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R Underwood

Publications and source records attributed to R Underwood.

At least 55 records · Page 3Linked to original sources
PubMed1992

Increased apolipoprotein E and c-fms gene expression without elevated interleukin 1 or 6 mRNA levels indicates selective activation of macrophage functions in advanced human atheroma.

Cells found within atherosclerotic lesions can produce in culture protein mediators that may participate in atherogenesis. To test whether human atheromata actually contain transcripts for certain of these genes, we compared levels of mRNAs in carotid or coronary atheromata and in nonatherosclerotic human vessels by polymerase chain reaction (PCR) amplification of cDNAs reverse-transcribed from RNA. We measured PCR products (generated during exponential amplification) by incorporation of 32P-labeled primers. Levels of interleukin 1 alpha, 1 beta, or 6 mRNAs in plaques and controls did not differ. Compared to uninvolved vessels, plaques did contain higher levels of mRNA encoding platelet-derived growth factor A chain (42 +/- 24 vs. 12 +/- 10 fmol of product; mean +/- SD; n = 8 and 8, respectively; P = 0.007) and B chain (41 +/- 36 vs. 4 +/- 3 fmol of product, n = 14 and 6, respectively; P = 0.024). Atherosclerotic lesions consistently had much higher levels of apolipoprotein E (apoE) mRNA than did control vessels (131 +/- 71 vs. 5 +/- 3 fmol of product; n = 12 and 10, respectively; P less than 0.001). Direct RNA blot analyses confirmed elevated levels of apoE mRNA in plaque extracts. To test whether mononuclear phagocytes might be a source of the apoE mRNA, we studied a selective marker for cells of the monocytic lineage, the c-fms protooncogene, which encodes the receptor for macrophage colony-stimulating factor. Plaques also contained elevated levels of c-fms mRNA (30 +/- 17 vs. 5 +/- 3 fmol of product; n = 10 and 7, respectively; P = 0.002). Immunohistochemical colocalization demonstrated apoE protein in association with macrophages in plaques, whereas nonatherosclerotic vessels showed no immunoreactive apoE. ApoE produced locally in atheroma might modulate the functions of lesional T cells or promote "reverse cholesterol transport" by associating with high density lipoprotein particles, thus targeting them for peripheral uptake. Macrophages within the advanced human atheroma appear to exhibit a selective program of activation as they express high levels of apoE, whereas overall levels of interleukin 1 or 6 mRNAs in plaques are not elevated.

Apolipoproteins E↗
PubMed1992

Herpes zoster and human immunodeficiency virus infection.

The interaction of herpes zoster and the human immunodeficiency virus (HIV) was evaluated in a cohort study of 287 homosexual men with well-defined dates of HIV seroconversion and 499 HIV-seronegative homosexual men. The incidence of herpes zoster was significantly higher among HIV-seropositive men (29.4 cases/1000 person-years) than among HIV-seronegative men (2.0 cases/1000 person-years); the overall age-adjusted relative risk (RR) was 16.9 (95% confidence interval [CI], 8.7-32.6). When compared with that of age-matched population controls from 1945 to 1959, the incidence of zoster was significantly higher among seropositive men (RR, 26.7; 95% CI, 19.3-37.1) and slightly higher among seronegative men (RR, 1.85; 95% CI, 1.0-3.3); the latter may reflect increasing background rates over several decades. The risk of herpes zoster was not associated with duration of HIV infection and was not predictive of faster progression to AIDS.

Adult↗
PubMed1992

A survey of nuclear cardiological practice in Great Britain. The British Nuclear Cardiology Group.

There is little information on the practice of nuclear cardiology in Great Britain. On behalf of the British Nuclear Cardiology Group in October 1988 we sent a postal questionnaire to 143 hospitals with nuclear medicine facilities (at least 70% of such hospitals). Sixty nine replies were received (48%), of which 23 (33%) were from teaching hospitals and 46 (39%) non-teaching. In these hospitals 147,904 isotope investigations were performed annually (mean 2311 per centre) of which 17,298 (12%) (mean 254 per centre) were cardiac studies. Of these, 59% were equilibrium radionuclide ventriculograms, 14% first pass ventriculograms, and 27% thallium-201 scans. Rest studies were performed more commonly by radiographers or technicians (63%) than by doctors (20%), but doctors were more commonly involved in stress studies (48%). Radiologists reported the studies more often (28%) than they performed them (6%). Methods of acquisition and analysis were varied and, for instance, the lower limit of normal left ventricular ejection fraction ranged from 35% to 75% (mean 49%). For thallium imaging 42% of centres used dipyridamole in some patients and 24% used tomography. These data show that nuclear cardiology techniques are used much less frequently in Great Britain than in countries such as the United States and Germany, that the ratio of blood pool to myocardial perfusion imaging is much higher than elsewhere, and that methods are poorly standardised. They may provide the impetus to improve the service and serve as a baseline for future surveys.

Cardiology↗
PubMed1992

Impact of HIV infection on mortality and accuracy of AIDS reporting on death certificates.

To assess the impact of HIV infection on mortality and the accuracy of AIDS reporting on death certificates, we analyzed data from 6704 homosexual and bisexual men in the San Francisco City Clinic cohort. Identification of AIDS cases and deaths in the cohort was determined through multiple sources, including the national AIDS surveillance registry and the National Death Index. Through 1990, 1518 deaths had been reported in the cohort and 1292 death certificates obtained. Of the 1292 death certificates, 1162 were for known AIDS cases, but 9% of the AIDS cases did not have HIV infection or AIDS noted on the death certificate. Only 0.7% of the decedents had AIDS listed as a cause of death and had not been reported to AIDS surveillance. AIDS and HIV infection was the leading cause of death in the cohort, with the highest proportionate mortality ratio (85%) and standardized mortality ratio (153 in 1987), and the largest number of years of potential life lost (32,008 years). The devastating impact of HIV infection on mortality is increasing and will require continued efforts to prevent and treat HIV infection.

Abstracting and Indexing↗
PubMed1992

Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis.

The infiltration of monocytes into the vascular wall and their transformation into lipid-laden foam cells characterizes early atherogenesis. Macrophages are also present in more advanced human atherosclerotic plaques and can produce many mediators that may contribute to lesion formation and progression. Macrophage colony-stimulating factor (MCSF) enhances the proliferation and differentiation of monocyte progenitors and is required for the survival and activation of mature monocytes and macrophages. The authors therefore examined the expression of the MCSF gene in cultured human vascular endothelial (EC) and smooth muscle cells (SMC) as well as in atheromatous lesions from rabbits and humans. Growth arrested EC and SMC contain a low level of MCSF mRNA. Bacterial lipopolysaccharide (LPS), recombinant human interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor alpha (TNF alpha) induced MCSF mRNA accumulation in a concentration-dependent manner in both EC and SMC. These stimuli induced large increases in MCSF mRNA with peak induction between 4-8 hours after treatment. LPS, IL-1 alpha, and TNF alpha stimulated EC and SMC also showed increased fluorescent antibody staining for MCSF protein and released immunoreactive MCSF in a time-dependent manner. In contrast, phorbol 12-myristate 13-acetate (PMA) was a less potent inducer of MCSF gene expression and iron-oxidized low-density lipoproteins (ox-LDL) did not increase consistently MCSF mRNA or the synthesis and secretion of immunoreactive protein. Northern analysis of mRNA isolated from the atheromatous aorta of rabbits fed a 1% cholesterol diet for 10 weeks showed elevated MCSF mRNA compared with controls. Immunostaining of atheromatous arterial lesions of rabbits demonstrated MCSF protein in association with intimal SMC as well as macrophages. Furthermore, polymerase chain reaction (PCR) analysis of MCSF mRNA in human atheromata showed higher levels than found in nonatherosclerotic arteries and veins. Since the authors found no mRNA for the MCSF receptor, c-fms, in cultured EC or SMC macrophages are likely the primary target for MCSF within atheromatous vessels. The authors therefore investigated the effects of MCSF on monocyte functions related to foam cell development. Treatment of cultured human monocytes with recombinant human MCSF (10(3) U/ml, 72 hr) led to the accumulation of mRNA for the acetyl-LDL (scavenger) receptor and apolipoprotein E (apo E). These studies establish that vascular EC and SMC produce substantial MCSF in response to a variety of stimuli. The local production of MCSF during atherogenesis may contribute to macrophage survival and proliferation or activate specific macrophage functions such as expression of the scavenger receptor and secretion of apo E.

Animals↗
PubMed1990

Vena caval flow: assessment with cine MR velocity mapping.

The authors used cine magnetic resonance (MR) velocity mapping to study flow in the superior vena cava (SVC) and inferior vena cava (IVC) of 13 healthy control subjects and 13 patients with right-sided cardiac disease. In the control subjects, peaks of flow in systole and diastole were observed, and mean SVC flow was 35% of the cardiac output. Respiratory gating was used in six control subjects to acquire images at end inspiration and end expiration, and although the systolic peak was reduced at end expiration, total flow was unchanged. A reduced systolic peak and retrograde flow in the IVC were observed in patients with tricuspid regurgitation. A reduced diastolic peak was seen in patients with pulmonary hypertension, pericardial constriction, and right ventricular dysplasia, reflecting reduced diastolic compliance of the right ventricle. In the patient with obstruction of the SVC, absence of flow was confirmed, and retrograde flow was seen in the azygos vein. The authors believe that cine MR velocity mapping is a reliable method of studying vena caval flow noninvasively and that it has important potential applications for the investigation of disorders of the right side of the heart.

Adult↗
PubMed1989

Coarctation of the aorta: MR imaging in late postoperative assessment.

Thirty-six patients were studied with magnetic resonance (MR) imaging 2-29 years after repair of coarctation of the aorta, and the findings were compared with clinical data and results of echocardiography, catheterization, angiography, and surgery. A satisfactory echocardiographic examination of the isthmus was achieved in 28 patients. Comparison with data from gradient measurements at catheterization and Doppler ultrasound shows that the reduction of lumen diameter correlates well with the gradient and that restenosis at the site of the repair can be suspected when the percentage of stenosis at the isthmus is greater than 50%. MR imaging showed a Dacron patch aneurysm in three patients. Cine MR imaging showed systolic signal loss in the ascending aorta that was presumed to be due, among other factors, to turbulent flow generated from a bicuspid valve. Similar signal loss was seen in the descending aorta distal to the site of the coarctation repair, but this was not related to the presence or absence of a gradient. Aortic compliance measured from transverse MR systolic and diastolic images was abnormally low, suggesting it may be a factor causing systolic hypertension after coarctation repair. MR imaging is a reliable and accurate noninvasive method likely to supersede other methods of assessing the aorta and isthmus following coarctation repair.

Adolescent↗
PubMed1988

Comparison of magnetic resonance imaging with echocardiography and radionuclide angiography in assessing cardiac function and anatomy following Mustard's operation for transposition of the great arteries.

The Mustard operation in infancy and childhood has successfully palliated many patients with transposition of the great arteries who have now survived to adulthood. Right ventricular dysfunction and tricuspid regurgitation are important determinants of late morbidity and mortality. The value of noninvasive magnetic resonance imaging (MRI) in the assessment of cardiac function and anatomy 9 to 20 years after this procedure has been investigated, and compared with findings on echocardiography, radionuclide ventriculography and angiography in 17 adult patients. Ejection fractions measured by MRI were higher compared with radionuclide ventriculography. The correlation for the left ventricle was closer (r = 0.75) than for the right ventricle (r = 0.49). Tricuspid regurgitation was assessed by Doppler echocardiography and by MRI using the right/left ventricular stroke volume ratio. The mean stroke volume ratio in those with Doppler evidence of tricuspid regurgitation was 1.6:1 compared to 1.1:1 in those without, and this difference reached significance (p less than 0.01). The anatomy of the great arteries was clearly visible in all patients. Five patients had a residual ventricular septal defect which, with the exception of 1 small defect, was easily visualized. The intraatrial baffle was best seen in transverse slices, and the systemic venous connection showed as a relatively narrow channel lying in the posterior part of the cavity. In general, baffle anatomy was easier to assess on 2-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Adrenal steroids in maternal and cord blood after dexamethasone administration at midterm.

We undertook a study designed to evaluate whether it is feasible to suppress fetal adrenal secretion of androgens at mid-pregnancy by giving dexamethasone (DX) to the mother. Levels of DX and adrenal steroids were measured in maternal and cord plasma of 13 DX-treated and 16 untreated mothers undergoing abortion at 18-20 weeks of pregnancy. Maternal adrenal suppression was evidenced by a sharp fall of plasma cortisol (F), cortisone (E), corticosterone (B), and dehydroepiandrosterone sulfate (DHEA-S). However, in cord blood no fall of DHEA-S or corticosterone sulfate (BS) was found up to 20 hours after DX administration, and cord plasma ACTH remained detectable. The failure of DX to suppress the fetal adrenal at mid-pregnancy suggests that this drug would not be effective in the intrauterine treatment of congenital adrenal hyperplasia (C.A.H.).

Adrenal Cortex Hormones↗