Controlling health care expenditures.
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Cost Control↗
Biomedical subjects
J L Kirkland
Publications and source records attributed to J L Kirkland.
Fat depot origin affects fatty acid handling in cultured rat and human preadipocytes.
Regional differences in free fatty acid (FFA) handling contribute to diseases associated with particular fat distributions. As cultured rat preadipocytes became differentiated, FFA transfer into preadipocytes increased and was more rapid in single perirenal than in epididymal cells matched for lipid content. Uptake by human omental preadipocytes was greater than uptake by abdominal subcutaneous preadipocytes. Adipose-specific fatty acid binding protein (aP2) and keratinocyte lipid binding protein abundance was higher in differentiated rat perirenal than in epididymal preadipocytes. This interdepot difference in preadipocyte aP2 expression was reflected in fat tissue in older animals. Carnitine palmitoyltransferase 1 activity increased during differentiation and was higher in perirenal than in epididymal preadipocytes, particularly the muscle isoform. Long-chain acyl-CoA levels were higher in perirenal than in epididymal preadipocytes and isolated fat cells. These data are consistent with interdepot differences in fatty acid flux ensuing from differences in fatty acid binding proteins and enzymes of fat metabolism. Heterogeneity among depots results, in part, from distinct intrinsic characteristics of adipose cells. Different depots are effectively separate miniorgans.
Acyl Coenzyme A↗
Altered expression of C/EBP family members results in decreased adipogenesis with aging.
Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte differentiation decrease between middle and old age. We show that expression of CCAAT/enhancer binding protein (C/EBP)-alpha, a key regulator of adipogenesis and fat cell function, declined substantially with aging in differentiating preadipocytes cultured under identical conditions from rats of various ages. Overexpression of C/EBP alpha in preadipocytes cultured from old rats restored capacity to differentiate into fat cells, indicating that downstream differentiation-dependent genes maintain responsiveness to regulators of adipogenesis. C/EBP alpha-expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBP beta, which modulates C/EBP alpha-expression, did not change with age, but the truncated, dominant-negative C/EBP beta-liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBP beta-LIP in preadipocytes from young rats impaired adipogenesis. C/EBP delta, which acts with full-length C/EBP beta to enhance adipogenesis, decreased with age. Thus processes intrinsic to adipose cells involving changes in C/EBP family members contribute to impaired adipogenesis and altered fat tissue function with aging. These effects are potentially reversible.
Adipocytes↗
Nutritional risk in an urban homebound older population. The nutrition and healthy aging project.
PURPOSE: To establish the prevalence of nutritional problems and their related socio-demographic and health-related risk factors in the homebound elderly population. METHODS: Subjects included 239 men and women, ages 65 to 105 years. Trained, two-person field teams conducted comprehensive in-home assessments. Medical record reviews assessed co-morbidity and medication use. RESULTS: The majority of these urban study subjects are of very advanced age (mean age 81 years), female (72%), non-white (73%), living alone (51%), of low income (76%), and somewhat socially isolated (26% had no weekly social contact). More older women than men were widowed (60 vs. 33%, respectively) and poor (80 vs. 67%). The disease burden and functional dependency were both high in men and women; 77% had three or more chronic medical conditions; 76% were functionally dependent in one or more ADL's and 95% in one or more IADL's. Poor dietary quality was universal in these older men and women; half or more consumed diets that deviated from recommended standards for at least 13 of the 24 nutritional guidelines studied. Five percent of subjects were underweight (Body Mass Index (BMI) <18.5); 22% were overweight (BMI 25.0-29.9); and 33% were obese (BMI >30.0). Fasting albumin, hemoglobin, and absolute lymphocyte concentrations were borderline to very low in 18-32%. Dyslipidemia was more common in women; however, men and women had similar Total:HDL cholesterol ratios. CONCLUSIONS: Nutritional status is poor in homebound persons of very advanced age with substantial co-morbidity and functional dependency. The complexities of nutritional risk necessitate multi-disciplinary and individualized nutritional intervention strategies.
Activities of Daily Living↗
Esterification of free fatty acids in adipocytes: a comparison between octanoate and oleate.
Medium-chain triacylglycerols (MCT) are present in milk, coconut oil and other foods, and are used therapeutically in special diets for certain disorders of lipid and glucose utilization. Recently, it has become apparent that MCT are not only oxidized in the liver, but are also present in lymph and fat tissue, particularly after chronic treatment. To evaluate the influence of MCT on metabolism in fat cells, we compared incorporation of octanoate and oleate into cellular triacylglycerols of 3T3-L1 adipocytes as well as their effects on preadipocyte differentiation. We found that less octanoate than oleate was stored and that more octanoate than oleate was oxidized. Octanoate was esterified to a greater extent at the sn-1,3 position of glyceryl carbons than at the sn-2 position, whereas the opposite was true for oleate. Glycerol release from fat cells pre-treated with octanoate was also greater than from cells pre-treated with oleate, presumably related to the preferential release of octanoate from the sn-1,3 position. Octanoate was not incorporated into lipids in undifferentiated cells and did not induce differentiation in these cells, whereas oleate was readily stored and actually induced differentiation. Incorporation of octanoate into lipids increased as cells differentiated, but reached a maximum of about 10% of the total stored fatty acids. If these effects in vitro also occur in vivo, substitution of octanoate for oleate or other long-chain fatty acids could have the beneficial effect of diminishing fat-cell number and lipid content.
3T3 Cells↗
Improved inpatient billing metrics by physician-directed billing software.
Billing may not be prominent on academic physicians' lists of priorities because of other demands and commitments for their time. The authors developed and examined the use of an electronic inpatient billing tool that also facilitated physician rounding responsibilities. The results show that use of an electronic tool was more acceptable to physicians than their original card system, and it significantly decreased charge-processing lag time.
Academic Medical Centers↗
Incorporation of [1-13C]oleate into cellular triglycerides in differentiating 3T3L1 cells.
Oleate is one of the most abundant dietary fatty acids, and much remains to be learned about its metabolism in fat cells. We studied the incorporation of exogenous [1-13C]oleate into triglycerides (TG) in differentiating 3T3L1 preadipocytes using 13C NMR spectroscopy. The quantity of oleate incorporated into TG was found to increase as preadipocytes differentiated into fat cells. The ratio of unesterified [1-13C]oleate to total stored fatty acids was higher in less differentiated cells, and declined at later stages of differentiation as cells accumulated fatty acids through de novo synthesis. When added as the only exogenous fatty acid, oleate was largely esterified at the sn-2 position. When equimolar unlabeled linoleate was co-provided at the same time, the ratio of [1-13C]oleate esterified at the sn-1,3 position increased, implying competition between linoleate and oleate for esterification, especially at the sn-2 position. When cells pre-enriched with [1-13C]oleate (esterified to TG) were treated with isoproterenol, a lipolytic agent, most of the [1-13C]oleate was still found in TG, despite a high rate of lipolysis determined by measuring glycerol release. This implies extensive re-esterification of the oleate released by lipolysis.
3T3 Cells↗
Commentary: aging, differentiation-dependent gene expression, and fat cell function.
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Adipocytes↗
Inhibitors of preadipocyte replication: opportunities for the treatment of obesity.
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Adipocytes↗
A 13C nuclear magnetic resonance study of free fatty acid incorporation in acylated lipids in differentiating preadipocytes.
To understand the role of free fatty acid (FFA) incorporation in the accumulation of lipids in the adipocyte and ultimately in the development of obesity, 13C nuclear magnetic resonance was used to study lipid metabolism in differentiating preadipocytes. The incorporation of 13C=O-labeled FFA into cellular lipids in primary cultured rat preadipocytes and 3T3L1 preadipocytes at different stages of differentiation was monitored by the 13C carbonyl chemical shift. Significant incorporation of palmitic acid into phosphatidylcholine in both the alpha and beta acyl chain positions was found in cells at early stages of differentiation. At later differentiation stages or after extended incubation periods, most of the 13C=O signals were found in the triacylglycerol (TG) molecules. Unsaturated 13C=O-labeled acyl chains were detected in the TG molecules when cells were incubated with saturated 13C=O-labeled FFA, indicating that intracellular dehydrogenation had occurred in the 13C=O-labeled palmitoyl chain. By using 13C-labeled methyl myristate as an internal intensity reference, incorporation of 13C FFA into each acyl chain position of the major intracellular lipids was determined quantitatively.
3T3 Cells↗
Phorbol ester inhibition of estrogen-induced uterine deoxyribonucleic acid synthesis.
Protein kinase C (PKC) is a key regulatory enzyme in the control of growth and differentiated function in many cell types. Recently it has become clear that cross talk occurs between PKC and steroid hormone-activated signaling pathways. In this work we have thus used the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to investigate the relationship between PKC activation and estrogen-induced proliferation in an in vivo model of hormone action, the immature rat uterus. A single injection of estradiol (E2) to immature female animals increases DNA synthesis in all major uterine cell types. Administration of TPA alone, simultaneous administration of TPA and E2, or administration of TPA 12 h after E2 did not alter uterine DNA synthesis. However, administration of TPA 6 h after E2 markedly decreased [3H]thymidine incorporation and the labeling indices in uterine epithelial, stromal, and myometrial cells. This inhibition represents a decrease in DNA synthesis per se rather than a change in the time course of the tissue response to the hormone. The inhibitory effect of TPA was reversible within 72 h and did not appear to be due to a decrease in the level or degree of occupancy of uterine estrogen receptors. These results suggest that a discrete regulatory event(s) in the pathway of estradiol-induced proliferation is inhibited by PKC activation approximately 6 h after hormonal stimulation.
Animals↗
A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens.
We recently noted that immature rats failed to exhibit a normal uterine response to exogenously administered estradiol as assessed by both biochemical (induction of gene expression) and morphological (altered uterine and vaginal histology and size) end points. An initial analysis suggested that this was due to a high degree of estrogenization from a dietary source which was producing a near maximal uterotrophic response prior to hormone treatment. Subsequent chemical analysis indicated that the feed in question contained high amounts of two well-known phytoestrogens, genistein (210 mg/kg) and daidzen (14 mg/kg), and the lot of feed in question produced a large uterotrophic effect when fed to immature ovariectomized rats. These findings illustrate that, despite increased awareness of phytoestrogens, some batches of animal feed contain very high amounts of estrogenic components which have marked effects on in vivo end points of hormone action. These observations have important implications for both basic research and screening methods that utilize in vivo approaches.
Animal Feed↗
Telephone charges and payments in a diabetes clinic.
OBJECTIVES: To determine reimbursement rates after initiation of charges for certain telephone calls in a pediatric diabetes care center. DESIGN: A review of charges and payments data during 1996. RESULTS: Four hundred seventy-two telephone calls initiated by patients and parents were billed during the study period. These calls regarded treatment of hypoglycemia, hyperglycemia, ketonuria, sick day treatment, and insulin dose changes. Insured patients were charged for 384 telephone calls and indigent patients were charged for 88 telephone calls. Telephone calls from insured patients generated charges of $9215 and payments of $3074. Insurance payments were $1677 (18% of charges), and patient payments were $1396 (15% of charges). Telephone calls from uninsured patients covered by Texas Medicaid or Chronically Ill and Disabled Children funding generated charges of $2193 and no payments. CONCLUSIONS: Telephone charges were reimbursed by all payors at an overall rate of 27%.
Ambulatory Care Facilities↗
Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation. Inter-tissue and inter-species expression of CPT I and CPT II enzymes.
The outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (CPT I) represents the initial and regulated step in the beta-oxidation of fatty acids. It exists in at least two isoforms, denoted L (liver) and M (muscle) types, with very different kinetic properties and sensitivities to malonyl-CoA. Here we have examined the relative expression of the CPT I isoforms in two different models of adipocyte differentiation and in a number of rat tissues. Adipocytes from mice, hamsters and humans were also evaluated. Primary monolayer cultures of undifferentiated rat preadipocytes expressed solely L-CPT I, but significant levels of M-CPT I emerged after only 3 days of differentiation in vitro; in the mature cell M-CPT I predominated. In sharp contrast, the murine 3T3-L1 preadipocyte expressed essentially exclusively L-CPT I, both in the undifferentiated state and throughout the differentiation process in vitro. This was also true of the mature mouse white fat cell. Fully developed adipocytes from the hamster and human behaved similarly to those of the rat. Thus the mouse white fat cell differs fundamentally from those of the other species examined in terms of tis choice of a key regulatory enzyme in fatty acid metabolism. In contrast, brown adipose tissue from all three rodents displayed the same isoform profiles, each expressing overwhelmingly M-CPT I. Northern blot analysis of other rat tissues established L-CPT I as the dominant isoform not only in liver but also in kidney, lung, ovary, spleen, brain, intestine and pancreatic islets. In addition to its primacy in skeletal muscle, heart and fat, M-CPT I was also found to dominate the testis. The same inter-tissue isoform pattern (with the exception of white fat) was found in the mouse. Taken together, the data bring to light an intriguing divergence between white adipocytes of the mouse and other mammalian species. They also raise a cautionary note that should be considered in the choice of animal model used in further studies of fat cell physiology.
3T3 Cells↗
Preadipocyte function and aging: links between age-related changes in cell dynamics and altered fat tissue function.
OBJECTIVE: To review recent findings about changes with age in the replication and differentiation of preadipocytes, the progenitor cells in fat tissue that are capable of differentiating into fat cells, and to examine possible links between these alterations and age-related changes in fat tissue function. DESIGN: A survey and analysis of recent literature concerning changes in preadipocyte and fat cell function with age. CONCLUSIONS: Intrinsic aging changes in fat cells and preadipocytes as well as in factors extrinsic to fat tissue (such as food intake and absorption and hormonal status) contribute to age-related alterations in fat tissue function and cellularity. Changes with age in preadipocyte number, replicative potential, and capacity for differentiation, which may be linked to aging changes in fat cell size, number, and function, have been identified. The decline in preadipocyte capacity for differentiation and the associated decline in fat cell lipogenic capacity may be particularly important in contributing to the decrease in fat mass and alterations in fat tissue function that occur between middle- and old age. These declines result from blunting of the changes in gene expression that occur during preadipocyte differentiation and may, in turn, be related to altered regulation of particular transcription factors that control the preadipocyte differentiation program and maintenance of fat cell function.
Absorption↗
Frequency and necessity of thyroid function tests in neonates and infants with congenital hypothyroidism.
OBJECTIVE: The American Academy of Pediatrics recommends frequent thyroid function tests in infants and children with congenital hypothyroidism (CH). Data supporting the recommended frequency are lacking. This review was conducted to assess the validity of these recommendations. METHODS: The thyroxine (T4) and thyroid-stimulating hormone (TSH) levels of 50 neonates diagnosed between 1988 to 1993 were reviewed to assess the length of time on a specific dose of levothyroxine. RESULTS: 1) Changes in the dose of levothyroxine occurred 35 times during the first year of life for the 39 children treated with .025 mg/day, five times during the first year of life for the 9 children treated with .0375 mg/day, and three times during the first year of life for the 2 children treated with .050 mg/day. 2) These dose changes occurred at varying time intervals. 3) The T4 and TSH levels obtained at visits requiring dose changes were statistically different from the T4 and TSH levels obtained at the previous two visits. The T4 and TSH levels at the two visits before the change in dosage did not differ statistically. CONCLUSIONS: 1) An initial levothyroxine dose of .0375 mg/day requires fewer dose changes than a dose of .025 mg/day. 2) A lack of statistical change in T4 or TSH levels obtained at visits before the change-in-dose visit and the variable time span between dose changes necessitate frequent monitoring regardless of the dose of levothyroxine, the previous T4 or TSH levels, or the length of time at a specific dose. 3) These data support the recommendations of the American Academy of Pediatrics regarding the frequency of thyroid function studies during the first 2 years of life.
Congenital Hypothyroidism↗
Glomerular dysfunction in the aging Fischer 344 rat is associated with excessive growth and normal mesangial cell function.
BACKGROUND: Fischer 344 (F344) rats display focal and diffuse glomerulosclerosis with aging postulated to result from loss of normal mesangial cell intrinsic function, e.g., vasoactive hormone signaling, or preservation of normal responsiveness to extrinsic growth factors. METHODS: In 3-, 17-, and 24-month-old F344 male rats, glomerular structure, measured by PC-based morphometry, and function were compared. Immunoperoxidase staining of glomerular proliferating cell nuclear antigen (PCNA) detected cellular proliferation. Primary cultured mesangial cells from the 3 age groups were studied in parallel. Calcium (Ca2+) signaling, measured by Fura-2 fluorescence, contraction to vasopressin (AVP) 1 microM, measured by videomicroscopy, and proliferative response to platelet-derived growth factor-beta beta (PDGF) were compared. RESULTS: Proteinuria was 13 +/- 4, 38 +/- 17, and 110 +/- 35 mg/24 hours at 3, 17, and 24 months, respectively (n = 5, mean +/- SE, p < .01, 3 vs 24 months), with no change in 24-hour creatinine clearances. Glomerular volumes (n = 200/group) for 3, 17, and 24 months, respectively, were .30 +/- .01, .60 +/- .02, .74 +/- 0.2 x 10(6) micron3 (p < .001, 3 months vs 17 months, and 17 vs 24 months). Glomerular basement membrane (GBM) widths and fractional mesangial volumes increased significantly with aging. Glomerular cell PCNA staining remained positive at 24 months. Cultured mesangial cell Ca2+ signaling and contraction to AVP were unchanged with aging. Proliferation to PDGF, which was partially inhibited with verapamil, was similar at 3 and 24 months. CONCLUSIONS: In the Fischer 344 rat, mesangial cell Ca2+ signaling, contraction, and proliferation responsiveness are unchanged with aging. Continued growth is associated with the glomerulosclerosis of aging.
Aging↗