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Biomedical subjects

L C Moore

Publications and source records attributed to L C Moore.

At least 55 records · Page 3Linked to original sources
PubMed1990

Indirect assessment of renal dysfunction in patients taking cyclosporin A for autoimmune diseases.

The reliability of increases in serum creatinine and serum urea above initial values in detecting decreases in glomerular filtration rate below initial values was assessed in patients taking cyclosporin A (CyA) for autoimmune diseases. Both serum creatinine and serum urea provided reasonable estimates of the decline in glomerular filtration rate when measured simultaneously and when compared to patients' own baseline values. Combination of both serum creatinine and serum urea improved the assessment of renal dysfunction, partly by reducing the influence of any analytical errors. Frequent measurements, precise baseline evaluation and standardization of procedures can be expected to increase further the precision of assessing renal dysfunction from serum measurements. Hence, careful evaluation of changes in serum creatinine, with the option to include changes in serum urea, can provide a simple and reliable way of monitoring changes in renal function in patients taking CyA for autoimmune diseases.

Autoimmune Diseases↗
PubMed1990

Autoregulation and tubuloglomerular feedback in juxtamedullary glomerular arterioles.

Videometric measurements of changes in vessel lumen diameters were made to investigate autoregulatory and tubuloglomerular feedback (TGF) responses of early efferent arterioles (EA), mid-to-late afferent arterioles (MAA), and terminal, juxtaglomerular afferent arterioles (JAA) in rat juxtamedullary nephrons in vitro. High-contrast shadow-cast images of blood-perfused arterioles at the glomerular vascular pole were obtained with incident illumination and long-working-distance objectives fitted to a compound microscope. In response to an increase in blood perfusion pressure from 60 to 140 mmHg, strong autoregulatory vasoconstriction was observed in the MAA and JAA, with respective reductions in mean luminal diameter of 23 +/- 4 and 40 +/- 4% (mean +/- SE); EA diameter was unchanged. In response to TGF excitation by direct microinjection of Ringer solution into the cortical thick ascending limb segment near the macula densa, JAA luminal diameter decreased by 34 +/- 5%. The TGF responses were completely inhibited by the addition of 0.1 mM furosemide to the tubular injectate. Calcium channel blockade achieved by adding 1 microM nimodipine to the superfusate had no effect on early EA diameter but produced a blood pressure-dependent JAA and MAA vasodilation and complete inhibition of autoregulatory responses. These results provide direct evidence that the distal afferent arteriole in juxtamedullary nephrons is a major effector site for both renal autoregulation and tubuloglomerular feedback.

Animals↗
PubMed1990

Arteriolar renin and vascular effects of angiotensin II in juxtamedullary nephrons.

The SJMNs made accessible in the in vitro juxtamedullary nephron preparation possess an arteriolar renin and Ang II distribution similar to other nephron populations; renin-rich cells prevail in the JAA. Physiological studies have documented that exogenous Ang II constricts both pre- and postglomerular vessels of SJMNs. However, Ang II predominantly increases afferent resistance along the JAA. A functional interaction between Ang II and prostaglandins is likely to occur in preglomerular vessels and deserves further assessment. An additive, functional interaction was demonstrated between Ang II and autoregulation in afferent arterioles. Calcium channel blockers interfere with Ang II-induced constriction only in preglomerular vessels of SJMNs.

Angiotensin II↗
PubMed1989

Cyclosporine nephrotoxicity: blood volume, sodium conservation, and renal hemodynamics.

Glomerular filtration rate (GFR) and renal blood flow (RBF) are depressed by chronic cyclosporine treatment. We examined the hypothesis that depletion of extracellular or intravascular fluid volume contributes to the renal vasoconstriction of early cyclosporine nephrotoxicity (CCN). Control and CCN rats were given 10 mg/kg cyclosporine A or vehicle intramuscularly daily for 7 days. The effects of extracellular volume expansion, both acute (AVE, 10% body wt saline) and chronic (CVE, 10% body wt/day saline ip, 10 days including cyclosporine A treatment period), on renal hemodynamics were measured. In CCN, AVE completely normalized GFR and RBF, whereas CVE partially prevented the development of CCN. Renal autoregulatory ability was depressed in CCN but was largely restored by AVE. Intravascular volumes were measured with Evans blue and 51Cr-labeled red cells. Plasma and red cell volumes were reduced by 24% in CCN, indicating circulatory hypovolemia. Acute repletion of the deficit in blood volume by acute administration of an isoncotic solution (1.8 ml/100 g body wt of 5% albumin in isotonic saline) restored GFR and RBF to levels similar to those in control rats. Extracellular fluid volume, estimated as inulin space, was similar in both CCN and control groups. A metabolic study (7 day) showed stool Na loss in CCN to be twice that in controls but both groups remained in sodium balance. We conclude that the renal vasoconstriction produced in the rat by short-term cyclosporine treatment is, at least in part, prerenal in origin and related to the development of circulatory hypovolemia.

Animals↗
PubMed1989

Transport-coupling hypothesis of tubuloglomerular feedback signal transmission.

A mathematical model was used to explore the transport-coupling hypothesis of tubuloglomerular feedback (TGF) signal transmission from the macula densa (MD) to the extraglomerular mesangium (EGM) within the juxtaglomerular apparatus (JGA). The transport-coupling hypothesis supposes that changes in MD transport alter the ionic composition of the EGM interstitium, thereby stimulating the Goormaghtigh cells. This hypothesis is based on the avascularity of the EGM and the presence of a narrow cleft (JGA cleft) between the MD and Goormaghtigh cells. The model describes NaCl and water transport by MD cells and mass conservation in the JGA cleft. It calculates cleft water flow and NaCl concentration [( NaCl]). If the cleft is narrow, the model predicts that cleft [NaCl] will vary directly with luminal [NaCl] and net MD NaCl transport. With strong active NaCl transport, the MD cell plaque may act as an ionic amplifier, in that small changes in luminal [NaCl] might elicit much larger concentration changes within the cleft. Even without active NaCl transport, cleft [NaCl] could remain coupled to luminal [NaCl] if the MD cells passively secrete NaCl. With high hydraulic conductivity, cleft [NaCl] also varies with luminal osmolarity. With a wide cleft, a low diffusional resistance of the EGM interstitium, or swollen MD lateral intercellular spaces, the transport coupling between cleft and luminal [NaCl] is markedly attenuated. The predictions of our model of large changes in JGA interstitial composition agree well with published measurements made in Amphiuma. However, the low Na+-K+-ATPase content and high water permeability of mammalian MD suggest that the transport-coupling effects in mammals may be significantly less pronounced than in Amphiuma.

Animals↗
PubMed1987

Cyclosporine nephrotoxicity: sodium excretion, autoregulation, and angiotensin II.

Cyclosporine-induced nephrotoxicity (CIN) was studied in rats treated for 7 days with cyclosporine (10 mg x kg-1 x day-1 im) or vehicle (CON). CIN rats displayed characteristic reductions in glomerular filtration (GFR) and renal blood blood flow (RBF), and electron microscopy showed injury to proximal cells. Metabolic studies (7 day) showed significantly lower renal sodium excretion in conscious CIN rats compared with CON. In anesthetized rats at similar blood pressures, nephron GFR (SNGFR) was lower in CIN than CON, but fractional Na reabsorption was similar. In CIN, SNGFR, measured proximally to block flow to the sensing site of tubuloglomerular feedback (TGF) at the macula densa, was not significantly different than distal SNGFR. The rate of distal fluid delivery was significantly lower in CIN than in CON. Inhibition of the renin-angiotensin system (RAS) with captopril (CAP, 10 mg/kg iv), or saralasin (SAR, 0.3 mg x kg-1 x h-1 iv) caused marked arterial hypotension in CIN and a fall in renal vascular resistance (RVR). With arterial pressure controlled, CAP or SAR increased GFR and RBF, and reduced RVR in CIN, but did not reverse the renal deficits compared with similarly treated CON. RBF autoregulation in CIN was impaired between 90 and 140 mmHg but was partially restored by CAP. We conclude that both the filtered load and excretion rate of sodium in CIN are significantly reduced compared with controls, that SNGFR in CIN is not depressed by TGF in response to elevated distal fluid delivery, and that the RAS is not a primarily mediator of the renal vasoconstriction in CIN.

Angiotensin II↗
PubMed1987

In vivo measurement of tubular fluid ferrocyanide with carbon-fiber microelectrodes.

Techniques to construct carbon-fiber microelectrodes and to measure ferrocyanide ion concentration in single nephrons are described. The measurement involves polarizing an inert carbon-fiber microelectrode 500 mV positive with respect to a Ag-AgCl reference, while measuring the faradic current produced by the oxidation of ferrocyanide. A carbon fiber (5-7 micron diam) is heat sealed into a glass micropipette that is then sharpened, silanized, and electrochemically pretreated to minimize electrode degradation by protein. Circuit diagrams for an inexpensive voltage clamp-current monitor and a data sampling device are presented. The electrodes show a linear response to changes in ferrocyanide concentration in large and very small (20 nl) volumes in vitro. The electrodes were used in an electrochemical microassay to determine tubular fluid-to-plasma ferrocyanide concentration ratios and nephron filtration rates with proximal micropuncture samples. The results show excellent agreement with paired determinations using [3H]inulin. In vivo proximal tubule perfusion experiments show a rapid linear response to changes in tubular fluid ferrocyanide concentration. These electrodes permit rapid quantitative measurements of ferrocyanide concentration and water transport in the proximal tubule and may be useful in other biological systems.

Animals↗
PubMed1986

Tubuloglomerular feedback control of distal fluid delivery: effect of extracellular volume.

A closed-feedback loop micropuncture method was used to examine tubuloglomerular feedback (TGF) and the regulation of distal fluid delivery in hydropenic rats (CON), moderately hemorrhaged rats (HEM), and rats given desoxycorticosterone (DOC) and 0.6% saline to drink. Distal delivery and TGF response curves were measured with four samples per nephron: a spontaneous early distal collection, two distal collections during moderate (7.5 nl/min) and saturating (30 nl/min) perturbations in nephron fluid load, and a proximal collection to measure single-nephron glomerular filtration rate (SNGFR) during TGF inhibition. Arterial pressure, predistal volume reabsorption, SNGFR, and early distal flow were significantly higher in DOC than in HEM; the CON group exhibited intermediate values. Except for a greater maximum TGF response in HEM, the normalized TGF responses were similar in all three groups, as was the regulation of distal fluid delivery. However, the TGF onset threshold and the TGF operating point, defined by the spontaneous rates of early distal flow and SNGFR, were reset such that distal fluid delivery and SNGFR were higher in DOC than in HEM, as was renal sodium excretion. The results show that the level around which TGF stabilizes distal fluid delivery is reset when extracellular fluid volume is altered.

Analysis of Variance↗
PubMed1985

Multiple epitopes on human and murine cells expressing HLA-B7 as defined by specific murine cytotoxic T cell clones.

Eleven cytotoxic T lymphocyte (CTL) clones were derived from C57BL/6 spleen cells immunized with HLA-B7 expressing human lymphoblastoid cell lines. Reactivity against HLA-B7 was initially established because the clones lysed 2 target cells that shared only HLA-B7 with the immunizing cell line and they did not lyse five other cell lines that were HLA-B7 negative but expressed other class I or class II antigens found on the immunizing cell. Six of the clones were subsequently shown to lyse all tested HLA-B7-positive B and T lymphoid cell lines, peripheral blood lymphocytes, and a murine L cell that expressed HLA-B7 as a consequence of DNA-mediated gene transfer. On the basis of the inability of the clones to lyse a panel of HLA-B7-negative cell lines, up to 18 other class I antigens could be eliminated as being cross-reactively recognized. However, two of the clones recognized a single HLA-B7-negative cell line. It is suggested that in these cases the clones were cross-reactively recognizing the HLA-B27 or HLA-B40 antigens that were present on these target cells. The remaining five CTL clones failed to lyse one out of seven tested HLA-B7-positive lymphoid lines (either RPMI-1788 or DR1B) and failed to lyse peripheral blood lymphocytes from one out of three tested HLA-B7-positive individuals. These five clones also did not recognize the HLA-B7-positive murine L cell. However, based on analysis with a large target cell panel, the reactivity pattern of these five clones could only be correlated with recognition of HLA-B7. This conclusion is further supported by antibody-blocking studies to be reported elsewhere. As before, lysis of single HLA-B7-negative target cells by two of the clones could be ascribed to recognition of HLA-B27 or HLA-B40. The results show that murine clones raised against HLA-B7 exhibit a high degree of specificity for determinants that are unique or largely confined to the HLA-B7 alloantigen. In addition, these clones define different antigenic determinants on the molecule. Thus, such clones appear to be excellent candidates for use as human tissue typing reagent. The results further show that there is a strong correlation between recognition of particular HLA-B7-positive human cell lines and recognition of the HLA-B7 expressing murine L cell. Possible reasons for such a correlation and their relationship to the general phenomenon of CTL recognition are discussed.

Animals↗
PubMed1984

General method for the derivation and numerical solution of epithelial transport models.

A general method is presented for the formulation and numerical evaluation of mathematical models describing epithelial transport. The method is based on the principles of conservation of mass, and maintenance of electroneutrality within the cells and bathing solutions. It is therefore independent of the specific membrane transport mechanisms, and can be used to evaluate different models describing arbitrary transport processes (including passive, active and cotransport processes). Detailed numerical methods are presented that allow computation of steady-state and transient responses under open-circuit, current-clamp and voltage-clamp conditions, using a general-purpose laboratory minicomputer. To evaluate the utility of this approach, a specific model is presented that is consistent with the Koefoed-Johnson and Ussing hypothesis of sodium transport in tight epithelia (Acta Physiol. Scand. 42:298-308, 1958). This model considers passive transport of an arbitrary number of permeant solutes, active transport of sodium and potassium, and osmotically induced water transport across the apical and basolateral membranes. Results of the model are compared to published experimental measurements in rabbit urinary bladder epithelium.

Animals↗
PubMed1984

Tubuloglomerular feedback and SNGFR autoregulation in the rat.

Experimental and simulation studies were undertaken to examine what influence the state of filtration dynamics has on single nephron glomerular filtration rate (SNGFR) autoregulation, to verify the presence of partial autoregulation during tubuloglomerular feedback (TGF) inhibition, and to determine whether small changes in tubular reabsorption could enhance the ability of TGF to regulate SNGFR during autoregulation. The experimental studies in hydropenic rats revealed partial autoregulation of glomerular capillary pressure (using the stop-flow method) and SNGFR during TGF inhibition and complete SNGFR autoregulation with functional TGF. A small significant decrease in fractional volume reabsorption was observed in the distal measurements with increased arterial pressure. Results from a mathematical model of glomerular filtration suggest that SNGFR is inherently more sensitive to changes in arterial pressure in animals exhibiting filtration pressure equilibrium rather than filtration pressure disequilibrium. These data and the simulation results provide additional support for the existence of a TGF-independent autoregulatory mechanism that appears to be an intrinsic property of the preglomerular vasculature. Finally, analysis of autoregulation with a simple control-system model suggests that small changes in proximal tubule or loop of Henle volume reabsorption can provide some or all of the stimulus for TGF activation, thereby significantly increasing the ability of TGF to stabilize SNGFR in response to a rise in arterial pressure.

Absorption↗
PubMed1984

Cytotoxic T lymphocyte recognition of HLA-A/B antigens introduced into EL4 cells by cell-liposome fusion.

HLA-A2 and -B7 antigens were introduced into EL4 (H-2b) cells by cell-liposome fusion and were used as targets or stimulators for cytotoxic T lymphocytes (CTL) generated in C57B1/6 (H-2b) mice. It was found that such EL4-HLA cells were not recognized by CTL that had been raised against either a human cell line bearing these HLA antigens or the purified HLA-A2 and -B7 antigens reconstituted into liposomes. In addition, EL4-HLA cells were not capable of inducing CTL that could recognize a human cell line bearing HLA-A2 and -B7 antigens. Instead, EL4-HLA cells induced CTL that specifically lysed EL4-HLA cells and not human cells expressing HLA-A2 and -B7. CTL recognition required the presence of HLA antigens on the EL4 cell surface and was inhibited by antibodies against either H-2b or HLA-A/B. Monoclonal antibody binding studies showed that the expected polymorphic determinants of the HLA-A2 and -B7 antigens were still present on EL4-HLA cells. However, the specificity of CTL or their precursors that are capable of recognizing HLA-A2 or -B7 was altered after these antigens became associated with the EL4 surface. Possible explanations for these results are discussed.

Animals↗
PubMed1983

Perturbation analysis of tubuloglomerular feedback in hydropenic and hemorrhaged rats.

A closed-feedback-loop method was used to investigate regulation of SNGFR and distal fluid delivery by tubuloglomerular feedback (TGF) in hydropenic and hemorrhaged rats. Unblocked nephrons were perturbed by early proximal perfusion of previously collected, inulin-free, tubular fluid at 0, 7.5, and 15 nl/min, thereby increasing nephron fluid load. The resultant changes in SNGFR, tubular reabsorption, proximal intratubular pressure, and early distal flow were measured. During perfusion, SNGFR decreased and distal flow increased; the effect on reabsorption was variable. Analysis of the data indicated that the combined action of TGF and changes in proximal tubule and Henle's loop reabsorption were able to provide a maximum of 56% compensation for the effect of the perturbation on distal delivery in hydropenic rats and 70% compensation in hemorrhaged rats. In one group of hydropenic rats in which a significant fall in reabsorption was found, the total fluid load presented to the nephron, SNGFR plus the perfusion rate, was significantly better regulated than distal delivery. This result is consistent with the behavior of a model used to estimate the contribution of TGF to the observed regulation. The results indicated that TGF alone could provide 56% compensation for the perturbation in hydropenia and a significantly greater 72% compensation following hemorrhage. The conclusions are 1) that the properties of TGF are sufficient to result in significant regulation of distal fluid delivery and SNGFR, 2) that hemorrhage increases the strength of the TGF response, and 3) that TGF regulation of SNGFR and distal delivery is strongly influenced by changes in proximal tubule and loop of Henle reabsorption.

Animals↗
PubMed1982

Interaction of tubuloglomerular feedback and proximal nephron reabsorption in autoregulation.

The relationship between tubuloglomerular feedback (TGF) and SNGFR autoregulation has been analyzed, and the results show that renal autoregulation is much more complex than a single feedback-loop control system that regulates SNGFR or renal blood flow. At least two mechanisms seem to be involved. First, there appears to be a TGF-independent component in autoregulation that is probably myogenic in nature, located in the renal vasculature, and responsive to changes in intravascular pressure or transmural pressure difference. The second mechanism is TGF, which involves both vascular and tubular elements, responds to changes in either SNGFR or proximal nephron reabsorption, and acts in concert with glomerulotubular balance (GTB) to stabilize distal delivery of tubular fluid. In a strict sense, neither SNGFR nor renal blood flow are "controlled" during autoregulation. The stabilization of these important variables is an intermediate result of the action of the control mechanisms to directly regulate other system variables. Moreover, because both TGF and GTB are influenced by changes in extracellular volume (ECV), autoregulation is an adaptive control mechanism. Thus, in autoregulation, TGF acts to ensure a balance between filtration and proximal and loop of Henle reabsorption that is appropriate for the prevailing ECV status of the animal.

Absorption↗