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P R Dow

Publications and source records attributed to P R Dow.

11 recordsLinked to original sources

Alterations in muscle spindle morphology in advanced stages of murine muscular dystrophy.

Muscle spindles in the soleus of 1-year-old dystrophic mice of the C57BL/6J dy2J/dy2J strain were studied by microscopic and morphometric methods, and comparisons were made with those in age-matched normal tissue. Transverse epon sections were cut through various regions of an individual receptor, and subsequent 90 degrees reorientation enabled longitudinal examination of the same spindle. In dystrophy, alterations were detected in the outer capsule and consisted of a significant increase in its overall thickness in equatorial regions. Perineurial proliferation accompanied histiocyte and collagen infiltration. Within the equator, intrafusal fibers and sensory terminals appeared unaffected by dystrophy. Alterations in the intrafusal fibers were restricted to polar zones where the mean diameters of chain and bag fibers were significantly reduced. Polar chain fibers exhibited a greater degree of atrophy in dystrophy with a 40% diminution in size. Ultrastructural changes in intrafusal fiber polar regions were less pronounced compared to the surrounding dystrophic muscle. Mitochondrial alterations in affected intrafusal fibers included intramatrix inclusions and glycogen deposition. Vacuolization of the sarcoplasmic reticulum and subsarcolemmal tubular aggregates were also observed in polar regions of dystrophic chain fibers. Regional variation in spindle involvement in advanced murine dystrophy provides evidence that the equatorial contents of this receptor are sequestered from the deleterious effects of the disease. Capsular thickening in the equator may be an adaptive response, preventing the intrafusal fibers from undergoing the moderate change and atrophy observed at their polar ends.

Animals

Metabolism of testosterone by human semen.

Following the incubation of human sperm and seminal plasma with 13C2-labelled testosterone, the main metabolite, identified by gas chromatography-mass spectrometry (GC-MS), was 4-androstene-3,17-dione. In addition, 6 alpha- and 6 beta-hydroxytestosterone were identified. The more common metabolites of testosterone were not detected, and it is possible that the high substrate-tissue ratio influenced the result. Incubation of individual sperm and seminal plasma specimens with [14C]testosterone resulted in the identification, by specific activity measurements, of 4-androstene-3,17-dione in almost every specimen but with a widely varying conversion rate. Dihydrotestosterone, which on general grounds was considered a likely metabolite, could not be positively confirmed as such, although in some samples its presence was suspected. Gas chromatography-mass spectrometry was also used to identify steroids in sperm and seminal plasma extracts. Some, but not all the steroids identified as present in such extracts by other investigators, were found. During the course of this work C18 Sep-Pak cartridges were successfully used to prepare fractions suitable for SP-Sephadex and TEAP-Lipidex chromatography and subsequent analysis by GC-MS. Their use eliminated the need for purification steps otherwise necessary.

Androstenedione

Comparative ultrastructure of the inner capsule of the muscle spindle and the tendon organ.

The ultrastructure of inner capsule cells of the vertebrate muscle spindle was studied by transmission electron microscopy and compared with that of homologous cells in the tendon organ. Aside from variations in their complexity and pattern of organization, cells of the inner capsule in these two sensory receptors exhibited marked similarities in fine structure. The virtual absence of basal lamina in the region of the nucleated soma as well as on the branching cytoplasmic extensions of these cells was noted. In the inner capsule of both end organs, three kinds of intercellular specialization were encountered. Cell processes were typically linked together at multiple sites by intermediate junctions. In addition, focal points of membrane fusion between two or more cellular profiles were identified as tight junctions. In more extensive regions of plasma membrane overlap, gap junctions were also discerned. It seems probable that these sites along the inner capsule represent areas of mechanical and electrical linkage, enabling contiguous cells to function as a synchronous unit. Tight junctions may also provide the inner capsular sheath with specific permeability-barrier characteristics. Elements of the Golgi complex and associated presecretory vesicles and cytoplasmic granules were prominent. Their presence implicates these cells in the elaboration of the paracellular connective-tissue matrix occupying the intracapsular spaces of both receptors. The close resemblance of these cells to endoneurial fibroblasts of peripheral nerve and to hyalocytes of the vitreous body is emphasized. It is likely that, regardless of species examined, cells of the inner capsule in both receptors play an overall protective role in the formation, maintenance and regulation of their luminal paracellular contents.

Animals

Ultrastructural study of a blood-muscle spindle barrier after systemic administration of horseradish peroxidase.

The permeability of the normal muscle spindle capsule to the entrance of an exogenous protein tracer was assessed by the use of horseradish peroxidase (HRP). Adult mice were injected intravenously with a solution of HRP (MW 40,000). After varying intervals, ranging from two to 240 minutes, animals were perfused aortically with fixative, and anterior tibialis muscles were removed, processed, and examined. The results were evaluated by electron microscopic cytochemical techniques, and attention was directed to the movement of tracer and its relationship to the outer and inner capsule of the muscle spindle. HRP was first demonstrated in cytoplasmic vesicles crossing the continuous capillary endothelium supplying the muscle spindle, and was then detected in the interstitial space surrounding the outer capsule. In polar regions, HRP had entered the periaxial space by two minutes, and it was seen in cytoplasmic vesicles of the attenuated outer capsule. Later, HRP abutted the sarcolemma of intrafusal fibers, and by 12.5 minutes there was evidence of tracer in T-tubules of these muscle cells. Whereas at no time was tracer observed traversing any of the numerous intracellular junctions of the capsule, it appeared that polar regions were leaky and open-ended at their distal portions. The sensory equatorial zone was considerably less permeable to the entrance of tracer. Whereas HRP was visible intially in cytoplasmic vesicles of the subjacent capillary endothelium, it was not until 12.5 minutes that racer could be demonstrated within some vesicles of equatorial outer capsule cells. At later times, a small amount of HRP was observed in the equatorial periaxial space, where it was phagocytosed and finally sequestered by cells of the inner capsule as membrane-bound lysosomal deposits. Consequently, at no time was tracer incorported into either intrafusal fibers or their sensory nerve terminals. Thus, in contract to polar regions, the muscle spindle capsule in the equatorial zone appears to be effective in preventing the indiscriminate penetration of HRP from the bloodstream. This suggests dissimilar paths of tracer movement from the microvasculature into sensory and non-sensory regions of the muscle spindle.

Animals