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Biomedical subjects

E Young

Publications and source records attributed to E Young.

At least 217 records · Page 12Linked to original sources

Thyroid autoantibody synthesis by cultures of thyroid and peripheral blood lymphocytes. I. Lymphocyte markers and response to pokeweed mitogen.

Thyroid lymphocytes from Graves' and Hashimoto patients have been investigated and compared with lymphocytes from the peripheral blood. Considerably more lymphocytes (20-30 X 10(6)/g) could be isolated from Hashimoto thyroids than from Graves' tissue (1-5 X 10(6)/g) but the cell suspensions extracted from Hashimoto and Graves' glands were similar in terms of cell surface markers and the ability to synthesize immunoglobulin. Thyroid lymphocytes contained a lower proportion of T cells (OKT3+ cells) and in some cases more B cells than the peripheral blood but the ratio of helper to suppressor T cells (OKT4+:OKT8+ cells) was similar to the values obtained for blood lymphocytes. Further, thyroid lymphocytes (unlike blood lymphocytes) synthesized relatively large amounts of microsomal and/or thyroglobulin antibody when cultured in medium only and these levels were significantly decreased by the addition of pokeweed mitogen. The results of this study provide further evidence for the role of the thyroid as a major site of thyroid autoantibody synthesis and emphasize the importance of characterizing the cells infiltrating the gland in autoimmune thyroid disease.

Adult↗

Asymmetric distribution of sites with high affinity for antithrombin III in rat skin heparin proteoglycans.

The distribution of sites with high affinity for antithrombin III in [35S]heparin proteoglycans from rat skin was studied by affinity chromatography of the intact proteoglycans (Mr congruent to 1 x 10(6)) and degradation products. Unfractionated proteoglycan and proteoglycan fractions with low affinity and high affinity separated on antithrombin III-agarose were treated with alkali, releasing heparin chains (Mr congruent to 1 x 10(5)). Each chain preparation was fractionated on antithrombin III-agarose into fractions with low affinity and high affinity. Unfractionated proteoglycan and proteoglycan fractions with low affinity and high affinity were incubated with rat serum at pH 6.0, which gave products of similar size to commercial heparins (Mr congruent to 1 x 10(4)) termed heparin fragments. Each fragment preparation was fractionated on antithrombin III-agarose, yielding fractions with no affinity, low affinity, and high affinity, 40% of the proteoglycan preparation had low affinity, containing 4% high affinity chains and 7% high affinity fragments. The high affinity proteoglycan fraction yielded 40% high affinity chains and 22% high affinity fragments. The data show that the distribution of binding sites with high affinity for antithrombin III in heparin proteoglycans is highly asymmetric. Therefore, the concept that polymer modification reactions occurring during heparin biosynthesis, which must be involved in the formation of high affinity binding sites, occur in a random way must be reappraised.

Animals↗

Sleep related breathing disorders in older men: a search for underlying mechanisms.

The incidence of sleep-related breathing disorders (SRBDs) associated with hemoglobin desaturation was determined by nocturnal polygraphic evaluations in 26 healthy men, aged 55-70 years. Sixteen subjects (62%) had abnormal rates of at least 12 episodes per hour of sleep: 8 had occlusive, and 8 had central apnea or hypopnea. During waking ten of 16 SRBD subjects and only one subject without SRBDs exhibited either an elevated nasopharyngeal airway resistance (n = 4) or a reduced ventilatory response to hypercapnia (n = 4) and/or hypoxia (n = 3). However, these abnormalities were not related to the type or severity of SRBDs, and 6 subjects with SRBDs demonstrated no respiratory defect. We conclude that SRBDs have a very high incidence in older males and are not usually secondary to pulmonary cardiac, neurological, or behavioral disorders. Additionally, we hypothesize that abnormalities in ventilatory control or upper airway resistance contribute to SRBDs, but depression of brain stem reticular formation activity during sleep plays a primary role in these disorders. Factors related to both aging and SRBDs are reviewed. These include reduced chemoreceptor responses, altered steroid hormone metabolism, and use and metabolism of hypnotic drugs and alcohol.

Aged↗

Leaf water potential, stomatal resistance, and photosynthetic response to water stress in peach seedlings.

Individual groups of peach (Prunus persica [L.] Batsch) seedlings stressed to -17, -26 and -36 bars recovered to control levels within 1, 3, and 4 days, respectively. Stomatal resistance was significantly correlated with both leaf water potential and net photosynthesis. In seedlings stressed to -52 bars, leaf water potential and stomatal resistance recovered sooner than net photosynthesis, despite recovery of 0(2) evolution at a rate similar to leaf water potential. Therefore, some nonstomatal factor other than reduction in photochemical activity must be responsible for the lag in recovery of CO(2) assimilation following irrigation.

Journal Article↗

Report on the presence of a toxic substance, dimethyl formamide, in sodium fluorescein used for fluorescein angiography.

The revelation that intravenous sodium fluorescein is not all that it might seem to be may be a significant finding in the light of the adverse reactions to fluorescein that have been previously reported. Analysis of commercially prepared intravenous sodium fluorescein by mass spectroscopy and nuclear magnetic resonance has indicated that an industrial solvent used in the manufacturing process has not been eliminated. Dimethyl formamide is an industrial solvent with a maximum acceptable exposure level of 10 parts per million for dermal contact. It has been found in quantities of 5000 parts per million in the fluorescein for intravenous use. This investigation was prompted by a significant increase in the adverse reactions in patients receiving intravenous fluorescein in the retinal photographic unit at the Manchester Royal Eye Hospital.

Dimethylformamide↗

Natural history of autoimmune thyroiditis.

One hundred and sixty-three asymptomatic people with thyroid antibodies or raised serum thyrotrophin (TSH) concentrations, or both, and 209 age-matched and sex-matched controls without either marker of thyroid disorder were followed up for four years to determine the natural history of autoimmune thyroiditis. Mildly raised TSH concentrations alone and the presence of thyroid antibodies alone did not significantly increase the risk of developing overt hypothyroidism during the four years compared with the controls. Overt hypothyroidism developed at the rate of 5% a year in women who initially had both raised TSH concentrations and thyroid antibodies. Prophylactic treatment with thyroxine may be justified in women found to have both markers of impending thyroid failure. The cost effectiveness of screening the adult population remains to be evaluated.

Adult↗

A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.

Four hundred thirty-eight subjects underwent an overnight dexamethasone suppression test (DST) to standardize the test for the diagnosis of melancholia (endogenous depression). Abnormal plasma cortisol concentrations within 24 hours after dexamethasone administration occurred almost exclusively in melancholic patients. The best plasma cortisol criterion concentration, above which a DST result may be considered abnormal, was 5 microgram/dL. The optimal dose of dexamethasone was 1 rather than 2 mg. Two blood samples obtained at 4 and 11 PM after dexamethasone administration detected 98% of the abnormal test results. This version of the DST identified melancholic patients with a sensitivity of 67% and a specificity of 96%. Baseline nocturnal plasma cortisol concentrations were not useful. Abnormal DST results were found with similar frequency among outpatients and inpatients with melancholia; but they were not related to age, sex, recent use of psychotropic drugs, or severity of depressive symptoms. Extensive evidence validates this practical test for the diagnosis of melancholia.

Adolescent↗

Opiate binding properties of naturally occurring N- and C-terminus modified beta-endorphins.

Beta-endorphin is further processed within the pituitary and brain by either N-terminal acetylation, carboxy-terminal proteolysis, or both. These naturally occurring analogues are stored intracellularly and, in some tissues, represent the majority of beta-endorphin immunoreactivity detected by antisera. It is therefore critical to determine their relative potencies at the opiate receptor. This study demonstrates that cleavage of the C-terminus tetrapeptide brings about a 10-fold decrease in opiate binding potency of either camel or human beta-endorphin. N-Acetylation, on the other hand, causes over a thousand fold loss in opiate potency rendering the peptide effectively inactive. Since unmodified beta-endorphin is approximately equipotent at multiple opiate receptors, we tested for possible differential shifts towards mu or delta-type receptors which may result from the modification. Our results show no change in selectivity, but simply an overall loss of potency.

Amino Acid Sequence↗

Antenatal diagnosis of Niemann-Pick disease in a twin pregnancy.

An Ashkenazi Jewish woman had a child with Niemann-Pick disease in her first marriage. She subsequently remarried a man who was also heterozygous for the condition and conceived twins. Prenatal diagnostic tests were performed and one twin was shown to be homozygous and the other heterozygous for Niemann-Pick disease. The problems of prenatal diagnosis and counselling in twin pregnancies are discussed.

Diseases in Twins↗

An evaluation of a whole-blood platelet counter.

The performance of the platelet count in the hematology laboratory remains a laborious, time-consuming technic requiring separation of platelet-rich plasma, correction for leukocyte counts, lysis of erythrocytes, etc. The availability of an instrument that would count platelets in whole blood would appear to be a distinct advantage. One such instrument has been recently evaluated. The Ultra-Flo 100 Whole Blood Platelet Counter was found to be a reliable instrument for performing platelet counts on microspecimens of untreated whole blood. Counts were both accurate and precise, with no carry-over from specimen to specimen. The major advantage of the system is the speed with which platelet counts may be performed (25 sec) and results produced, a distinct advantage in those laboratories serving large outpatient hematology/oncology clinics. Six months of day-to-day experience in the laboratory has shown a favorable frequency-of-repair record, with little downtime.

Evaluation Studies as Topic↗

Therapy of psoriasis: comparison of photochemotherapy and several variants of phototherapy.

Four treatments involving light were compared in two series of patients with severe psoriasis. The first series consisted of ten patients, who were treated by the method of paired comparisons. The treatments given were: (1) exposure to fluorescent sunlamps (B); (2) the same, supplemented by fluorescent UV-A lamps (A + B); (3) the same as (2) with the addition of the radiation from germicidal lamps (A + B + C); (4) photochemotherapy with oral 8-MOP followed by UV-A (PUVA); (5) one of the fields served as control, receiving no light at all. The second series consisted of thirty patients. They were treated either with PUVA or with a placebo capsule followed by A + B (pUVAB). The phototherapies examined differed from many previous attempts in that the increments in dose were made sufficiently large to overcome the increasing tolerance of the skin to light during the treatment. It is concluded (a) that phototherapy, if conducted in this way, is as effective as PUVA, and (b) that the effectiveness achieved with the phototherapies examined is due to the light from the fluorescent sunlamps (B).

Clinical Trials as Topic↗

Segregation of Tay-Sachs and Sandhoff alleles in a non-Jewish family.

A non-Jewish family is presented in which the genes for Tay-Sachs disease and Sandhoff disease are segregating. Individuals heterozygous for both alleles have low serum and white cell total hexosaminidase levels together with a proportion of heat-labile hexosaminidase A (HEX A) which falls in the normal range. The individuals would not be detected as carriers of Tay-Sachs disease or Sandhoff disease in a population screening program.

False Negative Reactions↗

The assay and partial characterization of macromolecular heparin depolymerase activity in rat small intestine.

Homogenates of rat small intestine can depolymerize macromolecular rat skin heparin (RS heparin) to products similar in size to commercial heparin [Horner (1972) Proc. Natl. Acad. Sci. U.S.A. 69, 3469--3473]. This activity is attributed to an enzyme provisionally named 'macromolecular heparin depolymerase'. An assay for macromolecular heparin depolymerase activity in rat small intestine has been developed, based on the action of the enzyme on 35S-labelled macromolecular RS heparin. The depolymerized products are separated into two peaks by gel chromatography through columns of Bio-Gel A-15m. The amount of label in the second peak, expressed as a percentage of the total radioactivity, is the index of enzyme activity. The pH optimum was found to be 6.0 and the temperature optimum 45 degrees C. The enzyme was shown to be most stable in 50mM-Tris/maleate buffer containing 1 mM-EDTA. Macromolecular heparin depolymerase activity measured as a function of time and substrate concentration produced curves typical of an enzymic reaction. Evidence was obtained demonstrating that the activity did not originate from bacteria in the intestine. Macromolecular heparin depolymerase activity was increased by dilution and storage at 7 degrees C for 24 h. This suggests that homogenates of rat small intestine contain an unstable inhibitor of the enzyme.

Animals↗

Immunological cross-reactivity between a glycoprotein isolated from Trichophyton mentagrophytes and human isoantigen A.

A glycoprotein isolated from the cell wall of Trichophyton mentagrophytes was assessed for its cross-reaction with human blood group isoantigens. Rabbit antiglycoprotein antibodies agglutinated human erythrocytes of blood groups A1 and A2, and precipitated Blood Group Substance A in agarose gels. Erythrocytes of blood group B were only slightly agglutinated, and O(Rho+) and O(Rho-) erythrocytes were not. Additionally, the glycoprotein was shown to specifically inhibit isoagglutination of erythrocytes of group A. Partial identity between the glycoprotein and a crude extract of the fungus was demonstrated by immunodiffusion. Analyses revealed the glycoprotein to be composed of approximately 17% protein and 80% carbohydrate. The glycoprotein was found by indirect immunofluorescence to be located in the mycelial cell wall. The possibility that cross-reacting antigens may lead to a chronic, spreading infection is discussed.

ABO Blood-Group System↗