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BackgroundB-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.MethodsWe investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.ResultsOur analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.ConclusionsThis is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.

Grazing Neotyphodium coenophialum- infected forages results in a variety of reduced animal performance parameters, collectively known as "fescue toxicosis." The initial, limited evaluations of hepatic mechanisms affected by fescue toxicosis have used transcriptomic expression profiling of experimental phenotypes developed by short-term feeding of concentrated ergot alkaloids or fescue seeds to rodents and steers. To assess the effects of fescue toxicosis in growing cattle using a commercially relevant phenotype, we induced fescue toxicosis in beef steers by summer-long grazing (89 to 105 d) of a single high toxic endophyte-infected tall fescue pasture (HE; 0.746 µg/g ergot alkaloids; 5.7 ha; n = 10; BW = 267 ± 14.5 kg) vs. a low toxic endophyte tall fescue- mixed pasture (LE; 0.023 µg/g ergot alkaloids; 5.7 ha; n = 9; BW = 266 ± 10.9 kg). High toxic endophyte tall fescue-mixed pasture steers had decreased BW (313 vs. 338 kg) and an increased potential for hepatic gluconeogenesis from AA-derived carbons. To gain a greater perspective into fescue toxicosis-induced hepatic metabolism and identify candidate regulatory mechanisms, the goal of the current research was to examine liver samples for changes in gene (mRNA) expression profiles using a Bovine Affymetrix microarray and selected reverse-transcription PCR and immunoblot analyses. The expression (false discovery rate < 10%; P < 0.01) of 147 genes was increased (7 to 268%) and that of 227 was decreased (4 to 87%) in livers of HE vs. LE steers. The top (1) functional gene category was cell-mediated immune response (33 genes; P ≤ 0.012), (2) canonical cell signaling pathway was primary immunodeficiency signaling (8 genes; P ≤ 0.0003), and (3) canonical metabolic pathways were oxidative phosphorylation (5 genes; P ≤ 0.016) and purine metabolism (8 genes; P ≤ 0.029). High toxic endophyte tall fescue-mixed pasture steers had increased (P ≤ 0.022) expression of genes critical for increased (1) Pro (PYCR1) and Ser (PSPH) synthesis, (2) shunting of AA carbons into pyruvate (ALT2) and ATP synthesis (NDUFC1, NDUFV2, UCRC, COX4, ATP5D, and ATP5F1), and (3) mitochondrial mass (COX4). Targeted reverse-transcribed PCR or immunoblot assays corroborated (P ≤ 0.035) these latter microarray findings for PYCR1, PSPH, ALT2, PEPCK, and COX4. Moreover, network analysis identified glucocorticoid receptor-mediated signaling as the most probable mechanism to coordinate the above findings. These results greatly extend our knowledge of the consequences of summer-long grazing of endophyte-infected tall fescue to the hepatic metabolism of growing steers. [ABSTRACT FROM AUTHOR]

L-Glutamate (Glu) is a major excitatory neurotransmitter responsible for neurotransmission in the vertebrate central nervous system. Vesicular Glu transporters VGLUT1 and VGLUT2 concentrate (50 mM) Glu [Michaelis constant (measuring affinity), or Km, = 1 to 4 mM] into synaptic vesicles (SV) for subsequent release into the synaptic cleft of glutamatergic neurons. Vesicular Glu transporter activity is dependent on vacuolar H+ -ATPase function. Previous research has shown that ergopeptines contained in endophyte-infected tall fescue interact with dopaminergic and serotoninergic receptors, thereby affecting physiology regulated by these neuron types. To test the hypothesis that ergopeptine alkaloids inhibit VGLUT activity of bovine cerebral SV, SV were isolated from cerebral tissue of Angus-cross steers that were naive to ergot alkaloids. Immunoblot analysis validated the enrichment of VGLUT1, VGLUT2, synaptophysin 1, and vacuolar H+ -ATPase in purified SV. Glutamate uptake assays demonstrated the dependence of SV VGLUT-like activity on the presence of ATP, H+ -gradients, and H+ -ATPase function. The effect of ergopeptines on VGLUT activity was evaluated by ANOVA. Inhibitory competition (IC50) experiments revealed that VGLUT-mediated Glu uptake (n = 9) was inhibited by ergopeptine alkaloids: bromocriptine (2.83 ± 0.59 µM) < ergotamine (20.5 ± 2.77 µM) < ergocornine (114 ± 23.1 µM) < ergovaline (137 ± 6.55 µM). Subsequent ergovaline kinetic inhibition analysis (n = 9; Glu = 0.05, 0.10, 0.50, 1, 2, 4, 5 mM) demonstrated no change in apparent Km. However, the maximum reaction rate (Vmax) of Glu uptake was decreased when evaluated in the presence of 50, 100, and 200 µM ergovaline, suggesting that ergovaline inhibited SV VGLUT activity through a noncompetitive mechanism. The findings of this study suggest cattle with fescue toxicosis may have a decreased glutamatergic neurotransmission capacity due to consumption of ergopeptine alkaloids. [ABSTRACT FROM AUTHOR]

Although cationic amino acids (CAA) are considered essential to maximize optimal growth of cattle, transporters responsible for CAA absorption by bovine small intestinal epithelia have not been described. This study was conducted to test 2 hypotheses: 1) the duodenal, jejunal, and ileal epithelia of beef cattle differentially express 7 mRNA associated with 4 mammalian amino acid (AA) transport activities: y+ (CAT1), B (ATB0,+>), b0,+> (b0,+> AT and rBAT), and y+>L (y+>LAT1, y+>LAT2, and 4F2hc), and 2) the expression of these mRNA is responsive to small intestinal luminal supply of AA substrates (derived from ruminal microbes) glucose-derived energy (from starch hydrolysate, SH), both. Eighteen ruminally and abomasally catheterized Angus steers (body weight = 260 ± 17 kg) fed an alfalfa cube-based diet at 1.33 x net energy for maintenance requirement were assigned to 3 treatments (n = 6): ruminal and abomasal water infusion (control); ruminal SH and abomasal water infusion; and ruminal water and abomasal SH infusion. The dosage of SH infusion amounted to 20% of metabolizable energy intake. After 14 or 16 d of infusion, steers were slaughtered, duodenal, jejunal, and ileal epithelia were harvested, and total RNA was extracted. The relative amounts of mRNA expressed by epithelia were quantified using real-time reverse transcription-PCR. All 7 mRNA species were expressed by the epithelium from each region, but their abundance differed among the regions. Specifically, duodenal expression of CAT1 and ATB0,+> mRNA greater than jejunal or ileal expression; ileal expression of b0,+>AT, rBAT, and y+>LAT1 mRNA was greater than jejunal or duodenal expression, whereas the expression of y+>LAT2 and 4F2hc mRNA did not differ among the 3 epithelia. With regard to SH infusion effect, ruminal infusion down-regulated or tended to down-regulate the jejunal expression of CAT1, rBAT, y+>LAT2, and 4F2hc mRNA. Abomasal infusion down-regulated the jejunal expression of y+>LAT2 mRNA and tended to down-regulate the jejunal expression of 4F2hc mRNA. This study characterized the pattern of CAA transporter mRNA expressed by growing beef cattle fed an alfalfa-based diet. Moreover, this study demonstrated that increasing the luminal supply of microbe-derived AA (by ruminal supplementation of SH) results in a reduced capacity of apical and basolateral membrane to transport of CAA, whereas increasing luminal glucose supply (by abomasal supplementation of SH) reduces only the basolateral transport capacity, assuming that CAA transporter mRNA content represents functional capacity. [ABSTRACT FROM AUTHOR]

In ruminants microbial-derived nucleic acids are a major source of X and are absorbed as nucleosides by small intestinal epithelia. Although the biochemical activities of 2 nucleoside transport systems have been described for cattle, little is known regarding the regulation of their gene expression. This study was conducted to test 2 hypotheses: (1) the small intestinal epithelia of beef cattle differentially express mRNA for 3 concentrative (CNT1, 2, 3) and 2 equilibrative (ENT1, 2) nucleoside transporters (NT), and (2) expression of these NT is responsive to small intestine luminal supply of rumen-derived microbes (hence, nucleosides), energy (cornstarch hydrolysate, SH), or both. Eighteen ruminally and abomasally catheterized Angus steers (260 = 17 kg of BW) were fed an alfafa cube-based die at 1.33 x NEm requirement. Six steers in each of 3 periods were blocked by BW (heavy vs. light). Within each block, 3 steers were randomly assigned to 3 treatments (n = 6), ruminal and abomasal water infusion, or ruminal water infusion/abomasal water infusion. The dosage of SH infusion amounted to 20% of ME intake. After a 14- or 16-d infusion period, steers were slaughtered, and duodenal, jejunal, and ileal epithelia were harvested for total RNA extraction and the relative amounts of mRNA expressed were determined using real-time RT-PCR quantification methodologies. All 5 NT mRNA were found expressed by each epithelium, but their abundance differed among epithelia. Specifically, jejunal expression of all 5 NT mRNA was higher than that by the ileum, whereas jejunal expression of CNT1, CNT3, and ENT1 mRNA was higher, or tended to be higher, than duodenal expression. Duodenal expression of CNT2, CNT3, and ENT2 mRNA was higher than ileal expression. With regard to SH infusion treatments, ruminal infusion increased duodenal expression of CNT3 (67%), ENT1 (51%), and ENT2 (39%) mRNA and ileal expression of CNT3 (210%) and ENT2 (65%) mRNA. Abomasal infusion increased (54%) ileal expression of ENT2 mRNA and tended to increase (50%) jejunal ENT2 mRNA expression. This study has uniquely characterized the pattern of NT mRNA expression by growing beef cattle and found that the mRNA abundance for CNT3, ENT1, and ENT2 in small intestinal epithelia can be increased by increasing the luminal supply of nucleotides (CNT3, ENT1, ENT2) or glucose (ENT2). [ABSTRACT FROM AUTHOR]

The regulation of key metabolic pathways responsible for muscle protein turnover by dietary amino acids (AAs) in pigs is closely associated with the concomitant responses of some growth-related hormones. This study was undertaken to investigate the effects of dietary lysine supply at different levels on blood plasma concentrations of 3 key growth-related hormones in late-stage finishing pigs: insulin, growth hormone (GH), and insulin-like growth factor 1 (IGF-1). Nine crossbred (Large White × Landrace) finishing pigs (initial BW 94.4 ± 6.7 kg) were assigned to 3 dietary treatments according to a randomized experimental design (3 pigs/treatment). Three corn and soybean meal based diets were formulated to meet the NRC (2012) requirements for various nutrients except for lysine, whose concentrations were 0.43, 0.71, and 0.98% (asfed basis) for Diets 1 (lysine-deficient), 2 (lysine-adequate), and 3 (lysine-excess), respectively. The feeding trial lasted 4 weeks, during which time the pigs were allowed ad libitum access to the experimental diets and fresh water. After 4 weeks, blood was collected from the jugular vein, and plasma samples were separated by centrifugation. The plasma concentrations of 3 hormones were measured by using 3 respective commercial assay kits. Data were statistically analyzed with the GLM Procedure of SAS (v9.4) with P ≤ 0.05 and ≤ 0.10 as significant difference and a tendency, respectively. Results showed that there were no differences in the plasma insulin and GH concentrations (P > 0.10) among the three dietary treatments, which suggests that the plasma insulin and GH levels of the late-stage finishing pigs were not affected by the dietary lysine concentration, at least at the range from 0.43 to 0.98%. The plasma IGF-1 concentration of the pigs fed either Diet 1 or 3, however, was lower (P < 0.05) than that of the pigs fed Diet 2, which suggests that either dietary lysine deficiency or excess can lead to a lower level of plasma IGF-1 concentration in late-stage finishing pigs. Therefore, it can be concluded that IGF-1, instead of insulin or GH, in the blood circulation may be a controlling growth factor in response to dietary provision of lysine for regulating muscle growth in late-stage finishing pigs. This study was supported by a USDA-NIFA's Hatch/Multistate Project (under No. 1007691). [ABSTRACT FROM AUTHOR]

It has been known that some amino acids, such as leucine, can function as signaling molecules to regulate the skeletal muscle growth of pigs. However, which signaling pathway (s) that may be regulated by dietary lysine is unclear. This study was conducted to identify the genes that may be regulated by dietary lysine and that are responsible for the muscle growth of pigs. Nine crossbred barrows (94.4 ± 6.7 kg BW) were randomly allotted to 3 dietary treatments (3 pigs/treatment). Three corn and soybean-meal based diets were formulated to meet the NRC (2012) requirements for nutrients except for lysine, whose concentrations were 0.43, 0.71, and 0.98% (as-fed basis) for the lysine-deficient, lysine-adequate, and ly sine-excess diets, respectively. The feeding trial lasted 5 wk, during which time the pigs were allowed ad libitum access to diets and water. After the trial, all pigs were harvested and muscle samples were collected from longissimus dorsi (between the 10th and 12th ribs). Total RNA was extracted from 50 mg of each sample using the TRIzol reagent. The Porcine Gene 1.0 ST Array (Affymetrix, Inc.) was used to quantify the expression levels of 19,211 genes. Raw microarray data were normalized with the gcRMA algorithm and analyzed with ANOVA using Partek Genomics Suite (Partek, Inc.). A total of 674 transcripts were differentially expressed (p < 0.05); 60 out of 131 transcripts (atp < 0.01) belong to 58 genes and 71 were unannotated. Canonical pathway analysis of these 58 genes using the IPA software (Qiagen.com) revealed that the protein ubiquitination pathway was significantly affected (P < 0.01) by dietary lysine level, which involved at least 6 genes. Specifically, when compared to the lysine-adequate group, the expression of DNAJA 1, HSP90AB 1, and UBE2B was up-regulated in the lysine-deficient group, while the expression of DNAJA 1, HSP90AA 1, HSPH 1, and UBE2D3 was downregulated in the lysine-excess group. The protein ubiquitination pathway plays a major role in the degradation of short-lived or regulatory proteins by the 26 S proteasome complex, affecting a variety of cellular processes including cell cycle, cell proliferation, apoptosis, and transcription regulation. Taken together, decreasing dietary lysine level may activate, while increasing dietary lysine level may inhibit, the ubiquitin-proteasome pathway and regulate protein accretion in skeletal muscle of late-stage finishing pigs. Further studies are needed to elucidate how the proteins coded from these genes influence pig skeletal muscle degradation. This project is supported by USDA Hatch/Multistate Project 233803. [ABSTRACT FROM AUTHOR]

Growth performance, especially muscle growth, of pigs is dependent on the constant supply of balanced AA and other nutrients from the blood circulation. Lysine is typically the first limiting AA in grain-based swine diets. This project was conducted to study how dietary lysine restriction affects plasma concentrations of AA and other metabolites in growing pigs. Twelve individually penned crossbred barrows (Yorkshire × Landrace; 22.6 ± 2.04 kg initial BW) were assigned to 2 dietary treatments according to a completely randomized design (n = 6). Two corn and soybean meal-based diets were formulated to contain 0.65% (lysine deficient; Diet I) and 0.98% (lysine adequate; Diet II) standardized ileal digestible lysine. During the 8-wk feeding trial, pigs had ad libitum access to their respective diets and fresh water. Pigs' BW and feed intake were measured biweekly, and ADG, ADFI, and G:F were calculated biweekly as well as for the overall feeding period. Immediately after the feeding trial, jugular vein blood was collected for plasma sample preparation. The plasma AA contents were analyzed with the established HPLC method, and plasma contents of selected metabolites were determined using Alfa Wassermann's ACE Clinical Chemistry System. Data were statistically analyzed using Student's t-test. Overall, the final BW and ADG in pigs fed Diet I were lower (P < 0.01) than in pigs fed Diet II. However, no difference in ADFI was found between the 2 groups. Therefore, the G:F of Diet I pigs was lower than that of Diet II pigs (P = 0.04). Although the plasma concentration of b-alanine in Diet I pigs was higher (P < 0.01) than in Diet II pigs, the plasma concentrations of lysine, methionine, leucine, arginine, tyrosine, and total protein in Diet I pigs was lower (P < 0.05) than in Diet II pigs. The plasma concentrations of all other AA and metabolites (including urea nitrogen, albumin, glucose, and cholesterol) were not different (P > 0.10) between the 2 groups. Based on these results and nutrition knowledge, dietary lysine restriction is responsible for the reduced plasma lysine level and growth performance of Diet I pigs. Reduced levels of plasma methionine, leucine, arginine, tyrosine, and total protein indicate that pigs consuming a lysine-deficient diet may utilize these metabolites for other metabolic functions. In conclusion, dietary lysine restriction can affect the plasma profile of free AA and other metabolites in addition to free lysine in growing pigs. [ABSTRACT FROM AUTHOR]

Methionine is the second or third limiting AA in a typical grain-based swine diet and plays a very important role in promoting growth performance, especially the muscle growth of pigs. This study was conducted to evaluate the effects of a dietary Met deficiency on the growth performance and blood plasma concentrations of selected metabolites that include total protein, albumin, urea nitrogen, glucose, triglycerides, and cholesterol in growing pigs. Twenty individually penned crossbred barrows (Yorkshire × Landrace; 23.6 ± 2.41 kg initial BW) were assigned to 2 dietary treatments according to a completely randomized design. A basal corn-soybean meal diet (Diet 1; Met deficient) was formulated using analyzed ingredient AA contents and published standardized ileal digestible (SID) coefficients to contain 0.22% SID Met and 0.52% SID Met + Cys but to meet or exceed the NRC (2012) recommendations for other essential AA (e.g., 1.08% SID Lys), energy (2,545 kcal/kg NE), minerals, and vitamins. Crystalline dl-Met was supplemented to the basal diet at the expense of corn (0.15%) to create Diet 2 adequate in Met (0.37% SID Met and 0.67% SID Met + Cys). During the 4 wk of the ad libitum feeding trial, the BW and feed intake were measured weekly and the ADG, ADFI, and G:F were calculated weekly as well as for the overall feeding period. Immediately before and after the feeding trial, jugular vein blood was collected for plasma sample analyses. The plasma concentrations of the selected metabolites were determined using an ACE Clinical Chemistry System (Alfa Wassermann, Inc.). Data were analyzed using Student's t-test. After the 4-wk trial, pigs fed Diet 1 had a lower (P < 0.001) ADG (870 vs. 980 g/d) and G:F (0.45 vs. 0.50) than the pigs fed Diet 2. Pigs fed Diet 1 had a higher (P < 0.001) plasma concentration of urea nitrogen than those fed Diet 2 (6.6 vs. 4.2 mg/dL). Pigs fed Diet 1 tended to have a higher (P = 0.085) plasma albumin concentration. There were no differences (P > 0.10) between the 2 treatments in all other parameters measured. These findings indicated that dietary Met deficiency can reduce the rate of body protein synthesis or growth performance as suggested by the plasma urea nitrogen level. Increasing plasma urea nitrogen concentration will lead to increased nitrogen excretion to the environment. However, what mechanisms at the cell signaling level are responsible for the AA utilization warrants further investigation. [ABSTRACT FROM AUTHOR]

Although L-Lysine (Lys) is a dietarily-essential amino acid (AA) for cattle fed a high corn diet, proteins responsible for absorption of Lys by cattle have not been described. CAT1 is a major intestinal transporter of cationic AA. CAT1 demonstrates a high-affinity (μM) System y+ activity that differs from b0,+, y+L, and B0,+ cationic AA transporter systems due to its independence of Na+ (-Na+) and/or insensitivity to neutral AA. This project was conducted to determine if Madin-Darby Bovine Kidney (MDBK) cells and steer hepatocytes express CAT1 activity and/or mRNA. Putative System y+ activity was assessed in wells (n = 8-12) of 2-d cultured MDBK cells (250,000/2 cm2 well) by characterizing the -Na+ uptake (pmol/mg protein) of Lys (10 μM; [H3]Lys, radiotracer) in the presence and absence of 2 mM L-Arg or L-Leu. System y+ Lys uptake accounted (P < 0.001) for 50% of total -Na+ Lys uptake, as did Systems B0,+ and/or y+L. Km determination for -Na+ Lys in the presence of 5 mM L-Leu was 250 μM, consistent with CAT1 activity. RT-PCR of total RNA extracted from MDBK cells (and bovine kidney, and ileal epithelium), using the full-length pig CAT1 as a template, produced a single cDNA product of about 700 bp. Sequencing of the MDBK and kidney products revealed a 695-bp cDNA that possessed 89, 87, 99% homology with corresponding regions of the pig, human, and predicted bovine CAT1 mRNA, respectively. The expression of System y+ activity and CAT1 mRNA next was evaluated in wells (4-6) of 2-d cultured hepatocytes (200,000/2 cm2 well) isolated (collagenase perfusion) from the caudal lobe of 30-d old Angus steer livers (n = 4), using transport and RT-PCR parameters identical to those used for MDBK cells. Systems y+, b0,+, and y+L accounted (P < 0.034) for 19, 34, and 47% of -Na+ Lys uptake, respectively, and RT-PCR yielded a product of about 700 bp. These results demonstrate that MDBK cells and steer hepatocytes express CAT1 activity and mRNA and indicate their usefulness to study bovine CAT1 function and expression. [ABSTRACT FROM AUTHOR]

Study Design: Comparison group design., Objective: To compare the temporal distance factors during gait initiation between patients with incomplete cervical spinal cord injury, incomplete lumbosacral spinal lesion, and unimpaired control adults., Setting: Human performance and movement analysis laboratory, Taiwan., Participants: Five patients with an incomplete cervical spinal cord injury (Group 1), five patients with an incomplete lumbosacral spinal lesion (Group 2) and nine unimpaired control adults (Group 3)., Methods: Subjects underwent a three-dimensional gait analysis. The total gait initiation period, reaction time, each relative phasing of gait initiation and the length of the first step were identified by using the kinematic measurement system., Main Outcome Measures: The total gait initiation period (start of the auditory cue for gait initiation to heel-strike of the first swing leg); each relative phasing of gait initiation indicated that the duration of the preparatory phase (start of auditory cue for gait initiation to heel-off of the first swing leg), the duration of the push-up phase (heel-off to toe-off of the first swing leg), and the duration of the single-stance phase (toe-off to heel-strike of the first swing leg) established by the total gait initiation period; and the length of the first step., Results: The gait initiation period was greater in Groups 1 and 2 than that of Group 3 (P<0.05). Each relative phasing including the duration of the preparatory phase, the push-up phase, and the swing phase relative to the total gait initiation period, did not differ among Groups 1-3 (P>0.05). The length of the first step, measured while the nonpreferred leg stepped first in Groups 1 and 2, was shorter than that of Group 3 (P<0.05)., Conclusions: Patients with incomplete cervical spinal cord injuries or lumbosacral spinal lesions took more time in gait initiation than unimpaired control adults. The first step length also reduced in these patients while the nonpreferred leg stepped first, as compared to unimpaired control adults. The data indicated that centrally programmed gait initiation might be preserved in ASIA-D spinal patients who, in this study, executed gait initiation with varying temporal distance strategies to compensate for peripheral impairments, as compared to unimpaired control adults.

The presence of clinical autonomic dysfunction in patients with neurologic diseases, such as multiple sclerosis, Parkinson's disease, and cerebrovascular accident, has become increasingly recognized in the past decade. Very few autonomic tests have been done on pediatric patients thus far. The purpose of this study was to investigate the autonomic function in patients with cerebral palsy using two noninvasive tests: sympathetic skin response (SSR) and R-R interval variation (RRIV). Twenty-four patients with cerebral palsy and 24 control subjects between the ages of 4 and 12 yr were enrolled in this study. There was no significant difference of mean latency, amplitude, or amplitude ratio of SSR between the two groups under electric stimulus, startling stimulus, and deep breathing conditions. No significant difference in frequency of absent response and asymmetric response was also noted. Mean heart rate under relaxed sitting condition was significantly higher in the study group. Significant negative correlation between heart rate and age was noted in the control group but was not present in the study group. Also, there was no statistical difference of mean RRIV between the two groups. No objective evidence of autonomic disturbance in patients with cerebral palsy was found in this study.