PubMed Health⌕ Search

Biomedical subjects

R L Wollmann

Publications and source records attributed to R L Wollmann.

At least 37 records · Page 2Linked to original sources
PubMed1992

Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo.

Victims of major electrical trauma frequently suffer extensive skeletal muscle and nerve damage, which is postulated to be principally mediated by electroporation and/or thermally driven cell membrane permeabilization. We have investigated the efficacy of two blood-compatible chemical surfactants for sealing electroporated muscle membranes. In studies using cultured skeletal muscle cells, poloxamer 188 (P188; an 8.4-kDa nonionic surfactant) blocks, and neutral dextran (10.1 kDa) substantially retards, carboxyfluorescein release from electropermeabilized cell membranes. To test whether P188 administered intravenously could have the same therapeutic effect in vivo, the rat biceps femoris muscle flap attached by its arteriovenous pedicle was electropermeabilized until its electrical resistivity dropped to 50% of the initial value. P188 (460 mg/kg) administered intravenously 20 min postshock restored the resistivity to 77% of the initial value. When P188 was administered intravenously 5 min before shock, a dose-dependent impedance recovery rate was observed. Neither neutral dextran (460 mg/kg) nor sterile saline was effective. Histopathologic studies indicated that postshock poloxamer administration reduced tissue inflammation and damage in comparison with dextran-treated or control tissues. Electrophysiologic evidence of membrane damage was not observed in flaps of animals pretreated with poloxamer. These results suggest that it may be possible to seal in vivo tissue membranes injured by electrical, thermal, or other membrane-damaging forces.

Animals↗
PubMed1992

Sympathectomy augments adoptively transferred experimental allergic encephalomyelitis.

Adoptively transferred experimental allergic encephalomyelitis (EAE) was significantly augmented in Lewis rats with ablated sympathetic nervous system. Sympathectomy was obtained by treatment of newborn rats with 6-hydroxydopamine. Sham-injected rats were used as a control. EAE was elicited in 7-8-week-old donor Lewis rats by immunization with a suspension of guinea pig (GP) brain and spinal cord in complete Freund's adjuvant. Successful transfer of EAE was accomplished with 50 x 10(6) lymph node cells (LNC)/rat, incubated for 72 h with GP myelin basic protein. LNC were obtained from draining lymph nodes, 9 days after immunization for EAE. The severity of passively transferred EAE was significantly augmented when donor LNC obtained from normal Lewis rats immunized for EAE were injected into sympathectomized rats as compared to sham-injected rats. When LNC were obtained from sympathectomized or sham-injected donors, the disease was significantly more severe in recipients of cells from sympathectomized animals. The severity of histological lesions in the brain and spinal cord was greater in rats with passively transferred EAE which received LNC from sympathectomized donors.

Animals↗
PubMed1992

SAG: a Schwann cell membrane glycoprotein.

We report on characterization of a 170,000 Da glycoprotein found exclusively in the PNS. We refer to this protein as the Schwann cell membrane glycoprotein (SAG). SAG contains the HNK-1 carbohydrate, which is considered by some to be a marker of adhesion molecules. Its N-terminal sequence is not similar to previously known polypeptide sequences. SAG is found exclusively in the PNS, is present in rat sciatic nerve prior to myelination, and is in both myelinating and nonmyelinating Schwann cells. Tumors of Schwann cell lineage express SAG where axons are present (neurofibromas) but do not in the absence of axons (schwannomas). Schwannoma cells in culture do not express SAG even when exposed to forskolin, an activator of adenylate cyclase. However, schwannoma cells grown in the presence of a neuronal cell line (PC12) express SAG.

Amino Acid Sequence↗
PubMed1991

Cellular neuropathology of tuberous sclerosis.

The study of cerebral lesions of TSC by special histologic methods suggests that two populations of neurons and glia occur in TSC brains. One is a population of normally differentiated cells that form a normally constituted cortical plate. The other is a group of cells that are poorly differentiated, fail to organize into a normal cortical architecture, and form a variety of abnormal cellular aggregates in cortex and in subcortical locations. The proportion of these abnormal cells varies greatly from patient to patient. In some the central nervous system appears to be entirely spared. In others, only one or a few islands of dysplastic cells occur, whereas in still others a large number, perhaps even a majority, of neuroectodermal cells in the forebrain may be affected. The proportion of total cells that undergo abnormal differentiation apparently is an important factor relative to cortical function in TSC. At present we have no explanation for this marked heterogeneity in expression of the TSC gene or genes, and it remains one of the many unsolved mysteries of this illness.

Brain↗
PubMed1991

Inflammation at the neuromuscular junction in myasthenia gravis.

To better define the pathogenic mechanisms in the antibody-mediated autoimmune disease myasthenia gravis (MG), we analyzed the morphology and electrophysiology of the neuromuscular junction in anconeus muscle biopsy specimens from eight patients with MG and seven control subjects. There were inflammatory cells at the neuromuscular junction in seven of the eight biopsies from MG patients. The endplate index (length of the postsynaptic membrane divided by the length of the apposed presynaptic membrane) was abnormally reduced in all the MG patients, and fiber type grouping, suggestive of reinnervation, was present in six of the eight MG patients. Intracellular recording revealed diminished amplitude of miniature endplate potentials and miniature endplate currents in the MG patients compared with the controls. The time constant of decay of miniature endplate currents did not differ from that of controls, suggesting no change in mean channel open time of the acetylcholine receptor. The endplate receptor sensitivity to iontophoretically applied acetylcholine was also decreased in MG patients compared with controls. The quantal content of neurally evoked endplate potentials was reduced in six of the eight MG patients, demonstrating abnormal presynaptic function as well. The presence of inflammatory cells at the neuromuscular junctions of limb muscles in MG reconciles an apparent disparity between the animal model of MG, experimental autoimmune myasthenia gravis, and the human disease. This study also demonstrates a frequent presynaptic component to the abnormal neuromuscular transmission in MG.

Action Potentials↗
PubMed1990

Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin.

Patients with myasthenia gravis (MG) and thymoma have in their sera antibodies which react with non-receptor antigens from striated muscle. The purpose of this investigation was to characterize the antigen(s). Polypeptides in homogenates from rat skeletal muscle were separated by SDS-PAGE and trans-blotted to nitrocellulose. Sera from six patients with MG and thymoma stained a large (molecular weight greater than 500 kD) polypeptide, while no staining was observed with sera from 20 non-thymoma MG patients. Titin is one of the large (greater than 500 kD) polypeptides of striated muscle and the antibody containing MG sera have antibodies that bind to titin in a preparation of myofibrillary proteins from rabbit skeletal muscle. The staining pattern is identical to that obtained with antiserum to titin, showing that the antigen has the same electrophoretic mobility as titin. Antibodies from the sera of the patients with MG and thymoma, affinity-purified on the large polypeptide, reacted with skeletal muscle sections in a cross-striational pattern, near the A/I band junction but within the I band, corresponding to the localization of one of the epitopes of titin. Our findings therefore indicate that the muscle antibodies found in the sera from some MG patients with thymoma are directed against titin.

Animals↗
PubMed1988

The effect of fetal hypothalamus grafts on weight gain resulting from lesions of the ventromedial hypothalamus.

Bilateral ventromedial hypothalamic lesions in female adult rats which resulted in hyperphagia and rapid weight gain were followed by placement of fetal brain tissue in the anterior third ventricle. The treatment group received fetal hypothalamus grafts, and fetal cortical tissue of identical age was grafted into the control group. A significant reduction in average daily weight gain was noted from 4 to 12 weeks following transplantation in the treatment group. At 12 weeks posttransplantation, the animals were sacrificed for histological analysis. Examination of the hypothalamus grafts revealed neurons, ependymal clusters, and axonal processes which appeared to infiltrate the surrounding hypothalamic parenchyma.

Animals↗
PubMed1987

Late denervation in patients with antecedent paralytic poliomyelitis.

The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted a controlled study of this syndrome by analyzing clinical, electromyographic, and muscle-biopsy features in 18 patients with a history of poliomyelitis--13 reporting 1 to 20 years of new weakness and 5 without new symptoms. The patients with new weakness also reported new muscle atrophy (9 of 13) and fatigue (10 of 13), symptoms not reported by the controls. The age at the time of acute poliomyelitis, severity of poliomyelitis, residual disability, number of years since acute poliomyelitis, and age at the time of study were comparable in the weakening and control groups. Evidence of remote denervation consistent with antecedent poliomyelitis was demonstrated in all patients by electromyography or muscle biopsy or both. In addition, active denervation (as evidenced by spontaneous activity on conventional electromyography, increased jitter on single-fiber electromyography, or atrophic myofibers) was found in 12 patients in the weakening group and in all 5 controls. Immunohistochemical detection of myofibers expressing the neural-cell adhesion molecule corroborated ongoing denervation in both patient groups. When muscle data from both groups were pooled, correlations were observed between the extent of past reinnervation and the degree of ongoing motor-unit instability. We conclude that the extensive reinnervation of denervated muscle that occurs in paralytic poliomyelitis may be followed by late denervation of the previously reinnervated muscle fibers. Electromyographic and muscle-biopsy evidence of ongoing denervation does not distinguish between stable patients with prior paralytic poliomyelitis and those with new weakness.

Adult↗
PubMed1987

Refractoriness to a second episode of experimental myasthenia gravis. Correlation with AChR concentration and morphologic appearance of the postsynaptic membrane.

Rats injected with anti-acetylcholine receptor (anti-AChR)2 monoclonal antibodies (mAb) develop the acute phase of experimental autoimmune myasthenia gravis characterized by a macrophage inflammation of muscle endplates (EP). These animals are subsequently refractory to induction of a second such episode up to 8 wk after the initial injection. Analysis of this phenomenon to date has shown that mechanisms such as anti-idiotypic regulation, epitopic modulation, and cellular suppression or deletion are not significantly involved. In the present study, animals reinjected from 11 wk on developed a second episode of cellular EP inflammation. This renewed susceptibility correlated temporally with an increase in postsynaptic membrane length and AChR content. When the second injection of anti-AChR mAb was given at 8 wk, mAb bound to muscle EP caused a small reduction in AChR content in the absence of cellular inflammation. These observations suggested that total inaccessibility of AChR to mAb is not responsible for the refractoriness to cellular EP inflammation. More likely, a certain AChR concentration or density is necessary to bind a critical amount or density of antibody to activate complement and set in motion the events leading to a cellular inflammatory response. In human myasthenia gravis, in which initially damaged EP are continuously exposed to anti-AChR antibodies, this critical AChR concentration or density may not be reached again because of continuous complement-mediated lysis and/or increased AChR turnover. Hence, these data may explain the infrequency of cellular EP inflammation in motor point muscle biopsies in this disease.

Animals↗
PubMed1986

N-acetyl-beta-hexosaminidase beta locus defect and juvenile motor neuron disease: a case study.

A patient with partial deficiency of N-acetyl-beta-hexosaminidase (Hex) developed a progressive motor neuron syndrome beginning at age 7, characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Minor clinical features have included tremor and late distal sensory abnormalities. Rectal biopsy at age 24 demonstrated membranous cytoplasmic bodies in submucosal ganglion cells. Biochemical evaluation revealed nearly absent Hex B activity in serum, leukocytes, and fibroblasts, with partial Hex A activity in serum and leukocytes, and low normal Hex A activity in fibroblasts. Motor neuron disease can be a presentation of a Hex beta locus defect, in addition to the previously recognized Hex alpha locus defects.

Adult↗
PubMed1986

Diffuse nodular hyperplasia and fibrosis of the liver in lead-poisoned mandrills.

Two sibling mandrills with clinical evidence of lead intoxication showed previously unreported hepatic alterations. The younger animal had high lead concentrations in blood, kidneys, and liver and characteristic intranuclear inclusions in renal tubules and hepatocytes. The liver showed diffuse nodular regenerative hyperplasia. The older mandrill had high lead concentrations in blood only and resolving intranuclear inclusions in liver and kidneys. The liver showed prominent portal fibrosis with evidence of resolving diffuse nodular hyperplasia. Occipital horn hydrocephalus was also present.

Animal Diseases↗
PubMed1986

Aortic dissection in a gorilla.

Autopsy findings in a 39-year-old male gorilla included aortic dissection, internal rupture of the aortic arch with axial direction of the tear, external rupture of the ascending aorta, cardiac tamponade, myocardial hypertrophy, cystic and basophilic degeneration of the aortic media, marked obesity, severe degenerative joint disease, focal glomerulonephritis, and widespread hemosiderosis.

Aortic Dissection↗
PubMed1984

Induction of the morphologic changes of both acute and chronic experimental myasthenia by monoclonal antibody directed against acetylcholine receptor.

To investigate pathogenic mechanisms in experimental autoimmune myasthenia gravis (EAMG) and myasthenia gravis (MG), we studied the acute and chronic effects in rats of injection of rat monoclonal antibodies ( MCABs ) directed against the acetylcholine receptor (AChR). Animals were severely weak 12 h after a single injection, at which time macrophages were found invading endplate regions of muscle and cholinesterase-stained regions were separted from the underlying muscle fibers. Ultrastructural studies showed findings identical to the acute phase of EAMG: degenerating postsynaptic membranes and invasion and phagocytosis of endplate regions by macrophages. Animals receiving sublethal doses of MCAB recovered clinically by 4-5 days after injection. Recovery was accompanied by a progressive decrease in the number of macrophages associated with endplates and reapposition to the myofibers of the cholinesterase-stained regions. Animals injected once, or repeatedly over several months, remained clinically and electromyographically normal after recovery from the initial episode of weakness, but their endplate ultrastructure was highly simplified with blunted or absent synaptic folds and shallow or absent secondary synaptic clefts. These studies demonstrate that anti-AChR MCABs can induce the changes of both acute and chronic EAMG. There is good correlation between the inflammatory changes and the acute clinical disease but poor correlation between morphological and clinical parameters in the chronic syndrome. The latter observation suggests that severe ultrastructural changes, similar to those seen in chronic EAMG and MG, cannot account, at least in rats, for the clinical and electrophysiologic abnormalities of MG.

Animals↗
PubMed1984

Ultrasound evaluation of experimental hydrocephalus in dogs.

The use of real time ultrasound to evaluate experimental hydrocephalus in craniectomized dogs is described. Fifteen dogs were longitudinally evaluated by ultrasound after injection of silicone into the suprasellar cistern and injection of kaolin into the cisterna magna, and later killed. Ventricular size was classified as normal, moderately or severely hydrocephalic according to lateral ventricular width. In 93% (14/15) of the animals the classifications as determined by ultrasound and pathological examination agreed. Both lateral ventricular width and biventricular width as measured by ultrasound had a linear correlation with measurements on the pathologic specimens (p less than 0.001).

Animals↗
PubMed1983

Neuropathy accompanying IgM lambda monoclonal gammopathy.

A set of observations made on a patient with IgM lambda monoclonal gammopathy and neuropathy implicate humoral immunity in the pathogenesis of the neuropathy. A sural nerve biopsy from the patient showed a characteristic increase in the width of the intraperiod lines. Deposits of mu-heavy chains and lambda-light chains were found in myelin sheaths of the nerve biopsy. Immunohistochemically, it was demonstrated that mu-heavy chains and lambda-light chains from the patient's serum bound to myelin sheaths of normal peripheral nerves and to a lesser extent to myelin sheaths in the central nervous system (CNS). By immunoblots it was demonstrated that mu-heavy chains and lambda-light chains from the patient's serum bound to myelin associated glycoprotein but to no other antigens from the peripheral and central nervous systems. gamma and alpha heavy chains and chi light chains from the patient's serum were also shown to bind to myelin-associated glycoprotein but not as distinctly as the mu and lambda chains. It is postulated that the monoclonal gammopathy may have arisen on the background of polyclonal autoimmune attack directed against myelin-associated glycoprotein.

Biopsy↗
PubMed1983

Venous angiomas of the posterior fossa should be considered as anomalous venous drainage.

Venous angioma of the posterior fossa has been described, and the existing literature has been reviewed. The patient presented had a venous angioma located in the pons, and both cerebellar hemispheres and was drained by an enlarged and anatomically anomalous vein within the fourth ventricle. The patient had a "cough headache" and later had signs of cerebellar involvement. A surgical attempt at collapsing the anomalous vein resulted in death in the immediate postoperative period due to venous infarction of the brain stem and cerebellum. Emphasis has been given to the following: 1. "Cough Headache" can be a presenting feature for venous angiomas of the posterior fossa. 2. Venous angiomas of the posterior fossa are developmental anatomic anomalies with enlargement of certain venous structures as a result of inadequate alternative venous drainage. 3. The enlarged vein, which is the pathognomonic feature of venous angiomas, serves a vital function in drainage of blood from structures in the posterior fossa as the usual drainage pathways are inadequate or absent. 4. Operative intervention aimed at resection or collapse of such large veins, which has been successful in treatment of venous angiomas of the frontal lobe, can be disastrous in the treatment of those lesions occurring in the posterior fossa.

Adult↗