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Biomedical subjects

S Gleason

Publications and source records attributed to S Gleason.

14 recordsLinked to original sources
PubMed2004

Markedly elevated GAD antibodies in SPS: effects of age and illness duration.

Five hundred seventy-six patients with suspected stiff-person syndrome (SPS) underwent immunocytochemistry (ICC). Of these, 286 underwent radioimmunoassay (RIA) for glutamic acid decarboxylase (GAD) antibodies; 116 were GAD antibody positive by one or both tests. Ninety-six percent of those positive by ICC had RIA values several standard deviations above normal. RIA did not correlate with age or illness duration. Marked elevations of RIA for GAD antibodies were characteristic of ICC-confirmed SPS, and modest elevations were not.

Age Factors↗
PubMed2004

The Resource Mothers Study of Maternal Phenylketonuria: preliminary findings.

Women with phenylketonuria (PKU) must follow a strict low-phenylalanine diet during pregnancy in order to protect the fetus from the deleterious effects of high maternal blood phenylalanine. The Resource Mothers Study of Maternal PKU was undertaken to determine whether a home visitation programme was effective in helping women with PKU attain blood phenylalanine control earlier during pregnancy. Resource Mothers were trained to provide social support and practical assistance to women with PKU during pregnancy. Eight metabolic clinics in the United States participated in the study. Women with PKU who were planning pregnancy or already pregnant were enrolled in the study and were treated with a low-phenylalanine diet aimed at controlling blood phenylalanine to 120-360 micromol/L. They were randomly assigned to receive the services of a Resource Mother (RM group) or to a control group. Fifty women were enrolled, and accounted for 44 pregnancies which resulted in 28 live births, and 6 spontaneous abortions. Ten women are currently pregnant and another 6 have not become pregnant. Fifty-six percent of enrolled women began the diet prior to becoming pregnant. Fifty-three percent of women in the Resource Mother group were in metabolic control by 10 weeks gestation as compared to 39% in the control group. In addition, women who began diet after pregnancy and had a Resource Mother attained metabolic control earlier (mean gestational age of 22.4 weeks in the RM group vs 29.8 weeks in the control group). There was no difference in birth measurement z -scores of offspring born to women in the RM group compared to controls. All but 4 women rated themselves as feeling worse about the diet at the end of pregnancy than at the beginning, and few women in either group remained on diet after delivery.

Female↗
PubMed2001

Autoimmunity to beta IV spectrin in paraneoplastic lower motor neuron syndrome.

Paraneoplastic neurological disorders may result from autoimmunity directed against antigens shared by the affected neurons and the associated cancer cells. We have recently reported the case of a woman with breast cancer and paraneoplastic lower motor neuron syndrome whose serum contained autoantibodies directed against axon initial segments and nodes of Ranvier of myelinated axons, including the axons of motoneurons. Here, we show that major targets of the autoantibodies of this patient are betaIVSigma1 spectrin and betaIV spectrin 140, two isoforms of the novel betaIV spectrin gene, as well as a neuronal surface epitope yet to be identified. Partial improvement of the neurological symptoms following cancer removal was associated with a drastic reduction in the titer of the autoantibodies against betaIV spectrin and nodal antigens in general, consistent with the autoimmune pathogenesis of the paraneoplastic lower motor neuron syndrome. The identification of betaIV spectrin isoforms and surface nodal antigens as novel autoimmune targets in lower motor neuron syndrome provide new insights into the pathogenesis of this severe neurological disease.

Autoantibodies↗
PubMed2001

Potential influence of acute CT on inpatient costs in patients with ischemic stroke.

RATIONALE AND OBJECTIVES: Patients presenting with ischemic brain symptoms have widely variable outcomes dependent to some degree on the pathologic basis of their stroke syndrome. The purpose of this study was to determine the cost implications of the emergency use of a computed tomographic (CT) protocol comprising unenhanced CT, head and neck CT angiography, and whole-brain CT perfusion. MATERIALS AND METHODS: By using a retrospective patient database from a tertiary care facility and publicly available cost data, the authors derived the potential savings from the use of CT angiography. CT perfusion, or both at hospital arrival by means of a cost model. The cost of the CT angiography-CT perfusion protocol was determined from Medicare reimbursement rates and compared with that of traditional imaging protocols. Cost savings were estimated as a decrease in the length of stay for most stroke patients, whereas the most benign (lacunar) strokes were assumed to be managed in a non-acute setting. Misdiagnosis cost (erroneously not admitting a patient with nonlacunar stroke) was calculated as the cost of a severe complication. Sensitivity testing included varying the percentage of misdiagnosed patients and admitting patients with lacunar stroke. RESULTS: The nationwide net savings that would result from the adoption of the CT angiography-CT perfusion protocol are in the $1.2 billion range (-$154 million to $2.1 billion) when patients with lacunar strokes are treated nonacutely and $1.8 billion when those patients are admitted for acute care. CONCLUSION: The results demonstrate the potential effect of implementing a CT angiography-CT perfusion protocol. In particular, prompt CT angiography-CT perfusion imaging could have an effect on the cost of acute care in the treatment of stroke.

Cerebral Angiography↗
PubMed2001

Cost-effectiveness of colorectal cancer screening.

PURPOSE: To determine the most cost-effective colorectal cancer screening strategy costing less than $100,000 per life-year saved and to determine how available strategies compare with each other. MATERIALS AND METHODS: Standardized methods were used to calculate incremental cost-effectiveness ratios (ICERs) from published estimates of cost and effectiveness of colorectal cancer screening strategies, and the direction and magnitude of any effect on the ratio from parameter estimate adjustments based on literature values were estimated. RESULTS: Strategies in which double-contrast barium enema examination was performed emerged as optimal from all studies included. In average-risk individuals, screening with double-contrast barium enema examination every 3 years, or every 5 years with annual fecal occult blood testing, had an ICER of less than $55,600 per life-year saved. However, double-contrast barium enema examination screening every 3 years plus annual fecal occult blood testing had an ICER of more than $100,000 per life-year saved. Colonoscopic screening had an ICER of more than $100,000 per life-year saved, was dominated by other screening strategies, and offered less benefit than did double-contrast barium enema examination screening. CONCLUSION: Double-contrast barium enema examination can be a cost-effective component of colorectal cancer screening, but further modeling efforts are necessary.

Barium Sulfate↗
PubMed2001

Antibodies to SOX13 (ICA12) are associated with type 1 diabetes.

SOX13 is an islet cell autoantigen (ICA12), identified by antibody screening of an islet cDNA library, using sera from patients with Type 1 diabetes. We ascertained the frequency of antibody reactivity to SOX13 and compared it with other Type 1 diabetes autoantibody reactivities. Antibodies were measured by radioimmunoprecipitation (RIP) using (35) S labelled SOX13 expressed in rabbit reticulocyte lysate. Sera from 109 subjects with Type 1 diabetes, 29 with Type 2 diabetes, 144 with other autoimmune diseases and from 201 controls were tested for anti-SOX13, and results were compared with the frequency of antibodies to glutamic acid decarboxylase (anti-GAD), islet cell antigen 512 (anti-ICA512) and islet cell cytoplasm (ICA). Anti-SOX13 were detected in 20 (18.3%) of 109 subjects with Type 1 diabetes, and more frequently in adults than in children (29% vs 10%). Anti-SOX13 usually occurred with anti-GAD but rarely with anti-ICA512. Seven sera positive for anti-SOX13 did not react with either GAD, ICA512 or islet cell cytoplasm indicating that anti-SOX13 represented a distinct population of antibodies. Reactivity to SOX13 represents a further autoantibody response in adults with Type 1 diabetes and may provide a useful disease marker in subjects in whom other autoantibody tests are negative.

Adolescent↗
PubMed1998

The selective norepinephrine reuptake inhibitor, LY368975, reduces food consumption in animal models of feeding.

The compound, LY368975 ((R)-thionisoxetine) is a potent and selective inhibitor of the norepinephrine (NE) reuptake site. We evaluated the in vivo properties of LY368975 in various animal models. In mice, LY368975 prevented heart NE depletion by 6-hydroxydopamine with an ED50 of 1.22 mg/kg. In rats, orally administered LY368975 inhibited 3H-NE uptake into hypothalamic synaptosomes ex vivo with an ED50 of 2.5 mg/kg and 3H-tomoxetine binding to the NE transporter with an ED50 of 2.7 mg/kg. When rats were deprived of food for 18 hr, 10 mg/kg LY368975 was able to suppress food intake 1, 2 and 4 hr after reintroduction of the feed. In nonfasted rats trained to drink sweetened condensed milk, LY368975 produced a dose-dependent reduction in consumption with a 44% decrease at 3 mg/kg. At doses up to 10 mg/kg p.o., LY368975 produced no significant effects on locomotor activity suggesting the compound does not activate or sedate the animals at pharmacologically relevant doses. Therefore, LY368975 is an orally available and centrally active NE reuptake inhibitor that is capable of reducing food consumption in rodents. Compounds of this class may have use in the treatment of obesity and eating disorders.

Adrenergic Uptake Inhibitors↗
PubMed1982

A single domain of human prostatic acid phosphatase shows antibody-mediated restoration of catalytic activity.

By limited proteolysis with mouse submaxillaris protease, human prostatic acid phosphatase (EC 3.1.3.2) was cleaved into three fragments, Sp1, Sp2, and Sp3, which individually had no enzymatic activity. One of the fragments, Sp3, regained enzymatic activity after interaction with rabbit antibody to prostatic acid phosphatase. The Sp3 fragment was purified and characterized as to its molecular weight, amino acid composition, and carbohydrate content. The Sp3 fragment behaved like the parent molecule in L(+)-tartrate affinity and in trapping of a phosphoryl intermediate. The same Sp3 fragment also bears the most prominent antigenic determinants. This evidence suggest that Sp3 is the enzymatically active domain of prostatic acid phosphatase.

Acid Phosphatase↗
PubMed1982

Characterization of antigenic sites of human prostatic acid phosphatase.

Human prostatic acid phosphatase [PAP] is antigenically uniquely different from acid phosphatases of other tissue origins. Nevertheless, a small degree of antigenic cross-reactivity between PAP and other lysosomal acid phosphatase(s) [LAP] has been suspected. In order to resolve this question, we have adopted two approaches: one involving structural studies by peptide mapping, and the other involving topological mapping through the use of uniquely defined antibodies. Purified PAP was dissociated into subunits and was further cleaved by chemical and enzymological methods. The limited digestion of PAP by submaxillary protease yielded three fragments [Sp-1, 2, and 3]. One of the fragments, Sp-3 [Mr = 11,000-12,000], was shown to regain catalytic activity after interaction with anti-PAP antibodies. This along with other data suggested that the active site is localized in the Sp-3 fragment. These submaxillary protease fragments were also used in the antigenic studies. For the detailed antigenic mapping studies, we prepared 12 monoclonal anti-PAP antibodies. These monoclonal anti-PAP antibodies exhibited a remarkably specific binding to PAP, particularly to the Sp-1 fragment, without binding to other acid phosphatase preparations. We also prepared lysosomal acid phosphatase [LAP] and raised anti-LAP antibodies in rabbits. The anti-LAP antibodies were fractionated into subpopulations by the preparative isoelectric focusing method. Three anti-LAP antibody subpopulations [pI 5.2, 6.9, and 7.5] exhibited specific binding to LAP. However, two anti-LAP subpopulations [pI 5.3 and and 6.8] showed binding to the Sp-3 fragment, an active site fragment of PAP. Thus, the PAP molecule seems to consist of three domains, namely, Sp-1, Sp-3, and Sp-2. Sp-3, which is the active site domain, is an antigenically cross-reactive region. The Sp-1 domain represents an antigenically unique region of PAP, whereas none of the antibodies studied thus far bind to the Sp-2 fragment.

Acid Phosphatase↗