Biomedical subjects

H H Goebel

Publications and source records attributed to H H Goebel.

At least 145 records · Page 8Linked to original sources

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↗

PubMed1990

Acute infantile spinal muscular atrophy. Muscle apoptosis as a proposed pathogenetic mechanism.

Biopsy as well as autopsy studies of a child who died 8 weeks after birth from the acute infantile form of spinal muscular atrophy revealed classical morphological changes, including degeneration and loss of motoneurons in the spinal cord, loss of large myelinated fibres in anterior roots and neurogenic atrophy in muscle. New ultrastructural findings include massive muscle cell elimination by apoptosis with the formation of membrane-bound muscle cell fragments, apoptotic bodies. In addition, numerous immature muscle fibres were observed. The morphological findings raise the possibility that in a severely growth-retarded muscle, the process of muscle cell apoptosis removes the peripheral target of anterior horn cells resulting in secondary motoneuron death.

Acute Disease↗

PubMed1990

Polyneuropathy due to acute arsenic intoxication: biopsy studies.

A 41-year-old vintner attempting suicide ingested 8-9 g of arsenic and developed a symmetric polyneuropathy with acute Wallerian degeneration of myelinated fibers. Under treatment with modified British Anti-Lewisite (BAL; "Dimaval") his polyneuropathy slowly, but incompletely, subsided over three years at which time another sural nerve biopsy specimen showed regenerative proliferation of myelinated and unmyelinated axons but no signs of Wallerian degeneration. By laser microprobe mass analysis (LAMMA) arsenic was located in the first biopsied sural nerve specimen but not in the second specimen. These findings demonstrated: 1) arsenic induced serial morphometric and electron microscopic findings of nerve fiber degeneration and regeneration, 2) documentation of arsenic within myelinated nerve fibers, and 3) the usefulness of the LAMMA technique as a diagnostic procedure in this context.

Acute Disease↗

PubMed1990

Neonatal form of nemaline myopathy, muscle immaturity, and a microvascular injury.

An infant with a neonatal form of nemaline myopathy showed ultrastructural features of muscle immaturity. Immaturity was characterized by an abnormal presence of myotubes, as well as cells in clusters within a common basement membrane and a great number of satellite cells adhering to very small muscle fibers. In addition, degenerative changes and a severe microvascular lesion were observed. The pathologic findings in the muscle of this patient were those of neonatal nemaline myopathy complicating severe microvascular injury, possibly induced by an unknown toxic agent.

Asphyxia Neonatorum↗

PubMed1990

Late-onset globoid cell leukodystrophy: unusual ultrastructural pathology and subtotal beta-galactocerebrosidase deficiency.

An 11-year-old girl was found to have severely reduced beta-galactocerebrosidase activity as evidence of late-onset globoid cell leukodystrophy, while her mother had almost normal enzyme activity in circulating white blood cells. Clinically, the patient showed a remitting course marked by seizures, ataxia, white-matter disease on computed tomographic scan, and reduced conduction velocities of peripheral nerves. Symptoms improved somewhat around the age of 10 years. Two sural nerve biopsies, performed 6 years apart, disclosed a demyelinating neuropathy. By electron microscopy, membrane-bound vacuolar lysosomes in Schwann cells of myelinated axons, unlike the typical needlelike inclusions seen in classic infantile globoid cell leukodystrophy, were present in both specimens. Thus, clinical, morphologic, and biochemical data in this patient--and her mother--emphasize, compared with past reports on late-onset globoid cell leukodystrophy, considerable variation in the nosologic spectrum of late-onset globoid cell leukodystrophy and conspicuous differences from classic infantile globoid cell leukodystrophy.

Adolescent↗

PubMed1990

An ultrastructural study on retinal neural and pigment epithelial cells in ovine neuronal ceroid-lipofuscinosis.

Ovine neuronal ceroid-lipofuscinosis represents another well studied model for human neuronal ceroid-lipofuscinosis (NCL). Accumulation of abnormal lipopigments in various retinal neurons, and loss of photoreceptors are similar to the lesions in human juvenile NCL and indicate that the sheep is a suitable model in which to study the pathogenesis of both NCL lipopigment formation and retinopathia pigmentosa. However, this latter process is not as advanced in NCL-diseased sheep as in human patients but far more obvious than in canine NCL in which retinopathy cannot be unequivocally documented. Ovine NCL shares with canine NCL peculiar lamellar inclusions in retinal pigment epithelial cells which may indicate an impaired catabolism of phagocytosed photoreceptor outer segments. As the peculiar lamellar inclusions seen in RPE cells of both NCL-diseased sheep and dogs do not very much resemble the phagocytosed photoreceptor outer segments, it may be assumed that in NCL the final steps in complete removal of these phagocytosed photoreceptor outer segments are also defective.

Animals↗

PubMed1990

Hereditary metabolic neuropathies.

Hereditary metabolic neuropathies (HMN) are marked by inherited enzyme or other metabolic defects. They comprise lysosomal, mitochondrial, and peroxisomal diseases, i.e. multiorgan, single-organelle system disorders, vitamin E deficiency, porphyrias, and Tangier disease. In addition to non-specific morphological pathology such as demyelinating or axonal lesions certain groups of HMN are marked by disease-specific inclusions only precisely elucidated with the electron microscope, e.g. lysosomal disorders, vitamin E deficiency, and Tangier disease. The lack of clinical and/or electrophysiological abnormalities in some of the HMN, the predominant involvement of the CNS in others and the occurrence of certain HMN in very young children have often delayed systematic investigations of the PNS in HMN and thus also procrastinated knowledge of the morphological and nosological HMN spectrum.

Biopsy↗

PubMed1990

Amyloid-related neuropathies.

Formation of amyloid within peripheral nerves, resulting in amyloid-related neuropathies, may occur when myeloma-associated amyloid (AL) is deposited in an immune-related neuropathy or in familial amyloid polyneuropathy where prealbumin/transthyretin variants are marked by AF amyloid deposition. Refined histochemical and recent immunohistochemical techniques identify the correct type of amyloid and thus the nosologically precise form of amyloid-related neuropathy. Neuropathy is an inherent thought not obligate clinical and morphological component in two of the three systemic amyloidoses. Multiple causative factors in adult forms of neuropathy render a search for amyloid mandatory whenever respective biopsied nerve specimens are examined.

Amyloid↗

PubMed1989

Internalized myofiber capillaries: observations on their origin and clinical features.

Internalized capillaries limited to type 1 muscle fibers were noted in seven patients. They occurred in each case in association with a similar admixture of neurogenic and myopathic features that included atrophic and hypertrophic fibers, internal nuclei, fiber splitting, and endomyseal and perimyseal fibrosis. Internalized capillaries in enlarged type 1 fibers arose from fiber splits on step section study of four patients. They occurred in the gastrocnemius, quadriceps, and soleus muscles from patients with a variety of disorders that included Becker dystrophy, diabetes mellitus and strenuous leg activities, Achilles tendon rupture, and myotonic dystrophy. Exercise-induced myalgias were noted in the four patients with the most plentiful intramuscular capillaries, and in three of these muscle hypertrophy was present. The concurrence of internalized myofiber capillaries and exercise-induced myalgias may represent an associated biochemical/pathological defect.

Adolescent↗