Teaching medical students about bereavement is hard.
Explore the source record for details and available documents.
Bereavement↗
Biomedical subjects
J Fuller
Publications and source records attributed to J Fuller.
Down-regulation of liver and heart specific fatty acid binding proteins by endotoxin and cytokines in vivo.
Fatty acid binding proteins (FABPs) are abundantly present in tissues that actively metabolize fatty acids (FA). While their precise physiological function is not known, FABPs have been shown to play a role in the uptake and/or utilization of FA within the cell. FA metabolism is markedly altered during the host response to infection and inflammation. Previous studies have demonstrated that endotoxin or bacterial lipopolysaccharide (LPS) enhances hepatic FA synthesis and re-esterification while inhibiting FA oxidation in liver, heart and muscle. Now, we have examined the in vivo effects of LPS and cytokines on FABPs in liver (L-FABP), heart and muscle (H-FABP). Syrian hamsters were injected with LPS, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and the mRNA and protein content for L-FABP and H-FABP were analyzed. 16 h after administration, LPS (100 microg/100 g body weight) produced a 72% decrease in L-FABP mRNA levels in liver and this effect was sustained for 24 h. LPS also produced a 41% decrease in the protein content of L-FABP in liver after 24 h of treatment. TNF-alpha and IL-1beta decreased L-FABP mRNA levels in liver by 30 and 45%, respectively. LPS decreased H-FABP mRNA levels in skeletal muscle by 60% and in heart by 65%. LPS also produced a 49% decrease in H-FABP protein content in muscle. Neither TNF-alpha nor IL-1beta had any significant effect on H-FABP mRNA expression in heart and muscle. Taken together, these results indicate that LPS decreases FABP mRNA and protein levels in liver, heart and muscle, tissues that normally utilize FA as their primary fuel, whereas the inhibitory effect of cytokines is limited to the liver. The LPS-induced decrease in L-FABP and H-FABP may be an additional mechanism contributing to the decrease in FA oxidation that is associated with the host response to infection and inflammation.
Animals↗
Constitutive HOXA5 expression inhibits erythropoiesis and increases myelopoiesis from human hematopoietic progenitors.
The role of the homeobox gene HOXA5 in normal human hematopoiesis was studied by constitutively expressing the HOXA5 cDNA in CD34(+) and CD34(+)CD38(-) cells from bone marrow and cord blood. By using retroviral vectors that contained both HOXA5 and a cell surface marker gene, pure populations of progenitors that expressed the transgene were obtained for analysis of differentiation patterns. Based on both immunophenotypic and morphological analysis of cultures from transduced CD34(+) cells, HOXA5 expression caused a significant shift toward myeloid differentiation and away from erythroid differentiation in comparison to CD34(+) cells transduced with Control vectors (P =.001, n = 15 for immunophenotypic analysis; and P <.0001, n = 19 for morphological analysis). Transduction of more primitive progenitors (CD34(+)CD38(-) cells) resulted in a significantly greater effect on differentiation than did transduction of the largely committed CD34(+) population (P =.006 for difference between HOXA5 effect on CD34(+) v CD34(+)CD38(-) cells). Erythroid progenitors (burst-forming unit-erythroid [BFU-E]) were significantly decreased in frequency among progenitors transduced with the HOXA5 vector (P =.016, n = 7), with no reduction in total CFU numbers. Clonal analysis of single cells transduced with HOXA5 or control vectors (cultured in erythroid culture conditions) showed that HOXA5 expression prevented erythroid differentiation and produced clones with a preponderance of undifferentiated blasts. These studies show that constitutive expression of HOXA5 inhibits human erythropoiesis and promotes myelopoiesis. The reciprocal inhibition of erythropoiesis and promotion of myelopoiesis in the absence of any demonstrable effect on proliferation suggests that HOXA5 diverts differentiation at a mulitpotent progenitor stage away from the erythroid toward the myeloid pathway.
Cells, Cultured↗
[Effect of lisinopril on progression of retinopathy and microalbuminuria in normotensive subjects with insulin-dependent diabetes mellitus].
Effect of lisinopril on progression of retinopathy and microalbuminuria in normotensive subjects with insulin-dependent diabetes mellitus. Retinopathy and nephropathy are the most important microvascular complications in diabetes with hyperglycaemia and hypertension as important risk factors. Antihypertensive treatment with angiotensin-converting enzyme inhibitors has been shown to delay progression of nephropathy, but the effect on retinopathy has not been established. We, therefore, performed a trial of the effect of the ACE-inhibitor lisinopril on retinopathy and nephropathy in normotensive patients with IDDM. We performed a two year randomized double-blind placebo-controlled trial of the ACE-inhibitor lisinopril on 530 normotensive IDDM patients within the age group 20-59 years from 18 European centres. Patients were either normo- or microalbuminuric. Retinopathy was classified from retinal photographs into five levels (none to proliferative). The primary endpoint of the trial was progression of albuminuria. Mean albumin excretion rate (AER) was 8.0 micrograms/min at baseline in both treatment groups. After two years AER was 2.2. micrograms/min lower in the lisinopril than in the placebo group, a difference of 18.8% (p = 0.03). The difference in AER was 38.5 micrograms/min between treatment groups in patients with microalbuminuria at baseline (p = 0.001), and 0.23 microgram/min in patients with normoalbuminuria at baseline (p = 0.6). Retinopathy was a secondary endpoint. Patients treated with lisinopril had significantly lower Hb-A1c at baseline than the placebo group (6.9%-7.3%). Retinopathy progressed with at least one level in 13.2% of lisinopril treated and 23.4% of placebo treated patients (odds ratio 0.50, p = 0.02). Progression by two levels or progression to proliferative retinopathy were also significantly reduced in the lisinopril group compared to the placebo group (odds ratio 0.27 and 0.18, respectively). In conclusion, lisinopril delays progression of retinopathy and nephropathy in normotensive IDDM patients with micro- or normoalbuminuria.
Adult↗
Update on emerging infections from the Centers for Disease Control and Prevention. Outbreak of Vibrio parahaemolyticus infection associated with eating raw oysters and clams harvested from Long Island Sound--Connecticut, New Jersey, and New York, 1998.
This article is part of a regular series on emerging infections from the Centers for Disease Control and Prevention (CDC) and the EMERGEncy ID NET, an emergency department-based and CDC-collaborative surveillance network. Important infectious disease public health information with relevance to emergency physicians is reported. The goal of this series is to advance knowledge about communicable diseases in emergency medicine, and foster cooperation between the front line of clinical medicine and public health agencies.
Animals↗
Establishing a new university department of rural health: the first 2 years of the South Australian Centre for Rural and Remote Health.
This study aimed to describe the establishment of a new University Department of Rural Health (UDRH) in South Australia and to report early achievements. In May 1997, the UDRH was established, key staff were recruited, infrastructure was developed and in April 1998 a Joint University Committee on Rural and Remote Health was formed. By mid-1999, 14 full-time equivalent staff were employed in Whyalla and Adelaide. Early achievements include: review of undergraduate rural placements; increased rural clinical placements by 1000 student-weeks; partnership with the Dental School resulting in training opportunities and falling public waiting lists; multidisciplinary teaching practices in four rural sites; priority public health projects established; competitive research grants won; and a capital grant to strengthen Aboriginal health services infrastructure secured. These early achievements demonstrate UDRH potential to have a real impact on health worker education, service delivery, and public health status in rural and remote areas. This strong foundation must now be built on.
Curriculum↗
Vietnamese women and Pap smears: issues in promotion.
OBJECTIVE: Australian data indicate that Vietnamese-born women in Australia have a significantly higher incidence of cervical cancer than other Australian women. This study explored self-reported factors associated with Vietnamese-born women's participation in cervical screening. METHOD: A structured 60-item questionnaire was used to conduct an interview survey with 199 Vietnamese-born women over the age of 18 years and resident in Adelaide. RESULTS: Eighty-seven per cent (87%) of the women had heard of a Pap smear and 75% had had a test at some time. Reported participation increased with age, education level, marriage and length of stay in Australia. The family doctor was the most important source of information about Pap smears and the majority of the women reported they would have a smear if recommended by their doctor. Friends and family were the second information source about cervix screening. CONCLUSIONS AND IMPLICATIONS: These findings have clear implications for practice. Strategies to promote preventive health messages to this group of women should involve general practitioners and peer networks.
Adult↗
In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response.
Plasma platelet-activating factor acetylhydrolase (PAF-AH) hydrolyzes PAF and oxidized phospholipids and is associated with lipoproteins in the circulation. Endotoxin [lipopolysaccharide (LPS)], a potent inducer of the acute phase response (APR), produces marked changes in several proteins that play important roles in lipoprotein metabolism. We now demonstrate that LPS produces a 2.5- to 3-fold increase in plasma PAF-AH activity in Syrian hamsters. The plasma PAF-AH activity is found in the high-density lipoprotein (HDL) fraction and is increased threefold with LPS treatment despite a decrease in plasma HDL levels, indicating that plasma PAF-AH activity is increased per HDL particle. LPS markedly increased PAF-AH mRNA levels in liver, spleen, lung, and small intestine. The maximal increase in plasma PAF-AH activity and mRNA expression in liver and spleen is seen 24 h after LPS treatment. Both tumor necrosis factor and interleukin-1 modestly increased plasma PAF-AH activity and mRNA levels in liver and spleen, suggesting that they may partly mediate the effect of LPS on PAF-AH. Surgical removal of spleen had no effect on basal or LPS-induced plasma PAF-AH activity, suggesting that spleen per se may not contribute to plasma PAF-AH activity. Finally, LPS, turpentine and zymosan increased plasma PAF-AH activity in mice and/or rats, indicating that multiple APR inducers upregulate plasma PAF-AH and this effect is consistent across different rodent species. Taken together, our results indicate that plasma PAF-AH activity and mRNA expression is markedly upregulated during the host response to infection and inflammation. An increase in plasma PAF-AH may enhance the degradation of PAF as well as alter the structure and function of HDL during infection and inflammation.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Regulation of putative fatty acid transporters and Acyl-CoA synthetase in liver and adipose tissue in ob/ob mice.
The hyperlipidemia associated with obesity and type 2 diabetes is caused by an increase in hepatic triglyceride synthesis and secretion that is secondary to an increase in de novo lipogenesis, a decrease in fatty acid (FA) oxidation, and an increase in the flux of peripherally derived FA to the liver. The uptake of FA across the plasma membrane may be mediated by three distinct proteins--FA translocase (FAT), plasma membrane FA binding protein (FABP-pm), and FA transport protein (FATP)--that have recently been characterized. Acyl-CoA synthetase (ACS) enhances the uptake of FAs by catalyzing their activation to acyl-CoA esters for subsequent use in anabolic or catabolic pathways. In this study, we examine the mRNA levels of FAT, FABP-pm, FATP, and ACS in the liver and adipose tissue of genetically obese (ob/ob) mice and their control littermates. FAT mRNA levels were 15-fold higher in liver and 60-80% higher in adipose tissue of ob/ob mice. FABP-pm mRNA levels were twofold higher in liver and 50% higher in adipose tissue of ob/ob mice. FATP mRNA levels were not increased in liver or adipose tissue. ACS mRNA levels were higher in adipose tissue but remained unchanged in liver. However, the distribution of ACS activity associated with mitochondria and microsomes in liver was altered in ob/ob mice. In control littermates, 61% of ACS activity was associated with mitochondria and 39% with microsomes, whereas in ob/ob mice 34% of ACS activity was associated with mitochondria and 66% with microsomes; this distribution would make more FA available for esterification, rather than oxidation, in ob/ob mouse liver. Taken together, our results suggest that the upregulation of FAT and FABP-pm mRNAs may increase the uptake of FA in adipose tissue and liver in ob/ob mice, which, coupled with an increase in microsomal ACS activity in liver, will enhance the esterification of FA and support the increased triglyceride synthesis and VLDL production that characterizes obesity and type 2 diabetes.
Adipose Tissue↗
Freshwater: will the world's future needs be met? An interview with David Foster Hales, Deputy Assistant Administrator of the Global Center for Environment at the U.S. Agency for International Development [USAID].
Explore the source record for details and available documents.
Conservation of Natural Resources↗
Back pain following epidural anaesthesia in labour.
PURPOSE: To determine the factors associated with the development of post-partum back pain following epidural anaesthesia for labour and delivery and its incidence. METHODS: A prospective observational cohort study was conducted in a University affiliated tertiary care hospital. Women presenting for labour and delivery who were planning to have epidural anaesthesia were eligible for study. Baseline data were obtained from the women and obstetrical and anaesthetic data from the hospital chart. Women were contacted by phone at four to six weeks post-partum and questioned regarding the presence of any back pain and pain lasting longer than 14 days. RESULTS: Three hundred women entered the study and follow-up was obtained in 270 (90%). The incidence of back pain was 30.7% and back pain lasting longer than 14 days was 8.5%. Nulliparity was associated with a decreased risk of developing back pain post-partum but this decrease was only associated with pain lasting more than 14 days: Odds Ratio (OR) [95% confidence interval] 0.32 [0.11-0.94]. A previous history of back pain was strongly associated with the development of any back pain (OR 43.85 [9.97-192.9] but not with pain lasting longer than 14 days (OR 2.16 [0.71-6.58]). Age, weight and the duration of the second stage of labour were not associated with the development of back pain. CONCLUSIONS: Back pain following epidural anaesthesia is common but persistent back pain is much less common. A previous history of back pain increases the likelihood of post-partum back pain following epidural anaesthesia. Nulliparity is associated with a decreased risk.
Adult↗
Regulation of fatty acid transport protein and fatty acid translocase mRNA levels by endotoxin and cytokines.
The cloning of two novel fatty acid (FA) transport proteins, FA transport protein (FATP) and FA translocase (FAT), has recently been reported; however, little is known about their in vivo regulation. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleukin-1 (IL-1) stimulate adipose tissue lipolysis and enhance hepatic lipogenesis and reesterification while suppressing FA oxidation in multiple tissues. Hence, in this study we examined their effects on FATP and FAT mRNA levels in Syrian hamsters. Our results demonstrate that LPS decreased FATP and FAT mRNA expression in adipose tissue, heart, skeletal muscle, brain, spleen, and kidney, tissues in which FA uptake and/or oxidation is decreased during sepsis. In the liver, where FA oxidation is decreased during sepsis but the uptake of peripherally derived FA is increased to support reesterification, LPS decreased FATP mRNA expression by 70-80% but increased FAT mRNA levels by four- to fivefold. The effects of LPS on FATP and FAT mRNA levels in liver were observed as early as 4 h after administration and were maximal by 16 h. TNF and IL-1 mimicked the effect of LPS on FATP and FAT mRNA levels in both liver and adipose tissue. These results indicate that the mRNAs for both transport proteins are downregulated by LPS in tissues in which FA uptake and/or oxidation are decreased during sepsis. On the other hand, differential regulation of FATP and FAT mRNA in liver raises the possibility that these proteins may be involved in transporting FA to different locations inside the cell. FATP may transport FA toward mitochondria for oxidation, which is decreased in sepsis, whereas FAT may transport FA to cytosol for reesterification, which is enhanced in sepsis.
Adipose Tissue↗
In vivo regulation of acyl-CoA synthetase mRNA and activity by endotoxin and cytokines.
Acyl-CoA synthetase (ACS) catalyzes the activation of fatty acids (FA) to acyl-CoA esters, which are further metabolized in either anabolic or catabolic pathways. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleukin-1 (IL-1) enhance hepatic FA synthesis and reesterification and inhibit FA oxidation. LPS also decreases triglyceride storage in adipose tissue and inhibits the uptake of FA by heart and muscle. Therefore, in this study we examined the effects of LPS and cytokines on ACS (now also known as ACS1) mRNA expression and activity in multiple tissues in Syrian hamsters. LPS markedly decreased ACS1 mRNA levels in liver, adipose tissue, heart, and skeletal muscle. The inhibitory effects of LPS on ACS1 mRNA levels in liver and adipose tissue were observed as early as 2-4 h after administration, became maximal by 4-8 h, and were sustained for >/=24 h. Very low doses of LPS (0.1-1 microg/100 g body wt) were needed to reduce ACS1 mRNA levels in liver and adipose tissue. TNF and IL-1 mimicked the effect of LPS on ACS1 mRNA levels in liver and adipose tissue. LPS decreased ACS activity in adipose tissue, heart, and muscle. In liver, where ACS is localized in several subcellular organelles, both LPS and cytokines decreased mitochondrial ACS activity, whereas they increased microsomal ACS activity. Taken together, these results indicate that LPS and cytokines decrease ACS1 mRNA expression and ACS activity in tissues where FA uptake and/or oxidation is decreased during sepsis. In liver, where FA oxidation is decreased during sepsis but the reesterification of FA is increased, LPS and cytokines decrease ACS1 mRNA and mitochondrial ACS activity, which may inhibit FA oxidation, but increase microsomal ACS activity, which may support the reesterification of peripherally derived FA for triglyceride synthesis.
Adipose Tissue↗
IL-1 beta mediates leptin induction during inflammation.
Interleukins (IL) are key mediators of the host response to infection and inflammation. Leptin is secreted by adipose tissue and plays an important role in the control of food intake. Administration of lipopolysaccharide (LPS), tumor necrosis factor (TNF), or IL-1 acutely increases leptin mRNA and protein levels. To investigate the role of IL-1 beta and IL-6 in leptin expression during inflammation, we used IL-1 beta-deficient (-/-) and IL-6 -/- mice. Mice were injected intraperitoneally with LPS or subcutaneously with turpentine, as models of systemic or local inflammation, respectively. In IL-1 beta +/+ mice, both LPS and turpentine increased leptin mRNA and circulating leptin. In contrast, neither LPS nor turpentine increased leptin levels in IL-1 beta -/- mice. In IL-6 +/+ or IL-6 -/- mice, turpentine increased leptin protein to comparable levels. We conclude that IL-1 beta is essential for leptin induction by both LPS and turpentine in mice, but IL-6 is not.
Animals↗
Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin.
Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections. We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters. Administration of LPS induced a 2-fold increase in hepatic SPT activity. The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours. Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 0.3 microg LPS/100 g body weight. LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA. LPS treatment also produced 75% and 2.5-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively. Many of the metabolic effects of LPS are mediated by cytokines. Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells. IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL. IL-1 also increased the secretion of sphingolipids into the medium. Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin. Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis.
Acyltransferases↗
Comparison of attitudes about communication in children and adolescents with sickle cell disease.
Survey responses of 24 African-American children and adolescents with sickle cell disease suggest similar, generally positive communication attitudes.
Adolescent↗
Preparing for multiracial practice.
Explore the source record for details and available documents.
Culture↗
Wirth: Key to slowing population growth -- education of girls.
Explore the source record for details and available documents.
Adolescent↗