A Hodgkin cell-specific antigen is expressed on a subset of auto- and alloactivated T (helper) lymphoblasts

A Hodgkin cell-specific antigen detected by the monoclonal antibody Ki- 1 was found on T helper lymphocytes after activation by autologous and allogeneic stimulator cells. About 50% of lymphoblasts generated by auto- and alloactivation reacted with the antibody. In contrast, only less than 6% of lymphoblasts stimulated with Con-A, phytohemagglutinin (PHA), or protein A, and none of lymphoblasts activated by oxidative mitogenesis, expressed this antigen. Among several permanent cell lines tested, the K562, MOLT-4, HL-60, and EBV transformed B lymphoblastoid cells reacted with the Ki-1 antibody. The results may indicate possible relationships between the autoreactive subset of T lymphocytes and the pathogenesis of Hodgkin's disease.     

Abnormal function of the bone marrow microenvironment in chronic myelogenous leukemia: role of malignant stromal macrophages

The bone marrow microenvironment supports and regulates the proliferation and differentiation of hematopoietic cells. Dysregulated hematopoiesis in chronic myelogenous leukemia (CML) is caused, at least in part, by abnormalities in CML hematopoietic progenitors leading to altered interactions with the marrow microenvironment. The role of the microenvironment itself in CML has not been well characterized. We examined the capacity of CML stroma to support the growth of long-term culture-initiating cells (LTC-IC) obtained from normal and CML marrow. The growth of normal LTC-IC on CML stroma was significantly reduced compared with normal stroma. This did not appear to be related to abnormal production of soluble factors by CML stroma because normal LTC- IC grew equally well in Transwells above CML stroma as in Transwells above normal stroma. In addition, CML and normal stromal supernatants contained similar quantities of both growth-stimulatory (granulocyte colony-stimulating factor (CSF), interleukin-6, stem cell factor, granulocyte-macrophage CSF, and interleukin-1 beta) and growth- inhibitory cytokines (transforming growth factor-beta, macrophage inflammatory protein-1 alpha, and tumor necrosis factor-alpha). The relative proportion of different cell types in CML and normal stroma was similar. However, polymerase chain reaction and fluorescence in situ hybridization studies showed the presence of bcr-abl-positivo cells in CML stroma, which were CD14+ stromal macrophages. To assess the effect of these malignant macrophages on stromal function, CML and normal stromal cells were separated by fluorescence-activated cell sorting into stromal mesenchymal cell (CD14-) and macrophage (CD14+) populations. CML and normal CD14- cells supported the growth of normal LTC-IC equally well. However, the addition of CML macrophages to normal or CML CD14- mesenchymal cells resulted in impaired progenitor support. This finding indicates that the abnormal function of CML bone marrow stroma is related to the presence of malignant macrophages. In contrast to normal LTC-IC, the growth of CML LTC-IC on allogeneic CML stromal layers was not impaired and was significantly better than that of normal LTC-IC cocultured with the same CML stromal layers. These studies demonstrate that, in addition to abnormalities in CML progenitors themselves, abnormalities in the CML marrow microenvironment related to the presence of malignant stromal macrophages may contribute to the selective expansion of leukemic progenitors and suppression of normal hematopoiesis in CML.     

The effect of three human recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony- stimulating factor, and interleukin-3) on phagocyte oxidative activity

Hematopoietic growth factors not only modulate blood progenitor cell activity but also alter the function of mature phagocytes. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 1 ng/mL for 60 min) did not stimulate luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMNs) in suspension but primed PMN for as much as a 15-fold increase in chemiluminescence in response to f-met- leu-phe (fMLP). Mixed mononuclear leukocytes (monocytes [approximately 20%] and lymphocytes [approximately 80%]; MNL) chemiluminescence was very low even after rhGM-CSF priming, but MNLs added to the PMNs (PMN- MNL) resulted in near doubling of rhGM-CSF-primed PMN fMLP-stimulated chemiluminescence. The enhancing factor(s) from MNLs were inherent rather than induced by the GM-CSF, and purified lymphocytes increased GM-CSF-primed PMN chemiluminescence equal to mixed MNLs. We could not detect cell-free "enhancing factor(s)," but cell-to-cell contact further enhanced rhGM-CSF-primed fMLP-stimulated PMN-MNL oxidative activity by 40%. Polyclonal rabbit anti-tumor necrosis factor (TNF) (but not preimmune serum) decreased both fMLP-stimulated rhGM-CSF- primed PMNs and PMN-MNL chemiluminescence, suggesting that TNF on the PMN surface is enhancing GM-CSF-primed chemiluminescence. GM-CSF priming markedly increased PMN superoxide release (sevenfold), but PMN superoxide release was not further enhanced by the presence of MNLs. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) and interleukin-3 (rhIL-3) displayed much smaller effects on pure PMNs and mixed PMN-MNL chemiluminescence and superoxide release than rhGM-CSF. rhGM-CSF primes PMNs for increased oxidative activity more than rhG-CSF and rhIL-3. Maximal oxidative activity was observed when mixed PMN-MNL were primed with GM-CSF in a cell pellet-promoting cell-to-cell contact. This enhanced activity can be attributed, in part, to both inherent enhancing factor(s) on lymphocytes and PMN-associated TNF induced by GM-CSF.     

Feeding problems in young PKU children

Behavioural feeding problems were found to be more prevalent in a group of 15 PKU children aged 1-5 years when compared to non-PKU controls. The parents of PKU children identified poorer appetites ( p < 0.01), a more limited range of foods consumed ( p < 0.03) and more gastrointestinal symptoms such as vomiting and constipation ( p < 0.03) than control children. The children were slower to feed ( p < 0.03), were more likely to dislike sweet foods and some ate separately from the rest of the family at mealtime ( p < 0.03). The effects on normal feeding behaviour should be considered when advocating strict diet therapy for young PKU children.     

Primary-care visits and hospitalizations for ambulatory-care-sensitive conditions in an inner-city health care system.

OBJECTIVE: Hospitalizations for ambulatory-care-sensitive conditions (ACSCs) are a marker for access barriers for children and a possible outcome measure for primary-care interventions. We assessed the relationship between primary-care utilization and subsequent ACSC hospitalization among inner-city children. METHODOLOGY: We conducted a nested, case-control study of children born in 1993 in Denver Health (DH), a "safety-net" delivery system in Denver, Colo. Utilization of preventive care and other primary-care services was compared between children hospitalized for ACSCs and nonhospitalized children, who were matched by age and duration of care. Comparisons were adjusted for demographics, payer, and chronic health conditions. RESULTS: Of 2531 children, 115 (4.5%) were hospitalized for ACSCs. Sixty-eight percent were Hispanic, and 78% were enrolled in Medicaid. Children with ACSC hospitalization and nonhospitalized children made a similar number of preventive-care visits (2.7 +/- 2.0 vs 3.0 +/- 2.1 visits, P =.30) and other primary-care visits (4.4 +/- 4.6 vs 3.6 +/- 4.6, P =.16) between birth and hospitalization (for cases) or the same time period (for controls). After multivariate adjustment, each additional preventive-care visit (odds ratio = 0.87; 95% confidence interval: 0.67-1.12) was associated with a nonsignificant reduction in the risk of hospitalization for ACSC. CONCLUSIONS: Because ACSC hospitalizations are uncommon and the association between primary care and subsequent hospitalization is weak, a reduction in ACSC hospitalizations may not be a feasible outcome measure for interventions to increase the rate of preventive- or primary-care visits for underserved children within individual delivery systems.     

Evaluation of ultrasonic scaling unit waterline contamination after use of chlorine dioxide mouthrinse lavage

BACKGROUND: An infection control problem in dental operatories which is not fully controlled is waterline contamination by heterotrophic mesophilic bacteria. These bacteria are present in water supplies as a planktonic phase and adhere to the lumen of tubings as a biofilm comprised of their external cell surface glycocalyx and by production of extracellular carbohydrate polymers. The adherent film is most difficult to remove. The accumulated planktonic phase can be reduced significantly by flushing water from the lines before use in patient treatment, but will return when the equipment is idle through the accumulation of more planktonic phase and by slough of the biofilm surface-adsorbed phase not yet enmeshed in the carbohydrate matrix. Chlorine dioxide has antimicrobial activity against many bacteria, spores, and viruses. It is used in water supply treatment as a disinfectant and slime preventive and has an advantage over chlorine in that carcinogenic trihalomethanes are not generated. METHODS: This study compared use of phosphate buffer-stabilized chlorine dioxide (0.1%) mouthrinse as a lavage in ultrasonic dental scaler units with the use of tap water as a control. Sterile water flushed through the units onto heterotrophic plate count (HPC) sampler plates was cultured 7 days at room temperature and colonies were counted at 12x. One test and one control unit were used for biopsy of internal tubing and scanning electron microscopy imaging. RESULTS: The HPC counts, in colony forming units (CFU)/ml, were reduced 3- to 5-fold by flushing tap water through the units, but they returned after units were idle overnight. When phosphate-buffered chlorine dioxide mouthrinse was used as a lavage, CFU/ml were reduced 12- to 20-fold. Holding chlorine dioxide in waterlines overnight reduced recurrent buildup compared to water (P <0.05). Scanning electron microscopy images indicated a significant reduction of biofilm coverage by chlorine dioxide as compared to water (P<0.001). CONCLUSIONS: Phosphate-buffered chlorine dioxide mouthrinse was effective in these short-term trials for control of waterline contamination in ultrasonic dental scaling units. It should prove as useful in dental professional waterline applications as it has in industrial uses for biofilm control.