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Biomedical subjects

C D Scott

Publications and source records attributed to C D Scott.

At least 19 recordsLinked to original sources
PubMed1996

Insulin-like growth factor II/mannose 6-phosphate-receptor expression in liver and serum during acute CCl4 intoxication in the rat.

The liver is reported to be the main source of soluble insulin-like growth factor-II/mannose 6-phosphate (IGF-II/M6P) receptor in adults. In view of the role of this receptor in the activation of transforming growth factor beta (TGF-beta) during hepatic fibrogenesis, we have investigated the correlation between serum levels and tissue expression of the receptor during acute CCl4 intoxication of the rat. Sixteen hours after CCl4, injection, the level of the soluble receptor in serum, as measured by radioimmunoassay (RIA), increased threefold. At 24 hours, values almost returned to normal, but increased again by twofold at 48 hours. By 96 hours, nearly normal values were obtained. Northern blot analysis showed peaks in tissue IGF-II/M6P receptor messenger RNA (mRNA) levels at 24 hours and at 48 hours. In normal liver, immunostaining for IGF-II/M6P receptor showed weak positivity in parenchymal cells. CCl4-induced hydropic changes appeared in centrilobular parenchymal cells (PCs) at 8 hours. These changes extended to the midzonal region at 16 hours. Hydropic cells were devoid of receptor staining. The hydropic wave became extinct at 32 hours. At 48 hours, we observed a collapse of PCs in the centrilobular zone, coinciding with strongly positive staining for IGF-II/M6P receptor in fat-storing cells (FSCs), identified by dual IGF-II/M6P receptor and desmin immunostaining. Between 48 and 72 hours, the liver gradually regained its normal appearance. As shown by Western blotting, in vitro differentiated FSCs released soluble receptor in the medium. Northern blot analysis showed this release to be preceded by an increased receptor-mRNA expression, whereas immunostaining showed an increase of intracellular receptor. In conclusion, we have shown that acute CCl4 intoxication induces two peaks in serum levels of soluble receptor. While the first peak at 16 hours coincides with the loss of receptor-staining in hydropically damaged PCs, the second peak at 48 hours is paralleled by an increase in positive staining in FSCs and tissue mRNA level. Differentiated FSCs shed soluble receptor in vitro. As a consequence, these cells might contribute to the serum levels of soluble receptor in vivo. These results indicate that measuring serum soluble IGF-II/M6P receptor might useful in the diagnosis of early acute liver damage.

Animals↗
PubMed1996

Reproducibility of electrophysiological measurements in cardiac transplant recipients.

The clinical usefulness of certain electrophysiological measurements, particularly those of sinus node function, is limited by variation in autonomic tone resulting in poor reproducibility. The denervated transplanted heart is not susceptible to direct autonomic control and, therefore, electrophysiological measurements may be more reproducible in this group. To our knowledge, this hypothesis has not previously been systematically evaluated. Ten adult recipients underwent serial electrophysiological studies between 10-18 days after cardiac transplantation. Five studies were performed at 2-hour intervals during a single day, between 9:00 a.m. and 5:00 p.m. Spontaneous cycle length (SCL) was recorded. Sinus node recovery time (SNRT), sinoatrial conduction time (SACT), and atrioventricular (AV) Wenckebach cycle length were measured using standard techniques. The effective refractory periods of the complete AV conducting system (AVERP), atrium (AERP), and ventricle (VERP) were measured. Corrected maximal SNRT was normal in all subjects. Mean coefficients of variation (Cv) for SCL, corrected maximal SNRT, and SACT were 2.8%, 7.4%, and 3.5%, respectively. AVERP was less than AERP in seven subjects, limiting further analysis. The mean Cv for AV Wenckebach cycle length was 2.1%. The mean coefficients of variation for AERP were 3.6% and 3.7%, and for VERP 3% and 3.3%, at 600- and 400-ms drive cycle lengths, respectively. Previous studies report much greater variation in innervated subjects particularly of indices of sinus node function. Thus, the reproducibility of electrophysiological measurements of sinus and AV node function in the transplanted heart is better than in normal subjects. This may have important implications for the reliability of electrophysiological testing in transplant recipients.

Atrioventricular Node↗
PubMed1996

Permanent pacemaker use after cardiac transplantation: completing the audit cycle.

OBJECTIVE: To determine the effects of delaying permanent pacemaker implantation in cardiac transplant recipients from less than tree weeks to three weeks or more post transplantation-a change prompted by an earlier audit. DESIGN: Retrospective review of resting 12 lead electrocardiograms and prospective 24 hour ambulatory electrocardiograms. Comparison of pacemaker usage before (period 1) and after (period 2) the policy change in November 1990. SETTING: Outpatient department, supra-regional cardiopulmonary transplant unit. PATIENTS: All 30 consecutive orthotopic cardiac transplant recipients who received a permanent pacemaker within one month of transplantation between May 1985 and August 1995. MAIN OUTCOME MEASURES: Presence of pacing on the 12 lead electrocardiogram and during 24 hour ambulatory electro-cardiogram monitoring (pacemaker programmed to 50 beats per minute). RESULTS: 16/152 (10.5%) cardiac transplant recipients received permanent pacemakers in period 1 compared with 14/180 (7.8%) in period 2 (P = NS). Evidence of pacing was seen on 12 lead electrocardiograms at three months in 37.5% recipients in period 1 compared with 78.6% in period 2 (P = 0.03). At six months pacemaker usage had declined to 18.8% in period 1 and 35.7% in period 2 and at three years to 13.3% in period 1 and 40% in period 2 (P = NS for both). 21% patients in period 1 paced on ambulatory 24 hour monitoring compared with 38.5% in period 2 (P = NS). CONCLUSIONS: Delaying permanent pacemaker implantation to three weeks or more after cardiac transplantation reduced the proportion of permanent pacemaker implantations, slightly but not significantly. There was a significant increase in permanent pacemaker usage at three months post transplantation with trends towards increased usage at later times, suggesting more appropriate selection of patients for permanent pacing.

Clinical Protocols↗
PubMed1996

Soluble insulin-like growth factor-II/mannose 6-P receptor inhibits deoxyribonucleic acid synthesis in cultured rat hepatocytes.

Insulin-like growth factor-II/mannose 6-P (IGF- II/M6P) receptor is released from cultured cells and tissues in a soluble form that retains its affinity for IGF-II. To test the possibility that soluble receptor can therefore modulate the activity of IGF-II, we determined the effect of purified soluble receptor on DNA synthesis in cultured rat hepatocytes stimulated with epidermal growth factor (EGF) (5 ng/ml) and IGF-II (200 ng/ml). Thymidine incorporation in hepatocytes in the presence of EGF and IGF-II was inhibited by soluble receptor (50% inhibition at 212 +/- 45 ng/ml). However, thymidine incorporation in the presence of EGF alone was also inhibited with similar potency. This inhibitory effect was removed by immunodepletion of receptor from the purified preparation, demonstrating the absence of nonspecific cytotoxic effects of the preparation. Although soluble receptor blocked IGF-II binding to hepatocytes, inhibition of EGF-stimulated DNA synthesis was not due to inhibition of EGF binding or uptake by the cell. These results suggest that soluble IGF-II/M6P receptor not only plays a role in modulating the action of IGF-II but may also have IGF-independent actions on cells, possibly by modulating M6P protein action.

Animals↗
PubMed1996

Regulation of soluble insulin-like growth factor-II/mannose 6-phosphate receptor in hepatocytes from intact and regenerating rat liver.

A soluble, circulating form of the insulin-like growth factor-II/mannose 6-phosphate receptor has been proposed to result from proteolytic cleavage of intact cellular receptors. This study examines receptor release in hepatocytes from normal and regenerating rat liver, where receptor levels are elevated. After partial hepatectomy, serum receptor increased from 0.64 +/- 0.02 to 1.36 +/- 0.15 microgram/ml at 72 h after surgery, reflected by an increase in receptor secretion from 18.5 +/- 3.6 ng/mg protein per 24 h in cells from sham-operated animals (n = 14) to 100.9 +/- 10.8 ng/mg protein per 24 h in cells from regenerating liver (n = 8). A wide range of protease inhibitors had little or no effect on soluble receptor secretion, indicating that extracellular proteolysis of cell surface receptor is not the major route of production in hepatocytes. Neither insulin-like growth factor-II nor mannose 6-phosphate altered receptor secretion, suggesting that neither ligand has a role in elevating receptor levels in liver regeneration. Inhibitors of endocytosis were examined to determine whether soluble receptor formation occurred during receptor recycling. Chloroquine, NH4Cl and monensin did not inhibit soluble receptor release, whereas the microtubule disrupting agents, colchicine and nocodazole, caused a dose-related increase that was reversible by the microtubule stabilizing agent, taxol. This suggests that alteration of early endosome pH does not alter soluble receptor production, but that subsequent disruption of late endosomes may result in increased formation and release of soluble receptor into the culture medium.

Animals↗
PubMed1995

Evolution of the chronotropic response to exercise after cardiac transplantation.

The chronotropic response to exercise is abnormal in cardiac transplant recipients as a result of autonomic denervation. Differences in the response between recent transplant recipients and longer-term survivors have been described in previous cross-sectional studies. These changes have not been assessed directly using serial studies. The effect of sinus node dysfunction on the chronotropic response has not previously been determined. Thirty-one transplant recipients underwent serial treadmill exercise tests using the chronotropic exercise assessment protocol 3 and 6 weeks and 3 and 6 months after transplantation. Sinus node function was assessed using standard electrophysiologic techniques. The chronotropic response increased between 3 and 6 weeks after transplantation in all subjects. Six months after transplantation, there was a further marked increase in the response in a subgroup of 5 subjects. These subjects also had a dramatic decrease in heart rate on cessation of exercise. Three subjects had abnormal sinus node function. Although heart rates and chronotropic response were below average in these subjects, 2 other subjects with normal sinus node function on electrophysiologic testing had lower heart rates and worse chronotropic responses. Thus, the chronotropic response to exercise evolves over the first 6 weeks after cardiac transplantation in all subjects. In a number of recipients (16%), there is a marked increase in chronotropic response between 3 and 6 months, which suggests efferent sympathetic reinnervation. There was no clear difference in chronotropic response between subjects with and without evidence of sinus node dysfunction.

Adult↗
PubMed1994

Sinus node function after cardiac transplantation.

OBJECTIVES: This study aimed to examine changes over time in sinus mode function after cardiac transplantation; to determine the incidence, natural history and etiology of sinus node dysfunction in transplant recipients; and to identify any early predictors of long-term sinus node function. BACKGROUND: Bradyarrhythmias caused by sinus node dysfunction are common immediately after cardiac transplantation. Existing electrophysiologic studies have been limited by small numbers and have reported an unexpectedly high incidence of sinus node dysfunction (approximately 50%) compared with the incidence of bradyarrhythmias in other studies. There have been no previous studies reporting serial electrophysiologic data. Thus, the natural history of sinus node dysfunction after transplantation has not been adequately described. METHODS: Serial electrophysiologic studies of sinus node function and 24-h ambulatory electrocardiographic recordings were performed at 1, 2, 3 and 6 weeks and 3 and 6 months after transplantation in 40 adult recipients. RESULTS: The overall incidence of sinus node dysfunction was 17.5% (7 of 40). Six patients (15%) had sinus node dysfunction from week 1; one developed sinus node dysfunction at 3 months. Sinus node recovery time returned to normal by 6 weeks in all six patients with early sinus node dysfunction, but abnormalities of sinoatrial conduction persisted in two. Two patients who required pacing during ambulatory monitoring at 2 weeks after transplantation (temporary pacemaker 50 beats/min, demand) received a permanent pacemaker. One patient required pacing at 3 weeks and continued to require pacing 6 months after transplantation. CONCLUSIONS: The incidence of sinus node dysfunction after cardiac transplantation is lower than has been previously reported in electrophysiologic studies. Sinus node automaticity improves with time, although abnormalities of sinoatrial conduction may persist. The best predictor of permanent pacing requirements is the temporary pacing requirements during 24-h Holter monitoring 2 and 3 weeks after transplantation, with temporary pacing set at 50 beats/min on demand.

Arrhythmia, Sinus↗
PubMed1994

Igf2r and Igf2 gene expression in androgenetic, gynogenetic, and parthenogenetic preimplantation mouse embryos: absence of regulation by genomic imprinting.

Genomic imprinting in mammals is believed to result from modifications to chromosomes during gametogenesis that inactivate the paternal or maternal allele. The genes encoding the insulin-like growth factor type 2 (Igf2) and its receptor (Igf2r) are reciprocally imprinted and expressed from the paternal and maternal genomes, respectively, in the fetal and adult mouse. We find that both genes are expressed in androgenetic, gynogenetic, and parthenogenetic preimplantation mouse embryos. These results indicate that inactivation of imprinted genes occurs postfertilization (most likely postimplantation) and that genomic imprinting and gene inactivation are separate processes. We propose that imprinting marks the chromosome so that regulatory factors expressed in cells at later times can recognize the imprint and selectively inactivate the maternal or paternal allele. For these genes, this finding invalidates models of genomic imprinting that require them to be inactive from the time of fertilization.

Alleles↗
PubMed1994

Vasodepressor reactions after orthotopic cardiac transplantation: relationship to reinnervation status.

Ventricular vagal nerve endings are thought to trigger vasodepressor syncope. Reports of vasodepressor reactions associated with donor bradycardia after cardiac transplantation have led to speculation that vagal reinnervation occurs. We assessed reinnervation status in seven patients 23-36 months (median 24 months) post-transplantation. Heart rate responses to vagal manoeuvres (respiration, Valsalva) and sympathetic stimuli (exercise and injection of tyramine into the coronary artery supplying the sinus node) were measured. All patients underwent 60 min of 60 degrees head-up tilt with foot plate support. During tilt four of the seven had vasodepressor reactions with a fall in mean arterial pressure of 20-90 mmHg. During vasodepression two patients had falls in donor heart rate of 13 and 40% relative to peak heart rate during tilt. These two patients had evidence of functional sympathetic reinnervation. By contrast the two patients without donor bradycardia during vasodepression had only limited or no evidence of sympathetic reinnervation. No patient had consistent evidence of parasympathetic reinnervation as judged by the heart rate response to vagal manoeuvres. Head-up tilt can thus produce vasodepressor reactions with donor bradycardia after cardiac transplantation in the absence of consistent evidence of vagal reinnervation. Left ventricular nerve endings may not be the only mediators of tilt-induced vasodepressor reactions in man. Donor bradycardia during vasodepression may reflect sympathetic withdrawal and not vagal reinnervation.

Blood Pressure↗
PubMed1994

Regulation of the acid-labile subunit of the insulin-like growth factor complex in cultured rat hepatocytes.

The acid-labile subunit (ALS) is a glycoprotein that forms a ternary complex in serum with insulin-like growth factors and insulin-like growth factor-binding protein-3. This study investigates the regulation of ALS production, measured by RIA, and messenger RNA (mRNA) content, measured by Northern analysis, in primary rat hepatocyte monolayer cultures. Hepatocytes produced ALS at a linear rate over 48 h. Exposure to human GH (30 ng/ml) caused a maximum 2.2-fold stimulation of ALS production compared to that in control cultures, giving a rate of 200 ng/10(6) cells.48 h. ALS mRNA appeared as a predominant 2-kilobase band and increased 4-fold by administration of 30 ng/ml GH. Both dexamethasone and epidermal growth factor (EGF) inhibited ALS production, with maximal effects at 100 nM dexamethasone and 50 ng/ml EGF (both approximately 50% inhibition). ALS mRNA levels measured 24 or 48 h after dexamethasone addition were decreased 75-80% compared to the control value. A similar decrease in ALS mRNA was observed 24 h after EGF addition, but a second addition of EGF at 24 h was required to maintain this decrease for 48 h. This study demonstrates that rat hepatocytes secrete immunoreactive ALS under GH regulation, and that EGF and corticosteroid inhibit ALS production and mRNA levels. The quantitative discrepancies between ALS production rates and mRNA levels suggest that posttranscriptional events may have a role in ALS regulation.

Acids↗
PubMed1993

Upper gastrointestinal dysmotility in heart-lung transplant recipients.

Recipient pneumonectomy and the necessity for meticulous hemostasis in heart-lung transplantation can result in injury to the vagus nerves as they course through the posterior mediastinum, with consequent delay in gastric emptying. This has been reported to lead to chronic aspiration and associated pulmonary sequelae. To study the association between delayed gastric emptying, bronchiectasis, and bronchiolitis obliterans after heart-lung transplantation, we performed esophageal manometry, 24-hour pH monitoring, and radioisotopic gastric emptying in 10 patients who underwent heart-lung transplantation. Three patients had grossly delayed liquid and solid emptying that was compatible with complete vagotomy. Six other patients had delayed liquid but normal solid emptying--an unexplained finding that is the reverse of what one would expect from vagal injury. Two of these 9 patients had esophageal dysmotility, but none demonstrated gastroesophageal reflux. One remaining patient had faster than normal gastric emptying for both solids and liquids. Of the 10, 2 patients have radiologic changes of bronchiectasis and 3 have biopsy evidence of obliterative bronchiolitis. There is no relationship between these sequelae and the occurrence of esophageal dysmotility, gastroesophageal reflux, or vagotomy. We conclude that gastric emptying abnormalities can occur after heart-lung transplantation, but such abnormalities are not associated with gastroesophageal reflux and the development of pulmonary sequelae, as previously reported.

Adult↗
PubMed1993

Heart rate and late mortality in cardiac transplant recipients.

There are currently 104 patients at this centre who have survived at least 3 months after orthotopic cardiac transplantation. Seven of these long-term survivors have subsequently died and in three cases death was sudden and unexpected. All three of these patients had been noted to have inappropriately high resting heart rates (> 130 b.min-1). The rhythm was sinus tachycardia, supraventricular tachycardia or both intermittently. The heart rates of all 104 long-term survivors were recorded from ECGs taken at routine follow-up visits every 3 months for one year and annually thereafter. The overall mean heart rate was 100 +/- 13.2 b.min-1. Four patients, including the three identified above, had mean heart rates greater than the 95th centile. The mortality rate in this group is 75%. Four deaths have occurred in the remaining 100 patients (P < 0.001). In our series, an inappropriately high resting heart rate due to sinus tachycardia or supraventricular tachycardia in long-term survivors of cardiac transplantation, is an adverse prognostic sign.

Adult↗
PubMed1993

Morphology of the cardiac conduction system in patients with electrophysiologically proven dual atrioventricular nodal pathways.

INTRODUCTION: Although the electrophysiologic criteria for dual atrioventricular nodal pathways are well established, the anatomical substrate is still unclear. METHODS AND RESULTS: We examined the hearts from 10 patients who had been studied electrophysiologically prior to cardiac transplantation. All 10 patients were male, aged 22 to 60 years. Nine of the 10 patients had dual atrioventricular nodal pathways according to accepted criteria. Histologic studies of the atrioventricular conduction system showed normal structure of the atrioventricular node in all 10 hearts, with minor variations within the node in 3 cases, within the penetrating bundle in 3 cases, and within the nonbranching bundle in 3 cases. The atrial approaches to the atrioventricular node were generally scanty in 6 hearts. The solitary case that was shown electrophysiologically to lack dual pathways had no obvious difference in the structure of the nodal area other than sparsity of transitional cells. We were unable to locate any extranodal atrial tracts as described by other investigators. CONCLUSION: The anatomical substrate for conduction over dual pathways may be too subtle to be detected by gross morphologic studies. Since dual pathways were unmasked in all patients but one during electrophysiologic studies, it may be that the potential for these pathways is ubiquitous.

Adult↗
PubMed1993

Permanent pacing after cardiac transplantation.

OBJECTIVE: To determine the need for long-term pacing and optimum mode of pacing in cardiac transplant recipients. DESIGN: (a) A retrospective review of patient records. (b) A prospective study of pacemaker use by 24 hour ambulatory electrocardiography before and after reprogramming to minimise use of pacemakers. SETTING: Outpatient clinic, supra-regional cardiopulmonary transplant unit. PATIENTS: All 21 patients at this centre who had received permanent pacemakers after cardiac transplantation. 18 of 19 survivors completed the prospective part of the study. MAIN OUTCOME MEASURE: The presence of pacing during a 24 hour ambulatory electrocardiographic recording (programming: 50 beats/min, rate sensor inactivated). RESULTS: 21 of 191 (11%) recipients surviving one month or more received permanent pacemakers. The indication was sinus node dysfunction in 13 (62%) and atrioventricular (AV) block in eight (38%). Patients who paced on follow up 12 lead electrocardiograms declined from 38% at three months to 10% at three years after transplantation. After programming to 50 beats/min only five of 18 (28%) patients paced during a 24 hour ambulatory recording. Four of 11 (36%) recipients who received pacemakers for sinus node dysfunction paced compared with one of seven patients (14%) paced for AV block. No patient who had a pacemaker before the 16th day after operation continued to pace whereas five of nine implanted later were used long-term. CONCLUSION: Only five of 18 (28%) patients with pacemakers continued to pace long-term. Continued pacing was more common in those with persistent sinus node dysfunction after the second week after operation but the need for long-term pacing was not predictable.

Cardiac Pacing, Artificial↗
PubMed1992

Arrhythmias after cardiac transplantation.

The etiology and clinical significance of sustained arrhythmias, and atrial and ventricular premature complexes (APCs and VPCs, respectively) after heart transplantation are controversial. Fifty adult recipients surviving > 2 weeks were studied by continuous telemetry while in the hospital and by ambulatory electrocardiographic monitoring at 2, 4, 6, 12 and 24 weeks after transplantation. The median APC frequency was greater among subjects who experienced allograft rejection in the early postoperative period (0.7/hour, range 0 to 23) than among those who did not (0.2/hour, range 0 to 10.4) (p = 0.04). The APC frequency in all subjects decreased from 0.25/hour (range 0 to 23) early to 0/hour (0 to 14) later (p = 0.04). Atrial flutter was the most frequent sustained arrhythmia; it was recorded in 5 of 21 rejectors and in 1 of 29 nonrejectors (p = 0.04), and 11 of 16 episodes (69%) were related to acute rejection temporally. VPCs were recorded in all patients early after transplantation, but the median frequency subsequently decreased from 4.6/hour (range 0.5 to 470) early to 1.25/hour (range 0 to 225) later (p < 0.001). VPC frequency was unrelated to rejection. Sustained ventricular tachycardia was recorded once and was caused by the proarrhythmic effect of flecainide. Thus, APCs and VPCs occur frequently after transplantation. Frequent APCs are associated with rejection, whereas the main determinant of VPC frequency is time after transplantation. Atrial flutter is closely associated with rejection and should be regarded as an indication for endomyocardial biopsy. Ventricular tachycardia occurs seldom, and in this study was due to proarrhythmic drug effects.

Adult↗
PubMed1992

Paediatric cardiac transplantation with steroid-sparing maintenance immunosuppression.

In order to determine the results of steroid-sparing maintenance immunosuppression in paediatric patients who have undergone orthotopic heart transplantation (OHT), a retrospective study was undertaken in 12 children and five infants (median age 3.5 years). Preoperative diagnoses were cardiomyopathy in seven and congenital heart disease in 10 patients. Immunosuppression was induced by cyclosporin, azathioprine, methylprednisolone, and antihuman lymphocyte immune globulin. It was maintained with cyclosporin and azathioprine. After induction, five patients received no further steroids. The remainder, except one, required only pulses for rejection (13 episodes or 0.51 episodes/patient year). Long term complications included hypertension in six, and renal impairment in three children. There were no early or late deaths from infection. Actuarial survival was 94% at one year. Of the children followed up for more than one year, all demonstrated an increase in height SD scores (mean (SD) -2.15 (1.35) to -1.15 (1.16)). We conclude that a steroid-sparing maintenance immunosuppression regimen can be successfully employed in paediatric OHT, and that significant catch-up growth can be achieved postoperatively.

Azathioprine↗
PubMed1992

Radioimmunoassay of soluble insulin-like growth factor-II/mannose 6-phosphate receptor: developmental regulation of receptor release by rat tissues in culture.

The soluble form of the insulin-like growth factor-II/mannose 6-phosphate receptor, which has been detected in serum from a variety of species, is synthesized and released by rat tissue explants in culture. Investigations into its regulation and function, however, have been hampered by inadequate means of quantification. In this paper a RIA that enables sensitive and specific quantification of soluble receptor from serum and conditioned medium is described. In order to further clarify the source of soluble receptor in serum and to determine whether release of receptor from rat tissues is under developmental regulation, receptor release from rat explants was examined and compared to serum levels of receptor. Heart, skeletal muscle, kidney, and liver explants from fetal, neonatal, weanling, and adult rats were cultured in serum-free medium, and the conditioned medium was analyzed by RIA for the presence of receptor. Soluble receptor release was highest for fetal and neonatal tissues, with weanling and adult tissues showing dramatically decreased levels. Release of soluble receptor varied between tissues, with the tissue-specific pattern altering during development, such that while heart and muscle appeared as major tissues of release in fetal animals, the liver was the tissue of highest release in adult animals. It is concluded that release of soluble receptor by rat tissues is developmentally regulated, with levels of receptor in serum reflecting the pattern of release from tissues. The RIA will prove a useful tool for further examination of the regulation and function of the soluble insulin-like growth factor-II/mannose 6-phosphate receptor.

Animals↗