RESUMO
We report for the first time a novel room temperature methane (CH(4)) sensor fabricated using porous tin oxide (SnO(2)) nanorods as the sensing material. The porous SnO(2) nanorods were synthesized by using multiwall carbon nanotubes (MWCNTs) as templates. Current versus time curves were obtained demonstrating the room temperature sensing capabilities of the sensor system when exposed to 0.25% CH(4) in air. The sensor also exhibited a wide temperature range for different concentrations of CH(4) (25-500 °C), making it useful in harsh environments as well.
RESUMO
Phytosterolemia is an autosomal recessive disorder characterized by the excessive absorption, reduced excretion, and consequent high tissue and plasma levels of plant sterols, by the presence of tendon xanthomas, and by premature atherosclerosis. Low HMG-CoA reductase (HRase) activity and mass have been reported in liver and mononuclear leucocytes and low mRNA levels in liver from phytosterolemic subjects. These results led to the proposal that the primary defect in this condition involves the HRase gene locus. We examined this hypothesis in phytosterolemic subjects and heterozygous parents from four unrelated families. A variable number tandem repeat (VNTR) polymorphism of the HRase gene in the three informative families and a ScrFI restriction fragment length polymorphism (RFLP) within intron 2 of the gene in one of these families, segregated independently of the disease phenotype. Biological parentage was confirmed in the family in whom both polymorphisms failed to segregate with the disorder. These results conclusively exclude the HRase gene locus as the site of the primary defect in phytosterolemia. The study was extended by examining plasma levels of mevalonic acid and lathosterol, both markers of cholesterol biosynthesis, in response to cholestyramine, a bile acid sequestrant that is known to up-regulate HRase. Oral administration of cholestyramine resulted in a substantial (7.7-fold) increase in mevaIonic acid levels in two phytosterolemic subjects, compared with a 2.2-fold rise in their obligate heterozygote parents and a 2.3-fold increase in three healthy control subjects. The lathosterol/cholesterol (L/C) ratio showed a quantitatively similar response. Baseline levels of mevalonate and the L/C ratio were low in the phytosterolemic patients in conformity with reports of reduced cholesterol biosynthesis and HRase activity in this disorder. These functional data provide support for the concept that the primary defect in phytosterolemia does not affect a trans gene locus responsible for the constitutive expression or regulation of HMG-CoA reductase.
Assuntos
Hidroximetilglutaril-CoA Redutases/fisiologia , Erros Inatos do Metabolismo Lipídico/enzimologia , Fitosteróis/sangue , Adolescente , Adulto , Arteriosclerose/complicações , Arteriosclerose/enzimologia , Arteriosclerose/genética , Criança , Resina de Colestiramina , Feminino , Ligação Genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Erros Inatos do Metabolismo Lipídico/complicações , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/genética , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites , Linhagem , Polimorfismo Genético , Xantomatose/complicações , Xantomatose/enzimologia , Xantomatose/genéticaRESUMO
OBJECTIVE: To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. SUBJECTS: A three-generation kindred with clinically and biochemically diagnosed medullary thyroid cancer. METHOD: Identification of a heterozygote mutation by nucleic acid sequencing and restriction analyses. RESULTS: A heterozygote T-->C (Cys-->Arg) mutation at codon 618 in exon 10 of the RET proto-oncogene was identified in 4 family members who had previously been diagnosed with medullary thyroid cancer. The same mutation was also found in one of the proband's presymptomatic children who subsequently underwent a pre-emptive thyroidectomy. The genetic diagnosis was confirmed by histology. No mutations were detected in any other family members. CONCLUSION: Identification of heterozygote germline mutations in multiple endocrine neoplasia is direct, highly accurate and cost-effective. This study demonstrates that, appropriately used, molecular diagnosis can supersede conventional biochemical methods in the management of patients with inherited cancers.
Assuntos
Carcinoma Medular/diagnóstico , Análise Mutacional de DNA , Testes Genéticos , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Adulto , Calcitonina/sangue , Carcinoma Medular/genética , Criança , Pré-Escolar , Feminino , Mutação em Linhagem Germinativa , Humanos , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Linhagem , Pentagastrina , Proto-Oncogene Mas , Análise de Sequência de DNARESUMO
Coronary heart disease is common amongst South Africans of Indian (Asian) ancestry. As part of an investigation into risk factors in premenopausal and post-menopausal Indian nurses, we determined the apolipoprotein E genotype by means of restriction isotyping on 173 healthy nurses between the ages of 25-55 years. The apolipoprotein E allele frequencies on 346 chromosomes were: epsilon 2, 1.2% (95% confidence interval 0.06-2.66); epsilon 3, 87.6% (95% confidence interval 84.1-91.1 and epsilon 4, 11.3% (95% confidence interval 7.94-14.60). No epsilon 2/2 homozygotes were encountered. Our results demonstrate an extremely low frequency of the epsilon 2 allele, a low-normal apo epsilon 4 and a high epsilon 3 allele frequency. It is unlikely that apolipoprotein E polymorphism contributes to the high incidence of coronary heart disease in this population.
Assuntos
Apolipoproteínas E/genética , Adulto , África Austral , Apolipoproteína E2 , Apolipoproteína E3 , Apolipoproteína E4 , Feminino , Frequência do Gene , Humanos , Índia , Pessoa de Meia-IdadeRESUMO
The effect of the menopause on insulin metabolism has not received specific attention in populations prone to non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). Insignificant or slight alterations in insulin levels have been reported in postmenopausal women of mainly European ancestry. We thus report on the results of a cross-sectional study on the correlates of fasting insulin levels in 177 healthy, Indian nurses aged between 25 and 55 years. Fasting insulin concentration was markedly higher in the 75 postmenopausal subjects (23.9 mU I-1) than in the 102 premenopausal women (11.7 mU I-1 (p < 0.0001). Forty-three (57%) of the postmenopausal subjects had insulin values more than 20 mU I-1 (the upper normal limit). Stepwise regression analysis on the entire group revealed menopause (p < 0.0001), waist:hip ratio (p = 0.0001), apolipoprotein E genotype (p = 0.002), and the testosterone: sex hormone binding globulin ratio (p = 0.0002) as statistically significant, independent predictors of log insulin levels. Age did not account for the difference between premenopausal and postmenopausal subjects. The apolipoprotein E genotype emerged as a significant correlate of insulin levels, only in postmenopausal women: epsilon 3/3, 26.3 mU I-1; epsilon 3/4, 51.8 mU I-1 (p = 0.0007). Hyperinsulinaemic postmenopausal subjects had higher fasting glucose levels than normoinsulinemic nurses (p = 0.03), but glycosylated haemoglobin and fructosamine values were all within the normal range. Thus fasting hyperinsulinaemia was marked and common among a group of healthy, postmenopausal Indian nurses below the age of 55 years, suggesting that the menopausal transition may permit or provoke insulin resistance in this susceptible population.
Assuntos
Insulina/sangue , Pós-Menopausa/sangue , Adulto , Apolipoproteínas E/genética , Estudos Transversais , Feminino , Genótipo , Humanos , Índia , Pessoa de Meia-Idade , Pré-Menopausa/sangue , Valores de Referência , Análise de Regressão , Fatores de RiscoRESUMO
The recommendation that not more than 300 mg cholesterol be consumed daily to prevent high serum cholesterol levels and coronary heart disease is often used to justify a restriction of egg intake to three or four per week. One egg contains about 200 mg of cholesterol, but eggs are also excellent and relatively inexpensive sources of essential amino acids and certain vitamins. In this paper, the place of eggs in a prudent, cholesterol-lowering diet as a substitute for other animal products, is scrutinised. The extra cholesterol, where considered as the only variable, will increase serum cholesterol levels, but the effect is relatively small. The exclusion of eggs from the diet should be weighed against deprivation of essential nutrients especially in vulnerable groups. While restriction of egg intake in westernised populations seems justifiable, the upper limit of three or four per week may not always be applicable, depending on the overall diet and lipid profile of the individual.
Assuntos
Colesterol na Dieta/efeitos adversos , Ovos/efeitos adversos , Colesterol/análise , Doença das Coronárias/etiologia , Dieta com Restrição de Gorduras , Análise de Alimentos , Humanos , Valor Nutritivo , Fatores de RiscoRESUMO
Phytosterolaemia (beta-sitosterolaemia), a rare, autosomal recessive disorder, has not hitherto been reported in Southern Africa. We report four new homozygous patients, from three unrelated families with significant beta-sitosterolaemia (6.6-11.3%), campesterolaemia (2.2-4.6%) and clearly detectable, though unquantified, levels of cholestanol. Three of the four patients had characteristic cutaneous and tendinous xanthomas within the first decade of life. The fourth patient, a 5 year old, was free of xanthomas despite persistently elevated concentrations of plant sterols in her plasma. All our patients were female bringing the male:female ratio in reported cases to 8:23. All were at or below the 50th percentile for height and weight, and presented at some stage with borderline, hypochromic anaemia associated with red cell abnormalities and thrombocytopaenia. The oldest patient showed suggestive clinical evidence of atherosclerosis affecting her aorta, ileofemoral bifurcation and possibly coronary arteries. All homozygotes responded to a diet restricted in phytosterols and the administration of cholestyramine with falls in plasma sterols of up to 68%. The recent discovery of a possible inherited defect in the synthesis of HMG CoA reductase in patients with phytosterolaemia makes this disorder a model system for studying the biological role of this enzyme in regulating the absorption and clearance of sterols other than cholesterol, and the factors governing the sterol composition of cell membranes.
Assuntos
Hidroximetilglutaril-CoA Redutases/deficiência , Fitosteróis/sangue , Xantomatose/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Linhagem , África do Sul , Tendões , Xantomatose/genéticaRESUMO
This study defines and illustrates the connections and differences between an idealizing and capacitating relationship. We first identified the patient's requirements for an idealized object, both to facilitate the reinforcement of a circumscribed but positive sense of herself, and to ward off dysphoric affect states in the domains of core- and intersubjective relatedness. These requirements were then distinguished from her need at a deeper level (the true self) to find a capacitating object to affirm, tolerate, and contain the full range of affects in her lived experience with others. These two sets of requirements have a different feel in the transference; and countertransference responses may be a valuable means of recognizing and distinguishing each as elements of different structures of self-organization.
Assuntos
Desenvolvimento da Personalidade , Teoria Psicanalítica , Terapia Psicanalítica , Autoimagem , Adulto , Feminino , Humanos , Individuação , Relações Interpessoais , Apego ao Objeto , Relações Médico-PacienteRESUMO
Lipoprotein lipase (LPL) plays a crucial role in the hydrolysis of the triglyceride core of circulating chylomicrons and very low density lipoproteins (VLDL) and also has a major effect on the levels and lipid composition of high density lipoproteins (HDL). LPL deficiency is inherited as an autosomal recessive trait and most commonly presents with chylomicronaemia, abdominal pain, and eruptive xanthomata. We have previously described a mutation in exon 5 of the LPL gene which results in a substitution of glutamic acid for glycine at amino acid 188. We have now assessed 16 South African LPL deficient patients from nine separate kindreds for this mutation. Nine of these probands were homozygous for the mutation and were from four families, all of Indian descent. The ancestors of these probands have their origins in villages close to Bombay, India, which suggests a common ancestral mutation for the four Indian kindreds, particularly as the mutant allele in each family carried the identical restriction fragment length polymorphism (RFLP) haplotype. The presence of at least nine affected subjects in this small community around Cape Town is evidence for a higher than expected gene frequency for LPL deficiency in this population.
Assuntos
Lipase Lipoproteica/genética , Mutação/genética , Sequência de Bases , DNA/genética , DNA/isolamento & purificação , Feminino , Frequência do Gene , Glutamina , Glicina , Humanos , Índia/etnologia , Lipase Lipoproteica/deficiência , Masculino , Dados de Sequência Molecular , Linhagem , Polimorfismo de Fragmento de Restrição , África do SulRESUMO
A comparison of the effects of two low-dose oral contraceptives on lipid metabolism was undertaken in an open-group comparative design study at the Family Planning Clinic, Groote Schuur Hospital, Cape Town. Sixty healthy women aged 18-35 years requesting oral contraception were allocated alternately to use a monophasic oral contraceptive containing 30 micrograms ethinyloestradiol and 150 micrograms desogestrel (Marvelon, group A), or a triphasic oral contraceptive containing 30-40 micrograms ethinyloestradiol and 50-125 micrograms levonorgestrel (Triphasil, group B). The changes in the lipoprotein profile elicited by the two preparations differed significantly. Group A subjects had a much greater triglyceridaemic response (42.4%) than group B (14.6%) and had a significant increase in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (Apo-A1). In group B, HDL-C decreased and Apo-A1 showed little change. Non-HDL-C (NHDL-C) and Apo-B levels hardly changed in either group. The atherogenic ratios, NHDL-C/HDL-C and Apo-B/Apo-A1 were higher in group B. This study confirmed a significant difference in the response of plasma lipoproteins to the two oral contraceptive preparations. The evidence suggests that the desogestrel-containing oral contraceptive elicits a less atherogenic lipoprotein profile than does the levonorgestrel-containing preparation. Although unsupported by direct clinical evidence that changes in the lipoprotein pattern induced by oral contraceptives cause atherosclerosis, these effects should be considered when prescribing oral contraceptives for women who have risk factors for cardiovascular disease.
Assuntos
Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Sintéticos/farmacologia , Etinilestradiol/farmacologia , Lipoproteínas/sangue , Norgestrel/farmacologia , Norpregnenos/farmacologia , Congêneres da Progesterona/farmacologia , Adolescente , Adulto , Fatores Etários , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , HDL-Colesterol/sangue , Desogestrel , Combinação Etinil Estradiol e Norgestrel , Feminino , Humanos , Triglicerídeos/sangueRESUMO
Serum cholinesterase (CHE) activity falls dramatically with organophosphate poisoning. In view of the need for an accurate, reproducible and inexpensive method for screening large numbers of farmworkers and others exposed to organophosphates, a manual commercial method was modified for use on an automated (centrifugal) chemistry analyser. The resultant procedure can be performed rapidly with a 24-fold cost-saving over the manual method. The volume of sample required is small, results of the automated and manual method showed excellent correlation and the reproducibility characteristics of the automated assay procedure was adequate for clinical use. Reference ranges were determined on children and adults. The results best fitted two reference ranges: children and adult females had a combined mean of 5,687 U/I with a lower (2,5 percentile) and upper (97,5 percentile) limit of 3,070 U/I and 8,483 U/I, respectively. The corresponding figures for adult men were 8,607 U/I (mean), 4,687 U/I and 9,116 U/I. The results also strongly suggested that pregnant women and women taking oral contraceptives had CHE activities approximately 12% lower than the female reference range quoted above. The numbers evaluated were too small, however, to construct a separate reference range for this category.
Assuntos
Colinesterases/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Métodos , Pessoa de Meia-Idade , Gravidez , Kit de Reagentes para Diagnóstico , Valores de ReferênciaRESUMO
An automated assay for plasma cholinesterase (CHE) activity (EC 3.1.1.8) was used to screen 44 farmworkers engaged in fruit crop spraying in the Somerset West, CP, area. Seven had markedly reduced CHE activity, at least 30% below the lower limit of the urban reference range, while the group as a whole had moderately depressed levels. A screen of 14 nursery-workers from the same farm showed a similar picture with the 1 individual engaged in spraying duties having an extremely low CHE activity of 1,595 U/I (lower normal limit for adult males is 4,687 U/I). Clinical complaints were few and were described as 'asthma' and 'chronic bronchitis' by the nursing sister in charge of the staff clinic. The mean body mass of the 7 farmworkers with substantially reduced CHE activities was 7,4 kg lower than the others and this was accompanied by significantly diminished body mass index. Removal of the 7 worst affected individuals from spraying duties for a period of 6 weeks resulted in a statistically significant increase in CHE activity of 1,700 U/I, whereas the values in the remaining workers remained unchanged. These results strongly suggest that at least 17,5% of male rural workers engaged in crop spraying suffer from chronic organosphosphate poisoning. The somewhat depressed levels of CHE activity in the rural group as a whole may also reflect chronic exposure of a lesser degree. All 7 female workers tested had enzyme activities within the normal range.
Assuntos
Doenças dos Trabalhadores Agrícolas/enzimologia , Colinesterases/sangue , Inseticidas/intoxicação , Compostos Organofosforados , Feminino , Humanos , Masculino , Exposição Ocupacional , População RuralRESUMO
The retinyl palmitate fat tolerance test was used to measure chylomicron remnant clearance in 10 normal subjects (apolipoprotein E [apo E] isotypes 3 or 4 only), 6 normolipidemic apo E2/2 homozygotes and 5 familial hypercholesterolemic homozygotes. Skin fibroblasts with fully upregulated LDL receptors from the latter subjects degraded rabbit 125I-beta VLDL in vitro at rates ranging from less than 10-48% of normal. Experiments in vivo revealed no significant differences between the normal and homozygous familial hypercholesterolemic (FHH) subjects in chylomicron remnant clearance assessed on the basis of "areas under the curves" for retinyl palmitate levels present in post-prandial serum, chylomicron remnants (Sf. less than 1,000), or chylomicrons (Sf. greater than 1,000). Remnant clearance was greatly decreased at all times in the apo E2/2 homozygotes, indicative of an important degree of flux control exerted by a receptor-mediated step involving apo E as ligand. The absence of any excess remnant accumulation in FHH subjects with varying "impairment" of LDL receptor-mediated degradation of apo E-containing lipoproteins, permits the conclusion that chylomicron remnants are initially cleared from the plasma by apo E-recognizing receptors which are genetically distinct from LDL receptors.
Assuntos
Quilomícrons/metabolismo , Hiperlipoproteinemia Tipo II/metabolismo , Receptores de LDL/fisiologia , Adolescente , Adulto , Células Cultivadas , Diterpenos , Feminino , Homozigoto , Humanos , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/metabolismo , Masculino , Taxa de Depuração Metabólica , Ésteres de Retinil , Vitamina A/análogos & derivados , Vitamina A/metabolismoRESUMO
A black patient with homozygous familial hypercholesterolaemia associated with ischaemic heart disease and a fatal outcome is described. The appearances of the coronary artery and aortic lesions on histological examination at autopsy were identical to those of typical atherosclerosis.
Assuntos
Doença da Artéria Coronariana/complicações , Hiperlipoproteinemia Tipo II/complicações , Adulto , População Negra , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Humanos , MasculinoRESUMO
To determine whether the metabolism of diet-derived triglycerides (TG) is acutely regulated by the consumption of insulinogenic carbohydrates, we measured the effects of glucose ingestion on oral and intravenous fat tolerance, and on serum triglyceride concentrations obtained during duodenal fat perfusion. Postprandial lipemia was diminished by the ingestion of 50 g (148 +/- 121 mg.dl-1 x 7 h-1 vs 192 +/- 124 mg.dl-1 x 7 h-1, P less than 0.05) and 100 g (104 +/- 106 mg.dl-1 x 7 h-1 vs 171 +/- 104 mg.dl-1 x 7 h-1, P less than 0.05) glucose. Peak postprandial TG concentrations occurred later after meals containing glucose and fat than after meals containing fat alone. This effect could be reproduced when an iso-osmotic quantity of urea was substituted for glucose in the test meal. Starch ingestion had no discernible effect on postprandial lipemia. Intravenous fat tolerance was similar before (4.9 +/- 1.2%.min-1) and 2 h (4.4 +/- 1.3%.min-1) and 4 h (4.8 +/- 1.5%.min-1) after 50 g glucose ingestion. During duodenal fat perfusion, glucose ingestion caused a progressive decrease in plasma triglyceride concentrations. These data suggest that glucose ingestion diminishes postprandial lipemia in a dose-dependent manner, but that this effect is not due to increased clearance of triglyceride from the circulation. The hypotriglyceridemic effects of glucose appear to reflect delayed gastric emptying and decreased hepatic secretion of triglyceride.
Assuntos
Gorduras na Dieta/administração & dosagem , Glucose/administração & dosagem , Lipase Lipoproteica/metabolismo , Triglicerídeos/sangue , Adulto , Ingestão de Alimentos , Emulsões Gordurosas Intravenosas/administração & dosagem , Feminino , Heparina/farmacologia , Humanos , Masculino , Fatores de TempoRESUMO
PURPOSE: To determine the biochemical and clinical response of two patients with homozygous familial hypercholesterolemia to three different schedules of low-density lipoprotein apheresis compared with plasmapheresis. PATIENTS AND METHODS: Two female patients aged 17 years, both affected by homozygous familial hypercholesterolemia, underwent low-density lipoprotein apheresis using a dextran-sulfate/cellulose affinity column on successive twice-weekly, weekly, and biweekly schedules. Plasmapheresis was carried out only at biweekly intervals. Plasma lipids and apolipoproteins A1 and B were assayed before and after each procedure. Cardiac status was assessed before and after the study. RESULTS: On schedule 1 of apheresis, the immediate post-procedure low-density lipoprotein cholesterol levels declined to 60 mg/100 dL plasma. Quasi-steady-state values of low-density lipoprotein cholesterol and apolipoprotein B were also markedly reduced, with levels approaching the upper limits of normal for age and sex. This response was attenuated as the intervals between procedures were prolonged. No advantage of low-density lipoprotein apheresis over plasmapheresis was observed during the biweekly protocol except that after plasmapheresis high-density lipoprotein cholesterol levels declined by 50% or more compared with less than 10% after apheresis. The latter procedure, especially on schedules 1 and 2, caused an increase in the quasi-steady-state concentrations of both high-density lipoprotein cholesterol and apolipoprotein A1. Thus, mean low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apolipoprotein B/apo A1 ratios were reduced by more than three- to four-fold during twice-weekly apheresis. Other laboratory parameters remained stable throughout except for iron and hemoglobin levels, which were reduced with both plasmapheresis and apheresis. Xanthomas regressed significantly in the one patient who had not been treated prior to the current trial. Cardiac changes were minor in both patients. CONCLUSION: Low-density lipoprotein apheresis proved safe and effective on an accelerated protocol as well as during more conventional schedules. Owing to its simplicity, selectivity, and safety, apheresis using a dextran-sulfate/cellulose column is possibly the optimum means currently available for the extracorporeal removal of low-density lipoprotein cholesterol.
Assuntos
Remoção de Componentes Sanguíneos/métodos , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/terapia , Plasmaferese , Adolescente , Apolipoproteína A-I , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , Colesterol/sangue , HDL-Colesterol/sangue , Feminino , Dermatoses da Mão/terapia , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Lipoproteínas HDL/sangue , Triglicerídeos/sangue , Xantomatose/terapiaRESUMO
Ten restriction fragment length polymorphisms of the LDL receptor gene were used for haplotype analysis in 12 unrelated patients with homozygous familial hypercholesterolemia. These patients were drawn from the Black, Coloured, and White population groups and collectively represent 24 mutant alleles underlying the FH phenotype. Five distinct haplotypes were detected. Hybridization analysis using DNA codigested with EcoRI and PstI revealed that haplotype IV was associated with two distinct mutations. When coupled to the recent demonstration by other workers of two receptor defects in South African Afrikaners homozygous for FH and haplotype I, these data are suggestive of at least seven distinct LDL receptor mutations in the FH patients examined and thus in the general South African population.