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Biomedical subjects

J D French

Publications and source records attributed to J D French.

7 recordsLinked to original sources

Analysis of IL-6-mediated growth control of myeloma cells using a gp130 chimeric receptor approach.

Interleukin 6 (IL-6) has been shown to be a key growth factor for myeloma cells. To study IL-6 signal transduction in multiple myeloma (MM), we employed chimeric receptors composed of the epidermal growth factor receptor (EGFR) extracellular domain, gp130 transmembrane domain, and full-length or truncated gp130 cytoplasmic domains lacking regions previously shown to be necessary for MAPK, STAT1, and STAT3 activation. The IL-6-dependent KAS-6/1 MM cell line was transfected with various chimeric receptor constructs and assayed for EGF responsiveness. EGF stimulation surprisingly stimulated DNA synthesis in all transfectants, regardless of receptor length. When cell proliferation was assayed instead, only transfectants capable of inducing high levels of STAT3 activation proliferated in response to EGF. Additional studies revealed that EGF stimulation resulted in tyrosine phosphorylation of endogenous gp130 in cells expressing the chimeric receptor. Replacing the gp130 transmembrane region with the EGFR transmembrane domain diminished but did not disrupt this interaction. This receptor interaction was also observed in the IL-6-dependent MM cell line ANBL-6. In summary, although our results suggest that STAT activation is crucial in gp130-mediated proliferation of myeloma cells, these results must be interpreted with caution given our demonstration of the interaction between chimeric and endogenous receptors in myeloma cells. Importantly, this interaction has not been noted in studies utilizing the same gp130 chimeric receptor system in non-MM cells.

Amino Acid Sequence↗

Dissection of the signalling requirements of interleukin-6-stimulated myeloma cell growth.

The growth characteristics of myeloma cells are in striking contrast with those of normal, non-dividing end-stage plasma cells. Interleukin 6 (IL-6) has been shown to be a key growth factor for myeloma cells, however, IL-6 only acts as a differentiation factor for normal B cells. Wc have hypothesized that the differential response of myeloma cells to IL-6 may either result from altered IL-6 signal transduction and or from inappropriate IL-6-induced expression of genes whose products are key for continued tumor cell growth. To test this hypothesis, we have employed two experimental strategies. First, we are using cDNA array screening technology to identify IL-6 responsive genes in myeloma cells. Second. we are using a chimeric receptor approach to identify the regions of gp130, the signal transducing component of the IL-6 receptor, that are essential for myeloma cell proliferation. To this end, we have utilized a panel of IL-6 growth-responsive myeloma cell lines and a panel of mutant gp130 chimeric receptors. This combined approach has the potential to assess the relative importance of several signalling events in myeloma cell growth control and identify IL-6 responsive genes in this malignancy.

Antigens, CD↗

Office screening for asymptomatic urinary tract infections. The evaluation of a practical, economic and reliable method screening the urines of asymptomatic girls in a busy pediatric office.

The urines of 3,270 asymptomatic girls were screened at annual physical examinations. The urines were collected in Dixie Cups without prior preparation of the perineum and cultured on 5% sheep cell agar. Less than 2 per cent of the specimens showed significant growth, thus requiring no follow-up visits by 98 per cent of the patients. Slightly less that 1/2 of one per cent were found to have asymptomatic urinary tract infections. The procedure was found to be practical, economically feasible and reliable, and was well accepted by both the parents and patients.

Economics, Medical↗

Subcutaneous clostridial infection in broilers.

A flock of 12,500 broilers 36 days of age experienced a sudden increase in mortality. Post-mortem lesions were emphysema, severe enteritis, and a serosanguineous fluid in the subcutaneous tissue of the breast and thighs; there was no evidence of a loss in the integrity of the skin. Clostridium perfringens and C. septicum were isolated from the affected subcutaneous tissue. Histopathological and serological examination indicated previous infection with infectious bursal disease virus. The subsequent immunosuppression and severe enteritis may have permitted the clostridia access to the circulatory system, with localization in the subcutaneous areas of the breast and thighs. Mortality returned to normal 48 hours after potassium penicillin G was administered via the drinking water.

Animals↗

Ophthalmopathy in a broiler breeder flock reared in dark-out housing.

Eight 22-week-old broiler breeder replacements were presented from a flock experiencing a mild mortality problem. Approximately 2-3% of the birds were not getting onto the slats to eat or drink. The birds had been reared in dark-out houses under an experimental lighting schedule. Upon examination, several birds appeared blind or partially blind; others exhibited a photophobic response. Two birds lacked a unilateral menace reflex. No other gross abnormalities or lesions were noted. Histopathologic sections of the eyes revealed retinal degeneration and detachment with early degenerative lesions in one lens. The breeder flock came into production normally but peaked below average. Light intensity in the pullet house was measured at 0.3 footcandles (3.2 lux). Although the lighting program under which the pullets were grown is suspect, the etiology of the disorder remains unclear.

Animal Husbandry↗