Biomedical subjects

A J King

Publications and source records attributed to A J King.

At least 19 recordsLinked to original sources

PubMed1995

Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study.

OBJECTIVE: To examine the relations among proteinuria, prescribed and achieved blood pressure, and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study. DESIGN: 2 randomized trials in patients with chronic renal diseases of diverse cause. SETTING: 15 outpatient nephrology practices at university hospitals. PATIENTS: 840 patients, of whom 585 were in study A (glomerular filtration rate, 25 to 55 mliters/min.1.73 m2) and 255 were in study B (glomerular filtration rate, 13 to 24 mliters/min.1.73 m2). Diabetic patients who required insulin were excluded. INTERVENTIONS: Patients were randomly assigned to a usual blood pressure goal (target mean arterial pressure, < or = 107 mm Hg for patients < or = 60 years of age and < or = 113 mm Hg for patients > or = 61 years of age) or a low blood pressure goal (target mean arterial pressure, < or = 92 mm Hg for patients < or = 60 years of age and < or = 98 mm Hg for patients > or = 61 years of age). MAIN OUTCOME MEASURES: Rate of decline in glomerular filtration rate and change in proteinuria during follow-up. RESULTS: The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01). Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A (r = -0.20; P < 0.001) and study B (r = -0.34; P < 0.001), and these correlations were stronger in persons with higher baseline proteinuria (P < 0.001 in study A; P < 0.01 in study B). In study A, the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial pressure. In both studies, the low blood pressure goal significantly reduced proteinuria during the first 4 months after randomization. This, in turn, correlated with a slower subsequent decline in glomerular filtration rate. CONCLUSIONS: Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease. For patients with proteinuria of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable. The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of this therapy in slowing the progression of renal disease.

Adolescent↗

PubMed1995

Selective proteolysis of arrestin by calpain. Molecular characteristics and its effect on rhodopsin dephosphorylation.

Visual arrestin (48 kDa) plays a role in the deactivation of rhodopsin by binding to the light-activated, phosphorylated form of the receptor. In bovine rod outer segments that were prepared in the presence of protease inhibitors, two faster migrating forms of arrestin, with apparent molecular masses of 46 and 44 kDa, were observed by Western blot analysis. The 46-kDa form was more evident in rod outer segments of eyes kept in the light than those placed in darkness and was found to be identical to that generated by in vitro proteolysis of arrestin by pure retinal calpain II. In vitro analysis showed that arrestin was proteolyzed only when bound to rhodopsin; soluble arrestin was not significantly cleaved by calpain. Proteolysis involves sequential cleavage at two, possibly three sites, resulting in the removal of 27 amino acids from the COOH terminus. The remaining 46-kDa protein was resistant to further proteolysis by calpain. Unlike intact arrestin, the 46-kDa truncated arrestin was not readily released from the receptor after the receptor had lost its chromophore, nor was it released upon the addition of 11-cis-retinal to regenerate the receptor. Truncated arrestin was found to inhibit receptor dephosphorylation to the same extent as intact arrestin. In conclusion, these results provide evidence that a 46-kDa form of arrestin in rod outer segments is a product of selective proteolysis by calpain. Furthermore, they suggest that this proteolysis may provide a mechanism for prolonging the phosphorylated state of the visual receptor.

Adenosine Triphosphate↗

PubMed1995

Effects of eye position on auditory localization and neural representation of space in superior colliculus of cats.

The maps of visual and auditory space within the superior colliculus are in approximate register both with each other and with the underlying motor maps associated with orienting responses. The fact that eyes and ears can move independently poses a problem for the sensorimotor organization of these two modalities. By monitoring eye and pinna positions in alert, head-fixed cats, we showed that the accuracy of saccadic eye movements to auditory targets was little affected by eye eccentricity (range +/- 15 deg) at the onset of the sound. A possible neural basis for this behavioral compensation was suggested by recordings from superior colliculus neurons. The preferred sound directions of some neurons in the deep layers of this midbrain nucleus exhibited a shift with the direction of gaze, while in others the response throughout the auditory receptive field was either increased or decreased, suggesting that changes in eye position alter the gain of the auditory response.

Acoustic Stimulation↗

PubMed1995

Spontaneous recovery rates for unilateral sixth nerve palsies.

Two hundred and thirteen patients with unilateral isolated sixth nerve palsies were assessed to determine what proportion of them underwent spontaneous recovery and over what period of time this recovery occurred. All were primary ophthalmic referrals from which trauma was excluded. In all, 78.4% of patients experienced spontaneous recovery of their palsy, 36.6% recovering by 8 weeks and 73.7% by 24 weeks. Only 16.4% failed to recover. Of this group, however, nearly 40% had serious underlying pathology accounting for their palsy.

Abducens Nerve↗

PubMed1995

Diffusive and convective transfer of cytokine-inducing bacterial products across hemodialysis membranes.

The widespread use of bicarbonate dialysate, and high-flux and high-efficiency dialyzers have raised concerns regarding the transmembrane passage of bacterial products from the dialysate into the blood compartment. To study the mechanisms as well as magnitude of the transmembrane transfer of bacterial products from the dialysate, we developed a computerized in vitro dialysis model which provides continuous pressure recording from the arterial, venous, dialysate inflow and outflow ports. By virtue of a computer controlled on-line infusion pump, this model permits control of ultrafiltration/backfiltration. Heparinized (10 U/ml) whole blood (150 ml) was circulated through the blood compartment for 120 minutes at 100 ml/min. Bicarbonate dialysate contaminated with Pseudomonas maltophilia filtrate was circulated through the dialysate compartment at 100 ml/min. A two-point pressure of -10 mm of Hg (ultrafiltration) was maintained for the first 60 minutes and -10 mm of Hg (backfiltration) for the next 60 minutes. Whole blood samples (10 ml) were drawn from the blood at 0, 60 and 120 minutes. Peripheral blood mononuclear cells (PBMC) harvested from these samples were incubated for 24 hours in tissue culture medium. In addition, 0.5 ml samples of dialysate were collected at 0, 60 and 120 minutes and incubated with PBMC from the same donor for 24 hours. After 24 hour incubation, total cell-associated IL-1Ra and IL-1 beta were measured by specific radioimmunoassay. Paired experiments were performed with eight high-flux synthetic membranes (polyamide) and eight low-flux cellulose membranes (hemophan). Cytokine production is expressed as pg/2.5 million PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

PubMed1992

Endothelin-1 stimulates the Na+/H+ and Na+/HCO3- transporters in rabbit renal cortex.

Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor identified to date, raising the strong possibility of its involvement in the pathogenesis of systemic hypertension. Whether ET-1 exerts a direct stimulating effect on sodium reabsorption in the renal proximal convoluted tubule, the dominant locus of sodium reabsorption in the nephron, is currently unknown. Such an effect would suggest yet another mechanism by which ET-1 might mediate systemic hypertension. In studies on membrane vesicles prepared from rabbit renal cortex, we show that ET-1 (10(-8) to 10(-11) M) exerts dose-dependent stimulation of the apical Na+/H+ exchanger and the basolateral Na+/HCO3- cotransporter; preincubation of vesicles with 10(-10) M ET-1 for five minutes enhanced the activity of each transporter by approximately 25%. This stimulation reflected an increase in the Vmax of each transporter but no change in the Km for sodium. The stimulatory effect of ET-1 was blocked in the presence of an ET-1 antiserum. Moreover, the stimulation of the apical Na+/H+ exchanger and the basolateral Na+/HCO3- cotransporter by ET-1 displayed specificity as indicated by the lack of effects on the activities of the apical Na(+)-glucose transporter and the basolateral Na(+)-succinate transporter. The data implicate ET-1 as a novel, direct and specific modulator of sodium reabsorption in the proximal tubule. As such, ET-1 might be a direct determinant of extracellular fluid volume under normal and pathophysiologic circumstances, including hypertensive disorders.

Animals↗

PubMed1992

In vitro production of interleukin-1 receptor antagonist in chronic renal failure, CAPD and HD.

Dialysis-related symptoms are believed to be mediated, at least in part, by monocyte/macrophage-derived pro-inflammatory cytokines including interleukin-1 (IL-1) and tumor necrosis factor (TNF). Measuring the production of interleukin-1 receptor antagonist (IL-Ra), a naturally occurring inhibitor of IL-1, opens avenues to study the balance between these two cytokines in patients. We studied the cell content and production of IL-1 beta and IL-Ra by unstimulated and endotoxin- or IgG-stimulated peripheral blood mononuclear cells (PBMC) in undialyzed patients with chronic renal failure (CRF), patients on continuous ambulatory peritoneal dialysis (CAPD) and patients on chronic hemodialysis with reuse cuprophan membranes (HD), and compared them to healthy controls. IL-1 beta and IL-Ra were measured by specific radioimmunoassay. IL-1 beta was undetectable in freshly harvested PBMC from healthy controls, CRF, CAPD or HD. In contrast, the content of IL-Ra in HD patients (2828 +/- 466 pg/ml) was significantly higher than that in healthy controls (643 +/- 53 pg/ml, P < 0.01), CRF (1097 +/- 320 pg/ml, P < 0.01) or CAPD (1398 +/- 390 pg/ml, P < 0.05). In endotoxin-stimulated PBMC, IL-1 beta production by HD patients (9375 +/- 1687 pg/ml) was not significantly different from healthy controls (8429 +/- 1621 pg/ml). However, endotoxin-stimulated IL-Ra production by HD patients (32,350 +/- 8276 pg/ml) was greater than that from healthy controls (11,284 +/- 1250 pg/ml, P < 0.001), CRF (12,263 +/- 2680 pg/ml, P < 0.01) or CAPD patients (11,822 +/- 1797 pg/ml, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Plasticity of auditory maps in the brain.

The central auditory pathway contains maps of sound frequency that reflect the functional organization of the cochlea, as well as topographic representations of other stimulus features, such as sound location, that are synthesized within the brain. Both types of map undergo changes during development and are shaped by experience. This is particularly true of the representation of auditory space in the superior colliculus, which can be modified by alteration of auditory and visual inputs early in life. Although experience-induced plasticity in this map is restricted primarily to the developmental period, the frequency representation in the cortex of adult animals can re-organize following partial deafness.

Acoustic Stimulation↗

PubMed1991

Endothelium-derived vasoactive factors and the renal vasculature.

The endothelium is now recognized to transduce intravascular hemodynamic and chemical signals into appropriate changes in vascular smooth muscle (VSM) tone. The effector branch of this transduction is due, at least in part, to endothelial release of potent soluble vasoactive mediators. Two such mediators, endothelium-derived relaxing factor (EDRF) and endothelin, have markedly different chemical composition and contrasting effects on VSM tone. EDRF, identified to be nitric oxide or a nitrosothiol, is a vasodilator, whereas endothelin, a 21-amino acid polypeptide, is the most potent vasoconstrictor yet described. Considerable evidence has been amassed to suggest that these molecules play an important role in the regulation of basal renal hemodynamics and in the pathogenesis of acute renal failure. The purpose of this editorial review is to examine the data supporting a role for the endothelium in the regulation of renal hemodynamics in normal and pathological states.

Acute Kidney Injury↗

PubMed1991

Re-examination of the basicranial anatomy of the Megachiroptera.

Basicranial anatomy is helpful in attempts at reconstructing phylogenetic relationships. Recent descriptions of megachiropteran basicrania contradict earlier reports from the beginning of the century and support a monophyletic origin of the Chiroptera. The anatomy of the carotid circulation and the tympanic cavity in the Megachiroptera is examined here, and the results are compared with the two previous conflicting reports. The results from this investigation support the earlier studies and refute some of the basicranial synapomorphies supporting chiropteran monophyly.

Animals↗

PubMed1991

Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.

The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1991

Endothelium-derived relaxing factor and the vascular reply to systemic hypertension.

Endogenous nitric oxide is an important modulator of vascular smooth muscle tone. The role of nitric oxide in the vascular adaptation to systemic hypertension was examined by using N omega-monomethyl-L-arginine (L-NMMA; 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused i.v. into several rat models of acute and chronic systemic hypertension. The response to L-NMMA was compared either in uninephrectomized Sprague-Dawley rats treated with deoxycorticosterone on either a high- or low-sodium diet or in untreated uninephrectomized rats on normal chow. Hypertensive deoxycorticosterone rats had a significantly greater pressor response to L-NMMA (139 +/- 2 to 169 +/- 3 mm Hg; N = 9) than did normotensive uninephrectomized rats (112 +/- 4 to 129 +/- 3 mm Hg; N = 7) or deoxycortisterone treated rats on a low-sodium diet (108 +/- 2 to 121 +/- 3 mm Hg; N = 9). By contrast, hypertension induced by the vasoconstrictor angiotensin II did not have an enhanced response (134 +/- 3 to 154 +/- 4 mm Hg; N = 7) nor did spontaneously hypertensive rats (164 +/- 4 to 175 +/- 4 mm Hg; N = 6). This dose of L-NMMA had minimal effects on renal hemodynamics in the normotensive and hypertensive animals, except for those receiving angiotensin II where it led to substantial reductions of inulin and para-aminohippurate clearance. In conclusion, these data point to a role for nitric oxide in the vascular adaptation to volume-mediated hypertension, an effect that was not observed in vasoconstrictor-induced hypertension.

Acute Disease↗

PubMed1990

Systemic hemodynamic effects of endothelin in rats.

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.

Angiotensin II↗

PubMed1990

Combined endoscopic cytology and biopsies in the diagnosis of duodenal malignancy.

The value of combined cytohistochemical examination in the diagnosis of malignant duodenal lesions was assessed in 78 patients with suspicious duodenal lesions seen at endoscopy. Cytological smears were taken using the direct-vision brushing technique and all were processed by the same experienced cytologist. Duodenal malignancy was confirmed histologically in four patients. Endoscopic biopsy was positive for malignancy in three of the patients and cytology was suspicious of malignant change in two patients and positive for malignant change in one patient. Cytology alone confirmed the diagnosis of malignancy in one patient. The cumulative diagnostic yield using both biopsy and cytology was 100%.

Biopsy↗

PubMed1989

Highlights from the Canada youth and AIDS study.

The identification of Acquired Immunodeficiency Syndrome (AIDS) in 1981, and the subsequent isolation of the human immunodeficiency virus (HIV) in 1983, signaled the beginning of worldwide concern over the potential impact of the disease. As the global incidence of AIDS and HIV infection increased, Canadians expressed growing apprehension about the epidemic's affect on themselves. Because adolescents potentially are at risk for HIV infection, a special need existed to determine how Canadian youth were responding to the AIDS epidemic. During the summer of 1987, the Federal Centre for AIDS, in conjunction with the National Health Research and Development Program and the Canadian Public Health Association, commissioned a nationwide study. A national sample of more than 38,000 youth in grades 7, 9, 11, and the first year of college and university were surveyed about their knowledge, attitudes, and behavior concerning AIDS and other sexually transmitted diseases (STDs). Also included in the total sample were youth who had recently dropped out of school and those who lived on the streets of large cities. In this article, the authors summarize findings from the study and offer conclusions and recommendations for action.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Endothelin: a potent renal and systemic vasoconstrictor peptide.

Endothelin is an endothelial cell-derived peptide recently shown to possess potent vasoconstrictor properties. Bolus intravenous injections of endothelin (5-450 pmol) into anesthetized Munich-Wistar rats induced a marked pressor effect, the magnitude and duration of which were dose dependent. Maximal systemic and renal responses occurred within 20 min and persisted for greater than 90 min in the higher dose range. In response to bolus dosages of 25 pmol or greater, renal plasma flow fell proportionately more than glomerular filtration rate, resulting in an increase in filtration fraction. In micropuncture studies of rats given continuous intravenous infusions of endothelin (0.63 pmol/min), the peptide caused a proportionately greater elevation of efferent than afferent arteriolar resistance, with a marked elevation of glomerular capillary hydraulic pressure and a lower glomerular capillary ultrafiltration coefficient. Endothelin was modestly natriuretic when systemic pressure rose and renal function was not severely impaired. This potent renal and systemic vasoconstrictor may play an important role in glomerular injury and in the pathophysiology of a variety of clinical microvasculopathies.

Animals↗

PubMed1989

Hyperlipidemia and glomerular sclerosis: an alternative viewpoint.

Clinical and experimental observations suggest an association between hypercholesterolemia and progressive glomerular injury. In the main, most investigators have assumed that hypercholesterolemia induces an atherosclerotic process in the renal microvasculature analogous to that well recognized in larger vessels. The evidence for this line of reasoning is well described in other papers in this symposium. It is our belief that hypercholesterolemia may also lead to glomerular injury by hemodynamic mechanisms. In support of this latter view, diet-induced hypercholesterolemia often raises blood pressure in experimental animals and markedly impairs endothelial cell-dependent vascular relaxation in vitro. A high cholesterol diet also increases renal vascular resistance and contributes to glomerular capillary hypertension, a hemodynamic maladaptation known to cause glomerular sclerosis. In addition, hypercholesterolemia results in hyperviscosity, a rheologic abnormality leading to increased efferent arteriolar resistance and glomerular hypertension. The similar glomerular hemodynamic responses to two hyperviscosity states, elevated hematocrit and hypercholesterolemia, implicate efferent arteriolar hyperviscosity as a potential mechanism of injury common to hyperviscosity states. It therefore seems likely that as in atherosclerosis, multiple risk factors act synergistically to initiate glomerular structural injury. Specifically, we suggest that hypercholesterolemia and glomerular hypertension act synergistically to initiate structural injury. Although modification of either risk factor may limit injury, it seems likely that therapy targeted to each of multiple risk factors may afford superior protection.

Animals↗

PubMed1989

Auditory brain stem of the ferret: some effects of rearing with a unilateral ear plug on the cochlea, cochlear nucleus, and projections to the inferior colliculus.

To examine the influence of acoustic experience on the development of the mammalian auditory brain stem, darkly pigmented ferrets were reared with a plug inserted in the right outer ear. The plugs were first inserted on postnatal day 23-34 and produced a variable, frequency-dependent attenuation of up to 60 dB. Between 3-15 months after the ear plug was begun, animals were prepared for physiological recording and injection of wheat germ agglutinin-HRP (WGA-HRP) in the left inferior colliculus (IC). The plug was removed and the condition of the right ear was assessed by pure-tone stimulation and recordings from neurons in the left IC. Neural audiograms for each animal showed a residual deficit in most cases. Following 24-60 hr survival, the animals were perfused and the right ear was examined. Brain-stem sections were reacted with tetramethylbenzidine. Outer and/or middle ear pathology was present in over half of the animals. However, the cochleas appeared to be normal and the spiral ganglion cells were normal by several quantitative criteria: number, area, and nucleolar eccentricity. The volume of each division of the cochlear nuclei (CN) and the areas of individual neurons in the anteroventral CN were the same on the right and left sides. The number of CN neurons retrogradely labeled from the left IC injection of WGA-HRP was found to be significantly increased in the left CN, relative to normal animals, when expressed as a ratio of the number labeled in the right CN. We conclude that the residual hearing loss in the previously plugged ears was predominantly or exclusively conductive. Neonatal, unilateral conductive hearing loss in the ferret does not lead to degeneration of the CN on the side of the loss, but it does lead to at least one rearrangement of auditory brain-stem connectivity. We suggest that the extent to which the brain stem is modified by early auditory deprivation is dependent on the type, degree, and symmetry of the hearing loss.

Animal Husbandry↗