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Biomedical subjects

R Ramakrishnan

Publications and source records attributed to R Ramakrishnan.

At least 91 records · Page 5Linked to original sources
PubMed1994

PCR-based analysis of herpes simplex virus type 1 latency in the rat trigeminal ganglion established with a ribonucleotide reductase-deficient mutant.

Competitive quantitative PCR and reverse transcriptase-PCR were used to quantitate DNA and RNA from an attenuated ribonucleotide reductase-deleted herpes simplex virus type 1 (HSV-1) mutant in the rat trigeminal ganglion after peripheral inoculation following corneal scarification. Amplification of ganglionic DNA with oligonucleotide primers specific for the HSV-1 glycoprotein B (gB) gene and for the latency-associated transcript (LAT) gene indicated that there were approximately 2 x 10(5) genome equivalents per ganglion at 2 days, 7 days, and 8 weeks after inoculation. Amplification of ganglionic RNA with primers specific for HSV-1 LAT indicated that the amount of LAT RNA was also stable over 8 weeks, with 10(7) LAT molecules per ganglion at 2 days and at 7 days postinoculation and 1.4 x 10(7) LAT molecules per ganglion at 8 weeks. In situ hybridization with a digoxigenin-labeled riboprobe specific for LAT detected an average of one to two LAT-positive cells in each positive 6-microns section of trigeminal ganglion. In situ PCR detection of HSV-1 genomes in similar sections, using digoxigenin-labeled nucleotides with primers specific for HSV-1 gB, identified as many as 120 genome-positive cells per section. These results indicate that there are approximately 50 LAT molecules per latent HSV-1 genome in the trigeminal ganglion, compared with 15 LAT molecules per latent HSV-1 genome in the central nervous system (R. Ramakrishnan, D. J. Fink, G. Jiang, P. Desai, J. C. Glorioso, and M. Levine, J. Virol. 68:1864-1873, 1994), but that cells with detectable LATs by in situ hybridization represent only a small proportion of those ganglionic neurons containing HSV-1 genomes. The presence of latent HSV-1 genomes in a large number of neurons suggests that HSV-1 may be more efficient in establishing the latent state than would be anticipated from previous reports.

Animals↗
PubMed1994

Competitive quantitative PCR analysis of herpes simplex virus type 1 DNA and latency-associated transcript RNA in latently infected cells of the rat brain.

Competitive quantitative PCRs were used to examine the consequences of stereotactically injecting a highly attenuated herpes simplex virus type 1 mutant into rat brains. This mutant virus, designated RR1CAT/RR2lacZ, was engineered so that coding sequences of the genes UL39 and UL40 specifying the subunits of the viral ribonucleotide reductase were replaced by the chloramphenicol acetyltransferase (CAT) and the lacZ gene coding sequences, respectively. Stereotactic injection of this virus into the hippocampal region of the rat brain resulted in a localized infection. Viral gene products were visualized by immunochemical, cytochemical, or in situ hybridization techniques in the injected hippocampal region at 2 days postinjection. Viral genomes, represented by glycoprotein B (gB), latency-associated transcript (LAT), and lacZ sequences could be amplified by PCR from templates obtained by scraping hippocampal tissue off single 10-microns frozen sections. Both gB message and LAT could be detected by reverse transcriptase (RT)-PCR. At day 7 postinjection, neither CAT message, gB message, nor beta-galactosidase activity could be visualized by the same techniques, although viral DNA was detected by PCR and LAT could be detected by RT-PCR. A similar pattern was seen at 8 weeks, suggesting that latency was established by the mutant virus in cells of the injected hippocampus. By competitive quantitative PCR, hippocampal sections were determined to contain 2.6 x 10(5) genome equivalents (represented by the gB gene) on day 2, 6.2 x 10(4) on day 7, and 8.3 x 10(4) at 8 weeks. By competitive quantitative RT-PCR, the numbers of LAT molecules at the same time points were 3.2 x 10(6), 1.3 x 10(6), and 1.2 x 10(6), respectively. The numbers of LAT molecules per genome equivalent were 12.5, 20.3, and 14.5, respectively, being approximately the same for each of the three time points. The data permit the conclusion that the RR mutant virus establishes latency in the rat brain with the persistence of the viral genome and the production of LAT molecules. Once latency is established, the numbers of viral genomes and LAT RNA molecules remain constant. Thus the competitive quantitative PCR and RT-PCR techniques provide very sensitive and reliable methods to quantitate viral DNA and RNA present in infected tissue.

Animals↗
PubMed1994

A dose-response study of the effects of dietary cholesterol on fasting and postprandial lipid and lipoprotein metabolism in healthy young men.

Despite many previous studies, controversy remains concerning the effects of dietary cholesterol on plasma cholesterol concentrations. In addition, the focus of previous studies has been fasting lipid and lipoprotein concentrations; there are no published studies with postprandial measurements. We studied the effects of four levels of dietary cholesterol intake on fasting lipid, lipoprotein, and apoprotein levels, as well as postprandial lipid levels, in a group of young, healthy men who were otherwise eating a low-fat, American Heart Association step 1 diet. Twenty young, healthy men completed a randomized, four-way crossover design study to test the effects of an American Heart Association step 1 diet containing 0, 1, 2, or 4 eggs per day. Dietary cholesterol ranged from 128 to 858 mg cholesterol per day. Each diet was eaten for 8 weeks, with a break between diets. Three fasting blood samples were obtained at the end of each diet period. In addition, blood samples were obtained just before and 2, 4, and 6 hours after ingestion of a standard lunch containing the various amounts of egg cholesterol. We also obtained blood 4 and 8 hours after the subjects ingested a standard, high-fat formula. Fasting plasma total cholesterol concentrations increased by 1.47 mg/dL (0.038 mmol/L) for every 100 mg dietary cholesterol added to the diet (P < .001). Low-density lipoprotein (LDL) cholesterol increased in parallel. Responsiveness varied but appeared to be normally distributed. Fasting plasma apoprotein B concentrations increased approximately 10% between the 0- and 4-egg diets and were correlated with changes in total and LDL cholesterol concentrations. Although there was a trend toward a greater response in men with an apoprotein E4 allele, this was not statistically significant. Fasting plasma cholesteryl ester transfer protein levels were higher only on the 4-egg diet, and changes in cholesteryl ester transfer protein levels between the 0- and 4-egg diets correlated with changes in total and LDL cholesterol. There were no differences in the postlunch or post-fat-formula responses of plasma lipids across the diets. Incubation of the 4-hour postlunch serum with J774 macrophages did not affect cell cholesteryl ester content at any level of dietary cholesterol. Cellular free cholesterol levels were slightly higher on each of the egg-containing diets versus the 0-egg diet. In summary, increases in dietary cholesterol resulted in linear increases in fasting total and LDL cholesterol in young, healthy men.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Effects of increasing dietary polyunsaturated fatty acids within the guidelines of the AHA step 1 diet on plasma lipid and lipoprotein levels in normal males.

We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men, in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet. Study A employed a randomized parallel design in which subjects first consumed an average American diet (AAD) containing 37% of calories as fat (saturated fat, 16% calories; monounsaturated fat, 14% calories; and polyunsaturated fat, 7% calories). After 3 weeks, one third of the subjects continued with the AAD, one third switched to a step 1 diet in which total fat calories were reduced to 30% by replacing saturated fat with carbohydrate, and one third switched to a polyunsaturated fat-enriched (Poly) diet with the same 30% fat calories and a reduction of monounsaturated fat from 14% to 8% and an increase of polyunsaturated fat from 7% to 13% of calories. The randomized period lasted 6 weeks. Total and low-density lipoprotein (LDL) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD (P < .001). Total and LDL cholesterol did not differ between the step 1 and Poly diets, although comparison between the two diets is limited by the small study groups. Serum apolipoprotein (apo) B levels fell on the Poly diet compared with the AAD. Total high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol levels were not significantly affected by the diets. Postprandial lipid and lipoprotein concentrations did not significantly differ either. In study B, a randomized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets. In the eight subjects studied, the values for fasting plasma total, LDL, and HDL cholesterol; triglycerides; apoB; and apoA-I were essentially identical at the end of each diet period. Postprandial triglyceride areas obtained after ingestion of a large, standard fat load were also the same. Finally, LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates. In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism, which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol.

Adult↗
PubMed1994

Overexpression of apolipoprotein CII causes hypertriglyceridemia in transgenic mice.

We have generated transgenic mice expressing the human apolipoprotein CII (apoCII) gene under the transcriptional control of the human cytochrome P-450 IA1 (CYPIA1) promoter. Human apoCII transgenic (HuCIITg) mice exhibited significant basal expression of the transgene (plasma apoCII level = 26.1 +/- 4 mg/dl) and showed further induction of transgene expression after treatment with beta-naphthoflavone. Unexpectedly, HuCIITg mice were hypertriglyceridemic and human apoCII levels correlated strongly to triglyceride levels (R = 0.89, P < 0.0001). Triglyceride levels (mg/dl +/- SEM) were elevated compared to controls in both the fed (804 +/- 113 vs 146 +/- 18, P < 0.001) and fasted (273 +/- 39 vs 61 +/- 4, P < 0.001) states. HuCIITg mice accumulated triglyceride-rich very low density lipoproteins (VLDL) with an increased apoC/apoE ratio. Tracer kinetic studies indicated delayed clearance of VLDL-triglyceride, and studies using Triton inhibition of VLDL clearance showed no increase in VLDL production. Plasma from these mice activated mouse lipoprotein lipase normally and radiolabeled VLDL were normally hydrolyzed. However, HuCIITg VLDL showed markedly decreased binding to heparin-Sepharose, suggesting that apoCII-rich, apoE-poor lipoprotein may be less accessible to cell surface lipases or receptors within their glycosaminoglycan matrices. HuCIITg mice are a promising model of hypertriglyceridemia that suggests a more complex role for apoCII in the metabolism of plasma triglycerides.

Animals↗
PubMed1994

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system.

Animals↗
PubMed1994

Evaluation of a mathematical model for predicting the relationship between protein and energy intakes of low-birth-weight infants and the rate and composition of weight gain.

A model for predicting the relationship between protein and energy intakes of low-birth-weight (LBW) infants and the rate and composition of weight gain is described. It is based on linear multiple regression equations summarizing the rates of weight gain, nitrogen retention, and energy retention of 101 previously studied LBW infants fed protein intakes ranging from 2.25 to 3.9 g.kg-1.d-1 and concomitant energy intakes ranging from 115 to 147 kcal.kg-1.d-1 plus current theory concerning nutrient retention and body composition. To test the validity of the model, three combinations of protein and energy intake predicted by the model to result in specific rates and compositions of weight gain were fed to 44 LBW infants, and the observed rates of weight gain, protein accretion, and fat accretion were compared with the rates predicted by the model. Differences in these and other outcome variables between two of the groups, the intakes of which differed only in energy, also were compared to provide additional insight into the effect of concomitant energy intake on protein utilization. Across groups, actual outcomes correlated closely with predicted outcomes, supporting the validity of the model for the total population. However, outcomes of individual infants deviated as much as 30% from predicted outcomes; the magnitude of the deviation was independent of birth weight, gestational age, or size for gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗
PubMed1994

Human plasma LDL cryopreserved with sucrose maintains in vivo kinetics indistinguishable from freshly isolated human LDL in cynomolgus monkeys.

We previously reported that freeze-thawing of LDL causes marked alterations in its structure and in vitro biological behavior, and that such changes can be completely abolished by the addition of sucrose to the LDL solution prior to freezing. (Rumsey, S. C. et al., J. Lipid Res. 1992. 33: 1551-1561). We now questioned whether the cryopreservative action of sucrose would be equally effective in maintaining the in vivo metabolic characteristics of LDL. Two dual-label LDL turnover studies were performed in cynomolgus monkeys (n = 8) comparing freshly isolated human LDL with human LDL that was frozen in sucrose (10% w/v) for a short (20 h) or long period (6 months). The same sucrose-cryopreserved LDL was used for both the short- and long-term studies; different fresh LDL preparations were used in each study. Absorption spectrophotometry, gel filtration, and electron microscopy of LDL samples frozen with sucrose showed no evidence of physical alterations or aggregation, and there was no evidence of very rapid clearance of cryopreserved LDL from monkey plasma after injection. Fractional catabolic rates (FCR) of fresh and frozen LDL were very similar in either the short-term or long-term experiments: 2.09 +/- 0.86 versus 2.16 +/- 0.88, short-term and 3.03 +/- 2.28 versus 3.08 +/- 2.29, long-term (pools per day; mean +/- SD). The difference between FCR of fresh and frozen LDL for each animal averaged -0.076 +/- 0.074 and 0.01 +/- 0.22 (mean +/- SD), for short-term and long-term freezing, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Safety and efficacy of mitomycin C trabeculectomy in southern India. A short-term pilot study.

PURPOSE: Glaucoma is a major cause of blindness in developing nations. Medical and laser therapy have limitations in this environment. Filtration surgery alone often fails in young, darkly pigmented, individuals. The authors, therefore, evaluated the safety and efficacy of filtration surgery, using topical mitomycin C, in patients undergoing trabeculectomy in India. METHODS: A short-term pilot study used mitomycin C at the time of trabeculectomy in a population of southern Indians with various forms of glaucoma. A single 5-minute intraoperative application of 0.4 mg/ml mitomycin C was given to 76 consecutive patients requiring filtration surgery for the control of intraocular pressure (IOP). All patients were admitted for 6 days and were seen at 6-week intervals for a minimum of 18 weeks. RESULTS: The mean preoperative IOP was 35.3 +/- 9.6 mmHg. Postoperative IOP control was attained in 93.4% of patients as defined by an IOP of 20 mmHg or less without additional glaucoma medications (or an IOP reduction > 25% if the preoperative IOP was < or = 20 mmHg). No corneal epithelial defects or wound leaks were seen. The major complications were cataract formation and a decreased visual acuity in ten (13%) eyes. CONCLUSION: Mitomycin C-aided trabeculectomy was highly successful in controlling IOP in this darkly pigmented population and may become an important adjunct in the treatment of glaucoma in developing countries.

Administration, Topical↗
PubMed1993

The RR1 gene of herpes simplex virus type 1 is uniquely trans activated by ICP0 during infection.

As has been demonstrated for herpes simplex virus type 2, we show in this report that the herpes simplex virus type 1 ribonucleotide reductase large subunit (RR1) gene is trans activated in transient transfection assays by VP16 and ICP0 but not by ICP4. Deletion analysis demonstrated that responsiveness to induction to VP16 resides in an octamer/TAATGARAT sequence of the RR1 promoter and that the TATA box alone is sufficient to provide induction by ICP0. The induction of the RR1 gene by ICP0 but not by ICP4 suggested that it might be possible to identify the cis-acting element(s) responsive to ICP4 in an ICP4-inducible promoter. To this end, a series of chimeric promoters containing various portions of the regulatory sequences of the RR1 promoter and thymidine kinase (TK) promoter were constructed. The TK promoter is trans activated by both ICP0 and ICP4 in transient transfection assays and by ICP4 in infection. The data show that replacing the RR1 TATA region with the TK TATA region permits ICP4 inducibility even if the rest of the RR1 promoter elements remain intact. To test whether the RR1 gene is induced by ICP0 during infection, four mutant viruses were constructed. (i) TAATGARAT+ has the wild-type RR1 promoter driving chloramphenicol acetyltransferase (CAT) and the RR2 promoter driving the lacZ gene. The RR2 gene codes for the small subunit of the ribonucleotide reductase and is expressed as a beta gene. (ii) TAATGARAT- has a triple-base change in the octamer/TAATGARAT element which renders it unresponsive to VP16 trans activation, eliminating that portion of the activation of the RR1 gene. (iii) TAATGARAT- delta alpha 0 has a deletion of the alpha 0 gene. (iv) TAATGARAT- delta alpha 4 has a deletion of the alpha 4 gene. Infections were carried out in Vero cells at a multiplicity of infection of 10 per cell; cells were assayed for CAT and beta-galactosidase (beta-Gal) activities and for virus yields. The first two infections gave strong CAT and beta-Gal activities and high yields of progeny virus. Infection with the third virus showed no CAT activity but did produce high levels of beta-Gal activity and virus progeny. The fourth infection resulted in strong CAT activity but no beta-Gal activity or progeny virus. The data demonstrated that the RR1 promoter was activated in the absence of ICP4 but not in the absence of ICP0 in these infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Increased production rates of LDL are common in individuals with low plasma levels of HDL cholesterol, independent of plasma triglyceride concentrations.

Reduced plasma levels of high density lipoprotein (HDL) cholesterol are associated with increased risk for coronary heart disease. Although plasma HDL levels are, in general, inversely related to plasma triglyceride (TG) concentrations, a small proportion of individuals with low HDL cholesterol concentrations have normal plasma TG levels. We wished to determine whether subjects with low plasma levels of HDL cholesterol could be characterized by common abnormalities of lipoprotein metabolism independent of plasma TGs. Therefore, we studied the metabolism of low density lipoprotein (LDL) apolipoprotein B (apo B) and HDL apolipoprotein A-I (apo A-I) in subjects with low plasma HDL cholesterol concentrations with or without hypertriglyceridemia. Nine subjects with low plasma HDL cholesterol levels and normal levels of plasma TGs and LDL cholesterol were studied. Autologous 131I-LDL and 125I-HDL were injected intravenously, and blood samples were collected for 2 weeks. LDL apo B and HDL apo A-I levels were measured by specific radioimmunoassays. Fractional catabolic rates (FCRs, pools per day) and production rates (PRs, milligrams/kilogram.day) for each apolipoprotein were determined. The results were compared with those obtained previously in nine subjects with low plasma HDL cholesterol levels and hypertriglyceridemia and in seven normal subjects. The normal subjects had an HDL apo A-I FCR (mean +/- SD) of 0.21 +/- 0.04. Despite large differences in plasma TG levels, the HDL apo A-I FCRs were similar in the low-HDL, normal-TG group (0.30 +/- 0.09) and the low-HDL, high-TG group (0.33 +/- 0.10), although only the latter value was significantly increased versus control subjects (p < 0.03). Increased apo A-I FCRs were associated with reduced HDL apo A-I levels in both groups of patients. Apo A-I PRs were similar in all groups. In contrast, LDL apo B PR was increased approximately 50% in the low-HDL, normal-TG group (19.3 +/- 6.6; p < 0.01) compared with normal subjects (12.5 +/- 2.6). There was a strong trend toward a greater LDL apo B PR in the low-HDL, high-TG group (17.6 +/- 4.5; p = 0.06 versus normal subjects) as well. LDL apo B FCRs were similar in all three groups. LDL apo B concentrations were also increased in the group with low HDL cholesterol and normal TG levels. Both groups with low HDL cholesterol levels had cholesterol-depleted LDL and HDL particles.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol.

Plasma levels of HDL apo A-I are reduced in individuals with low HDL cholesterol (HDL-C) concentrations as a result of increased fractional catabolic rates (FCRs). To determine the basis for the high apo A-I FCRs, seven subjects with low HDL-C levels (31.0 +/- 4.3 mg/dl) were compared with three subjects with high HDL-C levels (72.0 +/- 4.5 mg/dl). Each subject received autologous HDL that was labeled directly by the iodine-monochloride method (whole-labeled) and autologous HDL that was labeled by exchange with homologous radiolabeled apo A-I (exchange-labeled). Blood was obtained for 2 wk, specific activities determined, and FCRs (d-1 +/- SD) estimated. In every subject, whether in the low or high HDL-C group, the exchange-labeled FCR was greater than the whole-labeled FCR. The exchange-labeled FCR was higher in the low HDL-C group (0.339 +/- 0.043) versus the high HDL-C group (0.234 +/- 0.047; P < 0.009). The whole-labeled FCR was also greater in the low HDL-C group (0.239 +/- 0.023) versus the high HDL-C group (0.161 +/- 0.064; P < 0.02). In addition, in both low and high HDL groups ultracentrifugation resulted in more radioactivity in d > 1.210 (as percentage of total plasma counts per minute) with the exchange-labeled tracer than with the whole-labeled tracer (12.55 +/- 4.95% vs. 1.02 +/- 0.38%; P < 0.003). With both HDL tracers, more radioactivity was found in d > 1.210 in the low versus the high HDL-C groups. When apo A-I catabolism was studied by perfusing isolated rabbit kidneys with whole-labeled HDL, there was twice as much accumulation (cpm/g cortex) of HDL apo A-I isolated from subjects with low HDL-C than from subjects with high HDL-C (P < 0.0025). Finally, HDL that had been isolated from subjects with high levels of HDL-C was triglyceride enriched and exposed to partially purified lipases before perfusion through kidneys. Threefold more apo A-I from modified HDL accumulated in the cortex compared with the unmodified preparation (P < 0.007). The results of these in vivo and ex vivo studies indicate that individuals with low HDL-C levels have more loosely bound, easily exchanged apo A-I and that this exchangeable apo A-I is more readily cleared by the kidney.

Adult↗
PubMed1993

Intraocular lens implantation in rural India.

We performed 379 extracapsular cataract surgeries with implantation of intraocular lenses (IOLs) in a public eye camp in Ganeshpuri, India (50 miles north of Bombay). Ninety percent (341) of the patients returned for follow up. At 8 weeks postoperatively, 48% of the patients had a visual acuity of 6/18 or better uncorrected; with correction, this figure rises to 71.5%. In general, surgical complications were neither severe nor frequent. More serious difficulties were associated with measuring initial IOL power, obtaining refractive data (including astigmatism), follow up of astigmatism (suture cutting), posterior capsule opacification, and associated preoperative pathology. On the basis of our data, we believe that IOL implantation in public eye camps, under controlled conditions of asepsis and with appropriate instrumentation, is a safe and effective way to provide visual rehabilitation to the rural populations of third-world countries.

Cataract Extraction↗
PubMed1993

Cardiorespiratory costs of growth in low birth weight infants.

The energy cost of growth includes two components: the energy stored in new tissues and the energy expended in all energy requiring steps associated with nutrient intake and net tissue accretion. Most of the energy expended in growth is accounted for by the energy cost of tissue anabolism: peptide bonds, lipogenesis, substrate transport, etc. However, to the extent that additional work is required of the heart and lungs for growth-related increases in O2 and CO2 transport, increased energy is also expended in cardiorespiratory work. Indirect estimates of these costs can be gained by examining the effects of diet and weight gain on heart rate and respiratory frequency. We studied 66 healthy low birth weight infants, mean study weight = 2010 g, fed constant intakes of protein (2.25-3.9 g/kg per day) and energy (100-150 kcal/kg per day). These diets led to rates of weight gain ranging from 13.9 to 21.7 g/kg per day, among the diet groups. Bi-weekly 6-h assessments of energy expenditure, heart rate, respiratory frequency and state of sleep were made after full enteral intake was achieved. After adjustment of heart rate for the effect of postnatal age, heart rate during active sleep was related to weight gain (y = 0.97 x + 144, r2 = 0.15), nitrogen-energy ratio of the diet (y = 5.9 x + 139,2 r2 = 0.22), and energy expenditure (y = 0.53 x + 129, r2 = 0.13). Multiple regression analysis revealed that age-adjusted heart rate during active and quiet sleep was significantly related to a combination of the same three variables (r2 = 0.31).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Triacylglycerol and phospholipid hydrolysis in human plasma lipoproteins: role of lipoprotein and hepatic lipase.

To explore the interactions of triacylglycerol and phospholipid hydrolysis in lipoprotein conversions and remodeling, we compared the activities of lipoprotein and hepatic lipases on human VLDL, IDL, LDL, and HDL2. Triacylglycerol and phospholipid hydrolysis by each enzyme were measured concomitantly in each lipoprotein class by measuring hydrolysis of [14C]triolein and [3H]dipalmitoylphosphatidylcholine incorporated into each lipoprotein by lipid transfer processes. Hepatic lipase was 2-3 times more efficient than lipoprotein lipase at hydrolyzing phospholipid both in absolute terms and in relation to triacylglycerol hydrolysis in all lipoproteins. The relationship between phospholipid hydrolysis and triacylglycerol hydrolysis was generally linear until half of particle triacylglycerol was hydrolyzed. For either enzyme acting on a single lipoprotein fraction, the degree of phosphohydrolysis closely correlated with triacylglycerol hydrolysis and was largely independent of the kinetics of hydrolysis, suggesting that triacylglycerol removed from a lipoprotein core is an important determinant of phospholipid removal via hydrolysis by the lipase. Phospholipid hydrolysis relative to triacylglycerol hydrolysis was most efficient in VLDL followed in descending order by IDL, HDL, and LDL. Even with hepatic lipase, phospholipid hydrolysis could not deplete VLDL and IDL of sufficient phospholipid molecules to account for the loss of surface phospholipid that accompanies triacylglycerol hydrolysis and decreasing core volume as LDL is formed (or for conversion of HDL2 to HDL3). Thus, shedding of whole phospholipid molecules, presumably in liposomal-like particles, must be a major mechanism for losing excess surface lipid as large lipoprotein particles are converted to smaller particles. Also, this shedding phenomenon, like phospholipid hydrolysis, is closely related to the hydrolysis of lipoprotein triacylglycerol.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Effects of intralipid-induced hypertriglyceridemia on plasma high-density lipoprotein metabolism in the cynomolgus monkey.

Low plasma levels of high-density lipoprotein (HDL) and apolipoprotein (apo) A-I often accompany human hypertriglyceridemia. In an animal model of hypertriglyceridemia, the lipoprotein lipase (LPL)-inhibited cynomolgus monkey, we reported that plasma levels of apo A-I were decreased and the fractional catabolic rate (FCR) of HDL apo was increased. To explore whether hypertriglyceridemia alone would alter plasma apo A-I levels and catabolism, hypertriglyceridemia was produced by intravenous (IV) infusion of 20% Intralipid into female cynomolgus monkeys. Baseline plasma triglyceride (TG) levels averaged 106 mg/dL. With infusion of 200 mg/kg/h Intralipid TG, plasma TG levels peaked at 967 mg/dL (range, 413 to 1,069; n = 6). More prolonged or more severe hypertriglyceridemia caused serious complications in several monkeys. Despite the severe hypertriglyceridemia, HDL TG content, HDL apoproteins, and plasma apo A-I levels did not markedly change, suggesting that very little HDL remodeling had occurred. Kinetic studies of HDL protein and apo A-I were performed in four pairs of monkeys. The two tracers were removed from the plasma at identical rates. In five pairs of animals, apo A-I turnover during control and Intralipid-induced hypertriglyceridemia was not significantly different. We hypothesize that apo A-I FCR is a function of HDL composition. Because Intralipid infusion did not alter HDL composition to the same degree as did LPL inhibition, its effects on HDL apo catabolism were not apparent.

Animals↗