Preoperative irradiation therapy and radical hysterectomy: prognostic value of tumor regression after initial irradiation of squamous cell carcinoma of the cervix

OBJECTIVE: To investigate the role of tumor persistence in patients submitted to irradiation therapy and radical hysterectomy. DESIGN: A retrospective analysis of prognostic factors. LOCATION: Hospital A.C. Camargo, S?o Paulo, Brazil, a private non-profitmaking foundation and tertiary referral centre. PATIENTS: A total of 629 cases of invasive squamous cell carcinoma of the cervix were studied. Criteria for inclusion in the study were: confirmed histological diagnosis of squamous cell carcinoma and no previous treatment (except for preoperative radiotherapy carried out at the Hospital A.C. Camargo itself). At the end of the follow-up period, 410 patients (65%) had no evidence of disease and 219 (34.8%) had died because of the tumor. INTERVENTION: The patients were submitted to radical surgery and radiation therapy, separately or in combination between 1953 and 1982. MAIN OUTCOMES MEASURES: Multivariate analysis of the different variables was performed according to the Cox regression method. RESULTS: The variables of prognostic value were, in decreasing order of importance: the decade of patient admission (p = 0.0001), the modality of therapy employed (p = 0.0005), the presence of residual tumor in the surgical specimens (p = 0.0055) and the clinical stage of the disease (p = 0.0575). CONCLUSION: Radiation therapy controlled a considerable number of local tumors and pelvic lymph nodes but not all of them in every patient. There is a specific group of patients for whom radical surgery is necessary to achieve control of the disease.     

Dual flaA1 flaB1 mutant of Serpulina hyodysenteriae expressing periplasmic flagella is severely attenuated in a murine model of swine dysentery

The motility imparted by the periplasmic flagella (PF) of Serpulina hyodysenteriae is thought to play a pivotal role in the enteropathogenicity of this spirochete. The complex PF are composed of multiple class A and class B polypeptides. Isogenic strains containing specifically disrupted flaAl or flaB1 alleles remain capable of expressing PF, although such mutants display aberrant motility in vitro. To further examine the role that these proteins play in the maintenance of periplasmic flagellar structural integrity, motility, and fitness for intestinal colonization, we constructed a novel strain of S. hyodysenteriae which is deficient in both FlaA1 and FlaB1. To facilitate construction of this strain, a chloramphenicol gene cassette, with general application as a selectable marker in prokaryotes, was developed. The cloned flaAl and flaB1 genes were disrupted by replacement of internal fragments with chloramphenicol and kanamycin gene cassettes, respectively. The inactivated flagellar genes were introduced into S. hyodysenteriae, and allelic exchange at the targeted chromosomal flaA1 and flaB1 loci was verified by PCR analysis. Immunoblots or cell lysates with antiserum raised against purified FlaA or FlaB confirmed the absence of the corresponding sheath and core proteins in this dual flagellar mutant. These mutations selectively abolished the expression of the targeted genes without affecting the synthesis of other immunologically related FlaB proteins. The resulting flaA1 flaB1 mutant exhibited altered motility in vitro. Surprisingly, it was capable of assembling periplasmic flagella that were morphologically normal as evidenced by electron microscopy. The virulence of this strain was assessed in a murine model of swine dysentery by determining the incidence of cecal lesions and the persistence of S. hyodysenteriae in the gut. Mice challenged with the wild-type strain or a passage control strain showed a dose-related response to the challenge organism. The dual flagellar mutant was severely attenuated in murine challenge experiments, suggesting that the FlaA1 and FlaB1 proteins are dispensable for flagellar assembly but critical for normal flagellar function and colonization of mucosal surfaces of the gastrointestinal tract. This strain represents the first spirochete engineered to contain specifically defined mutations in more than one genetic locus.     

The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1

The specificity of lymphocyte homing from the blood into a tissue is determined in part by complementary pairs of adhesion receptors on lymphocytes and endothelial cells termed homing receptors and vascular addressins, respectively. The mucosal vascular addressin involved in lymphocyte homing to Peyer's patches is a 66-kDa glycoprotein, MAdCAM-1. Investigation of the regulation and molecular genetics of MAdCAM-1 have been hampered by the lack of a murine cell line expressing this adhesion molecule. We show herein using indirect immunofluorescence studies that MAdCAM-1 can be induced on a murine endothelial cell line, bEnd.3, by cytokines and LPS. Western blot analysis of MAdCAM-1 purified by affinity column chromatography from TNF-alpha-treated bEnd.3 cells demonstrates a 66-kDa protein that comigrates in SDS-PAGE with the MAdCAM-1 constitutively found on high endothelial venules in murine mesenteric lymph nodes. Comparison of MAdCAM-1 expression on the bEnd.3 cells was made to the expression of adhesion molecules ICAM-1 and VCAM-1. MAdCAM-1 and VCAM-1 are not constitutively expressed on the bEND.3 surface but can be induced in a concentration-dependent manner by LPS, TNF-alpha, and IL-1. ICAM-1 is constitutively expressed on the endothelioma surface and expression is increased by TNF-alpha, IL-1, LPS, and IFN-gamma. Surface expression of MAdCAM-1 peaks 12 to 18 h after exposure to TNF-alpha and remains elevated at 48 h, whereas expression of VCAM-1 peaks at 4 h and inducible ICAM-1 peaks between 4 and 18 h. Interestingly, IFN-gamma has differential effects on expression of these three adhesion receptors. IFN-gamma alone induces VCAM-1 and enhances ICAM-1 expression, but does not induce MAdCAM-1. Furthermore, although, preincubation of bEND.3 cells with IFN-gamma modestly increases the induction of ICAM-1 and VCAM-1 in response to TNF-alpha and IL-1, it dramatically reduces the TNF-alpha, IL-1, and LPS-induced expression of MAdCAM-1. MAdCAM-1 on bEnd.3 cells is functional as the murine T lymphoma TK1, known to bind MAdCAM-1, also binds to TNF-alpha-stimulated endothelioma but not to unstimulated cells. This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of angiotensin II on platelet intracellular free magnesium and calcium ionic concentrations in essential hypertension

OBJECTIVE: To assess the effects of angiotensin II on intracellular free Mg2+ and Ca2+ concentrations in platelets from normotensive and hypertensive subjects. DESIGN AND METHODS: Seventeen normotensive, 25 untreated hypertensive and 18 treated hypertensive patients were studied. Intracellular Mg2+ concentrations were measured with the fluorescent dye mag-fura-2-acetyoxymethylester (AM) and intracellular Ca2+ concentrations with the fluorescent dye fura-2AM under basal conditions and after stimulation by angiotensin II, saralasin (angiotensin II antagonist), arginine vasopressin and endothelin-1. The effects of increased extracellular Mg2+ concentrations on intracellular Mg2+ and Ca2+ concentrations were also determined. RESULTS: The intracellular basal Ca2+ concentration was significantly higher in the untreated hypertensives compared with the normotensives and treated hypertensive subjects (150 +/- 14 nmol/l versus 120 +/- 17 nmol/l for normotensives and 124 +/- 8 nmol/l for treated hypertensives). The basal intracellular Mg2+ concentration was significantly lower in the untreated hypertensive compared to the normotensive and treated hypertensive groups (0.37 +/- 0.08 mumol/l versus 0.58 +/- 0.09 mumol/l for normotensives and 0.52 +/- 0.11 mumol/l for treated hypertensives). In the hypertensive groups, inverse correlations were found between intracellular Ca2+ and intracellular Mg2+ concentrations (r = -0.44, P < 0.05) and between intracellular Mg2+ and diastolic blood pressure (r = -0.35, P < 0.05), while a positive correlation was found between intracellular Ca2+ and systolic blood pressure (r = 0.41, P < 0.05). Exposure of the platelets to 1 nmol/l angiotensin II significantly increased intracellular Ca2+ and significantly decreased intracellular Mg2+ concentrations in all three groups. The angiotensin II-evoked effect on intracellular Ca2+ was exaggerated in the untreated hypertensives and blunted in the treated patients (basal versus stimulated: 150 +/- 14 versus 217 +/- 20 nmol/l in untreated hypertensives; 124 +/- 8 versus 140 +/- 10 nmol/l in treated hypertensives). Saralasin (0.1 mumol/l) abolished the effects of angiotensin. Arginine vasopressin (1 mumol/l) increased the intracellular Ca2+ concentration, whereas endothelin-1 (1 nmol/l) had no significant effect on either intracellular Ca2+ or intracellular Mg2+. Increasing extracellular Mg2+ concentrations led to significant reductions in intracellular Ca2+ concentrations in all groups and a significant elevation of the intracellular Mg2+ concentration in the untreated hypertensive patients only. CONCLUSIONS: These data demonstrate a relationship between angiotensin II and intracellular magnesium and calcium. In hypertension, angiotensin II-stimulated calcium responses may be related to simultaneously decreased intracellular magnesium concentrations.     

弃武从文的卡司克

<正>不必质疑卡司克的精密、耐用和可靠程度,因为孕育它的母体可是战争中那把直接致命的武器——左轮手枪。我打赌你以前没有拿过枪。面对着正在把玩.32口径左轮手枪的乔恩·索洛萨巴尔(Jon Solozabal),很难相信这句话竟是一位文具制造商的开场白。对乔恩和他的这座超过90岁的企业王国而言,手枪所代表的不仅是一段历史,更是一笔宝贵的遗产。     

Stabilization of controlled positive discrete‐time T‐S fuzzy systems by state feedback control

This paper deals with sufficient conditions of asymptotic stability and stabilization for nonlinear discrete‐time systems represented by a Takagi–Sugeno‐type fuzzy model whose state variables take only nonnegative values at all times t for any nonnegative initial state. This class of systems is called positive systems. The conditions of stabilizability are obtained with state feedback control. This work is based on multiple Lyapunov functions. The results are presented in linear matrix inequalities form. A real plant is studied to illustrate this technique. Copyright © 2010 John Wiley & Sons, Ltd.