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L Robinson

Publications and source records attributed to L Robinson.

At least 91 records · Page 5Linked to original sources
PubMed1994

The EndoA enhancer contains multiple ETS binding site repeats and is regulated by ETS proteins.

EndoA is a type II keratin and with EndoB (type I keratin), constitutes intermediate filaments in various simple epithelial tissues. EndoA is developmentally regulated and has an enhancer that is located at the 3'- end of the gene. This enhancer contains two single and five dual Ets binding sites. Thus far, no other promoter or enhancer has been shown to contain as many potential clustered Ets binding sites. To study the transcriptional regulation of EndoA by the ETS family proteins, we amplified the EndoA enhancer fragment from mouse genomic DNA by PCR, and cloned it into the pBLCAT2 vector upstream from the CAT reporter gene. Several pBLCAT-ENDOA clones were sequenced to verify the presence of all the ETS binding sites. Clones that did not show any point mutations in the ETS binding sites were chosen to study the transcription regulation by ETS1, ETS2 and ERGB/FLI-1 gene products. EMSA results indicated that the ETS1, ETS2 and ERGB/FLI-1 proteins bind to the enhancer sequence, and DNase I protection data demonstrated that the ETS proteins protect all seven EBS core sequences. Cotransfection of the COS cells with the pBLCAT-ENDOA construct, along with increasing amounts of different ETS expression vectors, resulted in a significant induction of CAT reporter gene expression. Previously, we have shown that the overexpression of the ETS1 gene transforms NIH3T3, and these transformed cells (7AQS2.1) produce high levels of ETS1 protein (Seth & Papas, 1990). In this report, we show that the undifferentiated P19 EC cells do not express detectable levels of ETS1; however, an elevated level of ETS1 is expressed in differentiated derivatives of these cells. We therefore used these two cell lines to examine the activity of the EndoA enhancer with the ETS1 product. Transfection of the pBLCAT-ENDOA construct alone in undifferentiated P19 EC cells results in very low CAT gene expression; however, upon differentiation with retinoic acid the level of CAT gene activity increases dramatically. Similarly, an increase in CAT expression from the same construct (pBLCAT-ENDOA) was also observed in 7AQS2.1 cells. Our results therefore indicate that the EndoA enhancer is regulated by ETS proteins via interaction with multiple ETS-binding site sequences.

Animals↗
PubMed1994

Palliative care in the community: setting practice guidelines for primary care teams.

BACKGROUND: Previous studies have demonstrated deficiencies in palliative care in the community. One method of translating the results of research into clinical practice, in order to produce more effective health care, is the development of clinical guidelines. Setting standards for such care has been performed by care teams in both hospital and hospice settings but not in primary care. AIM: This study set out to develop guidelines for primary care teams to follow in the provision of palliative care in the community using facilitated case discussions with the members of such teams, as a form of internal audit. METHOD: Five practices were randomly chosen from the family health services authority medical list. Meetings between the facilitators and primary care teams were held over a period of one year. The teams were asked to describe good aspects of care, areas of concern and suggestions to improve these, in recent cases of patient deaths. RESULTS: In total 56 cases were discussed. All practices felt that cohesive teamwork, coordinated management, early involvement of nursing staff and the identification of a key worker were essential for good terminal care. Concerns arose in clinical and administrative areas but the majority were linked to poor communication, either between patient and professionals within the primary care team or between primary and secondary care. All the positive aspects of care, concerns and suggestions were collated by the facilitators into guidelines for teams to refer to from the initial diagnosis of a terminal illness through to the patient's death and care of the relatives afterwards. CONCLUSION: Developing multidisciplinary as opposed to medical guidelines for palliative care allows primary health care teams to create standards that are acceptable to them and stimulates individuals within the teams to accept responsibility for initiating the change necessary for more effective care. The process of facilitating teams to discuss their work allows for recognition and respect of individuals' roles and more importantly provides shared ownership, an important contributory factor in the implementation of guidelines.

Clinical Protocols↗
PubMed1994

Scintigraphic manifestations of "sternal cupping".

Sternal abnormalities in sickle-cell disease have been documented by bone scintigraphy and radiography in patients with homozygous sickle-cell anemia, but not in patients with sickle-thalassemia. We present here two unusual cases of sternal abnormalities in complicated sickle-cell disease. One is an infant with radiographic findings of "sternal cupping" and transient hypo-ossification of the sternum and sickle-thalassemia. The other patient is also a male infant with unusual, persistent under-ossification of bone, in association with radiographic findings of "sternal cupping." The second patient also had a 4P-chromosomal defect (Wolf-Hirschhorn syndrome) in which sternal hypo-ossification was described.

Abnormalities, Multiple↗
PubMed1993

3-Acyl-4-hydroxyquinolin-2(1H)-ones. Systemically active anticonvulsants acting by antagonism at the glycine site of the N-methyl-D-aspartate receptor complex.

Most full antagonists at the glycine site of the NMDA receptor contain a carboxylic acid, which we believe to be detrimental to penetration of the blood-brain barrier. By consideration of a pharmacophore, novel antagonists at this site have been designed in which the anionic functionality is a vinylogous acid, in the form of a 4-hydroxyquinolin-2(1H)-one. In this series, a 3-substituent is necessary for binding, and correct manipulation of this group leads to compounds such as the 3-(3-hydroxyphenyl)propargyl ester 24 (L-701,273), with an IC50 for displacement of [3H]-L-689,560 binding of 0.17 microM and Kb against NMDA in the cortical slice of 1.39 microM. Compounds were tested for their ability to prevent audiogenic seizure in DBA/2 mice; the most potent compound in this series is the cyclopropyl ketone 42 (L-701,252), with an ED50 of 4.1 mg/kg ip. A model is proposed for binding to the glycine site, in which an important interaction is of a putative receptor cation with the pi-system of the 3-substituent.

Acylation↗
PubMed1993

Pump-assisted hemofiltration in infants with acute renal failure.

Hemofiltration is accepted management for acute renal failure in critically ill patients. However, in infants, obtaining arterial access or adequate flow through the access is often difficult. We report our technique and experience with pump-assisted hemofiltration (PAHF) in ten infants with acute renal failure. In five patients, double-lumen venous catheters provided access, while two catheters at separate sites were used in the remaining patients. In all patients, hemofilters were used with standard intravenous tubing added to pre-filter tubing and placed through a standard volumetric infusion pump for regulation of blood flow. The infants, aged 5-575 days, weighed from 2.8 to 11.4 kg and had primary diagnoses of post-operative congenital heart disease in five, sepsis in four, and renal dysplasia in one. The duration of PAHF averaged 158 +/- 115 h (range 20-332 h). Complications included bleeding at a catheter or surgical site in one patient each and asymptomatic hyponatremia in five patients. Thus, with adequate nurse training, PAHF using a volumetric infusion pump for blood regulation can be acceptable therapy in acute renal failure in infants.

Acute Kidney Injury↗
PubMed1993

ETS family proteins activate transcription from HIV-1 long terminal repeat.

ets is a multigene family and its members share a common ETS DNA-binding domain. ETS proteins activate transcription via binding to a purine-rich GGAA core sequence located in promoters/enhancers of various genes, including several that are transcriptionally active in T cells. The ETS1, ETS2, and ERBG/Hu-FLI-1 gene expression pattern also suggests a role for these genes in cells of hematopoietic lineage. The HIV-1 LTR core enhancer contains two 10-base pair direct repeat sequences (left and right) that are required for regulation of HIV-1 mRNA expression by host transcription factors, including NF kappa B. Two ETS-binding sites are present in the core enhancer of all the HIV-1 isolates reported so far. In our studies, we utilized HIV-1 HXB2 and HIV-1 Z2Z6 core enhancers because the Z2Z6 strain has a single point mutation flanking the right ETS-binding site. We demonstrate that the ETS1, ETS2, and ERGB/Hu-FLI-1 proteins can trans-activate transcription from both the HXB2 and Z2Z6 core enhancer when linked to a reporter (cat) gene. In addition, we show that the DNA binding and trans-activation with the Z2Z6 core enhancer is at least 40-fold higher than that observed with the HXB2 core enhancer. Further, we provide evidence that the marked increase in binding and trans-activation with Z2Z6 core enhancer sequences is due to the substitution of a flanking T residue in HXB2 TGGAA) by a C residue in Z2Z6 (CGGAA) isolate, thus generating an optimal ETS-binding core (CGGAA) sequence.

Animals↗
PubMed1993

Transactivation of GATA-1 promoter with ETS1, ETS2 and ERGB/Hu-FLI-1 proteins: stabilization of the ETS1 protein binding on GATA-1 promoter sequences by monoclonal antibody.

Ets family proteins activate transcription via binding to the GGAA core sequence located in the promoter/enhancer elements of many cellular and viral genes. GATA-1 is an erythroid-specific transcription factor. The promoter of the chicken GATA-1 gene contains multiple ets binding sites (EBS), two of them are present in palindromic form. The GATA-1 promoter has been shown to be activated by the E26 virus. In this study, we have analysed whether the palidromic EBS of the chicken GATA-1 promoter is a target for binding and activation by members of the cellular ets gene family products. The results herein indicate that both EBS in the palindrome are required for DNA-binding because mutations in either site reduces the activity by at least 95%. Moreover, DNA binding of ETS1 to the EBS palindrome is dramatically stabilized in the presence of a specific monoclonal antibody whose epitope maps between amino acid positions 240-260. Although each of the single sites bind, the efficiency of binding is extremely low. Furthermore, for efficient binding the two sites must be in an inverted configuration because of the fact that the oligonucleotide containing the left and right EBS in the same orientation binds 10-fold less than the oligonucleotide containing the EBS palindrome. Additionally, we show that the transcription of a reporter gene (CAT) either linked to the GATA-1 EBS palindrome or GATA-1 promoter can be activated by cotransfection with ETS1, alternatively-spliced ETS1, ETS2 or ERGB/Hu-FLI-1 expression vectors.

Animals↗
PubMed1992

Ultrasonic and computed tomographic appearances of paraganglioma simulating pancreatic mass.

We report two cases of paraganglioma in which the tumour was situated adjacent to the head of the pancreas simulating a pancreatic mass lesion. The absence of biliary or pancreatic duct dilatation on ultrasound in the presence of a large mass suggested a retroperitoneal tumour rather than a pancreatic adenocarcinoma. Functional activity in these tumours is common and should be excluded before biopsy.

Diagnosis, Differential↗
PubMed1992

Contrast enhancing lymph nodes in bladder cancer: a potential pitfall on CT.

We report three cases of bladder cancer in which contrast enhanced computed tomography (CT) demonstrated minimally enlarged lymph nodes. These showed uniform uptake of contrast medium to a similar degree as adjacent venous structures, making the distinction between vessels and lymph nodes difficult. Magnetic resonance imaging (MRI) examination resolved the problem in two of the three patients.

Carcinoma, Transitional Cell↗
PubMed1992

Mammary hamartoma--a review of 35 cases.

Mammary hamartomas are macroscopically well-delineated tumours composed of a variable mixture of epithelial elements, fat and fibrous tissue. Such lesions are an under-recognized entity and, as they can be visualized by mammography, may be seen more frequently with the advent of the UK National Breast Screening Programme. The clinical and pathological features of 35 cases of mammary hamartoma seen at the Imperial Cancer Research Fund Clinical Oncology Unit at Guy's Hospital between 1979 and 1990 have been reviewed. Hormone receptor analysis on nine cases gave high progesterone with low oestrogen levels, probably reflecting their premenopausal status. Immunohistochemistry showed that the positive receptor staining was confined to the epithelial elements. In 25 cases pseudo-angiomatous hyperplasia was evident in the stroma of the lesion. The importance of distinguishing the inter-anastomosing stromal spaces seen in the latter condition from low-grade angiosarcoma is emphasized; the relationship between pseudo-angiomatous hyperplasia and mammary hamartoma is discussed; and the possibility that the former represents a permanently dilated form of the lymphatic labyrinth suggested.

Adolescent↗
PubMed1992

Cognitive-behavioural treatment of panic disorder during pregnancy and lactation.

The treatment of panic disorder during pregnancy and lactation poses special problems. It is important that both the practitioner and patient consider a number of issues to find the most appropriate treatment for the patient. New cognitive-behavioural treatment options often circumvent the problems of pharmacotherapy for pregnant or lactating women while providing therapeutic benefits which are at least equivalent.

Adult↗
PubMed1991

Registration and display of the combined bone scan and radiograph in the diagnosis and management of wrist injuries.

A system has been developed for the registration and combined display of the X-ray image and isotope bone scan. This system has been evaluated by prospectively studying 23 patients who were referred for suspected injury of the wrist. The registration system has an inherent precision for registration of about 1 mm. When patient positioning errors are included, this increases to about 4 mm. Two observers evaluated the sets of images prior to registration and after registration and combined display. They judged that in 16 out of 17 cases judged abnormal (observer 1) and 12 out of 18 cases judged abnormal (observer 2), the registration technique improved localization of a lesion. One case was rejected as registration was not possible due to incorrect positioning of the hand.

Carpal Bones↗
PubMed1991

Risks associated with an elevated maternal serum alpha-fetoprotein level.

Among 58,187 women tested, 1002 had a maternal serum alpha-fetoprotein measuring greater than or equal to 2.5 multiples of the median after correction for race, weight, and insulin-dependent diabetes. They were stratified into three groups: group 1, 2.5 to 2.9; group 2, 3.0 to 5.0; group 3, greater than or equal to 5.0 multiples of the median. The initial risk of a serious abnormality detected by ultrasonography or amniocentesis was 17% (5%, 12% and 65% in groups 1, 2, and 3, respectively). After correction for twins and dates, this risk became 23% (7%, 18%, and 71% in groups, 1, 2, and 3, respectively). Among the women with high maternal serum alpha-fetoprotein levels, 556 (77%) had normal ultrasonographic and amniocentesis studies, and the risk of adverse pregnancy outcome ws 27% (19%, 29%, and 70% in groups 1, 2, and 3, respectively). There was a statistically significant increase in late fetal and perinatal death, prematurity and growth retardation, oligohydramnios, abruptio placentae, preeclampsia, and congenital abnormalities. The overall risk for abnormality or adverse outcome was 24% in group 1, 41% in group 2, and 91% in group 3.

Congenital Abnormalities↗
PubMed1991

Familial Hirschsprung's disease: report of autosomal dominant and probable recessive X-linked kindreds.

Multifactorial sex-modified inheritance has been proposed as the model of transmission in familial Hirschsprung's disease (HD). A review of two separate kindreds suggests that aganglionosis may be inherited as an X-linked recessive or an autosomal dominant trait. Chromosomal anomalies and other syndromes, including G6PD deficiency, may occur with familial HD. Recurrence risk counseling for family members depends on accurate pedigree analysis and a comprehensive understanding of the genetic factors involved.

Female↗
PubMed1991

Renal artery stenosis in children.

In a large paediatric renal unit over the last 14 years, 19 children (10 male and 9 female, aged 1 week to 16 years, mean 7 years) with renal artery stenosis (RAS) were evaluated. Transplant RAS cases were not included. All 19 children were hypertensive. In 10 this was an incidental finding. Based on clinical findings and arteriography, the causes of RAS included a middle aortic syndrome (MAS) (n = 5), neurofibromatosis (n = 3), William's syndrome (n = 3), fibromuscular hyperplasia (FMH) (n = 4), idiopathic RAS (n = 2) and isolated branch artery stenosis (n = 2). Previous studies have suggested FMH is the commonest cause of RAS in the paediatric population. In our study the largest subgroup are MAS/William's syndrome children, in whom the angiographic appearances were indistinguishable. Where possible, management, both surgical and radiological, and eventual outcomes have been described.

Adolescent↗
PubMed1991

A field trial to evaluate a whole cell vaccine for the prevention of caseous lymphadenitis in sheep and goat flocks.

A field trial to evaluate a whole cell vaccine for the prevention of caseous lymphadenitis (CLA) in sheep and goats was performed in one goat herd and one sheep flock over a period of three years. In goats, there was a nonstatistically significant trend for fewer cases of CLA in the vaccinated animals compared to the controls. In sheep, from six months to 36 months postinitial vaccination, the proportion of vaccinated sheep that developed CLA was significantly less (p less than 0.05) than in the control sheep. The antibody titers to Corynebacterium pseudotuberculosis as detected by microagglutination assay were significantly different (p less than 0.0001) at all times except at the initial vaccination. Swellings occurred at the vaccination site at an incidence level of 29.6% in goats and 34.1% in sheep. The vaccine appeared to be efficacious in reducing the proportion of sheep that developed CLA when challenged naturally in a field situation.

Agglutination Tests↗