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Biomedical subjects

J Shields

Publications and source records attributed to J Shields.

At least 19 recordsLinked to original sources
PubMed1992

Purification and characterization of biologically active human recombinant 37 kDa soluble CD23 (sFc epsilon RII) expressed in insect cells.

Human recombinant soluble 37 kDa CD23 has been expressed in insect cells and secreted into the culture medium using the IL-2 leader sequence. The 37 kDa CD23 was purified 600-fold to homogeneity by monoclonal antibody affinity chromatography and gel filtration. The pure protein is monomeric, glycosylated, depleted of one N terminal amino acid and contains four disulphide bonds. It degrades into smaller fragments of 33, 29 and 25 kDa if purified in the absence of protease inhibitors. The same pattern of proteolytic fragments is observed when the pure preparation is incubated at room temperature for 3 weeks. Physical characterization of the 37 kDa CD23 by circular dichroism indicates that the protein contains mainly beta sheet and 20% of alpha helical structures. Specific binding of IgE to natural CD23 (low affinity IgE receptor) was inhibited by purified recombinant 37 kDa CD23. Moreover, purified recombinant 37kDa CD23 and interleukin-1 promoted the survival of germinal centre B cells.

Amino Acid Sequence↗
PubMed1992

Consolidation hemibody radiotherapy following induction combination chemotherapy in high-tumor-burden multiple myeloma.

PURPOSE: Curative therapy for multiple myeloma continues to be an elusive goal. This report discusses the Northern California Oncology Group (NCOG) phase I and II trial in high-tumor-burden disease that used a strategy that consisted of induction chemotherapy (vincristine, melphalan, cyclophosphamide, and prednisone [VMCP]) for eight cycles followed by sequential hemibody radiation therapy (RT) and subsequent chemotherapy for an additional eight cycles. PATIENTS AND METHODS: Seventy-two previously untreated stage III myeloma patients were entered onto the study. Sixty-nine received induction chemotherapy, 40 received induction chemotherapy and hemibody RT, and 23 received induction chemotherapy, hemibody RT, and consolidative chemotherapy. RESULTS: Twenty-two complete responses (CRs) were obtained by induction chemotherapy, with four additional CRs after RT and consolidative chemotherapy. Nineteen patients developed grade 4 hematologic toxicity primarily after upper hemibody RT. Eight of these developed long-standing neutropenia or thrombocytopenia. Median survival of the group was 134 weeks, which was not significantly different from other approaches. CONCLUSIONS: Hemibody RT can be combined with chemotherapy as induction therapy and can be safely administered in a community setting. However, as administered here no survival advantage was demonstrated.

Adult↗
PubMed1991

Growth regulation of the AML-193 leukemic cell line: evidence for autocrine production of granulocyte-macrophage colony-stimulating factor (GM-CSF), and inhibition of GM-CSF-dependent cell proliferation by interleukin-1 (IL-1) and tumor necrosis factor (TNF alpha).

The human leukemic cell line AML-193 was tested for its proliferative response to endogenously produced autocrine factors and to a variety of cytokines and colony-stimulating factors. Cells grown in the absence of GM-CSF incorporated tritiated thymidine, and this was partially reversed by adding neutralizing anti-GM-CSF antibodies to the culture medium, suggesting that it was due, at least in part, to autocrine GM-CSF production. This was confirmed by immunopurification of a GM-CSF-like activity from cell supernatant of AML-193 cells grown in serum free medium in the absence of exogenous GM-CSF. When AML-193 cells were cultured with GM-CSF in combination with other cytokines, Interleukin-1 alpha and beta (IL-1 alpha and beta), Interleukin-3 (IL-3), Interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha), none of them affected the concentration of GM-CSF required to induce 50% of maximum proliferation (D50). However, the maximum proliferation induced by GM-CSF alone was drastically decreased by IL-1 alpha, IL-1 beta and TNF alpha. Inhibition caused by exposure of the AML-193 to IL-1 for up to 24 hr was reversible, ruling out a direct cytotoxic effect.

Cell Division↗
PubMed1991

Ambient air arsenic levels along the Texas-Mexico border.

The Texas-Mexico border region is one of the most rapidly developing areas in the state. Unprecedented economic and demographic growth is placing stress on a system already overburdened with air, water, waste, and public health problems. This paper reports the results of an initial survey of the past and present ambient air levels of arsenic along the Texas side of the border. Ambient air arsenic levels have increased over time, exhibit seasonal variations, and are higher in specific areas when compared to the rest of the state. Five of the 20 areas in Texas having the highest 24-hour levels of arsenic are found along the border. In areas where emissions have been significantly reduced at the source, arsenic levels remained high in the environment for over two years. This provides a potential continuum for human exposure. The results of this study emphasize the need for bi-national development and implementation of air quality control programs along the Texas-Mexico border.

Air Pollutants, Occupational↗
PubMed1991

Expression of human recombinant CD23 in insect cells.

Human CD23 (low affinity receptor for IgE) has been expressed in insect cells (Sf9) using the baculovirus expression system and the baculovirus transfer vector pAc373. Insect cells infected with a recombinant baculovirus coding for CD23 synthesized a polypeptide not found in wild-type infected insect cells that had antigenic properties similar to natural CD23 produced in RPMI 8866 cells. Surface expression of recombinant CD23 was demonstrated by its ability to bind IgE. Recombinant CD23 expressed in insect cells had a slightly lower molecular weight (43 kDa) than that of natural CD23 (45 kDa) from RPMI 8866 cells as detected by SDS-PAGE followed by Western-blotting. Affinity-purified recombinant CD23 from infected insect cells showed B-cell growth promoting activitiy. These observations demonstrate for the first time that biologically active recombinant CD23 can be produced by the baculovirus expression system, thus providing a useful source of recombinant material to elucidate the biological functions of CD23.

Animals↗
PubMed1991

Semantic-pragmatic disorder: a right hemisphere syndrome?

Following right hemisphere lesions, adults' speech can become copious and inappropriate, with abnormal prosody, and they may be unable to comprehend metaphor or humour. Their symptoms resemble those of children with semantic-pragmatic language disorder, who use fluent, grammatically complex language, but with poor sensitivity to the communicative situation. The hyperlexia found in some of these children reflects an underlying cognitive problem in integrating semantic information with knowledge of the world. Both groups of patients fail comprehend inferential meaning or to make use of paralinguistic features. It is hypothesised that the disorders of communication and cognition found in semantic-pragmatic language disorder may be linked to right hemisphere dysfunction, but this has yet to be confirmed by research.

Autistic Disorder↗
PubMed1990

Radiotherapy of retinoblastoma. A review of 63 children treated with different irradiation techniques.

This is a retrospective review of treatment results in 63 children with retinoblastoma (RB) who received therapeutic irradiation from January 1975 to June 1988. Patient ages ranged from birth to 5 years with a mean age of 12.5 months. Three treatment groups were identified. In Group A, episcleral plaque was the only irradiation modality. In this group, 24 patients and 25 eyes with tumors of Reese-Ellsworth Stages I to III, and selected Stage VB tumors were irradiated using eye plaques. Twenty-two of 25 (88%) eyes are without evidence of disease (NED), and all patients are alive. Two eyes were enucleated for recurrent RB. Two of 23 eyes developed minimal cataracts. In Group B, external-beam was the only irradiation modality. Twelve patients with 21 involved eyes comprise this group. Thirteen eyes received EBRT alone. Seventy-seven percent of 13 eyes have NED. Four eyes developed cataracts. Three of 13 eyes required enucleation for progression of disease; one of these was Stage IVA and two of them were Stage VA. For Group C, external-beam plus episcleral plaque was used. Twenty-seven patients and 51 eyes with advanced retinoblastoma were included in this group. Episcleral plaque was used in 29 eyes as a salvage procedure for recurrent RB, or in selected cases was used as a boost after initial external beam irradiation. Fifteen of 29 eyes (52%) remain with NED with useful vision, and nine developed cataracts. Enucleation was performed in 14 eyes for recurrent RB. The authors conclude that radiation therapy has a major role in the management of RB due to its ability to control even advanced disease, allowing preservation of vision in a significant number of patients.

Cataract↗
PubMed1990

Inhibition of human interleukin 4-induced IgE synthesis by a subset of anti-CD23/Fc epsilon RII monoclonal antibodies.

Specific monoclonal antibodies (mAb) directed against the CD23 antigen were used to study human interleukin 4 (hIL4)-induced IgE production by blood and tonsillar mononuclear cells. Both peripheral blood and tonsillar mononuclear cells stimulated by hIL4 expressed membrane CD23 as detected by the binding of all anti-CD23 mAb. Nevertheless, two sets of anti-CD23 mAb could be distinguished. The first set, including mAb 25, was able to decrease significantly hIL4-induced IgE synthesis by mononuclear cells. The second set, including EBVCS#1, did not affect hIL4-induced IgE synthesis. All the anti-CD23 mAb were able to bind specifically to a human B cell line expressing recombinant CD23. Inhibition experiments revealed that the two sets of anti-CD23 mAb did not recognize the same epitope on the CD23 antigen. In fact, all the anti-CD23 mAb, except EBVCS#1, were able to inhibit IgE binding to CD23 on RPMI 8866 cells. Moreover, the first set of antibodies, which decreased IgE production, was able to up-regulate membrane CD23 expression on hIL4-stimulated tonsillar mononuclear cells. Conversely, EBVCS#1, which had no effect on IgE production, did not affect hIL4-induced CD23 expression. These results indicate that CD23 plays a key role in human IgE synthesis.

Antibodies, Monoclonal↗
PubMed1990

Production of a 26,000-dalton interleukin 1 inhibitor by human monocytes is regulated by granulocyte-macrophage colony-stimulating factor.

An interleukin 1 (IL 1) inhibitor is secreted into culture medium by a human promyelocytic cell line, H-161, upon stimulation with (PMA) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Since the morphological characteristics of this cell line were macrophage-like, human monocytes were tested for their ability to produce similar activity using the same induction conditions. Upon induction of adherent peripheral blood monocytes with rhGM-CSF and/or PMA, an IL 1 antagonistic activity was found in the cell supernatants, as determined by IL 1 receptor binding assay, using the murine EL-4.6.1C10 cell line as the cell target. Most of the inhibition of IL 1 binding induced by PMA or by PMA/rhGM-CSF was shown to be caused by IL 1, since it was neutralized by a mixture of anti-IL 1 alpha/beta antibodies and was active in the murine thymocyte proliferation assay (LAF). The activity induced by GM-CSF alone was not neutralized by anti-IL 1 alpha/beta antibodies and showed no LAF activity. The IL 1 inhibitor activity was induced by rhGM-CSF with a D50 around 40 pg/ml. The activity was produced for more than 3 wk in the presence of GM-CSF; removal of GM-CSF was followed by a rapid decrease of IL 1 antagonistic activity. The specific binding of biosynthetically labeled IL 1 inhibitor to target cells (EL-4.6.1C10) showed a protein of 26 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This molecule shares biological and physical characteristics with the urinary IL 1 inhibitor and the promyelocytic H-161-derived IL 1 inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Culture Media↗
PubMed1989

Population ecology of preimaginal Culex tarsalis (Diptera: Culicidae) in Kern County, California.

The effects of abiotic and biotic mortality factors on preimaginal survivorship and the production of adults were investigated for populations of Culex tarsalis Coquillett at a stable foothill breeding site during 1985 and at seven ephemeral breeding sites during 1986. Female abundance was correlated temporally with larval abundance and spatially with first instar to adult survivorship. Catastrophic events, such as fluctuations in water level and pollution, drastically reduced larval and pupal abundance. Under relatively stable conditions, the effect of natural mortality factors was estimated by comparing preimaginal survivorship rates, estimated horizontally for fed and unfed cohorts in predator exclusion cages, with survivorship, estimated vertically from the age structure of the natural population using a life table approach. Mortality for fed cohorts ranged from 8.5 to 90.0% and was attributed to abiotic factors, including temperature and water quality. Mortality caused by lack of food was comparatively low (less than 15%); however, the low nutrient level at three of six sites lengthened the duration of the fourth stadium, delayed pupation, and resulted in the emergence of small-sized adults with a reduced expression of autogeny. Predation mortality ranged from 3.7 to 84.5% and was the most important cause of larval death at five of six study sites. Based on relative abundance and correlation over time and space, zygopteran naiads were the most important predator at a stable foothill breeding site during 1985, and coleopteran larvae were the most important predator at ephemeral breeding sites sampled during 1986.

Animals↗
PubMed1989

Cross-institutional stability of behavioral criteria desirable for success in radiology residency.

Certain dimensions of job performance are critical to radiology residents, and several of these dimensions are noncognitive in nature (eg, interpersonal skills, conscientiousness, recognition of limits). Our initial study examined these factors in only one residency program, so the general nature of these dimensions must be documented. The current study was a cross institutional analysis involving 31 faculty radiologists at three separate academic institutions (82% of total faculty) who participated in a critical incident interview to obtain data on important resident behaviors and attitudes. The resultant 172 incidents were sorted by two physicians into the six categories (knowledge, technical skills, attitudes toward self and [both recognitions of limits and confidence in abilities], conscientiousness, curiosity, and interpersonal skills); inter-rater reliability was 92%, kappa = .89. A Chi square analysis revealed similar distributions of incidents across categories (x2 12 = 17.22) among the three institutions, supporting the general reliability of these dimensions across the institutions studied. Further, the distributions of these incidents demonstrated that the noncognitive dimensions again were given considerable importance by faculty radiologists. For example, more than 40% of the critical incidents pertained to the conscientiousness dimension. These findings documented the generalization of these behavioral dimensions across several sites and support their importance in selection and evaluation of residents.

Attitude of Health Personnel↗
PubMed1987

Retinoblastoma. Immunohistochemistry and cell differentiation.

Tumor from eight enucleated eyes was analyzed by immunohistochemistry, using a panel of specific antibodies including interphotoreceptor retinoid-binding protein (IRBP), S-antigen (S-Ag), opsin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), laminin, and vimentin. In addition, immunoelectron microscopy and enzyme-linked immunosorbent assay (ELISA) for IRBP were performed. Immunohistochemical staining disclosed the most pronounced labeling of tumor cells with NSE and IRBP antibodies. A correlation was found between the degree of tumor differentiation and amount of IRBP, a protein specifically synthesized by photoreceptor cells. Moderate labeling of the better differentiated tumors was also observed with antibodies against S-Ag and focal labeling in a few tumors with opsin antibodies. Anti-GFAP labeling was limited to a smaller number of reactive glial cells and perivascular glial cells. These data indicate the essential neuronal nature of retinoblastoma tumor cells in situ as well as at least partial photoreceptor-like features, as shown by the presence of recognized photoreceptor cell markers (IRBP, S-Ag, opsin). Tissue culture studies using the human Y-79 retinoblastoma cell line also demonstrate that the tumor cells are primitive multipotential retinoblasts capable of at least partial differentiation along neuronal, glial, or pigment epithelial cell lines.

Antibodies, Anti-Idiotypic↗
PubMed1986

B cell growth and differentiation induced by supernatants of transformed epithelial cell lines.

Growth and differentiation of B cells is thought to be regulated by soluble factors derived from T cells. However, human T cell lines and hybridomas have proved to be notoriously unreliable and unstable sources of such factors. We report here that three stable human bladder carcinoma cell lines T24, RT4 and 5637 produce, in a constitutive fashion, factors which promote growth and differentiation of human B cells.

Antigens, Differentiation, B-Lymphocyte↗