Showing papers by "University of Medicine and Dentistry of New Jersey published in 1989"
TL;DR: MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP.
Abstract: The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine.
504 citations
Patent•
17 Aug 1989TL;DR: In this article, a functional biocompatible intervertebral disc spacer is described, which is useful for a replacement for a degenerated disc in certain treatments of back pain and spinal disease.
Abstract: The construction and manufacturing technique for a functional biocompatible intervertebral disc spacer is described. This device is useful for a replacement for a degenerated disc in certain treatments of back pain and spinal disease. The disc spacer possesses mechanical properties akin to those of the normal disc and will preserve normal functions of the spinal motion segment. The device achieves the desired properties by varying the hardness of the elastomeric material in its nucleus and annulus.
494 citations
TL;DR: Since the initial discoveries of the avian and rat intestinal calbindin, calbindins have been reported in a variety of species and in many other tissues including kidney, bone, and tissues which are not regulators of serum calcium such as pancreas, placenta, and organs not regulated by serum calcium.
Abstract: I. Forward One of the most important contributions to the vitamin D field has been the discovery by Wasserman and Taylor in 1966 (1) of vitamin D-dependent calcium binding protein [calbindin-D (2)]. Early studies using competitive ion exchange methods as well as equilibrium dialysis indicated that administration of vitamin D to rachitic chicks resulted in an increase in the calcium binding activity of crude extracts of intestinal mucosa (1). Further investigations showed that the calcium binding activity was associated with a protein of about 28,000 mol wt (3, 4). Soon after the discovery of avian intestinal calbindin (1), a vitamin D-responsive calcium binding protein was also shown to be present in rat intestine (5, 6). Since the initial discoveries of the avian and rat intestinal calbindins, calbindins have been reported in a variety of species (7–19) and in many other tissues including kidney (20–25), bone (26), and tissues which are not regulators of serum calcium such as pancreas (27–32), placenta (...
419 citations
TL;DR: In this article, an active-centre mutant of pro-subtilisin (Asp 32 → Asn) was constructed, which is not processed to active enzyme, unlike the wild-type prosubilisin, because intramolecular processing is prevented.
Abstract: SUBTILISIN E, an alkaline serine protease consisting of a single polypeptide chain of 275 amino acids is produced from a pre-pro-protein1. The pre-sequence functions as the signal peptide for protein secretion across the membrane2. Deletion of the pro-sequence yields mature but inactive subtilisin3: the 77-amino acid pro-sequence must precede the mature subtilisin to guide the latter into an active conformation. Pro-subtilisin denatured in 6 M guanidine-HCl can be self-processed to the active enzyme intramolecularly, with concomitant cleavage of the pro-sequence, when dialysed against renaturing buffer4. We have constructed an active-centre mutant of pro-subtilisin (Asp 32 → Asn)3 which is not processed to active enzyme, unlike the wild-type pro-subtilisin, because intramolecular processing is prevented4. Here we report an intermolecular pathway for the refolding of the inactive mature protein to an active enzyme in vitro with the aid of exogenously added pro-sequence. We establish conditions under which the mature inactive form, as well as acid-denatured subtilisins Carlsberg and BPN', can be renatured by the mutant pro-subtilisin.
335 citations
TL;DR: It is concluded that dephosphorylation of a key protein(s) is required to complete mitosis in Aspergillus nidulans and that the wild-type gene encodes a type 1 protein phosphatase.
301 citations
TL;DR: Interestingly TFIIF was absolutely required for the formation of a preinitiation complex; however, it also affected the elongation phase of the transcription cycle, and was required for efficient elongation.
297 citations
TL;DR: This work shows that the soluble cytoplasmic domain of the transmembrane modulator protein EnvZ is phosphorylated in vitro by [gamma-32P]-ATP and demonstrates that the phosphate group can, in turn, be transferred to the transcription activator protein OmpR.
Abstract: EnvZ and OmpR, the regulatory proteins for ompF and ompC expression in Escherichia coli, belong to a modulator-effector family of regulatory proteins which are essential for the response to environmental signals. We show that the soluble cytoplasmic domain of the transmembrane modulator protein EnvZ is phosphorylated in vitro by [gamma-32P]-ATP. We also demonstrate that the phosphate group can, in turn, be transferred to the transcription activator protein OmpR. The pH stability properties of the phosphate groups linked to EnvZ indicate that this molecule contains histidyl phosphate. The invariant His-243 of EnvZ corresponds to the phosphorylated His-48 of the chemotactic modulator protein CheA. Substitution of His-243 with valine produces an EnvZ that is refractory to phosphorylation and can no longer catalyze the transfer of phosphate to OmpR. Furthermore, in a delta envZ strain of E. coli, containing the envZ Val-243 plasmid, ompC expression is elevated 7-fold relative to that found in cells carrying the wild-type envZ plasmid. Based on these results we propose a model in which the phosphorylated state of OmpR modulates the expression of the ompF and ompC genes.
268 citations
TL;DR: The results indicate that high-strength collagen fibres can be reconstituted in vitro and that these fibres may be useful in repair of dermal, dental, cardiovascular and orthopaedic defects.
265 citations
TL;DR: The DNA structures of the ends of retroviral mutants defective in the integration (IN) function are examined and the results show that the formation of the recessed ends requires the presence of IN.
253 citations
TL;DR: The Beck Depression Inventory, Hopelessness scale, and Suicidal Intent scale and SIS Precautions subscale were used in multiple logistic regression analyses to predict the risk of eventually committing suicide and only a diagnosis of alcoholism predicted eventual suicide.
246 citations
TL;DR: It is demonstrated here that the dimerization of NS1 is associated with a change in hydrophobicity and sedimentability of this protein, which is consistent with NS1 becoming membrane-associated.
TL;DR: The Tar chemoreceptor of Escherichia coli is a membrane-bound sensory protein that facilitates bacterial chemotaxis in response to aspartate and the EnvZ molecule has a membrane topology similar to Tar and is a putative osmosensor that is required for osmoregulation of the genes for the major outer membrane porin proteins.
Abstract: The Tar chemoreceptor of Escherichia coli is a membrane-bound sensory protein that facilitates bacterial chemotaxis in response to aspartate. The EnvZ molecule has a membrane topology similar to Tar and is a putative osmosensor that is required for osmoregulation of the genes for the major outer membrane porin proteins, OmpF and OmpC. The cytoplasmic signaling domain of Tar was replaced with the carboxyl portion of EnvZ, and the resulting chimeric receptor activated transcription of the ompC gene in response to aspartate. The activation of ompC by the chimeric receptor was absolutely dependent on OmpR, a transcriptional activator for ompF and ompC.
Journal Article•
TL;DR: This study demonstrates the efficacy of mobile bearing elements for use in knee replacement arthroplasty and shows it is essential that flexion and extension gaps be controlled to maintain contact pressure on such bearings to avoid problems of subluxation or dislocation.
TL;DR: It is suggested that since the major function of CTL appears to be control of viruses, CTL may be able to halt viral replication without inducing rapid lysis, and it may be more useful to think of C TL as virus control cells rather than as cytolytic cells.
Patent•
13 Jan 1989TL;DR: In this article, the authors provide graft, prothesis, orthopaedic structures, implants and like body replacement parts which are constituted of synthetic collagen fibers, an embodiment of which is a tendon or a ligament prosthesis, graft or implants.
Abstract: The invention provides graft, prothesis, orthopaedic structures, implants and like body replacement parts which are constituted of synthetic collagen fibers, an embodiment of which is a tendon or a ligament prosthesis, graft or implants. These body parts have a combination of very useful properties, particularly high tensile strength combined with biocompatability.
TL;DR: It is concluded that a diagnostic approach to chronic dyspnea based on objective findings and verification, rather than clinical impression alone, will consistently lead to an accurate diagnosis and an improved therapeutic outcome.
Abstract: To test whether, in patients with chronic dyspnea, a diagnostic approach based on objective confirmation of suspected diagnoses would be superior to one based on clinical impression alone, we prospectively studied 85 patients with a primary complaint of dyspnea seen in a pulmonary subspecialty clinic. We achieved 100% success in determining the causes of dyspnea compared with only 66% accuracy based on clinical impression alone. Four groups of disorders, asthma, chronic obstructive pulmonary disease, interstitial lung diseases, and cardiomyopathy accounted for two thirds of the cases. Findings on the history and physical examination were too nonspecific to determine the specific diagnosis. Pulmonary function testing, including a methacholine bronchoprovocation challenge, were the most useful diagnostic tests, particularly for chronic obstructive pulmonary disease and asthma. Chest roentgenogram was most useful for interstitial lung disease, and comprehensive exercise testing for dyspnea due to psychogenic factors or deconditioning. Specific therapy was effective in reducing or eliminating dyspnea in the majority of cases. We conclude that a diagnostic approach to chronic dyspnea based on objective findings and verification, rather than clinical impression alone, will consistently lead to an accurate diagnosis and an improved therapeutic outcome.
TL;DR: This study highlights the need to understand more fully the rationale behind the continued use of Clozaril in the treatment of obsessive-compulsive disorder.
Abstract: John M. Kane 1, Gilbert Honigfeld 2, Jack Singer 2' 3, Herbert Meltzer 2' 4, and the Clozaril Collaborative Study Group* 1 Department of Psychiatry, Hillside Hospital, Division of Long Island Jewish Medical Center, Glen Oaks, NY 11004, USA and the Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY, USA 2 Sandoz Research Institute, Route 10, P.O. Box 11, East Hanover, NJ 07936, USA Department of Psychiatry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, USA 4 Department of Psychiatry, Case Western Reserve School of Medicine, 2040 Abington Road, Cleveland, OH 44106, USA
TL;DR: A brief but systematic assessment of functional status should be incorporated into the routine medical management of elderly patients, because of its demonstrated usefulness.
Abstract: A brief but systematic assessment of functional status should be incorporated into the routine medical management of elderly patients, because of its demonstrated usefulness.
TL;DR: It is demonstrated, for the first time, that the membrane FBP of cultured human KB cells contains a glycosyl-phosphatidylinositol (GPI) tail which is responsible for its hydrophobic properties and distinguishes it from the soluble FBP released into the medium.
TL;DR: The review describes the dramatic change in prevalence of the different laboratory methods for measuring serum sodium over the past decade, and emphasizes the need for clinicians to be familiar with the methods of their clinical laboratory in order to properly interpret a reported serum sodium determination.
TL;DR: The data suggest that multicopy micF inhibits OmpF synthesis primarily through translational inactivation of ompF mRNA and that a limiting factor in addition to micF RNA is necessary to destabilize oMPF mRNA.
TL;DR: The assembly of discontinuous fibril segments and bundles was studied in 14-day chicken embryo tendons by using serial sections, transmission electron microscopy, and computer-assisted image reconstruction, suggesting that the amino/carboxyl polarity of the fibrIL segment is reflected in its architecture.
Abstract: The assembly of discontinuous fibril segments and bundles was studied in 14-day chicken embryo tendons by using serial sections, transmission electron microscopy, and computer-assisted image reconstruction. Fibril segments were first found in extracytoplasmic channels, the sites of their polymerization; they also were found within fibril bundles. Single fibril segments were followed over their entire length in consecutive sections, and their lengths ranged from 7 to 15 microns. Structural differences in the ends of the fibril segments were identified, suggesting that the amino/carboxyl polarity of the fibril segment is reflected in its architecture. Our data indicate that fibril segments are precursors in collagen fibril formation, and we suggest that postdepositional fusion of fibril segments may be an important process in tendon development and growth.
TL;DR: Following the substitution of the nucleotide sequence, 126-504, from SVLM21 cDNA for the corresponding sequence of the Toto 1101 plasmid, the authors were able to generate recombinant Sindbis virus (SVMS-65a) with the LMR phenotype, and it is concluded that the RNA methyltransferase activity generated by SV is associated with nsP1.
TL;DR: A model in which nonuniform distribution of radioactivity in the tumor is taken into account is developed, and high-energy beta emitters, such as 90Y, are most effective in treating large tumors, whereas for small tumors, medium energy Beta emitters such as 67Cu are better suited.
Abstract: In the context of radioimmunotherapy of cancer, there is a need for continued improvement of dosimetry of radionuclides localized in tumors. Current methods assume uniform distribution of radionuclides in the tumor despite experimental evidence indicating nonuniformity. We have developed a model in which nonuniform distribution of radioactivity in the tumor is taken into account. Spherically symmetric radionuclide distributions, depending linearly and exponentially on the radial position, are considered. Dose rate profiles in the tumor are calculated for potentially useful beta-emitting radionuclides, including /sup 32/P, /sup 67/Cu, /sup 90/Y, /sup 111/Ag, /sup 131/I, and /sup 188/Re, and for /sup 193//sup m/Pt, an emitter of conversion electrons and low-energy Auger electrons. For the radionuclide distributions investigated, high-energy beta emitters, such as /sup 90/Y, are most effective in treating large tumors (diameter, dapprox. >1 cm), whereas for small tumors (dapprox.1 mm), medium energy beta emitters such as /sup 67/Cu are better suited. Very small tumors (d<1 mm), and micrometastases are best handled with low-energy electron emitters such as /sup 193//sup m/Pt.
TL;DR: The pharmacokinetics and bioavailability of low-dose methotrexate (MTX) (10 mg/m2) were evaluated in 41 subjects who had definite or classical rheumatoid arthritis as defined by the American Rheumatism Association criteria, indicating that at least within that time range serum and synovial fluid concentrations are approximately equal.
TL;DR: In this article, the role of monoamine oxidase B and the dopamine transport system in mediating the actions of MPTP has been investigated in a mouse model for Parkinson's disease.
Abstract: The discovery that a rather simple chemical substance can produce such a highly selective neuronal degeneration in the substantia nigra, the brain area most affected in Parkinson’s disease, has resulted in a vast amount of research with MPTP. We and others have hoped that by gaining an understanding of its mechanism of action, we might come closer to discovering the cause(s) of idiopathic Parkinson’s disease. Indeed, we have learned some fascinating things regarding the roles of monoamine oxidase B and the dopamine transport system in mediating the actions of MPTP. It is clear that the MPTP-treated mouse is a good model for Parkinson’s disease. As such, it may help to define the role of dopamine deficiency in the pathophysiology of Parkinson’s disease as well as provide a model in which potential anti-Parkinsonian therapeutic agents can be tested.
Journal Article•
TL;DR: Weight gain during pregnancy and pregnancy outcome in a cohort of 1790 teenage gravidas from Camden, New Jersey is studied to suggest that supplementation, intervention, or prenatal care protocols for adolescents that do not focus on balanced weight gain during adolescence may reduce preterm delivery but may not significantly affect the incidence of intrauterine growth retardation.
TL;DR: Genetic analysis indicated that the major histocompatibility complex (H-2), C5 hemolytic complement (Hc), Newcastle disease virus-induced interferon (IF-1), and athymic (nu/nu) loci were involved in regulating susceptibility to pristane-induce arthritis.
Abstract: Pristane was injected intraperitoneally into mice of several strains, inducing an inflammatory seropositive arthritis in susceptible strains. The evolving histologic features included synovial hyperplasia, periostitis, and progressive marginal erosions. Multiple serologic immune abnormalities, including rheumatoid factor and anticollagen antibodies, also developed. Genetic analysis indicated that the major histocompatibility complex (H-2), C5 hemolytic complement (Hc), Newcastle disease virus-induced interferon (IF-1), and athymic (nu/nu) loci were involved in regulating susceptibility to pristane-induce arthritis. This experimental murine disease may provide a novel model of rheumatoid arthritis.
TL;DR: Eight mouse strains were identified that have complement levels comparable to those of other mammals, and recombinant strains derived from them will be useful in a wide range of biomedical research.
TL;DR: Examination of the effects of ethanol on the proliferation of cells in the two cortical germinal zones, the ventricular and subventricular zones found ethanol reduces the numbers of neurons generated between gestational day (G) 12 and G19 but paradoxically increases neuronogenesis after G19.
Abstract: Prenatal exposure to ethanol alters the generation of neocortical neurons; ethanol reduces the numbers of neurons generated between gestational day (G) 12 and G19 but paradoxically increases neuronogenesis after G19. The present study used [3H]thymidine autoradiography to examine the effects of ethanol on the proliferation of cells in the two cortical germinal zones, the ventricular and subventricular zones. Pregnant rats were fed one of three diets: a liquid ethanol-containing (6.7% v/v) diet (Et), a nutritionally matched isocaloric liquid diet (Ct), or chow and water (Ch). Fetuses were administered with [3H]thymidine on G13, G17, or G20 and killed 45–60 minutes later. Autoradiographs were prepared to identify radiolabeled and mitotic cells. Additional brains from 13–23-day-old fetuses were processed for cytoarchitectonic analyses.
The size of the lateral ventricles in the fetuses was not significantly affected by the prenatal exposure. Both the ventricular and subventricular zones were evident throughout the period from G13 to G23. In all three groups, the ventricular zone was thickest from G13 to G17, but from G15 on, the ventricular zone of Et-treated fetuses was significantly thinner than those of either controls. On G13, G17, and G20, the labeling index (the ratio of radiolabeled cells to the total population) was significantly less in Et-treated fetuses. The mitotic index was similar in Et-, Ch-, and Ct-treated fetuses. The subventricular zone of all fetuses was most prominent during later fetal ages and it was thicker in Et-treated fetuses than in controls. Moreover, the labeling and mitotic indices for the subventricular zone of Et-treated rats were significantly greater than for controls.
Thus, ethanol had different effects on the two neocortical germinal zones: the proliferation of ventricular cells was inhibited, whereas the proliferation of subventricular cells was stimulated. These data suggest that ethanol-induced changes in neuronogenesis result from alterations in proliferative activity.