Interview with James Weil.
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Health Benefit Plans, Employee↗
Biomedical subjects
J Weil
Publications and source records attributed to J Weil.
Influence of diurnal rhythm, posture and right atrial size on plasma atrial natriuretic peptide levels.
A diurnal rhythm of plasma atrial natriuretic peptide (ANP) and cyclic 3'5'guanosine monophosphate (cGMP) was found in nine healthy adult volunteers. Significantly higher levels of both parameters were found in the morning (8 a.m.) than later during the day and night (p less than 0.05). Different postures had only a little influence on plasma ANP and cGMP levels in seven healthy adult volunteers using a tilt table. Tilted from supine into upright, head-down (-20 degrees) and then again into supine posture, significant differences of both parameters were only found between levels shortly after the end of the upright posture and those at the end of the head-down posture (p less than 0.05). Furthermore, in infants with various congenital heart diseases (n = 19) and control infants (n = 35) the right atrial area was determined by two-dimensional echocardiography and related to plasma ANP levels. Out of 19 infants with cardiac disease, 11 showed an enlarged right atrial area (i.e. above the 95th percentile in the range of control infants). All these 11 infants also had higher plasma ANP levels (range 115-670 pg/ml) than the healthy infants (range 5-98 pg/ml). These data support the assumption that atrial wall distension seems to be a stimulus for ANP release.
Adult↗
Is cyclic GMP a clinically useful marker for ANF action?
The action of ANF is, at least in part, mediated by the activation of particulate guanylate cyclase. Increases in plasma ANF levels induce a marked increase in the plasma levels and urinary excretion of cyclic GMP. In contrast to agents that stimulate particulate guanylate cyclase, activators of soluble guanylate cyclase, such as the bioactive molsidomine metabolite, SIN 1, induce only a modest, not significant, increase in plasma cyclic GMP levels. Thus, increases in plasma cyclic GMP levels appear to be specific for the activation of particulate guanylate cyclase. Cyclic GMP is stable in whole blood in the presence of EDTA and can easily be measured in plasma and urine. It may therefore be a valuable alternative for ANF measurement in the clinical routine. In contrast to urinary ANF excretion, the urinary excretion of cyclic GMP sensitively reflects increases in plasma ANF levels. Measurement of cyclic GMP excretion may therefore be an alternative for plasma ANF and plasma cyclic GMP measurement especially in situations where blood drawing is difficult, e.g. in newborns. Measurement of basal cyclic GMP followed by determination of increases in cyclic GMP levels after injection of a small ANF bolus dose tests the cellular sensitivity to ANF. This may give further insight in the mechanism of the regulation of ANF effects. Therefore, cyclic GMP in many cases appears to be a sensitive marker for the action of ANF in man.
Atrial Natriuretic Factor↗
[Homozygous infant in a family with hereditary protein C deficiency].
We report on a female infant homozygous for protein C deficiency in a Jordanian family with frequent intermarriage. A protein C antigen of 0.6% was determined. The parents first noticed painful nodular indurations in subcutanous tissue as well as blue-red skin coloration at the age of 6 months. The girl repeatedly suffered from microthrombotic events in parts of the body with large areas of subcutaneous fat. In contrast, the numerous heterozygous carriers with partial protein C deficiency did not show an increased tendency to thrombosis. From the history an autosomal-recessive inheritance may be inferred. Other authors reporting on homozygous cases also postulate the presence of a recessive gene. It is of interest that the infant described here differs from those in other case reports in the age at manifestation of the disease. The homozygous infant showed the first symptoms as late as the age of 6 months, whereas other case reports describe severe symptoms immediately after birth. All symptoms of disease were treated successfully with prothrombin complex concentrate without additional heparin protection. Microthrombotic events subsided quickly, and a large ulcer in the left flank healed almost completely within 6 days.
Adult↗
14C-urea breath analysis, a non-invasive test for Campylobacter pylori in the stomach.
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Breath Tests↗
Platelet receptors for atrial natriuretic peptide in man.
The aim of our study was to characterize the receptor binding of human alpha-atrial natriuretic peptide (ANP) to human blood cells. Whereas no receptors were detected on red cells, on mononuclear cells and on granulocytes, we found ANP-receptors on human platelets. The binding studies were performed by incubating 40 X 10(6) platelets with 125I-ANP and with the competing ligand, when used, in a total incubation volume of 1 ml. Centrifugation was used to separate bound from free hormone. Specific binding of 125I-ANP was rapid, saturable and reversible. A steady state was achieved within 90 minutes. Scatchard analysis of saturation and competition experiments demonstrated the existence of one class of high affinity binding sites for ANP with a Kd of 8-16pM and 10-26 receptors per cell. The Kd obtained in our binding studies was in the range of physiological ANP concentrations in human plasma (8-20pM). Although characterization of platelet ANP receptors has the inherent disadvantage that there are only few of them, they could be a useful model to investigate the ANP receptor-status under different physiological and pathological conditions in man.
Atrial Natriuretic Factor↗
Acute increase in right atrial pressure by intracardiac stimulation releases atrial natriuretic peptide.
We studied the effect of an increase in heart rate and/or in right atrial pressure (RAP) on the release of atrial natriuretic peptide (ANP) in 18 patients. In group 1 (n = 6), right ventricular stimulation (100, 120, 140 and 150 bpm) was used to increase RAP by asynchronous contraction of the right atrium and ventricle. Mean RAP increased from 3.9 +/- 0.2 to 8.3 +/- 0.6 mmHg (mean +/- SEM). Median ANP levels increased from 120 to 440 pg ml-1 (P less than 0.05). In group 2 (n = 6), right atrial stimulation below 140 bpm did not have any effect on ANP or RAP, but at a rate above 140 bpm RAP increased from 5.8 +/- 0.5 to 7.5 +/- 0.5 mmHg and ANP from 226 to 396 pg ml-1 (P less than 0.05). In group 3 (n = 6), RAP or ANP were not influenced by continuous right atrial stimulation at 110 bpm. Plasma cyclic GMP levels paralleled the changes in plasma ANP. Thus, an acute increment of RAP results in a release of ANP, but acceleration of heart rate alone has no effect on ANP secretion.
Atrial Natriuretic Factor↗
Plasma atrial natriuretic peptide levels in children with cardiac diseases: correlation with cGMP levels and haemodynamic parameters.
In children with various forms of cardiac diseases (aged 2 months to 16 years) significantly higher plasma atrial natriuretic peptide (ANP; range 36-680, median 247 pg/ml) and cyclic 3'5'-guanosine monophosphate (cGMP; range 0.2-46, median 8.2 pmol/ml) levels were found than in control children (p less than 0.0001). In control children (aged 4 months to 17 years) plasma ANP and cGMP levels were measured in the range of 2.4-98 pg/ml and of 0.2-2.8 pmol/ml, respectively. There was a linear correlation between the two parameters in children with cardiac diseases (r = 0.62, p less than 0.01). Children with elevated mean right atrial pressure (i.e., greater than 6 mm Hg) showed significantly higher plasma ANP levels than children with normal atrial pressure (p less than 0.01). However, there was only a weak linear correlation between mean right atrial pressure and plasma ANP levels (r = 0.48, p less than 0.01). Plasma ANP levels from right atrium, pulmonary artery, left atrium and left ventricle were significantly higher than those from vena cava (p less than 0.05). Analysis of ANP-like immunoreactive material by high performance liquid chromatography suggested that alpha-ANP is the major form of circulating ANP in blood of children with cardiac diseases.
Adolescent↗
Orthopaedic growth guidance and stimulation for patients with cleft lip and palate.
The growth potential of the craniofacial complex of a child with a congenital cleft is not at variance with that of the normal craniofacial complex. Early surgery including mucoperiosteal undermining and the formation of scar tissue generally results in considerable growth retardation. Primary bone grafting seriously inhibits maxillary growth. 15 years' experience with the treatment of cleft patients applying "growth stimulators" combined with postponing surgical corrections is reported, and the results of this treatment method are compared with those found in literature. As a criterion an accurately measurable and reliable parameter, namely the crossbite relation, was opted for. The frequency of crossbite occurrence is now only 16% for deciduous dentitions and 21% for mixed dentitions. In comparison with the most favourable treatment results found in the literature this constitutes a reduction of more than 50%. This implies that the development of maxillary morphology is normalised, leading to an improvement of the oro-nasal functions including speech development.
Cleft Lip↗
Abnormalities in the interferon response and immune systems in Down syndrome: studies in human trisomy 21 and mouse trisomy 16.
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Animals↗
Effects of clonidine and dihydralazine on plasma ANF and cyclic GMP levels in humans during volume loading.
Acute volume loading increases plasma atrial natriuretic factor (ANF) levels in man and animals. In the present work we have compared the effects of a 1-week oral application of clonidine (2 x 0.075 mg/day) to dihydralazine (2 x 25 mg/day) in eight healthy volunteers on changes in plasma ANF and plasma and urine cyclic GMP levels after acute volume loading with 2 I physiological saline i.v. Basal plasma ANF levels before infusion were decreased by clonidine to 65% of the untreated controls and remained unaltered with dihydralazine. Volume loading increased plasma ANF levels by about 40% in the control and 30% in the dihydralazine treated group, whereas plasma ANF remained unchanged by volume loading in the clonidine-treated group. Dihydralazine increased basal cyclic GMP levels and urinary cyclic GMP excretion by 30 and 90%, respectively. Basal cyclic GMP levels were identical without treatment and after clonidine treatment. Saline infusion increased cyclic GMP levels by 40% in the control and clonidine-treated groups, and by 25% in the dihydralazine-treated group. Urinary cyclic GMP excretion increased by 2.1-, 1.6-, and 1.2-fold, respectively, in the controls, after clonidine, or after dihydralazine. The results of this study suggest that ANF is involved in the hormonal and hemodynamic effects that are induced by clonidine, but not in those induced by dihydralazine.
Adult↗
Increased plasma cyclic guanosine monophosphate concentrations in children with high levels of circulating atrial natriuretic peptide.
Simultaneous measurements of plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (GMP) concentrations were performed in children with various forms of cardiac diseases (n = 22) and in control children (n = 29). In healthy children, plasma ANP and cyclic GMP levels ranged between 2.4 and 98.0 (mean 45.8) pg/mL and 0.2 to 2.8 (mean 1.40) pmol/mL, respectively. In children with cardiac diseases, plasma ANP (26.0 to 499.7 [mean 188.7] pg/mL) and cyclic GMP (0.2 to 6.0 [mean 2.9] pmol/mL) levels were significantly higher than in control children (both P less than .0001). There was a linear correlation between the two values in children with cardiac diseases (P less than .01). Because the effects of ANP to target tissues are mediated by cyclic GMP, cyclic GMP appears to be a marker for the cellular responses to ANP. The increased cyclic GMP levels in children with cardiac diseases indicate that ANP exerts its effects on target organs also in states of chronically enhanced ANP levels.
Adolescent↗
Cellular mechanisms of action of atrial natriuretic factor.
Atrial natriuretic factor (ANF) interacts with its target cells through specific receptors. This interaction induces, in most cell types, the activation of particulate guanylate cyclase and decreased Calcium mobilisation. In addition, ANF also decreases adenylate cyclase activity in some tissues. Activation of particulate guanylate cyclase, and additionally inhibition of adenylate cyclase, appear to initiate the cellular responses to circulating ANF. The activation of particulate guanylate cyclase is tissue-specific, immediate and can be demonstrated also on the solubilized enzyme. The ANF receptor appears to be tightly coupled to particulate guanylate cyclase. The increased formation of cyclic GMP induces cGMP-dependent protein phosphorylation in target cells. In addition, cyclic GMP inhibits Calcium mobilisation in several tissues. This may explain observations of inhibition of Calcium mobilisation after ANF. Cyclic GMP is not only degraded by phosphodiesterase, but is also extruded from target cells. As a consequence of cGMP extrusion, ANF increases the levels of cyclic GMP in plasma and urine in animals and man. Cyclic GMP is also increased in various disease states, in which ANF is increased. In contrast, cyclic AMP plasma levels are unaltered after ANF elevations. At present, the exact mechanisms, by which cellular functions are altered by ANF are still incompletely understood. It is anticipated, that the close correlation between the cyclic GMP system and effects of ANF in various target tissues is a key finding that will help elucidate the exact mechanisms of ANF action.
Adenylyl Cyclase Inhibitors↗
Hindlimb hyperesthesia associated with rabies in two horses.
Rabies was diagnosed in 2 adult Quarter Horses with hindlimb hyperesthesia and progressive weakness. Microscopic examination of the cord and brain of the first horse revealed nonsuppurative meningomyelitis and ganglioneuritis in the cord extending cranially to the 6th cervical segment. Fluorescent antibody test results of both horses were positive for rabies in hindlimb peripheral nerve specimens, but negative in sections of the upper lip. Salivary gland, cerebrum, cerebellum, hippocampus, musculocutaneous nerve, cornea, and optic nerve specimens were tested for rabies by fluorescent antibody technique to determine viral distribution in the body of the second horse.
Animals↗
Intrapulmonary hemorrhages and immune complex glomerulonephritis masquerading as Goodpasture's syndrome.
The case of a patient who presented clinically with hemoptysis and was shown to have bilateral pulmonary infiltrates and renal abnormalities is described. This typical clinical setting was initially diagnosed as Goodpasture's syndrome. Open biopsies of lung and kidney were performed. Light microscopy failed to demonstrate the renal abnormalities most often associated with Goodpasture's syndrome. Immunofluorescence and electron microscopic findings were compatible with a diagnosis of immune complex glomerulonephritis. No immunologic lesions were demonstrated by lung biopsy. Antiglomerular basement membrane antibodies were not detected in the patient's serum. In view of the drastic prognostic and therapeutic consequences of Goodpasture's syndrome, it is essential that this diagnosis be confirmed by tissue examination and serologic testing.
Adult↗
Comparison of plasma atrial natriuretic peptide levels in healthy children from birth to adolescence and in children with cardiac diseases.
An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2-4 days of life, significantly higher plasma ANP plasma levels (range 129-356 pg/ml, mean 227) were found compared with older infants and children (p less than 0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.
Adolescent↗
Mechanisms of action of atrial natriuretic factor: clinical consequences.
Atrial natriuretic factor (ANF) acts through specific receptors at its target tissues. Receptor-occupancy by ANF induces activation of particulate guanylate cyclase, increased cyclic GMP formation and also inhibition of adenylate cyclase which results in a decrease of cyclic AMP formation. These second messenger systems appear to mediate the effects of ANF in target tissues. Following receptor-mediated activation of particulate guanylate cyclase, cyclic GMP is extruded from the cells, which leads to elevated cyclic GMP levels in plasma and urine in man, whereas cyclic AMP levels remain unchanged. Since cyclic GMP has a much longer half-life than ANF, it is more sensitive as a marker for ANF release than ANF itself, which has a half-life of just a few minutes. Since cyclic GMP is excreted into urine, determinations of urine cyclic GMP can also allow conclusions about the ANF system when blood sampling is impractical. Thus, cyclic GMP and not cyclic AMP is a sensitive biological marker for ANF.
Adenylyl Cyclases↗
Concomitant increase in plasma atrial natriuretic peptide and cyclic GMP during volume loading.
To investigate the effects of fluid expansion on endogenous atrial natriuretic peptide (ANP) and cyclic 3',5'-guanosine monophosphate (cGMP), four male volunteers were studied before, during and after intravasal volume loading. Volume expansion was performed by intravenous infusion of 2,000 ml isotonic saline solution within 30 min. Mean plasma ANP levels increased 2.5-fold from 31.2 pg/ml to 81.7 pg/ml 40 min after the start of infusion. Plasma cGMP levels paralleled the rise in ANP, showing a mean cGMP increment from 2.7 pmol/ml to a maximum of 8.2 pmol/ml. Both ANP and cGMP levels were back to basal levels 120 min after termination of the infusion. Stimulation of endogenous ANP release by volume loading suggests that ANP is involved in the regulation of fluid homeostasis in man. The parallel rise in plasma cGMP levels supports the idea that cGMP is a mediator for the effects of ANP.
Adult↗