Some new thoughts on feline stomatitis/gingivitis complex.
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Animals↗
Biomedical subjects
G Goldstein
Publications and source records attributed to G Goldstein.
Myasthenic sera recognize the human acetylcholine receptor bound to thymopoietin.
The thymic hormone, thymopoietin (Tpo), from human (HTpo), bovine (BTpo) and from synthetic (sHTpo) origins bound to the acetylcholine receptor (AChR) solubilized by Triton 1.5% from human muscle. This binding was demonstrated either by inhibition of formation of radiolabeled alpha bungarotoxin (alpha Bgt)-AChR complexes measured after precipitation by ammonium sulfate or by a myasthenic serum containing a high concentration of anti-AChR antibodies, or directly by incubating the human AChR with radiolabeled sHTpo or BTpo. The 125I-labeled alpha Bgt-AChR complexes were totally inhibited by 10(-6) M sHTpo or BTpo. The complexes formed by AChR and the radiolabeled Tpo were recognized specifically by sera containing anti-AChR antibodies from myasthenic patients. The active pentapeptide derivative of Tpo, thymopentin, another thymic hormone, thymulin, as well as bovine insulin did not interfere with the specific binding of alpha Bgt to human AChR. Tpo and anti-AChR antibodies could participate together in the inhibition of neuromuscular conduction with Tpo modulating the depressive effect of the antibodies on the neuromuscular junction in myasthenia gravis.
Autoantibodies↗
In vitro effects of thymopentin on the gamma-interferon production by peripheral blood mononuclear cells from normal subjects and from patients with rheumatoid arthritis.
The in vitro production of gamma-interferon (gamma-IFN) by peripheral blood mononuclear cells (MNC) was measured using a specific radioimmunoassay in 16 patients presenting with active rheumatoid arthritis (RA), in 14 patients with inactive disease, and in 36 control subjects (CS). Unstimulated cultures produced undetectable levels of gamma-IFN and did not incorporate tritiated thymidine. In response to phytohemagglutinin (PHA) 0.2 microgram/ml, MNC from active RA produced 9 times less, and under PHA 2.5 micrograms/ml, 4 times less gamma-IFN than did MNC from inactive RA or from CS. The uptake of tritiated thymidine was, however, similar in the 3 groups. In unstimulated cultures of the 3 groups, thymopentin (TP-5), at all concentrations tested, did not influence either the levels of gamma-IFN or the uptake of tritiated thymidine. In the presence of PHA 0.2 microgram/ml and TP-5, lambda-IFN levels were increased in CS, unchanged in inactive RA and reduced in active RA, whereas no changes were observed in the uptake of tritiated thymidine. Our results show that under our experimental conditions, TP-5 was able to increase the levels of gamma-IFN produced by normal MNC in vitro, but could not reverse the profound defect observed in active RA.
Adult↗
OKT3 monoclonal antibody reversal of renal and hepatic rejection in pediatric patients.
The monoclonal antibody OKT3 was previously shown to be superior to conventional high-dose steroid therapy for reversal of acute rejection of renal allografts. Furthermore, OKT3 was effective in reversing acute renal or hepatic allograft rejection that was resistant to treatment with steroids, anti-thymocyte globulin, or both. Our analysis demonstrates that OKT3 is also effective in pediatric patients in reversing acute rejection of renal allografts (rescue treatment) or hepatic allografts (primary or rescue treatment).
Adolescent↗
OKT3 monoclonal antibody in pediatric kidney transplant recipients with recurrent and resistant allograft rejection.
Twelve pediatric patients, aged 28 months to 17 years, received OKT3 to reverse renal allograft rejection. In 11 patients, the rejection crisis was resistant to conventional antirejection therapy with high doses of prednisone or polyclonal antithymocyte globulin. Reversal of rejection was successful in 10 patients who completed a treatment course. Because of recurring resistant rejection, five patients received a second course of OKT3, which was successful in reversing the rejection crisis in two. Among these patients, the persistence or the appearance of high levels of circulating T3 lymphocytes after initiating the second treatment course correlated with treatment failure. The immediate side effects associated with OKT3 therapy were transient and medically manageable. We conclude that this monoclonal antibody preparation is a safe and effective treatment for pediatric renal allograft in recipients experiencing rejection crisis resistant to conventional therapy. However, the potential impact of this immunosuppressive medication on long-term renal allograft survival in this patient population remains to be determined.
Adolescent↗
Diagnostic accuracy of the Halstead-Reitan and Luria-Nebraska Neuropsychological Batteries: performance of clinical raters.
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Adult↗
Calcium-dependent effect of the thymic polypeptide thymopoietin on the desensitization of the nicotinic acetylcholine receptor.
The effects of the thymic polypeptide thymopoietin (Tpo) on the properties of the nicotinic acetylcholine receptor (AcChoR) were investigated by patch clamp techniques on mouse C2 myotubes and by biochemical assays on AcChoR-rich membrane fragments purified from the Torpedo marmorata electric organ. At high concentrations (greater than 100 nM), Tpo inhibits the binding of cholinergic agonists to the AcChoR in a Ca2+-insensitive manner. At lower concentrations (2 nM), Tpo applied on C2 myotubes simultaneously with nondesensitizing concentrations of acetylcholine results in the appearance of long closed times separating groups of openings. This effect depends on the presence of Ca2+ in the external medium. Outside-out recordings, performed with various concentrations of EGTA in the intracellular medium, suggest that Ca2+ acts on the cytoplasmic face of the membrane after entry through acetylcholine-activated channels. Parallel studies with T. marmorata AcChoR-rich membranes show that in the presence of Ca2+ Tpo causes a decrease in the apparent equilibrium dissociation constant of the noncompetitive blocker [3H]phencyclidine, enhances, at low concentrations, the binding of [3H]acetylcholine, and also alters the binding kinetics of the fluorescent agonist 6-(5-dimethylamino-1-naphthalenesulfonamido)-n-hexanoic acid beta-(N-trimethylammonium bromide) ethyl ester to the AcChoR. It was concluded that, in the presence of Ca2+, Tpo displaces the conformational equilibrium of the AcChoR towards a high-affinity desensitized state and increases the transition rate towards the same state.
Acetylcholine↗
Isolation and complete amino acid sequence of human thymopoietin and splenin.
Human thymopoietin and splenin were isolated from human thymus and spleen, respectively, by monitoring tissue fractionation with a bovine thymopoietin RIA cross-reactive with human thymopoietin and splenin. Bovine thymopoietin and splenin are 49-amino acid polypeptides that differ by only 2 amino acids at positions 34 and 43; the change at position 34 in the active-site region changes the receptor specificities and biological activities. The complete amino acid sequences of purified human thymopoietin and splenin were determined and shown to be 48-amino acid polypeptides differing at four positions. Ten amino acids, constant within each species for thymopoietin and splenin, differ between the human and bovine polypeptides. The pentapeptide active site of thymopoietin (residues 32-36) is constant between the human and bovine thymopoietins, but position 34 in the active site of splenin has changed from glutamic acid in bovine splenin to alanine in human splenin, accounting for the biological activity of the human but not the bovine splenin on the human T-cell line MOLT-4.
Amino Acid Sequence↗
Flow cytometric resonance energy transfer measurements support the association of a 95-kDa peptide termed T27 with the 55-kDa Tac peptide.
Two monoclonal antibodies (OKT27 and OKT27b) have been produced that react with distinct epitopes of a 95-kDa peptide. The T27 antigen is widely distributed, being expressed on B lymphocytes, monocytes, and adult T-leukemic cells but not on polymorphonuclear leukocytes or platelets. There was a low level of T27 expression on resting T cells that increased on T-cell activation. In preliminary studies, the OKT27b antibody coprecipitated a 55-kDa peptide, as well as the 95-kDa peptide, from the radiolabeled cells of the HuT 102B2 cell line. Preclearance with anti-Tac, a monoclonal antibody to the 55-kDa peptide of the multichain interleukin 2 receptor, removed the 55-kDa but not the 95-kDa peptide from subsequent OKT27b immunoprecipitates of HuT 102B2 extracts, suggesting the possibility that the T27 peptide was associated with the Tac peptide. However, the precipitation of the p55 Tac peptide by OKT27b was quite inconsistent. Thus, additional information was sought using a flow cytometric energy transfer technique to provide a physical estimation of the proximity between the Tac and the T27 peptides. The flow cytometric version of the fluorescence resonance energy transfer technique permits the determination of inter- and intramolecular distances at 2- to 10-nm levels on a cell-by-cell basis. Using this approach, there was a mean energy transfer of 7.3% with HuT 102B2 cells when fluorescein isothiocyanate anti-Tac served as the donor and tetramethylrhodamine isothiocyanate OKT27 served as the acceptor. In contrast, there was no energy transfer in comparable studies observed when fluorescein anti-Tac and rhodamine anti-transferrin receptor antibodies were used. These observations support the conclusion that there is a close nonrandom proximity in HuT 102B2 cells between the 95-kDa peptide identified by the OKT27 monoclonal antibody and the p55 Tac peptide of the multichain interleukin 2 receptor.
Antibodies, Monoclonal↗
Adjunctive hyperbaric oxygen therapy in the treatment of chronic refractory osteomyelitis.
Twenty-eight consecutive patients with chronic refractory osteomyelitis uncomplicated by persistent fracture nonunion, septic arthritis, total joint arthroplasty, or major systemic disease (immune deficiency, malignancy, malnutrition, renal or hepatic failure) were treated from January 1980 through December 1985 to evaluate the potential benefits of hyperbaric oxygen (HBO) therapy. Patients were classified by a staging system taking into account: the bone involved; subchondral, periarticular bone involvement; extent of bone involvement; quality of soft-tissue envelope and vascular supply; and general health status of the patient. Using this staging system patients were assigned to either hyperbaric oxygen therapy or control status after their initial debridement. Hyperbaric oxygen therapy on a 100% oxygen, 2 atmospheres pressure, 2-hour duration, one dive per day, six dives per week regimen was utilized in 14 of the 28 patients. Hyperbaric oxygen had no effect on length of hospitalization, rapidity of wound repair, initial clinical outcome, or recurrence of infection noted to date.
Adolescent↗
Monoclonal antibody specificity: Orthoclone OKT3 T-cell blocker.
Orthoclone OKT3, a murine monoclonal antibody of the IgG2a class, was initially developed as a pan-T cell monoclonal antibody for use as a marker to differentiate between cell subsets. Only later did its potential role in treating allograft rejection become apparent. At first, its mechanism of action in such cases was not understood. Subsequent investigations demonstrated that OKT3 not only removed all T cells, but also specifically interacted with the T3 antigen recognition complex found on late thymocytes and mature T cells, consequently blocking the immunologic function of these cells. When injected into a patient, OKT3 can act in three ways to reverse allograft rejection. It initially coats, or opsonizes, the circulating T cells, which are then removed by the reticuloendothelial cells in the liver and spleen. OKT3 also modulates the T3 antigen recognition complex of circulating T cells, producing cells with all their phenotypic characteristics, except for the T3 molecules and the antigen recognition complex. The key mechanism of action of OKT3 in treating allograft rejection may be its ability to block the killer function of sessile T cells. In contrast to polyclonal antiserums, each molecule of OKT3 monoclonal antibody is virtually identical and has an identical specificity, thereby producing consistent reactivity to human T cells with a defined and relatively low degree of toxicity. Although derived from a hybridoma and grown in mouse ascites, OKT3 undergoes numerous purification steps to ensure that the final product is sterile, biochemically pure, homogeneous IgG2a. Furthermore, each batch is checked to make sure that its functional activity is the same as the standard.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗
Comparison of antimouse and antihorse antibody production during the treatment of allograft rejection with OKT3 or antithymocyte globulin.
Antimouse antibody is produced from 40 to 68% of the time after administration of Orthoclone OKT3. In patients treated with OKT3, however, if the concomitant immunosuppression is not decreased, the incidence of the antibody production is reduced to 40%. Similarly, 33% of patients developed antihorse antibody after the initial antithymocyte globulin (ATG) administration. Most of the time, the antibody production is low-titered for both OKT3 and ATG.
Animals↗
Survivors of imprisonment in the Pacific theater during World War II.
Data were obtained from 41 survivors of imprisonment by the Japanese during World War II. Interview data suggested that these individuals, despite the 40 years that had passed since their prisoner of war experiences, showed manifestations of posttraumatic stress disorder, notably a sleep disturbance marked by recurrent nightmares. MMPI data suggested significant pathology, characterized as an anxiety state, in this group. Half of the subjects met the full set of DSM-III criteria for posttraumatic stress disorder.
Acting Out↗
Spotting heart disease: Leopard syndrome.
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Cardiomyopathy, Hypertrophic↗
Comparisons of the cognitive functioning of familial and nonfamilial alcoholics.
Alcoholic men (N = 81) participating in a Veterans Administration inpatient program were classified using four different strategies to describe the extent of familial alcoholism. These classification schemes included: (1) a comparison of alcoholics with no familial alcoholism, parental alcoholism or alcoholism in other relatives, (2) a unilineal-bilineal approach, (3) a multigenerational approach and (4) an approach that quantified the degree of familial alcoholism. Comparisons were made of the performance of the different familial history groups on a series of neuropsychological tests. No differences in cognitive functioning were found using any of the four classification schemes.
Alcoholism↗
Thymopoietin and thymopentin enhance the levels of ACTH, beta-endorphin and beta-lipotropin from rat pituitary cells in vitro.
Thymopoietin and thymopentin are well characterized polypeptides influencing immunoregulation by several mechanisms. Proposed as a therapy in diseases with major immune abnormalities such as rheumatoid arthritis, thymopentin improved within 2 weeks some clinical parameters as pain and joint swelling. The hypothesis that this spectacular effect could be mediated through interactions with anti-inflammatory (ACTH) and pain relieving (beta-endorphin) hormones producing cells was tested on the rat isolated pituitary cell model. Thymopentin and thymopoietin can enhance in vitro the levels of ACTH, beta-endorphin and beta-lipotropin in a time- and dose-dependent fashion for physiological concentrations ranging from 10(-12) to 10(-8) mol/l. The action on pituitary cells was restricted to those molecules as no changes occurred in LH, FSH, GH, TSH and PRL levels, after otherwise identical experimental conditions.
Adrenocorticotropic Hormone↗
Costs of illness, 1980: a comparison of hospital costs in New South Wales and the United States.
Cost of illness studies are an important component of cost-benefit analysis and a useful tool in health policy analysis. In this study an attempt is made to emulate major US cost of illness studies in NSW, for hospital costs only, and to compare the NSW results to the US. In NSW circulatory diseases are the greatest single disease category by a considerable margin ($230 million), with injury the next highest category ($139 million) and then digestive disorders, mental disorders and neoplasm ranking almost equal third (around $110 million each). In both the US and NSW the top 5 ranking categories in per capita expenditure are circulatory diseases, injury, digestive disorders, mental disorders and neoplasm. Per capita costs are greater in the US. In NSW a higher proportion of hospital costs is expended on patients over the age of 65 years in comparison to the US.
Bed Occupancy↗
Classification with the Luria-Nebraska neuropsychological battery: an application of cluster and ipsative profile analysis.
A sample of 114 subjects, 23 with predominantly left hemisphere brain damage, 25 with predominantly right hemisphere brain damage, 26 with diffuse brain damage, and 40 with adult learning disability were administered the Luria-Nebraska Neuropsychological Battery (LNNB). The clinical scale data were cluster analyzed and subjected to an ipsative analysis of the cluster profiles. A four cluster solution was utilized. It was found that while stable clusters were produced, they were relatively unrelated to actual diagnoses. The first cluster had a normal mean profile, the second reflected specific language impairment, the third, nonverbal skill, memory, and intellectual impairment and the fourth, generalized impairment. The results were discussed in terms of the capacity of the LNNB to generate meaningful neuropsychological profiles.
Journal Article↗