Compensated Semimetal LaSb with Unsaturated Magnetoresistance.

By combining angle-resolved photoemission spectroscopy and quantum oscillation measurements, we performed a comprehensive investigation on the electronic structure of LaSb, which exhibits near-quadratic extremely large magnetoresistance (XMR) without any sign of saturation at magnetic fields as high as 40 T. We clearly resolve one spherical and one intersecting-ellipsoidal hole Fermi surfaces (FSs) at the Brillouin zone (BZ) center Γ and one ellipsoidal electron FS at the BZ boundary X. The hole and electron carriers calculated from the enclosed FS volumes are perfectly compensated, and the carrier compensation is unaffected by temperature. We further reveal that LaSb is topologically trivial but shares many similarities with the Weyl semimetal TaAs family in the bulk electronic structure. Based on these results, we have examined the mechanisms that have been proposed so far to explain the near-quadratic XMR in semimetals.

Roles of peripheral B1 cells in the individualized treatment of adult idiopathic thrombocytopenic purpura.

We aimed to explore the changes of peripheral B1 cells before and after treatment of adult idiopathic thrombocytopenic purpura (ITP) and to investigate the association of these changes with the disease condition and prognosis. Ninety-seven ITP patients were divided into the effective or ineffective groups, based on their response to hormone therapy. Forty healthy volunteers were enrolled into the control group (HC). The percentages of CD19+ cells, B1 cells, and platelet-associated immunoglobulin (PAIg) in peripheral blood from healthy volunteers and ITP patients before and after treatment were evaluated, and blood platelet (PLT) counts were determined. The percentages of CD19+ cells [(21 ± 10.0) vs (11.2 ± 7.1)%], B1 cells [(8.85 ± 5.23) vs (2.2 ± 1.3)%], and PAIg [(28 ± 19) vs (11.7 ± 8)%] in whole blood from ITP patients before treatment were significantly higher than those in whole blood from healthy controls (P < 0.05). Before treatment, the percentage of B1 cells and PAIg in ITP patients was negatively correlated with the PLT level (r = -0.89, P < 0.05 and r = -0.814, P < 0.05, respectively). Further, the B1 cell percentage was positively associated with the PAIg percentage in ITP patients before treatment. In the effective group, the B1 cell percentage was reduced sharply at 1 month after treatment [(2.45 ± 1.75) vs (8.74 ± 5.04)%, P < 0.05)], so as at 3 and 6 months. However, in the ineffective group, there was no difference in the B1 cell percentage before and after treatment [(7.9 ± 5.6) vs (8.76 ± 5.26)%]. This obvious association of changes in peripheral B1 cells with disease condition and prognosis in ITP patients may be of certain clinical significance for guiding the individualized treatment of ITP.

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients.

Albuminuria is an independent predictor of renal and cardiovascular complications in hypertensive subjects. We previously showed that lectin-like oxidized low density lipoprotein receptor 1 (OLR-1) polymorphisms at G501C are associated with susceptibility to essential hypertension and serum C-reactive protein levels. We have now investigated a possible association between OLR-1 polymorphisms at G501C, genotyped by PCR-RFLP, and severity of albuminuria in 307 hypertensive Chinese subjects and 225 age- and sex-matched controls. Urine albumin concentration /urine creatinine concentrations (ACR) were measured to evaluate the severity of albuminuria. Hypertensive subjects had a significantly higher frequency of the CC genotype and the C allele of the OLR-1 polymorphism than controls; this was also true for . hypertensive subjects with macroalbuinuria and microalbuminuria compared to those with normoalbuminuria. The mean ACR levels and mean serum C-reactive protein levels in CC carriers were significantly higher than in GG and GC carriers. There was a significant, positive correlation between serum hs-C-reactive protein levels and ACR levels. We conclude that OLR-1 polymorphisms at G501C affect the severity of albuminuria in essential hypertension patients.

Influence of membrane fluidity modifiers on lysosomal osmotic sensitivity.

Since lysosomes are prone to osmotic lysis, we have examined the correlation between their physical state and sensitivity to osmotic challenge, using agents which modify membrane fluidity. The latency loss of beta-hexosaminidase after an incubation in hypotonic sucrose medium was followed under different conditions of membrane fluidity, recorded by steady-state fluorescence anisotropy of 1,6-diphenyl-1,3, 5-hexatriene. Increasing fluidity of the lysosomal membranes with benzyl alcohol (BA) and greater rigidity caused by cholesteryl hemisuccinate (CHS) increased and decreased the enzyme latency loss, respectively. The effects of BA and CHS treatments on osmotic sensitivity were reversible subsequently by reciprocal treatments of the lysosomes with CHS and BA, respectively. The results indicate that the physical state of the membrane does indeed affect lysosomal osmotic stability.

Influence of membrane physical state on the lysosomal proton permeability.

Influence of membrane physical state on the proton permeability of isolated lysosomes was assessed by measuring the membrane potential with 3,3'-dipropylthiadicarbocyanine iodide and monitoring their proton leakage with p-nitrophenol. Changes in the membrane order were examined by the steady-state fluorescence anisotropy of 1, 6-diphenyl-1,3,5-hexatriene. Both the membrane potential and proton leakage increased with fluidizing the lysosomal membranes by benzyl alcohol and decreased with rigidifying the membranes by cholesteryl hemisuccinate. The proton permeability increased to the maximum of 42% by the benzyl alcohol treatment and decreased to the minimum of 38.1% by the cholesteryl hemisuccinate treatment. Treating the lysosomes with protonophore CCCP increased the proton permeability by 58%. The effects of the membrane fluidization and rigidification can be reversed by rigidifying the fluidized membranes and fluidizing the rigidified membranes, respectively. The results indicate that the proton permeability of lysosomes increased and decreased with increasing and decreasing their membrane fluidity, respectively. Moreover, the lysosomal proton permeability did not alter further if the changes, either an increase or a decrease, in the fluidity exceeded some amount. The results suggest that the proton permeability of lysosomes can be modulated finitely by the alterations in their membrane physical state.

Plasma leptin is directly related to body adiposity in subjects with spinal cord injury.

We addressed the relationship between plasma leptin and body mass index in 48 able-bodied male controls and 34 male subjects with spinal cord injury, as well as the association between plasma leptin with body fat by dual energy x-ray absorptiometry in those with spinal cord injury. In subjects with spinal cord injury, the effect of an oral glucose tolerance test and the relationship of the serum lipid profile with plasma leptin levels were determined. Body mass index was not significantly different between the spinal cord injury and control groups. Plasma leptin was significantly higher in the group with spinal cord injury than in the control group (12.7 +/- 1.7 vs. 7.6 +/- 0.9 ng/ml, p < 0.005). A linear relationship was found between plasma leptin and body mass index in both groups separately (spinal cord injury: r = 0.59, p < 0.0002; control: r = 0.67, p < 0.0001). In those with SCI, a polynomial relationship was evident between plasma leptin and percent fat (r = 0.82, p < 0.0001). After an oral glucose load, plasma insulin levels and serum glucose concentrations were not related to plasma leptin levels. Serum triglycerides were found to be weakly correlated with plasma leptin levels (r = 0.35, p < 0.05). The higher plasma leptin levels in the group with spinal cord injury compared with the control group was probably due to a relatively increased percentage of adiposity in those with spinal cord injury.

Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.

Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose.

Vitamin D deficiency in veterans with chronic spinal cord injury.

Chronic spinal cord injury (SCI) is associated with osteopenia, increasing the prevalence of long-bone fractures. Although disuse may be the primary cause of osteopenia, identification of any additional mechanisms of bone loss may lead to potential therapeutic interventions. We investigated the relationships of serum calcium (Ca), phosphorus (PO4), albumin, alkaline phosphatase (Alk P), and parathyroid hormone (PTH) with serum 25-hydroxyvitamin D [25(OH)D] in 100 subjects with chronic SCI and 50 control subjects. in a subgroup of 50 subjects with SCI and 50 control subjects, we correlated these parameters with serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Mean ages for the group with SCI and the controls were the same. In subjects with SCI, the duration of injury was 20 +/- 1 years (mean +/- SD). Thirty-two of 100 subjects with SCI, as compared with eight of 50 controls, had serum 25(OH)D levels less than the normal range (chi2 = 4.36, P < .05). In subjects with SCI, a negative correlation was demonstrated between serum 25(OH)D and PTH (r = .29, P < .005). Mean serum 1.25(OH)2D levels were significantly elevated in subjects with SCI as compared with controls (61 +/- 21 v 46 +/- 18 pg/mL, P < .0005). Twenty of 50 subjects with SCI had serum 1.25(OH)2D levels greater than 62 pg/mL, as compared with 10 of 50 controls (chi2 = 4.76 P < .05). A positive correlation was found between serum PTH and 1,25(OH)2D in subjects with SCI and controls (r = .41, P < .005 and r = .30, P < .05, respectively). Twelve subjects with SCI had serum PTH levels greater than the normal range. In this high-serum PTH subgroup, serum 15(OH)D concentration was significantly lower (P < .05) and serum 1,25(OH)2D and Alk P concentrations were significantly higher (P < .005 and P < .05, respectively) as compared with the subgroup with serum PTH values within the normal range. In subjects with SCI, 17 had a serum Ca concentration less than 8.5 mg/dL. In persons with SCI, depressed levels of serum 25(OH)D, as well as other factors, may result in forces inclined to reduce the serum calcium concentration. A state of mild secondary hyperparathyroidism may result, thus increasing the conversion of serum 25(OH)D to 1.25(OH)2D. These data suggest that in chronic SCI subjects, as in the general population, secretion of PTH and the increase of circulating 1.25(OH)2D are subject to control by negative-feedback mechanisms. Higher levels of serum PTH would be expected to accelerate bone resorption of a skeleton already regionally osteoporotic as a consequence of the bone mineral loss due to acute immobilization.

The relationships among serum uric acid, plasma insulin, and serum lipoprotein levels in subjects with spinal cord injury.

Relationships were investigated among serum uric acid (UA), the insulin response to a standard oral glucose load (75 g), and serum lipoprotein levels in 197 individuals with chronic spinal cord injury (SCI). All subjects had normal liver and renal function. None had a prior history of diabetes mellitus or gout. The mean age of subjects was 50 +/- 1 years, duration of injury (DOI), 18 +/- 1 years, and body mass index (BMI), 25 +/- 0.4 kg/m2. No significant differences were found between those with paraplegia or quadriplegia for any of the parameters measured. The mean serum UA values were not significantly different among the subgroups of subjects with normal glucose tolerance, impaired glucose tolerance, or diabetes mellitus (5.6 +/- 0.2 mg/dl, 5.6 +/- 0.2 and 5.7 +/- 0.3, respectively). Approximately one-half of the subjects had an abnormality in oral glucose tolerance. The levels of serum UA (p < 0.001) and serum triglycerides (TG) (p < 0.01) in the subgroup with hyperinsulinemia were significantly higher than in the subgroup with normal insulin levels. By linear regression analyses, the serum UA concentration was positively correlated with peak plasma insulin level (r = 0.31, p < 0.001), and BMI (r = 0.20, p < 0.01), but not with age, DOI, or peak glucose. The data suggest that in subjects with chronic SCI, as in the healthy able-bodied population, hyperuricemia is associated with hyperinsulinemia, obesity and abnormal lipoprotein metabolism.

Serum testosterone and growth hormone/insulin-like growth factor-I in adults with spinal cord injury.

Aging is associated with relative growth hormone and/or testosterone (T) hormone deficiency, and those with SCI may have a premature deficiency of these two hormones. The effects of SCI, duration of injury (DOI), and advancing age with that of human growth hormone (hGH) and insulin-like growth factor I (IGF-I), as well as potential associations between them, were studied. Data were obtained from 20 male subjects with SCI and 16 gender- and age-matched controls. Serum total and free T were lower in subjects with SCI compared with controls (mean +/- SEM, 3.12 +/- 0.29 versus 4.68 +/- 0.28 ng/ml, p < 0.001 and 1.89 +/- 0.18 versus 2.46 +/- 0.22 ng/ml, p < 0.05, respectively). Nine of the 20 subjects with SCI, but none of the controls, had abnormally low serum total T. Arginine-stimulated values for hGH were lower in the group with SCI compared with controls (198 +/- 18 versus 267 +/- 27 ng/ml, p < 0.05). Serum luteinizing hormone and follicular stimulating hormone, as well as body mass index, were not significantly different between the groups. Serum total and free T were correlated with advancing age in controls (r = 0.62, p < 0.01 and r = 0.51, < 0.05, respectively) but not in SCI (r = 0.19, p > 0.43 and r = 0.39, p = 0.09). However, serum total and free T declined with increasing DOI in SCI (r = 0.56, p < 0.01 and r = 0.44, p = 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic baclofen therapy improves the blunted growth hormone response to intravenous arginine in subjects with spinal cord injury.

Human GH (hGH) secretion is stimulated by vigorous physical activity, whereas immobilization reduces its release. In paralyzed subjects with spinal cord injury (SCI), it has recently been shown that the release of hGH to provocative stimulation and plasma insulin-like growth factor-I (IGF-I) levels are reduced. The acute administration of baclofen, a gamma-aminobutyric acid derivative, has been shown to stimulate hGH release. The present study investigated the effect of chronic administration of baclofen on the provocative testing of hGH secretion and plasma IGF-I levels. Sixteen subjects with SCI were studied; eight subjects were treated (40-80 mg/day; > 6 months) with baclofen (Bac+), and eight were not (Bac-). Additionally, 8 non-SCI subjects were studied as controls. The groups were matched for gender and age. The subjects were not receiving any medications known to influence hGH secretion. After an overnight fast, arginine hydrochloride (30 g/subject) was infused iv over 30 min, with blood drawn for hormone determinations at baseline and 30, 60, 90, and 120 min. In the Bac- group compared with the Bac+ group, the arginine-stimulated mean plasma hGH levels at 30 and 60 min (P < 0.05) and peak and sum plasma hGH levels (P < 0.01) were reduced. There were no significant differences in the plasma hGH response between the Bac+ group and the control group. Plasma IGF-I levels may reflect the integrated tissue response to hGH. A significant inverse relationship was present between age and plasma IGF-I levels for the control and Bac+ groups, but not for the Bac- group. The mean plasma IGF-I level was significantly reduced in the Bac- compared with the Bac+ group. No significant differences in mean plasma IGF-I levels were noted between the Bac+ and control groups. SCI is associated with body composition changes and metabolic alterations that may be exacerbated by reduced activity of the hGH-IGF-I axis. Oral chronic baclofen therapy appears to reverse the deleterious effects of paralysis and immobilization on hGH physiology.

Blunted growth hormone response to intravenous arginine in subjects with a spinal cord injury.

The influence of the activities of daily living on human growth hormone (hGH) release and plasma insulin-like growth factor (IGF-I) levels is not known. Individuals with spinal cord injury (SCI) and paralysis generally have reduced levels of activity compared with ambulatory subjects. We studied sixteen subjects with SCI and sixteen nonSCI subjects matched for age, gender and body mass index (BMI) as controls. After an intravenous infusion of arginine hydrochloride (30 g/subject over 30 minutes), mean plasma hGH values at 30 and 60 minutes were significantly lower in the group with SCI compared with the control group (3.4 +/- 0.7 versus 10.7 +/- 2.5 ng/ml, p < 0.01; and 5.2 +/- 1.5 versus 12.5 +/- 2.7 ng/ml, p < 0.05). Also, peak and sum hGH responses were significantly lower in the group with SCI than in the control group (5.8 +/- 1.5 versus 14.1 +/- 2.8 ng/ml, p < 0.01; and 15.2 +/- 3.1 versus 34.8 +/- 7.2 ng/ml, p < 0.02). Controlling for age and BMI, the results remained significant. However, the mean plasma IGF-I level was significantly lower in SCI subjects younger than 45 years old than in the similar subgroup of age-restricted controls (202 +/- 19 versus 324 +/- 27 ng/ml, p < 0.05), whereas, a comparison of subgroups of subjects 45 years or older did not reveal a significant difference. These findings support the hypothesis that decreased daily physical activity results in depression of the hGH/IGF-I axis in younger individuals with SCI and may be considered to be a state of premature aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressed serum high density lipoprotein cholesterol levels in veterans with spinal cord injury.

Cardiovascular diseases are the most frequent cause of death among persons with spinal cord injury (SCI), and these diseases are reported to occur prematurely in the disabled compared to the able bodied population. The mechanism of accelerated coronary heart disease (CHD) in persons with SCI may be partially explicable on the basis of the lipoprotein profile. We performed fasting lipoprotein determinations on 100 veterans with SCI, 50 with paraplegia and 50 with quadriplegia, and 50 veteran controls. The mean age of the subjects with SCI was 47.8 +/- 1.4 years with a duration of injury of 16.3 +/- 1.2 years. The mean serum high-density lipoprotein (HDL) cholesterol was depressed in subjects with paraplegia or quadriplegia compared to controls (37 +/- 1 or 40 +/- 1 versus 48 +/- 2 mg/dL, p < 0.0001). Although serum total cholesterol was lower (p < 0.01) in subjects with SCI than in controls, there was no significant difference in mean serum low-density lipoprotein (LDL) cholesterol. Thirty-seven percent of subjects with SCI have serum HDL cholesterol levels less than 35 mg/dL with no significant difference in lipoprotein distribution between high and low cord lesions. Eighteen percent of individuals with SCI have an absolute elevation of LDL cholesterol (greater than 160 mg/dL). About 40% of those with SCI and LDL cholesterol levels between 130 and 160 mg/dL also have serum HDL cholesterol values below 35 mg/dL, all of whom would have their serum HDL cholesterol level undetected if lipoprotein profiles were performed according to present recommendations--that is, only if the serum total cholesterol is elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery disease: metabolic risk factors and latent disease in individuals with paraplegia.

Individuals with spinal cord injury (SCI) currently have a longer life span as a result of recent improvements in medical care. As in the able-bodied population, cardiovascular disease is the leading cause of death in persons with SCI, but it appears to occur at younger ages in those with SCI than in the able-bodied population. The reduction in level of activity and adverse changes in body composition caused by SCI have profound metabolic consequences that may influence the progression and severity of coronary artery disease. Metabolic sequelae of SCI include disorders of carbohydrate and lipid metabolism. Almost half of the 45 active, healthy subjects with paraplegia we studied have a disorder of carbohydrate tolerance, 1 in 5 subjects having a diabetic oral glucose tolerance test. Hyperinsulinemia is found in those with abnormal glucose tolerance. Subjects with paraplegia having impaired glucose tolerance or diabetes mellitus are significantly older than those with normal glucose tolerance. High-density lipoprotein cholesterol is markedly depressed, and low density lipoprotein is relatively elevated. Radionuclide myocardial perfusion imaging after upper body ergometry exercise reveals latent coronary artery disease in 12 of 19 subjects with paraplegia.

[The distribution of 3H-alpha-sec-butyl-p hydroxybenzyl alcohol in mice].

alpha-sec-butyl-p-hydroxybenzyl alcohol is a derivative of gastrodigenin. It dissolves in lipid and passes through the blood-brain barrier more easily than gastrodin does. The distribution experiment has demonstrated that 3H-alpha-sec-butyl-p-hydroxybenzyl alcohol in the brain of mice is higher than in other organs, such as the liver, kidney and intestines. Radioactivity of brain tissue rises to the highest peak in about 1/2-2 min after intravenous injection. Each gram of the brain tissue takes up 21.89% radioactivity of the total dose administered. The sedative effect of alpha-sec-butyl-p-hydroxybenzyl alcohol on the center is rapid and short. It has been proved by the reactions in mice, results indicated by the electrocorticogram obtained from the mice after giving alpha-sec-butyl-p-hydroxybenzyl alcohol, and the correspondence with the distribution of alpha-sec-butyl-p-hydroxybenzyl alcohol in the mouse brain.