Developmental biology of the dendritic cell system

Aim : To determine whether an imbalance of dendritic cell subsets might contribute to diminished adaptive host responses observed in newborn infants. It was hypothesized that the proportion of lymphoid dendritic cells would be greater than that of myeloid dendritic cells in cord blood. Methods : To investigate this, dendritic cell subsets were evaluated in whole cord blood by flow cytometry. Circulating dendritic cells were also isolated from cord blood based on CD1c and BDCA-2 expression. Myeloid dendritic cells were also obtained by culturing cord and adult blood monocytes. Surface phenotypes of these cells were determined by flow cytometry using monoclonal antibodies directed against lineage, major histocompatibility, adhesion, co-stimulation and cytokine receptor molecules. Antigen-presenting functions of dendritic cell subsets were determined by mixed leukocyte reactions. Results : Circulating myeloid dendritic cells were higher in cord blood than previously reported in adult blood, whereas lymphoid dendritic cell numbers were similar between cord and adult blood. Expression of CD11c, CD45RA and CD45RO did not accurately differentiate between dendritic cell subsets circulating in cord blood. Fresh and culture-derived cord blood myeloid dendritic cells stimulated adult allogeneic leukocyte proliferation, while lymphoid dendritic cells were less effective inducers of an adult allogeneic leukocyte response. Culture-derived dendritic cells induced modest autologous cord blood leukocyte proliferation, but freshly isolated myeloid and lymphoid dendritic cells did not stimulated autologous leukocytes.
Conclusion : Contrary to the hypothesis, an imbalance in the ratio of circulating myeloid to lymphoid dendritic cell subsets does not exist and, therefore, does not contribute to diminished adaptive immune responses in newborn infants.     

MRI of female genital and pelvic organs during sexual arousal

We utilized contrast enhanced magnetic resonance imaging (MRI) to delineate the anatomy of the female genital and pelvic organs during sexual arousal. Eleven healthy pre-menopausal women and eight healthy post-menopausal women underwent MRI of the pelvis while watching an erotic video. A 1.5 Tesla MR system was used to produce T1-weighted images following administration of MS-325, a gadolinium-based blood pool contrast agent. Selected structural dimensions and enhancement were measured prior to and during sexual arousal. In both pre- and post-menopausal subjects, vestibular bulb and labia minora width increased with arousal. Enhancement measurements increased in the bulb, labia minora and clitoris in both pre- and post-menopausal subjects, and in the vagina in pre-menopausal subjects. There were no marked changes in size or enhancement of the labia majora, urethra, cervix, or rectum during sexual arousal in pre- or post-menopausal subjects. Using MRI, we observed specific changes in the female genitalia and pelvic organs with sexual arousal, in both pre- and post-menopausal women. MRI can potentially provide detailed anatomical information in the assessment of female sexual function, particularly with regard to changes in blood flow.     

Orthostatic hypotension due to quinidine and propranolol

Orthostatic hypotension developed in a 65-year-old man during treatment with quinidine and propranolol. Quinidine reduced standing blood pressure, attenuated the Valsalva response, and increased plasma norepinephrine concentrations, suggesting the presence of nonselective alpha-adrenergic blockade. The addition of propranolol inhibited the compensatory tachycardia and produced symptomatic orthostatic hypotension. Physicians should be alerted to the possibility of orthostatic hypotension when the alpha blocking effects of quinidine are combined with a beta blocking agent such as propranolol.     

Characterization of rat glomerular thromboxane A2 receptors: comparison to rat platelets.

This study was designed to characterize rat glomerular thromboxane A2 (TxA2) receptors and compare them to rat platelet TxA2 receptors. The radioligand binding characteristics of the receptors were characterized using [125I][1S-(1 alpha,2 beta(5Z),3 alpha-(1E,3R*),4 alpha]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo- [2.2.1]heptan-2yl]-5-heptenoic acid ([125I]BOP), a TxA2 agonist. Equilibrium binding with [125I]BOP, as well as competitive binding assays between [125I]BOP and 13-azapinane TxA2 receptors antagonists, were performed in rat glomerular membranes (RGM) and washed rat platelets (WRP). [125I]BOP identified a single class of TxA2 receptor sites in glomerular membranes with a Kd of 318 +/- 55 pM and a Bmax of 260 +/- 62 fmol/mg protein (n = 14). [125I]BOP was displaced by the TxA2 agonist 15S-hydroxy-11 alpha,9 alpha(epoxymethano)-prosta-5Z,13E-dienoic acid (U-46,619) (IC50 = 22 +/- 6 nM, n = 3), the antagonist SQ-29,548 (IC50 = 41 +/- 7 nM, n = 4), and stereoselectively by the antagonists (-)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid (L-657,925) (IC50 = 0.27 +/- 0.04 nM, n = 3) and (+)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid (L-657,926) (IC50 = 124 +/- 0 nM, n = 2). The ability of six 13-azapinane TxA2 antagonists to compete with [125I]BOP was evaluated. The rank orders for the 13-azapinanes showed no significant correlation between RGM and WRP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years

Although well studied in families at high-risk, the roles of mutations in the BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very young. We examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 women without breast cancer who participated in a multicenter population-based case-control study of Black and White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and demographic factors were significantly associated with BRCA1 and, to a lesser extent, BRCA2 carrier status, when examined individually. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA1 carrier status, whereas BRCA2 predictors were fewer and more modest in magnitude. Both the combinations of predictors and effect sizes varied across racial/ethnic and age groups. These results provide first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among understudied racial and age groups and show key predictors of mutation carrier status for both White and Black women and women of a wide age spectrum with breast cancer in the general population.     

Retrievable Gunther Tulip inferior vena cava filter: Experience in 317 patients

The aim of our study was to assess our experience with the retrievable Gunther Tulip (GT) inferior vena cava (IVC) filter, with regard to its insertion, efficacy, ease of placement and retrieval, and associated complications. Between November 2001 and October 2005, 322 GT filters were placed in 317 patients. Insertion indications included the following: pulmonary embolus (PE) prophylaxis in trauma patients (n = 232), PE prophylaxis in perioperative patients (n = 27), PE prophylaxis in moribund intensive care unit patients (n = 22), recent PE (n = 48), extensive deep venous thrombosis (n = 66), contraindication to anticoagulation (n = 63), anticoagulation complication (n = 8) and deep venous thrombosis with failed anticoagulation (n = 8). Some patients had more than one indication for caval filter placement. Two hundred and five attempted retrievals have been carried out, with 15 failures. Our successful retrieval rate is 92%. Nineteen filters were originally inserted permanently. There have been three minor complications associated with insertion and five with retrieval. The mean time from filter insertion to attempted retrieval was 76.95 days. The ideal filter implantation time gives the patient the benefit of PE protection, while avoiding the long‐term risks associated with caval filters. Although GT retrieval times have lengthened considerably, our data suggest that this is at the expense of successful retrieval rates.     

Breast cancer risk and hormone receptor status in older women by parity, age of first birth, and breastfeeding: a case-control study

BACKGROUND: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)-positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers. METHODS: We used multivariable logistic regression analysis to investigate whether age at first birth (<25 or > or =25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages > or =55 years who participated in the Women's Contraceptive and Reproductive Experiences Study. RESULTS: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (P(heterogeneity) = 0.0007). This protective effect was restricted to ERPR-positive breast cancer (P(heterogeneity) = 0.004). Late age at first birth increased the risk of ERPR-negative cancers. Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (P(trend) = 0.0001) and among women who breastfed (P(trend) = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer. CONCLUSIONS: These findings suggest that the effect of parity on a woman's long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding.     

用(+)-FLEC手性试剂自动柱前衍生高效液相色谱法拆分麻黄碱类药物对映体

报道了以(+)-FLEC作为手性衍生化试剂,用反相高效液相色谱技术分离麻黄碱类药物对映异构体的方法。dl-麻黄碱、dl-伪麻黄碱、dl-去甲麻黄碱、dl-去甲伪麻黄碱先与(+)-FLEC形成衍生物后,经过一ODSHypersil柱分离,以水和乙腈为流动相梯度洗脱.二极管阵列检测器在266nm检测。该法从样品衍生化到最终报告全部自动完成。上述各对对映体均达到基线分离,分离度R均大于1.5,方法灵敏度高,最低检出限达10pmo1,保留时间和峰面积的上现性较好,RSD分别为1.1/和3.0%。