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Biomedical subjects

M C Johnson

Publications and source records attributed to M C Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Differential expression of vasoactive intestinal peptide receptors 1 and 2 (VIP-R1 and VIP-R2) mRNA in murine lymphocytes.

Vasoactive intestinal peptide (VIP), a neuropeptide present in the lymphoid microenvironment, modulates cytokine expression and affects T cell proliferation. Recent molecular studies identified two VIP receptors. VIP-R1 and VIP-R2, primarily in nonlymphoid cells. In this study, we investigate the expression of VIP-R1 and VIP-R2 mRNA in unstimulated and stimulated lymphocytes and thymocytes, and in various lymphocyte subpopulations. In contrast to VIP-R1 which is constitutively expressed, the expression of VIP-R2 is induced only following stimulation through the TCR-associated CD3 complex. Both CD4+ and CD8+ T cells express VIP-R1 and VIP-R2. Two T cell lines, EL-4.IL-2 and D10.G4.1 express exclusively VIP-R2. VIP induces the expression of the VIP-R2 gene in the absence of additional stimuli. Differential expression and regulation of the two VIP receptors in T lymphocytes suggests different physiological roles in mediating the immunomodulatory activities of VIP and related neuropeptides.

Animals↗
PubMed1996

Murine T-lymphocytes express vasoactive intestinal peptide receptor 1 (VIP-R1) mRNA.

Vasoactive intestinal peptide (VIP), a neuropeptide present in primary and secondary lymphoid organs has been previously reported to inhibit IL-2 and IL-4 production as well as the proliferation of mitogen- or antigen-stimulated T-cells. Binding studies suggested that the immunoregulatory effects of VIP are mediated through specific VIP-binding sites present on lymphocyte subpopulations. Here we report on the expression of VIP-R1 mRNA in various murine lymphocyte subpopulations. By using RT-PCR. RNase protection assay, cDNA cloning, and sequence analysis, we show that stimulated and unstimulated murine spleen cells, thymocytes. CD4+ and CD8+ T-cells express VIP-R1. The VIP-R1 fragment amplified from murine brain, thymocytes, spleen cells and CD4+ T-cells share identical nucleotide sequences, and a high degree of homology with the corresponding nonlymphoid rat and human VIP-R1 sequences. The expression of VIP-R1 in thymocytes and peripheral lymphocytes, and especially in the CD4+ T-cell subset supports the idea that VIP produced or released locally in the lymphoid microenvironment could directly affect cytokine production and proliferation of T-lymphocytes.

Animals↗
PubMed1996

Localization of insulin-like growth factor (IGF-I) and IGF-I receptor expression in human corpora lutea: role on estradiol secretion.

OBJECTIVE: To determine whether insulin-like growth factor (IGF-I) and its receptors are expressed by human corpus luteum (CL) and to establish the effect of IGF-I on E2 biosynthesis in human luteal cell cultures. DESIGN: Middle corpora lutea were obtained from women undergoing surgical sterilization. The tissue was frozen for binding and in situ studies or dispersed for cell cultures. SETTING: Procedures were performed at the San Borja-Arriarán Hospital, National Health Service, and Institute of Maternal and Child Research, Faculty of Medicine, University of Chile. PATIENTS: Twelve patients aged 30 to 40 years requesting surgical sterilization in our institution. The laparotomy was scheduled 6 to 8 days after ovulation. MAIN OUTCOME MEASURES: Expression of IGF-I and IGF-I receptor messenger RNAs (mRNAs) by in situ hybridization. Concentration of IGF-I receptor and binding characteristics. Production of E2 by luteal cells. RESULTS: The binding of IGF-I was detected in middle human CL membranes. In addition, this tissue expressed the mRNAs of IGF-I and its receptor. In culture, IGF-I caused a progressive increase on E2 production. CONCLUSION: These data suggest that the IGF-I system is present in middle human CL. The topographic distribution of IGF-I and its receptors and the ability of IGF-I to stimulate E2 secretion strongly suggest that IGF-I has a role as a paracrine or autocrine regulator of the human luteal function.

Adult↗
PubMed1996

The genetic basis of pediatric cardiovascular disease.

Congenital heart disease (CHD), cardiomyopathy, and vasculopathies are common causes of mortality and morbidity in pediatrics, including the perinatal period. This article reviews evidence that single gene defects cause many of the pediatric heart diseases. Vasculopathies discussed include Marfan's syndrome, supravalvar aortic stenosis and Williams' syndrome, Alagille's syndrome, and hereditary telangiectasia, the Osler-Weber-Rendu syndrome. Genetic causes of hypertrophic cardiomyopathy caused by sarcomeric protein mutations (beta-cardiac myosin heavy chain) and of dilated cardiomyopathy secondary to structural protein deficiencies (dystrophin) are presented. Defects in proteins essential for myocardial energy production such as oxidative phosphorylation proteins and fatty acid oxidation genes that cause cardiomyopathy or sudden death are described. Gene ablation models in mice, such as RXR alpha and homeobox gene knockouts, which result in cardiac phenotypes resembling human congenital heart disease, are described. Familial types of human CHD which are being investigated for genetic causes by positional cloning methods and known cytogenetic causes of CHD, including the CATCH-22 syndrome and monosomy at 22q11, are presented. General lessons and principles derived from these new and exciting discoveries in human cardiovascular development are surmised.

Animals↗
PubMed1995

Deletion within chromosome 22 is common in patients with absent pulmonary valve syndrome.

Interstitial deletions in chromosome 22 and features associated with CATCH-22 syndrome have been reported in patients with conotruncal congenital heart anomalies. Absent pulmonary valve syndrome is characterized by absent or rudimentary pulmonary valve cusps, absent ductus arteriosus, conoventricular septal defect, and massive dilation of the pulmonary arteries. Because absence of the ductus arteriosus is a key element in the pathogenesis of this syndrome and aortic arch malformations are frequently seen in patients with CATCH-22 syndrome, we hypothesized that patients with absent pulmonary valve syndrome would have a high incidence of deletions in the critical region of chromosome 22. Eight patients with absent pulmonary valve syndrome were studied. Metaphase preparations were examined with fluorescent in situ hybridization of the N25 (D22S75) probe to the critical region of chromosome 22q11.2. Deletions were detected in 6 of 8 patients. The presence of deletions in chromosome 22 in most of the patients we have examined with a diagnosis of absent pulmonary valve syndrome supports a specific genetic and embryologic mechanism involving the interaction of the neural crest and the primitive aortic arches as one cause of congenital absence of the pulmonary valve.

Chromosome Deletion↗
PubMed1995

Toward a molecular understanding of congenital heart disease.

BACKGROUND: This review discusses the incidence and importance of congenital heart disease (CHD), the reasons that investigation of causative mechanisms for human CHD has been slow, and the limitations of the multifactorial theory for the etiology of CHD. METHODS AND RESULTS: The molecular defects underlying three vasculopathies--Marfan's syndrome (fibrillin), supravalvar aortic stenosis, and Williams' syndrome (elastin)--and hereditary telangiectasia are presented to emphasize the role of microfibrils and extracellular matrix in the pathophysiology of these vascular defects. Animal models of CHD, including situs inversus, canine conotruncal malformations, and chick neural crest ablation, are examined to emphasize how such studies relate to human CHD, especially by pointing to single-gene defects for conotruncal malformations, candidate loci for situs inversus, and phenotypic variability caused by neural crest lesions. The crucial role of cardiac transcription factors in heart morphogenesis is emphasized by review of gene knockout studies of these factors, which cause fetal death secondary to heart maldevelopment. Several lines of evidence demonstrating genetic etiologies of human CHD are also presented, including the mapping of familial atrial septal defects, to prove that one anatomic type of CHD may be due to single-gene defects at different loci. Review of atrioventricular canal, both secondary to trisomy 21 and as an autosomal-dominant familial defect, reiterates this conclusion. The evidence that monosomy on chromosome 22 causes multiple types of CHD, including aortic arch and conotruncal defects as part of the CATCH-22 syndrome, is presented, with results supporting the idea that deletions at this site alone may cause 5% of surgically treated CHD. CONCLUSIONS: We conclude that (1) human CHD is frequently due to single-gene defects and that even sporadic defects may arise from a single-gene abnormality; (2) a common genetic defect may cause several apparently different forms of CHD; (3) elucidation of the genetic basis of CHD provides clues to normal cardiovascular developmental biology; (4) the same cardiac malformation can be caused by mutant genes at different loci; and (5) interactions of clinical investigators (cardiologists and cardiothoracic surgeons) with basic scientists should allow more rapid progress in defining the genetic basis of CHD.

Animals↗
PubMed1995

Delayed intrapleural migration of a ventriculoperitoneal shunt.

We report a case of delayed intrapleural migration of the peritoneal catheter of a ventriculoperitoneal shunt. This is an unusual but life-threatening complication of peritoneal shunting for the treatment of hydrocephalus. A method of treatment and abbreviated review of shunt complications is included.

Cerebral Ventricles↗
PubMed1995

Anomalous origin of the right pulmonary artery from the aorta and CATCH 22 syndrome.

We report repair of anomalous origin of the right pulmonary artery from the ascending aorta in a premature neonate with a deletion in the CATCH 22 region of chromosome 22. This case suggests that the pathogenesis of anomalous origin of the right pulmonary artery involves genetically determined abnormalities of the neural crest. Repair of this defect in a premature infant can prevent the development of severe pulmonary vascular disease.

Aorta↗
PubMed1995

Activation of human endothelial cells by viable or heat-killed gram-negative bacteria requires soluble CD14.

In response to bacterial lipopolysaccharides (LPS; endotoxin), endothelial cells are converted to an activation phenotype expressing both proinflammatory and procoagulant properties that include the induction of leukocyte adhesion molecules and tissue factor expression. LPS-induced endothelial cell activation requires a soluble form of the monocyte LPS receptor, sCD14. We evaluated the capacity of multiple strains of gram-negative and gram-positive bacteria to induce endothelial E-selectin and tissue factor expression through sCD14-dependent pathways with cultured human umbilical vein endothelial cells (HUVE). Both viable and heat-killed gram-negative bacteria (Bacteroides fragilis, Enterobacter cloacae, Haemophilus influenzae, and Klebsiella pneumoniae) but not viable or heat-killed gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae) induced prominent E-selectin surface expression detected by enzyme-linked immunosorbent assay. Tissue factor activity on HUVE, indicated by factor X activation, was induced in response to gram-negative bacteria but not in response to gram-positive bacteria. Gram-negative bacteria induced transcriptional activation in HUVE, indicated by the appearance of E-selectin-specific mRNA and by the demonstration of activation of NF-kappa B, a trans-activating factor necessary for E-selectin and tissue factor gene transcription. In contrast, neither E-selectin mRNA nor activation of NF-kappa B was detected in HUVE treated with gram-positive bacteria. Endothelial cell activation by gram-negative bacteria in each of these assays was inhibited with a monoclonal antibody (60bd) against CD14. Furthermore, CHO-K1 cells, transfected with human recombinant CD14, responded to all strains of gram-negative bacteria (viable or heat killed), indicated by CHO-K1 NF-kappa B activation. We conclude that gram-negative bacteria induce endothelial cell activation through a common sCD14-dependent pathway.

Animals↗
PubMed1995

Meningiomatosis cranii in childhood: a case report.

Tumors of the meninges in infancy and childhood are unusual; childhood meningiomatosis is thought to be more common in neurocutaneous diseases. The case presented here is one of multiple recurrent and de novo benign meningeal tumors in a child who has no other signs or symptoms of a neurocutaneous syndrome.

Cerebral Cortex↗
PubMed1995

The genetic basis of paediatric heart disease.

This review focuses on recent advances in understanding the pathogenesis of paediatric heart disease and on the known single gene defects responsible for these diseases. Many paediatric cardiovascular diseases are heritable, have clinical manifestations in adult ages, are frequent in occurrence, and can have significant social and economic impact. Specific gene defects have been identified for hypertrophic and dilated cardiomyopathies, mitochondrial cardiomyopathies, Marfan's syndrome, Williams syndrome, familial supravalvar aortic stenosis, CATCH-22 syndrome and atrioventricular canal. Limited phenotypic response of the developing heart accounts for similar cardiovascular defects from differing gene defects. Although environmental factors affect expression of many of these genes, it is clear that single gene defects can be identified which cause paediatric cardiovascular disease. Interactions among cardiologists, cardiovascular surgeons, geneticists and basic scientists are vitally important in understanding the genetic basis of paediatric heart disease, its diagnosis and its therapy.

Abnormalities, Multiple↗
PubMed1994

Cloning of two rabbit GRO homologues and their expression in alveolar macrophages.

We cloned two rabbit GRO homologue cDNAs from a lipopolysaccharide-stimulated rabbit alveolar macrophage (AM) cDNA library. One cDNA contains the complete coding sequence for a new mature GRO protein, RabGRO, which shares 68, 78 and 70% amino-acid identity with human GRO-alpha, -beta and -gamma, respectively. The other cDNA contains previously unreported sequence encoding a second GRO protein, rabbit permeability factor 2. The two Rab GRO proteins share 93% identity. Northern analysis shows that Rab AM GRO expression is rapidly induced by lipopolysaccharide. These findings suggest that GRO chemokines may be important in the pulmonary inflammation that occurs with septic lung injury.

Amino Acid Sequence↗
PubMed1994

Comparison of ventricular mass and function in early versus late repair of coarctation of the aorta.

Left ventricular (LV) mass and function in 11 patients (group I) with coarctation of the aorta repaired at a mean age of 35 days were compared with that of 14 patients (group II) who underwent repair at a mean age of 8 years. Each group was compared to age- and sex-matched normal control subjects. All patients were normotensive and had resting arm-leg peak systolic blood pressure gradients < 20 mm Hg. Quantitative M-mode echocardiography was used to determine LV mass index and systolic performance. Magnetic resonance imaging was performed to assess residual narrowing of the descending aorta. LV mass index was increased in both groups when compared with control subjects (group I p = 0.01; group II p = 0.007). Whereas systolic performance in group I was similar to its control group, group II patients had enhanced LV systolic performance as measured by shortening fraction (p = 0.007). Multiple regression analysis of combined group I and II patients demonstrated a significant positive correlation of residual aortic narrowing with LV mass index (p = 0.01). Thus, LV mass remains increased in normotensive patients without major blood pressure gradients after repair of coarctation of the aorta in infancy or childhood. Small degrees of residual aortic narrowing were associated with increased postoperative LV mass regardless of the age at repair.

Adolescent↗