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Biomedical subjects

S B Miller

Publications and source records attributed to S B Miller.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Expression of insulin-like growth factor in adult and embryonic kidney.

Insulin-like growth factors (IGFs) I and II are proinsulin-like peptides. IGF I is produced in adult and embryonic kidney. It is likely that IGF I produced locally in adult kidney regulates processes of renal transport, metabolism and growth. Renal IGF I production is stimulated by growth hormone (GH) and by epidermal growth factor (EGF). The identity of additional factors that regulate IGF I gene expression in settings such as compensatory hypertrophy and diabetes mellitus is unknown. IGF I and IGF II produced in embryonic kidney promote the metanephrogenic process. The identity of factors that regulate metanephric IGF gene expression is yet to be determined.

Autoradiography↗
PubMed1991

Renal cellular biology of growth hormone and insulin-like growth factor I.

Growth hormone (GH) and insulin-like growth factor I (IGF-I) exert a variety of actions in renal tissue. To shed light upon the renal GH-IGF I axis we have characterized the cell biology of GH and IGF I in two parts of the nephron that are targets for these peptides, proximal tubule and collecting duct. Receptors for both GH and IGF I are present in the basolateral membrane of the renal proximal tubular cell. GH activates phospholipase C and IGF I stimulates phosphorylation of its receptor at this site. Both peptides directly enhance gluconeogenesis in proximal tubule. GH stimulates IGF I gene expression in collecting duct. IGF I of collecting duct origin could act as a paracrine growth factor in other portions of the nephron. IGF I may be causative of renal hypertrophy that occurs in the settings of hypersomatotropism, unilateral nephrectomy (compensatory hypertrophy) and diabetes mellitus.

Animals↗
PubMed1991

Exaggerated sympathetic nervous system response to extended psychological stress in offspring of hypertensives.

The cardiovascular responses of 24 healthy young adult males with a parental history of hypertension and 24 males without a parental history of hypertension to an extended active-coping psychological stressor were compared under three drug conditions: placebo, the beta 1-blocking agent metoprolol, and the alpha 1-blocking agent prazosin. In the placebo condition, offspring of hypertensives exhibited significantly greater heart rate, blood volume pulse, and forearm blood flow responses to the task. They also exhibited a significantly greater initial decrease in forearm vascular resistance, which, in contrast to the offspring of normotensives, was no longer significantly different from baseline levels by the end of the session. No group differences in blood pressure response were observed. Metoprolol eliminated the differences in heart rate and forearm vascular resistance responses. Prazosin eliminated the difference in blood volume pulse response and elicited a sustained group difference in forearm vascular resistance. These results implicate the sympathetic nervous system in the exaggerated cardiovascular responsivity to psychological stress in individuals with a family history of essential hypertension. They also suggest that the pattern of increasing vascular resistance in response to this stressor observed in this and other studies in this laboratory reflects alpha-adrenergic activity and not neurohumorally independent autoregulation.

Adult↗
PubMed1991

Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor.

The renal collecting duct is a site of insulin-like growth factor I (IGF I) synthesis. Epidermal growth factor (EGF) is also synthesized within the kidney in the thick ascending limb of Henle's loop and the distal tubule. EGF has been shown to regulate IGF I expression in nonrenal tissues. To shed light upon a role of EGF in intrarenal regulation of IGF I gene expression, plasma membranes prepared from collecting ducts isolated from rat kidney and collecting ducts themselves were incubated in the presence and absence of recombinant human EGF (hEGF). hEGF enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for EGF signal transduction at this site. Inclusion of hEGF in suspensions of collecting ducts increased production of immunoreactive IGF I in a concentration-dependent manner. Production was stimulated significantly by addition of 10(-8) or 10(-6) M hEGF to suspensions for 2 h. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M hEGF in vitro. Our findings demonstrate a direct action of hEGF to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect an effect of EGF to stimulate IGF I production in the collecting duct of the intact kidney. Since EGF is produced in kidney, our findings are consistent with intrarenal paracrine regulation of IGF I gene expression by EGF.

Animals↗
PubMed1991

Pneumothorax with Pneumocystis carinii pneumonia in AIDS. Incidence and clinical characteristics.

A retrospective review of the charts of patients with the acquired immunodeficiency syndrome (AIDS) was performed at three university-affiliated teaching hospitals in Denver between May 1982 and April 1987. Patients were evaluated for the presence or absence of Pneumocystis carinii pneumonia (PCP) and for the occurrence of pneumothorax at any time during their clinical course. The incidence of pneumothorax in AIDS patients with PCP was 9.0 percent (8/89), compared with 0 percent (0/45) in AIDS patients without PCP (p less than 0.03). All of the pneumothoraces resolved, most without chest tube placement. This study suggests that in patients with AIDS, PCP is associated with an increased incidence of pneumothorax, while AIDS patients without PCP are not at increased risk for the development of pneumothorax.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Intravenous immunoglobulin therapy in systemic lupus erythematosus-associated thrombocytopenia.

Seven patients with thrombocytopenia and systemic lupus erythematosus were treated with intravenous (IV) doses of human immunoglobulin to assess clinical response and to examine the mechanism of action of IV immunoglobulin in these patients. Five of 7 patients had a greater than 50% increase in their platelet counts. Four of these patients had a sustained benefit of at least 6 months duration. The initial effectiveness of IV immunoglobulin therapy was not dependent on the reduction of levels of circulating platelet-binding IgG or circulating immune complexes.

Antigen-Antibody Complex↗
PubMed1990

Renal expression of IGF I in hypersomatotropic states.

We examined insulin-like growth factor I (IGF I) gene expression in kidney in two models of hypersomatotropism, rats implanted with GH3 pituitary tumors, and rats administered exogenous growth hormone (GH). Both GH3 tumor-bearing rats and rats administered GH gained weight more rapidly than control animals, and had kidneys that were larger than those of controls. Tumor-bearing rats had increased levels of circulating IGF I. Glomeruli from tumor-implanted rats were sclerotic. Immunostainable IGF I was increased in medullary collecting ducts from tumor-bearing and GH-injected rats compared with kidneys from control animals. Levels of IGF I mRNA in kidneys of rats implanted with GH3 tumors and GH-injected rats were elevated compared with levels in kidneys from controls. Our findings demonstrate enhanced renal IGF I gene expression in hypersomatotropism. Stimulation of renal IGF I synthesis by GH could be causative of changes in renal function and renal size that occur in states of GH excess such as acromegaly.

Animals↗
PubMed1990

Growth hormone stimulates IGF I gene expression in isolated rat renal collecting duct.

To determine whether growth hormone (GH) directly stimulates insulin-like growth factor I (IGF I) gene expression in renal collecting duct, plasma membranes prepared from collecting ducts isolated from rat kidney, and collecting ducts themselves were incubated in presence and absence of GH. GH enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for GH-signal transduction. Inclusion of GH in suspensions of collecting ducts increased production of immunoreactive IGF I in a time-dependent and concentration-dependent manner. Production was stimulated significantly by addition of 10(-10), 10(-8), or 10(-6) M GH to suspensions for 2 h. IGF I produced in isolated collecting ducts was released into the suspending media. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M GH in vitro. IGF I of collecting duct origin was indistinguishable from recombinant human IGF I in terms of its size and receptor-binding characteristics. Our findings demonstrate a direct action of GH to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect the mechanism by which GH stimulates renal IGF I production in intact kidney.

Animals↗
PubMed1990

Effects of growth hormone and IGF-I on renal function in rats with normal and reduced renal mass.

To characterize actions of growth hormone (GH) and insulin-like growth factor ( (IGF-I) on renal function in rats with normal and reduced renal mass, we administered recombinant bovine growth hormone (bGH) or human IGF-I (hIGF-I) to normal rats or to rats that had undergone unilateral nephrectomy and two-thirds infarction of the contralateral kidney, and measured inulin and p-aminohippurate clearances over 10-17 days. Administration of either bGH (100-200 micrograms/day) or hIGF-I (200 micrograms/day) to rats with normal renal mass increased inulin and p-aminohippurate clearances compared with those measured in animals that received vehicle. Filtration fractions were not affected by either bGH or hIGF-I. Inulin clearance was decreased to approximately 17% of normal 1 day after reduction of renal mass in rats. Over the next 3 days insulin clearance increased significantly in rats with reduced renal mass that were administered vehicle. No further enhancement occurred during the next 7 days. Neither bGH nor hIGF-I affected inulin clearance in rats with reduced renal mass. We conclude that both GH and IGF-I enhance glomerular filtration rate when administered to rats with normal renal mass, but not when administered in the same quantities to rats in which renal functional mass is reduced. Glomerular filtration rate increases within 4 days of renal mass reduction independent of exogenous GH or IGF-I.

Animals↗
PubMed1989

Individual differences in heart rate and peripheral vascular responses to an extended aversive task.

Psychophysiological research on situations requiring active coping has to this point dealt primarily with cardiac responses. Recent studies of vascular responses to such stressors have found conditions in high cardiac reactors that are possible precursors to autoregulatory vasoconstriction. The present study exposed 32 healthy male undergraduates to a one-hour shock avoidance procedure, with avoidance made contingent on video-game performance. Subjects also participated in a separate counterbalanced baseline session. The relationships among individual differences in heart rate, forearm blood flow, forearm vascular resistance, and digital blood volume pulse responses at different points in the stress session were examined. Decreases in forearm vascular resistance were observed only among high and medium heart rate reactors. As the session progressed, however, forearm vascular resistance responses of the medium heart rate reactors were sustained whereas those of the high heart rate reactors habituated despite the fact that heart rate and forearm blood flow responses remained elevated. The potential implications of this pattern of results to an autoregulation theory of hypertension development are discussed. Heart rate reactivity was inversely related to performance on the video-game task but was unrelated to Type A or anxiety.

Adult↗
PubMed1989

Risk for hypertension in female members of multigenerational male-limited alcoholic families.

Cardiovascular hyperreactivity to psychological stress has been implicated as a risk factor for cardiovascular disease. Recent reports have suggested that male offspring of multigenerational male-limited alcoholic families display cardiovascular hyperreactivity to stress. Data concerning cardiovascular disease in 371 individuals from multigenerational male-limited alcoholic families and other family types of differing risk for alcoholism were subjected to chi 2 analyses. Results indicated a significantly greater incidence of hypertension in female members of multigenerational male-limited alcoholic families as compared to the other family types.

Adult↗
PubMed1989

Forearm blood flow responses of offspring of hypertensives to an extended stress task.

The forearm blood flow and other cardiovascular responses of 10 healthy young men with a parental history of hypertension to an extended laboratory stressor were compared with the responses of 10 age-matched men with normotensive parents. To eliminate the effects of the anticipation of stress on baseline measures, all subjects participated in a separate 1-hour counterbalanced baseline session in which no stress was presented. There were no significant differences between the two groups in resting blood pressure, heart rate, blood volume pulse, forearm blood flow and vascular resistance, and self-report anxiety, although offspring of hypertensive parents exhibited marginally greater (p = 0.08) forearm blood flow at rest. During the stress session, subjects played video games for 1 hour and avoided mild electric shocks depending on performance. Offspring of hypertensive parents exhibited significantly greater heart rate (+19 +/- 6 vs. +3 +/- 2%), forearm blood flow (+52 +/- 14 vs. +9 +/- 4%), and self-report anxiety (+25 +/- 6 vs. +9 +/- 3%) responses to the task. There were no significant group differences in blood pressure response to the task. Significant positive correlations between forearm blood flow and heart rate responses to the task were observed. These findings extend earlier results that suggested healthy young offspring of hypertensive and normotensive parents may exhibit different patterns of hemodynamic response to stress in the absence of differences in resting blood pressure or blood pressure responsiveness to stress.

Adult↗
PubMed1989

Shame as an impetus to the creation of conscience.

Shame 'absorbed by' guilt is an issue that was flagged for consideration by Erikson. The most compelling reason for using guilt to obscure shame is that guilt is associated with a sense of the self as strong, though burdened and culpable, whereas shame brings with it a painful sense of vulnerability. Erikson described the way in which compulsive ordering-about of the self allows a child to feel less helpless and less vulnerable to the shame affect. In instituting this type of self-directive behaviour, the child is developing conscience. The irony of this type of self-manipulation is that ultimately the child, or adult, finds himself again burdened by impotence, though it is the impotence of guilt rather than that of shame. The topic of shame yielding to guilt is of interest in part because it demonstrates the highly interactive relationship between narcissistic concerns and superego responses to impulse-expression, and the role of such interactions in the formation of psychological structures.

Adolescent↗