The activity of the high-affinity K+ uptake system Kdp sensitizes cells of Escherichia coli to methylglyoxal

Expression of the Kdp system sensitizes cells to methylglyoxal (MG) whether this electrophile is added externally or is synthesized endogenously. The basis of this enhanced sensitivity is the maintenance of a higher cytoplasmic pH (pHi) in cells expressing Kdp. In such cells, MG elicits rapid cytoplasmic acidification via KefB and KefC, but the steady-state pHi attained is still too high to confer protection Lowering pHi further by incubation with acetate increases the sensitivity of cells to MG.     

Causes of death in Canadians with haemophilia 1980-1995. Association of Hemophilia Clinic Directors of Canada

The life expectancy of individuals with haemophilia was close to that of the general population in the early 1980s. Since then, life expectancy has decreased, due to transfusion-transmitted virus infections. Deaths in individuals with haemophilia were investigated by analysing 2450 records from the Canadian Hemophilia Registry, for the years 1980-1995. Deaths were tabulated by age, year and cause, and compared with that of the Canadian male population by calculating standardized mortality ratios (SMRs). The median life expectancy at 1 year of age was calculated for various subpopulations and the impact of various population characteristics was assessed by survival regression modelling. There were 359 deaths and the annual number of deaths increased significantly after 1986. Risk factors were seropositivity to human immunodeficiency virus (relative risk 16.7, 95% CI 11.1-25.1), severe haemophilia (1.9, 1.3-2.7) and moderate haemophilia (1.8, 1.2-2.6). In HIV antibody negative individuals, the overall death rate was not increased (SMR 0.9, 95% CI 0.7-1.1) and only haemorrhage was significantly increased. In HIV antibody positive individuals, causes of death which were significantly increased were acquired immunodeficiency syndrome, liver failure, haemorrhage, lymphoma, liver cancer, nonspecific infections, and trauma or violence. Deaths due to the acquired immunodeficiency syndrome accounted for only 66% of the excess deaths in individuals who were HIV antibody positive. Life expectancy has markedly decreased since the onset of the HIV epidemic. The impact of HIV is underestimated by considering only deaths due to the acquired immunodeficiency syndrome; other HIV-linked causes need also to be considered.     

'Rescue' after failed thrombolysis for acute myocardial infarction

Prompt restoration of coronary artery patency in acute myocardial infarction is associated with substantial improvements in morbidity and mortality. The pivotal role of thrombolysis and aspirin in achieving these goals is well established. However, despite the success of thrombolytic therapy in large trials, clinical assessment in individual patients often suggests that reperfusion has not occurred after initial therapy. This review considers the validity of such bedside predictions and discusses whether such patients should be managed differently.     

Imaging of abdominal manifestations of melanoma

Despite an increasing incidence of melanoma in this country, innovative new therapies are allowing patients to receive aggressive experimental treatments. Diagnostic imaging remains crucial for tumor staging and for follow-up of patients being treated with these protocols. Because metastases occur in the abdomen and pelvis in approximately 60% of patients, it is important to accurately identify all sites of tumor spread. A variety of imaging techniques are used to image these patients, with CT currently being used for staging purposes and to guide diagnostic biopsies. Other imaging techniques, such as MR, ultrasound, and fluoroscopy, are currently reserved for investigating specific complications of melanoma, such as vascular invasion, hemorrhage from a tumor, and small bowel involvement, including intussusception. Recently, whole body positron emission tomography (PET) imaging using 2-deoxy-2-fluoro-D-glucose (FDG) has been shown to be highly accurate in assessing patients with metastatic malignant melanoma. This review illustrates the spectrum of manifestations of metastatic melanoma throughout the abdomen and pelvis, including solid organ, hollow lumen, and retroperitoneal involvement, and demonstrates some of the typical and atypical manifestations that may be identified.     

IL-7 overexpression in transgenic mouse keratinocytes causes a lymphoproliferative skin disease dominated by intermediate TCR cells: evidence for a hierarchy in IL-7 responsiveness among cutaneous T cells

IL-7 is a keratinocyte-derived lymphocyte growth factor critical for the development of gammadelta T cells including murine dendritic epidermal T cells (DETC). We derived transgenic mice that overexpress IL-7 in basal keratinocytes under the control of the human K14 promoter. These K14/IL-7 mice develop dermal and epidermal T cell infiltrates associated with alopecia. This lymphoproliferative skin disease is substantially more severe in mice homozygous for the K14/IL-7 transgene. Conventional DETC expressing a Vgamma5 Vdelta1 TCR are rare or absent among the cutaneous T cells in these mice. The T cells in the skin infiltrates of young K14/IL-7 mice are predominantly gammadelta T cells that express intermediate levels of TCR, are negative for E-cadherin, often lack expression of CD2, and include cells that coexpress NK1.1. T cells expressing intermediate levels of a TCR-alphabeta are also present in transgenic skin, and progressively increase in number as the mice age. Phenotypically similar intermediate gammadelta and alphabeta T cell subsets also constitute the major lymphocyte populations recovered from organ culture of normal mouse skin in the presence of IL-7, suggesting that the T cells that accumulate in the epidermis of K14/IL-7 mice are derived from precursors normally resident in skin. We conclude that intermediate TCR cells, some of which coexpress NK1.1, can be selectively expanded in skin under the influence of IL-7 produced locally. Our results also suggest that features of the epidermal microenvironment besides keratinocyte-derived IL-7 account for the normal predominance of Vgamma5 Vdelta1 DETC in mouse epidermis.     

Influence of carcinogen binding by lactic acid-producing bacteria on tissue distribution and in vivo mutagenicity of dietary carcinogens

The aims of this investigation were to determine whether viable cultures of lactic acid-producing organisms (LAB) can bind dietary carcinogens and to assess the consequences of binding for the absorption from the gut, distribution in the body and in vivo genotoxicity of ingested carcinogens. The carcinogens used in this study were ones known to be present in the human diet, namely benzo[a]pyrene (B(a)P, aflatoxin B1 (AFB1) and the cooked food carcinogens 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 5-phenyl-2-amino-1-methylimidazo [4,5-f]pyridine (PhIP) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). They represent a range of structural types so that the specificity of any binding effects could be addressed. Of the carcinogens tested, B(a)P and Trp-P-2 were bound most effectively by the two LAB strains Bifidobacterium longum and Lactobacillus acidophilus. AFB1 was poorly bound, while MeIQx, MeIQ, PhIP and IQ were bound to an intermediate degree. The extent of the binding of the heterocyclic amine carcinogens was dependent on the pH conditions during incubation and this effect was more apparent with B. longum than with L. acidophilus. Using the host-mediated assay (HMA), an in vivo bacterial mutation assay, it was demonstrated that the administration of bacterial cell suspensions of B. longum and L. acidophilus did not lead to a reduction in induced mutagenicity by MeIQ, MeIQx or Trp-P-2, detectable in the liver of treated mice compared with controls. The lack of a protective effect could not be attributed to a short period of contact between bacterial cells and mutagens, since similar results were obtained after preincubating bacteria and mutagens together at pH 5 for 50-60 min, to maximize the binding, before gavaging the mice. Lack of activity of B(a)P in the HMA prevented the determination of the effect of LAB on genotoxicity of the polycyclic aromatic hydrocarbon. However, it is clear from the radiolabel distribution study that the amount of the carcinogen entering the blood was not significantly reduced by B. longum administration. In addition, the amount of radiolabelled B(a)P that reached the target organs (liver, lungs and heart) was also not affected by the LAB administration. A similar lack of inhibitory effect of B. longum on blood concentration and accumulation in the liver of Trp-P-2 was apparent. The results of the present study suggest that although LAB may bind carcinogens in vitro, this does not lead to major changes in absorption and distribution of carcinogens in the body, or in their genotoxic activity in the liver.     

Do vaginal lactobacilli prevent preterm labour?

OBJECTIVE: To determine the prevalence of Lactobacillus spp. in vaginal flora during pregnancy and to assess the protective effects of lactobacilli against preterm labour. DESIGN: Cross-sectional analysis of Lactobacillus spp. in the vaginal flora of the pregnant coloured population of the Western Cape. PARTICIPANTS: A total of 480 consecutive pregnant women, aged 13-48 years, seen at their first visit to the Tygerberg Hospital antenatal clinic. MAIN OUTCOME MEASURES: Preterm labour, i.e. before 34 and 37 weeks' gestation, premature rupture of membranes, intra-uterine growth retardation and perinatal deaths. RESULTS: A total of 163 patients had negative cultures and 317 positive cultures for lactobacilli, aerobes or both. Delivery before 37 weeks occurred in 18% and 20% of the two groups, respectively. Lactobacillus only was cultured from 116 patients and Lactobacillus and/or other aerobes from 201 patients. Preterm labour occurred in 20% of the first group and in 19% of the second group. The perinatal outcome in patients from whom lactobacilli only were cultivated did not differ from patients from whom other aerobes and lactobacilli or other aerobes only were cultured. CONCLUSION: In patients at high risk for preterm labour, the presence of lactobacilli in the vagina does not seem to play a protective role.