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Biomedical subjects

A Lucas

Publications and source records attributed to A Lucas.

At least 145 records · Page 8Linked to original sources
PubMed1997

Programming of hepatic insulin-sensitive enzymes in offspring of rat dams fed a protein-restricted diet.

Hepatic enzymes associated with glucose hemostasis were studied in offspring of dams fed either a 20% protein (control) or an isocaloric 8% protein (low-protein) diet during pregnancy and lactation. Additionally, offspring were exposed to maternal 8% protein diet only during gestation (recuperated) or lactation (postnatal low-protein). Glucokinase activity decreased (approximately 50%), whereas phosphoenolpyruvate carboxykinase (PEPCK) activity increased (approximately 100%), in the low-protein and recuperated offspring compared with controls (P < 0.001) at 21 days of age. However, the postnatal low-protein offspring had enzyme activities comparable with those of controls. These changes were still evident in 11-mo-old offspring weaned onto a normal laboratory chow. Parallel changes were apparent in mRNA levels of glucokinase and PEPCK in the low-protein male offspring. Thus the effect of programming metabolism extends not only to protein biochemistry but possibly also to the regulation of gene expression. Furthermore, these changes could not be attributed to glucagon or insulin, because ratios of these hormones were comparable between the control and low-protein groups.

Animals↗
PubMed1997

Calreticulin, a potential vascular regulatory protein, reduces intimal hyperplasia after arterial injury.

Both thrombotic and inflammatory responses to arterial injury have been implicated in atherosclerotic plaque growth. Calreticulin is a ubiquitous calcium-binding protein with antithrombotic activity and, in addition, is associated with leukocyte activation. We are investigating calreticulin as a potential vascular regulatory protein. The development of intimal hyperplasia was studied at sites of balloon injury in iliofemoral arteries from 91 rats. Calreticulin was infused directly into the artery immediately before balloon injury, and plaque growth was then assessed at 4 weeks' follow-up. Parallel studies of the effects of each calreticulin domain as well as a related calcium-binding protein, calsequestrin, were examined. The effects of calreticulin on platelet activation, clot formation, and mononuclear cell migration were also studied. When infused before balloon injury in rat iliofemoral arteries, calreticulin, or its high-capacity Ca(2+)-binding C domain, significantly reduces plaque development, whereas calsequestrin, a related calcium-binding protein that lacks the multifunctional nature of calreticulin, does not decrease plaque area (saline: 0.037 +/- 0.007 mm2, calsequestrin: 0.042 +/- 0.021 mm2, calreticulin: 0.003 +/- 0.002 mm2, n = 46, P < .04). The N domain and more specifically the P domain, a low-capacity, high-affinity calcium-binding domain in calreticulin, do not reduce intimal hyperplasia (N + P domain: 0.038 +/- 0.012 mm2, C domain: 0.003 +/- 0.002 mm2, n = 45 rats, P < .0001). Calreticulin reduces macrophage and T cell staining in the arterial wall after injury but has no direct effect on monocyte migration in vitro (percent medial area staining positive for macrophage 24 hours after injury (N + P: 4.06 +/- 1.42, calreticulin: 0.273 +/- 0.02; n = 26, P < .009). Calreticulin does, however, reduce platelet-dependent whole blood clotting time, in vitro (baseline: 78.23 +/- 2.04 seconds, calreticulin: 113.5 +/- 1.95 seconds; n = 5, P < .002). We conclude that calreticulin significantly reduces intimal hyperplasia after arterial injury, potentially acting as a vascular regulatory protein.

Angioplasty, Balloon↗
PubMed1997

Medical therapy of Graves' disease: does thyroxine prevent recurrence of hyperthyroidism?

Sixty patients with Graves' disease (GD) hyperthyroidism were distributed in two randomized groups. Patients in group A (n = 30) received carbimazole by a titration regimen, and patients in group B (n = 30) were treated with higher doses of carbimazole plus T4. Clinical and analytical evaluations were done at baseline, during treatment (18.4 +/- 2.6 months), and after, until the relapse of hyperthyroidism, or for 4.98 +/- 1.6 yr in patients who did not relapse. There were no differences in clinical parameters, thyroid hormones, or TSH binding inhibitory immunoglobulins (TBII) levels between the two groups, either at baseline or at the end of treatment. Serum TSH persisted undetectable in 16 out of 60 patients (group A: 9; group B: 7), after treatment. Relapse occurred in 38 patients (63.3%), (group A: 18 (60%) vs. group B: 20 (66.7%)). Patients who relapsed had bigger goiters at baseline (P = 0.02) and at the end of treatment (P = 0.03). Eighty-seven percent (14/16) of patients with undetectable TSH after therapy relapsed, vs. 54.5% (24/44) of those with normal TSH (P = 0.01). Undetectable TSH at the end of treatment was the only independent variable in the logistic analysis to predict relapse. Treatment modality did not influence the relapse rate. This study has found that, in Spanish patients, the use of high doses of carbimazole with T4 offers no advantages in the treatment of GD hyperthyroidism.

Adolescent↗
PubMed1997

[Evaluation of carboxy-angiography in the study of arteriopathy of the lower limbs].

PURPOSE: We prospectively compared the safety and the usefulness of CO2 with iodinated contrast material in the study of lower limb arteries. PATIENTS AND METHOD: The study included 30 patients (20 men, 10 women, mean age 67) suffering from lower limb ischemia: stage II (3), stage III (13), stage IV (9), Leriche syndrome (1), post-operative (4). We systemically performed an aortic injection (L3), via a 4F catheter, of (1) CO2-DSA (5 to 6 injections of 75 ml at a flow rate of 20 ml/s) and (2) DSA with iodine contrast material (100 ml at a flow rate of 8 ml/s). Patients were monitored for pain and vital signs. Four reviewers did a subjective evaluation of the vessel visibility at five levels (pelvis, thigh, knee, calf, ankle). RESULTS: No side effect was found. Concerning pain, the patients had the same sensation in 53%; pain was more disagreeable with CO2 in 40%, more disagreeable with iodine in 7%. Concerning vessel visualization, there was a good coherence between the readers and we found the same quality in 61%. CO2 was less informative in 35%, and more informative in 4%. Image quality decreased with fragmentation of the gas and remoteness of injection site. CONCLUSION: CO2 angiography, with electronic injection, is a safe alternative to conventional angiography with iodinated contrast material. The disagreeable sensations can be reduced with explanations given before injection and reducing flow rate. Image stacking software could imitate the side effects of fragmentation of the CO2 bubble. This method appears to be a good alternative for patients with severe renal impairment or allergic problems.

Adult↗
PubMed1997

Neonatal insulin secretion: implications for the programming of metabolic homeostasis.

Patterns of metabolic adaptation are described in the neonate, which generate two fundamental concepts. First, that early nutritional experiences may have long-term effects on the control of metabolic homeostasis, and second, that insulin has a fundamental role in this process. The endocrine pancreas in the neonate is unable to regulate insulin secretion in relation to blood glucose concentration with the same level of tight control seen in the older child and adult. Moreover, the pattern of metabolic adaptation in the fullterm infant in the first postnatal week is different to that of the preterm baby and the infant born small-for-gestational-age (SGA), with both preterm and SGA infants being unable to generate counter-regulatory ketogenesis as blood glucose concentrations fall. The inability to initiate ketogenesis and switch off insulin secretion after birth persists for several weeks in preterm infants. Methods of feeding term and preterm infants have profound effects on the neonatal endocrine milieu and it is suggested that patterns of insulin secretion provoked in the newborn period may 'programme' the subsequent development of metabolic control. The recently described molecular mechanisms that underlie the pathogenesis of abnormal insulin secretion in the syndrome of persistent hyperinsulinaemic hypoglycemia of infancy (or pancreatic nesidioblastosis) may offer insights into how such programming may occur.

Adaptation, Physiological↗
PubMed1997

Effect of angiotensin-converting enzyme inhibition on infarct collagen deposition and remodelling during healing after transmural canine myocardial infarction.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition for six weeks after myocardial infarction (MI) lowers the collagen content of infarct scars in dogs. However, temporal changes in collagen content of the infarct zone (IZ) with ACE inhibition during healing over six weeks after MI and their possible relation to IZ remodelling have not been determined. METHODS: IZ collagen (hydroxyproline) was measured over six to seven weeks in dogs treated with captopril (50 mg bid), enalapril (2.5 mg bid) or placebo, beginning on the second day following transmural anterior MI (or sham). In vivo changes in IZ and global left ventricular (LV) remodelling, mass and function (echocardiograms) and hemodynamics among six-week survivors were also measured. RESULTS: Compared with placebo, both inhibitors decreased IZ collagen (P < 0.001) over the seven weeks. Among the six-week survivors, both inhibitors lowered IZ collagen (P < or = 0.001) and increased the collagen type I:III ratio. However, preload was lower, increase in diastolic volume and mass were less and systolic function improved. Although the doses of captopril (but no enalapril) decreased afterload, inhibition of IZ collagen was less, IZ bulging and global LV dilation were less and systolic function was better with captopril than with enalapril. In all three MI groups, deaths over the seven weeks correlated with greater infarct size, LV volume and dysfunction and lower IZ collagen. CONCLUSIONS: ACE inhibition suppresses the temporal increase in IZ collagen and attenuates IZ expansion, thinning and bulging, and LV enlargement and aneurysm formation during healing after MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Results of carotid surgery in elderly patients.

METHODS: We have evaluated the results of carotid surgery in 252 patients of 75 years and over age (A group) including 281 interventions between June 1st 1985 and December 31st 1993. RESULTS: These results have been compared to those obtained in 660 patients of less 75 years (B group), operated on over the same period of time (741 interventions). In the A group, the mean age was 78.2 (from 75 to 89) and 37.3% were women. Nicotinism, obesity and dyslipaemia was significantly more frequent in A group. An angor was shown in 48% in A group (versus 38.8% in B group). In A group, 34.5% (n = 97) of patients were neurologically asymptomatic against 41.7% (n = 309) in B group. Four patients aged over 75 died (1.42% per intervention), one from myocardial infarction, the other from postoperative stroke. Three other patients showed a non regressive postoperative neurological deficiency. The Cumulated Rate of Mortality Morbidity (CRMM) in A group is then 2.49% per intervention. It does not significantly differ from B group results: mortality = 1.48% (n = 11, 10 of neurological origin), CRMM = 3.23% per intervention. We counted 4 myocardial infarctions (1.58%) in A group and 5 (0.75%) in B group. The mean time after the interventions was 58 months. The five years actuarial survival is 73% of A group patients and 85% for B group patients. In A group patients, 44% of deaths are of coronary origin and 35% in B group patients. The actuarial rate of people free from neurological deficiency, after 5 years, is 90.9% in A group and 92.4% in B group. CONCLUSIONS: In this study, age does not seem to be a risk factor in carotid surgery. The elderly patients must be selected according to the same criteria as the under 75, save the estimation of intellectual faculties and autonomy.

Age Factors↗
PubMed1997

[Mammaplasty with triple interposition of glandular flaps. Technical note].

The unfavorable breast contours resulting from a reductive mammaplasty or a mastopexy influenced the authors into developing a technique that provided reduction of the breast base and axillary pole, convenient medial position of the lateral pole and substantial conification of the breast tissue to help project the areolomamillary complex to the apex of that cone. From March 1987 to May 1996 two hundred and seventeen operations were performed with this technique that consists of construction of three glandular flaps and maximum preservation of the skin covering. The results obtained showed to be very satisfactory and more lasting.

Adipose Tissue↗
PubMed1996

Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty.

BACKGROUND: Recurrent atherosclerotic plaque growth, restenosis, is a significant clinical problem after interventional procedures. Initiation of restenosis involves activation of inflammatory and thrombotic cascades, which are regulated by serine proteinase enzymes and inhibitors. We have investigated the use of a viral serine proteinase inhibitor, SERP-1, to reduce plaque development after primary balloon angioplasty. This is the first experimental report of the use of a viral anti-inflammatory protein for the prevention of atherosclerosis. METHODS AND RESULTS: Seventy-four cholesterol-fed rabbits were treated with either local or systemic infusions of SERP-1 protein (or control solutions) after balloon-mediated injury. Sites of SERP-1 infusion in rabbits had dramatically reduced plaque compared with control infusions at the 4-week follow-up. At low-dose infusions (30 to 300 pg), only the primary infusion site had a demonstrable decrease in plaque, whereas at higher-dose infusions (> 3000 pg), a generalized reduction in plaque development was detected. An associated decrease in mononuclear cell infiltration of the arterial wall was detected after SERP-1 infusion within the first 24 hours. Infusion of an active-site mutant of SERP-1 (P1-P1', ala-ala) lacking serine proteinase inhibitory activity failed to prevent plaque growth. CONCLUSIONS: Purified SERP-1, a virus-encoded secreted glycoprotein, reduces plaque growth after primary balloon-mediated injury. Plaque development is decreased by inhibition of serine proteinase activity and is associated with a focal reduction in macrophage infiltration immediately after injury. Investigation of serine proteinase inhibitors may provide new insight into the regulation of arterial responses to injury.

Angioplasty, Balloon↗
PubMed1996

Development of an avian model for restenosis.

Recurrence of atherosclerotic plaque growth after interventional therapy, restenosis, is a significant clinical problem occurring in 20%-50% of cases. We have developed a new avian model for the investigation of restenosis after arterial injury in cholesterol fed White Leghorn roosters. Atherosclerotic plaque growth 1-30 weeks after angioplasty balloon mediated endothelial injury in the abdominal aorta was studied in 37 roosters. Roosters were maintained on either normal poultry diet or high cholesterol diet. Twelve cholesterol fed roosters were also fed a hormone supplemented diet in order to modify plaque morphology. The procedural success rate was high. Angiographic stenoses (mean 36% with maximum of 74%) were detectable in cholesterol fed roosters after balloon angioplasty with associated histological evidence of plaque growth (P < 0.017). Cholesterol feeding enhanced fatty plaque growth; hormone manipulation increased calcific and ulcerated plaque but with high associated morbidity. Three interventional devices were subsequently examined in 32 roosters (16 laser angioplasty, 7 atherectomy, and 9 stent implant). Plaque development was again assessed by contrast angiography and histological analysis. We conclude that balloon mediated arterial injury in cholesterol fed roosters produces early proliferative and late, complex atherosclerotic lesions providing an inexpensive model for plaque development after intimal injury.

Angioplasty, Balloon↗
PubMed1996

Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a critical virulence factor for the development of myxomatosis in European rabbits.

Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively little, if any, cellular activation of germinal centers of spleen and lymph node by Day 4. We conclude that M-T7 functions early in infection to (1) retard inflammatory cell migration into infected tissues and (2) disrupt the communication between sentinel immune cells at the site of primary virus infection in the subdermis and lymphocytes in the secondary lymphoid organs, thereby disabling the host from mounting an effective cellular immune response. To summarize, in addition to neutralizing host interferon-gamma at infected sites, we propose that M-T7 protein also modifies leukocyte traffic in the vicinity of virus lesions, thus effectively severing the link between antigen presenting cells of the infected tissue and the effector lymphocytes of the peripheral immune organs.

Animals↗
PubMed1996

Expression of Haemophilus influenzae type b idiotype 1 on naturally acquired antibodies.

The Chinese population in Hong Kong has a low incidence of invasive Haemophilus influenzae type b(Hib) disease, as well as carriage of the microorganism. Likely stimuli for the natural antibodies to Hib, which might protect against Hib infection, are cross-reactive antigens of bacteria like Escherichia coli K 100. Our aim was to determine the isotype and idiotype distribution and cross-reactivity of natural antibodies against Hib capsular polysaccharide (CP) in healthy Hong Kong Chinese. Titration of 20 sera by ELISA showed IgG antibodies reacting with Hib CP in all individuals. The antibodies were mainly IgG2, and their avidity index ranged widely. Isoelectric focusing (IEF) combined with immunoblotting showed patterns of IgG2 antibody clones against the CP of Hib and E. coli K 100 which were similar in 10 cases. Absorption with Hib CP only eliminated some bands in two sera. Absorption with K 100 CP did not remove any anti-Hib CP bands. In three sera additional clones of antibodies reacting to K 100 CP only, disappeared after absorption with this CP. Spectrotypic analyses of IgG antibodies reacting with anti-Hib idiotype 1 (Id-1) revealed stronger IEF patterns with bands in differing locations compared with anti-Hib CP antibodies. The strong reactivity of serum IgG, IgA and IgM antibodies with monoclonal anti-Hib Id-1 was confirmed by ELISA. This reactivity was not abolished after absorption of the sera with either Hib CP, or K 100 CP. The data indicate a high prevalence of Id-1 among Hong Kong Chinese. However, only one individual had Id-1 antibodies specific for Hib CP, judging from absorption experiments. Others had much lower activity of Id-1 anti-Hib CP antibodies compared with the total IgG Id-1, suggesting that Hong Kong subjects have Id-1-positive antibodies in their serum which are not specific for Hib CP. This is consistent with the nature of Id-1, which is a marker of A2VL region usage rather than a marker of a Hib CP paratope. We suggest that natural antibodies reacting with Hib CP in healthy Hong Kong Chinese are the product of exposure to some cross-reactive antigen(s), different from both Hib and E. coli K 100 CP.

Adult↗
PubMed1996

Organ-selective growth in the offspring of protein-restricted mothers.

Recent epidemiological studies in people whose birth weights were recorded many years ago suggest links between impaired growth during early life and the development of diseases, including diabetes, much later in life. The long-term effects of retarded early growth are proposed to result from malnutrition at critical periods of fetal or infant development leading to reduction in the growth of organs and permanent changes in their metabolism or structure, or both. In order to investigate this, a rat model was established which involved feeding either a diet containing 200 g protein/kg or an isoenergetic diet containing 80 g protein/kg to pregnant and lactating rats. In addition, cross-fostering techniques were employed which allowed a separate evaluation of the prenatal or the postnatal periods. The offspring were studied at 21 d of age or were weaned onto a normal laboratory chow and studied at 11 months of age. The 80 g protein/kg diet during pregnancy did not affect the overall reproductive although more subtle differences were evident. Permanent growth retardation was evident in offspring subjected to maternal protein restriction during the postnatal period. At 21 d of age the offspring of protein-restricted mothers exhibited selective changes in organ growth: compared with the body weight, the lung and brain experienced a smaller decrease in weight: the heart, kidney and thymus decreased proportionately: whereas, the pancreas, spleen, muscle and liver showed a greater reduction in weight. In older animals the muscle weight was lower in the male rats and the relative weight of pancreas was increased in the female rats.

Animals↗
PubMed1996

Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring.

Epidemiological studies in human show that size in early life is related to blood cholesterol concentrations in adult life, raising the hypothesis that early nutrition programs later lipid metabolism, affecting risk for later vascular disease. Here, we tested the hypothesis that nutrition during pregnancy or lactation in the rat programs lipid metabolism in the offspring, studied in adult life (mean 6 months). Rats (n 35) from normally-fed dams (controls) were compared with (1) rats (n 22) from dams protein-restricted in pregnancy and lactation; (2) rats (n 9) born to normally-fed mother crossed to protein-restricted lactating dams and (3) those (n 9) born of protein-restricted dams and crossed to normally-fed lactating animals. In these latter three groups the offspring showed long-term reduction in plasma cholesterol, HDL-cholesterol and triacylglycerol concentrations compared with controls. The effects were predominantly in males. These findings suggest that in the rat the sensitive period for nutritional programming of cholesterol and triacylglycerol metabolism is both pre- and postnatal (pre-weaning) and that rats may be 'indirectly' programmed by altering the maternal nutritional milieu during gestation or lactation. Whilst it has been hypothesized that early human undernutrition programs risk for vascular disease, one aspect of undernutrition, low maternal protein intake, in this rat model programmed lower plasma cholesterol and triacylglycerol concentrations.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Randomized outcome trial of human milk fortification and developmental outcome in preterm infants.

Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.

Acid-Base Equilibrium↗