol and Xamoterol Infarction Study (MEXIS).

Two hundred and ten patients with clinical evidence of heart failure, developing after an acute myocardial infarction, were randomized to treatment with the beta 1-receptor antagonist metoprolol 50-100 mg b.i.d. (n = 106) or the beta 1-receptor partial agonist xamoterol 100-200 mg b.i.d. (n = 104). Left ventricular systolic and diastolic function were assessed with echocardiography and transmitral Doppler cardiography before and after 3 and 12 months of double-blind treatment. E-point septal separation and percent left ventricular fractional shortening were used as indices of systolic function. The ratio between peak early and late mitral diastolic flow (E/A ratio) and isovolumic relaxation time were used as indices of diastolic function. In the xamoterol group, there was a deterioration in E-point septal separation (P < 0.05). A difference between the treatment groups was present both at 3 months (E-point septal separation 11.4 vs 13.0 mm, P < 0.01, fractional shortening 27.1 vs 25.2%, P < 0.05) and 12 months (E-point septal separation 11.1 vs 13.2 mm. P < 0.005, fractional shortening 26.9 vs 25.0%, P < 0.05). E/A ratio increased in the metoprolol group (P < 0.05) but not in the xamoterol group. At 3 months there was a significant difference (0.85 vs 0.67, P < 0.005) between the groups but not at 12 months. In comparison with the beta 1-receptor antagonist metoprolol, the beta 1-receptor partial agonist xamoterol impaired left ventricular systolic function in patients with clinical evidence of heart failure after an acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1996

Effects of BDNF and NT-4/5 on striatonigral neuropeptides or nigral GABA neurons in vivo.

Supranigral infusions of the TrkB-receptor-preferring neurotrophins BDNF or NT-4/5 augment locomotor behaviours, pars compacta firing rates and striatal dopamine metabolism. However these actions of BDNF or NT-4/5 may involve other neurotransmitter systems in addition to dopamine neurons in the substantia nigra. We thus investigated the effects of 2-week supranigral infusions of BDNF or NT-4/5 on rat peptidergic striatonigral neurons and nigral GABAergic neurons. Radioimmunoassay revealed that BDNF and NT-4/5 elevated substantia nigra levels of substance P (by 46 and 57% respectively) and substance K (by 64 and 81%). In addition, BDNF elevated substance K by 59% in a nigral projection area, the superior colliculus. NT-4/5 elevated dynorphin A in the substantia nigra (by 52%) and met-enkephalin in substantia nigra and globus pallidus (by 89%). None of these neuropeptides were altered in the striatum. Consistent with these findings, supranigral infusions of BDNF elevated the mRNA for preprotachykinin A in striatal neurons. In the same animals, glutamic acid decarboxylase (GAD)67 mRNA was increased by 48% in the substantia nigra. The cross-sectional area of GAD67-positive neuronal somata in the BDNF-infused nigra was increased by 59%, and 70% of nigral GABAergic neurons had a cross-sectional area > 550 microns2, whereas 95% of the neurons in vehicle-infused animals had cross-sectional areas < 550 microns2. Thus, supranigral infusions of BDNF or NT-4/5 increase tachykinin mRNA and protein levels within striatonigral neurons and increase the size and GAD67 mRNA expression levels of nigral GABAergic neurons. These results suggest that BDNF or NT-4/5 may modify the output of the basal ganglia not only through effects on dopamine neurons but also by increasing neurotransmission in striatonigral peptidergic and nigral GABAergic pathways.

Amphetamine↗
PubMed1996

Invasin of Yersinia pseudotuberculosis activates human peripheral B cells.

The Yersinia pseudotuberculosis cell surface-located protein invasin was found to promote binding between the pathogen and resting peripheral B cells via beta 1 integrin receptors (CD29). B cells responded by expressing several activation markers and by growing, In contrast, T cells did not react, although these cells express CD29. An isogenic invA mutant failed to activate B cells. The mutation could be complemented by providing the invA+ gene in trans. Purified invasin alone did not activate B cells, although it was able to block the binding of bacteria to the cells.

Adhesins, Bacterial↗
PubMed1996

Doxorubicin-melphalan with and without cisplatin in advanced ovarian cancer--ten-year survival results from a prospective randomized study by the Swedish Cooperative Ovarian Cancer Study Group.

In a controlled prospective randomized study the regimen doxorubicin (A) 40 mg/m2 + melphalan (M) 0.4 mg/kg was compared with A + M + cisplatin (C) 50 mg/m2 given every four weeks in advanced ovarian cancer, FIGO stage III or IV and with serous or anaplastic histology. From 1981 to 1983, 300 patients entered the study and 295 patients were evaluable for response, toxicity and long-term survival. All patients were followed for at least 10 years. The majority of patients had large residual tumours >2 cm. Patients treated with MAC had a higher response rate compared with patients treated with MA (76% vs. 50%, p < 0.01) and treatment with MAC resulted in significantly more pathological complete responders than MA. There was a significant difference in median duration of response (19 months vs. 13 months, p < 0.006) and in median survival time (26 months vs. 19 months, p = 0.05). After 5- and 10 years a significant difference in progression-free and overall survival was found. The independent prognostic factors in this study were residual tumour after primary surgery, treatment with MAC, tumour grade, ascites, and stage. Objective and subjective side effects were significantly worse with MAC, although tolerable. In conclusion, this study shows that incorporating C into MA improves the duration of progression-free survival and overall survival in women with incompletely resected Stage III or Stage IV ovarian epithelial cancer. A 5- and 10-year survival of 25% and 18%, respectively, is impressive.

Adolescent↗
PubMed1995

Alcohol dehydrogenase of class I: kiwi liver enzyme, parallel evolution in separate vertebrate lines, and correlation with 12S rRNA patterns.

Alcohol dehydrogenase class I from kiwi liver has been purified, analyzed, and compared with that of other alcohol dehydrogenases. The results show that several avian and mammalian forms of the enzyme exhibit parallel evolutionary patterns in two independent lineages of a single protein, establishing a pattern in common. Furthermore, the data correlate the enzyme evolutionary pattern with that of 12S rRNA. Biologically, the patterns complement those on ratite and other avian relationships. Functionally, the enzyme has a low Km with ethanol and a branched-chain residue at position 141, like the mammalian enzymes but in contrast to the other characterized ratite enzyme (with Ala-141 and a higher Km). This pattern of natural variability suggests a frequent but not fully complete correlation between a large residue size at position 141 and tight ethanol binding.

Alcohol Dehydrogenase↗
PubMed1995

Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons.

The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity. The amounts of NT-4 messenger RNA present decreased after blockade of neuromuscular transmission with alpha-bungarotoxin and increased during postnatal development and after electrical stimulation in a dose-dependent manner. NT-4 immunoreactivity was detected in slow, type I muscle fibers. Intramuscular administration of NT-4 induced sprouting of intact adult motor nerves. Thus, muscle-derived NT-4 acted as an activity-dependent neurotrophic signal for growth and remodeling of adult motor neuron innervation. NT-4 may thus be partly responsible for the effects of exercise and electrical stimulation on neuromuscular performance.

Animals↗
PubMed1995

Regulatory region in choline acetyltransferase gene directs developmental and tissue-specific expression in transgenic mice.

Acetylcholine, one of the main neurotransmitters in the nervous system, is synthesized by the enzyme choline acetyltransferase (ChAT; acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6). The molecular mechanisms controlling the establishment, maintenance, and plasticity of the cholinergic phenotype in vivo are largely unknown. A previous report showed that a 3800-bp, but not a 1450-bp, 5' flanking segment from the rat ChAT gene promoter directed cell type-specific expression of a reporter gene in cholinergic cells in vitro. Now we have characterized a distal regulatory region of the ChAT gene that confers cholinergic specificity on a heterologous downstream promoter in a cholinergic cell line and in transgenic mice. A 2342-bp segment from the 5' flanking region of the ChAT gene behaved as an enhancer in cholinergic cells but as a repressor in noncholinergic cells in an orientation-independent manner. Combined with a heterologous basal promoter, this fragment targeted transgene expression to several cholinergic regions of the central nervous system of transgenic mice, including basal forebrain, cortex, pons, and spinal cord. In eight independent transgenic lines, the pattern of transgene expression paralleled qualitatively and quantitatively that displayed by endogenous ChAT mRNA in various regions of the rat central nervous system. In the lumbar enlargement of the spinal cord, 85-90% of the transgene expression was targeted to the ventral part of the cord, where cholinergic alpha-motor neurons are located. Transgene expression in the spinal cord was developmentally regulated and responded to nerve injury in a similar way as the endogenous ChAT gene, indicating that the 2342-bp regulatory sequence contains elements controlling the plasticity of the cholinergic phenotype in developing and injured neurons.

Aging↗
PubMed1995

Synergistic trophic actions on rat basal forebrain neurons revealed by a synthetic NGF/BDNF chimaeric molecule.

Basal forebrain cholinergic neurons, which degenerate in Alzheimer's disease, respond to multiple trophic factors, including the neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This dual responsiveness prompted us to investigate the effects of a synthetic chimaeric molecule, containing the active domains of both NGF and BDNF. The NGF/BDNF chimaeric factor exhibited synergistic actions, and was 100-fold more potent than wild-type BDNF in enhancing survival of cultured dissociated basal forebrain cholinergic neurons. This effect was apparently due to true BDNF/NGF synergy, since addition of the two wild-type trophins simultaneously reproduced the effect of the chimaera. Synergy was selective for neurons which respond to both factors; substantia nigra dopaminergic neurons, which respond to BDNF but not NGF, exhibited no potentiation. The chimaeric factor thus revealed a synergy that may normally occur in the brain, and constitutes a potentially novel therapeutic agent with greater potency than naturally occurring individual trophins.

Animals↗