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PubMed1996

The trough: peak ratio and the normalization of blood pressure profiles.

Experts from the Food and Drug Administration (FDA) of the USA have assumed that hypertensive patients are likely to achieve greatest benefit from therapy in which the antihypertensive effects do not vary excessively during the course of the day. They suggested that the ratio of the minimal (trough) effect to the maximal (peak) effect of the drug should be no lower than 0.5. The concept of the trough: peak ratio (TPR) raises many practical problems. Using actual data, the effect of a drug often shows erratic fluctuations with several local minima and maxima. Mean blood pressure levels for several hours have been used to estimate the trough and peak effects. Blood pressure averages over 4 h may e a good choice, because blood pressures measured 4 h apart are not correlated. The statistical distribution of the TPR is not Gaussian. Negative and very low or positive and very high individual ratios are frequently observed. Therefore, the individual TPR is of questionable clinical value, except when the ratio is applied for responders only. The TPR can be calculated for a sample. In that case, the bootstrap method can be used to estimate the error of the TPR. Most important is the question of why the TPR should be higher than 0.5. We introduced the concept of 'normalization of the blood pressure profile', namely 'reducing the blood pressure profiles in hypertensives to match those profiles in normotensives'. This concept leads very naturally to the TPR and justifies the lower limit of 0.5 for the TPR.

Journal Article↗

PubMed1986

Correlation of treponemicidal activity in normal human serum with the presence of IgG antibody directed against polypeptides of Treponema phagedenis biotype Reiter and Treponema pallidum, Nichols strain.

Normal human serum (NHS) was shown to have complement-dependent treponemicidal activity against both Treponema pallidum and Treponema phagedenis biotype Reiter (TPR) by employing in vitro-in vivo neutralization and TPR plaque assays, respectively. The molecular basis of NHS treponemicidal activity was studied by immunoblot analysis in conjunction with treponemicidal assays. Five major T. pallidum polypeptide bands (47kDa, 35kDa, 33kDa doublet, and 30 kDa) and three major TPR polypeptide bands (47kDa and 33kDa doublet) bound IgG present in NHS. Absorption of NHS with TPR completely removed both TPR and T. pallidum treponemicidal activity; corresponding immunoblots demonstrated a significant removal of IgG antibody against all three TPR polypeptide bands as well as four T. pallidum polypeptide bands (30kDa, 33kDa doublet, and 35kDa). In contrast, T. pallidum absorption of NHS was found to remove treponemicidal activity against T. pallidum but not TPR; corresponding Western blots showed the complete removal of IgG antibody against all but one T. pallidum polypeptide band (47kDa) but no detectable loss in IgG antibody against the TPR polypeptides. These results suggest that antibody in NHS generated against nonpathogenic, indigenous treponemes is responsible for the T. pallidum treponemicidal activity. Furthermore, the treponemicidal activity against T. pallidum correlated with the presence of IgG antibody against T. pallidum polypeptides of 30kDa, 35kDa, and a 33kDa doublet.

Antibodies, Bacterial↗

PubMed1994

Use of trough:peak ratio in the assessment of antihypertensive drug therapy.

The trough:peak ratio (TPR) has been used to describe the extent to which an antihypertensive drug achieves adequate blood pressure control over the entire dosing interval. The TPR represents the net fall in blood pressure just before the next dose of medication is taken divided by the maximum reduction in blood pressure. For dihydropyridine calcium antagonists, the TPR is highly dependent upon the pharmacokinetics of the individual compound since the antihypertensive response correlates with the log drug plasma concentration. Accordingly, longer acting formulations exhibit a TPR close to unity with the maximum fall in blood pressure similar to the reduction at the end of the dosing interval. The application of TPR to angiotensin-converting enzyme inhibitors has unmasked a number of methodological problems associated with this approach to evaluating a drug's antihypertensive profile. The TPR has been calculated with and without subtracting responses to placebo with first doses and after several weeks of chronic therapy, and in responders only versus all subjects. Different approaches have also been taken to calculate the TPR, leading to marked variations in values. A review of the existing literature leads to the conclusion that improvements in the standardization of study design and data analysis are needed before TPR can become an accepted measure of 24 h blood pressure control.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

[Pulmonary hemodynamics and long-term outcome in patients with chronic pulmonary thromboembolism and pulmonary hypertension].

We examined pulmonary hemodynamics and long-term outcome in 78 consecutive patients with chronic pulmonary thromboembolism and pulmonary hypertension. These patient's ages ranged from 19 to 75 years; the mean was 51.0 +/- 13.8 years and there was no difference in sex distribution. Mean pulmonary-artery pressure (PAm) was 44 +/- 14 mmHg and total pulmonary resistance (TPR) was 1138 +/- 634 dyne.sec.cm-5. Overall five-year survival was 58.4%, but in patients whose PAm was below 30 mmHg, the outcomes were better: all of these patients survived for at least 5 years. In patients whose PAm was above 30 mmHg, no correlation was found between the outcome and the magnitude of PAm. We divided the patients into four subgroups according to their TPR: 500 dyne.sec.cm-5 (TPR, 500 > or = TPR < 1000 dyne.sec.cm-5, 1000 < or = TPR < 1500 dyne.sec.cm-5, and 1500 dyne.sec.cm-5 < or = TPR. The five-year survivals in these groups were 100%, 88.9%, 52.4%, and 40.0%, respectively. Outcome correlated with the magnitude of TPR. TPR was useful for predicting the outcome of chronic pulmonary thromboembolism.

Adult↗

PubMed1996

Hemodynamic profile of activation of histamine H3 receptors by R-alpha-methylhistamine in the guinea pig.

1. The effect of R-alpha-methylhistamine, a histamine H1 receptor agonist, was studied on cardiovascular hemodynamics in bilateral vagotomized, anesthetized guinea pigs. 2. R-alpha-methylhistamine (100 micrograms/kg, IV) a dose that selectively activates histamine H3 receptors, produced hypotension and bradycardia. Total peripheral resistance (TPR) and rate pressure product (RPP) were also decreased at this dose. 3. Pretreatment with the ganglionic blocker hexamethonium (20 mg/kg, IV) blocked the blood pressure (BP), heart rate (HR), TPR, and RPP effects of R-alpha-methylhistamine (100 micrograms/kg, IV). Hexamethonium did not block the hypotensive and TPR lowering actions of the muscarinic agonist methacholine (1 and 3 micrograms/kg, IV). 4. Pretreatment with the alpha 1-adrenoceptor antagonist prazosin (0.5 mg/kg IV), blocked R-alpha-methylhistamine's (100 micrograms/kg, IV) effects on BP, TPR, and RPP. Prazosin did not antagonize the bradycardia effect of R-alpha-methylhistamine. 5. Pretreatment with the beta-adrenoceptor antagonist atenolol (1 mg/kg, IV) did not alter the BP, TPR, or RPP actions of R-alpha-methylhistamine. The HR effects of R-alpha-methylhistamine were blocked by atenolol. 6. The hemodynamic effects of R-alpha-methylhistamine were compared to the hemodynamic profile of the calcium channel blocker, verapamil (0.5 mg/kg, IV). Verapamil had little effect on TRP and had a greater cardiac depressant effect as evidenced by a significant reduction in HR and cardiac output (CO). 7. In summary, these results show that activation of prejunctional H3 receptors with R-alpha-methylhistamine decreases basal, BP, HR, TPR, and RPP in anesthetized guinea pigs. The fall in BP is mediated by a decrease in TPR. Furthermore, the inhibitory effects of R-alpha-methylhistamine on sympathetic control of the vasculature appears to impart a greater physiologic effect on the H3-histamine mediated hypotension than its inhibitory effects on sympathetic agents to the heart.

Animals↗

PubMed2004

Surgeon reimbursement for trauma care.

BACKGROUND: Trauma care is a well-known financial burden for hospitals, yet reimbursement for the surgeon has not been reported. METHODS: For 1999, the percent of the surgeons' bills reimbursed for general surgery services (gPR) was compared with that for trauma services (tPR). Mean tPR for various groups were compared. Factors predictive of tPR lower than gPR were identified. RESULTS: The gPR was 49%, and, for 371 trauma patients, tPR was 45% (P = 0.03). The mean tPR for injury severity score (ISS) < or =10 was 48%, and for ISS > or =11, 57% (P = 0.03). Patients transferred from outside facilities did not have a significantly lower mean tPR. Penetrating trauma (odds ratio 3.7, P = 0.008) was predictive of tPR lower than gPR. CONCLUSIONS: Surgeon reimbursements for trauma care was significantly, yet only slightly less than for all general surgery care. Surgeons should not be reluctant to take trauma call based on perceptions of low reimbursement.

Adult↗

PubMed1994

Molecular characterization of Theileria parasites: application to the epidemiology of theileriosis in Zimbabwe.

Forty Theileria schizont-infected lymphocyte culture isolates from Zimbabwe were characterized using a panel of antischizont monoclonal antibodies (MAbs) and 4 Theileria parva DNA probes containing cloned extrachromosomal element, Tpr repetitive, ribosomal and telomeric sequences. The Theileria isolates were assigned as T. parva or T. taurotragi on the basis of reactivities with MAbs and restriction fragment length polymorphisms (RFLPs) detected using the extra-chromosomal element probe. Cattle-derived T. parva isolates were relatively homogeneous on the basis of reactivities with MAbs and RFLPs detected using Tpr repetitive and ribosomal DNA probes. In contrast to previous results from Kenya, most of the cattle-derived isolates from Zimbabwe exhibited very similar Tpr restriction fragment patterns, although the Tpr genotypes of buffalo-derived isolates were heterogeneous. This suggests that selection for a particular Tpr genotype may be occurring in cattle. Many isolates with similar Tpr genotypes were differentiated by RFLPs detected using the telomeric DNA probe. The T. parva Boleni immunizing stock was distinguished from all other isolates by telomeric RFLPs. The T. parva Boleni Tpr repetitive DNA probe cross-hybridized with T. taurotragi DNA and detected RFLPs between different T. taurotragi isolates.

Animals↗

PubMed2005

Local and long-range stability in tandemly arrayed tetratricopeptide repeats.

The tetratricopeptide repeat (TPR) is a 34-aa alpha-helical motif that occurs in tandem arrays in a variety of different proteins. In natural proteins, the number of TPR motifs ranges from 3 to 16 or more. These arrays function as molecular scaffolds and frequently mediate protein-protein interactions. We have shown that correctly folded TPR domain proteins, exhibiting the typical helix-turn-helix fold, can be designed by arraying tandem repeats of an idealized TPR consensus motif. To date, three designed proteins, CTPR1, CTPR2, and CTPR3 (consensus TPR number of repeats) have been characterized. Their high-resolution crystal structures show that the designed proteins indeed adopt the typical TPR fold, which is specified by the correct positioning of key residues. Here, we present a study of the thermodynamic properties and folding kinetics of this set of designed proteins. Chemical denaturation, monitored by CD and fluorescence, was used to assess the folding and global stability of each protein. NMR-detected amide proton exchange was used to investigate the stability of each construct at a residue-specific level. The results of these studies reveal a stable core, which defines the intrinsic stability of an individual TPR motif. The results also show the relationship between the number of tandem repeats and the overall stability and folding of the protein.

Amino Acid Motifs↗

PubMed1996

The tetratricopeptide repeat domain of protein phosphatase 5 mediates binding to glucocorticoid receptor heterocomplexes and acts as a dominant negative mutant.

We previously identified a protein-serine phosphatase designated PP5, based on the binding of its tetratricopeptide repeat (TPR) domain to the atrial natriuretic peptide receptor (Chinkers, M. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 11075-11079). We have now identified another protein complex to which PP5 is targeted through its TPR domain. A 90-kDa protein, identified as heat shock protein 90 (hsp90) by immunoblotting, specifically co-immunoprecipitated from COS-7 cell lysates with the FLAG-tagged TPR domain of PP5. hsp90 also co-immunoprecipitated with full-length FLAG-tagged PP5 overexpressed in COS-7 cells and with endogenous PP5 from untransfected COS-7 cells or rat brain. During gel filtration, PP5 and hsp90 comigrated in a high molecular weight complex. Since glucocorticoid receptors (GR) exist as large heterocomplexes containing hsp90 bound to TPR proteins, we hypothesized that PP5 might be associated with these complexes. Consistent with this hypothesis, PP5 specifically co-immunoprecipitated with GR from mouse L cell lysates. To test the functional importance of this TPR-mediated association in living cells, we used a dominant negative PP5 mutant consisting only of its TPR domain. The mutant inhibited GR-mediated transactivation by approximately 70% in transfected CV-1 cells. This is the first evidence that the TPR proteins in steroid receptor heterocomplexes may be required for signaling in vivo.

Animals↗

PubMed1998

p50(cdc37) binds directly to the catalytic domain of Raf as well as to a site on hsp90 that is topologically adjacent to the tetratricopeptide repeat binding site.

Several protein kinases (e.g. pp60(src), v-Raf) exist in heterocomplexes with hsp90 and a 50-kDa protein that is the mammalian homolog of the yeast cell cycle control protein Cdc37. In contrast, unliganded steroid receptors exist in heterocomplexes with hsp90 and a tetratricopeptide repeat (TPR) domain protein, such as an immunophilin. Although p50(cdc37) and TPR domain proteins bind directly to hsp90, p50(cdc37) is not present in native steroid receptor.hsp90 heterocomplexes. To obtain some insight as to how v-Raf selects predominantly hsp90.p50(cdc37) heterocomplexes, rather than hsp90.TPR protein heterocomplexes, we have examined the binding of p50(cdc37) to hsp90 and to Raf. We show that p50(cdc37) exists in separate hsp90 heterocomplexes from the TPR domain proteins and that intact TPR proteins compete for p50(cdc37) binding to hsp90 but a protein fragment containing a TPR domain does not. This suggests that the binding site for p50(cdc37) lies topologically adjacent to the TPR acceptor site on the surface of hsp90. Also, we show that p50(cdc37) binds directly to v-Raf, with the catalytic domain of Raf being sufficient. We propose that the combination of exclusive binding of p50(cdc37) versus a TPR domain protein to hsp90 plus direct binding of p50(cdc37) to Raf allows the protein kinase to select for the dominant hsp90.p50(cdc37) composition that is observed with a variety of protein kinase heterocomplexes immunoadsorbed from cytosols.

Animals↗

PubMed2003

C-terminal sequences outside the tetratricopeptide repeat domain of FKBP51 and FKBP52 cause differential binding to Hsp90.

Hsp90 assembles with steroid receptors and other client proteins in association with one or more Hsp90-binding cochaperones, some of which contain a common tetratricopeptide repeat (TPR) domain. Included in the TPR cochaperones are the Hsp70-Hsp90-organizing protein Hop, the FK506-binding immunophilins FKBP52 and FKBP51, the cyclosporin A-binding immunophilin CyP40, and protein phosphatase PP5. The TPR domains from these proteins have similar x-ray crystallographic structures and target cochaperone binding to the MEEVD sequence that terminates Hsp90. However, despite these similarities, the TPR cochaperones have distinctive properties for binding Hsp90 and assembling with Hsp90.steroid receptor complexes. To identify structural features that differentiate binding of FKBP51 and FKBP52 to Hsp90, we generated an assortment of truncation mutants and chimeras that were compared for coimmunoprecipitation with Hsp90. Although the core TPR domain (approximately amino acids 260-400) of FKBP51 and FKBP52 is required for Hsp90 binding, the C-terminal 60 amino acids (approximately 400-end) also influence Hsp90 binding. More specifically, we find that amino acids 400-420 play a critical role for Hsp90 binding by either FKBP. Within this 20-amino acid region, we have identified a consensus sequence motif that is also present in some other TPR cochaperones. Additionally, the final 30 amino acids of FKBP51 enhance binding to Hsp90, whereas the corresponding region of FKBP52 moderates binding to Hsp90. Taking into account the x-ray crystal structure for FKBP51, we conclude that the C-terminal regions of FKBP51 and FKBP52 outside the core TPR domains are likely to assume alternative conformations that significantly impact Hsp90 binding.

Amino Acid Sequence↗

PubMed2006

Differential mapping of the amino acids mediating agonist and antagonist coordination with the human thromboxane A2 receptor protein.

Despite the well documented involvement of thromboxane A(2) receptor (TPR) signaling in the pathogenesis of thrombotic diseases, there are currently no rationally designed antagonists available for clinical use. To a large extent, this derives from a lack of knowledge regarding the topography of the TPR ligand binding pocket. On this basis, the purpose of the current study was to identify the specific amino acid residues in the TPR protein that regulate ligand coordination and binding. The sites selected for mutation reside within or in close proximity to a region we previously defined as a TPR ligand binding region (i.e. the C terminus of the second extracellular loop and the leading edge of the fifth transmembrane domain). Mutation of these residues caused varying effects on the TPR-ligand coordination process. Specifically, the D193A, D193Q, and D193R mutants lost SQ29,548 (antagonist) binding and exhibited a dramatically reduced calcium response, which could not be restored by elevated U46619 (agonist) doses. The F184Y mutant lost SQ29,548 binding and exhibited a reduced calcium response (which could be restored by elevated U46619); and the T186A and S191T mutants lost SQ29,548 binding and retained a normal U46619-induced calcium response. Furthermore, these last three mutants also revealed a divergence in the binding of two structurally different antagonists, SQ29,548 and BM13.505. Two separate mutants that exhibited SQ29,548 binding yielded either a normal (F196Y) or reduced (S201T) U46619 response. Finally, mutation of other residues directly adjacent to those described above (e.g. E190A and F200A) produced no detectable effects on either SQ29,548 binding or the U46619-induced response. In summary, these results identify key amino acids (in particular Asp(193)) involved in TPR ligand coordination. These findings also demonstrate that TPR-specific ligands interact with different residues in the ligand-binding pocket.

Amino Acid Sequence↗

PubMed1999

Role of the sympathetic control of vascular resistance in ethanol-clonidine hemodynamic interaction in SHRs.

Our previous studies showed that ethanol selectively counteracts centrally mediated hypotensive responses. In this study, we investigated the role of sympathetic nerve activity, cardiac output (CO), and total peripheral resistance (TPR) in this antagonistic hemodynamic interaction between ethanol and clonidine. Changes in blood pressure (BP), heart rate (HR), CO, stroke volume (SV), and TPR elicited by intracisternal (i.c.) clonidine and subsequent ethanol or saline were evaluated in conscious freely moving spontaneously hypertensive rats (SHRs). Clonidine (0.5 microg, i.c.) evoked hypotension was due to a significant reduction in TPR (from 3.6+/-0.21 to 2.8+/-0.17 mm Hg/ml/min/100 g), which was associated with a significant (p < 0.05) reduction in plasma norepinephrine (NE, from 660+/-115 to 310+/-50 pg/ml), measured as index of sympathetic activity. Ethanol (1 g/kg, i.v.) counteracted the hypotensive effect of clonidine and produced significant (p < 0.05) increases in plasma NE and TPR. Further support for the hypothesis that ethanol selectively counteracts centrally mediated hypotension was sought by investigating the effect of ethanol on peripherally mediated hemodynamic responses to hydralazine. Hydralazine (0.4 mg/kg, i.v.) produced a hypotension similar in magnitude to that produced by clonidine, which was also due to a significant reduction in TPR. However, unlike the case with clonidine, reflex increases in HR, SV, and hence CO were evident. Ethanol given after hydralazine produced a short-lived pressor effect (<10 min vs. 60 min in case of clonidine) in spite of a sustained increase in TPR. The latter was offset by the simultaneous decreases in CO, SV, and HR. A 30% increase in plasma NE caused by hydralazine returned to baseline level after ethanol or saline. Blood ethanol concentrations were similar in all treatment groups. These findings suggest that ethanol selectively counteracts centrally evoked hypotensive responses by counteracting the sympathoinhibition-mediated decreases in TPR elicited by centrally administered clonidine in conscious SHRs.

Animals↗

PubMed2001

The effect of trauma program registry on reported mortality rates.

BACKGROUND: This study assesses the relationship that the brand of trauma program registry (TPR) has on mortality rate (MR) in the reports prepared by the American College of Surgeons Committee on Trauma (ACSCOT) trauma center (TC) site surveyors. METHODS: Data from 242 ACSCOT adult TC survey reports (88 Level I, 115 Level II, and 39 Level III) were analyzed for annual trauma volume, injury severity score (ISS), MR, and TPR. Six TPR (A through F) were identified; group F was a composite of several infrequently used TPRs. This report focuses on the ISS range 16-24 because of the likelihood that the mean for each TC would be near 20 and MR is high enough so that a difference, if present, could be statistically documented. RESULTS: For the total group, MR showed no correlation with TC volume or TC level for ISS 16-24. MR was significantly different according to which TPR was used by the TCs. The MR is less (4.8%) for 14 high volume TCs (over 1200 admits) using TPR A compared with 33 low volume TCs (below 800 admits) using TPR A (6.34%). CONCLUSION: The MR for ISS 16-24 in ACSCOT-surveyed TCs differs within subgroups based on type of TPR utilized. This may reflect improper use of the software programs. Enhanced skill in the application of software programs designed to generate ISS scores is essential if meaningful studies on the effects of improved trauma care on MR are to be conducted. Hand scored ISS by trained personnel may circumvent this problem.

Confounding Factors, Epidemiologic↗

PubMedDate not supplied

Acute effects of transcendental meditation on hemodynamic functioning in middle-aged adults.

OBJECTIVE: Increased peripheral vasoconstriction (ie, total peripheral resistance, or TPR) has been implicated as playing an important role in the early development of essential hypertension. Some studies have demonstrated that Transcendental Meditation (TM) reduces high blood pressure, but the hemodynamic adjustments behind these blood pressure reductions have not been elucidated. The aim of this study was to provide a preliminary investigation of the acute effects of TM on TPR. METHODS: Subjects were 32 healthy adults (16 women and 16 men; 30 white and two African American; mean age, 46.4 +/- 3.9 years). Subjects were divided into a TM group of long-term TM practitioners (eight white women, nine white men, and one African American man; mean years of twice-daily TM practice, 22.4 +/- 6.7) and a control group (eight white women, five white men, and one African American man). Hemodynamic functioning was assessed immediately before and during three conditions: 20 minutes of rest with eyes open (all subjects), 20 minutes of TM (TM group), and 20 minutes of eyes-closed relaxation (control group). RESULTS: During eyes-open rest, the TM group had decreases in systolic blood pressure (SBP) and TPR, compared with increases in the control group (SBP: -2.5 vs. +2.4 mm Hg, p < .01; TPR: -0.7 vs. +0.5 mm Hg/liter per minute, p < .004). During TM, there was a greater decrease in SBP due to a concomitantly greater decrease in TPR compared with the control group during eyes-closed relaxation (SBP: -3.0 vs. +2.1 mm Hg, p < .04; TPR: -1.0 vs. +0.3 mm Hg/liter per minute, p < .03). CONCLUSIONS: TPR decreased significantly during TM. Decreases in vasoconstrictive tone during TM may be the hemodynamic mechanism responsible for reduction of high blood pressure over time. The results of this study provide a preliminary contribution to the understanding of the underlying hemodynamic mechanisms responsible for the beneficial influence of TM on cardiovascular risk factors.

Adult↗

PubMed2003

Comparison of the smoothness index, the trough : peak ratio and the morning : evening ratio in assessing the features of the antihypertensive drug effect.

OBJECTIVE: To provide a direct comparison of the trough : peak ratio (TPR), the morning : evening home blood pressure ratio (MER) and the smoothness index (SI) in assessing the features of the antihypertensive drug effect. PATIENTS AND METHODS: A total of 27 untreated hypertensives were randomized to receive lisinopril 20 mg o.d. or losartan 50 mg o.d. for 5 weeks and were subsequently crossed-over to the alternative treatment for a second 5-week period. Twenty-four hour ambulatory and 5-day home blood pressure were monitored before randomization and at the end of each treatment period. TPR, MER and SI were calculated for each drug for the total study population and for responders only. RESULTS: When all patients were considered, lisinopril provided higher values of TPR [0.63/0.66 for systolic/diastolic blood pressure (SBP/DBP)], MER (1.02/0.77) and SI (1.01/0.87) than losartan (0.35/0.51, 0.60/0.60 and 0.64/0.53, respectively). Analysis of responders only, again showed a clear advantage of lisinopril over losartan in TPR (0.77/0.67 versus 0.44/0.47, respectively) and MER (0.86/0.87 versus 0.48/0.61), whereas there was no difference in SI (1.25/1.13 for lisinopril versus 1.11/1.12 for losartan). CONCLUSIONS: These data suggest that the assessment of the duration of the antihypertensive drug effect provided by the MER is consistent to that by the TPR and that two drugs with different levels of TPR and MER may have the same level of SI. It appears that the SI is not simply a more reliable index of the features of the antihypertensive drug effect, but offers a different type of information complementary to that provided by the TPR and the MER, in regard to the homogeneity and the magnitude but not the duration of the antihypertensive effect.

Adult↗

PubMed1999

The alpha-subunit of protein prenyltransferases is a member of the tetratricopeptide repeat family.

Lipidation catalyzed by protein prenyltransferases is essential for the biological function of a number of eukaryotic proteins, many of which are involved in signal transduction and vesicular traffic regulation. Sequence similarity searches reveal that the alpha-subunit of protein prenyltransferases (PTalpha) is a member of the tetratricopeptide repeat (TPR) superfamily. This finding makes the three-dimensional structure of the rat protein farnesyltransferase the first structural model of a TPR protein interacting with its protein partner. Structural comparison of the two TPR domains in protein farnesyltransferase and protein phosphatase 5 indicates that variation in TPR consensus residues may affect protein binding specificity through altering the overall shape of the TPR superhelix. A general approach to evolutionary analysis of proteins with repetitive sequence motifs has been developed and applied to the protein prenyltransferases and other TPR proteins. The results suggest that all members in PTalpha family originated from a common multirepeat ancestor, while the common ancestor of PTalpha and other members of TPR superfamily is likely to be a single repeat protein.

Alkyl and Aryl Transferases↗

PubMed1990

A comparison of different challenge methods for induction of atrophic rhinitis in pigs.

Transmission and development of atrophic rhinitis (AR) was studied in 5- to 15-week-old pigs (Groups 2-7) originating from a herd free of AR, and compared to unexposed healthy pigs (Group 1), and pigs from a herd with endemic AR (Group 8). At the start of the trial, pigs in Groups 2-5 were challenged intranasally twice a week for 3 weeks with pure cultures of bacteria originating from the endemic AR herd: Nontoxigenic Pasteurella multocida type A (PmA) plus Bordetella bronchiseptica phase I (Bb) (Group 2); PmA + toxigenic Pm type D (PmD) (Group 3); PmD only (Group 4); and PmD + Bb (Group 5). Group 6 pigs were challenged with nasal wash of pigs from the endemic AR herd, and Group 7 pigs were challenged by being housed together in the same pen with Group 8 pigs throughout the study. Nasal swabs of all pigs were cultured 5 times during the study. Serum was collected at 6 weeks post challenge. Average daily gain (ADG) and turbinate lesions (turbinate gross lesions by visual scoring and by Turbinate Perimeter Ratio, TPR, scoring, and histopathological lesions) were measured at the time of slaughter at 15 weeks of age. Mean TPR value for the Group 1 pigs was 1.64, which was significantly (P less than 0.05) different from the mean TPR value of 0.58 for the pigs from the endemic AR herd (Group 8), the 0.79 value for Group 6 pigs, and 1.03 value for Group 7 pigs. Of pigs challenged with pure bacterial cultures, only Group 5 (PmD + Bb) developed significant AR (mean TPR = 1.24). Only one pig in each of Groups 2 and 3, and two pigs in Group 4 showed TPR values indicative of AR (TPR less than 1.30). However, histopathological examination showed that those pigs were recovering from the infection 7 weeks post challenge. Constant exposure to certain bacteria or other factors in nasal washings, stress of crowding or poor environmental conditions might be required to experimentally produce AR in 5-week and older pigs similar to that in naturally infected pigs. There was no relationship between turbinate lesions and the isolation frequency or quantity of PmA, PmD, or Bb. Antibody levels against PmA or PmD had moderate to high correlation with TPR values (r = -0.694 and -0.503 respectively). ELISA values also corresponded well with the type of bacteria inoculated in each group of pigs and appeared to be a sensitive test for PmA, PmD, and Bb infections in pigs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗