Antigen-induced death of mature T lymphocytes: analysis by flow cytometry.
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Biomedical subjects
Publications and source records attributed to T Pohl.
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Subclinical thyroid disorders have received increasing attention in recent years due to refined laboratory methods and a stronger emphasis on the role of preventive medicine. We performed a screening for thyroid-stimulating hormone (TSH) on 6884 persons in a working population. In cases in which TSH was not within the normal range we also measured the levels of triiodothyronine (T3), thyroxine (T4), and thyroxine-binding globulin (TBG). All persons who did not present with exclusion criteria or other nonthyroidal illnesses (n = 59) and the controls (n = 39) were submitted to thyrotropin-releasing hormone (TRH)-testing. Additionally, sonography of the thyroid was performed on 120 persons (59 subjects with abnormal hormone levels and 61 controls) to determine thyroid size and rule out morphological abnormalities. Based on the TRH test and T3, T4, and TBG measurements we found a prevalence of 0.03% (2/6884) for overt hyperthyroidism, 0.33% (23/6884) for subclinical hypothyroidism, 0.09% (6/6884) for subclinical hypothyroidism, and 0.015% (1/6884) for overt hypothyroidism in the healthy population. In subjects with overt or subclinical hyperthyroidism the prevalence of goiters (thyroid volume > 18 ml in women, > 25 ml in men) was 28%. Of this group 48% had structural abnormalities. All persons with goiters and/or structural abnormalities were over 35 years of age. Among the euthyroid, 20% had thyroid enlargement, and the same proportion presented with structural abnormalities. There were no differences between the two age groups. In the group with overt/subclinical hypothyroidism 47% presented with structural abnormalities of the thyroid; however, none presented with thyroid enlargement. Thyroid nodules were found only in older persons (> 35 years) with euthyroidism or hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)
Programmed cell death (apoptosis) is triggered in immature thymocytes and T-cell hybridomas by signalling via the CD3-T-cell receptor pathway. In this paper, Dieter Kabelitz and colleagues catalogue the recently accumulating evidence that apoptosis can also be initiated in mature peripheral T cells; this may constitute an important aspect of cellular immune regulation.
The interaction of LDL and LDL subfractions from a patient homozygous for familial defective apoB-100 (FDB) has been studied. His LDL cholesterol ranged from 2.65 to 3.34 g/liter. In cultured fibroblasts, binding, internalization, and degradation of the patient's LDL was diminished, but not completely abolished. The patient's apolipoprotein E concentration was low, and the amount of apolipoprotein E associated with LDL was not elevated over normal. LDL were separated into six subfractions: LDL-1 (1.019-1.031 kg/liter), LDL-2 (1.031-1.034 kg/liter), LDL-3 (1.034-1.037 kg/liter), LDL-4 (1.037-1.040 kg/liter), LDL-5 (1.040-1.044 kg/liter), and LDL-6 (> 1.044 kg/liter). LDL-5 and LDL-6 selectively accumulated in the patient's plasma. Concentrations of LDL-1 to 3 were normal. The LDL receptor-mediated uptake of LDL-1 and LDL-2 could not be distinguished from normal LDL. LDL-3 and LDL-4 displayed reduced uptake; LDL-5 and LDL-6 were completely defective in binding. When apolipoprotein E-containing particles were removed by immunoabsorption before preparing subfractions, LDL-3 and LDL-4, but not LDL-1 and LDL-2, retained some receptor binding activity. We conclude that in FDB, LDL-1 and LDL-2 contain sufficient apolipoprotein E to warrant normal cellular uptake. In LDL-3 and LDL-4, the defective apoB-100 itself displays some receptor binding; LDL-5 and LDL-6 are inable to interact with LDL receptors and accumulate in plasma.
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We investigated whether subclinically hyperthyroid individuals selected from a nonpatient working population exhibit similar impairments to those found in studies with patients. Sixteen subclinically hyperthyroid subjects without apparent reason (SH-0) and 15 subclinically hyperthyroid subjects on levothyroxine (SH-T4) were compared with 27 euthyroid controls with respect to signs and symptoms of hyperthyroidism, sleep, depressivity, ability to concentrate, anxiety, and other dimensions of well-being. We found that SH-T4 exhibited significantly higher TT4 levels, TT4/TBG ratios, and more palpitations than controls. Furthermore, they slept less. The SH-0 subjects reported being in a better mood and less touchy than controls. Psychometric results of all groups were within the normal range. A comparison of this study to previous studies reveals that TT4 levels or TT4/TBG ratios may play a crucial role in the development of the predominantly nervous symptoms in subclinical hyperthyroidism. Possible reasons for the discrepancies between results in hospital and nonhospital settings are discussed.
A novel mouse homeobox-containing gene, Nkx-2.2, has been isolated. Nkx-2.2 is a member of a family of genes whose homeodomains are homologous to that of the Drosophila NK-2 gene. Nkx-2.2 transcripts are found in localized domains of the brain during mouse embryogenesis. Nkx-2.2 expression in the brain abuts and partially overlaps with the expression domains of two other related homeobox-containing genes, TTF-1 and Dlx. The expression domains of the three genes in the developing prosencephalon coincide with anatomical boundaries, particularly apparent in the diencephalon. This result raises the possibility that these genes may specify regional differentiation of the developing diencephalon into its anatomically and functionally defined subregions. Nkx-2.2 may be involved in specifying diencephalic neuromeric boundaries.
A glutaminyl cyclase (QC) that is probably involved in the biosynthesis of pyroglutamyl peptides such as gonadotropin-releasing hormone and thyrotropin-releasing hormone has been purified to homogeneity from bovine anterior pituitary. On the basis of N-terminal sequence analysis, a 2088-base-pair cDNA clone was isolated from a bovine anterior pituitary library. From the nucleotide sequence of this clone, the primary structure of a 330-residue protein and a preceding 31-residue prepropeptide sequence was deduced. By transfection of COS-7 monkey cells with a QC cDNA/pCDM8 vector construct, QC activity was expressed. Hybridization with mRNAs of various bovine tissues revealed expression of QC mainly in brain tissue.
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alpha-L-Iduronidase (IDUA) has been intensively studied due to its causative role in mucopolysaccharidosis type I (Hurler, Scheie and Hurler/Scheie syndromes). The recent cloning of a human IDUA cDNA has resulted in a reevaluation of the chromosomal location of this gene. Previously assigned to chromosome 22, IDUA now has been localized to 4p16.3, the region of chromosome 4 associated with Huntington's disease (HD). The existence of a battery of cloned DNA, physical map information, and genetic polymorphism data for this region has allowed the rapid fine mapping of IDUA within the terminal cytogenetic band of 4p. IDUA was found to be coincident with D4S111, an anonymous locus displaying a highly informative multiallele DNA polymorphism. This map location, 1.1 X 10(6) bp from the telomere, makes IDUA the most distal cloned gene assigned to 4p. However, it falls within a segment of 4p16.3 that has been eliminated from the HD candidate region, excluding a role for IDUA in this disorder.
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Escherichia coli 30 S ribosomal subunits and 70 S ribosomes were treated with the bifunctional reagent diepoxybutane, acting as a cross-linker. One major cross-linked protein pair in the 30 S subunit was generated in relatively high yields. This cross-link was shown to consist of ribosomal proteins S13 and S19. Purification of this complex was achieved by a series of conventional and/or high pressure liquid chromatography techniques allowing its isolation in milligram quantities. To reveal the exact position of the two amino acids involved in the cross-link formation, the purified protein pair S13-S19 was subjected to several enzymatic fragmentations, and the resulting peptides were characterized by sequence analysis, amino acid analysis, and fast atom bombardment mass spectrometry. After isolation of the cross-linked peptides, Cys84 in protein S13 and His68 in S19 could be unequivocally identified as the amino acids cross-linked by the bifunctional reagent. This result demonstrates that, despite neutron scattering data which place the centers of mass of S13 and S19 85 A apart, at least these regions of the two proteins are located within a 4-A distance in the ribosomal particle.
A rapid method for desalting and concentrating dilute protein solutions using short reversed-phase columns (3-4 cm) has been described. The recovery of proteins is usually 90-100%. The method is simple and rapid and allows the desalting and concentration of protein samples simultaneously. A wide variety of proteins in the range up to 80 kDa can be desalted in microgram to milligram amounts, and volumes up to 1 liter can be concentrated to a few milliliters by a single injection.
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