Resistance to radial expansion limits muscle strain and work

The collagenous extracellular matrix (ECM) of skeletal muscle functions to transmit force, protect sensitive structures, and generate passive tension to resist stretch. The mechanical properties of the ECM change with age, atrophy, and neuromuscular pathologies, resulting in an increase in the relative amount of collagen and an increase in stiffness. Although numerous studies have focused on the effect of muscle fibrosis on passive muscle stiffness, few have examined how these structural changes may compromise contractile performance. Here we combine a mathematical model and experimental manipulations to examine how changes in the mechanical properties of the ECM constrain the ability of muscle fibers and fascicles to radially expand and how such a constraint may limit active muscle shortening. We model the mechanical interaction between a contracting muscle and the ECM using a constant volume, pressurized, fiber-wound cylinder. Our model shows that as the proportion of a muscle cross section made up of ECM increases, the muscle’s ability to expand radially is compromised, which in turn restricts muscle shortening. In our experiments, we use a physical constraint placed around the muscle to restrict radial expansion during a contraction. Our experimental results are consistent with model predictions and show that muscles restricted from radial expansion undergo less shortening and generate less mechanical work under identical loads and stimulation conditions. This work highlights the intimate mechanical interaction between contractile and connective tissue structures within skeletal muscle and shows how a deviation from a healthy, well-tuned relationship can compromise performance.     

High affinity GDP binding sites on brown adipose tissue mitochondria of genetically obese ‘fa/fa’ rats

The number of high affinity [³H]GDP binding sites in brown adipose tissue mitochondria is normal in obese ( f a / f a ) rats in contrast to the reduced number of low affinity GDP binding sites. Adrenalectomy corrected the loss of low affinity binding sites in fa/fa rats but had no effect on the number of high affinity sites in either lean or obese rats. Equilibrium dialysis was used to show the presence of both high and low affinity binding sites on the purified 32 kdalton protein.     

Methimazole and generation of oxygen radicals by monocytes: potential role in immunosuppression.

A study was conducted investigating the possibility that the immunosuppressive action of methimazole (the active metabolite of the antithyroid drug carbimazole) might be due to an effect on the production of oxygen radicals by monocytes. Techniques comprised measurement of luminol dependent chemoluminescence in monocytes and a spectrophotometric assay for production of hydrogen peroxide. The results showed definite inhibition of formation of oxygen radicals by resting and stimulated monocytes, which may explain the immunosuppressive action of the drug in Graves'' disease. The findings also suggest that the formation of oxygen radicals and the initiation of the immune response may be closely related.     

Cell fusion competence and its induction in Physarum polycephalum and Didymium iridis

In heterothallic Myxomycetes, diploid plasmodia arise when haploid amoebae of two different mating types are cultured together. In this mating process, the amoebae fuse in pairs, and the resulting zygotes develop directly into plasmodia. It has been shown previously that plasmodia start to form in this fashion only when the growing amoebae in a mixed culture reach a critical density. We have investigated the cellular basis of this phenomenon by growing amoebae of different mating type separately from one another and then mixing them to test their mating ability. Amoebae from cultures above and below the critical density were, respectively, competent and incompetent to mate. Furthermore, both partners had to be competent in order for mating to occur. No binucleate cells were formed in mixtures of incompetent amoebae, indicating that they failed to fuse with one another. Incompetent amoebae growing at low density on filters with 0.2-μm pores became competent when the filters were placed on dense cultures of amoebae. We suggest that amoebae release a filter-transmissible material that accumulates during growth and induces the cells to become fusion competent.     

Production of acoustic signals during aggression in Coosa bass, <Emphasis Type="Italic">Micropterus coosae</Emphasis>

Although sound production has been described for sunfishes, it is previously unknown for basses, both groups of fishes in the family Centrarchidae. We document production of acoustic signals during aggressive encounters in Coosa bass, Micropterus coosae. During dyadic encounters, presumptive winners of contests produced sounds associated with a variety of behaviors, including chases, lateral displays, circle swims, nudging, jerking and during post aggression, while fish were stationary. These sounds are low-frequency, non-harmonic and consist of one to 41 separate pulses. In most trials larger fish won contests, regardless of territory ownership (which fish was put into the test tank first) and size difference.     

Goblet Cell Carcinoids: Characteristics of a Danish Cohort of 83 Patients

BackgroundAppendiceal goblet cell carcinoids (GCCs) exhibit neuroendocrine and adenocarcinoma features.ResultsMedian age for f/m was 59/58 years, respectively, and similar for localized and disseminated disease. At diagnosis 54 patients had localized appendiceal disease (f/m: 29/25). According to TNM 24% had Stage I, 70% had Stage II and 6% had Stage III. Twenty-nine patients had disseminated disease (f/m: 27/2). Chromogranin A, synaptophysin and p53 were positive in >90%. Serotonin was positive in 70%. Median Ki67 index was 32% (6-75%) and higher in Tang group C (50%) compared to group A (30%; p<0.0001), and group B (30%; p<0.004). All patients had surgery. Sixty-three (76%) had radical resections including all patients with localized disease. Median OS was 83 months. The 1-, 5- and 10-year survival rates were 90%, 58%, and 38%, respectively. For localized disease OS was 164 months and 1-, 5- and 10-year survival rates were 100%, 80%, and 55%, respectively. For disseminated disease OS was 19 months and 1-, 5- and 10-year survival rates were 73%, 18% and 6%, respectively. The 1-, 5- and 10 year-survival rates for f/m were 87%/96%, 49%/76% and 31%/57%, respectively (p = 0.02). According to the Tang classification group A, B, and C OS was 118, 83 and 20 months, respectively (p = 0.0002).ConclusionThe Tang classification was found to be a significant prognostic factor, while the Ki67 index was not. Localized GCCs occurred equally in males and females, while disseminated GCCs were mostly seen in females. Median age of patients with localized disease and disseminated disease was identical. Cox regression analysis found Stage IV, focally positive synaptophysin and non-radical surgery as strongest negative prognostic factors.     

Effects of peptidoglycans from periodontal pathogens on selected biological activities of CD-1 murine peritoneal macrophages

Resident CD-1 murine peritoneal macrophages were exposed to various concentrations of purified peptidoglycan isolated from members of the genera Bacteroides, Eikenella, and Actinomyces. Macrophage viability, the release of lysozyme, acid phosphatase, and prostaglandins E1 and E2 were assayed as a function of peptidoglycan concentration and time. Macrophages responded as a function of peptidoglycan concentration with increased release of acid phosphatase and prostaglandins; all cells remained greater than 90% viable during the course of the experiments. However, concentrations of peptidoglycan greater than 50 micrograms/mL were toxic to the macrophages, while the peptidoglycan from B. capillus strain 925.08 and Actinomyces viscosus strain T14AV consumed complement by both the classical and the alternate pathways. Cellular lysozyme activity and phagocytosis of Saccharomyces cerevisiae were significantly reduced in the presence of peptidoglycan. When viewed by scanning electron microscopy, the activated macrophages were rounded, lacked distinct pseudopod extensions, and possessed an increased number of microvilli and plasma membrane associated vesicles. These morphological alterations occurred as early as 3 h. Transmission electron microscopy revealed the purified peptidoglycan to have been taken up into numerous phagosomes; however, even after 24 h incubation, it was only partially degraded.