Indomethacin reduces raised intraluminal gallbladder pressure in acute cholecystitis

Indomethacin was recently shown to have a potent analgesic effect on biliary pain. The underlying mechanism is not fully clear, although reduction of increased gallbladder pressure by inhibition of prostaglandin synthesis had been suggested. For further clarification of this mechanism, the effect of intravenous indomethacin on the intraluminal gallbladder pressure was investigated in patients undergoing operation for acute cholecystitis. After laparotomy, gallbladder pressure was measured continuously during 25 min in 20 patients, 10 of whom received 100 mg indomethacin intravenously, while 10 were untreated controls. High intraluminal gallbladder pressure was found in all patients. Indomethacin reduced the average pressure by 11% in 20 min, whereas the corresponding pressure in the controls was constant. The results indicate that acute cholecystitis is associated with substantially raised intraluminal pressure, and that the analgesic action of indomethacin on biliary pain may be attributable to a local effect on gallbladder function, resulting in reduction of intraluminal pressure.     

Effects of intraluminal prostaglandin E2 in vivo on secretory behavior and ultrastructural changes in mouse gallbladder epithelium

It has been suggested that glycoproteins play an important role as a nucleating agent in the pathogenesis of gallstone formation. Arachidonic acid, by an indomethacin-sensitive mechanism, is known to enhance gallbladder mucus release, suggesting that prostaglandins may regulate gallbladder epithelial release of mucus. In this study, the glycoprotein granules of the principal cells of the mouse gallbladder epithelium were morphometrically analyzed using electron microscopy. It was shown that 5 micrograms of prostaglandin E2, injected into the gallbladder lumen of the anesthetized mouse, reduced the relative volume of glycoprotein granules from 3.0% to 0.7% of the cytoplasmic volume within 20 min, whereas injection of the same amount of the solvent for prostaglandin E2 had no such effect.     

Immunohistochemical characterization of human masseter muscle spindles

An enzyme- and immunohistochemical study has been performed on human masseter muscle spindles. Antibodies selective for different myosin heavy chain (MHC) isoforms and M-band proteins (M-protein, myomesin, and MM-CK) were used. The expression of these proteins was determined in the different intrafusal fiber types. Nuclear bag₁ and nuclear bag₂ fibers expressed predominantly slow-twitch and slow-tonic MHCs. The bag₂ fibers in addition contained fetal MHC. Nuclear chain fibers coexpressed embryonic, fetal, and fast-twitch MHCs. The bag₂ and chain fibers contained all three M-band proteins, whereas the bag₁ fibers contained only myomesin. In general the MHC expression in the human masseter intrafusal fiber types was similar to that previously reported for limb muscles in man as well as for limb and masseter muscles in other species. However, the number of intrafusal fibers per spindle was unusually high (up to 36). This reinforces the idea that masseter muscle spindles have a strong proprioceptive impact during the control of jaw movements. © 1994 John Wiley & Sons, Inc.     

Enzyme-histochemical differences in fibre-type between the human major and minor zygomatic and the first dorsal interosseus muscles

Human masticatory muscles, innervated by the trigeminal nerve, differ in fibre-type composition from limb and trunk muscles, but the anterior and the posterior belly of the human digastric muscle, innervated by the trigeminal and facial nerves, respectively, do not. The major and minor zygomatic muscles from adult males, which originate from the second branchial arch and are supplied by the facial nerve, were analysed enzyme-histochemically and compared with the first dorsal interosseus hand muscle, which has spinal innervation and, like the masticatory and facial muscles, a large cortical representation. Both zygomatic muscles had a marked predominance of type II fibres, the minor one having the largest proportion (89.1 per cent) ever reported in human skeletal muscle. Besides type I, IIA, IIB, and a few type IIC fibres, there was a large group with an ATPase reaction at pH 4.6, between that of type IIA and type IIB, and termed IIAB. This fibre-type profile may reflect a special isomyosin composition. Type I and II fibres were of about equal diameter, corresponding to that of type I fibres in the masticatory muscles. Individual and intra-muscular variability in fibre size and shape was considerable. The unusually high frequency of type II fibres in the zygomatic muscles suggest that they have fast-contraction properties and relatively large motor units, and therefore are poorly adapted to finely-graded movements. The absence of muscle spindles supports this view. The hand muscle had a chequer-board pattern of type I, IIA and IIB fibres, similar to that of large limb and trunk muscles, with no difference between its two heads.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of cytokeratins and vimentin in salivary gland carcinomas as revealed with monoclonal antibodies

Summary The expression and distribution of cytokeratins and vimentin in fifteen malignant salivary neoplasms were examined by immunocytochemical techniques using, five monoclonal antibodies (mAbs) against different epitopes of Cytokeratins (CKs) (mAbs PKK1, PKK2, and PKK3, identifying CKs 8, 18 and 19, CKs 7, 17 and 19, and CK 18, respectively) and Vimentin (mAbs V9 and V24). Antibody PKK1 gave strong reactions in all neoplasms showing the similarity of these tumours to other digestive system adenocarcinomas. Three general staining patterns of the neoplasms were recognized with respect to the reactivity of mAbs PKK2, PKK3, and V9. Mucoepidermoid cancer, salivary duct carcinoma and a clear cell carcinoma had a higher relative content of CKs 7, 17 and 19 than of CK 18. Adenoid cystic carcinoma showed the same CK pattern but in the periphery of the tumour cords vimentin was readily detected. In two acinic cell carcinomas, the relative content of CK 18 was higher than that of CKs 7, 17 and 19. Furthermore vimentin was expressed in the tumour cells. However, one mucoepidermoid carcinoma showed vimentin expression and two acinic cell carcinomas were vimentin negative and more reative for PKK2 than PKK3. Pecularities in CK expression were seen: squamous areas of mucoepidermoid carcinomas were stained by mAb PKK3 although CK 18 is not present in normal squamous epithelia or in squamous cell carcinomas of tongue and skin. In conclusion, the different salivary neoplasms can be distinguished on basis of IFP content. Such a differentiation fits with current theories of histogenesis, i.e. vimentin is seen in tumours presumed to arise from intercalated duct reserve cells, whilst the vimentin negative neoplasms would be expected to arise in excretory duct reserve cells.     

Fiber type composition of the human female trapezius muscle: Enzyme-histochemical characteristics

The anatomy of the human trapezius muscle is complex, with an extensive origin and fibers running in different directions. The muscle is commonly divided into three different muscle portions according to the fiber direction: the descending, transverse, and ascending portions. In a previous study in males, the structure of the muscle differed between different portions with respect to the enzyme-histochemical fibertype profile. The lower regions of the descending portion and the transverse and the ascending portions had a predominance of type I fibers. The type II fibers were more frequent in the upper regions of the descending portion, and the cross-sectional fiber area in this region of the muscle was smaller. In this study, we have investigated the trapezius muscle in females and compared the results with those from males. The different portions of the female muscle had a relatively even fiber-type composition. However, there tended to be fewer type I fibers and more type IIB fibers in the descending portion of the muscle, and the fibers of the lower regions of the descending portion were somewhat larger. The fiber-type distribution pattern was similar to that of the male trapezius muscle, but the mean cross-sectional area of the fibers in the female muscle was considerably smaller. Thus, our conclusion is that the trapezius muscle of females has a similar activity pattern as that of males. The significantly smaller cross-sectional fiber area, however, may indicate a lower functional capacity which may be of importance in the development of neck and shoulder dysfunction in females.     

Human single masseter muscle fibers contain unique combinations of myosin and myosin binding protein C isoforms

Striated craniofacial and limb muscles differ in their embryological origin, regulatory program during myogenesis, and innervation. In an attempt to explore the effects of these differences on the striated muscle phenotype in humans, the expression of myosin and myosin-associated thick filament proteins were studied at the single fiber level both in the human jaw-closing masseter muscle and in two limb muscles (biceps brachii and quadriceps femoris muscles). In the masseter, unique combinations of myosin heavy chain (MyHC) and myosin binding protein C (MyBP-C) isoforms were observed at the single fiber level. Compared to the limb muscles, the MyHC isoform expression was more complex in the masseter while the opposite was observed for MyBP-C. In limb muscles, a coordinated expression of three MyHC and three MyBP-C isoforms were observed, i.e., single fibers contained one or two MyHC isoforms, and up to three MyBP-C isoforms. Also, the relative content of the different MyBP-C isoforms correlated with the MyHC isoform expression. In the masseter, on the other hand, up to five different MyHC isoforms could be observed in the same fiber, but only one MyBP-C isoform was identified irrespective MyHC isoform expression. This MyBP-C isoform had a migration rate similar to the slow MyBP-C isoform in limb muscle fibers. In conclusion, a unique myofibrillar protein isoform expression was observed in the human masseter muscle fibers, suggesting significant differences in structural and functional properties between muscle fibers from human masseter and limb muscles. This revised version was published online in July 2006 with corrections to the Cover Date.     

Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle.

We have investigated the distribution of the laminin beta 2 chain (previously s-laminin) in human fetal and adult skeletal muscle and compared it to the distribution of laminin beta 1. Immunoblotting and transfection assays were used to characterize a panel of monoclonal and polyclonal antibodies to the laminin beta 2 chain. We found that laminin beta 1 chain was detected at all times during development from 10 weeks of gestation. Laminin beta 2 chain was first detected in 15 to 22-week-old fetal skeletal muscle as distinct focal immunoreactivity in the sarcolemmal basement membrane area of some myofibers. In the adult skeletal muscle, laminin beta 2 chain immunoreactivity was found along the entire perimeter of each of the individual myofibers in a large series of different muscles studied. Laminin beta 2 chain was similarly found in the skeletal muscle basement membranes in patients with Duchenne and Becker muscular dystrophy. Immunoaffinity chromatography of muscle extracts with a monoclonal antibody to the laminin alpha 2 chain followed by immunoblotting with various antibodies to the beta 2 chain demonstrated the presence of the laminin-4 (alpha 2-beta 2-gamma 1) isoform. Together the present results demonstrate a prominent extrasynaptic localization of laminin beta 2 in the human muscle, suggesting that it may have an important function in the sarcolemmal basement membrane.     

Myotilin: a prominent marker of myofibrillar remodelling

Myofibrillar remodelling with insertion of sarcomeres is a typical feature of biopsies taken from persons suffering of exercise-induced delayed onset muscle soreness. Here we studied the presence of the sarcomeric protein myotilin in eccentric exercise related lesions. Myotilin is a component of sarcomeric Z-discs and it binds several other Z-disc proteins, i.e. alpha-actinin, filamin C, F-actin and FATZ. Myotilin has previously been shown to be present in nemaline rods and central cores and to be mutated in limb girdle muscular dystrophy 1A (LGMD1A) and in a subset of myofibrillar myopathies, indicating an important role in Z-disc maintenance. Our findings on non-diseased muscle affected by eccentric exercise give new information on how myotilin is associated to myofibrillar components upon remodelling. We show that myotilin was present in increased amount in lesions related to Z-disc streaming and events leading to insertion of new sarcomeres in pre-existing myofibrils and can therefore be used as a marker for myofibrillar remodelling. Interestingly, myotilin is preferentially associated with F-actin rather than with the core Z-disc protein alpha-actinin during these events. This suggests that myotilin has a key role in the dynamic molecular events mediating myofibrillar assembly in normal and diseased skeletal muscle.     

Skeletal muscle telomere length in healthy, experienced, endurance runners

Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum terminal restriction fragment (TRF) length in the vastus lateralis muscle of 18 experienced endurance runners (mean age: 42 ± 7 years) to those of 19 sedentary individuals (mean age: 39 ± 10 years). The runners had covered almost 50,000 km in training and racing over 15 years. Minimum TRF lengths measured in the muscle of both groups were similar (P = 0.805) and within the normal range. Minimum TRF length in the runners, however, was inversely related to their years spent running (r = −0.63, P = 0.007) and hours spent training (r = −0.52, P = 0.035). Therefore, since exposure to endurance running may influence minimum TRF length, and by implication, the proliferative potential of the satellite cells, chronic endurance running may be seen as a stressor to skeletal muscle.