AIDS therapy. Failure isn't what it used to be...but neither is success.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J Cohen
Publications and source records attributed to J Cohen.
Rubber hands 'feel' touch that eyes see.
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Ego↗
Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: a randomized study.
BACKGROUND: The aims of the present study were to determine whether maternal hyperoxygenation affects human fetal pulmonary circulation and whether there is a gestational age-related response in the fetal pulmonary circulation to maternal hyperoxygenation during the second half of gestation. METHODS AND RESULTS: Twenty women between 20 and 26 weeks of gestation and 20 women between 31 and 36 weeks of gestation with normal singleton pregnancies were randomized to receive either 60% humidified oxygen or medical compressed air (room air) by a face mask. Fetal aortic and pulmonary valve; ductus arteriosus (DA); and right (RPA), left (LPA), and distal (DPA) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before, during, and after maternal administration of either 60% oxygen or room air. Left and right ventricular cardiac outputs, DA volume blood flow, and RPA and LPA volume blood flows (Qp) were calculated. Foramen ovale volume blood flow (left ventricular cardiac output-Qp) was estimated. Pulsatility index (PI) values of DA, RPA, LPA, and DPA were calculated. Maternal hyperoxygenation did not change any of the measured fetal parameters between 20 and 26 weeks, whereas between 31 and 36 weeks, the PI values of RPA, LPA, and DPA decreased (P<.0001) and the PI of DA increased (P<.0001). In addition, Qp increased (P<.001), and DA volume blood flow (P<.01) and foramen ovale volume blood flow (P<.03) decreased. Left and right ventricular cardiac outputs were unchanged. All changes returned to baseline after maternal hyperoxygenation was discontinued. CONCLUSIONS: Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases with advancing gestation; this suggests that fetal pulmonary circulation is under acquired vasoconstriction at least after 31 to 36 weeks of gestation.
Blood Flow Velocity↗
The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans.
In an attempt to identify proteins that might underlie membrane trafficking processes in ciliates, calcium-dependent, phospholipid-binding proteins were isolated from extracts of Paramecium tetraurelia. The major protein obtained, named copine, had a mass of 55 kDa, bound phosphatidylserine but not phosphatidylcholine at micromolar levels of calcium but not magnesium, and promoted lipid vesicle aggregation. The sequence of a 920-base pair partial cDNA revealed that copine is a novel protein that contains a C2 domain likely to be responsible for its membrane active properties. Paramecium was found to have two closely related copine genes, CPN1 and CPN2. Current sequence data bases indicate the presence of multiple copine homologs in green plants, nematodes, and humans. The full-length sequences reveal that copines consist of two C2 domains at the N terminus followed by a domain similar to the A domain that mediates interactions between integrins and extracellular ligands. A human homolog, copine I, was expressed in bacteria as a fusion protein with glutathione S-transferase. This recombinant protein exhibited calcium-dependent phospholipid binding properties similar to those of Paramecium copine. An antiserum raised against a fragment of human copine I was used to identify chromobindin 17, a secretory vesicle-binding protein, as a copine. This association with secretory vesicles, as well the general ability of copines to bind phospholipid bilayers in a calcium-dependent manner, suggests that these proteins may function in membrane trafficking.
Amino Acid Sequence↗
Scientists who fund themselves.
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History, 17th Century↗
Partial status epilepticus associated with asomatognosia and alien hand-like behaviors [corrected].
BACKGROUND: Paroxysmal alien hand syndrome (AHS) has been reported in association with ictal phenomena, but simultaneous electroencephalographic verification has not been made. OBSERVATION: A 61-year-old woman with a right hemisphere glioblastoma multiforme developed movements of the left hand that she claimed were not under her control, and she denied ownership of the affected limb. Simultaneous electroencephalograms documented continuous spikes in the right frontotemporal region. Intravenous diazepam therapy (2.5 mg) reversed both the abnormal movements and the spike activity on the electroencephalograms. CONCLUSIONS: Our case demonstrates that partial seizures can produce AHS along with asomatognosia. This variety of AHS appears to be different, both etiologically and phenomenologically, from other forms of AHS.
Aged↗
Selective loss of mouse embryos due to the expression of transgenic major histocompatibility class I molecules early in embryogenesis.
Among the numerous hypotheses proposed to explain the absence of fetal rejection by the mother in mammals, it has been suggested that regulation of expression of the polymorphic major histocompatibility complex (MHC) at the fetal-maternal interface plays a major role. In addition to a lack of MHC gene expression in the placenta throughout gestation, the absence of polymorphic MHC molecules on the early embryo, as well as their low level of expression after midgestation, could contribute to this important biologic phenomenon. In order to test this hypothesis, we have produced transgenic mice able to express polymorphic MHC class I molecules early in embryogenesis. We have placed the MHC class la gene H-2Kb under the control of a housekeeping gene promoter, the hydroxy-methyl-glutaryl coenzyme A reductase (HMG) gene minimal promoter. This construct has been tested for functionality after transfection into mouse fibroblast L cells. The analysis of three founder transgenic mice and their progeny suggested that fetoplacental units that could express the H-2Kb heavy chains are unable to survive in utero beyond midgestation. We have shown further that a much higher resorption rate, on days 11 to 13 of embryonic development, is observed among transgenic embryos developing from eggs microinjected at the one-cell stage with the pHMG-Kb construct than in control embryos. This lethality is not due to immune phenomena, since it is observed in histocompatible combinations between mother and fetus. These results are discussed in the context of what is currently known about the regulation of MHC expression at the fetal-maternal interface and in various transgenic mouse models.
Animals↗
Cryopreservation of unfertilized mouse oocytes: the effect of replacing sodium with choline in the freezing medium.
Although embryo cryopreservation has become commonplace in many species, effective methods are not available for routine freezing of unfertilized eggs. Cryopreservation-induced damage may be caused by the high concentration of sodium ions in conventional freezing media. This study investigates the effect of a newly developed low-sodium choline-based medium (CJ2) on the ability of unfertilized, metaphase II mouse eggs to survive cryopreservation and develop to the blastocyst stage in vitro. Specifically, the effects of cooling to subzero temperatures, thawing rate, LN2 plunge temperature, and equilibration with a low-sodium medium prior to freezing are examined. In contrast to cooling to 23, 0, or -7.0 degreesC in a sodium-based freezing medium (ETFM), cooling in CJ2 had no significant negative effect on oocyte survival or development. Oocytes frozen in CJ2 survived plunging into LN2 from -10, -20, or -33 degreesC at significantly higher rates than oocytes frozen in ETFM. With the protocol used (1.5 M PrOH, 0.1 M sucrose, -0.3 C/min, plunging at -33 degreesC) rapid thawing by direct submersion in 30 degreesC water was more detrimental to oocyte survival than holding in air for 30 or 120 s prior to transfer to water. Equilibration of unfertilized oocytes with a low-sodium medium prior to cryopreservation in CJ2 significantly increased survival and blastocyst development. These results demonstrate that the high concentration of sodium in conventional freezing media is detrimental to oocyte cryopreservation and show that choline is a promising replacement. Reducing the sodium content of the freezing medium to a very low level or eliminating sodium altogether may allow oocytes and other cells to be frozen more effectively.
Animals↗
Cytokine release and mitogenic activity in the viridans streptococcal shock syndrome.
Viridans streptococci are a heterogeneous group of Gram-positive bacteria that are normal inhabitants of the mouth, upper gastrointestinal tract and oropharynx. These organisms are typically thought of as of low virulence, classically as the cause of infective endocarditis, although recently they have been implicated in serious infections in other settings. In particular, viridans group streptococci have been described as responsible for the alpha-streptococcal shock syndrome in neutropenic patients. The mechanism by which viridans streptococci cause bacteraemia associated with adult respiratory distress syndrome (ARDS) in these patients has not been elucidated. Using enzyme-linked immunosorbent assays, we compared the ability of cell-free bacterial supernatants derived from commensal and clinical strains of viridans streptococci to induce the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha), tumour necrosis factor beta (TNF-beta) and interleukin 8 (IL-8) from human peripheral blood mononuclear cells (PBMC) in vitro. Supernatants of clinical isolates induced significantly more TNF-beta (P < 0.002) and IL-8 (P < 0.001) than did supernatants from commensal strains. The increased production of IL-8 by the clinical strains may be of importance in view of the role of IL-8 in the pathogenesis of the acute respiratory distress syndrome (ARDS), one of the principal clinical features of the alpha-streptococcal shock syndrome.
Adult↗
The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes.
Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family. Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated. The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha.
Aging↗
Appropriate timing and velocity of infusion for the selective staining of parathyroid glands by intravenous methylene blue.
BACKGROUND: Intraoperative parathyroid gland (PTG) identification by selective staining using methylene blue dye (MB) infusion has been shown effective but the degree of gland staining is inconsistent. METHODS: The effect of timing and rate of MB infusion on gland uptake was investigated in a canine model by infusing MB either rapidly over 3 to 5 minutes (n = 8) or slowly over 30 minutes (n = 4). The pattern of dye uptake in an exposed PTG was determined by standardized serial photography. RESULTS: Earliest uptake occurred between 10 and 20 minutes after infusion, and maximum uptake averaged 21 minutes, earlier than previously described. Rate of infusion did not affect staining. CONCLUSIONS: This rapid uptake of methylene blue by the parathyroid glands suggests that its selective intraoperative use when glands are difficult to locate intraoperatively, rather than a routine preoperative infusion, is possible without significant operative delay. Clinical experience has confirmed this impression.
Animals↗
First pregnancies after preconception diagnosis of translocations of maternal origin.
OBJECTIVE: To develop an approach to preimplantation diagnosis of translocations that would not require the use of specific DNA probes for each translocation type. DESIGN: Retrospective analysis. SETTING: Clinic. PATIENT(S): Two patients with 45XX,der(13;14)(q10;q10) karyotypes and one patient with a 46XX,t(4;14)(p15;q24) karyotype. INTERVENTION(S): Based on the observation that first polar body chromosomes remain at the metaphase stage for a few hours after oocyte retrieval, fluorescence in situ hybridization with chromosome-painting probes was used to perform preconception genetic diagnosis of translocation of maternal origin. MAIN OUTCOME MEASURE(S): Oocyte FISH analysis. RESULT(S): A total of 31 mature oocytes were produced, and results were obtained in 23 first polar bodies. After IVF-ET, all three patients became pregnant, preconception diagnoses being confirmed by prenatal diagnosis or birth. CONCLUSION(S): Preconception diagnosis of translocations may reduce significantly the risk of chromosomally unbalanced offspring and pregnancy loss. This method is simpler than previous approaches because the need to develop specific DNA probes for each translocation type is avoided.
Adult↗
Diagnostic yield and cost-effectiveness of endoscopy in chronic human immunodeficiency virus-related diarrhea.
BACKGROUND: Endoscopy is commonly performed in patients with chronic human immunodeficiency virus (HIV)-related diarrhea after negative stool studies. The aim of this study was to determine the diagnostic yield and cost-effectiveness of endoscopy in this setting. METHODS: Consecutive HIV-infected patients with chronic unexplained diarrhea who were referred for diagnostic endoscopy were identified. Patient charts, pathology reports, and endoscopy records were reviewed. RESULTS: A total of 479 endoscopic procedures were performed in 307 patients. A pathogen was identified in 147 patients (47.9%); cytomegalovirus was the most frequent organism found (21.5%). The average cost of identifying a pathogen by endoscopy was $3822.94. Colonoscopy had a greater diagnostic yield than flexible sigmoidoscopy (38.7% vs. 22.4%, p = 0.009) and was more cost-effective. The yield of upper endoscopy was 29.6%. In patients with a CD4 count of less than 100/mm3, endoscopy had a higher diagnostic yield (62.8% vs. 8.3%, p < 0.0001) and a lower cost of identifying a pathogen ($2943.92 vs. $21,583.51) than in those with higher CD4 counts. CONCLUSIONS: Endoscopy frequently identifies a pathogen in HIV-related chronic diarrhea. Colonoscopy is the most cost-effective procedure. Endoscopic evaluation has a significantly higher diagnostic yield and is considerably more cost-effective in patients with a CD4 count of less than 100/mm3 than in those with higher CD4 counts.
AIDS-Related Opportunistic Infections↗
Phosphorylation polymorphism in the yolk protein 2 of Drosophila hawaiiensis.
An intraspecific polymorphism in the electrophoretic migration pattern of the yolk proteins in D. hawaiiensis was established and characterized. The polymorphism includes yolk protein migration patterns of two, three, or four bands by polyacrylamide gel electrophoresis. Peptide mapping analysis demonstrates that in the two band migration pattern YP2 comigrates with YP3, whereas in the three and four band migration patterns YP2 migrates between YP1 and YP3 in addition to comigrating with YP3. It further demonstrates that the top two bands of the four band migration pattern consists of YP1. Phosphatase treatment of the yolk proteins establishes that the different electrophoretic migration patterns of YP2 are caused by different degrees of phosphorylation. It is suggested that the YP1 polymorphism is caused by a yp1 gene modification and that the YP2 polymorphism is caused by two different post-translational processing paths.
Journal Article↗
An EORTC multicentre prospective survey of invasive aspergillosis in haematological patients: diagnosis and therapeutic outcome. EORTC Invasive Fungal Infections Cooperative Group.
OBJECTIVES: The EORTC Invasive Fungal Infections Cooperative Group (IFICG) conducted a prospective survey by questionnaire of all cases of invasive aspergillosis (IA) in cancer patients to ascertain current diagnostic and therapeutic approaches. METHODS: All members of the IFICG were asked prospectively to complete a detailed questionnaire for each IA case identified in their institution over a 12-month period. RESULTS: One hundred and thirty questionnaires were returned. All cases were independently evaluated (DWD & JC) and 123 were eligible. Cases came from 20 hospitals in eight countries and the number of cases per institution varied from 1-21. Acute myeloid leukaemia (AML) (60, 49%), acute lymphoblastic leukaemia (ALL) (21, 17%) and lymphoma (11, 9%) were the most frequent underlying diseases, and 16 (12%) patients had received an allogeneic bone marrow transplant. Pulmonary involvement was present in 87%, infection of sinuses/nose in 16% and brain in 8%. The chest radiograph was initially normal in 9% of those with primary pulmonary disease. The diagnosis was confirmed in 50%, probable in 31% and possible in 19%. The evidence for IA was on the basis of clinical and radiological features alone in 28%, with culture or histology in another 31% and 9%, respectively, and with both culture and histology in 29%. In three (2%) patients with diagnosis was based on culture or histology alone. Treatment was given to 120 patients (98%)-amphotericin B 75%, lipid-associated amphotericin B 36%, itraconazole 40%, flucytosine 12%, growth factors 33%, lobectomy 5%. At 3 months after diagnosis or first suspicion of IA, 44 (36%) patients were alive and 79 (64%) dead. Outcome was best in those with AML (30% death and 46% with a complete antifungal response or cure). Growth factors (mostly granulocyte colony stimulating factor) appeared not to influence outcome (P = 0.99). CONCLUSION: IA remains a considerable diagnostic and therapeutic challenge. No single diagnostic procedure was universally successful and a multifaceted approach including surgery is necessary. There was no discernable difference in outcome between initial therapy with amphotericin B, itraconazole or lipid-associated amphotericin B, although numbers are limited and the study was retrospective.
Adolescent↗
The clinical significance of T-cell superantigens.
Superantigens are a diverse collection of molecules that share the ability to activate specific lymphocyte subsets. In animal models, many of these molecules delete T-cell populations or render them anergic. The clinical impact of superantigens is significant, but much of their pathophysiology remains unclear.
Animals↗
Neuromodulation and cognitive performance: recent studies of noradrenergic locus ceruleus neurons in behaving monkeys.
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Animals↗
Impaired development of zygotes with uneven pronuclear size.
The correlation between human zygote morphology and chromosomal anomalies after cleavage has not been well characterised. Commonly observed morphological qualities at the zygote stage have provided little insight into further development, and therefore selection for cryopreservation or transfer appears to be less specific than that at later stages of preimplantation development. The purpose of this work was to evaluate the relationship between aberrant pronuclear morphology and chromosomal anomalies after cleavage. Monospermic zygotes exhibiting two pronuclei where diameters differed by at least 4 microns were found to arrest at a significantly higher rate than zygotes with pronuclear diameters differing by less than 4 microns. In addition, a higher incidence of day 2 multinucleation was observed. Embryos deriving from zygotes with dysmorphic pronuclei that were not replaced or cryopreserved by day 3 of development were separated and fixed for fluorescence in situ hybridisation analysis of chromosomes X, Y, 13, 18 and 21. A significantly higher incidence of mosaicism was found in this group compared with others that had developed from zygotes with normal pronuclear morphology. Although the mechanism leading to this form of divergent pronuclear morphology is unclear, results suggest a correlation with oocyte cytoplasmic immaturity.
Cell Nucleus↗