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Biomedical subjects

D David

Publications and source records attributed to D David.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

6-hydroxydopamine induces the loss of the dopaminergic phenotype in substantia nigra neurons of the rat. A possible mechanism for restoration of the nigrostriatal circuit mediated by glial cell line-derived neurotrophic factor.

Intraparenchymal injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle in rats destroys the dopaminergic neurons in the pars compacta of the substantia nigra. In other transmitter systems it has been found that axotomy or neurotoxin exposure produces an initial loss of neurotransmitter phenotype, with cell death occurring over a much slower time course. To determine whether this also occurs in dopamine neurons after 6-OHDA, two approaches were utilized. First, the effect of injections of 6-OHDA into the medial forebrain bundle on nigral dopaminergic neurons was studied using combined fluorogold and immunocytochemical labeling. Four weeks after the 6-OHDA injection, there was an 85% reduction in the number of tyrosine hydroxylase (TH)-immunoreactive cells on the lesioned side. In contrast, there was only a 50% reduction in the number of fluorogold-labeled cells on the lesioned side. Second, the time course of the rescue of dopaminergic neurons after 6-OHDA by glial cell line-derived neurotrophic factor (GDNF) was determined using TH immunocytochemistry. Greater numbers of dopamine neurons were rescued 9 weeks after GDNF, compared with counts made 5 weeks after GDNF. Taken together, these results suggest loss of dopaminergic phenotype is greater than cell loss following 6-OHDA injections, and that GDNF restores the phenotype of affected cells.

Animals↗
PubMed1996

Psychiatric morbidity following Hurricane Andrew.

The nature of psychiatric morbidity in previously non-ill subjects from the area most affected by Hurricane Andrew was investigated at 6-12 months posthurricane. Preliminary associations of morbidity with personal and event-related risk factors were also determined. Fifty one percent (31/61) met criteria for a new-onset disorder, including posttraumatic stress disorder (PTSD) in 36%, major depression (MD) in 30%, and other anxiety disorders in 20%. Thirty four subjects (56%) had significant symptoms persisting beyond 6 months. Having sustained "severe damage" was the risk factor most strongly associated with outcome. Our data underscore the range of psychiatric morbidity related to a natural disaster, and suggest a relationship to chronic stressors.

Adult↗
PubMed1996

The effects of lidocaine on cardiac parasympathetic control in normal subjects and in subjects after myocardial infarction.

It has been widely accepted that lidocaine has little or no effect on the autonomic nervous system. However, we have previously shown that in dogs with vagally induced atrial fibrillation, lidocaine has a pronounced parasympatholytic effect. To study the possible effect of lidocaine on autonomic cardiac control in humans, we performed spectral analysis of heart rate fluctuations in 19 healthy volunteers, who received an i.v. bolus of lidocaine (1.4 mg/kg), as well as in 13 patients suffering from acute inferior myocardial infarction (IMI) and 13 patients suffering from acute anterior myocardial infarction (AMI), who received therapeutic doses of i.v. lidocaine infusion (4 mg/min). Heart rate variability and respiratory pattern were monitored according to a predetermined protocol, with and without lidocaine. Computing the heart rate power spectrum and integrating over predetermined frequency bands, we focused mainly on the respiratory frequency band, known to predominantly reflect parasympathetic control. The administration of lidocaine resulted in a significant overall increase in mean heart rate: for the healthy control group an increase of 5.5 +/- 2.2% (mean +/- SE), for the IMI group an increase of 9.4 +/- 3.5%, and for the AMI group an increase of 8.1 +/- 2.9% (p < 0.01 for all). Simultaneously, following the administration of lidocaine, there was a decrease in the power of respiratory fluctuations: for the healthy control group a decrease of 38.4 +/- 12.5%, for the IMI group a decrease of 46.3 +/- 32.9%, and for the AMI group a decrease of 33.9 +/- 16.2% (p < 0.01 for all). These findings indicate that lidocaine has a consistent and significant parasympatholytic effect on the human heart, in healthy volunteers as well as in patients in the acute phase of myocardial infarction.

Adult↗
PubMed1996

V(H) gene-family representation in peripheral activated B cells from systemic lupus erythematosus (SLE) patients.

A semiquantitative polymerase chain reaction (PCR) assay described in this study has been used to analyse the V(H)1, V(H)3 and V(H)4 repertoire expressed by total IgM+ and IgG+ B cells from normal individuals and lupus patients. This approach consists of a combination of B cell selection, utilization of the anchored PCR technique to avoid technical bias in the amplification of different V(H) gene family cDNA templates, and screening of the amplified IgM or IgG cDNA rearrangements by family-specific oligonucleotide probes. In four lupus patients, V(H) family representation in IgM+ and IgG+ in vivo activated B cells, selected by anti-CD71 antibody, and in total CD19+ B cells were compared. In all patients, V(H)4 gene family segments were preferentially under-represented in IgM+ activated B cells. In IgG+ B cells the results suggest that V(H)4 expression is variable, depending on the phase of the disease. Polyclonal B cell activation, which is usually considered as being the first event in autoantibody production in SLE, cannot explain our results. The data evoke the possible involvement of a V(H)4-specific B cell superantigen in the onset or development of SLE. This hypothesis is also supported by the sequence conservation of the fourth beta loop a putative superantigen binding site of functional V(H)4 gene segments which are preferentially used by anti-dsDNA lupus antibodies of established clones and hybridomas.

Adult↗
PubMed1996

Progressive decrease in VH3 gene family expression in plasma cells of HIV-infected patients.

We have analysed the expression of VH gene families in total peripheral plasma cells of mu and gamma isotypes from a group of HIV-infected patients. CD19- and CD20- cells were separated from B lymphocytes, and anchored RT-PCR products were hybridized with specific VH gene family probes and with a consensus JH region probe. The VH/JH hybridization intensity ratios were taken as a parameter to measure VH expression. In vivo VH3 gene family expression is reduced in plasma cells of all HIV-infected patients compared with adult healthy donors. This decrease is maximal in patients with AIDS: > 90%. This is true for both studied isotypes. Conversely, the two other main VH gene families, VH1 and VH4, show no significant variation in expression. We and others have previously shown that VH3 gene family expression is first expanded and then decreased in peripheral B lymphocytes of HIV-infected patients. The present results extend these observations and show that VH3 gene family expression is also affected in plasma cells. The existence of a B cell superantigen in HIV infection may explain these data. This pronounced reduction in VH3 family expression may participate in the impaired humoral responses against bacterial agents found in HIV-infected patients.

Adult↗
PubMed1996

Jumping translocation in a phenotypically normal female.

"Jumping translocation" jt refers to a rare type of chromosome mosaic, in which the same portion of a (donor) chromosome is translocated to different (recipient) chromosome sites. Jt have mainly been observed in lymphocyte cultures of patients with hematologic malignancies. We report a phenotypically normal female carrying a mosaic of two cell lines with the Xq26-qter segment translocated to the short arm of chromosomes 15 or 21 in peripheral blood lymphocytes. In skin fibroblasts, only the X/21 translocation was detected. We speculate that recombination between homologous repetitive sequences on non-homologous human acrocentrics may be the cause of such chromosomal rearrangements.

Abnormalities, Multiple↗
PubMed1996

C618R mutation in exon 10 of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease.

The cosegregation of multiple endocrine neoplasia (MEN) type 2A with Hirschsprung's disease (HSCR), two diseases associated with mutation of the RET proto-oncogene, is infrequent. A 30-yr-old man was referred for screening of MEN 2A. Surgery for HSCR was performed at 4 yr of age. Basal and pentagastrin-stimulated calcitonin levels were abnormal. Histological examination of the thyroid confirmed bilateral medullary thyroid carcinoma. Screening of family members revealed six subjects with medullary thyroid carcinoma or abnormal pentagastrin-stimulated calcitonin test; one had an unilateral pheochromocytoma and two were affected with HSCR. DNA sequence analysis showed a heterozygote C618R mutation in exon 10 of the RET proto-oncogene in the proband and his mother, as well as in second-degree relatives with MEN 2A phenotype or HSCR. In this study, we report on a novel kindred with MEN 2A and HSCR phenotype associated with a point mutation (C618R) in one of the cysteine codons at the extracellular domain of the RET proto-oncogene.

Adult↗
PubMed1996

Sudden death among the Israeli civilian population during the Gulf War--incidence and mechanisms.

The Gulf War in January 1991 provided a unique opportunity to evaluate the influence of acute stress on the incidence of sudden cardiac death (SCD) in the Israeli civilian population. Pursuing this intriguing issue seemed warranted as we documented and reported a pronounced increase in the incidence of acute myocardial infarctions during that period. The purpose of the present study therefore was to document the incidence of SCD in different regions of Israel during a 10 day period preceding the Gulf War and a similar period following its onset, and to try to identify a possible correlation between the intensity of threat and the incidence of SCD. Sixty-eight cases during the Gulf War study period were compared to 213 cases in 5 control periods; overall 281 cases of SCD were documented. A rise in the incidence of SCD during the first 10 days of the war as compared to previous periods was noted but did not reach statistical significance. No correlation was demonstrated for SCD incidence among different regions in relation to the intensity of threat. Mechanisms by which acute stress precipitates an acute coronary syndrome are discussed, and an explanation for the lack of a statistically significant difference in SCD incidence is offered.

Age Factors↗