Biomedical subjects
G Howard
Publications and source records attributed to G Howard.
Pregnancy and maternity: dismissals.
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Binding of a pancreatic nuclear protein is correlated with amylase enhancer activity.
The mouse amylase gene Amy-2.2 is expressed at high levels specifically in the acinar cells of the pancreas. The region between -172 and -110 of this gene includes sequence elements common to pancreas-specific genes. Nuclear proteins with specific affinity for this region were partially purified from rat pancreas. The consensus element of another pancreas-specific gene, elastase 1, competes for protein binding to the amylase sequences. Binding was localized by DNase I protection to the sequence -156 to -122. Site-directed mutagenesis of this sequence resulted in concomitant loss of protein binding and enhancer activity. Photo-affinity labelling of pancreatic nuclear extracts identified one predominant binding protein with a molecular weight of approximately 75 kDa. The data indicate that binding of this nuclear protein is essential for the enhancer activity of this pancreas-specific element.
Cigarette smoking cessation and extracranial carotid atherosclerosis.
Using B-mode ultrasonography, cigarette smoking was found to be a strong, independent risk factor for extracranial carotid atherosclerosis in 1692 black and white men and women admitted for diagnostic evaluation of the carotid arteries. We found that the difference in mean plaque thickness was smaller between past smokers and nonsmokers than between current smokers and nonsmokers, suggesting that the rate of progression of carotid atherosclerosis may be slower in people who quit smoking compared with people who continue to smoke.
Cerebral infarction in patients with transient ischemic attacks.
Cranial computed tomography of 284 patients with transient ischemic attacks (TIAs) and without previous stroke was evaluated. The sample population included patients with carotid and/or vertebrobasilar TIAs. Computed tomography revealed cerebral infarction in 34 patients, including 5 with multiple infarctions. The lesion location was consistent with TIA symptoms in 16 patients. In another 16 patients, however, the lesion location did not correspond to the TIA symptoms; these lesions were attributed to previous silent infarctions. Two patients with multiple infarctions had both symptomatic and asymptomatic lesions. Age and carotid stenosis were each significantly related to an increased chance of detecting cerebral infarction (either symptomatic or asymptomatic). No significant relationship between race, gender, hypertension, diabetes, cardiac disease, or smoking and the incidence of infarction was found by either univariate or multivariate analyses.
Human urine mutagenicity study comparing cigarettes which burn or only heat tobacco.
Cigarette smokers have been reported to void urine which is more mutagenic, as measured in the Ames bacterial mutation assay, than urine voided by non-smokers. Condensate from the mainstream smoke of a cigarette which heats, but does not burn tobacco (test cigarette) showed no evidence of mutagenicity in a battery of in vitro genotoxicity assays under conditions in which condensate from the mainstream smoke of cigarettes that burn tobacco was mutagenic. The objective of this study was to determine whether the absence of mutagenic activity observed in the in vitro assays would be reflected in the urine of smokers of the test cigarette. 72 subjects (31 smokers and 41 non-smokers) were enrolled in a 6-week study, with the smokers randomly divided into 2 groups. The study was designed as a double crossover, with each smoker smoking both test (tobacco-heating) and reference (tobacco-burning) cigarettes. This design allowed each smoker to serve as his or her own control while at the same time allowing comparisons between groups of non-smokers and smokers of both test and reference cigarettes. 24-h urine samples were collected twice a week and concentrated using XAD-2 resin. Urine concentrates were tested in Ames bacterial strains TA98 and TA100, with and without metabolic activation and with and without beta-glucuronidase/aryl sulfatase. Individuals who smoked the test cigarette voided urine which was significantly less mutagenic than that voided when they smoked reference cigarettes. The mutagenicity of urine from smokers who smoked the test cigarette and non-smokers did not differ under any of the assay conditions used in this study.
Effect of cooking methods on the mutagenicity of food and on urinary mutagenicity of human consumers.
The effects of cooking methods on the in vitro mutagenicity of individual foods, the in vitro mutagenicity of meals containing those foods, and the mutagenic exposure of human volunteers following consumption of the meals were examined using Ames bacterial strain TA98 with S-9 metabolic activation. Three methods of food preparation--boiling, baking and frying/flame-broiling--were compared. With meats, frying or broiling resulted in higher in vitro mutagenicity (10- to 50-fold) than did baking or boiling, whereas for carbohydrates, eggs or vegetables mutagenicity did not vary markedly with cooking method. The observed (experimental) mutagenic activity of the meals was quite similar to their calculated (predicted) mutagenicity, obtained by summing the mutagenicity of the individual foods in the meal. The close agreement between experimental and predicted mutagenicity indicated that components of the meal did not interact in either a synergistic or inhibitory manner. The mutagenicity of fried flame-broiled meals was approximately 10-fold greater than the mutagenicity of baked or broiled meals, which were similar in mutagenicity. The mutagenicity of human urine following consumption of the meals was related to the in vitro mutagenicity of the meals themselves. The in vitro mutagenicity of meals is markedly affected by the cooking method used to prepare them and the mutagenicity of the diet may be reflected in the mutagenicity of body fluids.
Cause specific mortality following cerebral infarction.
Mortality from four causes (index stroke, subsequent stroke, cardiac disease and non-cardiovascular causes) was examined during a 5 year follow-up of 1694 cerebral infarction patients admitted to 25 community hospitals between 1969 and 1973. The hazard for mortality from the index stroke was high initially, but declined to a negligible level by 6 months post-stroke. In contrast, hazards for mortality from subsequent strokes, cardiac diseases and non-cardiovascular causes each peaked midway through the first year, declined during the remainder of that year, and then increased in the latter part of the follow-up. Proportional hazards analysis indicated that advanced age and increased stroke severity were the only factors significantly related to increased risk from each of the four causes of death. Other risk factors were significant only for one or two select causes of death. White patients were less likely to die from subsequent strokes, but more likely to die from cardiac diseases, than were non-white patients (primarily blacks). Males were more likely to die from both the index stroke and non-cardiovascular causes than females. A history of cardiac disease increased the risk of death from both the index stroke and from future cardiac events, while a history of hypertension or diabetes increased the risk of death from non-cardiovascular causes, and a history of previous stroke increased the risk of death from subsequent stroke.
Risk factors for site specific extracranial carotid artery plaque distribution as measured by B-mode ultrasound.
The effect of age, sex, diabetes, hypertension, pulse rate and cigarette smoking on extracranial carotid artery plaque thickness evaluated by B-mode ultrasonography was investigated in a cross-sectional study of 698 white men, 730 white women, 77 black men and 76 black women as part of a clinical ultrasound registry. Subjects were between 24 and 98 years of age, with a mean age of 63 years. Arterial locations evaluated were: proximal, mid and distal common carotid; the bifurcation; and the proximal and mid internal and external carotids. In a general linear multivariate analysis with plaque thickness at each site as the outcome variable, cigarette smoking and age were the two most consistent risk factors, and affected plaque thickness at all the investigated sites. Hypertension affected more sites than diabetes, men had more plaques than women, and except for the common carotid, whites had more plaques than blacks. Thus, risk factors were not uniformly associated with atherosclerosis at all sites of the extracranial carotid arteries.
The effects of regional and general anesthesia on blood pressure control after carotid endarterectomy.
We retrospectively reviewed the influence of preoperative blood pressure control and regional vs. general anesthetic techniques on the incidence of intraoperative and postoperative (recovery room and intensive care unit) hypotension and hypertension in 249 carotid endarterectomy patients. Preoperative blood pressure was classified as uncontrolled hypertension (systolic blood pressure >/= 170 mm Hg and/or diastolic blood pressure >/= 95 mm Hg), controlled hypertension (blood pressure <170/95 mm Hg on chronic antihypertensive therapy), or normotension (blood pressure <170/95 mm Hg without antihypertensive therapy). Hypotension, as defined by the requirement for vasopressor administration to maintain a systolic blood pressure of at least 120 mm Hg, occurred more frequently after regional than after general anesthesia (p < 0.05). Postoperative hypertension was defined as a systolic blood pressure >/= 200 mm Hg and/or a diastolic blood pressure >/= 110 mm Hg in the recovery room or in the Intensive Care Unit. Preoperative hypertension was not associated with acute postoperative hypertension in the intensive care unit in either the regional anesthesia (n = 190) or the general anesthesia (n = 59) groups, although with either type of anesthesia, preoperative hypertension was associated with an increased incidence of hypertension in the recovery room (p < 0.01 regional; p < 0.005 general).
Effects of insulin on gene transcription.
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Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading.
Muscle atrophy resulting from disuse is associated with marked decrements in protein synthesis. The objective of the present investigation was to determine levels of total muscle RNA and the content and composition of the mRNA fraction as a qualitative assessment of the potential regulatory role of transcriptional alterations in unloaded skeletal muscles. Hindlimb muscle unloading was produced by whole-body suspension of rats for up to 7 days. The soleus, gastrocnemius, and extensor digitorum longus (EDL) were excised from 1-, 3-, and 7-day suspended and pair-fed controls, and RNA was extracted by homogenization in 5 M guanidinium thiocyanate. Total RNA and mRNA contents were lower in soleus and gastrocnemius after 7 days of suspension compared with pair-fed controls, but total RNA and mRNA concentrations (per g muscle and per microgram total RNA, respectively) were unaltered. alpha-Actin mRNA, assessed by dot blot hybridization, was significantly reduced in soleus after 1 (37%), 3 (28%), and 7 (59%) days of suspension and in gastrocnemius after 3 (44%) and 7 (41%) days. However, alpha-actin mRNA was unchanged in the EDL after suspension. Protein synthesis directed by RNA extracted from soleus and EDL indicated marked (30-400%) alterations in mRNAs coding for several small (15- to 25-kDa) proteins. The results of this study suggest that altered transcription and availability of specific mRNAs could contribute significantly to the regulation of protein synthesis during unloading of skeletal muscle.
Correlation of carotid bruits and carotid atherosclerosis detected by B-mode real-time ultrasonography.
The extent of carotid atherosclerosis evaluated by B-mode real-time ultrasound and the presence of bruits established by carotid phonoangiography were determined in 1,107 patients. Unilateral bruit was associated with increased atherosclerosis compared with no bruit (p less than or equal to 0.0001). However, there was no association between laterality of the bruit and the degree of atherosclerosis (p = 0.66). There was marginal evidence that patients with bilateral bruits had more severe atherosclerosis than patients with unilateral bruit (p = 0.046). The relation between bruit and atherosclerosis categorized by B-mode ultrasound was not sufficient to reliably predict the presence or absence of disease in an individual patient, though the presence of a bruit should be viewed as a risk factor for, or an indicator of, increased risk of systemic atherosclerosis.
Changes in survival following stroke in five North Carolina counties observed during two different periods.
We evaluated survival following stroke for patients from a five-county area of rural North Carolina enrolled in either of two community hospital-based stroke survey programs. In this area, the first program enrolled 843 stroke patients between 1970 and 1973 and the second program enrolled 786 stroke patients between 1979 and 1980. One-year survival increased from 49% in the first program to 62% in the second for all stroke patients, from 54% to 68% for patients with cerebral infarction, and from 18% to 55% for patients with cerebral hemorrhage. While other reports have attributed declining stroke mortality to a decline in the incidence of stroke, our study suggests that increased survival after stroke may account for a large portion of the decrease in stroke mortality.
Changes in survival after transient ischemic attacks: observations comparing the 1970s and 1980s.
We compared survival following transient ischemic attack (TIA) in 2 prospective cohorts of TIA patients admitted to Wake Forest University Medical Center. The 1st consisted of 177 patients admitted between 1961 and 1973, and the 2nd of 185 patients admitted between 1980 and 1983. Patients in the 2nd cohort had significantly greater longevity than patients in the 1st cohort, both univariately and after adjustment for cerebrovascular risk factors. The adjusted 1-year survival estimate increased from 91% in the 1st cohort to 98% in the 2nd, and the adjusted 3-year survival estimate increased from 83% in the 1st to 94% in the 2nd. The underlying causes for this dramatic improvement in survival may include early identification and aggressive management of TIAs or coexisting diseases, improved management of subsequent completed strokes or myocardial infarctions, or unadjusted differences in these cohorts. The data imply that reports of TIA survival from different periods may not be comparable.
The costs of going to court.
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'Please don't give my name'--the reluctant witness.
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Keep proper records of protective equipment.
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