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Biomedical subjects

J A Oliver

Publications and source records attributed to J A Oliver.

At least 19 recordsLinked to original sources
PubMed2006

Vasopressin administration facilitates fluid removal during hemodialysis.

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Antidiuretic Agents↗
PubMed2006

Receptor-mediated actions of renin and prorenin.

Renin can induce renal disease by generating angiotensin II and, thereby, increasing fibrosis. Huang et al describe a new mechanism of action whereby the renin-angiotensin system can also exert this effect. Direct activation of the renin/prorenin receptor in mesangial cells induced synthesis of TGF-beta and profibrotic proteins. Hence, like other proteases such as thrombin, renin and prorenin are capable of receptor-mediated cellular signaling.

Angiotensin II↗
PubMed2006

Blood pressure instability during hemodialysis.

Most patients with end-stage renal disease (ESRD) maintained on hemodialysis have chronic hypertension. However, hypotension is a frequent complication of hemodialysis, probably because of impaired baroreflex function. Less frequently, increases in pressure can be a complication of hemodialysis. Detailed studies of patients with these abnormalities in arterial pressure during hemodialysis may yield insights into the regulation of arterial pressure during ESRD.

Baroreflex↗
PubMed2004

Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system.

Using a cell-based model system of coagulation, we performed a systematic examination of the effect of varying individual procoagulant proteins (over the range of 0-200% of pooled plasma levels) on the characteristics of thrombin generation. The results revealed a number of features unique to the different coagulation factors, as well as common features allowing them to be grouped according to the patterns observed. Variation of those factors contributing to formation of the tenase complex, factor (F)VIII, factor (F)IX and factor (F)XI, primarily affected the rate and peak of thrombin production, but had little to no effect on total thrombin production. The effect of decreased FXI was milder than seen with decreased FVIII or FIX, and more variable between platelet donors. In contrast, varying the concentration of factors that contribute to formation of the prothrombinase complex, prothrombin or factor (F)V (with FV-deficient platelets), significantly affected all three measures of thrombin production: rate, peak and total. Additionally, while no thrombin generation was observed with no factor X, only very small amounts (between 1% and < 10% of normal plasma levels) were required to normalize the measured parameters. Finally, our results with this cell-based system highlight differences in thrombin generation on cell surfaces (platelets) compared with phospholipids, and suggest that platelets contribute more than simply a surface for the generation of thrombin.

Blood Coagulation Factors↗
PubMed2001

LRP: a new adhesion molecule for endothelial and smooth muscle cells.

We recently generated a monoclonal antibody that disrupted the association of endothelial cells with their target location during kidney development. Here, we purified the antigen of this monoclonal antibody to homogeneity using rat mesangial cell cytosol. Sequence revealed that it is a previously identified protein, termed the "laminin receptor precursor" (LRP). We found that this protein is expressed in most tissues, but immunocytochemistry revealed that it is present largely or entirely in blood vessels where it is located underneath endothelial cells and in between smooth muscle cells of the vascular wall. Vascular smooth muscle cells such as mesangial cells produce and secrete LRP into their extracellular matrix where it is present in several molecular weight forms. Endothelial cells produce very little if any of the protein, but they bind avidly to LRP-coated dishes. Anti-LRP antibodies prevent the binding of smooth muscle cells to uncoated plates, implying that cells that secrete it use it for attachment. In an assay for heterologous cell-to-cell interaction, antibodies to LRP inhibited the binding of smooth muscle cells to endothelial cells. Maturation and differentiation of blood vessels require interaction between endothelial and smooth muscle cells. LRP is a new component of the mesangial matrix, and we propose that it is an adhesion molecule that mediates an interaction between smooth muscle cells and endothelia.

Amino Acid Sequence↗
PubMed2001

Cardiac involvement in autosomal-dominant polycystic kidney disease: a hypertensive heart disease.

BACKGROUND: There is little information regarding the occurrence and distribution of cardiovascular abnormalities during the course of autosomal-dominant polycystic kidney disease (ADPKD). We conducted a cross-sectional study in three different groups of ADPKD patients to determine the profile and prevalence of cardiac involvement in this population. METHODS: Doppler color echocardiography was performed in 130 ADPKD patients. Patients were divided into normotensive (Group I, n=60), hypertensive (Group II, n=32) and those undergoing hemodialysis (Group III, n=38). RESULTS: There was a progressive increase in left ventricular mass (LVM) index (88.6+/-19.7, 127.6+/-40.4 and 150.5+/-56.5 g/m2, p < 0.0001) and in the prevalence of left ventricular hypertrophy (LVH) (3%, 43%, 62%, p < 0.0001) in Groups I, II and III, respectively. E/A ratio < 1 was found in 2% of normotensives, 46% of hypertensives and 62% of hemodialysis patients (p < 0.0001). Prevalence ofmitral valve prolapse and aortic and/or mitral regurgitation was 4.3% and 8.6%, respectively, in non-dialysis patients. The majority of valvular abnormalities occurred in dialysis patients, and were generally related to annular mitral calcification (28%) or aortic valve calcification (38%). Age, sex, systolic blood pressure (BP) and hemoglobin were independent predictors of LVM index in the entire population, systolic BP and creatinine in non-dialysis patients and systolic BP in dialysis patients. Age, heart rate and diastolic BP in the entire group, and age, heart rate and LVM index in non-dialysis patients remained as independent predictors of abnormal diastolic function. CONCLUSIONS: Cardiac involvement in ADPKD patients is a continuous process that evolves during the course of this disease. It is characterized by a low prevalence of specific valvular abnormalities, a progressive increase in LVM, LVH, and diastolic dysfunction, which are greatest in the latter stages of the disease. This study confirms the major influence of BP on cardiovascular abnormalities of ADPKD patients.

Adult↗
PubMed2000

Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure.

The use of phosphodiesterase inhibitors such as milrinone in the treatment of severe heart failure is frequently restricted because they cause vasodilation and hypotension. In patients with decompensated heart failure with hypotension after treatment with milrinone, low doses of vasopressin restored blood pressure without inhibiting the inotropic effect of milrinone.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Sonographic pattern of recessive polycystic kidney disease in young adults. Differences from the dominant form.

BACKGROUND: To study the sonographic pattern of autosomal recessive polycystic kidney disease (ARPKD) in early adulthood in order to identify imaging criteria to diagnose this disease and to distinguish between recessive and autosomal dominant polycystic kidney disease (ADPKD) in that age group. METHODS: An abdominal ultrasound was performed on four ARPKD subjects (with a mean age of 20.2) and on 33 ADPKD subjects in early adulthood (29 without renal failure with a mean age of 20.5, and four with renal failure with a mean age of 26.5). Linkage studies with ADPKD and ARPKD markers were compatible with the clinical diagnosis in all cases. RESULTS: The renal sonographic features in ARPKD subjects included multiple small cysts in a normal-sized kidney, increased cortical echogenicity and loss of corticomedullary differentiation. In ADPKD subjects without renal failure, sonographic features included few or multiple cysts of different sizes, in normal-sized kidneys in 22 out of 29 patients (75.8%), normal cortical echogenicity and conserved corticomedullary differentiation, except in patients with nephromegaly. All ADPKD subjects with renal failure had nephromegaly and loss of corticomedullary differentiation. The hepatic sonographic features in ARPKD patients included portal fibrosis and in some cases Caroli's disease, while in ADPKD patients a normal hepatic echostructure was detected in all but one case, in addition to simple hepatic cysts in a few cases. CONCLUSIONS: The evaluation of the sonographic features of the kidneys and those of the liver may help in the differential diagnosis between ARPKD and ADPKD in early adulthood.

Adult↗
PubMed2000

Vasopressin as an alternative to norepinephrine in the treatment of milrinone-induced hypotension.

OBJECTIVE: To determine whether vasopressin could be effective in treating the hypotension associated with phosphodiesterase III inhibition. Phosphodiesterase III inhibitors are cardiotonic agents that increase myocardial contractility and decrease vascular smooth muscle tone. The vasodilatory effect can be profound, and the resulting hypotension frequently requires the administration of catecholamine pressors. DESIGN: Retrospective analysis of existing data. SETTING: The medical or surgical intensive care unit of Columbia-Presbyterian Medical Center. PATIENTS: Three consecutive patients receiving milrinone and requiring catecholamine pressors to maintain systolic arterial pressure of > or =90 mm Hg. INTERVENTIONS: Vasopressin was administered to the three patients. MEASUREMENTS AND MAIN RESULTS: Vasopressin (0.03-0.07 units/min) increased systolic arterial pressure from 90+/-4.7 to 130+/-2.3 mm Hg while reducing the administration of catecholamine pressors. CONCLUSIONS: Vasopressin at very low doses appears to be an effective vasopressor for milrinone-induced hypotension.

Aged↗
PubMed1999

Mesenchymal to epithelial conversion in rat metanephros is induced by LIF.

Inductive signals cause conversion of mesenchyme into epithelia during the formation of many organs. Yet a century of study has not revealed the inducing molecules. Using a standard model of induction, we found that ureteric bud cells secrete factors that convert kidney mesenchyme to epithelia that, remarkably, then form nephrons. Purification and sequencing of one such factor identified it as leukemia inhibitory factor (LIF). LIF acted on epithelial precursors that we identified by the expression of Pax2 and Wnt4. Other IL-6 type cytokines acted like LIF, and deletion of their shared receptor reduced nephron development. In situ, the ureteric bud expressed LIF, and metanephric mesenchyme expressed its receptors. The data suggest that IL-6 cytokines are candidate regulators of mesenchymal to epithelial conversion during kidney development.

Animals↗
PubMed1999

Reversal by vasopressin of intractable hypotension in the late phase of hemorrhagic shock.

BACKGROUND: Hypovolemic shock of marked severity and duration may progress to cardiovascular collapse unresponsive to volume replacement and drug intervention. On the basis of clinical observations, we investigated the action of vasopressin in an animal model of this condition. METHODS AND RESULTS: In 7 dogs, prolonged hemorrhagic shock (mean arterial pressure [MAP] of approximately 40 mm Hg) was induced by exsanguination into a reservoir. After approximately 30 minutes, progressive reinfusion was needed to maintain MAP at approximately 40 mm Hg, and by approximately 1 hour, despite complete restoration of blood volume, the administration of norepinephrine approximately 3 micrograms . kg(-1). min(-1) was required to maintain this pressure. At this moment, administration of vasopressin 1 to 4 mU. kg(-1). min(-1) increased MAP from 39+/-6 to 128+/-9 mm Hg (P<0.001), primarily because of peripheral vasoconstriction. In 3 dogs subjected to similar prolonged hemorrhagic shock, angiotensin II 180 ng. kg(-1). min(-1) had only a marginal effect on MAP (45+/-12 to 49+/-15 mm Hg). Plasma vasopressin was markedly elevated during acute hemorrhage but fell from 319+/-66 to 29+/-9 pg/mL before administration of vasopressin (P<0.01). CONCLUSIONS: Vasopressin is a uniquely effective pressor in the irreversible phase of hemorrhagic shock unresponsive to volume replacement and catecholamine vasopressors. Vasopressin deficiency may contribute to the pathogenesis of this condition.

Adult↗
PubMed1999

Severe hyperkalemia with minimal electrocardiographic manifestations: a report of seven cases.

Severe hyperkalemia with minimal or nonspecific electrocardiographic (ECG) changes is unusual. We report data on seven patients with renal failure, metabolic acidosis, and severe hyperkalemia (K+ > or =8 mmol/L) without typical ECG changes. Initial ECGs revealed sinus rhythm and PR and QT intervals in the normal range. QRS intervals were slightly prolonged in two patients (110 ms), and incomplete right bundle branch block was evident in one. Thus, the absence of typical ECG changes does not preclude severe hyperkalemia.

Acidosis↗
PubMed1999

Echocardiographic evaluation in patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

Cardiovascular abnormalities have been considered important extrarenal manifestations of autosomal dominant polycystic kidney disease (ADPKD). However, little is known about their prevalence in patients with ADPKD undergoing hemodialysis (HD). To investigate whether cardiac abnormalities are more prevalent in these patients, clinical and echocardiographic manifestations of cardiovascular disease were evaluated in a group of 32 patients with ADPKD and a matched control group of 32 patients without diabetes treated by chronic HD for more than 6 months. Predialysis systolic and diastolic blood pressure (BP), prevalence of hypertension, and number of patients requiring antihypertensive medications were lower in the ADPKD group than controls. There was no difference in the prevalence of cardiac events, including cardiac failure, ischemic heart disease, and arrhythmia. Systolic dysfunction, diastolic patterns, and left ventricular hypertrophy were similar in the two groups. In patients with ADPKD, simple regression analysis showed left ventricular mass (LVM) index was correlated with hemoglobin level and predialytic systolic and diastolic BPs. In multiple regression analysis, predialysis systolic BP was the only independent variable linked to LVM index. The prevalence of aortic, mitral, and tricuspid valve disease did not differ between groups. In conclusion, the occurrence of cardiovascular complications in patients with ADPKD is similar to that of HD patients with other primary renal diseases, although hypertension is less prevalent.

Aged↗
PubMed1999

Thrombin activates factor XI on activated platelets in the absence of factor XII.

Thrombin can activate factor XI in the presence of dextran sulfate or sulfatides. However, a physiological cofactor for thrombin activation of factor XI has not been identified. We examined this question in a cell-based, tissue factor-initiated model system. In the absence of factor XII, factor XI enhanced thrombin generation in this model. The effect on thrombin generation was reproduced by 2 to 5 pmol/L factor XIa. A specific inhibitor of factor XIIa did not diminish the effect of factor XI. Thus, factor XI can be activated in a model system that does not contain factor XIIa or nonphysiological cofactors. Preincubation of factor XI with activated platelets and thrombin or factor Xa enhanced subsequent thrombin generation in the model system. Preincubation of factor XI with thrombin or factor Xa, but without platelets, did not enhance thrombin generation, suggesting that these proteases might activate factor XI on platelet surfaces. Thrombin and factor Xa were then directly tested for their ability to activate factor XI. In the presence of dextran sulfate, thrombin or factor Xa activated factor XI. Thrombin, but not factor Xa, also cleaved detectable amounts of factor XI in the presence of activated platelets. Thus, thrombin activates enough factor XI to enhance subsequent thrombin generation in a model system. Platelet surfaces might provide the site for thrombin activation of functionally significant amounts of factor XI in vivo.

Anticoagulants↗
PubMed1999

Tissue inhibitor of metalloproteinase-2 stimulates mesenchymal growth and regulates epithelial branching during morphogenesis of the rat metanephros.

Development of the embryonic kidney results from reciprocal signaling between the ureteric bud and the metanephric mesenchyme. To identify the signaling molecules, we developed an assay in which metanephric mesenchymes are rescued from apoptosis by factors secreted from ureteric bud cells (UB cells). Purification and sequencing of one such factor identified the tissue inhibitor of metalloproteinase-2 (TIMP-2) as a metanephric mesenchymal growth factor. Growth activity was unlikely due to TIMP-2 inhibition of matrix metalloproteinases because ilomastat, a synthetic inhibitor of these enzymes, had no mesenchymal growth action. TIMP-2 was also involved in morphogenesis of the ureteric bud, inhibiting its branching and changing the deposition of its basement membrane; these effects were due to TIMP-2 inhibition of matrix metalloproteinases, as they were reproduced by ilomastat. Thus, TIMP-2 regulates kidney development by at least 2 distinct mechanisms. In addition, TIMP-2 was secreted from UB cells by mesenchymal factors that are essential for ureteric bud development. Hence, the mesenchyme synchronizes its own growth with ureteric morphogenesis by stimulating the secretion of TIMP-2 from the ureteric bud.

Animals↗
PubMed1999

Ambulatory blood pressure and left ventricular mass in normotensive patients with autosomal dominant polycystic kidney disease.

Higher left ventricular mass (LVM) has been found in early stages of autosomal dominant polycystic kidney disease (ADPKD). The mechanisms involved in the increase of LVM are unknown. To investigate whether LVM in ADPKD may be influenced by abnormal diurnal BP variations, the 24-h ambulatory BP profile was analyzed in a group of young normotensive ADPKD patients. Ambulatory BP monitoring and two-dimensional echocardiography were performed in 26 young normotensive ADPKD with normal renal function and in 26 healthy control subjects. LVM index was higher in ADPKD patients than in controls (90.8+/-19.6 g/m2 versus 73.9+/-16.1 g/m2, P = 0.001). Average 24-h and daytime systolic, diastolic, and mean BP were similar in both groups. Nighttime diastolic and mean BP, but not systolic BP, were greater in ADPKD patients. The average and percent nocturnal decrease of systolic BP was lower in ADPKD patients than in control subjects (10.0 mm Hg [-3 to 24] versus 15.5 mm Hg [-4 to 31], P = 0.009, and 9.0% [-2 to 22] versus 14.2% [-2 to 25], P = 0.016, respectively). On the basis of their profile BP patterns, 54% of ADPKD subjects and 31% of controls were classified as nondippers (P = 0.092). There were no differences between dippers and nondippers in left ventricular wall thickness, chamber dimensions, and mass indexes. In ADPKD patients, simple regression analysis showed that LVM index was correlated with 24-h, daytime, and nighttime systolic BP. On multiple regression analysis, the 24-h systolic BP was the only variable linked to LVM index. It is concluded that young normotensive ADPKD patients have higher LVM that is closely related to the ambulatory systolic BP. The nocturnal fall in BP is attenuated in these patients, although it is not associated with the higher LVH that they present.

Adult↗
PubMed1999

TFPIbeta, a second product from the mouse tissue factor pathway inhibitor (TFPI) gene.

Tissue factor pathway inhibitor (TFPI) contains three Kunitz domains separated by two connecting regions. We have cloned another naturally occurring TFPI gene product from a mouse lung cDNA library which we have called TFPIbeta. TFPIbeta is derived from alternative splicing of the TFPI gene. Analysis of the cDNA shows that mouse TFPIbeta protein is identical to TFPI from the N'-terminus through the second connecting region. However, mouse TFPIbeta possesses neither a third Kunitz domain nor an Arg, Lys-rich C'-terminus but instead has a completely different C'-terminal (beta-domain) sequence which is not homologous to any known protein. Northern blot analyses show that the tissues for mouse TFPIbeta synthesis are heart and lung; in contrast, TFPI appears in Northern blots of heart and spleen. Both TFPIbeta and TFPI messages first appear in 7-day-old mouse embryos, but only the TFPI mRNA persists until 17 days. Purified recombinant TFPIbeta shows an apparent molecular weight of 38 kDa. Kinetic studies indicate that mouse TFPIbeta is a slow-binding enzyme inhibitor for human factor Xa. In addition, heparin does not enhance the inhibition of factor Xa by mouse TFPIbeta although it does accelerate factor Xa inhibition by TFPI.

Amino Acid Sequence↗