Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis

OBJECTIVES: Despite improved nutrition and intensive treatment, subjects with cystic fibrosis have difficulty in maintaining anabolism during intercurrent infections, which can result in reduced body mass index and impaired skeletal growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are sensitive to changes in nutritional status. The aim of this study was to determine the relation between circulating concentrations of these peptides, body mass index, and clinical status in cystic fibrosis. METHODS: Serum concentrations of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect to body mass index, pubertal stage, and clinical status as assessed by Shwachman score and forced expiratory volume in one second (FEV1). RESULTS: The mean height SD score of the children studied was -0.2 (SD 1.14) and the body mass index SD score -0.26 (1.4). The body mass index SD score declined with increasing age (r = -0.18) and paralleled changes in IGF-I concentrations, which also declined. The IGF-I SD score (calculated from control data) correlated with age (r = -0.53). The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3 concentrations were significantly reduced compared with those in control subjects matched for pubertal stage. The IGF-I SD score correlated with height SD score (r = 0.14) and the decline in IGF-I concentrations with the fall in body mass index SD score (r = 0.42). IGF-I SD scores also correlated with the Shwachman score (r = 0.33) and FEV1 (r = 0.17). CONCLUSIONS: The close relation between declining IGF-I and IGFBP3 concentrations and body mass index in patients with cystic fibrosis may simply reflect poor nutritional status and insulin hyposecretion. Nevertheless, IGF-I deficiency could also contribute towards the catabolism observed in these patients, and IGF-I SD scores correlated with other measures of clinical status such as the Shwachman score and FEV1.     

Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in A(e):E(a), complex expression causes a corresponding defect in antigen-presenting cell function

A series of experiments were performed to explore the role of complementing major histocompatability complex (MHC)-linked immune response Ir genes in the murine T cell proliferative response to the globular protein antigen pigeon cytochrome c. The functional equivalence of I-E-subregion-encoded, structurally homologous E(a) chains from different haplotypes bearing the serologic specificity Ia.7 was demonstrated by the complementation for high responsiveness to pigeon cytochrome c of F(1) hybrids between low responder B 10.A(4R) (I-A (k)) or B 10.S (I-A(8)) mice and four low responder E(a)- bearing haplotypes. Moreover, this Ir gene function correlated directly with both the ability of antigen-pulsed spleen cells from these same F(1) strains to stimulate pigeon cytochrome c-primed T cells from B10.A or B10.S(9R) mice, and with the cell surface expression of the two-chain Ia antigenic complex, A(e):E(a), bearing the conformational or combinatorial determinant recognized by the monoclonal anti-Ia antibody, Y-17. The B 10.PL strain (H-2(u)), which expresses an Ia.7-positive I-E- subregion-encoded E(a) chain, failed to complement with B10.A(4R) or B10.S mice in the response to pigeon cytochrome c. However, (B10.A(4R) × B10.PL)F(1) and (B10.S × B10.PL)F(1) mice do express A(k)(e):E(u)(a) and A(8)(e):E(u)(a) on their cell surface, although in reduced amounts relative to A(k,s)(e):E(k,d,p,r)(a) complexes found in corresponding F(1) strains. This quantitative difference in Ia antigen expression correlated with a difference in the ability to present pigeon cytochrome c to B 10.A and B 10.S(9R) long-term T cell lines. Thus, (B10.A(4R) × B10.PL)F(1) spleen cells required a 10-fold higher antigen dose to induce the same stimulation as (B10.A(4R) × B10.D2)F(1) spleen cells. In addition, the monoclonal antibody, Y-17, which reacts with A(e):E(a) molecules of several strains, had a greater inhibitory effect on the proliferative response to pigeon cytochrome c of B10.A T cells in the presence of (B10.A(4R) X B10.PL)F(1) spleen cells than in the presence of (B10.A(4R) X B10.D2)F(1) spleen cells. These functional data, in concert with the biochemical and serological data in the accompanying report, are consistent with the molecular model for Ir gene complementation in which appropriate two-chain Ia molecules function at the antigen-presenting cell (APC) surface as restriction elements. Moreover, they clearly demonstrate that the magnitude of the T cell proliferative response is a function of both the concentration of nominal antigen and of the amount of Ia antigen expressed on the APC. Finally, the direct correlation of a quantitative deficiency in cell surface expression of an Ia antigen with a corresponding relative defect in antigen-presenting function provides strong independent evidence that the I-region-encoded Ia antigens are the products of the MHC-linked Ir genes.     

芴甲醇类化合物的合成及抗疟作用

芴甲醇类化合物的合成及抗疟作用邓蓉仙钟景星赵德昌张洪北盛杏英丁德本杨俊德（军事医学科学院微生物流行病研究所，北京１０００７１）为寻找与氯喹无交叉抗药性的新抗疟药，国外合成了大量的芳基甲醇类化合物，其中甲氟喹（ｍｅｆｌｏｑｕｉｎｅ，Ｉ）经临床应用的结果...     

The in vitro evaluation of two filters (Erypur and Imugard IG 500) for white cell-poor platelet concentrates

White cell-poor blood components are useful in patients with white cell antibodies. White cells are efficiently removed by two different filters, Imugard and Erypur, which have used saline as the filter solution. This study evaluated these filters as to their production of white cell-poor platelets. Pools of random-donor platelet concentrates were filtered. Prefiltration and postfiltration samples were evaluated for percentages of platelet recovery, white cell (WBC) removal, and platelet function. The two filter solutions tested were normal-strength saline (NSS) and fresh-frozen plasma (FFP). Postfiltration samples using NSS showed no measurable platelet aggregation with ADP, epinephrine, or collagen. However, with FFP, both filters showed 100 percent platelet aggregation with ADP, epinephrine, and collagen. The FFP filter solution provided excellent white cell removal in both filters (Imugard: 100% WBC removal or less than 1.0 X 10(6) residual WBC; Erypur: 99.5% removal or greater than 1.0 X 10(7) residual WBC); however, platelet recovery was better with Imugard (95%) than with Erypur (55%). The filtration procedure is an excellent method for the preparation of white cell-poor platelets; however, the quantity of the saline solution recommended for the filtering of red cells must be minimized for platelets.     

Lack of effect of the α2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells

Background and purpose:

The α_2C-adrenoceptor has multiple functions, including inhibiting release of noradrenaline from presynaptic nerve terminals. A human α_2C polymorphism, Del322-325, a potential risk factor for heart failure, has been reported to exhibit reduced signalling in CHO cells. To further understand the role of the Del322-325 polymorphism on receptor signalling, we attempted to replicate and further study the reduced signalling in HEK293 cells.

Experimental approach:

Human α_2C wild-type (WT) and Del322-325 adrenoceptors were stably transfected into HEK293 cells. Radioligand binding was performed to determine affinities for both receptors. In intact cells, inhibition of forskolin-stimulated cyclic AMP production by WT and Del322-325 clones with a range of receptor densities (200–2320 fmol·mg⁻¹ protein) was measured following agonist treatment.

Key results:

Noradrenaline, brimonidine and clonidine exhibited similar binding affinities for WT and Del322-325. Brimonidine and clonidine also had similar efficacies and potencies for both receptors for the inhibition of cyclic AMP production at all receptor densities tested. A linear regression analysis comparing efficacy and potency with receptor expression levels showed no differences in slopes between WT and Del322-325.

Conclusions and implications:

The α_2C WT and Del322-325 adrenoceptors exhibited similar binding properties. Additionally, inhibition of cyclic AMP production by Del322-325 was similar to that of WT over a range of receptor densities. Therefore, in intact HEK293 cells, the α_2C-Del322-325 polymorphism does not exhibit reduced signalling to adenylyl cyclase and may not represent a clinically important phenotype.     

The cerebellopontine angle and internal auditory canal: neurovascular anatomy on gas CT cisternograms

We reviewed 103 normal gas CT cisternograms to delineate the appearance of normal neurovascular structures in the cerebellopontine angle (CPA) and internal auditory canal (IAC). Cranial nerves VII and VIII were identified in the CPA in 97% of cases, either separately (53%) or as a bundle (44%). Intracanalicular branches of the VIIIth cranial nerve were identified in 20% of cases, and cranial nerve V was visualized in the CPA in 14%. The characteristic vascular loop, usually the anterior inferior cerebellar artery, was visible in 35% of cases, and, in 22% of visualized cases, was in an intracanalicular location. The internal auditory artery was questionably visualized in one case. In 10% of cases, greater than 66% of the IAC was occupied by the neurovascular bundle. Familiarity with the normal anatomy and variants seen on gas CT cisternograms is necessary to prevent false-positive interpretations.