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Biomedical subjects

D David

Publications and source records attributed to D David.

At least 55 records · Page 3Linked to original sources
PubMed1998

Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging.

OBJECTIVES: This study sought to evaluate expression of adhesion molecules on neutrophils and monocytes throughout the acute phase of myocardial infarction. BACKGROUND: Neutrophil and monocyte counts increase within days from onset of acute myocardial infarction. Because leukocytes are recruited to the involved myocardial region, we postulated that these activated cells would display an increased expression of adhesion molecules necessary for effective endothelial transmigration. METHODS: We measured the expression of neutrophil and monocyte lymphocyte function associated antigen-1 (LFA-1), Mac-1, very late after activation antigen-4 (VLA-4) and intercellular adhesion molecule-1 (ICAM-1) by flow cytometry throughout the acute phase of acute myocardial infarction in 25 patients and 10 age-matched control subjects. RESULTS: Expression of Mac-1 on neutrophils increased significantly, whereas no expression of VLA-4 and ICAM-1 was detected. The expression of LFA-1, Mac-1, VLA-4 and ICAM-1 on the monocyte cell membrane in patients with an acute myocardial infarction was increased compared with that in control subjects by 22% (on day 7), 67%, 13% and 44% (all on day 4), respectively (all p < 0.001). Elevated density of monocyte-specific CD14 in the AMI versus the control group was also shown (30%, p < 0.001). CONCLUSIONS: Increased expression of neutrophil and monocyte adhesion molecules may contribute to their adhesion to endothelium in the ischemic territory. This adhesion could feasibly precipitate vasoconstriction or add a local thrombotic effect due to tissue factor expression secondary to Mac-1 engagement. In addition, the manifestation of increased density of LFA-1 and Mac-1 by activated leukocytes with monocytes also expressing ICAM-1 suggests that leukocytes may form microaggregates that could cause microvascular plugging. This mechanism may facilitate the occurrence of the "no-reflow" phenomenon or slow coronary filling after acute myocardial infarction.

Aged↗
PubMed1998

On proteins of the microsporidian invasive apparatus: complete sequence of a polar tube protein of Encephalitozoon cuniculi.

The microsporidian Encephalitozoon cuniculi is an obligate intracellular parasite that can cause opportunistic infections in AIDS patients. Spore invasion of host cells involves extrusion of a polar tube. After immunocytochemical identification of several polar tube proteins (PTPs) in E. cuniculi, a major PTP was isolated from two-dimensional gels and two peptide fragments were sequenced. The complete nucleotide sequence of the corresponding gene was obtained using a combination of PCR amplification and cloning techniques. The gene exists as a single copy per haploid genome and encodes an acidic proline-rich protein, with a deduced molecular mass of 37 kDa, that contains four tandemly arranged 26-amino-acid repeats. An N-terminal region of 22 residues represents a cleaved signal peptide, probably involved in the targeting of the PTP. No similarity with known proteins has been found. The protein was expressed in Escherichia coli, purified and injected into mice. The antisera reacted specifically with the polar tube in indirect immunofluorescence assays and electron microscope immunocytochemistry. Further identification of conserved and variable PTP structural motifs should be useful for diagnostic purposes and new therapeutic strategies.

Amino Acid Sequence↗
PubMed1998

New Q waves do not always a new infarct spell: right bundle branch block-dependent Q waves simulating infarct extension.

We present the electrocardiograms of three patients, representative of 14, with acute anterior wall infarction in whom, in contrast to current understanding, the appearance of right bundle branch block was associated with a shift of the initial vector of depolarization that resulted in 'new' Q waves in V1-V2 that mimicked extension of necrosis. This little-known electrocardiographic phenomenon should be kept in mind when consideration is given to attempts at reperfusion.

Aged↗
PubMed1998

Synthesis of lipopeptides using hydrazone chemical ligation.

In this paper we report that a hydrazinopeptide synthesized using solid-phase N-electrophilic amination with N-Boc-3-(4-cyanophenyl)oxaziridine reacted with a lipophilic peptide aldehyde to give the corresponding hydrazone plus an unexpected 1,3,4-oxadiazolidinopeptide containing two peptide aldehyde units. This methodology allows the synthesis of large lipopeptides.

Amination↗
PubMed1998

Effects of a selective A1-adenosine receptor agonist on heart rate and heart rate variability during permanent atrial fibrillation.

BACKGROUND: Mean heart rate and irregularity of the rate, i.e., heart rate variability (HRV), are two aspects of heart rate during atrial fibrillation (AF). An important goal of AF therapy is to control mean heart rate during exercise; the determinants of HRV during AF remain poorly known although its prognostic value has been established. OBJECTIVES: To investigate the effects of a stable, long-acting, selective A1-adenosine receptor agonist, SDZ WAG994, on heart rate during exercise and on HRV. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, parallel group study, patients with permanent AF performed a symptom-limited exercise test and underwent 24-hour ECG monitoring on day 1 during treatment with placebo, and on day 2 during treatment with either placebo or 2 mg SDZWAG994 orally. Changes in mean heart rate during exercise and changes in HRV indices between day 1 and day 2 were compared between the two groups. RESULTS: Thirty-two patients (64 +/- 8 years; 81% male; 25% in NYHA Class II; 38% with no structural heart disease) were included in the study. During active treatments, heart rate remained unchanged at rest and increased significantly during exercise. A significant daytime increase in short-term HRV indices (DpNN50 = 4.5% P = 0.01; DrMSSD = 6% P = 0.03; DSDNN Index = 6% P = 0.02) occurred during active treatment. CONCLUSIONS: Selective A1-adenosine receptor agonism with SDZ/WAG994 limits the increase in mean heart rate during exercise in patients with AF. In addition, this agonist selectively increases short-term HRV indices, suggesting that pNN50, rMSSD, and SDNN reflect vagal influences during AF.

Adenosine↗
PubMed1998

Peripheral monocytosis following acute myocardial infarction: incidence and its possible role as a bedside marker of the extent of cardiac injury.

Infiltration by mononuclear cells, mostly monocytes, into necrotic myocardial tissue can be detected beyond the 3rd day after the onset of infarction. These monocytes, mobilized by an unknown mechanism, initiate phagocytosis of necrotic tissue. We observed in patients having sustained an acute myocardial infarction (AMI) a significant increase in monocyte count 2-3 days following presentation, possibly representing peripheral recruitment of monocytes to the injured myocardium. To establish this observation, we prospectively documented monocyte and neutrophil counts throughout hospitalization in 186 consecutive patients (118 patients having sustained an AMI, 34 patients with angina, and 34 patients admitted for nonischemic reasons). Average monocyte count, which rose on the 2nd day and reached a peak on day 3, was significantly elevated in these patients compared with control subjects (p < 0.001). Neutrophil count exhibited a similar phase-shifted response. Peak monocyte count exceeded 800/mm3 (upper limit of normal range) in 69 (58%) of AMI patients but in only 3 of the 68 (4%) non-AMI patients, yielding a sensitivity and specificity of 58 and 95%, respectively, for the diagnosis of AMI by this criterion. A significant correlation between maximal creatine kinase (CK) representing the extent of myocardial necrosis and peak monocyte count was shown (r = 0.51, p < 0.0001). A correlation between CK and monocyte count sum of days 1-3 (r = 0.51, p < 0.001) was found in a substudy of 25 patients with AMI. Similarly, a correlation was shown with cardiac function score as evaluated by 2-dimensional echocardiography (p < 0.001 and p < 0. 008 for difference between CK sum and monocyte count sum of high and low echo score groups, respectively). Hence, the peak monocyte count recorded during the immediate postinfarction period provides a bedside marker of the extent of myocardial damage that is the preponderant prognostic determinant. If validated in future studies this phenomenon may have diagnostic and prognostic implications.

Adult↗
PubMed1997

Interleukin-2 receptor beta and gamma chain dysregulation during the inhibition of CD4 T cell activation by human immunodeficiency virus-1 gp120.

We have observed that CD4 T lymphocytes from human immunodeficiency virus (HIV)-infected patients marginally express interleukin-2 receptor (IL-2R) beta and IL-2R gamma chains which are essential for IL-2 signal transduction. To analyze this observation further, we studied the influence of gp120 on the cell surface expression of IL-2R beta and IL-2R gamma by purified CD4 lymphocytes in vitro. Cross-linking of the T cell receptors of these lymphocytes initiates entry into the cell cycle as measured by CD69 and CD71 cell surface expression and [3H]thymidine incorporation. It also induces the cell surface expression of IL-2R beta and IL-2R gamma. We have shown that treatment of the CD4 T lymphocytes with HIV-1 gp120 before anti-CD3 stimulation impedes cell cycle progression as measured by reduced CD71 expression and inhibition of [3H]thymidine incorporation. Furthermore, cell surface expression of IL-2R beta and IL-2R gamma subunits, which from the functional intermediate-affinity IL-2R, are significantly inhibited. More importantly, addition of exogenous IL-2 does not restore the proliferation of the CD4 T cells treated with gp120, suggesting that cells are anergic and/or that the remaining IL-2R are not functional. This is the first study of IL-2R beta and IL-2R gamma dysregulation in the context of HIV infection and shows that CD4 is also involved in IL-2R expression.

CD4-Positive T-Lymphocytes↗
PubMed1997

One or several semantic system(s)? Maybe none: evidence from a case study of modality and category-specific "semantic" impairment.

Following cerebral anoxia, EC a 55-year-old patient, exhibited a severe and clear-cut pattern of semantic impairments without general intellectual deficit or perceptual difficulty. EC demonstrated a complex neuropsychological picture including a massive visual agnosia and a complete lack of imagery, both of which involved all categories of objects (living and non living) and a category-specific word comprehension deficit limited to animal names. Findings are discussed in the light of the theoretical frameworks currently available in the area of neuropsychology. It is argued that neither the single nor the multiple view of semantics fully succeed in providing a satisfactory account of the data and a tentative interpretation of the whole pattern of impairment is proposed in the general framework of non abstractive conceptions of meaning.

Agnosia↗
PubMed1997

Assessment of a new self-rating scale for post-traumatic stress disorder.

BACKGROUND: In post-traumatic stress disorder (PTSD) there is a need for self-rating scales that are sensitive to treatment effects and have been tested in a broad range of trauma survivors. Separate measures of frequency and severity may also provide an advantage. METHODS: Three hundred and fifty-three men and women completed the Davidson Trauma Scale (DTS), a 17-item scale measuring each DSM-IV symptom of PTSD on 5-point frequency and severity scales. These subjects comprised war veterans, survivors of rape or hurricane and a mixed trauma group participating in a clinical trial. Other scales were included as validity checks as follows: Global ratings, SCL-90-R, Eysenck Scale, Impact of Event Scale and Structured Clinical Interview for DSM-III-R. RESULTS: The scale demonstrated good test-retest reliability (r = 0.86), internal consistency (r = 0.99). One main factor emerged for severity and a smaller one for intrusion. In PTSD diagnosed subjects, and the factor structure more closely resembled the traditional grouping of symptoms. Concurrent validity was obtained against the SCID, with a diagnostic accuracy of 83% at a DTS score of 40. Good convergent and divergent validity was obtained. The DTS showed predictive validity against response to treatment, as well as being sensitive to treatment effects. CONCLUSIONS: The DTS showed good reliability and validity, and offers promised as a scale which is particularly suited to assessing symptom severity, treatment outcome and in screening for the likely diagnosis of PTSD.

Adult↗
PubMed1997

Expression of the IL-2 receptor gamma subunit in resting human CD4 T lymphocytes: mRNA is constitutively transcribed and the protein stored as an intracellular component.

IL-2 receptor (IL-2R) is composed of three subunits named IL-2R alpha, IL-2R gamma. Here, we study the expression of the IL-2R gamma in highly purified, resting peripheral human CD4 T lymphocytes. We show by FACS analysis that the IL-2R gamma subunit is not detectable at the cell surface of peripheral CD4 T lymphocytes. This result has been verified after acid treatment of the cell surface and analysis with three specific anti-IL-2R gamma mAb. Using RT-PCR and intracellular FACS analysis, we demonstrate that IL-2R gamma is constitutively expressed at the mRNA level and the protein is stored as an intracellular component in resting CD4 T lymphocytes. IL-2R alpha and beta subunits are not detectable by these methods. In addition, we show that CD4 T cell remain insensitive to a variety of cytokines that share IL-2R gamma as a common subunit of their receptors (e.g. IL-2, IL-4, IL-7 and IL-15). The kinetics of cell surface expression of IL-2R gamma have been studied after activation of CD4 T lymphocytes and compared with induction of IL-2R alpha and IL-2R beta. Maximum expression of IL-2R gamma is observed after 2 days of stimulation, and remains constant and comparable to IL-2R beta up to day 5. We conclude from these studies that IL-2R gamma is translocated to the membrane only after T cell activation and induction of the IL-2R alpha and IL-2R beta genes. We hypothesize that in CD4 T cells a large intracellular pool of IL-2R gamma is present but that its cell surface translocation depends on the expression of alpha and/or beta chains specific for IL-2, IL-4, IL-7, IL-9 or IL-15.

CD4-Positive T-Lymphocytes↗
PubMed1997

Fronto-facio-nasal dysplasia.

Fronto-facio-nasal dysplasia is a rare cause of facial clefts. The syndrome is characterized by paramedian facial clefts which involve the nose and palpebral fissures resulting in defects of the alae nasi and blepharophimosis, lagophthalmos, and S-shaped palpebral fissures. In addition affected children have ocular malformations such as epibulbar dermoids and colobomata of the iris or optic disk and may have a posterior encephalocele; these features distinguish this condition from fronto-nasal dysplasia and early amnion rupture sequence. We describe a child with unilateral features. Unilateral craniofacial clefts are usually assumed to have a low recurrence risk. However, fronto-facio-nasal dysplasia is an autosomal recessive condition and must be considered in any child with paramedian facial clefts.

Abnormalities, Multiple↗
PubMed1997

Identification of three novel mutations in hereditary protein S deficiency.

We report the application of single-stranded conformation polymorphism (SSCP) analysis to the screening of 15 functionally important Protein S (PS) gene (PS alpha) regions (4.243 Kb) in 6 unrelated families with PS deficiencies. Direct sequencing of the fragments with altered migration patterns led to the identification of the corresponding molecular alterations. A missense mutation, G to T transversion at codon Cys598, and two different alterations, leading either to allelic exclusion, or premature termination of the protein translation: a G to A transition at codon Trp465 and a 1 nt (T) insertion at codon 265, were identified. The 1 nt insertion was observed in three apparently unrelated families but with a common geographical origin and the mutated allele was undetectable in platelet mRNAs of affected individuals. Family analysis confirmed, in each case, a perfect cosegregation of the mutation with the PS deficiency. We conclude that these alterations represent the causative mutations.

Alleles↗
PubMed1997

Possible pitfalls in the diagnosis of acute myocardial infarction in acutely psychotic patients.

The disturbed communication of the acutely psychotic patient with Emergency Room (ER) personnel can occasionally lead to a missed or delayed diagnosis of acute myocardial infarction. Conversely, miscommunication may also lead to a false positive diagnosis of acute myocardial ischemia or infarction. We describe a patient who failed to report lithium ingestion because of his psychotic and toxic state. Moreover, the patient was agitated and was treated with intramuscular haloperidol. These factors produced electrocardiographic changes due to the lithium and a rise in serum creatine kinase due to the intramuscular haloperidol, two criteria which could mislead an inexperienced observer to make the false diagnosis of acute myocardial ischemia or infarction. Lithium related electrocardiographic abnormalities and the causes for elevated creatine kinase isoenzymes are reviewed.

Acute Disease↗
PubMed1996

Comparison between metoprolol orally osmotic once daily and metoprolol two or three times daily in suppressing exercise-induced and daily myocardial ischemia.

Metoprolol is a widely used anti-ischemic drug with a relatively short half-life. To improve patient' compliance and to provide 24-hour coverage, its once daily ORally OSmotic (OROS) formulation was developed. In this multicenter double-blind study, the anti-ischemic effects of metoprolol OROS given once daily at doses of 190 and 285 mg were compared to the regular metoprolol formulation of 100 mg 2 or 3 times daily. Sixty-five patients with stable coronary artery disease, positive exercise tests, and ischemic episodes during daily activity as recorded by ambulatory electrocardiographic monitoring (AEM) were included. In the OROS group, 23 patients completed all 3 treatment periods. In these patients, the number of myocardial ischemic episodes decreased from 239 on placebo to 128 during the 190 mg/day dose (p < 0.0001) and to 86 during the 285 mg/day treatment period (p < 0.0001). In the metoprolol group, there were 204 episodes at baseline and 142 and 140 during the 100 mg 2 or 3 times daily treatment periods (p < 0.0001 for both). During exercise testing, time to 1-mm ST depression increased significantly in the OROS group from 6.3 minutes at baseline to 7.1 and 9.6 minutes during 190- and 285-mg treatment periods. In the metoprolol group, it increased from 5.8 to 7.2 and 8.2 minutes, respectively. Both formulations of metoprolol were well tolerated. The OROS formulation was highly effective in suppressing daily and exercise-induced ischemia and exerted its effect throughout the 24-hour period.

Administration, Oral↗
PubMed1996

Two separate functions are encoded by the carboxyl-terminal domains of the yeast cyclase-associated protein and its mammalian homologs. Dimerization and actin binding.

The yeast adenylyl cyclase-associated protein, CAP, was identified as a component of the RAS-activated cyclase complex. CAP consists of two functional domains separated by a proline-rich region. One domain, which localizes to the amino terminus, mediates RAS signaling through adenylyl cyclase, while a domain at the carboxyl terminus is involved in the regulation of cell growth and morphogenesis. Recently, the carboxyl terminus of yeast CAP was shown to sequester actin, but whether this function has been conserved, and is the sole function of this domain, is unclear. Here, we demonstrate that the carboxyl-terminal domains of CAP and CAP homologs have two separate functions. We show that carboxyl-terminals of both yeast CAP and a mammalian CAP homolog, MCH1, bind to actin. We also show that this domain contains a signal for dimerization, allowing both CAP and MCH1 to form homodimers and heterodimers. The properties of actin binding and dimerization are mediated by separate regions on the carboxyl terminus; the last 27 amino acids of CAP being critical for actin binding. Finally, we present evidence that links a segment of the proline-rich region of CAP to its localization in yeast. Together, these results suggest that all three domains of CAP proteins are functional.

Actins↗