Morphology of chronic lymphocytic leukemia and its relationship to survival

The morphology of lymphocytes in blood and bone marrow from patients with chronic lymphocytic leukemia was studied; blood lymphocyte morphology was related to survival. Three primary morphologic groups emerged. Group I was characterized by small to medium-sized lymphocytes with narrow rims of cytoplasm and coarsely clumped nuclear chromatin. In group II the predominant lymphocytes were large with abundant cytoplasm. Group III was characterized by a heterogeneous population of lymphocytes with characteristics of both groups I and II. Clinical features of the patients were studied, and B and T typing of the lymphocytes was done. The median survival in group I was 26+ months; In group II 46+ months; and in group III 50+ months. Our data are at variance with previous reports and suggest that survival in patients with large lymphocytes Is longer than in those with small lymphocytes.     

Non-invasive assessment of left internal mammary-coronary bypass patency using the external Doppler probe.

Non-directional blood velocity of left internal mammary bypass grafts was non-invasively studied with the Doppler ultrasonic probe. Thirteen of 14 subjects had angiographic evidence of bypass graft patency and their Doppler signals demonstrated high amplitude phasic blood velocities. A single patient with proximal left internal mammary arterial graft occlusion manifested marked attenuation of Doppler blood velocity signals. It is concluded that this technic offers a potential for ambulatory and in-office screening of internal mammary artery bypass graft function.     

In vitro analysis of boundary identification techniques used in quantification of two-dimensional echocardiograms

Echocardiographic cross-sectional areas of 10 formalin-fixed animal left ventricles were determined by 5 independent observers using black-white (B-W) and mid-spot (M-S) endocardial boundary identification techniques. The echocardiographic cross-sectional areas were compared with the true anatomic cross-sectional areas of the same 10 hearts to determine the accuracy, variability and reliability of each technique. The results of these comparisons revealed that the M-S technique was more accurate than the B-W technique (3.3 +/- 7.2 vs 34.9 +/- 8.6% error). However, the B-W technique was more reliable in that it had a smaller interobserver and estimated intraobserver variability. The M-S technique had a 6% greater intraobserver variability.     

Supraventricular tachycardia dependent upon accessory pathways in the absence of ventricular preexcitation

Paroxysmal supraventricular tachycardia is a common disorder of cardiac rhythm, generally thought to be due to reentry within the atrioventrlcular (A-V) node. The possibility that this disorder may be a manifestation of the Wolff-Parkinson-White syndrome should always be considered, but this etiology is usually rejected if the electrocardiogram in sinus rhythm falls to demonstrate a delta wave (i.e., ventricular preexcitatlon). Several recent reports have demonstrated that an accessory A-V pathway may conduct impulses only in the retrograde or ventriculo-atrial direction. Hence, reentrant tachycardia based on a mechanism identical to that observed in patients with classic Wolff-Parkinson-White syndrome may occur, and the electrocardiogram in sinus rhythm fail to show a delta wave. This report describes 11 patients who presented with paroxysmal supraventricular tachycardia without QRS changes in sinus rhythm that suggested the Wolff-Parkinson-White syndrome. Electrophysiologic studies demonstrated that an accessory pathway participated in the mechanism of the tachycardia. Eight of these 11 patients were successfully treated by surgical interruption of either the accessory pathway or the bundle of His. Accessory pathways are not rare among patients with paroxysmal supraventricular tachycardia; and it follows that this variant of the Wolff-ParkinsonWhite syndrome is more common than would be suspected if the Wolff-Parkinson-White syndrome is considered only when delta waves are observed on the electrocardiogram.     

Dissociation between sleep-related and TRH-induced prolactin secretion in seminiferous tubule failure

Prolactin (PRL) secretion has been measured during sleep and following TRH administration in 8 patients aged 24-39 yr with seminiferous tubule failure and 36 controls. Basal LH levels were 25.7 +/- 14.7 mIU/ml in the patients compared to 11.5 +/- 4.2 mIU/ml in the controls (p less than 0.01) Corresponding FSH levels were 26.2 +/- 10.7 mIU/ml and 5.9 +/- 2.1 mIU/ml (p less than 0.001) Mean estradiol 17B and testosterone levels were similar in the 2 groups. The mean PRL secretion during sleep was 16.5 +/- 11.7 ng/ml in the patients and not different in 11 of the controls (12.4 +/- 3.2 ng/ml). One patient had a mean nocturnal PRL concentration of 44.1 ng/ml. In both groups, the mean sleep related PRL concentration was greater than that during waking hours. The average number of peaks in the 2 groups was similar. In the same patients, the peak PRL response to TRH (200 ug IV) was 81.9 +/- 18.8 ng/ml as compared to 32.1 +/- 10.7 ng/ml in the controls (p less than 0.001). It is concluded that PRL concentrations following pharmacological stimulation are increased in seminiferous tubule failure, whereas levels are normal in relation to the physiological stimulus of sleep.     

beta-Adrenergic desensitization by chronic insulin exposure in 3T3-L1 cultured adipocytes

Cultured 3T3-L1 cells provide a model system for studies of the long-term regulation of lipolysis. Insulin acutely inhibits isoproterenol-stimulated lipolysis primarily by decreasing the apparent affinity apparent Km for isoproterenol. In contrast, chronic insulin exposure inhibits lipolysis by a reduction in the maximal effect of isoproterenol Vmax. The decrease in Vmax can be observed with insulin concentrations that are as low as 10(-9) mol/L at the time of addition. The effect is stable to washing, and the cells' responsiveness to isoproterenol returns partially with continued culture. Chronic insulin exposure also markedly reduced dibutyryl-cAMP-stimulated lipolysis indicating an insulin-induced change distal to cAMP concentration in the cascade of reactions controlling lipolysis in these cells. Time course and insulin dose-response experiments indicate an additional proximal alteration. These results indicate that: (1) 3T3-L1 cells are a useful model for studying the long-term regulation of lipolysis. (2) Chronic insulin exposure inhibits lipolysis by a mechanism that differs from the acute effect of insulin. (3) The chronic effects of insulin may be mediated through changes at multiple levels in the lipolytic cascade.     

Mechanisms of insulin resistance in cultured fibroblasts from a patient with leprechaunism: Impaired post-binding actions of insulin and multiplication-stimulating activity

The binding and action of insulin and of the insulin-like growth factor, multiplication-stimulating activity (MSA), were studied in cultured skin fibroblasts from an infant with leprechaunism and associated insulin resistance. Three actions of insulin were reduced in the leprechaun cells: activation of glycogen synthase was 30% as great as in control fibroblasts, the increase in 2-deoxyglucose transport was 33% of the control value, and the uptake of alpha-aminoisobutyric acid was sevenfold less sensitive to enhancement. On a molar basis, MSA was at least as effective as insulin in activating glycogen synthase in control fibroblasts; in the patient's cells there was a reduction in activation that paralleled the changes observed with insulin. To localize the site of insulin resistance, the binding of both [125I]-insulin and [125I]-MSA to fibroblasts was measured and found to be reduced in the leprechaun cells. However, the impairment of the actions of insulin and MSA in the patient's cells was not explained solely by the diminished binding of the two polypeptides. Since the hexose transport system and the terminal enzymes studied thus far are intact, the defect is postulated to involve the post-binding coupling mechanism and mediator formation.     

miR-214-5p通过靶向调控PTEN的表达对破骨分化和骨质疏松的影响

 目的 探讨miR-214-5p通过靶向调控PTEN的表达对破骨分化和骨质疏松的影响。方法 选取2019-03至2020-05在空军军医大学唐都医院外科进行脊柱手术的骨质疏松患者20例(骨质疏松组),同时选取非骨质疏松症患者20例为对照组,抽取两组骨髓血。将miR-214-5pmimics(miR-214-5pmimics组)、miR-214-5p空质粒(miR-214-5pvector组)、shZFAS1载体(sh PTEN组)、shZFAS1空载体(sh vector组)转染到骨质疏松患者细胞,对照组细胞不进行任何转染处理。采用RT-qPCR 检测骨髓单个核细胞中的miR-214-5p和PTEN mRNA及 Raw264.7单核巨噬细胞中NFaTc1、MMP9、TRAP、CTSK的mRNA水平;通过TRAP染色检测TRAP染色的阳性率;通过Western blot 检测PTEN、NFATc1、AKT和PI3K蛋白水平。结果 骨质疏松组miR-214-5p水平的表达明显高于对照组(P＜0.001),骨质疏松组PTEN的表达显著低于对照组(P=0.009);miR-214-5pmimics组中TRAP表达阳性率明显高于对照组和miR-214-5p vector组(P＜0.001);sh PTEN组中TRAP表达阳性率明显高于对照组和sh vector组(P＜0.001);miR-214-5p mimics组中的NFaTc1、MMP9、TRAP和CTSK水平显著高于对照组(P<0.001);sh PTEN组中的NFaTc1、MMP9、TRAP和CTSK水平显著高于对照组(P<0.001);与miR-214-5p mimics组相比,miR-214-5pmimics+PTEN组中TRAP表达阳性率显著降低(P＜0.001)。结论 骨质疏松症患者的骨髓单个核细胞中miR-214-5p表达上调,miR-214-5p可以调控PTEN表达,过表达miR-214-5p可能通过靶向PTEN促进破骨细胞分化。     

Macromolecular dispersion of human plasma low-density lipoproteins in hyperlipoproteinemia.

Low-density lipoprotein (LDL) has previously been reported to exist in either a polydisperse or a monodisperse state. Using the techniques of analytical velocity sedimentation and/or equilibrium density-gradient ultracentrifugation, the macromolecular dispersion of LDL has been investigated in 139 subjects classified by their lipoprotein phenotypes as follows: 63 normal, 25 type IIA, 6 type IIB, and 45 type IV. LDL polydispersion was found in 78% of subjects with hypertriglyceridemia (type IIB or IV phenotypes), while only 9% of normotriglyceridemic subjects had polydisperse LDL. A study of LDL dispersion in two families, one with hyperpreβ-lipoproteinemia and one with combined hyperlipoproteinemia, also demonstrated the frequent association of LDL polydispersity with increased plasma very low density lipoprotein (VLDL) concentrations. LDL polydispersion results from the presence of higher molecular weight, lipid-enriched lipoproteins of the LDL class. Among hyperlipoproteinemic subjects with a type IV phenotype and with polydisperse LDL, the concentrations of these higher molecular weight subspecies of LDL appear to increase with severity of the hyperlipemia. In 6 subjects, reduction of VLDL concentration resulted in a decrease in the concentration of the higher molecular weight LDL; however, LDL remained polydisperse. By contrast, approximately one-third of subjects with hypertriglyceridemia were observed to have monodisperse LDL, even in the presence of high VLDL concentrations. This observation raises the possibility of two separate populations of subjects with hypertriglyceridemia arising from increased VLDL concentration.