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D A White

Publications and source records attributed to D A White.

At least 55 records · Page 3Linked to original sources
PubMed1999

Modulation of the regression of atherosclerosis in the hamster by dietary lipids: comparison of coconut oil and olive oil.

The Golden Syrian hamster (Mesocricetus auratus) has been shown to be a useful model of both human lipoprotein metabolism and the development of atherosclerosis. We report the effects of dietary lipids on the progression and regression of atherosclerosis in this model. In the first study, hamsters fed on coconut oil (150 g/kg diet) and cholesterol (30 g/kg diet) developed lipid-rich lesions in the ascending aorta (0.28 (SD 0.14) mm2) and aortic arch (0.01 (SD 0.01) mm2) after 4 weeks that continued to progress over the next 8 weeks (0.75 (SD 0.41) mm2 and 0.12 (SD 0.11) mm2 for the ascending aorta and aortic arch respectively). Removal of cholesterol from the diet halted this progression. Furthermore, in animals fed on olive oil in the absence of added cholesterol, plasma LDL-cholesterol concentrations were lower (P < 0.05) and the extent of atherosclerotic lesions was reduced (P < 0.001 for both regions of the aorta) compared with animals fed on coconut oil (with no added cholesterol). In a second study, animals were fed on the atherogenic diet for 10 weeks, transferred to diets containing either coconut oil (150 g/kg diet) or olive oil (150 g/kg diet) without added cholesterol and monitored for up to 16 weeks. In the ascending aorta, lesion size doubled in animals fed on coconut oil but stabilized in those fed on olive oil. In the aortic arch, lesion size decreased linearly (P < 0.05, P < 0.001 for coconut oil and olive oil respectively) with the greatest reduction being seen in the olive-oil-fed animals (P < 0.05). Again, progression and regression of atherosclerosis appeared to reflect the relative concentrations of LDL-cholesterol and HDL-cholesterol in the plasma. We conclude that the male Golden Syrian hamster represents a useful model of dietary induced regression as well as progression of atherosclerosis.

Analysis of Variance↗
PubMed1999

Pulmonary nodule due to Mycobacterium haemophilum in an immunocompetent host.

We present a case of a pulmonary nodular lesion in an immunocompetent patient documented at open lung biopsy to be due to Mycobacterium haemophilum. This organism has recently been recognized as a cause of disease in immunocompromised patients, presenting predominantly as skin lesions, arthritis, and rarely pneumonia. Because this mycobacterium is fastidious and difficult to grow without the use of special media and conditions, our case raises the possibility that M. haemophilum could be an underrecognized cause of granulomatous pulmonary lesions and should be considered particularly in cases where smears for acid-fast bacteria are positive but cultures are negative.

Female↗
PubMed1999

Maternal histone deacetylase is accumulated in the nuclei of Xenopus oocytes as protein complexes with potential enzyme activity.

Reversible acetylation of core histones plays an important regulatory role in transcription and replication of chromatin. The acetylation status of chromatin is determined by the equilibrium between activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The Xenopus protein HDACm shows sequence homology to other putative histone deacetylases, but its mRNA is expressed only during early development. Both HDACm protein and acetylated non-chromosomal histones are accumulated in developing oocytes, indicating that the key components for histone deposition into new chromatin during blastula formation are in place by the end of oogenesis. Here we show that the 57 kDa HDACm protein undergoes steady accumulation in the nucleus, where it is organized in a multiprotein complex of approx. 300 kDa. A second, major component of the nuclear complex is the retinoblastoma-associated protein p48 (RbAp48/46), which may be used as an adaptor to contact acetylated histones in newly assembled chromatin. The nuclear complex has HDAC activity that is sensitive to trichostatin A, zinc ions and phosphatase treatment. The 57 kDa protein serves as a marker for total HDAC activity throughout oogenesis and early embryogenesis. The active HDACm complex and its acetylated histone substrates appear to be kept apart until after chromatin assembly has taken place. However, recombinant HDACm, injected into the cytoplasm of oocytes, not only is translocated to the nucleus, but also is free to interact with the endogenous chromatin.

Amino Acid Sequence↗
PubMed1998

Pulmonary toxicity of drugs used to treat systemic autoimmune diseases.

A number of drugs used to treat systemic autoimmune diseases can cause respiratory complications. These include bronchospasm, noncardiac pulmonary edema, interstitial pneumonitis and fibrosis, hypersensitivity, and numerous other disorders. Additionally, some of these drugs increase the risk of infections, particularly with opportunistic organisms. This article reviews the clinical presentation and mechanism of toxicity of drug related pulmonary complications.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

The effect of different dietary fatty acids on lipoprotein metabolism: concentration-dependent effects of diets enriched in oleic, myristic, palmitic and stearic acids.

While it is well established that the fatty acid composition of dietary fat is important in determining plasma lipoprotein cholesterol concentrations, the effects of changing the absolute quantities of the individual fatty acids are less clear. In the present study Golden Syrian hamsters were fed on isoenergetic, low cholesterol (0.05 g/kg) diets containing 100, 150 or 200 g added fat/kg. This consisted of triolein (TO) alone, or equal proportions of TO and either trimyristin (TM), tripalmitin (TP) or tristearin (TS). Each trial also included a control group fed on a diet containing 50 g TO/kg. As the mass of TO in the diet increased, plasma VLDL-cholesterol concentrations rose. The TM-rich diets produced a concentration-dependent increase in total plasma cholesterol which was a result of significant increases in both VLDL and HDL levels. The TP-rich diets increased plasma LDL- and HDL-cholesterol levels in a concentration-dependent manner. TS-containing diets did not increase the cholesterol content of any of the major lipoprotein fractions. Hepatic LDL-receptor mRNA concentrations were significantly decreased in animals fed on TP, while apolipoprotein B mRNA concentrations were significantly increased. Thus, on a low-cholesterol diet, increasing the absolute amount of dietary palmitic acid increases LDL-cholesterol more than either myristic or stearic acid. These effects on lipoprotein metabolism may be exerted through specific modulation of the expression of the LDL receptor and apolipoprotein B genes.

Animals↗
PubMed1998

Genetic and environmental factors affecting bone mineral density in large families.

This study assessed whether relatives with low bone mineral density (BMD) could be identified in five large families using historical, biochemical, and genetic markers for osteoporosis. Fifty of 65 relatives had their bone density and bone turnover markers measured, together with an assessment of their risk factors for osteoporosis. Only 33% (5/15) of siblings, 50% (6/12) of children and 43% (10/23) of nephews and nieces had entirely normal BMD. There was no difference in life-style risk factors for osteoporosis, history of previous fractures or body mass index between normal subjects and those with osteopenia or osteoporosis. Osteopenic individuals had a significantly higher than normal osteocalcin value. Within families, there was no clear association between BMD and any of the genetic markers (vitamin D receptor gene polymorphisms, COL 1A1 and COL 1A2 polymorphisms of the collagen gene), either alone or in combination. The addition of genetic markers to the other risk factors for low BMD did not improve the prediction of BMD. In conclusion, we suggest that the presence of osteoporosis in a first degree relative should be one of the clinical indications for bone density measurement as the individuals at risk would not be picked up by other methods.

Adult↗
PubMed1998

Working memory for nonverbal auditory information in dementia of the Alzheimer type.

Previous studies have revealed working memory impairments in individuals with dementia of the Alzheimer type (DAT) using visually and auditorily presented verbal materials, and visually presented nonverbal materials. Based on findings from behavioral and neuropathological studies, impairments in working memory for auditorily presented nonverbal materials have been hypothesized as well. Results of a study conducted by Kurylo, Corkin, Allard, Zatorre, and Growden (1993), however, failed to support this hypothesis. In the current investigation, perception and working memory for nonverbal auditory information (tones) were assessed using same-different discrimination tasks. Participants included individuals with no dementia, very mild DAT, and mild DAT. Unlike the findings from the study conducted by Kurylo and colleagues, our results suggest intact tone perception but a progressive decline in working memory for auditory nonverbal information with advancing DAT. A similar decline was also noted on a task assessing working memory for auditorily presented verbal information.

Journal Article↗
PubMed1998

A comparison of the social backgrounds and dental health of patients attending the Community Dental Service, the General Dental Service and non registered patients.

OBJECTIVE: To compare the dental health and social backgrounds of children in Southern Birmingham registered with the General Dental Service (GDS), the Community Dental Service (CDS) and those who were not registered with a dentist. DESIGN: Data characterising children as either registered with the GDS or not registered, which had been collected for a study in 1993/4 were analysed to distinguish those children attending the CDS within Southern Birmingham. The children were divided into three groups; those registered with the GDS, those attending the CDS and those not registered with a dentist. SUBJECTS: Three thousand two hundred and five eight-year-old children who attended schools in Southern Birmingham. RESULTS: Of the children attending the CDS 74% were in the lowest ACORN category compared with 44% of those registered with GDS. Only 10% of the children registered with the GDS were of Asian ethnic origin compared with 54% of those attending the CDS. The dmft of children from the same ethnic background and ACORN category was found to be higher in those children registered with the GDS (3.15 +/- 2.75) than those who were not registered (2.17 +/- 2.58), due to more filled and missing teeth. CONCLUSIONS: A higher proportion of children attending the CDS in Southern Birmingham come from a deprived social background and are of Asian ethnic origin than those registered with the GDS. The dental health of these children differs between those who have attended a dentist (GDS or CDS) and those who are non-registered (P < 0.05).

Child↗
PubMed1998

The assembly of triacylglycerol-rich lipoproteins: an essential role for the microsomal triacylglycerol transfer protein.

Raised plasma triacylglycerol is an independent risk factor for cardiovascular disease, and an understanding of factors which regulate the synthesis and degradation of lipoproteins which carry triacylglycerol in the blood may lead to novel approaches to the treatment of hypertriacylglycerolaemia. An active microsomal triacylglycerol transfer protein (MTP) is essential for the assembly of particles which transport triacylglycerol through the circulation. After absorption in the intestine, dietary fat and fat-soluble vitamins are incorporated into chylomicrons in the intestinal epithelial cells, and these lipoproteins reach the bloodstream via the lymphatic system. Patients with the rare genetic disorder, abetalipoproteinaemia, in which MTP activity is absent, present clinically with fat-soluble vitamin and essential fatty acid deficiency, indicating a key role for MTP in the movement of fat into the body. The triacylglycerol-rich lipoprotein found in fasting blood, VLDL, is assembled in the liver by an MTP-dependent process similar to chylomicron assembly, and transports triacylglycerol to extra-hepatic tissues such as adipose tissue and heart. In the absence of MTP activity, VLDL are not synthesized and only extremely low levels of triacylglycerol are present in the blood. Dietary components, including fat, cholesterol and ethanol, can modify the expression of the MTP gene and, hence, MTP activity. The present review summarizes current knowledge of the role of MTP in the assembly and secretion of triacylglycerol-rich lipoproteins, and the regulation of its activity in both animal and cell systems.

Abetalipoproteinemia↗
PubMed1997

Prose recall in dementia. A comparison of delay intervals.

OBJECTIVE: To explore one methodological variation, delay length, that may contribute to contradictory findings in the literature regarding the use of delayed recall in the detection of early-stage dementia of the Alzheimer type. DESIGN: Comparison of participants with dementia and without dementia on a prose recall task at both 10- and 30-minute delay intervals. SETTING: Washington University Alzheimer's Disease Research Center, St Louis, Mo. PARTICIPANTS: Participants with very mild dementia of the Alzheimer type (n = 136) and uncompromised elderly individuals (n = 197). MAIN OUTCOME MEASURES: Results of the Logical Memory subtest from the Wechsler Memory Scale with immediate recall and 10- and 30-minute delayed recall. RESULTS: Participants with dementia recalled significantly less material than elderly controls at both immediate and delayed recall (P < .001). Multiple regression analyses revealed that dementia classification failed to account for additional variance in the 30-minute delayed score beyond that which could be accounted for by the immediate score. A small but significant proportion of variance was accounted for in the 10-minute delayed score beyond that which could be accounted for by the immediate recall score. CONCLUSION: Delayed recall of a prose passage does not appear to enhance the differentiation of very mild dementia of the Alzheimer type from normal aging in a meaningful way, whether the recall delay is 10 or 30 minutes.

Aged↗
PubMed1997

Genetic determinants of plasma lipoprotein levels and their dietary response.

Hamsters were fed diets containing fat (5-20%, w/w) consisting of triolein (TO) alone or 50% triolein plus 50% trimyristin (TM), tripalmitin (TP) or tristearin (TS) for 28 days. Each fat had unique effects on lipoprotein concentrations which were related to changes in the expression of hepatic genes. Tripalmitin was the most hypercholesterolaemic of the saturated fats, causing dose-dependent increases in LDL and HDL cholesterol which correlated with decreases in the expression of HMGCoA reductase and LDL receptor genes. Tripalmitin also increased the expression of the apoB gene. It seems likely that fatty acids may regulate genes which are involved both in the synthesis and clearance of plasma lipoproteins. Inclusion of increasing amounts of cholesterol in diets containing 20% fat (50% TO plus 50% TP or TS) caused down-regulation of HMGCoAR and LDLR genes and up-regulation of the microsomal triglyceride transfer protein (MTP) gene for both fats. This was accompanied by increased LDL-cholesterol in the TP but not the TS group. In all experiments the concentration of VLDL-cholesterol correlated with the hepatic cholesterylester and MTP mRNA concentrations.

Animal Nutritional Physiological Phenomena↗
PubMed1997

Memory for verbal information in individuals with HIV-associated dementia complex. HNRC Group.

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan, & Price, 1986).

AIDS Dementia Complex↗
PubMed1997

Changes in bone mineral density in patients with Paget's disease treated with risedronate.

OBJECTIVES: To study changes in bone mineral density (BMD) in patients with Paget's disease of bone treated with risedronate. METHODS: Whole body dual energy x ray absorptiometry (DXA) scans were carried out on 20 patients with Paget's disease treated with oral risedronate. DXA scanning was carried out at baseline and 11 months. Whole body bone mineral content (BMC) was measured. In addition, regions of interest were drawn around the skull, individual lumbar vertebrae, hemipelvis, femora, and tibiae to obtain BMD for these sites. An uncoupling index was also calculated as the area under the curve for serum alkaline phosphatase (ALP) divided by the area under the curve for hydroxyproline excretion (HYPRO) for the period of treatment. RESULTS: Median whole body BMC increased from 3057 g to 3156 g (p < 0.001) resulting from an increase in pagetic and non-pagetic BMD. From the analysis of regions of interest it was found that pagetic trabecular bone showed the largest increase in BMD. The pretreatment HYPRO and the uncoupling index were significantly related to the change in BMD for all pagetic sites for a patient (r = 0.65, p < 0.01 and r = 0.57, p < 0.05 respectively). CONCLUSION: Bisphosphonate treatment of Paget's disease results in an increase in BMD of pagetic bone without redistribution of mineral from non-pagetic bone. The remodelling space and extent of uncoupling are significantly related to increases in BMD at pagetic sites.

Absorptiometry, Photon↗
PubMed1996

Hepatic microsomal triglyceride transfer protein messenger RNA concentrations are increased by dietary cholesterol in hamsters.

In hamsters fed high fat diets enriched in trimyristin, tripalmitin or tristearin, increased dietary cholesterol content was associated with increased plasma concentrations of very low density lipoprotein (VLDL) cholesterol and triacylglycerol (p < 0.0001 and p = 0.0017, respectively). Hepatic microsomal triglyceride transfer protein (MTP) mRNA concentration also increased (p < 0.0001), independent of the nature of dietary fat, and was significantly correlated with the plasma VLDL lipid concentrations (p = 0.0002 and p = 0.0106 for cholesterol and triacylglycerol, respectively) and hepatic cholesterol concentrations. Increased expression of the MTP gene may be part of a coordinated response to hepatic cholesterol accumulation leading to increased VLDL lipid secretion.

Analysis of Variance↗
PubMed1996

A CHO mutant, UV40, that is sensitive to diverse mutagens and represents a new complementation group of mitomycin C sensitivity.

A new mitomycin C (MMC)-sensitive rodent line, UV40, has been identified in the collection of ultraviolet light- (UV-) sensitive mutants of Chinese hamster ovary (CHO) cells isolated at the previous Facility for Automated Experiments in Cell Biology (FAECB). It was isolated from an UV mutant hunt using mutagenesis of AA8 cells with the DNA intercalating frameshift mutagen ICR170. It is complemented by CHO-UV-1, irsl, irs3, irslSF, MC5, V-C8 and V-H4 with respect to its MMC sensitivity based on cell survival. Despite having approx. 4 X normal UV sensitivity and increased sensitivity to UV inhibition of DNA replication, it has near-normal incision kinetics of UV irradiated DNA, and normal (6-4) photoproducts removal. It also is not hypermutable by UV, and shows near normal levels of UV inhibition of RNA synthesis. UV40 also has approx. 11 x .10 x .5 x and 2 x AA8 sensitivity to MMC, ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), and X-rays, respectively. Thus, its defect apparently does not involve nucleotide excision repair but rather another process, possibly in replicating past lesions. The spontaneous chromosomal aberration frequency is elevated to 20% in UV40, and the baseline frequency of sister chromatid exchange is also approximately 4-fold increased. The phenotype of UV40 appears to differ from all other rodent mutants that have so far been described.

Adenine↗
PubMed1996

Bystander injury of host lymphoid tissue during murine graft-verus-host disease is mediated by nitric oxide.

The suppressed lymphocyte proliferative responses characteristic of graft-versus-host disease (GVHD) are due, in part, to production of nitric oxide (NO). In order to more fully elucidate the role of NO during GVHD, an NO synthesis inhibitor, aminoguanidine (AG), was administered to unirradiated (C57BL/6J X DBA/2J)F1 mice injected with 5 X 10(7) C57BL/6J splenocytes. Administration of AG resulTed in abrogation of the elevation in serum NO2- + NO3- levels characteristic of GVHD. A significantly increased percentage of splenocytes of host phenotype (H2b/d, B220+, and THY1.2+) and a significantly higher hematocrit value were detected in GVHD animals receiving AG therapy. Additionally, the Con A-induced proliferative response of splenocytes obtained from GVHD mice receiving AG therapy was increased compared with the responses of splenocytes from animals that did not receive AG therapy. Parameters not affected by AG therapy included NO synthesis by recovered peritoneal macrophages, donor antihost cytolytic activity in splenocyte populations, serum GM-CSF levels and long-term engraftment of donor cells. These data indicate that NO may play a role in the destruction of both lymphoid and erythroid host tissue as well as the reduced lymphoproliferative responses associated with the acute phase of GVHD.

Animals↗