Structural studies on membrane-bound and soluble growth-hormone-binding proteins of rabbit liver.

Covalent cross-linking techniques have been used to investigate the structural characteristics of the growth-hormone (GH) receptor in a variety of rabbit liver cell membrane preparations (particulate and soluble). Two classes of GH-binding protein have been identified which differ in their Mr by gel filtration and susceptibility to precipitation with poly(ethylene glycol) (PEG). The first, a PEG-precipitable (Mr approximately 300,000) protein, contained Mr-65,000 and Mr-40,000 binding proteins linked by disulphide bonds. It was present in aqueous extracts derived from microsomal membranes but was not present in cytosol preparations. The second, a PEG-non-precipitable protein (Mr approximately 100,000) was composed of a non-disulphide-linked primary GH-binding subunit of Mr 60,000-66,000. This binding protein was present in all rabbit liver cell fractions and/or preparations. Both binding-protein classes contained intramolecular disulphide bonds. It is not clear whether the Mr-approximately 100,000 form, or perhaps higher-Mr species which have not been identified by cross-linking studies, represents the native, endogenous, form of the GH receptor present in particulate microsomal or plasma membranes. Accordingly, although these data have identified two classes of GH-binding protein, especially a primary GH-binding subunit of Mr 60,000-66,000, they indicate that, unlike studies on the insulin receptor, covalent cross-linking techniques alone are not sufficient to delineate the complete subunit structure of the native and endogenous form of the GH receptor.     

Different determinants of exercise capacity in HFpEF compared to HFrEF

Background

Quality of life is as important as survival in heart failure (HF) patients. Controversies exist with regards to echocardiographic determinants of exercise capacity in HF, particularly in patients with preserved ejection fraction (HFpEF). The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional exercise capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF.

Methods

In 111 HF patients (mean age 63?±?10 years, 47% female), an echo-Doppler study and a 6-MWT were performed in the same day. Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m).

Results

Group I were older (p?=?0.008), had higher prevalence of diabetes (p?=?0.027), higher baseline heart rate (p?=?0.004), larger left atrium - LA (p?=?0.001), longer LV filling time - FT (p?=?0.019), shorter isovolumic relaxation time (p?=?0.037), shorter pulmonary artery acceleration time - PA acceleration time (p?=?0.006), lower left atrial lateral wall myocardial velocity (a’) (p?=?0.018) and lower septal systolic myocardial velocity (s’) (p?=?0.023), compared with Group II.Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p?=?0.007), higher baseline heart rate (p?=?0.005), higher NT-ProBNP (p?=?0.001), larger LA (p?=?0.004), lower septal s’, e’, a’ waves, and septal mitral annular plane systolic excursion (MAPSE), shorter PA acceleration time (p?<?0.001 for all), lower lateral MAPSE, higher E/A & E/e’, and shorter LVFT (p?=?0.001 for all), lower lateral e’ (p?=?0.009), s’ (p?=?0.006), right ventricular e’ and LA emptying fraction (p?=?0.012 for both), compared with HFpEF patients.In multivariate analysis, only LA diameter [2.676 (1.242–5.766), p?=?0.012], and diabetes [0.274 (0.084–0.898), p?=?0.033] independently predicted poor 6-MWT performance in the group as a whole. In HFrEF, age [1.073 (1.012–1.137), p?=?0.018] and LA diameter [3.685 (1.348–10.071), p?=?0.011], but in HFpEF, lateral s’ [0.295 (0.099–0.882), p?=?0.029], and hemoglobin level [0.497 (0.248–0.998), p?=?0.049] independently predicted poor 6-MWT performance.

Conclusions

In HF patients determinants of exercise capacity differ according to severity of overall LV systolic function, with left atrial enlargement in HFrEF and longitudinal systolic shortening in HFpEF as the the main determinants.