Showing papers by "Paris Descartes University published in 1995"
TL;DR: The present work reveals a remarkable pattern of MHC gene expression in the pig and raises many questions on the real nature of these isoforms.
Abstract: The aim of this study was to analyze the temporal sequence of expression of the myosin isoforms in the populations of muscle fibers in the pig and to bring more information on the origin of the strikingly different pattern of fiber composition and distribution between the deep medial red (oxido-glycolytic) and superficial white (glycolytic) portions of semitendinosus (ST) muscle. Muscle samples were taken from 49-, 55-, 75-, 90-, 103-, and 113- (birth) day-old fetuses, from 6-, 11-, 21-, 35-, 50-, and 80-day-old piglets, and from a 3-year-old pig. Our results confirm the sequential formation of primary and secondary generation fibers. The use of immunohistochemistry and heterologous monoclonal antibodies (mAb) directed against specific myosin heavy chain (MHC) isoforms revealed a different pattern of gene expression between the two portions of the ST muscle for both generations of fibers. By 75 days of gestation (dg), primary myotubes from the deep medial portion stained positively for the anti-slow MHC mAb and negatively for the adult anti-fast MHC, whereas the opposite was observed in the superficial portion. Secondary fibers never expressed slow MHC until late gestation. Instead, they expressed an adult fast MHC isoform as soon as they formed in the deep medial portion and later on in the superficial portion. From late gestation to the first 3 postnatal weeks, slow MHC began to be expressed in a subpopulation of secondary fibers. These fibers were in the direct vicinity of primary myotubes in the deep medial portion, whereas their location could not be established in the superficial portion. The remaining secondary fibers matured to type IIA in the direct vicinity of these type I fibers and to type IIB at the periphery of the islets. In both portions of the muscle, a subpopulation of secondary fibers, the first ones to express slow MHC, also transitorily expressed a MHC that was identical or closely related to the alpha-cardiac MHC during the early postnatal period. A third generation of small diameter fibers was observed shortly after birth and reacted with the anti-fetal MHC mAb; their destiny remains to be established.(ABSTRACT TRUNCATED AT 400 WORDS)
141 citations
TL;DR: The results allowed us to assign a disease locus (SRN1) to a defined chromosomal region on 1q25-1q31, thus confirming the existence of a distinct entity of autosomal recessive nephrosis, and exclusion of linkage to the entire region in one family proves genetic heterogeneity.
Abstract: Idiopathic nephrotic syndrome (INS) in childhood is characterized by massive proteinuria and minimal glomerular changes. Most patients with INS respond to steroid therapy. INS is generally regarded as a sporadic disease with favorable outcome. We investigated a distinct subgroup of nephrosis--the familial form of steroid resistant INS (SRN). These patients always progress to end-stage renal failure within a few years and show absence of recurrence of the disease after renal transplantation. The occurrence of the disorder in siblings and the high incidence of inbreeding in these families made an autosomal recessive mode of inheritance very likely. We performed whole genome linkage analysis in nine multiplex families of European or Northern African origin. Our results allowed us to assign a disease locus (SRN1) to a defined chromosomal region on 1q25-1q31, thus confirming the existence of a distinct entity of autosomal recessive nephrosis. Exclusion of linkage to the entire region in one family proves genetic heterogeneity.
132 citations
TL;DR: In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity.
Abstract: Forty-four asymptomatic patients infected with human immunodeficiency virus type 1 (HIV-1), who had 200-799 CD4 cells/microL, received oral prednisolone (0.5 mg/kg for 6 months; 0.3 mg/kg thereafter). After 1 year of treatment, no major side effect or AIDS events had occurred. The percentage of DR+ and CD25+ phenotypes in CD4 T cells decreased significantly as did levels of serum IgG, IgA, and beta 2-microglobulin. Serum p24 antigen and HIV RNA levels remained stable. CD4 cell counts increased significantly at all time points (median increase at 1 year, 119 cells/microL). Peripheral blood mononuclear cell apoptosis after overnight stimulation with anti-CD3 monoclonal antibodies was strongly inhibited at all times. In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity.
121 citations
TL;DR: These findings provide the first evidence for the pathogenic role of abnormal splicing of COL4A3 and demonstrate the superiority of mutation screening at the mRNA level to detect a hitherto poorly recognized mutation mechanism in humans, splice-mediated insertion of an Alu fragment into a coding sequence.
Abstract: Alport syndrome is a mainly X-linked hereditary disease of basement membranes characterized by progressive renal failure, deafness, and ocular lesions. The alpha 3(IV) and alpha 4(IV) collagen genes have been recently shown to be involved in the less frequent autosomal recessive form. When screening lymphocyte COL4A3 mRNAs from Alport patients, we found a mutant whose transcripts were disrupted by a 74 bp insertion at the junction of exons IV or V and VI. The insertion derives from an antisense Alu element in COL4A3 intron V, which has been spliced into the alpha 3(IV) mRNA due to a G to T transversion activating a cryptic acceptor splice site in this Alu element. There is complete segregation of this mutation with the disease in the family. Our findings provide the first evidence for the pathogenic role of abnormal splicing of COL4A3. Moreover, we demonstrate the superiority of mutation screening at the mRNA level to detect a hitherto poorly recognized mutation mechanism in humans, splice-mediated insertion of an Alu fragment into a coding sequence.
117 citations
Journal Article•
TL;DR: It is demonstrated that it is possible to transfer the Escherichia coli lacZ gene in vivo into the central nervous system structures of rats after nasal instillation of replication-defective adenoviral vector AdRSV beta gal.
Abstract: Replication-deficient adenoviruses have been used successfully to transfer foreign DNA into postmitotic cells. This article demonstrates that it is possible to transfer the Escherichia coli lacZ gene in vivo into the central nervous system structures of rats after nasal instillation of replication-defective adenoviral vector AdRSV beta gal. Mitral cells from the olfactory bulb, neurons from the anterior olfactory nucleus, locus coeruleus and area postrema expressed beta-galactosidase for at least 12 days. No cytopathic effect was observed in the CNS structures studied at the viral titer used (1-3 x 10(9) plaque-forming units (p.f.u.)). This method could be useful for the gene therapy of diseases affecting different CNS structures.
106 citations
TL;DR: It is inferred that tenascin-C impedes the terminal sprouting of mossy fibres in CA3 of kainate-treated rats, which is associated with neuronal death, gliosis and sprouting in the hippocampus of human and rats.
Abstract: Temporal lobe epilepsy is associated with neuronal death, gliosis and sprouting of mossy fibres in the hippocampus of human and rats. In the present study we show that immunoreactivity for tenascin-C (an extracellular matrix glycoprotein) increases in the hippocampus of epileptic rats. However, this increase was only observed in the cases displaying neuronal cell loss and glial reaction (i.e. after kainate treatment but not after kindling). Tenascin-C increase was particularly striking at Ammon's horn, where the antibody labelled both reactive astrocytes (confirmed by double-labelling experiments) and axonal plasma membranes. In the molecular layer tenascin-C immunoreactivity remained unchanged in both kindled or kainate treated rats. It is interesting that increased tenascin-C immunoreactivity was observed within zones in which axonal regeneration did not occur (the CA3 area in kainate-treated animals) whereas zones in which reactive synaptogenesis occurred (such as the CA3 area of kindled rats or the molecular layer of both kindled and kainate-treated rats) were devoid of tenascin-C immunoreactivity. We infer from these results that tenascin-C impedes the terminal sprouting of mossy fibres in CA3 of kainate-treated rats.
62 citations
TL;DR: Investigation of intracellular distribution of carbohydrate binding protein 35 in mouse 3T3 fibroblasts indicated diffuse distribution of CBP35 within the nucleus, but the label appears to be excluded from certain "black holes," which most probably correspond to nucleoli.
61 citations
TL;DR: Results show that a 3-week treatment of NOD female mice starting at 4 weeks of age protects them from diabetes, again emphasizing the crucial role of GAD as autoantigen in type I diabetes.
57 citations
TL;DR: Diabetogenic cells in adult mice share phenotypic characteristics with activated/memory cells, and enter the pancreas using L‐selectin‐independent migratory pathways, and were fractionated spleen T cells from diabetic mice according to L‐ selectin expression.
Abstract: The process of mononuclear cell extravasation from the blood into the islets of Langerhans in nonobese diabetic (NOD) mice is dependent on the expression of a set of molecules, most of which remain to be defined. The observation that vascular addressins are expressed in inflamed islets raises the issue of the involvement of one of their ligands, L-selectin, in the pathogenesis of autoimmune diabetes. Treatment of NOD females with Mel-14, an antibody specific for L-selectin, reduced the spontaneous development of both insulitis and diabetes. Pretreatment of diabetic donors with Mel-14 decreased the capacity of their splenocytes to transfer the disease. However, the treatment of recipients had no effect on the transfer of diabetes by untreated diabetogenic splenocytes. To reconcile these apparently conflicting results, we fractionated spleen T cells from diabetic mice according to L-selectin expression. Diabetogenic cells were found only in the L-selectin subpopulation. Thus, diabetogenic cells in adult mice share phenotypic characteristics with activated/memory cells, and enter the pancreas using L-selectin-independent migratory pathways.
53 citations
TL;DR: For the first time it is demonstrated, by Western blots and in situ immunofluorescence localization using monoclonal as well as affinity-purified polyclonal antibody to gizzard calponin, that a 36-37 kDa and a 35-36 kDa calp onin-like proteins are expressed respectively in pig and rat brains and in rat cerebellar cultured cells.
Abstract: Calponin, an actin- and Ca(2+)-calmodulin-binding protein characterized as an inhibitory factor of the smooth-muscle actomyosin activity, has also been shown to be present in some non-muscle cells. However, there is a controversy as to whether calponin is present or not in brain. Several laboratories indicate that this protein is absent in chicken or bovine brains, while Applegate et al. [Applegate, Feng, Green and Taubman (1994) J. Biol. Chem. 269, 10683-10690] have recently reported the identification of an mRNA specific for a 36 kDa non-muscle calponin analogue in homogenates of rat brains. For the first time we demonstrate, by Western blots and in situ immunofluorescence localization using monoclonal as well as affinity-purified polyclonal antibody to gizzard calponin, that a 36-37 kDa and a 35-36 kDa calponin-like proteins are expressed respectively in pig and rat brains and in rat cerebellar cultured cells. The acidic pI (5.2-5.4) of the rat brain protein revealed by isoelectric focusing is in good agreement with that of the protein coded for by the calponin isoform mRNA described by Applegate et al. and is different from that of the protein from chicken gizzard (pI 9.9). Brain calponin-like protein is different from two other Ca(2+)-calmodulin-binding proteins previously identified in brain, namely caldesmon and adducin, and from tropomyosin.
49 citations
Journal Article•
TL;DR: This preliminary report shows the feasibility of in situ hybridization methodology for studying the expression of developmental genes during the early stages of human embryogenesis and opens the way to study the pathogenesis of polymalformative syndromes and tumorigenesis.
Abstract: Les genes PAX codent des facteurs de transcription qui jouent un role important au cours de l'embryogenese. Ils sont impliques dans plusieurs pathologies humaines, telles que le syndrome de Waardenburg, l'aniridie et les tumeurs. Nous rapportons une etude preliminaire, par hybridation in situ sur coupes de tissus, des schemas d'expression de 3 genes PAX (PAX3, PAX5 et PAX6), au cours du developpement humain. Le gene PAX3 est exprime dans la gouttiere neurale et dans le tube neural. Ensuite, il s'exprime au niveau du mesencephale, du rhombencephale, des somites et de la moelle epiniere. Le gene PAX5 s'exprime de facon specifique dans la jonction mesencephale-rhombencephale et dans la moelle epiniere. Le gene PAX6 s'exprime tres tot dans le tube neural, juste apres sa fermeture. Ensuite, il s'exprime dans le cerveau anterieur, le rhombencephale et la moelle epiniere. Ces patrons d'expression sont precoces et tres specifiques dans le temps et dans l'espace. Cette etude preliminaire illustre les possibilites d'etudier, par hybridation in situ, l'expression des genes du developpement au cours de l'embryogenese humaine, meme aux stades les plus precoces. Elle ouvre des perspectives importantes quant a l'etude des syndromes polymalformatifs et tumoraux chez l'homme
TL;DR: The determination of propranolol enantiomers in microsamples of human plasma and urine by HPLC using a chiral stationary phase is described and the use of alprenolol as I.S. improves significantly the coefficients of variation.
TL;DR: It is concluded that endothelin‐1 is a potent vasoconstrictor of the human placental vascular bed and placental villous endothelial cells synthesize and release relaxing factor(s) which could possibly be NO.
Abstract: As feto-placental vessels in humans are not innervated, regulation of vascular tone in the fetal extracorporeal circulation most likely depends on either circulating hormones or local paracrine mechanisms. However, the latter have not yet been fully investigated. The aim of our study was to characterize vasomotor behaviour of resistance stem villi arteries when challenged with various constrictor and dilator agents, with special emphasis on the physiological importance of endothelium. The latter is poorly characterized in this particular vascular bed in humans. Villous stem arterial rings (internal diameter 182 +/- 6 microns) were isolated under microscopy from term human placentae obtained after cesarean section. The vessels were mounted as ring preparations in an isometric myograph for tension measurements. Endothelium was removed from some of the rings by gentle insertion of a knotted human hair into the vascular lumen. Of the three vasoconstrictors tested, endothelin-1 (ET-1) showed the greatest potency, being 1,000 times more potent than serotonin and phenylephrine. The classical endothelium-dependent vasodilators, acetylcholine, adenosine diphosphate (ADP) and histamine, caused dose-dependent relaxation of the rings; an effect which was completely abolished by the removal of endothelium. Pre-treatment with the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine, also markedly reduced the endothelium dependent relaxant responses to ADP. By contrast, the vasodilatory response to sodium nitroprusside was not affected by endothelial removal. We conclude that i) ET-1 is a potent vasoconstrictor of the human placental vascular bed and ii) placental villous endothelial cells synthesize and release relaxing factor(s) which could possibly be NO.
TL;DR: Experimental evidence that accelerated eruption affects morphogenesis and histogenesis of the rat lower incisor is provided and an impeded incisors, especially the contralateral, may not serve as an ideal control is provided.
Abstract: The present investigation studies the effects of persistently cutting one lower rat incisor out of occlusion. Within four days, the rate of eruption of the cut (unimpeded) incisor increased to 216% and that of the uncut (impeded) contralateral to 136% of the baseline rate. While the former remained high, the latter decreased gradually to about 90% within three weeks. The rate of attrition of the impeded incisor increased to 233% of the baseline rate within two days, then fell abruptly, and remained at a slightly lower level than the rate of eruption. Accordingly, the length of the erupted part of the impeded incisor decreased initially, but increased gradually after about four days. Measurements made on SEM micrographs of the series of transverse tooth segments obtained when cutting the incisor out of occlusion, showed that growth-related increase in mesiodistal tooth width was arrested from the 10th segment, dentin thickness decreased gradually to about 50% in the 12th segment, and enamel thickness, after an initial increase, decreased to about 80% in the 11th segment. The present study provides experimental evidence that accelerated eruption affects morphogenesis and histogenesis of the rat lower incisor. An impeded incisor, especially the contralateral, may not serve as an ideal control.
TL;DR: In conclusion, endothelial cells modulate the vascular responses to ET‐1 through the release of NO and a substance acting on the ATP‐sensitive K+ channel of smooth muscle of stem villi small arteries from healthy parturients.
Abstract: 1. The aim of this study was to assess the role of endothelial cells in the modulation of vasocontractile responses to endothelin-1 (ET-1) of human placental vasculature. 2. Isolated stem villi small arteries (diameter = 170-250 microns) were obtained from healthy parturients who underwent caesarean surgery during the 39th week of pregnancy for cephalo-pelvic disproportion. Isometric tension was measured in vascular rings mounted in a myograph system and challenged with ET-1 (10(-12) to 10(-6) M). 3. The vasocontractile response to ET-1 was significantly (P < 0.001) increased in endothelial-denuded (active tension = 1156 +/- 214 mN mm-1) as compared with endothelial-preserved vascular rings (active tension = 458 +/- 48 mN mm-1). This difference was significantly (P < 0.05) but only partly abolished by the NO synthase inhibitor N omega-nitro-L-arginine (L-NOARG, 10(-4) M). 4. In endothelial-preserved rings submaximally precontracted with 5-hydroxytryptamine (10(-6) M), ET-1 (10(-12) to 10(-9) M) induced dose-dependent relaxation (maximum relaxation = 70 +/- 7%) at 10(-9) M, which was followed, at higher doses (10(-8) to 10(-6) M), by a contraction. In contrast, no relaxation was seen in endothelial-denuded rings. The relaxation in rings with endothelium was significantly (P < 0.001) reduced by L-NOARG (10(-4) M. Moreover, it was totally abolished by combined pretreatment with L-NOARG (10(-4) M) and the sulphonylurea glibenclamide (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Advances in defining the roles of immune system activation and T-cell apoptosis in the viro-immunopathogenesis of HIV disease were discussed at a recent symposium.
TL;DR: Chiral tetracyclic dasycarpidone-type compounds (αR, 1S, 5R)-4 and (α, 1R, 5S)-16 have been synthesized from 2-(1,3-dithian-2-yl)indole 6 and n-(β-hydroxy-α-phenylethyl)-Δ3-piperidein-2,one8 in three steps, following the methodology described recently as mentioned in this paper.
TL;DR: The data suggest that the leukotrienes are involved in the recruitment of osteoclast progenitors, and/or their differentiation into preosteoclasts, and that mast cells responded to leukOTriene inhibition.
TL;DR: In this paper, a cyclisation with potassium carbonate in DMF of the corresponding syn- or anti-2-chloro-3-hydroxyesters was used to synthesize (2 R,3 S )-3 -phenylisoserinc.
Abstract: Cis - and trans -glycidic esters may be synthesized in high enantiomeric purities by cyclisation with potassium carbonate in DMF of the corresponding syn - or anti -2-chloro-3-hydroxyesters, prepared by microbial reduction of 2-chloro-3-oxoesters. In contrast, more basic media such as sodium ethylate afford exclusively the trans -isomer, whatever the stereochemistry of the starting 2-chloro-3-hydroxyester is. Cyclisation of deuterated compounds showed that this result was due to a rapid isomerisation of the syn esters into anti isomers before cyclisation. An application of this reaction to the synthesis of (2 R ,3 S )-3-phenylisoserinc is described.
TL;DR: It is suggested that the function of killer cells which normally destroy cells at the periphery of the pulp may be impaired by the diet, leading to cell accumulation, in rats fed an essential fatty acid deficient (EFAD) diet.
Abstract: In rats fed an essential fatty acid deficient (EFAD) diet, either during pregnancy (DN) or for 4 wk postnatally (ND), the cell density in the central part of the pulp increased about two- and threefold, respectively, of that in rats who had received a conventional diet containing sunflower oil. Cells were especially numerous around capillaries. The cell density was also increased twofold in the subodontoblastic layer in the outer part of the pulp, cells being smaller in ND compared with DN. In contrast, the- odonloblasts were reduced in height, and the Hohl cells formed a thin layer in EFAD rats. This emphasizes some aspects of pulp specificity which reacted differently from odontoblasts. We suggest that the function of killer cells which normally destroy cells at the periphery of the pulp may be impaired by the diet, leading to cell accumulation.
TL;DR: Evidence is provided that DMS-79 is a valid model of tumors responsible for the ectopic ACTH syndrome and that the mechanism of POMC gene expression in these SCLC cells is different from that in pituitary cells.
Abstract: DMS-79 is a human cell line derived from a small cell lung carcinoma (SCLC), which expresses the pro-opiomelanocortin (POMC) gene. We took it as a model in which to study the mechanism of POMC gene expression in these tumors: precursor processing is altered and gene expression is essentially unresponsive to glucocorticoids. POMC gene structure appeared normal by Southern blot analysis, indicating that gene rearrangement was not responsible for its expression in DMS-79. Indeed, using transient expression of human POMC-luciferase fusion genes in DMS-79, we showed that (1) the normal human POMC promoter was functional in DMS-79, and (2) the same proximal promoter region (-417; + 21) produced the full transcriptional activity in DMS-79 and in the mouse pituitary cell line AtT-20. Progressive 5' deletion analysis revealed differences between AtT-20 and DMS-79: region (-611; -376) was active in AtT-20 and not in DMS-79, whereas region (-95; -161) was active in both cell lines and (-376; -417) was only active in DMS-79. The latter partially overlaps a motif homologous to the DE-2 rat element which confers the tissue-specific expression of POMC in AtT-20 cells; however, this motif had no effect in DMS-79. These data suggest that POMC gene transcription is achieved through a different set of transacting factors in DMS-79 and AtT-20. Altogether, our results provide evidence that DMS-79 is a valid model of tumors responsible for the ectopic ACTH syndrome and that the mechanism of POMC gene expression in these SCLC cells is different from that in pituitary cells.
TL;DR: This study showing site-specific effects of castration on preadipocyte proliferation and differentiation suggests that part of the decreased fatness induced by castration in the rat is related to the modulatory effect of androgenic status on adipogenesis in some deep fat depots.
Abstract: In the rat, castration induces a decreased weight of fat depots. One possible explanation for these alterations could be that the capacities of preadipocytes to proliferate and differentiate are reduced by castration. Considering the regional specification of adipose tissue metabolism, these capacities and their eventual modulation by the androgenic status were presently compared in cultured preadipocytes from rat subcutaneous (SC) and epididymal fat depots.
TL;DR: Only bone marrow cells (BMC) retained substantial amounts of radioactivity, in contrast to thymus, spleen, and peritoneal cells, and the characteristics of this interaction are consistent with histamine uptake rather than receptor binding.
TL;DR: The CAG expansion responsible for Huntington's disease is followed by an adjacent polymorphic CCG repeat region which may interfere with a PCR based diagnosis and this region is sequenced in 52 unrelated HD patients from both normal and HD chromosomes.
Abstract: The CAG expansion responsible for Huntington's disease (HD) is followed by an adjacent polymorphic CCG repeat region which may interfere with a PCR based diagnosis. We have sequenced this region in 52 unrelated HD patients, from both normal and HD chromosomes. Fifty percent of the normal alleles were (CCG)7(CCT)2, 48% (CCG)10(CCT)2, and 2% (CCG)7(CCT)3. In contrast (CCG)7(CCT)2 was found in 85% of the HD alleles which represents significant linkage disequilibrium with the HD mutation.
TL;DR: There is a wide variety of diuretic-induced metabolic abnormalities of unequal severity, and despite all the adverse reactions, it has been proven that diuretics are beneficial in many diseases.
Abstract: There is a wide variety of diuretic-induced metabolic abnormalities of unequal severity. Renal failure can be caused by excessive sodium loss, or by certain drug combinations comprising, for instance, a nonsteroidal anti-inflammatory drug (NSAID) or an ACE inhibitor. Hyponatraemia is uncommon. It is encountered with thiazides, especially among women. A sodium level less than 120 mmol/L may result in neurological complications. Hypokalaemia is frequent and might increase the risk of cardiac arrhythmia. Hyperkalaemia induced by potassium-sparing diuretics is often combined with another contributive cause. Glucidic, lipidic and uric acid abnormalities are common, but their clinical effects are slight. They do not seem to worsen cardiovascular risks among elderly patients. Nevertheless, prescribing diuretics for elderly patients requires special precautions. Reducing the diuretic dose, as is now recommended for treating hypertension, seems to lessen adverse effects, and despite all the adverse reactions just mentioned, it has been proven that diuretics are beneficial in many diseases.
TL;DR: It was found that, as hypothesized, patient history is a possible source of bias, and experienced clinicians are less prone to bias than less-experienced clinicians, and that bias mostly occurs with mildly pathologic larynges.
TL;DR: For the first time, caldesmon- and calponin-specific immunoreactivities in cerebellar cultured neurons are demonstrated and it is suggested that they are part of the contractile apparatus of neural cells.
TL;DR: It is suggested that factors other than pituitary PRL play the major role in regulating PRL-R expression on cells of the immune system.
Abstract: Previous reports demonstrated that prolactin receptors (PRL-R) are widely expressed on cells of the immune system. We analyzed a possible regulation of PRL-R expression on human mononucleated blood cells by prolactin (PRL) itself. PRL-R expression was analyzed by immunofluorescence on T and B lymphocytes and monocytes from peripheral blood mononucleated cells (PBMC) of patients with hyperprolactinemia or acromegaly compared with sex- and age-matched control subjects. The frequency of PRL-R positive cells and the intensity of PRL-R expression was only modified among the CD8+ T cell population of hyperprolactinemic patients with macroadenoma. No correlation was reported between PRL-R expression and circulating PRL levels. The percentage of PRL-R+ cells on B or T lymphocytes and monocytes as well as the capacity of PBMC to proliferate in response to T cell mitogens were not significantly different in bromocriptine-treated compared with untreated patients. These findings suggest that factors other than pituitary PRL play the major role in regulating PRL-R expression on cells of the immune system.
Journal Article•
TL;DR: Results support the hypothesis that in EDS IV, dominant inheritance should be assumed, in sporadic cases also, unless proven otherwise, and the applications of the tools of molecular biology, analysis of these defects if now within reach.
Abstract: The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility. Considerable clinical and genetic heterogeneity exists, and more than nine separate forms have been recognized. Recent advances in the molecular analysis of EDS have identify defects responsible for EDS VI (homozygous and compound heterozygous mutations in the lysyl-hydroxylase gene), EDS VIIA and EDS VIIB (mutations in the type I collagene genes), EDS VIIC (deficiency of procollagen N-proteinase), EDS IX (mutations in the MNK gene), and EDS IV (mutations in the type III collagen gene). Of the various types of Ehlers-Danlos syndrome the most severe is type IV (EDS IV). Early studies showed that fibroblasts from EDS IV patients secreted lower than normal amounts of type III procollagen (Pope et al., 1975). Later, the disease was linked to COL3A1, the gene encoding this protein. More recently, with the publication of full length cDNA and partial characterisation of the gene structure, detailed analysis of mutations in EDS IV patients has become possible. Nineteen different mutations in the type III procollagen gene have been reported in different families with EDS IV. Recent results support the hypothesis that in EDS IV, dominant inheritance should be assumed, in sporadic cases also, unless proven otherwise. Very little is known about the genetics or biochemicals defects responsible for the others EDS subtypes, but with the applications of the tools of molecular biology, analysis of these defects if now within reach.