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T Bennett

Publications and source records attributed to T Bennett.

At least 73 records · Page 4Linked to original sources
PubMed1996

An endogenous cannabinoid as an endothelium-derived vasorelaxant.

Since the identification of nitric oxide (NO) as an important mediator of endothelium-dependent relaxation, it has become clear that there is an additional endothelial relaxant factor, termed the endothelium-derived hyperpolarizing factor (EDHF). The identity of EDHF has remained elusive, but it is thought to be an arachidonic acid metabolite. We now report that EDHF-mediated relaxations in the rat mesenteric arterial bed are blocked by a highly selective cannabinoid receptor antagonist, SR141716A, consistent with EDHF being a cannabinoid-like substance. Furthermore, in conscious rats,. the NO-independent depressor and regional vasodilator effects of bradykinin were inhibited by SR141716A. The relaxations in the isolated mesentery were accompanied by the accumulation of an arachidonic acid metabolite, which co-eluted on TLC separation with arachidonoylethanolamide (anandamide), an endogenous cannabinoid derived from arachidonate. We further report that anandamide is a potent vasorelaxant in the mesentery, acting via a hyperpolarizing mechanism. These findings suggest that an endogenous cannabinoid is an endothelium-derived vasorelaxant, which may be EDHF.

Animals↗
PubMed1996

Identification of a novel myosin heavy chain gene expressed in the rat larynx.

Based on reactivity to antibodies against known myosin heavy chains, expression of a novel fast myosin heavy chain (MHC) gene was suspected in the thyroarytenoid (TA) muscle of the rat larynx. The 3' ends of MHC transcripts in the TA were amplified by RT-PCR using a primer to a highly conserved MHC sequence and to the poly(A) tail. The resultant products were cloned and fourteen PCR products were screened by dot-blotting with oligonucleotides specific for known skeletal muscle MHC genes. A clone that reacted weakly to the 2B oligo was sequenced and found to encode a novel fast MHC transcript, termed 2L, that appears to represent an eighth vertebrate skeletal muscle MHC gene. By homology analysis, the 2L sequence is most similar to the extraocular MHC, suggesting a possible evolutionary relationship between MHCs associated with the branchial arches.

Amino Acid Sequence↗
PubMed1996

Adverse effects of dextromethorphan on the spatial learning of rats in the Morris water maze.

The effects of the non-competitive NMDA receptor antagonist dextromethorphan on spatial learning were assessed using the Morris water maze. Dextromethorphan was administered to 4 groups of rats in 10, 20, 30, and 40 mg/kg doses. An additional group of rats was administered saline to serve as a vehicle control group. Dextromethorphan impaired learning dose dependently in the initial training phase of the experiment. During the probe trial, dose-dependent performance deficits were noted in the first 15 s of the trial only. Search strategy differences between the lowest and highest dose groups were also observed during the probe trial. During the reversal training phase, when the platform was moved to a new location, the dose-dependent impairment was seen again, but the 40 mg/kg group perseverated to the former location longer than the other groups. A cued control trial indicated that in addition to the learning impairment produced, the highest dose of dextromethorphan may also impair sensory-motor coordination.

Animals↗
PubMed1996

Initial experience with an implantable hemodynamic monitor.

BACKGROUND: Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS: The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS: Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.

Adult↗
PubMed1996

Long-term recording of cardiac output via an implantable haemodynamic monitoring device.

Long-term monitoring of central haemodynamics with implanted monitoring systems might be valuable in managing heart failure patients. Such systems offer an opportunity for repeated 'semi-invasive' cardiac output determinations according to the Fick principle. Five patients, four with chronic heart failure and one with chronic pulmonary disease, underwent supine exercise testing during cardiac catheterization at 0, 2, 6 and 11 months after implantation of a right ventricular mixed venous oxygen saturation sensor connected to an implantable haemodynamic monitor. The monitor provided a continuous measure of oxygen saturation via a radio-telemetry link to a metabolic cart capable of measurement of breath-by-breath oxygen consumption. Cardiac output was computed using oxygen consumption, mixed venous oxygen saturation, arterial oxygen saturation by pulse oximetry and haemoglobin oxygen capacity. Biosensor-derived oxygen saturation compared to blood samples from the pulmonary artery showed an excellent correlation over time, r2 = 0.94 (implant), r2 = 0.91 (6-11 months). There was a strong correlation between semi-invasive-determined cardiac output using the biosensor and the invasive technique, which persisted over the entire follow-up period. Repeated semi-invasive cardiac output measurements using an implanted haemodynamic monitoring system in chronic heart failure patients is feasible and the data may be of value for optimizing therapy.

Adult↗
PubMed1996

Effects of glibenclamide on the regional haemodynamic actions of alpha-trinositol and its influence on responses to vasodilators in conscious rats.

1. In conscious rats, alpha-trinositol (D-myo-inositol-1, 2, 6 triphosphate; 5-80 mg kg-1 h-1 infusion) caused dose-dependent hypotension, tachycardia and hyperaemic dilatation in renal, mesenteric and hindquarters vascular beds. These effects were accompanied by inhibition of the renal vasodilator effects of acetylcholine (ACh), and of the mesenteric vasodilator effects of sodium nitroprusside (SNP) and, particularly, of levcromakalim (LCK). 2. In the light of the latter finding, in a second experiment, we assessed the influence of the KATP channel inhibitor, glibenclamide (20 mg kg-1), on resting haemodynamics, on responses to ACh, bradykinin (BK), SNP and LCK, on the haemodynamic action of alpha-trinositol, and on the effects of the latter on responses to the vasodilators, over a period of 3 days. 3. In the presence of saline, glibenclamide caused a reproducible pressor effect, accompanied by renal, mesenteric, and hindquarters vasoconstrictions on all 3 experimental days; these effects were unrelated to changes in blood glucose. In the presence of glibenclamide, only the hindquarters vasodilator response to BK, and all the cardiovascular actions of LCK were inhibited. 4. On the first experimental day, the hindquarters vasodilator effect of alpha-trinositol was substantially inhibited by glibenclamide, the renal vasodilatation less so, and the mesenteric vasodilatation not at all. However, over the subsequent two days, the mesenteric vasodilator effect of alpha-trinositol became increasingly sensitive to glibenclamide. 5. In the presence of alpha-trinositol and glibenclamide, on the first experimental day, the inhibition of the renal vasodilator effect of ACh was no greater than with alpha-trinositol alone in the first experiment. Moreover, on the third experimental day, both before and after glibenclamide, the inhibition by alpha-trinositol of the renal vasodilator response to ACh was less than on the first experimental day. Similarly, the alpha-trinositol-induced inhibition of the mesenteric vasodilator effect of SNP, and of the hindquarters vasodilator action of BK, waned over the 3 experimental days. The inhibition of the cardiovascular effects of LCK were similar on all 3 experimental days, but no greater in the presence of alpha-trinositol and glibenclamide than with glibenclamide alone. 6. These results indicate that KATP channels are involved in the maintenance of resting vasodilator tone in renal, mesenteric and hindquarters vascular beds. However, although additional activation of KATP channels is responsible for all the haemodynamic effects of LCK, it contributes only to the hindquarters vasodilator action of BK and is not involved in any of the responses to ACh or SNP. The hindquarters, renal and mesenteric vasodilator effects of alpha-trinositol may involve (in the same rank order) activation of KATP channels, probably through an indirect mechanism. However, it is unlikely that direct or indirect interaction of alpha-trinositol with KATP channels explains the ability of the drug to inhibit the renal vasodilator action of ACh, or the mesenteric vasodilator effects of SNP or LCK.

Acetylcholine↗
PubMed1996

Effects of dexamethasone and SB 209670 on the regional haemodynamic responses to lipopolysaccharide in conscious rats.

1. Male (350-450 g) Long Evans rats were chronically instrumented to permit regional haemodynamics to be monitored in the conscious state. In the first experiment, either saline (0.4 ml h-1) or dexamethasone (3 mg kg-1, 125 micrograms kg-1 h-1) was infused continuously for 24 h, before co-infusion of lipopolysaccharide of (LPS, 150 micrograms kg-1 h-1) for 24 h. Dexamethasone prevented the delayed (5-24 h) fall in mean arterial blood pressure (MAP) and the renal and hindquarters vasodilatation seen with LPS infusion alone, but not the initial (about 2 h) fall in MAP or renal vasodilatation. However, at this dose, dexamethasone itself caused a significant rise in MAP and regional vasoconstrictions. 2. In the second experiment, dexamethasone at a lower dose (12.5 micrograms kg-1 h-1) had only slight pressor and vasoconstrictor effects. However, in its presence, infusion of LPS caused a substantial and progressive rise in MAP (maximum at 8 h, +32 +/- 3 mmHg) together with persistent mesenteric and hindquarters vasoconstriction and a transient renal vasodilatation. 3. In the third experiment, the non-selective endothelin antagonist, SB 209670 (600 micrograms kg-1 h-1), blocked the slight pressor and regional vasoconstrictor effects of the lower dose of dexamethasone. Furthermore, in the presence of dexamethasone and SB 209670, infusion of LPS caused marked, but transient hypotension (nadir at 5 h, -24 +/- 2 mmHg) and renal and mesenteric vasodilatation. 4. At the end of all experimental protocols, sequential administration of the AT1-receptor antagonist, losartan, followed by the V1-receptor antagonist, (+)-(CH2)5-O-Me-Tyr, vasopressin, caused effects indicating a variable involvement of angiotensin and vasopressin in the maintenance of cardiovascular status. 5. Collectively, the results indicate that, in the conscious rat, dexamethasone interacts with vasoconstrictor and vasodilator mechanisms, and hence its influence on the haemodynamic responses to LPS cannot be attributed, simply, to inhibition of the activity of inducible nitric oxide synthase and/or cyclo-oxygenase-2.

Angiotensin Receptor Antagonists↗
PubMed1996

Regional haemodynamic effects of antagonists of angiotensin II, endothelin and adrenoceptors in conscious, vasopressin-deficient, genetically hypertensive rats.

1. Male, vasopressin-deficient, normotensive (DI/N) and hypertensive (DI/H) rats were chronically instrumented (all surgery under sodium methohexitone anaesthesia) to allow assessment of resting haemodynamic status and responses to antagonism of AT1-receptors (Experiment 1), ET(A-) and ET(B-) receptors (Experiment 2) or adrenoceptors (Experiment 3). 2. Before any treatment, mean arterial blood pressure (MAP) was higher, and hindquarters vascular conductance was consistently lower in all groups of DI/H rats than in DI/N rats. 3. In Experiment 1, losartan (10 mg kg-1 i.v.), an AT1-receptor antagonist, was given 5 h after s.c. injection of saline, (DI/N, n = 8; DI/H, n = 8) or hyperoncotic polyethylene glycol, (DI/N, n = 9; DI/H, n = 9) to induce isosmotic hypovolaemia. In the volume-replete state, losartan caused similar small falls in MAP in the two groups (maximum delta MAP; DI/N, -9 +/- 2; DI/H, -15 +/- 5 mmHg), but the mesenteric and hindquarters vasodilatations were greater in DI/N rats. In the volume-depleted state the effects of losartan were augmented (delta MAP; DI/N, -32 +/- 3; DI/H. -31 +/- 3 mmHg), but its vasodilator effects were still greater in DI/N than in DI/H rats. 4. In Experiment 2, infusion of the ET(A-)ET(B-)receptor antagonist, SB 209670 (600 micrograms kg-1 h-1; DI/N, n = 8; DI/H, n = 9), had haemodynamic effects that were not different from those during saline infusion in DI/N (n = 7) and DI/H rats (n = 8). 5. In Experiment 3, sequential administration of the beta 2-adrenoceptor antagonist, ICI 118551 (0.2 mg kg-1 bolus, 0.1 mg kg-1 h-1 infusion), the alpha 2-adrenoceptor antagonist, idazoxan (0.75 mg kg-1 bolus, 1 mg kg-1 h-1 infusion), and losartan (10 mg kg-1 bolus) had only slight haemodynamic effects in DI/N (n = 8) and DI/H (n = 9) rats. Subsequent administration of the alpha 1-adrenoceptor antagonist, prazosin (0.5 mg kg-1 bolus, 0.8 mg kg-1 h-1 infusion) caused marked hypotension, although MAP was still higher in DI/H (95 +/- 4 mmHg) than in DI/N (75 +/- 4 mmHg) rats. However, in this circumstance there were no significant differences between renal, or mesenteric, or hindquarters vascular conductances in the two groups. 6. The results indicate that the hypertension and hindquarters vasoconstriction in DI/H rats is not dependent on AII or endothelin. Moreover, the relative elevation in MAP in DI/H persists in the presence of antagonism of beta 2, alpha 2- and alpha 1-adrenoceptors, in spite of no significant difference in regional vascular conductances.

Adrenergic Antagonists↗
PubMed1996

Effects of the non-peptide, non-selective endothelin antagonist, bosentan, on regional haemodynamic responses to NG-monomethyl-L-arginine in conscious rats.

1. Male, Long Evans rats (350-450 g) were chronically instrumented to allow monitoring of mean arterial blood pressure, heart rate and changes in renal, mesenteric and hindquarters haemodynamics. In the first experiment, animals (n = 8) were given a bolus i.v. injection of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine hydrochloride (L-NMMA; 30 mg kg-1) on four consecutive days. Fifteen min prior to L-NMMA administration on the fourth day, the endothelin, ETA-, ETB-receptor antagonist, bosentan, was injected (30 mg kg-1, i.v.). Relative to the response on the third day, bosentan caused 33 +/- 4%, 24 +/- 3%, 14 +/- 3%, and 18 +/- 5% inhibition of the pressor, and renal, mesenteric and hindquarters vasoconstrictor effects of L-NMMA, respectively. 2. In the second experiment, bosentan was given 15 min before L-NMMA in a group of rats (n = 6) which had not received L-NMMA previously. Relative to the responses to L-NMMA on the first day in the previous experiment, bosentan caused a 30%, 24%, 18% and 27% inhibition of the pressor, and renal, mesenteric and hindquarters vasoconstrictor effects of L-NMMA, respectively. 3. The results indicate a significant contribution from endothelin to the haemodynamic effects of L-NMMA in conscious rats. However, since our previous studies have shown the renin-angiotensin and sympathoadrenal systems are not involved, it is likely that the major component of the cardiovascular response to L-NMMA in conscious rats is due to loss of vasodilator action of endothelial nitric oxide.

Animals↗
PubMed1996

Influence of aminoguanidine and the endothelin antagonist, SB 209670, on the regional haemodynamic effects of endotoxaemia in conscious rats.

1. We compared the regional haemodynamic responses to lipopolysaccharide (LPS; 150 micrograms kg-1 h-1, i.v.) in the presence of saline, aminoguanidine (AG; 45 mg kg-1 bolus, 45 mg kg-1 h-1 infusion), or AG and the non-selective endothelin receptor antagonist, SB 209670 (600 micrograms kg-1 h-1), in conscious, chronically instrumented, Long Evans rats (350-450 g; n = 8 in all groups). We used AG because there is evidence that it is a selective inhibitor of inducible nitric oxide synthase (iNOS), although recently it has been claimed AG also inhibits constitutive NOS. 2. Infusion of LPS in the presence of saline caused an early, transient hypotension (1-2 h) and a renal vasodilatation, with a secondary, delayed fall in mean arterial blood pressure (MAP), progressive tachycardia, and renal and hindquarters vasodilatation. 3. AG alone caused a rapid (within 30 s) transient rise in MAP (delta 27 +/- 3 mmHg), accompanied by tachycardia and regional vasoconstrictions, but no reduction in regional flows, indicating the pressor effect of AG was, probably, largely due to an increase in cardiac output. These effects are not consistent with AG inhibiting constitutive NOS. In the presence of AG, LPS still caused an early, transient fall in MAP accompanied by a renal vasodilatation, but thereafter there was a significant rise in MAP (17 +/- 3 mmHg, 3 h after onset of LPS infusion) accompanied by bradycardia and marked mesenteric and hindquarters vasoconstrictions. However, 23 h after the onset of co-infusion of AG and LPS all variables were not different from baseline, except heart rate and renal vascular conductance, which were increased. 4. In the presence of AG and SB 209670, LPS caused progressive hypotension and increases in renal, mesenteric and hindquarters vascular conductances. Hence, SB 209670 prevented the rise in MAP and the regional vasoconstrictions seen with AG and LPS, indicating an involvement of endothelin in these events. 5. In the presence of AG and SB 209670, 23 h after the onset of LPS infusion, the AT 1-receptor antagonist, losartan (10 mg kg-1), and the V 1-receptor antagonist, d(CH2)5-0-Me-Tyr-AVP (10 micrograms kg-1, 10 micrograms kg-1 h-1) caused additional incremental falls in MAP and increases in renal, mesenteric and hindquarters vascular conductances. Under these circumstances, MAP was lower and regional vascular conductances higher than in the other experiments following administration of losartan and d(CH2)5-0-Me-Tyr-AVP. Thus, although the findings are consistent with AG inhibiting iNOS, thereby revealing the pressor and vasoconstrictor actions of endothelin released by LPS, it is clear that LPS activates a very powerful hypotensive/vasodilator mechanism(s) which is resistant to AG, and whose full influence is only unmasked when the actions of endothelin, angiotensin II and vasopressin are inhibited.

Animals↗
PubMed1996

Temporal differences between the involvement of angiotensin II and endothelin in the cardiovascular responses to endotoxaemia in conscious rats.

1. Male, Long Evans rats were instrumented chronically with pulsed Doppler probes and intravascular catheters to allow assessment of regional haemodynamic changes during i.v. infusion of lipopolysaccharide (LPS, 150 micrograms kg-1 h-1). 2. In the presence of the AT1-receptor antagonists, losartan (10 mg kg-1 + 10 kg-1 h-1), the initial (1-2 h) hypotensive and renal, mesenteric and hindquarters vasodilator responses to LPS were enhanced significantly. Thereafter these effects waned, but between 8-23 h after the onset of LPS infusion, a further fall in mean atrial blood pressure (MAP) and increases in renal and hindquarters flows and conductances occurred. All these changes were significantly greater than seen with losartan or LPS alone, and exceeded the sum of their effects. 3. In the presence of captopril (2 mg kg-1 + 2 mg kg-1 h-1), the initial hypotensive and renal vasodilator responses to LPS were enhanced, but less so than in the presence of losartan. However, the effects of LPS in the presence of losartan and captopril together were not different from those in the presence of losartan alone. These observations indicate that the ability of captopril to inhibit the degradation of bradykinin had no additional influence, and the differences between the effect of captopril and losartan on the initial effects of LPS were probably due to more effective suppression of the action of angiotensin II by losartan. 4. In the absence of LPS, co-infusion of losartan and the non-selective endothelin antagonist, SB 209670 (600 micrograms kg-1 + 600 micrograms kg-1 h-1), caused a substantial, progressive hypotension (-25 +/- 2 mmHg at 24 h) accompanied by increases in renal, mesenteric and hindquarters vascular conductances (31 +/- 13, 44 +/- 9 and 45 +/- 12%, respectively), indicating an involvement of angiotensin II and endothelin in the maintenance of normal cardiovascular status in conscious, Long Evans rats. 5. In the presence of losartan and SB 209670, the initial, LPS-induced fall in MAP (-42 +/- 2 mmHg) was not different from that in the presence of losartan (-39 +/- 4 mmHg), and the increases in renal, in mesenteric, and in hindquarters vascular conductances were similar in the two conditions. However, there was no recovery in MAP, and there were persistent renal, mesenteric and hindquarter vasodilatations. 6. In all experiments involving LPS, administration of the V1- receptor antagonist, d(CH2)5-O-Me-Tyr-AVP (10 micrograms kg-1), 23 h after the start of LPS infusion caused additional hypotension and mesenteric vasodilatation, particularly. This effect was most marked in animals pretreated with losartan and SB 209670. 7. The results indicate that the initial (1-2 h) depressor and dilator effects of LPS infusion in conscious Long Evans rats are opposed by the actions of angiotensins II, rather than endothelin. However, between 2-8 h after the onset of LPS infusion the involvement of endothelin develops and that of angiotensin II fades. By 24 h after the start of infusion of LPS, the pressor and vasoconstrictor actions of endothelin wane, and a role of vasopressin is apparent. At no stage is there clear evidence for an involvement of bradykinin in the haemodynamic sequelae of endotoxaemia in this model.

Angiotensin II↗
PubMed1996

The pathogenesis of multicystic dysplastic kidney disease: insights from the study of fetal kidneys.

The pathogenesis of multicystic dysplastic kidney disease (MCDKD) is unknown. Most morphologic studies of MCDKD kidneys have been performed when the kidneys are resected postnatally, when their architecture has been distorted by massive cyst enlargement. We obtained two MCDKD kidneys at an early stage of development (14 and 19 weeks' gestation) and examined the pattern of nephrogenesis in detail. In both affected kidneys, we identified islands of spatially dislocated metanephric blastema adjacent to zones containing all the normal structural elements of nephrogenesis, including aggregates of induced mesenchyme, S-shaped bodies and maturing glomerull, and proximal and distal tubules. Metanephric blastemal cells displayed characteristic vimentin and smooth muscle actin immunoreactivity and insulin-like growth factor II gene expression, whereas induced elements exhibited appropriate cytokeratin immunoreactivity and Wilms' tumor gene expression. In most other zones, renal cysts were lined with epithelia varying from a flattened squamous to a cuboidal morphology and expression of markers suggested their origin to be from all portions of the nephron including Bowman's space, proximal tubule, and collecting duct. In some cysts, small clusters of epithelial cells were identified within the cyst lumen. These studies suggest that in the early stages of MCDKD, normal nephrogenesis occurs in what seems to be a normal metanephric blastema; however, an intrinsic abnormality in the branching morphogenesis of the ureteric duct might be responsible for the development of the histopathologic changes described.

Actins↗
PubMed1996

Using relative value units (RVUs) to develop your pricing schedule.

This article presents a methodology by which a practice, using published Medicare Relative Value Units, can develop a logical and consistent pricing structure which recognizes the difference between procedures and is of a similar methodology to that used by Medicare and many major third-party payors in reimbursing practices. This approach utilizes available published information and can be done with relative ease by all physician practices.

Electronic Data Processing↗
PubMed1996

Physician directed networks: the new generation of managed care.

The external pressure to reduce cost while maintaining quality and services is moving the whole industry into a rapid mode of integration. Hospitals, vendors, MCOs, and now, physicians, are faced with the difficult decisions concerning how their operations will be integrated into the larger health care delivery system. These pressures have forced physicians to consolidate, build leverage, and create efficiencies to become more productive; thereby better positioning themselves to respond to the challenges and the opportunities that lie before them. This initial phase of consolidation has given many physicians the momentum to begin to wrestle back the control of health care and the courage to design the next generation of managed care: Physician Directed Managed Care. What will be the next phase? Perhaps, the next step will be fully-integrated specialty and multi-specialty groups leading to alternate delivery sites. "Everyone thinks of changing the world, but no one thinks of changing himself." - Leo Tolstoy

Community Networks↗
PubMed1996

Characterization of fetal ovine renal dysplasia after mid-gestation ureteral obstruction.

OBJECTIVE: The etiology and pathogenesis of renal dysplasia are poorly understood. To characterize the histologic changes in fetal renal dysplasia, we studied a fetal ovine model of urinary obstruction. DESIGN: Animal study. ANIMALS: Seven fetal lambs, and other lambs of the same gestational age as controls. INTERVENTIONS: Unilateral ureteral ligation on fetal lambs at approximately 70 days' gestation (term for sheep is 145 days), during nephrogenesis. Kidneys were subsequently collected, examined histologically and characterized by immunohistochemical tests involving cytokeratin antiserum and a monoclonal antibody to alpha-actin. OUTCOME MEASURES: Histologic changes in ligated fetal lamb kidneys, based on comparison with normal fetal lamb kidneys. RESULTS: At near term (140 days' gestation), the ligated kidney showed distorted and less abundant renal parenchyma than a normal control kidney. Upon microscopic examination, the ligated kidney displayed marked architectural distortion of the outer cortex, with abundant interstitial fibrosis, primitive ductules and glomeruli, and cysts of varying sizes lined by squamous and cuboidal epithelia and surrounded by a loose mesenchyme. The renal medulla contained differentiated collecting ducts, which were structurally distorted and less abundant than in normal control kidneys. The proximal and distal tubule elements were primitive and markedly underdeveloped. Cytokeratin immunoreactivity was present in the collecting duct epithelium and in the cuboidal epithelium lining many of the cortical cysts. Smooth muscle alpha-actin immunoreactivity was localized in the cortical region of the kidney, which highlighted the abundance and disorganization of the undifferentiated mesenchyme and identified the fibromuscular collars of the primitive ductules of the cortex and the distorted collecting ducts of the medulla. CONCLUSIONS: These results highlight the histologic changes resulting from unilateral ureteral ligation in fetal lambs. This model is useful in the study of the pathogenesis of fetal obstructive renal dysplasia.

Actins↗
PubMed1995

Identification of a short form of the P2xR1-purinoceptor subunit produced by alternative splicing in the pituitary and cochlea.

A truncated form of the P2xR1 purinoceptor subunit (which we designate P2xR1-2) was detected in rat pituitary gland and the secretory epithelial tissue (stria vascularis) of the cochlea using RT-PCR of solid-phase cDNA libraries. PCR products corresponding to the P2xR1 purinoceptor subunit (1) were obtained from vas deferens, brain and microdissected cochlear sensory epithelial tissues including organ of Corti, sacculus and crista ampullaris. Cloning and sequencing revealed that the P2xR1-2 product included an 85-bp insertion in a region corresponding to a novel C-terminal end of the second membrane spanning domain and continuing as the cytoplasmic domain. A stop codon sequence after the first 51 bp of the insert effectively truncates this subunit, reducing the final cytoplasmic domain by 90% compared with the previously published P2xR1(-1) sequence, thereby reducing the overall peptide by approximately 25%. The region of the receptor lost in the truncated version coded for a number of serine/proline rich regions which may act as potential intracellular regulatory sites.

Alternative Splicing↗