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Biomedical subjects

I C Taylor

Publications and source records attributed to I C Taylor.

32 records · Page 2Linked to original sources
PubMed1990

Factor substitution in a human HSP70 gene promoter: TATA-dependent and TATA-independent interactions.

To investigate interactions between transcription factors on mammalian promoters, we constructed a set of 24 variations of the human HSP70 gene promoter in which six upstream sequence motifs are paired in every possible combination with four TATA motifs. These promoters were analyzed for in vivo expression, and selected constructs were examined by in vitro template commitment studies. Activation transcription factor (ATF) and CP1 showed dramatically different interactions with the factor(s) bound to the TATA region. CP1 functioned in vivo regardless of the TATA motif that it was paired with and was not capable of sequestering the core promoter complex in a template commitment assay. ATF activity was dramatically altered by changing the TATA motif, and ATF was able to sequester the core promoter complex. These data suggest that CP1 and ATF function by distinct mechanisms that differ with respect to interaction with the factor(s) at the TATA box. Factor Sp1 also appeared to function by a TATA-independent mechanism. These data imply that the ability of a factor to function is determined not only by the intrinsic properties of the factor but also by promoter context.

Base Sequence↗
PubMed1990

E1a transactivation of human HSP70 gene promoter substitution mutants is independent of the composition of upstream and TATA elements.

We have analyzed 41 deletion, linker scan, and substitution mutants of the human HSP70 gene promoter for activation by the adenovirus E1a region. No natural element of the HSP70 gene promoter was required for activation. To investigate specific interactions between E1a and transcription factors, a set of 24 promoters containing all possible combinations of eight different upstream or TATA motifs was investigated for E1a stimulation. E1a transactivated the promoter regardless of the particular TATA motif present. Furthermore, there was no dramatic correlation between any upstream motif and activation by E1a. These data suggest that E1a does not stimulate transcription via an interaction with any specific transcription factor but instead suggest that E1a interacts via the general transcription machinery.

Adenovirus Early Proteins↗
PubMed1989

Stimulation of the human heat shock protein 70 promoter in vitro by simian virus 40 large T antigen.

Simian virus 40 large tumor (T) antigen stimulates transcription from the SV40 late promoter and some cellular genes. We report here the novel finding that purified T antigen preferentially stimulates transcription from the human heat shock protein 70 promoter in an in vitro transcription system. T antigen is thus capable of stimulating transcription by a process that does not require synthesis of other proteins and that may involve a direct interaction with preexisting cellular factors.

Animals↗
PubMed1988

Multidisciplinary assessment of applicants for residential accommodation.

Fifty of 62 applicants for residential accommodation underwent assessment at a geriatric day hospital. Twenty-five were suitable, 11 were suitable following rehabilitation and 14 were unsuitable for placement in residential accommodation. Around 35% of all applicants were not assessed. Seventy-nine per cent of assessed applicants, without dementia, either were unsure of how their application had been initiated or did not understand the implications of a move to residential accommodation. Twenty-two per cent of all applicants assessed were taking four or more drugs. To maximise the use of residential accommodation, all applicants should be assessed to reduce inappropriate referrals.

Aged↗
PubMed1987

Multiple basal elements of a human hsp70 promoter function differently in human and rodent cell lines.

The human heat shock protein 70 (hsp70) gene is expressed constitutively in a wide variety of cells. Two separate promoter domains determine this basal level of hsp70 expression. The proximal domain is contained within 84 bases of the transcription initiation site and consists of three elements which appear to interact with the TATA factor(s) and CCAAT-box-binding transcription factor and SP1, respectively. The proximal domain is sufficient for near-maximal basal expression to rodent cell lines. The distal promoter domain consists of sequences upstream of -84 and is necessary in conjunction with the proximal domain for full basal expression in human cell lines. Although in BALB/c 3T3 cells the distal promoter domain plays little role in basal expression, it is functional as evidenced by the ability to compensate efficiently for mutations in the proximal CCAATC homology. The distal domain does not compensate as efficiently for proximal-domain mutations in HeLa cells. Basal expression of this human hsp70 promoter is, therefore, determined by multiple elements. Fewer elements are required for basal expression in rodent cell lines than in human cell lines, suggesting that there are significant differences between the rodent and human transcription apparatuses.

Animals↗
PubMed1986

Elderly patients in acute medical wards: factors predicting length of stay in hospital.

A prospective study of 419 patients aged 70 and over admitted to acute medical wards was carried out by medical staff from a geriatric unit. Data, including presenting problem, housing, social support, mental state, continence, and degree of independence before and after admission, were recorded. Of the 419 patients, 143 remained in hospital after 14 days and 65 after 28 days. The major factors associated with prolonged stay in hospital included advanced age, stroke, confusion and falls as reasons for admission to hospital, incontinence, and loss of independence for everyday activities. Social circumstances did not predict length of stay. Although these factors are interrelated, the most important influence on length of stay was the medical reason for admission. Early contact with the geriatric medical unit in these patients may speed up the recovery or result in more appropriate placement.

Age Factors↗
PubMed1983

The significance of cardiac arrhythmias in the aged.

Twenty-four-hour ambulatory electrocardiography was performed in 25 young and 29 active elderly subjects. Sinus bradycardia and sinus arrhythmia were common in the young but uncommon in the elderly. Ventricular and supraventricular premature beats and brief runs of supraventricular tachycardia were common in the elderly but uncommon in the young. Complex ventricular arrhythmias only occurred in the elderly but brief episodes of nocturnal Wenckebach AV block were quite common in young and old alike. No significant difference in arrhythmia frequency was found between elderly subjects with heart disease and those without heart disease or between elderly subjects without symptoms and those with non-episodic symptoms such as dizziness. None of the arrhythmias in the young or elderly subjects was associated with symptoms. In follow-up at 30 months, only one elderly subject was deceased (from pneumonia) and none had suffered a stroke or heart attack. It is concluded that transient cardiac arrhythmias are commoner in the elderly than in the young. However, their long-term significance remains unknown, but it is likely that they are relatively benign.

Adult↗
PubMed1983

Cardiac arrhythmias and femoral neck fracture.

Nineteen of 45 consecutive patients admitted to hospital with fracture of the neck of femur had ambulatory electrocardiography performed on the fourteenth post-operative day. The frequency of cardiac arrhythmias was compared with control subjects who had undergone total hip replacement operations. No significant difference was found. None of the cardiac arrhythmias in the fracture or control subjects was associated with symptoms. Two fracture patients and three control subjects suffered an acute myocardial infarct peri-operatively and were excluded from the study. Fracture patients on drug therapy for heart disease had an increased six-month mortality rate compared with those not on such therapy. Episodic cardiac arrhythmias do not appear to be an important contributory factor to fracture of the neck of femur in the elderly.

Age Factors↗
PubMed1983

Is ambulatory electrocardiography a useful investigation in elderly people with 'funny turns'?

Episodic diffuse cerebral symptoms and unexpected falls were investigated by ambulatory electrocardiography in nine men and 19 women aged 65 years or more. Eight subjects with episodic dizziness or syncope had cardiac arrhythmias which are known to be capable of causing these symptoms and four of these had symptoms at the time of the arrhythmia. However, only one was detected by ambulatory electrocardiography alone. No significant arrhythmias were found in any of the remaining subjects. When 17 symptomatic subjects were compared with 17 age- and sex-matched asymptomatic controls, cardiac arrhythmias known to be capable of causing symptoms were commoner in the symptomatic group, but the differences were not statistically significant. Ambulatory electrocardiography is of no more value than standard electrocardiography in the detection of arrhythmias associated with diffuse cerebral symptoms in elderly people.

Aged↗
PubMed1983

Are cardiac arrhythmias important in stroke?

Ambulatory electrocardiography was performed on 21 consecutive acute stroke patients on the day of admission and 14 and 42 days later. There was no statistically significant difference in cardiac arrhythmias between stroke patients and a group of age- and sex-matched controls. There was considerable variation in the frequency of cardiac arrhythmias on each day but none of the arrhythmias was associated with a sudden deterioration in the condition of the patients and no arrhythmias produced symptoms in either the stroke or the control groups. Fourteen per cent of stroke patients had an associated acute myocardial infarction and 57% had a history of previous heart disease. While a history of previous heart disease or the occurrence of major ventricular arrhythmias were associated with an increased six-week mortality rate, routine continuous monitoring of cardiac rhythm would not appear to be of value in acute stroke.

Aged↗
PubMedDate not supplied

HTS in the new millennium: the role of pharmacology and flexibility.

Over the past decade, high throughput screening (HTS) has become the focal point for discovery programs within the pharmaceutical industry. The role of this discipline has been and remains the rapid and efficient identification of lead chemical matter within chemical libraries for therapeutics development. Recent advances in molecular and computational biology, i.e., genomic sequencing and bioinformatics, have resulted in the announcement of publication of the first draft of the human genome. While much work remains before a complete and accurate genomic map will be available, there can be no doubt that the number of potential therapeutic intervention points will increase dramatically, thereby increasing the workload of early discovery groups. One current drug discovery paradigm integrates genomics, protein biosciences and HTS in establishing what the authors refer to as the "gene-to-screen" process. Adoption of the "gene-to-screen" paradigm results in a dramatic increase in the efficiency of the process of converting a novel gene coding for a putative enzymatic or receptor function into a robust and pharmacologically relevant high throughput screen. This article details aspects of the identification of lead chemical matter from HTS. Topics discussed include portfolio composition (molecular targets amenable to small molecule drug discovery), screening file content, assay formats and plating densities, and the impact of instrumentation on the ability of HTS to identify lead chemical matter.

Animals↗