Search PubMed⌕ Search

Biomedical subjects

H H Goebel

Publications and source records attributed to H H Goebel.

At least 109 records · Page 6Linked to original sources
PubMed1995

Pigment variant of neuronal ceroid-lipofuscinosis.

A 6-year-old girl had progressive ataxia, and visual disturbances resulting in blindness. She died in her sleep at age 22 years. She shared with her sister and paternal relatives bilateral pes cavus deformities and impaired deep-tendon reflexes which suggested Charcot-Marie-Tooth disease. Her sister, who also had both polyneuropathy and a progressive central nervous system (CNS) disease, did not have pigmentary retinopathy. At autopsy, the patient was found to have neuronal ceroid-lipofuscinosis (NCL) marked by intraneuronal accumulation of autofluorescent granular lipopigments in ballooned perikarya and conspicuous extraneuronal pigmentation of subcortical grey matter, but without axonal spheroids. These findings indicate a pigment variant of NCL and represent one of very few patients recorded. The ultrastructure of the intraneuronal pigments was uniformly granular, while that of the extraneuronal pigments found within processes of the neuropil and glial perikarya was more variegated. In addition to those patients with the pigment variant of NCL, described earlier by Jakob and Kolkmann [1973: Acta Neuropathol (Berl) 26:225-236], and Jervis and Pullarkat [1978: Neurology 28:500-503], our patient shared clinical symptoms with those described in a family afflicted with polyneuropathy and NCL by Wisniewski et al. [1987: J Child Neurol 2:33-41]. Currently, it is unclear whether they have similar atypical forms of juvenile NCL (JNCL). We conclude that the spectrum of pigment variants in lysosomal diseases is heterogeneous: only few and recently described patients have had NCL, while others most likely had other forms of lipidosis.

Cerebral Cortex↗
PubMed1995

Significance of lipopigments with fingerprint profiles in eccrine sweat gland epithelial cells.

Lipopigments with fingerprint profiles in eccrine sweat gland epithelial cells are regular findings in childhood NCL. They have also been described in adult NCL (ANCL) a few times, but not consistently. However, they have been considered nonspecific when not matched by similar abnormal profiles in noneccrine sweat gland epithelial cells. These conflicting reports may pose a diagnostic dilemma as outlined in the following 2 examples. Patient 1 is a 20-year-old man who developed severe tetraparesis and dementia over 2 years. Electroencephalogram was abnormal with epileptiform discharges. The patient died at age 21 years without autopsy; no other relatives are known to have a similar disease. Patient 2, a 49-year-old woman, developed ataxia and gait abnormalities when 44 years old, and, later, psychosis and dementia. The patient is still alive; no other family members are similarly affected. Both patient lacked evidence of a retinopathy clinically, funduscopically, and by electroretinography. Both patients showed lipopigments within secretory eccrine sweat gland epithelial cells which harbored unequivocal fingerprint profiles, but not within noneccrine sweat gland cells. Regular lipofuscin was observed in other cells, including skeletal muscle fibers of patient 2.

Adult↗
PubMed1995

Immunelectronmicroscopic characterization of T4 and T8 lymphocytes and natural killer cells in neuronal ceroid-lipofuscinosis.

CD4+, CD8+, and CD56+ cells were isolated with the immunomagnetic separation technique from peripheral blood mononuclear cells (PBMC) of 3 patients with neuronal ceroid-lipofuscinosis: one patient each with infantile (INCL), late infantile (LINCL), and juvenile (JNCL) neuronal ceroid-lipofuscinoses, all studied by light (LM) and electron (EM) microscopy. To compare the pathology of these cells with affected cells in other types of lysosomal diseases, the separation was also performed with PBMC of 1 patient with mucolipidosis (ML) type II, 2 patients with mucopolysaccharidosis (MPS) type I, and 4 patients with MPS type III. Disease-specific lysosomal inclusions were identified in CD4+, CD8+, and CD56+ cells. Subclass-specific storage products could not be found. T4 and T8 lymphocytes showed nearly the same ratio of affected to nonaffected cells. These results suggest that lysosomal storage can be found in most of the lymphocyte subclasses in these forms of neuronal ceroid-lipofuscinoses and other lysosomal diseases.

Adolescent↗
PubMed1995

X-linked dilated cardiomyopathy. Novel mutation of the dystrophin gene.

We report on a family with a severe form of X-linked dilated cardiomyopathy (DCM). Two brothers, the elder requiring heart transplantation, and a maternal cousin presented elevated creatine kinase levels, increased right ventricular diameters and electrocardiographic abnormalities. All complained of exertional cramping myalgia, but none had muscle weakness or a pathological electromyogram. Muscle biopsies of these individuals revealed a mild myopathic picture with atrophic type I and hypertrophic type II fibers. Immunofluorescence using N- and C-terminal antibodies (dys-2, dys-3) against the dystrophin protein showed preserved, but reduced intensity of staining of the sarcolemmal membranes. Using the same two antibodies, Western blot analyses revealed a dystrophin molecule of the expected molecular weight, which was quantitatively reduced by 80%. However, the dys-1 antibody, directed against the mid rod region of the dystrophin protein, did not react with dystrophin both on Western blot and immunofluorescence. Linkage analysis with polymorphic markers of the dystrophin gene revealed an identical haplotype at the 5' region in all affected individuals (two point lod score of 1.93, phi = 0). A deletion of exons 48, 45-53, 2-7 and 1 including the promoter region of the dystrophin gene, as described in rare cases with similar clinical signs could be excluded by multiplex PCR and Southern blot analyses of this DCM family. In addition, a major splice-mutation of dystrophin mRNA was excluded by RT-PCR of skeletal and heart muscle tissue. Therefore, we conclude that a novel mutation in the 5' region of the dystrophin gene phenotypically leads to this severe form of DCM. Extensive analyses of the dystrophin gene, in particular of the sequences coding for the antigenic determinants of the dys-1 antibody in the mid rod region, may identify the molecular cause of this monogenetic form of DCM.

Adult↗
PubMed1995

Desmin-related neuromuscular disorders.

Desmin, the intermediate filament protein of skeletal muscle fibers, cardiac myocytes, and certain smooth muscle cells, is a member of the cytoskeleton linking Z-bands with the plasmalemma and the nucleus. The pathology of desmin in human neuromuscular disorders is always marked by increased amounts, diffusely or focally. Desmin is highly expressed in immature muscle fibers, both during fetal life and regeneration as well as in certain congenital myopathies, together with vimentin. Desmin is also enriched in neonatal myotonic dystrophy and small fibers in infantile spinal muscular atrophy. Focal accretion of desmin may be twofold, in conjunction with certain inclusion bodies, cytoplasmic and spheroid bodies, and in a more patchy fashion, granulofilamentous material. Both lesions have been found in certain families, affected by a myopathy and/or cardiomyopathy. Other proteins, e.g., dystrophin, vimentin, actin, ubiquitin, and alpha-B crystallin, may also be overexpressed. Desmin pathology may be genetically regulated or may merely reflect profoundly impaired metabolism of several proteins within myofibers.

Desmin↗
PubMed1995

A new familial congenital myopathy in children with desmin and dystrophin reacting plaques.

In 5 children with a progressive congenital myopathy representing 3 different families, unusual histological, immunohistochemical and ultrastructural changes in skeletal muscle have been found. Histologically, this myopathy was characterized by the presence of fine hyaline plaques devoid of oxidative as well as ATPase enzyme activities. At the ultrastructural level plaques were composed of helical filaments and amorphous dense material. Helical filament storage corresponded to strong desmin as well as ubiquitin immunoreactivity. In addition they were also dystrophin positive. The exclusive appearance of desmin, ubiquitin and dystrophin positive plaques in muscle specimens from 5 children emphasize the uniqueness of these plaques as well as this special form of a congenital myopathy.

Adolescent↗
PubMed1995

Expression of cell adhesion molecules in inflammatory myopathies.

We examined the expression of cell adhesion molecules in 25 cases of inflammatory myopathies. Inflammatory myopathies showed upregulation of adhesion molecules. ICAM-1 was strongly expressed on endothelial cells as well as on fibroblasts and infiltrating leukocytes while the expression of VCAM-1, similar in its distribution, was much weaker. A few muscle fibers in polymyositis revealed sarcolemmal labeling for ICAM-1. ELAM-1 showed only weak expression on vessels. The inflammatory cellular infiltrates contained varying amounts of cells bearing the VCAM-1 ligand VLA-4 and the ELAM-1 ligand SLeX as well as large amounts of cells expressing LFA-1 alpha and beta, ligands of ICAM-1.

Cell Adhesion Molecules↗
PubMed1995

The neuronal ceroid-lipofuscinoses.

The neuronal ceroid-lipofuscinoses, a group of progressive neurodegenerative diseases in children and in adults, have now been recognized for some 90 years, and the childhood forms represent one of the largest groups of progressive neurodegenerative diseases in children. Apart from a core group of major clinical forms-the infantile, the late-infantile, the juvenile, and the adult forms--numerous atypical patients afflicted with neuronal ceroid-lipofuscinosis have now been identified, constituting 10% to 20% of all patients with neuronal ceroid-lipofuscinosis. These "atypical" patients have, over the past 10 years, prompted the suggestion of 15 atypical variants or minor syndromes, many of them displaying the lipopigments of classic curvilinear and fingerprint ultrastructure, but others displaying granular osmiophilic deposits. The former lipopigments contain the subunit C of the mitochondrial adenosine triphosphate synthase, but lipopigments of the granular osmiophilic deposits including the classic infantile type Santavuori-Haltia, apparently do not, the latter type exhibiting sphingolipid activator proteins. The nosologic significance of both the subunit C of the adenosine triphosphate synthase and the sphingolipid activator proteins, although they make up a considerable amount of the crude auto-fluorescent lipopigments in neuronal ceroid-lipofuscinosis, is still unclear. In spite of numerous pathogenetic principles invoked, such as a defect in lipid peroxidation, abnormalities of dolichols and dolichol phosphates, and defects in protease inhibitors, precise pathogenesis and etiology of the neuronal ceroid-lipofuscinoses remain elusive. Recent promising molecular genetic studies have, however, revealed the gene for infantile neuronal ceroid-lipofuscinosis, CLN1, on chromosome 1p32; the gene for juvenile neuronal ceroid-lipofuscinosis, CLN3, on chromosome 16p12.1-11.2; and the gene for a Finnish variant of late-infantile neuronal ceroid-lipofuscinosis, CLN5, on chromosome 13q31-32. The genes for classic late-infantile neuronal ceroid-lipofuscinosis, CLN2, and for adult neuronal ceroid-lipofuscinosis, CLN4, have not been located, the former having been excluded from chromosomes 1 and 16. However, the gene products of the normal allelic forms have not yet been identified. A considerable number of sporadic animal models is now available, largely equivalent to the juvenile and infantile forms of neuronal ceroid-lipofuscinosis, with those of the English setter and the South Hampshire sheep evaluated best. Recently, several mouse models have been added to this list of autosomal-recessive models, again the one most thoroughly studied being the motor-neuron disease mouse. Progress has also been made in the prenatal diagnosis of neuronal ceroid-lipofuscinosis: now the infantile, late-infantile, and juvenile forms can be recognized prenatally by a combined genetic and electron microscopic approach.

Animals↗
PubMed1995

Inclusion body myositis presenting with isolated erector spinae paresis.

We report a 70-year-old patient who presented with a 4-year history of weakness of paravertebral muscles. Electrodiagnostic studies revealed a mixed neurogenic-myopathic pattern. Light microscopic examination revealed atrophic fibers with rimmed vacuoles; electron microscopy demonstrated cytoplasmic and intranuclear filaments measuring about 16 nm in width, consistent with the diagnosis of inclusion body myositis. Therapy with corticosteroids provided only a mild and transient benefit. Ten months after the initial evaluation, clinical and electrodiagnostic examination demonstrated mild progression of the disease.

Aged↗
PubMed1994

[Clinical, neurophysiologic and biopsy findings in neurotoxic amiodarone syndrome].

PATIENTS: Three patients complained of proximal weakness and paraesthesia of the legs and difficulties in walking during amiodarone treatment. Examination showed signs of a predominantly distal sensory neuropathy, a proximal myopathy, and a cerebellar gait disorder. All had amiodarone dosages of 600 mg per day, amiodarone serum levels above 2.7 mg/l and a total amount of amiodarone ingestion of 300 to 500 g. The clinical symptoms subsided within six to eleven months after treatment was stopped. RESULTS: The neurophysiologic investigations showed slowing of sensory and motor nerve conduction velocities with dissociation of the action potentials and delay of SEP latencies. With discontinuation of the drug these abnormalities were progressive in one patient. The biopsy (muscle, nerve and skin) in the most severely affected patient showed numerous intracellular lysosomal inclusions in cells of different tissues. It is supposed that the storage of amiodarone in muscle cells results in a predominantly proximal myopathy whereas storage in Schwann cells results in a secondary neuropathy. A similar storage in Purkinje cells may be responsible for the cerebellar gait disorder. CONCLUSION: The clinical picture should be termed a neurotoxic amiodarone syndrome rather than amiodarone neuropathy.

Amiodarone↗
PubMed1994

[Cell therapy and its risks].

Parenteral administration of fresh cells, frozen cells (snapfrozen cell suspensions) or lyophilized cells (sicca cells), is known as cellular or cell therapy. While the German Health Office (BGA) provisionally banned the use of dried cell preparations in 1987, injection of fresh cells is still allowed. There have been repeated reports of life-threatening, and even fatal, complications of this type of therapy. Since it involves the administration of heterologous biological material, most of the complications that have been observed have been of the allergic/hyperergic type resembling experimental allergic encephalomyelitis (EAE) and experimental allergic neuritis (EAN). When evaluating the risks of this form of alternative-medical treatment, the well-known risks of injection therapy must also be borne in mind. In the case of cell therapy, too, the hoped for effect must be weighed against the risks of the procedure, and our guiding principle must be: nil nocere.

Cell- and Tissue-Based Therapy↗
PubMed1994

Morphology of experimentally denervated and reinnervated rat facial muscle. I. Histochemical and histological findings.

The morphological changes in rat facial muscles were evaluated after permanent denervation and were compared with findings after immediate reinnervation. Thirty rats underwent transection of the left and right facial nerves immediately followed by hypoglossal-facial nerve anastomosis on the right side (muscular reinnervation) and removal of 8-10 mm of the facial plexus on the left side (permanent muscular denervation). Levator labii muscle samples of both sides were collected sequentially at 2, 6, 7, 10, 20, and 24 weeks after surgery and submitted to routine histological and enzyme histochemical staining procedures. In normal levator labii muscles a typical "chessboard" pattern was found, with type I fibers being smaller than type II fibers. These latter fibers also were more prevalent than the type I fibers. Among the type II fiber subtypes, the type IIB fibers were larger and more frequent. Two weeks after surgery, there were no differences between denervated facial muscles and those undergoing reinnervation. Both showed atrophic myofibers among normal-sized fibers and slight fibrosis. Those muscles denervated for more than 2 weeks displayed increasing fiber atrophy with frequent loss of typability, as well as proliferation of connective tissue and fat cells in perimysial and endomysial sites. After denervation for 20 weeks only a few atrophic fibers were found in wide areas of fibrosis and fat cells. Following nerve anastomosis the reinnervated levator labii muscle showed much less fiber atrophy. Regrowth to normal fiber diameters was found with only a few atrophic myofibers 10 weeks after anastomosis although a moderate fibrosis predominated at perimysial sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1994

Aberrant arrested in maturation neuromuscular junctions in centronuclear myopathy.

Unusual ultrastructural changes of the nerve terminals have been found in an infant born with severe, fatal XLR form of centronuclear myopathy. Aberrant neuromuscular junctions in myotubes decorated by N-CAM were observed. The junction changes were manifested by simplification of postsynaptic membrane and paucity of secondary synaptic clefts. These resembles fetal neuromuscular junctions. The findings suggest that the expression of N-CAM by arrested myotubes may be promoted by abnormal nerve-muscle cell interactions, induced by motor endplate immaturity.

Cell Adhesion Molecules, Neuronal↗
PubMed1994

Prenatal ultrastructural diagnosis in the neuronal ceroid-lipofuscinoses.

The neuronal ceroid-lipofuscinoses (NCL) are autosomal-recessive disorders in childhood of unknown enzymatic origin. They can be recognized by the presence of abnormal lipopigments identified by electron microscopy. Based on the study of circulating lymphocytes, individual clinical subtypes of NCL can be correlated. Prenatal diagnosis of NCL with the electron microscope is now feasible for the infantile (Finnish) from (INCL) and late-infantile form (LINCL). INCL-specific granular lipopigments are present in endothelial cells of biopsied chorion stroma vessels of homozygously affected fetuses. In LINCL, disease-typical curvilinear bodies can be identified in uncultured amniotic fluid cells. Prenatal ultrastructural recognition of juvenile NCL (JNCL) is still controversial as only one single case has been reported. Electron microscopic findings can also be corroborated by genetic analysis in INCL and JNCL because the defective genes have been localized to chromosomes 1 and 16, respectively, but not in LINCL. Documentation of the index patients in the family is essential before prenatal diagnosis, and post-abortive confirmation of fetal NCL is also desirable.

Amniotic Fluid↗
PubMed1994

Neonatal centronuclear myopathy with N-CAM decorated myotubes.

Muscle specimens from two baby males with fatal X-linked recessive (XLR) form of central nuclear myopathy (CNM) were studied by immunochemistry using cell surface molecules (N-CAM) and by electron microscopy. In both neonates muscle fibres with morphology of myotubes strongly expressed N-CAM. The expression of N-CAM in non regenerating postnatal human muscle suggests that neonatal X-linked fatal form of CNM is characterized by arrest or delay of maturation of muscle fibres.

Antibodies↗