Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro.

Recent studies indicate that a rare population of primitive quiescent BCR-ABL(+) cells are innately insensitive to imatinib mesylate (IM) and persist after IM therapy of patients with chronic myeloid leukemia (CML). New approaches to the eradication of these cells are therefore likely to be crucial to the development of curative therapies for CML. We have now found that Ara-C, LY294002 (a PI-3 (phosphatidylinositol-3' kinase) kinase inhibitor), 17AAG (a heat-shock protein (HSP)-90 antagonist) and lonafarnib (a farnesyltransfease inhibitor) all enhance the toxicity of IM on K562 cells and on the total CD34(+) leukemic cell population from chronic phase CML patients.

A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients.

A blinded prospective study was performed to determine whether screening of whole blood using a real-time, panfungal polymerase chain reaction (PCR) technique could predict the development of invasive fungal infection (IFI) in immunocompromised haemato-oncology patients. In all, 78 patients (125 treatment episodes) were screened twice weekly by real-time panfungal PCR using LightCyclertrade mark technology. IFI was documented in 19 treatment episodes (five proven, three probable and 11 possible), and in 12, PCR was sequentially positive.

Successful haemopoietic stem cell transplantation does not correct mannan-binding lectin deficiency.

It has been reported that in allogeneic stem cell transplantation, the mannan-binding lectin (MBL) status of the donor has prognostic value for the recipient. Two MBL-deficient patients, with coexisting haematological malignancy, were identified who were treated with bone marrow from donors with normal MBL concentrations. Although both patients engrafted successfully and remain in complete remission, neither seroconverted to the MBL sufficiency status of his donor over a follow-up period exceeding 2 years.

The role of ultrasound-guided fine-needle aspiration biopsy in the previously treated patient with thyroid cancer.

The aim of the present study was to evaluate the effectiveness of ultrasound-guided fine-needle aspiration in detecting locoregional recurrence in previously treated patients with thyroid cancer. A retrospective analysis of ultrasound-guided fine-needle aspiration (FNA) biopsy was carried out for suspected recurrence of thyroid cancer over a 5-year period at a single institution. There were 37 biopsies in 37 patients.

Differentiated thyroid cancer: radioiodine following lobectomy - a clinical feasibility study.

The surgical management of differentiated thyroid cancer remains controversial. Total thyroidectomy has been associated with higher rates of post-operative morbidity than more conservative surgery, but radioiodine ablation of residual thyroid tissue is considered to be particularly difficult after lobectomy. The purpose of this retrospective study was to assess the feasibility of 131I ablation after lobectomy, compared with total thyroidectomy, in patients who had undergone surgery for differentiated thyroid carcinoma.

Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial.

Context: Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug.

Objective: To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia.

Design And Setting: Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers.

Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control.

Background: The regression of clinical basal cell carcinoma (BCC) after photodynamic therapy (PDT) is poorly understood, but is potentially important when, as is increasingly the case, a second treatment is contemplated. High-frequency pulsed ultrasound provides noninvasive information on skin and lesion thickness.

Objectives: To relate pulsed ultrasound measurements before and after PDT to the probability of local control of BCC by PDT.

No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections.

Chemotherapy causes neutropenia and an increased susceptibility to infection. Recent reports indicate that mannan-binding lectin (MBL) insufficiency is associated with an increased duration of febrile neutropenia and incidence of serious infections following chemotherapy for haematological malignancies. We aimed to confirm or refute this finding and to extend the investigation to the plasma ficolins, P35 (L-ficolin) and the Hakata antigen (H-ficolin).

Genes to genetic immunization: identification of bacterial vaccine candidates.

Pathogenic bacteria still represent a major threat to human health worldwide and the need for new vaccines is great. Virulence factors, particularly surface-located molecules, often make good vaccine targets because they are essential for access to their niche within the host. The advent of whole-genome sequencing of bacterial pathogens has revolutionized the methods by which these organisms are studied and provides us with the possibility of identifying potential targets for vaccines by sequence scanning alone.

Differentiation potential of a mouse bone marrow stromal cell line.

In order to study osteoblast differentiation we subcloned a cell derived from a mouse a bone marrow stromal cell line, Kusa O, and obtained a number of clones representative of three different phenotypes. One that neither differentiated into osteoblasts nor into adipocytes, a second that differentiated into osteoblasts but not adipocytes, and a third that differentiated into both osteoblasts and adipocytes. Four subclones were selected for further characterization according to their ability to mineralize and/or differentiate into adipocytes.

Molecular detection and beta-glucuronidase expression of gus-marked Bacillus subtilis L-form bacteria in developing Chinese cabbage seedlings.

Aim: To detect L-form bacteria in developing Chinese cabbage seedlings.

Methods And Results: Stable Bacillus subtilis L-forms were genetically modified to express the gus gene (encoding beta-glucuronidase). Germinated seeds of Chinese cabbage were soaked in mannitol based suspensions of the L-form bacteria or with mannitol alone and after washing were grown in aseptic conditions on plant growth medium.

Non-invasive pulsed ultrasound quantification of the resolution of basal cell carcinomas after photodynamic therapy.

The probability of local control of basal cell carcinomas (BCC) treated by photodynamic therapy (PDT) depends strongly on lesion thickness, thicker lesions often requiring two treatments. We examine the utility of 20 MHz pulsed ultrasound (US) for the non-invasive measurement of thickness and rate of regression after PDT treatment. PDT was by topically applied 20% aminolaevulinic acid, followed at 6 h by a standard 100 J/cm(2) of 630 nm light.

Identification of N-acetylgalactosamine-containing glycoproteins PEB3 and CgpA in Campylobacter jejuni.

It was demonstrated recently that there is a system of general protein glycosylation in the human enteropathogen Campylobacter jejuni. To characterize such glycoproteins, we identified a lectin, Soybean agglutinin (SBA), which binds to multiple C. jejuni proteins on Western blots.

The symbiosis of Bacillus subtilis L-forms with Chinese cabbage seedlings inhibits conidial germination of Botrytis cinerea.

Aims: To establish whether germination of Botrytis cinerea was affected by the symbiosis of Bacillus subtilis L-form bacteria with Chinese cabbage.

Methods And Results: Germinating seeds of Chinese cabbage were co-cultivated with either L-forms of Bacillus subtilis or 5% (w/v) mannitol by soaking for 3 h. Seeds were then washed in sterile water, sown on a minimal medium and incubated in controlled conditions.

Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI571.

Despite the efficacy of STI571 (Glivec, Novartis, Basle, Switzerland) in treating chronic myeloid leukemia (CML), drug resistance has already been noted both in vitro and in vivo. As plasma proteins, including alpha-1-acid glycoprotein (AGP), may reduce drug efficacy through binding, AGP was investigated for its ability to interact with STI571. At all stages of CML, AGP plasma level was significantly higher than in normal controls (P <.

Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro.

In clinical trials, the tyrosine kinase inhibitor STI571 has proven highly effective in reducing leukemic cell burden in chronic myeloid leukemia (CML). The overall sensitivity of CML CD34(+) progenitor cells to STI571 and the degree to which cell death was dependent on cell cycle status were determined. Stem cells (Lin(-)CD34(+)) from the peripheral blood of patients with CML in chronic phase and from granulocyte-colony-stimulating factor-mobilized healthy donors were labeled with carboxy-fluorescein diacetate succinimidyl diester dye to enable high-resolution tracking of cell division.

Community perception of school-based delivery of anthelmintics in Ghana and Tanzania.

This paper presents the results of an evaluation of community perception of two large-scale, government-run, school-based health programmes delivering anthelmintic drugs to primary school children, in Ghana (80 442 children in 577 schools) and Tanzania (110 000 children in 352 schools). Most teachers (96% in Ghana and 98% in Tanzania) were positive about their role in the programme, including administration of anthelmintic drugs, and parents and children fully accepted their taking on this role. The benefits of the programme were apparent to teachers, parents and children in terms of improved health and well-being of the children.

Characterization of the low-pH responses of Helicobacter pylori using genomic DNA arrays.

Helicobacter pylori is unique among bacterial pathogens in its ability to persist in the acidic environment of the human stomach. To identify H. pylori genes responsive to low pH, the authors assembled a high-density array of PCR-amplified random genomic DNA.

The potential biocontrol agent Pseudomonas antimicrobica inhibits germination of conidia and outgrowth of Botrytis cinerea.

Aims: Antifungal metabolites of Pseudomonas antimicrobica have previously been shown to inhibit conidial germination of the grey mould pathogen Botrytis cinerea. In this study, metabolites of the bacterium have been tested at different stages of Botrytis germination to determine their effects on germ tube production and extension.

Methods And Results: Metabolites were added to conidia that had been pre-incubated for either 120 or 255 min.

Induction, growth and antibiotic production of Streptomyces viridifaciens L-form bacteria.

Aims: To induce, cultivate and investigate the characteristics of L-form bacteria derived from the filamentous actinomycete Streptomyces viridifaciens.

Methods And Results: L-forms were induced in a liquid medium supplemented with lysozyme and penicillin. A stable culture which no longer required inducing agents but could still revert, was obtained by the twelfth subculture.

An ELISA for the detection of Bacillus subtilis L-form bacteria confirms their symbiosis in strawberry.

Aims: To develop an ELISA for the detection of antigens derived from stable Bacillus subtilis L-form bacteria and to detect these in plants injected with L-form bacteria.

Methods And Results: A sandwich ELISA was developed and its specificity was investigated using L-forms and cell-walled forms of B. subtilis, different Bacillus species and a range of bacteria isolated from glasshouse-grown strawberry plants.