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D Francis

Publications and source records attributed to D Francis.

At least 55 records · Page 3Linked to original sources
PubMed1999

Nongenomic transmission across generations of maternal behavior and stress responses in the rat.

In the rat, variations in maternal care appear to influence the development of behavioral and endocrine responses to stress in the offspring. The results of cross-fostering studies reported here provide evidence for (i) a causal relationship between maternal behavior and stress reactivity in the offspring and (ii) the transmission of such individual differences in maternal behavior from one generation of females to the next. Moreover, an environmental manipulation imposed during early development that alters maternal behavior can then affect the pattern of transmission in subsequent generations. Taken together, these findings indicate that variations in maternal care can serve as the basis for a nongenomic behavioral transmission of individual differences in stress reactivity across generations.

Amygdala↗
PubMed1999

Connexin diversity and gap junction regulation by pHi.

The molecular mechanisms controlling pH-sensitivity of gap junctions formed of two different connexins are yet to be determined. We used a proton-sensitive fluorophore and electrophysiological techniques to correlate changes in intracellular pH (pHi) with electrical coupling between connexin-expressing Xenopus oocytes. The pH sensitivities of alpha 3 (connexin46), alpha 2 (connexin38), and alpha 1 (connexin43) were studied when these proteins were expressed as: 1) nonjunctional hemichannels (for alpha 3 and alpha 2), 2) homotypic gap junctions, and 3) heterotypic gap junctions. We found that alpha 3 hemichannels are sensitive to changes in pHi within a physiological range (pKa = 7.13 +/- 0.03; Hill coefficient = 3.25 +/- 1.73; n = 8; mean +/- SEM); an even more alkaline pKa was obtained for alpha 2 hemichannels (pKa = 7.50 +/- 0.03; Hill coefficient = 3.22 +/- 0.66; n = 13). The pH sensitivity curves of alpha 2 and alpha 3 homotypic junctions were indistinguishable from those recorded from hemichannels of the same connexin. Based on a comparison of pKa values, both alpha 3 and alpha 2 gap junctions were more pHi-dependent than alpha 1. The pH sensitivity of alpha 2-containing heterotypic junctions could not be predicted from the behavior of the two connexons in the pair. When alpha 2 was paired with alpha 3, the pH sensitivity curve was similar to that obtained from alpha 2 homotypic pairs. Yet, pairing alpha 2 with alpha 1 shifted the curve similar to homotypic alpha 1 channels. Pairing alpha 2 with a less pH sensitive mutant of alpha 1 (M257) yielded the same curve as when alpha 1 was used. However, the pH sensitivity curve of alpha 3/alpha 1 channels was similar to alpha 3/alpha 3, while alpha 3/M257 was indistinguishable from alpha 3/alpha 1. Our results could not be consistently predicted by a probabilistic model of two independent gates in series. The data show that dissimilarities in the pH regulation of gap junctions are due to differences in the primary sequence of connexins. Moreover, we found that pH regulation is an intrinsic property of the hemichannels, but pH sensitivity is modified by the interactions between connexons. These interactions should provide a higher level of functional diversity to gap junctions that are formed by more than one connexin.

Animals↗
PubMed1999

The impact of cachexia on cardiorespiratory reflex control in chronic heart failure.

BACKGROUND: The mechanism of persistent neurohormonal and cardiorespiratory reflex abnormalities in chronic heart failure remain unclear. Also, why chronic heart failure patients who develop cachexia demonstrate a particularly abnormal neurohormonal profile and have a high risk of death is not known. Impaired reflex control within the cardiac and respiratory systems, and abnormal heart rate variability have both been linked to a poor outcome. Muscle reflexes may contribute to persistent neurohormonal overactivity in wasted patients. Thus, we hypothesized that patients with cardiac cachexia might exhibit particularly profound abnormalities in cardiorespiratory reflexes and heart ratevariability. METHODS AND RESULTS: We investigated 39 chronic heart failure patients: 13 with cardiac cachexia (non-intentional, non-oedematous, documented weight loss of >7.5% of previous normal weight over more than 6 months), and 26 non-cachectic chronic heart failure patients matched according to the severity of chronic heart failure (all men, mean age: 59 vs 60 years, NYHA functional class: 2.6 vs 2.5, peak O(2)consumption: 16.2 vs 16.8 ml. kg(-1). min(-1), left ventricular ejection fraction: 23 vs 24%, all P>0.2 for cachectic vs non-cachectic). In the assessment of the cardiorespiratory reflex control we investigated: cardiac sympathovagal balance (using spectral analysis of heart rate variability to derive low (LF, 0. 04-0.15Hz) and high frequency (HF, 0.15-0.4Hz) components), baroreflex sensitivity (using the phenylephrine method), and peripheral chemosensitivity (using the transient hypoxic method). There was a severely abnormal pattern of cardiorespiratory reflex control in patients with cachexia compared with non-cachectic patients. The former group exhibited severely impaired autonomic reflex control, characterized by an abnormal profile of heart rate variability (reduced LF component), and depressed baroreflex sensitivity (P=0.0001 and P=0.02, respectively, vs non-cachectics). Patients with cachexia also demonstrated an increased peripheral chemosensitivity (0.91 vs0.46 l. min(-1). %SaO(2)(-1), P<0.001, cachectic vs non-cachectic, respectively). In the correlation analyses the degree of impairment in the reflex control was more closely related to wasting, and to the level of neurohormonal activation (as measured by the levels of epinephrine and norepinephrine) than to conventional markers of the severity of heart failure. CONCLUSIONS: Chronic heart failure patients who developed cardiac cachexia demonstrate an abnormal reflex control within the cardiovascular and respiratory systems. The nature of the link between this phenomenon and hormonal changes and the poor prognosis of cachectic chronic heart failure patients warrants further investigation.

Cachexia↗
PubMed1999

Can the Platelet Function Analyzer (PFA)-100 test substitute for the template bleeding time in routine clinical practice?

The bleeding time (BT) is widely used in clinical medicine as a screening test of platelet function, although its deficiencies in such a role are well recognized. The Platelet Function Analyzer (PFA)-100 measures the ability of platelets activated in a high-shear environment to occlude an aperture in a membrane treated with collagen and epinephrine (CEPI) or collagen and ADP (CADP). The time taken for flow across the membrane to stop (closure time) is recorded. This study compared the PFA-100 with the BT as a screening test of platelet dysfunction in 113 hospital inpatients. The PFA-100 test was performed initially using the CEPI cartridge; CADP tests were performed on those with abnormal (> 163 s) CEPI closure times. Whole blood platelet aggregation studies and chart review were performed on patients in whom the BT and PFA-100 results did not agree.Abnormal bleeding times and PFA-100 results were obtained in 20.4% and 35.4% of patients, respectively. The results of BT and PFA-100 agreed in 74.3% of patients. Of the 29 patients in whom the BT and PFA-100 results were discordant, whole blood platelet aggregation studies supported the PFA-100 result in 25 (86.2%). The PFA-100 was more sensitive to aspirin-induced platelet dysfunction and was more rapidly and cheaply performed than the BT. Since the PFA-100 test reflects platelet function better than the BT, we conclude that this test could replace the BT as a first-line screening test for platelet dysfunction in clinical practice.

Journal Article↗
PubMed1999

Directly inherited partial trisomy of chromosome 6p identified in a father and daughter by chromosome microdissection.

Cytogenetic analysis of a 4 year old girl with developmental delay and dysmorphic features showed extra chromosomal material of unknown origin on 20p (46,XX,add(20)(p13)). Familial chromosome studies showed direct inheritance of add(20)(p13) from the father, who had a similar, albeit milder, phenotype. Fibroblast chromosome studies of the father showed no karyotype mosaicism. The additional material could not be identified on the basis of the G banding pattern owing to its small size and ambiguous banding pattern. Chromosome microdissection of the unknown material was performed, the DNA was amplified and labelled using degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) and reverse painted to the proband's cells to show the karyotype 46,XX,der(20)t(6;20) (p23;p13), conferring partial trisomy 6p and presumed partial monosomy for 20p. Chromosome microdissection has made possible the first reported case of directly inherited partial trisomy 6p.

Child, Preschool↗
PubMed1999

Reproducibility of methods for assessing baroreflex sensitivity in normal controls and in patients with chronic heart failure.

Baroreflex sensitivity (BRS) conveys useful prognostic information in patients with heart disease, yet methods for its quantification suffer from poor reproducibility and test failure in some patients with heart failure. We set out to compare the short-term reproducibility and success rate of four different methods of assessing BRS in normal subjects and patients with chronic heart failure (CHF). A total of 31 patients with CHF and 18 normal controls underwent BRS testing using four techniques: (1) bolus phenylephrine (BRS(Phe)), (2) alpha-index in both low- and high-frequency bands (BRS(alphaLF) and BRS(alphaHF) respectively), (3) the sequence method (BRS(Seq)), and (4) a new 0.1 Hz controlled-breathing, time-domain analysis method (BRS(Cbr)). Each subject underwent two test episodes with each method on the same day. The average values for BRS in patients and controls respectively were: BRS(Phe), 4.4 (+/-4.4) ms/mmHg and 19.8 (+/-11.5) ms/mmHg; BRS(alphaLF), 5.6 (+/-4.1) ms/mmHg and 15.4 (+/-5.0) ms/mmHg; BRS(alphaHF), 7.1 (+/-7.0) ms/mmHg and 25.1 (+/-8.3) ms/mmHg; BRS(Seq), 7.7 (+/-6.3) ms/mmHg and 22.5 (+/-8.4) ms/mmHg; BRS(Cbr), 6.6 (+/-5.9) ms/mmHg and 22.8 (+/-10.8) ms/mmHg. The coefficients of variation (S.D. of the difference in repeated values divided by mean) in patients and controls respectively were: BRS(Phe), 85.6% and 52.2%; BRS(alphaLF), 65.9% and 33.7%; BRS(alphaHF), 99.7% and 52. 1%; BRS(Seq), 30.7% and 40.4%; BRS(Cbr), 30.7% and 19.6%. The numbers of test failures in patients were: BRS(Phen), 15; BRS(alphaLF), 7; BRS(alphaHF), 5; BRS(Seq), 14; BRS(Cbr), 1. Of the four techniques assessed for measuring BRS, the controlled breathing time-domain method yielded the best reproducibility and lowest failure rate in controls and in patients with CHF.

Adult↗
PubMed1998

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

AIDS Vaccines↗
PubMed1998

Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat.

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.

Amygdala↗
PubMed1998

Constant temperature monitoring: a study of temperature patterns in the postanesthesia care unit.

Patients admitted to the PACU from the operating room exhibit fluctuations in core body temperature during the course of their stay in the PACU. Some patients present with normothermia and experience temperature decreases later in their stay. PACU policy does not dictate that temperatures be measured at a predetermined frequency in the absence of hypothermia; thus, it is possible that hypothermia may not be detected at its onset. The major purpose of this study was to describe the core body temperature patterns of postsurgical patients during the PACU stay. Secondary objectives were to (1) identify at which point in time patients become hypothermic and (2) describe length of stay in patients who develop hypothermia. Hypothermia was defined as a core tympanic temperature of less than 35.5 degrees C. A descriptive design was used using a convenience sample of 150 elective surgical patients over the age of 1 month who were normothermic on admission to the PACU. Data were analyzed using descriptive statistics. Concurrent tympanic and continuous axillary temperatures were monitored for comparison and trend monitoring. Temperatures showed clinically significant decreases into the hypothermic range (< 35.5 degrees C). Fifty-seven percent of the sample (n = 86) had temperatures that dropped after PACU admission and another 13% fell below 35.5 degrees C. Hypothermia occurred within the first 15 minutes of the PACU stay. The average length of stay for those that developed hypothermia was 1.83 hours. Monitoring temperatures more frequently will result in detecting hypothermia at its onset. Nurses may use the axillary device as a trend for continuous monitoring. Length of stay may be shortened if temperature management is embraced by the PACU nurse.

Adolescent↗
PubMed1998

Expression of fission yeast cdc25 alters the frequency of lateral root formation in transgenic tobacco.

Lateral root formation was examined following the expression of a fission yeast mitotic regulator gene, cdc25, under the control of a tetracycline-inducible promoter in cultured roots of tobacco. Over expression of cdc25 in fission yeast results in premature cell division at a reduced cell size. Our aim was to examine whether cdc25 expression would affect cell size in the tobacco roots, and what effect this would have on lateral root morphogenesis. Transgene integration was confirmed by Southern blotting; it was inherited as a dominant Mendelian trait. Conditions for optimal expression, determined using plants transformed with gus under the control of the same promoter, were: addition of tetracycline (5 micrograms/ml) every 72 h, to cultured roots in Murashige-Skoog liquid medium in darkness at 27 degrees C. After the addition of tetracycline, cdc25 transcripts were detected using RT-PCR, initially after 48 h, and more strongly after 72 h. Appearance of cdc25 transcripts was followed by major changes in the roots. Compared with controls, lateral root primordia were initiated more frequently, were significantly smaller and comprised smaller cells at mitosis. However, cdc25 expression did not perturb normal development of the lateral roots. The data are consistent with cdc25 expression leading to a greater frequency of lateral root primordium formation and establishing a new threshold size for cell division in the primordia which was then maintained throughout subsequent development.

Cell Cycle Proteins↗
PubMed1998

'It comes together at the end': the impact of a one-year subject in Nursing Inquiry on philosophies of nursing.

This paper reframes an interpretive study as critical inquiry as the researchers interrogate their roles and authority in the 'reading' of what is valued as reflective. Working from data collected in written philosophies and interviews within the context of a one-year subject aimed at developing reflective practice and an appreciation of ways of knowing, this paper examines the change in philosophies of nursing perceived by three university-based educators and their students. The study reveals a growing appreciation of the complexity of nursing but a limited consideration of the dialectic of critical theorising and everyday engagement necessary to critical reflection and reconstruction of action. More importantly, the process of research collaboration raises questions of the soul-searching necessary for university educators to act against the institutionalised political context that determines what is seen to be of value in student learning.

Education, Nursing, Baccalaureate↗
PubMed1998

High frequency recombination during the sexual cycle of Dictyostelium discoideum.

Analysis of Dictyostelium development and cell biology has suffered from the lack of an ordinary genetic system whereby genes can be arranged in new combinations. Genetic exchange between two long ignored strains, A2Cycr and WS205 is here reexamined. Alleles which differ in size or restriction sites between these two strains were found for seven genes. Six of these are in two clusters on chromosome 2. Frequencies of recombinant progeny indicate that the genetic map of the two mating strains is colinear with the physical map recently worked out for the standard nonsexual strain, NC4. The rate of recombination is high, about 0.1% per kilobase in three different regions of chromosome 2. This value is comparable to rates found in yeast, and will permit fine dissection of the genome.

Animals↗
PubMed1998

Reducing parenteral requirement in children with short bowel syndrome: impact of an amino acid-based complete infant formula.

BACKGROUND: The aim of this study was to assess the impact of an amino acid-based complete infant formula on enteral feeding tolerance and parenteral nutrition requirement in children with severe short bowel syndrome. METHODS: Four children (23 months-4.75 years) with short bowel syndrome who required long-term parenteral nutrition due to persistent feeding intolerance while receiving an extensively hydrolyzed formula were assessed before and after the commencement of an amino acid-based complete infant formula for a mean follow-up period of 48 months (range 39-51 months). Assessment included clinical monitoring of feeding tolerance and nutritional status, biochemistry, stool analysis, skin-prick testing to common food antigens, esophagogastroduodenoscopy and colonoscopy or jejunoscopy with biopsies, and measurement of disaccharidase levels and intestinal permeability. RESULTS: All patients ceased parenteral nutrition within 15 months as a result of decreased stool output and resolution of vomiting. Patients had a reduction in hospitalization (mean: 198 versus 98 days/patient/year), episodes of proven (mean: 4.3 versus 3.3/patient/year) and suspected (mean: 6.5 versus 4.0/ patient/year) bacterial sepsis and central line insertions (mean: 2.5 versus 1.5/patient/year). Intestinal permeability to lactulose fell markedly (mean: 69% versus 2.7%). Disaccharidase levels increased in all three patients undergoing repeat studies. CONCLUSIONS: An amino acid-based complete infant formula improved feeding tolerance and eliminated the need for parenteral nutrition in four children with short bowel syndrome who had previously required long-term parenteral nutrition. The clinical improvement was mirrored by improvement in measurements of intestinal function.

Acidosis↗
PubMed1998

Expression of bcl-2 in fetal thymus, thymomas and thymic carcinomas. Association with p53 expression and review of the literature.

Bcl-2 is a proto-oncogene inhibiting apoptosis, and p53 is a tumor supressor gene which induces apoptosis. Both seem to take part in tumorigenesis. An inverse relationship between the two genes has been reported in some neoplasms, although the exact mechanism is not fully understood. We have analyzed the expression of bcl-2 and p53 in 18 fetal thymuses and 18 clinically benign and malignant thymomas: bcl-2 was expressed by most medullary lymphocytes and epithelial cells of the normal thymus; p53 was not expressed at all. Bcl-2 and p53 were co-expressed in the majority of the thymomas and the staining reaction was stronger in the clinically malignant ones. It is concluded that although co-expression of bcl-2 and p53 is of doubtful prognostic relevance, the staining pattern of bcl-2 supports the histogenetic classification system of Müller-Hermelink.

Fetus↗
PubMed1998

The geriatric resource nurse model of care: a vision for the future.

The geriatric resource nurse model of care is an innovative and effective method of integrating high quality, evidence-based geriatric nursing care into a clinical practice setting. The model creates expert bedside clinicians who recognize the vulnerability of older adults, who proactively educate and serve as consultants for peers, and who role model best practice geriatric nursing. This article describes the history and key features of this nursing model of care delivery with examples of how it was successfully implemented in a variety of hospitals around the country.

Aged↗
PubMed1997

Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.

Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > -0.6). These findings suggest that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.

Adrenocorticotropic Hormone↗