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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 271 records · Page 15Linked to original sources
PubMed1996

Modulating effects of propofol on metabolic and cardiopulmonary responses to stressful intensive care unit procedures.

OBJECTIVE: Patients in the intensive care unit (ICU) undergo acute increases in metabolic and cardiopulmonary demands in response to routine care interventions, such as chest physical therapy. This study examined whether the short-acting drug, propofol, could blunt the responses to chest physical therapy. DESIGN: Prospective, randomized, crossover (placebo vs. drug) study. SETTING: University hospital surgical ICU. PATIENTS: Postoperative ICU patients being ventilated in the synchronized intermittent mandatory ventilation mode. INTERVENTIONS: Two groups of 16 patients were studied. Each patient received two successive sessions of chest physical therapy. In random fashion, one was preceded by the administration of placebo and the other by an intravenous bolus of propofol (0.75 mg/kg in one group and 0.35 mg/kg in the other group). Each session was preceded and followed by a period of rest. MEASUREMENTS AND MAIN RESULTS: The increases in oxygen uptake, CO2 elimination, oxygen delivery, heart rate, and systolic blood pressure associated with chest physical therapy were attenuated with the low dose and suppressed with the high dose of propofol. The Paco2 concentration was slightly increased during both placebo and drug administration. CONCLUSIONS: Propofol, in the doses administered in this study, significantly reduced the hemodynamic and metabolic stresses caused by chest physical therapy.

Adult↗
PubMed1996

Modulation of multidrug resistance by SDZ PSC 833 in leukemic and solid-tumor-bearing mouse models.

P-Glycoprotein inhibitors, including the nonimmunosuppressive cyclosporin D analog SDZ PSC 833 (PSC 833), have been developed to circumvent multidrug resistance. In the present study, the potential of PSC 833 in reversing multidrug resistance was evaluated in various systemic treatment models with leukemic and solid-tumor-bearing mice. Having a relatively wide therapeutic window of daily p.o. doses from 12.5 to 75 mg/kg, PSC 833 significantly improved the antileukemic activity of the anticancer drugs adriamycin (ADM), vincristine (VCR) and etoposide (VP-16) given i.p. or i.v. against i.p.-inoculated vincristine-resistant P388 tumor (P388/VCR). PSC 833 in combination with i.p.-injected anticancer drugs in optimal schedule and dosage induced apparent cures in some leukemic mice, whereas no cures were obtained with the cyclosporin A/anticancer drug combinations. PSC 833 combined with i.v.-injected anticancer drugs was highly active, but not curative, against P388/VCR and parental P388 tumors (maximum T/C>175%) PSC 833 in combination with intravenous treatment with ADM showed prominent anti-solid-tumor activity against s.c.-inoculated colon adenocarcinoma 26 and human colorectal adenocarcinoma HCT-15. Against colon adenocarcinoma 26, the PSC 833/ADM combinations induced cure in two or three of six mice. PSC 833/ADM combinations significantly inhibited the growth of the tumor with maximum percent inhibitions of 83 and 73% in the early and advanced stages of the HCT-15 tumor models, respectively. The present study demonstrated that PSC 833 is highly active in potentiating the antitumor activity of systemically administered ADM, VCR and VP-16 against four murine and human tumors with a relatively wide therapeutic window of daily p.o. dose range of 12.5-100 mg/kg.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Detection of antibodies to Shigella lipopolysaccharide in urine after natural Shigella infection or vaccination.

The purpose of the present study was to explore the possibility of detecting antibodies to Shigella sonnei lipopolysaccharide (LPS) in urine after infection or vaccination. Urinary immunoglobulin A (IgA) and IgG antibodies and specific IgA secretory protein against S. sonnei LPS were measured by enzyme-linked immunosorbent assay (ELISA), after adjustment for urine concentration. A significant antibody level was defined as one above a cutoff value calculated from the geometric mean + 2 standard deviations of urinary anti-S. sonnei LPS levels in 43 healthy hepatitis B vaccinees (controls). Of 11 culture-proven cases of S. sonnei shigellosis, at convalescence 9 (82%) had significantly elevated levels of urinary antibodies to the homologous LPS. The S. sonnei conjugate vaccine, composed of S. sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, elicited a significant urine IgA or IgG anti-LPS response in 60% (6 of 10), 56% (9 of 16) 43% (16 of 37), and 14% (3 of 21) of the volunteers at 2 weeks, 6 weeks, 6 months, and 12 months after vaccination, respectively. The specificity of the urine antibody response to S. sonnei LPS was documented by the total lack of response in subjects who received parenteral Shigella flexneri 2a-recombinant exoprotein A conjugate (69 urine samples) or meningoccal tetravalent control vaccines (4 urine samples). All the volunteers who lacked a significant response to S. sonnei LPS in serum also lacked such response in urine samples. Seventy-four percent of the volunteers with a significant IgA or IgG anti-LPS response in serum at convalescence or 14 days after vaccination showed a similar response in urine. The ratio of the titer of secretory protein bound to IgA anti-S. sonnei LPS in urine to that in serum was 303 times higher than the ratio of anti-S. sonnei LPS total IgA titer in urine to that in serum, indicating that the urine IgA is of secretory origin. These findings suggest the possible use of urinary Shigella LPS antibodies as markers of systemic and secretory immune responses after natural infection or vaccination. At this stage, because of its limited sensitivity, the detection by ELISA of Shigella LPS antibodies in urine cannot replace the same assay in serum as a definitive test in an individual with a negative result.

Antibodies, Bacterial↗
PubMed1996

Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers.

The safety and immunogenicity of investigational conjugates, composed of the O-specific polysaccharides of Shigella sonnei and Shigella flexneri type 2a covalently bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), were evaluated in 192 Israeli soldiers. None had significant local reactions or fever. Fourteen days after injection, 90% of S. sonnei-rEPA recipients and 73 to 77% of S. flexneri-rEPA recipients had a fourfold or greater increase in serum immunoglobulin G (IgG) and IgA anti-lipopolysaccharide (anti-LPS) levels; at 2 years, these remained higher than at prevaccination (P < 0.01). There was a fourfold or greater increase in IgM anti-LPS in 20% of vaccinees at 2 weeks, but levels returned to prevaccination values at 6 to 12 months. IgG was the highest and most sustained class of LPS antibodies. Reinjection at day 42 did not boost antibody levels. Eighteen of 23 (78%) who received S. sonnei-rEPA and 13 of 19 (68%) who received S. flexneri-rEPA. had significant IgA-secreting cell responses. Significant IgG antibody-secreting cell responses were detected in 19 of 23 (83%) and 11 of 19 (58%) volunteers following vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA, respectively. On the basis of these data, further evaluation of the Shigella conjugates for protective efficacy in field trials in Israel was started.

Adolescent↗
PubMed1996

Encephalopathy associated with enteroinvasive Escherichia coli 0144:NM infection.

Central nervous system manifestations typically occur with Shigella gastroenteritis and also in enteric Salmonella and Campylobacter infections. To date no association between enteroinvasive Escherichia coli infection and neurologic symptoms has been described. Two children with diarrhea caused by E. coli 0144:NM had otherwise unexplained encephalopathy manifested by profound stupor in one child and by obtundation and meningismus in the other one. These cases of infection occurred in northern Israel during a period of an unusually high rate of enteric infection caused by this organism. None of the microbiologic properties studied were uniquely attributable to the encephalopathic cases. The two encephalopathic as well as all eight nonencephalopathic isolates studied possessed the 140-MDa invasive plasmid. All 10 isolates examined produced small amounts of cytotoxin by the HeLa cell assay, all were nonmotile, and all had identical antibiograms. Eight of 10 of the isolates had identical plasmid profiles, while 2 isolates (from nonencephalopathic patients) had slightly different plasmid profiles. This is the first report of encephalopathy associated with enteroinvasive E. coli.

Central Nervous System Diseases↗
PubMed1996

Detection of triplet repeat sequences in yeast artificial chromosomes using oligonucleotide probes: application to the SCA1 region in 6p23.

In this paper, we describe labeling and hybridization conditions for oligonucleotide probes that detect human triplet repeat sequences in yeast artificial chromosomes (YACs). Restriction digests of YACs containing the CAG repeat sequence of the SCA1 gene were used as positive controls. Several hybridization mixtures and temperatures and two different labeling techniques were tested in order to determine optimal conditions. CAG, CGG, AGG, and ATT repeat sequences were mapped on YACs from a contig in 6p23, where SCA1 is located.

Ataxin-1↗
PubMed1996

1.8-megabases fine physical map encompassing IFNAR and AML1 loci on human chromosome 21q22.1.

A long-range restriction map of the 1.8-megabases (mb) region encompassing the area between the interferon-alpha receptor and the acute myelogenous leukemia loci on human chromosome 21q22.1 was constructed after analysis of both the contiguous yeast artificial chromosome (YAC) clones and genomic DNA. Analysis of pulsed-field gel electrophoresis of lymphoblastoid DNA digested with three rare-cutting enzymes, Not I, Mlu I, and Nru I, revealed the positions of 17 markers on each restriction map. The 1.8-mb YAC contig that covers this region was obtained through YAC walking mediated by sequence-tagged sites (STSs), with 29 STSs including 12 newly generated YAC end-specific STSs. The consensus restriction map from 15 overlapping YACs and the positioning of the STS markers on each clone allowed 24 markers including 4 Not I-linking STSs to be ordered and mapped physically. Comparison of the maps revealed that the proximal region contains more unmethylated CpG islands than the distal region, which suggests that many expressed genes are in the proximal region. This fine consensus physical map will be informative and useful for construction of contigs of cosmid, P1, or BAC clones for further large-scale sequencing in this gene-rich region.

Base Sequence↗
PubMed1996

Analysis of workload predictions generated by multiple resource theory.

BACKGROUND: During the design process, operator workload assessments sometimes require subject matter experts (SME's) to predict the amount of physical and mental demands they expect during system employment. Often, these subjective estimates are considered within the context of models that partition human capabilities into discrete resources. Such models require the SME's to rate tasks on how they affect resource consumption. This type of assessment technique is based upon the premise that raters can effectively discriminate their own resources. METHODS: Subjective workload ratings based on multiple resource theory were collected independently from two highly experienced pilots for 225 different tasks of an anticipated mission for a future advanced strike aircraft. The data were examined using a factor analytic approach. RESULTS: Factor analysis of their responses suggest that while such ratings have high face validity and even high inter-rater reliabilities, the ratings could have little validity in terms of efforts required to use the seven postulated resource channels (i.e., visual or auditory input, spatial, verbal or analytical cognition, and manual or speech output). Ratings of efforts required for the cognitive resource channels were particularly suspect. We identified four independent factors for each pilot that accounted for virtually all of the intercorrelations among the 7 resource channels. Three factors (i.e., visual-spatial, verbal communications, and manual and speech output) were identical for both pilots and accounted for most of the explainable variance. CONCLUSION: Given these results, this analysis challenges the utility of a multiple resource framework for predictive workload assessments.

Adult↗
PubMed1996

Autistic barriers in the psychoanalysis of borderline adults.

The authors discuss Frances Tustin's work on childhood autism in order to clarify the nature and protective function of autistic barriers in adult patients who present challenging resistances in treatment. Tustin's thesis is that childhood autism constitutes a massive formation of avoidance reactions that develop in infancy to ward off traumatic awareness of bodily separateness. She describes two forms of childhood pathology that may develop: the encapsulated child who defends against all 'not me' experience by means of self-generated bodily sensations that augment the illusion of complete bodily continuity with the mother; and the entangled child who generates a protective illusion of being enfolded inside the body of the mother to minimise the experience of separateness. The transference resistances of borderline adults can be categorised according to Tustin's typology of encapsulation and entanglement. Clinical material is presented from the analyses of two borderline patients, one encapsulated and the other entangled. Despite seemingly different transference manifestations, both belong to the category of autistic barriers inasmuch as they ward off awareness of separation-induced injury to the primal self. The countertransference difficulties that the analyst encounters with patients who employ autistic barriers are discussed and treatment issues are reviewed.

Autistic Disorder↗
PubMed1995

A YAC contig and an EST map in the pericentromeric region of chromosome 13 surrounding the loci for neurosensory nonsyndromic deafness (DFNB1 and DFNA3) and limb-girdle muscular dystrophy type 2C (LGMD2C).

Two forms of inherited childhood nonsyndromic deafness (DFNB1 and DFNA3) and a Duchenne-like form of progressive muscular dystrophy (LGMD2C) have been mapped to the pericentromeric region of chromosome 13. To clone the genes responsible for these diseases we constructed a yeast artificial chromosome (YAC) contig spanning an 8-cM region between the polymorphic markers D13S175 and D13S221. The contig comprises 24 sequence-tagged sites, among which 15 were newly obtained. This contig allowed us to order the polymorphic markers centromere-D13S175-D13S141-D13S143-D13S115-AF M128yc1-D13S292-D13S283-AFM323vh5- D13S221-telomere. Eight expressed sequence tags, previously assigned to 13q11-q12 (D13S182E, D13S183E, D13S502E, D13S504E, D13S505E, D13S837E, TUBA2, ATP1AL1), were localized on the YAC contig. YAC screening of a cDNA library derived from mouse cochlea allowed us to identify an alpha-tubulin gene (TUBA2) that was subsequently precisely mapped within the candidate region.

Animals↗
PubMed1995

The activation of a specific DNA binding protein by neutron irradiation.

PURPOSE: To determine whether the quality of ionizing radiation is critical for activation of a radiation-specific DNA binding protein. METHODS AND MATERIALS: We have previously shown that after exposing Epstein Barr virus-transformed lymphoblastoid cells to ionizing radiation, a specific DNA binding factor appears in the nucleus apparently as a result of translocation from the cytoplasm. This protein binds to a number of different genomic sequences and a consensus motif has been identified. Because the protein was not activated by UV light, it was of interest whether high linear energy transfer (LET) radiation was capable of activation. RESULTS: We describe here the activation of a specific DNA binding protein by high LET neutron radiation. The protein binds a region adjacent to and overlapping with the distal repeat within a 179 base-pair fragment of the well-characterized Simian Virus (SV40) bidirectional promoter/enhancer element. The appearance of the DNA binding activity was dose dependent and reached a maximum level by 90 min postirradiation. A reduction in DNA binding activity was evident at later times after irradiation. CONCLUSIONS: The specific nature of this response and the rapidity of activation may indicate a pivotal role for this protein in repair or in some other aspect of the cellular response to radiation damage.

Base Sequence↗
PubMed1995

Phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by casein kinase I in vitro and in vivo.

DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, M(r) = 32,000) is a potent inhibitor of protein phosphatase-1 when it is phosphorylated on Thr-34 by cAMP-dependent protein kinase. DARPP-32 is highly enriched in some specific cell populations such as striatonigral neurons and choroid plexus epithelial cells. Here we show that recombinant rat DARPP-32 is phosphorylated by casein kinase I on seryl residues to a stoichiometry of approximately 2 mol of phosphate/mol of protein. DARPP-32 is one of the best known substrates for casein kinase I (Km = 3.4 +/- 0.3 microM), whereas the homologous phosphatase-1 inhibitor, inhibitor-1, is not. Phosphorylation of DARPP-32 by casein kinase I does not alter its ability to inhibit protein phosphatase-1. Residues phosphorylated by casein kinase I were identified as Ser-137 and Ser-189 by site-directed mutagenesis and by protein sequencing. Ser-137 and the preceding stretch of 16-18 acidic residues are conserved in DARPP-32 among all species examined, whereas Ser-189 is not. Phosphorylation of Ser-137 induces an unusual increase in DARPP-32 electrophoretic mobility in polyacrylamide gels in the presence of SDS. In striatonigral neurons, DARPP-32 is phosphorylated on Ser-137 and the stoichiometry of phosphorylation on this residue in vivo appears to be higher in the substantia nigra (axon terminals) than in the striatum (soma and dendrites). These results indicate that casein kinase I is highly active in striatonigral neurons in which it may play important roles, including in protein phosphatase-1 modulation via phosphorylation of DARPP-32.

Amino Acid Sequence↗
PubMed1995

PET imaging studies of dopamine D2 receptors: comparison of [18F]N-methylspiperone and the benzamide analogues [18F]MABN and [18F]MBP in baboon brain.

A series of positron emission tomography (PET) imaging studies was conducted in a baboon with the benzamide derivatives [18F]2,3-dimethoxy-N-[9-(4-fluorobenzyl)-9-azabicyclo[3.3.1]non an-3 beta-yl]benzamide ([18F]MABN) and [18F]2,3-dimethoxy-N-[1-(4-fluorobenzyl)piperidin-4-yl]be nza mide ([18F]MBP). Studies were also conducted with the butyrophenone [18F]N-methylspiperone (NMSP) for comparison. Tissue-time activity curves of [18F]MABN are similar to those of [18F]NMSP since both compounds displayed approximately the same uptake in the basal ganglia and displayed irreversible binding kinetics in vivo. However, the rapid rate of clearance from the cerebellum and high basal ganglia:cerebellum ratio of [18F]MABN indicate that this compound has a much lower amount of nonspecific binding than [18F]NMSP. [18F]MBP displayed a higher uptake in the basal ganglia relative to [18F]NMSP and [18F]MABN and exhibited reversible binding kinetics in vivo. This property of [18F]MBP is desirable since the uptake of radioactivity in D2-rich ligands is less likely to be influenced by changes in cerebral blood flow. The current data suggest that both [18F]MABN and [18F]MBP are promising ligands for studying dopamine D2 receptors with PET.

Animals↗
PubMed1995

Effects of acute exposure to hyperbaric oxygen on the rheology and morphology of the red blood cells in the rat.

The effects of acute exposure to hyperbaric oxygen (HBO) on the rheology and morphology of red blood cells (RBC) were studied in three groups of Sprague-Dawley rats: a control (CON) group comprised rats not exposed to HBO, a second group was exposed to HBO at 2.8 atm for 6 hr and studied immediately after the exposure (HBO), and a third group was examined after being allowed to recover in room air for 24 hr after exposure to HBO (REC). RBC deformability was assessed by two different techniques, the ektacytometer and the micropore filters. While the ektacytometer did not detect a significant difference among the three groups, the filtration method showed that acute exposure to HBO causes a significant increase in the filtration index (FI), denoting a significant reduction in RBC deformability. However, this reduction returned to the control level after 24 hr of recovery in air (FI, 7.1 +/- 1.2 in CON and 9.5 +/- 2.6 in REC compared to 36.2 +/- 3.7 in HBO, P < 0.0001). The morphology of RBC was studied by scanning electron microscopy. Immediately after exposure to HBO there was a marked increase in the echinocytes (41.6 +/- 5.9%) compared to a control level of 16.7 +/- 4.8%, P < 0.05. The increase in the echinocytes became less pronounced after 24 hr of recovery (23.5 +/- 9.3%). In conclusion, acute exposure to HBO causes significant alterations in RBC rheology and morphology. Due to the sensitivity of the micropore filters, we hypothesize that the decrease in RBC deformability might affect their flow through small-caliber blood vessels. These alterations, however, are reversible after a relatively short period of recovery in air.

Animals↗