Models of the physician-patient relationship.
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Female↗
Biomedical subjects
J Andre
Publications and source records attributed to J Andre.
Learning to see: moral growth during medical training.
During medical training students and residents reconstruct their view of the world. Patients become bodies; both the faults and the virtues of the medical profession become exaggerated. This reconstruction has moral relevance: it is in part a moral blindness. The pain of medical training, together with its narrowness, contributes substantially to these faulty reconstructions. Possible improvements include teaching more social science, selecting chief residents and faculty for their attitudes, helping students acquire communication skills, and helping them deal with their own pain. Most importantly, clearer moral vision requires time and scope for reflection.
Attitude of Health Personnel↗
Antiestrogens prevent the stimulatory effects of L-triiodothyronine on cell proliferation.
This paper studies the modulatory effects of two antiestrogens, the steroid ICI 164 384 and the nonsteroidal compound 4-hydroxytamoxifen (4-OH-tam), on the proliferation of L-T3-stimulated cell lines. Three cell lines known to be stimulated by thyroid hormones and to contain estrogen receptors but to have a different estradiol sensitivity to estradiol were used; F4Z2 and MCF-7 cells were stimulated, whereas GH3 cells were insensitive. Cells were counted 6-7 days after hormones and antihormones were added to the culture medium, separately or in association (a fixed hormone concentration and increasing antihormone concentrations and vice versa). In F4Z2 and MCF-7 cells, antiestrogens prevented noncompetitively the stimulatory effect of L-T3 and, as expected, competitively the stimulatory effect of estradiol. In GH3 cells, antiestrogens had proper inhibitory effects, but they did not prevent significantly the proliferative effect of L-T3. To investigate the mechanisms of the modulatory effects in F4Z2 cells we examined the consequences of antiestrogens on thyroid hormone receptors (nuclear binding of L-T3 and mRNAs of thyroid hormone receptors, i.e. c-erbA alpha and -beta) and insulin-like growth factor-I (IGF-I; secretion and mRNAs). Antiestrogens neither competed with L-[125I]T3 nor reproducibly decreased the number and affinity of thyroid hormone-binding sites. While 4-OH-tam frequently decreased the amount of c-erbA beta transcripts, ICI 164 384 did not alter the distribution of alpha and beta cDNA transcripts. Further, neither antiestrogen prevented the increases in IGF-I accumulation in conditioned medium and IGF-I mRNA concentrations induced by L-T3 (0.1 nM). In conclusion, 1) antiestrogens are potent noncompetitive inhibitors of the action of L-T3 on the proliferation of cells whose growth is responsive to estradiol (F4Z2 and MCF-7), but not of the action on a cell line whose growth is insensitive to estradiol (GH3). 2) The loss of L-T3 sensitivity is not due to a loss of thyroid receptors or a decrease in IGF-I production. 3) In addition to estrogen receptors, factors involved in the estradiol control of cell proliferation appear to be required for the antiestrogen inhibition of L-T3 action.
Breast Neoplasms↗
Comparative study of mercury accumulation in dolphins (Stenella coeruleoalba) from French Atlantic and Mediterranean coasts.
Total mercury concentrations (Hgt) have been determined in liver, kidneys, skeletal muscle, melon, stomach and intestine of 35 specimens of Stenella coeruleoalba stranded on French Atlantic and Mediterranean coasts. Very high mercury levels, with concentrations reaching 80 mg Hgt kg(-1) fresh weight (FW) in muscle and about 1500 mg Hgt kg(-1) FW in liver tissue, were observed. Liver has the highest concentration, followed by muscle and kidney. The lowest concentrations were found in the melon. The levels observed in the Mediterranean specimens are among the highest observed in marine organisms and confirm previous reports of high mercury levels in marine mammals from the Mediterranean. Comparison between Hgt accumulation levels in these two geographic groups of dolphins shows that Mediterranean individuals have much higher concentrations than specimens from the Atlantic. These differences provide additional confirmation for the higher Hgt concentrations observed previously in other pelagic species (tuna, sardine, anchovy, etc.) from the Mediterranean Sea. Taking into consideration the pelagic habitat of the dolphin and the local influence of anthropogenic mercury sources it seems reasonable to assume that the main source of the high mercury concentrations observed in Mediterranean biota is natural mercury deposits located in many regions of the Mediterranean basin.
Animals↗
Successful immunization of infants at 6 months of age with high dose Edmonston-Zagreb measles vaccine. Cite Soleil/JHU Project Team.
A group of 2097 Haitian infants 6 to 11 months of age were randomized to receive Schwarz or Edmonston-Zagreb strain measles vaccines containing 10- to 500-fold more vaccine viral particles than standard potency vaccines. No unusual adverse reactions were noted. Edmonston-Zagreb vaccines were more effective than equivalent doses of Schwarz vaccines as measured by the proportion of vaccinated children with measles antibody concentrations greater than or equal to 200 mIU/ml 2 months after vaccination and the persistence of antibody at 18 to 24 months of age. High titer Edmonston-Zagreb vaccine administered at 6 months of age induced antibody concentrations greater than or equal to 200 mIU/ml in 83% of infants by plaque reduction neutralization and 93% of infants by enzyme-linked immunosorbent assay with high rates of antibody persistence at 12 to 24 months of age. The World Health Organization recommends high titer Edmonston-Zagreb measles vaccines for routine use at 6 months of age in areas where measles is an important cause of mortality in young infants.
Antibodies, Viral↗
Multihormonal control of cell proliferation: opposite effects of two stimulators (17 beta-estradiol and L-triiodothyronine) and one inhibitor (dexamethasone) on F4Z2 pituitary tumor cells.
From the MtTF4 tumor of rat pituitary origin we established the F4Z2 cell line whose growth is stimulated by 17 beta-estradiol (E2). Taking E2 actions as references we investigated actions of other effectors on the proliferation, protein, and insulin growth factor-I (IGF-I) secretions of F4F2 cells. Dexamethasone (Dex) and L-T3 were chosen because they have also intracellular receptors and they act in pituitary cells. Cells were cultured in 96-well plates in RPMI 1640 medium supplemented either with charcoal-treated fetal calf serum (CT-FCS) or with BSA and transferrin. Hormones were added at the time of seeding and cells were counted 2-10 days later without renewing the culture medium. The accumulation of immunoreactive IGF-I in conditioned medium was used as an index of IGF-I secretion. For studies on protein secretion, cells were incubated for 24 h with [35S]methionine and labeled proteins were separated by polyacrylamide gel electrophoresis. We found that: 1) L-T3, like E2, stimulated in a dose-dependent and specific manner the proliferation of F4Z2 cells cultured in the presence of 5% CT-FCS; EC50 was: 1 X 10(-11) M and 0.2 X 10(-11) M for L-T3 and E2, respectively. In contrast, L-T3 but not E2 remained active in serum-free medium; 2) Dex was a strong inhibitor of cell proliferation in serum-free medium and in medium supplemented with 5% CT-FCS (EC50: 5 X 10(-9) M). The antiglucocorticoid RU 38 486 prevented this inhibitory effect; 3) when a stimulator (E2 or L-T3) was simultaneously incubated with the inhibitor (Dex) the number of cells depended on the ratio of hormone concentrations. When there was no large excess of one effector this number was intermediary between those counted in the presence of each hormone separately and L-T3 was more potent than E2 in preventing Dex inhibition; 4) Dex, E2, and L-T3 modified the electrophoretic patterns of secreted proteins but there was no evidence for a correlation between these modifications and the inhibition or the stimulation of cell proliferation, and 5) the accumulation of immunoreactive IGF-I was insensitive to E2, increased by L-T3, and markedly decreased by Dex. L-T3 but not E2 prevented the effect of Dex.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats. Influence of insulin and sorbinil treatments.
Kidney cortex sialic acid level, sialidase and sialyltransferase activities have been measured in spontaneously diabetic BB rats and in streptozotocin-diabetic rats (STZ). In untreated diabetic BB rats, at the onset of the disease, sialidase specific activity was found to be increased by 21% when compared with diabetes-resistant BB controls (P less than 0.05) whereas sialyltransferase activity was not significantly modified and bound sialic acid concentration was diminished (P less than 0.05). In diabetic BB rats submitted to a minimal insulin therapy, during 3 months of disease, sialidase activity and sialic acid concentration were similar to those of Wistar age-matched controls. In STZ-diabetic Wistar rats, sialidase specific activity was increased by 76% after 5 months of disease when compared to age-matched Wistar controls (P less than 0.01); in contrast, specific sialyltransferase activity was decreased by 21% (P less than 0.05); these enzymatic alterations were associated with a decrease in bound sialic acid concentration (P less than 0.01); 1 month's insulin therapy, started 4 months after onset of the disease, normalized sialidase activity but had no effect on sialyltransferase activity and sialic acid concentration; treatment with sorbinil prevented cataract development but had no effect on sialidase activity whereas it emphasized the decrease in sialyltransferase activity and sialic acid concentration. The disturbances in the enzyme activities concerned with sialoglycoconjugate metabolism observed in experimental and spontaneous diabetes may be responsible for the decreased bound sialic acid content observed in the rat kidney cortex.
Animals↗
Estradiol stimulation and inhibition of cell growth in new estrogen-sensitive cell lines and tumors established from the MtTF4 tumor.
Cell lines were established from the MtTF4 tumor, growth of which is inhibited by estradiol, in order to determine whether the effect observed in vivo was due to a direct action on tumor cells. Two different cell lines were obtained according to the medium in which tumor cells were dispersed and cultured. The F4P cells were obtained when the culture medium contained charcoal-treated fetal calf serum. The growth rate of these cells was slowed down by 17 beta-estradiol in animals and also in culture during the early passages. Thereafter, they became insensitive to 17 beta-estradiol in culture but remained negatively controlled in vivo. These cells, whatever their sensitivity to 17 beta-estradiol, secrete prolactin and carry functional D2 dopamine binding sites. The F4Z cells were established in medium containing fetal calf serum not treated with charcoal. The growth rate of these cells was stimulated by 17 beta-estradiol in animals but was 17 beta-estradiol insensitive in culture up to subculture 26. At this time, the growth rate of the subline also became stimulated by 17 beta-estradiol in culture, and this phenotype was still found at passage 108 (50% effective dose, 5 to 10 pmol; maximum stimulation, 180 to 300% of control). These cells neither secrete measurable amounts of prolactin nor have dopamine binding sites. Thus, according to the medium in which cells were dispersed and cultured, two different cell strains were derived from a tumor in which growth is inhibited by 17 beta-estradiol. The point of interest is that the growth rate of one strain was inhibited by 17 beta-estradiol, while the other was stimulated. Convergent data suggest that MtTF4 tumor was heterogeneous and that selection had occurred during the dispersion or the culture of cells. Since the growth of one of these cell lines was slowed down transiently in culture we conclude that the inhibition of tumor growth could be due to a direct action of 17 beta-estradiol on tumor cells. However, the dissociation between the response to 17 beta-estradiol in culture and in the animal observed at some time of cell evolution suggests that environment affects the sensitivity of cells to 17 beta-estradiol.
Animals↗
Cystic fibrosis with and without meconium ileus.
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Cystic Fibrosis↗
Size heterogeneity of affinity labeled estrogen receptors in the MtTF4 tumor whose growth is inhibited by estradiol, in pituitary gland and uterus.
UNLABELLED: Estrogen receptors (ER) of the MtTF4 tumor whose growth is inhibited by estradiol (E2) were analyzed and compared to those of tissues whose growth is stimulated by E2 (uterus and pituitary gland). Cytosol prepared in buffer containing protease inhibitors was incubated with [3H]tamoxifen aziridine ([3H]TAZ) in the presence or absence of non-radioactive competitor. The labeled proteins were precipitated, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in denaturing conditions and detected by fluorography. Two classes of ER were identified. The first class is of high molecular weight (Mr = 65,000-64,000). In normal tissues, it is indeed frequently made up of two subtypes as revealed by the presence of a doublet on autoradiograms. In the MtTF4 tumor these subtypes were only rarely suspected and never they were as marked and distinct as in normal tissues. The second class, of low molecular weight (Mr ! 54,000-52,000), is also frequently made up of two subtypes in the uterus and the proportion of this class is higher in the uterus of mature than of immature rats. The MtTF4 tumor contains this class of ER but, due to the presence of non-specifically labeled proteins in this region, its relative amount cannot be estimated and the doublet was exceptionally revealed. In the pituitary gland, this small receptor has not been found. CONCLUSIONS: (i) On the basis of molecular weight analyses, estrogen receptors are heterogeneous, (ii) the ER pattern depends on the type of tissue and the sexual maturity of rats but all the tissues examined contained at least one type of the "classic" high molecular weight receptor, and (iii) no evident correlation was found between the ER pattern and the positive or negative response to estradiol.
Animals↗
Gene conversions and rearrangements cause discordance between inheritance of forms of 21-hydroxylase deficiency and HLA types.
Congenital adrenal hyperplasia (CAH) can be caused by a variety of defects in the functional gene encoding 21-hydroxylase (P450c21), which lies in the midst of the human leukocyte antigen (HLA) locus on chromosome 6. As a result, Mendelian genetics permit clinically distinct forms of CAH to be traced genetically by HLA and complement typing of family members. The recent cloning of probes for P450c21 now permits tracing of the affected gene directly. A consanguineous family had three members affected with three clinically distinct forms of CAH. Two of these individuals had identical extended haplotypes, including nine HLA and complement loci. Despite this extensive identity, the patterns of genomic DNA fragments digested with endonuclease EcoRI and detected by a P450c21 cDNA probe differed greatly in these two individuals. Thus, the DNA diagnosis of allelic variation was much more sensitive than the HLA diagnosis. Genomic DNA digested with endonuclease TaqI and probed with P450c21 cDNA revealed the 3.2-kilobase (kb) band, which is generally associated with the nonfunctional P450c21 A pseudogene, in all family members, and also revealed the 3.7-kb band associated with the functional P450c21 B gene in all family members except the severely affected index case. Probing of the same blots with a genomic probe also permitted examination of the adjacent downstream TaqI fragments, showing retention of both the 2.4-kb (A pseudogene) and 2.5-kb (B gene) fragments. Similarly, BglII-digested genomic DNA from all individuals contained both the 12-kb (A pseudogene) and 11-kb (B gene) bands. These data indicate that the basis of 21-hydroxylase deficiency in the index case was due to a homozygous gene conversion event and not to gene deletion. These results show that the DNA in and around the 21-hydroxylase gene is genetically very active, so that the usual generalization concerning linkage and inheritance may yield incorrect conclusions and diagnoses.
Adolescent↗
[Value of ipratropium (Atrovent) in the treatment of chronic obstructive lung diseases in myasthenic patients treated with anticholinesterase agents. Apropos of a case].
We report a case of myasthenia gravis occurring in a 70-year old patient with old chronic bronchitis. Anticholinesterase therapy led to an increase in respiratory symptoms, but relief was obtained with inhaled ipratropium. The activity of this drug was confirmed by spirography. This clinical finding is compared with similar data found in the literature.
Aged↗
Inhibition of the MtTF4 tumor growth by dexamethasone.
It is known that estradiol, but not progesterone or dihydrotestosterone, slows down the growth of the MtTF4 tumor. In the present paper, it is shown that: (1) this tumor contains glucocorticoid receptors, (2) its growth is also inhibited by treatment with dexamethasone (Dex), and (3) the growth rate of a cell line and several clones established from the tumor is negatively controlled by Dex 10(-7) M in culture medium containing 10% gelding serum. Unlike estradiol, Dex does not induce cell hypertrophy. This work suggests that the inhibition of the MtTF4 tumor growth by Dex may be due in part to a direct action on tumor cells and, taking into consideration previous reports, it allows us to forward the hypothesis that both Dex and estradiol inhibit MtTF4 tumor growth in two different ways.
Adrenalectomy↗
Properties of the estrogen receptors contained in the MtTF4 tumor whose growth is inhibited by estradiol: 17 beta-estradiol, 17 alpha-estradiol and DNA bindings.
The steroid and the DNA bindings of the estrogen receptor of the MtTF4 tumor whose growth is inhibited by estradiol where characterized and compared to those of uterine estrogen receptors. In the tumor cytosol: E protects its binding sites against thermal denaturation, depending on the effects of sodium molybdate upon the dissociation rate of [3H]E at 20 degrees C and the ability of receptor to bind to DNA, the activation (or transformation) process, supposed to be necessary for the full action of estrogen ligand, occurs on estrogen receptor complexes and the calf thymus DNA interacts with estrogen receptor with an affinity similar to that of uterine estrogen receptor. Kinetic and equilibrium studies with 17 alpha-[3H]E both in uterus and tumor indicate that this ligand is fast-associating, fast-dissociating and that its affinity for ER is 2- to 4-fold lower than that of 17 beta-[3H]estradiol one. Competition experiments between 17 beta-[3H]estradiol and the unlabelled 17 alpha epimer reveal, in both uterus and tumor, a time-dependent decrease of the apparent potency of 17 alpha-E to inhibit the binding of [3H]E. It is concluded that the estrogen receptors are very similar in MtTF4 tumor and uterus and the diversity of the response of cell growth to E is due rather to differences at the post-receptor level.
Animals↗
Oral "hairy" leucoplakia in an African AIDS patient.
A 34-year-old African patient with AIDS developed a new form of oral leucoplakia closely resembling the "hairy" leucoplakia described by Greenspan in male homosexuals in the San Francisco area. A herpes-like virus was seen on ultrastructural analysis with electron microscopy. This case supplies further evidence suggesting that the syndrome in patients originating in Central Africa is similar to the acquired immunodeficiency syndrome (AIDS) reported in American patients.
Acquired Immunodeficiency Syndrome↗
Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses.
To study the factors affecting the serologic response to measles vaccination, we evaluated 595 Haitian infants from 6 through 12 months of age, and their mothers, at the beginning of an immunization program. Thirty-four per cent of the infants had preexisting serologic evidence of measles infections by 11 months of age. Among infants more than nine months of age, those who had had measles had a significantly lower nutritional status than those who had not (P less than 0.01). After vaccination, seroconversion rates increased from 45 per cent at 6 months to 100 per cent at 12 months. The lowest rate of vaccine failure compatible with acceptably low rates of natural infections could be achieved by vaccination after eight months of age. Infants born to mothers with low levels of antibody to measles (hemagglutination-inhibition antibody titers less than 1:40) were significantly more likely to have had natural measles (P less than 0.01) or to have seroconversion after vaccination (P less than 0.001) at 6 to 10 months of age than were infants born to mothers with higher of age than were infants born to mothers with higher titers. Malnutrition and acute infections did not affect seroconversion rates. These data support the World Health Organization recommendation to administer measles vaccine in under-developed countries as soon after nine months of age as possible, regardless of nutritional status or the presence of minor illnesses.
Age Factors↗
The plasmin system in human colonic tumors: an immunofluorescence study.
We studied the plasmin system with specific antisera to plasminogen, its 2 activators (urokinase-type and tissue-type) and the 2 plasmin inhibitors, alpha 2 anti-plasmin and alpha 2 macroglobulin on sections of 34 human colonic tumors by immunofluorescence. Anti-plasminogen serum showed a clear-cut reactivity at the surface of tumor cells, as it stained the contour of tumor glandular structures, foci, and isolated tumor cells. Intratumoral deposits and necrotic areas were stained as well, often strongly. Localization of plasminogen was quite different from that of fibrinogen, which was found only in peritumoral stroma, and never on tumor cells. Traces of both types of plasminogen activator were found, mainly on invasive tumor cells for urokinase type and on large tumor foci for tissue type. Images were weak and inconstant. Large amounts of both plasmin inhibitors were characterized in tumor stroma. Alpha-2 anti-plasmin was also found in intratumoral deposits and necrotic areas. It seems likely that plasminogen exudes from blood capillaries (since anti-plasminogen serum often stained the whole capillary wall), diffuses in the stroma and binds to tumor cells. Once formed, plasmin is likely to play a role in the invasion of surrounding tissues by tumor cells, in the dissociation of tumor cells from tumor glands and in the production of necrosis inside tumor areas.
Adenocarcinoma↗
Importance of specific IgM antibodies in 116 patients with various stages of syphilis.
We tested 222 serum samples obtained from 51 patients presenting with syphilis, before and after treatment; 117 from 65 patients with a history of syphilis (114) or yaws (3); 77 from 71 patients with no evidence of syphilis; and 1117 serologically negative serum samples. Our tests included the IgM fluorescent treponemal antibody absorbed (IgM-FTA-ABS) and solid phase haemadsorption assay (SPHA) techniques. According to the stage of development of syphilis, IgM antibodies were found in 83-100% of the serum samples. This permitted a precise diagnosis to be made and cure assessed. As IgM antibodies were absent in serum from patients with healed syphilis, resolved syphilis could be distinguished from developing syphilis. The sensitivity (92%) of the IgM-FTA-ABS test was comparable with that of the SPHA (96%), but the SPHA was more specific (97.4%) than the IgM-FTA-ABS test (89.61%).
Adolescent↗