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C D Scott

Publications and source records attributed to C D Scott.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Modulation of insulin-like growth factor-II/mannose 6-phosphate receptors and transforming growth factor-beta 1 during liver regeneration.

Transforming growth factor-beta 1 (TGF-beta 1) is a potent mito-inhibiting substance that is thought to play an important function in regulating hepatocyte proliferation during liver regeneration. In this investigation, we have shown by immunohistochemistry that hepatocytes containing significant intracellular concentrations of TGF-beta 1 12 h after a two-thirds partial hepatectomy. This increase in hepatocyte TGF-beta 1 concentration was initially confined to those cells that resided in the periportal region of the liver. The elevation of intracellular TGF-beta 1 was, however, transient, and within 36 h, the hepatocytes positive for TGF-beta 1 had changed in a wavelike fashion from the periportal to the pericentral region of the liver lobules. By 48 h, most hepatocytes no longer contained TGF-beta 1. Interestingly, this temporary increase in TGF-beta 1 always preceded the onset of hepatocyte replication by approximately 3-6 h. Since TGF-beta 1 mRNA has been shown to be absent from hepatocytes normally and throughout liver regeneration, these results imply that the increase in intracellular TGF-beta 1 resulted from an augmented uptake. We have further shown that the insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man-6-P) receptors were up-regulated during liver regeneration and that the increased expression of this receptor co-localized in those hepatocytes containing elevated concentrations of TGF-beta 1. The latent TGF-beta 1 phosphomannosyl glycoprotein complex has been shown to bind to the IGF-II/Man-6-P receptor. Therefore, our data are consistent with the hypothesis that this latent complex is internalized through the IGF-II/Man-6-P receptor to the intracellular acidic prelysosomal/endosomal compartments where the mature TGF-beta 1 molecule could be activated by dissociation from the latent complex.

Animals↗
PubMed1991

Synthesis of the acid-labile subunit of the growth-hormone-dependent insulin-like-growth-factor-binding protein complex by rat hepatocytes in culture.

Insulin-like growth factors (IGFs) circulate predominantly in a growth-hormone-dependent ternary complex of 125-150 kDa. This study investigates the production of the alpha-subunit of this complex, an acid-labile glycoprotein without intrinsic IGF-binding activity, which binds to the IGF-binding protein IGFBP-3 in the presence of IGFs. Medium conditioned by primary cultures of rat hepatocytes produced alpha-subunit with similar complex-forming activity to purified rat serum alpha-subunit. Bovine growth hormone stimulated hepatocyte production of both IGF-I and alpha-subunit. IGF-I tracer bound to pure rat IGFBP-3 was converted from approx. 60 kDa to 150 kDa by serum alpha-subunit, whole rat serum or rat hepatocyte culture medium; this converting activity was destroyed by transient acidification. In contrast, IGF-I bound to hepatocyte-medium IGF-binding proteins could not be converted into a high-molecular-mass from by purified rat serum alpha-subunit. Rat serum and hepatocyte-medium alpha-subunit appeared identical by electrophoretic analysis, since reaction of either with cross-linked IGF-I.IGFBP-3 tracer resulted in bands of molecular mass 130 kDa and 160 kDa, probably representing intact and partially deglycosylated complexes. However, IGF-binding proteins in rat serum and hepatocyte medium were different, in that affinity labelling of medium binding proteins, depleted of endogenous IGFs, showed no evidence of the 50-60 kDa cluster of bands characteristic of rat serum IGFBP-3. We conclude that rat hepatocytes in primary culture produce alpha-subunit similar to that in rat serum; however, alpha-subunit is unable to form ternary complexes with hepatocyte IGF-binding proteins, since cultured hepatocytes do not secrete IGFBP-3.

Animals↗
PubMed1991

Long-term pacing in heart transplant recipients is usually unnecessary.

The indications for and timing of permanent pacing were reviewed in all 17 of 154 adult heart transplant recipients at this center who have had permanent pacemakers implanted. Resting 12-lead ECGs recorded during routine follow-up were examined. A prospective study of pacing requirement was then undertaken. Holter monitoring was performed before and after reprogramming the pacemakers to VVI mode at 50 beats/min. Exercise responses in various pacing modes were then assessed in seven patients with rate responsive pacemakers using a standard Bruce protocol treadmill test. The indication for pacing was sinus node dysfunction in 59% (10/17) and atrioventricular (AV) block in 41% (7/17). The majority of pacemakers were implanted between seven and 21 days after transplantation. There was a progressive reduction in the frequency of pacing on 12-lead ECGs with time after transplantation. There was a progressive reduction in the frequency of pacing on 12-lead ECGs with time after transplantation. Eight of 14 patients with empirically selected programming paced during Holter monitoring. After reprogramming to 50 beats/min VVI mode only three of 14 patients, all with sinus node dysfunction, paced. Rate responsive pacing made no difference to exercise time. The requirement for long-term pacing in cardiac transplant recipients is small (3/154) and is limited to patients with sinus node dysfunction. Rate responsive pacing did not increase exercise tolerance.

Adult↗
PubMed1991

Secretion of soluble insulin-like growth factor-II/mannose 6-phosphate receptor by rat tissues in culture.

The insulin-like growth factor-II/mannose 6 phosphate receptor, which binds both IGF-II and mannose 6-phosphate containing proteins, such as lysosomal enzymes, has been detected in the serum of several species. Neither the source nor the role of this soluble, truncated form of the membrane receptor has been determined. This study has examined the ability of a variety of rat tissues in culture to synthesize and release soluble receptor. Explants (1 mm3) of 21-day fetal, neonatal and adult rat tissues were cultured in serum-free medium and the conditioned medium analyzed for the presence of receptor. Using IGF-II binding and immunochemical techniques, receptor was detected in media from heart, kidney, liver, lung and muscle explants. [35S]cysteine labeling indicated that de novo synthesis of the soluble receptor occurs in the cultured explants and can be inhibited by cycloheximide. This rat tissue explant culture system demonstrates that soluble receptor is released by a number of tissues, and should provide a useful model for further investigations into its function and regulation.

Affinity Labels↗
PubMed1990

Developmental regulation of insulin-like growth factor-II/mannose 6-phosphate receptor mRNA in the rat.

This study examined levels of insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-II/M6PR) mRNA in tissues of rats at different stages of growth. Northern blot analysis of total RNA from tissues of rats aged 2, 9, 21 and 42 days and from 21 day fetal rats was carried out using a cDNA probe to the IGF-II/M6PR. Northern blots showed this probe hybridized to a single 9kb band in all tissues tested. Highest hybridization signals were detected in fetal and neonatal tissues with levels rapidly decreasing after birth. For all age groups tested the highest signal was obtained with heart followed by muscle, lung, and kidney, with liver and brain showing lower levels of message. These results indicate that IGF-II/M6PR mRNA is developmentally regulated, and suggest a role for the IGF-II/M6PR in fetal and neonatal growth.

Aging↗
PubMed1990

Insulin-like growth factor-II/mannose-6-phosphate receptors are increased in hepatocytes from regenerating rat liver.

Insulin-like growth factor-II (IGF-II) receptor levels were determined in hepatocytes from sham-operated and two thirds hepatectomized rats. [125I]IGF-II binding to confluent cultures increased 2-fold in cells isolated 24 and 48 h after hepatectomy compared to that in cells from sham-operated rats. Receptor levels increased from 1.74 +/- 0.14 x 10(4)/cell (sham-operated) to 3.60 +/- 0.31 x 10(4)/cell (hepatectomized; P = 0.002), with no change in affinity of IGF-II binding (Ka = 6.4 x 10(9) M-1). As previously reported, receptor levels increased in cells plated at low density, but this effect was decreased in cells from hepatectomized rats (80% increase) compared to that in cells from control rats (300% increase). Serum IGF-I levels decreased 50% 24 h after partial hepatectomy (P less than 0.001), but returned to normal levels by 48 h. However, IGF-I synthesis was not decreased in hepatocytes isolated 24 h after partial hepatectomy, suggesting that decreased serum levels are due to decreased liver mass. Circulating IGF-II levels were not altered by partial hepatectomy, and IGF-II production was not detected in hepatocytes from sham-operated or hepatectomized rats. Transforming growth factor-beta is thought to terminate hepatocyte proliferation upon complete liver regeneration. In hepatocytes from sham-operated or hepatectomized rats transforming growth factor-beta totally blocked DNA synthesis, but had no effect on elevated IGF-II receptor levels after partial hepatectomy. Concomitant with increased IGF-II receptor levels, hepatocytes from hepatectomized rats were more sensitive to IGF-II stimulation of DNA synthesis. [3H]Thymidine incorporation in the presence of epidermal growth factor (50 ng/ml) was stimulated 66% by IGF-II (300 ng/ml) in control cells compared with 220% in cells from hepatectomized animals. These results suggest that IGF-II and the IGF-II receptor may play a role in liver regeneration.

Animals↗
PubMed1990

Increased expression of insulin-like growth factor-II/mannose-6-phosphate receptor in regenerating rat liver.

This study examined the effect of two thirds hepatectomy on rat liver insulin-like growth factor-II (IGF-II) receptors and IGF-II receptor messenger RNA (mRNA) levels. IGF-II receptor levels were determined in liver plasma membrane and Golgi/endosome fractions from sham-operated and hepatectomized rats by ligand binding and immunoblotting after electrophoresis. After hepatectomy, IGF-II receptors increased initially in the plasma membrane (within 24 h of surgery) to 4-fold control levels, remained elevated for 72 h, and declined to control levels at 120 h when liver regeneration is near complete. However, Golgi/endosome levels of IGF-II receptors did not increase until 48 h, showing a maximum increase of 3.5-fold at 72 h after surgery and returning to control values at 120 h. The 9-kilobase mRNA for IGF-II receptor, determined by slot blotting with a complementary DNA probe, increased 2.5-fold within 24 h of surgery, attaining a maximum stimulation of 4-fold at 48 h, and then decreasing to normal levels by 120 h. These changes show that, after partial hepatectomy, IGF-II receptors increase rapidly at the cell surface, possibly due to receptor translocation from intracellular pools. This is followed by an increase of IGF-II receptor mRNA and increased receptor synthesis, resulting in an increase in total cellular receptors. These results suggest a role for IGF-II receptors in regenerating liver, perhaps in cell proliferation and/or in tissue remodeling.

Animals↗
PubMed1989

Coping with stress.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed1989

Immunofluorescent localization of type II insulin-like growth factor receptor in rat liver and hepatoma cells.

We have used an immunofluorescent technique to localize type II insulin-like growth factor (IGF) receptors in rat liver, rat hepatocytes and three rat hepatoma cell lines (HTC, H-35 and 5123) using a polyclonal antibody (C-1) raised to purified rat liver type II IGF receptor. Specificity of the antiserum was confirmed by Western blotting of microsomal membranes prepared from hepatocytes and hepatoma cells which showed a single class of receptor in all cells, of Mr approximately 210,000 for hepatocytes, HTC and H-35 cells and approximately 220,000 for 5123 cells, on non-reduced, 4-15% polyacrylamide gradient gels. The specificity of the immunofluorescent technique was also verified by abolition of labelling after preincubation of antiserum with purified type II IGF receptor. Rat liver cryosections contained areas of juxtanuclear labelling in hepatocytes, consistent with the presence of type II IGF receptor in the Golgi region. Brightest immunofluorescence was seen in sections from fetal and neonatal rats with adult rat hepatocytes staining brightly only around central veins. Areas of labelling were also seen in connective tissue surrounding larger veins. Cultured adult rat hepatocytes and rat hepatoma cell lines also showed bright areas of juxtanuclear nuclear immunofluorescence, with HTC and H-35 cells staining more than 5123 and adult hepatocytes. Fetal rat hepatocytes in culture also labelled very brightly both in a juxtanuclear location and in small clusters over the cell, possibly on the cell surface. These observations indicate that type II IGF receptors are located predominantly on intracellular membranes and are most abundant in rapidly growing cells and tissues (such as fetal liver and hepatoma cells).

Aging↗
PubMed1989

Managing occupational stress associated with HIV infection. Self-care and self-management skills.

There is a crisis in health care that has to do with the ability of health-care workers to provide the long-term care and help for AIDS patients. Although more severe, it is just an extreme form of the denial among health care professionals of their own needs, and lack of ability to manage stress. The situation also reflects absence of explicit concern in health settings for creating environments that are healthy for staff. This paper has suggested some of the forms that a comprehensive response to this problem can take.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Differential regulation of insulin-like growth factor-II receptors in rat hepatocytes and hepatoma cells.

This study compares the regulation of IGF-II receptors in three rat hepatoma lines, HTC, H-35 and 5123tc, and primary rat hepatocytes. In all cell types [125I]IGF-II bound solely to a species of approximately 250 kDa. Cell surface IGF-II receptors in hepatoma cells had slightly lower affinities (1-2 liters/nmol) than in hepatocytes (4 liters/nmol), but slightly higher IGF-I cross-reactivity (2-4% compared to 1% in hepatocytes). In confluent cultures, the three hepatoma lines expressed 5- to 15-fold more cell-surface receptors per cell than hepatocytes. However, while hepatocyte receptors showed marked inverse density-dependence, increasing over 6-fold between dense (3 x 10(5) cells/3.8 cm2) and sparse (0.16 x 10(5) cells/3.8 cm2) cultures, receptors in all hepatoma lines remained at a constant high level regardless of culture density. These distinct regulatory patterns resemble those described for growth-related functions in hepatocytes and hepatoma cells, and are thus consistent with a role for IGF-II receptors in liver cell proliferation.

Animals↗