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Biomedical subjects

D Henry

Publications and source records attributed to D Henry.

At least 127 records · Page 7Linked to original sources

Lymphatic filariasis: detection of circulating and urinary antigen and differences in antibody isotypes complexed with circulating antigen between symptomatic and asymptomatic subjects.

A two-site immunoradiometric assay using a monoclonal antibody (MoAb) against Brugia malayi microfilariae allowed the detection of parasite molecules both in the serum and the urine of patients from Sri Lanka infected with Wuchereria bancrofti. Whereas 50% of patients had no antigen in their serum, all of them excreted detectable amounts of antigen in their urine, the levels being higher in symptomatic than in asymptomatic patients. The poor detection in serum appeared to be related to the presence of circulating immune complexes. It was shown that the isotype of the antibodies complexed with the circulating antigen was IgM in the asymptomatic group, while it was mainly IgG in the symptomatic patients (swelling and lymphoedema or elephantiasis). These results suggest the existence of regulatory immune mechanisms affecting the clinical expression of lymphatic filariasis.

Animals↗

Propranolol steady-state pharmacokinetics are unaltered by omeprazole.

In a randomised double-blind cross-over study, 8 normal subjects received propranolol 80 mg twice daily with omeprazole 20 mg or identical placebo each morning. Propranolol kinetics were measured on day 8 of both treatment periods. Areas under the propranolol concentration/time curves were not significantly increased by omeprazole treatment: off treatment mean 787.6, on treatment 802.5 ng-1.ml.h. Maximum and minimum steady-state propranolol concentrations were similarily unaffected. Omeprazole also failed to increase the clinical effect of propranolol, as assessed by exercise tests on Day 8 of treatment. We conclude that omeprazole in the dose likely to be used for peptic ulcer has no significant effect on the kinetics or action of propranolol.

Chromatography, High Pressure Liquid↗

Purification of the proteolytically solubilized, active catalytic subunit of adenylate cyclase from ram sperm. Inhibition by adenosine.

Ram spermatozoa adenylate cyclase is insensitive to all usual regulatory processes. The purification of its active catalytic subunit was accomplished after proteolytic solubilization of a particulate fraction by alpha-chymotrypsin. The purification (26,000-fold from the particulate fraction or 125,000-fold from the whole-sperm proteins) was achieved by conventional procedures (DEAE-Trisacryl, Ultrogel AcA 34, DEAE-Sephacel, hydroxyapatite), in the absence of detergent, and with a yield of 5-10% and a final specific activity of 19 mumol cyclic AMP formed mg protein-1 min-1 at 30 degrees C in the presence of manganese as cosubstrate. The solubilized enzyme, stable at the beginning of the purification procedure, became unstable at the later stages. After the last step (chromatography on hydroxyapatite) half-lives of 27 min, 50 min and 160 min were obtained at 30 degrees C, 20 degrees C and 4 degrees C respectively. The enzyme was stabilized by addition of bovine serum albumin and Lubrol PX, 80% of the activity remaining after 24 h at 4 degrees C. The purified enzyme exhibited a Km value similar to that of the native enzyme (Km = 1.4 mM). Unlike the native enzyme, the purified enzyme has an absolute requirement for MnATP; no significant activity was recovered in the presence of MgATP. Adenosine inhibited the activity of both the native and purified forms of the enzyme to the same extent and in a non-competitive manner. This indicates that adenosine acts on the catalytic component itself and the inhibition site and the catalytic site are different. Data obtained with adenosine analogs indicate that adenosine interacts with the cyclase catalytic subunit with a 'P-site' specificity. The purified adenylate cyclase, which had an apparent molecular mass of 38 kDa on a high-performance liquid chromatography column [Stengel, D., Guenet, L. and Hanoune, J. (1982) J. Biol. Chem. 257, 10,818-10,826], gave a doublet of 36 kDa and 34 kDa on sodium dodecyl sulfate gel electrophoresis. This represents the smallest protein entity associated with adenylate cyclase activity so far reported.

Adenosine↗

Inhibition of the catalytic subunit of ram sperm adenylate cyclase by adenosine.

Adenosine inhibits ram sperm adenylate cyclase activity which is membrane-bound and comprises only the catalytic subunit. The inhibition parameters of adenylate cyclase by adenosine were not modified when the enzyme was purified 3 to 5,000 fold. Optimal inhibition by adenosine was found to require a high concentration of manganese, and exhibited a noncompetitive pattern up to a concentration of 1 mM adenosine. Adenosine was the most potent inhibitor among various analogs tested with the following rank order of potencies: adenosine greater than 2'O-methyladenosine greater than 2'deoxyadenosine much greater than 2 chloroadenosine. Studies with agonists and antagonists of the "R"-type adenosine receptor led us to conclude that adenosine inhibits ram sperm adenylate cyclase via a "P"-site carried by the catalytic subunit itself.

Adenosine↗

Critical assessment of the platelet adenylate cyclase system as a potential model for testing alpha 2 adrenergic activity.

We have studied the effects of KUM 32 and CBS 1276, two clonidine-related drugs, upon the adenylate cyclase system of human platelets. Both drugs behaved as potent antagonists of epinephrine-induced platelet aggregation. [3H]Yohimbine binding studies revealed that the drugs bind to the alpha 2 adrenergic receptor of human platelets. KUM 32 and CBS 1276 also behaved as strong inhibitors of adenylate cyclase activity. This inhibition, which was not competitive with respect to ATP, is not an alpha 2 adrenergic phenomenon since it was not antagonized by yohimbine and was still observed in the absence of GTP. Moreover, pretreatment of platelet membranes with islet activating protein from Bordetella pertussis (IAP) had no effect on the inhibition by KUM 32, CBS 1276 and adenosine, although it completely reversed the effect of epinephrine and partially reversed the effect of clonidine. These results show that clonidine-like drugs may have different impacts on the adenylate cyclase system of human platelets. This system cannot be used as a pharmacological predictive test for alpha 2 adrenergic agonist activity, as various compounds, known to have central alpha 2 adrenergic agonist properties, do not behave as full agonists for the alpha 2 adrenergic receptor of human platelets.

Adenylate Cyclase Toxin↗

Comparative evaluation of four systems for determining susceptibility of gram-positive organisms.

A study was undertaken to compare four commercial systems for testing the antimicrobial susceptibility patterns of gram-positive cocci. The reference method was an agar dilution method. The systems evaluated were the MS-2 system (Abbott Diagnostics Div., Mississauga, Ontario), the AutoMicrobic system (AMS) (Vitek Systems, Inc., Hazelwood, Mo.) with the gram-positive susceptibility (GPS) card, the Sceptor system (BBL Microbiology Systems, distributed by Becton Dickenson, Canada Inc., Mississauga, Ontario), and the Micro-Media system (Beckman Instruments, Inc., Anaheim, Calif.). There was a greater than 98% essential accord (EA) between all test results and the reference method results when testing 134 isolates of Staphylococcus aureus. In testing 79 isolates of coagulase-negative staphylococci the EA was greater than 97% with all systems except the MS-2. In the MS-2 system only, 30% of tests were interrupted by the instrument because of insufficient growth in the control chamber. Excluding the Sceptor system, the EA was greater than 96% on testing 70 isolates of enterococcus. In testing 15 isolates of group B Streptococcus there was 91% EA with the AMS and Sceptor systems and only 71 and 88% EA with the MS-2 and Micro-Media systems, respectively. The new AMS GPS MIC card was tested against 29 methicillin-resistant S. aureus, 10 coagulase-negative staphylococci, and 9 enterococci, and it gave more accurate results than the earlier GPS breakpoint card. The Micro-Media and MS-2 systems did not reliably detect marginally methicillin-resistant S. aureus. The MS-2 was the least expensive system to operate on a cost per test basis ($3.59 Can.), whereas the Sceptor was the most expensive system ($5.29 Can.). The AMS ws the least labor intensive (0.9 min per test), and the Sceptor system was the most time consuming (2.9 min per test).

Anti-Bacterial Agents↗

Comparison of agar dilution, microdilution, and disk elution methods for measuring the synergy of cefotaxime and its metabolite against anaerobes.

The activities of cefotaxime (CTX) and desacetyl cefotaxime (des-CTX) were tested both singly and in combination against 173 anaerobic clinical isolates. The MIC of CTX for 50% of 60 Bacteroides fragilis isolates was 22.4 micrograms/ml in broth, compared with 47.4 micrograms/ml in agar. This reduced efficacy in agar was seen with all species tested and is in apparent conflict with reported clinical efficacy of the drug. Synergy between CTX and des-CTX was observed with 70 to 100% of the isolates, including 60% of all Bacteroides spp. tested. The susceptibility results in a synergy system correlated well with those noted in a broth-disk elution method incorporating 32 micrograms of CTX and 8 micrograms of des-CTX per ml. The correlation was poorer when the broth-disk method contained 16 micrograms of CTX and 8 micrograms of des-CTX per ml.

Bacteria, Anaerobic↗

In vitro activities of enoxacin, ticarcillin plus clavulanic acid, aztreonam, piperacillin, and imipenem and comparison with commonly used antimicrobial agents.

A total of 745 gram-negative and 313 gram-positive clinical isolates were tested against enoxacin, ticarcillin plus clavulanic acid, aztreonam, imipenem, and piperacillin and compared with commonly used antimicrobial agents. Ticarcillin plus clavulanic acid, imipenem, and piperacillin were active against Pseudomonas aeruginosa and Acinetobacter spp. and most Pseudomonas spp. Aztreonam was active against members of the family Enterobacteriaceae but was less effective against the nonfermenters. Enoxacin was active against the Enterobacteriaceae, P. aeruginosa, the staphylococci, and most Acinetobacter spp. but was less active against Pseudomonas spp. and streptococci. Imipenem was very active against all gram-positive and -negative organisms tested except for Pseudomonas maltophilia.

Anti-Bacterial Agents↗

Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding.

We studied the effects of tranexamic acid (an antifibrinolytic agent) and cimetidine on acute upper-gastrointestinal-tract bleeding in a double-blind randomized placebo-controlled trial in 775 patients with hematemesis or melena or both. Mortality was significantly reduced in patients receiving either tranexamic acid (mortality, 6.3 per cent) or cimetidine (7.7 per cent), as compared with patients receiving placebo (13.5 per cent) (P = 0.0092 for tranexamic acid vs. placebo, P = 0.045 for cimetidine vs. placebo). Ninety-nine patients were withdrawn before the code was broken, mainly because their primary illness was considered not to be due to acute upper-gastrointestinal-tract bleeding. Mortality among those withdrawn was high (22 per cent), and their exclusion reduced death rates to 4 per cent in those given tranexamic acid, 8 per cent in those given cimetidine, and 11 per cent in those given placebo (P = 0.0072 for tranexamic acid vs. placebo, P greater than 0.50 for cimetidine vs. placebo). The reduced mortality associated with tranexamic acid was detectable at both participating hospitals and in most of the main subgroups of patients classified according to site of bleeding. However, treatment with this agent was not associated with any decrease in the rate of rebleeding or the need for operation.

Acute Disease↗

Early experience with a vertical spinning-disc nebuliser.

A new device for the administration of bronchodilators to asthmatics by nebulisation has been developed. Nebuliser therapy, in many patients more effective than other forms of drug delivery, has been limited by the need to provide patients with units driven by compressed air. Solutions can be nebulised by contact with a rapidly spinning horizontal disc. Adaptation of this method to a small nebuliser for clinical use is difficult, since a constant delivery of fluid the centre of the disc is necessary. The problem has been overcome in the new device in which the disc spins vertically in a reservoir. The performance of the prototype device was compared with that of a conventional compressed air nebuliser. The improvement is spirometry values of 8 asthmatic patients was similar for both nebulisers.

Adult↗

The effect of frontal EMG biofeedback training on the behavior of children with activity-level problems.

N = 1 withdrawal designs were employed with three children evidencing activity-level problems. Tutoring sessions occurred daily over a 2 1/2-month period. Each child was reinforced for decreasing frontalis muscle tension during auditory feedback while working arithmetic problems. Feedback was faded while tension reduction reinforcement was maintained. These procedures were repeated with reinforcement for increasing, rather than decreasing, muscle tension. Frontal EMG level, percent time on task, and motoric activity rate were obtained during sessions. Parent ratings of problem behavior in the home were recorded daily. Biofeedback with reinforcement was effective in both raising and lowering muscle tension. Effects were maintained by reinforcement. Results suggest a direct relationship between tension and activity levels. Academic performance and problem behavior improved significantly with reductions in EMG activity, although individual exceptions to these findings were present. Results lend support to the efficacy of frontal EMG biofeedback training in reducing activity, increasing attention to an academic task, and reducing problem behaviors.

Biofeedback, Psychology↗

The possible role of the catecholamines of the corpora in penile erection.

The etiology of impotence, which effects 50 per cent of the men with diabetes, is unknown. The neurotransmitter (norepinephrine) released from adrenergic neurons is thought to be the most direct regulator of vascular smooth muscle. We have measured the norepinephrine content of the erectile tissue of diabetic men. Our results indicate the presence of a dual neural regulator mechanism of the corpora that controls penile erection.

Catecholamines↗