Showing papers by "Erasmus University Rotterdam published in 1988"
TL;DR: The incidence of restenosis proved to be progressive to at least the third month for all except NHLBI criterion II, and the lack of overlap between the different restenotic criteria applied affirms the arbitrary nature of angiographic definitions currently in use.
Abstract: Data from experimental, clinical, and pathologic studies have suggested that the process of restenosis begins very early after coronary angioplasty. The present study was performed to determine prospectively the incidence of restenosis with use of the four National Heart, Lung, and Blood Institute and the 50% or greater diameter stenosis criteria, as well as a criterion based on a decrease of 0.72 mm or more in minimal luminal diameter. Patients were recatheterized at 30, 60, 90, or 120 days after successful percutaneous transluminal coronary angioplasty (PTCA). After PTCA all patients received 10 mg nifedipine three to six times a day and aspirin once a day until repeat angiography. Of 400 consecutive patients in whom PTCA was successful (less than 50% diameter stenosis), 342 underwent quantitative angiographic follow-up (86%) by use of an automated edge-detection technique. A wide variation in the incidence of restenosis was found dependent on the criterion applied. The incidence of restenosis proved to be progressive to at least the third month for all except NHLBI criterion II. At 4 months a further increase in the incidence of restenosis was observed when defined as a decrease of 0.72 mm or more in minimal luminal diameter, whereas the criteria based on percentage diameter stenosis showed a variable response. The lack of overlap between the different restenosis criteria applied affirms the arbitrary nature of angiographic definitions currently in use. Restenosis should be assessed by repeat angiography, and preferably ascertained according to the change in absolute quantitative measurements of the luminal diameter.
953 citations
TL;DR: In this article, the authors summarize the efforts to define the specific helper T cells or lymphokines which transmit regulatory signals to B cells, and to clarify the individual events influenced by these signals.
Abstract: The process that immunologists rather casually refer to as \"T cell help\" is a complex series of interactions in which helper T cells (Tu) regulate virtually every aspect of the antigen-dependent response of B cells. Despite many years of cumulative evidence that TH cells are required for the activation, clonal expansion, differentiation and isotype regulation of B cells which respond to most antigens, many basic questions remain as to the specific regulatory signals involved. The development of clonal TH cell lines and the recent rapid progress in cloning the genes encoding many lymphokines have made it possible to begin to answer these questions. In this review, we summarize our efforts to define the specific TH products or lymphokines which transmit regulatory signals to B cells, and to clarify the individual events influenced by these signals. The particular focus of this work is on lymphokines that regulate the expression of dilTerent immunoglobulin (Ig) isotypes produced by a stimulated B cell population. What has emerged from this effort is the realization that isotype expression is regulated by many of the same molecules that control the activation, growth and differentiation of B cells.
724 citations
TL;DR: It is suggested that as many as one in five women with breast cancer may carry the AT gene and that the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients.
Abstract: Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood1,2 characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation3; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively4; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology5. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes6. Furthermore, heterozygous females are at an increased risk of breast cancer7,8. These findings, when coupled with an estimated carrier frequency of 0.5–5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene7 and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients10. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.
636 citations
Harvard University1, Letterman Army Medical Center2, Indiana University3, University of Hawaii4, University of Kansas5, Erasmus University Rotterdam6, Icahn School of Medicine at Mount Sinai7, Duke University8, Memorial University of Newfoundland9, Rutgers University10, University of Massachusetts Medical School11, Wayne State University12, University of Colorado Denver13, University of Iowa14
TL;DR: The VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4), which suggests that the defect responsible for the VHL phenotype is not a mutation in the RAF 1 gene itself.
Abstract: Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.
611 citations
TL;DR: The binocular co‐ordination of human horizontal saccades was analysed for the first time systematically over the full oculomotor range with a precise and accurate scleral sensor coil technique and showed an abduction‐adduction asymmetry and were not well yoked dynamically.
Abstract: 1. The binocular co-ordination of human horizontal saccades was analysed for the first time systematically over the full oculomotor range with a precise and accurate scleral sensor coil technique. Effects of amplitude (1.25-80 deg), direction (adduction vs. abduction and centrifugal vs. centripetal) and eccentricity (symmetrical about primary or between primary and secondary positions) were systematically investigated in three subjects). 2. To minimize extraneous effects of stimulus presentation on the programming of saccades, subjects were instructed to voluntarily change their gaze between two continuously visible targets. These were positioned on an iso-vergence locus, and thus contained no stimulus for disjunctive eye movements. 3. Under these conditions the amplitudes of the primary saccades of the two eyes were remarkably accurate; undershooting of the target by about 0.5 deg (independent of amplitude in the range 10-70 deg) was typical. This finding contrasts with the undershooting by about 10% described in the literature as characteristic for other stimulus conditions. 4. Saccadic peak velocities saturated at a mean asymptotic level of 502 +/- 32 (S.D.) deg/s for saccades of 40 deg and larger. The duration was linearly related to amplitude for saccades up to 50 deg; for saccades of larger sizes the duration increased progressively more steeply. Skewness values (acceleration time as a fraction of total saccadic duration) decreased from about 0.45 for saccades up to 10 deg to about 0.20 for saccades of 50 deg and larger. 5. Binocular saccades showed an abduction-adduction asymmetry and were not well yoked dynamically. The saccades of the abducting eye consistently had a larger size, a higher peak velocity, a shorter duration and were more skewed than the concomitant adducting saccades of the fellow eye. As a result, the eyes diverged transiently by as much as 3 deg during horizontal saccades. 6. Saccades also showed a marked centrifugal-centripetal asymmetry. Peak velocities of saccades towards the primary position were about 10% higher than peak velocities of corresponding centrifugal saccades. 7. These directional asymmetries were the main source of variability in the pool of saccades. In comparison, intra- and intersubject variability was minor in our sample. 8. Post-saccadic drift consisted of a vergence and a version component. The vergence component of this drift was a continuation of the vergence movement occurring during saccades. The version component, generally smaller than the vergence component, was directed towards the target position.(ABSTRACT TRUNCATED AT 400 WORDS)
463 citations
TL;DR: Evidence is provided that a cDNA that encodes a major part of the human androgen receptor is isolated from a library prepared of mRNA of human breast cancer T47D cells with an oligonucleotide probe homologous to parts of the region encoding the DNA-binding domain of steroid receptors.
368 citations
TL;DR: In this paper, it is concluded that society is more likely to flourish with happy citizens than with unhappy ones and that happiness buffers stress, thereby preserving health and lengthening life somewhat.
Abstract: The issue. Nineteenth century utilitarian philosophers considered happiness as the highest good (‘utility’ in their words) and claimed political priority for attempts to promote the greatest happiness for the greatest number. In reaction, many of their contemporaries cried out that happiness is not good at all, because it turns people into ‘contented cows’ and undermines social bonds. Modern psychologists, however, tend to suggest positive effects: sharper awareness, more activity, better social functioning and better health.
Data. No empirical investigations have yet focussed on consequences of happiness. Nevertheless, indications can be found in various studies covering other matters. This paper gathers the available data. These data do not allow definite conclusions, but do suggest several small yet noteworthy effects. Enjoyment of life seems to broaden perception, to encourage active involvement and thereby to foster political participation. It facilitates social contacts: in particular contacts with spouse and children. Further, happiness buffers stress, thereby preserving health and lengthening life somewhat. There is no evidence of harmful effects. It is concluded that society is more likely to flourish with happy citizens than with unhappy ones.
309 citations
TL;DR: The cloning and complete sequence of a cDNA encoding a low mol.
Abstract: IGF-I and IGF-II are growth-stimulating peptides with strong mitogenic properties. These polypeptide growth factors circulate in serum bound to specific binding proteins. We report the cloning and complete sequence of a cDNA encoding a low mol. wt IGF-binding protein from a human placenta cDNA library. We propose the designation IGF-binding protein 1 (IBP-1) for the gene and corresponding protein. Expression of the cDNA encoding IBP-1 in COS cells resulted in the synthesis of a 30-kd protein which binds IGF-I and is immunologically indistinguishable from the IGF-binding protein isolated from amniotic fluid or human serum. Northern blotting analysis demonstrated that expression of the IBP-1 gene is highly tissue specific and limited to placental membranes and fetal liver suggesting a rigid control. The IBP-1 gene is a single copy gene, located on chromosome 7. The results obtained suggest that most, if not all, lower mol. wt IGF-binding proteins originate from this gene.
281 citations
TL;DR: The physiological role of SRIF in the regulation of anterior pituitary function has been summarized as far as it contributes to the understanding of the use and use of this hormone in clinical practice.
Abstract: I. Introduction THE PRESENCE of GH-inhibitory substances in hypothalamic extracts was originally detected accidentally by Krulich et al. (1) during investigations into the distribution of GH-releasing factors throughout the rat hypothalamus. Several years later Brazeau et al. (2) isolated and characterized this somatotropin releaseinhibiting factor, called somatostatin (SRIF), which turned out to be a cyclic peptide consisting of 14 amino acids. SRIF was the first hormone to broaden the classic concepts of endocrinology because it has physiological effects both at the periphery and the central nervous system (3). Several reviews and proceedings from international symposia are available, which summarize the developments in the field of SRIF (4–12). In recent years SRIF analogs have been developed which can be used clinically. In the present review the physiological role of SRIF in the regulation of anterior pituitary function has been summarized as far as it contributes to the understanding of the use and ...
271 citations
242 citations
TL;DR: The binocular co‐ordination of human vertical saccades was analysed systematically over the full oculomotor range, with a precise and accurate scleral sensor coil technique, and changes in vergence were followed by converging horizontal post‐saccadic drift after upward saccade, and in diverging horizontal drift after downward s Accades.
Abstract: 1. The binocular co-ordination of human vertical saccades was analysed systematically over the full oculomotor range, with a precise and accurate scleral sensor coil technique. Effects of amplitude (1.25-70 deg), direction (upward vs. downward and centripetal vs. centrifugal), as well as position (upper or lower sector of vertical oculomotor range), were investigated systematically in three subjects. 2. All saccades were made voluntarily between continuously presented pairs of targets, which subtended equal angles of target vergence. 3. Vertical saccades were less accurate than horizontal saccades (as described by Collewijn, Erkelens & Steinman, 1988). For target distances between 10 and 70 deg, upward saccades undershot the target by about 10%, whereas downward saccades tended to overshoot the target. Downward saccades were about 1.5 deg larger than upward saccades between the same targets. 4. Peak velocities continued to increase monotonically with saccadic amplitude up to 513 +/- 27 (S.D.) deg/s for 70 deg saccades; a distinct asymptotic level was not reached. 5. Velocity profiles of upward and downward saccades, made symmetrically about the primary (straight-ahead) position, were very similar for amplitudes up to 30 deg. At larger amplitudes, velocity profiles of upward saccades remained single peaked, whereas those of downward saccades invariably developed a second velocity peak. 6. Parameters of upward saccades depended heavily on the position of the eye. In the upper oculomotor range such saccades had lower maximum speeds, longer durations, and were more skewed than similar saccades in the lower oculomotor range (below primary). Downward saccades were almost independent of eye position. 7. Vertical eye movements during vertical saccades were virtually identical in the two eyes. In contrast, disjunctive horizontal components were systematically present. Upward saccades, at all amplitudes, were associated with diverging eye movements. Converging eye movements occurred during downward saccades. These systematic effects suggest that the vergence subsystem is not turned off during saccades. 8. These changes in vergence were followed by converging horizontal post-saccadic drift after upward saccades, and in diverging horizontal drift after downward saccades.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: The cDNA encoding human "protective protein" is isolated and the predicted amino acid sequence bears homology to yeast carboxypeptidase Y and the KEX1 gene product, which suggests a protease activity for the "Protective protein."
TL;DR: A set of transgenic mouse lines carrying Ek alpha genes with promoter region deletions was created in an attempt to compartmentalize MHC class II gene expression, finding that one transgenic line is essentially devoid of E complex in the thymic cortex.
TL;DR: It is concluded that a defect in one of at least six different genes may underlie inherited radiosensitivity in humans, and a complete list of genetically characterized fibroblast strains is presented.
Abstract: Cultured cells from patients with ataxia telangiectasia (AT) or Nijmegen breakage syndrome (NBS) are hypersensitive to ionizing radiation. After radiation exposure, the rate of DNA replication is inhibited to a lesser extent than in normal cells, whereas the frequency of chromosomal aberrations is enhanced. Both of these features have been used in genetic complementation studies on a limited series of patients. Here we report the results of extended complementation studies on fibroblast strains from 50 patients from widely different origins, using the radioresistant DNA replication characteristic as a marker. Six different genetic complementation groups were identified. Four of these, called AB, C, D, and E (of which AB is the largest), represent patients with clinical signs of AT. Patients having NBS fall into two groups, V1 and V2. An individual with clinical symptoms of both AT and NBS was found in group V2, indicating that the two disorders are closely related. In AT, any group-specific patterns with respect to clinical characteristics or ethnic origin were not apparent. In addition to the radiosensitive ATs, a separate category of patients exists, characterized by a relatively mild clinical course and weak radiosensitivity. It is concluded that a defect in one of at least six different genes may underlie inherited radiosensitivity in humans. To facilitate research on defined defects, a complete list of genetically characterized fibroblast strains is presented.
TL;DR: Evidence is presented that oxygen free radicals are involved in the pathogenesis of rheumatoid arthritis (RA), and superoxide is able to release iron from ferritin, providing a suitable source of iron, for the formation of hydroxyl radicals.
TL;DR: Twenty patients with severe plaque psoriasis were selected to receive either low‐dose cyclosporin A ( CyA) or placebo (CyA vehicle) in a double‐blind randomized trial at two centres.
Abstract: Twenty patients with severe plaque psoriasis were selected to receive either low-dose cyclosporin A (CyA) or placebo (CyA vehicle) in a double-blind randomized trial at two centres. Within 4 weeks the mean reduction in the Psoriasis Area and Severity Index (PASI) in 10 patients receiving CyA (mean dose 5.5 mg/kg/day) differed significantly from the mean reduction in 10 patients receiving placebo. In eight patients given placebo a switch to CyA therapy resulted within 4 weeks in a mean reduction in PASI of 90%. In a total 15 out of 18 patients given CyA (83%) (mean dose 5.6 mg/kg/day) there was an improvement of greater than or equal to 75% in PASI within 4 weeks. In a 2-month tapering off phase a lower mean CyA dose (3 mg/kg/day) was effective in maintaining the reduced PASI scores in seven of nine patients. Four out of five CyA treated patients who entered a post-treatment observation phase had a relapse (PASI score greater than or equal to 50% of score at baseline) after a mean interval of 6.5 weeks. The most important side-effects were mild reversible hypertension in 5 of 18 patients (28%), and reversible elevated serum creatinine levels in 7 of 18 patients (39%). We consider that further studies are justified in severe chronic psoriasis to establish suitable regimens for maintenance of remission in psoriasis with low-doses of CyA or a combination of CyA with other anti-psoriatic agents.
TL;DR: It is reported that bone marrow transplantation results in increased galactosylceramidase levels in the central nervous system (CNS) and donor-derived macrophages infiltrate the affected brain tissue and are capable of inducing a partial reversal of the enzyme deficiency.
Abstract: The twitcher mouse is an animal model of galactosylceramidase deficiency, comparable to Krabbe's disease, a lysosomal storage disease in humans. As in most lysosomal storage diseases, neurological deterioration is a prominent feature of the disease in these mice. Transplantation of enzymatically normal congenic bone marrow was earlier found to result in prolonged survival and increased levels of galactosylceramidase in the visceral organs of twitcher mice. It is now reported that bone marrow transplantation results in increased galactosylceramidase levels in the central nervous system (CNS). Concomitantly, the levels of psychosine, a highly toxic lipid that progressively accumulates in the CNS of untreated twitcher mice, stabilized at much lower levels in the CNS of treated twitcher mice. Histologically, a gradual disappearance of globoid cells, the histological hallmark of Krabbe's disease, and the appearance of foamy macrophages capable of metabolizing the storage product were seen in the CNS. By immunohistochemical labeling it was demonstrated that these foamy macrophages were of donor origin. The infiltration of enzymatically competent, donor-derived macrophages was accompanied by extensive remyelination in the CNS. It is concluded that after bone marrow transplantation, donor-derived macrophages infiltrate the affected brain tissue and are capable of inducing a partial reversal of the enzyme deficiency.
TL;DR: A remarkable homology is observed between this soluble lysosomal alpha‐glucosidase and the membrane‐bound intestinal brush border sucrase‐isomaltase enzyme complex, and it is proposed that these enzymes are derived from the same ancestral gene.
Abstract: Lysosomal alpha-glucosidase (acid maltase) is essential for degradation of glycogen in lysosomes. Enzyme deficiency results in glycogenosis type II. The amino acid sequence of the entire enzyme was derived from the nucleotide sequence of cloned cDNA. The cDNA comprises 3636 nt, and hybridizes with a messenger RNA of approximately 3.6 kb, which is absent in fibroblasts of two patients with glycogenosis type II. The encoded protein has a molecular mass of 104.645 kd and starts with a signal peptide. Sites of proteolytic processing are established by identification of N-terminal amino acid sequences of the 110-kd precursor, and the 76-kd and 70-kd mature forms of the enzyme encoded by the cDNA. Interestingly, both amino-terminal and carboxy-terminal processing occurs. Sites of sugar-chain attachment are proposed. A remarkable homology is observed between this soluble lysosomal alpha-glucosidase and the membrane-bound intestinal brush border sucrase-isomaltase enzyme complex. It is proposed that these enzymes are derived from the same ancestral gene. Around the putative active site of sucrase and isomaltase, 10 out of 13 amino acids are identical to the corresponding amino acids of lysosomal alpha-glucosidase. This strongly suggests that the aspartic acid residue at this position is essential for catalytic function of lysosomal alpha-glucosidase.
TL;DR: The MTT test offers a high degree of precision and is easy to do, it is suitable for the purpose of (large‐scale) chemosensitivity testing, and serial measurements might easily be performed in order to provide additional information on the mode of action of the drugs tested, to discriminate between cytostatic and cytotoxic drug effects.
Abstract: In this study the usefulness of the MTT assay for the quantitation of growth modulating effects on cultured prostate cancer lines (PC-3, PC-93, and LNCaP) was investigated. The MTT test is based on the enzymatic reduction of the tetrazolium salt MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide++ +] in living, metabolically active cells but not in dead cells. The reaction is carried out in situ in multiwell plates, and the reaction product, a purple-colored formazan soluble in dimethylsulfoxide, is measured colorimetrically, using a multiwell plate reader. Optimal test conditions were established for each of the cell lines used. With the hormone-sensitive cell line LNCaP, and stimulatory effect of the synthetic androgen R1881 was demonstrable by the MTT test. A sharp optimum occurred at a concentration of 10(-10) M R1881. Treatment of cells of either cell line with antineoplastic agents resulted in a dose-dependent reduction of MTT converting activity, reflecting the impaired survival of the drug-treated cells. Good correlations of the results obtained with the MTT-test, as compared with a thymidine incorporation assay or with direct DNA measurements, were observed. As the MTT test offers a high degree of precision and is easy to do, it is suitable for the purpose of (large-scale) chemosensitivity testing. Moreover, serial measurements might easily be performed in order to provide additional information on the mode of action of the drugs tested, i.e., to discriminate between cytostatic and cytotoxic drug effects.
TL;DR: A protective effect of a high zinc status on the risk of cancer and cardiovascular disease is compatible with the data, and the excess mortality observed in subjects with low copper status suggests a U-shaped relation.
Abstract: To investigate the association of serum copper and zinc with mortality from cancer and cardiovascular disease, the authors performed a case-control analysis of data obtained in a Dutch prospective follow-up study. Cancer (n = 64) and cardiovascular disease (n = 62) deaths and their matched controls were taken from a cohort of 10,532 persons examined in 1975-1978. Trace elements were measured in baseline serum samples, which had been stored during the six to nine years of follow-up. The adjusted risk of death from cancer and cardiovascular disease was about four times higher for subjects in the highest serum copper quintile (greater than 1.43 mg/liter) compared with those with normal levels. The excess mortality observed in subjects with low copper status suggests a U-shaped relation. No significant change in the risk of death from cancer and cardiovascular disease was found for subjects with low or high baseline levels of serum zinc. However, a protective effect of a high zinc status on the risk of cancer and cardiovascular disease is compatible with the data. For definitive conclusions, analysis of larger prospective data sets is recommended.
TL;DR: The results suggest that most, if not all, of the WGA-HRP-labelled cerebellar terminals in the rostral medial accessory olive (MAO) and the roostral principal olive (PO) are GABAergic.
Journal Article•
TL;DR: OA is a heterogeneous condition and some site specific associations with obesity are strong, thus there is scope for prevention by weight reduction for some sites.
Abstract: The association between obesity and osteoarthritis (OA), was studied by analysis of data from an epidemiologic survey of a population of 1071 men and 1097 women in The Netherlands. A total of 20 joints and groups of joints were investigated. OA was clearly associated with obesity in the most frequently affected joints, weight bearing as well as nonweight bearing. This association was less strong for severely affected joints than for mildly affected joints. This pattern was neither compatible with a generalized (metabolic) abnormality nor with weight induced mechanical "wear-and-tear". OA is a heterogeneous condition and some site specific associations with obesity are strong, thus there is scope for prevention by weight reduction for some sites.
TL;DR: LNCaP cells (derived from a lymph node carcinoma of the human prostate) contain androgen receptors and show androgen‐responsive growth in vitro, and both compounds independently increased the growth rate 2–3 times.
Abstract: LNCaP cells (derived from a lymph node carcinoma of the human prostate) contain androgen receptors and show androgen-responsive growth in vitro. Maximal effects on growth were seen at 0.1 nM of the synthetic androgen R1881 or 0.2 nM of epidermal growth factor (EGF); both compounds independently increased the growth rate 2-3 times. EGF-receptors were measured after 6 days culture in the presence or absence of 0.1 nM R1881. A 2.3-fold increase in receptor number/cell was found when binding was measured at 0 degrees C (from 12,500 to 28,900 sites/cell in stimulated cells). The kD value (0.45 nM) was not affected by androgen treatment. The increase of EGF-receptor activity was first observed between 6 and 12 h after exposure to androgen. It is concluded that LNCaP cells are sensitive to low concentrations of EGF (or EGF-like compounds) and that one of the mechanisms involved in androgen action on these cells is an increase of EGF-receptor expression at the cell surface.
TL;DR: Correspondence analysis showed that coronary angioplasty for unstable angina can be performed with a high initial success rate, but at an increased risk of major complications.
TL;DR: The growth of LNCaP cells, derived from a lymph‐node carcinoma of the human prostate, was stimulated by different hormones and the number of EGF receptors per cell increased in a dose‐dependent manner upon treatment with various hormones.
Abstract: The growth of LNCaP cells, derived from a lymph-node carcinoma of the human prostate, was stimulated by different hormones. Optimal growth (3- to 4-fold increase in DNA content per culture versus controls) was observed at 0.1 nM R1881 (a synthetic androgen), 1 nM progesterone or 10 nM estradiol. Triamcinolone acetonide had no effect. Dihydrotestosterone maximally stimulated cell growth at 10 nM. When the culture medium was changed 4 times in 6 days instead of twice, optimal growth was observed at 1 nM dihydrotestosterone. This indicates that a rapid metabolism of dihydrotestosterone influenced growth response. LNCaP cells contained considerable amounts of androgen receptors (920 fmol/mg cytosol protein) while progestagen, estrogen and glucocorticoid receptors were absent. The affinity of steroids for the androgen receptor decreased in the order of: R1881 (relative binding affinity: 100.0) greater than dihydrotestosterone (67.7) greater than progesterone (29.4) greater than testosterone (23.8) greater than estradiol (4.3) greater than triamcinolone acetonide (less than 0.1). Effects on cell growth of these steroids paralleled their affinity for the androgen receptor. The number of EGF receptors per cell increased in a dose-dependent manner upon treatment with various hormones. Again the amount of steroid needed for maximal effects reflected the affinity of the steroid for the androgen receptor. An approximately 2-fold increase in EGF receptor number was observed within 24 hr and before an increase in growth could be detected. Actinomycin-D and cycloheximide inhibited the hormonally induced increase in EGF receptor numbers.
TL;DR: Monoclonal antibodies produced by this hybridoma were characterized by testing the effect of various inhibitors in a competitive enzyme‐linked immunosorbent assay (ELISA) and have a high specificity for thymine dimers in single‐stranded DNA or poly(dT), but do not bind UV‐irradiated d(TpC)5.
Abstract: — A hybrid cell line (hybridoma) has been isolated after fusion between mouse-plasmacytoma cells and spleen cells from mice immunized with a thymine dimer-containing tetranucleotide coupled to a carrier protein. Monoclonal antibodies produced by this hybridoma were characterized by testing the effect of various inhibitors in a competitive enzyme-linked immunosorbent assay (ELISA). The antibodies have a high specificity for thymine dimers in single-stranded DNA or poly(dT), but do not bind UV-irradiated d(TpC)5. Less binding is observed with short thymine dimer-containing sequences. In vitro treatment of UV-irradiated DNA with photoreactivating enzyme in the presence of light, or with Micrococcus luteus UV-endonuclease results in disappearance of antigenicity. Antibody-binding to DNA isolated from UV-irradiated human fibroblasts (at 254 nm) is linear with dose. Removal of thymine dimers in these cells during a post-irradiation incubation, as detected with the antibodies, is fast initially but the rate rapidly decreases (about 50% residual dimers at 20 h after 10 J/m2). The induction of thymine dimers in human skin irradiated with low doses of UV-B, too, was demonstrated immunochemically, by ELISA as well as by quantitative immunofluorescence microscopy.
TL;DR: CyCD3 expression is restricted to the T cell lineage and can be used as a diagnostic marker for immature SmCD3- T cell malignancies, and CyCD3 can be easily detected by use of MoAbs raised against denaturated CD3 chains such as those of the SP series.
TL;DR: The isolation and partial characterization of the human gene encoding IAPP are described and the DNA sequence predicts that IAPP is excised from a larger precursor protein and that its carboxy‐terminus is probably amidated.
TL;DR: Examples of the differences between the microheterogeneity patterns of transferrin in several biological fluids and the changes that can be observed in diseases such as rheumatoid arthritis, idiopathic hemochromatosis and Kahler's disease are presented.
Abstract: The heterogeneity of human transferrin results from (i) differences in iron content, (ii) genetic polymorphism and (iii) differences in the carbohydrate moiety. This article primarily deals with the last phenomenon, the microheterogeneity of human transferrin. Owing to the comparatively simple carbohydrate structure of human transferrin and the high resolving power of isoelectric focusing in immobilized pH gradients, microheterogeneous forms of transferrin can be separated. Differences between samples can be quantitated by crossed immunoelectrophoresis. Examples of the differences between the microheterogeneity patterns of transferrin in several biological fluids and the changes that can be observed in diseases such as rheumatoid arthritis, idiopathic hemochromatosis and Kahler's disease are presented. Special attention has been focused on changes occurring during pregnancy.
TL;DR: The results suggest that in human liver microsomes a single enzyme catalyzes the deiodination of the outer as well as the inner ring of iodothyronines by the same catalytic mechanism and with the same substrate specificity as the type I deiodinase of rat liver.
Abstract: Liver is an important site for the peripheral production of T3 by outer ring deiodination (ORD) of T4 as well as for the clearance of plasma rT3, which is produced by inner ring deiodination (IRD) of T4 in other tissues. However, little is known about the underlying enzymatic reactions, and current concepts about thyroid hormone deiodination are largely based on studies in rat tissue. Here we describe the results of detailed studies of the catalytic properties of the iodothyronine deiodinase activity of human liver. The results demonstrated a high degree of similarity with the type I deiodinase of rat liver. The enzyme activity was found in the microsomal fraction. rT3 was the preferred substrate, since its ORD was catalyzed roughly 400 times more efficiently than the ORD or IRD of T4 or the IRD of T3. The deiodination of sulfated substrates was more rapid, as demonstrated by the roughly 30-fold increase in the IRD of T3 sulfate (T3S) compared with T3. The deiodinations exhibited ping-pong-type kinetics with dithiothreitol as the cofactor. Inhibition by propylthiouracil was uncompetitive with substrate and competitive with dithiothreitol, and PTU was an equally effective inhibitor of the ORD of rT3 and the IRD of T3S (Ki, 0.10-0.16 mumol/L). Various compounds with widely different inhibitory potencies had similar effects on ORD (rT3) and IRD (T3S). These results suggest that in human liver microsomes a single enzyme catalyzes the deiodination of the outer as well as the inner ring of iodothyronines by the same catalytic mechanism and with the same substrate specificity as the type I deiodinase of rat liver.