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Biomedical subjects

J Russo

Publications and source records attributed to J Russo.

At least 145 records · Page 8Linked to original sources

Psychotherapy vs. pharmacotherapy: are psychiatrists polarized?--A survey of academic and clinical faculty.

Recent debate about the Osheroff vs. Chestnut Lodge case has highlighted the potential for polarization in psychiatric treatment. The degree to which community clinical psychiatric practice is polarized between psychological and biological treatments is not known. There are limitations in the combined treatment studies performed to date that influence their applicability to treatment planning in the community setting. A nearly exclusive focus on mood disorders and a neglect of the role of concurrent personality disorders and treatment interactions are among these. The data base available to guide a truly integrated practice of differential therapeutics is therefore quite limited. Against this background, we surveyed academic and clinical psychiatric faculty to determine treatment practices and rationales in three case with both Axis I and Axis II diagnoses. In each case, greater than 75% would utilize psychotherapy and consider its omission inappropriate. Medication use varied significantly from case to case. Our findings suggest that practicing psychiatrists combine psychotherapy and pharmacotherapy and that the perceived polarization between "biological" and "psychosocial" psychiatry may be more a matter of "philosophy" than practice.

Adult↗

Immunolocalization of inhibin in the mammary gland of rats treated with hCG.

Human chorionic gonadotropin (hCG) induces profuse lobular development in the mammary gland of young virgin rats. To clarify whether the effect of hCG is locally mediated by inhibin, a non-steroidal glycoprotein, we detected its localization immunocytochemically in the mammary gland with polyclonal antibodies against the alpha- and beta-chains. Virgin female Sprague-Dawley rats were sacrificed after treatment with a daily IP injection of 100 IU hCG for 5, 10, 15, or 21 days of treatment or 20 days after the last injection. Whereas the mammary gland of control animals did not contain immunoreactive inhibin, hCG treatment induced the expression of inhibin in the cytoplasm of alveolar cells but not in ductal cells. The reaction became evident by Day 10 of treatment and reached its maximal intensity by Day 15. Thereafter, the reaction became evident in the stroma, which exhibited maximal positivity by Day 20. Once hCG treatment was terminated, the mammary gland regressed to its pre-treatment condition, appearing similar both in morphology and inhibin content to that of control animals. The expression of this glycoprotein hormone in the mammary gland after hCG administration at the time of maximal lobulolveolar development, and its diffusion towards the stroma during regression, suggest a critical role of inhibin as a modulator of mammary growth and differentiation.

Animals↗

Physiological bases of breast cancer prevention.

The relevance of this work lies in the possibility of extrapolating conclusions drawn here to the human situation, since we have assessed the validity of the rat model for the study of breast cancer in women through comparative studies in these two species (Russo and Russo, 1988). The novelty of our studies is the evidence that hCG protects the mammary gland against carcinogenic initiation and progression, mimicking the physiological process of pregnancy, without crippling other reproductive or endocrine functions (Russo et al, 1990d; Russo and Russo, 1992). The importance of both differentiation and cell proliferation in tumour initiation and progression, which we have stressed in previous publications (Russo and Russo, 1980, 1987, 1988; Russo et al, 1982) validates the use of these end-points for assessing the effect of hormones under the influence of hCG on the mammary gland initiated in the process of carcinogenesis. Collectively, our results provide solid bases for developing physiological means of breast cancer prevention and control.

9,10-Dimethyl-1,2-benzanthracene↗

A critical approach to the malignant transformation of human breast epithelial cells with chemical carcinogens.

This work was undertaken with the purpose of clarifying the factors that modulate the transformation of human breast epithelial cells. For accomplishing this goal, it was necessary to establish the adequate culture conditions for maintaining primary cultures of breast tissue for their treatment with genotoxic agents. It also was determined whether primary cultures generated from these tissues maintained the basic biological properties of the host. In this work we have been able to show that the in vivo developmental stage of the gland is important in the expression of an early transformation phenotype after treatment with chemical carcinogens in vitro; furthermore, that the culture conditions, mainly the calcium concentration in the medium, are important in the selection of that specific phenotype. Four carcinogens, 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (BP), methyl-N-nitro-nitrosoguanidine (MNNG), and N-methyl-N-nitrosourea (NMU) were used for treating primary human breast epithelial cell (HBEC) cultures. Ten out of 20 samples tested expressed survival efficiency in agar methocel. The immortalized human breast epithelial cell line MCF-10 was treated with the same chemical carcinogens, which induced point mutations in codons 12 and 61 and the expression of malignant phenotypes in treated cells. MCF-10 cells transfected with the mutated c-Ha-ras gene exhibited the same malignant phenotypes shown by carcinogen-treated cells, mainly tumorigenesis in SCID mice. It was concluded that both chemical carcinogens and mutated ras gene induce malignant transformation of immortalized HBEC, which suggests that the critical point in the transformation pathway is the immortalization of the cell.

Breast↗

Antidepressant treatment of tinnitus patients: report of a randomized clinical trial and clinical prediction of benefit.

Ninety-two middle-aged and elderly patients with disabling tinnitus participated in a double-blind randomized clinical trial comparing nortriptyline (a tricyclic antidepressant) to placebo. The study was stratified for presence (n = 38) or absence (n = 54) of current major depression (by DSM-III criteria). Both active drug and placebo were given for 6 weeks following a dose adjustment phase; the median nightly dose of nortriptyline was 100 mg. The two primary outcome variables were global satisfaction questions: "Has the medication helped you in any way?" and "Has your tinnitus improved?" Sixty-seven percent of nortriptyline patients stated the drug had helped them, versus 40 percent of placebo patients (chi-square = 7.14, p = 0.008). However, tinnitus severity was not significantly affected by nortriptyline (active: 43%; placebo: 30%; chi-square = 1.567, p = N/S). Benefit was more likely to be reported by depressed patients, by patients with insomnia, by women, and by patients without cervical musculoskeletal disease. Nortriptyline is useful in some patients with disabling tinnitus, but has not been shown to directly affect tinnitus sensation. Placebo effects were strongly significant and must be considered important in tinnitus therapy. It is difficult to specify the most appropriate outcome measures for tinnitus therapeutic trials.

Aged↗

Nonrandom abnormalities involving chromosome 1 and Harvey-ras-1 alleles in rat mammary tumor progression.

Little is known about the role of chromosomal abnormalities in the widely used models of rat mammary carcinogenesis. In this study, we cytogenetically analyzed nitrosomethylurea-induced rat mammary adenocarcinomas at different time points of development. As tools to study more advanced stages of malignant progression, we also analyzed the cytogenetic progression of tumors transplanted into younger syngeneic hosts, and of tumors that did not regress or that developed after host ovariectomy. Our results indicate that rat mammary adenocarcinomas appear to start development as diploid lesions with cytogenetically "normal" karyotypes. However, upon progression, tumors showed coexistence of normal diploid clones with abnormal clones bearing specific abnormalities affecting mainly chromosomes 1 and 15. Almost every ovary-independent tumor presented stem lines with specific nonrandom chromosomal abnormalities. Numerical chromosomal abnormalities such as specific trisomies started to develop mainly after subsequent in vivo transplantations. The abnormalities affecting chromosome 1 observed in many tumors were: (a) interstitial deletions and breakpoints for translocation in region 1q22; and (b) partial or complete overrepresentation of chromosome 1 in the form of direct duplication of region 1q22q43 or as trisomy 1. Interestingly, Harvey-ras-1 gene maps to rat chromosome 1, and by Southern analysis we observed that 4 of 8 primary tumors and 6 of 9 ovary-independent tumors showed considerable loss of Harvey-ras-1 signal indicating probable allele loss. However, analyses of some tumor transplants in more advanced stages of progression showed, paradoxically, an increased copy number of the Harvey-ras-1 oncogene coinciding with the presence of the direct duplication observed in chromosome 1 or with trisomy 1 as possible mechanisms for gene amplification. Interestingly, rat chromosome 1 is the homologue to human chromosome 11, and in numerous cases of human breast cancer loss of heterozygosity of several genes in chromosome 11p15.5 has been reported. Some of the rat chromosome 1 abnormalities observed may be equivalent to those affecting 11p15 in human tumors. We also observed 8 tumors with abnormalities affecting chromosome 15. At least 3 genes of interest in breast cancer have been previously mapped to that rat chromosome. The similarities observed with human breast cancer may point to common mechanisms of tumor progression in both species.

Adenocarcinoma↗

Regulation of surface-differentiation molecules by epidermal growth factor, transforming growth factor alpha, and hydrocortisone in human mammary epithelial cells transformed by an activated c-Ha-ras proto-oncogene.

Spontaneously immortalized human mammary epithelial cells MCF-10A were transfected with an activated c-Ha-ras oncogene. Transfected cells (MCF-10T) acquire a malignant phenotype, as already reported. Studies of 125I-2'-deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF-alpha) showed that though MCF-10T had become almost independent on exogenous EGF and TGF-alpha, they continued to respond to the synergistic effect of HC and CT plus EGF. Both lines were phenotypically characterized with an immunoradiometric assay in live cells. Expression of MHC class-I molecules, human milk-fat-globule-I antigen, and EGF receptor was reduced in ras-transfected cells, although other differentiation markers were unchanged. Exogenous EGF down-regulated the expression of functional EGF-R, selectively in transformed cells. TGF-alpha failed to modulate EGF-R. In contrast, HC strongly stimulated the expression of EGF-R while depressing MHC class-I molecules. Thus, it appears that in vivo HC may co-operate with TGF-alpha and EGF in promoting the growth of transformed mammary cells. This hormone might also favor the escape from immune surveillance by reducing the expression of surface differentiation markers.

Antigens, Differentiation↗

Chronic fatigue syndrome criteria. A critique of the requirement for multiple physical complaints.

OBJECTIVE: The purpose of this study was to test the hypothesis that the patients with chronic fatigue who have the highest number of medically unexplained physical symptoms over their lifetime would also have the highest prevalence of current and lifetime affective and anxiety disorders, lifetime affective symptoms, and the most functional disability. A further goal was to use this information to modify the current case definition to better identify a subgroup of patients with chronic fatigue syndrome who are less likely to have psychiatric illness. DESIGN: Two hundred eighty-five consecutive patients with chronic fatigue were interviewed with the National Institute of Mental Health Diagnostic Interview Schedule and completed four self-rating questionnaires measuring psychologic distress, functional disability, and the tendency to amplify symptoms. Based on previously published data, patients were divided into four groups with a progressively higher number of lifetime medically unexplained physical symptoms. The prevalence of current and lifetime psychiatric disorders, lifetime psychologic symptoms, and extent of functional impairment was then compared in these four groups of patients. MAIN RESULTS: The prevalence of current and lifetime psychiatric diagnosis and lifetime depressive symptoms increased linearly with the number of lifetime physical symptoms that the patient experienced. The extent of impairment in activities of daily living and the tendency to amplify symptoms also increased linearly with the number of medically unexplained physical symptoms. CONCLUSION: The patients with the highest numbers of medically unexplained physical symptoms had extraordinarily high rates of current and lifetime psychiatric disorders. These data suggest that the current case definition for chronic fatigue syndrome inadvertently selects for patients with the highest prevalence of lifetime psychiatric diagnoses. A recommendation based on these results is to modify the case criteria for chronic fatigue syndrome to include patients with fatigue and few physical symptoms and to identify and consider excluding patients with high numbers of physical complaints.

Anxiety Disorders↗

Influence of age and parity on the development of the human breast.

Breast cancer is heavily influenced by the reproductive history of the individual. Pregnancy has a protective effect which is attributed to differences in the degree of differentiation of the breast. The purpose of this work was to determine whether the quantity and the type of parenchymal structures present in the human breast were related to the age and parity history of a woman. Fifty-one human breast samples were obtained from bilateral or unilateral reduction mammoplasties performed in 40 parous women ranging in age from 18 to 57 years, and 11 nulliparous women ranging in age from 14 to 54 years. An average of 100 grams of tissue/specimen were processed for whole mount. A total of 650 slides were examined and 31,222 structures were classified and counted under the light microscope. The following mammary structures were identified: terminal structures (TS), and lobules (LOB) type 1, 2, and 3. Results were plotted for the total patient population and separately for nulliparous and parous women against age. The total patient population contained similar proportions of LOb1, 2, and 3 between ages 14-18, with a reduction of percentage of Lob1 and increase in Lob3 between ages 23 to the middle forties, when Lob3 decreased and Lob1 increased to 70%. Lob2 and TS did not exhibit significant changes throughout the period of life analyzed. When analyzed separately it was found that the breasts of nulliparous women were predominantly composed of Lob1, fewer Lob2, with Lob3 almost completely absent, whereas parous women had a high frequency of Lob3, which were the predominant structures until the fourth decade of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A randomized trial of psychiatric consultation with distressed high utilizers.

This study reports the results of a randomized trial of a psychiatric consultation intervention with distressed, high utilizing patients of 18 physicians in two primary care clinics. Psychiatric consultation was associated with a significant increase in the use of antidepressants in intervention patients compared with controls in the first 6 months after intervention. Intervention patients were also significantly more likely to continue antidepressant treatment than control patients. The primary care physicians receiving psychiatric consultations increased the rate of prescribing antidepressant medications in their practice from 32 prescriptions filled per 1,000 visits before their participation in four consultations to 44 new prescriptions per 1,000 visits in the 12-month period after. There were no significant differences between intervention patients and controls at 6 and 12 months after randomization in psychiatric distress, functional disability, or utilization of health care (ambulatory visits, radiographic and laboratory testing services, admissions to inpatient medical care).

Ambulatory Care↗

Antidepressant treatment of tinnitus patients. Interim report of a randomized clinical trial.

Previous studies have shown that severe tinnitus is associated with current major depression, and that tricyclic antidepressant therapy reduces tinnitus disability, at least compared to brief placebo treatment. We are completing a randomized clinical trial of nortriptyline, stratified by presence or absence of current major depression, in 100 patients with severe chronic tinnitus. Preliminary analysis of global outcome on the first 52 patients reveals that those receiving nortriptyline were more likely to feel that their drug had been helpful (74% vs. 36%, p less than 0.01), but were equally likely to report that their tinnitus was improved (37% vs. 32%, NS). So far, neither audiometric nor self-report measures of tinnitus have demonstrated statistically significant differences between active drug and placebo. Simply administered visual rating scales, if externally-referenced, correlated better with global outcome than did the Iowa Tinnitus Handicap Questionnaire. As expected, nortriptyline was significantly superior to placebo with respect to reductions in the Hamilton Depression Scale, especially in depressed patients. Paradoxically, depressed patients reported more disability and loudness on all scales, but had lower 1 kHz tinnitus intensity matches and dynamic ranges. Our preliminary conclusions are that: 1) nortriptyline reduces depression in patients with severe tinnitus, 2) placebo effects are very important in the treatment of tinnitus, 3) depression may be associated with decreased tolerance for both internal and external sounds, and 4) it is still difficult to specify the appropriate measures of tinnitus loudness and disability for use in therapeutic trials.

Depressive Disorder↗

Image analysis of Feulgen-stained NIH/3T3 cells transformed with DNA of 4-nitroquinoline 1-oxide treated human breast epithelial cells.

The nuclear phenotypes of Feulgen-stained NIH/3T3 cells transformed with 4-nitroquinoline 1-oxide (4NQO) treated, human breast epithelial cell (HBEC) DNA were studied by scanning microspectrophotometry and image analysis and compared with data obtained for nontransformed cells and for NIH/3T3 cells under ras oncogene transfecting situations. The Feulgen-DNA content of the individual nuclei (NQ1, NQ2, and NQ3 phenotypes) of the transformed cells was found not to be deeply affected, although presence of chromatin structures resembling double minutes could be verified in part of the metaphases of the transformed cells. On the other hand, the chromatin supraorganization of these cells showed some changes involving increased (NQ2, NQ3) or decreased (NQ1) levels of condensation. The changes in chromatin packing states, however, were of small magnitude compared with those reported for NIH/3T3 cells transfected with a c-H-ras oncogene or an N-ras-containing MCF-7 cell DNA. It was assumed that the transformation of the NIH/3T3 cells is not always necessarily accompanied by high levels of chromatin condensation. The transformation of the NIH/3T3 cells induced by the 4NQO-treated HBEC DNA and particularly the changes in chromatin condensation in these transformed cells could not be attributed merely to a ras activation elicited by the carcinogen. It is suggested that a more complex transforming mechanism is involved, probably owing to the fact that a whole genomic DNA of the 4NQO-treated HBEC has been used for transfection.

3T3 Cells↗

Mutated c-Ha-ras oncogene alters cytokeratin expression in the human breast epithelial cell line MCF-10A.

MCF-10A, a spontaneously immortalized human breast epithelial cell line, has been transformed by transfection with the mutated c-Ha-ras oncogene obtained from T24 carcinoma cells. The pattern of cytokeratin expression was studied in MCF-10A cells in comparison with plasmid transfected or MCF-10Aneo cells, normal ras proto oncogene transfected or MCF-10AneoN cells, and transformed or MCF-10AneoT cells. Cytokeratin expression was studied by western immunoblot of total cellular proteins separated by two-dimensional gel electrophoresis. Blots with cytokeratin specific AE1 and AE3 antibodies showed identical molecular weight species of cytokeratins in MCF-10A, MCF-10Aneo, MCF-10AneoN, and MCF-10AneoT cells; however, in MCF-10AneoT cells, the intensity of immunostaining and the number of immunoreactive phosphorylated polypeptides keratins 7, 8, 15, and 16 was decreased. It was concluded that c-Ha-ras oncogene-induced transformation alters quantitatively the cytokeratin pattern of human breast epithelial cells and that these changes could explain some of the morphologic alterations observed in c-Ha-ras transformed cells.

Blotting, Western↗

Cement thickness and microleakage under metal-ceramic restorations with a facial butted margin: an in vivo investigation.

Ten metal-ceramic restorations with buccal porcelain butt margins and palatal metal beveled margins were fabricated for periodontally hopeless teeth. After cementation, the experimental crowns remained in the oral environment for 3 to 6 months; the teeth were then extracted and used for microscopic and microleakage evaluation. All ten crowns showed at least a small amount of microleakage, but adaptation of beveled margins proved to be superior to that of shoulder porcelain margins.

Cementation↗

Buffering of intracellular calcium in response to increased extracellular levels in mortal, immortal, and transformed human breast epithelial cells.

Extracellular levels of calcium at 1.05 mM or higher induce terminal differentiation and senescence in the mortal (MCF-10M) line of human breast epithelial cells, but does not retard the growth or induce differentiation in the immortal (MCF-10A) and oncogene transformed (MCF-10AneoT) lines. Intracellular levels of calcium and inositol triphosphate were determined in MCF-10M, MCF-10A, and MCF-10AneoT, under conditions of low and high extracellular calcium. We hereby report that increases in extracellular calcium is translated into significant increases in intracellular levels of calcium and inositol triphosphate in MCF-10M, but not in MCF-10A and MCF-10AneoT. This difference in the apparent calcium buffering capacity between the mortal and the immortalized human breast epithelial cells could account for the latter's unperturbed growth potential in high extracellular calcium environment.

Breast↗