Characterization of the lymphoid infiltrate in Hashimoto thyroiditis by immunohistochemistry and polymerase chain reaction for immunoglobulin heavy chain gene rearrangement

To determine which genes may be activated or inactivated during breast cancer development, we employed two cloning strategies (subtractive hybridization and differential display) using RNA samples from a human breast tumor and its matching normal breast cell line. Of 950 clones isolated, 102 cDNA inserts were analysed by DNA sequencing and database searching. We found 30 clones that were obviously unidentified, with no significant homology to any listed human gene. We focused upon one of the novel genes, Di12, that is differentially expressed as a 1.35 kb RNA in breast cancer tissues and cell-lines, and in several normal tissues. A full length cDNA of this gene was cloned, and its DNA sequence revealed an open reading frame of 339 amino acids. Antibodies to the ten N-terminal amino acids were developed to investigate the expression of Di12 in breast cancer cell-lines and tumors. The Di12 protein was found in tissue sections of infiltrating ductal carcinomas (IDCs), but not in benign or normal breast specimens. RT-PCR analysis confirmed expression of Di12 in 80% of infiltrating ductal carcinomas (IDCs). As IDC constitutes approximately 70% of breast cancers seen clinically, the level of Di12 expression may be predictive of disease progression.     

Does restricted distribution limit access and coverage of yellow fever vaccine in the United States?

BACKGROUND: While human immunodeficiency virus (HIV)-related causes of death have been well documented in developed countries, in Africa data are scanty and mainly based on autopsy studies from city hospitals which are highly selective and may not represent causes of HIV-associated deaths in the general population. This study, from a rural population, describes the causes of death in HIV-positive people and their HIV-negative controls. METHODS: A natural history cohort comprising HIV-1 infected participants and HIV-negative controls was established in rural Uganda in 1990. Causes of death were determined by reviewing the premorbid clinical and laboratory findings and from information obtained from relatives. Blindness to the deceased's HIV serostatus was maintained throughout. RESULTS: In all, 78 deaths occurred over a 6-year period: 63 deaths occurred in the HIV-positive cases (53 prevalent and 10 incident cases) and 15 deaths in the HIV-negative controls. Of the prevalent cases, 56%, and 9% the incident cases enrolled died, compared with 7% of the HIV-negative controls. Of the 55 HIV-positive cases with sufficient data to establish cause of death, 52 (95%) were assessed as having HIV-associated deaths and 48 (87%) died in WHO stage 4 (AIDS). The main causes of death were wasting syndrome (31%), chronic diarrhoea (22%), cryptococcal meningitis (13%) and chest infection (11%). CONCLUSIONS: Our results represent an unbiased selection of deaths in a rural area. The HIV-positive cases have high death rates and die of HIV-related pathologies. The main causes of death reflect the WHO clinical case definition of AIDS. Cryptococcal meningitis is also a common cause of death in this population.     

External Control in Markovian Genetic Regulatory Networks

Probabilistic Boolean Networks (PBN's) have been recently introduced as a rule-based paradigm for modeling gene regulatory networks. Such networks, which form a subclass of Markovian Genetic Regulatory Networks, provide a convenient tool for studying interactions between different genes while allowing for uncertainty in the knowledge of these relationships. This paper deals with the issue of control in probabilistic Boolean networks. More precisely, given a general Markovian Genetic Regulatory Network whose state transition probabilities depend on an external (control) variable, the paper develops a procedure by which one can choose the sequence of control actions that minimize a given performance index over a finite number of steps. The procedure is based on the theory of controlled Markov chains and makes use of the classical technique of Dynamic Programming. The choice of the finite horizon performance index is motivated by cancer treatment applications where one would ideally like to intervene only over a finite time horizon, then suspend treatment and observe the effects over some additional time before deciding if further intervention is necessary. The undiscounted finite horizon cost minimization problem considered here is the simplest one to formulate and solve, and is selected mainly for clarity of exposition, although more complicated costs could be used, provided appropriate technical conditions are satisfied.     

Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung carcinoma

BACKGROUND: Intrathecal injection of local anesthetic agents is associated frequently with hypotension. Conversely, intrathecal administration of neostigmine increases blood pressure by enhancing the accumulation of acetylcholine in the spinal cord. The current study examined directly the interaction of intrathecal injection of bupivacaine and neostigmine on splanchnic sympathetic efferent nerve activity. METHODS: Experiments were performed in rats with intrathecal catheters implanted for the long-term. Rats were anesthetized with ketamine (40 mg/kg, intramuscularly) and alpha-chloralose (60 mg/kg, intraperitoneally). The skin incision sites were infiltrated with 1% lidocaine. Sympathetic efferent activity was recorded from the left greater splanchnic nerve. Sympathetic nerve activity was measured continuously before and after intrathecal injection of saline, 430 nmol (140 microg) of bupivacaine, 25 nmol (7.6 microg) of neostigmine, and a combination of bupivacaine and neostigmine all in volumes of 5 microl. Each group consisted of six animals. RESULTS: Compared with baseline nerve activity, intrathecal injection of neostigmine increased splanchnic sympathetic nerve activity significantly by (mean +/- SEM) 112 +/- 29% after an onset latency of 6.8 +/- 0.9 min. In contrast, bupivacaine decreased splanchnic nerve activity significantly (-65 +/- 13%) after a latency of 3.3 +/- 0.5 min after intrathecal administration. Similar to the effect of saline, intrathecal coadministration of bupivacaine and neostigmine did not alter the splanchnic sympathetic nerve activity significantly. CONCLUSIONS: The current study provides electrophysiologic evidence that intrathecal injection of neostigmine increases whereas bupivacaine decreases sympathetic nerve activity. Further, addition of neostigmine effectively counteracts the inhibitory effect of spinal bupivacaine on the sympathetic nerve activity.     

Healthy behaviors among women in the United States and Ontario: the effect on use of preventive care

OBJECTIVES: This study examined how several healthy behaviors among women in Ontario and the United States explained (1) the use of preventive health services, (2) differences in use between socioeconomic groups, and (3) differences in use between the two health systems. METHODS: 1990 data on women from the Ontario Health Survey (n = 22,985) and the US National Health Interview Survey (n = 19,092) were analyzed. A woman who avoided smoking and obesity, used seatbelts, and regularly engaged in aerobic exercise was defined as having a healthy lifestyle. Women were considered screened if they reported a mammogram or a breast exam within the previous year or a Pap smear within 2 years. RESULTS: A healthy lifestyle was more common in the United States than Canada among more highly educated groups (odds ratio [OR] = 1.40; 95% confidence interval [CI] = 1.22, 1.60 for college educated) but less common in the United States for those with less than a high school education (OR = 0.52; 95% CI = 0.40, 0.67). Each additional unhealthy behavior decreased the odds of having undergone a mammogram in the previous year by 20%. However, adjusting for the number of unhealthy behaviors did not substantially change the relationship between socioeconomic status and use of preventive services. CONCLUSIONS: The number of healthy behaviors is an important measure of demand for preventive health services. This measure varies across country and socioeconomic group.     

Sex pheromone activity in a single component of tergal gland extract ofLutzomyia longipalpis (Diptera: Psychodidae) from Jacobina,Northeastern Brazil

The sex pheromone component of maleLutzomyia longipalpis tergal gland extract was isolated and its activity confirmed by bioassay. Whole tergal gland extract was analyzed by HPLC and fractions were collected as they eluted from the detector. Each fraction was tested in an attraction bioassay with virgin unfed femaleLutzomyia longipalpis. HPLC analysis showed that whole extract contained several peaks; one large peak, one small peak and several minor peaks. Purity of the HPLC fractions was determined by GC analysis. The bioassays revealed that the large peak was responsible for most of the observed female behavior. The addition of the small peak to the large peak improved the response although by itself the small peak failed to elicit any significant behavior. Minor peaks failed to elicit any response. Chemical analysis revealed the large peak to be a relatively nonpolar hydrocarbon.     

The effect of soil P sorption properties and phosphorus fertiliser application strategy on ‘incidental’ phosphorus fertiliser characteristics: a laboratory study

The application of phosphorus (P) fertilisers to grazed pasture systems can increase the export of P in surface runoff. This increase can arise from interaction of recently applied fertiliser P with surface runoff (incidental effects) or the interaction between pseudo-equilibrated soil P and surface runoff (systematic effects). The former can represent a large proportion of annual exports. In this paper we investigate the effect of soil P buffering properties and fertiliser application strategy—split versus single applications—on incidental fertiliser effects, using laboratory studies. We used a weak electrolyte solution as a surrogate measure of runoff P and consequently defined ‘fertiliser half-life’ for six soils with widely differing P buffering properties. There was a significant (P < 0.01) exponential decay relationship between soil P buffering and fertiliser half life. For soils with low P buffering capacity, fertiliser half life was up to ~4 days, whereas for highly P buffered soils the half life was <0.5 day. There was also a highly significant (P < 0.01) effect of P buffering capacity on the magnitude of the incidental fertiliser effect, with the magnitude increasing as P buffering decreased. On one of our soils with buffering properties typical of soils used for dairying in SE Australia, we compared the effect on soluble P of a single application of 40 kg P ha⁻¹ with three applications of 13 kg P ha⁻¹. A simple comparative measure of the risk associated with the two fertiliser strategies—the area under the time by concentration curves—suggests that there is greater risk with a single application. Our results show that particular attention should be paid to timing of P fertiliser application on poorly buffered soils.     

A dynamic broadband reflector built from microscopic silica spheres in the ‘disco’ clam Ctenoides ales

The ‘disco’ or ‘electric’ clam Ctenoides ales (Limidae) is the only species of bivalve known to have a behaviourally mediated photic display. This display is so vivid that it has been repeatedly confused for bioluminescence, but it is actually the result of scattered light. The flashing occurs on the mantle lip, where electron microscopy revealed two distinct tissue sides: one highly scattering side that contains dense aggregations of spheres composed of silica, and one highly absorbing side that does not. High-speed video confirmed that the two sides act in concert to alternate between vivid broadband reflectance and strong absorption in the blue region of the spectrum. Optical modelling suggests that the diameter of the spheres is nearly optimal for scattering visible light, especially at shorter wavelengths which predominate in their environment. This simple mechanism produces a striking optical effect that may function as a signal.