A live recombinant avirulent oral Salmonella vaccine expressing pneumococcal surface protein A induces protective responses against Streptococcus pneumoniae

A live oral recombinant Salmonella vaccine strain expressing pneumococcal surface protein A (PspA) was developed. The strain was attenuated with Deltacya Deltacrp mutations. Stable expression of PspA was achieved by the use of the balanced-lethal vector-host system, which employs an asd deletion in the host chromosome to impose an obligate requirement for diaminopimelic acid. The chromosomal Deltaasd mutation was complemented by a plasmid vector possessing the asd+ gene. A portion of the pspA gene from Streptococcus pneumoniae Rx1 was cloned onto a multicopy Asd+ vector. After oral immunization, the recombinant Salmonella-PspA vaccine strain colonized the Peyer's patches, spleens, and livers of BALB/cByJ and CBA/N mice and stimulated humoral and mucosal antibody responses. Oral immunization of outbred New Zealand White rabbits with the recombinant Salmonella strain induced significant anti-PspA immunoglobulin G titers in serum and vaginal secretions. Polyclonal sera from orally immunized mice detected PspA on the S. pneumoniae cell surface as revealed by immunofluorescence. Oral immunization of BALB/cJ mice with the PspA-producing Salmonella strain elicited antibody to PspA and resistance to challenge by the mouse-virulent human clinical isolate S. pneumoniae WU2. Immune sera from orally immunized mice conferred passive protection against otherwise lethal intraperitoneal or intravascular challenge with strain WU2.     

Mice overexpressing human lecithin: cholesterol acyltransferase are not protected against diet-induced atherosclerosis

Lecithin: cholesterol acyltransferase (LCAT) (EC 2.3.1.43) is generally assumed to participate in reverse cholesterol transport, i.e., cholesterol transport from peripheral tissues to the liver. LCAT is secreted by the liver and transported in plasma mostly associated with high density lipoprotein. It catalyzes the esterification of cholesterol, mainly high density lipoprotein cholesterol, and produces cholesteryl ester and lysolecithin. Transgenic mice overexpression human LCAT on a C57BL/6 background have elevated high density lipoprotein cholesterol and markedly reduced low and very low density lipoprotein cholesterol and triglyceride levels in plasma, suggesting that such mice may be less susceptible to diet-induced atherosclerosis than isogenic nontransgenic controls. To determine if the apparent anti-atherogenic lipoprotein profile of the LCAT transgenics reduced their susceptibility to atherogenesis, the atherosclerotic lesions developing in transgenic LCAT mice and controls when fed an atherogenic diet were compared by histology and morphometry. Histological examination of the aortas from mice fed a high fat diet for 12, 17 and 22 weeks revealed that the aortic lesions were no smaller or less developed in the transgenic LCAT mice than in the C57BL/6 controls. After 17 weeks there were significantly more "fatty streaks" in the transgenic mice than in the controls. Thus, overexpression of human LCAT in transgenic mice, in spite of their very favourable blood lipoprotein and lipid profile, does not protect against development of atherosclerosis.     

Antibodies against orthopoxviruses in wild carnivores from Fennoscandia

Pressure ulcer incidence has been reduced but not eliminated. A few patients still develop pressure ulcers despite using air-fluidized beds and other specialty beds. In the future, very high-risk patients may possibly be sent to space clinics to recuperate in zero gravity for extended periods. Another possibility is the creation of suspension devices to keep a patient off the areas of the body where pressure sores might occur. Being informed of what is available and and aware how to use it optimally is currently the best solution.     

抗沙丁胺醇单克隆抗体制备与鉴定

[目的]制备特异性抗沙丁胺醇单克隆抗体,为其免疫学检测方法的建立奠定基础.[方法]用SAL-BSA 抗原免疫BALB/c小鼠;使用细胞融合技术建立抗SAL 的单克隆抗体(SAL mAb)杂交瘤细胞株;体内诱生腹水法制备SAL mAb,并鉴定其免疫学特性.[结果]筛选出2D9和IC4两株杂交瘤细胞.其细胞培养上清效价达1:10<'4>,腹水效价达1:10<'6>;免疫球蛋白亚型鉴定为IgG<,1>;抗体对SAL 的半教抑制浓度(IC<,50>)为1.14ng/ml;与沙丁胺醇和盐酸克伦特罗的交叉反应率(CR)分别为100.00%和26.09%,与其他化合物无交叉反应.[结论]获得了高效价、敏感且异性的抗SAL 抗体,为沙丁胺醇残留的免疫学检测方法的建立奠定了基础.     

Antibodies against high-density lipoprotein binding proteins enhance high-density lipoprotein uptake but do not affect cholesterol efflux from rat hepatoma cells

High-density lipoprotein plays a key role in the reverse cholesterol transport pathway as well as in the delivery of cholesterol to the liver and steroidogenic tissues. Metabolism of high-density lipoprotein is determined by one of its apolipoproteins, apolipoprotein A-I; however, the identity and function of cellular protein which binds high-density lipoprotein remains unclear. The effect of antibodies against rat high-density lipoprotein binding proteins, HB1 and HB2, on high-density lipoprotein metabolism in a rat hepatoma cell line were studied. Cells were preincubated with the antibodies and 125I-labeled high-density lipoprotein binding and uptake as well as cholesterol biosynthesis and cholesterol efflux to human plasma or isolated high-density lipoprotein were studied. Both antibodies reacted specifically with HB1 and HB2 on the ligand and Western blots, but their binding was not blocked by high-density lipoprotein. Both antibodies inhibited 125I-labeled high-density lipoprotein binding to cells by 20-40%, but stimulated 125I-labeled high-density lipoprotein uptake by up to 2.5-fold. The antibodies had no effect on cholesterol efflux or on cholesterol synthesis. It is concluded that high-density lipoprotein binding proteins, HB1 and HB2, may be involved in high-density lipoprotein uptake in the liver rather than in mediating cholesterol efflux.     

Antibodies against human putamen in children with Tourette syndrome

BACKGROUND: Similar to the model for Sydenham's chorea, antineuronal antibodies, which develop in response to a preceding streptococcal infection, have been speculated to have a role in the development of Tourette syndrome (TS). METHODS: Serum antibodies against human caudate, putamen, and globus pallidus (interna and externa) were assayed by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques and results were correlated with clinical characteristics and markers of streptococcal infection. SUBJECTS: A total of 41 children with TS (mean age, 11.3 years) and 39 controls (mean age, 12.1 years) were included. RESULTS: Compared with controls, TS subjects had a significant increase in the mean (p=0.006) and median (p=0.002) ELISA optical density (OD) levels of serum antibodies against putamen, but not caudate or globus pallidus. Western blots on 20 control and 20 TS serum samples showed that specific antibodies to caudate/putamen occurred more frequently in TS subjects at 83, 67, and 60 kDa; antigens were present in a synaptosomal fraction. TS subjects with a positive family history of tics had higher OD values (p < or = 0.04), but no association was shown with age of tic onset, tic severity, sudden onset of tics, or presence of attention-deficit hyperactivity disorder or obsessive-compulsive disorder. Risk ratio calculations in TS and control groups and in study subjects dichotomized for high and low putamen OD values were similar for titers of antistreptolysin O > or = 166 or antideoxyribonuclease B > or = 170. A subgroup analysis limited to subjects with elevated streptococcal titers, however, showed a significantly (p < or = 0.004) larger number of TS subjects with elevated OD levels. CONCLUSION: Children and adolescents with TS had significantly higher serum levels of antineuronal antibodies against putamen than did controls, but their relation to clinical characteristics and markers for streptococcal infection remains equivocal.     

Fc receptors are not required for antibody-mediated protection against lethal malaria challenge in a mouse model

The mechanisms by which Abs mediate protection during blood-stage malaria infections is controversial, with some evidence pointing to the direct effect of Abs on parasite invasion and growth, while other studies suggest that Abs act in cooperation with monocytes to achieve parasite inhibition. To determine whether the effector phase of protection in vivo to the rodent parasite Plasmodium yoelii yoelii requires Fc receptor bearing cells, we passively transferred immune sera into FcR gamma-chain knockout mice. Inflammatory macrophages from these knockout mice were unable to mediate phagocytosis or Ab-dependent cell-mediated cytotoxicity (ADCC) through Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Passive transfer of either P. y. yoelii hyperimmune sera or anti-GST-PYC2 sera directed to the major merozoite surface protein (MSP-1) of this parasite enabled both BALB/cByJ mice and FcR gamma-chain-deficient mice to resist lethal P. y. yoelii 17XL (Py17XL) challenge. mAb302, a protective IgG3 Ab, also passively protected both strains of mice. Most of these samples contain Ab isotypes that would not be able to protect mice if their protective effects required Ab-dependent cell-mediated cytotoxicity. These results establish that, in this infection, protection is directly mediated by Abs and does not require the participation of Fc receptors.     

Antibodies binding to anionic phospholipids but not to oxidized low-density lipoprotein are associated with thrombosis in patients with systemic lupus erythematosus

OBJECTIVE: Elevated levels of antibodies against oxidized low-density lipoprotein (LDL) frequently occur in patients with systemic lupus erythematosus (SLE) and these antibodies crossreact in many sera with anticardiolipin antibodies, known to be associated with thrombosis. Therefore, a study was carried out to assess the mutual relationship between antibodies against oxidized LDL and thrombosis. METHODS: The occurrence of IgG class antibodies against oxidized LDL, cardiolipin and phosphatidyl serine were determined by enzyme-linked immunosorbent assay in a series of 146 patients with SLE. Twenty-one patients had had thromboembolic complications. At least one of three tests used to detect lupus anticoagulant was positive in 34 out of 133 patients. RESULTS: The level of antibodies against oxidized LDL correlated significantly with that of antibodies against cardiolipin (r = 0.52) but only marginally with antibodies against phosphatidyl serine (r = 0.18). Antibodies against cardiolipin and phosphatidyl serine, but not those against oxidized LDL, were significantly associated with the presence of lupus anticoagulant (odds ratios of the risk in the highest tertile relative to the lower tertiles of the antibody were 5.3, 6.9 and 1.1, respectively) and with thrombosis (odds ratios 2.5, 4.0 and 1.0, respectively). CONCLUSION: The observations suggest that only those antibodies reacting specifically with cardiolipin and phosphatidyl serine are associated with thrombosis and with the presence of lupus anticoagulant in patients with SLE, whereas antibodies crossreacting with oxidized LDL and those reacting specifically with oxidized LDL are not associated.     

Antidepressants are not placebos.

Comments on the article by I. Kirsch and S. J. Lynn (see record 1999-05760-005), which concerned the effects of expectancy in clinical behavior change. Kirsch and Lynn reviewed several meta-analyses of placebo-controlled trials of antidepressants, and examined areas of research in which response expectancies have been shown to affect experience, behavior, and physiology: placebo effects, the effects of false biofeedback on sexual arousal, and the alteration of perceptual and cognitive functions by hypnotic and nonhypnotic suggestion. The present author questions and argues against Kirsch and Lynn's conclusion that apparent drug effects of antidepressants may in fact be a placebo effect, magnified by differences in experienced side effects and the patient's subsequent recognition of the condition to which he or she has been assigned. Among other criticisms, the present author claims that evidence for the absence of the placebo effect in clinical practice effectively argues against its power. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DRGs are not enough.

Proposes that the federal government conduct research and demonstrations on community support maintenance organizations (CSMOs). Capitation would be given to CSMOs for providing a continuum of comprehensive, rehabilitatively oriented service packages that would reduce the use of inpatient and other costly and restrictive services by seriously or chronically mentally disabled persons. It is concluded that psychological theory, research, and practice can make a contribution to the development of prospective payment alternatives to DRG (diagnosis-related group) based systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Editors are not blind.

Comments on the continuing debate on anonymous reviewing (see record 1986-18404-001) and notes that the journal's editor decides whether a paper will be published, not the reviewer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of protective immunity against murine secondary hydatidosis

Significant protective immunity against secondary hydatidosis in mice was achieved by immunization with a preparation of surface molecules of E. granulosus protoscoleces with Freund's incomplete adjuvant (PSEx-IFA). Study of PSEx-IFA immunogenicity demonstrates that glucidic epitopes evoked mainly IgM responses while peptidic epitopes evoke mainly IgG responses; however both types of epitopes elicit both types of responses. Analysis of the possible association between susceptibility or resistance to infection and antibody responses after challenge was also performed. Cyst fluid antigen (CFAg) specific antibody titres on month eight after challenge correlated with number and size of cysts. On the other hand no correlation was observed between protection and PSEx specific IgG titres either on the day of challenge or one month later. Nonetheless, immunoblot analysis revealed that some PSEx molecules were recognized on day 30 after challenge only by sera from immunized mice.     

Antibodies against peripheral myelin glycolipids in people with HIV infection

Differential diagnosis between true and false left ventricular aneurysms is not always easy, despite the use of imaging techniques of great diagnostic accuracy. We report a case in which the distinction between these two situations offers some difficulty. Finally, we review the characteristics of ventricular aneurysms and that of pseudoaneurysms, focusing on the aspects that enable their differentiation.     

Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases

After 10 years of clinical trials in patients with advanced cancer, monoclonal antibodies (mAbs) against cell surface antigens have not lived up to their initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and melanomas. We have described a murine lymphoma (EL4) that is syngeneic in C57BL/6 mice and expresses GD2, a mAb against GD2 (mAb 3F8), and we have prepared a conjugate vaccine (GD2-keyhole limpet hemocyanin plus immunological adjuvant QS-21) that consistently induces antibodies against GD2. We demonstrate here, for the first time in a syngeneic murine model, that passively administered and vaccine-induced antiganglioside antibodies prevent outgrowth of micrometastases, and we use this model to establish some of the parameters of this protection. The level of protection was proportional to antibody titer. Treatment regimens resulting in the highest titer antibodies induced the most protection, and protection was demonstrated even when immunization was initiated after tumor challenge. Treatment with 3F8 1, 2, or 4 days after i.v. tumor challenge was highly protective, but waiting until 7 or 10 days after challenge resulted in minimal protection. The results were similar whether number of liver metastases or survival was used as the end point. These results suggest that unmodified mAbs or antibody-inducing vaccines against GD2 (and possibly other cancer cell surface antigens) should be used exclusively in the adjuvant setting, where circulating tumor cells and micrometastases are the primary targets.