Dataset concerning the analytical approximation of the Ae3 temperature.

In this paper we present a new polynomial function for calculating the local phase transformation temperature (Ae3 ) between the austenite+ferrite and the fully austenitic phase fields during heating and cooling of steel:[Formula: see text] The dataset includes the terms of the function and the values for the polynomial coefficients for major alloying elements in steel. A short description of the approximation method used to derive and validate the coefficients has also been included. For discussion and application of this model, please refer to the full length article entitled "The role of aluminium in chemical and phase segregation in a TRIP-assisted dual phase steel" 10.1016/j.actamat.2016.05.046 (Ennis et al., 2016) [1].

Diagnosing malnutrition in the elderly.

Numerous research studies have documented the inability of many health care providers to identify nutritional deficit vulnerability and early and advanced malnutrition states in the elderly. This article provides a clinical evaluation guide for identifying risks and diagnosing incipient and advanced malnutrition. Diagnosis and intervention can prevent loss of function and independence and decrease morbidity and mortality in the elderly.

Malnutrition in the elderly: what nurses need to know.

Identifying nutritional deficit vulnerability and early and advanced malnutrition states in the elderly can be challenging. This article provides a clinical evaluation guide for identifying risks and diagnosing incipient and advanced malnutrition. Diagnosis and intervention can prevent loss of function and independence and decrease morbidity and mortality in the elderly.

Induction of prostaglandin H synthase-2 and tumor necrosis factor-alpha in human amnionic WISH cells by various stimuli occurs through distinct intracellular mechanisms.

These studies examined the signal transduction mechanisms by which prostaglandin (PG) E2 production can occur in human amnionic WISH cells in response to the stimuli okadaic acid, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, phorbol-12-myristate-13-acetate (PMA) or combinations of PMA with IL-1beta or TNF-alpha. We also investigated whether WISH cells are capable of producing TNF-alpha or IL-1beta in response to stimulation, because these cytokines can be produced in an autocrine fashion to perpetuate an inflammatory response. Our data indicate that the magnitude of PGE2 production induced by a given stimulus correlated temporally with the level of PGH synthase-2 (PGHS-2) protein. PMA or IL-1beta induced PGE2 production 2 to 4 hr after treatment, whereas the combination of these agents produced the most rapid induction 2 hr after treatment. Only okadaic acid induced the production of both PGE2 and TNF-alpha, after a lag of 12 to 18 hr. PGE2 production by all stimuli was inhibited by dexamethasone, the IL-1 receptor antagonist (IL-1ra), the specific PGHS-2 inhibitor NS-398 and the protein kinase inhibitor staurosporin. In contrast, TNF-alpha production in response to okadaic acid was inhibited by the TNF-converting enzyme inhibitor GI 129471 and staurosporin but was unaffected by either IL-1ra, dexamethasone or NS-398. We conclude that WISH cells are capable of producing bioactive proinflammatory mediators such as TNF-alpha and PGE2 through separable intracellular signal transduction mechanisms. The ability of IL-1ra to reduce PGE2 production caused by all stimuli used suggests an autocrine role for IL-1 in PGHS-2 induction in these cells.

Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function.

BACKGROUND: Reperfusion after prolonged coronary artery occlusion may be followed by additional myocardial necrosis persisting for hours to days. Potential mechanisms include neutrophil-mediated injury and compromised flow within the microcirculation of the reperfused myocardium. Poloxamer 188 is a nonionic surfactant with beneficial hemorheological and neutrophil-inhibitory properties. The purpose of the present study was to determine if poloxamer 188 is capable of reducing the myocardial injury associated with sustained reperfusion and to examine the effect of treatment duration. METHODS AND RESULTS: Three groups of closed-chest dogs underwent 90 minutes of left anterior descending coronary artery occlusion (angioplasty balloon) and 72 hours of reperfusion. Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg.kg-1.h-1 continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours. The 48-hour infusion of poloxamer 188 resulted in a 42% reduction in infarct size (as a percent of the area at risk) compared with the control group (25.0 +/- 4.2% versus 43.3 +/- 4.3%, P D .01), whereas the 4-hour group demonstrated a 25% reduction in infarct size compared with the control group (32.4 +/- 4.3%, P = .08). ANCOVA demonstrated that the 48-hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P = .002 versus control). A trend toward infarct size reduction was observed in the 4-hour infusion group (P = .098 versus control by ANCOVA). Plasma creatine phosphokinase concentration was lower in both poloxamer 188-treated groups (P < .05 versus control). Global left ventricular ejection fraction at 72 hours of reperfusion was improved in the 48-hour infusion group compared with the control group (43 +/- 3.1% versus 33 +/- 2.0%, P < .05), whereas ejection fraction in the 4-hour group was 37 +/- 1.3% (P = NS versus control). Regional ventricular function was also significantly better in the 48-hour infusion group compared with the control group. In vitro studies demonstrated that at concentrations comparable to those achieved in vivo, poloxamer 188 inhibited neutrophil chemotaxis. This finding may represent a beneficial mechanism of action. CONCLUSIONS: A 48-hour infusion of poloxamer 188 reduced myocardial infarct size and improved left ventricular function in this dog model of 90 minutes of coronary artery occlusion and 72 hours of reperfusion. The finding that the 4-hour infusion of poloxamer 188 did not result in similar benefits suggests that additional reperfusion injury occurred between 4 and 48 hours.

Matrix degrading metalloproteinases.

Matrix degrading metalloproteinases are enzymes that degrade proteins in tissue extracellular matrices. These proteinases exhibit specific, well defined properties that allow them to be classified into a family of enzymes. They are secreted by various cell types as the cells effect their surrounding extracellular matrix. Such effects occur during normal physiologic tissue remodeling but also during pathologic processes such as tumor cell invasion and metastases. Currently there are seven proteases classified as members of the matrix metalloproteinase family and there are two putative members. Direct correlations can be made between the matrix metalloproteinases and normal tissue functions such as bone remodeling, uterine and mammary gland function and ovulation. The matrix metalloproteinases are also strongly associated with cancer progression in that they function to degrade epithelial basement membrane and stromal matrices in many different malignancies including brain tumors.

Characterization of a saphenous vein graft aneurysm by intravascular ultrasound and computerized three-dimensional reconstruction.

Aneurysmal dilatations in saphenous vein grafts are rare complications of coronary artery bypass surgery that mostly represent thin-wall pseudoaneurysms at anastomotic sites. We describe a case of an enlarging distal saphenous vein graft aneurysm in which intravascular ultrasound (IVUS) and computerized three-dimensional reconstruction (3DR) of the IVUS images was performed to conclusively demonstrate true aneurysm morphology. Although both atherosclerotic and nonatherosclerotic mechanisms for vein graft aneurysm formation have been previously suggested, IVUS images and 3DR of the aneurysm in this case did not reveal any of the features typical for atherosclerotic lesions. Further, the IVUS images and 3DR suggest that progressive atherosclerosis is not the likely cause of aneurysm formation in this case. This application of IVUS and 3DR provides detailed information about saphenous vein graft aneurysm structure, clues to aneurysm formation, and suggests a natural history that may differ from that of pseudoaneurysms.

Purification and characterization of a novel growth factor from human breast cancer cells.

We have purified and characterized a novel 30-kDa glycoprotein (gp30) with TGF alpha-like properties secreted from the estrogen receptor negative breast cancer cell line MDA-MB-231. This factor was immunoprecipitated by an anti-TGF alpha polyclonal antibody and also had TGF alpha-like biological activity, as assayed by EGF radioreceptor assay and anchorage-independent assays. In addition, the novel growth factor stimulated phosphorylation of the EGF receptor and erbB-2 receptor. However, the novel growth factor, unlike EGF and TGF alpha, bound to heparin-Sepharose. Purification of gp30 was obtained to apparent homogeneity by heparin affinity chromatography and subsequent reversed-phase chromatography. Tunicamycin treatment in vivo or N-glycanase deglycosylation in vitro revealed a putative precursor of approximately 22 kDa molecular mass in contrast to the "normal" 16-kDa precursor species for TGF alpha. In vitro translation of total mRNA from MDA-MB-231 cells confirmed the size of the putative precursor. Biochemical characterization of gp30 was begun by V8 protease digestion of the deglycosylated polypeptide and the translated products. Peptide mapping of V8-digested, immunoprecipitated material suggests that the amino acid sequence of this unique protein is distinct from mature TGF alpha and not the result of a posttranslational modification of the precursor. We conclude that this TGF alpha-like (gp30) polypeptide is a novel growth factor with agonistic activity for both EGF and erbB-2 receptors.

Tissue culture conditions determine the effects of estrogen and growth factors on the anchorage independent growth of human breast cancer cell lines.

We determined the effects of epidermal growth factor, insulin-like-growth-factor-1 and estradiol on the anchorage independent growth of the estrogen receptor positive human breast cancer cell lines MCF7 and T-47D. In serum free conditions growth factors but not estrogen induced a dose dependent stimulation of growth in both cell lines. The ability of estrogen to induce colony formation of early passage MCF7 cells (less than 100) was strictly correlated to the concentration of sulfatase and charcoal treated calf serum (CCS) with a maximal effect at a concentration of 5% CCS and 10 nM estradiol. CCS alone had no stimulatory effect on the anchorage independent growth of early passage MCF7 cells, but increased colony formation in late passage (greater than 1000) MCF7 and T-47D cells. The growth of late passage MCF7 cells was inhibited by antiestrogen. Thus, the presence of serum components is necessary for the effect of estrogen but not for the effects of growth factors on the anchorage independent growth of estrogen receptor positive human breast cancer cell lines; after a prolonged period of tissue culture serum components switch their function from indirectly modulating estrogen effects to directly stimulating growth in the absence of estrogen.

Laparoscopic hernia repair: the anatomic basis.

Laparoscopic hernia repair offers the potential for more rapid recovery in patients compared with standard anterior herniorrhaphy. Whether the procedure can be performed safely and effectively has yet to be determined. Long-term success will depend on the ability to adhere to the basic principles of traditional hernia repair, maintain low recurrence rates, and achieve rapid return of the patient to work. Inguinal anatomy as viewed through the laparoscope is unfamiliar to most surgeons. The potential for complications requiring laparotomy is increased with laparoscopic hernia repair and dissection in this region requires precise knowledge of the anatomic relationships. Photographic representations of cadaver dissections of the intra-abdominal inguinal region are displayed, and detailed descriptions applicable anatomic structures are presented. A laparoscopic approach for the repair of inguinal and femoral hernia is provided, based on sound comprehension of anatomic relationships.

The EGF receptor system as a target for antitumor therapy.

Monoclonal anti-EGF receptor antibodies, EGF receptor antibodies coupled to toxins, TGF alpha-toxin conjugates and tyrosine kinase inhibitors show great potential as antitumor agents. These compounds are effective inhibitors of the EGF receptor system as it functions in the mitogenic stimulation of malignant cells. The effectiveness of cell growth inhibition mediated by anti-EGF receptor antibody and tyrosine kinase inhibitors may prove to be limited and selective. This is in view of the possibility that malignant cell proliferation may be controlled by various mechanisms instead of that which involves the EGF receptor system, despite the expression of both EGF receptor and TGF alpha in the same cell. Other growth control mechanisms could involve hormone receptor systems such as estradiol and the estrogen receptor, oncogene activation or other growth factor-receptor systems. In those malignancies in which growth control resides in the EGF-receptor system, antitumor therapy using monoclonal anti-EGF receptor antibodies and tyrosine kinase inhibitors is a possibility worth pursuing. The effectiveness of immunotoxins and TGF alpha-toxin conjugates may only require the presence of EGF receptor and not be limited to those cells whose growth is controlled exclusively by the EGF receptor system. Nonspecific toxicity may, however, limit the use of these compounds. Further studies assessing the extent of such a toxicity are in order. In the face of the preceding reservations, however, one must not overlook the potential for great achievement as this novel therapeutic avenue is traversed.

Toxicity and effects of epidermal growth factor on glucose metabolism of MDA-468 human breast cancer cells.

Epidermal growth factor (EGF) has an in vitro inhibitory effect on tumor cells which exhibit a high number of EGF receptors (EGFR). Studies were performed in order to delineate the effects of EGF on glucose metabolism of MDA-468 human breast cancer cells, which have a large number of EGFR. Glucose consumption and lactate production were found to be substantially increased in MDA-468 cells following EGF exposure, while no such effects were detected in MCF-7 breast cancer cells, which have a very low number of EGFR. When glucose levels in the growth medium were increased, the toxicity of EGF was diminished. The energetic status of MDA-468 cells perfused with growth medium containing EGF was monitored by 31P magnetic resonance spectroscopy, and no signs of compromised metabolic state or viability were noted for up to 36 h. The rate of glucose transport and phosphorylation was quantitated by 13C magnetic resonance spectroscopy, utilizing [6-13C]2-deoxyglucose, and a 97% increase was found in MDA-468 cells following EGF administration. The profound effects of EGF on glucose metabolism in cells with very high numbers of EGFR and the lack of toxicity in the perfused system may indicate that the growth-inhibitory effect is confined to the in vitro cultured cells.

Expression of the transforming growth factor-alpha/epidermal growth factor receptor pathway in normal human breast epithelial cells.

To better understand the possible roles and interactions of transforming growth factor-alpha (TGF alpha) and its receptor, the epidermal growth factor (EGF) receptor in human breast epithelium, we have studied the expression of TGF alpha and the EGF receptor in a series of normal human mammary epithelial cells derived from reduction mammoplasty before in vitro propagation, during short term proliferation in vitro, and after immortalization. Increased TGF alpha mRNA expression coincided with conversion of the cells to a proliferative state in vitro. After establishment, propagation, and proliferation in vitro, the cells expressed high levels of both TGF alpha and EGF receptor mRNAs. Addition of diverse growth inhibitory agents, including 12-O-tetradecanoylphorbol-13-acetate (TPA), TGF beta, and sodium butyrate, to one of these rapidly proliferating cell populations (no. 184) failed to reduce the expression of either TGF alpha or the EGF receptor. Likewise, cessation of growth associated with both senescence and confluence of the 184 cells did not result in reduced expression. However, regulation of TGF alpha mRNA could be demonstrated by withdrawal of EGF from the medium or by antibody-mediated blockade of the EGF receptor in 184 cells. Antibody-mediated EGF receptor blockade also results in inhibition of growth and [3H]thymidine labeling. An autoregulatory autocrine loop appears operant in proliferating breast epithelial cells. Both growth and levels of TGF alpha mRNA expression are controlled by binding of ligand to the EGF receptor. These studies suggest a role for the TGF alpha/EGF receptor pathway in normal breast cell physiology.

Anti-epidermal growth factor receptor antibodies inhibit the autocrine-stimulated growth of MDA-468 human breast cancer cells.

The response of malignant and nonmalignant human breast cell lines to the growth inhibitory effects of monoclonal antibodies against the epidermal growth factor (EGF) receptor was studied. A series of human breast cell lines, which express EGF receptor, were used: MDA-468, MDA-231, and Hs578T human breast cancer cells and the transformed human mammary epithelial cell lines 184A1N4 and 184A1N4-T that have been benzo[a]pyrene immortalized and further transformed with SV40T, respectively. Four antibodies of two different classes were tested: 225 immunoglobulin G (IgG), 108.4 IgG, 96 immunoglobulin M (IgM), and 42 IgM. All four antibodies inhibited the anchorage-dependent and -independent, EGF-stimulated growth of 184A1N4 and 184A1N4-T cells, respectively, and this growth inhibition could be reversed by the addition of increasing concentrations of EGF. In contrast, the antibodies inhibited the anchorage-dependent and -independent growth of MDA-468 cells in the absence of exogenous EGF suggesting that the antibodies were acting to block access of an endogenously produced ligand to the EGF receptor. In the presence of antibody and increasing concentrations of EGF, MDA-468 cell growth was first stimulated then inhibited as the EGF concentration increased, thus, uncovering the growth stimulatory potential of low concentrations of EGF in these cells. Data is presented that indicates MDA-468 cells secrete a transforming growth factor with autocrine growth stimulatory capabilities. The growth of MDA-231 and Hs578T cells, which contain activated ras oncogenes, was not inhibited by the antibodies and the growth of these cell lines was not stimulated by EGF. Of the cell lines studied only MDA-468 cells appear to possess an autocrine growth stimulatory capacity.

Transforming growth factors type beta 1 and beta 2 are equipotent growth inhibitors of human breast cancer cell lines.

At least one member of the TGF-beta family, TGF-beta 1, has been previously shown to inhibit the anchorage-independent growth of some human breast cancer cell lines (Knabbe et al., 1987; Arteaga et al., 1988). Members of the TGF-beta family might, therefore, provide new strategies for breast cancer therapy. We have studied the inhibitory effects of TGF-beta 1 and TGF-beta 2 on the anchorage-independent growth of the oestrogen receptor-negative cell lines MDA-MB-231, SK-BR-3, Hs578T, MDA-MB-468, and MDA-MB-468-S4 (an MDA-MB-468 clone not growth inhibited by EGF) and the estrogen receptor-positive cell lines MCF7, ZR-75-1, T-47D. TGF-beta 1 and TGF-beta 2 caused a 75-90% growth inhibition of MDA-MB-231, SK-BR-3, Hs578T, and MDA-MB-468 cells and a 50% growth inhibition of ZR-75-1 and early passage (less than 100) MCF7 cells. T-47D cells responded to TGF-beta only in serum-free conditions in the presence of IGF-1 or EGF. The growth of MDA-MB-468-S4 cells and late passage (greater than 500) MCF7 cells was not inhibited by TGF-beta 1 or TGF-beta 2. TGF-beta-sensitive MCF7 and MDA-MB-231 cells did not respond to Muellerian inhibiting substance (MIS), a TGF-beta-related polypeptide. TGF-beta 1 or TGF-beta 2 were mutually competitive for receptor binding with a similar affinity (Kd 25-130 pM, 1,000-13,000 sites per cell). To determine the time course of the TGF-beta effect, an anchorage-dependent growth assay was carried out using MDA-MB-231 cells. Growth inhibition occurred at 6 days, and cell-cycle changes were seen 12 hr after the addition of TGF-beta. Cells accumulated in the G1 phase and were thus inhibited from entering the S-phase. These data indicate that TGF-beta is a potent growth inhibitor in most breast cancer cell lines and provide a basis for studying TGF-beta effects in vivo.

Endocrine therapy of human breast cancer cells: the role of secreted polypeptide growth factors.

Endocrine therapy is an important modality in the treatment of breast cancer. However, the precise molecular mechanisms underlying the growth inhibitory effect of endocrine therapy are unknown. Recently, it has been shown that breast cancer cells express and secrete polypeptide growth factors that can regulate the growth of the cells through autocrine and/or paracrine pathways. These growth factors are thought to be involved in the response to endocrine therapy. Three different mechanisms have been suggested: (1) stimulation of growth inhibitory peptides; (2) repression of mitogenic peptides; and (3) stimulation of mitogenic growth factors in cells overexpressing the corresponding receptor. This article reviews the scientific evidence on which these hypotheses are based.

Autoradiographic localization of [3H]hydroxytamoxifen to uterine oestrogen- and antioestrogen-binding sites.

Immature rats were injected subcutaneously with 0.36 micrograms of [3H]hydroxytamoxifen ([3H]TAM(OH)) or 0.24 microgram of [3H]oestradiol in oil, and 4 h later uteri were processed for thaw-mount autoradiography. The specificity of [3H]TAM(OH) localization was determined by injecting a 200-fold excess of unlabelled TAM(OH) or a 20-, 200- or 2000-fold excess of oestradiol 1 h before injection of [3H]TAM(OH). After injection of [3H]TAM(OH) or [3H]oestradiol, autoradiograms showed concentration of radioactivity in nuclei of stromal, epithelial and myometrial cells, but this labelling varied among the cell types depending upon which compound was injected. After [3H]TAM(OH) injection, the decreasing order of labelling intensity was stroma, myometrium, epithelium; after [3H]oestradiol injection the decreasing order was stroma, epithelium, myometrium. Injection of TAM(OH) before [3H]TAM(OH) eliminated nuclear labelling in all the uterine cell types. Injection of oestradiol before [3H]TAM(OH) decreased nuclear labelling and resulted in the concentration of label in the cytoplasm of luminal epithelium which was not present when [3H]TAM(OH) was injected alone. Cytoplasmic labelling increased initially as the oestradiol competition dose increased, but the increase in labelling did not continue with increasing concentrations of oestradiol. The results indicate that antioestrogen and oestrogen localize to nuclei of the same uterine cell types, but that cellular uptake differs among the tissue compartments. The results also suggest that a high concentration of antioestrogen-binding sites exist in the cytoplasm of the uterine luminal epithelium.

Binding of estrogen and antiestrogen in uterine cell nuclei: in vivo autoradiographic studies.

The in vivo binding of antiestrogen in nuclei within the uterine stromal, epithelial and myometrial tissue compartments was compared to that of estrogen 2-48 h after injection. Tissue binding and retention of radioactivity was also studied. Immature rats were injected s.c. with 0.36 microgram [3H]hydroxytamoxifen [( 3H]TAM(OH] or 0.24 microgram [3H]estradiol [( 3H]E2) in oil. At 2, 4, 8, 12, 24 and 48 h after injection, uteri were processed for thaw-mount autoradiography and, along with other tissues, for liquid scintillation counting. After [3H]TAM(OH) injection total radioactivity in uterus, cervix, vagina and liver reached peak levels by 8 h then decreased slowly so that by 48 h radioactivity still remained in the tissues. At all time intervals, the levels of radioactivity in heart and muscle remained low. After [3H]E2 injection radioactivity in uterus, cervix and vagina reached peak levels between 2 and 4 h then decreased rapidly so that by 12 h radioactivity was low and essentially the same as in liver, heart and muscle. These results were paralleled by the time course of nuclear binding of [3H]TAM(OH) and [3H]E2 in the uterine cell types: peak levels occurred at 8 h and 4 h, respectively. Nuclear binding was still present 48 h after [3H]TAM(OH) injection but was absent by 24 h after [3H]E2 injection. Different uterine cell types bound different amounts of both the drug and the hormone. After [3H]TAM(OH) injection the decreasing order of labeling intensity in the tissue compartments was stroma, myometrium, epithelium; in contrast, that after [3H]E2 injection was stroma, epithelium, myometrium. The results indicate that the dissimilar nuclear binding kinetics of estrogen and antiestrogen are influenced by the pharmacokinetics but the uterine cell types may also influence binding kinetics.

Differential induction of progestin-binding sites in uterine cell types by estrogen and antiestrogen.

Effects of antiestrogen on progestin binding in uterine cell types were determined and compared to those of estrogen. Effects on uterine morphology were also studied. Immature rats were treated with four daily sc injections of 100 micrograms hydroxytamoxifen [TAM(OH)], 5 micrograms estradiol (E2), or oil. On day 5 the rats were injected iv with 1 microgram of the synthetic progestin [3H]Org 2058, and 1 h later uteri were excised, weighed, and processed for thaw-mount autoradiography. Treatment with TAM(OH) or E2 resulted in uterine weight gain, which was greater in animals treated with E2. E2 treatment resulted in cellular hypertrophy in all tissue compartments, especially in the luminal epithelium and myometrium, but TAM(OH) treatment resulted in hypertrophy of only the luminal epithelium. Treatment with TAM(OH) or E2 changed the pattern and intensity of nuclear binding of [3H]Org 2058 from that in oil-treated controls. E2 increased progestin binding in stroma and myometrium and decreased it in luminal epithelium. TAM(OH), similarly, decreased progestin binding in the luminal epithelium and increased it, albeit less than E2, in the myometrium, but left it unchanged in the stroma. The results indicate that E2 and TAM(OH) differentially effect progestin binding among the uterine tissue compartments.