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J Russo

Publications and source records attributed to J Russo.

At least 163 records · Page 9Linked to original sources

Cell surface glycosylation changes accompanying immortalization and transformation of normal human mammary epithelial cells.

Fluorescent lectin binding to cell surfaces was quantitatively analysed by flow cytometry on mortal human breast epithelial cells MCF-10M, the immortalized cell line MCF-10A derived from MCF-10M and sublines of MCF-10A transfected with the neomycin resistance gene (MCF-10Aneo), the c-Ha-ras protooncogene (MCF-10AneoN), or transfected and transformed with the c-Ha-ras activated oncogene (MCF-10AneoT). Immortal MCF-10A cells bound 10-fold more peanut agglutinin (PNA) and soy bean agglutinin (SBA) than did MCF-10M cells. Transformed MCF-10AneoT cells bound approximately ten times more PNA than did non-transformed cells transfected with protooncogene (MCF-10AneoN). Treatment of the transfectants with neuraminidase abrogated the differences in PNA-binding and reduced the differences in SBA binding. SDS-PAGE separation of PNA binding glycoproteins revealed different patterns for all MCF-10A derived sublines.

Blotting, Western↗

Predictors of burden in spouse caregivers of individuals with Alzheimer's disease.

This study used the following model of distress: Distress = [Exposure to Stress + Vulnerability]/[Psychological and Social Resources]. The constructs in the model were operationalized as (a) distress in response to caregiver experiences (burden); (b) exposure to stress (care recipient functional impairment in activities of daily living [ADLs]); (c) vulnerability (caregiver health problems, anger, and anxiety); and (d) resources (coping, outlook on life, and social supports). Long-term burden (15-18 months after entry) was predicted by several baseline variables: burden, care recipient ADLs, vulnerability and resource variables, and specific interactions of burden, ADLs, vulnerability, and resource variables. The interactions showed that caregivers with high vulnerability and low resources had higher burden scores than caregivers with other combinations of these variables.

Activities of Daily Living↗

Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis.

Since it has been shown that pregnancy protects the mammary gland from chemically induced carcinogenesis, this study was designed with the dual purpose of determining whether treatment of young virgin rats with the placental hormone chorionic gonadotropin (hCG) mimics pregnancy-induced changes in the tumourigenic response of the mammary gland and also whether the effect induced by both pregnancy and hormonal treatments was transitory, or a more permanent one, exerting the same effect when the period of time between delivery or termination of treatment and exposure to the carcinogen is lengthened. Virgin Sprague-Dawley rats were utilised in two experimental protocols. For protocol I, 50 day-old rats were either mated (Group II), or started receiving a daily intraperitoneal injection of 100 IU hCG (Group III) at age 50. Age-matched untreated virgin rats were used as controls (Group I). Twenty-one days after either delivery or termination of treatment all the animals received an intragastric dose of 8 mg DMBA/100 gbw. For the second protocol, 50 day-old virgin rats were also mated (Group V) or were treated with hCG for 21 days (Group VI); the resting period between delivery or termination of treatment was lengthened to 63 days, at which time they received a dose of DMBA. Age-matched controls (Group IV) received DMBA only. Tumourigenesis was evaluated 24 weeks post-carcinogen administration in all the groups. Pregnancy and hCG followed by the 21-day resting period significantly depressed mammary carcinogenesis to 11% and 6% respectively, compared with 63% in control animals. When the resting period was prolonged to 63 days there was also a significant depression in adenocarcinoma incidence to 9% in pregnancy (Group IV) in which it was observed that tumour incidence was also reduced as a consequence of aging at the time of exposure to the carcinogen. These results clearly indicate that hCG is as efficient as pregnancy and significantly reduces mammary carcinogenesis, and that the protective effect of both pregnancy and hCG treatment is long-lasting and both are more efficient than aging in reducing mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Burden: a review of measures used among caregivers of individuals with dementia.

This paper critiques and discusses 10 measures of burden that have been used with caregivers of individuals with dementia. Current measures target diverse caregiver and care recipient populations, and vary in conceptualization and measurement of burden. Although many measures contain reliability data, relatively few report content validity, convergent/divergent validity, criterion validity, or sensitivity to change. Implications of these limitations for research and clinical practice are discussed.

Alzheimer Disease↗

The screen for caregiver burden.

The Screen for Caregiver Burden (SCB) is a measure designed to identify distressing caregiver experiences rapidly. The 25-item SCB, created specifically for spouse caregivers of Alzheimer's care recipients, provides scores for objective burden (OB; number of potentially negative experiences) and subjective burden (SB; appraised distress in response to the experiences). Three separate studies (total N = 191) demonstrate the internal consistency, test-retest reliability, and validity (content, divergent, convergent, and criterion) of the scales. Finally, evidence suggests that changes in OB and SB over time are explained by changes in care-recipient functioning and caregiver distress.

Aged↗

Somatization: a spectrum of severity.

OBJECTIVE: The DSM-III-R diagnosis of somatization disorder requires that a patient have a specific number of medically unexplained somatic symptoms. This number of symptoms was developed by committee consensus, and it is not clear whether patients with this specific number of symptoms can be differentiated from patients with lower but still substantial numbers of somatic symptoms. METHOD: Fifty-one percent of 767 high utilizers of two primary care clinics were identified as distressed by an elevated SCL anxiety, depression, or somatization scale score or by their primary care physician. The Diagnostic Interview Schedule (DIS) was completed on 119 distressed high utilizers who were randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The 119 distressed high utilizers were separated into four categories according to the number of unexplained somatic symptoms found on the DIS and were compared on demographic, psychiatric distress, disability, medical, and health utilization variables. RESULTS: The data suggest that many clinical and behavioral features of somatization are significantly more common in patients with four to 12 medically unexplained somatic symptoms rather than changing dramatically at the diagnostic threshold for somatization disorder. The data also showed that patients who meet the DSM-III-R criteria for somatization disorder are severely ill and have a high burden of psychiatric illness and disability. CONCLUSIONS: The results suggest that the DSM-IV somatoform disorders section should include somatization disorder, an abridged definition of somatization disorder often associated with anxiety and depression, as well as a type of somatization associated with an adjustment disorder.

Activities of Daily Living↗

Morphological expression of cell transformation induced by c-Ha-ras oncogene in human breast epithelial cells.

The present work describes the morphological pattern of c-Ha-ras-transformed MCF-10A cells. This immortalized human breast epithelial cell line was transfected utilizing the calcium phosphate technique with pHo6 containing the neomycin-resistant gene alone, and identified as MCF-10Aneo, or with the normal Ha-ras proto-oncogene, MCF-10AneoN, or with the human p24 mutated Ha-ras oncogene, MCF-10AneoT cells. These three cell types were studied by scanning and transmission electron microscopy at passages 6 and 20 post-transfection. It was observed that transfection with the plasmid alone did not induce any morphological changes in MCF-10A cells. These two cell types exhibited those features that are characteristic of mammary epithelial cells in culture. Amplification of the normal c-Ha-ras oncogene by transfection induced significant morphological changes at the level of cell shape, from flat to cuboidal, and cytoplasmic changes suggesting a more metabolically active cell. These changes were made more prominent by transfection with the mutated ras oncogene, which induced stratification of a cuboidal epithelium and increase in cell size as well as a more pleomorphic nuclear and cytoplasmic appearance. Distinctive features induced by the mutated c-Ha-ras oncogene were the lengthening and thickening of cell surface microvilli, formation of blebs and emission of filopodial projections. It induced cytoplasmic changes consisting of formation of intracellular lumina, and increased the number of lysosomes, mitochondria and glycogen content, significantly decreasing the number of intermediate filaments. This is the first report that describes the morphological characteristics of a human breast epithelial cell line transformed in vitro.

Breast Neoplasms↗

Progestagens and mammary gland development: differentiation versus carcinogenesis.

The role of hormones, especially progesterone and synthetic progestins, in the pathogenesis of breast cancer is highly debated and far from being clarified. The observation that differentiation of the mammary gland prior to exposure to a carcinogenic agent inhibits the initiation of mammary carcinomas, and the fact that this protection is mediated by cell kinetic changes induced in the gland parenchyma by hormonal stimuli such as that of pregnancy, led us to determine how ovariectomy and hormonal supplementation affect the cell kinetic characteristics in various terminal ductal structures of an intact animal mammary gland, i.e., terminal end buds, terminal ducts and alveolar buds. Fifty-day-old virgin Sprague-Dawley rats were either ovariectomized or treated for 21 days with norethynodrel and mestranol or medroxyprogesterone acetate in doses of 0.5 mg (low dose - LD), or 5.0 mg (high dose - HD); chorionic gonadotropin (hCG) in doses of 1 or 100 IU/day, or placental lactogen (PL) in a dose of 0.5 mg. Cell kinetics were studied by counting the number of cells incorporating [3H]-thymidine and expressed as the DNA labeling index. In the intact animal, the rate of cell proliferation was highest in terminal end buds, decreased progressively towards the ductal portions and was even lower in alveolar buds. Ovariectomy significantly reduced the proliferative activity of the mammary epithelium, ten-fold in terminal ducts and alveolar buds, and five-fold in terminal end buds. DNA labeling index was significantly reduced in terminal ducts and alveolar buds by all hormones at all doses, except PL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mammary tumorigenesis.

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9,10-Dimethyl-1,2-benzanthracene↗

Increased invasive, chemotactic and locomotive abilities of c-Ha-ras-transformed human breast epithelial cells.

Transfection of the immortalized human breast epithelial cells MCF-10A with the mutated ras oncogene resulted in cell transformation (MCF-10A-neoT). Since the transformed state is usually associated with enhanced migratory activity, increased capability to invade basement membranes and to grow in a three-dimensional basement membrane gel (growth in matrigel), we compared these properties in MCF-10A-neoT cells with those of MCF-10A cells transfected with either the neomycin resistance gene alone (MCF-10A-neo cells) or with the normal ras proto-oncogene (MCF-10A-neoN cells). MCF-10A-neoT cells exhibited enhanced migratory activity, as assessed by chemotaxis and chemokinesis assays. and increased capability to invade the basement membrane. These cells also formed large colonies in matrigel. MCF-10A-neo and MCF-10A-neoN cells, on the other hand, showed only marginal migratory, invasive and semisolid medium growth properties. These results indicate that the mutated ras oncogene induces in human breast epithelial cells phenotypic characteristics of malignant transformation.

Adenocarcinoma↗

Transfection of human breast epithelial cells with foreign DNA using different transfecting techniques.

The introduction of DNA into eukaryotic cells is a powerful technique for the study of gene regulation. This requires both a technique by which genes can efficiently be introduced into cells and a recipient cell representative of the tissue under study. We have utilized a spontaneously immortalized human breast epithelial cell line, CMF-10, which is phenotypically normal for introducing a neomycin-resistant gene contained in the plasmid Homer 6 (pHo6). Three different transfection methods were tested: calcium phosphate, with and without glycerol shock, using as control NIH/3T3 cells, and strontium phosphate and electroporation. In MCF-10 cells the efficiency of calcium phosphate mediated DNA transfection, which was measured as the number of colonies growing in neomycin-containing medium, was 21 and 140 fold higher than in MCF-10 cells transfected by electroporation and strontium phosphate methods, respectively. Glycerol shock enhanced three fold transfection efficiencies. NIH/3T3 transfected cells by calcium phosphate method showed a transfection efficiency similar to that of MCF-10 cells, however, glycerol shock did not improve the efficiency. These studies revealed that calcium phosphate combined with glycerol shock is the most efficient technique for transfection of genomic DNA into human breast epithelial cells.

Breast↗

Ultrastructural and immunocytochemical characterization of an immortalized human breast epithelial cell line, MCF-10.

The human breast epithelial cell line MCF-10 was derived from s.c. mastectomy tissue from a 36-year-old, parous, premenopausal woman with fibrocystic disease. It was initiated as a mortal cell line (MCF-10M), which senesces when transferred serially in 1.05 mM calcium. These cells spontaneously gave origin to two immortal sublines, MCF-10A, or attached cells, and MCF-10F, or floating cells, which have proliferated for more than 4 years in Dulbecco's modified essential medium and Ham's F-12 either with the customary calcium concentration of 1.05 mM (DMEM-H) or in medium containing 0.04 mM calcium or low calcium. Studies reported here indicate that MCF-10 is a mammary epithelial cell line. Electron microscopy showed that both MCF-10A and MCF-10F have characteristics of luminal ductal cells, but not of myoepithelial cells. When grown for more than 1200 days in Dulbecco's modified essential medium-Ham's F-12 and low calcium media, respectively, they maintained their epithelial characteristics, although the concentration of calcium exerted a powerful influence on cell morphology. Cells grown in Dulbecco's modified Eagle's medium-Ham's F12 medium are low cuboidal with numerous desmosomes and short microvilli, whereas those grown in low calcium medium have significantly reduced number of desmosomes, are more spherical, and have greater numbers of microvilli which are longer than those of cells grown in DMEM-H. The breast epithelial orgin of these cells was confirmed by immunocytochemical detection of epithelial sialomucins and keratins. The monoclonal antibodies MFA-breast and MC5 and the polyclonal antibody epithelial membrane antigen were used to detect the epithelial sialomucins. Keratins were characterized by using KA-4, K-14, AE1/AE3, and K-19 specific antibodies. It was concluded that MCF-10A and MCF-10F cells are breast epithelial cells and that they represent an important tool for studies of the basic processes of growth and carcinogenesis.

Adult↗

Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10.

Two sublines of a breast epithelial cell culture, MCF-10, derived from human fibrocystic mammary tissue exhibit immortality after extended cultivation in low calcium concentrations (0.03-0.06 mM) and floating transfers in low calcium (MCF-10F), or by trypsin-Versene passages in the customary (normal) calcium levels, 1.05 mM (MCF-10A). Both sublines have been maintained as separate entities after 2.3 years (849 days) in vitro and at present have been in culture for longer than 4 years. MCF-10 has the characteristics of normal breast epithelium by the following criteria: (a) lack of tumorigenicity in nude mice; (b) three-dimensional growth in collagen; (c) growth in culture that is controlled by hormones and growth factors; (d) lack of anchorage-independent growth; and (e) dome formation in confluent cultures. Cytogenetic analysis prior to immortalization showed normal diploid cells; although later passages showed minimal rearrangement and near-diploidy, the immortal cells were not karyotypically normal. The emergence of an immortal culture in normal calcium media was not an inherent characteristic of the original tissue from which MCF-10 was derived since reactivated cryo-preserved cells from cultures grown for 0.3 and 1.2 years in low calcium were incapable of sustained growth in normal calcium.

Animals↗

Human chorionic gonadotropin and rat mammary cancer prevention.

The observation that mammary cancer induced by 7,12-dimethylbenz[a]anthracene (DMBA) in young, virgin, Sprague-Dawley rats is abolished by pregnancy led us to test the possibility of protecting the mammary gland from chemically induced carcinogenesis by using the placental hormone human chorionic gonadotropin (hCG). Fifty-day-old, outbred, virgin, Sprague-Dawley rats were utilized in two different experimental protocols. In protocol 1, four groups of virgin rats received either no hCG (group I) or a daily intraperitoneal injection of hCG at 1 IU (group II), 10 IU (group III), or 100 IU (group IV) for 21 days; group I and groups II-IV, at 21 days after the last injection, were given a single intragastric dose of 8 mg of DMBA per 100 g of body weight. In protocol 2, 50-day-old rats were treated with a single intragastric dose of 8 mg of DMBA per 100 g of body weight; 21 days later, they were separated into groups V and VI. Group V rats remained undisturbed, except for palpation twice a week for detection of tumor development. Group VI rats received a daily intraperitoneal injection of 100 IU of hCG for 60 days. Tumorigenesis was evaluated 24 and 30 weeks after carcinogen administration in animals in protocols 1 and 2, respectively. In protocol 1, in which animals (with the exception of the control group) were treated with hCG prior to carcinogen administration, the incidence of adenocarcinomas decreased in a dose-dependent manner, from 43.8% in the controls (group I) to 34.4%, 18.2%, and 6.15% in groups II-IV treated with 1, 10, or 100 IU of hCG, respectively. Among animals in protocol 2, hCG treatment significantly reduced the incidence of adenocarcinomas, from 100% in DMBA-treated rats (group V) to 45.5% in rats treated with DMBA plus hCG (group VI). These data indicate that hCG can prevent both initiation and progression of mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Calcium-mediated modulation of microtubule assembly in human breast epithelial cells.

Normal human breast epithelial cells obtained from a reduction mammoplasty (S130) have been maintained in culture for up to a year in Ham's F12:Dulbecco's medium, with 5% equine serum and a low calcium concentration (0.04 mM). These cells undergo senescence and terminal differentiation if they are switched to high Ca2+ medium (1.05 mM). To clarify the mechanism by which Ca2+ regulates the growth of these cells, we studied the role of tubulin assembly-disassembly and the morphologic changes subsequent to high Ca2+ switch. An early Passage (9) of S130 breast epithelial cells growing in low Ca2+ medium was analyzed. Of a total of 785 counted cells, 720 (92%) were rounded and 65 (8%) were flat, elongated, and fibroblastlike. When the cells were switched to high Ca2+ medium, out of 553 cells, only 111 (20%) were rounded and the remaining 442 (80%) were elongated and fibroblastlike. Immunocytochemical localization of tubulin, using the immunogold silver enhancement technique, showed that the majority of low Ca2(+)-grown cells did not display a network of tubulin fibers, whereas high Ca2(+)-grown cells revealed extensive cytoplasmic network of polymerized tubulin, which seemed to stretch out the cells. Experiments designed to determine the mechanisms of tubulin polymerization in these cells revealed that: a) Cells grown in high Ca2+ medium containing 0.1 mM colchicine had a reduced proportion of elongated cells; b) treatment of the cells with the calcium ionophore A23187 in low calcium medium resulted in an increase in the number of elongated cells which had more polymerized tubulin; and d) treatment of the cells with cyclic-AMP in low Ca2+ medium had no observable effect on cell morphology. These results indicate that high levels of Ca2+ either favor tubulin polymerization or stabilize the polymerized state.

Breast↗

Distressed high utilizers of medical care. DSM-III-R diagnoses and treatment needs.

Among a sample of 767 high utilizers of health care, 51% were identified as distressed by an elevated score on the SCL anxiety and depression scales, the SCL somatization scale, or by their primary-care physician. These distressed high utilizers were found to have a high prevalence of chronic medical problems and significant limitation of activities caused by illness. In the prior year, they made an average of 15 medical visits and 15 telephone calls to the clinic. The Diagnostic Interview Schedule was completed on 119 distressed high utilizers randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The following DSM-III-R disorders were most common: major depression 23.5%, dysthymic disorder 16.8%, generalized anxiety disorder 21.8%, and somatization disorder 20.2%. Two thirds had a lifetime history of major depression. The examination resulted in an improved diagnostic assessment for 40% of intervention patients and a revised treatment plan for 67%.

Adolescent↗

Appraised changeability of a stressor as a modifier of the relationship between coping and depression: a test of the hypothesis of fit.

The goodness of fit among the appraised changeability of a stressor, coping, and depression in people with psychiatric, physical health, work, and family problems was examined (N = 746). It was expected that problem-focused coping (as opposed to emotion-focused coping) would be used more and be more adaptive in situations appraised as changeable as compared with situations appraised as not changeable. Although few relationships existed between appraisal and coping, tests of fit between coping and depressed mood (maladaption) were much stronger. In people with nonpsychiatric conditions, problem-focused coping and depressed mood were negatively related when a stressor was appraised as changeable but were unrelated when a stressor was appraised as not changeable. Emotion-focused coping was positively related to depression when a stressor was appraised as changeable. No general relations were observed in the people with psychiatric conditions.

Adaptation, Psychological↗

Coping profiles associated with psychiatric, physical health, work, and family problems.

Compares the coping profiles of 11 samples (total N = 1,298) of individuals experiencing psychiatric, physical health, work, or family problems. Comparisons are made in individuals with and without anxiety and depression to control for the effects of distress. Coping was similar for samples in similar problem categories but different for samples in different categories. Psychiatric patients made more use of avoidance and less use of social supports than individuals in the other categories. Samples with physical health problems were among the most frequent users of social supports. Individuals with a family problem were among the most frequent users of problem-focused coping and the least frequent users of self-blame. Groups with work stress were the most frequent users of self-blame. These results suggest that coping profiles may be useful in describing and differentiating groups of stressed individuals.

Adaptation, Psychological↗