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Biomedical subjects

J Russo

Publications and source records attributed to J Russo.

At least 127 records · Page 7Linked to original sources

Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens and c-Ha-ras transfection.

The objective of this work was to determine whether transformation of the human breast epithelial cell line MCF-10F by the chemical carcinogens 7, 12-dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP), or c-Ha-ras oncogene transfection, influence the expression of epidermal growth factor receptor (EGFR), estrogen (ER) or progesterone (PR) receptors, and the content of cathepsin-D (Cath.D). MCF-10F control cells did not express any of the phenotypes of neoplastic transformation, whereas carcinogen-treated cells and clones derived from the latter formed colonies in agar-methocel, and exhibited increased chemotaxis and chemoinvasion. Clone BP-1E was also tumorigenic in SCID mice. The BP1 cell line transfected with mutated c-Ha-ras oncogene, named BP1-Tras, became more aggressive after transfection and decreased the latency time to tumorigenesis. Radioligand binding and immunocytochemical reactions were utilized for determining the receptors and Cath.D content of control and carcinogen-treated cells and their derived clones. MCF-10F cells contained 37 fmol/mg of protein of EGFR, ER and PR were undetectable, and Cath.D content was 70 fmol/mg protein. EGFR content was significantly higher in D3-1 and BP1-E cell lines vs the control MCF-10F and the other DMBA and BP clones, correlating positively with the emergence of the transformation phenotype. Whereas EGFR levels were not significantly different in BP1-Tras cells when compared with BP1-E, the former were more tumorigenic in SCID mice, an observation suggesting an alternative pathway in these cells in the formation of tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

Subsyndromal ("mixed") anxiety--depression in primary care.

OBJECTIVE: To determine in primary care settings the prevalence, clinical characteristics, and functional status of patients who have anxious and depressive symptoms who did not meet diagnostic criteria for major mood and anxiety diagnoses. DESIGN: Patients were screened with the General Health Questionnaire and interviewed if they exceeded the cutoff score of 5. Also, one patient whose score was below the cutoff was interviewed for every two patients whose scores were above the cutoff. SETTING: Five primary care sites in the United States, France, and Australia. PATIENT: Two hundred sixty-seven patients presenting to their primary care physicians for general medical care and follow-up. METHODS: Structured diagnostic interviews were conducted and ratings of anxiety, depression, and functional impairment were obtained by trained interviewers. RESULTS: After adjustments for sampling, 5% of the patients had symptoms of anxiety, depression, and functional impairment, without meeting formal criteria for a major DSM-III-R mood or anxiety disorder. This was comparable to the prevalence of diagnosable DSM-III-R mood disorders but only one-fourth the prevalence of diagnosable anxiety disorders. These patients who had subsyndromal symptoms had rates of lifetime psychiatric disorders and prior psychiatric treatment comparable to those of patients meeting criteria for major mood and anxiety disorders. CONCLUSION: The comparable rates of symptomatic distress, functional impairment, and prior psychiatric illness and treatment suggest that patients with subsyndromal anxiety and depressive symptoms warrant clinical recognition and possibly specific treatment.

Anxiety↗

Coping and marital support as correlates of tinnitus disability.

Although there is increasing awareness that depression can add significantly to the disability associated with chronic medical illness, it is not clear whether all of the impact of psychosocial factors upon medical disability are mediated by or moderated by depression. It has not been determined whether treating depression alone is an adequate strategy for addressing psychosocial magnification of medical disability. We analyzed data collected at initiation of a treatment trial from 92 subjects with chronic severe tinnitus to assess the role of coping, and 49 subject-spouse pairs to assess the role of marital interaction in tinnitus-related role dysfunction. Three multiple regression models were developed. After accounting for gender, tinnitus loudness, and depressive severity among the 92 subjects, greater role dysfunction was associated appraisal of tinnitus as salient, and less role dysfunction with coping through avoidance or seeking social support. Marital interaction was assessed from patient and spouse perspectives. In the patient-rated set, less marital cohesion was associated with greater tinnitus-related role dysfunction. In the spouse-rated set, more punishing responses to subject illness behavior were associated with greater tinnitus-related role dysfunction. In each case the disabling effect was greater in the face of high levels of subject depression. This study provides evidence for the oft-stated analogy between chronic tinnitus and chronic pain, and provides justification for a similar multimodal treatment strategy. Reducing depression is an important means to reduce medical disability but should be supplemented by clinical attention to appraisal of the illness, modes of coping with the illness, and spousal response to the illness.

Adaptation, Psychological↗

Chronic neurological sequelae to organophosphate pesticide poisoning.

OBJECTIVES: This work was undertaken to determine whether there are any chronic neurological sequelae to acute organophosphate pesticide poisoning. METHODS: California surveillance data were used in a study of neurological function among 128 men poisoned by organophosphate pesticides in California from 1982 to 1990 and 90 referents. Tests included a neurological physical examination, 5 nerve conduction tests, 2 vibrotactile sensitivity tests, 10 neurobehavioral tests, and 1 postural sway test. RESULTS: After correcting for confounding, the poisoned group performed significantly worse than the referent group on two neurobehavioral tests (sustained visual attention and mood scales). When the data were restricted to men with documented cholinesterase inhibition (n = 83) or to men who had been hospitalized (n = 36), the poisoned subjects also showed significantly worse vibrotactile sensitivity of finger and toe. Significant trends of increased impairment were found with increased days of disability on a wide spectrum of tests of both central and peripheral nerve function. CONCLUSIONS: While these findings are limited by low response rates and by small sample sizes for specific pesticides, this study was based on a large surveillance database and is the largest study to date of the chronic effects of organophosphate pesticide poisoning. The evidence of some long-term effects of poisoning is consistent with two prior studies.

Adolescent↗

Scanning microphotometry image analysis of Ha-ras-transformed human breast epithelial cells.

Nuclei of the human breast epithelial cells, MCF-10A, transfected with the c-Ha-ras oncogene, the ras proto-oncogene and the plasmid Homer 6 only, were studied by image analysis after Feulgen staining. This material had been previously used to demonstrate that the experimental insertion of the activated c-Ha-ras oncogene into the DNA of the MCF-10A cells induces their tumoural properties. The ras-transformed nuclei of the MCF-10A cells exhibited differences in chromatin supraorganization in comparison with the nuclei of human breast carcinoma MCF-7 cells, or c-Ha-ras-transformed NIH/3T3 cells and, to a much lesser extent, with those of other MCF-10A transfectants and the non-transfected MCF-10A cells. All MCF-10A transfectants exhibited unravelling of both condensed and non-condensed chromatin, which, however, was less drastic in the ras-transformed MCF-10A cells. It is hypothesized that simultaneous to a general chromatin loosening as a response to foreign transfected DNA, a reverse mechanism may be elicited by ras transformation in the chromatin of the MCF-10A cells. The result in terms of elicited chromatin condensation was not as strong as that promoted in ras-transformed NIH/3T3 cells. Considering that early steps of tumour progression in vitro have previously been assumed to be involved in the ras-transformed MCF-10A cells, the differences in chromatin supraorganization of the ras-transformed MCF-10A cells as compared with MCF-7 cells are probably due to their different tumoural stages plus the putative effect of the transfected DNA vector on the transfected MCF-10A cells.

Breast Neoplasms↗

Toward a physiological approach to breast cancer prevention.

Breast cancer is one of the most frequent malignancies in women, and its incidence is increasing. No reduction in the mortality rate has resulted from advances in early diagnosis and new therapeutic modalities; therefore, new approaches to the understanding of this disease are required. The observation that, in an experimental animal model, full-term pregnancy prior to exposure to a carcinogenic agent protects the mammary gland from malignant transformation led us to study the mechanisms underlying this phenomenon. The protective effect observed after pregnancy did not depend upon gestational or lactational hyperplasia of the mammary gland, but upon structural changes induced in the mammary parenchyma by those processes. Those changes are permanent, since the protective effect is maintained after pregnancy and consists in the complete differentiation of terminal end buds to lobules. The protective effect exerted by pregnancy can be mimicked by treating young virgin rats with a single placental hormone, chorionic gonadotropin. Since the possibility of preventing breast cancer by treating young nulliparous females with hormones that mimic a fullterm pregnancy that results in complete differentiation of the gland is of practical interest to the human female population, we undertook the study of the human breast. The breast of postpubertal nulliparous women is composed of lobular structures reflecting different stages of development. Lobules type 1 (lob 1) are the most undifferentiated ones. Lobules type 2 evolve from the previous ones and have a more complex morphology, being composed of a higher number of ductular structures per lobule. They progress to lobules type 3 and 4, which are present in the pregnant and lactational periods of the mammary gland. In nulliparous women the structure most frequently found at all ages is the lob 1, whereas in parous women, lob 3 is the most frequent one. Lob 1 are considered to be the site of origin of ductal carcinoma in situ, which progresses to invasive carcinoma. Lob 2 originate lobular carcinoma and lob 3 originate adenomas, fibroadenomas, sclerosing adenosis, and apocrine cysts. These observations led us to test if the degree of lobular development influences the transformation of human breast epithelial cells exposed in vitro to chemical carcinogens. We found that primary cultures derived from breast tissues composed of lobules type 1 and 2 express phenotypes of cell transformation which were not observed in cells derived from lobules type 3.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms.

OBJECTIVE: To determine whether the antidepressant, nortriptyline, is effective for treatment of depression, tinnitus-related disability, and tinnitus symptoms in patients with severe chronic tinnitus. DESIGN: A 12-week, double-blind, randomized controlled trial. SETTING: A university otolaryngology clinic. PATIENTS: Ninety-two subjects with severe chronic tinnitus: 38 with current major depression and 54 with depressive symptoms and significant tinnitus-related disability. INTERVENTION: Nortriptyline (maintained at 50 to 150 mg/mL for 6 weeks) or placebo. MAIN OUTCOME MEASURES: Hamilton Depression Rating Scale, Tinnitus Disability Measures, and Audiometric Measures. RESULTS: Nortriptyline was superior to placebo by multivariate analysis of covariance for depression (10.6 vs 14.3 final Hamilton Depression score), for tinnitus-related disability (1.8 vs 2.4 final MPI Tinnitus Interference), and tinnitus loudness (13.6 vs 20.0 dB final loudness match [in worst ear at tinnitus frequency]). When major depression and depressive symptoms groups were considered separately, nortriptyline was superior to placebo on these same measures but differences did not achieve statistical significance. CONCLUSIONS: The antidepressant nortriptyline decreases depression, functional disability, and tinnitus loudness associated with severe chronic tinnitus. What appears to be irreversible disability of otologic origin may, in part, be reversible disability of psychiatric origin.

Aged↗

Psychiatric and otologic diagnoses in patients complaining of dizziness.

BACKGROUND: Dizziness is a common and disabling symptom in primary care practice, especially among the elderly. Though there are many organic causes of dizziness, the results of medical workups are negative in the majority of patients. METHODS: A total of 75 patients with dizziness who were referred to a community otolaryngology practice received a structured psychiatric diagnostic interview (National Institute of Mental Health Diagnostic Interview Schedule) and questionnaires that assessed psychological distress as well as a complete otologic evaluation, including electronystagmogram. Patients with evidence of a peripheral vestibular disorder were compared with those without such evidence. RESULTS: While psychiatric diagnoses were present in both those with and without evidence of a peripheral vestibular disorder, those without such evidence had a greater mean number of lifetime psychiatric diagnoses as defined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, and specifically, a greater lifetime prevalence of major depression and panic disorder. This group also more frequently met criteria for somatization disorder, had more current and lifetime unexplained medical symptoms, and had more severe current depressive, anxiety, and somatic symptoms. CONCLUSIONS: Psychiatric diagnoses are common among patients with dizziness referred for otologic evaluation who do not show evidence of a peripheral vestibular disorder. Specific psychiatric disorders should be part of the differential diagnosis of patients who present with dizziness.

Adult↗

Regional localization of 32 NotI-HindIII fragments from a human chromosome 13 library by a somatic cell hybrid panel and in situ hybridization.

Relatively few DNA probes have been regionally assigned to chromosome 13 bands, and these tend to be clustered in the proximal end of the chromosome in the regions where intensive mapping efforts have been focused because of the retinoblastoma and Wilson disease genes. We have developed a chromosome 13-specific half-linking library of NotI-HindIII fragments and regionally mapped 32 of these on chromosome 13, using a somatic cell hybrid panel that subdivides chromosome 13 into 11 regions and nonisotopic in situ hybridization with silver amplification of a digoxigenin-labeled probe.

Animals↗

Crossfostering and early development of natural killer cytotoxic activity in various inbred mouse strains.

In the present study using crossfostering among three inbred mouse strains (C57BL/6, DBA/2, and Balb/c) we compared the effects of lactation with milk of different compositions on the development of NK cells cytotoxic activity. The results show that the pups from C57BL/6 and DBA/2 mice exhibit a significant early increase of NK cells cytotoxic activity when fostered by Balb/c dams, in comparison to those fostered by natural mothers. The analysis of proteins, lactose, and lipids showed difference among the strains for all components. Strain effects for days of lactation were also observed. The naso-anal length and the body weight of young mice showed differences with the strain of fostering mothers. The results indicate that the characteristic of maternal milk composition interacts with the inbred genetic susceptibility of the pups to elicit the full expression of the level of NK activity.

Animals↗

Depressive symptoms and measures of disability: a prospective study.

OBJECTIVE: The purpose of this study was to test the hypothesis that decreases in severity of depressive symptoms in patients with chronic tinnitus would correlate with reductions in measures of functional disability. METHOD: This study describes the correlations between several measures of functional disability and Hamilton depression scores in two groups of patients with major depression and depressive symptoms (D-NOS) who were patients enrolled in a 12-week placebo-controlled, double-blind trial of nortriptyline. These patients had chronic severe tinnitus which was associated in most patients with high frequency hearing loss. The effect of whether affective symptoms improved and the patient's initial depression status (major depression versus depressive symptoms) are examined in order to increase understanding about the correlations between depressive symptoms and functional disability. RESULTS: Most measures of functional disability decreased synchronously with Hamilton Depression Scale scores in both patients with major depression and those with subclinical depressive symptoms. Patients whose depression improved had a significantly greater change in each disability measure than patients whose depression did not improve. This significant decrease in functional disability was seen in 11 of 13 scales in the improved D-NOS group, versus only 3 of the 13 scales in the unimproved D-NOS group; 9 of 13 scales of functional disability significantly decreased in the improved major depression group, versus 3 of 13 scales in the unimproved major depression group. CONCLUSIONS: The results suggest that there was a significant correlation between improvement in both major depression and depression-NOS symptoms, and decreases in measures of functional disability in an aging population with a chronic medical illness.

Adaptation, Psychological↗

Transformation of human breast epithelial cells by chemical carcinogens.

The present study was carried out to determine whether human breast epithelial cells (HBEC) are transformed by chemicals that have been proven to be carcinogenic in other model systems. A spontaneously immortalized human breast epithelial cell line, MCF-10F, was treated with dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B[a]P), N-methyl-N-nitrosoguanidine (MNNG) or N-methyl-N-nitrosourea (NMU) for 24 h. MCF-7 and T24 malignant cell lines were used as positive controls. All the carcinogens induced alterations in both cell morphology and pattern of growth, increased growth rate and anchorage-independent growth in agar-methocel, which became evident by the 8th to 10th passages post-treatment, at approximately 157 days in culture. Colonies formed in agar-methocel were isolated and expanded. The following clones were successfully grown: D1, D2 and D3, from DMBA, M4 from MNNG, and BP1, BP2, BP5, BP6, BP7, and BP10 from B[a]P treated cells. From clones BP1 and BP2, selected cell populations were isolated and the derived cell lines or clones were named BP1-E and BP2-B respectively; the D3-1 cell line was derived from clone D3. BP1 and BP1-E clones showed increased anchorage-independent growth, chemotaxis and invasiveness. Clone D3-1 showed increased chemotactic and invasive capabilities, but to a lesser degree than BP1-E. The tumorigenic potential of the cells was tested by inoculation into SCID mice. MCF-7, T24 and BP1-E cells formed tumors in 100% of the SCID mice at 28, 10 and 101 days of inoculation respectively. None of the other clones formed tumors. It was concluded that both polycyclic hydrocarbons and aromatic amines induced in the immortal cells MCF-10F changes indicative of neoplastic transformation. Our data show that the phenotypes associated with neoplastic transformation appear in a progressive fashion, and that the emergence of clones is associated with the expression of higher proliferative rate, anchorage independence, chemotactic and chemoinvasive abilities and, in certain cases, tumorigenicity.

Animals↗

Does expressed emotion in spouses predict subsequent problems among care recipients with Alzheimer's disease?

Researchers have observed that Expressed Emotion (i.e., criticism; EE) in caregivers is predictive of poorer functioning in psychiatric care recipients over time. Few studies have examined, however, whether EE has predictive validity for the decline of care recipients with a clearly defined organic illness such as Alzheimer's disease. This study evaluated whether Alzheimer's disease care recipient problems [in cognition, activities of daily living (ADLs), and negative behaviors] were predicted longitudinally by caregiver EE. As hypothesized, caregiver EE was not predictive of care recipient cognitive or ADL decline; however, data suggested that EE was predictive of increased negative behaviors over time. The specific predictions of negative care recipient behaviors, and not care recipient cognitive/ADL decline, suggest that the former outcomes may be determined by environmental factors as well as the organicity of the disease. These data may be important because researchers have reported that caregivers are more distressed by negative care recipient behaviors than by care recipient cognitive/ADL decline.

Activities of Daily Living↗

Posttraumatic stress disorder symptoms and precombat sexual and physical abuse in Desert Storm veterans.

The purpose of this research was to study the association between precombat sexual and physical abuse and combat-related posttraumatic stress disorder (PTSD) symptoms in a clinical sample of male and female Desert Storm veterans. Two hundred ninety-seven veterans provided data on precombat sexual and physical abuse, precombat psychiatric problems, sociodemographics, Desert Storm combat exposure, and PTSD symptomatology using the Mississippi Scale. Men reported significantly higher levels of combat exposure, and women described significantly more frequent precombat abuse. Precombat-abused veterans reported more frequent precombat psychiatric histories. Analysis of covariance revealed that gender significantly modified the impact of precombat abuse on combat-related and other PTSD symptomatology after adjusting for precombat psychiatric history and level of combat exposure. Specifically, females describing precombat abuse reported much greater PTSD symptomatology than did females denying precombat abuse. These results in conjunction with previous research suggest that a relationship between precombat abuse and combat-related PTSD may exist. Prospective, longitudinal studies of both men and women are needed.

Adult↗

Histories of sexual victimization in patients with irritable bowel syndrome or inflammatory bowel disease.

OBJECTIVE: Two reports have suggested a possible association between a history of sexual trauma and irritable bowel syndrome, but several factors in their study designs limited their generalizability. The authors used a more rigorous methodology to confirm this association. METHOD: They administered structured psychiatric and sexual trauma interviews to 28 patients with irritable bowel syndrome and 19 patients with inflammatory bowel disease and compared prevalence rates of sexual victimization in the two groups. RESULTS: Compared with patients diagnosed as having inflammatory bowel disease, patients with irritable bowel syndrome had a significantly higher rate of severe lifetime sexual trauma (32% versus 0%), severe childhood sexual abuse (11% versus 0%), and any lifetime sexual victimization (54% versus 5%). The nine patients who had experienced severe lifetime victimization had significantly higher odds ratios for lifetime depression, panic disorder, phobia, somatization disorder, alcohol abuse, functional dyspareunia, and inhibited sexual desire than the 38 patients who had experienced less severe sexual trauma or no trauma. A logistic regression analysis showed that gender, the number of medically unexplained physical symptoms, and self-reported anxiety and hostility accounted for all of the variance in the victimized group. CONCLUSIONS: These preliminary results suggest that sexual victimization may be an important factor in the development of irritable bowel syndrome in some patients. Future studies attempting to categorize subgroups of patients with irritable bowel syndrome should inquire into past histories of sexual victimization.

Adult↗