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Biomedical subjects

G M Breinin

Publications and source records attributed to G M Breinin.

At least 19 recordsLinked to original sources

Diltiazem reduces the contractility of extraocular muscles in vitro and in vivo.

Diltiazem, a Ca-channel blocker that is used clinically for the treatment of hypertension and cardiac arrhythmias, reduces the contractility of extraocular muscles. Exposure of rabbit extraocular muscle to diltiazem in vitro reduces the sustained tension that is generated by the tonic, multiply innervated fibers, and decreases the baseline, or resting, tension of the muscle. When diltiazem is injected into a selected extraocular muscle in the rabbit in vivo, it causes a temporary weakening of the muscle, which is indicated by a deviation of eye position. These in vivo effects are of short duration, are easily reproducible, and vary with dosage. The results of this study raise the possibility that diltiazem may be used as an alternative to the surgical treatment of strabismus and other oculomotor dysfunctions including blepharospasm.

Adenosine Triphosphatases

Cadmium reduces extraocular muscle contractility in vitro and in vivo.

Cadmium, a blocker of calcium channels in various excitable cells, reduces the contractility of extraocular muscles. When applied to rat extraocular muscles in vitro, it reduces the sustained or tonic tension generated by the tonic multiply innervated fibers of the global layer of the muscles. When injected in vivo into rabbit extraocular muscles, it produces a temporary paralysis of the muscles and a deviation of the eye position. These effects are presumed to involve a blockade of the calcium channels of the muscle fibers and of the neuromuscular junctions. It is proposed that, on the basis of these effects, a non-surgical treatment of strabismus could be developed.

Animals

Intermitochondrial junctions in the extraocular muscle of the rat.

Intermitochondrial junctions with a spacing of 17-21 nm were observed in the superior rectus muscle of a rat. Periodic rounded densities are aligned midway between the apposed outer mitochondrial membranes at some of these junctions. Such densities have a diameter of about 8-10 nm and a center-to-center spacing of about 26-30 nm. These junctions occur in cases where one mitochondrial profile is enclosed within another or where two profiles are interlocked so that their combined overall form has a smoothly contoured profile. Intermitochondrial junctions seem not to have been previously described in muscle, but have been reported in other kinds of tissues. In agreement with those previous reports, the presently observed intermitochondrial junctions usually involve mitochondria that display atypical features indicative of tissue abnormality or stress. Such junctions were never observed in normal extraocular muscle.

Animals

Latter reorganization of membrane-glycogen complexes in rabbit extraocular muscle.

Characteristic modes of secondary reorganization were observed in membrane-glycogen complexes of rabbit extraocular muscle. These included (a) an irregular widening or narrowing of the intracisternal space, (b) a loss of the typical intracisternal flocculent densities, and (c) the acquisition of intercisternal flocculent densities. In irregularly widened cisternae, the membranes tended to remain closely adjacent to the intervening glycogen layer, thereby forming triads composed of a glycogen layer enclosed within the apposing membranes of adjacent cisternae. In the absence of glycogen particles from contiguous portions of several lamellae, the membranes became compacted to form myeloidlike figures. Degenerating complexes sometimes displayed distention of intercisternal spaces and layers of atypically small particles. The above modifications of membrane-glycogen complexes would be compatible with the notion that these structures are involved in the process of glycogen metabolism, as opposed to the previously suggested notion that these structures are transient vehicles for the accumulation of glycogen masses.

Animals

Cytoplasmic inclusions in rabbit extraocular muscle.

Cytoplasmic inclusion bodies, similar to those previously described in abnormal and normal human extraocular muscle, were observed in the orbital surface layer of the superior rectus muscle in rabbit. These inclusion bodies are composed of a flocculent material of low density studded with granular foci of increased density. In sequential samples of serially reconstructed muscle fibers visualized by electron microscopy, cytoplasmic inclusion bodies were seen in 4.5% of 1187 samples through multiply innervated fibers that vary systematically in diameter along their length; inclusion bodies were also seen in 0.8% of 354 samples through multiple innervated fibers of constant diameter. Cytoplasmic inclusion bodies were not seen in 1838 samples through singly innervated fibers. These data suggest that such inclusion bodies may occur preferentially in multiply innervated fibers. The present findings are not compatible with previous suggestions that such cytoplasmic inclusion bodies may be indicative of a pathologic or aging process. These findings are consistent with previous suggestions that such inclusion bodies are to be considered as normal structures in extraocular muscle.

Animals

Oculocutaneous albinism associated with Apert's syndrome.

Five of nine patients with Apert's syndrome (acrocephalosyndactyly) showed an associated hypopigmentation of hair, skin, and eyes. The hair color of these five patients ranged from light brown to blond, the skin was pale, and the irides hazel or blue. Iris transillumination and hypopigmentation of the fundus were present and associated with absent or diffuse foveal reflexes. Unlike most forms of classic oculocutaneous albinism, however, there was good visual acuity and no pendular nystagmus. The evidence indicated that the lack of pigmentation associated with the characteristic skeletal anomalies of Apert's syndrome resulted from a disturbance of independent, genetically related, processes occurring at a common point in gestation.

Acrocephalosyndactylia

Structural alterations of extraocular muscle associated with Apert's syndrome.

An inferior oblique muscle from a patient with Apert's syndrome was examined by light and electron microscopy. Alterations in the muscle fibres, the myoneural junctions, and intramuscular nerves were observed. These data are not compatible with the widespread notion that motility disturbances in this syndrome are solely due to mechanical limitations.

Acrocephalosyndactylia

Double-membrane arrays in type II fibers of mouse extraocular muscle.

Double-membrane arrays were observed in singly innervated type II fibers of the global region of mouse superior rectus. These arrays were selectively confined to the endplate region of such cells. Close associations and continuities between the cisternae of the arrays with those of the intermyofibrillar sarcoplasmic reticulum suggest derivation of the former from the latter. These proliferations of the cellular smooth membranes might be related to the specialized functional requirements of the innervation site.

Animals

Light and electron microscopic serial analysis of mouse extraocular muscle: morphology, innervation and topographical organization of component fiber populations.

Mouse superior rectus extraocular muscle was examined in serial section by light and electron microscopy. By such analysis, it was possible to discriminate single versus multiple innervation, characteristics of internal cell morphology, and topographical distribution of the respective fiber populations within the muscle. Singly innervated (SIF) and multiply innervated fibers (MIF) were observed, both in an orbital surface layer and in the underlying global region of the muscle. Five morphologically distinct fiber types (three SIF and two MIF) were discriminable in terms of fiber diameter, mitochondrial richness, development of the sarcoplasmic reticulum, and myofibrillar size. Many fibers both SIF and MIF, terminated variously along the length of the muscle. The diameter of orbital MIF typically varied from one end of the fiber to the other by a factor of about three; the global MIF were of essentially constant diameter. The junctional complexity varied among the respective types of SIF. The MIF of both the global and orbital regions exhibited comparable ranges of complexity in their neuromuscular junctions.

Animals

Congenital total external ophthalmoplegia associated with infantile spinal muscular atrophy. Fine structure of extraocular muscle.

A case of total congenital external ophthalmoplegia associated with infantile spinal muscular atrophy is presented. In the first 29 months of life, ophthalmoplegia has remained complete. Ultrastructure of lateral rectus extraocular muscle indicates a neurogenic process as the basis of the ophthalmoplegia. Light microscopy alone is insufficient to distinguish primary "myopathic" from "neurogenic" disease in external eye muscles.

Child, Preschool

Structural alterations of the junctional region in extraocular muscle of dystrophic mice. I. Modifications of sole-plate nuclei.

Sole-plate nuclei of the C57Bl/6Jdy2j dystrophic mouse showed apparent selective susceptibility to various forms of structural alteration. Pyknosis and chromatin fragmentation were seen in addition to vacuolar and membranous nuclear inclusions. These were often associated with neuromuscular junctions with markedly reduced or virtually absent junctional folding. Membranous proliferations also occurred nearby sole-plate nuclei of such flattened junctions.

Animals

Structural alterations of the junctional region in extraocular muscle of dystrophic mice. II. Hypertrophy of the neuromuscular junctional apparatus.

The fine structure of end-plate abnormalities was studied in the Bar harbor C57Bl/6jdy2j dystrophic mouse. A marked increase in area and volume of junctional sarcoplasm was often apparent. Such hypertrophied end-plates were often penetrated by networks of axonal terminal branches. At times, pseudopod-like extensions of the junctional sarcoplasm encompassed and made protracted synaptic contact with the incoming axon. Such apparent remodeling of the neuromuscular apparatus might represent a compensatory cellular response to decreased impulse transmission efficiency, as might result from a flattening of the postjunctional folding seen on abnormal muscle fibers in these animals.

Animals

Morphological fiber types of retractor bulbi muscle in mouse and rat.

Retractor bulbi muscles of mouse and rat were examined by light and electron microscopy. Two morphological fiber types were observed, analogous to Type I and Type II cells of skeletal musculature and comparable to fibers observed in the global region of the rectus extraocular muscles of these species.

Animals