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Biomedical subjects

W K Engel

Publications and source records attributed to W K Engel.

At least 145 records · Page 8Linked to original sources
PubMed1982

Biochemical and morphological effects of 20,25-diazacholesterol on cultured muscle cells.

Effects of 20,25-diazacholesterol (DAC), a myotonia-inducing drug, were evaluated on certain biochemical and morphological properties of embryonic rat muscle cells grown in tissue culture. During DAC treatment, muscle fibers exhibited spontaneous contractions that changed from coarse twitches to finer fibrillation movements, The ultrastructural alterations produced by DAC were smeared Z-lines, disorganized myofibrils, occasional honeycomb appearance of membranes and large vacuoles connected to zipper-like structures. Biochemically, a microsomal fraction prepared from DAC-treated cells (compared to that of normal cells) showed a 30-45 per cent decrease in the isoproterenol-enhanced and the NaF-enhanced adenylate cyclase activity. however, the beta-adrenergic receptors, through which isoproterenol activates the enzyme, showed no change in density or affinity as judged by the binding of [125I]iodohydroxybenzylpindolol. That indicated that DAC treatment caused an uncoupling of beta-receptor-adenylate cyclase interaction. Guanylate cyclase and cyclic GMP-phosphodiesterase were both markedly increased in DAC-treated cells, indicating a greater turnover of cyclic GMP. Binding of [3H]concanavalin A to DAC-treated muscle membranes was decreased 20-40 per cent. The data indicate that DAC exert a direct influence on muscle fibers, affecting their functional, biochemical and morphological properties.

Animals↗
PubMed1982

Myosin isoenzymes in cultured human muscle.

Cultured human muscle grown aneurally and innervated by the ventral part of fetal rat spinal cord was examined using antimyosin antibodies specific for isomyosins from fast and slow mammalian skeletal muscle. Cultured muscle displayed multiple reactivity with antibodies against both types of myosins, with no evident compartmentalization of different forms of myosin into different muscle cells, such as seen in adult muscle. Innervation of cultured muscle resulted in better growth and longer survival of cultured muscle and its more advanced maturation, with a larger number of cross-striated muscle fibers. The pattern of immunofluorescence reaction, however, was the same in both innervated and noninnervated cultured muscle.

Antibodies↗
PubMed1982

Left ventricular relaxation, mitral valve prolapse, and intracardiac conduction in myotonia atrophica: assessment by digitized echocardiography and noninvasive His bundle recording.

Myotonia atrophica, a neuromuscular disease marked by autosomal dominant transmission and delayed relaxation of skeletal muscle, has been associated with cardiac failure, conduction abnormality and mitral prolapse (MVP). In order to determine the relaxation rate of cardiac muscle, left ventricular (LV) size and function, and the presence of MVP, 30 patients with myotonia atrophica were studied using digitized M-mode echocardiography (MME). Intracardiac conduction intervals were determined by noninvasive His bundle recording (HBR) from surface electrodes using a high-resolution, R-wave triggered, signal averaging computer. Neurologically unaffected first-degree relatives of the patients with myotonia atrophica were also studied to determine if cardiac abnormalities may be present in the absence of neurologic manifestations of the disease. Peak normalized diastolic endocardial velocity in patients with myotonia atrophica (3.7 +/- 0.8 sec-1) did not differ from unaffected first-degree relatives (3.8 +/- 0.8 sec-1) or normal subjects (3.6 +/- 0.8 sec-1). Systolic LV function and LV dimensions on MME were normal in both groups. However, MVP was present in 7 of 24 (29%) of patients who could be evaluated, but not in unaffected first-degree relatives. Despite normal LV systolic and diastolic function, infranodal intracardiac conduction was prolonged in patients with myotonia atrophica (average HV interval 50 +/- 5 SD msec) but not in neurologically unaffected relatives (average HV interval 40 +/- 5 msec). Delay in proximal intracardiac conduction was also found in patients with myotonia atrophica (average PH interval 140 +/- 20 msec) but not in neurologically unaffected relatives (average PH interval 115 +/- 6 msec). Hence cardiac findings in myotonia atrophica include proximal and distal conduction delay by external HBR even in the absence of abnormality of the standard 12-lead ECG. There may also be an increased frequency of MVP; however, early diastolic relaxation of the LV is unimpaired, and cardiac manifestations of myotonia are not transmitted independently of neurologic abnormality.

Adolescent↗
PubMed1982

Demonstration of 2',3'-cyclic nucleotide 3'-phosphohydrolase in cultured human Schwann cells.

Schwann cell cultures were established from adult human sural nerve biopsies. 2'3'-Cyclic nucleotide 3'-phosphohydrolase (CNPase) activity was estimated in the homogenates of those cells by a sensitive isotope assay using [3H]2',3'-cyclic AMP as substrate. A high level of CNPase activity was observed in cultured Schwann cells, whereas cultured human muscle and skin fibroblasts contained negligible levels of CNPase activity. CNPase of human Schwann cells followed typical enzyme-substrate kinetics, with an apparent Km of 1.6 mM for 2',3'-cyclic AMP, and the enzyme was stimulated by detergents such as Triton X-100 and deoxycholate. It was inhibited by p-chloromercuricbenzoate and 2'-AMP. These properties are typical of CNPase isolated from adult brain and spinal cord. CNPase can serve as a new biochemical marker of normal cultured human Schwann cells and can be useful in analyzing the properties of cultured Schwann cells from patients with dysschwannian neuropathies.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1982

Single cholinergic receptor channel currents in cultured human muscle.

Single cholinergic channel currents were recorded in adult human muscle tissue culture. The agonists suberyldicholine and carbamylcholine produce channels with the same conductance as channels produced by acetylcholine but with different closing kinetics. The antagonist tubocurarine, alone or mixed with suberyldicholine, activates channels which close very rapidly. For agonist-activated channels, the distribution of open state lifetimes shows deviations from the usual single exponential form. An excess of short duration openings indicates the presence of an additional faster kinetic process. The lifetime distribution data can be interpreted in terms of varying proportions of slow and fast components which are present in a ratio determined by curve-fitting the appropriate two-exponential function to observed open time distributions. This ratio shows great variability in muscle from older cultures, but the fast and slow time constants are relatively constant. The observation of double exponential open time distributions indicates that the mechanism of channel closing is more complicated than earlier evidence indicated.

Acetylcholine↗
PubMed1982

Effect of heme administration on hemopexin metabolism in the rhesus monkey.

Clinical conditions such as hemolytic anemias and certain neuromuscular diseases in which serum hemopexin levels are either increased or decreased were simulated in rhesus monkeys by administering heme intravenously daily at three dose levels over a period of 10 days. At the lower dose of heme (0.02 to 0.04 mg/kg/day), serum hemopexin levels were elevated to 150% of control (control = 53.3 +/- 2.8 U/100 ml). At the higher dose of heme (5.0 mg/kg/day), hemopexin levels decreased to 60% of control. After an intermediate dose of heme (0.6 mg/kg/day), no change was seen in the circulating hemopexin levels. These changes appeared to be specific for hemopexin, since neither the serum haptoglobin levels nor the transferrin level was affected by the heme administration at any of the dose levels. Parameters of hemopexin metabolism revealed that after administration of the low dose of heme there was a 76% increase in the net rate of hemopexin synthesis, resulting in a 65% increase in the intravascular pool size of hemopexin. At the intermediate dose there was a 43% increase in the rate of hemopexin synthesis accompanied by a 33% increase in catabolism, resulting in no net change in serum hemopexin concentrations. At the high dose of heme there was a 57% increase in catabolism of hemopexin without a concurrent increase in synthesis, resulting in lowered circulating hemopexin levels. These findings seem to indicate a relationship between the amount of heme presented to the liver and net hemopexin synthesis.

Animals↗
PubMed1982

Quantification of acute phase reactants after muscle biopsy.

Blood concentrations of six acute phase reactants (ESR, neutrophil count, fibrinogen, haptoglobin, alpha 1-antitrypsin, and ferritin), parameters of muscle necrosis (myoglobin, CK, ALT, and AST) as well as hemopexin, iron, and TIBC were determined before and for 7 consecutive days after muscle biopsy in patients and in a control group. A muscle biopsy was chosen as a standardized surgical procedure that induces a mild transient inflammatory response. After muscle biopsy, a significant increase occurred in five (ESR, neutrophil count, fibrinogen, haptoglobin, and alpha 1-antitrypsin) of the six acute phase reactants. The concentration of serum ferritin did not show a significant change. A significant decrease was noted in the serum iron concentration and a significant increase occurred with CK and myoglobin secondary to the muscle biopsy. Thus the inflammation of a muscle biopsy produces a significant acute phase reaction.

Adult↗
PubMed1981

Collagen localization in normal and fibrotic human skeletal muscle.

The distribution of types I to IV collagen, types I and III p-N collagen, and fibronectin in human skeletal muscle was studied by immunofluorescence using purified antibodies to those proteins. In normal muscle, types I and III collagen, types I and III p-N collagen, and fibronectin were localized in the endomysium and perimysium. Type IV collagen was restricted to basement membrane. Type II collagen was not present. In Duchenne's musclar dystrophy and dermatomyositis/polymyositis (DM/PM), the prominently increased endomysial and perimysial fibrosis consisted of types I and III collagen, types I and III p-N collagen, and fibronectin. In DM/PM, thickening of the walls of perimysial venular and arteriolar vessels was associated with accumulation of types I and III collagen, types I and III p-N collagen, and fibronectin, as well as type IV collagen. There was no disease-specific accumulation of collagen, p-N collagen, or fibronectin.

Adolescent↗
PubMed1981

Poly ICLC in the treatment of postinfectious demyelinating encephalomyelitis.

Three weeks after a mild and presumably infectious illness, a 21-year-old man developed a CNS disorder characterized by involvement of the cerebellum, cerebrum, and brainstem. It progressed, sometimes stepwise, without remission, over five months to being bedfast with total spastic paraplegia, severe ataxia, and unintelligible dysarthric speech. The CSF showed increased levels of protein, IgG, and myelin basic protein, as well as five oligoclonal bands. Because of failure of the patient's condition to respond to prolonged prednisone therapy, poly ICLC was given intravenously weekly for 20 weeks (median dose, 100 microgram/kg). Improvement, evident after the first dose, progressed to the point of ambulation with some assistance. Even though the relation of the patient's marked recovery to poly ICLC therapy remains unproved, this experience provides reason for considering a possible therapeutic role of the drug in postinfectious demyelinating encephalomyelitis and perhaps in multiple sclerosis.

Adult↗
PubMed1981

Amyloid in hereditary amyloid polyneuropathy is related to prealbumin.

The origin of amyloid in the several subsets of hereditary amyloid polyneuropathy (HAP) is unknown. A recent biochemical study of extracted amyloid indicated that in the "portuguese" type of HAP it consists of a prealbumin-related protein. With the use of specific antibodies against human prealbumin, AA, and kappa and lambda type proteins, we demonstrated by indirect immunofluorescence that the amyloid in muscle biopsy specimens from five Americans and one Brazilian with HAP and one Brazilian without a family history (but with typical clinical disease and no plasma cell dyscrasia) was stained exactly and specifically only with antiprealbumin. In contrast, amyloid in muscle biopsy specimens from patients with plasma cell dyscrasic polyneuropathy and in amyloid-negative control muscle biopsy specimens from patients with nonamyloid neuropathies did not bind antiprealbumin antibodies. Our findings suggest that prealbumin-like protein may be a commonality of amyloid deposits in many, and possibly all, subsets of HAP.

Adolescent↗
PubMed1981

Chronic relapsing (dysimmune) polyneuropathy: pathogenesis and treatment.

Chronic relapsing polyneuropathy is a distinct dysschwannian/demyelinating polyneuropathy characterized by usually slow onset, progressive or relapsing-remitting course, elevated cerebrospinal fluid (CSF) protein, marked slowing of nerve conduction velocity, segmental demyelination demonstrable in sural nerve biopsies, and absence of systemic illness or abnormal serum immunoglobulins. The cause of the disorder and the mechanisms underlying its chronicity and relapsing-remitting course are not clear. Immunoglobulin deposition observed in sural nerve biopsies and abnormal immunoglobulin patterns in the "CSF in some cases suggest a dysimmune pathogenesis; thus the term chronic relapsing (dysimmune) polyneuropathy (CRDP) is preferred. The disease is a treatable form of idiopathic polyneuropathy. In our series of 25 patients with CRDP, treatment with high-single-dose daily prednisone, slowly tapered to an alternate-day program, has been very successful in the majority. A low (10 to 20 mg) alternate-day-single-dose program, maintained indefinitely, seems to be required to prevent future recurrences. Evidence is provided that other immunosuppressants (azathioprine, cyclophosphamide, poly-ICLC) and possibly plasmapheresis, alone or in conjunction with corticosteroids, may have a beneficial role in controlling difficult cases of chronic relapsing polyneuropathy.

Adolescent↗
PubMed1981

Polyneuropathy with monoclonal gammopathy: studies of 11 patients.

Among patients with chronic idiopathic nonfamilial polyneuropathy studied 3 to 21 years after onset, we identified 11 cases associated with monoclonal gammopathy (MCG) (5 with IgGk, 4 with IgMk, 2 with IgG lambda). The patients, aged 29 to 80 years, presented with sensorimotor polyneuropathy of insidious onset and slow, nonfluctuating progression, delayed motor and sensory nerve conduction, and increased cerebrospinal fluid (CSF) protein. None of the patients in the initial or follow-up study (mean, 9.2 years) had or developed signs of multiple myeloma, malignant plasma cell dyscrasia, macroglobulinemia syndrome, amyloidosis, neoplasia, or other associated illness. The CSF revealed abnormalities of protein electrophoresis or immunoelectrophoresis in 9 of the 11 patients. Three of 5 sural nerve biopsies studied by immunofluorescence demonstrated deposition in nerve fibers of the light chain characteristic of the abnormal circulating immunoglobulin. The findings suggest that these patients form a distinct subset of the dysimmune neuropathies. Although the immunoglobulin deposition and abnormal protein patterns in serum and CSF could be secondary to nerve damage, we propose that an immunopathological mechanism underlies the neuropathy. Immunosuppressants had minimal to marked beneficial effect in 4 of 5 patients, indicating that this polyneuropathy is potentially treatable.

Adult↗
PubMed1981

Lysosomal abnormalities in cultured schwann cells from a patient with peripheral neuropathy and continuous muscle fiber activity.

Schwann cell cultures were established from a sural nerve containing large membrane-bound vacuoles in its Schwann cells, obtained from a patient with neuropathy and continuous muscle fiber activity. Cultured Schwann cells contained many large membrane-bound vacuoles, presumably lysosomes, resembling those present in the biopsied nerve. The acid phosphatase reaction was excessive in the patient's cultured Schwann cells but practically negative in normal cultured Schwann cells. This study indicates that the patient's neuropathy is primary dysschwannian with abnormal lysosomes as a major abnormality.

Acid Phosphatase↗
PubMed1981

Immunocytochemical localization of thymosin-alpha 1 in thymic epithelial cells of normal and myasthenia gravis patients and in thymic cultures.

Thymosin alpha 1 (alpha 1) is a potent thymic polypeptide hormone. With antibodies against synthetic thymosin alpha 1, indirect immunofluorescence was applied to human normal thymus and to hyperplastic, thymomatous or "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassall's corpuscles or proliferated in thymomas. In contrast to normal thymus, which had fewer and more weakly stained cells, MG hyperplastic thymus had many strongly positive epithelial cells: this was markedly evident in thymomas. "Involuted" MG thymus had a few but brightly stained cells lying within the fatty tissue. In tissue cultures of human thymus, anti-alpha 1 stained the epithelial cells, but not fibroblasts. These findings: (a) demonstrate the origin of the thymic hormone alpha 1 to be the thymic epithelial cell; (b) raise the possibility that excess alpha 1 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) suggest that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their positivity in tissue culture.

Adolescent↗
PubMed1981

Systemic manifestations of gyrate atrophy of the choroid and retina.

In ten patients with gyrate atrophy (GA) and hyperornithinemia, the head hair was fine, straight, and sparse. On microscopic examination, both scalp and pubic hair contained intermittent dark cores within the medullary zone, which was not a deposit, but appeared to be due to the unusual refractive properties of loosely formed macrofilaments amidst wide spaces containing a structureless electron lucent but compact substance, which was insoluble in both water and solvents. Seven of the ten patients had abnormal wave forms on electroencephalography. Three of the five patients who underwent muscle biopsy had tubular aggregates. Of particular interest was the toxicity of exogenous ornithine added to muscle cell culture from GA patients as compared with the lack of toxicity in muscle from control patients. What specific role the hyperornithinemia and absence of OAT is playing in the histopathology of hair and muscle and the EEG changes awaits further biochemical investigation.

Adolescent↗