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Biomedical subjects

T Evans

Publications and source records attributed to T Evans.

At least 73 records · Page 4Linked to original sources
PubMed1998

Inhibition of HIV type 1 infection with a RANTES-IgG3 fusion protein.

The natural ligands for the chemokine receptors CCR5 (RANTES, MIP-1alpha, and MIP-1beta) and CXCR4 (SDF-1) can act as potent inhibitors of infection by the human immunodeficiency virus type 1 (HIV-1) at the level of viral entry. Unlike antibody-mediated inhibition, chemokine-mediated inhibition is broadly effective. Different HIV-1 strains can utilize the same coreceptor(s) for viral entry and, therefore, can be blocked by the same chemokine(s). HIV-1 strains that are highly resistant to neutralization by V3-specific antibodies are sensitive to inhibition by chemokines. Therefore, the use of chemokine-derived molecules constitutes a potential therapeutic approach to prevent infection by HIV-1. We have generated a fusion protein between RANTES and human IgG3 (RANTES-IgG3). The effectiveness of RANTES-IgG3 inhibition of infection by HIV-1 was similar to that of rRANTES. Inhibition of HIV-1 by RANTES-IgG3 was specific for CCR5-dependent but not CXCR4-dependent HIV-1 isolates. Fusion of a chemokine to an IgG moiety offers two desirable properties with respect to the recombinant chemokine alone. First, IgG fusion proteins have extended half-lives in vivo. Second, molecules with IgG heavy chain moieties may be able to cross the placenta and potentially induce fetal protection.

Cells, Cultured↗
PubMed1998

CDX2, a human homologue of Drosophila caudal, is mutated in both alleles in a replication error positive colorectal cancer.

The Cdx2 gene is one of three murine homologues of the Drosophila homeobox gene caudal. Mice heterozygous for a null mutation in Cdx2 exhibit a variable phenotype including tail abnormalities, stunted growth and a homeotic shift of vertebrae. Most strikingly, however, 90% of heterozygous mice were reported to develop multiple intestinal adenomatous polyps, most notably in the proximal colon (Chawengsaksophak et al., 1997). These observations led us to propose that mutation of CDX2 may be involved in the genesis of some human colorectal tumours. A survey of DNA from 85 colorectal tumours revealed that one with extensive microsatellite instability (RER+ phenotype) has mutations in both alleles of CDX2. Both mutations occur in coding regions which contain repetitive elements and are consistent with those found in RER + tumours.

Adenocarcinoma↗
PubMed1998

Effects of dietary vitamin E supplementation during late pregnancy on lamb mortality and ewe productivity.

OBJECTIVE: To determine the effect of feeding vitamin E to ewes during late pregnancy on lamb mortality and ewe productivity. DESIGN: Prospective study. ANIMALS: 1,302 mature Rambouillet and Targhee ewes. PROCEDURE: During a 3-year period, approximately 430 ewes/y were randomly allocated to 2 groups; supplement-group ewes were fed additional vitamin E and control-group ewes were not. Beginning approximately 3 weeks before the first expected lambing date, ewes were fed 2.3 kg (5 lb) of alfalfa-grass hay/d and 0.23 kg (0.5 lb) of barley-based pellets/d with or without supplemental vitamin E. Pellets that were supplemented contained 1,450 mg of DL-alpha-tocopherol acetate/kg (658 mg/lb) of feed and provided an additional 330 IU of vitamin E/ewe/d. Selenium was incorporated into a trace mineral salt and fed free choice to all ewes throughout pregnancy. RESULTS: Supplemental vitamin E had no effect on ewe weight, body condition score, fertility, or prolificacy. In ewes that lambed in the early part of the lambing season, vitamin E supplementation significantly reduced lamb mortality, compared with no supplementation (12 vs 17%, respectively). Consequently, supplement-group ewes had significantly greater total body weight of lambs per ewe at the time of weaning, compared with control-group ewes. Differences were not observed between ewe groups in lamb mortality or total body weight of lambs per ewe at the time of weaning when ewes lambed during the late part of the lambing season. CLINICAL IMPLICATIONS: If ewes are fed additional vitamin E3 weeks before parturition, those that lamb in the early part of the lambing season may have low lamb mortality and, thus, higher total body weight of lambs per ewe at the time of weaning.

Animals↗
PubMed1998

No evidence for the H133Y mutation in SONIC HEDGEHOG in a collection of common tumour types.

The human homologue of the Drosophila segment polarity gene patched is mutated in the cancer predisposition syndrome naevoid basal cell carcinoma syndrome (NBCCS), as well as in several types of tumour associated with the disorder. It was recently reported that a single recurrent mutation in the SONIC HEDGEHOG gene, which encodes the PATCHED ligand, was found in one of 43 basal cell carcinomas (BCCs), one of 14 medulloblastomas and one of six breast carcinomas analysed (Oro et al., 1997). We have searched extensively for this same mutation in a large collection of BCCs, medulloblastomas and carcinomas of the breast, ovary and colorectum and have failed to detect the mutation in any sample analysed.

Adolescent↗
PubMed1998

Common role for each of the cGATA-4/5/6 genes in the regulation of cardiac morphogenesis.

The GATA-4/5/6 genes encode transcription factors implicated previously in the regulation of cardiac-specific differentiation programs. However, recent analyses of mouse GATA-4 null mutations found evidence for function in endoderm development (in vitro) and embryonic morphogenesis (in vivo). Whether each of the three cardiac-associated GATA factors function within distinct or common developmental programs was previously untested; past studies defined specific and distinct roles for each of the GATA-1/2/3 genes in embryonic hematopoiesis. In this study, we compare the transcript patterns of cGATA-4/5/6 during chick embryogenesis. Each of the three GATA factors is expressed in a similar pattern within gastrulating cells of the primitive streak, prior to determination of the cardiomyocyte progenitors, and later within the lateral plate mesoderm and associated endoderm layer. The patterns overlap but extend beyond the presumptive cardiomyocyte population expressing cNkx-2.5. Later in development, cGATA-4/5/6 are all transcribed throughout the differentiating heart, in similar but not identical patterns, within the endocardium, myocardium, and great vessels. In order to test the function of GATA factors during chick cardiogenesis, embryos were cultured in vitro in the presence of antisense oligomers designed to deplete specifically transcripts encoding cGATA-4/5/6, beginning around stage 7. When oligomers are used to target transcripts for all three genes, a high percentage of the embryos develop abnormal hearts related to the failure to form a normal primitive heart tube. In the most severe phenotype, cardiac bifida results in two bilateral beating hearts. In some embryos, the paired heart primordia undergo partial fusion but fail to form a single looping heart tube. In all cases, cellular differentiation is not obviously affected, as the abnormal hearts form beating tissue. Depletion of transcripts encoding any single GATA factor, or any combination of two GATA factors, does not affect development. The partial depletion of all three genes in chick results in a remarkably similar phenotype compared to the null GATA-4 mutation in mouse. Therefore, in the chick, each of the GATA-4/5/6 genes functions in a common pathway, at the time of cardiac crescent formation, for regulating early embryonic cardiac morphogenesis, apparently associated with embryonic folding or the migration of primordia to form a primitive tube.

Animals↗
PubMed1998

The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes.

Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family. Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated. The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha.

Aging↗
PubMed1998

The effects of perphenazine and bromocriptine on follicular dynamics and endocrine profiles in anestrous pony mares.

Nineteen anestrous pony mares were used in a project designed to determine the effects of altered prolactin concentrations on follicular dynamics and endocrine profiles during spring transition. The dopamine antagonist, perphenazine, was administered daily to mares (0.375 mg/kg body weight) in Group A (n = 6), while Group B mares (n = 7) received 0.08 mg/kg metabolic weight (kg75) dopamine agonist, 2-bromo-ergocriptine, intramuscularly twice daily. Mares in Group C (n = 6) received 0.08 mg/kg75, i.m., saline twice daily. Treatment began January 20, 1994, and continued until ovulation occurred. Mares were teased 3 times weakly with an intact stallion. The ovaries of the ponies were palpated and imaged weekly using an ultrasonic B-mode unit with a 5 Mhz intrarectal transducer until they either exhibited estrual behavior and had at least a 20-mm follicle, or had at least a 25-mm follicle with no signs of estrus. At this time, ovaries were palpated and imaged 4 times weekly. Blood samples were obtained immediately prior to ultrasonic imaging for measurement of prolactin, FSH and estradiol-17 beta. Perphenazine treatment advanced the spring transitional period and subsequent ovulation by approximately 30 d. Group A exhibited the onset of estrual behavior earlier (P < 0.01) than control mares. In addition, Group A mares developed large follicles (> 30 mm) earlier (P < 0.01) than Group B mares, with least square means for Groups A and B of 47.0 +/- 8.8 vs 88.1 +/- 8.2 d, respectively. Control mares developed 30-mm follicles intermediate to Groups A and B at 67.3 +/- 8.8 d. Bromocriptine decreased (P < 0.05) plasma prolactin levels throughout the study, while perphenazine had no significant overall effect. However, perphenazine treatment did increase (P < 0.05) mean plasma prolactin concentrations from Day 31 to 60 of treatment. There were no differences in mean plasma FSH or estradiol-17 beta between treatment groups. We concluded that daily perphenazine treatment hastened the growth of follicles and subsequent ovulation while bromocriptine treatment appeared to delay the growth of preovulatory size follicles without affecting the time of ovulation.

Anestrus↗
PubMed1998

Herpes. Atypical clinical manifestations.

Herpes simplex viruses (HSV) 1 and 2 are responsible for genital herpes which is usually recognized as vesicles that ulcerate and eventually heal but recur periodically. Atypical genital herpes is often described in immunocompromised patients and can present as large, chronic, hyperkeratotic ulcers. Acyclovir-resistant HSV is occasionally isolated from such ulcers. Most cases of HSV infection reproduce subtle signs and symptoms, or more commonly, asymptomatic viral shedding. Such subclinical presentations may be responsible for most of the 30% increase in the prevalence of genital herpes in the United States during the past two decades.

AIDS-Related Opportunistic Infections↗
PubMed1998

New antiviral agents for dermatologic disease.

The topic of antiviral agents for dermatologic disease is an area that is rapidly changing and expanding as our knowledge of herpes viruses, HIV, and human papilloma viruses continues to expand. New drugs are continuing to make therapy for these viruses more efficacious day by day. This review will discuss the recent advances in antiviral therapy, new therapies currently being developed or studied, and the future of antiviral vaccines.

Anti-HIV Agents↗
PubMed1998

A randomized phase II study comparing four different interferon therapies in patients with recalcitrant condylomata acuminata.

BACKGROUND: Interferon (IFN) alpha and IFN gamma have synergistic in vitro and in vivo effects and have each been used in the treatment of anogenital condylomata acuminata. STUDY GOALS: To compare the efficacy and safety of regional 3 x 10(6) U IFN alpha (Group A), 3 x 10(6) U IFN gamma (Group B), 1.5 x 10(6) U IFN alpha plus 1.5 x 10(6) U IFN gamma (Group C), and 3 x 10(6) U IFN alpha plus 1.5 x 10(6) U IFN gamma (Group D) in the treatment of recalcitrant anogenital condylomata acuminata. STUDY DESIGN: Six-week courses of regional IFNs were administered in a randomized, double-blind, multicenter study. Response was assessed as change in the total area affected by condylomata. RESULTS: The treatments of Groups A, B, and C were similarly effective (complete response in 13.6%, 18.5%, and 16.0%, respectively). Group D had the lowest rate of complete response (3.8%), but this combination was the most effective when partial and complete responses were combined (73.0%). CONCLUSION: Regional IFN is a moderately effective and safe treatment in patients with recalcitrant anogenital condylomata acuminata. Combinations of IFNs alpha and gamma were not superior to IFN monotherapy.

Condylomata Acuminata↗
PubMed1998

Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation.

Based on conserved expression patterns, three members of the GATA family of transcriptional regulatory proteins, GATA-4, -5, and -6, are thought to be involved in the regulation of cardiogenesis and gut development. Functions for these factors are known in the heart, but relatively little is understood regarding their possible roles in the regulation of gut-specific gene expression. In this study, we analyze the expression and function of GATA-4, -5, and -6 using three separate but complementary vertebrate systems, and the results support a function for these proteins in regulating the terminal-differentiation program of intestinal epithelial cells. We show that xGATA-4, -5, and -6 can stimulate directly activity of the promoter for the intestinal fatty acid-binding protein (xIFABP) gene, which is a marker for differentiated enterocytes. This is the first direct demonstration of a target for GATA factors in the vertebrate intestinal epithelium. Transactivation by xGATA-4, -5, and -6 is mediated at least in part by a defined proximal IFABP promoter element. The expression patterns for cGATA-4, -5, and -6 are markedly distinct along the proximal-distal villus axis. Transcript levels for cGATA-4 increase along the axis toward the villus tip; likewise, cGATA-5 transcripts are largely restricted to the distal tip containing differentiated cells. In contrast, the pattern of cGATA-6 transcripts is complementary to cGATA-5, with highest levels detected in the region of proliferating progenitor cells. Undifferentiated and proliferating human HT-29 cells express hGATA-6 but not hGATA-4 or hGATA-5. Upon stimulation to differentiate, the transcript levels for hGATA-5 increase, and this occurs prior to increased transcription of the terminal differentiation marker intestinal alkaline phosphatase. At the same time, hGATA-6 steady-state transcript levels decline appreciably. All of the data are consistent with evolutionarily conserved but distinct roles for these factors in regulating the differentiation program of intestinal epithelium. Based on this data, we suggest that GATA-6 might function primarily within the proliferating progenitor population, while GATA-4 and GATA-5 function during differentiation to activate terminal-differentiation genes including IFABP.

Animals↗
PubMed1998

Tissue specific HPV expression and downregulation of local immune responses in condylomas from HIV seropositive individuals.

OBJECTIVE: To study the effect of tissue specific human papillomavirus (HPV) expression and its effect on local immunity in condylomas from HIV positive individuals. METHODS: Biopsy specimens of eight penile and eight perianal condylomas from HIV seropositive individuals were analysed. Expression of viral genes (HIV-tat and HPV E7 and L1) was determined by RT-PCR. The status of local immunity also was determined by RT-PCR by measuring CD4, CD8, CD16, CD1a, HLA-DR, and HLA-B7 mRNA levels in the tissues. Differentiation was determined by measuring involucrin, keratinocyte transglutaminase, as well as cytokeratins 10, 16, and 17. Proliferation markers such as PCNA and c-myc were also determined. RESULTS: The transcription pattern of HPV in perianal condylomas, which preferentially expressed the early (E7) gene, was different from that of penile condylomas, which primarily expressed the late (L1) gene. This transcription pattern is in good correlation with the keratinisation and differentiation patterns of the two epithelia: perianal biopsies preferentially expressed K16 and K17 while penile warts mainly expressed K10, markers of parakeratotic and orthokeratotic epithelia, respectively. Perianal biopsies also showed a higher degree of proliferation (PCNA and c-myc). Interestingly, transcription of HIV-tat was also higher in perianal than in penile biopsies. A high degree of local immunodeficiency was observed in perianal biopsies--that is, levels of CD4, CD16, and CD1a mRNAs were significantly lower. A negative correlation between CD1a (Langerhans cells) levels and HPV E7 levels was established. HPV E7 levels positively correlated with HIV-tat levels. Perianal tissues demonstrated more CD1a depression and tat associated HPV upregulation. CONCLUSION: HIV influences the expression of HPV genes resulting in local immunosuppression that might lead to an inappropriate immune surveillance of viral infection. Also, tissue type is an important factor in controlling viral transcription in a differentiation dependent manner. These findings may explain the higher rate of dysplasia and neoplasia in the perianal area.

Antibody Formation↗
PubMed1998

Promoting equity in health.

There is evidence that widening income gaps are a global phenomenon; that in many advanced industrialised countries unemployment rates are rising; that globalisation of the world economy has led to several countries becoming marginalised with a concomitant increase in poverty; and that the absolute number of poor has steadily increased over the last decade. All of these phenomena emphasise the need to focus on equity as a global concern.

Adolescent↗
PubMed1998

The 'Bodywise' initiative.

Young people want access to good information in suitable settings so they can discuss sexual matters openly. Services are needed to bridge the gap between paediatric and adult health services. Interprofessional collaboration can provide effective, integrated and supportive services for users and providers. Static and outreach services are essential to facilitate young people's access to the services.

Adolescent↗
PubMed1998

A randomized controlled trial of exercise therapy for dizziness and vertigo in primary care.

BACKGROUND: 'Vestibular rehabilitation' (VR) is an increasingly popular treatment option for patients with persistent dizziness. Previous clinical trials have only evaluated the effects of specialist therapy programmes in small, selective, or uncontrolled patient samples. AIM: To determine the benefits of VR compared with standard medical care, using a brief intervention for dizzy patients in primary care. METHOD: Adults consulting their general practitioner (GP) with dizziness or vertigo were randomly assigned to treatment or control groups. Patients in both groups received the same evaluation at baseline, six-week follow-up, and six-month follow-up, comprising examination of nystagmus, postural control, and movement-provoked dizziness, and a questionnaire assessment of subjective status, symptoms, handicap, anxiety, and depression. At baseline and six weeks later, the treatment group also received an individualized 30-minute therapy session, in which they were taught head, eye, and body exercises designed to promote vestibular compensation and enhance skill and confidence in balance. RESULTS: The treatment group (n = 67) improved on all measures, whereas the control group (n = 76) showed no improvement, resulting in a significant difference between the two groups on physical indices of balance and subjective indices of symptoms and distress. Odds ratios for improvement in treated patients relative to untreated patients were 3.1:1 at six weeks (95% CI = 1.4-6.8) and 3.8:1 at six months (95% CI = 1.6-8.7). CONCLUSION: VR is a simple, inexpensive, and beneficial treatment, and may be an appropriate first stage of management for many dizzy patients in primary care.

Adult↗