Role of protein kinase C in calcium sensitization during muscarinic stimulation in airway smooth muscle.

Muscarinic receptor stimulation increases Ca2+ sensitivity, i.e., the amount of force produced at a constant submaximal cytosolic Ca2+ concentration ([Ca2+]i), in permeabilized smooth muscle preparations. It is controversial whether this increase in Ca2+ sensitivity is in part mediated by protein kinase C (PKC). With the use of a beta-escin permeabilized canine tracheal smooth muscle (CTSM) preparation, the effect of four putative PKC inhibitors [calphostin C, chelerythrine chloride, a pseudosubstrate inhibitor for PKC [PKC peptide-(19-31)], and staurosporine] on Ca2+ sensitization induced by acetylcholine (ACh) plus GTP was determined. Preincubation with each of the inhibitors did not affect subsequent Ca2+ sensitization induced by muscarinic receptor stimulation in the presence of a constant submaximal [Ca2+]i, neither did any of these compounds reverse the increase in Ca2+ sensitivity induced by ACh plus GTP. Administration of a 1,2-diacylglycerol analog, 1-oleoyl-2-acetyl-sn-glycerol, did not induce Ca2+ sensitization at a constant submaximal [Ca2+]i. Thus we found no evidence that PKC mediates increases in Ca2+ sensitivity produced by muscarinic receptor stimulation in permeabilized CTSM.

Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle.

1. Ketamine is a potent bronchodilator which relaxes airway smooth muscle (ASM). Clinically, ketamine is used as a 1:1 racemic mixture of enantiomers that differ in their analgesic and anaesthetic effects. The aim of this study was to determine whether there was a difference between the enantiomers in their ability to relax isolated ASM and to explore mechanisms responsible for any observed differences. 2. Canine tracheal smooth muscle strips were loaded with fura-2 and mounted in a photometric system to measure simultaneously force and [Ca2+]i. Calcium influx was estimated by use of a manganese quenching technique. 3. In strips stimulated with 0.1 microM ACh (EC50) R(-)-ketamine (1-100 microM) caused a significantly greater concentration-dependent decrease in force (P<0.0001) and [Ca2+]i than S(+)-ketamine (1-100 microM) (P<0.0005). In contrast, there was no significant difference between the enantiomers in their ability to inhibit calcium influx (45% decrease in influx rate for R(-)-ketamine and 44% for S(+)-ketamine, P =0.782). In strips contracted with 24 mM isotonic KCI (which activates voltage-operated calcium channels), the enantiomers modestly decreased force and [Ca2+]i; there was no significant difference between the enantiomers in their effects on force (P=0.425) or [Ca2+]i (P=0.604). 4. The R(-)-enantiomer of ketamine is a more potent relaxant of ACh-induced ASM contraction than the S(+)-enantiomer. This difference appears to be caused by differential actions on receptor-operated calcium channels.

On-line performance assessment using rating scales.

The purpose of this paper is to report on the development of the on-line performance assessment instrument--the Assessment of Motor and Process Skills (AMPS). Issues that will be addressed in the paper include: (a) the establishment of the scoring rubric and its implementation in an extended Rasch model, (b) training of raters, (c) validation of the scoring rubric and procedures for monitoring the internal consistency of raters, and (d) technological implementation of the assessment instrument in a computerized program.

Penile metastasis secondary to supraglottic squamous cell carcinoma: review of the literature.

We report an unusual supraglottic carcinoma metastasis to the penis. Review of the literature revealed more than 300 cases of metastatic lesions to the penis, excluding primary neoplasms from skin, urethra and blood. Of these metastatic neoplasms 16 originated above the diaphragm, only 4 of which were from the head and neck region. The most common neoplastic metastases to the penis in order of frequency were from the bladder, prostate, rectum and rectosigmoid areas, and kidney in 32, 30, 13 and 8% of the cases, respectively. The incidence of other primary tumor sites that metastasize to the penis is extremely rare.

Adjustment of provisional mortality series: the dynamic linear model with structured measurement errors.

The authors "consider the problem of adjusting provisional time series using a bivariate structural model with correlated measurement errors. Maximum likelihood estimators and a minimum mean squared error adjustment procedure are derived for a provisional and final series containing common trend and seasonal components. The model also includes measurement errors common to both series and errors that are specific to the provisional series. [The authors] illustrate the technique by using provisional data to forecast ischemic heart disease mortality."

Glossodynia after radiation therapy and chemotherapy.

Radiation therapy and chemotherapy have decreased the mortality rates of cancer patients, but the morbidity associated with oral complications is high in many cases. A pretreatment oral evaluation and institution of a preventive care program reduce oral symptoms such as glossodynia considerably. When oral symptoms are minimized, the dentist can improve the patient's quality of life.

Carrier detection of Duchenne dystrophy by frequency analysis of the electromyogram.

A new method for Duchenne muscular dystrophy (DMD) carrier detection based on frequency analysis of electromyograms (EMG) taken from relative force contractions shows great promise in classifying possible carriers. Nine carriers were examined and compared to nineteen normals in an attempt to define a discriminant function that would be effective in classification of possible carriers of the gene responsible for DMD. EMG data were taken at 20%, 40%, and 60% of maximum effort from the biceps brachii using a specially designed dynamometer apparatus. The apparatus was able to isolate the biceps muscle group and allowed for adjustment to accommodate different body sizes. Three signal processing methods were used to find variables in the frequency domain that would provide the best discriminant function based on the jackknife classification method. Of these methods, the most promising appears to be the high-to-low ratio method at 20% maximum contraction. When combining the high and low values found with this test in conjunction with the peak cepstrum values also found at 20% maximum contraction, discrimination was found to be 83.8% accurate. Because this classification is not based solely on definite carriers, and appears to be independent of serum creatine phosphokinase (CPK) values, it would seem that classification based on a definite carrier population could be performed with greater accuracy, especially with the addition of CPK values.

Modeling mortality fluctuations in Los Angeles as functions of pollution and weather effects.

Linear and nonlinear models are used to investigate possible associations between mortality and pollution and weather effects in Los Angeles County. State-space modeling and time and frequency domain regressions are used to modify the data base and to isolate significant weather factors and pollutants associated with increased daily mortality. Nonparametric and parametric regression methods are used to develop nonlinear dose-response profiles relating mortality to temperature and to the statistically significant pollutants. A parametric nonlinear time series model involving linear and squared terms in temperature and the logarithm of pollution provides a reasonable predictive model.