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Biomedical subjects

A Benjamin

Publications and source records attributed to A Benjamin.

At least 19 recordsLinked to original sources
PubMed2005

Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay.

Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane--an early hallmark of apoptosis--and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.

Animals↗
PubMed2005

Mutation scanning of the p53 tumor suppressor gene in renal and liver transplant patients in Hungary.

INTRODUCTION: The increased incidence of malignancies among transplanted patients is well known. Abnormal function of the p53 tumor suppressor gene has been reported in more than half of all tumors. The aim of our study was to detect point mutations of p53 gene in transplanted patients because the presence of mutations may be a predictive factor for tumor development. An earlier diagnosis can help to develop new strategies for immunosuppressive therapies. METHODS: Three point mutations were chosen based on the literature: exon5-codon175, exon7-codon248, exon8-codon273. Genomic DNA from the plasma of 60 liver, 362 renal transplants, and 45 nontransplanted patients with different tumors and 20 suspected healthy patients were analyzed with a real-time PCR method using the Roche LightCycler. The mutations were evaluated by melting curve analysis. RESULTS: We elaborated a special protocol for scanning the above mentioned p53 point mutations, which were proved by sequencing as well. Among 487 patients, 486 showed a wild-type genotype. The only patient carrying a mutation at codon 273 (heterozygous) was a liver transplant patient, who developed pancreas carcinoma and had already died. CONCLUSION: Our data suggest that mutations of the targeted codons in leukocyte DNA seem to be rare, but a mutation could be lethal. The evaluated three point mutations of p53 gene were not predictive for tumor development.

Base Sequence↗
PubMed2003

Obstetric implications of low-lying placentas diagnosed in the second trimester.

OBJECTIVES: To determine the obstetrical outcome of pregnancies initially complicated by a low-lying placenta in the second trimester. METHODS: We reviewed the obstetric outcome of all women with singleton deliveries from 1 January 1997 to 31 March 1999 and compared the 703 women with low-lying placentas (placentas in the lower uterine segment) with the 6938 women with placentas that were normally situated in the upper uterine segment at 16-22 weeks' gestation. RESULTS: Pregnancies complicated by a low-lying placenta in the second trimester were not associated with antepartum hemorrhage, preterm births, preterm prelabor rupture of membranes, pregnancy-induced hypertension, fetal growth restriction or cesarean births. However, they had a higher incidence of postpartum hemorrhage (odds ratio 1.768, 95% confidence interval 1.137, 2.748) than women with a normally situated placenta in the second trimester. CONCLUSIONS: Pregnant women with low-lying placentas in the second trimester have a higher incidence of postpartum hemorrhage and hence, it would be prudent to carefully manage the third stage of labor in these women.

Adult↗
PubMed2001

Outcome of pregnancy in women with hereditary thrombophilia.

OBJECTIVES: The aims of this study are to review the outcome of pregnancy in women with thrombophilia, and investigate the possible beneficial effect of heparin therapy in these women. METHODS: We reviewed the hospital records of 126 women who were referred to the high-risk obstetrical hematology clinic between June 1996 and December 1999. The placental histology and outcome of 39 pregnancies in 24 women with hereditary thrombophilia were studied, and pregnancies which were treated with heparin were compared with those without treatment. RESULTS: An adverse pregnancy outcome occurred in 54% of the pregnancies. All seven miscarriages (18%) occurred in pregnancies that were not treated with heparin. However, heparin treatment did not prevent the development of obstetric complications in later pregnancies (odds ratio=0.955, 95% C.I.=0.255-3.577, Fisher's exact test). Excluding miscarriages, 28% of the placentas had thrombotic lesions, and the pregnancies with placental thrombotic lesions were more likely to have complications than those pregnancies without placental abnormalities (P=0.023, C.I.=1.257-5.197, Fisher's exact test). CONCLUSIONS: Pregnancy complications in cases of hereditary thrombophilia may be related to placental abnormalities. Heparin therapy is likely to be useful in preventing miscarriage in cases of hereditary thrombophilia.

Activated Protein C Resistance↗
PubMed2001

Socio-economic disparities in preterm birth: causal pathways and mechanisms.

Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.

Adult↗
PubMed2001

Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality.

Valproate (VPA) is an effective, widely used antiepileptic drug. Unfortunately its use in pregnant women is associated with neural tube defects in the offspring. Although the etiology of neural tube defects is multifactorial, there is evidence that underlying genetic susceptibility plays a part. We describe two women taking moderate doses of VPA who repeatedly bore children with neural tube defects, despite folate supplementation. This suggests a pharmacogenetic susceptibility to the teratogenic effects of VPA.

Adult↗
PubMed2001

Lung cancer in pregnancy: case reports and review of the literature.

Lung cancer diagnosed in pregnancy is rare. The number of reported cases has been escalating in recent years, probably reflecting the increasing number of women of reproductive age who smoke. This review presents three cases of lung cancer in pregnancy with different manifestations and outcomes, with a review of the literature. Physicians should have a low threshold using different diagnostic tools for investigating unusual symptoms during pregnancy without fear for fetal safety. Once diagnosed, lung cancer represents a major ethical and medical dilemma. The optimal management of lung cancer in pregnancy is not known, because of the rarity of the cases reported during pregnancy and insufficient follow-up data.

Adenocarcinoma↗
PubMed1999

Obstetric admissions to the intensive care unit.

OBJECTIVE: To determine whether obstetric admissions to the intensive care unit (ICU) are useful quality-assurance indicators. METHODS: We analyzed retrospectively obstetric ICU admissions at two tertiary care centers from 1991 to 1997. RESULTS: The 131 obstetric admissions represented 0.3% of all deliveries. The majority (78%) of women were admitted to the ICU postpartum. Obstetric hemorrhage (26%) and hypertension (21%) were the two most common reasons for admission. Together with cardiac disease, respiratory disorders, and infection, they accounted for more than 80% of all admissions. Preexisting medical conditions were present in 38% of all admissions. The median Acute Physiology and Chronic Health Evaluation II score was 8.5. The predicted mortality rate for the group was 10.0%, and the actual mortality rate was 2.3%. CONCLUSION: The most common precipitants of ICU admission were obstetric hemorrhage and uncontrolled hypertension. Improved management strategies for these problems may significantly reduce major maternal morbidity.

Adult↗
PubMed1997

Uveitis as the only clinical manifestation of poststreptococcal syndrome.

PURPOSE: To report a case of streptococcal infection of the upper respiratory tract in which bilateral anterior uveitis was the only complication. METHOD: Serologic documentation of post-streptococcal immune disease. The duration of inflammation was consistent with other forms of poststreptococcal immune disease. RESULTS: Bilateral anterior uveitis was treated with corticosteroids alone and resolved without ophthalmic complications. CONCLUSION: Bilateral anterior uveitis may be the only clinical manifestation of poststreptococcal syndrome.

Adolescent↗
PubMed1996

Successful pregnancy complicated by peritonitis in a 35- year old CAPD patient.

A 35-year old woman conceived six months after initiating continuous ambulatory peritoneal dialysis (CAPD). A medical plan was developed to give the patient adequate dialysis for a 1.5 g/kg/day protein intake. In addition, alterations in calcium, magnesium, and erythropoietin administration were required to reach the objectives set by the obstetrical/renal team. Three weeks prior to delivery, an amniotic leak developed, and vaginal cultures were positive for Escherichia coli. Oral amoxicillin was administered (500 mg per os q.i.d.) until the day of delivery. A 1545-g baby girl was delivered by cesarean section at 32 weeks. Five days postpartum the patient developed severe peritonitis, which subsequently grew E. coli. The patient fully recovered from the peritonitis, but catheter removal was required. Successful pregnancy can be expected on CAPD, and adequacy can be achieved with aggressive dialysis. Cesarean section delivery should probably be accompanied by full peritonitis therapy.

Administration, Oral↗
PubMed1993

Caesarean section and phaeochromocytoma resection in a patient with Von Hippel Lindau disease.

This report describes the anaesthetic management of a women with a term gestation, Von Hippel Lindau disease (VHLD), and a phaeochromocytoma, scheduled for a combined phaeochromocytoma resection and Caesarean section. Von Hippel Lindau disease is characterized by diffuse haemangioblastomas of the central nervous system (CNS) and viscera. It is also associated with phaeochromocytomas and renal cell carcinomas. Patients frequently have asymptomatic spinal cord and intracranial pathology. The patient and her fetus presented a challenge because of the anaesthetic restrictions imposed by VHLD, and her pregnancy. She was also at risk of developing malignant hypertension from the phaeochromocytoma. The patient was not a candidate for regional anaesthesia because of the possibility of spinal cord haemangioblastomas. She had received adrenergic blockade with phentolamine (total 30 mg a day) and propranolol (total 40 mg a day) since the 27th wk of gestation in order to control hypertension secondary to the phaeochromocytoma. General anaesthesia was administered with aggressive management of hypertension with adrenergic blockers (labetalol 1.0 mg.kg-1 and esmolol 0.75 mg.kg-1) and sodium nitroprusside 1.5 micrograms.kg-1 (total). Before delivery of the baby, opioids, which could have resulted in a fetus with CNS depression, were avoided. After delivery, opioids (sufentanil 0.4 microgram.kg-1 x hr-1) were used to limit the use of inhalational anaesthesia which may contribute to uterine atony. Postoperative pain was managed with an intravenous narcotic infusion. Both patients had uneventful postoperative courses.

Adrenal Gland Neoplasms↗
PubMed1993

DNA sequences and expression in Streptomyces lividans of an exoglucanase gene and an endoglucanase gene from Thermomonospora fusca.

Two genes encoding cellulases E1 and E4 from Thermomonospora fusca have been cloned in Escherichia coli, and their DNA sequences have been determined. Both genes were introduced into Streptomyces lividans, and the enzymes were purified from the culture supernatants of transformants. E1 and E4 were expressed 18- and 4-fold higher, respectively, in S. lividans than in E. coli. Thin-layer chromatography of digestion products showed that E1 digests cellotriose, cellotetraose, and cellopentaose to cellobiose and a trace of glucose. E4 is poor at degrading cellotriose and cleaves cellopentaose to cellotetraose and glucose or cellotriose and cellobiose. It readily cleaves cellotetraose to cellobiose. E1 shows 59% identity to Cellulomonas fumi CenC in a 689-amino-acid overlap, and E4 shows 80% identity to the N terminus of C. fimi CenB in a 441-amino-acid overlap; all of these proteins are members of cellulase family E. Alignment of the amino acid sequences of Clostridium thermocellum celD, E1, E4, and four other members of family E demonstrates a clear relationship between their catalytic domains, although there is as little as 25% identity between some of them. Residues in celD that have been identified by site-directed mutagenesis and chemical modification to be important for catalytic activity are conserved in all seven proteins. The catalytic domains of E1 and E4 are not similar to those of T. fusca E2 or E5, but all four enzymes share similar cellulose-binding domains and have the same 14-bp inverted repeat upstream of their initiation codons. This sequence has been identified previously as the binding site for a protein that regulates induction.

Actinomycetales↗
PubMed1993

The value of radiographs in the management of the fractured nose.

Over a 6-month period a record was kept of all patients presenting to the accident and emergency (A&E) department with nasal injuries. The results of the nasal radiographs were analysed to gauge their benefit. It was found that there was poor correlation between the radiological findings and the presence of external deformity, the latter determining the decision to carry out treatment. Routine radiographs of the nose are unnecessary in patients with nasal trauma.

Adult↗
PubMed1992

Differential expression of retinal insulin receptors in STZ-induced diabetic rats.

A major complication of diabetes mellitus is retinopathy, which is characterized by increased neovascularization and neuronal degeneration in the retina. The biochemical processes underlying these changes are largely unknown. To better understand the role(s) of insulin or its lack and the resultant hyperglycemia in the etiology of these events, peripheral and neuronal (having 125 kDa and 115 kDa alpha subunits, respectively) insulin receptor subtype levels in the retinas of Streptozocin-induced diabetic rats were quantified. Immunoblot analysis of wheat germ agglutinin-agarose purified retinal membrane proteins revealed that retinas from diabetic rats expressed higher insulin receptor levels than retinas from control rats. This increase reflected a doubling of neuronal and a approximately 20% decrease in peripheral insulin receptor subtypes, respectively. Insulin-treated diabetic rats had neuronal receptor levels equal to control values, at the same time having a further reduced number of peripheral insulin receptors relative to controls. Affinity labeling analysis of WGA-purified retinal membrane proteins indicated a 1.5-fold increase in neuronal and a 9% decrease in peripheral receptor subtypes, corroborating the immunoblot analysis. Neuronal insulin receptors in WGA-purified cortical synaptosomal membranes also were increased in diabetic rats, with insulin treatment reducing this effect. The up-regulated receptors retained their ability to undergo insulin-dependent autophosphorylation and, as such, did not appear functionally impaired. These data suggest that the expression of neuronal insulin receptors in retina and brain and peripheral insulin receptors in the retina of diabetic rats is sensitive to levels of insulin/glucose in peripheral circulation.

Adenosine Triphosphate↗
PubMed1991

Characterization of a novel receptor in toad retina with dual specificity for insulin and insulin-like growth factor I.

The biochemical properties of insulin receptors from toad retinal membranes were examined in an effort to gain insight into the role this receptor plays in the retina. Competition binding assays revealed that toad retinal membranes contained binding sites that displayed an equal affinity for insulin and insulin-like growth factor I (IGF-I). Affinity labeling of toad retinal membrane proteins with 125I-insulin resulted in the specific labeling of insulin receptor alpha-subunits of approximately 105 kDa. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partially reduced (alpha beta-heterodimer) receptors affinity-labeled with 125I-insulin indicated the presence of a disulfide-linked beta-subunit of approximately 95 kDa. Endoglycosidase F digestion of the affinity-labeled alpha-subunits increased their mobility by reducing their apparent mass to approximately 83 kDa. This receptor was not detected by immunoblot analysis with a site-specific antipeptide antibody directed against residues 657-670 of the carboxy terminal of the human insulin receptor alpha-subunit, whereas this antibody did label insulin receptor alpha-subunits from pig, cow, rabbit, and chick retinas. In in vitro autophosphorylation assays insulin stimulated the tyrosine phosphorylation of toad retina insulin receptor beta-subunits. These data indicate that toad retinal insulin receptors have a heterotetrameric structure whose alpha-subunits are smaller than other previously reported neuronal insulin receptors. They further suggest that a single receptor may account for both the insulin and IGF-I binding activities associated with toad retinal membranes.

Animals↗