Relationship between myocardial collagen and echo amplitude in non-fibrotic hearts

The aim of the study was to investigate the relationship between myocardial collagen and regional echo amplitude in humans with non-fibrotic myocardium. The ratio of myocardial collagen to total myocardial protein was determined as the hydroxyproline/leucine ratio in endomyocardial biopsies obtained from the right ventricular side of the interventricular septum in orthotopically transplanted hearts. Regional echo amplitude was measured in the interventricular septum. Patients were studied prospectively. Twenty-five patients (five female, 20 male) who had undergone orthotopic cardiac transplantation were studied 355 to 2939 days (1009 +/- 718, mean +/- SD) post-transplantation at the time of annual cardiac catheterization and endomyocardial biopsy. Patient ages varied from 22 to 62 years (46 +/- 11). Donor ages were 14 to 47 years (25 +/- 8) and the ischaemic time, 90 to 245 min (151 +/- 42). Cardiac transplantation was performed for end-stage cardiac failure in all patients. The aetiology of cardiac failure was valvular heart disease in three, dilated cardiomyopathy in eight and ischaemic heart disease in the remainder. Echo amplitude studies were performed within 24 h of endomyocardial biopsy. All but one patient were on an immunosuppressive regime consisting of cyclosporine A and azathioprine with additional steroids in three. The remaining patient, who was the longest surviving patient in the study group, had never been treated with cyclosporine. This patient was maintained on steroids and azathioprine alone. No patient had clinical or histological evidence for acute cardiac rejection and all were clinically well. Five patients had angiographic evidence of coronary artery disease. All subject studies were performed at Harefield Hospital.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple epidural metastases and development of secondary metastatic spinal cord compression]

The purpose was to examine the frequency of initial multiple epidural metastases, and the occurrence of secondary spinal cord compression (SCC). One hundred and seven patients with SCC from a histologically verified solid tumour were followed prospectively with regular neurological examinations until death. Multiple metastases were demonstrated in 37 (35%). Eight (7.5%) patients developed a second occurrence of SCC all in a new location within the spinal canal. The second occurrence of SCC was found with the same frequency in patients with single metastases (7.1%) compared to patients with multiple metastases (8.1%). The median survival time after the diagnosis of spinal cord compression was 3.4 months, while in the group of patients who developed a second occurrence of SCC the median survival time was 9.2 months. We concluded that only symptomatic epidural metastases should be irradiated, and that all patients treated for SCC should be followed regularly and observed for development of a second SCC.     

Epidemiological observations on sarcoids in a population of donkeys (Equus asinus)

An epidemiological study of equine sarcoid in a population of 4126 donkeys showed that the peak incidence of the disease was 15.2 cases per 100 animal-years and occurred in animals in their fourth year of life. The crude incidence of the disease was 0.6 cases per 100 animal-years. The disease occurred most frequently in younger, male animals during their first five years in the population. The lesions were observed most commonly in the paragenital region. Pre-entry quarantine procedures did not appear to play a significant role in the spread of the disease but there was an indication that close in-contact animals were more likely to have sarcoids than animals in the general population. This suggested that a transmissible agent might have been involved in the aetiopathogenesis or that the animals had encountered some event that had predisposed them to the disease.     

L-arginine potentiates GABA-mediated synaptic transmission by a nitric oxide-independent mechanism in rat dopamine neurons

Effects of L-arginine in the nervous system are often attributed to nitric oxide. Using whole-cell patch pipettes to record membrane currents in voltage-clamp from dopamine neurons in the rat midbrain slice, the present studies found that L-arginine potentiates GABA-dependent membrane currents via a nitric oxide-independent mechanism. L-Arginine (0.3-10 mM) increased the peak amplitude, half-width duration and time constant of decay of GABA(B) receptor-mediated inhibitory postsynaptic currents in a concentration-dependent manner. In the presence of CGP 35348 (300 microM), a GABA(B) receptor antagonist, L-arginine also prolonged the duration of inhibitory postsynaptic currents mediated by GABA(A) receptors, but their amplitudes were reduced. L-Arginine (10 mM) also evoked 17+/-3 pA of outward current (at -60 mV) which was significantly increased in the presence of exogenous GABA (100 microM). Pressure-ejection of GABA from micropipettes produced outward currents mediated by GABA(B) receptors (recorded in bicuculline) or GABA(A) receptors (recorded in CGP 35348); both types of receptor-mediated currents were increased by L-arginine (10 mM). In contrast, outward currents evoked by baclofen, a GABA(B) receptor agonist, were not potentiated by L-arginine. The GABA transport inhibitors NO 711 (1 microM) and nipecotic acid (1 mM) significantly increased the half-width duration and time-constant of decay of GABA(B)-mediated inhibitory postsynaptic currents, thus mimicking effects of L-arginine. However, nitric oxide donors failed to mimic effects of L-arginine on GABA(B) inhibitory postsynaptic currents, and inhibitors of nitric oxide synthesis failed to selectively block the action of L-arginine. These findings suggest that L-arginine potentiates GABA synaptic transmission by a nitric oxide-independent mechanism. Similarities between effects of L-arginine, NO 711 and nipecotic acid suggest that L-arginine inhibits a GABA transporter.     

Effect of taurine on angiotensin II-induced hypertrophy of neonatal rat cardiac cells

T Lymphocytes (T cells) recognize short antigenic peptides bound to either MHC I or II molecules, in contrast to antibodies which can bind to native antigen. The mechanism by which antigens are processed into peptides, and the nature of the interactions of antigenic peptides with MHC molecules and with the T cell receptor have now been defined in some detail. Of significance to glycobiologists is the recent appreciation that the carbohydrate of glycoprotein antigens can contribute to the T cell recognition of epitopes presented by MHC molecules. Experiments using model T cell epitopes have demonstrated that carbohydrate can modulate T cell responses in a variety of ways; for example, there are a number of cases where glycopeptide-specific T cell responses have been identified. Many of these glycopeptide-specific T cell responses involve a peptide bearing a single glycosyl residue, thus it appears very likely that both glycan and peptide make contact with the T cell receptor binding site. Significantly, glycopeptide-specific T cell responses have also been detected to native glycoproteins. The ability of carbohydrate to influence T cell recognition of antigen has important consequences for a wide range of immune responses as well as the current strategies for mapping T cell determinants.     

Muscarinic receptor activation modulates Ca2+ channels in rat intracardiac neurons via a PTX- and voltage-sensitive pathway

With use of the whole cell patch-clamp technique, effects of the potent muscarinic agonist oxotremorine methiodide (oxo-M) on voltage-activated Ca2+ channel currents were investigated in acutely dissociated adult rat intracardiac neurons. In all tested neurons oxo-M reversibly inhibited the peak Ba2+ current. Inhibition of the peak Ba2+ current by oxo-M was associated with slowing of activation kinetics and was concentration dependent. The concentration of oxo-M necessary to produce a half-maximal inhibition of current and the maximal inhibition were 40.8 nM and 75.9%, respectively. Inhibitory effect of oxo-M was completely abolished by atropine. Among different muscarinic receptor antagonists, methoctramine (100 and 300 nM) significantly antagonized the current inhibition by oxo-M, with a negative logarithm of dissociation constant of 8.3 in adult rat intracardiac neurons. Internal dialysis of neurons with guanosine 5'-(thio)triphosphate (GTPgammaS, 0.5 mM) could mimic the muscarinic inhibition of the peak Ba2+ current and significantly occlude inhibitory effects of oxo-M. In addition, the internal dialysis of guanosine-5'-O-(2-thiodiphosphate) (GDPbetaS, 2 mM) also significantly reduced the muscarinic inhibition of the peak Ba2+ current by oxo-M. Inhibitory effects of oxo-M were significantly abolished by pertussis toxin (PTX, 200 and 400 ng/ml) but not by cholera toxin (400 ng/ml). Furthermore, the bath application of N-ethylmaleimide (50 microM) significantly reduced the inhibition of the peak Ba2+ current by oxo-M. The oxo-M shifted the activation curve derived from measurments of tail currents toward more positive potentials. A strong conditioning prepulse to +100 mV significantly relieved the muscarinic inhibition of peak Ba2+ currents by oxo-M and the GTPgammaS-induced current inhibition. In a series of experiments, changes in intracellular concentration of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid and protein kinase activities failed to mimic or occlude the current inhibition by oxo-M. The dihydropyridine antagonist nifedipine (10 microM) was not able to occlude any of the inhibitory effects of oxo-M, and oxo-M (3 microM) failed to reduce the slow tail currents induced by the L-type agonist methyl 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate (FPL 64176; 2 microM). However, omega-conotoxin (omega-CgTX) GVIA (1 microM) significantly occluded the muscarinic inhibition of the Ba2+ currents. In the presence of omega-CgTX GVIA (1 microM) and nifedipine (10 microM), oxo-M could further inhibit approximately 20% of the total Ca2+ current. After complete removal of N-, Q-, and L-type currents with use of omega-CgTX GVIA, omega-agatoxin IVA, and nifedipine, 70% of the R-type current (approximately 6-7% of the total current) was inhibited by oxo-M (3 microM). In conclusion, the M2 muscarinic receptor activation selectively inhibits N-, Q-, and R-type Ca2+ channel currents, sparing L-type Ca2+ channel currents mainly via a PTX- and voltage-sensitive pathway in adult rat intracardiac neurons.