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Biomedical subjects

E Peters

Publications and source records attributed to E Peters.

At least 37 records · Page 2Linked to original sources

Involvement of VEGFR-2 (kdr/flk-1) but not VEGFR-1 (flt-1) in VEGF-A and VEGF-C-induced tube formation by human microvascular endothelial cells in fibrin matrices in vitro.

Different forms of vascular endothelial growth factor (VEGF) and their cellular receptors (VEGFR) are associated with angiogenesis, as demonstrated by the lethality of VEGF-A, VEGFR-1 or VEGFR-2 knockout mice. Here we have used an in vitro angiogenesis model, consisting of human microvascular endothelial cells (hMVEC) cultured on three-dimensional (3D) fibrin matrices to investigate the roles of VEGFR-1 and VEGFR-2 in the process of VEGF-A and VEGF-C-induced tube formation. Soluble VEGFR-1 completely inhibited the tube formation induced by the combination of VEGF-A and TNF alpha (VEGF-A/TNF alpha). This inhibition was not observed when tube formation was induced by VEGF-C/TNF alpha or bFGF/TNF alpha. Blocking monoclonal antibodies specific for VEGFR-2, but not antibodies specifically blocking VEGFR-1, were able to inhibit the VEGF-A/TNF alpha-induced as well as the VEGF-C/TNF alpha-induced tube formation in vitro. P1GF-2, which interacts only with VEGFR-1, neither induced tube formation in combination with TNF alpha, nor inhibited or stimulated by itself the VEGF-A/TNF alpha-induced tube formation in vitro. These data indicate that VEGF-A or VEGF-C activation of the VEGFR-2, and not of VEGFR-1, is involved in the formation of capillary-like tubular structures of hMVEC in 3D fibrin matrices used as a model of repair-associated or pathological angiogenesis in vitro.

Animals↗

Impact of apolipoprotein(a) on in vitro angiogenesis.

Angiostatin, which consists of the kringle I-IV domains of plasminogen and which is secreted into urine, is an efficient inhibitor of angiogenesis and tumor growth. Because N-terminal apolipoprotein(a) [apo(a)] fragments, which also contain several types of kringle IV domains, are found in urine as well, we evaluated the potential angiostatic properties of these urinary apo(a) fragments and of a recombinant form of apo(a) [r-apo(a)]. We used human microvascular endothelial cell (hMVEC)-based in vitro assays of tube formation in 3-dimensional fibrin matrixes. Purified urinary apo(a) fragments or r-apo(a) inhibited the basic fibroblast growth factor/tumor necrosis factor-alpha-induced formation of capillary-like structures. At concentrations varying from 0.2 to 10 microgram/mL, urinary apo(a) fragments inhibited tube formation by as much as 70%, whereas there was complete inhibition by r-apo(a). The highest concentrations of both inhibitors also reduced urokinase plasminogen activator production of basic fibroblast growth factor-induced hMVEC proliferation. The inhibitors had no effect on plasminogen activator inhibitor-1 expression. If our in vitro model for angiogenesis is valid for the in vivo situation as well, our data point toward the possibility that apo(a) may also be physiologically operative in modulating angiogenesis, as the concentration of free apo(a) found in humans exceeds that tested herein.

Angiogenesis Inhibitors↗

Unfractionated and low molecular weight heparin affect fibrin structure and angiogenesis in vitro.

Cancer patients treated for venous thromboembolism with low molecular weight heparin (LMWH) have a better survival rate than patients treated with unfractionated heparin (UFH). Because fibrin-associated angiogenesis is an important determinant in the progression and metastasis of many solid tumors, the effects of heparins on in vitro angiogenesis were investigated. Both UFH and LMWH inhibited bFGF-induced proliferation of human microvascular endothelial cells (hMVECs) to the same the extent (36-60%). VEGF165-induced proliferation was inhibited to a to a lesser extent (19-33%). Turbidity measurements and electron microscopy showed that the presence of LMWH during polymerization of the fibrin matrix led to a more transparent rigid network with thin fibrin bundles, whereas the presence of UFH resulted in a more opaque more porous network with thick fibrin fibers. We used a human in vitro angiogenesis model, which consisted of hMVECs seeded on top of a fibrin matrix, and stimulated the cells with basic fibroblast growth factor plus tumor necrosis factor a to induce capillary-like tubular structures. The formation of capillary-like tubular structures was retarded with matrices polymerized in the presence of LMWH (46% inhibition compared with a control matrix for both 1.5 and 10 units/ml LMWH), whereas matrices polymerized in the presence of UFH facilitated tubular structure formation (72 and 36% stimulation compared with a control matrix for 1.5 and 10 units/ml UFH, respectively). Similar results were obtained for cells stimulated with vascular endothelial growth factor plus tumor necrosis factor alpha. These data demonstrate the inhibitory effect of heparins on proliferation of hMVECs and provide a novel mechanism by which LMWH may affect tumor progression, namely reduced ingrowth of microvascular structures in a fibrinous stroma matrix by rendering it less permissive for invasion.

Cell Division↗

Macroporous photopolymer frits for capillary electrochromatography

Macroporous polymer frits have been fabricated in fused-silica capillaries by the UV photopolymerization of a solution of glycidyl methacrylate and trimethylopropane trimethacrylate. This in situ preparation is a simple, rapid, and reproducible process. The frit can be placed at any desired position along the column. Photopolymer frits can withstand the short exposure to a high pressure (over 6000 psi). Bubble formation is no observed to occur with these frits under our experimental conditions. By choice of porogens, it is possible to control the porous properties. The use of such frits in capillaries to retain particles of chromatographic packing has been demonstrated to be stable and robust with continuous operation over 3 days.

Journal Article↗

Inhibition of angiogenesis by blockers of volume-regulated anion channels.

Osmotic cell swelling activates an outwardly rectifying Cl(-) current in endothelial cells that is mediated by volume-regulated anion channels (VRACs). In the past, we have shown that serum-induced proliferation of endothelial cells is arrested in the presence of compounds that potently block the endothelial VRACs. Here we report on the effects of four chemically distinct VRAC blockers [5-nitro-2-(3-phenylpropylamino)benzoic acid] (NPPB), mibefradil, tamoxifen, and clomiphene-on several models of experimental angiogenesis. Mibefradil (20 microM), NPPB (100 microM), tamoxifen (20 microM), and clomiphene (20 microM) inhibited tube formation by rat microvascular endothelial cells plated on matrigel by 42.9 +/- 8.8%, 25.3 +/- 10.4%, 32.2 +/- 4.5%, and 20 +/- 5.8%, respectively (p < 0.05). Additionally, NPPB (50-100 microM) and mibefradil (10-30 microM) significantly inhibited bFGF (10 ng/ml) + TNFalpha (2.5 ng/ml)-stimulated microvessel formation by human microvascular endothelial cells plated on fibrin by 30-70%. Furthermore, NPPB, mibefradil, and clomiphene concentration dependently inhibited spontaneous microvessel formation in the rat aorta-ring assay and vessel development in the chick chorioallantoic membrane assay. These results suggest that VRAC blockers are potent inhibitors of angiogenesis and thus might serve as therapeutic tools in tumor growth and other angiogenesis-dependent diseases.

Allantois↗

Comparison of clinical and histologic diagnoses in periapical lesions.

OBJECTIVE: To determine the frequency with which histopathologic examination of periapical biopsy specimens contributed information not anticipated clinically. STUDY DESIGN: Clinical and histopathologic information from 805 sequentially submitted periapical biopsy specimens over a 2-year period was compared. Clinical data included endodontic status, age and sex of patient, location of lesion, and submitting clinician. Histopathologic diagnoses were categorized as 1) sequelae of pulpal necrosis (SPN), 2) complicated SPN (CSPN) with infection or antral involvement, or 3) periapical lesions unrelated to pulpal necrosis (PLUPN). RESULTS: Of the 805 cases, 788 (97.9%) were SPN, 9 (1.1%) were CSPN, and 8 (1%) were PLUPN, representing a range of locally aggressive but benign lesions and 1 malignancy. Comparison of clinical and histologic diagnoses indicated that the clinical interpretation was inaccurate in 4.1% of cases (suggesting SPN in PLUPN cases or PLUPN in SPN cases). In another 0.9% of cases, the histologic analysis (indicating CSPN) contributed additional information to the clinical diagnosis. CONCLUSIONS: A histopathologic examination contributed clinically relevant information in 5.0% of submitted cases. General extrapolation of this figure is not possible. Theoretical considerations, which could positively or negatively bias this figure, are discussed.

Adult↗

Perceptions of flexible training in medicine.

Most flexible trainees believe that their full-time colleagues perceive flexible training as flawed in some way. However, most consultants and full-time trainees actually view flexible trainees and their posts in a positive light.

Attitude of Health Personnel↗

Our decision on a cochlear implant.

This essay sets forth why we, the hearing parents of a profoundly deaf child, have chosen not to seek a cochlear implant for our daughter. In controversial matters, participants in a debate should set forth, as best they can, their prejudices and biases (which are not necessarily bad things), thereby allowing others to assess the degree, if any, to which their positions might be based on feelings (however understandable) vs. facts. I do so in this essay first by describing who we are and how we view deafness and Deaf culture, and then by discussing our daughter Margaret and how we see her being affected by our decision about cochlear implantation. I then briefly consider some unconvincing reasons offered against implants, and conclude with a few thoughts on the decision process.

Attitude to Health↗

Pollination ecology of Agave macroacantha (Agavaceae) in a Mexican tropical desert. I. Floral biology and pollination mechanisms.

In a study of sexual reproduction in long-lived semelparous plants, we observed Agave macroacantha in the tropical desert of Tehuacán-Cuicatlán, Mexico, describing duration of flowering, flower phenology, and nectar production patterns. We also performed two manipulative experiments evaluating (a) the seed production efficiency of different crossing systems (selfing, cross-pollination, apomixis, and control), and (b) the effect of different pollinators (diurnal exposure to pollinators, nocturnal exposure, exclusion, and control) on the seeds produced. Flowering occurred from early May to late July and had a mean duration of 29 days in the individual rosettes. The flowers were protandrous; anthesis occurred in the afternoon of the third day after floral opening, and the pistils matured in the afternoon of the fifth day. The stigmas remained receptive from dusk to the following morning. Pollination was mostly allogamous. Nectar was produced principally during the night, from the first stages of floral aperture until the stigmas wilted and flowering ceased. The flowers were visited during the day by hymenoptera, butterflies, and hummingbirds and during the night by bats and moths. Only the nocturnal visitors, however, were successful pollinators. Agave macroacantha is extremely dependent on nocturnal pollinators for its reproductive success.

Journal Article↗

Pollination ecology of Agave macroacantha (Agavaceae) in a Mexican tropical desert. II. The role of pollinators.

We did a series of observational studies and manipulative experiments on the guild of nocturnal visitors of Agave macroacantha, including (1) a description of the hourly patterns of visits by moths and bats, (2) an evaluation of the relative contribution of bats and moths to flowering success, and (3) an evaluation of the pollination efficiency of the different bat species. Scapes exposed to moths but excluded to bats yielded ∼50% fewer fruits than those exposed to both pollinator groups. Flowers exposed to the bat species Leptonycteris curasoae showed similar fruiting success to those exposed to Choeronycteris mexicana and to those exposed to the whole nocturnal visitor guild. However, the fruits originated from flowers pollinated by Leptonycteris curasoae yielded significantly more seed than those exposed to Choeronycteris mexicana or to the whole pollinator guild. It is concluded that Agave macroacantha is extremely dependent on nocturnal pollinators for its reproductive success and that bats are especially important for successful pollination. Some of these pollinators are migratory and have been reported to be steadily declining. A continuing decline in the populations of pollinators may impede the successful sexual reproduction of the plant host and may put the long-term survival of this agave species under risk.

Journal Article↗

Dental Students with Hepatitis B e Antigen: A Survey of Canadian Dental Schools.

BACKGROUD: Health care workers who are e-antigen-positive carriers of hepatitis B virus have become a significant focus of concern in the development of public health policy. In cases of needle-stick injury, the risk of transmission of HBV has been estimated at 60-fold greater if the carrier is positive for e antigen than if the carrier does not have the e antigen. Debate continues regarding proposed public health policies to restrict e-antigen-positive health care workers from performing "exposure-prone procedures". Given the potentially greater risk of disease transmission to patients and the potential career implications for infected students, dental schools must responsibly address the issue of dental students and dental school applicants who have the hepatitis B e antigen. This paper reviews the controversies surrounding this issue and reports a survey of Canadian dental schools.

Journal Article↗

Antiretroviral drugs in the treatment of people living with human immunodeficiency virus: experience in a south Indian tertiary referral centre.

OBJECTIVE: A decrease in the number of new acquired immunodeficiency syndrome (AIDS) cases and AIDS--related deaths was seen in developed countries since 1996 due to the use of new combination of antiretroviral drugs. This retrospective study discusses the use of antiretroviral drugs in the treatment of people living with human immunodeficiency virus (HIV) in a developing country setting. METHODS: A retrospective case note analysis was done of patients receiving antiretroviral therapy at YRG Centre for AIDS Research and Education between Aug. 1996 and Feb. 1999. Out of 936 persons with HIV treated at this centre, 6.1% of the patients were prescribed three groups of drugs: Group A was the combination of the reverse transcriptase inhibitors (nRTI) zidovudine 600 mg daily and lamivudine 300 mg daily, Group B was the combination of zidovudine 600 mg daily, lamivudine 300 mg daily with protease inhibitor (PI) ritonavir 1200 mg daily and Group C was the combination of zidovudine 600 mg daily and lamivudine 300 mg daily with indinavir 2400 mg daily. Twenty HIV positive pregnant women were given zidovudine 500 mg daily during the third trimester (Group D) to reduce the vertical transmission of HIV. RESULTS: The mean CD4 gain was 188.0 cells/micro litre in Group A, 118.8 cell/microlitre in Group B and 223.3 cells/microlitre in Group C with a mean duration of 4.3, 3.1 and 3.5 months respectively. Many patients stopped antiretroviral drugs due to high cost of therapy. CONCLUSION: Hence, physicians should prescribe antiretroviral drugs only after ensuring that the patients can afford and will comply with a longterm treatment. Prescribing guidelines should be available to those working in this field and should be adhered to so that emergence of resistant strains could be prevented.

Adult↗

A brief motivational intervention to improve dietary adherence in adolescents. The Dietary Intervention Study in Children (DISC) Research Group.

Motivational interviewing offers health care professionals a potentially effective strategy for increasing a patient's readiness to change health behaviors. Recently, elements of motivational interviewing and the stages of change model have been simplified and adapted for use with patients in brief clinical encounters. This paper describes in detail a brief motivational intervention model to improve and renew dietary adherence with adolescents in the Dietary Intervention Study in Children (DISC). DISC is a randomized, multi-center clinical trial assessing the efficacy and safety of lowering dietary fat to decrease low-density lipoprotein cholesterol in high-risk children. In the first 3 years of follow-up covering ages 8-13, intervention participants (n = 334) were exposed to a family-based group intervention approach to change dietary choices. To address adherence and retention obstacles as participants moved into adolescence (age 13-17), an individual-level motivational intervention was implemented. The DISC motivational intervention integrates several intervention models: stages of change, motivational interviewing, brief negotiation and behavioral self-management. A preliminary test of the intervention model suggests that it was acceptable to the participants, popular with interventionists and appeared to be an age-appropriate shift from a family-based intervention model.

Adolescent↗

Cognitive asymmetry patterns in schizophrenia: active and withdrawn syndromes and sex differences as moderators.

Recognition memory for words and faces was examined in male and female schizophrenia patients for evidence of associations between putative left-right hemisphere asymmetry patterns and active (positive) versus withdrawn (negative) syndromes. Ninety-five normal controls and 104 schizophrenia patients with active, withdrawn, and mixed syndromes or in symptom remission were examined, including an unmedicated subgroup. Memory was poorer in patients than controls, while the remitted group had superior memory to psychotic patients. Active and withdrawn patients showed the hypothesized syndrome-dependent cognitive asymmetries: active (word > faces); withdrawn (faces > words), except active females who showed a word deficit. The results support selective lateralized temporoparietal impairment of either hemisphere in schizophrenia, with laterality related to active (face memory/right-sided impairment) and withdrawn (word memory/left-sided impairment) syndromes, except active syndrome females. These syndrome-related asymmetries moderated the sexually dimorphic asymmetries found in normal subjects. Consideration of individual differences both in sex and syndromes based on activity and withdrawal, and of left and right hemisphere memory modality, may assist in unraveling heterogeneity in schizophrenic cognition. The superior memory of recovered patients indicates that some memory impairment in schizophrenia is functional.

Adult↗

Delusional ideation in religious and psychotic populations.

OBJECTIVES: Previous research into schizotypy has shown that certain groups of people have similar experiences to the positive symptoms of schizophrenia but remain functioning members of society, such as those with profound religious experiences (Jackson & Fulford, 1997). METHOD: The focus of the present study was to explore the incidence of delusional ideation in New Religious Movements (NRMs). Hare Krishnas and Druids were compared to two control groups (non-religious and Christian), and to deluded, psychotic in-patients on two delusions measures. RESULTS: As predicted, individuals from the NRMs scored significantly higher than the control groups on all the delusional measures apart from levels of distress. They did not show as much florid symptomatology as the psychotic patients, but could not be differentiated from the deluded group on the number of delusional items endorsed on the Peters et al. Delusions Inventory (PDI; Peters, Day & Garety, 1996), or on levels of conviction. However, they were significantly less distressed and preoccupied by their experiences. No differences were found between the two control groups on any of the delusional measures, suggesting that religious beliefs per se do not account for the NRMs members' scores. DISCUSSION: These findings provide further support for, first, the notion of a continuum between normality and psychosis and, second, for the necessity to consider the multidimensionality of delusional beliefs.

Adaptation, Psychological↗