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Biomedical subjects

J Zamorano

Publications and source records attributed to J Zamorano.

At least 19 recordsLinked to original sources
PubMed2002

Carney's syndrome: complex myxomas. Report of four cases and review of the literature.

Cardiac myxomas are rare tumors. They usually appear as a sporadic isolated condition in the left atrium of middle-aged women with no other coincidental pathology. Carney and others have described in young people a special complex group of cardiac myxomas associated to a distinctive complex pathology, giving identity to the "Syndrome Myxoma" or "Carney's Syndrome". Four additional cases of this syndrome, treated from 1977 to 1999 at the Hospital Clínico de la Universidad de Chile are presented here with a comprehensive review of the literature, accumulating 100 cases. The main features of our cases include the presence of malignant non cardiac tumors, a familial trend, follow-up of 23 years and an iterative recurrence in the elder case. To date all patients are tumor free. Reviewing the literature, patients with Carney's Syndrome were younger, with a mean age of 26 years and female predominance (62%). Cardiac myxomas affected the four chambers of the heart: 64% the left atrium; 44% the right atrium; 14% the left ventricle and 12% the right ventricle. They were multiple tumors in 41% and involved more than one chamber in 31%, being synchronous or metachronous. There was a marked familial trend (52%), a high incidence of recurrence (20%), with more than one occurring in half the cases. Extra-cardiac involvement consisted of: 68% pigmented skin lesions, 40% cutaneous myxomas, 37% adrenal cortical disease, 27% myxoid mammary fibroadenoma and 34% male patients with testes tumors. A low percentage had pituitary adenoma, melanotic schwannomas and thyroid disease. The diagnosis is made when two or more of these criteria are present. In agreement with these findings the four chambers of the heart should be examined at surgery for atypical myxoma locations, right atriotomy and combined superior-transseptal approach improve exposure of the cavities, careful screening of the first degree family members should be conducted, and closed short and long term follow up controls are important. Complex myxoma appears as a multi-systemic disorder, occasionally having an ominous prognosis and malignant potentiality, and is still undergoing investigation for better understanding and identification.

Adolescent↗
PubMed2002

Congenital quadricuspid aortic valve associated with congenital complete heart block.

Congenital quadricuspid aortic valve is very uncommon, and is often associated with other cardiac disorders, such as patent ductus, ventricular septal defect, pulmonary stenosis, mitral valve malformation, hypertrophic cardiomyopathy and coronary abnormalities. We report a patient with congenital quadricuspid aortic valve associated with congenital complete heart block. To our knowledge, this association has not been reported so far.

Adult↗
PubMed2002

Weak concordance between wall motion and microvasculature status after acute myocardial infarction: study with myocardial contrast echocardiography in real time with power modulation.

AIMS: The microvasculature damage after myocardial infarction has important implications. The hypothesis of the study was that wall motion abnormalities and microcirculation status do not necessarily match after myocardial infarction, and therefore the study of only myocardial wall motion could offer an incomplete evaluation in these patients. METHODS: Wall motion and myocardial perfusion assessed by contrast echocardiography were evaluated by two different blinded investigators in 29 patients with recent (<1 week) myocardial infarction. Myocardial perfusion was assessed in real-time using power modulation after Optison (1.5-3.0 ml) intravenous administration. RESULTS: One hundred and ninety-nine segments could be adequately evaluated. Of these, 54 (27%) were akinetic. Regarding contrast opacification, 134 segments (67%) had a normal perfusion, whereas the remaining 65 (33%) had an impaired (n=37, 19%) or absent (n= 28, 14.1%) perfusion. Concordance between presence of akinesia and abnormal contrast opacification was only moderate (kappa index 0.42) and agreement only occurred in 116 segments (58%). Fourteen per cent of normoquinetic segments had an impaired perfusion, whereas 35% of akinetic segments had a preserved perfusion. Correlation between the proportion of segments with akinesia and the proportion of segments with impaired perfusion was moderate (r=0.41), and there was no correlation between the proportion of segments with akinesia and the percentage of segments with absent perfusion. CONCLUSION: There is a weak association between regional systolic function and myocardial perfusion after myocardial infarction, as assessed by real-time contrast myocardial echocardiography using power modulation.

Aged↗
PubMed2001

Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation.

IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3' kinase in both resting and activated cells. By contrast, association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2 in B cell blasts. The pattern of IL-4-induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEK1 inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts. These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2001

NF-kappa B activation plays an important role in the IL-4-induced protection from apoptosis.

IL-4 alone protects cells from apoptosis by insulin receptor substrate (IRS)-dependent and -independent mechanisms. However, in vivo cells are typically exposed to a number of signals at the same time. To determine the contribution of co-stimulatory signals to the regulation of apoptosis by IL-4, we first analyzed whether tumor necrosis factor (TNF)-alpha, which has been shown to inhibit the activation of IRS-1 by insulin, could modify IL-4 signaling and protection from apoptosis. We found that TNF-alpha cooperates with IL-4 in protecting 32D cells from factor withdrawal-induced apoptosis. This effect was independent of the expression of IRS-1, indicating that this cooperation is via an alternative anti-apoptotic pathway. Moreover, TNF-alpha had no effect on the activation of IRS-1 induced by IL-4. IL-4 enhanced TNF-alpha-induced activation of the transcription factor NF-kappaB. Interestingly, pharmacologic inhibition of NF-kappaB activation or protein synthesis resulted in the induction of cell death that could not be inhibited by IL-4, suggesting that IL-4 cooperates with NF-kappaB to signal protection from apoptosis. Supporting this hypothesis, IL-4 also increased NF-kappaB activation induced by anti-CD3 antibodies in primary T cells and protected them from apoptosis induced by receptor engagement. However, IL-4 was not able to inhibit apoptosis induced by anti-CD3 in T lymphocytes isolated from transgenic mice expressing a dominant-negative form of IkappaBalpha that prevents NF-kappaB activation. Thus, in addition to the previously identified IRS-1 pathway, IL-4-induced protection from apoptosis may also be mediated through cooperation with the NF-kappaB family of transcription factors.

Adjuvants, Immunologic↗
PubMed2001

Doppler tissue imaging.

This paper try to give a general overview of the main areas of DTI clinical application, its main technical limitations, new directions still under investigation and some potential future developments of this emerging imaging technique. In this review article we pretend to discuss the main aspects of the new DTI method, its present "state of the art" and future perspectives of scientific and technical development.

Diastole↗
PubMed2001

[Complications in children with varicella in 4 hospitals in Santiago, Chile: clinical spectrum and estimation of direct costs].

BACKGROUND: The knowledge of varicella complications and their associated cost may help for a better evaluation of varicella immunization benefits. AIM: To determine frequency, type, outcome and affected population of varicella complications in children requiring hospitalization, and to estimate their direct costs. MATERIAL AND METHODS: Retrospective analysis of medical records of children admitted to four hospitals in Santiago, Chile, due to varicella complications between January 1997 and February 1999. Calculation of direct costs of hospitalizations in a sample of 30 patients. RESULTS: One hundred fifty four patients were identified, 74% were younger than 5 years old, only one was immunocompromised. Complications identified were skin and soft tissue infections in 63%, invasive infections in 25.3%, neurological in 7.1% and miscellaneous in 4.5%. Staphylococcus aureus and Group A beta-haemolytic Streptococcus (GABS) were predominantly isolated. S. aureus was the main agent identified in superficial infections and GABS in invasive infections (sterile sites). Two patients died due to invasive infections (streptococcal toxic shock and S. aureus septicaemia) and 11 required surgical procedures. The average cost per hospitalization was US$ 600 in public hospitals and US$ 1,800 in the private hospital. CONCLUSIONS: Varicella complications requiring hospitalization are due mainly to bacterial infections and they affect immunocompetent toddlers. These complications can be severe and even fatal.

Adolescent↗
PubMed2001

[Acute myocardial infarction caused by total occlusion of the left main coronary artery treated with percutaneous endoluminal revascularization. Clinical case].

We report a 43 years old female who developed an intense precordial pain and arterial hypotension. The patient was admitted to the emergency room in cardiogenic shock. An emergency angiography revealed a total occlusion of the left main coronary artery. An endoluminal coronary angioplasty with the placement of two stents was performed and coronary reperfusion TIMI III was achieved. The patient had a good evolution and one month later, a surgical revascularization was done, to avoid new occlusions. She was discharged in good conditions and in functional capacity I.

Adult↗
PubMed1999

Cutting edge: effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction.

A mutation in the human (hu) IL-4R alpha, Q576R, has been linked with allergy in humans. Increased sensitivity of patients cells with this mutation to IL-4 suggest that a Q576R change enhances IL-4 signaling. To directly test this hypothesis, we analyzed the ability of huIL-4R alpha cDNA bearing the Q576R and Y575F mutations to signal tyrosine phosphorylation, DNA-binding activity, proliferation, protection from apoptosis, and CD23 induction in response to huIL-4 in murine cells. Responses generated by the Q576R and Y575F mutants were similar to those of the wild-type receptor, using various concentrations of huIL-4 and times of stimulation. These results indicate that neither the Q576R nor the Y575F mutations have a significant direct effect on IL-4 signal transduction, and that hypersensitive induction of CD23 in cells derived from human allergy patients may be due to different and/or additional alterations in the IL-4 signaling pathway.

Amino Acid Substitution↗
PubMed1999

The IL-4 receptor: signaling mechanisms and biologic functions.

Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4R alpha chain and the common gamma chain (gamma c), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation.

Amino Acid Sequence↗
PubMed1998

Regulation of apoptosis by tyrosine-containing domains of IL-4R alpha: Y497 and Y713, but not the STAT6-docking tyrosines, signal protection from apoptosis.

IL-4 is a cytokine with important antiapoptotic activity. We have analyzed the role that tyrosine-containing domains within the cytoplasmic tail of IL-4R alpha play in IL-4-mediated protection from apoptosis. 32D cells expressing a wt huIL-4R alpha or one truncated at aa 557 were protected by huIL-4 from apoptosis while cells expressing a receptor truncated at aa 657 were not, suggesting that the carboxyl-terminal domain signals protection from apoptosis. However, changing Y713 within this region to phenylalanine had no effect. To analyze the contribution of tyrosine-containing domains independently, we transplanted regions of the huIL-4R alpha to a truncated form of the huIL-2R beta that could not signal protection from apoptosis. Transplantation of the huIL-4R alpha domains containing Y497 or Y713 partially prevented cell death and together signaled protection from apoptosis in response to IL-2 as well as the wt IL-2R beta. Mutation of Y497 and Y713 to phenylalanine inhibited protection. In contrast, transplantation of the domain containing the potential STAT6-docking tyrosines alone had no effect, yet it inhibited the protection mediated by the other domains. Although IL-4R alpha signals Shc and SH2-containing inositol phosphatase (SHIP) phosphorylation, we could not establish an association between their activation and protection from apoptosis. Taken together, this study suggests that the domains of the huIL-4R alpha containing Y497 and Y713 positively regulate protection from apoptosis while the domain containing the STAT6 docking sites suppresses this protection, and that additional signaling molecules other than insulin receptor substrate-1 (IRS1), Shc, or SHIP may be involved in antiapoptotic signaling.

Animals↗
PubMed1998

A role for the insulin-interleukin (IL)-4 receptor motif of the IL-4 receptor alpha-chain in regulating activation of the insulin receptor substrate 2 and signal transducer and activator of transcription 6 pathways. Analysis by mutagenesis.

The interleukin (IL)-4 receptor alpha-chain (IL-4Ralpha) contains a sequence motif (488PLVIAGNPAYRSFSD) termed the insulin IL-4 receptor motif (I4R motif). Mutation of the central Tyr497 to Phe blocks the tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1) and diminishes proliferation in response to IL-4. Recent data suggest that the I4R motif encodes binding sites for several protein tyrosine binding (PTB) domain-containing proteins such as IRS1 and Shc and potentially for the Src homology 2 domain of signal transducer and activator of transcription 6 (STAT6). To analyze the function of the I4R motif in regulating IL-4 signaling, we changed conserved residues upstream and downstream of the central Tyr to Ala in the human IL-4Ralpha. We analyzed the ability of these constructs to signal the tyrosine phosphorylation of IRS2 and STAT6, the induction of DNA binding activity, and CD23 induction in response to human IL-4 (huIL-4) in transfected M12.4.1 cells. Mutagenesis of residues downstream of Tyr497, such as Arg498 or Phe500, to Ala had no effect on any of these responses, suggesting that the I4R motif may not be important for functional Src homology 2 domain interactions. However, mutagenesis of Pro488 to Ala (P488A) greatly diminished the tyrosine phosphorylation of IRS2 and abolished tyrosine phosphorylation of STAT6, induction of DNA binding activity, and CD23 induction in response to huIL-4. By contrast, a P488G mutant signaled these responses to huIL-4. Mutagenesis of hydrophobic amino acids previously shown to contact the PTB domain of IRS1, Leu489 or Ile491, to Ala had only minimal effects on responses to huIL-4. However, changing both Leu498 and Ile491 to Ala greatly diminished the tyrosine phosphorylation of IRS2 and abolished STAT6 activation. Taken together, these results indicate the important role of the I4R motif in regulating IRS docking and suggest that I4R docking to a PTB domain-containing protein regulates activation of the STAT6 pathway.

Alanine↗