Adaptive control of intracellular Ca2+ release in C2C12 mouse myotubes

Laser scanning confocal imaging was used to monitor release of Ca²⁺ from localized regions in a skeletal muscle cell line with sparsely distributed Ca²⁺ release sites. The goal was to distinguish between two schemes proposed to explain the phenomenon of “quantal” Ca²⁺ release from caffeine-sensitive Ca²⁺ stores in muscle and other tissues: (1) all-or-none (true quantal) Ca²⁺ release from functionally discrete stores that have different sensitivities to caffeine; or (2) adaptive behavior of individual release sites, each responding transiently and repeatedly to incremental caffeine doses. Our results showed that Ca²⁺ release induced by K⁺ or caffeine occurs in discrete loci within the cell. The image areas and fluorescence intensities of some of these evoked local signals were similar to those of Ca²⁺ sparks that were observed under resting conditions and which are believed to be due to spontaneous activation of single release units. In contrast to the expectations imposed by quantal models, incremental doses of caffeine activated the same sets of release sites throughout the cell. Ca²⁺ release, at a given site, triggered by a submaximal dose of caffeine was transient and could be reactivated by addition of a higher caffeine dose, showing the same type of adaptive behavior as measured globally from larger areas of the cell. These results suggest that incremental Ca²⁺ release is accounted for by adaptive behavior of individual Ca²⁺ release sites. Received: 9 August 1995/Received in revised form and accepted: 13 October 1995     

Acupressure and preoperative parental anxiety: a pilot study

In this randomized sham-controlled study we examined the anxiolytic and sedative effects of acupressure on parents in the preoperative holding area before their children's surgery. Sixty-one parents received acupressure either at the Yintang point (midpoint between the two eyebrows) or at a sham point. Anxiety (as measured by the Stait-Trait Anxiety Inventory), arterial blood pressure, and heart rate were assessed before and after the intervention and a Bispectral Index monitor was used to continuously monitor hypnotic sedation levels. Repeated-measures analysis of variance showed that parents in the acupressure group reported significantly less anxiety at 20 min post-intervention as compared with parents in the sham group (37 +/- 10 versus 45 +/- 13, P = 0.03). Bispectral Index values, heart rate, and arterial blood pressure, however, did not differ between the two study groups (P = not significant). We conclude that acupressure at the Yintang point may be used as a treatment for parental preoperative anxiety. Future studies are needed to quantify the magnitude and duration of the anxiolytic effect.     

Treatment of high-risk patients with diabetes: motivation and teaching intervention: a randomized, prospective 8-year follow-up study

The aim of this study was to examine whether motivating patients to gain expertise and closely follow their risk parameters will attenuate the course of microvascular and cardiovascular sequelae of diabetes. A randomized, prospective study was conducted of 165 patients who had type 2 diabetes, hypertension, and hyperlipidemia and were referred for consultation to a diabetes clinic in an academic hospital. Patients were randomly allocated to standard consultation (SC) or to a patient participation (PP) program. Both groups were followed by their primary care physicians. The mean follow-up was 7.7 yr. The SC group attended eight annual consultations. The PP patients initiated on average one additional consultation per year. There were 80 cardiovascular events (eight deaths) in the SC group versus 47 events (five deaths) in the PP group (P = 0.001). The relative risk (RR) over 8 yr for a cardiovascular event in the intervention (PP) versus the control (SC) group was 0.65 (95% confidence interval, 0.89 to 0.41). There were 17 and eight cases of stroke in the SC and PP groups, respectively (P = 0.05). RR for stroke was 0.47 (95% confidence interval, 0.85 to 0.32). In the SC group, 14 patients developed overt nephropathy (four ESRD) versus seven (one ESRD) in the PP group (P = 0.05). Throughout the study period, BP, LDL cholesterol, and hemoglobin A1c were significantly lower in the PP than in the SC patients. Well informed and motivated patients were more successful in obtaining and maintaining good control of their risk factors, resulting in reduced cardiovascular risk and slower progression of microvascular disease.     

Sevoflurane versus halothane: postoperative maladaptive behavioral changes: a randomized, controlled trial

BACKGROUND: The authors conducted a double-blind, randomized, controlled trial to determine whether the use of sevoflurane in children undergoing anesthesia and surgery results in a higher incidence of postoperative maladaptive behavioral changes as compared with halothane. METHODS: Children and their parents (n = 102) were randomly assigned to either a halothane group (n = 50) or a sevoflurane group (n = 52). The intraoperative anesthetic protocol was strictly controlled, and the postoperative analgesic consumption and pain levels were recorded. The effect of the group assignment on emergence status and maladaptive postoperative behavioral changes was assessed both by validated psychological measures and physiologic instruments (actigraphy) on postoperative days 1-7. Anxiety of the parent and child was also assessed, as was the child's postoperative recovery (Recovery Inventory). RESULTS: There were no group differences in preoperative state anxiety, postoperative analgesic requirements, postoperative pain, or the incidence of emergence delirium (P = not significant). Two-way repeated-measures analysis of variance showed no group differences in the incidence of postoperative maladaptive behaviors (F4,72 = 0.60, P = 0.701) or actigraphic variables such as percent sleep, number of night awakenings, and night awakenings that lasted for more than 5 min (P = not significant). CONCLUSION: The authors found no increased incidence of emergence delirium, maladaptive postoperative behavior changes, or sleep disturbances in children undergoing anesthesia with sevoflurane as compared with halothane.     

Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

We find that CD11c(+) cells with many markers of dendritic cells (DCs) are a major cell type in the skin lesions of psoriasis. These CD11c(+) cells, which are evident in both epidermis and dermis, are the sites for the expression of two mediators of inflammation, inducible nitric oxide synthase (iNOS) and TNF-alpha in diseased skin. These cells express HLA-DR, CD40, and CD86, lack the Langerin and CD14 markers of Langerhans cells and monocytes, respectively, and to a significant extent express the DC maturation markers DC-LAMP and CD83. Treatment of psoriasis with efalizumab (anti-CD11a, Raptiva) strongly reduces infiltration by these DCs in patients responding to this agent. Disease activity after therapy was more related to DC infiltrates and iNOS mRNA levels than T cell infiltrates, and CD11c(+) cells responded more quickly to therapy than epidermal keratinocytes. Our results suggest that a type of DC, which resembles murine "Tip-DCs" that can accumulate during infection, has proinflammatory effects in psoriasis through nitric oxide and TNF-alpha production, and can be an important target for suppressive therapies.     

Sil overexpression in lung cancer characterizes tumors with increased mitotic activity

Sil (SCL interrupting locus) was cloned from the most common chromosomal rearrangement in T-cell acute lymphoblastic leukemia. It is an immediate early gene whose expression is associated with cell proliferation. Sil protein levels are tightly regulated during the cell cycle, reaching peak levels in mitosis and disappearing on transition to G1. A recent study found Sil to be one of 17 genes whose overexpression in primary adenocarcinomas predicts metastatic spread. We hypothesized that Sil might have a role in carcinogenesis. To address this question, we utilized several approaches. Using a multitumor tissue array, we found that Sil protein expression was increased mostly in lung cancer, but also at lower levels, in a subset of other tumors. Microarray gene expression analysis and immunohistochemistry of lung cancer samples verified these observations. Sil gene expression in lung cancer correlated with the expression of several kinetochore check-point genes and with the histopathologic mitotic index. These observations suggest that overexpression of the Sil gene characterizes tumors with increased mitotic activity.     

Associations between measles antibody levels and the protein structure of class II human leukocyte antigens

In this study, we describe associations between variation in human leukocyte antigen (HLA) DP and DQ amino acid sequences and low measles antibody levels after measles immunization. We tested serum samples from 242 children for measles immunoglobulin G antibodies. We performed class II HLA typing and examined associations between DQ and DP exon 2 amino acid sequences and antibody levels. No DP amino acid variants were associated with seronegativity. However, 11 DQA and 6 DQB amino acid variants were associated with seronegativity (p<0.005). These amino acid variants were highly correlated, and the significant DQA amino acids were only found in alleles *0201, *0301, *0401, *0501, and *0601. Two of the amino acids associated with measles seronegativity were located in predicted binding pockets of the DQ molecule; one was present in the leader sequence. Among the DQB alleles, all of the amino acid variants associated with seronegativity were present only in the DQB*0201 allele. Two of the amino acids associated with seronegativity were located in predicted binding pockets of the DQ molecule; two were located in the leader sequence. Our data suggest that specific DQA and DQB amino acid variations are associated with measles seronegativity after vaccination.