Immunological effects of tumor vaccines: II. T cell responses directed against cellular antigens in the viral oncolysates

Peripheral blood mononuclear cells (PBMC) from patients with epithelial adenocarcinoma of the ovary treated in vivo with tumor vaccines administered as viral oncolysates (VO) exhibited significant proliferative responses in vitro to VO as well as to cellular oncolysates (CO). These responses were dependent on the concentration of VO or CO. VO consisted of lysates from the same ovarian tumor cell lines 2774 and CaOV3 infected in vitro with the avirulent strain of influenza virus A/PR8/34. CO were lysates from the same ovarian tumor cell lines without virus. Depletion experiments with the OKT3 monoclonal antibody plus complement demonstrated that these proliferative responses are T cell specific and under the control of the HLA-D region. Furthermore, these T cell responses are directed against both tumor tumor cellular components and tumor HLA class I molecules. These responses can be detected as early as two weeks after the first intraperitoneal injection of VO and reach a maximum 12-16 weeks after the first application of VO for treatment. PBMC from ovarian patients that received in vivo VO exhibited insignificant proliferative responses to CO prepared from human fibroblasts or tumor cell lines of hematopoietic origin. In contrast, they exhibited significant proliferative responses to CO prepared from a human cervix tumor cell line. These results demonstrate systemic T cell activation by antigens in the tumor vaccines in patients with epithelial ovarian carcinoma after in vivo intraperitoneal administration of VO.     

Detection of wheat gliadin contamination of gluten-free foods by a monoclonal antibody dot immunobinding assay

Unfractionated wheat gliadin was used to produce murine monoclonal antibodies to gliadin. A dot immunobinding assay, using these antibodies, was developed to detect possible gliadin contamination of nominally gluten-free flour, using dilute ethanol extracts spotted onto nitrocellulose membranes. The sensitivity of the assay was less than 10 micrograms/ml of unfractionated gliadin which permitted the detection of trace amounts of gliadin present in certain wheat starch based 'gluten-free' products. The assay detected not only wheat gliadin, but also prolamine extracts of rye, barley and oats; maize, soya and potato extracts as well as the control proteins casein and ovalbumin, gave negative results. The assay is of value as a simple and rapid method of screening foods for their suitability for consumption by patients with coeliac disease.     

Herpes zoster ophthalmicus with delayed cerebral infarction and meningoencephalitis

Herpes zoster ophthalmicus can be complicated by a delayed ipsilateral cerebral angiitis which may cause infarction and a smoldering meningoencephalitis. We describe such a case treated successfully with steroids and acyclovir. It is important to consider the diagnosis of this disorder early since therapeutic intervention may prevent an otherwise high morbidity and mortality. Steroids may have to be continued for some time after clinical resolution, using the ESR as a guideline for decreasing dosages.     

Quinine potently blocks single K+ channels activated by dopamine D-2 receptors in rat corpus striatum neurons

In single channel recordings from acutely dissociated neurons of the rat corpus striatum, a membrane K+ channel which is activated by dopamine D-2 receptors was blocked by nanomolar concentrations of quinine. An intermittent partial blockade was observed at 4-10 nM quinine, with a voltage dependence consistent with quinine binding to the channel near the extracellular surface of the membrane. A nearly complete blockade of channel current was observed at 100 nM quinine and above. Such concentrations are known to be too low to block various other ion channels, and may be attained in human brain at antimalarial dosages of quinine. Blockade of this channel by quinine may provide a useful experimental probe of dopaminergic function, as an alternative to D-2 receptor binding site blockade by neuroleptics.     

Association analysis of genes in the renin‐angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study

Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin‐angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima‐media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.     

Platelet cold agglutinins: a flow cytometric analysis.

Spontaneous EDTA-independent cold platelet agglutination is a rare phenomenon that produces pseudothrombocytopenia when blood samples are analyzed in automated cell counters. We report a case of platelet cold agglutinins and an analysis by flow cytometry. A 49 year old woman presented with abnormal vaginal bleed secondary to uterine fibroids. Platelet clumping was observed in blood samples taken in EDTA-, heparin- and citrate-containing tubes. In flow cytometric tests, patient serum agglutinated 16% of normal platelets at 22 degrees C, and 7% of platelets after incubation at 37 degrees C; in contrast, 3% and < 1% of platelets were agglutinated at 22 and 37 degrees C, respectively, after incubation with normal serum. Minimal agglutination (< 10%) was observed with patient serum at a titre of 1:5 or at temperatures > 30 degrees C. After incubation at 4 degrees C, IgM antibody and C3 were increased on the patient's platelets; no significant amount of IgM or C3 was detected on normal platelets. The specificity of the platelet cold agglutinin was determined by competitive inhibition by monoclonal anti-CD41(GPIIbIIIa). Before the addition of monoclonal antibody, patient's serum agglutinated 16% of normal platelets at 22 degrees C; after addition of anti-CD41 only 2% of the platelets were agglutinated. This blocking effect was not observed with anti-CD42. The patient's platelets functioned normally as determined by CD62 and CD63 expression in response to thrombin, normal platelet aggregation in response to collagen, ADP, and ristocetin, and a normal template bleeding time. In summary, platelet agglutination by a platelet cold agglutinin was quantitated by flow cytometry, the responsible antibody was characterized as a low titre IgM with minimal activity > 30 degrees C, and competitive binding studies supported the GPIIbIIIa complex as the binding site for the antibody. Since the antibody did not affect platelet function, we believe that these patients will not suffer complications from their platelet cold agglutinin, but it could pose a problem under circumstances such as cardiac surgery with hypothermia.     

嗜铬细胞瘤患者围手术期处理的改进

目的：探讨提高嗜铬细胞瘤患者围手术期安全性的措施。方法：对15例嗜铬细胞瘤患者、术前采用选择性α1受体阻滞剂多沙唑嗪控释片(可多华)控制高血压；11例患者采用3D DCEMRA进行肿瘤定位；术中均采用联合高容量血液稀释(AHH)和术中患者自体血回输纠正血容量。结果：除1例持续性高血压患者需联合钙离子拮抗剂和ACEI药物降压外．其余患者血压控制均为满意；根据3D DCEMRA定位选择手术径路者均顺利完成手术；AHH联合术中自体血回输使14例患者避免了异体输血。结论：本文围手术期处理改进．可多华可明显减少药物的不良反应；采用3D DCEMRA进行肿瘤定位，可增加手术安全性；AHH联合术中自体血回输可减少医疗成本和异体输血，以及由此而引起的并发症。