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Biomedical subjects

S Gross

Publications and source records attributed to S Gross.

At least 73 records · Page 4Linked to original sources

The detection and measurement of depersonalization disorder.

Depersonalization disorder comprises one of the four major dissociative disorders and yet remains poorly studied. There are no reports describing the application of dissociation scales to this population. Our goal was to investigate the applicability of four such scales to depersonalization disorder and to establish screening criteria for the disorder. Two general dissociation scales and two depersonalization scales were administered to 50 subjects with DSM-III-R depersonalization disorder and 20 healthy control subjects. The depersonalization disorder group scored significantly higher than the normal control group in all scales and subscales. Factor analysis of the Dissociative Experiences Scale (DES) yielded three factors as proposed previously, absorption, amnesia, and depersonalization/derealization. A DES cutoff score of 12, markedly lower than those previously proposed for the screening of other dissociative disorders, is required for the sensitive detection of depersonalization disorder. Alternatively, the DES pathological dissociation taxon (DES-taxon) score recently generated in the literature appears more sensitive to the detection of depersonalization disorder and is better recommended for screening purposes. The other three scales were fairly strongly correlated to the DES, suggesting that they may measure similar but not identical concepts, and cutoff scores are proposed for these scales also. General implications for the screening and quantification of depersonalization pathology are discussed.

Adult↗

Flow cytometry--principles and feasibility in transfusion medicine. Enumeration of epithelial derived tumor cells in peripheral blood.

Immunomagnetic selection of epithelial cells from peripheral blood was combined with flowcytometric or microscopic analysis to characterize and enumerate epithelium derived tumor cells in the circulation of patients with carcinoma of the breast. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with breast cancer. In addition, significant differences in the number of circulating epithelial cells were found in patients in whom the tumor is confined to the primary tumor and those with metastatic disease to local lymphnodes or distant sites [1]. The malignant nature of the cells was demonstrated by their cytology and immunophenotype. In following up the number of epithelial cells in the blood of patients with metastatic carcinoma of the breast, it was shown that it was well correlated with the activity of the disease.

Adult↗

Expressed copies of the MN7 (D15F37) gene family map close to the common deletion breakpoints in the Prader-Willi/Angelman syndromes.

Approximately 70% of patients with Prader-Willi syndrome or Angelman syndrome have a similar sized de novo deletion of 3-4 Mb in the proximal region of 15q. The distal breakpoints appear to cluster between the P gene (OCA2) and D15S24, whereas two deletion breakpoint clusters have been identified on the proximal side (one centromeric to D15S541 and one between D15S541 and D15S9). Based on the identification of a gene family in 15q11-->q13 (MN7, D15F37), we have previously proposed that the presence of multiple copies of this sequence may be related to the instability of this region. Using fluorescence in situ hybridization and YAC mapping, we have found that at least one D15F37 locus is centromeric to D15S9 and at least two are between OCA2 and D15S24. As determined by cDNA cloning and sequence analysis, each of the individual loci is expressed. The close proximity of the D15F37 loci and the deletion breakpoints suggests that the common deletions arise by unequal crossover events at or near these loci.

Adult↗

Medical, cognitive, emotional, and behavioral outcomes in school-age children conceived by in-vitro fertilization.

Assessed long-term effects of assisted reproduction technologies of in-vitro fertilization (IVF) and related techniques of embryo transfer (ET) on children's adjustment. 51 school-age Israeli children conceived by IVF/ET were compared with 51 control-matched children conceived spontaneously. The assessment included a comprehensive medical evaluation, a psychological examination, teachers' reports, parents' reports, and children's self-reports. As compared with controls, IVF/ET children did not reveal significant differences in physical and neurological status or on cognitive measures of IQ, visual-motor coordination, visual memory, and verbal comprehension. Nevertheless, the IVF/ET children were scored lower by teachers on measures of socioemotional adjustment in school and on self-report measures of anxiety, aggression, and depression. Among IVF/ET children, the tendency to be at a greater risk for emotional disturbances was exacerbated among boys and among children whose parents were older.

Affective Symptoms↗

Hrp1, a sequence-specific RNA-binding protein that shuttles between the nucleus and the cytoplasm, is required for mRNA 3'-end formation in yeast.

In yeast, four factors (CF I, CF II, PF I, and PAP) are required for accurate pre-mRNA cleavage and polyadenylation in vitro. CF I can be separated further into CF IA and CF IB. Here we show that CF IB is the 73-kD Hrp1 protein. Recombinant Hrp1p made in Escherichia coli provides full CF IB function in both cleavage and poly(A) addition assays. Consistent with the presence of two RRM-type motifs, Hrp1p can be UV cross-linked to RNA, and this specific interaction requires the (UA)6 polyadenylation efficiency element. Furthermore, the CF II factor enhances the binding of Hrp1p to the RNA precursor. A temperature-sensitive mutant in HRP1 yields mRNAs with shorter poly(A) tails when grown at the nonpermissive temperature. Genetic analyses indicate that Hrp1p interacts with Rna15p and Rna14p, two components of CF 1A. The HRP1 gene was originally isolated as a suppressor of a temperature-sensitive npl3 allele, a gene encoding a protein involved in mRNA export. Like Npl3p, Hrp1p shuttles between the nucleus and cytoplasm, providing a potential link between 3'-end processing and mRNA export from the nucleus.

Amino Acid Sequence↗

[High malignant B-cell non-Hodgkin lymphoma of the heart: intravital diagnosis by transesophageal echocardiography controlled biopsy].

We report about a 66-year old patient with Non-Q-wave infarction in coronary artery two-vessel disease. During an echo- and transesophageal multiplane echocardiography preoperatively before a coronary artery bypass surgery a right atrium septal tumor of unknown form was discovered. The computerized axial tomography (CAT) and nuclear magnetic resonance (NMR) scans did not demonstrate extracardiac pathologic findings. A transesophageal echocardiography-guided biopsy of the right atrial septum over the vena femoralis and the right atrium enabled intra vitam a very early diagnosis of high malignant B-cell Non-Hodgkin-lymphoma without the need for thoracotomy. The diagnosis was confirmed histopathologically and immunohistochemically and early treatment with cytostatic therapy could begin. To our knowledge the transesophageal echocardiography-guided biopsy has never been described in the worldwide literature.

Aged↗

The Uba2 and Ufd1 proteins of Saccharomyces cerevisiae interact with poly(A) polymerase and affect the polyadenylation activity of cell extracts.

Poly(A) polymerase is responsible for the addition of the adenylate tail to the 3' ends of mRNA. Using the two-hybrid system we have identified two proteins which interact specifically with the Saccharomyces cerevisiae poly(A) polymerase, Pap1. Uba2 is a homolog of ubiquitin-activating (E1) enzymes and Ufd1 is a protein whose function is probably also linked to the ubiquitin-mediated protein degradation pathway. These two proteins interact with Pap1 and with each other, but not with eight other target proteins which were tested in the two-hybrid system. The last 115 amino acids of Uba2, which contains an 82-amino acid region not present in previously characterized E1 enzymes, is sufficient for the interaction with Pap1. Both Uba2 and Ufd1 can be co-immunoprecipitated from extracts with Pap1, confirming in vitro the interaction identified by two-hybrid analysis. Depletion of Uba2 from cells produces extracts which polyadenylate precursor RNA with increased efficiency compared to extracts from nondepleted cells, while depletion of Ufd1 yields extracts which are defective in processing. These two proteins are not components of polyadenylation factors, and instead may have a role in regulating poly(A) polymerase activity.

Cloning, Molecular↗

[Pilot study of the characteristics of transfused patients and utilized labile blood products].

The aim of this study was to describe blood recipients and blood components transfused during the first 24 hours in 13 French hospitals. We included all blood recipients who had not had any blood transfusion within the past six months. Recipients were screened for red cell alloantibodies, the alanine aminotransferase activity and specific viral markers (hepatitis B and C, Human Immunodeficiency Virus). Eligible patients represented 47% of the all transfused. Among the 371 patients included, 57% were males and 71% were transfused in a surgical unit. Alloantibodies, non specific and specific viral markers were detected in 3%, 19% and 2% respectively. Among the patients included, 42 received 172 autologous units. In total, 1056 allogeneic units (an average of 3 units per patient) were transfused; blood products were leucocyte-depleted (49%) or leucocyte-poor (20%); 54% of red cell units were matched for antigens Rh and Kell. Neoplasms were the most frequently reported disease for which patients were transfused. This study provides baseline blood transfusion information on recipients and blood utilization for a specific period in French hospitals. Following this study, a national study will allow the clarification of the characteristics, for instance the surgical procedures requiring transfusion.

Adolescent↗

Sequence and functional analysis of the 5'-flanking region of the mouse growth inhibitory factor gene.

1. The growth inhibitory factor (GIF) is a 68-amino acid protein which is capable of inhibiting the growth of neuronal cells in vitro. 2. We have cloned and sequenced the 5'-flanking region of the mouse GIF gene, which spans from the transcriptional initiation site to the -1854 nucleotide. 3. This region contains sequences homologous to hgcs, SPE, and the JCV silencer domain that functions in a glial cell specific manner. This region also contains two metal responding elements and putative binding sites for AP-1, AP-2, Sp-1, SP-2, NF-1, and CREB. 4. An analysis of the reporter plasmids containing the various regions of the 5'-flanking sequence revealed that the region indeed functioned in a tissue-specific manner in glial cells and that the region between -328 and 175 is responsible for suppression, while the region between -175 and -49 is involved in the activation of gene expression.

3T3 Cells↗

Different mechanisms and recurrence risks of imprinting defects in Angelman syndrome.

Angelman syndrome (AS) is a neurogenetic disorder that appears to be caused by the loss of function of an imprinted gene expressed from maternal chromosome 15 only. Approximately 6% of patients have a paternal imprint on the maternal chromosome. In the few cases, this is due to an inherited microdeletion, in the 15q11-q13 imprinting center (IC), that blocks the paternal-->maternal imprint switch in the maternal germ line. We have determined the segregation of 15q11-q13 haplotypes in nine families with AS and with an imprinting defect. One family, with two affected siblings, has a microdeletion affecting the IC transcript. In the other eight patients, no mutation was found at this locus. In two families, the patient and a healthy sibling share the same maternal alleles. In one of these families and in two others, grandparental DNA samples were available, and the chromosomes with the imprinting defect were found to be of grandmaternal origin. These findings suggest that germ-line mosaicism or de novo mutations account for a significant fraction of imprinting defects, among patients who have an as-yet-undetected mutation in a cis-acting element. Alternatively, these data may indicate that some imprinting defects are caused by a failure to maintain or to reestablish the maternal imprint in the maternal germ line or by a failure to replicate the imprint postzygotically. Depending on the underlying cause of the imprinting defect, different recurrence risks need to be considered.

Angelman Syndrome↗

Characterization and phenotypic analysis of differentiating CD34+ human bone marrow cells in liquid culture.

Our current understanding of human haematopoietic stem cell biology is based in part on the characterization of human CD34+ bone marrow cell differentiation in vitro. CD34 is highly expressed on early stem cells and haematopoietic progenitor cells with clonogenic potential and is gradually lost during differentiation and commitment. However, CD71 (transferrin receptor) is expressed at low levels on early stem cells and generally increases during haematopoietic progenitor cell proliferation. We reasoned that the combination of these surface markers would provide a useful framework for the simultaneous analysis of multiple lineage differentiation of CD34+ haematopoietic progenitor cells in liquid culture. In this report, we identify the phenotype of distinct subpopulations of myeloid, erythroid and lymphoid cells in liquid suspension culture using differential expression of CD34 vs. CD71 in combination with specific lineage markers. Freshly isolated human CD34+ bone marrow cells were introduced into suspension culture and monitored over a 6-d period using 3-colour flow cytometry. This is the first demonstration that differential expression of CD34 vs. CD71 can be used to simultaneously monitor differentiation of multiple haematopoietic cell lineages in liquid suspension culture, facilitating the study of cytokine-, drug- or chemical-induced alterations in haematopoietic progenitor cell differentiation in vitro.

Antigens, CD↗

Protein-A-mediated targeting of bacteriochlorophyll-IgG to Staphylococcus aureus: a model for enhanced site-specific photocytotoxicity.

A model for studying the efficiency of photodynamic action with a photosensitizer placed exclusively on the bacterial cell wall has been used. Bacteriochlorophyllide molecules, conjugated to rabbit immunoglobulin G (IgG), were synthesized. The conjugated pigment bacteriochlorophyll (Bchl)-IgG bound with high specificity to protein-A residues naturally exposed on the cell wall of the bacterium Staphylococcus aureus Cowan I. In bacterial suspensions the phototoxicity of the targeted conjugates (0.5-2.5 pigment per IgG molecule) was dose dependent (LD50 = 1.7 microM) in the presence of light (lambda > 550 nm) and inhibited by native IgG but not by ovalbumin, suggesting selective interaction with protein-A on the bacterial cell wall. No dark toxicity was noticed even with the highest conjugate concentration tested. In contrast, the photocytotoxicity of bacteriochlorophyll-serine (Bchl-Ser, LD50 = 0.07 microM) used as a nontargeted control was not inhibited by IgG. In spite of its lower apparent potency, Bchl-IgG was found to be 30 times more efficacious than Bchl-Ser: At LD50, only 66,000 Bchl-IgG molecules were bound per bacterium compared to 1,900,000 molecules of Bchl-Ser. The higher efficacy of Bchl-IgG is explained by its exclusive position on the bacterial cell wall. Consequently, photogeneration of oxidative species is confined to the cell wall and its vicinity, a seemingly highly susceptible domain for photodynamic action. In considering the design of cell-specific sensitizers for bacterial and cancer therapies, it would be beneficial to identify the more discretely sensitive subcellular domains as targets.

Bacteriochlorophylls↗

Feeling unreal: 30 cases of DSM-III-R depersonalization disorder.

OBJECTIVE: In contrast to the recent surge of interest in other dissociative disorders, DSM-III-R depersonalization disorder has not been thoroughly investigated and characterized. The authors systematically elucidated its phenomenology, comorbidity, traumatic antecedents, and treatment history. METHOD: Thirty adult subjects (19 women and 11 men) were consecutively recruited and administered various structured and semistructured interviews as well as the self-rated Dissociative Experiences Scale. An age- and sex-matched normal comparison group was also recruited. RESULTS: The mean age at onset of depersonalization disorder was 16.1 years (SD = 5.2). The illness had a chronic course that was usually continuous but sometimes episodic. Severe distress and high levels of interpersonal impairment were characteristic. Unipolar mood and anxiety disorders were common, but none emerged as specifically related to the depersonalization. A wide variety of personality disorders was manifested; avoidant, borderline, and obsessive-compulsive were most common. Although not highly traumatized, the subjects with depersonalization disorder reported significantly more childhood trauma than the normal comparison subjects. Depersonalization had been typically treatment refractory; only serotonin reuptake inhibitors and, to a lesser extent, benzodiazepines had been of any therapeutic benefit. CONCLUSIONS: This study supports the conceptualization of depersonalization disorder as a distinct disorder with a characteristic course that is independent of mood, anxiety, and personality symptoms. A subtle relationship may exist between childhood trauma and depersonalization disorder that merits further investigation. The disorder appears to be highly treatment refractory, and prospective treatment trials are warranted.

Adolescent↗

Fixed drug eruption of the penis due to hydroxyzine hydrochloride.

OBJECTIVE: To report four cases of fixed drug eruption induced by hydroxyzine hydrochloride (Otarex, Teva, Israel). CASE SUMMARY: Four children with restlessness who were treated with hydroxyzine hydrochloride developed fixed drug eruption of the penis. Drug discontinuation was followed by complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration inhibiting factor (MIF) assay with hydroxyzine hydrochloride was positive. DISCUSSION: The pathogenesis of fixed drug eruption and the role of macrophage MIF assay in diagnosis is discussed. CONCLUSIONS: A fixed drug eruption induced by hydroxyzine hydrochloride is possible, but is a rare phenomenon.

Animals↗

A double-blind trial of fluoxetine in pathologic skin picking.

BACKGROUND: Our objective was to determine the efficacy of fluoxetine in the treatment of pathologic skin picking in a double-blind, placebo-controlled, parallel trial. METHOD: Twenty-one adults with chronic pathologic skin picking agreed to participate and received 10 weeks of placebo or fluoxetine with a flexible dosing schedule up to 80 mg/day. Three skin-picking measures were employed: the Clinical Global Impression-Improvement (CGI-I) scale, the Skin Picking Treatment Scale (SPTS), and a visual analog scale of self-rated change (VAS). In addition, depression, anxiety, and obsessions-compulsions were rated using the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Spielberger State-Trait Anxiety Inventory (STAI), and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for the duration of the study. RESULTS: Seventeen subjects (6 treated with fluoxetine and 11 treated with placebo) completed the trial, at a mean fluoxetine dose of 55 mg/day. Fluoxetine was significantly superior to placebo in the treatment of skin picking according to two of the three measures for the completer analysis and to one of the three measures for the intent-to-treat analysis. Neither baseline level nor change in depression, anxiety, or obsessive-compulsive symptoms was significantly related to change in skin picking. CONCLUSION: This first controlled trial of the treatment of pathologic skin picking suggests that fluoxetine may be of therapeutic benefit. Larger controlled studies are warranted.

Adult↗

Hybrids of chicken cystatin with human kininogen domain 2 sequences exhibit novel inhibition of calpain, improved inhibition of actinidin and impaired inhibition of papain, cathepsin L and cathepsin B.

Chicken cystatin and human kininogen domain 2 are members of the cystatin superfamily of protein-type cysteine proteinase inhibitors. They show structural and functional similarities, but only human kininogen domain 2 inhibits calpain. Using recombinant chicken cystatin as a scaffold for hybrid cassette analysis, the known reactive-site regions (N-terminus, first hairpin loop and second hairpin loop) were substituted by the corresponding sequences of human kininogen domain 2 in a single and combined manner. Seven hybrids were expressed, purified to homogeneity, characterized protein-chemically, and their inhibition of papain, actinidin, human cathepsin B, human cathepsin L and calpain (80-kDa subunit of rabbit skeletal muscle calpain II and porcine erthrocyte calpain 1) was determined. Strong but temporary inhibition of calpain by chicken cystatin hybrids carrying the N-terminus alone (variant sc1-KD2) or the N-terminus together with the first hairpin loop (variant sc1/2-KD2) was observed; hybrids of the second hairpin loop (sc3-KD2, sc1/3-KD2, sc2/3-KD2, sc1/2/3-KD2) were less strong calpain inhibitors. These data indicate that the inhibiton of calpain by human kininogen domain 2 requires the correct conformation and combination of several contact sites, and suggest that the N-terminus and the first hairpin loop play a major role in this ensemble. Remarkably, hybrid sc2-KD2 exhibited 5 or 150 times stronger inhibition of actinidin compared to native chicken cystatin or to proteolytically isolated human kininogen domain 2, respectively. This indicates an important role of the first hairpin loop of cystatins in the interaction with actinidin. Along with the impaired inhibition of cathepsin L, papain, actinidin, cathepsin B and calpain by the hybrids sc1/3-KD2, sc2/3-KD2 and sc1/2/3-KD2, these results support our hypothesis that all three predicted contact regions of kininogen domain 2 contribute to binding in the active-site clefts of papain-like enzymes in a finely balanced manner.

Amino Acid Sequence↗

Chemotactic response of human alveolar macrophages and blood monocytes elicited by exposure to sulfur dioxide.

An experimental study was undertaken to investigate the in vitro effect of sulfur dioxide on the chemotactic activity of alveolar macrophages (AM) and blood monocytes (BM). The cells were placed on a polycarbonate membrane and exposed to SO2 0.5, 1.5 and 2.5 ppm for 15 min. Control experiments were performed with exposure of the cells to synthetic air with 5% CO2. After gas exposure the cells were incubated with the chemotactic active agent C5a in 5% carbon dioxide (CO2) at 37 degrees C for 60 min. The numbers of AM and BM passing actively through the membrane were quantified using light microscopy. Our results show a dose-dependent reduction in the migration rate of cells under SO2 exposure. SO2 0.5 ppm induced a 29% and SO2 2.5 ppm a 53% decrease in migration of AM compared with the control exposure to synthetic air (P < 0.01). Identical experiments with BM resulted in a decrease in migration of up to 57% (P < 0.01). At SO2 concentrations of up to 2.5 ppm no significant cytotoxic effects were observed for AM or BM. The data demonstrate that exposure to SO2 may reduce the chemotactic activity of AM and BM. Our results further suggest that the decrease in cell migration induced by SO2 is due to changes in chemotactic mechanisms and not to cell death.

Aged↗