Showing papers by "Georgetown University published in 1993"

Distinguishing the experiences of envy and jealousy.

Abstract: This article describes the nature and significance of the distinction between the emotions of envy and jealousy and reports 2 experiments that empirically investigated it. In Experiment 1, Ss recalled a personal experience of either envy or jealousy. In Experiment 2, Ss read 1 of a set of stories in which circumstances producing envy and jealousy were manipulated independently in a factorial design. Both experiments introduced new methodologies to enhance their sensitivity, and both revealed qualitative differences between the 2 emotions. Envy was characterized by feelings of inferiority, longing, resentment, and disapproval of the emotion. Jealousy was characterized by fear of loss, distrust, anxiety, and anger. The practical importance of this distinction, the reasons for its confusion, and general issues regarding the empirical differentiation of emotions are discussed.

Returns to investment in education

Abstract: Returns to investment in education based on human capital theory have been estimated systematically since the 1950s. In the 60-plus year history of such estimates, there have been several compilations in the literature. This paper reviews and highlights the latest trends and patterns based on a database of 1,120 estimates in 139 countries. The review shows that the private average global rate of return to one extra year of schooling is about 9 percent a year and very stable over decades. Private returns to higher education have increased over time, raising issues of financing and equity. Social returns to schooling remain high, above 10 percent at the secondary and higher education levels. Women continue to experience higher average rates of return to schooling, showing that girls' education remains a priority. Returns are higher in low-income countries. Those employed in the private sector of the economy enjoy higher returns than those in the public sector, lending support to the productive value of education.

Bipolar surgical snare and methods of use

Abstract: A bipolar snare instrument (10) for use in surgery is provided. The snare instrument (10) has a snaring loop (12) comprising a flexible continuous electrically-insulating loop (20) to provide localized selected necrosis and hemostasis of a patient's protruding tissue. Methods of performing surgery with such devices are also described.

Closed-End Country Funds and U.S. Market Sentiment, Mitsui Life Financial Research Center

Abstract: The premiums on closed-end country funds tend to move in tandem, but do not move together with premiums on domestic closed-end funds. After controlling for foreign market fundamentals, changes in the stock price of country funds co-move with U.S. market returns, but changes in their net asset values do not. An index of changes in country fund premiums explains cross-sectional stock returns in the U.S. market. Collectively, these findings suggest U.S. stock prices are affected by market-wide sentiments which are reflected in closed-end country fund premiums.

Government Policies, Market Imperfections, and Foreign Direct Investment

Abstract: The internalization/eclectic theory of foreign direct investment includes the important insight that government policies create market imperfections, which make foreign direct investment an economically rational strategic alternative for firms. This paper reexamines the effects of government policies on market imperfections and foreign direct investment (FDI). It broadens and refines the analysis of the impact of government policies by developing the following arguments: (1) There is a wide range of government policies that affect firms' FDI decisions via their effects on market imperfections. (2) There are numerous dimensions of variability in government policies that need to be identified in order to understand fully the effects of government policies on market imperfections and hence FDI flows. (3) Some of the effects of government policies on market imperfections and FDI are the opposite of those previously noted in the FDI literature. (4) The effects of government policies vary across the several individual components of FDI flows. The paper thus examines the following variables and relationships more extensively and precisely than has the previous literature: government policy variables as causal factors affecting FDI; market imperfection variables as intervening factors in the causal connections between government policies and FDI; and the multiple indicators of the various dimensions of FDI as dependent variables.

Comparison of Atovaquone (566C80) with Trimethoprim-Sulfamethoxazole to Treat Pneumocystis carinii Pneumonia in Patients with AIDS

Abstract: Background Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. Methods We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). Results Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of the...

A genotype of hepatitis D virus that occurs in northern South America.

Abstract: Hepatitis D virus (HDV) is the cause of an unusually severe form of liver disease with distinct histologic features (morula cell) that occurs throughout northern South America and certain other areas of the world. Clinical studies of HDV disease worldwide indicate that there is, in fact, a wide variation in pathogenesis, and the reasons for these differences are presently unknown. One possible explanation is that factors associated with the viral genotype are determinants of HDV pathogenesis. In this study, nucleic acid sequences were determined for three different northern South American HDV isolates which were obtained from individuals with severe disease or a family history of severe disease, in areas that are hyperendemic for this disease pattern. The sequences of these three isolates are very similar to one another but only distantly related to other published HDV sequences. Comparison of the sequence of a semiconserved region from a total of 14 isolates indicates that there are at least three HDV genotypes. Most published HDV sequences, including those from North America, Europe, the Middle East, the South Pacific, and Asia, belong to a single genotype which may have some geographically based subtypes. A single Japanese isolate is the sole representative of a second HDV genotype. The South American sequences reported here constitute a third genotype. The association of a particular genotype with the severe form of type D hepatitis that occurs in northern South America supports the hypothesis that HDV genetic factors are important determinants in the pathogenesis of type D hepatitis.

The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein.

Abstract: The human papillomavirus (HPV) E5 proteins are predicted from DNA sequence analysis to be small hydrophobic molecules, and the HPV type 6 (HPV-6) and HPV-11 E5 proteins share several structural similarities with the bovine papillomavirus type 1 (BPV-1) E5 protein. Also similar to the BPV-1 E5 protein, the HPV-6 and HPV-16 E5 proteins exhibit transforming activity when assayed on NIH 3T3 and C127 cells. In this study, we expressed epitope-tagged E5 proteins from both the "low-risk" HPV-6 and the "high-risk" HPV-16 in order to permit their immunologic identification and biochemical characterization. While the HPV-6 and HPV-16 E5 proteins fail to form disulfide-linked dimers and oligomers, they did resemble the BPV-1 E5 protein in their intracellular localization to the Golgi apparatus, endoplasmic reticulum, and nuclear membranes. In addition, the HPV E5 proteins also bound to the 16-kDa pore-forming protein component of the vacuolar ATPase, a known characteristic of the BPV-1 E5 protein. These studies reveal a common intramembrane localization and potential cellular protein target for both the BPV and HPV E5 proteins.

Association of MMP-2 Activation Potential With Metastatic Progression in Human Breast Cancer Cell Lines Independent of MMP-2 Production

Abstract: Background Expression of matrix metalloproteinase-2 (MMP-2), the 72-kd type IV collagenase/gelatinase, by cancer cells has been implicated in metastasis through cancer cell invasion of basement membranes mediated by degradation of collagen IV. However, the abundance of this latent proenzyme in normal tissues and fluids suggests that MMP-2 proenzyme utilization is limited by its physiological activation rather than expression alone. We previously reported activation of this proenzyme by normal and malignant fibroblastoid cells cultured on collagen I (vitrogen) gels. Purpose Our purposes in this study were 1) to determine whether MMP-2 activation is restricted to the more invasive human breast cancer cell lines and 2) to localize the activating mechanism. Methods Zymography was used to monitor MMP-2 activation through detection of latent MMP-2 (72 kd) and mature species of smaller molecular weight (59 or 62 kd). Human breast cancer cell lines cultured on plastic, vitrogen, and other matrices were thus screened for MMP-2 activation. Collagen I-cultured cells were exposed to cycloheximide, a protein synthesis inhibitor, or to protease inhibitors to determine the nature of the MMP-2-activating mechanism. Triton X-114 (TX-114) detergent extracts from cells cultured on collagen I or plastic were incubated with latent MMP-2 and analyzed by zymography to localize the MMP-2 activator. Results MMP-2 activation was only induced by collagen I culture in the more aggressive, highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines (Hs578T, MDA-MB-436, BT549, MDA-MB-231, MDA-MB-435, MCF-7 ADR) and was independent of MMP-2 production. MMP-2 activation was detected in cells cultured on collagen I gels but not in those cultured on gelatin gels, Matrigel, or thin layers of collagen I or IV, gelatin, or fibronectin. Collagen-induced activation was specific for the enzyme species MMP-2, since MMP-9, the 92-kd type IV collagenase/gelatinase, was not activatable under similar conditions. MMP-2 activation was inhibited by cycloheximide and was sensitive to a metalloproteinase inhibitor but not to aspartyl, serine, or cysteinyl protease inhibitors. MMP-2 activation was detected in the hydrophobic, plasma membrane-enriched, TX-114 extracts from invasive collagen I-cultured cells. Conclusion Collagen I-induced MMP-2 activation is restricted to highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines, is independent of MMP-2 production, and is associated with metastatic potential. Our findings are consistent with plasma membrane localization of the activator. Implications The MMP-2 activation mechanism may represent a new target for diagnosis, prognosis, and treatment of human breast cancer.

Outcomes of Cataract Surgery: Improvement in Visual Acuity and Subjective Visual Function After Surgery in the First, Second, and Both Eyes

Abstract: • Objective. —No previous study documents improvement in visual acuity and subjective visual function associated with cataract surgery in the first eye, second eye, and both eyes. Measurement of subjective aspects of visual function and quality of life provides information that cannot be obtained with simple measurement of Snellen visual acuity. Methods. —From 76 ophthalmology practices in three cities, patients undergoing cataract extraction with intraocular lens implantation (n=613) and comparison patients (n=408) were enrolled in a prospective study. Questionnaires elicited visual function information before and after surgery, and visual acuity was obtained from the ophthalmologic record. Results. —Among patients with cataract and no other eye disease, baseline subjective visual function before surgery in the second eye was better than that before surgery in the first eye. Improvement in subjective visual function was approximately equal postoperatively in first and second eyes. Improvement in subjective function in both eyes postoperatively was significantly greater than that after surgery in the first eye or second eye alone. No statistically significant difference across surgical groups in the proportion of patients demonstrating improvement in visual acuity was observed. Conclusion. —Patients who underwent surgery in both eyes reported greater improvement in subjective visual function than did those who underwent surgery in one eye. Thus, there seems to be a benefit associated with restoring binocular vision in this population. These findings support the policy recommendation that cataract surgery in both eyes remains the appropriate treatment for patients with bilateral, cataract-induced visual impairment.

Vision change and quality of life in the elderly. Response to cataract surgery and treatment of other chronic ocular conditions.

Abstract: • Objective. —Evaluation of health care in older populations has increasingly focused on quality of life as a critical outcome of treatment. Vision is assumed to be central to functioning. Data suggest that aging, in itself, is associated with a decline in visual functioning, which, in turn, is related to a decline in physical and mental functioning. Other studies indicate that cataract surgery is followed by significant improvement in vision and visual function. Our objective was to test these assumptions. Design.—Prospective study of 1021 patients, consecutively drawn from 76 randomly selected ophthalmologists' offices in three cities. Structured interviews were completed at baseline, 2 months, and 1 year after entry. Patients. —Six hundred thirteen patients with cataracts and 408 other ophthalmic patients drawn from the same offices but treated for other chronic ocular disorders. All received refractive services as needed. Setting. —Patients from three cities (Baltimore, Md, St Louis, Mo, and San Diego, Calif) were interviewed once in their homes and twice by telephone. Interventions. —The study involved the measurement of the effects of usual treatment for cataracts and other degenerative eye diseases. Major Outcome Measures. —Visual, social, and psychological functioning. Results. —Within 1 year of treatment, change in visual function was accompanied by significant changes, in the same direction, in quality of life functions: nighttime driving, daytime driving, community activities, home activities, mental health, and life satisfaction. In addition, the patients with cataracts showed significantly greater improvement in measures of vision than did the noncataract group. Conclusions. —Regardless of treatment, improvement across quality of life functions occurred when visual function improved. Thus, many types of functional degeneration observed in older populations, attributed to a decline in vision, can be slowed, or evenreversed, when visual function is improved. Cataract surgery was effective in improving vision and quality of life functions.

bcl-2 Protein Inhibits Etoposide-induced Apoptosis through Its Effects on Events Subsequent to Topoisomerase II-induced DNA Strand Breaks and Their Repair

Abstract: Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclophosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNa-protein cross-links, DNA single-strand breaks, and double-strand breaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that ( a ) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks, DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and ( b ) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.

The Content and Cost of Cataract Surgery

Abstract: Although more than 1 million cataract surgeries are performed annually in the United States, little is known about the frequency of use or cost of various services provided in connection with this procedure. To assess the frequency with which various ophthalmic, optometric, anesthesia, and medical services are provided in conjunction with cataract surgery and to estimate the cost to Medicare associated with those services, we analyzed 1985 through 1988 Medicare claims records of a nationally representative 5% sample of Medicare beneficiaries. The experience of 57 103 Medicare beneficiaries who underwent extracapsular cataract surgery in 1986 or 1987 that was not combined with another ophthalmologic procedure formed the basis of our analysis. Projections for current costs were performed using 1991 charges allowed by Medicare for physician services. We estimate that the median charge allowed by Medicare for a "typical" episode of cataract surgery in 1991 was approximately $2500. In addition to the $3.4 billion that Medicare spent in 1991 on such "typical" episodes, Medicare spent more than $39 million on miscellaneous "atypical" preoperative ophthalmologic tests, such as specular microscopy (14% of cases) and potential acuity testing (8% of cases), more than $7 million on postoperative ophthalmologic diagnostic tests, such as fluorescein angiography (3% of cases), and more than $18 million on perioperative medical services (most commonly electrocardiography and chest roentgenography). The major determinants of the cost to Medicare associated with cataract surgery are the rate of performance of cataract surgery and neodymium-YAG laser capsulotomy and the charges allowed for these procedures. Many other ophthalmologic and medical services are often provided preoperatively and/or postoperatively, but total Medicare expenditures for these services are relatively small.

Violence against women: Physical and mental health effects. Part I: Research findings

Abstract: Interpersonal violence is a ubiquitous source of fear, distress, and injury in the lives of women in the United States, crossing lines of age, race, ethnicity, and economic status ( Coley & Beckett, 1988 ; Frieze & Browne, 1989 ; Koss, 1988 ; Straus, Gelles, & Steinmetz, 1980 ). In recent years, the public health community has become increasingly aware that “this violence is a serious public health problem … [and that] nonfatal interpersonal violence has far-reaching consequences in terms of morbidity and quality of life” ( Center for Disease Control, 1985 , p. 739). This article reviews the physical and mental health effects on adult women of physical abuse and sexual assault, and describes their implications for mental health research and practice.

ELISA for Antibody to Hepatitis E Virus (HEV) Based on Complete Open-Reading Frame-2 Protein Expressed in Insect Cells: Identification of HEV Infection in Primates

Abstract: A recombinant baculovirus containing the complete open-reading frame (ORF)-2 region of the hepatitis E virus (HEV) genome was constructed. The major protein synthesized in insect cells infected with recombinant virus was about the size expected for the complete ORF-2 product. This protein reacted in a Western blot assay with plasma from an HEV-infected chimpanzee. Lysates of the recombinant virus-infected insect cells were used in ELISA to monitor seroconversion of eight primate species (chimpanzees, four species of Old World monkeys, and three species of New World monkeys) inoculated with HEV. Homologous detector anti-immunoglobulin was more sensitive than heterologous anti-immunoglobulin for detecting anti-HEV by ELISA. All primate species except tamarins seroconverted after inoculation with HEV, although anti-HEV titers of Old World monkey species were generally higher than those of New World monkey species. The ELISA with complete ORF-2 antigen appeared to be a sensitive and practical method for detecting anti-HEV.

Development of antisera selective for m4 and m5 muscarinic cholinergic receptors: distribution of m4 and m5 receptors in rat brain.

Abstract: A portion of the cDNA sequence corresponding to the third intracellular loop of either the m4 or m5 muscarinic cholinergic receptor was ligated into the pRIT23 or pET-3a expression vector, respectively. The expressed fusion proteins were purified and used to develop selective polyclonal antisera to the m4 and m5 muscarinic receptors. These antisera were used in an immunoprecipitation protocol to examine quantitatively the distribution of receptor subtypes in regions of rat brain. The density of m4 receptors in rat brain increased in the caudal to rostral direction. The highest levels of m4 receptors were detected in the striatum (1280 fmol/mg) and olfactory tubercle (750 fmol/mg). Low levels of m5 receptors were detected in several brain regions (

MCF7/LCC2: A 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780

Abstract: The development of resistance to the antiestrogen tamoxifen occurs in a high percentage of initially responsive patients. We have developed a new model in which to investigate acquired resistance to triphenylethylenes. A stepwise in vitro selection of the hormone-independent human breast cancer variant MCF-7/LCC1 against 4-hydroxytamoxifen produced a stable resistant population designated MCF7/LCC2. MCF7/LCC2 cells retain levels of estrogen receptor expression comparable to the parental MCF7/LCC1 and MCF-7 cells. Progesterone receptor expression remains estrogen inducible in MCF7/LCC2 cells, although to levels significantly lower than observed in MCF-7 and MCF7/LCC1 cells. MCF7/ LCC2 cells form tumors in ovariectomized nude mice without estrogen supplementation, and these tumors are tamoxifen resistant but can be tstrogen stimulated. Significantly, MCF7/LCC2 cells have retained sensitivity to the steroidal antiestrogen ICI 182,780. These data suggest that some breast cancer patients who acquire resistance to tamoxifen may not develop cross-resistance to treatment with steroidal antiestrogens.

MR imaging of the pancreas.

Abstract: Magnetic resonance (MR) imaging sequences that reduce image artifact in upper abdominal examinations herald a role for MR in the investigation of pancreatic disease. Sequences that have been successful in imaging the pancreas are T1-weighted breath-hold gradient-echo imaging, which avoids phase artifact caused by respiration, and T1-weighted fat-suppressed spin-echo imaging, which reduces breathing artifact, removes chemical shift artifact, and improves dynamic range of signal intensities. Breath-hold gradient-echo sequences provide useful diagnostic information when used prior to and immediately following bolus intravenous administration of gadopentetate dimeglumine. This review addresses current clinically important roles for MR imaging and emphasizes the detection of islet cell tumors, non-organ-deforming pancreatic ductal adenocarcinomas, and the distinction between chronic pancreatitis and cancer.

Binding and Localization of Mr 72,000 Matrix Metalloproteinase at Cell Surface Invadopodia

Abstract: Degradation (turnover) of collagenous matrix occurs on the surface of specialized membrane extensions termed "invadopodia," which are sites of cell invasion into the extracellular matrix. Here we show the localization of the M(r) 72,000 type IV collagenase of the matrix metalloproteinase family at invadopodia. When added exogenously, latent M(r) 72,000 collagenase binds to invadopodia of chicken embryo fibroblasts transformed by Rous sarcoma virus, whereupon the bound collagenase loses its propeptide. The collagenase binds to a component contained within the detergent extract of transformed cells, and increased levels of the active M(r) 62,000 form of the collagenase are seen here. Such an association is not detected in the detergent extract derived from normal cells. Using a recently developed cell fractionation procedure to collect cell surfaces enriched in invadopodia, we show that the M(r) 72,000 collagenase associates with the invadopodial fraction and active forms of the enzyme become immobilized on the collagenous surface. Thus, invadopodia direct intense localized degradation of the extracellular matrix by concentrating active membrane-associated collagenases at sites of cellular invasion.

Recombinant Human Erythropoietin Therapy for Anemic Cancer Patients on Combination Chemotherapy

Abstract: BACKGROUND Patients with advanced cancer frequently experience clinically significant anemia, which is often exacerbated by myelosuppressive chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine (AZT) and in patients with chronic renal failure. PURPOSE This study was designed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy (excluding cisplatin). METHODS We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO (150 U/kg) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study. Response to rHuEPO therapy was assessed by measuring changes in hematocrit level, transfusion requirements, and quality of life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy. RESULTS The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to final evaluation, by an increase in hematocrit level of six percentage points or more unrelated to transfusion, and by a rise in hematocrit level to 38% or more unrelated to transfusion. There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients (0.91 U versus 1.65 U; P = .056). In addition, rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities (P < or = .05). The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis (P < .05) and diarrhea (P = .05) in the rHuEPO-treated group. CONCLUSIONS We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer.

MCF7/LCC2: A 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780

Abstract: The development of resistance to the antiestrogen tamoxifen occurs in a high percentage of initially responsive patients. We have developed a new model in which to investigate acquired resistance to triphenylethylenes. A stepwise in vitro selection of the hormone-independent human breast cancer variant MCF-7/LCC1 against 4-hydroxytamoxifen produced a stable resistant population designated MCF7/LCC2. MCF7/LCC2 cells retain levels of estrogen receptor expression comparable to the parental MCF7/LCC1 and MCF-7 cells. Progesterone receptor expression remains estrogen inducible in MCF7/LCC2 cells, although to levels significantly lower than observed in MCF-7 and MCF7/LCC1 cells. MCF7/LCC2 cells form tumors in ovariectomized nude mice without estrogen supplementation, and these tumors are tamoxifen resistant but can be estrogen stimulated. Significantly, MCF7/LCC2 cells have retained sensitivity to the steroidal antiestrogen ICI 182,780. These data suggest that some breast cancer patients who acquire resistance to tamoxifen may not develop cross-resistance to treatment with steroidal antiestrogens.

1,25-Dihydroxyvitamin D3 Receptor as a Marker of Human Colon Carcinoma Cell Line Differentiation and Growth Inhibition

Abstract: The antiproliferative action of 1,25-dihydroxyvitamin D3 in osteosarcoma, breast carcinoma, and colon carcinoma cell lines has been described. In this study, the level of vitamin D receptor was analyzed in a panel of colon adenoma and adenocarcinoma cell lines and the receptor level was correlated with the response to treatment with 1,25-dihydroxyvitamin D3. Ribonuclease protection and ligand-binding assays quantitated the level of vitamin D receptor mRNA expression and the level of functional receptors, respectively. The more well-differentiated cell lines, such as VACO 330, showed higher levels of vitamin D receptor than less-differentiated cell lines, such as SW620. Proliferation assay, clonogenic assay, and growth curve study in HT29 and SW620 cell lines assessed the antiproliferative effect of 1,25-dihydroxyvitamin D3 at concentrations ranging from 10(-11) to 10(-6) M. HT29 showed significant (P < 0.05) growth inhibition at 10(-9) to 10(-6) M concentrations, but growth of SW620 remained unchanged. The amount of vitamin D receptor in 12 malignant colonic tumors was compared with that of adjacent normal tissue, and in 9 cases, the tumor expressed a lower vitamin D receptor level. Our results suggest that the level of vitamin D receptor correlates with the degree of differentiation in human colon cancer cell lines and may serve as a useful biological marker in predicting clinical outcome in patients.

Method and apparatus for prediction of sudden cardiac death by simultaneous assessment of autonomic function and cardiac electrical stability

Abstract: A method and apparatus for predicting susceptibility to sudden cardiac death simultaneously assessing cardiac electrical stability and autonomic influence. Cardiac electrical stability is assessed by analyzing at least one of a beat-to-beat alternation in a T-wave of an ECG of a patient's heart and dispersion of repolarization in the ECG of the patient's heart. Autonomic influence on the patient's heart is assessed by analyzing at least one of a magnitude of heart rate variability in the ECG of the patient's heart and baroreceptor sensitivity.