Search PubMed⌕ Search

Biomedical subjects

L A Wanek

Publications and source records attributed to L A Wanek.

22 records · Page 2Linked to original sources

Effects of calcium "antagonists" on vertebrate skeletal muscle cells.

Clinically potent skeletal muscle relaxants are used primarily for their effects on the central nervous system. But they also have direct effects on muscle contraction that possibly involve Ca2+ channels. We compared the effects of dantrolene, an agent known to have a direct action on vertebrate skeletal muscle, with other substances used as (1) relaxants and (2) antagonists of Ca-dependent excitation-contraction coupling. Isolated intact frog muscle cells were injected with the photoprotein aequorin, and membrane potential changes, intracellular Ca2+ transients, and contractile force were measured. Dantrolene (10(-8) to 10(-5) M) decreased the amplitude of Ca2+ transients, did not affect their rates of decay, and reduced contractile force. We also used an integrated digital-imaging system to record microscopic changes, namely, active shortening in myofibrils and changes in striation spacing. Dantrolene did not increase the time between contraction in myofibrils near the surface compared with myofibrils near the center of a cell. Hence dantrolene does not suppress Ca2+ transients by disturbing current flow in the transverse tubular system. Each of the following actually increased Ca2+ transients and contractile force evoked by action potentials: baclofen (10(-7) to 10(-5) M) less than flordipine (10(-6) M) less than meprobamate (10(-7) to 10(-3) M) less than chlordiazepoxide (10(-5) X 10(-4) M) less than procaine (10(-5) to 5 X 10(-4] less than GABA (10(-5) M) less than D-600 (10(-6) M) less than nylidrin (10(-5) M)--in order of increasing potency. Ca2+ channels in the sarcoplasmic reticulum of intact skeletal muscle are evidently inhibited by dantrolene but not by Ca2+ antagonists.

Animals↗

Branched skeletal muscle fibers not associated with dysfunction.

We report the occurrence of large clefts and branches in some amphibian vertebrate skeletal muscle fibers. Such fibers can be isolated intact from various skeletal muscles of fully mature animals and apparently are normal in other respects. Electron micrographs showed no signs of degeneration in most fibers. Electrical and mechanical studies revealed that all branches were excitable and able to contract. Branches evidently can arise in the absence of abnormal influences such as experimentally induced overload. The apparent cause may be either fusion or splitting of fibers.

Animals↗

Skeletal muscle: length-dependent effects of potentiating agents.

The ability of vertebrae skeletal muscle to contract more vigorously than normal in the presence of potentiating agents depends on the initial length of a muscle cell. Other factors such as the intracellular calcium ion transient, temperature, chemical nature of the potentiating agent, and the ratio of intrinsic twitch to tetanic force influence the degree of contractile potentiation but cannot account for the length dependence. At least part of a muscle cell seems normally less than fully active during contractions not only at short lengths but also at optimal sarcomere lengths.

Aequorin↗

Increased incidence of second primary melanoma in patients with a previous cutaneous melanoma.

BACKGROUND: Patients with cutaneous melanoma reportedly have an increased risk of developing second primary melanoma; however, this increased risk has not been well characterized with respect to age and time from first melanoma. We hypothesized that, as a result of temporal variations in environmental exposure, genetic susceptibility, and impaired immune competence, the incidence of second primary melanoma varies significantly with respect to age and time. METHODS: A review of our prospective melanoma data base, containing records for 8928 patients, was undertaken to identify patients with American Joint Committee on Cancer stage I and II cutaneous melanoma, who were treated from 1971 to 1998. RESULTS: Second primary melanoma was identified in 113 (3.4%) of 3310 patients with American Joint Committee on Cancer stage I and II cutaneous melanoma. In 11 patients (0.3%), the second melanoma was identified within 2 months of the initial tumor; the remaining 102 patients had a metachronous lesion. The incidence rate of second primary melanoma was 325 per 100,000. The standardized incidence ratio, defined as the ratio of the number of observed second melanomas to the number of expected melanoma cases, was 25.6. The 5- and 10-year risk of developing a second melanoma was 2.8% and 3.6%, respectively. Both the annual risk of developing a second melanoma and the standardized incidence ratio were elevated in younger patients (ages 15-39 years) and in older patients (ages 65-79 years). CONCLUSIONS: Patients with cutaneous melanoma are at very high risk for development of second primary melanoma. This risk approximates 0.5% per year for the first 5 years of follow-up. Patients aged 15-39 and patients aged 65-79 have a particularly high incidence of second melanoma, suggesting different causes for the development of second primaries. All patients with melanoma should undergo careful surveillance for second melanomas in addition to routine screening for recurrence.

Adolescent↗