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Biomedical subjects

C Lombard

Publications and source records attributed to C Lombard.

At least 55 records · Page 3Linked to original sources
PubMed1996

Hypertension in the black community of the Cape Peninsula, South Africa.

Hypertension prevalence, treatment status and factors relating to high blood pressure were determined in an urban black community of the Cape Peninsula, South Africa. A study population of 986 subjects aged 15-64 years was randomly selected. Blood pressure, height, weight and serum cholesterol levels were measured, while demographic information, personal and family history relating to hypertension and attendance of health services were determined by questionnaire. Overall 9.2% of males and 12.9% of females were hypertensive according to WHO criteria. Blood pressures between 160/95 and 140/90 mmHg were found in 10% of males and 10.5% of females. The treatment status of hypertensives showed that 24.3% had a blood pressure below 160/95 mmHg, and 16% below 140/90 mmHg. Hypertensives used more alcohol and were more overweight than normotensives. Multiple logistic regression revealed that hypertension was independently related to age, being overweight and more urbanised. The degree of urbanisation also predicted to what extent hypertension prevalence increases with age. This black population had low hypertension rates compared with other similar groups in South Africa. These data suggest that as rural blacks increasingly undergo urbanisation, hypertension prevalence increases. Necessary diagnostic and treatment regimens and hypertension services are not yet in place in the South African health services, and need to be established.

Adolescent↗
PubMed1995

Amino acids of the third transmembrane domain of the AT1A angiotensin II receptor are involved in the differential recognition of peptide and nonpeptide ligands.

The differential role of amino acids of the third transmembrane domain on peptide and nonpeptide recognition by the AT1 angiotensin II receptor has been evidenced. The mutation of Ser105 into alanine completely abolished peptide agonist and antagonist binding, while the binding of nonpeptide ligands, including the original radioligands [3H] LF 7-0156 and [3H] LF 8-0129, was more moderately affected. Reverse pharmacological changes, i.e., unchanged affinities for peptide agonists or antagonists and drastically reduced affinities for nonpeptide antagonists, were observed upon alanine replacement of Asn111. These results confirm that the binding sites for peptide and nonpeptide molecules are not totally overlapping and delineate new amino acids as candidates for the selective receptor interaction with the two categories of ligands. Their integration in topographical studies is discussed.

Amino Acids↗
PubMed1995

Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat.

Plants contain compounds with oestrogen-like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30-70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively < 0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.

Adult↗
PubMed1994

Tyr292 in the seventh transmembrane domain of the AT1A angiotensin II receptor is essential for its coupling to phospholipase C.

An essential role of the conserved Asp74 in the coupling of the type 1 angiotensin II (AII) receptor (AT1) to phospholipase C has already been reported (Bihoreau, C., Monnot, C., Davies, E., Teutsch, B., Bernstein, K. B., Corvol, P., and Clauser, E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 5133-5137). Moreover, preliminary modeling studies have shown that a spatial proximity exists between Asp74, located in transmembrane domain II, and Tyr292, located in transmembrane domain VII and conserved in many, but not all, G protein-coupled receptors. We mutated Tyr292 into Phe and evaluated the pharmacological and activation characteristics of the mutated receptor (Y292F) stably expressed in Chinese hamster ovary cells. This receptor possessed unchanged binding properties for agonist or antagonist peptide ligands compared to the wild-type receptor, while its coupling to phospholipase C was severely impaired. Interestingly, competition binding experiments, using 125I-[Sar1]AII as a tracer ligand, showed that the Y292F receptor displayed an increased Ki value for DuP 753, an AT1-specific nonpeptide antagonist and a greatly decreased Ki value for the AT2-specific ligand CGP 42112A. These pharmacological changes are similar to those observed for the previously reported mutation of Asp74 into Asn. This apparently symmetrical role of Asp74 and Tyr292 is consistent with the hypothesis that an interaction between these two amino acids could be a key event in the molecular processes linking AII recognition and AT1 receptor activation.

Animals↗
PubMed1994

Urinary element concentrations in kidney stone formers and normal controls: the week-end effect.

Early morning urines were collected on each of three days (Monday-Wednesday) from 19 male stone-formers and 20 healthy male controls. Concentrations of 10 elements were determined using inductively coupled plasma atomic emission spectroscopy, graphite furnace atomic absorption spectroscopy and particle induced x-ray emission spectrometry. Data were treated using multivariate statistical methods. The results showed that the concentrations of several elements in the control urines were significantly raised on Mondays and that controls and stone formers differed with respect to certain elements, also on Mondays. The observed elevations were termed the "weekend effect". It is suggested that while stone-formers may regulate their diets throughout the entire week, normals may indulge in dietary excesses over the weekend. The weekend effect highlights the danger of placing too much emphasis on a single measurement of a urinary parameter and alerts investigators to take cognizance of the day on which urine collections are effected, especially when attempting to identify abnormal renal excretion patterns in stone-formers by comparison of their urinary variables with those of controls.

Humans↗
PubMed1994

Properties of [3H]LF 7-0156, a new nonpeptide antagonist radioligand for the type 1 angiotensin II receptor.

LF 7-0156 (2-[[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol- 5-yl]methyl]amino]benzoic acid) is a nonpeptide angiotensin II receptor antagonist selective for the type 1 angiotensin receptor. In rabbit aortic rings, LF 7-0156 competitively antagonized angiotensin II-induced contractile responses, with a pA2 value of 8.44. The synthesis of the radiolabeled compound [3H]LF 7-0156 has allowed direct binding studies with several membrane or cell preparations. Consistent with competition experiments, the binding of [3H]LF 7-0156 to purified rat liver membranes was characterized by a Kd value of 12.6 nM and very low pseudospecific or nonspecific binding; this latter characteristic confers to this compound an advantage over the structurally different compound [3H]DuP 753, which is the only commercially available nonpeptide radioligand. [3H]LF 7-0156 also bound to the type 1A angiotensin receptor expressed in Chinese hamster ovary cells, with high affinity (Kd = 3.5 nM) and a total absence of nonspecific binding. Functional antagonism in this cell system was assessed by the ability of LF 7-0156 to reverse angiotensin II-induced inositol phosphate production. These properties make [3H]LF 7-0156 an interesting pharmacological tool and should allow future evaluation of recognition of the nonpeptide ligand by mutated receptors expressed in Chinese hamster ovary cells; it will facilitate the analysis of possible differences in receptor amino acids involved in the binding of peptide and nonpeptide ligands, as well as the extent of spatial overlap between several nonpeptide antagonists displaying different structural properties.

Alkylating Agents↗
PubMed1993

Deglycosylation and fragmentation of purified rat liver angiotensin II receptor: application to the mapping of hormone-binding domains.

We report new structural data about the rat liver angiotensin II receptor, which belongs to the AT1 subclass. This receptor has been purified at analytical or semi-preparative levels by a previously described strategy involving its photolabelling with a biotinylated azido probe and selective adsorption of the covalent probe-receptor complexes to immobilized streptavidin [Marie, Seyer, Lombard, Desarnaud, Aumelas, Jard and Bonnafous (1990) Biochemistry 29, 8943-8950]. Chemical or enzymic deglycosylation of the purified receptor has shown a shift in its molecular mass from 65 kDa to 40 kDa. Fragmentation of the purified receptor was carried out with V8 protease from Staphylococcus aureus, CNBr and trypsin. It was possible to find trypsin-treatment conditions which allowed production of a 6 kDa probe-fragment complex with a satisfactory yield. Attempts to localize this small fragment (5 kDa after subtraction of the probe contribution) in the recently published rat AT1 receptor sequence are reported. As expected, this fragment is not glycosylated; moreover, its further fragmentation by CNBr induces a very slight decrease in its size. These data support the hypothesis that a receptor sequence comprising the third transmembrane domain and adjacent portions of extra- and intracellular loops is involved in photolabelling by the C-terminal azidophenylalanine of the angiotensin-derived probe. These preliminary results are discussed in terms of future prospects for the characterization of hormone-binding domains of angiotensin II receptors.

Amino Acid Sequence↗
PubMed1993

The ability of the hemizona assay to predict human fertilization in different and consecutive in-vitro fertilization cycles.

The objective of this prospective study was to examine the ability of the hemizona assay (HZA) to predict fertilization outcome of mature, pre-ovulatory oocytes under in-vitro fertilization (IVF) conditions. Since a large number of patients were evaluated over a long period, the power of the HZA to prognosticate fertilization results in the same and subsequent (consecutive) IVF cycles of those same patients was assessed. For IVF, only metaphase II oocytes were used. For the HZA, both fresh oocytes donated by patients at the time of IVF and oocytes recovered from surgically removed ovarian tissue (and salt-stored) were used, and bisected by micromanipulation techniques. Matching hemizonae were co-incubated either with spermatozoa from the patient (test) or from a fertile man (control) for 4 h. The number of spermatozoa tightly bound to the zona was counted. Patients (n = 112) were divided into two groups based on HZA results (expressed as HZA index or HZI): HZI > or = 30% (n = 72) and < 30% (n = 40). The patients with HZI < 30% had significantly lower fertilization rates in both the HZA-IVF cycle and in subsequent cycles compared to patients with HZI > or = 30% (P < 0.03). Linear discriminant analysis indicated the HZA to have a sensitivity of 84%, and positive and negative predictive values of 85 and 70% respectively, for prediction of fertilization outcome in a total of 233 cycles. It was concluded that the HZA is a good predictor of fertilization rate in vitro, and can be used in the IVF setting to supply additional clinical information in male-factor patients.

Female↗
PubMed1992

Protein purification using combined streptavidin (or avidin)-Sepharose and thiopropyl-Sepharose affinity chromatography.

The major problem usually encountered in the application of the (strept)avidin-biotin system to the purification of proteins (or other biological molecules) lies in the difficult reversion of the interaction between immobilized (strept)avidin and the adsorbed biotinylated protein. Among the proposed solutions is the selective biotinylation of the entity to be purified by a disulphide-containing biotinylated reagent which allows its recovery from (strept)avidin gels by dithiothreitol (DTT) treatment. As emphasized by the example of angiotensin II receptor purification, achieved using this strategy, optimum reduction of this disulphide bridge may require improvement of its accessibility using denaturating agents such as sodium dodecyl sulphate or urea. However, these agents release important amounts of (strept)avidin. Two general ways of solving this problem are proposed. One solution takes advantage of the absence of cysteine in the streptavidin sequence: the protein to be purified is selectively readsorbed to thiopropyl-Sepharose through the thiol function generated on DTT cleavage of the biotinylated reagent. The other solution is an empirical approach to make possible the use of avidin, which possesses cysteine residues: combined avidin-Sepharose and thiopropyl-Sepharose chromatography proved efficient when carried out in the presence of urea as denaturing agent.

Animals↗
PubMed1992

The effect of morphine and naloxone administration on plasma oxytocin concentrations in the first stage of labour.

OBJECTIVE: We investigated the effect of an opiate (morphine) and an opiate antagonist (naloxone) on the maternal secretion of oxytocin in the first stage of labour. DESIGN: Patients were randomized to receive either morphine 5 mg (n = 9), naloxone 1.2 mg (n = 10) or sterile water (n = 9) which was injected intravenously. PATIENTS: Healthy women in the first stage of labour between 3 and 6 cm dilated with no prior analgesia or oxytocin administration were recruited for the study. MEASUREMENTS: Peripheral maternal oxytocin levels were measured by radioimmunoassay for 15 minutes before and 15 minutes after administration of the assigned substance. Sampling was at 2.5 minute intervals. RESULTS: Significant reduction in the mean oxytocin concentration was found in the patients who received morphine (-2.62 pmol/l/sample) but no change was found in the naloxone group (+0.57 pmol/l/sample) when compared with controls (+0.64 pmol/l/sample). CONCLUSION: Maternal oxytocin secretion is inhibited by exogenous opiates in the first stage of labour while an effect of opiate antagonism was not demonstrated.

Adult↗
PubMed1991

Plasma arginine vasopressin and the syndrome of inappropriate antidiuretic hormone secretion in tuberculous meningitis.

Biochemical evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was documented in 17 of 24 (71%) children with tuberculous meningitis. Plasma arginine vasopressin concentrations in patients with signs of SIADH were significantly higher (median, 15.44 (range, 1.62 to greater than 24.52) pg/ml; n = 14) than those without (median, 1.91 (range, 0.44 to 4.91) pg/ml; n = 6) (P less than 0.002). Patients who developed evidence of SIADH were older than those who did not (median, 34 (range, 6 to 101) months vs. 10 (range, 6 to 38) months; P less than 0.007). Five patients with and none without died. In 9 patients evidence of SIADH developed only after hospitalization. These patients received a median of 58 (range, 28 to 109) ml/kg/day fluids (n = 7) before developing evidence of SIADH compared with 107 (range, 58 to 146) ml/kg/day received by patients who did not develop SIADH (n = 6) (P = 0.035). SIADH occurs commonly and its presence appears to influence the outcome of tuberculous meningitis in children.

Arginine Vasopressin↗
PubMed1991

Tetralogy of Fallot and segmental uterine aplasia in a three-year-old Morgan filly.

A 3-year-old Morgan filly was presented to the University of Florida, Veterinary Medical Teaching Hospital, for heart murmur, poor growth, and progressive exercise intolerance. Thoracic radiographs, cardiac ultrasound, cardiac catheterization, and differential blood gases were utilized to tentatively diagnose tetralogy of Fallot. Postmortem examination confirmed tetralogy of Fallot and additionally revealed segmental uterine aplasia.

Animals↗
PubMed1990

Affinity chromatography purification of angiotensin II receptor using photoactivable biotinylated probes.

We have developed biotinylated photoactivable probes that are suitable for covalent labeling of angiotensin II (AII) receptors and the subsequent purification of covalent complexes through immobilized avidin or streptavidin. One of these probes, biotin-NH(CH2)2SS(CH2)2CO-[Ala1,Phe(4N3)8]AII, which contains a cleavable disulfide bridge in its spacer arm and which displays, in its radioiodinated form, very high affinity for AII receptors (Kd approximately 1 nM), proved to be suitable for indirect affinity chromatography of rat liver receptor with facilitated recovery from avidin gels by use of reducing agents. This constituted the central step of an efficient partial purification scheme involving hydroxylapatite chromatography, streptavidin chromatography, and thiopropyl-Sepharose chromatography. SDS-PAGE analysis and autoradiography established the identity of the purified entity (molecular weight 65K) as the AII receptor. Possible ways of completing purification to homogeneity and extrapolation of the protocols to a preparative scale are discussed, as well as the potential contribution of our new probes to the study of the structural properties of angiotensin receptors.

Amino Acid Sequence↗
PubMed1990

Immunohistochemical and cytogenetic studies indicate that malignant angioendotheliomatosis is a primary intravascular (angiotropic) lymphoma.

The authors performed immunohistochemical and cytogenetic studies in a 73-year old man with malignant angioendotheliomatosis. The patient was referred for evaluation of fever of unknown origin, hepatic failure, and neurologic deterioration. Examination of a muscle biopsy revealed numerous, noncohesive atypical mononuclear cells within small vessels. These cells stained positively with a pan-leukocyte marker CD45(PD7/26/16) and with a B-cell marker L26 but negatively with Factor VIII-related antigen, an endothelial cell marker. Peripheral blood obtained before chemotherapy was cultured and analyzed by the G-band method. A new translocation and numerous chromosomal aberrations were identified. The major cell line karyotype was 53,XY, +X, +5q?,-6, +i(6p), +7, -10, +11, -12, +12p-, +12p-, +18, +mar1, +mar2, t(1;3)(p22;p21),3q+,8p+. This is the first cytogenetic study performed in a case of malignant angioendotheliomatosis. Our findings demonstrate that the neoplastic cells in this disorder circulate in the peripheral blood and provide further evidence that malignant angioendotheliomatosis is a diffuse intravascular neoplasm of lymphoid origin. Furthermore, the authors conclude that this malignant lymphoproliferative disorder should be reclassified as a primary intravascular (angiotropic) lymphoma.

Aged↗
PubMed1990

A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation.

Based on a clinicopathologic study of 34 patients with biopsy-confirmed diffuse pulmonary hemorrhage (DPH), we present an approach to the differential diagnosis of DPH with attention to histologic features such as capillaritis and the importance of laboratory tests such as anticytoplasmic autoantibodies (ACPA). The following DPH syndromes were encountered: antibasement membrane antibody (ABMA) disease (four cases); idiopathic pulmonary hemorrhage (four cases); Wegener's granulomatosis (WG) (five cases); probable WG (six cases); systemic necrotizing vasculitis otherwise unclassified (three cases); systemic lupus erythematosus (two cases); rheumatoid arthritis (one case); seronegative juvenile rheumatoid arthritis (one case); IgA nephropathy (one case); idiopathic glomerulonephritis (two cases--one with and one without immune complexes); and unclassified pulmonary-renal syndromes (five cases). Capillaritis was found in lung biopsy samples from 30 of the 34 patients (88%) and included patients with every type of DPH syndrome. Serologic testing for ACPA was useful in the diagnosis of WG. Identification of ABMA in the serum, kidney, or lung was the defining feature for the diagnosis of ABMA-mediated disease. Subclassification of the cases could not be done solely on histologic grounds except for cases of WG that showed granulomatous inflammation, foci of necrosis, or vasculitis. Classification of the remaining cases required correlation with (a) clinical and laboratory data; (b) biopsy samples from other sites such as the kidney, nasal sinuses, or skin; and (c) results of immunofluorescence or electron microscopy of kidney or lung biopsy samples.

Adolescent↗
PubMed1990

Characterization of the angiotensin II receptor.

We present a brief overview of the present knowledge on the structural and molecular properties of angiotensin II receptors and the various attempts to determine their primary structures, with special reference to our strategy for receptor purification. The strategy involves covalent labeling of the receptor with synthetic biotinylated photoactivatable probes, followed by indirect affinity chromatography on immobilized streptavidin. The various applications of these probes to the study of structural and molecular properties and to the cell biology of angiotensin II receptors are discussed.

Amino Acid Sequence↗