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Biomedical subjects

W K Engel

Publications and source records attributed to W K Engel.

At least 163 records · Page 9Linked to original sources
PubMed1981

Identification of human thymic epithelial cells with antibodies to thymosin alpha 1 in myasthenia gravis.

Thymosin-alpha 1 (alpha 1) is a potent thymic polypeptide hormone. Using anti-alpha 1 antibodies, we applied indirect immunofluorescence to human normal thymus of different ages and to hyperplastic, thymomatous, and "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassell's corpuscles, and proliferated in thymomas. Whereas normal thymuses and fewer and weakly stained cells, MG thymuses had many strongly positive epithelial cells; this was more evident in thymomas. Germinal centers were unstained. "Involuted" MG thymuses had small islands of brightly stained cells lying among the fatty tissue. In cultured thymuses from three MG patients, epithelial cells but not fibroblasts were brightly stained for alpha 1. Our findings (a) demonstrate the location, and presumably the origin, of alpha 1 to be the thymic epithelial cell; (b) suggest the possibility that excess alpha 1, because of its known effect on T-lymphocyte maturation and transformation of precursors to helper T-cells, may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) indicate that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their alpha 1 positivity in culture.

Adolescent↗
PubMed1981

Splenic and total-body irradiation treatment of myasthenia gravis.

X-irradiation is introduced as a new therapeutic technique in the treatment of otherwise intractable myasthenia gravis (MG) and polymyositis (PM), on the basis that these dysimmune diseases are "lymphocyte dyscrasias" and that lymphocytes are the circulating cells most sensitive to x-irradiation. Splenic irradiation, 1000 rads per two-week course, repeated up to three courses, in five MG patients produced objective improvement in three and subjective improvement in another. The improvement was transient and accompanied by a temporary lymphocytopoenia. Total Body Irradiation (TBI), 150 rads over five weeks, in one polymyositis patient was followed by remarkable improvement, sustained and still increasing now after one year, associated with a sustained lymphocytopoenia. One MG patient has had definite improvement, maintained to the present, seven months after TBI, associated with persistent lymphocytopoenia. We suggest TBI may also be a treatment applicable to other types of dysimmune (autoimmune) diseases.

Adult↗
PubMed1980

Human schwann cells in tissue culture: histochemical and ultrastructural studies.

Schwann cells cultures were established from 40 human peripheral nerves that underwent biopsy according to an explant-reexplantation technique that markedly reduces non-Schwann cells and achieves cultures greatly enriched in Schwann cells suitable for a wide range of studies. Described are the growth characteristics and histochemical, ultrastructural, and ultrastructural-cytochemical patterns of normal human cultured Schwann cells from 12 patients with demonstrable peripheral nerve abnormality. These findings serve as a basis of comparison when seeking abnormalities of Schwann cells grown from peripheral nerves of patients with putative dysschwannian neuropathies.

Adolescent↗
PubMed1980

Immunoglobulin and complement deposits in nerves of patients with chronic relapsing polyneuropathy.

Sural nerve biopsy specimens from seven patients with chronic relapsing polyneuropathy (CRP) were studied by direct immunofluorescence. Granular deposits containing IgM (7/7) and C3 (6/7) (and occasionally IgG, 3/7) were found in intraneural blood vessels. Linear deposits of IgM (6/7) (and occasionally IgG, 3/7) without C3 (0/7) were found on the Schwann cell plasmalemma (and sometimes extending deeper into the Schwann cell) of yet undemyelinated portions of nerve fibers. Albumin and fibrinogen were not found in any locus. In sural nerves of ten disease-control patients with non-dysimmune chronic perpheral neuropathies, no deposits were seen on the vessels or the nerve fibers. The Schwann cell deposits may reflect a complement-independent IgM antibody toxic to Schwann cells that underlies the pathogenesis of CRP, perhaps facilitated in its passage across the blood-nerve barrier by damage from the complement-binding IgM complexes in the intraneural vessels.

Adolescent↗
PubMed1980

Serum creatine kinase BB and MM concentrations determined by radioimmunoassay in neuromuscular disorders.

We measured the MM and BB isoenzymes of serum creatine kinase (CK) by radioimmunoassay in 89 patients with neuromuscular disorders and 44 definite or possible carriers of Duchenne muscular dystrophy (DMD). The CK-MM isoenzyme was closely associated with total CK enzymatic activity. CK-BB was not as closely correlated with total CK but was usually increased in the inflammatory myopathies and DMD and normal in myasthenia gravis, Guillain-Barré syndrome, and amyotrophic lateral sclerosis as well as in neuropathies in which CK is usually normal. In myopathies, CK-BB may be useful for assessing the level of disease activity or the regenerative component. More study is necessary to assess the role of CK-BB in detection of DMD carriers.

Child↗
PubMed1980

Substance P in human cerebrospinal fluid: reductions in peripheral neuropathy and autonomic dysfunction.

Substance P (SP), a putative peptide neurotransmitter, was measured in human lumbar cerebrospinal fluid (CSF) by radioimmunoassay. Substance P-like immunoreactivity (SPLI) was present in the CSF of 18 neurologically normal adults in concentrations ranging from 2.9 to 11.1 fmol per milliliter, with a mean of 7.0 /+- 0.6 fmol per milliliter (mean /+- SE). Slightly more than half of the CSF-SPLI cochromatographed with synthetic SP on Sephadex G-25. There was no apparent gradient in CSF-SPLI concentration over the first 30 ml of CSF removed by lumbar puncture. Mean concentrations CSF-SPLI in patients with Huntington disease, parkinsonism, miscellaneous dyskinesias, progressive supranuclear palsy, myopathy, and amyotrophic lateral sclerosis did not differ significantly from normal. Patients with neuropathy or multiple-system atrophy (Shy-Drager syndrome) had significantly reduced mean CSF-SPLI concentrations. These observations suggest that lumbar CSF-SPLI arises largely from spinal cord, nerve roots, or dorsal root ganglia, and that pathologic processes affecting these structures may be reflected by reduced levels of CSF-SPLI.

Adolescent↗
PubMed1980

CSF "monoclonal" bands in chronic relapsing polyneuropathy.

The characteristics and temporal profiles of cerebrospinal fluid (CSF) and serum immunoglobulin patterns on agarose gel electrophoresis were studied in 47 patients with acute idiopathic polyneuropathy (AIP) and 15 patients with chronic relapsing polyneuropathy (CRP). Nineteen of 47 patients with AIP had transient oligoclonal IgG bands, which disappeared when the neurologic signs subsided. By contrast, 14 of 15 patients with CRP had a "monoclonal" (single) IgG band, which (1) was unchanged on repeated CSF examinations over 18 months, (2) was unaffected by corticosteroid therapy, and (3) did not correlate with the severity or chronicity of the disease. Serum protein patterns and in situ central nervous system IGG synthesis and IgG:albumin index were normal in the CRP patients. The origin of the band and the nature of the putative antigen(s) that the band may be directed against were not identified. Our findings suggest that different immunopathogenic mechanisms may be operating in CRP, compared with AIP. The stable IgG band in CRP may reflect response to a persisting antigenic stimulation and, with further experience, may prove to be of prognostic significance by furnishing early in the illness: (1) a clue to the subsequent course of the disease, and (2) possible guidance on therapeutic decisions.

Chronic Disease↗
PubMed1980

The molecular mechanism of the inherited phosphofructokinase deficiency associated with hemolysis and myopathy.

Normal human erythrocyte phosphofructokinase (ATP: D-fructose-6, P-1-phosphotransferase, EC 2.7.1.11; PFK) has recently been shown to consist of a heterogeneous mixture of five tetrameric isozymes: M4, M3L, M2L2, ML3, and L4 (M, muscle type; L, liver type). In the light of these findings, we have investigated the molecular basis of the inherited erythrocyte PFK deficiency associated with myopathy and hemolysis (Tarui disease). The propositus, a 31-yr-old male, suffered from muscle weakness and myoglobinuria on exertion. He showed mild erythrocytosis despite laboratory evidence of hemolysis. In his erythrocytes a metabolic crossover point was found at the level of PFK; 2,3-diphosphoglycerate (2,3-DPG) was also significantly reduced. The PFK from the patient's erythrocytes consisted exclusively of the L4 isozyme, and there was a complete absence of the other four. The leukocyte and platelet PFKs from the patient showed normal activities, chromatographic profiles, and precipitation with anti-M4 antibody. These studies provide direct evidence that in Tarui disease the M-type subunits are absent; but the liver- and platelet-type subunits of PFK are unaffected. The paradox of mild erythrocytosis despite hemolysis reflects the decreased production of 2,3-DPG.

Adult↗
PubMed1979

In vitro characterization of skeletal muscle beta-adrenergic receptors coupled to adenylate cyclase.

[3H]Dihydroalprenolol, a potent beta-adrenergic antagonist, was used to identify the adenylate cyclase-coupled beta-adrenoceptors in isolated membranes of rat skeletal muscle. The receptor sites, as revealed by [3H]dihydroalprenolol binding, were predominantly localized in plasmalemmal fraction. That skeletal muscle fraction may also contain the plasmalemma of other intramuscular cells, especially that of blood vessels. Hence, the [3H]dihydroalprenolol binding observed in that fraction may be due partly to its binding to the plasmalemma of blood vessels. Small but consistent binding was also observed in sarcoplasmic reticulum and mitochondria. The level of [3H]dihydroalprenolol binding in different subcellular fractions closely correlated with the level of adenylate cyclase present in those fractions. The binding of [3H]dihydroalprenolol to plasmalemma exhibited saturation kinetics. The binding was rapid, reaching equilibrium within 5 min, and it was readily dissociable. From the kinetics of binding, association (K1) and dissociation (K2) rate constants of 2.21 . 10(7) M-1 . min-1 and 3.21 . 10(-1) min-1, respectively, were obtained. The dissociation constant (Kd) of 15 mM for [3H]dihydroalprenolol obtained from saturation binding data closely agreed with the Kd derived from the ratio of dissociation and association rate constants (K2/K1). Several beta-adrenergic agents known to be active on intact skeletal muscle also competed for [3H]dihydroalprenolol binding sites in isolated plasmalemma with essentially similar selectivity and stereospecificity. Catecholamines competed for [3H]dihydroalprenolol binding sites with a potency of isoproterenol greater than epinephrine greater than norepinephrine. A similar order of potency was noted for catecholamines in the activation of adenylate cyclase. Effects of catecholamines were stereospecific, (-)-isomers being more potent than (+)-isomers. Phenylephrine, an alpha-adrenergic agonist, showed no effect either on [3H]dihydroalprenolol binding or on adenylate cyclase. Known beta-adrenergic antagonists, propranolol and alprenolol, stereospecifically inhibited the [3H]dihydroalprenolol binding and the isoproterenol-stimulated adenylate cyclase. The Ki values for the antagonists determined from inhibition of [3H]dihydroalprenolol binding agreed closely with the Ki values obtained from the inhibition of adenylate cyclase. The data suggest that the binding of [3H]dihydroalprenolol in skeletal muscle membranes possess the characteristics of a substance binding to the beta-adrenergic receptor.

Adenylyl Cyclases↗
PubMed1979

CSF viral antibodies. Evaluation in amyotrophic lateral sclerosis and late-onset postpoliomyelitis progressive muscular atrophy.

Serum and CSF from 48 patients with amyotrophic lateral sclerosis and six patients with late-onset postpoliomyelitis progressive muscular atrophy were investigated for the presence of antibody to poliovirus types 1, 2, and 3, coxsackie viruses B3 and B4, influenza A, measles, rubella, mumps, herpes simplex types 1 and 2, cytomegalovirus, varicella-zoster, and Toxoplasma gondii. These results were compared with those from 53 control patients with neuromuscular disease matched for age, sex, race, and poliovirus vaccine exposure. There was no difference either in distribution of serum or CSF antibody titers or the geometric-mean antibody titers. There was no evidence suggesting the presence of locally produced specific viral antibody within the CNS to any of the agents studied. In particular, there was no serological evidence to suggest an association between persistent infection with any poliovirus type and amyotrophic lateral sclerosis or late-onset postpoliomyelitis progressive muscular atrophy.

Adult↗