Duplication 3q(q21 → qter) without limb anomalies

We report on a 2.5-month-old boy with hypertelorism, hypertrichosis, anteverted nostrils, malformed ears, thin lips, downturned corners of the mouth, micrognathia, short neck, cryptorchidism, and bilateral simian creases without limb anomalies. Cytogenetic studies showed a duplication 3q → qter 46,XY,der(6),t(3;6)(q21;p25)pat. The absence of limb anomalies is noteworthy; all 12 previously reported patients with the same duplication had limb anomalies. The uniqueness of this report provokes speculations regarding limb morphogenesis in embryos with chromosome anomalies. The concepts of chronogenetics, heterochrony, and developmental field defects appear relevant to yet another set of patients with chromosome anomalies.     

Increase in the proportion of granulated CD56+ T cells in patients with malignancy.

Evidence is presented for the existence of a unique T cell population which expressed one of the natural killer (NK) markers, CD56 antigen, in humans. Although such CD56+ T cells were a minor population in the peripheral blood (< 10%), they were abundant in the liver (up to 50%), which was recently demonstrated to be a major organ for extrathymic T cell differentiation in mice. As in the case of extrathymic T cells in mice, these CD56+ T cells in humans contained a higher proportion of gamma delta T cells than did CD56- T cells, contained double-negative CD4-8- cells, and had the morphology of large granular lymphocytes. This unique population of CD56+ T cells tended to be elevated in the blood and among tumour-infiltrating lymphocytes in patients with colorectal cancer, especially in advanced cases. These results raise the possibility that, as in mice, CD56+ T cells with extrathymic T cell properties may also be associated with tumour immunity in humans.     

Control of self-reactive cytotoxic T lymphocytes expressing γδ T cell receptors by natural killer inhibitory receptors

The majority of peripheral blood γδ T cells in human adults expresses T cell receptors (TCR) with identical V regions (Vγ9 and Vδ2). These Vγ9Vδ2 T cells recognize the major histocompatibility complex (MHC) class I-deficient B cell line Daudi and broadly distributed nonpeptidic antigens present in bacteria and parasites. Here we show that unlike αβ or Vγ9^? γδ T cells, the majority of Vγ9Vδ2T cells harbor natural killer inhibitory receptors (KIR) (mainly CD94/NKG2A heterodimers), which are known to deliver inhibitory signals upon interaction with MHC class I molecules. Within Vγ9δ2 T cells, KIR were mainly expressed by clones exhibiting a strong lytic activity against Daudi cells. In stark contrast, almost all Vγ9Vδ2 T cell clones devoid of killing activity were KIR^?, thus suggesting a coordinate acquisition of KIR and cytotoxic activity within Vγ9Vδ2 T cells. In functional terms, KIR inhibited lysis of MHC class I-positive tumor B cell lines by Vγ9Vδ2 cytotoxic T lymphocytes (CTL) and raised their threshold of activation by microbial antigens presented by MHC class I-positive cells. Furthermore, masking KIR or MHC class I molecules revealed a TCR-dependent recognition by Vγ9Vδ2 CTL of ligands expressed by activated T lymphocytes, including the effector cells themselves. Taken together, these results suggest a general implication of Vγ9Vδ2 T cells in immune response regulation and a central role of KIR in the control of self-reactive γδ CTL.     

Alpha 1-antitrypsin deficiency and anti-proteinase 3 antibodies in anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis.

alpha 1-antitrypsin (alpha 1-AT) is a naturally occurring inhibitor of proteinase 3 (PR3) and elastase, two of the target antigens of anti-neutrophil cytoplasmic antibodies (ANCA). An increased incidence of alpha 1-AT phenotypes associated with dysfunctional alpha 1-AT or low serum levels has been reported in patients with anti-PR3 antibodies. We have studied the relationship between ANCA, and phenotypes and serum levels of alpha 1-AT. Phenotypes usually associated with a moderate or severe reduction in alpha 1-AT serum levels or in dysfunctional activity were found more often in individuals with anti-PR3 antibodies than in the general population: four of the 31 patients (13%) with anti-PR3 antibodies had phenotypes MZ (n = 2), S (n = 1) or Z (n = 1) (P < 0.05). However, the corresponding alpha 1-AT serum levels were normal (n = 3) or elevated (n = 1). None of the 31 sera with anti-PR3 antibodies had low levels of alpha 1-AT. No abnormal alpha 1-AT phenotype was demonstrated in seven patients with anti-elastase antibodies, despite a low level of alpha 1-AT in one serum. Anti-myeloperoxidase antibodies are common in patients with ANCA, but no abnormal phenotype or low serum alpha 1-AT level was demonstrated in any of 29 sera containing these antibodies. Finally anti-glomerular basement membrane (GBM) antibodies occur occasionally in patients with ANCA-associated diseases, but again none of 10 sera had an abnormal alpha 1-AT phenotype or low serum level. ANCA were not demonstrated by indirect immunofluorescence in any serum from 73 patients with abnormal alpha 1-AT phenotypes. These results confirm that patients with anti-PR3 antibodies often have alpha 1-AT phenotypes that are usually associated with low serum levels of alpha 1-AT or with dysfunctional protein. Nevertheless, the incidence of anti-PR3 antibodies in patients with abnormal alpha 1-AT phenotypes is very low. This probably reflects the rarity of Wegener's granulomatosis, the major disease associated with anti-PR3 antibodies, and the relative frequency of abnormal alpha 1-AT phenotypes. The mechanism for the development of anti-PR3 antibodies in patients with abnormal alpha 1-AT phenotypes is not clear, but may relate to the increased propensity of unbound and uninhibited PR3 to stimulate autoantibody production.     

Longer term progesterone treatment induces changes of GABAA receptor levels in forebrain sites in the female hamster: quantitative autoradiography study

Summary Quantitative receptor autoradiography was applied to evaluate the effects of one and three injections of 1 mg progesterone (P) on ³H muscimol binding levels in the different forebrain areas of the female hamster. The overall effect of P resulted in substantial increases in ³H muscimol binding in brain areas containing gonadal steroid receptors: medial preoptic area and ventromedial hypothalamic nucleus as well as in bed nucleus stria terminalis and subiculum. Similarly, the caudate putamen, a region where gonadal steroid receptors are not abundant, also showed substantial increases of ³H muscimol binding receptor levels. Moreover, female hamsters treated with P for 3 days presented altered ³H muscimol binding levels in the amygdala and thalamic nucleus that were, in some cases, not produced by one dose of P. P treatment also decreased GABA_A binding in two areas of the thalamus. These results are consistent with the proposal that P may alter GABAergic inhibitory activity via changes in the levels of GABA_A receptors in certain forebrain areas in the female hamster, changes which may be linked to the mediation of anxiolytic effects and to the inhibition of aggressive behavior. These data also suggest that P treatment increases the binding of high affinity GABA receptors in some forebrain sites and may be responsible for maintenance of the anxiolytic effects.     

Lymphopenia in acute nitrofurantoin pleuropulmonary reactions

Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.     

Biomorphometric analysis of human prostatic carcinoma by using three-dimensional computer models

Advances in the detection of carcinoma of the prostate during the last 15 years have accounted for a sharp increase and then an abrupt decrease in the incidence of the disease. A more recent decline in its mortality rates has been variously interpreted as either the success of early detection and improved treatment or lead-time bias. The recently reported Prostate Cancer Prevention Trial had an overall detection rate that approached the 30%-40% prevalence rates reported in autopsy series in which men died of other causes. However, the prognostic information that can be obtained from prostate cancer found on biopsy is limited. Three-dimensional computer modeling is one technique that allows multiple studies on "immortal" prostates to test methods of biopsy sampling accuracy and to assist in the determination of the disease's severity. Computer modeling can assess detection rates and assesses tumor multifocality and heterogeneity. It can provide a more accurate representation of tumor volume, aiding in therapeutic decision making, and can assess sampling errors of various biopsy methods. It has been shown to be superior to wire-frame technique by immortalizing the original shape and dimensions of the surgically excised prostate gland. Moreover, our 3-dimensional computer modeling system improves upon other systems: It is more than a simple extension of the planimetric technique, and it is able to demarcate clearly the boundaries of Gleason grades just 1 grade apart.     

Human serum IgE-mediated mast cell degranulation shows poor correlation to allergen-specific IgE content

BACKGROUND: Although allergen-specific IgE content in serum can be determined immunochemically, little is known about the relationship between this parameter and the strength of the degranulation response upon allergen triggering. OBJECTIVES: Analyse the degranulation capacity of immunochemically defined purified and serum IgE after challenge with anti-IgE or allergen using a rat mast cell line (RBL) transfected with the alpha-chain of the human high-affinity IgE receptor (FcepsilonRI). METHODS: Purified IgE specific for 4-hydroxy-3nitrophenylacetyl, purified IgE of unknown specificity, and sera from allergic patients sensitive to Dermatophagoides pteronyssinus and Dactylis glomerata were assessed. Degranulation was measured by a beta-hexosaminidase release assay after anti-IgE or allergen-specific challenge. RESULTS: For purified monoclonal IgE a significant correlation (r = 0.97) was found between the proportion of bound allergen-specific IgE and the strength of the degranulation response. In contrast, no correlation (r = 0.27) was detected after sensitization with serum IgE. CONCLUSION: Our studies demonstrate that mast cell activation mediated through IgE from allergic patients is a result of complex relationships that are not only dependent on allergen-specific IgE content but also relate to the capacity to efficiently sensitize and trigger the signalling responses that lead to degranulation.     

Galectin-3与CDC25B在胃癌中的表达及意义

目的 探讨半乳糖凝集素3 mRNA(Galectin-3)和细胞分裂周期蛋白25B mRNA(cell division cycle 25B,CDC25B)在胃癌中的表达及其与临床病理参数及预后的关系.方法 应用组织微阵列技术和原位杂交法检测220例胃癌组织和31份正常胃黏膜组织中Galectin-3 mRNA和CDC25B mRNA 的表达情况.结果 220例胃癌中Galectin-3 mRNA和CDC25B mRNA的阳性表达率分别为58.6%、54.1%;Galectin-3 mRNA表达与肿瘤大小、TNM(tumor,lymph node,metastasis)分期、浸润深度、脉管侵犯、淋巴结转移及远处转移呈正相关;CDC25B mRNA表达也与肿瘤大小、TNM分期、脉管侵犯、淋巴结转移及远处转移呈正相关;Galectin-3 mRNA表达与CDC25B mRNA表达呈正相关;Galectim3 mRNA和CDC25B mRNA阳性表达病例的平均生存时间和5年生存率均明显低于阴性表达的病例.结论 Galectin-3 和CDC25B基因的表达促进了胃癌的发生和发展,是指导临床治疗及评估预后的有效指标.     

Polyelectrolyte‐in‐Ionic‐Liquid Electrolytes

Novel polymer electrolyte materials based on a polyelectrolyte‐in‐ionic‐liquid principle are described. A combination of a lithium 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid (AMPSLi) and N,N′‐dimethylacrylamide (DMMA) are miscible with the ionic liquid, 1‐ethyl‐3‐methylimidazolium dicyanamide (EMIDCA). EMIDCA has remarkably high conductivity (≥ 2 · 10^?2 S · cm^?1) at room temperature and acts as a good solvating medium for the polyelectrolyte. At compositions of AMPSLi less than or equal to 75 mol‐% in the copolymer (P(AMPSLi‐co‐DMAA)), the polyelectrolytes in EMIDCA are homogeneous, flexible elastomeric gel materials at 10 ? 15 wt.‐% of total polyelectrolyte. Conductivities higher than 8 · 10^?3 S · cm^?1 at 30 °C have been achieved. The effects of the monomer composition, polyelectrolyte concentration, temperature and lithium concentration on the ionic conductivity have been studied using thermal and conductivity analysis, and pulsed field gradient nuclear magnetic resonance techniques.

Comparison of the measured and calculated lithium conductivity at 30 °C.