Circulating immune complexes, complement and complement component levels in childhood Hodgkin's disease.

Serum levels of circulating immune complexes (CIC) assayed by the Raji cell radioimmunoassay, total haemolytic complement (TCH50), Clq and C3 were correlated with clinical stage, histological type, age, sex and treatment of eighty-six children with Hodgkin's disease over a period of 4 years. Most significant findings were the changes of levels of CIC, TCH50, Clq and C3 during disease activity and following treatment. Significant perturbations were also seen in association with relapse. Levels of C and CIC were significantly elevated (P less than 0.001) at the time of diagnosis prior to splenectomy and/or any treatment. In the group before treatment, 81 percent of CIC levels were above 16 micrograms/ml with a maximum value of 1120 micrograms/ml. During treatment 33 percent were still above normal with a maximum of 320 micrograms/ml. Within 1 year after cessation of treatment, 37 percent also remained above normal levels with a maximum of 240 micrograms/ml. At relapse prior to treatment, 63 percent were again elevated with a maximum of 1280 micrograms/ml. The most significant difference on TCH50 levels relates to treatment periods. Sera of patients with active disease who are previously untreated show elevation of TCH50 levels (P less than 0.001) (average 127 CH50 mu/ml. During and after treatment eht TCH50 levels drop to 96 and 102 CH50 mu/ml, as compared to normal control of 100 CH50 mu/ml. In sera of patients at the first, second or third relapse, the combined TCH50 levels are significantly different from controls and across treatment periods (P less than 0.005).     

Controlled elimination of intracellular H(2)O(2): regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification

The predominant enzymes responsible for elimination of hydrogen peroxide (H(2)O(2)) in cells are peroxiredoxins (Prxs), catalase, and glutathione peroxidases (GPxs). Evidence suggests that catalytic activities of certain isoforms of these H(2)O(2)-eliminating enzymes are extensively regulated via posttranslational modification. Prx I and Prx II become inactivated when phosphorylated on Thr(90) by cyclin B-dependent kinase Cdc2. In addition, the active-site cysteine of Prx I-IV undergoes a reversible sulfinylation (oxidation to cysteine sulfinic acid) in cells. Desulfinylation (reduction to cysteine) is achieved by a novel enzyme named sulfiredoxin. c-Abl and Arg nonreceptor protein tyrosine kinases associate with catalase in cells treated with H(2)O(2) by mechanisms involving the SH3 domains of the kinases and the Pro(293)PheAsnPro motif of catalase and activate catalase by phosphorylating it on Tyr(231) and Tyr(386). Similarily, GPx1 is activated by c-Abl- and Arg-mediated phosphorylation. The tyrosine phosphorylation is critical for ubiquitination-dependent degradation of catalase.     

COMT and DRD3 polymorphisms, environmental exposures, and personality traits related to common mental disorders

In a community sample of 2,327 Caucasians, we tested the hypotheses that polymorphisms in the COMT and DRD3 genes are associated with personality traits conferring vulnerability to anxiety, depression, or alcohol misuse, or with current symptoms of these; and that the association is stronger in persons who also have been exposed to stressor experiences. To conserve resources and to allow replication, the genetic analysis was undertaken in two stages. For the COMT polymorphism, no statistically significant associations were found in the first sample of 862 persons. The remainder of the sample was therefore not analysed for that gene. For the DRD3 polymorphism, those in the first sample with at least one of the Ser(9) alleles had significantly higher scores in neuroticism (p=0.006) and behavioral inhibition (p=0.003). There was a trend, failing to meet the 1% significance criterion, for those with this genotype also to have higher depression and anxiety. The groups did not differ in alcohol use. In persons with the Ser(9) allele who were also exposed to stressors, there was a higher level of depression at the 5% level; and the depression level was higher in homozygotes. But when the remainder of the sample (1,465) was analysed, none of the associations reached statistical significance. We conclude that neither the COMT nor DRD3 polymorphisms are associated with anxiety, depression, or alcohol abuse. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:102-107, 2000 Copyright 2000 Wiley-Liss, Inc.     

Optokinetic nystagmus in the rabbit and its modulation by bilateral microinjection of carbachol in the cerebellar flocculus

Summary 1. In the alert, pigmented rabbit, eye movements were recorded during optokinetic nystagmus (OKN) and during optokinetic afternystagmus (OKAN). These responses were elicited by steps in surround-velocity ranging from 5–110°/s during binocular as well as monocular viewing. 2. In the baseline condition, OKN showed an approximately linear build-up of eye velocity to a steady-state, followed by a linear decay of eye velocity during OKAN after the lights were turned off. Build-up during binocular viewing was characterized by a constant, maximum eye-acceleration (about 1°/s²) for stimulus velocities up to 60°/s. OKAN, instead, was characterized by a fixed duration (about 10 s) for stimulus velocities up to 20°/s. Steady-state eye velocity saturated at about 50°/s. 3. Monocular stimulation in the preferred (nasal) direction elicited a build-up that was on average twice as slow as during binocular stimulation. Steady-state velocity during monocular stimulation saturated at about 20°/s. OKAN was of equal duration as during binocular stimulation. In the non-preferred direction, a very irregular nystagmus was elicited without velocity build-up. The stronger response to binocular stimulation, compared to the responses under monocular viewing condition in either nasal and temporal direction suggests potentiation of the signals of either eye during binocular viewing. 4. OKN and OKAN were re-assessed after intra-floccular microinjection of the nonselective cholinergic agonist carbachol. In the binocular viewing condition, eye-acceleration during build-up was strongly enhanced from 1°/s² before to 2.5°/s² after injection. The saturation level of steady-state eye velocity was also increased, from 50°/s before to more than 60°/s after carbachol. The duration of OKAN, however, was shortened from 10 s before to 6 s after injection. The response to monocular stimulation in the preferred direction revealed similar changes. 5. The flocculus appears to be involved in the control of the dynamics of OKN in the rabbit. Cholinergic mechanisms affect the floccular control of the rate at which slow-phase velocity can be built up and the rate of decay of eye velocity during OKAN. Cholinergic stimulation of the flocculus enhances the dynamics of OKN, while velocity storage is shortened.     

Interleukin-6 regulates the cytotoxic effect of tumour necrosis factor on U937 cells.

In this study, we demonstrate that low but not high concentrations of interleukin-6 (IL-6) potentiate the cytotoxic effect of tumour necrosis factor-alpha (TNF-alpha) on U937 cells, in a dose-dependent manner. Killing of U937 cells by 100 U/ml of TNF-alpha, was maximally potentiated by 50 U/ml of IL-6. No potentiation of cell killing was observed when the concentration of IL-6 was increased to 4000 U/ml. At a concentration of 50 U/ml, IL-6 up-regulated TNF receptor expression but no change in TNF receptor number was observed when the concentration of IL-6 was increased to 4000 U/ml. Low concentrations of IL-6 can also induce sub-cytotoxic doses of TNF-alpha (0.1 and 0.33 U/ml) to kill U937 cells. Up-regulation of TNF receptors by IL-6 is dependent on de novo protein synthesis since receptor induction is abolished in the presence of cycloheximide. Taken together the data suggest that the potentiation of cell killing observed by a combination of these lymphokines is mediated in part by IL-6-induced changes in TNF receptor expression.     

Repertoire of transcribed peripheral blood T-cell receptor beta chain variable-region genes in acute rheumatic fever.

Patients with severe group A streptococcal infections have abnormalities in the Vbeta repertoire of peripheral blood T cells that are consistent with superantigen stimulation by cytoplasmic membrane proteins. The purpose of this study was to determine whether similar changes in Vbeta repertoire could be found for patients with acute rheumatic fever (ARF). The mean Vbeta repertoire of peripheral blood T cells in nine hospitalized ARF patients was similar to that of 34 controls and did not change during 6 months of follow-up in 6 of the ARF subjects. We were unable to detect changes in the Vbeta repertoire of peripheral blood T cells from patients with ARF that could be attributed to the influence of a superantigen.     

Subtle translocation (18;21) confirmed by FISH in a patient with Down syndrome

The patient presented with the typical features of Down syndrome: hypotonia, brachycephaly, flattened occiput, bilateral prominent medical epican-thic folds, flat nasal bridge, protruding tongue, low-set dysplastic ears, short broad hands, bilateral clinodactyly and simian crease. The karyotype of this child was originally reported as normal. High-resolution chromosomes revealed extra material on the long arm of chromosome 18. The mother's karyotype showed a reciprocal translocation between the long arm of 18 and the long arm of 21 at band q23 and q22.1, respectively. FISH performed separately with two different 21q cosmid probes gave two signals on the mother's metaphases and three signals on the prob-and. These findings confirmed that the proband is trisomic for the long arm of chromosome 21 at loci D21S65 and D21S19.     

KOCH三角的解剖

本实验解剖了110例人心标本(成人70、儿童40)的Koch三角区,观察和测量了房室结的形态、大小、毗邻和标志。房间隔及冠状窦口上、下方均有肌束连于房室结。Todaro腱在儿童多全部为腱性;在成人,其后部为肌性。三角区的深面为左、右心房壁和室间隔顶所构成的锥形间隙,其内为进入房室结区的血管和神经。根据构成不同,可将三角区分为5个区,即前上角的纤维支架区和房室结区,其余部分自上向下分别为房间隔区、右房壁区和室间隔区。本文还讨论了这些形态结构的功能及外科意义。     

A surface molecule on guinea pig lymphocytes involved in adhesion and homing

A monoclonal antibody, CT 4, which recognizes an antigenic determinant on the majority of guinea pig lymphocytes, was tested for its ability to interfere with adherence and homing capacity of lymphocytes. Incubation with F(ab')2 fragments of the antibody blocks the in vitro binding to high endothelial venules (HEV) of both peripheral lymph nodes and Peyer's patches. When tested in vivo using a short-term homing assay with radiolabeled cells also a reduction of migration into the spleen was observed. Fluorescence-activated cell sorter analysis of lymph node cells showed a separation into duller and brightly positive cells whereas in the thymus the bright population is absent. Thymus cells adhere less effectively to HEV and this binding can only marginally be blocked by CT 4 incubation. The results suggest a role of CT 4 in adhesion processes.     

显性遗传性聋─大家系研究

本文报告江苏省淮阴县运南地区方氏家族六代６８３人的系谱、皮纹学、染色体和ＡＢＯ血型等遗传学方法的调查与检测，确定属常染色体显性遗传性聋患者１３７例。经检索这是我国首例显性遗传性聋大家系，亦是国际上的第三例聋人大家系的报告。