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Biomedical subjects

K Price

Publications and source records attributed to K Price.

At least 55 records · Page 3Linked to original sources

Expression of the human placental folate receptor transcript is regulated in human tissues. Organization and full nucleotide sequence of the gene.

The primary structures of the human KB cell (FR-KB1) folate receptor (FR) and of a human placental (FR-P2) FR, proteins important in cellular accumulation of folates, have been deduced from cDNA sequences. Herein, we report a novel human FR cDNA (FR-P3) isolated from a placental library and the chromosomal organization of the human FR-P3 gene. Compared to the FR-P2 cDNA, the composite 1084 base-pair (bp) FR-P3 cDNA is homologous, but contains a unique 5' terminus and sequence differences within the open reading frame (ORF) and at the exon I-II junction. Polymerase chain reaction and RNase protection assays demonstrate that the FR-P3 cDNA represents the major transcript, and suggest that the FR-P2 cDNA is encoded by an independent FR gene. The nucleotide sequences of two non-overlapping human genomic clones contain the FR-P3 gene, which spans 5148 bp, is composed of five exons, and is polymorphic relative to 5' restriction sites. The transcript size (1084 bp) predicted from structural analysis of the FR-P3 gene correlates with the size (1100 bp) determined by Northern blots. Based on RNase protection assays, both FR-P3 and FR-KB1 transcripts are expressed in human fetal and adult tissues, and the abundance of each transcript varies among the tissues studied. These results indicate that the FR transcripts are products of independent, conserved genes; that neither FR gene is preferentially expressed during fetal development; and that specific FR transcripts are differentially expressed in human tissues, suggesting that transcription of each FR gene is regulated independently. The isolation of the FR-P3 gene will permit functional analysis of the cis and trans regulatory elements of the FR-P3 gene and the mechanisms involved in tissue-specific FR gene expression.

Amino Acid Sequence↗

Developing and implementing a bereavement program for a children's hospital.

The grief of parents after the loss of a child is well recognized. However, the concept of grief in children after the loss of a sibling or a parent has been accepted only recently. This paper describes the development and implementation of a bereavement program for staff and families in a children's hospital. The program is unique in that support is provided to both staff and families. Data gathering, goals of the program, the phases of implementation, and the specific components of support for each group are described. Initial efforts in evaluating the program and implications for the future are discussed.

Bereavement↗

Rat glioma cell lines C6 and 9L synthesize type 1 collagen in vitro.

Glial cell lines (C6, a glioma and 9L, a gliosarcoma) grown in vitro produce type 1 collagen which is detectable in the extracellular matrix by immunocytochemistry. Northern blot analysis using a cDNA specific for the proalpha2 (I) chain of procollagen indicates the presence of a single transcript with an apparent size of 4.8 kb in the C6 cell line, whereas two transcripts with apparent sizes of 5.8 and 4.8 kb are visualized in the 9L cells. The stimulatory effect of ascorbic acid on collagen production is detectable by a 20-27% increase in the concentration of hydroxyproline in the culture medium from the two glioma cell lines. Therefore these glioma cell lines provide a valuable model system for comparative investigations on the regulation of type 1 collagen synthesis by nonmesenchymal cells of neuroepithelial origin.

Animals↗

Sequential estrogen receptor determinations from primary breast cancer and at relapse: prognostic and therapeutic relevance. The International Breast Cancer Study Group (formerly Ludwig Group).

We retrospectively evaluated 401 selected patients who had estrogen receptor (ER) assays both at primary surgery and at relapse in an accessible site to determine the clinical relevance of the subsequent ER determination. The median time between ER assessments was 27 months (range: 2-122 months). The median follow-up time from diagnosis was 6 years (range: 2-12 years). For patients with ER+ tumors at primary diagnosis, 29% (76/261) had ER- tumors at relapse, while for ER- primaries, the conversion rate was 33% (46/140). Conversions from ER+ to ER- occurred more often when the time interval between assays was less than one year (p = 0.004), while conversions from ER- to ER+ tended to occur late (beyond three years; p = 0.0003). Treatments received between assays (usually adjuvant therapy) had only a slight influence on ER status conversion. Post-relapse survival was poor for patients who had the biopsy accessible recurrence within one year; an expression of the aggressive nature of the disease. Among patients whose accessible relapse was beyond one year, those with ER- primaries who converted to ER+ had a longer survival than those whose recurrence was classified again as ER- (p = 0.006). This group of patients with ER- primaries who recurred beyond one year with an ER+ tumor in an accessible site represented 29% (40/140) of all patients with ER- primaries and had an estimated overall survival rate of more than 60% at 6 years from the accessible relapse. ER determination upon relapse within one year has very little clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Partial purification and characterization of a factor produced by mitogen-stimulated sheep mononuclear cells with thymocyte-activating and cartilage-degrading properties.

Ovine peripheral blood mononuclear cells stimulated with concanavalin A released a soluble factor capable of inducing cartilage resorption and thymocyte activation in vitro, but not lysis of the murine L929 cell line. The active moiety has a molecular mass of around 15-20 kDa on gel filtration columns, and can be separated into two molecular species with isoelectric points of 6.3 and 4.6 respectively. These two species were partially purified by gel filtration, chromatofocusing, high performance liquid chromatography on hydroxylapatite and anion exchange columns, and SDS-polyacrylamide gel electrophoresis. Both partially purified species showed a major band on gels at 16 kDa. When the band from the acidic factor was excised and eluted from gels it was found to retain some cartilage-degrading and thymocyte-activating properties. The biochemical and biological characteristics of the two factors is consistent with their being members of the interleukin-1 family of cytokines.

Animals↗

Effects of bone marrow transplantation and polyinosinic-polycytidylic acid (poly I:C) on the rescue of animals from busulfan-induced NK suppression.

Repeated injections of busulfan (Bu) in CAF1 mice caused a long-lasting (greater than 16 weeks) decrease in their natural killer (NK) cell activity and impaired their resistance to transplantable lymphoma. Bu-treated mice had fewer spleen cells capable of binding to NK-sensitive YAC-1 target cells and reduced lymphokine-activated killer (LAK) cell activity as compared to normal age-matched controls. In contrast, interleukin 1 (IL-1) and interleukin 2 (IL-2) production were normal. Transplantation of normal bone marrow cells into Bu-treated mice resulted in an elevation of IL-2 production as well as in complete restoration of NK activity, target cell binding, and partial restoration of LAK activity. Resistance to transplantable lymphoma was equal to that of age-matched control mice. Polyinosinic-polycytidylic acid (Poly I:C) treatment resulted in immunomodulation in both control and Bu-pretreated mice. Twenty-four hours after Poly I:C injection, control and Bu-treated mice had higher levels of NK activity than did normal age-matched control mice, but the NK activity of Poly I:C/Bu-treated mice remained significantly lower than that of Poly I:C/control mice. The super-normal levels of NK activity in control and Bu-treated mice following Poly I:C administration were attributable, in part, to endogenous LAK activity. The generation of splenic LAK cells in vitro and target binding cells, which were reduced in Bu-pretreated mice, normalized following treatment with Poly I:C. Poly I:C treatment caused an increase in both IL-1 and IL-2 production in control and Bu-pretreated mice and in the ability of the treated mice to reject transplanted lymphoma cells. These results suggest that repeated injections of Bu decrease NK and LAK activity, but do not eliminate NK and LAK precursor cells. Thus, treatment with agents that increase IL-2 and/or interferon production can activate these cells to become effective killers and counter the long-lasting immunosuppressive effects of chemotherapy.

Animals↗

Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes.

NIH 3T3 cells cotransfected with the human c-fms proto-oncogene together with a 1.6-kilobase cDNA clone encoding a 256-amino-acid precursor of the human mononuclear phagocyte colony-stimulating factor CSF-1 (M-CSF) undergo transformation by an autocrine mechanism. The number of CSF-1 receptors on the surface of transformed cells was regulated by ligand-induced receptor degradation and was inversely proportional to the quantity of CSF-1 produced. A tyrosine-to-phenylalanine mutation at position 969 near the receptor carboxyl terminus potentiated its transforming efficiency in cells cotransfected by the CSF-1 gene but did not affect receptor downmodulation. CSF-1 was synthesized as an integral transmembrane glycoprotein that was rapidly dimerized through disulfide bonds. The homodimer was externalized at the cell surface, where it underwent proteolysis to yield the soluble growth factor. Trypsin treatment of viable cells cleaved the plasma membrane form of CSF-1 to molecules of a size indistinguishable from that of the extracellular growth factor, suggesting that trypsinlike proteases regulate the rate of CSF-1 release from transformed cells. The data raise the possibility that this form of membrane-bound CSF-1 might stimulate receptors on adjacent cells through direct cell-cell interactions.

Animals↗

Factors related to the use of ambulatory mental health services in three provider plans.

The use of ambulatory mental health (MH) services by adults was studied in three provider plans: Blue Cross (BC), Group Health Cooperative (GHC) and United Healthcare (UHC), an experimental new plan in which a patient's primary care physician managed all of his care. Approximately 8.3% of the enrollees in each plan had some MH use in the 18 months of the study. We studied correlates of MH use (yes/no). Sex was not a significant predictor of MH use. In general, worse health and lower socioeconomic status (SES) were correlated with having at least one MH visit, but better health and higher SES were correlated with a higher quantity of use for those who had some MH use. The three insurance plans did not differ significantly in the proportion of people who had any MH services, but BC users of MH services had 2-3 times more MH visits and higher costs than GHC and UHC users. This suggests that the reliance on primary care providers in UHC and GHC may have changed the nature of MH care as compared to Blue Cross. The effects of income, MH need and symptom sensitivity on MH use were different among the three plans.

Ambulatory Care↗

Influence of saponins on gut permeability and active nutrient transport in vitro.

The influence of four saponins, three triterpenoid glycosides and one steroidal amine glycoside, upon intestinal transport was investigated in vitro. In the presence of Gypsophylla saponin, carrier-mediated galactose transport was inhibited, although the uptake of the passively transported L-isomer of glucose increased. The uptake of the extracellular space marker, polyethylene glycol 4000, was also higher, indicating that the saponin inhibited active transport by increasing the general permeability of the enterocytes. Gypsophylla saponin, in contact only with the mucosal surface of everted jejunal sacs, induced a rapid decline in glucose-stimulated transmural potential difference. The rate of decline increased as the saponin concentration was raised over the approximate range of 0.3 to 8 mM. Saponaria saponin and alpha-tomatine also reduced transmural potential difference, but soya saponins were much less effective. The results indicate that some saponins readily increase the permeability of the small intestinal mucosal cells, thereby inhibiting active nutrient transport, and facilitating the uptake of materials to which the gut would normally be impermeable.

Animals↗

Busulfan and chloramphenicol induced T cell lymphoma: cell surface characteristics and functional properties.

We report the immunological studies on three transplantable lymphoma lines that developed when CAF1 mice were injected with busulfan and chloramphenicol. The lymphoma cells displayed Thy-1.2, brain associated antigen, and H-2d alloantigen. They were negative for surface IgM and Ia antigens. Expression of T cell differentiation antigens differed among the three lines. The 508 tumour line displayed only Thy-1.2: 408 tumour line displayed Thy-1.2, Lyt-2.2 and TL; and 808 tumour line was positive for Thy-1.2, Lyt-1.2, Lyt-2.2 and TL antigens. We established in vitro culture lines from 508 and 808 lymphoma cells. The lymphoma cells did not respond to mitogens and antigens. The splenic cells from mice bearing 508 or 808 had decreased phytohaemagglutinin (PHA), concanavalin A (Con A) and mixed leucocyte responses (MLR). When mitomycin-C treated lymphoma cells from the tumour bearing mice were cocultured with normal splenic mononuclear cells, the 808 lymphoma cells suppressed the mitogenic responses of the normal cells more profoundly than 508 lymphoma cells. Adherent cells from both tumours suppressed the Con A responses of normal spleen cells. Cells from in vitro 508 or 808 cell lines had no effect on mitogenic responses of normal cells. Plasma from tumour bearing mice, but not the supernatants taken from cultures of these lymphoma cells, suppressed the mitogenic responses of normal lymphocytes. Spleen cells from normal CAF1 mice responded in mixed leucocyte tumour reactions (MLTR) when cocultured with lymphoma cells. Mice immunized with mitomycin-C treated tumour cells had greater response. Responder cells taken from mice with established 508 or 808 tumors had suppressed MLTR responses. Although prior immunization with tumor antigen increased the MLTR response, injection of live tumour cells into immunized mice resulted in a more rapid tumour growth and suppression of MLTR response.

Animals↗

Use of outpatient somatic health services by patients who use or need mental health services in three provider plans.

A major topic in mental health (MH) research addresses the problem that patients who use mental health services have inappropriately high levels of somatic use, and examines whether provision of mental health services can decrease the inappropriate use (the so-called offset effect). However, the research showing higher somatic use by mental health patients has usually been unable to control for the patients' health status, or for their mental health status. In this paper we examine use of somatic health services by enrollees in three provider plans as a function of both mental health use and mental health need. In two of the provider plans (an HMO and a prepaid independent practice association), MH users used significantly more outpatient somatic services than non-MH patients, after control for age and sex, and after control for the number of chronic conditions they had. People with MH need, however, did not use significantly more MH services than those without MH need. In the third plan, a Blue Cross/Blue Shield type of plan, results were different; MH users did not have significantly higher somatic utilization after control for chronic conditions, and those with MH need did have significantly higher somatic utilization after control for age and sex, but not after control for the number of chronic conditions. These results suggest that the form of inappropriate use of outpatient somatic services, and the nature of an offset effect, may be specific to the type of insurance provided.

Adult↗

Ambulatory mental health services utilization in three provider plans.

This article examines the use of mental health services in three insurance plans: Blue Cross (BC), a health maintenance organization (HMO), and an independent practice association (IPA) in which the primary care physician was to manage all care for an individual. Approximately 7.3% of the enrollees in all three plans used some mental health care in the 18-month study period. The percent of enrollees with mental health utilization was lower in BC than in the other two plans, but the total quantity of mental health care use per enrollee and per user was much higher in BC than in the HMO and the IPA. Use was highest in the 19-44-year-old age group, and there were no significant differences between men and women in use of mental health services. There were substantial differences by race in all three plans: white persons were more likely to use any mental health care and had more visits than nonwhite persons after seeking mental health use. A similar study was conducted in the early 1970s on a poverty-level population enrolled in BC and the HMO. The findings of this study are similar, except that in the low-income study mental health care use was lower, and males used less mental health care than females. These differences might be attributable to the difference in enrollees' socioeconomic status in the two studies or to the increasing acceptability of mental health care utilization, particularly for males.

Adolescent↗