Biomedical subjects
Publications and source records attributed to C L Johnston.
Registered nurse job satisfaction is one of the most written about topics in the nursing literature. Is it possible to achieve in an organizational setting? Can the administrative structures control this phenomenon? This article suggests that job satisfaction is strongly influenced by individual perceptions of certain key variables. In addition, job satisfaction is presented as a responsibility of each individual nurse.
We have raised specific antibodies to the second immunoglobulin-like domain of fibroblast growth factor receptors (FGFRs) and used these to investigate the expression and subcellular localization of FGFR-1, -2, -3, and -4 in breast epithelial cells. All four receptors classes could be detected in breast cell lines; however, FGFR-4 and FGFR-2 appeared to be expressed at a higher level in breast cancer cell lines than in normal epithelial cells. Surprisingly, FGFR-3 localized in the cell nucleus by immunofluorescence. A second antibody to a separate epitope confirmed this finding and showed that the form of FGFR-3 present must contain an intact kinase domain as well as the growth factor binding domain. Western analysis of fractionated cells revealed the presence of two forms of FGFR-3 of 135 and 110 kDa. The 110-kDa form was predominantly found in the nucleus, whereas the 135 kDa form was sometimes found in the nucleus. RT-PCR analysis of FGFR-3 mRNA showed the presence of a splice variant in which exons 7 and 8 are deleted. This results in the translation of FGFR-3 missing the transmembrane domain but with an intact kinase domain, which could be a soluble, intracellular receptor. Transfection experiments showed that FGFR-3 containing this deletion and no signal peptide gave an identical nuclear staining pattern to that seen in breast epithelial cells. We conclude that two forms of FGFR-3 are present in breast epithelial cells; a full-length 135-kDa receptor, which has a conventional membrane localization, and a novel soluble form of 110 kDa.
The expression of variant mRNAs encoding isoforms of fibroblast growth factor receptor (FGFR)1 with either 2 or 3 Ig-like loops in the extracellular domain was investigated in human breast tissues and cell lines using a polymerase chain reaction amplification method. Almost all tissues contained both forms of FGFR1, but cancers (n = 137) had a significantly lower proportion of the transcript that encoded the full 3-loop form compared with non-malignant biopsies (n = 34). This was confirmed using microdissected populations of normal and cancerous cells from frozen tissue sections. A high ratio of the 2- to 3-loop form was found to be predictive of reduced relapse-free survival. In both groups, however, the predominant form of FGFR1 was that encoding the 2-loop receptor. Cell lines derived from a variety of tissues, including breast, also co-expressed both variants of FGFR1, suggesting their presence within the same cell type. Again, there was a similar preponderance of the shorter isoform. Our results were confirmed at the protein level, where out of 5 cancers analysed 4 expressed more of the 2-loop form than the 3-loop form. Our findings suggest that cells may normally simultaneously express several splice variants of FGFR1, and aberrant expression or a change in their relative amounts (i.e., in malignancy) could contribute to modified responses to either autocrine or paracrine factors.
Acidic and basic fibroblast growth factors (aFGF and bFGF) are growth factors which may have a physiological role in the normal breast and in breast cancer. A study of the effects of aFGF and bFGF on a variety of breast cell lines and epithelial cells purified from normal breast organoids showed that whereas normal breast cells did not exhibit membrane ruffling in response to either of these growth factors, some breast cancer cell lines did. This difference was not due to lack of receptor since all the cell lines tested were mitogenically stimulated by bFGF. Dominant negative mutations of FGF receptor 3 (FGFR-3) and the small GTP-binding protein p21rac inhibited membrane ruffling, showing that receptor dimerization and phosphorylation and p21rac activation are prerequisites for membrane ruffling in response to aFGF and bFGF. Transient transfection of individual FGFRs into cos-7 cells showed that FGFR-1, FGFR-2 and FGFR-3 could not mediate a membrane ruffling response whereas FGFR-4 could. These studies elucidate one signalling mechanism of FGF and point to differences in the response of normal and cancer breast epithelial cells which may be important in cell motility.
We have measured the amount of fibroblast growth factor 1 (FGF-1) mRNA and protein in primary breast cancers and non-malignant breast tissue and have found greatly reduced levels in breast cancer compared with non-malignant tissue. A total of 116 breast cancers and 37 biopsies taken from non-malignant breast were compared for FGF-1 mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and significantly lower levels were found in the cancer tissues (P < 0.001). These findings were confirmed at the protein level where four out of five breast cancers contained no detectable FGF-1 and a fifth cancer had a low level of FGF-1 compared with three samples from reduction mammoplasties. Similar results were obtained from breast cell lines in which 80% of cancer cell lines had very low levels of FGF-1, whereas all non-malignant breast cell lines contained higher levels of FGF-1. Immunohistochemical analysis indicated that FGF-1 was present in the luminal epithelial cells of the non-malignant breast but was absent from cancer cells. The decreased levels of FGF-1 in breast cancer may indicate that stimulation of cancer cells is resulting in down-regulation of FGF-1 expression or may implicate FGF-1 as a differentiation factor rather than a growth factor at its physiological concentration in the breast.
The Council on Graduate Education for Administration in Nursing (CGEAN) was established to further develop and improve graduate education for administration in nursing. The Council seeks to identify the nature and direction of education for administration in nursing in various healthcare systems, providing guidelines for programs offering administration. A major goal of CGEAN is facilitating dialogue between nursing service administrators and graduate level educators who are engaged in teaching and research related to administration in nursing. This column, sponsored by the members of the Council, analyzes and responds to position statements and trends related to the delivery of health services and graduate education for administrators in nursing.
The function of rac, a ras-related GTP-binding protein, was investigated in fibroblasts by microinjection. In confluent serum-starved Swiss 3T3 cells, rac1 rapidly stimulated actin filament accumulation at the plasma membrane, forming membrane ruffles. Several growth factors and activated H-ras also induced membrane ruffling, and this response was prevented by a dominant inhibitory mutant rac protein, N17rac1. This suggests that endogenous rac proteins are required for growth factor-induced membrane ruffling. In addition to membrane ruffling, a later response to both rac1 microinjection and some growth factors was the formation of actin stress fibers, a process requiring endogenous rho proteins. Using N17rac1 we have shown that these growth factors act through rac to stimulate this rho-dependent response. We propose that rac and rho are essential components of signal transduction pathways linking growth factors to the organization of polymerized actin.
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Ménière's disease is generally accepted to be a consequence of distention of the endolymphatic sac of the inner ear. Although the exact etiology is unclear, there is a body of research suggesting that Ménière's disease is of psychosomatic origin. While we do not intend to review the literature exhaustively, we briefly review several frequently cited studies. Even though this literature is so severely flawed that no solid conclusions may be drawn from it, certain questions about the psychological aspect of this disorder continue to surface. Our limited access to patients with vertigo has not allowed us to undertake a carefully designed study. However, in clinical practice we have noted that many persons who complain of vertigo (whether due to Ménière's disease or other causes) also report symptoms of depersonalization and derealization. In this paper we present the cases of two women with Ménière's disease who also experienced concurrent feelings of unreality. It appears likely that feelings of unreality may occur regularly in association with syndromes causing vertigo, presumably as a consequence of vestibular dysfunction. We argue that emotional disturbances previously identified as predisposing causes of Ménière's disease are more likely effects of the disease. Although the discussion of two uncontrolled cases can do little to help solve nagging questions about a psychosomatic component to this disorder, we believe it may suggest a different perspective from which to investigate these complex phenomena.
Although obese women with histories of gestational diabetes mellitus (former GDM) are highly predisposed to develop noninsulin-dependent diabetes mellitus (NIDDM), lean former GDM women are less predisposed. To explore reasons for this difference, we performed measures of islet B-cell function and insulin action in eight lean former GDM women [ideal body weight (IBW), 107 +/- 2% (mean +/- SEM)], 11 obese former GDM (IBW, 161 +/- 11%), and 19 normal women subjects who were individually pair-matched to former GDM for % IBW and age. The first phase (0-10 min) insulin secretory response to iv glucose was significantly lower in both lean and obese former GDM compared to that in normal women (3,480 +/- 548% vs. 8,234 +/- 1,337% basal . min and 3,444 +/- 682 vs. 10,251 +/- 2,465). The second phase (10-60 min) insulin response to glucose was also significantly lower in lean former GDM women and tended to be lower in obese former GDM women compared to that in their respective controls. Insulin action was assessed by the insulin sensitivity index (SI) using Bergman's minimal modeling technique. SI values in lean former GDM women were similar to those in their controls (4.42 +/- 1.3 X 10(-4) ml min-1 microU-1 vs. 5.19 +/- 1.2 X 10(-4). In contrast, SI values in obese former GDM women were significantly lower than those in their controls (0.77 +/- 0.28 X 10(-4) vs. 2.04 +/- 0.43 X 10(-4). To assess whether differences in fat distribution and fat cell size were associated with these differences in insulin sensitivity, the waist to thigh circumference ratio, the waist to hip ratio, and abdominal fat cell diameter were measured. All three were significantly greater in the obese former GDM women than in controls. Thus, an abnormal central distribution of adiposity appears to be associated with the insulin action defect in obese former GDM women. We conclude that both lean and obese former GDM women have insulin secretion defects. Although a modest insulin action defect in lean former GDM women may have been missed by this technique, only in the obese former GDM women, who have a higher risk for future NIDDM, was an insulin action defect demonstrable. Thus, impairments of both insulin secretion and insulin action may be necessary to cause a marked predisposition toward NIDDM.
NIDDM is characterized by decreased insulin secretory responses to glucose and to nonglucose stimuli, hyperglucagonemia, and decreased tissue sensitivity to insulin. However, it has been unclear which of these abnormalities, if any, precedes the others. Since women with histories of gestational diabetes mellitus (GDM) are at high risk for eventual development of NIDDM, we measured B- and A-cell function and tissue sensitivity to insulin in eight normoglycemic, postpartum women with recent histories of GDM and in eight control subjects pair-matched for age and percent of ideal body weight. Fasting plasma glucose levels in subjects with former GDM tended to be slightly higher than in matched controls (98 +/- 3 versus 92 +/- 2 mg/dl, P = 0.07). Basal plasma insulin in subjects with former GDM was significantly higher than in controls (22 +/- 4 versus 14 +/- 2 microU/ml, P = 0.05). During an intravenous glucose tolerance test (IVGTT), relative first- and second-phase insulin responses to glucose were decreased in subjects with former GDM (2316 +/- 560 versus 7798 +/- 1036% of basal X min, P = 0.004; and 8340 +/- 946 versus 14,509 +/- 2556, P = 0.04). An index of sensitivity to insulin, SI, calculated from the IVGTT, was also lower in former GDM (1.23 +/- 0.69 X 10(-4) versus 3.58 +/- 0.78 X 10(-4) min-1/microU/ml, P = 0.001). Acute insulin responses to 5 g i.v. arginine were measured at plasma glucose levels of approximately 95, 215, and 600 mg/dl. The response at 600 mg/dl is termed the AIRmax and is used as an index of glucose-regulated insulin secretory capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to provide performance standards for instruments utilizing automated cell differentiation, a study was undertaken using the NCCLS Standard H20-T. The ELT-800/WS using light scattering technology was compared with a manual reference method. These were compared using normal values developed in the study for determination of sensitivity of the method, utilizing arbitration where necessary. Statistical analyses were performed including ANOVA, imprecision, sample size efficiency, and clinical sensitivity. Whereas the two methods (manual and automated) are quite different technologically, the mean differences are not significantly different for clinical purposes. The automated method is very precise. The normal values developed for the ELT 800/WS are comparable not only to the manual values developed by NCCLS but also to earlier values used for reference in the laboratory. In studies to identify or to classify samples as either normal or distributionally or morphologically abnormal, a false abnormal rate of 6.3% and a morphologically false abnormal rate of 8.7% were found. When the specific types are considered, in only two instances (3.2%) did the test method fail to show an operator alert with an abnormal specimen. The performance of the ELT-800/WS seems to be as accurate and as sensitive as the reference manual method and is satisfactory for clinical decision-making.
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Bone marrow examinations in 146 patients with small cell carcinoma of the lung were reviewed. The results of trephine biopsy and aspiration were compared in 128 patients in whom both techniques were performed. Twenty-seven of the 128 examinations (21.2%) showed positive aspirates and 30 biopsies (23.4%) revealed metastatic disease. The overall agreement between the aspirates and biopsies was 96.1%. Thirty-one patients (24.2%) had metastatic tumor in either aspirate or biopsy: 4 of these (12.9%) had a positive biopsy with negative aspirate, and 1 (3.2%) showed a positive aspirate and negative biopsy. The Jamshidi needle was used, yielding an average of 4.1 cm of core material per biopsy. The authors conclude that bone marrow biopsy using the Jamshidi needle is equivalent to aspiration. Although both procedures are complementary, a satisfactory specimen obtained with the Jamshidi needle alone may yield nearly equal detection to the combined procedures. Some guidelines for obtaining an optimal biopsy specimen are suggested.
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A case is reported of primary late-onset hypogammaglobulinaemia associated with a chronic seronegative, nonerosive arthritis, which was complicated by an episode of septic arthritis due to Mycoplasma pneumoniae. The patient had subcutaneous nodules which have not been regarded previously as a feature of the chronic arthritis associated with hypogammaglobulinaemia. The diagnosis of septic arthritis was delayed for 2 months until synovial fluid was specifically cultured for mycoplasmas. This delay resulted in considerable joint destruction. The importance of searching for mycoplasmas in similar cases is emphasised.