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M Levin

Publications and source records attributed to M Levin.

At least 91 records · Page 5Linked to original sources
PubMed1998

Evolutionary conservation of mechanisms upstream of asymmetric Nodal expression: reconciling chick and Xenopus.

Recent experiments have suggested a pathway of genes that regulate left-right asymmetry in vertebrate embryogenesis. The most downstream member of this cascade is nodal (XNR-1 in frogs), which is expressed in the left-side lateral mesoderm. Previous work in the chick [Levin, 1998] suggests that an inductive interaction by Shh (Sonic hedgehog) present at the midline was needed for the left-sided expression of nodal, which by default would not be expressed. Interestingly, it has been reported [Lohr et al., 1997] that in Xenopus, right-side mesoderm that is explanted at st. 15 and allowed to develop in culture, goes on to express nodal, suggesting that lateral mesoderm expresses this gene by default and that a repression of nodal by the midline is needed to achieve asymmetry. Such a contradiction raises interesting questions about the degree of conservation of the mechanisms upstream of nodal asymmetry and, in general, about the differences in the LR pathway among species. Thus we examined this issue directly. We show that in the chick, as in the frog, explanted mesoderm from both sides does, indeed, go on to express nodal, including both the medial and lateral expression domains. Ectopic nodal expression in the medial domain on the right side is not sufficient to induce an ectopic lateral domain. We also show that explanted lateral tissue regenerates node/notochord structures exhibiting Shh expression. Furthermore, we show that Xenopus explants done at st. 15 also regenerate notochord by the stage at which XNR-1 would be expressed. Thus explants are not isolated from the influence of the midline. In contrast to the midline repressor model previously suggested [Lohr et al., 1997] to explain the presence of nodal expression in explants, we propose that the expression is due to induction by signals secreted by regenerating node and notochord tissue (Shh in the chick). Thus our results are consistent with Shh being necessary for nodal induction in both species, and we provide an explanation for both sets of data in terms of a single conserved mechanism upstream of nodal expression.

Animals↗
PubMed1998

Left-right asymmetry and the chick embryo.

Left-right (LR) asymmetry provides a fascinating example of the patterning of a major body axis during embryonic development. The chick embryo was the first system in which a molecular basis for left-right patterning was characterized, revealing that molecules known to play a role in other aspects of embryogenesis likewise are involved in the establishment of left-right asymmetry. The chick has been instrumental in the identification of a pathway of genes which regulate the sidedness of major body organs, as well as providing a basis for understanding laterality disturbances in twins. This review summarizes the advances in LR asymmetry which have been made in the chick system within the context of laterality research in general.

Animals↗
PubMed1998

Blood pressure and diurnal variation in sodium, potassium, and water excretion.

The objective of this study was to examine associations of blood pressure (BP) with ratios of overnight to 24-h urinary excretion of sodium, potassium, and water. Each of 125 men 27-64 years of age, not taking diuretics, had BP measured during the day on a Monday. Beginning Monday evening, each participant provided three carefully timed 24-h urine collections, divided into daytime and overnight (bedtime to awakening) specimens. Proportion of total 24-h excretion of sodium, potassium, and water in the overnight specimen, standardised for creatinine excretion, was determined for each 24-h period. Associations of systolic and diastolic BP (SBP/DBP) with these proportions were examined with control for age, body mass index, alcohol intake, and heart rate. Mean BP was 116/71 mm Hg; 15 men were on non-diuretic anti-hypertensive therapy. Mean 24-h urinary excretion was 168 mmol for sodium, 68 mmol for potassium, and 16 mmol for creatinine. Mean overnight to 24-h proportions averaged over the 3 days were 30.7% for sodium, 22.0% for potassium, 32.1% for urinary volume, and 33.2% for creatinine. Partial correlations of SBP and DBP with the 3-day averages were 0.257 (P < 0.01) and 0.210 (P < 0.05) for sodium; 0.223 (P < 0.05) and 0.222 (P < 0.05) for potassium; 0.127 and 0.091 for urinary volume; and -0.033 and 0.014 for creatinine. Correlations for sodium proportions were larger for the first 24-h period, compared to the second or third 24-h period. These results indicate that higher BP was associated with a relatively greater proportion of sodium and potassium excretion at night. Further work is needed to clarify temporal sequence, ie, whether a relatively greater sodium and potassium excretion at night is a risk factor for higher BP (eg, via renal mechanisms), or whether higher BP results in relatively greater sodium and potassium excretion at night, or both.

Adult↗
PubMed1998

Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens.

Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2beta. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.

Amino Acid Sequence↗
PubMed1998

Kawasaki disease thirty years on.

This year marks the 30th anniversary of the first description of Kawasaki disease. The disease has emerged as an important cause of acquired heart disease in children. The cause of Kawasaki disease remains unknown and this presents many problems in the diagnosis and management of the disease. This paper reviews recent publications on the pathogenesis, diagnosis, and the short- and long-term management of Kawasaki disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Avoidable deficiencies in the delivery of health care to children with meningococcal disease.

OBJECTIVES: It is apparent that delays and inadequate or inappropriate management occur frequently and may contribute to the continued high mortality seen in meningococcal disease. An attempt has been made to define the major sources of delay or inappropriate treatment. METHODS: A prospective, descriptive study of children with meningococcal disease referred to a tertiary centre paediatric intensive care and infectious disease unit. Definitions of optimal care were established at three stages: parental; general practitioner (GP)/accident and emergency (A&E) department; and hospital. Duration of symptoms and management were recorded from direct questioning of parents and carers, and from hospital records. RESULTS: 54 consecutive children with meningococcal disease were recruited to the study. Delayed parental recognition occurred in 16 children. GPs correctly diagnosed 19 of 35 children. Delay of 2.5-21 hours occurred in those who were incorrectly diagnosed. Two of 15 children who presented to the A&E department with specific features were incorrectly diagnosed. Hospital treatment was suboptimal in 71%. Shock was not recognised or treated in 50%, 20% of children had unnecessary lumbar punctures. Time from illness onset to treatment was longer in fatal disease (median 18.3, range 8-24 hours), compared with survivors (median 12, range 2-48 hours; p < 0.01, Mann-Whitney U test). CONCLUSION: Suboptimal treatment in meningococcal disease is due to failure of parents, GPs, and hospital doctors to recognise specific features of the illness. Improvement by public education and better training of clinicians in recognition, resuscitation, and stabilisation of seriously ill children.

Adolescent↗
PubMed1998

Acute oliguric renal failure associated with unilateral renal embolism: a successful treatment with iloprost.

A 66-year-old woman presented with acute-onset rapid atrial fibrillation and right upper quadrant pain which had appeared 24 h prior to admission. The patient also manifested acute oliguric renal failure (serum creatinine 6.9 mg/dl). Selective renal angiography revealed total occlusion of the right renal artery with normal visualization of the left kidney vasculature. The patient was treated with intra-arterial urokinase and intravenous heparin, with no response. Intravenous administration of the prostacyclin analogue, iloprost, resulted in rapid resolution (within hours) of the oliguric acute renal failure, in spite of the continuing presence of a nonfunctioning right kidney. We conclude that the etiology of the acute renal insult in this patient is probably related to unilateral renal arterial embolization accompanied by arterial spasm of the unaffected kidney. The contralateral vasospasm can be reversed by iloprost, which then leads to a rapid recovery from acute renal failure. We are unaware of prior reports documenting the beneficial effect of iloprost in a clinical setting as described here.

Acute Kidney Injury↗
PubMed1998

CSF and MRI findings in patients with acute herpes zoster.

OBJECTIVE: To explore MRI and CSF findings in patients with herpes zoster (HZ) and to correlate the findings with clinical manifestations of the disease. METHODS: Fifty immunocompetent patients (mean age, 59 years; range, 17 to 84 years) with HZ of fewer than 18 days duration participated. None had clinical signs of meningeal irritation, encephalitis, or myelitis. In 42 patients (84%), the symptoms constituted pain and rash only. Six patients (12%) had motor paresis, and three patients (6%) had ocular complications. One to three CSF samples were obtained from 46 patients (the first sampling taken 1 to 18 days from onset of rash), and 16 patients (all with either trigeminal or cervical HZ) underwent MRI of the brain. The clinical follow-up continued at least 3 months. RESULTS: CSF was abnormal in 28/46 patients (61%): pleocytosis (range, 5 to 1,440 microL) was detected in 21, elevated protein concentration in 12, varicella zoster virus (VZV) DNA in 10, and immunoglobulin G antibody to VZV in 10. These changes were more common in patients with acute complications, although they did not predict development of postherpetic neuralgia (PHN). In 9/16 patients (56%), MRI lesions attributable to HZ were seen in the brainstem and cervical cord. At 3 months, 5/9 patients (56%) with abnormal MRI had PHN, whereas none of the 7 patients with no HZ-related lesions on MRI had any remaining pain. CONCLUSIONS: Subclinical extension of viral inflammation into the CNS occurs commonly in HZ. This finding may have implications for treatment of HZ and prevention of various associated complications.

Acute Disease↗
PubMed1998

A comparative analysis of integrating visual representations with haptic displays.

As further advances in visual display technologies and force feedback devices are integrated in virtual systems, questions remain: What level of reality does the system provide to the user? Is the environment convincing enough to engage the user and to maximize transfer? Are the visual and haptic displays fully integrated to provide seamless operation in the simulated environment? Does the system provide not only the ability to navigate through a simulated environment, but also realistic interaction with instrumentation and structures? We report on our advances in developing a virtual simulation system for training in functional endoscopic sinus surgery (FESS). Specifically, we will present work on subject trials exploring the realism provided by integrated visual and haptic displays, and compare and contrast surface vs. volume representation for presenting realistic models of the anatomy for surgical interaction.

Computer Simulation↗
PubMed1998

Review and consideration of coagulopathies.

Blood components bring nutrients to the tissues, remove wastes, provide defenses against microorganisms and foreign bodies, and retain sufficient fluidity to keep the system functioning properly. Coagulation factors are also present in the blood as part of a sensitive system that stems the flow of blood from a wound and maintains homeostasis. These factors include anuclear platelets that originate from megakaryocytes in the bone marrow, as well as soluble factors in precursor form, and calcium ion. Faults in single or multiple parts of this system, which can be determined in the patient's history, may result in bleeding problems that may be clinically relevant. Clarification of coagulation defects requires cooperation with a hematologist before medication that affects the coagulation system is prescribed or before any procedures that may result in bleeding are undertaken.

Blood Coagulation Disorders↗
PubMed1998

The roles of activin and follistatin signaling in chick gastrulation.

Activin, a TGF-beta family member, and follistatin, an activin antagonist, encode signaling proteins which have been implicated in fundamental events in early vertebrate embryogenesis, such as mesoderm and neural tissue induction, and axial patterning. In this study I examine the roles of activin and follistatin in gastrulation in the chick. Activin betaB is found to be expressed at the base of the primitive streak prior to its formation, consistent with a role in streak induction. Follistatin has a more complex and dynamic expression in Hensen's node, and exhibits a left-right (LR) asymmetry. Antagonizing endogenous activin by ectopic application of follistatin protein causes the partial dissolution of the primitive streak and node, both morphologically and as assayed by loss of expression of molecular markers. This suggests that activin is necessary for the maintenance of streak morphology, and that follistatin may be involved in termination of the anterior progress of streak growth or in suppression of supernumerary streaks. Cell ingression through the node following follistatin application is normal, suggesting that it does not depend on the pit-like morphology of the wild-type node. Finally, follistatin temporally extends the asymmetric pattern of expression of HNF3-beta, this, as well as the stronger right-sided expression of follistatin, suggests a possible role in LR patterning.

Activins↗