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Biomedical subjects

C R Weber

Publications and source records attributed to C R Weber.

12 recordsLinked to original sources
PubMed2001

Allosteric regulation of Na/Ca exchange current by cytosolic Ca in intact cardiac myocytes.

The cardiac sarcolemmal Na-Ca exchanger (NCX) is allosterically regulated by [Ca](i) such that when [Ca](i) is low, NCX current (I(NCX)) deactivates. In this study, we used membrane potential (E(m)) and I(NCX) to control Ca entry into and Ca efflux from intact cardiac myocytes to investigate whether this allosteric regulation (Ca activation) occurs with [Ca](i) in the physiological range. In the absence of Ca activation, the electrochemical effect of increasing [Ca](i) would be to increase inward I(NCX) (Ca efflux) and to decrease outward I(NCX). On the other hand, Ca activation would increase I(NCX) in both directions. Thus, we attributed [Ca](i)-dependent increases in outward I(NCX) to allosteric regulation. Ca activation of I(NCX) was observed in ferret myocytes but not in wild-type mouse myocytes, suggesting that Ca regulation of NCX may be species dependent. We also studied transgenic mouse myocytes overexpressing either normal canine NCX or this same canine NCX lacking Ca regulation (Delta680-685). Animals with the normal canine NCX transgene showed Ca activation, whereas animals with the mutant transgene did not, confirming the role of this region in the process. In native ferret cells and in mice with expressed canine NCX, allosteric regulation by Ca occurs under physiological conditions (K(mCaAct) = 125 +/- 16 nM SEM approximately resting [Ca](i)). This, along with the observation that no delay was observed between measured [Ca](i) and activation of I(NCX) under our conditions, suggests that beat to beat changes in NCX function can occur in vivo. These changes in the I(NCX) activation state may influence SR Ca load and resting [Ca](i), helping to fine tune Ca influx and efflux from cells under both normal and pathophysiological conditions. Our failure to observe Ca activation in mouse myocytes may be due to either the extent of Ca regulation or to a difference in K(mCaAct) from other species. Model predictions for Ca activation, on which our estimates of K(mCaAct) are based, confirm that Ca activation strongly influences outward I(NCX), explaining why it increases rather than declines with increasing [Ca](i).

Allosteric Regulation↗
PubMed1998

Control of maximum sarcoplasmic reticulum Ca load in intact ferret ventricular myocytes. Effects Of thapsigargin and isoproterenol.

In steady state, the Ca content of the sarcoplasmic reticulum (SR) of cardiac myocytes is determined by a balance among influx and efflux pathways. The SR Ca content may be limited mainly by the ATP-supplied chemical potential that is inherent in the gradient between SR and cytosol. That is, forward Ca pumping from cytosol to SR may be opposed by energetically conservative reverse pumping dependent on intra-SR free [Ca]. On the other hand, SR Ca loading may be limited by dissipative pathways (pump slippage and/or pump-independent leak). To assess how SR Ca content is limited, we loaded voltage-clamped ferret ventricular myocytes cumulatively with known amounts of Ca via L-type Ca channels (ICa), using Na-free solutions to prevent Na/Ca exchange. We then measured the maximal resulting caffeine-released SR Ca content under control conditions, as well as when SR Ca pumping was accelerated by isoproterenol (1 micro M) or slowed by thapsigargin (0.2-0.4 micro M). Under control conditions, SR Ca content reached a limit of 137 micro mol.liter cytosol-1 (nonmitochondrial volume) when measured by integrating caffeine-induced Na/Ca exchange currents lintegraINaCaXdt) and of 119 micro mol.liter cytosol-1 when measured using fluorescence signals dependent on changes in cytosolic free Ca ([Ca]i). When Ca-ATPase pumping rate was slowed 39% by thapsigargin, the maximal SR Ca content decreased by 5 (integralINaCaXdt method) or 23% (fluorescence method); when pumping rate was increased 74% by isoproterenol, SR Ca content increased by 10% (fluorescence method) or 20% (integralINaCaXdt method). The relative stability of the SR Ca load suggests that dissipative losses have only a minor influence in setting the SR Ca content. Indeed, it appears that the SR Ca pump in intact cells can generate a [Ca] gradient approaching the thermodynamic limit.

Animals↗
PubMed1994

Evaluation of dexamethasone for reducing postoperative edema and inflammatory response after orthognathic surgery.

A randomized, prospective, double-blind study was conducted to determine the efficacy of intravenous dexamethasone in reducing postoperative edema after bilateral sagittal split osteotomies of the mandible. Twenty-three patients were enrolled in the study and randomly assigned to one of the three groups. Each patient received one preoperative infusion and three postoperative infusions every 6 hours. Seven patients served as controls and received placebos for all infusions. Eight patients received dexamethasone, 16 mg preoperatively and three placebo postoperative doses. Eight patients received dexamethasone, 16 mg preoperatively and three 8-mg postoperative doses. Facial edema was quantified by computer scanning of standardized photographs. The underlying inflammatory process also was measured using C-reactive protein, erythrocyte sedimentation rate, and complete blood counts. Five sets of photographic and laboratory data were obtained for each patient: preoperative, day of surgery, and postoperative days 1, 2, and 3. Patients receiving dexamethasone demonstrated significantly less postoperative edema only on postoperative day 1 (P < .05) when measured photographically. C-reactive protein was significantly reduced on postoperative days 1, 2, and 3 (P < .05) in both dexamethasone groups. No significant difference was found between the two dexamethasone groups. Measurement of C-reactive protein seems to be the most sensitive method for comparing the effect of dexamethasone on postoperative inflammation. Preoperative intravenous dexamethasone significantly reduced postoperative inflammation and its associated edema after orthognathic surgery.

Adolescent↗
PubMed1993

Undiagnosed shrapnel of the tongue.

A case of a large metal fragment in the tongue is reported in a soldier injured in Operation Desert Storm. The fragment was not diagnosed for 57 days as the patient was evacuated through multiple U.S. Army medical facilities for other injuries. Diagnosis and treatment of the case are discussed.

Adult↗
PubMedDate not supplied

Intraoperative nasal transillumination for maxillary sinus augmentation procedures: a technical note.

This article presents a simple, inexpensive method for precisely locating the floor of the maxillary sinus, as well as the presence of any septa, at the time of sinus augmentation surgery. Using an anesthesia light wand placed transnasally to illuminate the sinus, the surgeon can reliably elevate the lateral maxillary wall overlying the sinus with relative ease without fear of placing the osteotomy cuts too far from the sinus floor. The same procedure can be used postoperatively to evaluate the density of the bone graft placed into the sinus prior to closure.

Bone Transplantation↗