Immunohistochemical and ultrastructural observations on Homer Wright (neuroblastic) rosettes and the "pale islands" of human cerebellar medulloblastomas.

A combined immunohistochemical and ultrastructural study of 20 cerebellar medulloblastomas has demonstrated features of early neuronal differentiation. The differentiation features are primarily encountered in the Homer Wright rosettes and in the reticulin-free "pale islands," or "follicles," of the desmoplastic variant. They consist of parallel arrays of aggregated neurite-like processes containing longitudinally oriented microtubules (immunoreactive for polyvalent antisera to tubulin and gamma-enolase, but nonreactive for a monoclonal antibody to the 150/200 kD subunits of neurofilament protein) and junctional adhesion plaques. We consider the inherent property of self-aggregation of the neurite-like processes with adhesion plaques a significant mechanism in the formation of Homer Wright rosettes. Further differentiation and elongation of these cell processes may lead to the formation of "pale islands" in the desmoplastic medulloblastoma. A meshwork of astroglial cells, coexpressing glial fibrillary acidic protein and S-100 protein immunoreactivity, forms an integral part of the "pale island." The histogenetic significance of these astrocytes and their relationship to tumor cells expressing early neuronal differentiation remains to be defined.

Amyloidosis presenting as a penile mass.

We report a unique case of amyloidosis presenting as a localized soft tissue mass in the shaft of the penis unassociated with systemic amyloidosis, trauma, penile ulcers, syphilis or other venereal diseases. The patient presented with a penile mass and intermittent hematuria. Biopsy revealed homogeneous deposits of amorphous eosinophilic material, and histochemistry and electron microscopy demonstrated the classical features of amyloid.

Soluble age-related factors from skeletal muscle which influence muscle development.

Successful regeneration of damaged striated muscle in adult mice is dependent on the regeneration of newly differentiated myofibers from proliferating satellite cells and inhibition of scar tissue formation by fibroblasts. As with most tissues, the ability of skeletal muscle to regenerate decreases in older animals. In this study, we have analysed soluble extracts from intact and regenerating skeletal muscle from mice of different ages for their ability to affect avian myogenesis in tissue culture. We were interested in determining whether an age-dependent difference could be detected with this tissue culture bioassay system. Total cell proliferation in the cultures, measured by [3H]thymidine incorporation was increased equally by muscle extracts from both young and older mice but the resulting cell populations differed in proportion of cell types. The ratio of myoblasts to fibroblasts was significantly greater in cultures exposed to extracts from younger mouse muscle as compared with cultures exposed to extracts from older animals. This age-related activity was found to reside in a low molecular weight (MW) (greater than 12 kD) component of the extract. This fraction had dissimilar effects on myoblasts and fibroblasts. Relative to saline controls, myoblast proliferation was increased and fibroblast proliferation decreased. The low MW fraction from younger mouse muscle extracts stimulated myogenic cell proliferation and myotube formation to a greater extent than the similar fraction prepared from older mouse muscle. Conversely, younger mouse muscle fractions had significantly greater inhibitory activity against fibroblast proliferation than did older mouse muscle fractions.

Intraskeletal myofiber metastasis of breast carcinoma.

The authors report a case of chest skeletal muscle involvement by recurrent adenocarcinoma of the breast, in which individual myofibers were invaded by breast carcinoma cells. This unusual type of skeletal muscle involvement is especially interesting because it is known that the sarcolemma of skeletal myofibers is very resistant to enzymatic, mechanical, and chemical breakage.

Interstitial space of mouse skeletal muscle.

1. A new preparation of mouse skeletal muscle, prepared from pectoral muscles, is described.2. The sorbitol space of this muscle, both in vivo and in vitro, has been measured with dynamic loading of the muscle in vitro as an experimental variable.3. The Na(+) and K(+) contents of the muscle have been determined and the apparent intracellular concentration for these ions calculated both in vivo and after incubation in vitro.4. Histological studies on the incubated muscle have been made so as to permit comparison of the changes in the chemical measurements with changes in the ultrastructure of the muscle.5. The results of these experiments show that there is an increase in the apparent extracellular space of the muscle following incubation. This increase is constant, and independent of the load, with the important exception that unloaded muscles do not reach an equilibrium during the period of incubation and have a much greater apparent extracellular space.6. Intracellular Na(+) and K(+) concentrations are consistent with the sorbitol being restricted to an extracellular phase in the loaded muscle; but the evidence implies that sorbitol in the unloaded muscle penetrates into a space from which Na(+) is excluded.7. The total water content of the muscle per unit weight is unchanged by incubation, indicating that the apparent change in sorbitol space is in the ratio of intracellular space to extracellular space rather than by addition of water to the extracellular space. The significance of these results is discussed with reference to the use of such preparations for in vitro studies.

Periosteal and metaplastic bone formation in mouse minced muscle regeneration.

Structures resembling exostoses derived from periosteum and metaplastic nodules of cartilage and bone were induced in mouse legs by isotopic implants of minced skeletal muscle or heterotopic implants of nonlimb skeletal and cardiac muscle that does not regenerate. Liver mince implants produced no periosteal response. Control experiments demonstrated that, after excision of the muscle without the placing of any implant, no periosteal response or metaplastic bone occurred unless the periosteum was deliberately injured. Metaplastic nodules of cartilage and bone arose from the fibrous stroma that constituted the greater part of the implant when muscle mince regeneration was unsuccessful. The development of both the periosteal response and the metaplastic bony nodules is inversely related to the efficiency of phagocytosis by macrophages that remove the implanted debris and the concomitant degree of regeneration of new muscle. These phenomena, and, therefore, bone and cartilage formation, are strongly age related. The rapidity and extent of development of both abnormal bone and cartilage--less than 7 days--and its reproducibility may make this phenomenon a useful model for studies on the pathophysiology of bone and cartilage formation, particularly with regard to age.

Age-related impeded regeneration of mouse minced anterior tibial muscle.

The effect of increasing age on the completeness of anterior tibial muscle regeneration from autotransplants of minced muscle has been studied in Swiss Webster and C57/B6J mice aged 18 to 120 days. A progressively declining capability to regenerate new myofibers was associated with a decreasing phagocytic clearance of implanted myofiber debris. Concurrently, there was decreased presumptive myoblast proliferation and new myofiber formation. The importance of age-related host factors, including nonspecific macrophage activity, in muscle mince regeneration was demonstrated by: (1) the successful regeneration of muscle in heterotransplanted muscle minces from older mice implanted in younger animals and (2) the failure of muscle regeneration when the reverse experiment was performed in syngeneic animals. Heterologous striated muscle from the diaphragm regenerated in the bed of the excised anterior tibial muscle, whereas heterologous cardiac muscle failed to regenerate as expected because of the absence of satellite cells. The failure of phagocytic clearance of implanted myofiber mince and concurrent retardation of regeneration suggests a major age-related nonimmune role of phagocytic macrophages in the early stages of regeneration of anterior tibial muscle from isotopic minced muscle implants.

'Agenesis' of the temporal lobe. A case report with autopsy findings.

The temporal lobe agenesis syndrome is a rare congenital abnormality. In previous case reports, this syndrome has been described in association with arachnoid cysts or abnormal collections of CSF. An autopsy performed in the case of our 25-year-old patient revealed agenesis of frontal and temporal lobes without an anatomic cyst. During life the patient had no neurologic abnormalities that could be related to the lesion.

Muscle protein synthesis in MED myopathy.

A fatal, rapidly developing progressive muscle disease of delayed onset in mice is produced by the effects of an autosomal recessive gene (MED). We recognize two stages of this disease. The earlier stage, observed between the 11th and 14th postnatal day, is characterized by structurally normal small myofibers, cessation of increase in body weight, and increasing muscular weakness, particularly of the hind limbs. The second stage is characterized by a spheromembranous degeneration of myofibers and almost complete cessation of voluntary movement. Previous studies have revealed neither anatomic abnormalities in neuromuscular junctions nor major changes in oxidative metabolism or electrolyte concentrations in striated myofibers in the early stages of the disease. In this paper we report investigations designed to determine whether the failure of growth of striated muscle in the first stage is due to a defect in muscle protein synthesis or, as has been found in muscular dystrophies, is due to an increased rate of degradation of muscle. We conclude that MED animals demonstrate a different kind of defect than that occurring in dystrophic mice. In MED mice, the failure of growth is primarily due to a diminished rate of protein synthesis.

Regeneration and differentiation of minced anterior tibial muscle explants from mice with MED myopathy.

Rapid regeneration of mouse anterior tibial muscle occurs when minced muscle is explanted into the leg of a recipient previously prepared by excision of the corresponding anterior tibial muscle. This technique was used to study regeneration of muscle from mice with a delayed, recessive myopathy, motor endplate disease (MED). There was rapid regeneration of the explanted muscle and functional restoration after 15 weeks without signs of MED disease or evidence of the myofiber degeneration which normally occurs after 14 days in homozygous animals. Therefore, MED disease is not intrinsic in the affected muscles but appears to be dependent on the general humoral or possibly neural, environment present in mice with MED disease.

Myopathies related to diabetes mellitus and other metabolic diseases.

Although it has long been known that both large and small blood vessels are abnormal in the tissues of diabetic patients, recent work has emphasized the widening of capillary basement membranes in diabetic tissues. Current views of the nature of this lesion and its relationship to diabetes are discussed and diabetic muscle and nerve lesions are emphasized. Other metabolic diseases with significant muscle pathology are types II, III and VII glycogen storage diseases. Myopathy with abnormal mitochondria is reviewed.

Pathology of the neuromuscular junction.

Diagnosis of neuromuscular disease by the study of motor endplate structure in the light and electron microscopes is probably one of the most specialized examinations in the field of neuropathology. The classical means of staining endplates using gold, silver or methylene blue are described as well as more modern techniques suitable for light microscopy. Specific abnormalities in patterns of terminal innervation after methylene blue staining are noted. Techniques for localizing endplates suitable for electron microscopic study are given and some of the typical changes that occur in endplate structure in some neuromuscular diseases are indicated.