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Biomedical subjects

R A Davis

Publications and source records attributed to R A Davis.

At least 55 records · Page 3Linked to original sources
PubMed1995

The Brigham Diary of Loyal Davis: a portrait of Harvey Cushing and a neurosurgical acolyte.

At 27 years of age, Loyal Davis wrote the Brigham Diary while training as an Associate in Surgery with Dr. Harvey Cushing. The diary is a daily record of the Cushing neurosurgical service between 1923 and 1924. The literary tone of the document is one of youthful enthusiasm and candor. Its contemporary portrayal of Harvard University's third Moseley Professor displays a demanding surgeon and scholar whose primary concern was the care of his patients and who taught the meticulous techniques of neurosurgery by example. In contrast to the experiences offered by current neurosurgical residency programs, Loyal Davis examined 107 patients, observed 81 operations, assisted Dr. Cushing during 23 operations, assisted Dr. Gilbert Horrax in 13 operations, and never performed an operation independently during his year at the Peter Bent Brigham Hospital. Despite these technical constraints, the young assistant learned the Cushing method of surgery and skilled patient care and was encouraged to continue laboratory investigations. Davis also emulated Cushing's exacting method of preparation of medical manuscripts, which were characterized by scientific innovation and an engaging literary style. The diary shows that Cushing often held inflexible surgical and scientific opinions and was contentious in their defense. These opinions were modified only when he was presented with unequivocal facts. The young surgeon sought Cushing's approval which carried a genuine but restrained benevolence. Harvey Cushing's impression on Davis was lasting and profound. The diary conveys the philosophy that uncompromised discipline is a necessary virtue and hard work is full satisfaction in itself. In the following years, Loyal Davis systematically patterned his surgical and scholarly endeavors after those of Harvey Cushing, an exemplar whose unstinting resolve was the pursuit of excellence.

History, 20th Century↗
PubMed1994

Proteolysis-coupled secretion of the N terminus of apolipoprotein B. Characterization of a transient, translocation arrested intermediate.

We have shown that non-hepatic Chinese hamster ovary cells (CHO) have a specific inability to translocate and secrete apolipoprotein B (apoB), leading to its complete degradation in the endoplasmic reticulum (Thrift, R. N., Drisko, J., Dueland, S., Trawick, J. D., and Davis, R. A. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 9161-9165). To gain an understanding why a protein having no predictable trans-membrane sequences can be stably integrated into the endoplasmic reticulum, we determined the topography and metabolic fate of apoB in both CHO cells and human hepatoma cells (HepG2). Using epitope-specific antibodies, we show that in microsomes from both cell types, apoB assumes a trans-membrane orientation having 69 kDa of its N terminus in the lumen and the remaining portion of the C terminus residing on the cytoplasmic surface. In both cell types, proteolytic cleavage of the translocation arrested apoB by a process that can be blocked by acetyl-leucine, leucine, norleucal, produces an 85-kDa N-terminal fragment that resumes translocation and is secreted. This same N-terminal 85-kDa fragment is also found in human plasma. These results show that sequences residing outside of the membrane spanning domain can block translocation. Moreover, our data provide compelling evidence showing that apoB undergoes an unusual transient, translocation arrest, that serves as an entrance into the intracellular degradative pathway regulating its secretion.

Animals↗
PubMed1994

A long-term outcome analysis of 984 surgically treated herniated lumbar discs.

This paper presents a long-term follow-up study of 984 patients operated on for a herniated lumbar disc between 1959 and 1991. It was possible to follow 98% of patients from the time of operation to the time of writing. The mean follow-up period was 10.8 years. The most common presenting complaint was back pain with sciatica in one leg; the most frequent neurological finding was impaired straight-leg raising. Myelography confirmed the diagnosis in 80% of patients, but more recently enhanced computerized tomography and magnetic resonance imaging have been the preferred studies. The operative procedure was either hemilaminectomy or laminectomy with x 3.5 magnification and fiberoptic lighting. Herniated lumbar discs involved L4-5 and L5-S1 with equal frequency (47%). The recurrence rate was 6%, one-third of which developed during the 1st year after operation. The complication rate was 4%; there were no intraoperative vascular or intestinal injuries. The Prolo Functional Economic Outcome Rating Scale was used to measure long-term outcome and the results were compared to those of Pappas, et al. Patients who did sedentary work and housewives had statistically higher total and economic Prolo scores (p < 0.01) than those who did strenuous work. The majority of patients with the "failed-back syndrome" had pending legal or Workers' Compensation claims, or were at psychological risk for surgery. In 89% of patients the outcome was good--defined as a Prolo score of 8 in 10%, 9 in 19%, and 10 in 60%.

Adolescent↗
PubMed1993

Assessment of the reproductive toxic potential of dermally applied 2-hydroxy-4-methoxybenzophenone to male B6C3F1 mice.

The potential of 2-hydroxy-4-methoxybenzophenone (HMB) to cause male reproductive toxicity was assessed in B6C3F1 mice. HMB was administered topically for 13 weeks (5 days/week) to groups of 10 mice each at dosages of 0, 10, 20, 100, or 400 mg/kg/day. Additional high dosage and control mice were also included and euthanized at interim time points to characterize the time course of any effects. After 91 days (or at interim periods) mice were euthanized and reproductive organ weights, cauda epididymal sperm concentration and proportion of motile and abnormal sperm, and testicular spermatid concentration were determined. Testicular histology was evaluated in fixed tissue. HMB treatment had no effect on body weight gain or any of the male reproductive parameters assessed at any time point. These results indicate that topically applied HMB has no reproductive toxic potential in male B6C3F1 mice at dosages as high as 400 mg/kg/day.

Administration, Topical↗
PubMed1993

Enzyme selectivity analyses of arylsulfonylamino acid aldose reductase inhibitors.

Arylsulfonylamino acids, displaying a wide range of inhibitory activities versus rat lens aldose reductase (RLAR), were analyzed for enzyme selectivity in several test systems. These RLAR inhibitors were found not to produce significant inhibition of genetically-linked reductases (aldehyde reductase, ALR), catalytically similar reductases (Pachysolen tannophilus xylose reductase, PTXR), functionally distinct oxidoreductases (glutathione reductase, GR, lactate dehydrogenase, LDH, and gamma-transaminase, GABA-T), and thymidylate synthase (TS). These data suggest that aldose reductase differs significantly from other oxidoreductases in its inhibitor binding domain(s). Furthermore, the aldose reductase selectivity demonstrated by the arylsulfonylamino acids suggests that these compounds may not inhibit other key metabolic transformations in various cell types and that they may function as selective probes for studies of the relationship between aldose reductase mediated biochemical changes and the pathologies of chronic diabetes.

Aldehyde Reductase↗
PubMed1993

Effect of dietary cholesterol and taurocholate on cholesterol 7 alpha-hydroxylase and hepatic LDL receptors in inbred mice.

Compared to BALB/c mice, inbred C57BL/6 mice are more susceptible to developing fatty streak atherosclerotic lesions when fed a cholesterol-rich diet containing taurocholate. We examined the metabolic basis for the taurocholate requirement. In contrast to widely accepted assumptions, taurocholate did not increase cholesterol absorption in either strain of mouse. However, in susceptible C57BL/6 mice, taurocholate was required to increase plasma concentrations of apoB. In both strains, the cholesterol-rich diet increased both the activity and mRNA for 7 alpha-hydroxylase, a compensatory response to maintain cholesterol homeostasis. In both strains, adding taurocholate to the diet suppressed both the activity and mRNA for 7 alpha-hydroxylase, thus blocking this important compensatory response. The cholesterol-rich diet (without taurocholate) significantly increased hepatic cholesterol content in both strains of mice, but repressed low density lipoprotein (LDL) receptor mRNA only in BALB/c mice (not in C57BL/6 mice). However, adding taurocholate to the cholesterol-rich diet did decrease LDL receptor mRNA in C57BL/6 mice. In C57BL/6, but not in BALB/c mice, there was a linear parallel relationship between 7 alpha-hydroxylase mRNA and LDL receptor mRNA. These data show the existence of strain-specific differences in the effects of dietary cholesterol and taurocholate on 7 alpha-hydroxylase and LDL receptor expression. The combined data suggest that genetic factors determine how the expression of hepatic LDL receptors responds to dietary cholesterol and taurocholate.

Animals↗
PubMed1993

Exposure to TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. Clinical and immunological evaluation of 96 workers.

We evaluated 96 workers employed at facilities that manufacture or use TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. We used immunoglobulin (Ig) and IgG serum antibody enzyme-linked immunosorbent assay (ELISA) studies and a questionnaire designed to identify symptoms compatible with work-related syndromes such as asthma and hypersensitivity pneumonitis. There were no workers with immunologically induced disease due to TMI isocyanate or TMXDI isocyanate nor were there any workers whose questionnaires suggested new onset of asthma. Approximately 40% of workers experienced some irritant symptoms, mostly upper respiratory or ocular. One worker had low level IgE antibody against TMXDI-HSA but had no work-related respiratory symptoms. Very low-level IgG against TMI-HSA or TMXDI-HSA was present in 7% of workers, all of whom were in the high-exposure category.

Air Pollutants, Occupational↗
PubMed1992

Expression of 7 alpha-hydroxylase in non-hepatic cells results in liver phenotypic resistance of the low density lipoprotein receptor to cholesterol repression.

The goal of this study was to understand why the expression of low density lipoprotein (LDL) receptors by the liver is poorly down-regulated by cholesterol. We examined the hypothesis that 7 alpha-hydroxylase may indirectly induce the expression of the LDL receptor by metabolizing, i.e. inactivating oxysterol repressors. Non-hepatic Chinese hamster ovary cells, transfected with a plasmid encoding 7 alpha-hydroxylase, expressed both the mRNA and functional activity of this liver-specific enzyme. In the presence of 5% serum, expression of the LDL receptor by transfected cells was > 20 times that of non-transfected cells despite a 50% increased content of cholesterol ester. Both cell types displayed an almost complete repression of the LDL receptor by the oxysterol 25-hydroxycholesterol, suggesting that transcriptional control of the LDL receptor gene remained intact in the transfected cells. However, only cells expressing 7 alpha-hydroxylase showed a derepression of the LDL receptor with time. This transient sensitivity to 25-hydroxycholesterol repression was attributed to a 3-fold greater rate of metabolism of [3H]25-hydroxycholesterol. The paradoxical induction of LDL receptor mRNA in transfected cells having greater amounts of cholesterol esters suggests that 7 alpha-hydroxylase may preferentially use oxysterols rather than cholesterol as substrates. The combined data are consistent with the proposal that 7 alpha-hydroxylase indirectly induces the LDL receptor gene by metabolizing (inactivating) oxysterol repressors. Liver-specific expression of 7 alpha-hydroxylase can account for the relative resistance of hepatic LDL receptors to down-regulation.

Actins↗
PubMed1992

Translocation of apolipoprotein B across the endoplasmic reticulum is blocked in a nonhepatic cell line.

To explore the process of lipoprotein assembly, plasmids encoding truncated forms of apolipoprotein B (apoB) were transfected into Chinese hamster ovary (CHO) fibroblasts. (One, encoding apoB53, the N-terminal 53% of apoB100, can direct the assembly and secretion of lipoproteins when expressed in hepatoma cells, while the other, encoding the shorter apoB15, does not direct lipoprotein assembly.) Expression of apoB15 in CHO cells resulted in the accumulation of apoB15 protein in both medium and cells. In contrast, apoB was not detectable in medium or within CHO cells transfected with the plasmid encoding apoB53, despite the expression of apoB53 mRNA. ApoB53 did accumulate within transfected cells incubated with the thiol protease inhibitor N-acetylleucylleucylnorleucinal (ALLN), suggesting that it is synthesized but completely degraded in the absence of the inhibitor. ApoB53 was not secreted despite its presence within ALLN-treated cells. Essentially all the apoB53 that accumulated in microsomes from ALLN-treated cells was associated with the membrane and was susceptible to degradation by exogenous trypsin, indicating exposure on the cytoplasmic face of the membrane. Thus, translocation of apoB53 across the endoplasmic reticulum membrane is blocked. However, the apoB53 bound to concanavalin A, suggesting that it is glycosylated and therefore partly exposed to the lumen as well. ApoB requires a unique process, not expressed in CHO fibroblasts, for its complete translocation and entrance into the secretory pathway. This process might account for the inability of abetalipoproteinemic patients to secrete apoB.

Animals↗
PubMed1992

Development and validation of a high-performance liquid chromatographic method for the determination of benzophenone-3 in rats.

A precise, accurate, selective and sensitive liquid chromatographic method for the determination of benzophenone-3 in rat biological fluids and different tissues has been developed. The minimum detection limit for benzophenone-3 was 2.0 ng ml-1 and the retention time was 6.01 min. Standard curves for benzophenone-3 were linear in a wide range of concentrations in methanol and different body fluids, ranging from 6.25 ng ml-1 to 100 micrograms ml-1. To detect benzophenone-3 in rat whole blood after oral administration, HCl hydrolysis was required. Benzophenone-3 was found to produce a peak blood concentration 1 h after administration. Free benzophenone-3 in urine represented a very small percentage during the first 12 h after administration, while a higher concentration of the glucuronide conjugate was detected in the same time period.

Animals↗
PubMed1992

Comparison of the catalytic and inhibitory properties of Pachysolen tannophilus xylose reductase to rat lens aldose reductase.

The catalytic and inhibitory profiles of xylose reductase isolated from the yeast Pachysolen tannophilus (PTXR) are compared to those of aldose reductase (AR) obtained from rat lens. While both PTXR and rat lens AR are NADPH-specific enzymes and have an affinity for a variety of substrates such as D-xylose, D,L-glyceraldehyde, and 4-nitrobenzaldehyde, the enzymes differ in their substrate affinity profiles. Also, PTXR is not inhibited by standard inhibitors of AR thus supporting a hypothesis that this enzyme may not possess the inhibitor binding site found in rat lens AR.

Aldehyde Reductase↗
PubMed1992

Psychopharmacological effects of smoking a cigarette with typical "tar" and carbon monoxide yields but minimal nicotine.

Five male smokers were tested, after 48-h abstention from tobacco-product use, smoking a leading "lights" category cigarette (Control-FTC nicotine yield 0.6 mg) and another cigarette yielding similar amounts of "tar" and carbon monoxide (CO), but only 0.06 mg nicotine (Test). Heart rate (HR) and the electroencephalogram (EEG) were monitored before, during and after the smoking of each cigarette. Other measures obtained included the subjects' puffing and breathing behaviors during smoking, plasma nicotine concentrations, blood carboxyhemoglobin concentrations and expired-air CO. The results indicated no significant differences in the way the subjects puffed and inhaled the two cigarettes and they were therefore assumed to have inhaled similar amounts of particulate matter and gas-phase components. Plasma nicotine concentrations were significantly higher following smoking of the Control cigarette. HR (percent relative change) increased following smoking of either cigarette; however, HR increase was significantly greater following smoking of the Control cigarette. Smoking the Test cigarette had no effect on the EEG. Smoking the Control cigarette produced a significant increase in beta 2 magnitude and a significant decrease in delta magnitude. This indicates that the effects of smoking on the EEG are a function of nicotine absorbed from cigarette smoke upon inhalation and not a function of inhaled particulate matter, CO, or other gas-phase components.

Analysis of Variance↗
PubMed1992

Neurosurgeons and ideas before their time.

As a complementary inquiry to previous studies on citation analysis in neurosurgery, a group of ideas before their time has been arbitrarily selected by the author from 3792 first-authored papers written between 1897 and 1980 by 50 of the first American neurosurgeons. There were eight neurosurgeons who proposed 12 original theories or procedures whose importance was not recognized at the time of publication. Although the value of these ideas was not initially judged to be significant, these concepts became a part of the intellectual consensus of neurosurgery or related disciplines after varying periods of time. Technical constraints constituted the most important reason for delayed recognition of these innovative and creative ideas. Other factors were an unsuitable medium of communication, fixed scientific attitudes, prestige of previous authors, incomplete literature review by later authors, and a failure to verify observations by other investigators. The question is raised as to whether these factors might continue to affect present and future clinical investigation and laboratory research in neurosurgery.

Aneurysm↗
PubMed1992

Reversible arteriovenous malformation-induced venous hypertension as a cause of neurological deficits.

A case of a dural arteriovenous malformation with prominent localizing neurological deficits is reported. The venous drainage of the lesion and the lack of a significant pial supply implicate venous hypertension as the mechanism of neurological dysfunction. This mechanism is supported further by the angiographic changes and the prompt resolution of the deficits after endovascular treatment. This case illustrates the potential for this frequently postulated but rarely confirmed pathophysiological mechanism to cause reversible neurological dysfunction.

Cerebral Veins↗
PubMed1992

Studies on aldose reductase inhibitors from fungi. I. Citrinin and related benzopyran derivatives.

The fungal metabolites, citrinin (4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6- oxo-3H-2-benzopyran-7-carboxylic acid) and DHMI (3,4-dihydro-6-methoxy-3,7-dimethyl-1H-2-benzopyran-8-ol), as well as certain synthetic derivatives, have been evaluated for aldose reductase inhibitory activity using a rat lens enzyme preparation. Citrinin and its reduction product, dihydrocitrinin, were found to have significant activity (IC50 approximately 10 microM), whereas the other compounds were 3-10 times less potent. Kinetic studies showed that citrinin was not an irreversible inhibitor of the enzyme, as might be expected of a quinone methide. Spectroscopic (NMR) evidence is presented for the existence of citrinin predominantly in the form of its hemi-acetal in aqueous solutions, suggesting that it is this benzo[c]pyran derivative which interacts with the enzyme, rather than the quinone methide form.

Aldehyde Reductase↗
PubMed1991

Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats.

We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.

Alkaline Phosphatase↗
PubMed1991

Dietary nicotine: a source of urinary cotinine.

Foods, principally from plants in the family Solanaceae, and a number of teas were examined for the presence of nicotine. Dietary nicotine would give rise to cotinine in urine and compromise estimates of exposure to tobacco smoke that depend on urinary cotinine. All foods were homogenized, extracted and analysed for nicotine and cotinine by gas chromatography with nitrogen-sensitive detection (GC) and/or GC/MS (mass spectrometry). Weak acid and aqueous extracts of the teas were analysed in a similar manner. Nicotine was not detected (less than 1 ng/ml of extract) in egg plant or green pepper. The average values for nicotine in tomato and potato were 7.3 ng/g wet weight and 15 ng/g wet weight, respectively. Black teas, including regular and decaffeinated brands, had nicotine contents ranging from non-detectable to greater than 100 ng/g wet weight. Instant teas yielded the highest nicotine contents observed (up to 285 ng/g wet weight). The possible sources of nicotine in these foods are discussed. A range of potential values for urinary cotinine concentrations (0.6 to 6.2 ng/ml) was calculated based upon estimated average and maximal consumptions of these foods and beverages. Because of the potential for exposure to nicotine by way of these routes, the use of urinary cotinine as a biomarker of exposure to environmental tobacco smoke may be compromised.

Chromatography, Gas↗