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Biomedical subjects

David Hirsch

Publications and source records attributed to David Hirsch.

7 recordsLinked to original sources
PubMed2006

Targeted deletion of FATP5 reveals multiple functions in liver metabolism: alterations in hepatic lipid homeostasis.

BACKGROUND & AIMS: Fatty acid transport protein 5 (FATP5/Slc27a5) has been shown to be a multifunctional protein that in vitro increases both uptake of fluorescently labeled long-chain fatty acid (LCFA) analogues and bile acid/coenzyme A ligase activity on overexpression. The aim of this study was to further investigate the diverse roles of FATP5 in vivo. METHODS: We studied FATP5 expression and localization in liver of C57BL/6 mice in detail. Furthermore, we created a FATP5 knockout mouse model and characterized changes in hepatic lipid metabolism (this report) and bile metabolism (the accompanying report by Hubbard et al). RESULTS: FATP5 is exclusively expressed by the liver and localized to the basal plasma membrane of hepatocytes, congruent with a role in LCFA uptake from the circulation. Overexpression of FATP5 in mammalian cells increased the uptake of 14C-oleate. Conversely, FATP5 deletion significantly reduced LCFA uptake by hepatocytes isolated from FATP5 knockout animals. Moreover, FATP5 deletion resulted in lower hepatic triglyceride and free fatty acid content despite increased expression of fatty acid synthetase and also caused a redistribution of lipids from liver to other LCFA-metabolizing tissues. Detailed analysis of the hepatic lipom of FATP5 knockout livers showed quantitative and qualitative alterations in line with a decreased uptake of dietary LCFAs and increased de novo synthesis. CONCLUSIONS: Our findings support the hypothesis that efficient hepatocellular uptake of LCFAs, and thus liver lipid homeostasis in general, is largely a protein-mediated process requiring FATP5. These new insights into the physiological role of FATP5 should lead to an improved understanding of liver function and disease.

Animals↗
PubMed2003

Quality grand rounds.

Explore the source record for details and available documents.

Education, Medical, Continuing↗
PubMed2003

Palivizumab prophylaxis of respiratory syncytial virus disease in 2000-2001: results from The Palivizumab Outcomes Registry.

The objective of the Registry was to characterize the population of infants receiving prophylaxis for respiratory syncytial virus (RSV) disease by describing the patterns and scope of usage of palivizumab in a cross section of US infants. RSV hospitalization outcomes were also described. The Palivizumab (Synagis, MedImmune, Inc., 25 West Watkins Mill Road, Gaithersburg, MD 20878) Outcomes Registry was a prospective multicenter survey conducted at 63 sites. Demographics, injection history, and RSV hospitalization outcomes were collected on 2,116 infants receiving palivizumab. Infants were enrolled in the Registry between September 1, 2000-March 1, 2001, at the time of their first injection. Infants born at less than 32 weeks of gestation accounted for 47% of infants enrolled, and those between 32-35 weeks accounted for 45%; approximately 8% were greater than 35 weeks of gestation. Lower RSV hospitalization rates were observed in infants who had greater adherence to regularly scheduled injections. Nearly one-half of all hospitalizations occurred within the first and second injection intervals, suggesting the importance of early RSV protection. The confirmed RSV hospitalization rate of all infants in the Registry was 2.9%; the rate was 5.8% in infants with chronic lung disease of infancy, and 2.1% in premature infants without chronic lung disease. In conclusion, these data support the continued effectiveness of palivizumab prophylaxis for severe RSV lower respiratory tract disease in a large cohort of high-risk infants from geographically diverse pediatric offices and clinics. The Palivizumab Outcomes Registry provides an opportunity to assess palivizumab utilization and clinical effectiveness in the US.

Antibodies, Monoclonal↗
PubMed2002

Insulin causes fatty acid transport protein translocation and enhanced fatty acid uptake in adipocytes.

Fatty acid uptake into 3T3 L1 adipocytes is predominantly transporter mediated. Here we show that, during 3T3 L1 adipocyte differentiation, expression of fatty acid transport proteins (FATPs) 1 and 4 is induced. Using subcellular membrane fractionation and immunofluorescence microscopy, we demonstrate that, in adipocytes, insulin induces plasma membrane translocation of FATPs from an intracellular perinuclear compartment to the plasma membrane. This translocation was observed within minutes of insulin treatment and was paralleled by an increase in long chain fatty acid (LCFA) uptake. In contrast, treatment with TNF-alpha inhibited basal and insulin-induced LCFA uptake and reduced FATP1 and -4 levels. Thus, hormonal regulation of FATP activity may play an important role in energy homeostasis and metabolic disorders such as type 2 diabetes.

3T3 Cells↗
PubMed2002

Access flow monitoring of patients with native vessel arteriovenous fistulae and previous angioplasty.

Screening strategies based on measurement of access blood flow (Qa) allow detection and angioplasty of subclinical stenosis in native vessel arteriovenous (AV) fistulae. However, little is known about the efficacy of Qa measurements for detecting recurrent stenoses in fistulae and that of angioplasty for correcting them. A total of 303 patients were studied over 30 mo; 69 (23%) of these had stenoses, of whom 53 underwent angioplasty. Of those undergoing angioplasty, 30 patients had 46 episodes of recurrent positive studies and underwent repeat fistulography. In 31 of these episodes (19 patients), stenosis was again identified and treated successfully with angioplasty. Overall positive predictive values for stenosis were similar in first and subsequent episodes of stenosis (71% versus 67%), and angioplasty was associated with sustained increases in Qa for both first and subsequent episodes. Assisted patency in fistulae that required repeat angioplasty was 87% (median follow-up 10 mo after the second angioplasty). In conclusion, Qa is effective for detecting first and subsequent lesions in patients with AV fistulae, and angioplasty of first or subsequent lesions is associated with sustained increments in Qa. Continued screening after correction of first stenoses appears reasonable, because of both the frequency of recurrent stenosis and the success of repeat intervention.

Angioplasty, Balloon↗
PubMed2001

Screening for subclinical stenosis in native vessel arteriovenous fistulae.

Guidelines recommend the use of ultrasound dilution techniques (UDT), including measurement of access recirculation (AR) and access blood flow (Q(a)), to screen for subclinical vascular access dysfunction. Although these techniques are efficacious in polytetrafluoroethylene grafts, data in native vessel arteriovenous fistulae (AVF) are lacking. A prospective observational study was conducted to evaluate the utility of UDT screening in AVF. Q(a) and AR were measured bimonthly. Positive studies required fistulograms and were defined by Q(a) < 500 ml/min, DeltaQ(a) > 20% from baseline or AR > 5%. Accesses with stenosis underwent percutaneous angioplasty. After 1 yr, there were 1355 mo of follow-up in 177 patients. There were 44 positive studies in 40 patients. Q(a) was <500 ml/min in 36 (82%), DeltaQ(a) was >20% in 5 (11%), and AR was >5% in 6 (14%). Of patients with Q(a) < 500 ml/min, 29 (81%) had stenosis. Only two patients (40%) with DeltaQ(a) > 20% but Q(a) > 500 ml/min had stenosis. No patient with AR > 5% had stenosis unless Q(a) was also <500 ml/min. Immediate patency rate was 93% post-PTA. Mean Q(a) increased from 303 +/- 154 ml/min to 602 +/- 220 ml/min (P < 0.0001), and mean urea reduction ratio increased from 70.4 +/- 8.4% to 74.6 +/- 6.5% (P = 0.003) post-PTA. The results demonstrate that UDT could detect subclinical stenoses in AVF, and most lesions were amenable to angioplasty. AVF that underwent PTA delivered higher Q(a) and urea reduction ratio, and immediate patency rates were acceptable. Access failure after negative UDT was unusual. Measuring AR increases the time required to perform UDT but does not improve utility. Serial measurements of Q(a) alone may be the best strategy for screening AVF.

Aged↗