Developing a district diabetes register.
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Diabetes Mellitus↗
Biomedical subjects
C Lambert
Publications and source records attributed to C Lambert.
The development of monoclonal antibodies to the human mitochondrial 60-kd heat-shock protein, and their use in studying the expression of the protein in rheumatoid arthritis.
OBJECTIVE: To assess the claim that the human 60-kd heat-shock protein (HSP) is highly expressed in the joints of patients with rheumatoid arthritis (RA), but is not readily detected in normal tissues. METHODS: Monoclonal antibodies were raised against the human 60-kd mitochondrial heat-shock protein (P1 protein; hsp60), and their specificity was established. They were then applied to synovial tissue. RESULTS: HSP was expressed similarly in normal, osteoarthritic, and RA synovium. Low levels of hsp60 were detected in synovial fluid by immunoprecipitation. CONCLUSION: Minor differences in the distribution of hsp60 in synovium from RA joints were attributable to increased cellularity and to the disorganization of the tissue architecture.
Animals↗
Effect of congestive heart failure on clentiazem pharmacokinetics in a dog model.
Clentiazem, 8-chloro diltiazem, is a calcium channel blocker currently undergoing evaluation for the treatment of stable angina and hypertension. As patients with ischaemic disorders often present some degree of heart failure, the aim of this study was to investigate the effect of congestive heart failure on clentiazem (200 micrograms kg-1, i.v. bolus) pharmacokinetics in a canine model. Congestive heart failure was induced in six dogs by rapid ventricular pacing (240 beats min-1) for 3-5 weeks. Clentiazem pharmacokinetics was studied in each dog under the control condition and after the development of clinical signs of heart failure (ascites, dyspnea, fatigue). Blood samples were collected up to 480 min post-dose. Clentiazem plasma concentrations were determined by high performance liquid chromatography. The area under the plasma concentration versus time curves (AUC0-infinity) was significantly increased in congestive heart failure dogs (8.8 +/- 1.6 vs 21.8 +/- 1.4 micrograms min ml-1) (mean +/- SEM). These changes were related to a reduction of the volume of distribution of the central compartment (0.9 +/- 0.1 vs 0.2 +/- 0.11 kg-1) and total body clearance (1.9 +/- 0.4 vs 0.7 +/- 0.21 h-1 kg-1). It is concluded that, in our model, congestive heart failure significantly modifies clentiazem disposition. These results suggest that caution should be exercised when clentiazem is given to patients with a low ejection fraction and a compromised cardiac function. Reduced loading and maintenance doses might be recommended in patients with severe congestive heart failure.
Animals↗
Evaluation of osmium(II)-nitrosyl complexes as a method to increase the yield of the 191Os-191mIr generator.
The nitrosyl complexes pentachloronitrosylosmate(II), [OsCl5(NO)]2-, and hydroxytetranitronitrosylosmate(II), [Os(OH)(NO2)4(NO)]2-, were evaluated as parent species for use on the 191Os-191mIr generator in an attempt to increase the 191mIr yield of the generator by providing a direct route to a chemically stable 191mIr daughter. The uptake of the 191Os-labeled complexes by the inorganic ion-exchangers ZrO2, SnO2, PbS, MnO2 and Al2O3 and the organic resin AG MP-1 was measured and prototype generators were prepared using those exchangers that demonstrated greater than 90% uptake of the 191Os-labeled complexes. The 191mIr(III)-nitrosyl complexes produced subsequent to beta- decay of the 191Os-nitrosyl parent complexes were found to undergo secondary chemical reactions to form nitro (NO2-) complexes that were tightly retained on the ion exchanger limiting 191mIr yield to less than 5%.
Iridium Radioisotopes↗
Characterization of regulatory functions of the varicella-zoster virus gene 63-encoded protein.
Varicella-zoster virus (VZV) gene 63 encodes a protein (IE63) with a predicted molecular mass of 30.5 kDa which has amino acid similarities to the immediate-early (IE) protein 22 (ICP22) of herpes simplex virus type 1. ICP22 is a polypeptide synthesized in herpes simplex virus type 1-infected cells, and as is the case for its VZV counterpart, its regulatory functions are unknown. On the basis of the VZV DNA sequence, it has been shown that IE63 exhibits hydrophilic and acidic properties, suggesting that this protein could play a regulatory role during the infectious cycle. We report in this article cotransfection experiments which demonstrate that the VZV gene 63 protein strongly represses, in a dose-dependent manner, the expression of VZV gene 62. On the other hand, transient expression of the VZV gene 63 protein can promote activation of the thymidine kinase gene but cannot affect the expression of the genes encoding glycoproteins I and II. The results of transient expression experiments strongly suggest that the VZV gene 63 protein could play a pivotal role in the repression of IE gene expression as well as in the activation of early gene expression.
Animals↗
Carotene-oxygen radical interactions.
All-trans beta-carotene radical anion efficiently transfers an electron to oxygen but the reverse reaction is not observed and, instead we suggest the formation of a beta-carotene-superoxide radical addition complex. On the other hand, all-trans lycopene undergoes a reversible electron transfer with the superoxide radical. This distinctive behaviour may be related to the anti-cancer properties of these molecules.
Anticarcinogenic Agents↗
Modern management practices applied in a county health department.
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Health Services Administration↗
Functional complementation of ataxia-telangiectasia group D (AT-D) cells by microcell-mediated chromosome transfer and mapping of the AT-D locus to the region 11q22-23.
The hereditary human disease ataxia-telangiectasia (AT) is characterized by phenotypic complexity at the cellular level. We show that multiple mutant phenotypes of immortalized AT cells from genetic complementation group D (AT-D) are corrected after the introduction of a single human chromosome from a human-mouse hybrid line by microcell-mediated chromosome transfer. This chromosome is cytogenetically abnormal. It consists primarily of human chromosome 18, but it carries translocated material from the region 11q22-23, where one or more AT genes have been previously mapped by linkage analysis. A cytogenetically normal human chromosome 18 does not complement AT-D cells after microcell-mediated transfer, whereas a normal human chromosome 11 does. We conclude that the AT-D gene is located on chromosome 11q22-23.
Ataxia Telangiectasia↗
The role of oil and agalactosyl IgG in the induction of arthritis in rodent models.
The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 micrograms of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50-75 days, although levels at 150-200 days were not affected. The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p less than 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal(O) is raised, is more likely to evoke disease. Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.
Animals↗
Tissue distribution and bioactivity of amphotericin B administered in liposomes to cancer patients.
Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes). These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone). The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp. and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes. Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes. Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58-81% of concentrations measured by HPLC, whereas only 15-41% was recovered from the unextracted homogenates. Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC. These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes). Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue-bound amphotericin B is not bioactive. However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate.
Adult↗
Alpha-adrenoceptor subtypes and regional myocardial blood flow distribution during coronary occlusion in dogs.
The involvement of postsynaptic alpha-adrenoceptors in the distribution of regional myocardial blood flows (RMBFs, microsphere technique) within the left ventricle has been investigated during intermittent coronary artery occlusion in open-chest anesthetized dogs. Two types of RMBFs distribution were assessed: (1) between endocardial (endo) and epicardial (epi) layers (endo/epi ratio) and (2) between nonischemic (NIZ) and ischemic zones (IZ) (IZ/NIZ ratio). Equipressor does of selective alpha 1-(cirazoline after rauwolscine) and alpha 2-(UK-14,304 after prazosin) adrenoceptor agonists were infused in dogs previously submitted to ganglionic and muscarinic blockade. In a control group, aortic pressure was mechanically raised by aortic stenosis to levels similar to those reached with both alpha-adrenoceptor agonists. Cirazoline and aortic stenosis increased RMBFs in IZ and NIZ but did not alter the calculated coronary resistance in NIZ and did not affect endo/epi and IZ/NIZ ratios. In contrast, UK-14,304 preferentially augmented coronary resistance in NIZ, increased IZ/NIZ ratio (both P less than 0.05) but did not affect endo/epi ratio in IZ and NIZ. Thus, we conclude that if transmural distribution of RMBFs (endo/epi ratio) is not preferentially controlled by any alpha-adrenoceptor subtype, postsynaptic alpha 2-adrenoceptors are of importance during coronary occlusion in promoting a favorable redistribution of RMBFs from NIZ towards IZ by inducing a selective NIZ coronary vasoconstriction (ie a "reverse coronary steal").
Adrenergic alpha-Agonists↗
Direct effects in vivo of angiotensins I and II on the canine sinus node.
The chronotropic responses to angiotensins I and II (5 micrograms in 1 mL Tyrode's solution) injected into the sinus node artery were assessed before and after the intravenous administration of captopril (2 mg/kg) and saralasin (20 micrograms/kg) in anaesthetized dogs. The effects of angiotensin II given intravenously were also observed. The animals (n = 8) were vagotomized and pretreated with propranolol (1 mg/kg, i.v.) to prevent baroreceptor-mediated responses to increases in blood pressure. Injection of angiotensin I into the sinus node artery induced significant increases in heart rate (114 +/- 6 vs. 133 +/- 6 beats/min) and in systemic systolic (134 +/- 13 vs. 157 +/- 14 mmHg; 1 mmHg = 133.3 Pa) and diastolic (95 +/- 10 vs. 126 +/- 13 mmHg) blood pressures. Similar results were obtained when angiotensin II was injected into the sinus node artery, but intravenous injection induced changes in systolic (138 +/- 8 vs. 180 +/- 25 mmHg) and diastolic (103 +/- 8 vs. 145 +/- 20 mmHg) blood pressures only. Captopril induced a significant decrease in systolic (118 +/- 11 vs. 88 +/- 12 mmHg) and diastolic (84 +/- 9 vs. 59 +/- 9 mmHg) blood pressures without affecting the heart rate (109 +/- 6 vs. 106 +/- 6 beats/min). Saralasin produced a significant increase in systolic (109 +/- 7 vs. 126 +/- 12 mmHg) blood pressure only. Increments in heart rate and systolic and diastolic blood pressures in response to angiotensins I and II were, respectively, abolished by captopril and saralasin. It was concluded that angiotensin II has, in vivo, a direct positive chronotropic effect that can be blocked by saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Amiodarone antagonizes the effects of T3 at the receptor level: an additional mechanism for its in vivo hypothyroid-like effects.
Amiodarone is a diiodinated benzofuran derivative that has some structural similarities to the thyroid hormones and contains two iodine atoms per molecule. It has exhibited hypothyroid-like effects that are thought to be the result of an inhibition of thyroid hormone synthesis due to iodine load, a decrease in the T4 to T3 conversion, and (or) a competitive binding for T3 receptors. The aim of this study was to determine if this third mechanism contributes to the hypothyroid-like effects of amiodarone in vivo. To do so, some characteristic features known to be influenced by hypothyroidism were determined in surgically thyroidectomized rats (n = 48), which received replacement doses of T3 (0.5 and 1.0 microgram.100 g-1.day-1) with or without amiodarone (60 mg.kg-1.day-1). Thyroidectomy produced a hypothyroid state upon which amiodarone had no detectable effects except a negative body weight gain. T3 (0.5 microgram) nearly normalized the thyroid status of the animals, but the concomitant administration of amiodarone induced hypothyroid-like effects suggesting that these effects are dependent on T3. Higher doses of T3 (1.0 microgram) produced hyperthyroid-like effects and attenuated the effects of amiodarone. Unexpectedly, amiodarone decreased T3 plasma concentrations. To determine if the effects of amiodarone were the results of a decrease in T3 plasma and myocardial concentrations or a competition with T3 for its receptors, exogenous T3 pharmacokinetics were studied in thyroidectomized rats receiving T3 (0.5 microgram) with or without amiodarone. The results suggested that amiodarone increased T3 cardiac concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Amiodarone↗
Adaptations to swimming training: influence of training volume.
In an effort to assess the contributions of a period of increased training volume on swimming performance, two matched groups of collegiate male swimmers were studied before and during 25 wk of training. For the first 4 wk of this study, the two groups trained together in one session per day for approximately 1.5 h.d-1. During the following 6 wk (weeks 5-11), one group (LONG) trained two sessions per day, 1.5 h in the morning and 1.5 h in the afternoon. The other group (SHORT) continued to train once each day, in the afternoon with the LONG group. Over the final 14 wk of the study, both groups trained together in one session per day (1.5 h.d-1). Although the swimmers experienced significant improvements in swimming power, endurance, and performance throughout the 25 wk study, there were no differences between the groups. However, during the 6 wk period of increased training, the LONG group experienced a decline in sprinting velocity, whereas the SHORT group showed a significant increase in sprinting performance. The test results suggest that a 6 wk period of two 1.5 h training sessions per day does not enhance performance above that experienced with a single training session of 1.5 h each day. It was also noted that both groups showed little change in swimming endurance and power after the first 8 wk of training, though their performances improved significantly after each taper period.
Analysis of Variance↗
[Renin secreting tumor and severe hypertension. Apropos of a new case].
A renin-secreting tumour has been observed in a 32-year-old female with severe hypertension known for 17 years. The excision of the tumour lead to the complete normalisation of the blood pressure. Histological examination showed that the tumour was benign, contained secretion granules at different stages of maturation, and derived from the juxta-glomerular apparatus. After reviewing the 40 cases previously reported in the literature we discuss the clinical presentation of this type of tumour and the approach to their diagnosis.
Adult↗
Uptake of glutamate in Corynebacterium glutamicum. 1. Kinetic properties and regulation by internal pH and potassium.
The active uptake system for glutamate in Corynebacterium glutamicum is inducible by growth on glutamate as sole energy and carbon source and is also susceptible to catabolite repression by glucose. The basic level of uptake activity is low in glucose-grown cells (1.5 nmol.mg dry mass-1.min-1), it is intermediate when acetate is the carbon source (3.8 nmol.mg dry mass-1.min-1) and becomes fully induced by glutamate (15 nmol.mg dry mass-1.min-1). In all cases the uptake has, except for different Vmax values, identical kinetic and energetic properties, and is characterized by a low apparent Km value of 0.5-1.3 microM and by high substrate specificity. The transported substrate species is the deprotonated form which can also be concluded from the extremely high pH optimum of transport above pH 9. Glutamate uptake in cells grown in media with low K+ concentration is not influenced by external Na+ but is drastically stimulated by addition of K+. Stimulation by K+ could be separated into two different mechanisms. (a) Addition of K+ increases the internal pH, thereby stimulating glutamate uptake which is regulated by the internal pH in C. glutamicum. The apparent pK of the internal 'pH switch' is 6.6; below this value, uptake of glutamate is inhibited. (b) Internal K+ also directly promotes glutamate uptake. Effective uptake of glutamate can be observed only when the cytosolic K+ concentration exceeds a threshold value of about 200 mM. Stimulation of glutamate uptake by external K+ is not due to functional coupling of K+ and glutamate transport but reveals the necessity to replenish the internal K+ pool.
Biological Transport↗
Uptake of glutamate in Corynebacterium glutamicum. 2. Evidence for a primary active transport system.
The inducible glutamate uptake system in Corynebacterium glutamicum (Krämer, R., Lambert, C., Hoischen, C. & Ebbighausen, H., preceding paper in this journal) was characterized with respect to its mechanism and energy coupling. All possible secondary active uptake mechanisms can be excluded. Glutamate transport is not coupled to the translocation of H+, Na+ or K+ ions. Although changes in membrane potential and uptake activity cannot completely be separated, no correlation between these two parameters is observed. The uptake of glutamate resembles a primary active, ATP-dependent transport mechanism in several respects. (a) The substrate affinity is very high (1.3 microM). (b) Accumulation of glutamate reaches values of greater than 2.10(5), at least as high as those reported for binding-protein-dependent systems in Gram-negative bacteria. (c) The uptake is unidirectional. Even after complete deenergization, the accumulation ratio was not significantly reduced. (d) The rate of glutamate uptake is directly correlated to the cytosolic ATP content and also to the ATP/ADP ratio. This is shown by varying internal ATP by different procedures applying inhibitors (NaCN, dicyclohexyl carbodiimide), uncouplers (carbonyl m-chlorophenylhydrazone), ionophores (valinomycin), and even by shifting the cells to anaerobiosis. Uptake is not promoted by cytosolic ATP levels below 1.5 mM, the maximum uptake rate is reached at 4-5 mM ATP.
Adenosine Diphosphate↗