Citations

Reduced shoulder endurance in rotator cuff tear patients has been observed clinically. A simple and inexpensive shoulder endurance test protocol was developed. This study reports the test-retest reliability of the protocol. Twenty healthy volunteers without a history of shoulder pathology participated in the study. Each subject was tested twice, each on a separate day. Test-retest correlation coefficients of the arm endurance times were 0.59 and 0.60 for the dominant and nondominant sides, respectively. The protocol appears promising for assessing shoulder function.

Thumb motion and stability were examined after sequential division of support ligaments of the trapeziometacarpal (TMC) to simulate the pathologic condition of ligament laxity. The motion obtained with passive circumduction was measured with a magnetic tracking system. The lengths of the TMC joint ligaments were approximated by measuring the distance between origin and insertion of each ligament. The change in this apparent interorigin distance of the ligaments was measured before and after ligament sectioning. The anterior oblique ligament (AOL) and the ulnar collateral ligament (UCL) had the greatest effect on TMC joint stability during circumduction of the thumb. Division of the first intermetacarpal ligament (IML) did not produce a change in apparent length of other ligaments. We conclude that small changes in ligament length affect thumb stability and alter the path of circumduction. Neither the IML or posterior oblique ligaments were major stabilizers of the TMC joint during circumduction, prehensile grasp, or tip pinch. Reconstruction of the AOL and UCL ligaments should be considered for treatment of the initial stages of TMC instability.

Macromolecules are transported in and out of the nucleus through nuclear pores. It is poorly understood how these megadalton conduits support nucleocytoplasmic traffic during genetic reprogramming associated with cell commitment to a specific lineage. Murine embryonic stem cells were differentiated into cardiomyocytes within embryoid bodies, and contracting cells expressing myocardial-specific proteins were isolated from the mesodermal layer. Compared with postmitotic cardiac cells from heart muscle, these proliferative and differentiating stem cell–derived cardiomyocytes demonstrated a significantly lower density of nuclear pores. At nanoscale resolution, the pore channel was commonly unoccupied in heart muscle–isolated cardiac cells, yet a dense material, presumably the central transporter, protruded toward the cytosolic face of the nuclear pore complex in stem cell–derived cardiomyocytes. Stem cell–derived cardiac cells distributed the nuclear transport factor Ran in the nucleus, decreased the number of spare nuclear pore complexes from the cytosolic annulate lamellae reservoir, and expressed a set of nucleoporins, NUP214, NUP358, NUP153, and p62, involved in nuclear transport. Stem cell–derived cardiomyocytes secured transport of nuclear constitutive proteins, cardiogenic transcription factors, and cell cycle regulators, including the prototypic histone H1, myocyte enhancer binding factor 2, and p53. Thus, differentiating stem cell–derived cardiomyocytes undergo structural adaptation and mobilize nuclear transport regulators in support of nucleocytoplasmic communication during commitment to mature cardiac lineage.

One half million patients suffer from colorectal cancer in industrialized nations, yet this disease exhibits a low incidence in under-developed countries. This geographic imbalance suggests an environmental contribution to the resistance of endemic populations to intestinal neoplasia. A common epidemiological characteristic of these colon cancer-spared regions is the prevalence of enterotoxigenic bacteria associated with diarrheal disease. Here, a bacterial heat-stable enterotoxin was demonstrated to suppress colon cancer cell proliferation by a guanylyl cyclase C-mediated signaling cascade. The heat-stable enterotoxin suppressed proliferation by increasing intracellular cGMP, an effect mimicked by the cell-permeant analog 8-br-cGMP. The antiproliferative effects of the enterotoxin and 8-br-cGMP were reversed by L- cis -diltiazem, a cyclic nucleotide-gated channel inhibitor, as well as by removal of extracellular Ca 2+ , or chelation of intracellular Ca 2+ . In fact, both the enterotoxin and 8-br-cGMP induced an L- cis -diltiazem-sensitive conductance, promoting Ca 2+ influx and inhibition of DNA synthesis in colon cancer cells. Induction of this previously unrecognized antiproliferative signaling pathway by bacterial enterotoxin could contribute to the resistance of endemic populations to intestinal neoplasia, and offers a paradigm for targeted prevention and therapy of primary and metastatic colorectal cancer.

Abstract Pneumocystis carinii (PC) causes severe pneumonia in immunocompromised patients. PC is intrinsically resistant to treatment with azole antifungal medications. The enzyme lanosterol 14α-demethylase (Erg11) is the target for azole antifungals. We cloned PCERG11 and compared its sequence to Erg11 proteins present in azole-resistant organisms, and performed chromosomal and Northern blot analysis for PCERG11. Of 13 potential sites which could confer resistance to azoles, two were identical to azole-resistant Candida. By site-directed mutagenesis we changed these two sites in PCERG11 to those present in azole-sensitive Candida to generate PCERG11-SDM (E113D, T125K). We tested the susceptibility of ERG11 deletion strains of Saccharomyces cerevisiae (SC) expressing PCERG11, PCERG11-SDM, and wild-type SCERG11 to three azole antifungals: fluconazole, itraconazole, and voriconazole. PCERG11 required a 2.2-fold higher dose of voriconazole and 3.5-fold higher dose of fluconazole than SCERG11 for a 50% reduction in growth. No difference was observed in the sensitivity to itraconazole. PCERG11-SDM has increased sensitivity to fluconazole and voriconazole, but not itraconazole. We believe that the molecular structure of the lanosterol 14α-demethylase encoded by PCERG11 confers inherent resistance to azole antifungals and plays an integral part in the overall resistance of this PC to azole therapy.

Coupled vibration of arterial tubes is analyzed with the wave propagation approach and first-order shear deformation theory. Both the interior and exterior fluids are considered as compressible so that acoustic waves can be generated and propagated in the fluids. Results obtained using the theory have been evaluated against those available in the literature and the agreement has been found to be good. The theory can be used for future research on the vibration and acoustics of arterial walls. Vibration experiments were carried out on a silicone rubber tube in a water tank with a novel ultrasound stimulated optical vibrometry system. This system uses the radiation force of ultrasound to vibrate the tube at low frequency and records the resulting response by a laser vibrometer. Both the excitation and measurement are remote and noncontact. The silicone rubber tube was chosen because it has mechanical properties close to those of arteries. The fundamental frequency is well excited by the radiation force and measured with the laser. The measured fundamental frequency is in good agreement with the present theory.

Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment. Results: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P = .73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P = .12). Conclusion: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.

Purpose: Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population. This study hypothesized that use of an easy-to-read consent statement, when compared with a standard consent statement, will result in higher patient comprehension of the clinical treatment protocol, lower patient anxiety, higher patient satisfaction, and higher patient accrual.Methods: A randomized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups. Institutions were randomly assigned to administer either an easy-to-read consent statement or the standard consent statement to patients being recruited to participate in selected cancer treatment trials. Telephone interviews were conducted with a total of 207 patients to assess study outcomes.Results: Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm. Patient comprehension and state anxiety were not affected by the intervention. Accrual rates into the parent studies also did not differ significantly between the two study groups.Conclusion: Clinical trial informed consent statements can be modified to be easier to read without omitting critical information. Patient anxiety and satisfaction can be affected by the consent document. The generalizability of these study results is limited by the characteristics of the patient sample. Ninety percent of the sample were white women, and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64, indicating a literacy level at or above the ninth grade.