Phenotypic heterogeneity of melanoma.
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Antibodies, Monoclonal↗
Biomedical subjects
L J Davis
Publications and source records attributed to L J Davis.
Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells.
Phenotypic heterogeneity is a characteristic feature of tumor lesions in patients with melanoma. Variability can be observed in cell morphology, pigmentation, and antigen expression. To test whether phenotypic heterogeneity could be the result of events regulated during cell differentiation, we evaluated the expression of a panel of differentiation traits on melanoma cells. Metastatic melanoma lesions from two patients, designated FD and AP, were examined histologically and found to contain mixed populations of cells. Established melanoma cell lines derived from each of these lesions were subcloned at early passage in culture (passages 7 and 8) to create a panel of clones derived from each tumor. There was heterogeneity in the expression of differentiation-related traits in clones, corresponding to distinct phenotypes observed within the original tumors. Clones from patient FD corresponded to early to intermediate stages of melanocyte differentiation, and clones from patient AP ranged from intermediate to late stages. The influence of cholera toxin and PMA on differentiation of parental cultures and subclone was studied. Results of induction studies demonstrated a number of features of differentiation of melanoma cells: regulation of differentiation traits is coordinated as a program of traits expressed sequentially at specific stages; early traits, such as the epidermal growth factor receptor and the melanoma chondroitin sulfate proteoglycan antigen, are downregulated as melanoma cells differentiate, whereas late markers, including melanin, tyrosinase activity, and antigens expressed in mature melanosomes, are upregulated; Ia (class II major histocompatibility) antigens are characteristically expressed on melanomas corresponding to early or intermediate stages of differentiation and are regulated as part of the differentiation program; minimal changes in stage of differentiation were observed during induction of parental cultures with either cholera toxin or PMA, whereas definite shifts in differentiation could be induced in selected cloned subpopulations. We conclude that melanoma cells are not frozen at a specific stage of differentiation, but rather are capable of differentiating when exposed to appropriate signals. Diversity in the differentiation state of melanoma cells can account for much of the phenotypic heterogeneity observed in melanoma lesions.
Antigens, Neoplasm↗
Patient-spouse agreement on the drinking behaviors of alcoholics.
Because investigators have expressed concern about the validity of alcoholism self-report measures, attention has been focused on the use of spouse or other collateral ratings of patient drinking behaviors. Previous studies have shown that spouse ratings of alcoholics on the Self-Administered Alcoholism Screening Test (SAAST) were reliable and a valid means of screening for alcoholism. In the current study, our objectives were to attempt to replicate the earlier findings in a new and larger sample and to determine whether the various content dimensions of the SAAST show similar patient-spouse agreement. The SAAST results of 240 patient-collateral pairs showed that the mean percentage agreement over the 35 items of the SAAST was 76.5%. Patient-spouse agreement ranged from 84.7% on the component "family alcohol problems" to 68.5% on "loss of control." When patients were classified as alcoholic or nonalcoholic on the basis of spouse ratings on the SAAST, correct classification occurred 98% of the time. Correct conjoint classification by both patient and spouse occurred 95.4% of the time. Thus, we found a high level of agreement between patient and spouse on the SAAST ratings and confirmed that spouse SAAST ratings of drinking behavior of patients provide a reliable diagnosis of alcoholism.
Adult↗
Discriminant analysis of the Self-Administered Alcoholism Screening Test.
For a sample of 1156 patients (520 alcoholics and 636 nonalcoholics), discriminant function analyses were performed on the total score, a nine-item version, and a two-item version of the Self-Administered Alcoholism Screening Test (SAAST). With sensitivities set at 90 and 95%, specificities for the total score and nine-item versions ranged from 96.4 to 99.4%. Cross-validation of the nine-item version with the "jackknife" procedure resulted in only one additional misclassification of the 1156 subjects. Separate analyses of the male and female samples revealed that more items entered the discriminant function for women than for men and resulted in a higher, although clinically nonsignificant, percentage of correct classification for women. The results strongly support the use of either the total score or the nine-item version of the SAAST in large-scale screening for alcoholism in a medical patient population.
Adult↗
Validity of the MacAndrew scale in a general medical population.
The Minnesota Multiphasic Personality Inventory (MMPI) was scored for the MacAndrew (MAC) Scale in a series of samples totaling 14,789 subjects. These samples included 1077 substance-dependent patients (739 men), 7090 selected medical outpatients (2853 men), 5000 unselected medical outpatients (2500 men), 214 psychiatric inpatients (92 men) and 1408 contemporary normal (646 men). Overall, the MAC Scale correctly classified only 70.7% of the men and 37.9% of the women alcoholics. However, when samples of men and women alcoholics were broken down into four age groups, the MAC Scale correctly identified 90% of men alcoholics in the 18- to 24-year age group but only 41% of women alcoholics in the same age group. In addition, the predicted rate of alcoholism in the samples that were not substance-dependent, using the MAC Scale, was approximately 1.5 to 4 times the estimated lifetime prevalence rate (this was also true in the 18- to 24-year age group). MMPI item 215 ("I have used alcohol excessively") correctly identified 95% of the men and 94% of the women alcoholics. It was concluded that, except for men less than 24 years old, the MAC Scale is not an appropriate screening test for substance dependence in a predominantly middle-class medical population.
Adolescent↗
Age and sex differences in the responses of alcoholics to the Self-Administered Alcoholism Screening Test.
The Self-Administered Alcoholism Screening Test (SAAST) was completed by 583 inpatients (437 men; 146 women) who were undergoing evaluation and treatment for alcoholism. Endorsement frequencies were computed separately for men and women, and a principal components analysis was performed on the item intercorrelation matrix. Six components (or factors) were retained for interpretation. Men were significantly more likely to engage in occupationally and socially disruptive behaviors (component II) and to elicit concern on the part of others (component V). Women were significantly more likely to admit to loss of control (component I), to experience emotional consequences and request help (component IV), and to report alcohol problems in their families (component VI). Younger alcoholics were more likely to admit to a loss of control, to have occupational and social disruption, to experience emotional consequences and request help, and to obtain higher total scores on the SAAST. Older alcoholics were more likely to report physical consequences of drinking (component III). Twenty-two alcoholics who scored in the nonalcoholic range (6 or below) were likely to be initially resistant and unaccepting of treatment.
Adult↗
Immune dysfunction in primary biliary cirrhosis (PBC): I. Increased sensitivity of PHA stimulated lymphocyte cultures to indomethacin.
A reduced responsiveness of peripheral blood lymphocytes from PBC patients to phytohaemagglutinin (PHA) was observed. Such an alteration may be related either to an intrinsic defect of T cells to proliferate or to a derangement of endogenously secreted mediators with regulatory functions, i.e., prostaglandins (PG). The role of the PG mediated suppressor system in 14 PBC patients and in 12 age and sex matched controls was evaluated. After the addition of indomethacin, the lymphocyte responsiveness to PHA increased in both controls and in PBC patients. However, this increment was statistically significantly only in PBC patients. The addition of PGE1 and PGE2 to PHA stimulated cultures decreased the lymphocyte proliferative activity. No differential sensitivity to PGEs was detectable in lymphocytes from PBC patients. Our data suggest, that, after polyclonal stimulation, mononuclear cells from PBC patient may release increased levels of PGEs which in turn affect the proliferative activity of mitogen activated lymphocytes.
Adult↗
Effects of fentanyl and diazepam in dogs deprived of autonomic tone.
In contrast to reports of the untoward hemodynamic effects of fentanyl and diazepam in intact organisms, we found that neither a bolus of 100 micrograms/kg fentanyl nor the addition of intravenous doses of diazepam, up to and including 1 mg/kg (cumulative dose 2 mg/kg) caused cardiovascular depression in 13 anesthetized dogs after elimination of their sympathetic and parasympathetic tone. There were no significant changes in mean arterial blood pressure, cardiac output, heart rate, peak left ventricular dP/dt, cardiac filling pressures, or systemic vascular resistance. Rapid bolus injection of 3 mg/kg diazepam (cumulative dose 5 mg/kg) caused a significant (P less than 0.05) but transient (time to 50% recovery less than 2 min) decrease in systemic vascular resistance, blood pressure, and dP/dt. When corrected for pressure changed (dP/dt divided by simultaneous left ventricular pressure), the decrease in dP/dt did not attain statistical significance, nor did changes in cardiac output or filling pressures, even after this large dose of diazepam. We conclude that previously reported decreases in hemodynamic function in subjects with intact autonomic function after fentanyl alone, or after the combination of fentanyl and diazepam, are indirect in nature, that is, are caused by a centrally mediated decrease in vasoregulatory (mainly sympathetic) outflow from the central nervous system.
Animals↗
Can we still recommend mediation?
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Humans↗
Lay consultation of older people.
The study of lay consultation has drawn attention to how social interaction supports, validates and influences the perception and response to health problems. Until now, such research has not considered how the particular circumstances of older people alter the process, i.e. (1) disruption of support networks, (2) experience of chronic rather than acute illness and (3) suffering of diseases shared by a sizable proportion of their agemates . Using case study data, the authors show how everyday discussions of health problems lead to the transmission to the sufferer of new information about the health condition, the reinforcement of health actions and in some cases attempts to persuade or to intervene actively. The authors use the case study material to identify variables shaping the process of consultation and suggest the importance of this process in the adaptation of older people to declining health.
Aged↗
Drug-induced infertility.
Primary infertility may result from the use of various drugs. This phenomenon may be the result of an effect on the hypothalamic-pituitary-gonadal axis or a direct toxic effect on the gonads. Some of the drugs considered in this article demonstrate sex-related differences in their ability to cause infertility; there also may be age-related differences. The drugs described in this review, in regard to their association with the development of infertility, include various individual antineoplastic agents (cyclophosphamide, chlorambucil, busulphan, and methotrexate) and combinations of these chemotherapeutic drugs, glucocorticosteroids, hormonal steroids (diethylstilbestrol, medroxyprogesterone acetate, estrogen, and the constituents of oral contraceptives), antibiotics (sulfasalazine and co-trimoxazole), thyroid supplements, spironolactone, cimetidine, colchicine, marihuana, opiates, and neuroleptic agents.
Adolescent↗
Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family.
We have isolated eight rat lymphocyte-myeloma hybrid cell lines producing monoclonal antibodies that react with the 21,000-dalton transforming protein (p21) encoded by the v-ras gene of Harvey murine sarcoma virus (Ha-MuSV). These antibodies specifically immunoprecipitate both phosphorylated and non-phosphorylated forms of p21 from lysates of cells transformed by Ha-MuSV. All eight react with the products of closely related ras genes expressed in cells transformed by two additional sarcoma viruses (rat sarcoma virus and BALB sarcoma virus) or by a cellular Harvey-ras gene placed under the control of a viral promoter. Three of the antibodies also react strongly with the p21 encoded by the v-ras gene of Kirsten MuSV. These same three antibodies immunoprecipitate the predominant p21 species synthesized normally in a variety of rodent cell lines, including the p21 produced at high levels in 416B murine hemopoietic cells. This suggests that an endogenous gene closely related to Kirsten-ras is expressed in these cells. The monoclonal antibodies have been used to confirm two properties associated with p21; localization at the inner surface of the membrane of Ha-MuSV-transformed cells, assayed by immunofluorescence microscopy, and binding of guanine nucleotides.
Animals↗
Computed tomography in the evaluation of chest lesions in the pediatric patient.
The role of computed tomography (CT) in the management of chest masses in the pediatric patient is emphasized and illustrated. Thirty-seven patients with various chest lesions who had both CT and conventional radiologic evaluations are reviewed. CT was the most consistently accurate examination, especially in the evaluation of disease extent and relationship with other organs. CT was the only modality to provide clinically useful information in 27% of the cases, and it provided significant additional information in another 24% of the group.
Adolescent↗
Government shouldn't reimburse union-busters.
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Insurance, Health↗
Shaping the mental health role of family physicians.
Family physicians have an important role in mental health care delivery. The psychiatry and family practice faculty at the University of Alabama College of Community Health Sciences recently examined the principal elements of this role and the ways in which these elements might best be incorporated into the teaching/learning process of a family medicine residency. Competency based approaches to curriculum development were chosen to permit flexibility of implementation and to allow involved physicians to participate in definition of their mental health roles. Methods used to construct the curriculum included interviews with graduated residents of the first four classes of the program, literature review, and a modified delphi/nominal group technique with family medicine and psychiatry faculty. The result was a competency based psychiatric curriculum supervised cooperatively by both psychiatry and family medicine faculty. This program is begun early in the residency, is integrated longitudinally into the rest of the residents' curriculum, and utilizes seminars, clinical experience, and liaison with a mental health team in the training design.
Alabama↗
Effect of telephone follow-up on medication compliance.
This study compared the effectiveness, in improving patient compliance with a 10-14 day course of antibiotic therapy, of the following two strategies: (1) a follow-up telephone call and (2) written instructions and oral consultation by a pharmacist. The 82 study patients were randomly assigned to four groups: 1--control; 2--call-back; 3--written and oral consultation; and 4--written and oral consultation plus a call-back. The follow-up telephone call was made on the fourth or fifth day of the prescription course. The need to take the medication as directed and until completion was explained and reinforced. Any problems with the medication were determined. Compliance was assessed on the ninth or tenth day of therapy by a patient dosage unit count, and the patient's knowledge of the medication regimen was evaluated by a structured interview. The mean compliance was 76.6% for the control group, 86.6% for Group 2, 87.5% for Group 3, and 85.4% for Group 4. The compliance in the control group was significantly less than for each of the study groups (p = 0.0295), but the three study groups were not significantly different (p less than 0.05). Patients receiving written and oral consultation had significantly greater knowledge about side effects and what to do if they missed doses (p less than 0.002). After follow-up telephone call was equal to, but did not enhance, written and oral consultation in improving patient compliance.
Adolescent↗
Rubella vaccine--therapeutic abortion.
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Abortion, Therapeutic↗