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Biomedical subjects

J D Watson

Publications and source records attributed to J D Watson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Expanding access to coronary artery bypass surgery: who stands to gain?

OBJECTIVE: To determine the perceptions of general practitioners (GPs) about the benefits of coronary artery bypass surgery, in terms of gains in life expectancy, for different groups of patients. DESIGN: A questionnaire survey of all GPs in Northern Ireland. SETTING: A survey conducted collaboratively by the departments of public health medicine in each of the four health boards in the province, serving a total population of 1.5 million. MAIN OUTCOME MEASURES: The median and mean gain in life expectancy perceived by groups of doctors for smoking and non-smoking male and female 55 year old patients. The percentage of 50 year old and 70 year old non-smoking patients considered likely to have their lives extended with bypass surgery. Differences were assessed using the Mann-Whitney U test for unpaired samples and the Wilcoxon signed rank tests for paired. RESULTS: 541 GPs replied (response rate 56%). The median (and mean) perceived gain in life expectancy after cardiac surgery for non-smoking 55 year old subjects was 120 (104) months for men and 120 (112) months for women (z = 6.42; P < 0.0001; Wilcoxon signed rank test). For male and female smokers of the same age, the perceived gains were 48 (47) and 60 (52) months respectively (z = 6.72; P < 0.0001; Wilcoxon signed ranks test), both figures being significantly different than for non-smokers. The median (and mean) percentage of patients that the doctors considered would have their lives extended by bypass surgery was 70 (64) of every 100 "young" patients and 40 (42) of every 100 "old" patients, (z = 16.2; P < 0.0001). CONCLUSIONS: These results point to a significant overestimation of the benefits of coronary artery bypass surgery by GPs in Northern Ireland and to a need to develop guidelines for referral.

Age Factors↗
PubMed1995

ANP secretion from small cell lung cancer cell lines: a potential model of ANP release.

Although atrial distension is widely accepted as the primary stimulus for atrial natriuretic peptide (ANP) release, a number of agonists are also known to induce its secretion. The mechanisms underlying these processes are not well understood. Studies of this nature are hampered by the inherent difficulty in culturing homogeneous populations of cardiac myocytes in sufficient quantities to perform molecular investigations. For this reason, we have examined the possibility of using other cell types as a model of ANP release. It has been reported that a number of tumor samples from small cell lung cancer (SCLC) patients express the ANP gene. Characterization of a large number of cell lines derived from SCLC tumor samples indicated that two of these cell lines, OS-A and SHP-77, secrete ANP at rates of approximately 10(-20) g.cell-1.min-1. This is a sufficient quantity to facilitate secretion studies using a perifusion system. We have demonstrated that ANP is released through regulated secretory pathways, as the Ca2+ ionophore A-23187, arginine vasopressin (AVP), and the sodium ionophore, monensin, were capable of modifying secretion rates. High-pressure liquid chromatography (HPLC) analysis indicated that the primary secretory product is ANP-(99-126), the circulating form of this hormone. Intracellularly, both ANP-(99-126) and ANP-(1-126) were present, suggesting the synthesis and appropriate cleavage of pro-ANP-(1-126). Because both of these cell lines have doubling times in the range of 3-5 days, they could serve as a rapidly proliferating and easily maintainable supply of homogeneous tissue for release studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗
PubMed1994

The delta-subunit of murine guanine nucleotide exchange factor eIF-2B. Characterization of cDNAs predicts isoforms differing at the amino-terminal end.

Protein synthesis in mammalian cells is regulated at the level of the guanine nucleotide exchange factor, eIF-2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. We have isolated and sequenced cDNA clones encoding the delta-subunit of murine eIF-2B. The cDNA sequence encodes a polypeptide of 544 amino acids with molecular mass of 60 kDa. Antibodies against a synthetic polypeptide of 30 amino acids deduced from the cDNA sequence specifically react with the delta-subunit of mammalian eIF-2B. The cDNA-derived amino acid sequence shows significant homology with the yeast translational regulator Gcd2, supporting the hypothesis that Gcd2 may be the yeast homolog of the delta-subunit of mammalian eIF-2B. Primer extension studies and anchor polymerase chain reaction analysis were performed to determine the 5'-end of the transcript for the delta-subunit of eIF-2B. Results of these experiments demonstrate two different mRNAs for the delta-subunit of eIF-2B in murine cells. The isolation and characterization of two different full-length cDNAs also predicts the presence of two alternate forms of the delta-subunit of eIF-2B in murine cells. These differ at their amino-terminal end but have identical nucleotide sequences coding for amino acids 31-544.

Alternative Splicing↗
PubMed1994

Cloning of a gene encoding a human leukocyte protein characterised by extensive heptad repeats.

Complementary DNA (cDNA) clones, encoding a fusion protein that was recognised by an antiserum raised against a purified polypeptide fragment of a 180-kDa human leukocyte protein, were isolated from a lambda gt11 expressed library. The clones encoded a unique amino acid (aa) sequence interspersed with heptad repeats that typify coiled-coil proteins, and hybridised to a 5-kb transcript universally expressed in a panel of eight human tissues. Comparatively high levels of RNA expression were seen in testis, ovary and mitogen-activated peripheral blood leukocytes (PBLs). The deduced 1300-aa sequence reveals a protein with a typical signal peptide, a hydrophilic domain containing an N-terminal globular head with a nuclear localization signal sequence, a C-terminal region of coiled-coil structure, a candidate transmembrane domain, and a short 10-aa C-terminal domain. Rabbit polyclonal antisera raised against a truncated lambda gt11 fusion protein recognized a 150-170-kDa protein (non-reduced) in mitogen-activated PBLs. The protein designated here as CG-1 may exist as a homodimer destined for translocation to the nucleus, with a role in leukocyte differentiation and/or effector function.

Amino Acid Sequence↗
PubMed1994

Steel factor (c-kit ligand) stimulates the in vitro growth of immature CD3-/CD4-/CD8- thymocytes: synergy with IL-7.

The ability of Steel factor (SLF) to stimulate the growth of immature thymocytes alone and in combination with IL-7 was assessed. In suspension cultures of CD4-/CD8- thymocytes, SLF itself did not induce significant proliferation, but in combination with IL-7, it induced a greater response than did IL-7 alone. In fetal thymus lobe submersion cultures, SLF stimulated the growth of cells to a magnitude similar to that of IL-7 and the combination resulted in a synergistic response. Phenotypic analysis of these cells revealed that SLF in comparison to IL-7 stimulated the growth of a less mature population. The synergistic growth stimulated by the combination of IL-7 and SLF occurred in a population of IL-2R+/CD4-/CD8-/CD3- cells. Cells grown in SLF expressed low levels of IL-2R and overnight culture in IL-7 dramatically increased IL-2R expression. Thus, these results are consistent with the hypothesis that SLF stimulates the growth of a less mature thymocyte population than does IL-7.

Animals↗
PubMed1994

Dosimetry of intravenously administered oxygen-15 labelled water in man: a model based on experimental human data from 21 subjects.

Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H2(15)O because of the short half-life (2.04 min) of 15O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H2(15)O concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 microSv.MBq-1 compared with a value of about 0.5 microSv.MBq-1 predicted by uniform water distribution models. Based on the human data, a method of approximating H2(15)O absorbed dose values from body surface area is described.

Adult↗
PubMed1994

Brain activity during reading. The effects of exposure duration and task.

Brain activity during reading tasks was investigated using PET. The aim was to account for differences in the results of two previous studies [those of Petersen et al. (Science 1990; 249: 1041-4) and Howard et al. (Brain 1992; 115: 1769-82)] by systematically varying the type of reading task and the exposure duration of the word stimuli. Both variables strongly influenced patterns of brain activity. There were three types of task: (i) reading aloud; (ii) reading silently; and (iii) lexical decision on visually presented words and pseudowords. Reading aloud and reading silently engaged the left middle and superior temporal regions, confirming the important role of these areas in visual word processing. The areas principally engaged during lexical decision were the left inferior and middle frontal cortices and the supplementary motor area; activity in these areas suggests that the subjects were using a phonological strategy to perform the task. There was also a significant effect of exposure duration, with activity being greater for short (150 ms) exposure durations than for long (1000 ms or 981 ms) exposure durations. We conclude that until we understand how subtle variations in experimental design influence brain activity during reading tasks, the association of specific processing functions with individual anatomical areas activated during reading is premature.

Adult↗
PubMed1994

Reversal of T cell unresponsiveness by augmentation of antigen presenting cell function.

We have previously described epitopes of the 18 kDa protein of Mycobacterium leprae which stimulate T and B cell responses in different strains of mice. A series of overlapping 20-mer peptides that span the 18 kDa protein were used as immunogens to examine T and B cell recognition of different epitopes. Strain-specific variation in the epitopes which induce the strongest responses was affected by genes linked to the H-2 complex and the T cell responses revealed by re-challenge with antigen were at least partially controlled by factors other than T cell specificity. We have examined the responses to one such antigen, peptide 1-20, which contains strongly immunogenic epitopes for T and B cells. T cells from draining lymph nodes of peptide 1-20 immunized B10.BR, but not BALB/c mice, proliferated in vitro in response to rechallenge with peptide 1-20 or whole protein. Immunization with the same peptide also induced specific antibody only in B10.BR mice. However, immunization of BALB/c mice results in 'silent' priming of T cells since these can be induced to respond in vitro to this antigen when cultured with activated macrophages as antigen presenting cells (APC). The failure of APC from mBALB/c mice primed with peptide 1-20 to stimulate CD4+ proliferation when re-challenged in vitro and the failure to elicit antibody responses to peptide 1-20 are presumably due to the same defect in antigen-presenting cell function, since presentation of peptide 1-20 by activated macrophages is sufficient to restore both responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography.

The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to non-painful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the "medial pain system". The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes.

Adult↗
PubMed1994

Is choice of general practitioner important for patients having coronary artery investigations?

OBJECTIVE: To determine whether particular sociodemographic characteristics of patients with stable angina affected their general practitioners' (GPs') decisions to refer them for revascularisation assessment. DESIGN: Postal questionnaire survey. SETTING: Collaborative survey by the departments of public health medicine in each of the four health boards in Northern Ireland, serving a total population of 1.5 million. SUBJECTS: All (962) GPs. MAIN MEASURES: The relation between GPs' referral decisions and patients' age, sex, employment status, home circumstances, smoking habits, and obesity. RESULTS: 541 GPs replied (response rate 56%). Most were "neutral" towards a patient's sex (428, 79%), weight (331, 61%), smoking habit (302, 56%), employment status (431, 80%), and home circumstances (408, 75%) in making decisions about referral. In assigning priority for surgery most were neutral towards the patient's sex (459, 85%), employment status (378, 70%), and home circumstances (295, 55%). However, most GPs (518, 95%) said that younger patients were more likely to be referred, and a significant minority were less likely to refer patients who smoked (202, 37%) and obese patients (175, 32%) and more likely to refer employed patients (97, 18%) and those with dependents (117, 22%) (compared with patients with otherwise comparable clinical characteristics); these views paralleled the priority which GPs assigned these groups. The stated likelihood of referral of young patients was independent of the GPs' belief in ability to benefit from revascularisation, but propensity to refer and perception of benefit were significantly associated for all other patient characteristics. CONCLUSION: GPs' weighting of certain characteristics in reaching decisions about referral for angiography is not uniform and may contribute to unequal access to revascularisation services for certain patient groups.

Age Factors↗
PubMed1994

Reconstitution properties of thymus stem cells in murine fetal liver.

Injection of day-12 murine fetal liver cells into thymus lobes of Thy-1 congenic adult recipients results in a wave of thymocyte development. The kinetics of repopulation by donor cells reaches a peak after 20-25 days. The frequency of thymic stem cells (TSC) in day-12 fetal liver was estimated, by limit dilution, as 1 in 4 x 10(4) cells. Within 8 hr of injection into a thymus lobe, fetal liver TSC commit to T-cell development, losing stem-cell activity. When fetal liver cells are maintained in culture for 7 days, with no exogenous cytokines added, and then injected intra-thymically (I.T.), thymus recolonization is not observed. However, TSC can be maintained in culture for 7 days with IL-1 beta, IL-3, IL-6, or LIF added, alone or in combination, with steel factor (SLF). Poisson analysis of fetal liver cells cultured with SLF and IL-3 together revealed a precursor frequency of 1 in 1.8 x 10(5) cells. In contrast, the frequency of TSC in adult bone marrow was estimated by limit dilution as 1 in 12,000 cells.

Animals↗
PubMed1994

Basal cell carcinomas: do they need to be followed up?

Basal cell carcinoma (BCC) is the commonest of the malignant skin tumours. The follow-up of patients following excision of these lesions varies immensely. The aim of this study was to assess the need for outpatient follow-up of patients who had a primary BCC excised. A retrospective study was performed using the case notes of 206 patients who had a primary BCC excised in Bangour General Hospital in the years 1986 and 1987. Fourteen were excluded from the study, leaving 192 patients with 215 lesions. The overall recurrence rate was 5.1% with 39% of lesions recurring if the tumour was incompletely excised compared with 1% if it was excised completely. Complete excision is therefore the key to surgical control and we feel that there is no need to follow up patients routinely if the BCC has been completely excised.

Adult↗
PubMed1994

Vascular effects of a modified cold pressor test in spinal cord injured and able-bodied men.

The vascular reflex responses of the hands of ten spinal cord injured (SCI) men (sensory and motor complete) to a modified cold pressor test were compared to ten age-matched, able-bodied men. The skin temperature of the left index finger was measured before, during, and after the immersion of the feet in ice water for 20 seconds. The heart rate and blood pressure were measured 5 minutes before and 15 minutes after the cold stimulus. The able-bodied subjects showed an immediate vasoconstriction and fall in finger temperature after cold stimulation of the feet, followed by vasodilation and an increase in finger temperature (p < .0001), whereas, the SCI subjects did not show any change in finger temperature during this test. Prior to application of the cold stimulus, the SCI subjects had a significantly low diastolic blood pressure compared with the diastolic blood pressure of able-bodied subjects, which "normalized" after the cold stimulus. These data support the concept that regulation of vascular tone occurs at both spinal and supraspinal levels.

Adult↗
PubMed1993

Looking forward.

We are now entering the genome era of genetics, this phase being preceded by prior intellectual movements which gave the world: (1) Mendelian analysis, (2) DNA as the molecule of genetics, (3) the DNA-->RNA-->protein Central Dogma, (4) the molecular basis of gene expression and regulation, (5) the use of recombinant DNA procedures for gene isolation and manipulation, and (6) DNA sequencing and genome analysis. Soon, the human genetic information made possible by genome analysis will lead to subsequent logically following eras of predictive genetics and gene therapy.

Animals↗