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Biomedical subjects

N Sattar

Publications and source records attributed to N Sattar.

At least 73 records · Page 4Linked to original sources
PubMed1998

The atherogenic lipoprotein phenotype and vascular endothelial dysfunction.

There is accumulating evidence that elevated plasma triglycerides and related abnormalities constitute an independent cardiovascular risk factor. Although the pathogenetic basis for the apparent relationship between elevated triglyceride-rich lipoproteins and CAD is still uncertain, evidence is accumulating to suggest that endothelial dysfunction is involved. There is evidence to suggest that triglyceride-rich particles may be directly damaging to the endothelium; this may be principally via oxidative mechanisms. Triglyceride-rich particles can cross the endothelial barrier and enter the arterial wall, thus placing them in a position to promote direct endothelial damage. These particles stimulate endothelial expression of adhesion molecules and the prothrombotic factor PAI-1. By reducing LDL size and HDL cholesterol concentrations, thereby further increasing the endothelial oxidative burden, triglyceride-rich particles may indirectly promote endothelial dysfunction. In addition, free fatty acids, which are the major substrates for endogenous synthesis of triglyceride-rich particles, are also potentially damaging to the endothelium. This occurs via oxidative stress, by facilitating transfer of LDL across the endothelium, and by enhancing toxicity of triglyceride-rich particles. Finally, there is recent strong evidence to suggest that increased postprandial circulating concentrations of triglyceride-rich particles and remnant particles may be deleterious to the endothelium.

Animals↗
PubMed1998

Associations of indices of adiposity with atherogenic lipoprotein subfractions.

OBJECTIVE: To investigate the associations of indices of adiposity with cardiovascular risk factors. SUBJECTS: 93 men and 98 women aged 18-69 y. OUTCOME MEASURES: Body mass index (BMI), waist to hip ratio (WHR), waist circumference, waist to height ratio, blood pressure, fasting concentrations of blood glucose, insulin, plasma lipids and lipoprotein subfractions, apoproteins, lipoprotein(a) and post-heparin lipases. RESULTS: BMI and waist showed similar associations (P < 0.01) with a cluster of major cardiovascular risk factors including total cholesterol, low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol in men, and ratio of low density lipoprotein-/high density lipoprotein-cholesterol for both genders. Large waist circumference was significantly (P < 0.01) associated (controlled for age and smoking) with features of the metabolic syndrome, including raised insulin concentration (men: r=0.37, women: r=0.49), reduced high density lipoprotein2 (men: r=-0.30, women: r=-0.34), increased very low density lipoprotein1 mass (men: r=0.31, women: r=0.42), raised small, dense low density lipoprotein (men: r=0.30, women: r=0.31), elevated blood pressure (men: r=0.27, women: r=0.28), increased triglyceride (men: r=0.43, women: r=0.48) and apolipoprotein-B (men: r=0.32, women: r=0.35). Waist circumference also correlated with hepatic lipase/lipoprotein lipase ratio in women (r=0.52). Height adjustment did not substantially change relationships between waist circumference and risk factors. WHR correlated with fewer risk factors. CONCLUSION: For the purpose of health promotion to prevent cardiovascular disease associated with overweight and intra-abdominal fat accumulation, the general public should be advised to be aware of the risk associated with large waist circumference.

Adipose Tissue↗
PubMed1998

Leptin levels in pregnancy: marker for fat accumulation and mobilization?

BACKGROUND: Leptin, an adipose tissue-derived signalling factor encoded by the obese gene has been shown to be present as a 16-kDa protein in the blood of mice and humans. Resistance to leptin occurs in human obesity. Leptin has also been shown to associate with plasma insulin concentrations and there is currently considerable debate about the potential link between insulin resistance and resistance to leptin. In non-pregnant individuals, circulating leptin concentrations associate strongly with both total body fat mass and body mass index (BMI). In normal human pregnancy, the maternal fat stores increase to a peak in the late second trimester, before declining towards term as fat stores are mobilized to support the rapidly growing fetus. Insulin resistance increases during late pregnancy and is believed to be further enhanced in pregnancies complicated by pre-eclampsia. The aim of this study was to examine if leptin levels were altered in pregnancy and, if so, whether the pattern of change in circulating leptin related to previously established changes in fasting insulin concentrations or fat mass. METHODS: We measured third trimester plasma leptin concentrations in 12 uncomplicated pregnant women, nine women with pre-eclampsia matched for age and booking BMI, and 18 non-pregnant women similarly matched. We also examined the longitudinal course of leptin concentrations occurring throughout gestation (from 10 weeks gestation and at five week intervals thereafter), in five normal pregnancies and two women with gestational-onset diabetes. RESULTS: Leptin concentrations were significantly higher in the normal pregnant women (37.1 microg/L, [15.4-117.0], geometric mean, [range]; p=0.049), and women with pre-eclampsia (45.3 microg/L, [21.3-98.4]; p=0.001), than in non-pregnant controls (17.85 microg/L, [1.3-36.5]), however, there was no significant difference between uncomplicated and pre-eclamptic pregnancies (p=0.22). On examination of the longitudinal course of leptin concentrations occurring throughout gestation, in all seven women plasma leptin concentrations initially increased relative to booking (10 weeks) concentrations, but did so by varying amounts (ranging between 30-233%). Significantly, however, in all seven women plasma leptin concentrations peaked at around 20-30 weeks of gestation before declining towards term. CONCLUSION: On the basis of these observations, we postulate that plasma leptin levels increase significantly in human pregnancies and that the pattern of change in circulating leptin parallels the process of fat accumulation and mobilization.

Adult↗
PubMed1998

Effect of weight loss and the inflammatory response on leptin concentrations in gastrointestinal cancer patients.

Animal research suggests that leptin may have an important role in the regulation of energy balance. The role of leptin in the progressive involuntary weight loss associated with cancer in humans is of considerable interest. However, such studies are limited. In this study, we compared circulating leptin concentrations in gastrointestinal cancer patients and weight loss (n = 27) with those of healthy subjects (n = 27). The effect of the presence of an inflammatory response on leptin concentrations was also examined. There were significantly lower leptin concentrations in male (median, 2.4 microg/liter; range, <0.5-6.0 microg/liter) and female (median, 3.4 microg/liter; range, <0.5-9.8 microg/liter) cancer patients than there were in male (median, 6.5 microg/liter; range, 3.1-10.9 microg/liter) and female (median, 18.7 microg/liter; range, 8.0-31.5 mcirog/liter) healthy subjects (P < 0.001). However, the leptin concentrations in both patients and normal subjects were related to the predicted percentage of body fat (r = 0.731; P < 0.001). Circulating leptin concentrations in the cancer patients were not altered by the presence of an inflammatory response. These results suggest that cancer anorexia/cachexia is not due to a simple dysregulation of leptin production.

Adult↗
PubMed1997

Lipoprotein subfraction concentrations in preeclampsia: pathogenic parallels to atherosclerosis.

OBJECTIVE: To determine whether large triglyceride-rich lipoproteins, very-low-density lipoprotein1 (VLDL1), and small, dense low-density lipoprotein (LDL-III), are significantly increased in women with preeclampsia compared with concentrations seen in normal pregnancy. METHODS: Plasma concentrations of very-low-density and low-density lipoprotein subfractions and pre-heparin hepatic lipase activity were measured in eight women with preeclampsia and in eight healthy pregnant controls matched for age, gestational age, and weight. RESULTS: Women with preeclampsia exhibited higher median plasma triglyceride concentrations (3.68 versus 1.93 mmol/L, P = .004) compared with controls. This was reflected in an almost threefold increase in median VLDL1 (184 versus 68 mg/dL, P = .002) and a twofold increase in very-low-density lipoprotein2 (VLDL2) (146 versus 76 mg/dL, P = .014), whereas total plasma cholesterol, intermediate-density lipoprotein, and total LDL concentration were the same in subjects and controls. Furthermore, women with preeclampsia demonstrated significantly lower concentrations of the large, buoyant LDL subfractions, LDL-I and LDL-II, and markedly elevated median plasma concentrations of small, dense LDL, LDL-III (170 versus 55 mg/dL, P = .024). High-density lipoprotein-cholesterol concentration also was significantly lower (P = .021), and pre-heparin hepatic lipase activity was significantly elevated (29 versus 18 mumol fatty acids/mL/hour, P = .041) in the preeclamptic group. The concentration of small, dense LDL correlated positively with plasma triglyceride concentration (r2 = 0.504, P = .002). CONCLUSION: Women with preeclampsia exhibit markedly elevated concentrations of triglyceride-rich lipoproteins in the circulation. These particles are potential contributors to endothelial dysfunction and the expression of preeclampsia, both directly and, indirectly, through the generation of small, dense LDL.

Adult↗
PubMed1997

Insertion of 2 kb of bacteriophage DNA between an immunoglobulin promoter and leader exon stops somatic hypermutation in a kappa transgene.

Somatic hypermutation in rearranged immunoglobulin variable genes occurs in a 2kb region of DNA that is delimited on the 5' side by the promoter and on the 3' side by intron DNA. To identify sequence features that activate the mutation mechanism, we increased the distance between the promoter and the leader region to test whether the spacing of these elements was important. The promoter was separated from the leader sequence by inserting a 2 kb fragment of noncoding bacteriophage lambda DNA between the TATA box and ATG initiator codon in a kappa transgene. Mice from three founder lines were immunized, RNA and DNA were isolated from spleen and Peyer's patch B cells, and transcription of the transgene was confirmed. The frequency of mutation in endogenous heavy chain genes was high, indicating that some B cells underwent hypermutation. However, no hypermutation was found in the transgenic bacteriophage or variable region sequences. Hypermutation did occur in another kappa transgene that had a deletion of the VJ coding sequence, showing that the basic construct is functional and that the VJ exon is not necessary for the mutation mechanism. It is likely that the bacteriophage sequence is a potential substrate for mutation because other heterologous sequences have been shown to undergo mutation if placed downstream of the leader exon. The results suggest that the promoter should be contiguous with the leader exon for the mutation mechanism to function.

Animals↗
PubMed1997

Characteristics of antibody responses induced in mice by protein allergens.

Whereas many foreign proteins are immunogenic, only a proportion is also allergenic, having the capacity to induce the quality of immune response necessary to support the production of IgE antibody. We have demonstrated previously that intraperitoneal administration to mice of proteins such as ovalbumin (OVA) or the industrial enzyme A. oryzae lipase, which possess significant allergenic potential, stimulates the production of both IgG and IgE antibody. Identical exposure to bovine serum albumin (BSA), a protein with limited potential to cause immediate respiratory or gastrointestinal hypersensitivity reactions, induced IgG responses only. In the current investigations, the quality of immune responses induced following exposure to these proteins via mucosal tissue (intranasal) has been compared with those provoked following administration via a non-mucosal (intraperitoneal) route of exposure. Intranasal or intraperitoneal administration of BSA, OVA or A. oryzae lipase elicited in each case vigorous IgG and IgG1 antibody responses. For all three proteins, at every concentration tested, and via both routes of exposure, IgG1 antibody titres paralleled closely IgG titres. However, the three materials displayed a differential potential to provoke IgE responses and this correlated with their known allergenic potential in humans. Thus, OVA and A. oryzae lipase stimulated strong IgE antibody responses, whereas BSA provoked low titre IgE only at the highest concentration tested (5% administered intraperitoneally). The quality of induced responses was not affected by the route of exposure. It would appear, therefore, that the stimulation of IgG and IgG1 antibody responses is a reflection of protein immunogenicity whereas protein allergenicity is associated with the induction of strong IgE responses.

Administration, Intranasal↗
PubMed1997

Acute-phase reactants and plasma trace element concentrations in non-small cell lung cancer patients and controls.

This study examined the effect of an acute-phase response on plasma trace element concentrations of non-small cell lung cancer (NSCLC) patients. In normal subjects (n = 13) and NSCLC patients (n = 22), fasting concentrations of albumin, C-reactive protein, the trace elements iron, zinc, copper, and selenium, and their associated proteins transferrin, albumin, ceruloplasmin, and glutathione peroxidase were measured. The NSCLC patients were subdivided into two equal groups depending on whether they had a C-reactive protein concentration < 35 mg/l (Group 1) or > 35 mg/l (Group 2). Circulating zinc, iron, and transferrin concentrations were significantly lower in NSCLC Group 1 than in the control group (p < 0.05). Circulating concentrations of iron, zinc, and the binding proteins transferrin and albumin were significantly lower in NSCLC Group 2 than in the control group and NSCLC Group 1 (zinc not significantly different) (p < 0.01). In contrast circulating concentrations of copper and its binding protein ceruloplasmin were significantly increased in NSCLC Group 2 compared with NSCLC Group 1 and the control group (p < 0.01). Additionally, plasma selenium and glutathione peroxidase concentrations were significantly lower (p < 0.05) in NSCLC Group 2 than in NSCLC Group 1 and the control group. In the NSCLC patients there were significant negative correlations between concentrations of C-reactive protein and iron, transferrin, zinc, albumin, and selenium (p < 0.05). Furthermore, there were also significant positive correlations between C-reactive protein and copper (r = 0.788, p < 0.001) and ceruloplasmin (r = 0.831, p < 0.001) concentrations. The presence of an acute-phase response has implications for the interpretation of circulating trace element concentrations, the status of patients with NSCLC, and supplementation with trace elements in patients with NSCLC.

Acute-Phase Proteins↗
PubMed1997

Lipoprotein subfraction changes in normal pregnancy: threshold effect of plasma triglyceride on appearance of small, dense low density lipoprotein.

A detailed longitudinal examination of plasma lipoprotein subfraction concentrations and compositions in pregnancy was performed with the objective of discovering the pattern of change in lipoprotein subfractions. Plasma triglyceride, cholesterol, very low density lipoprotein (VLDL1), very low density lipoprotein (VLDL2), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and its subfractions (LDL-I, LDL-II, LDL-III), and high density lipoprotein-cholesterol (HDL cholesterol) were quantified in 10 normal pregnant women from 10 weeks of gestation and at 5 weekly intervals thereafter, until 35 weeks of gestation, together with circulating hepatic lipase (at 10 and 35 weeks) and serum estradiol concentration. Median concentrations of VLDL1 (19-109 mg/dL), VLDL2 (17-103 mg/dL) and IDL (26-124 mg/dL) increased in parallel (maximum increase around 5-fold) as plasma triglyceride increased with advancing gestation. This contrasts with observations in the normal non-pregnant female, where higher concentrations of plasma triglyceride are associated with preferentially higher VLDL1 concentrations. The rise in IDL was also remarkable as this does not normally accompany changes in plasma triglyceride. LDL mass increased by 70% (200-353 mg/dL) between 10 and 35 weeks, and in 6 of the 10 women studied, the LDL subfraction pattern was modified towards a smaller denser pattern in a manner suggestive of a "threshold" transition, with the proportion of LDL-III increasing at the expense of LDL-II, whereas in the other 4 women, LDL subfraction profile remained unchanged throughout pregnancy. Interestingly, this "threshold" transition, if it occurred, did so at varying gestational ages and triglyceride concentrations for different women. The likelihood of LDL subfraction change and the final concentration of small, dense. LDL-III were related to the 10-week triglyceride concentration (R2 = 36.7%, P = 0.063) and to the rate of change in triglyceride for a given increment in estrogen (R2 = 48.6%, P = 0.025). In addition, VLDL1 mass exceeded 100 mg/dL during pregnancy only in those individuals in whom LDL profile perturbation was evident (chi 2, P < 0.001). LDL profile change was evident at the lowest triglyceride concentrations in the 2 individuals with the highest increments in triglyceride corrected for estrogen. On the basis of these longitudinal observations, we conclude the following: 1) as plasma triglyceride increases in pregnancy, there are parallel rises in median concentrations of VLDL1, VLDL2 and IDL, around 5-fold; 2) as a result of this progressive increase in plasma triglyceride, in particular in VLDL1, the LDL profile is altered in some individuals towards smaller, dense particles; 3) in general, the higher the initial (booking) fasting plasma triglyceride concentration or the larger the rate of change in triglyceride for a given increment in estradiol, the greater the probability of change in LDL profile towards smaller denser species; 4) significantly, LDL subclass perturbation towards smaller denser species occurs not in a gradual and progressive manner but exhibits "threshold" behavior; and finally, 5) this threshold is achieved at differing gestational ages and triglyceride concentrations for different women.

Adult↗