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Biomedical subjects

D Sawyer

Publications and source records attributed to D Sawyer.

35 records · Page 2Linked to original sources
PubMed1990

Calcium binds cooperatively to the regulatory sites of the cardiac thin filament.

To investigate the relationship between thin filament Ca2+ binding and activation of the MgATPase rate of myosin subfragment 1, native cardiac thin filaments were isolated and characterized. Direct measurements of 45Ca binding to the thin filament were consistent with non-cooperative binding to two high affinity sites (Ka 7.3 +/- 0.8 x 10(6) M-1) and either cooperative or non-cooperative binding to one low affinity site (Ka 4 +/- 2 x 10(5) M-1) per troponin at 25 degrees C, 30 mM ionic strength, pH 7.06. Addition of a low concentration of myosin subfragment 1 to the native thin filaments produced a Ca2+-regulated MgATPase activity with Kapp (2.5 +/- 1.3 x 10(5) M-1), matching the low affinity Ca2+ site. The MgATPase rate was cooperatively activated by Ca2+ (Hill coefficient 1.8). To determine whether Ca2+ binding to the low affinity sites was cooperative, native thin filament troponin was exchanged with troponin labeled on troponin C with 2-(4'-iodoacetamidanilo)naphthalene-6-sulfonic acid. From the Ca2+-sensitive fluorescence of this complex, Ca2+ binding was cooperative with a Hill coefficient of 1.7-2.0. Using the troponin-exchanged thin filaments, myosin subfragment 1 MgATPase rate activation was also cooperative and closely proportional to Ca2+ thin filament binding. Reconstitution of the thin filament from its components raised the Ca2+ affinity by a factor of 2 (compared with native thin filaments) and incorporation of fluorescently modified troponin raised the Ca2+ affinity by another factor of 2. Stoichiometrically reconstituted thin filaments produced non-cooperative MgATPase rate activation, contrasting with cooperative activation with native thin filaments, troponin-exchanged thin filaments and thin filaments reconstituted with a stoichiometric excess of troponin. The Ca2+-induced fluorescence transition of stoichiometrically reconstituted thin filaments was non-cooperative. These results suggest that Ca2+ binds cooperatively to the regulatory sites of the cardiac thin filament, even in the absence of myosin, and even though cardiac troponin C has only one Ca2+-specific binding site. A theoretical model for these observations is described and related to the experimental data. Well-known interactions between neighboring troponin-tropomyosin complexes are the proposed source of cooperativity and also influence the overall Ka. The data indicate that Ca2+ is four times more likely to elongate a sequence of troponin-tropomyosin units already binding Ca2+ than to bind to a site interior to a sequence of units without Ca2+.

Actins↗
PubMed1990

Laser-assisted vasectomy reversal: experience in 32 patients.

A Food and Drug Administration approved protocol using a microsurgical carbon dioxide laser to assist in vasectomy reversal was instituted in January 1987. Between January 1987 and December 1988 the procedure was performed on 32 patients, 31 of whom submitted sperm and were available to evaluate. Success rates for sperm in the ejaculate in patients who underwent vasectomy less than 10 years previously were excellent, approaching 95%. The pregnancy rate in this group was 35%. In patients whose vasectomy was performed more than 10 years before reversal the results were much poorer. The success rate for sperm in the ejaculate was only 36% and the pregnancy rate was only 9%. The advantage of laser-assisted vasectomy reversal is that it is a simpler technical procedure that requires considerably less time than a 2-layer microsurgical technique. There were no significant complications, sperm granuloma, or even significant swelling or hematoma in any patient operated upon. Laser-assisted vasectomy reversal is at least equal to conventional microsurgical techniques and definitely easier to perform surgically.

Adult↗
PubMed1988

K.T.P. 532 laser in treatment of urethral strictures.

We have had experience in the treatment of 20 patients with 22 strictures with this new laser that has a unique ability to cut and coagulate with minimal forward scatter to help prevent the formation of new scar tissue. All of the patients have had attempts of treatment of the strictures unsuccessfully in the past. The laser was effective in 68.2% of the patients to keep the urethra open and patent although the follow-up periods have been short at the time of this report ranging from six months to fourteen months. This new laser may have some promise in the treatment of urethral stricture disease.

Follow-Up Studies↗
PubMed1987

Binding and functional effects of atrial natriuretic factor in isolated rat kidney.

A new methodological approach was developed to study the relationship between specific binding and dose-response curves of the renal effects of atrial natriuretic factor (ANF) in isolated perfused rat kidneys (IK). IK were perfused with 125I-labeled and unlabeled ANF 1-28 (4 pM to 1 microM) to determine the following: 1) distribution, capacity (Cmax), and apparent affinity (S50) of specific binding of ANF 1-28 in cortex, outer medulla, and papilla and 2) dose-response curves of the effects of ANF 1-28 on renal hemodynamics and excretion of fluid and electrolytes. The kidney had a very high density of high-affinity binding sites for ANF. Cortex had greater than 90% of total binding sites (Cmax = 6.8 pmol/g tissue; S50 = 54 pM), whereas papilla had less than 2% of total binding sites with a 10-fold lower apparent affinity (S50 = 860 pM) than in cortex. ANF-induced increases in glomerular filtration rate and excretion of fluid and electrolytes were detectable at 10-100 pM and maximal effects occurred at 1-10 nM ANF. Below 1 nM there was no dissociation between the renal hemodynamic and natriuretic effects of ANF. There was a close agreement between dose-response and binding curves of ANF to cortex. Results demonstrate that binding site occupancy in kidney cortex and renal effects of ANF occur at near physiological concentrations of the hormone.

Animals↗
PubMed1984

Effect of pertussis toxin on alpha 2-adrenoceptors: decreased formation of the high-affinity state for agonists.

Administration of pertussis toxin to hamsters abolishes the alpha 2-adrenergic inhibition of adenylate cyclase in their adipocytes. The toxin did not modify the number of adipocyte alpha 2-adrenoceptors or their affinity for antagonists. In contrast, the affinity for agonists was significantly diminished in adipocyte membranes obtained from pertussis toxin-treated hamsters as compared to the controls. This decrease in affinity was due to a significant diminution in the proportion of sites displaying the high-affinity state for agonists. It is concluded that pertussis toxin induces a shift in the proportion of sites in high- and low-affinity states. for agonists towards the low-affinity conformation.

Adenylate Cyclase Toxin↗
PubMed1981

Cimetidine: adverse reactions and acute toxicity.

Recent reports of cimetidine toxicity are summarized. Summaries of specific cases and categorized according to cardiovascular, central nervous system, dermatologic, endocrine, gastrointestinal, hematologic, or renal toxicity, or overdosage. Adverse reactions reported secondary to cimetidine during its investigational period and shortly after marketing were minimal. In several studies in which over 1200 patients were treated with cimetidine, the incidences of adverse clinical symptoms was no higher than in the nearly 500 placebo-treated patients. However, subsequent reports indicate that elderly patients, patients with impaired renal function, and patients with liver disease appear quite susceptible to mental confusion. Potentially serious hematologic depression, cardiac depression, and hypersensitivity-type hepatitis have also been reported. As a result of the reports of impotence and oligospermia, controlled trials evaluating the effect of cimetidine on fertility in young men are needed.

Cardiovascular Diseases↗
PubMed1980

Drug information services for consumers and health professionals.

Provision of drug information services to both health professionals and consumers is described. The Rocky Mountain Drug Consultation Center (RMDCC) has been available to health professionals at Denver General Hospital since 1977. In April 1979, the RMDCC began promotion of combined health-professional- and consumer-oriented services. The service operates 8 a.m. to 6 p.m., Monday through Friday, with 24-hour on-call service. It is staffed by pharmacists who devote 70 man-hours per week to it. Training is primarily on the job. Most of the $80,500 budget is funded through a public health grant from the State of Colorado. a nine-member physician advisory board periodically reviews quality of responses. During a one-year period (April 1979-March 1980), 2264 calls were received from consumers and 1762 calls from health professionals--an increase of 197% over the previous year. Approximately 90% of consumer calls were not considered serious problems or were informational requests; 10% were considered potentially serious or serious drug-related problems. Less than 1% of consumers' questions required the use of anything more than basic drug information references. Of 76 follow-up calls made to consumers for serious or potentially serious problems, 73 were successfully recontacted, and 70 said they either followed RMDCC's recommendations or contacted their physician. The authors believe that combined consumer-oriented and health-professional-oriented drug information services help prevent misuse of medications by consumers.

Colorado↗
PubMed1978

Triton shells of intact erythrocytes.

About 40% of human erythrocyte membrane protein is resistant to solubilization in 0.5% Triton X-114. These components comprise a structure called a Triton shell roughly similar in size and shape to the original erythrocyte and thus constitute a cytoskeleton. With increasing concentrations of Triton the lipid content of the Triton shell decreases dramatically, whereas the majority of the protein components remain constant. Exceptions to this rule include proteins contained in band 3, the presumed anion channel, and in band 4 which decrease with increasing Triton concentration. The Triton-insoluble complex includes spectrin (bands 1 and 2), actin (band 5), and bands 3' and 7. Component 3' has an apparent molecular weight of 88,000 daltons as does 3; but unlike 3, it is insensitive to protease treatment of the intact cell, has a low extinction coefficient at 280 nm, and is solubilized from the shells in alkaline water solutions. Component 7 also has a low extinction coefficient at 280 nm. Spectrin alone is solubilized from the Triton shells in isotonic media. The solubilized spectrin contains no bound Triton and coelectrophoreses with spectrin eluted in hypotonic solutions from ghosts. Electron micrographs of fixed Triton shells stained with uranyl acetate show the presence of numerous filaments which appear beaded and are 80--120 A in diameter. The filaments cannot be composed mainly af actin, but enough spectrin is present to form the filaments. Triton shells may provide an excellent source of material useful in the investigation of the erythrocyte cytoskeleton.

Actins↗
PubMedDate not supplied

The human factors implications of peritoneal dialysis: cycler overfill incident reports.

Serious errors can occur with many medical devices (e.g., infusion pumps, ventilators, anesthesia machines), and even highly trained professionals can make critical errors. The FDA now requires that manufacturers consider the user when designing medical equipment and has issued a guidance document describing human factor (HF) problems and the HF design process. The Association for Advancement of Medical Instrumentation has also published guidelines, and the American Medical Association's National Patient Safety Foundation has selected reduction of medical errors as their mission. It is important that the medical community reinforce the patient-safety initiative by evaluating user-interface design and instructional manuals when purchasing such equipment. The payoff will be fewer incidents and less time required in device training. The FDA actively solicits help in identifying and reporting adverse events associated with medical devices. Health care practitioners employed by facilities subject to the FDA's user-facility reporting requirements should follow the user-reporting procedures established by their facility. Practitioners and users may want to directly report an incident to the MedWatch Program, the FDA's voluntary Medical Products Reporting Program.

Aged↗