Fatty acid synthase expression in endometrial carcinoma: correlation with cell proliferation and hormone receptors

BACKGROUND: Fatty acid synthase (FAS), a biosynthetic enzyme, normally functions in the liver to convert dietary carbohydrate to fat, but it is minimally expressed in most other normal adult tissues. FAS is expressed at markedly elevated levels in subsets of human breast, ovarian, and prostate carcinomas that are associated with poor prognoses. During the menstrual cycle, the expression of FAS in the human endometrium is closely linked to the expression of the proliferation antigen Ki-67, estrogen receptor (ER), and progesterone receptor (PR). METHODS: This study reports the expression patterns of these antigens in 35 endometrial carcinomas as determined by immunohistochemical analysis. RESULTS: All cases demonstrated a close direct correlation between FAS and Ki-67 expression. Average FAS expression levels were correlated with tumor grade. Twenty-five carcinomas that were positive for ER and PR showed close correlation in expression of FAS, Ki-67, and hormone receptors. Individual tumors displayed varying degrees of heterogeneity of expression. A few well-differentiated carcinomas showed very low expression of all four antigens, similar to the antigenic profile of secretory endometrium. Nine high grade carcinomas that were negative for ER and PR also showed close correlation in expression of FAS and Ki-67 with uniformly high expression. CONCLUSIONS: These data suggest the following hypothesis: In hormone-dependent endometrial cells, FAS expression is part of the estrogen-driven cellular response that leads to proliferation; however, its linkage to proliferation is such that FAS expression is maintained in proliferating cells in endometrial carcinomas that acquire hormone independence. The use of these four antibodies as a panel may increase the diagnostic utility of ER and PR immunohistochemistry for tumor classification and prediction of the responsiveness of tumors to hormonal therapy.     

Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group

AIMS: To estimate the impact of co-morbid disorders for suicidal ideas in alcohol-dependent subjects seeking treatment. DESIGN: Life-time psychiatric co-morbidity and previous suicidal behaviours were assessed retrospectively after detoxification (t1). In addition, suicidal behaviours were assessed 12 months after discharge (t2). SETTING: An inpatient detoxification treatment unit. PARTICIPANTS: Two hundred and fifty dependent inpatients were studied after detoxification. One hundred and forty-nine of them participated in the follow-up face-to-face interviews. MEASUREMENTS: Using two extended standardized interviews (CIDI and IPDE) psychiatric co-morbidity (DSM-III-R, Axes I and II) was assessed at t1; suicide attempts were reported at t1 and t2, and suicidal ideas were assessed at t2. FINDINGS: A history of suicide attempts was reported by 29.2% at t1, and suicidal ideas by 14.1% and suicide attempts by 5.4% at the follow-up (t2). One female patient committed suicide within 6 months of discharge from hospital. The following co-morbidity patterns were associated with the greatest risk for suicidal ideas. Anxiety and depressive disorders, Axes I and 11 disorders, and a history of suicide attempt (for suicidal ideas at (t2). CONCLUSION. Our results underline the importance of psychiatric co-morbidity for the suicidal risk in alcohol-dependent patients, while alcoholism itself appears to be only a moderate risk factor.     

Medical and public health services at the 1996 Atlanta Olympic Games: an overview

Planning for the 2000 Sydney Olympic Games may benefit from the experience of the 1996 Atlanta Olympics. Excellent health promotion and prevention activities before and during the Games resulted in fewer medical and public health problems than anticipated. Despite this, there was room for improvement in the level of communication and cooperation between the many service providers to ensure the most appropriate and efficient responses.     

Neonatal MSG reduces hypothalamic DA, beta-endorphin, and delays weight gain in genetically obese (A viable yellow/alpha) mice

Neonatal treatment with monosodium glutamate (MSG) decreases proopiomelanocortin (POMC) peptides and results in obesity. The yellow mouse is a model of obesity induced by the viable yellow (Avy) gene at the agouti locus on Chromosome 2, which results in overproduction of a POMC receptor antagonist. Thus we hypothesized that MSG, when imposed on the genetically susceptible model, would alter the development of obesity. Both yellow obese (Avy) and black lean (alpha/alpha) males were injected on Postnatal Days 1, 3, 5, 7, and 9 with 2.0 mg/g body weight MSG or saline SC. Their food intake, growth parameters, and neurochemical status were examined. Paradoxically, MSG interacted with the yellow phenotype to delay the rapid rate of weight gain characteristic of this model (p < 0.05). Food intake was decreased (p < 0.05) in both phenotypes treated with MSG, as was hypothalamic content of dopamine (p < 0.05) and of the POMC peptide, beta-endorphin (p < 0.001). The yellow obese phenotype was more sensitive than the black lean phenotype to the neurochemical effect of early postnatal MSG administration. Recent reports suggest the agouti locus protein is an antagonist of the receptor for another POMC peptide, melanocyte-stimulating hormone (MSH). Therefore, the balance of functional activity between various POMC peptides appears to be an important factor in the development of both acquired and genetic obesity.     

Minimally invasive cardiac valve surgery improves patient satisfaction while reducing costs of cardiac valve replacement and repair

OBJECTIVE: This study compares the quality of valve replacement and repair performed through minimally invasive incisions as compared to the standard operation for aortic and mitral valve replacement. SUMMARY BACKGROUND DATA: With the advent of minimally invasive laparoscopic approaches to orthopedic surgery, urology, general surgery, and thoracic surgery, it now is apparent that standard cardiac valve operations can be performed through very small incisions with similar approaches. METHODS: Eighty-four patients underwent minimally invasive aortic (n = 41) and minimally invasive mitral valve repair and replacement (n = 43) between July 1996 and April 1997. Demographics, procedures, operative techniques, and postoperative morbidity and mortality were calculated, and a subset of the first 50 patients was compared to a 50-patient cohort who underwent the same operation through a conventional median sternotomy. Demographics, postoperative morbidity and mortality, patient satisfaction, and charges were compared. RESULTS: Of the 84 patients, there were 2 operative mortalities both in class IV aortic patients from multisystem organ failure. There was no operative mortality in the patients undergoing mitral valve replacement or repair. The operations were carried out with the same accuracy and attention to detail as with the conventional operation. There was minimal postoperative bleeding, cerebral vascular accidents, or other major morbidity. Groin cannulation complications primarily were related to atherosclerotic femoral arteries. A comparison of the minimally invasive to the conventional group, although operative time and ischemia time was higher in minimally invasive group, the requirement for erythrocytes was significantly less, patient satisfaction was significantly greater, and charges were approximately 20% less than those in the conventional group. CONCLUSIONS: Minimally invasive aortic and mitral valve surgery in patients without coronary disease can be done safely and accurately through small incisions. Patient satisfaction is up, return to normality is higher, and requirement for postrehabilitation services is less. In addition, the charges are approximately 20% less. These results serve as a paradigm for the future in terms of valve surgery in the managed care environment.     

Obstructive intestinal herniation due to improper use of a seat belt: a case report

The term "seat belt syndrome" has been used to describe injuries to the abdominal viscera caused by seat belts during car accidents. These injuries are usually sustained as a result of the rapid deceleration that occurs in front-end collisions, with the consequent compression of the abdominal viscera. The spectrum of injuries includes intestinal perforation or stenosis, mesenteric disruption, and lumbar fracture-dislocation. We present an uncommon case of obstructive herniation in a 2-year-old girl which we believe was due to improper use of a seat belt.     

Ventilation and hypoxic ventilatory responsiveness in Chinese-Tibetan residents at 3,658 m

When breathing ambient air at rest at 3,658 m altitude, Tibetan lifelong residents of 3,658 m ventilate as much as newcomers acclimatized to high altitude; they also ventilate more and have greater hypoxic ventilatory responses (HVRs) than do Han ("Chinese") long-term residents at 3,658 m. This suggests that Tibetan ancestry is advantageous in protecting resting ventilation levels during years of hypoxic exposure and is of interest in light of the permissive role of hypoventilation in the development of chronic mountain sickness, which is nearly absent among Tibetans. The existence of individuals with mixed Tibetan-Chinese ancestry (Han-Tibetans) residing at 3,658 m affords an opportunity to test this hypothesis. Eighteen men born in Lhasa, Tibet, China (3,658 m) to Tibetan mothers and Han fathers were compared with 27 Tibetan men and 30 Han men residing at 3,658 m who were previously studied. We used the same study procedures (minute ventilation was measured with a dry-gas flowmeter during room air breathing and hyperoxia and with a 13-liter spirometer-rebreathing system during the hypoxic and hypercapnic tests). During room air breathing at 3,658 m (inspired O2 pressure = 93 Torr), Han-Tibetans resembled Tibetans in ventilation (12.1 +/- 0.6 vs. 11.5+/- 0.5 l/min BTPS, respectively) but had HVR that were blunted (63 +/- 16 vs. 121 +/- 13, respectively, for HVR shape parameter A) and declined with increasing duration of high-altitude residence. During administered hyperoxia (inspired O2 pressure = 310 Torr) at 3,658 m, the paradoxical hyperventilation previously seen in Tibetan but not Han residents at 3,658 m (11.8 +/- 0.5 vs. 10.1 +/- 0.5 l/min BTPS) was absent in these Han-Tibetans (9.8 +/- 0.6 l/min BTPS). Thus, although longer duration of high-altitude residence appears to progressively blunt HVR among Han-Tibetans born and residing at 3, 658 m, their Tibetan ancestry appears protective in their maintenance of high resting ventilation levels despite diminished chemosensitivity.     

Cell population mechanisms of inhibition of erythropoiesis in polycythemia

The ciliary activity of Ctenophore bolinopsis is inhibited by decreasing concentration of Mg2+ and increasing concentration of Ca2+ in the medium. The same changes in Mg2+ and Ca2+ concentration trigger muscle contractions and bioluminescence. Co2+ arrests the cilia beating in the rectangular position. An increase in Mg2+ concentration or decrease in Ca2+ concentration switch off the nervous inhibitory mechanisms of ciliary activity, suppress muscle contractions and bioluminescence. Ni2+ produces a similar effect, but the ciliary heating is only slightly accelerated, by the contrast to the effect of increased Mg2+ concentration. A Cl-free medium Mn2+ and tetrodotoxin in commonly used concentrations are of no effect on the systems studied. Experiments involving changes in K+ concentrations and administration of tetraethylammonium suggest that the resting potential in the examined cells may be due to K+ as the most permeant ion, and that K+-channels in the cell membrane may be voltage--controlled. The proposal about "biionic" (Ca2+/Mg2+) bioelectric control of a number of intracellular reactions is discussed.     

Aortic valve operations under deep hypothermic circulatory arrest for the porcelain aorta: "no-touch" technique

BACKGROUND: Aortic valve replacement or repair becomes a high-risk procedure in patients in whom the ascending aorta cannot be clamped either because of extensive calcification and risk of cerebral embolus or because of extensive adhesions precluding safe dissection and clamping. METHODS: We report the results of aortic valve replacement or repair with deep hypothermic circulatory arrest in 3 patients. Techniques to improve results include routine use of epiaortic and transesophageal echocardiography, avoidance of manipulation of the ascending aorta until the circulation is arrested, avoidance of antegrade cardioplegia, routine use of retrograde cardioplegia and retrograde cerebral perfusion, when feasible, and minimal aortotomy (just enough to excise and replace or repair the valve). RESULTS: Operations were accomplished in approximately 1 hour each with minimal manipulation of the aorta, thus minimizing aortic trauma and subsequent risk of cerebral embolus. Each patient had an unremarkable recovery without neurologic complications. CONCLUSIONS: Aortic valve replacement or repair using the "no-touch" technique and deep hypothermic circulatory arrest is the preferred method when dealing with the porcelain or unclampable aorta.     

Ribonuclease L, a 2-5A-dependent enzyme: purification to homogeneity and assays for 2-5A binding and catalytic activity

We have already presented a two-dimensional cell motility assay using a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1 as a motility model of tumour cells of epithelial origin. In this model, L-10 cells showed locomotion as a coherent sheet when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement "cohort migration". Electron and immunoelectron microscopic study of the migrating cell sheets demonstrated localized release from cell-cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex, including beta-catenin. Cell-extracellular matrix (ECM) interactions involved in this TPA-induced cohort migration and their effect on tyrosine phosphorylation of the E-cadherin-catenin complex have now been investigated. L-10 cell cohort migration was almost completely inhibited by addition of Arg-Gly-Asp (RGD) peptide into the medium, and thus RGD dependent. Cohort migration was stimulated on type I and IV collagens, fibronectin (FN)- and laminin-coated substratum, but was inhibited by RGD only on FN-coated surface. By using immunofluorescent techniques, FN was demonstrated preferentially around migrating cells, and a protein synthesis inhibitor, cycloheximide, inhibited the migration by about 75%. FN produced by L-10 cells were found to be mostly EDA+ FN when analysed by RT-PCR. Moreover, anti-FN antibody, but not anti-vitronectin antibody, inhibited the TPA-induced cohort migration almost completely. Thus, it was likely that L-10 cells produced FN themselves and moved on the FN substrate in an RGD-dependent manner. However, stimulation of migration by type I collagen coating and inhibition by RGD treatment did not affect the tyrosine phosphorylation of the E-cadherin-catenin complex induced by TPA, indicating that cell-cell interactions were adjusted to suit cell migration, irrespective of the condition of cell-ECM adhesion, during TPA-induced cohort migration.