SEARCH · PubMed Health

Results for “TPR”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed1987

Systemic and renal hemodynamic consequences of manipulation of serum calcium and/or parathyroid hormone in the intact conscious mongrel dog.

Studies were undertaken in conscious mongrel dogs to separate the systemic and renal hemodynamic effects of alterations in serum calcium (Ca) from those of parathyroid hormone (PTH) in an intact conscious animal. Blood pressure was measured intra-arterially, cardiac output was determined by dye-dilution or thermodilution, total peripheral resistance (TPR) was calculated from standard formulae, and renal hemodynamics were estimated by the clearance of inulin and para-aminohippurate. Measurements were made before and after a 2 hour calcium chloride (CaCl2) infusion in 10 dogs (group 1). These animals had previously received a dose of PTH to prevent suppression of PTH during the CaCl2 infusion. Ionized calcium (Ca++) and TPR increased significantly. Blood pressure increased but not significantly. Administration of EDTA did not significantly change any systemic hemodynamic variable in eight thyroparathyroidectomized dogs (group 2). Chelation in seven dogs with intact parathyroid glands (group 3) reduced mean arterial blood pressure and total peripheral resistance. Renal hemodynamic measurements were not affected. Isolated acute elevation of serum Ca++, independent of suppression of PTH, increased total peripheral resistance. Decreased serum Ca++ required normal activity of parathyroids to reduce total peripheral resistance. The renal circulation was resistant to acute manipulation of ionized serum calcium and PTH. CaCl2 infusion to intact dogs (group 1) decreased serum magnesium significantly, increased urine flow rate, and decreased urinary PGE2 excretion. Comparisons between group 2 and group 3 revealed a greater decline in serum Mg and urinary prostaglandin E2 excretion in group 2 vs group 3. Elevation of peripheral resistance due to acute Ca elevations was accompanied by decreased serum Mg and decreased renal prostaglandin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Hemodynamic effect of indium chloride in pregnant rats.

Daily indium chloride doses of control (0) or 200 mg/kg were administered orally to pregnant Sprague-Dawley (SD) rats by gavage, on d 6-15 of gestation. On d 16 of gestation hemodynamic tests were performed; Arterial blood pressure, cardiac output (CO), and volume organ blood flow were determined with radioactive microspheres using the reference sample method (McDevitt & Nies, 1976). Indium chloride increased the cardiac index (CI), but did not change arterial blood pressure and total peripheral resistance (TPR). Indium decreased the organ fractions of the cardiac output to kidneys, ovaries, uterus, and placenta, while those to brain, lungs, and liver were not affected. In the placenta the blood flow was reduced significantly while the vascular resistance increased. The blood flow and vascular resistance did not change in the rest of the organs studied. The changes in arterial blood pressure, CO, Cl, TPR, organ fraction of cardiac output, blood flow, and vascular resistance in most of the organs displayed normal responsiveness to noradrenaline (NA) infusion. The reduction of uterine and placenta fractions and placental blood flow, produced by NA infusion were significantly greater in control than in the indium-treated group. Data indicate that the hemodynamic changes induced by indium are detrimental to the fetus. Indium chloride exposure modifies the maternal effect of noradrenaline such that there is maternal survival at the expense of fetal mortality.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Arterial stiffness: pathophysiology and clinical impact.

The ill effects of hypertension are usually attributed to a reduction in the caliber or the number of arterioles, resulting in an increase in total peripheral resistance (TPR). This definition does not take into account the fact that BP is a cyclic phenomenon with systolic and diastolic BP being the limits of these oscillations. The appropriate term to define the arterial factor(s) opposing LV ejection is aortic input impedance which depends on TPR, arterial distensibility (D), and wave reflections (WR). D defines the capacitive properties of arterial stiffness, whose role is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of D. These parameters are BP dependent, and arteries become stiffer at high pressure. In to D which provides information about the < > of artery as a hollow structure, the elastic incremental modulus (Einc) characterizes the properties of the arterial wall biomaterials, independently of vessel geometry. As an alternative, arterial D can be evaluated by measuring the pulse wave velocity (PWV) which increases with the stiffening of arteries. Arterial stiffening increases left ventricular (LV) afterload and alters the coronary perfusion. With increased PWV, the WR impacts on the aorta during systole, increasing systolic pressures and myocardial oxygen consumption, and decreasing diastolic BP and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix (arteriosclerosis) as classically observed during aging or in arterial hypertension. The arterial stiffening estimated by changes in aortic PWV and intensity of WR are independent predictors of survival in end stage renal disease (ESRD) and general population. Improvement of arterial stiffening could be obtained by antihypertensive treatmen as observed with the calcium-channel blocker and ACE inhibitors. ACE inhibitors increased AC and reduced WR, and it has been shown that reversibility of aortic stiffening and use of ACE inhbitors had favorable independent effect on survival in hypertensive patients with advanced renal disease.

Arteries↗

PubMed1994

Bypassing anaphase by fission yeast cut9 mutation: requirement of cut9+ to initiate anaphase.

A novel anaphase block phenotype was found in fission yeast temperature-sensitive cut9 mutants. Cells enter mitosis with chromosome condensation and short spindle formation, then block anaphase, but continue to progress into postanaphase events such as degradation of the spindle, reformation of the postanaphase cytoplasmic microtubule arrays, septation, and cytokinesis. The cut9 mutants are defective in the onset of anaphase and possibly in the restraint of postanaphase events until the completion of anaphase. The cut9+ gene encodes a 78-kD protein containing the 10 34-amino acid repeats, tetratricopeptide repeats (TPR), and similar to budding yeast Cdc16. It is essential for viability, and the mutation sites reside in the TPR. The three genes, namely, nuc2+, scn1+, and scn2+, genetically interact with cut9+. The nuc2+ and cut9+ genes share an essential function to initiate anaphase. The cold-sensitive scn1 and scn2 mutations, defective in late anaphase, can suppress the ts phenotype of cut9.

Amino Acid Sequence↗

PubMed1994

Photon beam quality specification by narrow-beam transmission measurements.

Radiation quality specifications in megavoltage photon beams are usually based on depth-dose measurements performed under reference conditions. Stopping-power ratios and various correction factors are then related to parameters such as TPR(10)20, which are extracted from depth-dose measurements. Stopping-power ratio determinations based on this concept were shown to be in error by more than 2% at high energies. Furthermore, electrons generated in the treatment head can, at high energies, contribute to the dose at a depth of 10 cm and thus significantly affect the TPR(10)20 ratio. This method was further shown to be inadequate when the dose in other parts of the field than the reference point was to be measured with ionization chamber dosimetry. A new standardized device for determining photon beam quality based on half value layer (HVL) measurements in water was developed and thoroughly investigated in both a low-energy, (4 MV) and a high-energy beam. A relation between HVL and stopping-power ratios water-to-air was determined by comparative measurements with air ionization chambers and liquid-filled ionization chambers together with Fricke dosimetry. Furthermore, different radiation quality gradients in the photon fields for different types of field-flattening systems, and field-compensating methods were discussed.

Equipment Design↗

PubMed1998

Spectral reconstruction of clinical megavoltage photon beams and the implications of spectral determination on the dosimetry of such beams.

An analysis technique, based on simulated annealing, is described which is employed to derive megavoltage photon beam spectral information from narrow beam attenuation measurements. Megavoltage photon beam spectra have been determined using this technique for linear accelerators from different manufacturers, and different models from individual manufacturers at a range of energies from nominal 6 MV to nominal 25 MV. All of the photon beams included in the study are in routine clinical use. The subsequent effects on dosimetry of employing derived primary spectra to specify beam quality are examined. The results suggest that the quality index TPR(20)10 may be insensitive to beam quality changes for high-energy beams in the range of 15 MV to 25 MV. Although the quality index may be insensitive as a beam quality specifier at these higher qualities, the actual difference in the calculated dose delivered using derived spectra as the quality specifier rather than TPR(20)10 is likely to be small, the results obtained indicating a difference of between 0.2% and 0.7% in the calculated dose delivered.

Biophysical Phenomena↗

PubMed2006

Orthostatic hypotension and autonomic pathways after spinal cord injury.

Individuals with spinal cord injury (SCI) are prone to orthostatic hypotension (OH). We aimed to develop a simple bedside test to evaluate autonomic control following chronic SCI, and to identify those most at risk of OH and cardiovascular dysfunction. We studied 14 subjects with cervical SCI, 11 with thoracic SCI, and 17 able-bodied controls. We continuously recorded heart rate (HR; ECG) and beat-to-beat systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures (Finometer) while supine, and following the passive assumption of an upright seated position. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were calculated. Plasma catecholamines were determined. Motor and sensory loss was assessed using the American Spinal Injury Association (ASIA) impairment scale. Autonomic pathways were assessed from sympathetic skin responses (SSR). Cervical SCI subjects had lower supine HR, SAP, and noradrenaline levels than thoracic SCI and controls (p < 0.05), and lower DAP and MAP than controls (p < 0.05). When upright, HR increased in all groups (p < 0.05); SAP, DAP, and MAP increased (p < 0.01) in thoracic SCI and controls, but not in cervical SCI. Cervical SCI had larger postural falls in SV (p < 0.05) and CO, with smaller increases in TPR than the other two groups. Upright catecholamine levels were lower in cervical SCI (p < 0.05) than thoracic SCI and controls. Completeness of SCI assessed by ASIA scale did not necessarily correlate with autonomic completeness assessed by SSR. Cardiovascular control during orthostasis was impaired and OH was common in cervical SCI, but not thoracic SCI. SSR may identify those at greatest risk of orthostatic hypotension and impaired cardiovascular control. We advocate that assessments of autonomic function be included in the neurological evaluation of SCI, in addition to the ASIA assessment.

Adult↗

PubMed2003

Routing of Hansenula polymorpha alcohol oxidase: an alternative peroxisomal protein-sorting machinery.

Import of Hansenula polymorpha alcohol oxidase (AO) into peroxisomes is dependent on the PTS1 receptor, HpPex5p. The PTS1 of AO (-LARF) is sufficient to direct reporter proteins to peroxisomes. To study AO sorting in more detail, strains producing mutant AO proteins were constructed. AO containing a mutation in the FAD binding fold was mislocalized to the cytosol. This indicates that the PTS1 of AO is not sufficient for import of AO. AO protein in which the PTS1 was destroyed (-LARA) was normally sorted to peroxisomes. Moreover, C-terminal deletions of up to 16 amino acids did not significantly affect AO import, indicating that the PTS1 was not necessary for targeting. Consistent with these observations we found that AO import occurred independent from the C-terminal TPR-domain of HpPex5p, known to bind PTS1 peptides. Synthesis of the N-terminal domain (amino acids 1-272) of HpPex5p in pex5 cells restored AO import, whereas other PTS1 proteins were mislocalized to the cytosol. These data indicate that AO is imported via a novel HpPex5p-dependent protein translocation pathway, which does not require the PTS1 of AO and the C-terminal TPR domains of HpPex5p, but involves FAD binding and the N-terminus of HpPex5p.

Alcohol Oxidoreductases↗

PubMed1990

Atrial natriuretic peptide in patients with diabetes mellitus type I. Effects on systemic and renal hemodynamics and renal excretory function.

In the present study the effects of 1 h intravenous infusion of alpha-human atrial natriuretic peptide (24 ng/min/kg) on systemic and renal hemodynamics and on renal excretory function were studied in six insulin-treated and metabolically well-controlled patients with diabetes mellitus (DM) type I and in six healthy control subjects (C). Basal plasma atrial natriuretic peptide (ANP) concentration was 14.6 +/- 2.0 in DM patients and 14.9 +/- 1.3 pmol/L in C and rose similarly in both groups to 87.1 +/- 22.1 and to 86.9 +/- 11.1 pmol/L, respectively, during alpha-hANP infusion (P less than .05). Maximal effects of alpha-hANP occurred between 30 and 60 min after the start of the infusion. Mean arterial pressure (MAP) (83 +/- 5 v 81 +/- 3 mm Hg), heart rate (HR) (63 +/- 2 v 64 +/- 4/min) and total peripheral resistance (TPR) (11 +/- 1 v 10 +/- 1 mm Hg.min/L) remained unaltered in patients with DM. In contrast, in C MAP and TPR decreased from 83 +/- 3 to 77 +/- 2 mm Hg and from 12 +/- 1 to 10 +/- 1 1 mm Hg.min/L, respectively (P less than .05), whereas HR increased from 53 +/- 2 to 59 +/- 3 beats/min (P less than .05). Cardiac output (CO) rose initially by 11% and by 9% in DM and C, respectively. Urine flow increased from 4.1 +/- 0.9 to 11.3 +/- 1.5 mL/min in DM patients and from 3.9 +/- 1.0 to 8.4 +/- 0.8 mL/min in C (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1983

Central haemodynamic effects of beta blockers in hypertension. A comparison between atenolol, metoprolol, timolol, penbutolol, alprenolol pindolol and bunitrolol.

While it is well established that the acute haemodynamic effects of the beta blockers used in antihypertensive therapy vary considerably, it is still uncertain if this is true during chronic treatment. We have studied seven different beta blockers (one year follow-up): atenolol and metoprolol (cardioselective, without ISA), timolol (non-cardioselective, without ISA), and penbutolol, bunitrolol, alprenolol and pindolol (non-cardioselective, with different degrees of ISA). All drugs induced statistically significant reductions in heart rate (HR), cardiac output (CO) and blood pressure (BP) at rest as well as during exercise. During 100 and 150 W exercise CO and HR were generally decreased by 20-25% on beta blockers without ISA, less on beta blockers with strong ISA. Only in very few patients did total peripheral resistance (TPR) fall more than 10% below pre-treatment level both at rest and during exercise and TPR was not significantly reduced below pre-treatment level in any series. Drugs with combined beta-blocking and vasodilating (or alpha-blocking) properties (prizidilol and labetalol) induced clear reduction in TRP. HR was reduced, but since SI increased there was less reduction in CO on labetalol than on pure beta blockers and actually a small increase in CO on prizidilol.

Adrenergic beta-Antagonists↗

PubMed1988

Multiresistant Staphylococcus aureus: genetics and evolution of epidemic Australian strains.

Molecular and genetic analysis of multiresistant isolates of Staphylococcus aureus from widely separated hospitals in Australia has demonstrated that these are clearly related, and that the predominant strains possess up to three different plasmids, which fall into the following classes: (i) small 1.6 kb plasmids, such as pSK3, which are phenotypically cryptic, (ii) 4.5 kb chloramphenicol resistance plasmids, such as pSK2, and (iii) the pSK1 family of multiresistance plasmids, which range in size from 20 to 42 kb and variously encode resistance to antiseptics and disinfectants, trimethoprim (Tpr), penicillin (Pcr) and the aminoglycosides gentamicin, tobramycin and kanamycin (Gmr Tmr Kmr). Gmr Tmr Kmr is encoded on the pSK1 family plasmids by transposon Tn4001, which was also detected on the chromosomes of some clinical isolates. Tn4001 is composed of inverted repeats of the insertion sequence IS256; these repeats flank a Gmr Tmr Kmr sequence encoding for a 57,000 dalton bifunctional protein with aminoglycoside acetyltransferase [AAC(6')] and phosphotransferase [APH(2")] activities. A Tn4001-like structure, which is defective in transposition but encodes for a Gmr Tmr Kmr determinant homologous with that on Tn4001, occurs on conjugative plasmids from strains isolated in North America. Physical studies indicate that Pcr, via a beta-lactamase, and Tpr, via a trimethoprim-insensitive dihydrofolate reductase (DHFR), are also encoded on the pSK1 family by transposons; these transposons have been designated Tn4002 and Tn4003, respectively. Tn4003 is flanked by direct repeats of the insertion sequence IS257. The evolution of the pSK1 family of multiresistance plasmids is traced through the transposition and genetic rearrangement of resistance determinants. Transposition and genetic rearrangement have also contributed to the evolution of a multiresistant chromosome in Staph. aureus. In the majority of contemporary multiply resistant Staph. aureus strains the determinants for resistance to erythromycin (Emr), fusidic acid, methicillin (Mcr), minocycline, rifampicin, spectinomycin, streptomycin, sulphonamides, tetracycline (Tcr), cadmium (Cdr), and mercury (Hgr) are chromosomally encoded; these strains also possess chromosomally encoded Pcr, via a beta-lactamase. Evidence indicates that some of these determinants, Pcr, Cdr, Hgr, and Tcr, were plasmid encoded in isolates collected from Australian hospitals prior to 1970. Through transposition and site-specific integration, they have since been acquired by the chromosome in more recent Staph. aureus strains.(ABSTRACT TRUNCATED AT 400 WORDS)

Australia↗

PubMed2004

MGOUN3, an Arabidopsis gene with TetratricoPeptide-Repeat-related motifs, regulates meristem cellular organization.

In order to understand the functioning of apical meristems in Arabidopsis more clearly, a new mutant, mgoun3 (mgo3), affected in the structural organization and the functional regulation of both shoot and root meristems has been isolated. mgo3 plants display perturbations in leaf morphogenesis, in the spatial and the temporal formation of primordia, and frequent fasciation of the inflorescence stem. Cellular analysis showed that both cellular organization and cell identity patterning are impaired in the mutant meristems. The MGO3 gene has been isolated by positional cloning. The protein deduced from the cDNA sequence contains TetratricoPeptide Repeats (TPR) and Leucine-Rich Repeats (LRR), two motifs that are thought to act in protein-protein interactions. This gene appears to be unique in the Arabidopsis genome. Although the MGO3 protein presents TPR as in the Arabidopsis proteins HOBBIT and SPINDLY, the MGO3 motifs are more similar to those present in LGN-related proteins, which are regulators for some of the asymmetric cell divisions in animal development. These features suggest a key role for MGO3 in meristematic cell divisions and would be of interest for the comparison between plant and animal development.

Amino Acid Sequence↗

PubMed1991

A novel RNA product of the tyrT operon of Escherichia coli.

The tyrT operon of E. coli and several other tRNA operons of E. coli show striking structural features: they contain repeated sequence units including a 19bp motif resembling the 3' end of the corresponding mature tRNA. A novel RNA, encoded by the repeated sequence of the tyrT operon, was identified. The RNA, characterized by primer extension and Nuclease-S1 analysis, contained 171 nucleotides and terminated with the 19bp motif of the CCA-end of tRNA(1Tyr). The RNA, designated as rtT RNA, is probably released from the primary transcript of tyrT during tRNA processing, it includes the coding capacity for the arginine rich peptide Tpr. Predictions of secondary folding resulted a rather stable RNA structure with a free energy of -44.3kcal/mol. A weak ribosome binding site was found, preceding the second possible AUG initiator codon for Tpr. The comparison of rtT RNA with putative transcripts from the repeated sequences associated with related tRNA genes showed common features with respect to primary structure, arrangement and secondary folding. In E. coli cultures the lag-phase during growth, caused by transient glycine or by isoleucine limitation, was found to be overcome or markedly shortened in the presence of rtT RNA. These and previously reported results suggest a modulatory effect of rtT RNA on stringent response.

Amino Acid Sequence↗

PubMed2005

Hypertonic glucose-based peritoneal dialysate is associated with higher blood pressure and adverse haemodynamics as compared with icodextrin.

BACKGROUND: Little is known about the haemodynamic effects of continuous ambulatory peritoneal dialysis (CAPD) despite its widespread use in the management of end-stage renal failure. We undertook a study to delineate the haemodynamic effects of CAPD using glucose-containing fluids (1.36 and 3.86% glucose) and icodextrin. METHODS: Eight CAPD patients were recruited for a prospective crossover study. Patients attended for two investigatory days (in random order). CAPD was carried out using 1.36% followed by 3.86% glucose (buffered with lactate/bicarbonate, Physioneal) on one study day and 1.36% glucose followed by 7.5% icodextrin (Extraneal) on the other day. Dwell times were 150 min. Blood pressure (BP) and a full range of haemodynamic variables including pulse (HR), stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were measured non-invasively using continuous arterial pulse wave analysis. RESULTS: BP was significantly higher during 3.86% glucose dwells as compared with 1.36% glucose or icodextrin dwells (P<0.0001). TPR during all three dwells was similar; the higher blood pressure was due to an increased HR, SV and, therefore, CO during 3.86% glucose dwells. The higher blood pressure during the 3.86% glucose dwells was present despite the highest ultrafiltration volume and sodium removal. CONCLUSION: This study demonstrates large magnitude haemodynamic changes in response to CAPD. In addition to the well-recognized adverse effects on blood glucose and long-term peritoneal membrane viability, CAPD fluids containing high glucose concentrations may also exert undesirable effects on systemic haemodynamics, with potential long-term consequences for patient outcomes.

Aged↗

PubMed1990

Different patterns of left ventricular filling in arterial hypertension.

To determine whether left ventricular (LV) filling dynamics may be influenced by the type of LV morphological adaptation to arterial hypertension, pulsed Doppler mitral flow velocity recordings were performed in 30 hypertensive patients and in 18 normotensive subjects matched for age, body surface and heart rate. Peak early (E) and late (A) mitral flow velocity, A/E ratio (A/E), time to peak E (TP), acceleration (AHT) and deceleration half-time (DHT) of early mitral flow and isovolumic relaxation time (IRT) were measured. Compared with the control group, hypertensive patients showed prolonged IRT and DHT, increased A and A/E, whereas TP, AHT and E were unchanged. Hypertensive patients were classified into two subgroups on the basis of h/r ratio (h/r). Subgroup 1: 16 patients with normal h/r, less than 0.42, (five patients with increased LV mass index, greater than 129.2 g m-2, and 11 patients with normal LV mass index, less than 129.2 g m-2). Subgroup 2: 14 patients with increased h/r, greater than 0.42, (nine patients with increased LV mass index, greater than 129.2 g m-2 and five patients with normal LV mass index, less than 129.2 g m-2). In Subgroup 1 the cardiac output (CO) was increased and the total peripheral resistance (TPR) was unchanged in comparison with the control group. In Subgroup 2 the opposite haemodynamic profile was detected: normal CO and increased TPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1983

Acute effects of alcohol, beta blockade, and their combination on left ventricular function and hemodynamics in normal man.

Twenty-three healthy males, aged 23 to 62 years, were examined by M-mode echocardiography and systolic time intervals for 3 h after (1) ethanol 1 g/kg by mouth taken over 60 minutes; (2) atenolol 100 mg by mouth; (3) ethanol (1 g/kg) + atenolol (100 mg). The peak mean blood ethanol (+/- s.e.) was 112 +/- 4 mg/100 ml in test 1 and 104 +/- 7 mg/100 ml in test 3. During increasing blood ethanol, heart rate (HR), systolic blood pressure (BP), cardiac output (CO) and echocardiographic indices of left ventricular (LV) function were significantly augmented, while total peripheral resistance (TPR) decreased. During declining blood ethanol, systolic BP, LV end-diastolic and end-systolic diameters, stroke volume (SV) and circumferential wall stress were significantly reduced; echocardiographic indices of LV function were unaltered, but the pre-ejection period/LV ejection time ratio was increased. Atenolol decreased HR, systolic BP, SV, CO, and all estimates of LV function, but increased TPR. Ethanol + atenolol tended to cause smaller depressions in the indices of LV function than did atenolol alone, in spite of similar plasma atenolol concentrations (n = 6). It is concluded that ingestion of modest doses of ethanol evokes vasodilation and enhances LV function during increasing blood ethanol, and reduces LV preload and afterload during decreasing blood ethanol without impairing contractility. Social drinking and beta blockade seem not to have any harmful acute combined effects on the heart and circulation, at least in normal subjects.

Adult↗

PubMed1998

Molecular characterization of the mouse mtprd gene, a homologue of human TPRD: unique gene expression suggesting its critical role in the pathophysiology of Down syndrome.

We and others recently isolated a human TPRD gene, possessing a motif of the tetratricopeptide repeat (TPR), from the Down syndrome-critical region (DCR) of chromosome 21q22.2. In this study, we isolated a mouse homologue of TPRD cDNA, mtprd, and examined its expression profile in mouse embryos. The gene was mapped to mouse chromosome 16C3.3-4, consistent with the location of DCR, and encodes 1,979 amino acid residues with 76% identity to TPRD. The mtprd protein has three units of the TPR motif with 91% homology to TPRD. The protein also has two regions homologous to several matrix proteins with 86 and 70% identities to those of TPRD. Several splicing variants of the 5' portion of the open reading frame of mtprd were identified by RT-PCR and sequencing of mRNAs. In situ hybridization showed that mtprd is ubiquitously expressed in mouse embryos but predominantly in the central nervous system, including the telencephalon, mesencephalon, and metencephalon. These results suggest that the TPRD gene is one of the genes responsible for not only the morphological anomalies but also the neurological abnormalities observed in Down syndrome. The presence of splicing variants indicates that the protein may also have several isoforms in mice.

Amino Acid Sequence↗

PubMed1992

Increased peripheral resistance during reduced uterine perfusion pressure hypertension in pregnant rabbits.

The role of an increase in total peripheral resistance (TPR) and the contribution of angiotensin II (ANG II) to the hypertension induced by reduced uterine perfusion pressure (RUPP) was explored in pregnant rabbits. On the 22nd day of gestation, a catheter and a microthermocouple were placed in the aorta to measure mean arterial pressure (MAP) and cardiac output (CO), respectively. Three days later, RUPP was induced by a clip on the aorta proximal to the ovarian and distal to the renal arteries. Mean arterial pressure distal to the clip (uterine perfusion pressure) was reduced to 56 +/- 8% (mean +/- SD) of the initial level. Twenty-four hours later, MAP rose from 65 +/- 3 to 84 +/- 11 mm Hg; CO index decreased from 207 +/- 18 to 169 +/- 27 ml/min/kg; and TPR index increased from 0.32 +/- 0.03 to 0.51 +/- 0.08 mm Hg kg/ml/min, respectively (n = 7, all p less than 0.01). Sham-operated pregnant rabbits (n = 7) and non-P rabbits (n = 5) with a comparable distal aortic pressure reduction experienced no change in MAP or CO. Infusion of a receptor antagonist of angiotensin II (Sar1,Ile8-Ang II, 1 microgram/kg/min for 20 min) decreased MAP in sham-operated pregnant rabbits from 64 +/- 6 to 54 +/- 6 mm Hg (p less than 0.01) but did not change MAP in RUPP hypertensive rabbits (86 +/- 9 mm Hg before and 87 +/- 8 at the end of infusion, n = 6). These data indicate that RUPP in pregnant rabbits leads to a high resistance form of hypertension in which the formation of Ang II is not increased.

Angiotensin II↗