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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 37 records · Page 2Linked to original sources
PubMed2005

Expression of genes regulating chromosome segregation, the cell cycle and apoptosis during human preimplantation development.

BACKGROUND: Appropriate gene expression is vital for the regulation of developmental processes. Despite this fact there is a remarkable paucity of information concerning gene activity during preimplantation development. METHODS: We employed reverse transcription and real-time fluorescent PCR to quantify the expression of nine genes (BRCA1, BRCA2, ATM, TP53, RB1, MAD2, BUB1, APC and beta-actin) in oocytes and embryos. A full characterization of all genes was achieved in 42 embryos and four oocytes. The genes analysed have a variety of important cellular functions. RESULTS: Oocytes displayed relatively high levels of mRNA transcripts, while 2-3-cell embryos were seen to contain very little mRNA from any of the genes examined. Recovery of expression levels was not seen until the 4-cell stage or later, with the presumptive activation of the embryonic genome. Some genes displayed sharp increases in expression in embryos composed of 4-8 cells, but, for most, maximum expression was not achieved until the blastocyst stage. CONCLUSIONS: Our data show that it is possible to define characteristic gene expression profiles for each stage of human preimplantation development. The identification of genes active at defined preimplantation phases may provide clues to the cellular pathways utilized at specific stages of development. Expression of genes that function in DNA repair pathways indicate that DNA damage may be common at the cleavage stage. We suggest that specific patterns of gene expression may be indicative of embryo implantation potential.

Apoptosis↗
PubMed2005

Preoperative colonoscopy decreases the need for laparoscopic management of colonic polyps.

PURPOSE: Patients are commonly referred to surgeons for surgical resection of polyps that cannot be excised colonoscopically. Repeating the colonoscopy may be met with resistance by both the patient and the referring endoscopist. However, there are two distinct benefits. First, if the lesion was not marked, tattooing facilitates laparoscopic resection. Second, and more importantly, many of these polyps can be removed endoscopically by an experienced colorectal surgeon, avoiding unnecessary colon resection. Over a period of five years, we have reviewed preoperative colonoscopy in patients who were referred for surgical treatment of benign polyps. METHODS: From January 1999 through September 2003 all patients referred for surgical resection of a benign polyp were consecutively entered into a database by a single group of colorectal surgeons. All patients underwent preoperative colonoscopy on the day before the planned colon resection. Patient charts were reviewed, and demographics were recorded. The referral and preoperative colonoscopy reports and all pathology results were reviewed to record the polyp size, location, histology, and subsequent treatment. RESULTS: Altogether, 71 patients were included in this study. The average size of the polyps was 24 mm (range, 10-60 mm). The location of the polyp as determined by preoperative colonoscopy differed from the location noted on referral colonoscopy in nine patients (13 percent). Surgery was canceled in 23 patients (32 percent), primarily because of complete polypectomy at preoperative colonoscopy. Of the 48 who underwent surgery, 23 (47 percent) had a colonic tattoo placed, at the discretion of the surgeon. Lesions clearly located in the cecum were not tattooed routinely. Of the 48 patients who underwent surgery, 45 (94 percent) underwent laparoscopic colon resection. CONCLUSIONS: We concluded that patients referred for surgical resection of a polyp should undergo repeat colonoscopy preoperatively, given that in our study one-third of patients were spared unnecessary colectomy. In addition, repeat endoscopy by the operating surgeon offers an opportunity to confirm the location of the lesion and place a colonic tattoo to facilitate laparoscopic resection.

Aged↗
PubMed2005

SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA.

Long-lasting alternative splicing of neuronal acetylcholinesterase (AChE) pre-mRNA occurs during neuronal development and following stress, altering synaptic properties. To explore the corresponding molecular events, we sought to identify mRNAs encoding for abundant splicing factors in the prefrontal cortex (PFC) following stress. Here we show elevated levels of the splicing factor SC35 in stressed as compared with naïve mice. In cotransfections of COS-1 and HEK293 cells with an AChE minigene allowing 3' splice variations, SC35 facilitated a shift from the primary AChE-S to the stress-induced AChE-R variant, while ASF/SF2 caused the opposite effect. Transfection with chimeric constructs comprising of SC35 and ASF/SF2 RRM/RS domains identified the SC35 RRM as responsible for AChE mRNA's alternative splicing. In poststress PFC neurons, increased SC35 mRNA and protein levels coincided with selective increase in AChE-R mRNA. In the developing mouse embryo, cortical progenitor cells in the ventricular zone displayed transient SC35 elevation concomitant with dominance of AChE-R over AChE-S mRNA. Finally, transgenic mice overexpressing human AChE-R, but not those overexpressing AChE-S, showed significant elevation in neuronal SC35 levels, suggesting a reciprocal reinforcement process. Together, these findings point to an interactive relationship of SC35 with cholinergic signals in the long-lasting consequences of stress on nervous system plasticity and development.

Acetylcholinesterase↗
PubMed2005

Approaches to developing biological H(2)-photoproducing organisms and processes.

The development of efficient biological systems for the direct photoproduction of H(2) gas from water faces several challenges, the more serious of which is the sensitivity of the H(2)-evolving enzymes (hydrogenases) to O(2), an obligatory by-product of photosynthesis. This high sensitivity is common to both FeFe and NiFe hydrogenases, and is caused by O(2) binding to their respective metallocatalytic sites. This overview describes approaches to (i) molecular engineering of algal FeFe-hydrogenase to prevent O(2) access to its catalytic site; (ii) transform a cyanobacterium with an O(2)-tolerant bacterial NiFe hydrogenase or (c) partially inactivate algal O(2)-evolution activity to create physiologically anaerobiosis and induce hydrogenase expression.

Animals↗
PubMed2005

Molecular dynamics and experimental investigation of H(2) and O(2) diffusion in [Fe]-hydrogenase.

The [Fe]-hydrogenase enzymes are highly efficient H(2) catalysts found in ecologically and phylogenetically diverse microorganisms, including the photosynthetic green alga, Chlamydomonas reinhardtii. Although these enzymes can occur in several forms, H(2) catalysis takes place at a unique [FeS] prosthetic group or H-cluster, located at the active site. Significant to the function of hydrogenases is how the surrounding protein structure facilitates substrate-product transfer, and protects the active site H-cluster from inactivation. To elucidate the role of protein structure in O(2) inactivation of [Fe]-hydrogenases, experimental and theoretical investigations have been performed. Molecular dynamics was used to comparatively investigate O(2) and H(2) diffusion in CpI ([Fe]-hydrogenase I from Clostridium pasteurianum). Our preliminary results suggest that H(2) diffuses more easily and freely than O(2), which is restricted to a small number of allowed pathways to and from the active site. These O(2) pathways are located in the conserved active site domain, shown experimentally to have an essential role in active site protection.

Catalysis↗
PubMed2005

Objective benefit of a 1-day training course in endoscopic hemostasis using the "compactEASIE" endoscopy simulator.

BACKGROUND AND STUDY AIMS: The Erlangen Active Simulator for Interventional Endoscopy (EASIE) was introduced in 1997 as a training model for interventional endoscopy. Objective evidence of the benefits of training with this model has not previously been published. As part of two long-term projects, the benefits of a 1-day training course with the "compactEASIE" simulator were evaluated. MATERIALS AND METHODS: Fourteen American and 18 French gastroenterology fellows were enrolled. These fellows were participants in the intensive groups performing training in endoscopic hemostasis, with a total number of 28 fellows in New York and 36 in France. Gastrointestinal endoscopy faculty members in New York and France evaluated and timed the fellows in four disciplines to establish baseline skills (manual skills; injection and coagulation; Hemoclip application; and variceal ligation) with the compactEASIE simulator. The trainees were reevaluated after an intensive 1-day course (with two or three fellows and one instructor per station), also including preparation and assistance for each procedure. The assessment (overall and parts) was done by expert tutors using an ordinal scale ranging from 1 to 10 (1 = poorest, 10 = best), recording also mistakes and performance time. The compactEASIE simulator, equipped with an upper gastrointestinal organ package and an artificial blood perfusion system, was used as the training tool. RESULTS: A highly significant improvement ( P < or = 0.001) was observed in the performance of all endoscopic techniques. A significant reduction in performance time was also observed with three of the four endoscopic techniques. Successful hemostasis was significantly improved in two out of three techniques. CONCLUSIONS: A 1-day training course on endoscopic hemostasis using the compactEASIE simulator is capable of improving the performance of hemostasis procedures. Long-term effects of repeated training sessions are currently subject of collaborative studies in New York and France.

Clinical Competence↗
PubMed2005

Relationship of granulocyte colony stimulating factor with other acute phase reactants in man.

The non-specific acute phase response in mice is associated with increased resistance to bacterial infection, which is critically mediated by granulocyte colony stimulating factor (G-CSF), but the behaviour of G-CSF in the human acute phase response is not known. Cardiothoracic surgery is a powerful acute phase stimulus and we show here that this procedure caused increased production of G-CSF, in addition to increases in the circulating concentrations of the proinflammatory cytokine interleukin (IL)-6 and the acute phase plasma proteins C-reactive protein (CRP) and serum amyloid A protein (SAA). Values of G-CSF correlated positively with IL-6 concentrations and circulating neutrophil counts, but not with CRP values. These results confirm that G-CSF is a physiological component of the acute phase response in humans that shares some of the same regulatory controls as IL-6, but its downstream effects are on neutrophils, not hepatic acute phase protein synthesis. Our observations are compatible with a protective role against bacterial infection for G-CSF in the human acute phase response, and support investigation of the prophylactic use of G-CSF in at-risk patients.

Acute-Phase Proteins↗
PubMed2005

Development of a time-to-positivity assay as a tool in the antibiotic management of septic patients.

Optimal use of antibiotics is a key component of the management of sepsis. The purpose of this study was to develop a modification of the time-to-positivity (T(pos)) assay for use in the acute management of septic patients. Initial laboratory experiments, followed by ex-vivo validation and pilot studies, were performed with a small number of healthy human volunteers and 46 septic patients on a general intensive care unit, chosen on the basis of their antibiotic regimen. The study demonstrated that the T(pos) assay could be used as a surrogate for antimicrobial activity, and provided preliminary data to demonstrate how this approach might be used to monitor the efficacy of antibiotic therapy in septic patients. The T(pos) assay might offer a quick and convenient way to improve the efficacy of antibiotic therapy in septic patients, and further prospective large-scale studies are now warranted.

Anti-Bacterial Agents↗
PubMed2004

Taskforce 8: ethics of medically assisted fertility treatment for HIV positive men and women.

In this 8th statement of the ESHRE Taskforce on Ethics and Law, the focus is on the ethical issues raised by (assisted) reproduction for HIV positive men and women. Due to treatment improvements, their life expectancy has increased substantially. This, in combination with the reduction of perinatal transmission to the child, makes the creation of a family more acceptable. Recommendations are made concerning methods of avoiding HIV transmission in the couple and to their offspring. It is concluded that, if certain precautions are taken, medical assistance to reproduction of HIV positive people is ethically acceptable. For the time being, only cases of serodiscordant couples should be considered.

Anti-Retroviral Agents↗
PubMed2004

An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis.

Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole.

Adolescent↗
PubMed2004

Predictability of preimplantation genetic diagnosis of aneuploidy and translocations on prospective attempts.

The aim of this study was to determine if the outcomes of aneuploidy and translocation testing by preimplantation genetic diagnosis (PGD) at the 8-cell stage have a predictive value for new genetic diagnosis cycles. In total, 83 cycles (39 patients) undergoing PGD of translocations and 378 cycles (176 patients) of aneuploidy were included. Predictability, defined as having similar rate (+/-20%) of euploid embryos in the first and successive cycles, was found in 66% of patients undergoing aneuploidy testing. Predictability was found significantly more often in patients undergoing PGD of translocations (90%, P = 0.006). In addition, patients with 0, <30 or > or =30% euploid embryos in the first cycle were compared and groups 0 and <30% had significantly fewer euploid embryos in the second cycle (22-26%) than those of the group with > or =30% (37%) (P < 0.05). Patients who did not become pregnant after the first attempt were stimulated more aggressively than those becoming pregnant, producing significantly more embryos in the second than in the first cycle (P < 0.001). Therefore, correlation between euploidy rate and pregnancy rate could not be assessed objectively between cycles. In conclusion, the PGD results of a first cycle can predict the results of the second cycle, but this is likely to be of more value when the condition investigated is translocation rather than aneuploidy. The chance of pregnancy is usually related to the number of euploid embryos.

Abortion, Habitual↗
PubMed2004

Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia.

Vaccination of malaria-naive humans with recombinant RTS,S/AS02, which includes the C-terminus of the circumsporozoite protein (CS), has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS. Here we show that strong T cell responses were also observed in a semi-immune population in The Gambia, West Africa. In a Phase I study, 20 adult male volunteers, lifelong residents in a malaria-endemic region, were given three doses of RTS,S/AS02 at 0, 1 and 6 months. Responses to RTS,S, hepatitis B surface antigen and peptides from CS were tested using lymphocyte proliferation, interferon (IFN)-gamma production in microcultures, and IFN-gamma ex vivo and cultured ELISPOT, before and after vaccination. Cytotoxic responses were tested only after vaccination and none were detected. Before vaccination, the majority of the volunteers (15/20) had detectable responses in at least one of the tests. After vaccination, responses increased in all assays except cytotoxicity. The increase was most marked for proliferation; all donors responded to RTS,S after the third dose and all except one donor responded to at least one peptide after the second or third dose. There was a lack of close association of peptide responses detected by the different assays, although in microcultures IFN-gamma responses were found only when proliferative responses were high, and responses by cultured ELISPOT and proliferation were found together more frequently after vaccination. We have therefore identified several peptide-specific T cell responses induced by RTS,S/AS02 which provides a mechanism to investigate potentially protective immune responses in the field.

Adolescent↗