Biomedical subjects

H H Goebel

Publications and source records attributed to H H Goebel.

At least 19 recordsLinked to original sources

PubMed1992

Incidence of neuronal ceroid-lipofuscinoses in West Germany: variation of a method for studying autosomal recessive disorders.

The incidence of neuronal ceroid-lipofuscinoses (NCL) in West Germany was determined using a novel method which is applicable to other autosomal recessively inherited diseases. Questionnaires were sent to all pediatric departments (answer rate 189/276, 68%), schools for the blind (39/46, 85%), and neuropathological institutes (15/22, 68%). Diagnoses were accepted only when based on firm clinical and/or electron microscopic criteria; 207 such identified patients were sorted according to year of birth. Plotting the cumulative number of new cases per year against the year of birth resulted in a slightly S-shaped curve. Before the year 1962, the curve is relatively flat, probably due to inefficient case registration. Between 1968 and 1977, the slope of the curve is constant--a steep, nearly straight line. Thereafter the curve flattens out again, likely due to inefficient registration of young, still undiagnosed patients. We interpret the central segment of the curve, which is continuously straight over a period of 10 years and corresponds to 92 patients, as a period in which efficient registration of new cases occurred. The number of live births being 7,211,543 during the same period, the NCL incidence is calculated to be 1.28 per 100,000 live births (0.71 for juvenile NCL and 0.46 for late infantile NCL).

Child↗

PubMed1992

Retina in various animal models of neuronal ceroid-lipofuscinosis.

The childhood forms of human neuronal ceroid-lipofuscinosis (NCL) are invariably associated with a severe progressive retinopathy which commences at the photoreceptor level morphologically and proceeds to a final loss of neuronal cells accompanied by severe gliosis. In respective spontaneous animal conditions of NCL, in English setters, Dalmatian dogs, and New Zealand sheep, retinal involvement is not commensurate although the retina does not seem to be completely unaffected. In canine NCL, there might be functional and electro-physiological impairment of retinal cells, but retinal atrophy is not obvious. In ovine NCL, the retina, apart from accumulating NCL-specific lipopigments within neuronal perikarya, also shows loss of photoreceptors. Conversely, retinal pigment epithelial cells (RPE) in canine and ovine NCL contain peculiar lamellar inclusions, not seen in unaffected animals, possibly an indication of a disturbed phagocytic process of photoreceptor outer segments. Similar such lamellar inclusions have not been observed in RPE cells in human childhood NCL.

Animals↗

PubMed1992

Phagocytic capacity of human muscle fibers.

Isolated dead muscle cell fragments (apoptotic bodies [ABs]) were investigated by electron microscopy in different stages of phagocytosis. Phagocytosis of ABs was carried out by neighboring muscle cells. The mechanism of internalization took place in both mature and immature muscle cells and consisted of the progressive engulfment of ABs within cytoplasmic vacuoles and craters. In addition, concentrated microfilaments formed a dense ring in the muscle cytoplasm adjacent to the engulfed ABs. The above combination of membrane evagination and phagocytic vacuole formation as well as the extensive microfilament organization at the site of AB engulfment were analogous to the cytoplasmic response seen in the tissue of mononuclear phagocytic cells.

Humans↗

PubMed1992

Neuronal ceroid-lipofuscinoses: the current status.

In view of the epidemiological connotation of childhood neuronal ceroid-lipofuscinosis (NCL) as one of the most frequent progressive lysosomal diseases and neurodegenerative disorders in children, the recognition of the individual clinical forms of childhood NCL is still based on invasive diagnostic electronmicroscopy which, currently, may be applied also for prenatal diagnosis. Like other inherited disorders, the NCL group has finally also benefited from the genetic breakthroughs of localization of the genes for infantile NCL and juvenile NCL on chromosomes 1 and 16, respectively. This review concerns recent advances in morphological studies, broadening of the clinical spectrum of childhood NCL, new biochemical findings, and preliminary therapeutic results. Hereditary animal models, largely for human juvenile NCL, have been successfully employed in elucidation of the nosology of NCL, but the basic defect in human, canine and ovine NCL remains unknown.

Humans↗

PubMed1992

A mild juvenile variant of type IV glycogenosis.

The mild juvenile form of type IV glycogenosis, confirmed by a profound deficiency of the brancher enzyme in tissue specimens is reported from three Turkish male siblings who, foremost, suffered from chronic progressive myopathy. Muscle fibers contained polyglucosan inclusions of typical fine structure i.e. a mixture of granular and filamentous glycogen. They reacted strongly for myophosphorylase, but were resistant to diastase. These inclusions were ubiquitinated and reacted with antibody KM-279 which previously has been shown to bind to Lafora bodies, corpora amylacea and polyglucosan material in hepatic and cardiac cells of type IV glycogenosis as well as polyglucosan body myopathy without brancher enzyme deficiency. Our findings confirm that although rate, a mild form of type IV glycogenosis is marked by polyglucosan inclusion not only in myofibers, but also in smooth muscle and sweat gland epithelial cells. This further implies that when polyglucosan inclusions are observed within myofibers it is mandatory to examine the muscle tissue for brancher enzyme activity since the brancher enzyme activities in circulating erythrocytes and leucocytes were normal in all three affected siblings and their parents. Therefore, it can be concluded that the patients reported on here represent a variant form of type IV glycogenosis, in which the defect is limited to muscle tissue. This further indicates that there are several different types of type IV glycogenosis with variable clinical manifestations.

Child↗

PubMed1992

Adult polyglucosan body myopathy.

This report describes a sporadic late-onset myopathy in two unrelated adults which was marked by polyglucosan inclusions surrounded by abnormally structured mitochondria, the latter finding a localized, possibly reactive phenomenon. The polyglucosan material was characterized by a battery of histochemical and enzyme histochemical techniques; revealed common antigenicity with Lafora bodies, corpora amylacea and muscle fiber inclusions in types IV and VII glycogenoses; and contained ubiquitin. Additional lectin histochemical and associated digestion preparations disclosed the presence of alpha-glycosyl residues as apparently the sole carbohydrate component in polyglucosan bodies while the above mentioned common antigenicity with Lafora bodies and other inclusions suggests an additional, so far unidentified, protein component.

Atrophy↗

PubMed1992

Ultrastructural study of the retina in late infantile metachromatic leukodystrophy.

The autopsy of a 2-year-old girl revealed a clinically unrecognized metachromatic leukodystrophy (MLD) due to an aryl-sulfatase A deficiency, characteristically affecting the central and peripheral nervous system by demyelination and by accumulation of metachromatic material. The retina though reported clinically as normal, showed the same demyelinating process in the optic nerve including the papilla but an additional intraneuronal storage of MLD-typical lysosomal residual bodies in ganglion cell perikarya of the retina. Cells of the bipolar and photoreceptor layers as well as pigment epithelial cells were not affected by MLD-specific lysosomal storage. Thus, sulfatides seem to play a particular metabolic role in ganglion cells but not in other neuronal cells of the retina in MLD.

Brain↗

PubMed1992

[An intermediate, generalized form of neuroaxonal dystrophy--light- and electron microscopic findings].

This report concerns a 11-year-old girl--at the time of death--who developed normally until the age of 2 years when further psychomotoric maturation stopped and then regressed. The disease was diagnosed as neuroaxonal dystrophy (NAD) by sural nerve biopsy at the age of 7. Further course was characterized by complete loss of all motoric and sensory functions and dementia as well. Finally there was decerebration. The autopsy revealed generalized NAD associated with pallidal deposition of iron pigment to classify as generalized intermediate NAD type II according to Gilman and Barrett (1973). The main histological findings were axonal swellings and spheroids consisting ultrastructurally of membrano-tubular profiles, lamellar structures, vacuoles, glycogen granules and mitochondrial aggregates. Immunohistologically there was partial positive expression of synaptophysin and neurofilament protein in the spheroids. Firstly described electron microscopical findings in the retina include the typical axonal lesions largely in interior layers. Photoreceptors and their synaptic contacts were preserved. The present blindness is of the neuronal type. The current etiopathogenetic opinions, aspects of bioptic diagnosis and problems of classification of primary NADs are discussed.

Axons↗

PubMed1991

Human ontogenesis. 3. Cell death in fetal muscle.

Naturally occurring muscle cell death in normal human fetal muscle was examined to determine the timing and structural differences with respect to muscle maturity. Two types of degenerative changes in developing muscle were found: cytoplasmic and nuclear. Degeneration of the primary and mature myotubes between 10 and 16 weeks of gestation entailed cytoplasmic condensation and disruption, swelling of mitochondria and dilatation of sarcoplasmic reticulum. In contrast, the formation of immature muscle fibres was associated with disintegration of satellite myofibres characterized by nuclear degenerative changes. These findings indicate that naturally occurring muscle cell death appears as a two-successive-stage phenomenon of cell necrosis. Initially, at the myotube stage, a number of muscle cells are eliminated. In the later stage a single cell is removed from the cluster which seemingly is responsible for final shape and size of the muscle fibre.

Cell Nucleus↗

PubMed1991

Capillaries within human skeletal muscle fibers.

Internalized capillaries, i.e. capillaries within muscle fibers, represent a rare myopathological feature. This was systematically studied in 923 muscle biopsy specimens and found in 24, chiefly in the gastrocnemius muscle, more rarely in the biceps and quadriceps muscles affecting males more often than females and most frequently associated with juvenile spinal muscular atrophy or Becker's muscular dystrophy. Internalized capillaries, often multiple, ran along the long axis of the muscle fiber within an "internalized" extracellular space and were almost exclusively seen in type I myofibers. Internalization seems to start at the site of fiber splitting while penetration through the intact sarcolemma and invasion into transverse tubules were never observed. The presence of internalized capillaries within type I myofibers and increased density of intramuscular capillaries/fiber though not per muscle fiber area suggested hypoxia to play a possible if not crucial role in the formation of internalized capillaries. Our findings do not distinguish between active proliferation of capillaries into myofibers at the site of myofibers and internalization by fusion of vicinal myofibers as the morphogenetic principles suggest that both of these mechanisms may occur.

Atrophy↗

PubMed1991

Infantile neuroaxonal dystrophy: diagnosis by skin biopsy.

A child who shows progressive motor and mental deterioration after the first year of life, who has pyramidal signs, marked muscle hypotonia, but no seizures, suggests to have infantile neuroaxonal dystrophy (INAD). Beyond the age of two years, the EEG also entails characteristic findings. Diagnosis may be obtained by an ultrastructural examination of biopsied skin. The respective clinical and morphological findings are recorded and illustrated from four patients in this report.

Biopsy↗

PubMed1991

Dystrophin as a diagnostic marker in Duchenne and Becker muscular dystrophy. Correlation of immunofluorescence and western blot.

Dystrophin is the gene product of the Duchenne (DMD) and Becker (BMD) muscular dystrophy gene locus on the short arm of the X chromosome. Complete lack of dystrophin is pathognomonic for DMD and variable changes of the molecule may be observed in the milder allelic form of BMD. In the present study the two methods available for dystrophin assessment, immunofluorescence detections on cryosections (IF) and Western blotting (WB) were systematically compared using polyclonal and monoclonal antibodies to various regions along the dystrophin molecule. A total of 95 patients with DMD or BMD were investigated including two female patients. Dystrophin assessment revealed abnormal abundance and/or distribution in all 95 patients with DMD or BMD. Only trace amounts of dystrophin were detected in 29% of the DMD patients and complete lack of dystrophin was found in 71%. In two females with DMD but with normal karyotype single dystrophin-positive fibres were found among more than 90% negative fibres. Out of 26 patients with BMD 19 (73%) had a dystrophin molecule of abnormal molecular weight. The results of IF were largely compatible with those from WB but differences were also observed, e.g. one barely symptomatic BMD patient with dystrophin of increased molecular weight showed normal IF. Out of four carriers of BMD three showed evidence of reduced dystrophin immunostaining in some muscle fibres. In 20 other patients limb girdle muscualar dystrophy with "Duchenne-like" or "Becker-like" phenotype was suspected because dystrophin showed normal abundance and distribution. Focal discontinuity of muscle cell-surface dystrophin staining was observed in one patient with a congenital, autosomal recessive muscular dystrophy and in one out of five patients with polymyositis/dermatomyositis. The study emphasizes the need for, and value of, dystrophin assessment in every case of suspected BMD or DMD.

Adolescent↗

PubMed1991

B and T lymphocytes are affected in lysosomal disorders--an immunoelectron microscopic study.

Circulating lymphocytes of four patients with mucopolysaccharidoses II and IIIA, four patients with juvenile neuronal ceroid-lipofuscinosis, one patient each with glycogenosis type II, infantile neuronal ceroid-lipofuscinosis, and Gaucher disease were classified by immunoelectron microscopy as B or T lymphocytes. Disease-specific lysosomal inclusions as well as non-specific lysosomal organelles, especially Gall bodies were identified in B and T lymphocytes. These non-quantitative studies indicate that both B and T lymphocytes participate in the lysosomal storage process.

B-Lymphocytes↗

PubMed1991

Congenital myopathies.

About forty different congenital myopathies (CM) are defined by clinical and morphological criteria. Classical types like central core disease, centronuclear myopathy, and nemaline/rod myopathy are now well established and recognized as neuromuscular conditions. Clinical subtypes as infantile, juvenile, and adult forms have been recognized in several CM. Not infrequently, different disease-specific morphological features may occur in muscle tissue of the same patient combined. Other CM are marked by aggregates of desmin filaments indicating the importance of recent immunohistochemical techniques. Modern myopathological techniques enabled nosological separation of CM, immunohistochemistry, actually, may usher in a new period of research in and understanding of CM. However, application of molecular genetic and molecular biological methods to CM may clarify still unsolved aspects of gene localisation for which the hereditary nature of many CM is particularly conducive, aspects of heterogeneity versus homogeneity of certain CM or clinical variants, of prenatal diagnosis of CM, of pathogenetic and nosological significance of muscle fiber proteins in CM, and of a new nosological classification of CM.

Child↗

PubMed1991

Spheroid-cytoplasmic complexes in a congenital myopathy.

The most striking pathological finding in the deltoid muscle biopsy specimens of 2 unrelated adult male patients consisted of large spheroid-cytoplasmic complexes of intricate structure, as previously described only under experimental conditions (Chou and Mizuno, 1986). These large cytoplasmic masses were characterized by a granular centre and a filamentous halo. Immunohistology revealed the presence of intermediate filaments of the desmin and vimentin types. Clinically, both patients showed mild and slowly progressive proximal myopathy of adult onset. In one patient, the myopathy was strongly suspected to be inherited. In concordance with previous reports on cytoplasmic and spheroid body congenital myopathies, these spheroid-cytoplasmic bodies further enlarge the spectrum of late onset congenital myopathies.

Adult↗

PubMed1991

[Polyneuropathy in Duhring dermatitis herpetiformis].

Polyneuropathies in patients with dermatitis herpetiformis (Duhring's disease) can be due to dapsone therapy as well as due to an associated enteropathy. Dapsone causes an axonal, purely motor neuropathy, whereas the neuropathy due to an enteropathy is mainly sensory in type. The characteristics of both neuropathies are described considering the clinical and electrophysiological findings in a patient with enteropathic neuropathy and improvement during continuous dapsone therapy.

Biopsy↗

PubMed1990

Topographic heterogeneity of amyloid B-protein epitopes in brains with various forms of neuronal ceroid lipofuscinoses suggesting defective processing of amyloid precursor protein.

To verify our hypothesis of defective protease inhibitor domains that are encoded by abnormal processing of amyloid precursor protein (APP) in brains of patients with neuronal ceroid lipofuscinoses (NCL), immunohistochemical and cytochemical studies were performed with monoclonal antibodies (mAbs) directed against various domains of APP. For the studies, 22 autopsy brains were used: 12 with different forms of NCL, and 10 control brains. The staining procedure for the avidin-biotin complex (ABC) technique and the postembedding gold-labelled procedure for electron microscopy (EM) were employed. Of all mAbs used for the study, only mAbs generated against amyloid B-protein bound to neural tissue were affected with NCL. The strongest immunostaining of neurons and of some reactive glial cells was found in brains with the juvenile form of NCL. Only in the infantile form of the disease were some neurons overloaded with storage material weakly immunoreactive. In brains of patients with the adult form of NCL, immunoreactivity was found in affected neurons and in extracellularly deposited material of senile plaques. The results of EM study showed that the immunoreactivity was restricted to lysosomal cytosomes in neural tissue with any form of NCL selectively localized on the curvilinear and fingerprint proteinaceous component of ceroid lipofuscin. Studies performed on control aging brains and Alzheimer's disease (AD) brains confirmed previous observations of immunoreactivity being found diffusely in the protein component of some neurons containing lipopigment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Myxoma of the orbit: a clinicopathologic report.

A 27-year-old white man developed proptosis of his left eye over a period of 2 years. It was associated with vertical diplopia and displacement of the left globe down and laterally. Ultrasonography showed a cystic mass in the superior orbital region. Computed tomography (CT) demonstrated a solid, well-defined lesion behind the globe displacing the optic nerve medially. A transfrontal craniotomy revealed a nodular mass in the posterior and superior orbit, which extended anteriorly up to the globe. Histopathology, immunohistochemistry, and transmission electron microscopy proved the tumor to be a myxoma.

Adult↗