Re-establishment of a normal apoptotic process as a therapeutic approach in B-CLL

Even though the capacity of B-CLL leukemic cells to proliferate has been underestimated until recently, the accumulation of tumor cells in patients mostly results from a defect in the apoptotic program. Several mechanisms can account for this deficient cell death pathway. These include overexpression of anti-apoptotic molecules such as members of the Bcl-2 family, which control the opening of the mitochondrial transition permeability pore, and of the IAP (inhibitors of apoptosis) family, which inhibit the activity of caspases. The latter is also suppressed by nitric oxide (NO) released through an inducible NO synthase present in the leukemic cells. The activity of the receptors with a death domain (Fas, TRAIL) is impaired, thus contributing to the resistance to spontaneous and/or drug-induced apoptosis. Interferons as well as several cytokines and angiogenic factors are also involved in the failure of programmed cell death, either by providing efficient signals for survival (BAFF) or by counteracting the apoptotic process. A better knowledge of the mechanisms of survival and escape from apoptosis of B-CLL cells has led to the proposal of new drugs that selectively interfere at the different steps of these cascades. Their study is complicated by the lack of suitable cell lines and pre-clinical models. Nevertheless, some of these chemotherapeutic agents appear to be promising, provided they are correctly targeted to the leukemic cells.     

Social and health determinants of the efficiency of cotton farmers in Northern Côte d'Ivoire

This article assesses the role of malaria and some social determinants on the agricultural development and more precisely on efficiency in the context of cotton crop in the Korhogo region in the North of C?te d'Ivoire. Data envelopment analyses (DEA) was first applied for the purpose of calculating relative efficiencies in production. A Tobit regression model was then used to explain the variation in the DEA scores and check the hypotheses that the efficiency deviations between farmers can be explained by the disparity of malaria morbidity rate among the farmers and their family, by social cohesiveness and cultural behaviour. Field data were collected by the authors between March 1997 and February 1998 on 700 rural households living in three rice production systems differently exposed to the malaria risk. Two malaria indicators were used for the active (11-55 years old) family members of the farm: Plasmodium falciparum infection rate and high parasite density infection rate. The DEA model was applied on the sub-sample of cotton growers (about one third of the households of the full sample). Results of the different DEA and Tobit models (depending of the production process hypothesis) show that high parasite density infection has a direct and indirect negative effect on efficiency in the cotton crop. They also show that more cotton growers in the village improve efficiency, although villages where cotton is growing more widespread have weaker social cohesion.     

Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants

Several mechanisms have been suggested as mediating the inhibitory influence of maternal antibodies (MatAb) on infant responses. This inhibition is B cell determinant-specific, depends on the ratio between MatAb titers at the time of immunization and the dose of vaccine antigen, and leaves infant T cell responses largely unaffected. Neutralization of vaccine replication or FcgammaRIIB-mediated inhibitory signalling to infant B cells would not account for these characteristics. In contrast, determinant-specific masking of B cell epitopes and APC uptake of MatAb:vaccine antigen immune complexes, followed by antigen processing and presentation, explain the pattern of pre-clinical and clinical responses to infant vaccines. This allows the definition of the main determinants of the influence of MatAb on infant immunity.     

Factors associated with positive HIV serostatus among women who use drugs: continued evidence for expanding factors of influence

OBJECTIVE: To identify risk factors associated with positive HIV serostatus among African American women who smoke crack and/or inject drugs and who are not enrolled in drug treatment or another institutional setting. METHODS: Baseline interviews were conducted from June 1998 to June 2000 with 379 heterosexually active women (ages 18 to 59) who had been recruited for potential enrollment into an HIV intervention trial. RESULTS: Adjusted for age and drug using status, women who expressed more difficulty saying no to sex with male partners were more likely to be HIV-positive (adjusted odds ratio [aOR]=3.08, 95% confidence interval [CI] 2.02, 4.83). Similarly, those who indicated greater communication with casual sex partner(s) were less likely to test positive (aOR=0.29, 95% CI 0.10, 0.89). Lower HIV internal control and a history of cuts or burns on lips due to crack smoking were also associated with positive serostatus, and were important confounders in the final multivariate model. A higher level of internal control was associated with a decreased likelihood of positive serostatus, while a history of cuts or burns on the lips was associated with an increased likelihood of HIV antibodies, even after controlling for the amount of oral sex. CONCLUSIONS: A broad array of factors may promote or avert infection with HIV. The degree to which personal attributes and beliefs, and relationship characteristics contribute to the likelihood of infection must continue to be addressed. The importance of oral sex and presence of oral sores and their potential role in transmission was suggested.     

Teaching physicians-in-training to address racial disparities in health: a hospital-community partnership

Racial and ethnic disparities in health care continue to be a major impediment to improving the health of many communities in the United States. Efforts must be directed at the multiple social, economic, and historic determinants of health disparities. In addition, health care providers must be aware of these determinants and must have the tools to address them in their individual relationships with patients. This article describes a partnership that arose out of the mutual recognition by a community organization and public hospital of the need to (a) teach physicians how to recognize the root causes of health disparities, (b) improve their cross-cultural understanding and communication, and (c) enhance their awareness of the capacity of community resources to positively impact their patients' lives.     

Sequential bio- and phototransformation of the herbicide methabenzthiazuron in water

We investigated the transformation of methabenzthiazuron in water by microorganisms and solar light. This compound was very slowly phototransformed when irradiated at lambda > 290 nm, but it could be successfully oxidized into 6-hydroxymethabenzthiazuron by Aspergillus niger, as shown by nuclear magnetic resonance experiments. The toxicity of this metabolite, as determined by the standardized Microtox test, was sixfold lower than that of the parent molecule. The 6-hydroxymethabenzthiazuron was not further metabolized by A. niger but was photooxidized with ring cleavage of the aromatic ring and photodimerized on irradiation at lambda > 290 nm. In the presence of humic substances, the photodegradation was slower. We demonstrate that the transformations of methabenzthiazuron, observed either with the fungus A. niger or by the action of solar light, do not proceed via the urea chain N-dealkylation, as usually reported, but only via hydroxylation or cleavage of the benzene ring. This work shows the complementarity of both approaches, photo- and biodegradation, to study the fate of herbicides in the environment.     

Who's getting the message? Intervention response rates among women who inject drugs and/or smoke crack cocaine

BACKGROUND: Injection drug users (IDUs) who also smoke crack may be at greatest risk for infection with HIV as well as other blood-borne and sexually transmitted infections and in most need of positive behavioral changes. METHODS: Three hundred and thirty-three women (aged 18-59 years) were randomly assigned to one of two enhanced gender- and culturally specific HIV intervention conditions or to the NIDA standard condition. Of primary interest in this study were baseline risk and intervention response rates among three groups of drug users--IDUs who did not smoke crack, IDUs who did smoke crack, and crack smokers who did not inject. Univariate and multivariate methods were utilized, including generalized estimating equations. RESULTS: The intervention produced positive behavioral changes over time, but response rates varied according to drug using group. Overall, women falling into the crack smoking IDU category appeared to be less responsive to the intervention than those in the other drug using groups, and participants in the crack smoking only group were less responsive than those in the IDU only group. CONCLUSIONS: Results presented here indicate the continuing need to develop and target effective interventions to particular subgroups of high-risk individuals who may be most resistant to change.