Complete remission in a patient with acute myelogenous leukemia treated with leukocyte α-interferon and cimetidine

Summary A 76-year-old woman with acute myelogenous leukemia with approximately 65% myeloblasts on bone marrow examination was treated daily with a combination of 4 megaU of leukocyte interferon IM and 1,000 mg cimetidine PO. During therapy there was a gradual decrease of bone marrow myeloblasts down to 9% and a normalization of peripheral white blood cells. The treatment was discontinued after 6 weeks because of increasing fatigue and anorexia. The general condition improved greatly during the following weeks and the patient entered complete remission, which has continued for 6 months so far. In the course of therapy there was a gradual appearance of antibodies showing a selective binding capacity to autochthonous leukemic cells with no tendency to increased binding to remission cells. The aim of this report is to stimulate a further evaluation of this form of therapy in additional AML patients whenever this might be justified as an alternative to conventional chemotherapy.     

Chilling outweighs photoperiod in preventing precocious spring development

It is well known that increased spring temperatures cause earlier onset dates of leaf unfolding and flowering. However, a temperature increase in winter may be associated with delayed development when species' chilling requirements are not fulfilled. Furthermore, photosensitivity is supposed to interfere with temperature triggers. To date, neither the relative importance nor possible interactions of these three factors have been elucidated. In this study, we present a multispecies climate chamber experiment to test the effects of chilling and photoperiod on the spring phenology of 36 woody species. Several hypotheses regarding their variation with species traits (successional strategy, floristic status, climate of their native range) were tested. Long photoperiods advanced budburst for one‐third of the studied species, but magnitudes of these effects were generally minor. In contrast to prior hypotheses, photosensitive responses were not restricted to climax or oceanic species. Increased chilling length advanced budburst for almost all species; its effect greatly exceeding that of photoperiod. Moreover, we suggest that photosensitivity and chilling effects have to be rigorously disentangled, as the response to photoperiod was restricted to individuals that had not been fully chilled. The results indicate that temperature requirements and successional strategy are linked, with climax species having higher chilling and forcing requirements than pioneer species. Temperature requirements of invasive species closely matched those of native species, suggesting that high phenological concordance is a prerequisite for successful establishment. Lack of chilling not only led to a considerable delay in budburst but also caused substantial changes in the chronological order of species' budburst. The results reveal that increased winter temperatures might impact forest ecosystems more than formerly assumed. Species with lower chilling requirements, such as pioneer or invasive species, might profit from warming winters, if late spring frost events would in parallel occur earlier.     

A microcalorimetric vessel for monitoring cytotoxic reactions in the micro-submicrowatt region

A microcalorimetric vessel for monitoring the initial phases of cytotoxic reactions in the micro-submicrowatt region has been designed and tested. The vessel is intended to be used with a multichannel microcalorimetric system from Thermometric, J?rf?lla, Sweden and can be built up stepwise in a modular way. The different functions of perfusion, stirring and addition of small amounts of soluble immune reactants can be used separately but also in combination. This is accomplished by the use of a vertical stirring mechanism and a reaction vessel of low volume, 200 microliters. The simplicity of the vessel permits an identical vessel to be used on the reference side, handled in parallel with the measuring vessel. No gas phase is present.     

Club cell protein (CC16) in plasma,bronchial brushes,BAL and urine following an inhaled allergen challenge in allergic asthmatics

Background: Club cell protein (CC16) is a pneumoprotein secreted by epithelial club cells. CC16 possesses anti-inflammatory properties and is a potential biomarker for airway epithelial damage. We studied the effect of inhaled allergen on pulmonary and systemic CC16 levels.

Methods: Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Bronchoscopy with bronchoalveolar lavage (BAL) and brushings was performed before and 24?h after the challenge. CC16 was quantified in BAL and CC16 positive cells and CC16 mRNA in bronchial brushings. CC16 was measured in plasma and urine before and repeatedly after the challenge. Thirty subjects performed a mannitol inhalation challenge prior to the allergen challenge.

Results: Compared to baseline, CC16 in plasma was significantly increased in all subjects 0–1?h after the allergen challenge, while CC16 in BAL was only increased in subjects without a late allergic response. Levels of CC16 in plasma and in the alveolar fraction of BAL correlated significantly after the challenge. There was no increase in urinary levels of CC16 post-challenge. Mannitol responsiveness was greater in subjects with lower baseline levels of CC16 in plasma.

Conclusions: The increase in plasma CC16 following inhaled allergen supports the notion of CC16 as a biomarker of epithelial dysfunction.     

First flowering of wind‐pollinated species with the greatest phenological advances in Europe

Increasing risk of pollinosis (hay fever) is one of the most anticipated consequences of climate change on human health. Wind‐pollinated plants are representative of allergenic species because they include species with the highest capability of causing allergy‐related diseases in humans. Therefore, changes in wind‐pollinated species may reflect impacts of climate change on allergenic plants. In particular, flowering is one of the developmental stages most affected by climate change. This report specifically addresses changes in flowering dates that have occurred during the three decades 1971–2000 as a function of pollination mode and woodiness. The assessment is made using a phenological data set comprising trends of flowering dates of 29 species in 983 locations in Europe. Linear mixed models assessing the statistical significance of trends while adjusting for spatial correlation are used. The main results indicate for the first time that the onset of flowering of wind‐pollinated plants advanced more than for insect‐pollinated plants, while full flowering phases tended to advance less. These novel findings are contrary to the results of Fitter and Fitter (2002) for Oxfordshire, who reported larger advances of insect‐pollinated plants. Onset of flowering and full flowering of insect‐pollinated species are more likely to advance for seasons early in the year; instead, wind‐pollinated plants showed no dependence of trends on the season (first flowering) or a decreased advance of phases that are early in the year (full flowering). The effect of woodiness could not be unambiguously defined, but seems to be of minor importance. The presented findings suggest a lengthening of the flowering period in general, which might lead to an increasing time of exposure to airborne pollen of allergic subjects, with consequent likely increment in severity and incidence of allergic symptoms.     

Updating risk prediction tools: a case study in prostate cancer

Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision-making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [-2]proPSA measured on an external case-control study performed in Texas, U.S.. Recent state-of-the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network.     

Cytotoxicity of Adenovirus-Antibody Aggregates: Sensitivity to Different Cell Strains, and Inhibition by Hexon Antiserum and by Complement

Adenovirus-antibody aggregates under defined conditions are cytotoxic in vitro. All members of adenovirus groups I, II, and III caused toxicity upon aggregation. The toxicity of the clusters is exerted by the virions. Toxicity is temperature dependent and may be caused by a mechanism similar to that used in viral penetration. Cells permitting direct viral penetration were all sensitive to the toxic aggregates. The toxicity seems to be related to hexon antigens on the surface of the virions since antihexon sera neutralized the toxicity. No evidence was obtained showing that pentons are required for this kind of cytotoxicity. Adenovirus types 3, 5, and 9 were used in the experiment. Cytotoxicity was estimated by the (51)Cr release assay. Complement factors could be excluded as mediators of the cytolytic reactions. Instead, complement was shown to prevent the formation of toxic aggregates or to neutralize the toxicity of preformed ones.     

Association of the MC4R V103I polymorphism with the metabolic syndrome: the KORA Study

Objective: Epidemiological studies showing an association between the melanocortin‐4‐receptor (MC4R) 103I variant (rs2229616) and decreased BMI are complemented by functional studies; these suggest a mechanism for appetite regulation and a linkage signal for physical activity and dietary intake for the region encompassing the MC4R. This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators. Methods and Procedures: We analyzed this polymorphism in 7,888 adults of a population‐based cross‐sectional study applying regression‐based statistical models. Results: Carriers of the MC4R 103I (3.7%) exhibited a significantly decreased waist circumference (–1.46 cm, P = 0.020), decreased glycosylated hemoglobin (HbA_1c) (–0.09%, P = 0.040), and increased HDL‐cholesterol (HDL‐C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of MC4R 103I (odds ratio (OR) = 0.46, P = 0.003). Controlling for BMI reduced the HbA_1c and HDL‐C association. Mediator analyses revealed a borderline association of MC4R 103I with carbohydrate intake (OR = 1.26, P = 0.059) possibly mediating association with leanness. Discussion: Our representative study of well‐phenotyped Europeans is the first to describe the association of the MC4R V103I with the metabolic syndrome and with a nutrient‐related phenotype. Our data support the idea that this polymorphism plays a role in appetite regulation that not only affects BMI, but also other features of the metabolic syndrome. It further establishes that the association of the MC4R V103I with obesity and related phenotypes is genuine.