Serotonin responsive and nonresponsive diurnal depressive mood disorders and pathological affect in thalamic infarct associated with myoclonus and blepharospasm.
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Biomedical subjects
Publications and source records attributed to J G Jackson.
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Two cases of basal ganglia calcification involving the globus pallidus are presented. Both patients had cognitive dysfunction, temporal lobe-like symptoms (including amnestic state, perceptual distortions, or complex visual hallucinations), and myoclonus. Patient 1 manifested depression, auditory hallucinations, anxiety, paranoia, and postural tremor; patient 2 manifested multifocal dystonia with dystonic tremor. These cases supplement other reports of psychotic features and dementia associated with pallidal pathology. Additionally, the phenomena encountered in these cases are considered in light of recent advances in our understanding of basal ganglia functional pathways. These cases afford a potential pathophysiological window to the possible role of the globus pallidus in these neuropsychiatric conditions. In concert with other recent findings, these cases suggest specific pathway involvement in hallucinations, paranoia, depression, myoclonus, and dystonia. Further research will indicate if these pathways play a role in schizophrenia, mood disorders, and anxiety disorders.
Eighty breast cancer specimens were examined for insulin-like growth factor binding protein (IGFBP) expression by ligand blotting. Five distinct IGFBP species were found: a doublet at 48 and 44 kDa was IGFBP-3, the 34-kDa band was IGFBP-2, and a band at 24 kDa was IGFBP-4. A 32-kDa band was compatible with the migration position reported for IGFBP-5. IGFBP-3 was inversely correlated with ER expression, while IGFBP-4 was positively correlated with both ER and PgR. IGFBP-4 was also inversely correlated with S-phase fraction. Thus, IGFBP expression correlates with other parameters of breast cancer biology and may play a role in regulating tumor growth.
Autocrine expression of polypeptide growth factors may be important in the growth regulation of cancer cells. Different growth factor activities have been identified in a variety of tumors. This article describes a case of malignant ascites in a patient recently treated for breast cancer. The use of growth factor mRNA expression as a factor to differentiate between breast and ovarian origins of cancer cells contained in malignant ascites was examined. Expression of insulin-like growth factor-I (IGF-I), IGF-II, and transforming growth factor alpha mRNA was examined by ribonuclease protection assay. The tumor cells expressed IGF-II and transforming growth factor alpha, but not IGF-I mRNA. This pattern of growth factor expression is compatible with a breast cancer primary of the malignant cells contained in the ascites fluid. Therefore, IGF-I mRNA expression may be useful in distinguishing between adenocarcinomas of breast or ovarian origins.
Interactions between insulin-like growth factor I (IGF-I) and the type of I IGF receptor may be affected by high-affinity extracellular binding proteins. To date, six distinct IGF binding proteins (IGFBPs) have been identified, but their physiological roles are not well understood. For example, depending on experimental conditions, IGFBP-1 has been shown to both enhance and inhibit IGF-I mediated mitogenesis. We have previously shown that excess exogenous IGFBP-1 inhibited IGF-I mediated growth of MCF-7 cells. In this study, we examined whether or not endogenously expressed IGFBP-1 could interfere with IGF-I mediated growth of MCF-7 cells. Cells were stably transfected with an IGFBP-1 expression vector. IGFBP-1 mRNA was produced by the cells, and protein was detected in the conditioned media by ligand blot and immunoblot. Type I IGF receptor could not be phosphorylated by IGF-I in cells expressing IGFBP-1; however, an IGF-I analogue (Arg-3-IGF-I), which cannot complex with IGFBPs, stimulated receptor phosphorylation. IGF-I did not stimulate cell growth in IGFBP-1 expressing cells. These results suggest that IGFBP-1 expression in MCF-7 breast cancer cells inhibits IGF-I induced growth by interrupting the interaction between IGF-I and its receptor.
The insulin-like growth factors (IGFs) have been implicated in the growth regulation of human breast cancer. Since the IGFs are associated with specific binding proteins (IGFBPs) which may modulate receptor/ligand interactions, production of IGFBPs by breast cancer cells could alter their IGF-dependent growth. This study examined the expression of IGFBPs 4, 5, and 6 in eight breast cancer cell lines (BCCLs) using ribonuclease (RNase) protection assays. IGFBP-4 mRNA was detected in all BCCLs studied. IGFBP-5 expression was higher in estrogen receptor (ER) positive cells, while IGFBP-6 mRNA was detected in only two ER negative BCCLs. We also found that E2 treatment enhanced the expression of IGFBPs 2, 4, and 5 in T47-D cells. We next studied IGFBP mRNA expression in 40 primary breast tumors. All tumors expressed mRNA for IGFBPs 2-6 but none expressed IGFBP-1 message. IGFBP-3 expression was higher in ER negative tumors, while that of IGFBP-4 and -5 was higher in ER positive specimens. These differences were statistically significant (P < .05). Ligand blot analysis of tumor extracts confirmed the presence of IGFBPs in breast cancer tissues. Thus, differential IGFBP expression in ER positive and negative tumors suggests an important role for this protein in breast cancer biology.
The insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells and their activity is modulated by high affinity binding proteins (IGFBPs). We have recently shown that IGFBP-1 purified from human amniotic fluid neutralizes IGF-I-dependent growth of MCF-7 cells. In this study we examined the effects of recombinant IGFBP-1 (rBP-1) on IGF-I, estradiol (E2), and serum-induced monolayer and anchorage independent growth (AIG) of MCF-7 cells. Under serum-free conditions, rBP-1 had no effect on MCF-7 basal monolayer growth. However, 40 nM rBP-1 completely blocked the mitogenic action of both IGF-I and 5% charcoal stripped serum (CSS). This concentration of rBP-1 partially inhibited E2-induced growth, while 80 nM rBP-1 completely abolished E2 mitogenicity. The addition of either excess IGF-I or 5 nM [Arg3]IGF-I, a species that does not bind IGFBPs, neutralized rBP-1 inhibitory effects. In AIG assays, 80 nM rBP-1 reduced colony number by at least 70% and decreased colony size in all treatment groups compared to control. We examined rBP-1 effects on both IGF-I binding to MCF-7 membranes and activation of type I IGF receptor (IGFR1) and found that 80 nM rBP-1 reduced IGF-I receptor binding to levels of nonspecific binding and completely abolished ligand-dependent IGFR1 phosphorylation. However, neither treatment with 5% CSS nor exposure to E2 resulted in IGFR1 phosphorylation suggesting that different mechanism(s) are responsible for rBP-1 inhibitory action under this condition. Our data suggest rBP-1 may serve as an antagonist of human breast cancer growth by interfering with growth factor-mediated cell proliferation.
Insulin-like growth factor-I (IGF-I), its receptor and its binding proteins are expressed by ovarian cancer cells. In this study, we examined oestradiol (E2) regulation of IGF-I and IGF binding proteins (IGFBP) in an oestrogen-responsive ovarian cancer cell line, PE04. In serum-free conditions, PE04 cell monolayer growth was increased 1.64-fold by 3 nmol/l E2 compared with controls, although IGF-I mRNA levels were not increased. In contrast to IGF-I mRNA, IGFBP mRNA was regulated by E2. E2 caused a marked decrease in IGFBP-3 RNA, but IGFBP-2, -4 and -6 levels were only minimally depressed. IGFBP-5 mRNA levels were increased by E2. Tamoxifen had less effect on IGFBP mRNA regulation. Ligand blotting showed that E2 reduced IGFBP levels in conditioned media. IGFBP RNA was also detected in human ovarian tissue samples. Thus, IGFBP expression can be regulated in oestrogen-responsive ovarian cancer by E2.
BACKGROUND: The insulin-like growth factors (IGFs) play an important role in normal growth and development. Evidence suggests they may also regulate the growth of several cancer cell types. This regulation is mediated by interactions between the receptors and ligands. There is now ample evidence to suggest that these interactions are also influenced by extracellular IGF-binding proteins (IGFBPs). Six different IGFBPs have been cloned. Some species may act to inhibit the mitogenic effects of the IGFs. Since breast cancer cells are responsive to the IGFs, it is possible that regulated expression of the IGFBPs affects tumor growth. Furthermore, inhibitory binding proteins could be used as neutralizers of IGF action. PURPOSE: We conducted this study to fully characterize the expression and hormonal regulation of IGF-binding protein expression in human MCF-7 breast cancer cells and to test the ability of purified IGFBP-1 to inhibit IGF-I action. METHODS: We used ribonuclease protection assays and Western ligand blotting to examine IGFBP expression in MCF-7 cells. The effect of IGF-I, IGFBP-1, and 17 beta-estradiol on serum-free cell growth was also studied. RESULTS: MCF-7 cells expressed IGFBP-2, IGFBP-4, and IGFBP-5 RNA and protein. These cells are dependent on estrogen for growth. In short-term culture, IGF-I can substitute for estrogen. Concomitant addition of IGF-I and estrogen enhanced stimulation above the level achieved by either factor alone. Estrogen also increased IGFBP production, making it unlikely that the IGFBPs induced by estrogen in MCF-7 cells could function as major inhibitors of IGF action. In contrast, exogenous addition of IGFBP-1 could block IGF-I-induced mitogenesis; this effect was reversible by excess IGF-I. CONCLUSIONS: The studies suggest that cancer cell growth may be regulated by endogenous IGFBP expression. Furthermore, the exogenous addition of the IGFBP-1 blocked IGF-I action and potentially could be used as a pharmacologic inhibitor of IGF action.
Renal oncocytomas are uncommon, benign tumors that classically are treated by local excision or heminephrectomy. Preoperative differentiation from renal cell carcinoma is invaluable in the planning of treatment. Cases of renal oncocytoma treated conservatively have been reported. This is a case report of bilateral multifocal renal oncocytomas of which only three previous cases have been reported. Diagnosis was made from multiple fine needle biopsies and present treatment consists only of conservative observation.
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The subcutaneous administration of the anticoagulant heparin sodium is a frequently performed nursing intervention. Bruising (discoloration) and induration (hardening) occur after some but not all such injections. This has implications for nursing; not only does the patient experience the physical discomfort and the psychologic impact of visible body trauma, but bruising and induration limit possible sites for future injections. Administration technique is frequently cited as a possible cause of bruising and induration. The purpose of this study was to compare two administration techniques currently being used by nurses. Variables studied included syringe size, change of needles after drawing medication into the syringe, use of an air bubble, and type of sponge (dry or alcohol) applied to the site after injection. The sample included 50 medical-surgical patients aged 23 to 88 years. Each subject received two injections by the same investigator using two different techniques. Sites were inspected and bruises and induration measured 52 hours after each injection. To compare the size of bruises and indurations, the data were analyzed by the Mann-Whitney U-Wilcoxon rank sum test, which showed a 0.003 level of significance for bruises and a 0.02 level of significance for induration. To compare the number of subjects in whom bruises and indurations developed, the data were analyzed by the chi-square test, which showed a 0.0458 level of significance for induration but only a 0.1371 level of significance for bruising.(ABSTRACT TRUNCATED AT 250 WORDS)
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Extracranial metastases of meningioma are very rare, with a reported incidence of less than one in 1000 cases of meningioma. Metastases have been reported in the lungs and pleura, in the liver, in the lymph nodes, and in bone. The appearance of osseous metastases in the bony pelvis from intracranial angioblastic meningioma is described.
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