Age-dependent changes of protein structure II. Conformational differences of aldolase of young and old rabbits

Conformational differences between aldolase from old and young rabbit muscle are revealed and described by means of UV difference spectroscopy, thermal perturbation difference spectra, and UV fluorescence. These two objects differ in thermal stability of protein conformation, but similar conformational transitions are observed on substrate binding.     

The effect of hormones on the haemodynamics in animals of different age groups

The investigation was undertaken to study to effect of varying doses of epinephrine, vasopressin, insulin, thyroxin, estradiol-dipropionate on the haemodynamics and contractility of the myocardium of rats in different age groups, as well as the effect of epinephrine and vasopressin on coronary blood circulation in dogs of various age groups. The age group peculiarities of reactions to the hormones were compared with changes in their content in the blood of animals of different age groups.Upon administering small concentrations of the hormones in this study, more pronounced changes in haemodynamics and contractility of the myocardium were observed in senile animals. The administration of larger doses led to more pronounced changes in mature animals. During the process of aging, there is a decrease in the range of the reactions of the cardiovascular system to the action of hormones.In case of long term (14 days) administration of thyroxin, it was found that in senile animals the contractility of the heart was lower than that in short term (4 days) administration. In long term administration of thyroxin, it was found that in mature animals the index for the myocardium's contracting ability was more pronounced than in short term administration.Irregular changes in the concentrations of different hormones in the blood, changes in sensitivity and ability of the myocardium to respond to their action lead to changes in the hormonal regulation of the heart, and to the development of aging metabolic and functional changes.     

抗血小板药物在心脑血管疾病中的临床应用

抗血小板治疗是冠心病、缺血性脑卒中、心房颤动等心脑血管疾病的重要治疗措施之一。近年来,随着抗栓领域基础及临床研究的逐步深入,出现了许多新型的抗血小板药物。本文通过对各种抗血小板药物的临床应用进行综述,以期为血栓栓塞性疾病,尤其是心脑血管疾病提供规范化、个体化的抗血小板治疗。     

Age-dependent changes of protein structure. I. Tissue-specific, electrophoretic and catalytical properties of muscle aldolase of old rabbits

The comparative study of highly purified muscle aldolase from young (6–8 months) and old (52–70 months) rabbits has been performed by the methods of affinity and ion-exchange chromatography, gel electrophoresis under different conditions and enzyme kinetics. The old muscle aldolase is A-type aldolase consisting of equal amounts of α- and β-subunits within a tetramer and does not differ in these properties from the “young” enzyme. The lower specific activity of the “old” enzyme has been observed and the determination of Km and V_max showed the decrease of these parameters with age. The age-dependent change of protein conformation has been suggested.     

Effects of HIV Infection on Pulmonary Artery Pressure in Children

BackgroundPulmonary hypertension may complicate human immunodeficiency virus (HIV) infection and result in right ventricular (RV) failure and premature death. There are limited data of the effects of childhood HIV infection or antiretroviral therapy (ART) on pulmonary artery pressure (PAP).ObjectivesTo establish if there is an association between childhood HIV infection or its treatment and pulmonary artery pressure.MethodsThe study conducted a cross-sectional study of 102 HIV-infected (48 ART-naïve, 54 ART-exposed) and 51 HIV-uninfected children in Jakarta, Indonesia, to estimate PAP using echocardiography parameters: tricuspid regurgitation peak velocity (TRV), left ventricular systolic index and diastolic eccentricity index (EI), and RV systolic function, assessed by tricuspid annulus plane systolic excursion. The association between either ART-naive or ART-exposed HIV and PAP was explored using general linear modelling adjusted for potential confounders.ResultsART-exposed HIV-infected children had higher TRV (adjusted difference: 0.36 m/s; 95% confidence interval [CI]: 0.12 to 0.60; p = 0.003) and diastolic EI (adjusted difference 0.06; 95% CI: 0.01 to 0.11; p = 0.02) than did uninfected children. The EI in ART-exposed children was significantly higher than normal. ART-naive HIV-infected children had a lower tricuspid annulus plane systolic excursion (adjusted difference: –2.2 mm; 95% CI: –3.73 to –0.71; p = 0.004), despite no difference in TRV (adjusted difference: 0.18 m/s; 95% CI: –0.06 to 0.43 m/s; p = 0.14). Seven (13%) ART-exposed and 4 (8.3%) ART-naïve HIV-infected children had pulmonary hypertension. Within-HIV group comparisons showed that accounting for lower respiratory tract infections attenuated the lower RV systolic function in ART-naïve children but not in ART-exposed children (difference: –1.1 mm; 95% CI:–2.8 to 0.7 mm; p = 0.22), but not the higher left ventricular eccentricity indexes in the ART-exposed children (systolic difference: 0.07; 95% CI: 0.02 to 0.12; p = 0.007; diastolic difference: 0.08; 95% CI: 0.02 to 0.14; p = 0.006).ConclusionsART-exposed HIV infection is associated with higher estimated PAP. Reduced RV systolic function is seen in ART-naïve HIV infection. Lower respiratory tract infection partly explains lower systolic RV function in ART-naïve relative to ART-exposed HIV infection.     

Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.     

Biological age and its estimation. II. Assessment of biological age of albino rats by multiple regression analysis

Multiple regression model of biological age (BA) theoretically gives agreement with the main concept of BA. When assessment of BA is based on the model, the age being in regression center, the method provides satisfactory results, whereas BA estimates of individuals in extreme age groups are erroneous. Investigation of male and female Wistar rats of age 5–29 months showed the BA estimates calculated from 4–10 physiological indices in young (5–7 mo) animals are overestimated, and in old (24–28 mo) animals are underestimated. Coincidence of average BA in one-age group of animals with its chronological age served as a criterion for the correspondence of the estimate to “real” BA. The paper also examines the following questions: the necessary and sufficient number of physiological indices; the sample size from the intact animal population to establish normal aging standard; the relationship between BA and animal weight.     

Regression of atherosclerotic stenosing lesions of the renal arteries and spontaneous cure of systemic hypertension through control of hyperlipidemia

We describe a 49 year old woman with impressive regression of renal artery stenosing atherosclerotic lesions in response to sustained excellent control of hyperlipidemia.Initially, she had high blood pressure necessitating combined drug therapy with chlorothiazide, methyldopa and propranolol, with only moderately satisfactory control. Renal arteriography revealed a 90 per cent stenosing lesion of the right renal artery and 75 per cent narrowing of the left renal artery. Peripheral vein plasma renin was markedly increased at 32 ng/ml. With a combination of cholestyramine and clofibrate, serum lipids were maintained at normal values for several years. Increased blood pressure diminished spontaneously, and the patient has maintained normal blood pressures after discontinuation of antihypertensive therapy. Repeat renal arteriograms showed almost complete regression of the right renal artery lesion and a possible decrease in left renal artery disease. Peripheral vein plasma renin became normal at 3 ng/ml.This case illustrates that sustained control of hyperlipidemia could lead to regression of atherosclerotic nodules and impressive clinical improvement in certain patients.     

淡色库蚊和致倦库蚊对广东株班氏丝虫易感性的研究

本文用南京株和合肥株淡色库蚊以及广东株致倦库分别人工感染广东株周期型班氏丝虫，并对其易感性进行比较，用一名微丝蚴密度为２４条／６０μｌ的班氏丝虫微丝蚴血症者血液感染南京株淡色库蚊３３４只，合肥株淡色库蚊１３９只和致倦库蚊２４１只，Ｌ３阳性率分别为１２．５７％、．５．７６％和５．８０％。     

The effects of proteins upon the filtration coefficient of individually perfused frog mesenteric capillaries.

The filtration coefficients (L_p) of the walls of individually perfused frog mesenteric capillaries have been measured using the methods described by Michel et al. (1974). When a vessel was perfused with frog Ringer solution containing no protein, L_p was four to five times greater than its value for the same capillary perfused with frog plasma. The increase of L_p seen on perfusion with protein-free solutions was readily reversible and could be prevented by adding to the Ringer perfusate bovine serum albumin, bovine γ-globulin and human haemoglobin. The addition of whale myoglobin (0.5 g 100 ml^?1) to the Ringer perfusate did not prevent an increase in L_p. Ringer solutions containing 0.1 g of bovine serum albumin 100 ml^?1 were as effective as those containing higher concentrations of albumin in preventing the increase in L_p, but the L_p of capillaries perfused with solutions containing 0.01 g of albumin 100 ml^?1 did not differ from the values for the same capillaries perfused with protein-free solutions. It was shown that in any given capillary, L_p was independent of the direction of fluid flow across the vessel wall and was the same when the capillary was perfused with 9.0 g of bovine albumin 100 ml^?1 and 3 g of bovine γ-globulin 100 ml^?1. Whereas the effects of L_p are seen within 1 min of removing the protein from the perfusate, no changes in L_p were observed during the first 20 min of perfusion and superfusion of capillaries with solutions free of Ca²⁺ and Mg²⁺. L_p also appeared to be unaffected after 20 min perfusion with neuraminidase. It is suggested that plasma proteins are adsorbed onto capillary walls and greatly modify capillary permeability.     

Choriocarcinoma as a cause of thyrotoxicosis

Three patients with choriocarcinoma had clinical and biochemical evidence of hyperthyroidism. Diminution in the thyrotoxicosis closely paralleled the fall in human chorionic gonadotrophin (hCG) levels. Three patients originally presented to internal medicine units as a problem of hemoptysis. Thyroid-stimulating hormone bioassay activity was demonstrated in the serum of all three patients prior to therapy.

Recently evidence has been presented that hCG has intrinsic thyrotropic activity and that in conditions, such as hydatidiform mole, in which serum hCG levels are grossly elevated this thyrotropic activity can be sufficient to produce hyperthyroidism. Two of our cases supported the concept that hCG was also the substance with thyroid-stimulating activity in patients with choriocarcinoma. The third case left open the possibility that, in addition to the thyroid-stimulating activity of hCG, there may also be the production of a true ectopic thyroid-stimulating hormone (TSH).

It is considered that the development of biochemical and clinical thyrotoxicosis in patients with choriocarcinoma depends upon the duration of the choriocarcinoma and the level of hCG.     

The value of ileoscopy with biopsy in the diagnosis of intestinal Crohn's disease

Studies to determine the diagnostic value of ileoscopy and biopsy are not available. In an attempt to clarify the role of this technique in the diagnosis of intestinal Crohn's disease, 110 patients with a radiological diagnosis of inflammatory disease of the terminal ileum were examined in a prospective study. Suspicion of Crohn's disease was rejected in 28 patients. In 18 patients the terminal ileum was normal, while 10 patients had lymphoid nodular hyperplasia. Endoscopic lesions with a predictive value of 0.96 were found in 25 of 48 patients with the final diagnosis of Crohn's disease. Diagnostic granulomas were only found in 4 patients, but lesions consistent with Crohn's disease were present in the pathology sections of 17 patients. It was concluded that ileoscopy with biopsy is a valuable tool in the diagnosis of inflammatory ileal disease and can provide useful information about the nature and extent of the inflammation.     

The Spike of Concern—The Novel Variants of SARS-CoV-2

The high sequence identity of the first SARS-CoV-2 samples collected in December 2019 at Wuhan did not foretell the emergence of novel variants in the United Kingdom, North and South America, India, or South Africa that drive the current waves of the pandemic. The viral spike receptor possesses two surface areas of high mutagenic plasticity: the supersite in its N-terminal domain (NTD) that is recognised by all anti-NTD antibodies and its receptor binding domain (RBD) where 17 residues make contact with the human Ace2 protein (angiotensin I converting enzyme 2) and many neutralising antibodies bind. While NTD mutations appear at first glance very diverse, they converge on the structure of the supersite. The mutations within the RBD, on the other hand, hone in on only a small number of key sites (K417, L452, E484, N501) that are allosteric control points enabling spike to escape neutralising antibodies while maintaining or even gaining Ace2-binding activity. The D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open spike protomers in the homo-trimeric receptor complex. This review discusses the recent spike mutations as well as their evolution.     

Evidence for the early reduction of the 24,25 double bond in the conversion of lanosterol to cholesterol in cerebrotendinous xanthomatosis

The metabolism of lanosterol and 24,25-dihydrolanosterol (DL) was examined in a patient with cerebrotendinous xanthomatosis after intravenous pulse labeling with a mixture of DL-2-¹⁴C and 3S,4S,3R, 4R-(4-³H)mevalonate. Sterols were isolated from the feces and purified by silver nitrate thin-layer chromatography, and their identities were confirmed by gasliquid chromatography and mass spectrometry. Their specific activities were then determined and plotted as a function of time. These isotope ratio measurements and specific activity decay curves were consistent with 24,25-dihydrolanosterol and Δ⁷-cholestenol being intermediates in the synthesis of cholesterol from mevalonate and lanosterol, and they suggested that reduction of the lanosterol side chain may occur as an early step in the synthesis of cholesterol. These results are in contrast to the results reported after the administration of triparanol, a Δ²⁴-reductase inhibitor.