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Biomedical subjects

D David

Publications and source records attributed to D David.

At least 19 recordsLinked to original sources
PubMed1999

Psychotic symptoms in combat-related posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is known often to be comorbid with other anxiety, mood, and substance use disorders. Psychotic symptoms have also been noted in PTSD and have been reported to be more common in Hispanic veterans. However, the occurrence of psychotic symptoms, including the degree to which they are accounted for by comorbid disorders, have received limited systematic investigation. Our study objectives were to assess psychotic symptoms according to DSM-III-R criteria in patients with a primary diagnosis of combat-related PTSD and determine the associations of those symptoms with psychiatric comorbidity and ethnicity. METHOD: Fifty-three male combat veterans consecutively admitted to a PTSD rehabilitation unit were assessed for psychotic symptoms and Axis I disorders. Ninety-one percent were Vietnam veterans; 72% were white, 17% were Hispanic, and 11% were black. Associations between psychotic symptoms and comorbid depression, substance use disorders, and minority status were compared by chi-square analyses; associations between psychotic symptoms and both PTSD and dissociative symptom severity were compared by t test analysis. RESULTS: Forty percent of patients reported a psychotic symptom or symptoms in the preceding 6 months. These symptoms featured auditory hallucinations in all but 1 case. The psychotic symptoms typically reflected combat-themes and guilt, were nonbizarre, and were not usually associated with formal thought disorder or flat or inappropriate affect. Psychotic symptoms were significantly associated with current major depression (p < .02), but not with alcohol or drug abuse or with self-rated PTSD and dissociation severity. Psychotic symptoms and current major depression were more common in minority (black and Hispanic) than white veterans (p < .002). CONCLUSION: Psychotic symptoms can be a feature of combat-related PTSD and appear to be associated with major depression. The association with minority status may be a function of comorbidity.

Adult↗
PubMed1998

Involvement of long chain fatty acid elongation in the trafficking of secretory vesicles in yeast.

Members of the synaptobrevin/VAMP family of v-SNAREs are thought to be essential for vesicle docking and exocytosis in both lower and higher eukaryotes. Here, we describe yeast mutants that appear to bypass the known v-SNARE requirement in secretion. Recessive mutations in either VBM1 or VBM2, which encode related ER-localized membrane proteins, allow yeast to grow normally and secrete in the absence of Snc v-SNAREs. These mutants show selective alterations in protein transport, resulting in the differential trafficking and secretion of certain protein cargo. Yet, processing of the vacuolar marker, carboxypeptidase Y, and the secreted protein, invertase, appear normal in these mutants indicating that general protein trafficking early in the pathway is unaffected. Interestingly, VBM1 and VBM2 are allelic to ELO3 and ELO2, two genes that have been shown recently to mediate the elongation of very long chain fatty acids and subsequent ceramide and inositol sphingolipid synthesis. Thus, the v-SNARE requirement in constitutive exocytosis is abrogated by mutations in early components of the secretory pathway that act at the level of lipid synthesis to affect the ability of secretory vesicles to sort and deliver protein cargo.

Alleles↗
PubMed1998

Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy.

The interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system is the main regulatory determinant of T cell reactivity. Although it is well known that IL-2 secretion is impaired during HIV infection, up to now IL-2R expression has not been extensively studied in HIV-infected patients despite the use of IL-2 in clinical therapy trials. We show here that IL-2R expression in HIV patients with high viral load (group 1 in the study) is greatly enhanced on B lymphocytes, CD8 T lymphocytes, and monocytes, but not on CD4 T lymphocytes, compared with noninfected individuals. Paradoxically, this modified IL-2R expression does not lead to increased IL-2 responsiveness, except for B lymphocytes. In patients receiving triple combination therapy (TCT, two reverse transcriptase inhibitors and one protease inhibitor) that has triggered a drastic reduction in plasma viral load and an increase in CD4 counts (group 2 patients), IL-2R expression is significantly lower than in group 1 patients. Moreover, cells involved in cellular immunity and CD4 T lymphocytes have the capacity to respond to IL-2 after TCT. These results allow us to anticipate a beneficial role of IL-2 immunotherapy in combination with TCT.

B-Lymphocytes↗
PubMed1998

Further analysis of interleukin-2 receptor subunit expression on the different human peripheral blood mononuclear cell subsets.

We have investigated the expression of the three components of the interleukin-2 receptor (IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma) on the surface of the various peripheral blood mononuclear cell (PBMC) subsets by flow cytometry analysis. The PBMC were immediately isolated (ficoll) from blood collected on heparin as anticoagulant. The three IL-2R components are absent or only marginally detectable on CD4 T lymphocytes. No expression of the IL-2R chains is found for the B lymphocytes. In most donors, the three chains are not detectable on CD8 T lymphocytes, but for a few of them, IL-2Rbeta or IL-2Rgamma are clearly expressed. CD56 high (IL-2Ralpha+) and CD56 low (IL-2Ralpha-) natural killer (NK) cells express IL-2Rbeta, but not IL-2Rgamma. IL-2Rgamma is expressed by monocytes of all donors although with variable intensity. When blood is collected on other anticoagulants or when cells are isolated 1 day after collection, IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma are largely expressed on the surface of most PBMC. This observation provides a possible explanation for divergent data previously reported on IL-2R expression. Finally, we show that IL-2Rgamma, which is not detectable on the cell surface of lymphocytes, is nevertheless expressed and stored as an intracellular component. This result is in agreement with the constitutive expression of the IL-2Rgamma gene and suggests a specific regulatory mechanism for IL-2Rgamma membrane translocation.

Anticoagulants↗
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↗