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J Cohen

Publications and source records attributed to J Cohen.

At least 217 records · Page 12Linked to original sources

Mitochondrial DNA heteroplasmy after human ooplasmic transplantation.

OBJECTIVE: To determine the patterns of mitochondrial inheritance in embryos, fetuses, and infants after ooplasmic transplantation using the technique of mitochondrial DNA (mtDNA) fingerprinting. DESIGN: Prospective clinical study. SETTING: The IVF program at Saint Barnabas Medical Center, a nonprofit community hospital. PATIENT(S): In a total of 23 cases with recurrent implantation failure after IVF ooplasmic transplantation was performed. Thirteen embryos from two patients and amniotic cells from four patients were investigated for heteroplasmy. Placenta and fetal cord blood cells from four newborn babies/infants were also investigated. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): mtDNA fingerprinting, polymerase chain reaction, and DNA sequencing analysis. RESULT(S): In addition to the recipient maternal mitochondrial DNA, a small proportion of donor mitochondrial DNA was detected in samples with the following frequencies: embryos (n = 6/13), amniocytes (n = 1/4), placenta (n = 2/4), and fetal cord blood (n = 2/4). Fingerprinting showed that nuclear DNA was not inherited from the donor in placenta or fetal cord blood of the babies. CONCLUSION(S): Ooplasmic transfer can result in sustained mtDNA heteroplasmy representing both donor and recipient. This was shown by mtDNA fingerprinting of embryos, amniocytes, fetal placenta, and cord blood. These results show that the donor-derived mitochondrial population persists after ooplasmic transfer and may be replicated during fetal development.

Cytoplasm↗

Sperm deposition site during ICSI affects fertilization and development.

OBJECTIVE: To evaluate the effects of sperm placement during ICSI relative to the M-II spindle location on fertilization and preimplantation development. DESIGN: Retrospective analysis of oocyte fertilization and embryo development with respect to sperm deposition site during ICSI. SETTING: A program of IVF-ET. PATIENT(S): Seven hundred seventy-six patients. INTERVENTION(S): Egg quality, sperm deposition site, and polar-body position were recorded during ICSI; fertilization was assessed on day 1; embryo development was evaluated on days 2 and 3. MAIN OUTCOME MEASURE(S): Fertilization, embryo development, and implantation rates. RESULT(S): Normal fertilization is not affected by polar-body orientation, with the exception of a significantly lower fertilization rate from a 9 o'clock polar-body orientation. Injections with the polar-body positioned at 7 or 11 o'clock result in the greatest number of high-quality embryos, significantly more than the adjacent 6 or 12 o'clock polar-body orientations and irrespective of oocyte anomaly frequency. Embryos originating from the 7 or 11 o'clock polar-body category implant at a higher rate, although the data are not significant. CONCLUSION(S): The placement of the sperm during ICSI relative to the presumed location of the meiotic spindle significantly impacts fertilization and high-quality embryo development. Sperm deposition in the M-II spindle area should be avoided. It appears that development, and not fertilization, is improved by decreasing the distance between the sperm cell and the spindle.

Cell Nucleus↗

A randomized, double-blind study of the use of droperidol for conscious sedation during therapeutic endoscopy in difficult to sedate patients.

BACKGROUND: Droperidol has been used in combination with narcotics and benzodiazepines to achieve conscious sedation. We performed a randomized, double-blind, study of droperidol in patients at risk for difficult sedation scheduled for therapeutic endoscopy. METHODS: Patients with regular ethanol, narcotic, or benzodiazepine usage, suspected sphincter of Oddi dysfunction, or a history of difficult sedation were eligible for the study. Patients were randomized to receive either droperidol or placebo along with midazolam and meperidine as preprocedure sedation. Time to achieve sedation, interruptions due to undersedation, medication dosages, recovery time, and subjective assessments of sedation were recorded. RESULTS: One hundred one patients were randomized. The droperidol group had significantly fewer procedure interruptions and observer ratings of difficulty with sedation and required significantly less midazolam (23%) and meperidine (16%) than the placebo group. There were no significant differences in time to achieve sedation, incomplete procedures, procedure length, recovery room time, or complications. There were significantly higher observer ratings of the quality of sedation for patients who received droperidol. CONCLUSIONS: Droperidol is a useful adjunct to conscious sedation in patients who are difficult to sedate. Its use results in significantly fewer interruptions due to poor sedation and improved sedation ratings compared with sedation using midazolam and meperidine alone.

Adjuvants, Anesthesia↗

[Clinical significance of antiribosomal antibodies. Study Group on Autoimmunity (GEAI)].

PURPOSE: Autoantibodies directed against the ribosomal P proteins, P0, P1 and P2 (anti-P), have been related to lupus-related psychosis and/or depression. The diagnostic value of antibodies directed against other ribosomal proteins or 28S RNA (anti-no-P) remains unknown. A multicenter study including ten centers belonging to the study group for autoimmune diseases (GEAI) was conducted in order to determine the diagnostic value of anti-P and anti-no-P antibodies in a large population of patients. METHODS: The patients were selected on the basis of the presence of serum anti-ribosomal antibodies detected by indirect immunofluorescence (IF) on rat liver/kidney/stomach/pancreas sections and human HEp2 cells. The clinical course of all patients was studied using a predetermined survey. The specificity of anti-P antibodies were determined by Western blot. RESULTS: Anti-ribosomal antibodies were found in 82 patients. Fifty-five of them had systemic lupus erythematosus and 27 had another disease. Only 54% of the anti-ribosomal antibodies detected by IF were anti-P and were found in 69% of the patients with systemic lupus erythematosus. Anti-no-P antibodies (46%) were preferably detected in patients who suffered from another disease (78%). In patients with systemic lupus erythematosus, neurological and psychiatric disorders were more frequent in the no-P group (47% vs. 16%, P < 0.01) than arthritis, which was found more frequently in the P group (78% vs. 53%, P < 0.05). CONCLUSION: Anti P antibodies do not constitute a specific diagnostic marker of systemic lupus erythematosus, and lupus-related neuropsychiatric disorders would be preferably associated with the presence of anti no-P antibodies.

Animals↗

ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy.

Angiotensin-converting enzyme inhibitors (ACEi) are a class of antihypertensive agents that decrease mortality in congestive heart failure and have established efficacy in the treatment of hypertension and the slowing of established diabetic nephropathy and other proteinuria-associated glomerulonephritides. These drugs have not gained wide acceptance in the treatment of hypertension in renal transplant recipients (RTRs) because of a potential for decreased renal blood flow and glomerular filtration rate associated with a single kidney and concomitant cyclosporine use. Experimental animal models suggest that ACEi may be of benefit in slowing the progression of chronic renal allograft rejection. We undertook a retrospective chart analysis of all RTRs in our institution who had been treated with an ACEi or an angiotensin II (AT II) antagonist, with the objectives of determining the safety, efficacy, and side effect profile of these medications. The minimum follow-up period was 6 months. One hundred seventy-seven of 642 RTRs were prescribed an ACEi or AT II antagonist. Forty-seven patients discontinued therapy, with the most common causes of discontinuation being cough (8 patients) and hyperkalemia (6 patients). The mean arterial blood pressure at each follow-up period was lower than that at the time of initiation of ACEi or AT II antagonist therapy, with a decrease from 92 +/- 12 mm Hg to 86 +/- 9 mm Hg (P < 0.05) after 3 years of treatment. The serum creatinine concentrations did not change throughout the follow-up period. There was a nonsustained increase from the baseline serum potassium of 4.4 +/- 0.5 to 4.6 +/- 0.6 mEq/L at 3 months (P < 0.05), but no further increases in potassium beyond this time. The mean hemoglobin concentration for the cohort did not change, but 13 RTRs given an ACEi for posttransplantation erythrocytosis (PTE) had a decrease in hemoglobin from 17.1 +/- 1.0 g/dL at the start of ACEi therapy to 14.8 +/- 2.2 g/dL at 3 years (P < 0.05). ACEi and AT II antagonists were generally effective antihypertensives, and were safe and well-tolerated agents in this cohort of RTRs. ACEi were also effective in the treatment of PTE.

Adult↗

Molecular genetics of regulated secretion in paramecium.

Paramecium is a unicell in which cellular processes are amenable to genetic dissection. Regulated secretion, which designates a secretory pathway where secretory products are first stored in intracellular granules and then released by exocytotic membrane fusion upon external trigger, is an important function in Paramecium, involved in defensive response through the release of organelles called trichocysts. In this review, we focus on recent advances in the molecular genetics of two major aspects of the regulated pathway in Paramecium, the biogenesis of the secretory organelles and their exocytosis.

Animals↗

Inhibition of farnesyltransferase with A-176120, a novel and potent farnesyl pyrophosphate analogue.

Farnesylation of Ras is required for its transforming activity in human cancer and the reaction is catalysed by the enzyme farnesyltransferase. Recently, we discovered a novel chemical series of potent farnesyl pyrophosphate (FPP) analogues which selectively inhibited farnesyltransferase. Our most potent compound to date in this series, A-176120, selectively inhibited farnesyltransferase activity (IC(50) 1.2+/-0.3 nM) over the closely related enzymes geranylgeranyltransferase I (GGTaseI) (IC(50) 423+/-1.8 nM), geranylgeranyltransferase II (GGTaseII) (IC(50) 3000 nM) and squalene synthase (SSase) (IC(50)>10000 nM). A-176120 inhibited ras processing in H-ras-transformed NIH3T3 cells and HCT116 K-ras-mutated cells (ED(50) 1.6 and 0.5 microM, respectively). The anti-angiogenic potential of A-176120 was demonstrated by a decrease in Ras processing, cell proliferation and capillary structure formation of human umbilical vein endothelial cells (HUVEC), and a decrease in the secretion of vascular endothelial growth factor (VEGF) from HCT116 cells. In vivo, A-176120 reduced H-ras NIH3T3 tumour growth and extended the lifespan of nude mice inoculated with H- or K-ras-transformed NIH3T3 cells. A-176120 also had an additive effect in combination with cyclophosphamide in nude mice inoculated with K-ras NIH3T3 transformed cells. Overall, our results demonstrate that A-176120 is a potent FPP mimetic with both antitumour and anti-angiogenic properties.

Alkyl and Aryl Transferases↗

A study of functional status among elders at two academic nursing centers.

Using the Older Americans Resources and Services (OARS) tool, this study examined quality of life related to functional status in 68 elderly clients at two community-based nurse-managed centers (NMCs) in California. Undergraduate and graduate nursing students administered the OARS to three cohort groups. Data from the tool were used to assess functional independence among these clients and organize and evaluate the quality of nursing care delivered at the centers. The study provides the basis for evidence-based nursing care that integrates research strategies and the nursing process.

Activities of Daily Living↗

Mitochondrial DNA point mutation in human oocytes is associated with maternal age.

Mitochondrial DNA (mtDNA) point mutations are known to accumulate in an age-dependent fashion in somatic tissues. This study investigated whether a point mutation (T414G) in the mtDNA control region was present in oocytes from women of advanced age. In all, 66 non-viable discarded human oocytes were analysed for the presence of a T414G transversion mutation. DNA sequence analysis confirmed the presence of this mutation in one oocyte from 11 patients between the ages of 26 and 36 years (n = 23), compared to 17 oocytes from 10 patients between the ages of 37 and 42 years (n = 43). The younger group exhibited this mtDNA point mutation in only 4.4% of oocytes compared to 39.5% from the older group (P < 0.01). Therefore, single human oocytes contain the mtDNA T414G transversion point mutation that accumulates in an age-dependent manner. The potential significance of this point mutation may be its association with reproductive senescence. Furthermore, since this mutation exists in the control region of the mtDNA it may affect the regulation of mtDNA transcription and replication during oocyte and post-embryonic development.

Journal Article↗

Quantification of mtDNA in single oocytes, polar bodies and subcellular components by real-time rapid cycle fluorescence monitored PCR.

Oocytes, in general, are greatly enriched in mitochondria to support higher rates of macromolecular synthesis and critical physiological processes characteristic of early development. An inability of these organelles to amplify and/or to accumulate ATP has been linked to developmental abnormality or arrest. The number of mitochondrial genomes present in mature mouse and human metaphase II oocytes was estimated by fluorescent rapid cycle DNA amplification, which is a highly sensitive technique ideally suited to quantitative mitochondrial DNA (mtDNA) analysis in individual cells. A considerable degree of variability was observed between individual samples. An overall average of 1.59 x 10(5) and 3.14 x 10(5) mtDNA molecules were detected per mouse and human oocyte, respectively. Furthermore, the mtDNA copy number was examined in polar bodies and contrasted with the concentration in their corresponding oocytes. In addition, the density of mtDNA in a cytoplasmic sample was estimated in an attempt to determine the approximate number of mitochondria transferred during clinical cytoplasmic donation procedures as well as to develop a clinical tool for the assessment and selection of oocytes during in vitro fertilisation procedures. However, no correlation was identified between the mtDNA concentration in either polar bodies or cytoplasmic samples and their corresponding oocyte.

Animals↗

Protection against Plasmodium falciparum malaria in chimpanzees by immunization with the conserved pre-erythrocytic liver-stage antigen 3.

In humans, sterile immunity against malaria can be consistently induced through exposure to the bites of thousands of irradiated infected mosquitoes. The same level of protection has yet to be achieved using subunit vaccines. Recent studies have indicated an essential function for intrahepatic parasites, the stage after the mosquito bite, and thus for antigens expressed during this stage. We report here the identification of liver-stage antigen 3, which is expressed both in the mosquito and liver-stage parasites. This Plasmodium falciparum 200-kilodalton protein is highly conserved, and showed promising antigenic and immunogenic properties. In chimpanzees (Pan troglodytes), the primates most closely related to humans and that share a similar susceptibility to P. falciparum liver-stage infection, immunization with LSA-3 induced protection against successive heterologous challenges with large numbers of P. falciparum sporozoites.

Animals↗

Fatal hepatitis and renal failure during treatment with nimesulide.

A healthy 70-year-old woman who took nimesulide for 5 days, presented 2 weeks later with jaundice for which no other cause was found. Laboratory evidence of coagulopathy, hypoalbuminaemia and hypoglycaemia were present on admission, and liver biopsy showed massive necrosis of hepatocytes and severe inflammatory infiltrate. Despite supportive and corticosteroid treatment, her jaundice deepened and progressive acute renal failure developed, characterized by a 'prerenal' profile changing into irreversible acute tubular necrosis pattern, coma, occult Gram-negative sepsis and death. Although rare, nimesulide-associated hepatotoxicity and nephrotoxicity may occur and should be recognized as early as possible, to ensure immediate drug withdrawal and treatment.

Acute Kidney Injury↗

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Journal Article↗