The STAFF studies of the first 5 minutes of percutaneous coronary angioplasty balloon occlusion in man

The Staff Studies comprise a database of 228 patients undergoing elective 5 minute coronary artery balloon occlusion angioplasty at a single center in the pre-stent era in whom standard and high-frequency electrocardiographic and nuclear information was obtained immediately before, during and after balloon occlusion. The data were then analyzed by multiple investigators at different international academic centers from different perspectives. Simulating in a clinical setting the first 5 minutes of a heart attack, this database, now in digital format, is the largest database to date documenting standard and high-frequency ECG changes from the onset and for 5 minutes during acute coronary artery occlusion, with resting and occlusion imaging in a subset of these patients. The history, methodology, and legacy of these studies are discussed in this paper.     

The delicate balance in genetically engineering live vaccines

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.     

Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

Invasive Salmonella infections for which improved or new vaccines are being developed include enteric fever caused by Salmonella enterica serovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidal Salmonella (NTS) serovars, particularly S. enterica serovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developed in vitro assays to quantify serum bactericidal antibody (SBA) activity induced by S. Typhi, S. Paratyphi A, S. Typhimurium, and S. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. For S. Enteritidis, S. Typhimurium, and S. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast, S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administered S. Typhimurium, S. Enteritidis, and S. Paratyphi A but not S. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited by Salmonella vaccine candidates.     

Extensive cutaneous metastatic breast carcinoma of the hand and upper extremity: a case report

Cutaneous metastatic breast carcinoma involving the hand is extremely rare. We report a case of a 39-year-old woman with a history of recurrent invasive ductal adenocarcinoma of the breast who had a right modified radical mastectomy, chemotherapy, and radiation therapy before presenting to our institution with extensive cutaneous metastasis to the upper limb including the hand. The presentation, pathogenesis, incidence, prognosis, management, and differential diagnosis of cutaneous metastatic breast carcinoma to the hand and upper limb are discussed.     

幽门螺杆菌cagⅡ对胃上皮细胞IL-8基因转录的影响及机制

目的探讨HpcagⅡ对胃上皮细胞IL-8基因转录的影响及信号传导机制。方法构建 cagⅡ基因位点缺失Hp突变株及带有IL-8报告基因的人胃癌细胞系L5F11,用液体闪烁计数仪测定荧光素酶(IL8转录)活性,用ELISA法测定IL8蛋白浓度。结果所有Hp突变株诱导荧光素酶活性与IL8蛋白浓度较亲代菌株26695均降低[(0．13±0．01)×cpm比(0．59±0．05)×(P<0．01);(0．73±0．13)ng／ml比(2．22±0．65)ng／ml,(P<0．05)]。PTK抑制剂herbimycinA不仅抑制Hp诱导的荧光素酶活性[(0．71±0．18)×cpm比(1．51±0．23)×cpm,(P<0．05)],而且抑制IL-8蛋白表达[(0．83±0．41)ng／ml比(3．22±0．59)ng／ml,(P<0．05)],但herbimycinA对TNFα诱导的荧光素酶活性及IL8蛋白表达均无影响(P均>0．05);PKA抑制剂H7抑制TNFα诱导的荧光素酶活性[(0．74±0．16)×cpm比(2．62±0．26)×cpm,(P<0．001)]及IL8蛋白表达[(1．45±0．38)ng／ml比(4．12±0．43)ng／ml,(P<0．01)],而对Hp诱导的荧光素酶活性无影响(P>0．05)。结论HpcagⅡ中的多基因能够调节胃上皮细胞IL-8基因转录,且这一作用主要经蛋白酪氨酸激酶途径。     

Comparison of the correlation of the Selvester QRS scoring system with cardiac contrast-enhanced magnetic resonance imaging-measured acute myocardial infarct size in patients with and without thrombolytic therapy

Background

After an acute myocardial infarction (MI), it is important to define the infarct size because it is related to mortality and morbidity. The Selvester QRS Score is an electrocardiographic (ECG) method that has been developed for estimating MI size. It has been shown to correlate well with postmortem anatomically measured sizes of single MI in patients who did not receive thrombolytic therapy. The aim of this study was to test the hypothesis that correlation between Selvester QRS Score-estimated MI size and contrast-enhanced magnetic resonance imaging (ceMRI)-measured MI size is equivalent in patients who did vs those who did not receive thrombolytic therapy.

Methods

Thirty-six patients with MI (24 with thrombolytic therapy and 12 without) received ceMRI and ECG at admission and at 1 or 6 months after admission. Indeed, in 23 of the patients, the therapy was intravenous only. The Selvester QRS Score was calculated using the 1-month ECG or, if not available, the 6-month ECG. The correlation between the 2 measures of MI size was determined for all patients and for the 2 groups separately.

Results

The mean MI size in the group that did not receive thrombolytic therapy was 8.5% ± 6.4% estimated by the Selvester QRS Score and 11.7% ± 10.2% measured by ceMRI. For the group that received thrombolytic therapy, Selvester QRS Score was 13.9% ± 11.1% and ceMRI was 20.2% ± 11.3%. The mean MI size in both groups combined was 12.1% ± 10.0% estimated by the Selvester QRS Score and 17.3% ± 11.5% measured by ceMRI. The Spearman rank correlation coefficient between Selvester QRS Score and ceMRI was 0.74 (P < .0001) for all patients, 0.74 (P < .0001) for the group that received thrombolytic therapy, and 0.64 (P = .024) for the group that did not receive thrombolytic therapy.

Conclusions

The associations between Selvester QRS Score and ceMRI-based MI were statistically significant and similar in both groups.     

Cytokine production by primary bone marrow megakaryocytes

Primary human bone marrow megakaryocytes were studied for their ability to express and release cytokines potentially relevant to their proliferation and/or differentiation. The purity of the bone marrow megakaryocytes was assessed by morphologic and immunocytochemical criteria. Unstimulated marrow megakaryocytes constitutively expressed genes for interleukin-1 beta (IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), by the polymerase chain reaction (PCR) and Northern blot analysis. At the protein level, megakaryocytes secreted significant amounts of IL-1 beta (53.6 +/- 3.6 pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/- 4 pg/mL) but not TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta increased the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture supernatants. Transforming growth factor- beta was also able to stimulate IL-6, IL-1 beta, and GM-CSF secretion, but was less potent than stimulation with phorbol-12-myristate-13- acetate (PMA). The secreted cytokines acted additively to maintain and increase the number of colony-forming unit-megakaryocytes colonies (approximately 35%). These studies demonstrate the production of multiple cytokines by isolated human bone marrow megakaryocytes constitutively or stimulated in vitro. The capacity of human megakaryocytes to synthesize several cytokines known to modulate hematopoietic cells supports the concept that there may be an autocrine mechanism operative in the regulation of megakaryocytopoiesis.