Intercellular communication in the rat anterior pituitary gland: an in vivo and in vitro study

The concept of "stimulus-secretion coupling" suggested by Douglas and co-workers to explain the events related to monamine discharge by the adrenal medulla (5, 7) may be applied to other endocrine tissues, such as adrenal cortex (36), pancreatic islets (4), and magnocellular hypothalamic neurons (6), which exhibit a similar ion-dependent process of hormone elaboration. In addition, they share another feature, that of joining neighbor cells via membrane junctions (12, 26, and Fletcher, unpublished observation). Given this, and the reports that hormone secretion by the pars distalis also involves a secretagogue-induced decrease in membrane bioelectric potential accompanied by a rise in cellular [Ca++] (27, 34, 41), it was appropriate to test the possibility that cells of the anterior pituitary gland are united by junctions.     

Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

Background and methods

Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.

Results

We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10⁵ viral copies/ml in nasal lavage and 1.88 × 10⁵ viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.

Conclusion

HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.     

Natural products as starting points for future anti-malarial therapies: going back to our roots?

Background

Population movements along the Thailand-Cambodia border, particularly among highly mobile and hard-to-access migrant groups from Cambodia and Myanmar, are assumed to play a key role in the spread of artemisinin resistance. Data on treatment-seeking behaviours, knowledge and perceptions about malaria, and use of preventive measures is lacking as characteristics of this population prevent them from being represented in routine surveillance and the lack of a sampling frame makes reliable surveys challenging.

Methods

A survey of migrant populations from Cambodia and Myanmar was implemented in five selected rural locations in Thailand along the Thai-Cambodian border using respondent driven sampling (RDS) to determine demographic characteristics of the population, migratory patterns, knowledge about malaria, and health-care -seeking behaviours.

Results

The majority of migrants from Myanmar are long-term residents (98%) with no plans to move back to Myanmar, understand spoken Thai (77%) and can therefore benefit from health messages in Thai, have Thai health insurance (99%) and accessed public health services in Thailand (63%) for their last illness. In comparison, the majority of Cambodian migrants are short-term (72%). Of the short-term Cambodian migrants, 92% work in agriculture, 18% speak Thai, 3.4% have Thai health insurance, and the majority returned to Cambodia for treatment (45%), self-treated (11%), or did not seek treatment for their last illness (27%).

Conclusion

Most highly mobile migrants along the Thai-Cambodia border are not accessing health messages or health treatment in Thailand, increasing their risk of malaria and facilitating the spread of potentially resistant Plasmodium falciparum as they return to Cambodia to seek treatment. Reaching out to highly mobile migrants with health messaging they can understand and malaria diagnosis and treatment services they can access is imperative in the effort to contain the spread of artemisinin-resistant P. falciparum.     

植物的遗传转化及其应用(英文)

近年来,植物遗传转化研究有了长足的发展。已经达到能够通过简单的遗传控制手段研究具有新表现型的植物,甚至达到进入商业化的程度。这些手段包括植物生物学的主要研究技术以及植物组织培养和树种改良的一些实用方法。尽管采用农瘤杆菌和鸟枪法等技术的植物遗传转化系统已经得到了广泛的应用,但是在如何开发具有能够得到控制表达的转基因高产植物方面,在如何使所得到的转基因植物远离遗传危害等方面,目前的转化系统遇到了极大的技术挑战。已经提出了各种各样的方法用于将新基因稳定地导入120多种不同植物的核基因组。本文将讨论这些遗传转化系统所需的生物学要求和实际应用方面的需求、基因转化和转基因表达的研究策略、遗传转化植物的鉴定以及转基因植物与大众的认可。本文将分为七个部分加以讨论:一、导言;二 、基因转化到细胞里的方法;三、植物遗传转化策略;四、植物遗传转化的鉴定;五、植物遗传转化的实际应用;六、转基因植物与环境;七、未来植物遗传转化的需求与发展方向。     

Enhanced Activity of Deoxycytidine Kinase After Pulsed Low Dose Rate and Single Dose Gamma Irradiation

In both pulsed low dose rate (LDR) and single high dose radiation schedules, gemcitabine pretreatment sensitizes tumor cells to radiation. These radiosensitizing effects could be the result of decreased DNA repair. In this study, the effect of irradiation on the deoxycytidine kinase (dCK) needed for DNA repair was investigated. The activity of dCK, a deoxynucleoside analogue-activating enzyme was increased upon irradiation in both schedules. No change in dCK protein expression was observed that indicates a post-translational regulation. The benefit of this increased activity induced by irradiation should be further investigated in combination with deoxynucleoside analogues activated by this enzyme.     

The effect of patients' sex on physicians' recommendations for total knee arthroplasty

Background

The underuse of total joint arthroplasty in appropriate candidates is more than 3 times greater among women than among men. When surveyed, physicians report that the patient''s sex has no effect on their decision-making; however, what occurs in clinical practice may be different. The purpose of our study was to determine whether patients'' sex affects physicians'' decisions to refer a patient for, or to perform, total knee arthroplasty.

Methods

Seventy-one physicians (38 family physicians and 33 orthopedic surgeons) in Ontario performed blinded assessments of 2 standardized patients (1 man and 1 woman) with moderate knee osteoarthritis who differed only by sex. The standardized patients recorded the physicians'' final recommendations about total knee arthroplasty. Four surgeons did not consent to the inclusion of their data. After detecting an overall main effect, we tested for an interaction with physician type (family physician v. orthopedic surgeon). We used a binary logistic regression analysis with a generalized estimating equation approach to assess the effect of patients'' sex on physicians'' recommendations for total knee arthroplasty.

Results

In total, 42% of physicians recommended total knee arthroplasty to the male but not the female standardized patient, and 8% of physicians recommended total knee arthroplasty to the female but not the male standardized patient (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.4–7.3, p < 0.001; risk ratio [RR] 2.1, 95% CI 1.5–2.8, p < 0.001). The odds of an orthopedic surgeon recommending total knee arthroplasty to a male patient was 22 times (95% CI 6.4–76.0, p < 0.001) that for a female patient. The odds of a family physician recommending total knee arthroplasty to a male patient was 2 times (95% CI 1.04–4.71, p = 0.04) that for a female patient.

Interpretation

Physicians were more likely to recommend total knee arthroplasty to a male patient than to a female patient, suggesting that gender bias may contribute to the sex-based disparity in the rates of use of total knee arthroplasty.Disparity in the use of medical or surgical interventions based on patient characteristics, such as sex, ethnic background or socioeconomic status, is an important health care issue.¹ Women are less likely than men to receive lipid-lowering medication after a myocardial infarction,² receive kidney dialysis,³ be admitted to an intensive care unit,⁴ or undergo cardiac catheterization,⁵ renal transplantation⁶ or total joint arthroplasty.⁷ Although women''s preferences for surgery or the information needed to make an informed decision may differ from men and explain sex-based differences in care,^8,9 subtle or overt gender bias may inappropriately influence physicians'' clinical decision-making.^2,5,7 A more pronounced gender bias might be expected when the clinical decision involves an elective surgical procedure such as total joint arthroplasty.Total hip and knee arthroplasty is the definitive treatment for relieving pain and restoring function in people with moderate to severe osteoarthritis for whom medical therapy has failed.¹⁰ Although age-adjusted rates of total joint arthroplasty are higher among women than among men,¹¹ based on a population-based epidemiologic survey, underuse of arthroplasty is 3 times greater in women.⁷ In prior opinion surveys, more than 93% of referring physicians and orthopedic surgeons have reported that patients'' sex has no effect on their decision to refer a patient for, or perform, total knee arthroplasty.^12,13 However, there may be a difference between what is reported in a survey and what occurs in clinical practice. The purpose of our study was to determine whether physicians would provide the same recommendation about total knee arthroplasty to a male and a female standardized patient presenting to their offices with identical clinical scenarios that differed only by sex.     

Properties of microtubule sliding disintegration in isolated tetrahymena cilia

Properties of the sliding disintegration response of demembranated tetrahymena cilia have been studied by measuring the spectrophotomeric response or turbidity of cilia suspensions at a wavelength of 350 nm relative to changes in the dynein substrate (MgATP(2-)) concentration. The maximum decrease in turbidity occurs in 20 muM ATP, and 90 percent of the decrease occurs in approximately 5.9 s. At lower ATP concentrations (1-20 muM), both the velocity and magnitude of the turbidity decreases are proportional to ATP concentration. The velocity data for 20 muM ATP permit construction of a reaction velocity curve suggesting that changes in turbidity are directly proportional to the extent and velocity of disintegration. At ATP concentrations more than 20 muM (50muM to 5mM), both velocity and magnitude of the turbidimetric response are reduced by approximately 50 percent. This apparent inhibition results in a biphasic response curve that may be related to activation of residual shear resistance or regulatory components at the higher ATP concentrations. The inhibitory effects of elevated ATP can be eliminated by mild trypsin proteolysis, whereupon the reaction goes to completion at any ATP concentration. The turbidimetric responses of the axoneme-substrate suspensions are consistent with the extent and type of axoneme disintegration revealed by electron microscope examination of the various suspensions, suggesting that the turbidimetric assay may prove to be a reliable means for assessing the state of axoneme integrity.     

Purification and characterization of a magnesium-dependent neutral sphingomyelinase from bovine brain

The magnesium-dependent, plasma membrane-associated neutral sphingomyelinase (N-SMase) catalyzes hydrolysis of membrane sphingomyelin to form ceramide, a lipid signaling molecule implied in intracellular signaling. We report here the biochemical purification to apparent homogeneity of N-SMase from bovine brain. Proteins from Nonidet P-40 extracts of brain membranes were subjected to four purification steps yielding a N-SMase preparation that exhibited a specific enzymatic activity 23,330-fold increased over the brain homogenate. When analyzed by two-dimensional gel electrophoresis, the purified enzyme presented as two major protein species of 46 and 97 kDa, respectively. Matrix-assisted laser desorption/ionization-mass spectrometry analysis of tryptic peptides revealed at least partial identity of these two proteins. Amino acid sequencing of tryptic peptides showed no apparent homologies of bovine N-SMase to any known protein. Peptide-specific antibodies recognized a single 97-kDa protein in Western blot analysis of cell lysates. The purified enzyme displayed a K(m) of 40 microM for sphingomyelin with an optimal activity at pH 7-8. Bovine brain N-SMase was strictly dependent on Mg(2+), whereas Zn(2+) and Ca(2+) proved inhibitory. The highly purified bovine N-SMase was effectively blocked by glutathione and scyphostatin. Scyphostatin proved to be a potent inhibitor of N-SMase with 95% inhibition observed at 20 microM scyphostatin. The results of this study define a N-SMase that fulfills the biochemical and functional criteria characteristic of the tumor necrosis factor-responsive membrane-bound N-SMase.