Inhomogeneous exercise uptake and accelerated washout of a radioiodinated fatty acid analogue in syndromeX A SPECT study of the left ventricle

Myocardial metabolism in exercise was determined by studying 21 syndromeX patients and 14 healthy volunteers with an aromatic fatty acid analogue IPPA and a gamma camera. We developed criteria for visual semiquantitative assessment of relative segmental radiotracer uptake and washout, and tested a new computer program for quantitative evaluation. One volunteer (7%) and 12 patients (57%) showed visually inhomogeneous uptake (p=0.006, χ²-test) in SPECT polar tomograms after a maximal ergometry test. Images in none of the volunteers and seven patients (33%) gave the impression of a slowed regional washout (p=0.057). Only six patients (29%) had a normal radial polarogram. Patients with irregular coronary angiograms (showing ‘slow flow’ or minor sclerosis) and those with chest pain during the IPPA exercise test had a very low frequency of normalcy, but this was not significant. Total washout was higher in patients than in the reference population, as the exercise to rest activity ratio was 1.36 SD 0.13 versus 1.25 SD 0.11 in computerized quantitation (p=0.015, t-test). Washout did not correlate with age, sex or exercise heart rate. Regarding computerized analysis of uptake and slow washout, the number of deviant segments was not significantly higher in patients than in reference population. Semiquantitative and quantitative analysis correlated in the assessment of uptake, but not in the assessment of washout. Possible reasons for the discrepancy are discussed. Conclusions of this study are not straightforward. SyndromeX was associated with inhomogeneous IPPA uptake, which is not at variance with the theory of microvascular dysfunction. On the other hand, the analysis of washout presumably implies higher fatty acid utilization in patients than in normal controls, which is not a characteristic phenomenon in myocardial ischemia.     

Spatial distribution of CD44 and hyaluronan in the proximal tibia of the growing rat

CD44 has been described as a cell surface hyaluronan receptor present on a variety of different cells, and it is generally assumed to be prevalent in most connective tissues that contain hyaluronan. A major aim of this study was to test that presumption by localizing CD44 and hyaluronan within several tissues of the proximal tibia of the growing rat. Comparison of these profiles would reveal whether CD44 and hyaluronan co-localize with high fidelity, as would be expected if CD44 were a major hyaluronan binding protein. Using in situ hybridization and immunohistochemistry, CD44 was identified on osteoclasts, chondroclasts, osteocytes, hematopoietic marrow cells, synovial cells, and connective tissue fibroblasts (ligaments, tendons, and fascia). Although the majority of osteocytes expressed CD44, reduced expression was observed for osteoblasts and osteoprogenitor cells. Additionally, CD44 was not detected on chondrocytes from epiphyseal and metaphyseal growth cartilages or in meniscal fibrocartilage. Using biotinylated G1 domain from aggrecan and link protein, hyaluronan was observed in the maturational and hypertrophic zones of all growth cartilages, the synovium and other fibroblastic connective tissues, regional areas of the periosteum and endosteum (around osteoblasts, osteoprogenitor cells, and osteoclasts), osteocyte lacunae, and surrounding blood vessels. In regions of co-localization for CD44 and hyaluronan, it seems that CD44 is a likely hyaluronan binding protein in several tissues of the proximal tibia. However, it does not appear to be the predominant hyaluronan binding protein in growing cartilages of the weanling rat.     

预测2型糖尿病的基因

2 0 0 2年 4月 2 6日～ 2 9日 ,德国拜耳制药有限公司在葡萄牙里斯本召开了“国际IGT论坛” ,近 4 0个国家的 4 0 0多位医师参加了本次大会。会上国内外 10余名著名专家就“糖尿病流行病学”、“糖尿病的预防”及“糖尿病基础与临床最新资料”等作了精彩的报告 ,强调了对IGT患者早期干预的重要性及其措施。为使广大读者对该论坛有较全面的了解 ,本刊刊登了其中的大部分内容。     

Peripheral blood neutrophil leukotriene B4 release and migration in rheumatoid arthritis

The present study was designed to compare peripheral blood neutrophil migration and leukotriene (LT) release between patients with rheumatoid arthritis (RA) and healthy controls and to correlate the neutrophil functions with clinical disease activity. Nineteen patients with moderately active RA and 19 age and sex matched healthy volunteers participated in this study. Isolated peripheral blood neutrophils from RA patients released equal amounts of LTB₄ but their random migration was enhanced as compared with neutrophils from healthy controls. LTB₄ release in whole blood was significantly lower in samples from RA patients than in those from the healthy volunteers (13.5±1.4 and 19.1±1.4 ng/10⁶ neutrophils respectively; P<0.001). LTB₄ release from isolated RA neutrophils correlated with the levels of C-reactive protein, duration of morning stiffness and Ritchie articular swelling index. Concentrations of hyaluronate, cyclic AMP and 13,14-dihydro-15-keto-prostaglandin were not different between patients with RA and healthy volunteers. Neither was there any difference in TXB₂ production by platelets during blood clotting. In conclusion, peripheral blood neutrophils of RA patients seem to be primed and/or activated as their random migration is enhanced as compared with those of healthy volunteers. In RA, LTB₄ release from peripheral blood neutrophils seems to reflect the clinical activity of the disease. However, RA neutrophils released smaller (in whole blood) or equal (isolated cells) amounts of LTB₄ as compared with the respective controls. These contradictory findings suggest that LTB₄ release from peripheral blood neutrophils has no major role in the regulation of disease activity in rheumatoid arthritis.     

Testicular infarction following ethanol embolization of a renal neoplasm

A case of infarction of the left testis secondary to transcatheter embolization of a malignant left renal tumor with absolute ethanol is presented. The mechanism producing this complication was due to the anomalous nature of the left testicular artery, originating from the left renal artery distal to the site of the balloon occlusion catheter. The importance of this anomaly is discussed and the literature reviewed.     

Bacterial infection in under school age children with expiratory difficulty

Serological evidence of bacterial infection was prospectively studied in less than 6 years old patients during 188 acute episodes of expiratory difficulty requiring hospital treatment. Such evidence indicated by antibody or antigen assays was found in 40 patients (21%). Streptococcus pneumoniae was identified in 25 cases; antigenemia was found in 10, antigenuria in 2 and seroconversion in 14 cases. Seroconversion to nontypable Haemophilus influenzae was found in 9 and to Branhamella catarrhalis in 2 cases. Seroconversion to Chlamydia spp. was demonstrated in 8 patients, but specific tests for C. trachomatis were negative. C-reactive protein was over 40 mg/L in 35 patients (19%); serological evidence of bacterial infection was present in 14 and absent in 21 of them. Thus, either serological evidence of bacterial infection or an elevated C-reactive protein was found in 61 of the 188 cases (32%). We conclude that bacterial infection is commonly associated with acute wheezing in children under school age. We suggest that bacterial, as well as viral, infections may trigger an acute obstructive attack in children with reactive airways.     

Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus.

OBJECTIVE: To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We studied mutations in MODY1-4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum. RESULTS: There was no increase in type 1 diabetes-associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1alpha gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum. CONCLUSIONS: MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes.     

Glycodelin from seminal plasma is a differentially glycosylated form of contraceptive glycodelin-A

Glycodelin-A is a human amniotic fluid-derived glycoproteinwith contraceptive and immunosuppressive activities. An immunoreactiveform of glycodelin was detected in seminal plasma over a decadeago, but definitive characterization of this glycoprotein wasnot pursued. We considered it unlikely that the seminal plasmaof fertile men would contain an appreciable amount of contraceptiveglycodelin-A. To address this issue we purified seminal plasmaglycodelin (glycodelin-S) and performed comparative studieswith glycodelin-A. Glycodelin-S behaved differently when comparedwith glycodelin-A during sodium dodecyl sulphate-polyacrylamidegel electrophoresis (SDS-PAGE) and isoelectric focusing butidentically after enzymatic deglycosylation. N-terminal sequencingof glycodelin-A and glycodelin-S gave identical results, anddigestion with trypsin gave identical peptide fragments. Theglycoproteins were also found to be indistinguishable from eachother based upon immunological analyses. These results indicatethat glycodelin-S and glycodelin-A have similar overall proteinstructure, suggesting the likelihood that these glycoproteinsare differentially glycosylated forms of very similar proteins.This latter possibility is supported by lectin binding studiesindicating that, unlike glycodelin-A, glycodelin-S does notmanifest any affinity for lectins from Wisteria floribunda orSambucus nigra. The results of sugar analysis and neuraminidasedigestion also lead us to conclude that glycodelin-S and glycodelin-Aare differentially glycosylated forms of similar proteins. Ourevidence indicates that glycodelin-A mediates its biologicalactivities via its unusual oligosaccharide sequences that arenot associated with glycodelin-S. In lectin-immunoassay no appreciableamount of contraceptive glycodelin-A was found in the 22 seminalplasma samples studied. contraception/glycodelin/glycosylation/lectin/PP14