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Biomedical subjects

S B Miller

Publications and source records attributed to S B Miller.

At least 55 records · Page 3Linked to original sources
PubMed1994

Parasympathetic nervous system control of heart rate responses to stress in offspring of hypertensives.

The elevated heart rate response to stress in normotensive offspring of hypertensives (PH+) has been suggested to be a function of sympathetic nervous system activity. This study examined whether parasympathetic nervous system activity may also underlie familial differences in the heart rate response. Twenty-four subjects, half of whom were PH+, were exposed to four stressor tasks administered in counterbalanced order. Stressors were chosen based on previous research that suggested vagal contributions to the heart rate response. Stressors were a cold pack to the forehead, isometric hand grip, a noxious film, and a shock-avoidance video game task. Physiological measures included heart rate (HR), respiration rate (RR), and respiratory sinus arrhythmia (RSA). RSA values were corrected for corresponding RR by analysis of covariance. Familial differences in HR were observed in response to the hand grip and video game tasks. However, in both cases analyses suggest that familial differences in reactivity were a function of primarily sympathetic as opposed to parasympathetic influences. Familial differences in RSA were not observed for rest or tasks. This study found no evidence for parasympathetic mediation of familial differences in the heart rate response to the stressors employed.

Adult↗
PubMed1994

Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in rats.

Effects of hepatocyte growth factor (HGF) administration were examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered 20 micrograms HGF subcutaneously 30 min postischemia had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion, enhanced insulin clearances measured on day 2 postocclusion, reduced mortality, and much less injury evident by examination of kidney histologies 7 days postinjury. The tubular regeneration that occurred postischemic injury was reflected by increased incorporation of 5-bromo-2'-deoxyuridine (BrdU) in cortical tubular epithelium compared with incorporation in kidneys from noninjured rats. HGF enhanced BrdU incorporation compared with vehicle, indicating enhanced mitogenesis. The weight loss that occurs postischemic injury was not ameliorated by the dose of HGF we employed. We conclude that administration of HGF postischemic injury to rats stimulates the recovery of normal kidney function and the regeneration of proximal tubular epithelium.

Animals↗
PubMed1994

Rat models for clinical use of insulin-like growth factor I in acute renal failure.

Insulin-like growth factor I (IGF-I) improves kidney function and histopathology, when given within a short time (0.5 or 5 h) after an ischemic renal insult in rats. To examine the effects of IGF-I at times that would be more applicable if it were to be used as a therapeutic agent for acute renal failure in humans, we administered IGF-I to rats 24 h after ischemic injury or prior to the induction of injury (pretreatment). In rats that received IGF-I 24 h postischemia, serum creatinine and blood urea nitrogen (BUN) values were significantly lower during the subsequent 6 days than in vehicle-treated rats, and incorporation of 5-bromo-2'-deoxyuridine into tubular cells of the regenerating cortex, measured 48 h postischemia, was enhanced. When examined 7 days postinjury, kidneys from rats that received IGF-I 24 h postischemia were improved in histopathological appearance compared with kidneys from vehicle-treated animals. Whereas creatinine and BUN values were elevated above baseline in both vehicle and IGF-I-pretreated groups, recovery of normal renal function was accelerated by pretreatment with IGF-I. In addition, although we could detect no differences in histopathology at 24 h postinjury, IGF-I pretreatment resulted in more normal renal histology at 7 days postischemic injury and reduced weight loss after injury. Our data show that IGF-I hastens recovery and accelerates regeneration or repair of damaged epithelia following acute renal failure in rats when administered either 24 h postinjury or prior to induction of acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1994

Effects of growth hormone on rat renal epidermal growth factor expression.

The kidney is a site of synthesis for several polypeptide growth factors including epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I). Interactions between growth hormone (GH) and growth factors have been described that regulate renal growth factor expression. For example, GH and EGF each enhances the expression of IGF-I in kidney. To further define interrelationships in this renal GH-growth factor axis, we characterized the effect of GH on renal EGF expression in hypophysectomized, pituitary-intact (normal) rats, and hypersomatotropic rats. Levels of extractable immunoreactive mature EGF, levels of a 142-kDa EGF-precursor present in renal membrane fractions, and levels of EGF mRNA were significantly reduced in kidneys from hypophysectomized rats compared with levels in normal rats. Each was increased significantly after the administration of GH to hypophysectomized rats. In contrast, induction of hypersomatotropism in normal rats by injection of GH for 17 days did not affect levels of extractable mature EGF or EGF mRNA measured in kidneys. We conclude that GH enhances the renal synthesis of EGF in hypopituitary, but not in hypersomatotropic states.

Animals↗
PubMed1994

Therapeutic use of growth factors in renal failure.

Polypeptide growth factors regulate kidney development, growth, and function and participate in processes of repair after renal injury. The use of one or more growth factors as therapeutic agents has been proposed in the settings of acute and chronic renal failure. In animal models of acute renal injury, the administration of epidermal growth factor, insulin-like growth factor I (IGF-I), or hepatocyte growth factor accelerates the restoration of kidney function and the normalization of histology post-acute renal injury and reduces mortality. The mechanisms by which the growth factors act in acute renal failure include the stimulation of anabolism, the maintenance of glomerular filtration, and the enhancement of tubular regeneration. IGF-I has been safely administered to humans with chronic renal failure. The growth factor enhances GFR and RPF in these individuals. Further studies will be required to establish a role for IGF-I or other growth factors as therapeutic agents for acute renal failure in humans and to define the utility of IGF-I as a medical therapy for chronic renal insufficiency.

Acute Kidney Injury↗
PubMed1994

Optimal management of gout in older patients.

Gout in older patients tends to be sub-acute to chronic, often tophaceous, polyarticular, erosive, symmetrical, and causes persistent, recurrent and chronic arthritis. Clinically, it may closely mimic rheumatoid arthritis; thus, a correct diagnosis requires a high index of clinical suspicion and the identification of uric acid crystals. An optimal therapeutic strategy for most older patients with chronic tophaceous gout could involve the following: avoidance of alcohol and diuretic use if possible; avoidance of long term nonsteroidal anti-inflammatory drug (NSAID) therapy; use of short term corticosteroids (systemic or intra-articular) for acute exacerbations; prophylactic colchicine daily or every other day according to the degree of renal dysfunction present; and long term allopurinol therapy in dosages adjusted to the degree of hyperuricaemia and renal dysfunction.

Aged↗
PubMed1993

Symptomatic cytomegalovirus infection in renal transplant recipients given either Minnesota antilymphoblast globulin (MALG) or OKT3 for rejection prophylaxis.

To compare the impact of using Minnesota antilymphoblast globulin (MALG) versus the monoclonal antibody, OKT3, on the development of symptomatic cytomegalovirus (CMV) infection, we reviewed a cohort of 130 cadaveric renal transplant recipients enrolled in a prospective comparison of MALG versus OKT3 for rejection prophylaxis. Among the 112 patients at risk for CMV, prophylactic MALG was associated with an increased risk of symptomatic infection (relative hazard [rh] = 3.31; 95% confidence interval CI], 1.50 to 7.30; P = 0.003). Transplantation of kidneys from CMV-seropositive donors into CMV-seronegative recipients (rh = 5.22; 95% CI, 2.34 to 11.63; P = 0.00004), first transplantation (rh = 4.76; 95% CI, 1.06 to 21.3; P = 0.039), and acute rejection therapy (rh = 2.03; 95% CI, 0.98 to 4.21; P = 0.055) were also associated with an increased risk. Prophylactic MALG followed by treatment with any agent for acute rejection was strongly correlated with symptomatic CMV infection (rh = 4.46; 95% CI, 3.71 to 5.21; P = 0.00006). Symptomatic CMV infection was not only more frequent, but more severe in recipients of prophylactic MALG, and more MALG recipients were treated with ganciclovir. There was no difference in rejection rate for the two rejection prophylaxis regimens (P = 0.625). Prophylactic OKT3 results in less risk of symptomatic CMV infection than prophylactic MALG in cadaveric renal transplant recipients who are seropositive for CMV or whose donors are seropositive for CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Roles of growth hormone and growth factors in the pathogenesis and treatment of kidney disease.

Growth hormone and a number of polypeptide growth factors exert actions on renal development, growth, and metabolism and on repair processes following renal injury. There is increasing evidence that under selected circumstances, these agents play roles in the pathogenesis of kidney disease and that under others, they may be useful in its treatment. Growth hormone, platelet-derived growth factor, or transforming growth factor-beta may be causative of glomerulosclerosis. The reduction in epidermal growth factor expression within the kidney in the setting of acute ischemic injury could delay regeneration, and replacement may be therapeutic. Insulin-like growth factor I may play a role in the regenerative response to acute renal injury. Pharmacologic properties of growth hormone or insulin-like growth factor I to enhance glomerular filtration rate and renal plasma flow and to increase skeletal growth may be harnessable for treating chronic renal failure and its complications. It is likely that strategies designed to employ growth hormone or growth factors as pharmacologic agents or to block their activities will assume increasingly important roles in therapy for renal disease.

Animals↗
PubMed1993

Role of growth factors in regulation of renal growth.

It is clear that a number of growth factors are synthesized within the adult and the developing kidney. Compelling evidence exists that several of these agents orchestrate the nephrogenic process. A growing body of data supports roles for one or more of these agents in the adult kidney as regulators of renal function, growth, and repair processes. Growth factor expression may be the cause of glomerulosclerosis in one or more pathophysiological states. Our knowledge of the sites of growth factor synthesis and actions in the kidney and of the mechanisms by which growth factor synthesis is regulated and actions are exerted is rudimentary. Expansion of this knowledge base is likely to result in a greater understanding of renal disease mechanisms and thereby generate strategies by which kidney damage can be halted, prevented, or reversed.

Animals↗
PubMed1993

Effects of IGF-I on renal function in patients with chronic renal failure.

Insulin-like growth factor I (IGF-I) has been shown to increase glomerular filtration rate and renal plasma flow in rats and humans with normal renal function. However, rats with reduced renal function are resistant to these effects. To determine whether IGF-I affects glomerular filtration rate and renal plasma flow in humans with reduced renal function, we administered recombinant human IGF-I (rhIGF-I) to patients with moderate chronic renal failure. Four patients whose baseline inulin clearances were 21.9, 23.2, 34.9, and 55.1 ml.min-1.1.73 m-2 were placed on a 1 g.kg-1.day-1 protein diet and studied over a 10-day period (0-10). On days 4-7, 100 micrograms/kg of rhIGF-I was subcutaneously administered twice daily to the patients. The effects of rhIGF-I on levels of circulating IGF-I, inulin clearance, p-aminohippurate (PAH) clearance, kidney volume, plasma glucose, plasma and urine calcium and phosphate, and urine sodium and protein were determined. Administration of rhIGF-I increased levels of circulating IGF-I, inulin clearances, PAH clearances, and kidney size in each of the four patients receiving the growth factor. IGF-I did not cause weight gain, natriuresis, proteinuria, or hypoglycemia. Plasma calcium and phosphate were not affected by rhIGF-I. However, the percent tubular reabsorption of filtered phosphate was increased. We conclude that administration of rhIGF-I can enhance glomerular filtration rate and renal plasma flow at least in some humans with moderately reduced renal function. The enhancement is associated with an increase in kidney volume.

Adolescent↗
PubMed1993

Enhanced renal IGF-I expression following partial kidney infarction.

Renal insulin-like growth factor (IGF)-I expression is enhanced in tissue that remains following removal of kidney mass. To characterize the expression of renal IGF-I after reduction of kidney mass by partial unilateral infarction, we measured levels of IGF-I extracted from noninfarcted (remnant) renal tissue that remained after one-half unilateral kidney infarction that was performed without (1/2NX) or with (1 1/2NX) contralateral nephrectomy. Levels of IGF-I extracted from remnant renal tissue after 1/2NX increased significantly, peaking on day 3 after renal mass reduction, and then returned toward baseline. Steady-state levels of IGF-I mRNA were also elevated on day 3, suggesting that the increase in IGF-I results from enhanced synthesis. A similar pattern of increased extracted IGF-I and elevated IGF-I mRNA occurred after 1 1/2NX. Levels of IGF-I extracted from remnant renal tissue 3 days after 1 1/2NX were not higher than levels extracted from remnant tissue 3 days after 1/2NX, and both were higher than levels of IGF-I extracted from contralateral kidneys 3 days after unilateral nephrectomy. Therefore, levels of IGF-I did not correlate with the extent of reduction of renal mass per se. We conclude that partial renal infarction provides a stimulus to enhance IGF-I expression. Increased renal IGF-I must be considered in the interpretation of findings originating from use of remnant kidney models of chronic renal failure.

Animals↗
PubMed1993

The growth hormone insulin-like growth factor axis in kidney revisited.

Studies characterizing actions of growth hormone (GH) and insulin-like growth factors (IGF) in kidneys of adult and developing animals and humans have provided a good deal of insight into the functions of these peptides. Although certain of the actions may be mediated directly by GH, most appear to result from effects of GH to increase levels of circulating IGF or IGF produced in kidney. In addition to GH, epidermal growth factor (EGF) enhances the renal synthesis of IGF-I. Enhancement of renal IGF-I expression is GH independent in compensatory hypertrophy. Stimulation of kidney IGF-I production also occurs in diabetes mellitus. Renal IGF-I production is elevated in these settings in the absence of changes in circulating IGF-I, consistent with a causative role of renal IGF-I for the accompanying increased glomerular filtration rate and kidney growth. Actions of IGF in kidney are initiated following binding of peptides to specific receptors. Receptor number may be altered during compensatory growth and in diabetes mellitus. In addition to IGF, several IGF binding proteins (IGFBP) are produced in kidney and are likely to both inhibit and enhance the actions of IGF in different circumstances through sequestration of peptides and regulation of peptide interactions with their receptors. Administration of IGF-I to rats following acute ischemic injury hastens the recovery of normal renal function and accelerates the regeneration of the damaged proximal tubular epithelium. IGF-I increases the glomerular filtration rate in humans with normal and reduced functional kidney mass. These findings establish the potential for use of this peptide as a therapeutic agent in the settings of acute and chronic renal failure.

Animals↗
PubMed1992

Insulin-like growth factor I accelerates recovery from ischemic acute tubular necrosis in the rat.

The effects of administering insulin-like growth factor I (IGF-I) were examined in a model of ischemic acute tubular necrosis in rats. Injury was induced by 75 min of bilateral renal artery occlusion. Compared to rats administered vehicle, rats administered IGF-I (100 micrograms/day via continuous subcutaneous infusion) had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion. Glomerular filtration rate as determined by inulin clearance was examined on day 2 postocclusion and was significantly increased in IGF-I-treated animals (0.16 +/- 0.02 ml per min per 100 g of body weight) compared to vehicle-treated controls (0.08 +/- 0.02 ml per min per 100 g of body weight). The weight loss that occurred during the course of acute tubular necrosis was ameliorated by IGF-I. Mortality was reduced from 36.7% in vehicle-treated rats to 7.1% in rats administered IGF-I. Histologically, there was much less renal injury evident at day 7 postocclusion in the IGF-I-treated rats compared to vehicle-treated controls. In contrast, growth hormone (200 micrograms administered subcutaneously for 4 days) did not affect recovery of renal function or reduce mortality postreperfusion. This report demonstrates a beneficial effect of IGF-I administration in the setting of acute tubular necrosis. Several properties of IGF-I render it a pharmacological agent with excellent potential for treatment of this condition in humans.

Animals↗
PubMed1992

Affective moderators of the cardiovascular response to stress in offspring of hypertensives.

The present study examined the influence of trait anxiety on the cardiovascular responses of normotensive offspring of hypertensives and normotensives. Forty-eight young adult males, half of whom were offspring of hypertensives (PH+), were exposed to an extended active coping stressor. This was a 1 hr shock avoidance procedure with avoidance made contingent on video-game performance. Trait anxiety status interacted with parental history of hypertension in predicting cardiovascular response. PH+ subjects who scored high on trait anxiety exhibited greater elevations of heart rate and forearm blood flow, and decreases in forearm vascular resistance than did PH+/low trait anxiety subjects or offspring of normotensives (PH-). Cardiovascular responses of PH+/low trait anxiety subjects did not differ significantly from those of PH- subjects. Results suggest affective factors may moderate cardiovascular responses of individuals at risk for hypertension.

Adult↗
PubMed1992

CD4-independent inhibition of lymphocyte proliferation mediated by HIV-1 envelope glycoproteins.

The cytopathic effects of HIV-1 produced by direct infection of human T cells do not account for the disproportionate loss of CD4-positive lymphocytes during the course of HIV infection. Previous studies have demonstrated the inhibition of uninfected human T cell activation and proliferation by the HIV-1 envelope glycoproteins, presumably due to gp120-CD4 interactions. To examine the ability of HIV-1 to inhibit T cell proliferation in the absence of both direct infection and gp120-CD4 interactions, we tested the effect of HIV-1 on mouse T cell proliferation. Culture media containing HIV-1 released from infected cells inhibited T lymphocyte proliferation in response to interleukin-2 (IL-2). Studies to explore the mechanism of this inhibition suggested that the decrease in proliferation resulted from interactions between HIV-1 and the mouse cells, but did not involve IL-2/IL-2 receptor interactions. We used monoclonal antibodies to demonstrate that the HIV-1 envelope glycoproteins were required for the inhibition of murine T cell proliferation. Anti-gp120 antibodies completely restored proliferation, indicating that the surface protein gp120 was primarily required for the inhibition of proliferation. However, antibodies directed against the transmembrane protein of HIV-1 (gp41) also partially restored lymphocyte proliferation. The functional significance of the HIV-1 envelope protein epitopes recognized by the monoclonal antibodies is discussed.

Animals↗
PubMed1992

Increased distal nephron EGF content and altered distribution of peptide in compensatory renal hypertrophy.

Epidermal growth factor (EGF) precursor is synthesized within kidney in the thick ascending limbs of Henle's loop and in distal tubule. Under baseline conditions EGF precursor is localized to the luminal membrane. In contrast, functional EGF receptors are present in basolateral membranes of sensitive renal cells. Immunostainable EGF is increased in contralateral kidneys following uninephrectomy of rats. To confirm this increase and determine whether the distribution of EGF changes in this setting, we measured immunostainable EGF in kidneys originating from rats 1, 2, 5, or 14 days following unilateral nephrectomy or sham surgery. There was a suggestion of an increase in immunostainable EGF in distal tubules 5 days postnephrectomy and a definite increase 14 days postnephrectomy. At 1 or 2 days postnephrectomy, and following sham surgery, immunostainable EGF was present predominantly at luminal membranes. In contrast, immunostainable EGF was present more diffusely throughout distal tubular cells at 5 and 14 days postnephrectomy and clearly localized adjacent to both luminal and antiluminal membranes in kidneys obtained 14 days postnephrectomy. EGF extractable from kidneys was increased significantly 5 and 14 days postnephrectomy. This material is the size of mature EGF. The altered localization of immunostainable peptide indicates that a redistribution of intracellular EGF accompanies increased synthesis postnephrectomy. Antiluminal EGF precursor or mature EGF present within kidney could act as a paracrine growth factor.

Adaptation, Physiological↗