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Biomedical subjects

S A Greenberg

Publications and source records attributed to S A Greenberg.

16 recordsLinked to original sources
PubMed2005

Plasma cells in muscle in inclusion body myositis and polymyositis.

BACKGROUND: Previous immunohistochemical studies of muscle from patients with inclusion body myositis and polymyositis found many more T cells than B cells, suggesting a role for intramuscular cell-mediated immune mechanisms rather than humoral mechanisms. METHODS: Microarray studies were performed on muscle biopsy specimens from 40 patients with inclusion body myositis (IBM; n = 23), polymyositis (PM; n = 6), and without neuromuscular disease (n = 11). Reverse transcription PCR of selected immunoglobulin gene transcripts was performed on two patient samples. Qualitative immunohistochemical studies for B-cell lineage cell surface markers were performed on 28 muscle specimens and quantitative studies performed on a subset of 19 untreated patients with IBM or PM. CD138+ cells were isolated from muscle using laser capture microdissection, and immunoglobulin transcripts were PCR amplified to determine the presence or absence of immunoglobulin gene rearrangements unique to the B-cell lineage. RESULTS: Immunoglobulin gene transcripts accounted for 59% in IBM and 33% in PM of the most stringently defined highest differentially expressed muscle transcripts compared with normal. Plasma cells, terminally differentiated B cells expressing CD138 but not CD19 or CD20, are present in IBM and PM muscle in numbers several times higher than B cells. CONCLUSIONS: There are differentiated B cells in the form of CD138+ plasma cells within the muscle of patients with inclusion body myositis and polymyositis. The principle of linked recognition of B-cell activation predicts several strategies for autoantigen discovery that could not otherwise be pursued through the study of the infiltrating T-cell population alone.

Antigens, Surface↗
PubMed2002

Molecular profiles of inflammatory myopathies.

OBJECTIVE: To describe the use of large-scale gene expression profiles to distinguish broad categories of myopathy and subtypes of inflammatory myopathies (IM) and to provide insight into the pathogenesis of inclusion body myositis (IBM), polymyositis, and dermatomyositis. METHODS: Using Affymetrix GeneChip microarrays, the authors measured the simultaneous expression of approximately 10,000 genes in muscle specimens from 45 patients in four major disease categories (dystrophy, congenital myopathy, inflammatory myopathy, and normal). The authors separately analyzed gene expression in 14 patients limited to the three major subtypes of IM. Bioinformatics techniques were used to classify specimens with similar expression profiles based on global patterns of gene expression and to identify genes with significant differential gene expression compared with normal. RESULTS: Ten of 11 patients with IM, all normals and nemaline myopathies, and 10 of 12 patients with Duchenne muscular dystrophy were correctly classified by this approach. The various subtypes of inflammatory myopathies have distinct gene expression signatures. Specific sets of immune-related genes allow for molecular classification of patients with IBM, polymyositis, and dermatomyositis. Analysis of differential gene expression identifies as relevant to disease pathogenesis previously reported cytokines, major histocompatibility complex class I and II molecules, granzymes, and adhesion molecules, as well as newly identified members of these categories. Increased expression of actin cytoskeleton genes is also identified. CONCLUSIONS: The molecular profiles of muscle tissue in patients with inflammatory myopathies are distinct and represent molecular signatures from which diagnostic insight may follow. Large numbers of differentially expressed genes are rapidly identified.

Adolescent↗
PubMed2001

DNA microarray gene expression analysis technology and its application to neurological disorders.

DNA microarray technology is currently an area of great interest. Also called "genechip" technology, it incorporates molecular genetics and computer science on a massive scale. This technology can rapidly provide a detailed view of the simultaneous expression of entire genomes and provide new insights into gene function, disease pathophysiology, disease classification, and drug development. In this review, the author discusses the basic theory behind genechip and the other biologic chip technologies, their limitations given the current state of biologic knowledge and computational abilities, and their potential applications to the understanding of neurologic disorders.

Animals↗
PubMed2001

Inflammatory myopathy associated with mixed connective tissue disease and scleroderma renal crisis.

Mixed connective tissue disease is a rheumatological syndrome with neuromuscular manifestations that may include inflammatory myopathy and carpal tunnel syndrome. We report a patient who presented with an inflammatory myopathy and bilateral carpal tunnel syndrome prior to the diagnosis of a connective tissue disorder. Early in the course of treatment, a syndrome of acute renal failure developed. Knowledge of this syndrome, scleroderma renal crisis, and its possible relation to corticosteroid treatment is important to clinicians involved in the management of patients with inflammatory myopathies.

Acute Kidney Injury↗
PubMed2001

Methodologic issues in conducting research on hospitalized older people.

OBJECTIVE: To describe challenges in conducting research with hospitalized geriatric patients. DESIGN: Quasi-experimental longitudinal study with inperson interviews at baseline and discharge and a three-month postdischarge telephone interview. Study protocol required baseline interviews within 48 hours of admission for patients or 72 hours for proxies. SETTING: 813-bed urban teaching hospital. PARTICIPANTS: 240 patients, mean age 83.8 years, at moderate to high risk for functional decline during hospitalization, admitted from the emergency room to a general medical unit. MEASUREMENTS: Delays starting or interruptions continuing interviews; patient and environmental conditions potentially affecting data quality; and information on proxy use. RESULTS: Timely access to patients or proxies was a major difficulty, resulting in the screening of only 53.1% of 867 potentially eligible patients. Multiple patient contacts and visits were required to complete interviews. Only 61.3% of baseline and 28.1% of follow-up interviews were completed on the initial day of contact. Despite having on-site interviewers 7 days a week, 29% of discharge interviews were conducted by telephone. Interviews were >90% complete in 487 of 503 of encounters (97%). Baseline delays and interruptions were usually due to the presence of medical staff, off-unit tests, patient illness, nurse unavailability for interview, and need for a proxy. Most in-hospital interviews were conducted with others present. Proxies were required for approximately one-third of patients at all three interviews. CONCLUSION: Conducting clinical research with older adults in the current inpatient setting, where patients are more severely ill yet have shorter lengths of stay now than in the past, proves a challenging yet achievable goal. Effective procedures for negotiating the acute care environment are critical to successful studies.

Acute Disease↗
PubMed1996

Dejerine-Sottas disease with sensorineural hearing loss, nystagmus, and peripheral facial nerve weakness: de novo dominant point mutation of the PMP22 gene.

A 32 year old woman with Dejerine-Sottas disease and negative family history is reported. Clinical onset of her condition was with congenital weakness of her distal four extremities, accompanied by peripheral facial nerve weakness, deafness, and nystagmus. She has used a wheelchair all her life. Sural nerve biopsy showed proliferation of Schwann cells, extensive endoneural fibrosis, axon loss, and demyelination. MNCVs showed marked slowing. MRI of the brain was normal. Molecular genetic studies indicated a de novo dominant missense point mutation of exon 3 of the peripheral myelin protein 22 gene at nucleotide 264 causing replacement of serine with leucine.

Adult↗
PubMed1994

Pseudochoreoathetosis. Movements associated with loss of proprioception.

OBJECTIVE: To describe seven patients with proprioceptive sensory loss and choreoathetoid movements. DESIGN: Case series. SETTING: Outpatient and inpatient university referral. PATIENTS: Patients with sensory loss and abnormal movements. INTERVENTION: None. MAIN OUTCOME MEASURE: None. RESULTS: One patient had a parietal cortex injury, one had a thalamic infarction, two had spinal cord lesions, two had dorsal root ganglion neuronopathies, and one had an ulnar neuropathy. In each case, the duration of abnormal movements correlated with the duration of proprioceptive sensory loss, and the abnormal movements were restricted to body parts with proprioceptive sensory loss. The movements varied from chorea and athetosis to dystonia. CONCLUSIONS: These cases suggest that proprioceptive sensory loss can lead to a movement disorder, termed pseudochoreoathetosis, which occurs following the appearance of lesions anywhere along proprioceptive sensory pathways, from peripheral nerves to the cerebral cortex. It is hypothesized that pseudochoreoathetosis occurs because of the failure to process limb proprioceptive information in the striatum. Therefore, both choreoathetosis and pseudochoreoathetosis may be manifestations of the failure of the striatum to properly integrate cortical motor and sensory inputs.

Adult↗
PubMed1991

Binder's syndrome (nasomaxillary dysplasia): an uncommonly common disorder.

Binder's syndrome or nasomaxillary dysplasia is a disorder characterized by hypoplastic development of the midportion of the midfacial skeleton and its associated soft tissue manifestations. The disorder is probably more common than initially believed with only 40 cases described previous to 1980. However, since 1980, 127 cases have been reported. One case of Binder's syndrome treated with onlay split cranial (calvarial) bone grafts is presented. The technique of using split calvarial bone grafts has become increasingly popular in craniofacial surgery and facial trauma reconstruction. A literature review of Binder's syndrome is outlined and the technique of using split calvarial bone grafts is described. An analysis of the skeleton and soft tissue characteristics of Binder's syndrome is detailed and treatment options discussed.

Adult↗
PubMed1989

Temporomandibular joint dysfunction: evaluation and treatment.

Temporomandibular joint dysfunction is a complicated problem requiring interdisciplinary cooperation for diagnosis and treatment. Functional problems including bruxism and psychological disorders frequently occur with joint dysfunction making evaluation more difficult. Many new diagnostic modalities are now available to supplement the history and physical examination to provide an accurate assessment of the joint. Although conservative treatment is successful in a majority of the patients, some form of surgical treatment remains the only option for those who do not respond to conservative management. We have discussed the etiology, diagnosis, and treatment of the pathological conditions of the TMJ and introduced a new modality of treatment, temporalis fascia interpositional arthroplasty. Further work is necessary to elucidate the etiology of TMJ dysfunction and develop treatment modalities that avoid the use of alloplastic materials.

Arthroscopy↗
PubMed1987

The response of rat brain protein synthesis to ethanol and sodium barbital.

Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from "Control," "Ethanol" and 24 h "Ethanol Withdrawn" rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of 14(C) leucine into protein by all three groups of ribosomes. Under these conditions, the "Ethanol Withdrawn" group displayed the largest inhibition of the 14(C) leucine incorporation into protein when compared to the "Control" and "Ethanol" groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of 14(C) leucine into protein by "Control" and "Ethanol" polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units.

Alcoholism↗
PubMed1975

Cell-mediated immunity in the uremic rat.

The popliteal node assay of the graft-versus-host reaction in the inbred rat provides a sensitive measure of cell-mediated immunity. Spleen cells from uremic Lewis rats as well as normal cells cultured in uremic serum demonstrated significant immunosuppression which was proportional to the severity of the uremia.

Animals↗