Acute myopathy with selective lysis of myosin filaments.

An acute reversible myopathy characterized by extensive lysis of myosin occurred in a patient who suffered from severe shock, hypoxia, and acidosis. This new clinical pathologic entity illustrates an unusual structural change in muscle associated with these catastrophic clinical circumstances.

Centronuclear myopathy heterogeneity: distinction of clinical types by myosin isoform patterns.

We studied muscles from 3 patients with centronuclear myopathy (CNM) by immunocytochemistry using myosin heavy chain (MHC)-specific monoclonal antibodies to determine whether subtypes of CNM express prenatal MHC and to assess if there is an arrest in development of these muscles. Muscle from a woman with childhood-onset CNM did not express prenatal MHC, yet this prenatal MHC was strongly expressed in the muscle fibers of 2 brothers with X-linked CNM. This finding represents the 1st immunocytochemical evidence of the expression of a prenatal myosin isoform in nonregenerating postnatal human muscle and suggests that the X-linked form of CNM differs from the other types because of a true arrest in maturation of the muscle.

Monoclonal antibody ALD 180: a reagent specific for a human prenatal skeletal muscle myosin isoform.

We report the characterization of monoclonal antibody (MAb) ALD 180, prepared against the myosin of slow avian muscle, for studies of human muscle development and disease. With the use of radioimmunoassays, Western immunoblots of native and denatured myosins, and epifluorescent indirect immunocytochemistry, we show that ALD 180 is specific for an epitope in human prenatal skeletal muscle myosin heavy chain (MHC), which is expressed in diminishing abundance in fetal fibers from at least 19-22 weeks' gestation to term and also in regenerating muscle fibers seen in diseased muscles from both children and adults. ALD 180 recognizes an epitope apparently different from those reacting with anti-prenatal human myosin MAb previously described, and therefore affords a complementary reagent for use in future studies of human myosin isoform expression and regulation.

An immunocytochemical study of type I muscle fibres in developing human skeletal muscles.

An immunocytochemical study was done on the skeletal muscles of human fetuses (19-36 weeks gestation), infants and adults using a new monoclonal antibody (McAb) ALD-47. The antibody was generated against slow myosin of chicken and is specific for myosin heavy chain (MHC). In human infants and adults the type I muscle fibres are strongly reactive with this McAb and the type II fibres uniformly non-reactive. In the fetuses from 19-20 weeks gestation (in whom the fibre types are not distinguishable by the histochemical myosin ATPase test) a proportion of muscle fibres react specifically with ALD-47. Other muscle fibres at this stage react positively with a fast specific MHC McAb HM-1.2 or are negative to both ALD-47 and HM-1.2 antibodies. These McAbs, thus, identify three distinct fibre populations in the early fetal muscle which by histochemical staining appears homogeneous. The percentage of ALD-47 positive fibres increases in fetuses at later gestational periods; at all stages these fibres lack reactivity with the HM-1.2 antibody. Because of its selective fibre type reactivity in differentiating muscles, the McAb ALD-47 in conjunction with HM-1.2 should be useful in immunoaffinity fractionation and biochemical studies of myosin isoforms in developing human muscles.

Werdnig-Hoffmann disease: myosin isoform expression not arrested at prenatal stage of development.

It has been suggested, on the basis of mostly morphological and some biochemical evidence, that defective innervation of muscle of patients with Werdnig-Hoffmann (WH) disease results in maturational arrest of the fibers at a stage comparable to 20-week gestational muscle. Therefore, with the use of recently developed and characterized, myosin-isoform-specific monoclonal antibodies (McAbs), an immunocytochemical study of muscle of 6 children with Werdnig-Hoffmann disease was done to determine if the pattern of expression of myosin heavy chain isoforms (MHC) in these fibers was similar to that of 20-week gestation muscle. This work showed that the MHC isoform expression in the muscle of the children with WH did not mimic that seen in 20-week gestation muscle since only a few fibers (less than 1-11%) in each specimen expressed prenatal MHC as detected by reactivity to McAb, ALD 180 (specific for a prenatal MHC) whereas virtually all of the fibers from 20-week gestation muscle were strongly reactive with ALD 180. The majority of the fibers expressed either adult fast MHC or adult slow MHC similar to that seen in normal muscle, although some co-expressed multiple MHC isoforms. Our results indicate that the difference of adult MHC isoforms in the muscle fibers of WH patients either proceeds in the absence of innervation or that denervation of muscle fibers is subsequent to the neural input required to initiate myosin isoform transitions to the adult isoforms.

I-cell disease (mucolipidosis II). Differential expression in satellite cells and mature muscle fibers.

A well documented case of I-cell disease is presented. Light- and electron-microscopic studies of muscle revealed marked accumulation of characteristic I-cell inclusions in satellite cells and only scattered autophagic vacuoles in muscle fibers. Correlation with previous tissue culture studies indicated an amelioration of structural abnormalities with differentiation from satellite cell to mature muscle fiber. Histochemically, the muscle demonstrated paucity of type I fibers without evidence of denervation thus suggesting a developmental disturbance in motor unit organization. Selective type I fiber dysfunction and reduced satellite cell regenerative capacity may be related factors in the neuromuscular disability of patients with I-cell disease.

A morphological comparison of the regional distribution of methadone in human and rat brain as demonstrated by immunofluorescence.

The brains of ten narcotic addicts who had died from an overdose of methadone, and the brains of ten rats, given methadone for one month, were examined by the immunofluorescent technic. Positive neuronal fluorescence was seen primarily in the limbic systems of both species as well as in closely associated areas. In the human, Purkinje cell fluorescence was seen in the cerebellum, whereas only stellate cell staining was observed in rat cerebellum. Neurons of the hippocampal denate gyrus often fluoresced in man while only pyramidal cell staining was seen in this region of rat brain. The method should prove to be of value in the detection and tracing of narcotic drugs and may be helpful in investigations of drug tolerance and dependence.

Spinal cord compression by extramedullary hemopoietic tissue in sickle cell anemia. Case report.

The authors report a patient with sickle cell anemia who suffered from paraplegia of 18 months duration due to spinal cord compression by a hemopoietic mass. Recovery following removal of the mass was complete.

Development of cerebellar malignant astrocytoma at site of a medulloblastoma treated 11 years earlier. Case report.

A child treated for a desmoplastic medulloblastoma of the left cerebellar hemisphere at the age of 10 months developed a malignant astrocytoma in the same site 11 years later. Theories of origin of the second tumor, particularly in relation to concepts of the genesis of medulloblastoma in general, are discussed.

Marginal glioneuronal heterotopias in nine cases with and without cortical abnormalities.

Nine cases of marginal glioneuronal heterotopias over the cerebral cortex were reviewed from the morphological point of view. There were developmental disabilities in all cases except one (case 8), who was stillborn. All subjects died before 1 year of age except one (case 5). The common features of small glioneuronal heterotopias and abundant heterotopic glioneuronal proliferation are described. The correlation of glioneuronal heterotopias with polymicrogyria and other cortical malformations, as well as their appearance over a normal cortex, are described. The glioneuronal heterotopias are considered to be a separate type of malformation that could arise during the second half of intrauterine life. A breach of the neuropial border seems to be the most acceptable pathomechanism for our presented cases. Their morphological features indicate that damage to this barrier leads to involvement of glioneuronal heterotopias in fusion of opposite cortical convolutions.

Lissencephaly: two distinct clinico-pathological types.

The present study is a review of four new cases of lissencephaly and two others previously reported. This study demonstrates that lissencephaly is a gross feature of the brain occurring in two different groups of cortical malformations. The first group, the classic agyria syndrome extensively analyzed by Jellinger and Rett [8] includes two types of abnormal cortical organization. They may be found in familial syndromes and also can appear sporadically. The second group includes smooth brains with the internal features of polymicrogyria and a more severely disorganized cortex. This type appears in familial lissencephaly in the cerebro-oculo-muscular syndrome, belonging to the same group as Fukuyama congenital-cerebro-muscular dystrophy. The other incidences of this type of cortical malformation require further investigation. The clinico-pathological differential diagnosis of two types of lissencephaly are also discussed.

An autopsy case of hemimegalencephaly.

This case report is a neuropathological study of a ten-month-old infant with unilateral megalencephaly . In this anomaly neuronal migration defect and disturbances of cortical organization resulting in micropolygyria were the most striking neuropathological feature.

Brain morphology in the Galloway syndrome.

The Galloway syndrome is a rare autosomal recessive disease consisting of congenital microencephaly associated with congenital nephrotic syndrome, and in some cases with hiatus hernia [Galloway and Mowatt, 1968]. The case presented is that of a microencephalic infant with the nephrotic syndrome who died at 11 3/4 months after a course characterized by convulsions, developmental delay, hypotonia and hyperreflexia. Brain weight was 270 g. The frontal, parietal, and rostral temporal cortex was pachygyric. Microscopically there was lack of cortical stratification, immature cortical neurons, improper orientation of cortical neurons (seen in the Golgi stained sections), and glioneuronal ectopias in the leptomeninges. There was hypomyelination in the brain stem and spinal cord, and no myelin in the hemispheres. There was also complete absence of the internal granular layer of the cerebellum. The dentate gyrus within the hippocampal formation was absent and the inferior olivary nuclei were hypoplastic. The mechanism of neuronal migration abnormalities and the significance of associated nephrosis is discussed.

Amebic meningoencephalitis in a patient with AIDS caused by a newly recognized opportunistic pathogen. Leptomyxid ameba.

A fatal case of meningoencephalitis due to a leptomyxid ameba in a patient with the acquired immunodeficiency syndrome is presented. This opportunistic organism has not been previously recognized as a human pathogen. A 36-year-old male intravenous drug abuser died after an 18-day hospital course heralded by fever and headache and followed by nuchal rigidity and hemiparesis. Computed tomography of the head showed multiple hypodense lesions. Neuropathologic examination showed that in addition to human immunodeficiency virus encephalomyelitis, there was multifocal meningoencephalitis with trophozoites and cysts morphologically indistinguishable from those of Acanthamoeba. These organisms were also found in the kidneys and adrenal glands. By immunofluorescence, the parasites showed antigenic identity with a free-living leptomyxid ameba and failed to react with any of a spectrum of antiacanthamoeba antisera. This emphasizes the importance of immunofluorescence identification of morphologically indistinguishable ameba species.

Hyperdipsia associated with hypothalamic-midbrain hemorrhage.

A case of diencephalic-midbrain hemorrhage presenting with excessive thirst, coma, and death is discussed. Some diencephalic dysfunction syndromes are reviewed, as well as their physiological basis. Thirst and drinking behavior can provide a valuable localizing symptom and sign in clinical-pathological correlations.

Orbital metastasis of prostatic carcinoma.

This paper describes a man with previously undetected prostatic carcinoma who presented with mild symptoms due to an orbital metastasis. The case is unusual in that the patient was relatively asymptomatic and had 6/7 vision. Carcinoma of the prostate metastatic to the orbit is rare; this is only the 22nd case in the literature.

Interlamellar refractive keratoplasty in rabbits.

The suitability and effectiveness of hydrophilic soft contact lenses and donor corneal buttons for interlamellar refractive keratoplasty were evaluated in a study with rabbits. In each experimental eye a trephined button of Bausch & Lomb Soflens (polymacon), Cooper Permalens (perfilcon A) or rabbit cornea 6.5 mm in diameter was inserted in a corneal pocket created with a lamellar dissector. Among the inserts available for long-term follow-up all five of the Soflens inserts showed "melting" (perforation and sloughing) by 3 weeks, whereas six of the seven Permalens inserts and all four of the donor corneal inserts were clear at 3 to 6 months. Myopia was induced and the corneal curvature steepened with all but the high-minus Soflens inserts. Thus, interlamellar refractive keratoplasty with soft contact lenses of high water content or lathe-cut donor corneal buttons has potential for the correction of aphakia in rabbits and may well have similar potential in humans.

A clinical technique for temporization of teeth to receive porcelain laminate veneers.

Temporization of teeth prepared for porcelain laminate veneers is sometimes necessary to preserve occlusal relationships, prevent sensitivity or maintain esthetics. The literature describes several techniques which satisfy different requirements for temporization. A modified technique is presented that satisfies at once: occlusion, sensitivity and esthetic needs. Clinical time spent with the patient is minimized by fabricating a matrix on a diagnostic cast prior to the preparation/ impression appointment.