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Biomedical subjects

J Rothstein

Publications and source records attributed to J Rothstein.

At least 19 recordsLinked to original sources
PubMed2000

Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase.

Recent studies in Saccharomyces cerevisiae suggest that the delivery of copper to Cu/Zn superoxide dismutase (SOD1) is mediated by a cytosolic protein termed the copper chaperone for superoxide dismutase (CCS). To determine the role of CCS in mammalian copper homeostasis, we generated mice with targeted disruption of CCS alleles (CCS(-/-) mice). Although CCS(-/-) mice are viable and possess normal levels of SOD1 protein, they reveal marked reductions in SOD1 activity when compared with control littermates. Metabolic labeling with (64)Cu demonstrated that the reduction of SOD1 activity in CCS(-/-) mice is the direct result of impaired Cu incorporation into SOD1 and that this effect was specific because no abnormalities were observed in Cu uptake, distribution, or incorporation into other cuproenzymes. Consistent with this loss of SOD1 activity, CCS(-/-) mice showed increased sensitivity to paraquat and reduced female fertility, phenotypes that are characteristic of SOD1-deficient mice. These results demonstrate the essential role of any mammalian copper chaperone and have important implications for the development of novel therapeutic strategies in familial amyotrophic lateral sclerosis.

Alleles↗
PubMed2000

Cytotoxicity by matrix metalloprotease-1 in organotypic spinal cord and dissociated neuronal cultures.

Extracellular matrix (ECM) proteins, including collagens and laminins, are critical to the structure of the neuronal synapse and may also be involved in cell survival. In the present study, we therefore examined the possibility that select ECM degrading proteins might be toxic to organotypic spinal cord and dissociated neuronal cultures. Of those proteins tested, including MMP-1, -7, and -9, we observed that MMP-1 was toxic to spinal cord cultures as determined by release of lactic acid dehydrogenase as well as uptake of propidium iodide. Pretreatment of cell cultures with 50 microM alpha-tocopherol partially reversed these effects. We also observed that MMP-1 was toxic to human neurons grown in dissociated cultures and that increased amounts of MMP-1 were released by astrocytes following their stimulation with IL-1beta. These results suggest that further studies may be warranted to determine whether MMP-1 contributes to neurodegenerative conditions in which activated astrocytes may play a role.

Animals↗
PubMed1998

Endocarditis prophylaxis.

This article attempts to simplify the decision-making process regarding endocarditis prophylaxis. Cardiac conditions are stratified as to risk and oral procedures for which prophylaxis is or is not recommended are outlined. The cardiac conditions are paired with various oral procedures to clarify which require prophylaxis. Antibiotic regimens are described. A distinction is made between MVP patients who require prophylaxis and those who do not. Finally, the value of professional oral healthcare for cardiac patients is confirmed.

Adult↗
PubMed1997

Structure and expression of the human FHIT gene in normal and tumor cells.

The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8) translocation break at 3p14.2, the FRA3B common fragile region, and homozygous deletions in various cancer-derived cell lines. Because some of these genetic landmarks (e.g., the t(3;8) break between untranslated FHIT exons 3 and 4, a major fragile region that includes a viral integration site between exons 4 and 5, and cancer cell homozygous deletions in intron 5) do not necessarily affect coding exons and yet apparently affect expression of the gene product, we examined the FHIT locus and its expression in detail in more than 10 tumor-derived cell lines to clarify mechanisms underlying aberrant expression. We observed some cell lines with apparently continuous large homozygous deletions, which included one or more coding exons; cell lines with discontinuous deletions, some of which included or excluded coding exons; and cell lines that exhibited heterozygous and/or homozygous deletions, by Southern blot analysis for the presence of specific exons. Most of the cell lines that exhibited genomic alterations showed alteration of FHIT transcripts and absence or diminution of Fhit protein.

Acid Anhydride Hydrolases↗
PubMed1997

Hypoxia-ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum.

The neonatal striatum degenerates after hypoxia-ischemia (H-I). We tested the hypothesis that damage to astrocytes and loss of glutamate transporters accompany striatal neurodegeneration after H-I. Newborn piglets were subjected to 30 minutes of hypoxia (arterial O2 saturation, 30%) and then 7 minutes of airway occlusion (O2 saturation, 5%), producing cardiac arrest, followed by cardiopulmonary resuscitation. Piglets recovered for 24, 48, or 96 hours. At 24 hours, 66% of putaminal neurons were injured, without differing significantly thereafter, but neuronal densities were reduced progressively (21-44%). By DNA nick-end labeling, the number of dying putaminal cells per square millimeter was increased maximally at 24 to 48 hours. Glial fibrillary acidic protein-positive cell body densities were reduced 48 to 55% at 24 to 48 hours but then recovered by 96 hours. Early postischemia, subsets of astrocytes had fragmented DNA; later postischemia, subsets of astrocytes proliferated. By immunocytochemistry, glutamate transporter 1 (GLT1) was lost after ischemia in the astroglial compartment but gained in cells appearing as neurons, whereas neuronal excitatory amino acid carrier 1 (EAAC1) dissipated. By immunoblotting, GLT1 and EAAC1 levels were 85% and 45% of control, respectively, at 24 hours of recovery. Thus, astroglial and neuronal injury occurs rapidly in H-I newborn striatum, with early gliodegeneration and glutamate transporter abnormalities possibly contributing to neurodegeneration.

ATP-Binding Cassette Transporters↗
PubMed1996

Clinical trials of riluzole in patients with ALS. ALS/Riluzole Study Group-II.

Two double-blinded, placebo-controlled clinical trials of riluzole have now been carried out in more than 1,100 patients with ALS. The results of both studies show a modest benefit in prolonging survival that is statistically significant. These results led to the availability of this drug by the Food and Drug Administration for use in the United States beginning in early 1996. This is the first drug that has been available for ALS. It begins a new era in both basic and clinical research in an attempt to find a cure for this disease.

Adult↗
PubMed1996

A check of cheeks.

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Burns, Chemical↗
PubMed1996

A taste of tongues.

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Diagnosis, Differential↗
PubMed1995

A look at lips.

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Biopsy↗
PubMed1993

Ambulatory tonsillectomy and adenoidectomy: complications and associated factors.

This is a case-control study of over 500 cases of tonsillectomy and adenotonsillectomy performed at the Montreal Children's Hospital over a 10-month period. Demographics of patient population and selection criteria for out-patient procedure are presented. The hot (cautery) and cold (knife) dissection techniques are compared. Complications including intraoperative and postoperative hemorrhage are presented. The recognition of aerodigestive tract complications necessitating re-admission or emergency room management cannot be over emphasized. Recent history of upper airway infection (UAI) was noted to be associated with postoperative aerodigestive tract complications. The triad of UAI, knife dissection technique and increased intraoperative bleeding was found to be associated clinically and statistically with primary postoperative hemorrhage.

Adenoidectomy↗
PubMed1992

Coronary artery disease: metabolic risk factors and latent disease in individuals with paraplegia.

Individuals with spinal cord injury (SCI) currently have a longer life span as a result of recent improvements in medical care. As in the able-bodied population, cardiovascular disease is the leading cause of death in persons with SCI, but it appears to occur at younger ages in those with SCI than in the able-bodied population. The reduction in level of activity and adverse changes in body composition caused by SCI have profound metabolic consequences that may influence the progression and severity of coronary artery disease. Metabolic sequelae of SCI include disorders of carbohydrate and lipid metabolism. Almost half of the 45 active, healthy subjects with paraplegia we studied have a disorder of carbohydrate tolerance, 1 in 5 subjects having a diabetic oral glucose tolerance test. Hyperinsulinemia is found in those with abnormal glucose tolerance. Subjects with paraplegia having impaired glucose tolerance or diabetes mellitus are significantly older than those with normal glucose tolerance. High-density lipoprotein cholesterol is markedly depressed, and low density lipoprotein is relatively elevated. Radionuclide myocardial perfusion imaging after upper body ergometry exercise reveals latent coronary artery disease in 12 of 19 subjects with paraplegia.

Adult↗
PubMed1986

Electronic reanimation of facial paralysis--a feasibility study.

We set out to adapt the concept of functional electrical stimulation to the reanimation of the paralyzed face. In the New Zealand white rabbit model we studied the strength-duration curves of both innervated and denervated facial muscles. We next studied the electromyographic signals corresponding to different strengths of contraction of innervated facial muscles. With Teflon-coated stainless steel electrodes implanted at opposite ends of the denervated muscle groups under study, bipolar stimulation yielded useful mimetic function that was modifiable by varying the voltage output and the rate of pulse generation. We demonstrated that an electronic circuit can indeed respond to the voltage generated within a functioning facial muscle, and then reproducibly trigger a corresponding graphic signal in synchrony with the mimetic function. The next step will be to adapt an electronic circuit that will deliver a predetermined electrical current to a denervated facial muscle in response to a determined generated voltage in the contralateral corresponding innervated facial muscle.

Action Potentials↗
PubMed1984

Relationship of optic neuritis to disease of the paranasal sinuses.

The relationship of paranasal sinusitis to optic neuritis remains an intriguing curiosity to both the otolaryngologist and the ophthalmologist. The literature is replete with anecdotal case reports of patients whose sinusitis appears to have caused optic neuritis. There is much speculation about the pathophysiological mechanisms which relate these two distinct disease entities. Five new cases are described which highlight distinct pathophysiologic routes through which paranasal sinus disease has caused optic neuritis. These include compressive optic neuropathy secondary to mucoceles and/or pyoceles; direct extension of sinus infection to the optic nerve from suppurative paranasal sinusitis; and, in one case, from osteomyelitis of the ethmoid and sphenoid sinuses. The usefulness of computerized axial tomography of the orbits and paranasal sinuses to evaluate optic neuritis and to elucidate in detail the pathophysiology of its relationship to disease of the paranasal sinuses is emphasized. Currently, optic neuritis is felt to be a rare complication of paranasal sinusitis. Paranasal sinus surgery is advocated in those cases where sinus suppuration is suspected, or when a compressive optic neuropathy is caused by a sinus mucocele or pyocele. Since in most cases, however, optic neuritis is self-limited, it is difficult to evaluate the results of surgery in circumstances other than those mentioned already. Continued careful evaluation, management, and documentation of this group of patients is necessary to help better define the relationship between these two disease entities.

Adult↗