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Biomedical subjects

X Zhou

Publications and source records attributed to X Zhou.

At least 595 records · Page 33Linked to original sources
PubMed1996

Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen.

Covalent attachment of activated products of the third component of complement to antigen enhances its immunogenicity, but the mechanism is not clear. This effect is mediated by specific receptors, mCR1 (CD35) and mCR2 (CD21), expressed primarily on B cells and follicular dendritic cells in mice. To dissect the role of mCR1 and mCR2 in the humoral response, we have disrupted the Cr2 locus to generate mice deficient in both receptors. The deficient mice (Cr2-/-) were found to have a reduction in the CD5+ population of peritoneal B-1 cells, although their serum IgM levels were within the range of normal mice. Moreover, Cr2-/- mice had a severe defect in their humoral response to T-dependent antigens that was characterized by a reduction in serum antibody titers and in the number and size of germinal centers within splenic follicles. Reconstitution of the deficient mice with bone marrow from MHC-matched Cr2+/+ donors corrected the defect, demonstrating that the defect was due to B cells themselves. These results indicate an obligatory role of B cell complement receptors in responses of the B cells to protein antigens.

Animals↗
PubMed1996

Ascaris, people and pigs in a rural community of Jiangxi Province, China.

A longitudinal investigation on natural populations of Ascaris in humans and pigs and an investigation of soil contamination with Ascaris eggs were carried out from June 1993 to June 1994 in 2 villages, Manhu area, Xinjian County, Jiangxi Province, China. Results from these studies indicate that although human ascariasis is endemic there is significant fluctuation in both prevalence and the mean number of eggs/g faeces (epg) of the communities. Fluctuation of age-stratified prevalence and mean epg was detected in children but not in most adult groups. Most cases of human ascariasis were judged to involve low intensities of infection and a typical overdispersion distribution pattern was observed through the year. It was estimated that during the year, nearly half of the eggs discharged in the environment came from infections in children aged between 2 and 15 years which accounted for about 30% of the total population. Soil in and around houses and in vegetable gardens was found to be contaminated by Ascaris eggs and this situation remained relatively stable throughout the year. Monthly developmental rate of Ascaris eggs in soil was detected and the results suggest that the fluctuation in prevalence observed during the year should be directly attributed to the effect of seasonality of egg development. Features of Ascaris infection in pigs were found to be similar to those in humans except for a lower mean intensity of infection. The possibility of cross-infection of Ascaris between human and pig hosts is discussed.

Adolescent↗
PubMed1996

Effect of acute exhausting exercise on cytokine gene expression in men.

Because of recent interest in the effects of physical exercise on immunologic function, we decided to use state-of-the-art methods to evaluate cytokines in the peripheral blood leukocytes (PBLs) of 7 men before and after a maximal treadmill stress test. Change in cytokine gene expression was quantified from PBLs using a reverse transcriptase polymerase chain reaction assay (RT-PCR). In contrast to reports on serum levels or using in vitro testing, direct gene expression of TNF-alpha decreased after the stress test (p < 0.008). However, the 47% decrease was relatively small and of questionable biological significance. Levels of IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-10, and INF-gamma did not change.

Adult↗
PubMed1996

Production of interleukin-10 in human fracture soft-tissue hematomas.

Clinical trauma suppresses immunity and experimental wound fluids have been shown to be immunosuppressive. To ascertain whether human wounds contain immunosuppressive cytokines, we assayed serum from fracture/soft-tissue hematomas (FSTH) of 22 patients for interleukin (IL)-10, transforming growth factor (TGF)-beta 1, and IL-4. Results were correlated to concurrent plasma cytokine concentrations in the same patients and in volunteer plasma. IL-10 was present in high concentration (1376 +/- 539 pg/mL) in all (7/7) FSTH < 24 h old. In FSTH > 24 h old, IL-10 was found intermittently and at lower levels (239 +/- 106 pg/mL, p = .011 vs. FSTH < 24 h old). IL-10 was rarely detectable in fracture patient plasma and never detectable (< 20 pg/mL) in normal plasma. No significant variations of IL-4 or total TGF-beta 1 were found in FSTH or plasma. FSTH are significant potential sources of IL-10 activity in trauma patients, which may be overlooked when only plasma is assayed. The potential for a relationship between cytokines found locally at sites of injury and clinical immune modulation in trauma requires further study.

Adult↗
PubMed1996

An 18-base-pair sequence in the mouse proalpha1(II) collagen gene is sufficient for expression in cartilage and binds nuclear proteins that are selectively expressed in chondrocytes.

The molecular mechanisms by which mesenchymal cells differentiate into chondrocytes are still poorly understood. We have used the gene for a chondrocyte marker, the proalpha1(II) collagen gene (Col2a1), as a model to delineate a minimal sequence needed for chondrocyte expression and identify chondrocyte-specific proteins binding to this sequence. We previously localized a cartilage-specific enhancer to 156 bp of the mouse Col2a1 intron 1. We show here that four copies of a 48-bp subsegment strongly increased promoter activity in transiently transfected rat chondrosarcoma (RCS) cells and mouse primary chondrocytes but not in 10T1/2 fibroblasts. They also directed cartilage specificity in transgenic mouse embryos. These 48 bp include two 11-bp inverted repeats with only one mismatch. Tandem copies of an 18-bp element containing the 3' repeat strongly enhanced promoter activity in RCS cells and chondrocytes but not in fibroblasts. Transgenic mice harboring 12 copies of this 18-mer expressed luciferase in ribs and vertebrae and in isolated chondrocytes but not in noncartilaginous tissues except skin and brain. In gel retardation assays, an RCS cell-specific protein and another closely related protein expressed only in RCS cells and primary chondrocytes bound to a 10-bp sequence within the 18-mer. Mutations in these 10 bp abolished activity of the multimerized 18-bp enhancer, and deletion of these 10 bp abolished enhancer activity of 465- and 231-bp intron 1 segments. This sequence contains a low-affinity binding site for POU domain proteins, and competition experiments with a high-affinity POU domain binding site strongly suggested that the chondrocyte proteins belong to this family. Together, our results indicate that an 18-bp sequence in Col2a1 intron 1 controls chondrocyte expression and suggest that RCS cells and chondrocytes contain specific POU domain proteins involved in enhancer activity.

Animals↗
PubMed1996

Transmembrane potential changes caused by shocks in guinea pig papillary muscle.

To study transmembrane potential (Vm) changes (delta Vm) caused by extracellular field stimulation, Vm was recorded in 10 guinea pig papillary muscles by a double-barrel microelectrode. A 10-ms shock was delivered during the action potential plateau or during diastole. Six shock strengths (1.8 +/- 0.4, 3.8 +/- 0.7, 5.6 +/- 0.9, 7.2 +/- 1.1, 11.1 +/- 1.9, and 17.8 +/- 1.5 V/cm) were given with both polarities. The tissue was then treated with either 30 microM tetrodotoxin (TTX; n = 5) or 30 microM TTX plus Ca(2+)-free (n = 5) perfusion. For shocks during the action potential plateau, delta Vm caused by the six potential gradients was 22.4 +/- 9.6, 43.6 +/- 17.4, 54.7 +/- 17.9, 60.4 +/- 18.1, 65.4 +/- 13.7, and 66.4 +/- 12.2 mV for shocks causing depolarization and 41.1 +/- 16.5, 68.3 +/- 22, 80.5 +/- 20.4, 84.0 +/- 19.5, 93.6 +/- 16.3, and 98.9 +/- 15.4 mV for shocks causing hyperpolarization. The relationship between delta Vm and shock potential gradient was not linear. During diastole, hyperpolarizing shocks induced initial hyperpolarization, then depolarization followed again by hyperpolarization. A new depolarization upstroke occurred immediately after the shock. After TTX or TTX plus Ca(2+)-free perfusion, point stimuli 10 times diastolic threshold could not induce an action potential, but a shock field of 1.8 +/- 0.2 V/cm still induced action potentials. The peak value of depolarization measured with respect to resting potential (-87 +/- 5 mV) during the hyperpolarizing shock decreased from +14 +/- 22 before to -66 +/- 30 mV with TTX perfusion (P < 0.01). The fast upstroke rate of depolarization both during and immediately after the end of hyperpolarizing shocks was inhibited by TTX perfusion. Thus 1) the relationship between delta Vm and shock potential gradient is not linear; 2) field but not point stimulation can induce an action potential when Na+ channels are inactivated; and 3) during diastole Na+ channels are activated twice by a 10-ms hyperpolarizing shock, once during shock-induced hyperpolarization and again immediately after the end of the shock.

Action Potentials↗
PubMed1996

The ability of bile to scavenge superoxide radicals and pigment gallstone formation in guinea pigs.

After partial ligation of the common bile duct (CBD) of guinea pigs, 14 of 16 animals developed pigment gallstones within one week (S group). Intraperitoneal injection of Vit. E and C, each 10 mg/kg daily from 3 days before CBD ligation to one week after the operation (S+V group), decreased the gallstone incidence to 5/14 (exact probability < 0.01). The gallstone incidence in the control group, that only received laparotomy without ligation of the CBD, was 0/15. Biochemical analysis of the gallbladder bile showed that stricture of the CBD was associated with a significant increase in levels of unconjugated bilirubin (UCB) and Ca2+ (p < 0.05 and < 0.01). Simultaneously the scavenging rate (SR) of superoxide radical in bile significantly decreased (p < 0.05). Comparing S+V group with S group, the effect of Vit. E and C on the concentrations of UCB and Ca2+ in bile was not significant (both p > 0.05), but Vit. E and C normalized the SR, and the difference between S group and S+V group was significant (p < 0.05). These results suggested that Vit. E and C, known as antioxidants, enhanced the ability to scavenge oxygen radical in S+V group; and that in addition to the increases of UCB and Ca2+ concentrations, the participation of oxygen radicals might be of importance for pigment gallstone formation induced by bile duct obstruction.

Animals↗
PubMed1996

Preconditioning of bovine endothelial cells. The protective effect is mediated by an adenosine A2 receptor through a protein kinase C signaling pathway.

We tested the hypothesis that anoxic preconditioning could protect coronary endothelial cells against anoxic and reoxygenation injury and that this preconditioning effect could be mediated by an adenosine A2 receptor via the protein kinase C (PKC) pathway. Cells were preconditioned with 10-minute anoxia and 10-minute reoxygenation and were then subjected to anoxia for 60 minutes, followed by 120 minutes of reoxygenation. In some groups, the preconditioning effect was prevented by 8-sulfophenyltheophylline (SPT [50 mumol/L], a nonselective adenosine receptor antagonist), or calphostin C (100 nmol/L, a PKC inhibitor). In other groups, 2-p-(2-carboxyethyl)phenethylamino-5'N-ethylcarboxyamido- adenosine (CGS-21680 [20 nmol/L], an adenosine A2 receptor agonist, R-(--)-N6-(2-phenylisopropyl)-adenosine (R-PIA [50 nmol/L], an adenosine A1 receptor agonist), or 4 beta-phorbol 12-myristate 13-acetate (PMA [100 nmol/L], a PKC activator) was given as a pretreatment to mimic the preconditioning effect. Endothelial cells were also pretreated with 100 nmol/L calphostin C to confirm whether inhibition of PKC can block the effects of adenosine A2 receptor activation by CGS-21680 on anoxia and reoxygenation injury. Preconditioning reduced LDH release, increased adenosine release, promoted translocation of PKC from cytosol to membrane, increased cell viability, and preserved ATP content and cell morphology. Pretreatment with either CGS-21680 or PMA resulted in protection similar to that seen with anoxic preconditioning. The protection was totally abolished by SPT or calphostin C. The results suggest that (1) preconditioning protects coronary endothelial cells against anoxia and reoxygenation injury, (2) the protection is probably mediated by activation of adenosine A2 receptors through the PKC pathway, and (3) the preservation of endothelial cells may be one of the mechanisms of myocardial preconditioning.

Adenosine↗
PubMed1996

Calcium preconditioning elicits strong protection against ischemic injury via protein kinase C signaling pathway.

We tested the hypothesis that elevation of [Ca2+]i during Ca2+ preconditioning (CPC) is a strong activator of protein kinase C (PKC) and confers unique protection against ischemic injury. CPC consisted of three cycles of Ca2+ depletion (1 minute each) and Ca2+ repletion (5 minutes each). Langendorff-perfused rat hearts were subjected to 40 minutes of global ischemia followed by 30 minutes of reperfusion. Significant functional recovery and decreased lactate dehydrogenase release were observed in CPC hearts compared with ischemic control hearts. In addition, ATP contents were significantly higher and cell structure was better preserved in CPC hearts than in ischemic control hearts. Administration of chelerythrine, a specific PKC inhibitor, completely abolished the CPC-induced cardioprotection. In other groups, in which Ca2+ influx during CPC was inhibited with verapamil, amiloride, and low Na+ perfusion, cardioprotection was significantly reduced. The prominent increase in the membrane PKC activity after CPC was in agreement with immunolocalization of PKC-alpha and PKC-delta in the cell membrane of CPC hearts. These results demonstrate that (1) a transient increase in [Ca2+]i is a prominent feature of CPC and is a strong stimulus for the activation of PKC, (2) the elevation of [Ca2+]i likely occurs via an L-type Ca2+ channel and Na(+)-Ca2+ exchanger, and (3) PKC plays a crucial role in the subcellular mechanisms of protection by CPC.

Animals↗
PubMed1996

Insulin stimulates phospholipase D-dependent phosphatidylcholine hydrolysis, Rho translocation, de novo phospholipid synthesis, and diacylglycerol/protein kinase C signaling in L6 myotubes.

Previous studies have provided conflicting findings on whether insulin activates certain, potentially important, phospholipid signaling systems in skeletal muscle preparations. In particular, insulin effects on the hydrolysis of phosphatidylcholine (PC) and subsequent activation of protein kinase C (PKC) have not been apparent in some studies. Presently, we examined insulin effects on phospholipid signaling systems, diacylglycerol (DAG) production, and PKC translocation/activation in L6 myotubes. We found that insulin provoked rapid increases in phospholipase D (PLD)-dependent hydrolysis of PC, as evidenced by increases in choline release and phosphatidylethanol production in cells incubated in the presence of ethanol. In association with PC-PLD activation, Rho, a small G protein that is known to activate PC-PLD activation, translocated from the cytosol to the membrane fraction in response to insulin treatment. PC-PLD activation was also accompanied by increases in total DAG production and increases in the translocation of both PKC enzyme activity and DAG-sensitive PKC-alpha, -beta, -delta, and -epsilon from the cytosol to the membrane fraction. A potential role for PKC or a related protein kinase in insulin action was suggested by the finding that RO 31-8220 inhibited both PKC enzyme activity and insulin-stimulated [3H]2-deoxyglucose uptake. Our findings provide the first evidence that insulin stimulates Rho translocation and activates PC-PLD in L6 skeletal muscle cells. Moreover, this signaling system appears to lead to increases in DAG/PKC signaling, which, along with other related signaling factors, may regulate certain metabolic processes, such as glucose transport, in these cells.

Animals↗
PubMed1996

Measurement of coronary artery calcium with dual-slice helical CT compared with coronary angiography: evaluation of CT scoring methods, interobserver variations, and reproducibility.

OBJECTIVE: This study was performed to evaluate new scoring methods for quantitating coronary artery calcifications with helical CT and to compare the results with those of quantitative coronary angiography in patients with suspected coronary artery disease. SUBJECTS AND METHODS: Unenhanced dual-slice helical CT and coronary angiography were performed within 24 hr of each other in 101 patients with symptoms of coronary artery disease. Coronary artery calcifications with a density above 90 H were identified on each slice and, with the same regions of interest, quantitative scoring was performed at thresholds of 90 H (new) 130 H (old). Two mathematical algorithms (one new and one old) were evaluated for both thresholds (yielding four scoring systems). By CT imaging, we defined disease as a score of greater than zero. By angiography, we defined disease as a 50% or greater reduction in the luminal diameter of any major vessel. Interobserver variations in calcification scoring were evaluated. Seventeen of our patients. also underwent a second, consecutive CT scan to determine reproducibility. RESULTS: With the new threshold and the new algorithm, the sensitivity, specificity, and accuracy of helical CT in predicting disease were 88%, 52%, and 76%, respectively. We found a moderate positive association between the total CT calcification score and the number of stenotic coronary arteries at angiography (Pearson's correlation coefficient, .43; p = .05 [analysis of variance]). The accuracy and the area under the receiver operating characteristic curve were higher with the new threshold and the new algorithm. Interobserver agreement in calcification scoring was high (intraclass correlation coefficient, .99 [n = 85]), as was reproducibility (intraclass correlation coefficient, .94 [n = 17]). Reproducibility was higher when scoring was based on the new threshold and the new algorithm. CONCLUSION: The quantity of coronary artery calcifications as measured by helical CT correlated positively with obstructive coronary artery disease as measured by angiography. Interobserver agreement and reproducibility were excellent. A new scoring method showed promise.

Adult↗
PubMed1996

Chronic activation of protein kinase C in soleus muscles and other tissues of insulin-resistant type II diabetic Goto-Kakizaki (GK), obese/aged, and obese/Zucker rats. A mechanism for inhibiting glycogen synthesis.

We examined the possibility that protein kinase C (PKC) is chronically activated and may contribute to impaired glycogen synthesis and insulin resistance in soleus muscles of hyperinsulinemic type II diabetic Goto-Kakizaki (GK) rats. Relative to nondiabetic controls, PKC enzyme activity and levels of immunoreactive PKC-alpha, beta, epsilon, and delta were increased in membrane fractions and decreased cytosolic fractions of GK soleus muscles. In addition, PKC-theta levels were decreased in both membrane and cytosol fractios, whereas PKC-zeta levels were not changed in either fraction in GK soleus muscles. These increases in membrane PKC (alpha, beta, epsilon, and delta) could not be accounted for by alterations in PKC mRNA or total PKC levels but were associated with increases in membrane diacylglycerol (DAG) and therefore appeared to reflect translocative activation of PKC. In evaluation of potential causes for persistent PKC activation, membrane PKC levels were decreased in soleus muscles of hyperglycemic streptozotocin (STZ)-induced diabetic rats; thus, a role for simple hyperglycemia as a cause of PKC activation in GK rats was not evident in the STZ model. In support of the possibility that hyperinsulinemia contributed to PKC activation in GK soleus muscles, we found that DAG levels were increased, and PKC was translocated, in soleus muscles of both (1) normoglycemic hyperinsulinemic obese/aged rats and (2) mildly hyperglycemic hyperinsulinemic obese/Zucker rats. In keeping with the possibility that PKC activation may contribute to impaired glycogen synthase activation in GK muscles, phorbol esters inhibited, and a PKC inhibitor, RO 31-8220, increased insulin effects on glycogen synthesis in soleus muscles incubated in vitro. Our findings suggested that: (1) hyperinsulinemia, as observed in type II diabetic GK rats and certain genetic and nongenetic forms of obesity in rats, is associated with persistent translocation and activation of PKC in soleus muscles, and (2) this persistent PKC activation may contribute to impaired glycogen synthesis and insulin resistance.

Adipocytes↗
PubMed1996

Effect of vitamin A deficiency on the early response to experimental Pseudomonas keratitis.

PURPOSE: Vitamin A-deficient humans and animals are more susceptible to infections than are healthy humans and animals. This study compares the early corneal response (within 24 hours) to an experimental Pseudomonas aeruginosa infection between vitamin A deficient and control rats. METHODS: Male WAG/Rij/MCW rats were fed either a vitamin A- deficient diet (A-) or the same diet with retinyl palmitate added back in a nonrestricted manner (N) or under pair-fed conditions (A+) to yield weight-matched rats. Some A-rats were repleted wih retinyl palmitate 16 days before being killed and then given free access to the retinyl palmitate-supplemented diet (R). Twenty-four hours before being killed, the corneas of anesthetized rats were scratched and P. aeruginosa organisms were applied to the corneal surface. The rats were killed using an overdose of sodium pentobarbital. Corneas were either processed for light and electron microscopic examination or extracted for proteinase and myeloperoxidase determination. Corneal myeloperoxidase concentrations relative to neutrophil myeloperoxidase concentrations were used to determine the number of neutrophils in the cornea. Zymography was used to study caseinases, gelatinases, and plasminogen activators. Reverse zymography was used to detect proteinase inhibitors. Similar results were noted at early, mid, and late weight plateau stages of vitamin A deficiency. RESULTS: Ulceration occurred within 24 hours when low numbers of P. aeruginosa (10(4) cpu) were applied topically onto scratched A- corneas, whereas no ulceration was observed in the A+, R, and N corneas. When higher numbers of P. aeruginosa (10(7)-10(8)) were applied to the scratched corneas, all corneas became ulcerated within 24 hours. The extent of ulceration in the control corneas was greater than that in A- corneas by a factor of two. Only the A- corneas contained inflammatory cells with unusual striated deposits in phagolysosomes. The total number of neutrophils in the cornea and the concentrations of caseinases, plasminogen activators, and gelatinases in the infected corneal extracts were similar; however, the concentrations of cysteine proteinase inhibitors were elevated under A- conditions. CONCLUSIONS: Vitamin A deficiency alters the response of the cornea to a P. aeruginosa infection during the first 24 hours. The alterations observed are probably due to multiple factors: an insufficient tear film for bacterial clearance and migration of neutrophils, epithelial keratinization, alterations in corneal wound healing, and changes in polymorphonuclear function.

Animals↗
PubMed1996

Evidence for a local immune response in atherosclerosis. CD4+ T cells infiltrate lesions of apolipoprotein-E-deficient mice.

It has been suggested that immune responses are involved in the development of atherosclerosis. We have evaluated this possibility by analyzing immunocompetent cells in a murine model of the disease. Apolipoprotein E knockout (apoE -/-) mice are genetically hypercholesterolemic due to targeted disruption of the apolipoprotein E gene and develop severe atherosclerosis. Such mice were fed either standard pellets or a diet containing 1.25% cholesterol. Lesions were analyzed from mice at 9 and 16 weeks of age. Immunohistochemical staining of fatty streaks showed that CD4+ T cells were frequent, both in clusters and as single cells. In advanced atherosclerotic plaques, CD4+ T cells were prominent in the fibrous cap and subendotbelially, whereas CD8+ T cells were sparse. The CD25 subunit of the interleukin-2 receptor, which is a marker for activated T cells, was expressed in CD4-rich areas and the major histocompatibility complex class II antigen, I-A(b), which is induced by cytokines released from activated T cells, was also found in the lesions. These data indicate that CD4+ T cells participate in the formation of atherosclerotic lesions in genetically hypercholesterolemic apoE -/- mice. They suggest that immune activation is part of the disease process, and we speculate that a direct link may exist between cholesterol accumulation and T cell activation, possibly by autoimmune responses to modified lipoproteins.

Animals↗
PubMed1996

[The study of DNA fingerprint of hydatidiform moles and the clinical outcome].

OBJECTIVE: To study the genetic origin of hydatidiform moles (HM) and the clinical outcome. METHODS: 41 cases of hydatidiform mole were collected mainly from Beijing area and studied for genetic components by DNA fingerprints. The diagnosis of persistent gestational trophoblastic disease (PTD) was made if blood hCG remained higher than normal 8 weeks after mole evacuation. RESULTS: Among 41 HM samples, 32 produced identifiable DNA fingerprints. DNA from only paternal origin was found in 21, in which 6 were PTD, DNA from both parents in 11, none of which developed PTD. CONCLUSIONS: DNA from only paternal origin was more frequently found than from both parents in HM, and there was a higher risk of PTD in the former group than in the latter.

DNA Fingerprinting↗
PubMed1996

[A study of the association between EBV and B-cell lymphoma].

Extensive studies have demonstrated that Epstein-Barr virus (EBV) is associated with Burkitt's lymphoma, immunodeficiency related lymphoma, Hodgkin's disease and T-cell lymphoma. In order to investigate whether an association exists between EBV and B-cell lymphoma in patients without overt immunodeficiency, we examined 127 B-cell lymphomas without overt immunodeficiency for expression of EBV-encoded small RNA (EBER-1) using RNA/RNA in situ hybridization. EBER-1 expression was found in nuclei of tumor cells in 8 of 127 cases (6.3%) of B-cell lymphomas. This result is similar to that of studies in Europe and the United States (about 5%). The low frequency of EBV in B-cell lymphomas suggests that EBV does not pay an important role in the pathogenesis of B-cell lymphomas without overt immunodeficiency.

Herpesviridae Infections↗
PubMed1996

Growth hormone action is blunted by acidosis in experimental uremia or acid load.

The effects of rhGH (H) daily injection (2 IU/d) and of vehicle (V) during two weeks were studied in young (60 g) growing rats. Experiment I was performed in uremic rats (mean plasma creatinine: 65-71 mumol/l) either acidotic (mean HCO3-:11.5 mmol/l: UAH, n = 20; UAV, n = 18), or with corrected acidosis by addition of NaHCO3 in the diet (mean HCO3-:26 mmol/l: UBH, n = 25; UBV, n = 23). Experiment II used rats with normal renal function (plasma creatinine: 25 mumol/l), either non-acidotic but food restricted to the dietary intake of uremic rats (CRH: n = 18, CRV: n = 18), or rendered acidotic by NH4Cl (CAH: n = 16, CAV: n = 16). GH induced an augmentation of body weight and length gains in non-acidotic uremic rats (+33% and +41%: p < 0.01), and in non-acidotic food restricted rats (+13% and 42%: p < 0.05 and p < 0.0001). This was associated with increased protein synthesis rate in muscle and with little change of food intake as well as of plasma IGF 1. Plasma IGF 1 kept the same relationship to food intake, regardless of treatment, but length gain for each level of plasma IGF 1 was enhanced by GH in GH responding groups. In both acidotic rat groups, GH altered none of the parameters studied. Thus: 1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats. 2) The increment of growth rate does not depend on a rise of plasma IGF 1.

Acidosis↗