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Biomedical subjects

B C Chen

Publications and source records attributed to B C Chen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Use of nonautologous microencapsulated fibroblasts in growth hormone gene therapy to improve growth of midget swine.

The aim of the present study was to investigate the expression activity, both in vitro and in vivo, of the porcine growth hormone complementary DNA (pGH cDNA) in porcine fetal fibroblast (PFF) cells. The pGH gene had been constructed inside the bicistronic retroviral vector PSN and subsequently transfected into PFF cells further encapsulated with immunoprotective microcapsules. This would provide a way to evaluate the improvement in growth performance of Tao-Yuan swine by the use of nonautologous microencapsulated fibroblasts carrying the pGH cDNA via the technique of somatic gene therapy. Results from Southern blot analysis confirmed that the full length of the pGH cDNA was completely integrated into the genome of the PFF cells after they had been infected one to four times using a PSN retroviral vector. Moreover, Northern blot analysis showed that high transcription activity was present in clones infected twice, and exogenous pGH secretion was found when the pGH-infected PFF had been further cultured for 48 hr in vitro and subjected to immunoblot assay. Encapsulation of the pGH-PFF with an alginate-poly-L-lysine-alginate membrane did not show any deterioration in their proliferation and survival both in vitro and in vivo. The pGH gene in encapsulated recombinant fibroblasts was fully expressed after it had been transplanted into the peritoneal cavity of the Tao-Yuan swine, and reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed on the microcapsules retrieved 1 month later. The feasibility of pGH gene therapy to improve midget Tao-Yuan swine growth enhancement is further supported by the fact that transplantation of the encapsulated recombinant fibroblast cells resulted in a much more significant increase in weight gain than in those swine in either the age-matched untreated control group or in those that had been transplanted with uncapsulated recombinant PFF cells (10.56 +/- 1.01 kg versus 6.95 +/- 0.94 and 5.27 +/- 1.30 kg; p < 0.05). These experimental data suggest that growth hormone gene therapy did provide an alternative approach for growth improvement in midget Tao-Yuan swine.

Animals↗
PubMed1998

Pharmacological comparison of UTP- and thapsigargin-induced arachidonic acid release in mouse RAW 264.7 macrophages.

1. Although stimulation of mouse RAW 264.7 macrophages by UTP elicits a rapid increase in intracellular free Ca2+ ([Ca2+]i), phosphoinositide (PI) turnover, and arachidonic acid (AA) release, the causal relationship between these signalling pathways is still unclear. In the present study, we investigated the involvement of phosphoinositide-dependent phospholipase C (PI-PLC) activation, Ca2+ increase and protein kinase activation in UTP-induced AA release. The effects of stimulating RAW 264.7 cells with thapsigargin, which cannot activate the inositol phosphate (IP) cascade, but results in the release of sequestered Ca2+ and an influx of extracellular Ca2+, was compared with the effects of UTP stimulation to elucidate the multiple regulatory pathways for cPLA2 activation. 2. In RAW 264.7 cells UTP (100 microM) and thapsigargin (1 microM) caused 2 and 1.2 fold increases, respectively, in [3H]-AA release. The release of [3H]-AA following treatment with UTP and thapsigargin were non-additive, totally abolished in the Ca2+-free buffer, BAPTA (30 microM)-containing buffer or in the presence of the cPLA2 inhibitor MAFP (50 microM), and inhibited by pretreatment of cells with pertussis toxin (100 ng ml(-1)) or 4-bromophenacyl bromide (100 microM). By contrast, aristolochic acid (an inhibitor of sPLA2) had no effect on UTP and thapsigargin responses. 3. U73122 (10 microM) and neomycin (3 mM), inhibitors of PI-PLC, inhibited UTP-induced IP formation (88% and 83% inhibition, respectively) and AA release (76% and 58%, respectively), accompanied by a decrease in the [Ca2+]i rise. 4. Wortmannin attenuated the IP response of UTP in a concentration-dependent manner (over the range 10 nM-3 microM), and reduced the UTP-induced AA release in parallel. RHC 80267 (30 microM), a specific diacylglycerol lipase inhibitor, had no effect on UTP-induced AA release. 5. Short-term treatment with PMA (1 microM) inhibited the UTP-stimulated accumulation of IP and increase in [Ca2+]i, but had no effect on the release of AA. In contrast, the AA release caused by thapsigargin was increased by PMA. 6. The role of PKC in UTP- and thapsigargin-mediated AA release was shown by the blockade of these effects by staurosporine (1 microM), Ro 31-8220 (10 microM), Go 6976 (1 microM) and the down-regulation of PKC. 7. Following treatment of cells with SK&F 96365 (30 microM), thapsigargin-, but not UTP-, induced Ca2+ influx, and the accompanying AA release, were down-regulated. 8. Neither PD 98059 (100 microM), MEK a inhibitor, nor genistein (100 microM), a tyrosine kinase inhibitor, had any effect on the AA responses induced by UTP and thapsigargin. 9. We conclude that UTP-induced cPLA2 activity depends on the activation of PI-PLC and the sustained elevation of intracellular Ca2+, which is essential for the activation of cPLA2 by UTP and thapsigargin. The [Ca2+]i-dependent AA release that follows treatment with both stimuli was potentiated by the activity of protein kinase C (PKC). A pertussis toxin-sensitive pathway downstream of the increase in [Ca2+]i was also shown to be involved in AA release.

Animals↗
PubMed1998

Distinct PKC isoforms mediate the activation of cPLA2 and adenylyl cyclase by phorbol ester in RAW264.7 macrophages.

The modulatory effects of protein kinase C (PKC) on the activation of cytosolic phospholipase A2 (cPLA2) and adenylyl cyclase (AC) have recently been described. Since the signalling cascades associated with these events play critical roles in various functions of macrophages, we set out to investigate the crosstalk between PKC and the cPLA2 and AC pathways in mouse RAW 264.7 macrophages and to determine the involvement of individual PKC isoforms. The cPLA2 and AC pathways were studied by measuring the potentiation by the phorbol ester PMA of ionomycin-induced arachidonic acid (AA) release and prostagladin E1 (PGE1)-stimulated cyclic AMP production, respectively. PMA at 1 microM caused a significant increase in AA release both in the presence (371%) and absence (67%) of ionomycin induction, while exposure of RAW 264.7 cells to PMA increased PGE1 stimulation of cyclic AMP levels by 208%. Treatment of cells with staurosporine and Ro 31-8220 inhibited the PMA-induced potentiation of both AA release and cyclic AMP accumulation, while Go 6976 (an inhibitor of classical PKC isoforms) and LY 379196 (a specific inhibitor of PKCbeta) inhibited the AA response but failed to affect the enhancement of the cyclic AMP response by PMA. Long term pretreatment of cells with PMA abolished the subsequent effect of PMA in potentiating AA release, but only inhibited the cyclic AMP response by 42%. Neither PD 98059, an inhibitor of MEK, nor genistein, an inhibitor of tyrosine kinases, had any effect on the ability of PMA to potentiate AA or cyclic AMP production. The potentiation of AA release, but not of cyclic AMP formation, by PMA was sensitive to inhibition by wortmannin. This effect was unrelated to the inhibition of PKC activation as deduced from the translocation of PKC activity to the cell membrane. Western blot analysis revealed the presence of eight PKC isoforms (alpha, betaI, betaII, delta, epsilon, mu, lambda and xi) in RAW 264.7 cells and PMA was shown to induce the translocation of the alpha, betaI, betaII, delta, epsilon and mu isoforms from the cytosol to the cell membrane within 2 min. Pretreatment of cells with PMA for 2-24 h resulted in a time-dependent down-regulation of PKCalpha, betaI, betaII, and delta expression, while the levels of the other four PKC isozymes were unchanged after PMA treatment for 24 h. A decrease in the potentiation of AA release by PMA was observed, concomitant with the time-dependent down-regulation of PKC. These results indicate that PKCbeta has a crucial role in the mediation of cPLA2 activation by the phorbol ester PMA, whereas PMA utilizes PKC epsilon and/or mu to up-regulate AC activity.

Adenylyl Cyclases↗
PubMed1997

Inhibition of ecto-ATPase by the P2 purinoceptor agonists, ATPgammaS, alpha,beta-methylene-ATP, and AMP-PNP, in endothelial cells.

Ecto-ATPase is a plasma membrane-bound enzyme that sequentially dephosphorylates extracellular nucleotides such as ATP. This breakdown of ATP and other nucleotides makes it difficult to characterize and classify P2 purinoceptors. We have previously shown that the P2 purinergic antagonists, PPADS, suramin and reactive blue, act as ecto-ATPase inhibitors in various cell lines. Here, we show that the P2 purinergic agonists, ATPgammaS, alpha,beta-methylene ATP (alpha,beta-MeATP) and AMP-PNP, inhibit the ecto-ATPase of bovine pulmonary artery endothelial cells (CPAE), with pIC50 values of 5.2, 4.5 and 4.0, respectively. In CPAE, FPL67156, a selective ecto-ATPase inhibitor, also inhibits ecto-ATPase activity, with a pIC50 value of 4.0. In addition, alpha,beta-MeATP (3-100 microM), which itself does not induce phosphoinositide (PI) turnover, left-shifted the agonist-concentration effect (E/[A]) curves for ATP, 2MeS-ATP and UTP by approximate 100-300 fold, while those for ATPgammaS and AMP-PNP were only shifted approximately 2-3 fold. Moreover, in the presence of alpha,beta-MeATP, not only was the potentiation effect of PPADS on the UTP response lost, but a slight inhibition of the UTP response by PPADS was also seen. Thus, we conclude that the action of ATPgammaS, alpha,beta-MeATP and AMP-PNP as ecto-ATPase inhibitors account for their high agonist potency, and also provide information for the development of ecto-ATPase inhibitors of high selectivity and potency.

Adenosine Triphosphatases↗
PubMed1997

Involvement of protein kinase C in the UTP-mediated potentiation of cyclic AMP accumulation in mouse J774 macrophages.

1. We have investigated the effects of nucleotide analogues on cyclic AMP formation in mouse J774 macrophages and the mechanisms involved. 2. UTP, in the concentration range 0.1-100 microM, induced concentration-dependent potentiation of prostaglandin E1 (PGE1)-induced cyclic AMP formation, but had no effect on basal cyclic AMP formation. UDP showed an equal potency, while 2-methylthio ATP, alpha, beta-methylene ATP and beta,gamma-methylene ATP gave either a slight increase or had no effect at concentrations up to 100 microM. ATP, although 100 fold less effective than UTP, also caused cyclic AMP potentiation, but had no effect on agonist-stimulated or basal cyclic AMP levels. 3. The cyclic AMP potentiation effect of UTP correlated with increased [Ca2+]i and inositol phosphate (IP) formation over the same concentration range. 4. Ionomycin, which evokes an increase in [Ca2+]i without affecting IP formation, did not cause an increase in cyclic AMP content, indicating that UTP-induced cyclic AMP regulation is not due to activation of Ca(2+)-sensitive adenylyl cyclase isoforms. 5. Although reduced, UTP potentiation was seen in cells incubated in a Ca(2+)-free and/or BAPTA-containing medium. Under these conditions, the UTP-increased IP accumulation was similarly reduced. 6. Exposure of cells to phorbol 12-myristate 13-acetate (PMA) also increased PGE1 stimulation of cyclic AMP levels, and the UTP-induced potentiation of cyclic AMP formation was inhibited by either staurosporine or Ro 31-8220. Pretreatment of cells with PMA for 4-24 h resulted in marked attenuation of UTP-stimulated cyclic AMP potentiation. 7. Pretreatment with pertussis toxin (24 h, 100 ng ml-1) did not significantly affect UTP-induced cyclic AMP potentiation and IP formation, although it increased the cyclic AMP response to PGE1. 8. Analysis of J774 cells by Western blotting with antibodies specific for different protein kinase C (PKC) isoforms shows the presence of the beta I, beta II, delta, epsilon, eta, mu, lambda and zeta isoforms. Moreover, UTP significantly increased the level of PKC beta I, beta II, delta, epsilon, mu, lambda and zeta immunoreactivity in the membrane fraction and decreased the cytosolic reactivity of PKC beta II, delta, epsilon and zeta. 9. Immunoblot studies also indicate the presence of type II adenylyl cyclase. 10. These results indicate that PKC is required for the potentiation of adenylyl cyclase activity by macrophage pyrimidinoceptors, which exhibit a higher specificity for UTP and UDP than for ATP.

Adenylate Cyclase Toxin↗
PubMed1996

Characterization of signaling pathways of P2Y and P2U purinoceptors in bovine pulmonary artery endothelial cells.

The actions of ATP on the endothelium are mediated by P2 purinoceptors. We have shown that P2Y and P2U purinoceptors coexist in bovine pulmonary artery endothelial cells (CPAE), where they induce phosphoinositide (PI) turnover and Ca2+ mobilization. The relative order of potency (based on the threshold concentration) of nucleotide analogues (1-100 microM) in stimulating the accumulation of inositol phosphate (IP) was 2-methylthio-ATP (2MeSATP) = 2-methylthio-ADP (2MeSADP) > or = 2ClATP > UTP = ATP = ADP. alpha, beta-methylene ATP, beta, gamma-methylene ATP, UDP, adenosine-5'-tetraphospho-5'-adenosine, and adenosine-5'-pentaphospho-5'-adenosine had no effect at concentrations as high as 100 microM. At maximal concentrations, the IP responses to 2MeSATP and UTP were additive, whereas those to ATP and either 2MeSATP or UTP were not. Moreover, the maximal response to 2MeSADP was additive to that to UTP but not to that of 2MeSATP. Pretreatment with pertussis toxin slightly inhibited 2MeSATP- and UTP-stimulated IP generation by 15%. Under Ca(2+)-free conditions, UTP-induced IP formation was inhibited more markedly than that induced by 2MeSATP. Short-term treatment of the cells with phorbol 12-myristate-13-acetate (PMA) resulted in a dose-dependent inhibition of 2MeSATP-induced IP formation greater and more sensitive than that induced by UTP; similar results were obtained for the sensitivity of inhibition by suramin and reactive blue. Stimulation of the cells with either 2MeSATP or UTP induced a rapid increase in intracellular Ca2+ level, followed by a slow decrease to basal levels, followed by Ca2+ level oscillation. In the absence of extracellular Ca2+, [Ca2+]i responses were quantitatively less and did not show the slow phase and oscillation. Together these results suggest that both P2Y and P2U purinoceptors are expressed in bovine pulmonary artery endothelial cells and are coupled to phospholipase C (PLC) activation and Ca2+ mobilization through pertussis toxininsensitive G proteins.

Animals↗
PubMed1996

Inhibition of ecto-ATPase by PPADS, suramin and reactive blue in endothelial cells, C6 glioma cells and RAW 264.7 macrophages.

1. Previous studies have shown that bovine pulmonary artery endothelium (CPAE) has P2Y and P2U purinoceptors, rat C6 glioma cells have P2U purinoceptors and mouse RAW 264.7 cells have pyrimidinoceptors, all of which are coupled to phosphoinositide-specific phospholipase C (PI-PLC). The dual actions of PPADS, suramin and reactive blue as antagonists of receptor subtypes and ecto-ATPase inhibitors were studied in these three cell types. 2. In CPAE, suramin, at 3-100 microM, competitively inhibited the PI responses induced by 2MeSATP and UTP, with pA2 values of 5.5 +/- 0.3 and 4.4 +/- 0.4, respectively. Reactive blue, at 1-3 microM, produced shifts to the right of the 2MeSATP and UTP curves, but no further right shift at 10 microM. PPADS, at 10 microM, caused a 3 fold right shift of the 2MeSATP curve, but no further shift at concentrations up to 100 microM. In contrast, a dose-dependent shift to the left of the UTP curve and a weak inhibition of the ATP response were seen with PPADS. 3. In RAW 264.7 cells, suramin and reactive blue, but not PPADS, competitively inhibited the UTP response, with pA2 values of 4.8 +/- 0.5 and 5.8 +/- 0.7, respectively. 4. In C6 glioma cells, although suramin and reactive blue inhibited the ATP response, a potentiation effect on ATP and UTP responses was seen with PPADS. 5. The ecto-ATPase inhibitory activity of these three receptor antagonists were determined. All three inhibited ecto-ATPase present in CPAE, C6 and RAW 264.7 cells, with IC50 values of 4, 4.8 and 4.7 for PPADS, 4, 4.4 and > > 4 for suramin, and 4.5, 4.7 and 4.7 for reactive blue. 6. This study indicates that PPADS, suramin and reactive blue ar ecto-ATPase inhibitors. This property, combined with their antagonistic selectivity for receptor subtypes, can result in inhibition of, potentiation of, or lack of effect on agonist-mediated PI responses. Reactive blue is a more potent antagonist than suramin on P2Y, P2U and pyrimidinoceptors, and PPADS is a weak antagonist for P2Y receptors.

Adenosine Triphosphatases↗
PubMed1994

On the rapid deprotection of synthetic oligonucleotides and analogs.

The efficiency of oligodeoxynucleotide deprotection is greatly enhanced using a combination of: (a) ethanolamine, and especially a mixture of hydrazine, ethanolamine and methanol, in place of the usual aqueous ammonia; (b) tert-butylphenoxyacetyl amino protecting groups, and (c) oxalyl link between the first nucleotide and the polymeric support. The extent of base modification, particularly of C, is shown to be extremely low, and the quality of deprotected oligonucleotides is as high as in the case of ammonia deprotection. This method is also shown to be applicable to the preparation of phosphorothioate and methylphosphonate oligodeoxynucleotides and oligoribonucleotides.

Base Sequence↗
PubMed1993

Seroprevalence of Chlamydia pneumoniae in Taiwan.

Chlamydia pneumoniae (TWAR) is a relatively newly discovered respiratory tract pathogen which was first isolated in Taiwan. In order to describe the seroepidemiology of C. pneumoniae in Taiwan, we evaluated 1,085 stored serum samples: 904 from patients, 97 from umbilical cord blood samples, and 84 from medical personnel at the Veterans General Hospital-Kaohsiung, between January 1 and April 30, 1991. Antibodies were determined by the use of a microimmunofluorescence test using elementary bodies of C. pneumoniae AR-39 as antigen. Sera were tested with screening titres of 16 and 512 for immunoglobulin G antibody. The antibody prevalence was found to be 23.1% in young children (6 months to 10 years old), rising to 66.7% in teenagers, and to 96.2% in older age groups. These rates were higher than any reported earlier. The progressively increasing rates of seropositivity found in older individuals indicated a surge of reinfection in these age groups. Only 5 cases were found with micro-IF IgG titres equal to or greater than 512. All were asymptomatic according to the hospital records. In addition to a high prevalence rate in Taiwan, the data also showed high infection rates in teenagers and elderly people.

Adolescent↗
PubMed1993

Adjusted resistive index: a method to estimate rapidly renal blood flow: preliminary validation in hypertensives.

The Doppler RI, measured in a blinded fashion, was correlated with RBF, RVR, and GFR calculated by simultaneous clearance measurements. Nine hypertensive patients were studied weekly while receiving increasing doses of the vasodilator minoxidil. In 36 studies, RI was significantly correlated with RBF (r = -0.42) but not with RVR or GFR. When RI values were adjusted for ERV, correlations strikingly improved and were further improved by adjustment for pulse pressure. The ARI allowed semiquantitative predictions of RBF and RVR more accurately than blood urea nitrogen or serum creatinine levels. Correlation with GFR was weak.

Adult↗
PubMed1992

Systematic study of nuclear Overhauser effects vis-à-vis local helical parameters, sugar puckers, and glycosidic torsions in B DNA: insensitivity of NOE to local transitions in B DNA oligonucleotides due to internal structural compensations.

A method has been developed to solve structures of DNA oligomers in solution from the experimental NOE data. The method is a combination of two approaches: (1) full matrix NOESY simulations and (2) conformational calculations of DNA double helix based on generalized helical parameters. The process of the refinement of a solution structure does not involve NMR-derived interproton distance constraints; rather it consists of a direct fitting of a structure to the experimental NOE data, a weighted sum of energy, and R factor being under minimization. A helical parameters-based generation of DNA forms makes it possible to organize the search for the optimal structure more effectively, systematically varying starting conformations. The method has been used to calculate a structure for the self-complementary DNA hexamer GGATCC, which is consistent with the available experimental data. The structure belongs to the B family of forms, although the local structural heterogeneity is very strong. Sugar puckers vary from O4'-exo to C3'-exo; helical steps are open with different magnitudes toward the minor groove. Next, we have addressed the question of how uniquely the structure is defined by the existing NMR data. Different structural parameters have been systematically varied, and their effect on individual NOE's and the R factor has been studied. Two energetically conjugated parameters, sugar puckers and glycosidic angles, can be determined very reliably, because of the strong dependences of the intraresidue H6/H8 to H2'/H2''/H3' NOE's. In contrast, the local helical conformation of DNA and the geometry of base pairs proved to be underdetermined by the existing NOE information, because the effect of any helical parameter on interproton distances can be compensated by the concerted changes in other parameters.

Base Composition↗
PubMed1992

Infantile spasms: II. Lenticular nuclei and brain stem activation on positron emission tomography.

Infantile spasms are generalized seizures specific to early infancy, and are believed to result from complex cortical-subcortical interactions during a critical period of development. We used positron emission tomography (PET) to determine local cerebral metabolic rates for glucose (1CMRG1c) in 44 infants with spasms, in an attempt to define the neuroanatomical substrates that mediate these seizures. All infants were studied in the awake state during continuous electroencephalographic monitoring. The most consistent abnormality on PET, seen in 32 infants, was the symmetrical increase in 1CMRG1c in the lenticular nuclei, compared to age-matched normal infants (p less than 0.05). In 21 infants, even though the brain stem appeared to be visually more prominent compared to normal infants, statistically significant differences could not be demonstrated. Relative hypermetabolism of the lenticular nuclei (1) occurred irrespective of whether the spasms were cryptogenic or symptomatic, (2) was associated with focal cortical hypometabolism in 22 and focal cortical hypermetabolism in 5 of the 44 infants, and (3) was not characterized by any specific electroencephalographic abnormality during PET. These findings suggest that the lenticular nuclei may contribute to the pathophysiological state that predisposes to infantile spasms, and is consistent with the observation that spasms are clinically symmetrical even when focal cortical lesions are present. A scheme describing the neuronal circuitry likely to be involved in the generation of infantile spasms is proposed.

Brain Stem↗
PubMed1992

A new noninvasive quantification of renal blood flow with N-13 ammonia, dynamic positron emission tomography, and a two-compartment model.

In order to determine if dynamic positron emission tomography (PET) and N-13 ammonia can be used to quantitate regional RBF (rRBF) noninvasively, six anesthetized dogs were examined with PET imaging after an iv bolus administration of 5 mCi of N-13 ammonia. Renal time activity curves and the arterial input function were derived from regions of interest drawn over the renal cortex and abdominal aorta, respectively. For calculation of rRBF, less than 120 s of the initial data were used to minimize contamination by plasma metabolites of N-13 radioactivity. rRBF was quantitated with a two-compartment model, and the results were compared with simultaneously acquired microsphere blood flow measurement. Fourteen experiments were performed in six dogs, and four regions of interest on renal cortex were selected on each PET image. RBF derived from dynamic PET imaging with N-13 ammonia was linearly related to microsphere (MS) values (rRBF = 1.06 x MS - 0.17; r = 0.91). Mean rRBF in the canine experiments was 4.0 mL/min/g. The results indicate that dynamic N-13 ammonia renal PET can provide noninvasively quantitative rRBF.

Ammonia↗
PubMed1992

[Low back pain as a presenting symptom in patients with infective endocarditis report of three cases and literature review].

Infective endocarditis may have different clinical manifestations that result from involvement of different organ systems. These include heart murmur, valvular bacterial vegetation, arterial emboli induced hematuria, conjunctival petechiae, subcutaneous Janeway's spots and Osler's nodes. Musculoskeletal manifestation yields arthralgia, arthritis, low back pain and myalgia, etc. Early recognition of these manifestations can lead to earlier treatment and recovery without delay. We report three cases of infective endocarditis who first presented low back pain. Their clinical features resolved with treatment. The pathogenesis of low back pain in infective endocarditis is not well-known. However, vertebral arterial embolization, vertebral septic necrosis or immune complex deposition is elucidated.

Aged↗
PubMed1992

Use of the abdominal aorta for arterial input function determination in hepatic and renal PET studies.

A method using the activity in the abdominal aorta of human and animal subjects to noninvasively estimate blood-pool input function in dynamic, abdominal PET scans is proposed and validated in this paper. Partial volume effects due to the aorta's dimensions are corrected by a semi-automated algorithm based on the transaxial resolution in the reconstructed images. The technique was validated by comparing PET measurements of abdominal aortic activity to well counter measurements of arterial blood samples (eight canine renal studies) and to PET measurements of left ventricular cavity activity (eight human hepatic studies). In renal studies, correlation analysis of the areas subtended by the two input functions yielded an essentially unitary slope (1.03 +/- 0.09), with high correlation (R2 greater than 0.95, p less than 0.001). In hepatic studies, similar values (0.99 +/- 0.03 and R2 greater than 0.85, p less than 0.001) were found. Correlation of the blood flow estimates based on the two input functions and a two-compartment model produced slopes of 1.07 +/- 0.16 and 1.03 +/- 0.07, and correlations of (R2 greater than 0.98, p less than 0.001) and (R2 greater than 0.97, p less than 0.001) for the renal and hepatic studies, respectively. We conclude that noninvasive, accurate measurements of the arterial input function by dynamic PET imaging are possible and represent a clinically viable alternative to arterial blood sampling.

Animals↗
PubMed1991

Noninvasive quantification of hepatic arterial blood flow with nitrogen-13-ammonia and dynamic positron emission tomography.

To determine if dynamic PET and 13N-ammonia can be utilized to quantitate regional hepatic arterial blood flow (rHABF) noninvasively, eight anesthetized dogs and eight human volunteers were examined with PET following intravenous bolus administration of 13N-ammonia. Hepatic time-activity curves and the arterial input function were derived from ROIs drawn over the right lateral superior segment of the liver and the left ventricle of the heart, respectively. rHABF was quantitated using a two-compartment model, with comparison with simultaneously acquired microsphere blood flow measurement (MS) in the canine studies. rHABF derived from canine dynamic PET with 13N-ammonia were linearly related to microsphere values (rHABF = 0.92 x MS + 0.04, r = 0.98), with a mean of 0.40 ml/min/g. The results in eight normal volunteers gave a rHABF value of 0.26 +/- 0.07 ml/min/g. Dynamic 13N-ammonia hepatic PET allows noninvasive quantification of rHABF.

Adult↗
PubMed1990

[Pharmacological localization of Horner's syndrome. Case report].

Horner's syndrome is derived from an interruption of the sympathetic pathway at any point along its course between the hypothalamus and the orbit. This pathway is generally considered to consist of three neurons. It had been suggested that the pupillary response to various pharmacologic agents will aid in localizing the lesioned neuron in the sympathetic pathway. We had the opportunity to observe a patient who developed Horner's syndrome as a consequence of pulmonary apex adenocarcinoma. Clinical, radiologic and pharmacologic studies are presented. The methods of pharmacologic localization are discussed.

Amphetamines↗