Effect of 10-day cast immobilization on sarcoplasmic reticulum calcium regulation in humans.

This study investigated the effects of 10-day lower limb cast immobilization on sarcoplasmic reticulum (SR) Ca2+ regulation. Muscle biopsies were analysed in eight healthy females for maximal rates of SR Ca2+ release, Ca2+ uptake and Ca2+ ATPase activity at control, during immobilization at day 3 (IM 3), day 6 (IM 6) and day 10 (IM 10). Quadriceps muscle cross-sectional area (CSA) and 1-repetition maximum (1RM) leg extension strength were measured to determine the extent of muscle size and strength adaptations. Muscle CSA and strength decreased following 10 days of immobilization (11.8 and 41.6%, respectively, P < 0.01). A decrease in SR Ca2+ uptake rate (analysed per g wet wt) was found at IM 3 (13.2%, P=0.05), with a further decrease at IM 10 (19.8% from control, P < 0.01). At IM 10, a decrease in SR Ca2+ uptake rate (per mg protein) also occurred (19.9%, P < 0.01). Sarcoplasmic reticulum Ca2+ ATPase activity and rate of Ca2+ release were not altered with 10 days of immobilization. This study observed a decrease in SR Ca2+ uptake rate, muscular atrophy and strength loss over 10 days of immobilization in humans.

An analysis of the sidestep cutting manoeuvre.

The sidestep cutting manoeuvre is a common mechanism of noncontact or isolated ACL ruptures in athletes. We analyzed the amount and direction of tibial rotation that occurred at the knee joint with a triaxial electrogoniometer on 11 male subjects who performed the sidestep cutting manoeuvre. The mean total tibial rotation was 19.84 +/- 5.63 degrees and the mean maximum point of internal tibial rotation occurred at 34.77 +/- 5.30% of the stance phase. However, greater values for internal tibial rotation occurred in the swing phase in association with a greater angle of knee flexion. Therefore, in our subjects, during the sidestep cutting manoeuvre, internal tibial rotation did occur at the knee but was not maximal. Under normal circumstances when performing the sidestep cutting manoeuvre, maximum internal tibial rotation does not occur and so the ACL is not placed under excessive strain in such a manoeuvre. If the ACL ruptures during a sidestep cutting manoeuvre then a possible cause may be the athlete's loss of the ability to control internal tibial rotation of the knee.

Local distribution and concentration of intravenously injected 131I-9.2.27 monoclonal antibody in human malignant melanoma.

Regional measurements of 131I-9.2.27 distribution in human melanoma tumors were obtained using quantitative autoradiography. Tumors were removed from patients 72-96 h after they had received an i.v. injection of 9.15 mCi (100 mg) of 131I-9.2.27. The autoradiographic images showed that the radioactivity reaching the tumor was heterogeneously distributed. Areas of relative high and low uptake were selected in each tumor. Regions of high activity contained from 51 to 1371 nCi/g, while areas with low uptake had radioactivity ranging from 12 to 487 nCi/g. The reliability of the autoradiographic measurements was demonstrated by the strong positive correlation with direct tissue sample counting (r = 0.994 P less than 0.001). Since comparative immunocytochemistry showed a homogeneous and diffuse staining of target antigen on viable tumor cells, variability of monoclonal antibody uptake within individual tumors was not primarily due to heterogeneity of antigen expression in these cases. However, antigen levels accounted for some of the variation from tumor to tumor. When immunoperoxidase staining was repeated on adjacent sections without the addition of 9.2.27, it confirmed the nonuniform distribution of monoclonal antibody found at autoradiography. Thus, quantitative autoradiography gives information about the distribution and the local concentration of radioactive antibody in tumors allowing calculation of the radiation dose delivered to small regions within tumors.

Effects of halothane on dipalmitoylphosphatidylcholine liposomes: a Raman spectroscopic study.

Raman spectroscopy has been used to monitor the concentration of halothane (1-bromo-1-chloro-2,2,2-trifluoroethane) in 20% aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC) as well as to follow changes in the acyl chain order within the hydrocarbon interior of the liposomes. Temperature profiles for the gel to liquid-crystalline phase transitions for the liposomes were constructed from changes in peak height intensity ratios in the C-H stretching mode and C-C stretching mode regions. Halothane present at the clinical level produces a change of -0.5 degrees C in the phase transition temperature. A limiting transition temperature of about 21 degrees C and saturation of the gel phase occur when the molar ratio of halothane to DPPC reaches about 1.25. At molar ratios above 2.1, the liquid-crystalline phase is also saturated with halothane. Calculations of the distribution of halothane between the various phases in the system are presented and used to interpret literature data as well as the present experiments. Ideal solution theory accounts rather well for the depression in the transition temperature over most of the mole ratio range, an outcome which implies that halothane is excluded from the hydrocarbon interior but not the head-group region in the gel phase. The role of halothane in the head-group region is discussed.

Monoclonal antibody imaging of human melanoma. Radioimmunodetection by subcutaneous or systemic injection.

Fab fragments of monoclonal antibodies (MoAb) to melanoma, radiolabeled with 131I, were evaluated as diagnostic reagents to determine their ability to localize systemic--MoAb injected intravenously (IV)--or nodal metastatic disease--injected subcutaneously (SQ) at a site proximal to draining lymph nodes. Sixty-one scans were performed (40 IV, 21 SQ) in 59 patients who had injections of 0.2-50 mg of 131I coupled (0.2-12 mCi) antibody. These included 48.7, which identifies a high molecular weight antigen (HMW), or 96.5, which identifies a transferrin like molecule, p97. 125I coupled nonspecific Fab 1.4, reacting with murine leukemia virus, or the whole antibody BL3, reactive with a human B cell idiotypic determinant, was generally used in tandem with the patients injected SQ as a nonspecific control. All patients had immunohistochemical studies performed on biopsied lesions and demonstrated binding to the antibodies injected. Of the IV patients, 22/38 (58%) had (+) scans, 13 at SQ or nodal sites, four at visceral sites, and five at visceral and SQ sites. Patients with clinical stage II disease had SQ injection of MoAb, including 11 additional patients injected with the whole antibody 9.2.27 (anti-HMW) labeled with 111In (6 patients) or 131I (5 patients). Nodal dissection was performed 2-4 days later. All 111In coupled antibodies demonstrated excellent nodal delineation without specific identification of tumor deposits. Of the 21 patients injected SQ with MoAb, 17 had confirmed tumor in nodes. Of patients injected with Fab fragments, 4/8 (50%) had specific uptake of MoAb, although only two were successfully imaged. Increased uptake of antimelanoma antibodies was observed in some patients in lymph nodes not containing tumor and was possibly related to antigen shedding. Clearance of labeled antibody from the injection site occurred with a half life of 16-50 hours. Toxicity was limited to local discomfort at the site of SQ injection. Melanoma metastases can be identified with IV or SQ injection or radiolabeled antibodies. These reagents may be useful in the diagnosis or therapy of human melanoma. Further evaluation will be required before they could be considered clinically useful.