Biomedical subjects

X Hu

Publications and source records attributed to X Hu.

At least 253 records · Page 14Linked to original sources

PubMed1998

Architecture and mechanism of the light-harvesting apparatus of purple bacteria.

Photosynthetic organisms fuel their metabolism with light energy and have developed for this purpose an efficient apparatus for harvesting sunlight. The atomic structure of the apparatus, as it evolved in purple bacteria, has been constructed through a combination of x-ray crystallography, electron microscopy, and modeling. The detailed structure and overall architecture reveals a hierarchical aggregate of pigments that utilizes, as shown through femtosecond spectroscopy and quantum physics, elegant and efficient mechanisms for primary light absorption and transfer of electronic excitation toward the photosynthetic reaction center.

Crystallography, X-Ray↗

PubMed1998

Cloning, expression, and biochemical characterization of a functionally novel alpha class glutathione S-transferase with exceptional activity in the glutathione conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene.

The present study describes cDNA cloning, expression, and kinetic characterization of the two subunits of a murine alpha-class glutathione (GSH) S-transferase (GST) isoenzyme (previously designated as GST 9.5), which, unlike other alpha-class mammalian GSTs, is exceptionally efficient in the GSH conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+)-anti-BPDE] [X. Hu, S. K. Srivastava, H. Xia, Y. C. Awasthi, and S. V. Singh (1996) J. Biol. Chem. 271, 32684-32688]. The cDNAs for both subunits of GST 9.5 (GST 9.5-1 and GST 9.5-2) were cloned by RT-PCR. The deduced amino acid sequences of GST 9.5-1 and GST 9.5-2 clones were identical to those of mGSTA1 and mGSTA2, respectively. Both these subunits were expressed in Escherichia coli to determine the relationships between recombinant mGSTA1-1 and mGSTA2-2 and corresponding subunits of tissue-isolated GST 9.5. The pI values of recombinant mGSTA1-1 and mGSTA2-2 (9.49 and 9.45, respectively) were similar to that of the tissue-isolated isoenzyme (pI 9.5). The reverse-phase HPLC elution profiles and immunological cross-reactivities of recombinant mGSTA1-1 and mGSTA2-2 were also similar to those of the corresponding subunits of tissue-isolated GST 9.5. The catalytic efficiency of recombinant mGSTA1-1 toward (+)-anti-BPDE, 131 mM-1.s-1, was approximately 9.5-to 655-fold higher compared with tissue-isolated mGSTP1-1, mGSTA3-3, mGSTM1-1, and mGSTA4-4. Moreover, the catalytic efficiency of mGSTA1-1 toward (+)-anti-BPDE was about 3.3-fold higher compared with recombinant mGSTA2-2. The mGSTA1 and/or mGSTA2 subunits were expressed to varying degrees in female A/J mouse tissues. For example, mGSTA1, but not mGSTA2, subunit expression was observed in the skin, which is a target organ for benzo(a)pyrene (BP)-induced cancer in mice. On the other hand, the expression of either mGSTA1 or mGSTA2 subunit could not be detected in the lung, which is another target organ for BP-induced cancer in mice. Interestingly, relatively large amounts of both mGSTA1 and mGSTA2 subunits were detected in the kidney. In conclusion, the results of the present study clearly indicate that the A1-type subunit of GST 9.5 is responsible for its exceptional catalytic efficiency in the GSH conjugation of (+)-anti-BPDE, which is the ultimate carcinogen of widespread environmental pollutant BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1998

[Expression of human ciliary neurotrophic factor gene in Escherichia coli].

OBJECTIVE: To express biologically active human ciliary neurotrophic factor(hCNTF) gene in Escherichia coli. METHODS: Total RNA was extracted from human peripheral nerves and cDNA was synthesized by superscript reverse-transcriptase, a polymerase chain reaction(PCR) was conducted to obtain a full length cDNA fragment encode for hCNTF gene. After recovery from gel and purification, the PCR product was cloned into the pGEM-5Zf(+) vector and DNA sequence analysis was performed to verify hCNTF gene. The hCNTF gene was then placed under control of T7 promoter in the expression vector pET-11d and transformed into Escherichia coli strain BL21(DE3). Cultures of this transformat were induced by IPTG for the expression of recombinant protein. The bioactivity of recombinant protein was evaluated by its ability to support the survival of embryonic chick dorsal root ganglion neurons in culture. RESULTS: The human CNTF gene was cloned and biologically active hCNTF was expressed efficiently. Based on densitometry of stained gel,the recombinant hCNTF accounted for more than 25% of the total bacterial protein. CONCLUSION: The cloning and expression at high level of hCNTF gene in E.coli provides a basis for understanding the structure-activity relationship of CNTF and its potential clinical application.

Cells, Cultured↗

PubMed1998

Differential induction of NAD(P)H:quinone oxidoreductase by anti-carcinogenic organosulfides from garlic.

This study was undertaken to elucidate the mechanism of organ specificity and differential efficacy of garlic organosulfides (OSCs) [diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS)] in preventing benzo(a)pyrene (BP)-induced tumorigenesis in mice. The results of the present study reveal a good correlation between chemopreventive efficacies of garlic OSCs and their inductive effects on the expression of NAD(P)H:quinone oxidoreductase (NQO), an enzyme implicated in the detoxification of activated quinone metabolites of BP. Treatment of mice with DADS and DATS, which are potent inhibitors of BP-induced forestomach tumorigenesis, resulted in a statistically significant increase (2.4- and 1.5-fold, respectively) in forestomach NQO activity. In addition, DADS and DATS were much more potent inducers of forestomach NQO activity than DAS, which is a weak inhibitor of BP-induced forestomach tumorigenesis than the former compounds. Propyl-group containing OSCs (DPS and DPDS), which do not inhibit BP-induced tumorigenesis, did not affect forestomach NQO activity. Similar to forestomach, a good correlation was also observed between effects of these OSCs against BP-induced pulmonary tumorigenesis and their effects on NQO expression in the lung. For example, treatment of mice with DAS, which is a potent inhibitor of BP-induced pulmonary tumorigenesis, resulted in about 3.2-fold increase in pulmonary NQO activity. On the other hand, this activity was increased by about 1.5-fold upon DATS administration, which does not inhibit BP-induced cancer of the lung. In conclusion, our results suggest that induction of NQO may be important in anti-cancer effects of garlic OSCs.

Allyl Compounds↗

PubMed1998

Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269).

Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x) (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously reported biphenyl-based inhibitors that would provide additional interactions with the protein. These compounds were assayed for the ability to inhibit the binding of sialyl Lewis(x) (sLe(x), 2) bearing HL-60 cells to E-, P-, and L-selectin fusion proteins. We report that dimeric or trimeric compounds containing multiple components of simple nonoligosaccharide selectin antagonists inhibit sLe(x)-dependent binding with significantly enhanced potency over the monomeric compound. The enhanced potency is consistent with additional binding interactions within a single selectin lectin domain; however, multivalent interaction with multiple lectin domains as a possible alternative cannot be ruled out. Compound 15e (TBC1269) showed optimal in vitro activity from this class of antagonists and is currently under development for use in the treatment of asthma.

Anti-Asthmatic Agents↗

PubMed1998

[DNA sequencing of human ciliary neurotropic factor gene by silver staining method].

OBJECTIVE: To introduce a non-radioactive protocol for DNA sequence analysis which employs a silver staining procedure METHODS: DNA template is amplified by Taq DNA polymerase to generate sequence ladder, No labeled nucleotide or primer is involved in the thermal-cycling sequencing reaction. A sensitive silver staining procedure is employed to visualize bands in sequencing gel. RESULTS: This silver staining method is used for DNA sequence analysis of human cilliary neurotrophic factor (hCNTF) gene. The resulted band resolution is comparable to radioactive sequencing method, and data can be obtain within less than 2 hours after sequencing reaction. CONCLUSION: Silver staining is a rapid, inexpensive and reliable method for DNA sequence analysis.

Ciliary Neurotrophic Factor↗

PubMed1998

Cloning and sequencing of an alternative splicing-derived cDNA variant of the GM-CSF receptor alpha subunit, which encodes a truncated protein.

GM-CSF interacts with the low affinity GM-CSF receptor alpha-subunit, which leads to high affinity association with the alpha-subunit/common beta-subunit complex and transduction of intracellular signals leading to proliferation, differentiation, and/or activation of hemopoietic cells, predominantly in the neutrophil and monocyte/macrophage lineages. Several alternative splicing-derived variants of the GM-CSF receptor alpha-subunit have been described previously by this and other laboratories. A newly discovered alternative-splicing derived variant was isolated from the peripheral blood mononuclear cells of a patient with juvenile myelomonocytic leukemia. This variant lacks 397 base pairs corresponding to exons 8-11 of the wild type GM-CSF receptor alpha-subunit cDNA and potentially encodes a 233 amino acid protein lacking a membrane-anchoring domain and creating the fourth known potential soluble isoform of the alpha-subunit of the GM-CSF receptor.

Alternative Splicing↗

PubMed1998

Tenascin pattern of expression and established prognostic factors in invasive breast carcinoma.

BACKGROUND AND OBJECTIVES: Immunohistochemical methods were used to study Tenascin (TN) expression in invasive duct cell carcinoma (IDCC) of the breast and its established prognostic factors. METHODS: We studied 115 patients with IDCC. The mean patient age was 62 years; all tumors were graded according to Scarf-Bloom and Richardson. Complete survival information was available for all patients (median follow-up 65 months). Formalin-fixed, paraffin-embedded archival tissue from all 115 IDCC were immunostained with monoclonal mouse Anti-Human Tenascin (DAKO-TN2M636; 1/50 dilution). Positivity was recorded on a scale of 0-4 for percentage of TN staining in the tumor stroma. RESULTS: TN showed thick bands around advancing tumor nests and in poorly differentiated tumors, TN fibers had an interstitial pattern surrounding single tumor cells. TN score was significantly positively correlated with high nuclear grade (P < 0.05), histologic grade (P < 0.01), mitotic grade (P < 0.005), and combined grade (P < 0.01). TN score did not correlate with long-term survival or with other prognostic factors studied. CONCLUSIONS: TN expression was more prominent in tumors with a high combined histologic grade. Our results may suggest that while TN may play a role in limiting tumor spread as proposed by other studies, it may not represent a prognostic factor in invasive breast carcinoma.

Animals↗

PubMed1998

Worker sensitivity and reactivity: indicators of worker susceptibility to nasal irritation.

This study examines the determinants of susceptibility to the irritant effects of sodium borate in 18 responsive workers identified through repeated self-reports of nasal irritation. For each worker, susceptibility was characterized by two features; reactivity and sensitivity, as estimated from the slope and intercept parameters from their individual exposure-response regression model. Individual estimates of reactivity and sensitivity were then examined to evaluate the importance of personal and environmental characteristics in determining susceptibility. The use of nasal sprays, current smoking and allergies were associated with lower reactivity, while high exposures to borate dust were associated with higher sensitivity. To examine possible biologic mechanisms for the irritant response, a toxicokinetic dose model was used to calculate nasal osmolarity during symptom intervals. The estimated levels suggest that osmolar activation of mast cells to release histamine and other mediators is a plausible mechanism by which these workers may experience nasal irritation.

Adult↗

PubMed1998

Reproducibility of fMRI results across four institutions using a spatial working memory task.

Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods. The primary purpose of this consortium was to examine the reliability and reproducibility of fMRI results. FMRI data were collected on healthy adults during performance of a spatial working memory task at four different institutions. Two sets of data from each institution were made available. First, data from two subjects were made available from each site and were processed and analyzed as a pooled data set. Second, statistical maps from five to eight subjects per site were made available. These images were aligned in stereotactic space and common regions of activation were examined to address the reproducibility of fMRI results when both image acquisition and analysis vary as a function of site. Our grouped and individual data analyses showed reliable patterns of activation in dorsolateral prefrontal cortex and posterior parietal cortex during performance of the working memory task across all four sites. This multisite study, the first of its kind using fMRI data, demonstrates highly consistent findings across sites.

Adult↗

PubMed1998

Saquinavir enhances the mucosal toxicity of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma.

Protease inhibitors are an important new class of agents for the treatment of human immunodeficiency virus (HIV) infection. The purpose of our trial was to determine the feasibility of combining the protease inhibitor saquinavir with a 96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M2), doxorubicin (50 mg/M2, and etoposide (240 mg/M2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE every 28 or more days. All patients received saquinavir (600mg PO TID), filgrastim and Pneumocystis carinii and fungal prophylaxis. Patients also received either stavudine (n = 2) or both stavudine and didanosine (n = 10). Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and the data were compared with the data from our prior study of CDE plus didanosine. An interim analysis was performed after accrual of the first 12 patients in order to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12 patients (67%) treated with CDE plus saquinavir compared with three of 25 patients (12%) in our prior study treated with CDE without saquinavir (P < 0.001). In logistic regression analysis, saquinavir use was the only factor associated with a significantly greater risk of severe mucositis (relative risk 7.9; P = 0.03). Saquinavir use was not associated with a significant difference in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes for patients treated with saquinavir (absolute decrease of 23/microL, or a 26% decrease from baseline) was significantly less than for patients treated without saquinavir in the prior study (absolute decrease of 91/microL, or 42% decrease from baseline; P = 0.05). Four of 10 patients (40%) treated with saquinavir had an increase in CD4 lymphocytes of > or = 10/microL compared with none of 25 patients (0%) treated without saquinavir (P < 0.001). Combination of the protease inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma was associated with a significant increase in the incidence of severe mucositis. This finding suggests that saquinavir may alter the metabolism of one of more of the cytotoxic agents in the CDE regimen, and underscores the need for careful investigation regarding the use of the protease inhibitors in patients receiving chemotherapy.

Adult↗

PubMed1998

Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs.

PURPOSE: To test the hypothesis that lidocaine prolongs the safe period of circulatory arrest during deep hypothermia. METHODS: Sixteen dogs were subjected to cooling, first surface cooling to 30 degrees C and then core cooling to 20 degrees C rectal temperature). The circulation was then stopped for 90 min. In the lidocaine group, 4 mg.kg-1 lidocaine was injected into the oxygenator two minutes before circulatory arrest and 2 mg.kg-1 at the beginning of reperfusion and rewarming. The control group received equivalent volumes of normal saline. Post-operatively, using a neurological deficit scoring system (maximum deficit score-100; minimum-zero indicating that no scored deficit could be detected). Neurological function was evaluated hourly for six hours and then daily for one week, the pharmacokinetic parameters were calculated using one compartment model. RESULTS: On the seventh day, the neurological deficit score and overall performance were better in the lidocaine (0.83 +/- 2.04) than in the control group (8.33 +/- 4.08 P < 0.05). During the experiment, the base excess values were also better in the lidocaine than in the control group (at 30 min reperfusion: -4.24 +/- 1.30 vs -8.20 +/- 2.82 P < 0.01, at 60 min reperfusion was -3.34 +/- 1.87 vs -7.52 +/- 2.40 (P < 0.01). On the eighth day the extent of pathological changes were milder in the lidocaine group than that in the control group. The elimination half life of lidocaine was 40.44 +/- 7.99 during hypothermia and 2.01 +/- 4.56 during rewarming. CONCLUSIONS: In dogs lidocaine prolongs the safe duration of circulatory arrest during hypothermia.

Anesthetics, Local↗

PubMed1998

Model for the light-harvesting complex I (B875) of Rhodobacter sphaeroides.

The light-harvesting complex I (LH-I) of Rhodobacter sphaeroides has been modeled computationally as a hexadecamer of alphabeta-heterodimers, based on a close homology of the heterodimer to that of light-harvesting complex II (LH-II) of Rhodospirillum molischianum. The resulting LH-I structure yields an electron density projection map that is in agreement with an 8.5-A resolution electron microscopic projection map for the highly homologous LH-I of Rs. rubrum. A complex of the modeled LH-I with the photosynthetic reaction center of the same species has been obtained by a constrained conformational search. This complex and the available structures of LH-II from Rs. molischianum and Rhodopseudomonas acidophila furnish a complete model of the pigment organization in the photosynthetic membrane of purple bacteria.

Amino Acid Sequence↗

PubMed1998

Ultrasonographic and clinical predictors of intussusception.

OBJECTIVE: The objective of this study was to determine the positive and negative clinical predictors of intussusception and the correlation of ultrasonography and air enema in establishing this diagnosis. STUDY DESIGN: This was a prospective descriptive cohort study. SETTING: This study was performed in a tertiary care pediatric emergency department. PARTICIPANTS: Eighty-eight of 245 candidates were assessed for clinical predictors of intussusception. All 245 cases were examined for correlation between ultrasonography and air enema. INTERVENTIONS: A questionnaire, ultrasonography, and air enema were used. RESULTS: Thirty-five of the 88 patients assessed for clinical predictors were positive for intussusception. Significant positive predictors were right upper quadrant abdominal mass (positive predictive value [PPV] 94%), gross blood in stool (PPV 80%), blood on rectal examination (PPV 78%), the triad of intermittent abdominal pain, vomiting, and right upper quadrant abdominal mass (PPV 93%, p = 0.0001), and the triad with occult or gross blood per rectum (PPV 100%, p = not significant). Significant negative predictors were a combination of > or = 3 of 10 clinically significant negative features (negative predictive value 77%, p = 0.035). Of the total 245 cases, intussusception (as confirmed by doughnut, target, or pseudokidney sign) was ruled out by ultrasonography in 97.4%. Alternate ultrasound findings comprised 27% of negative cases. CONCLUSIONS: Excellent positive predictors of intussusception were identified prospectively. Although no reliable negative predictors were found, patients at low risk may be screened by ultrasonography.

Air↗

PubMed1998

Characterization of a unique factor-independent variant derived from human factor-dependent TF-1 cells: a transformed event.

A factor-independent variant (TF-1a) has been isolated from the factor-dependent TF-1 cell line. The subline has been grown continuously in culture for > 1.5 years without added cytokines. The cells retain the ability to respond to multicytokines, with a different response pattern from its parental cell line. The TF-1 cells appeared singly in liquid culture. In contrast. TF-1a cells formed aggregates which increased markedly in size and in number upon TGFbeta1 treatment and showed a diminished TGFbeta-mediated growth inhibition. TF-1a, but not TF-1 cells, formed colonies in soft agar culture in the absence of any added growth factors, and developed the capacity to generate an invasive tumor(s) in nude mice. There was a constitutive activation of MAPK and MEK in TF-1a but not in TF-1 cells, which may be one of the mechanisms leading to factor-independent growth of TF-1a cells. Phenotypically, TF-1 cells were CD34+ /CD38+, whereas TF-1a cells were CD34+ /CD38-. This suggests that TF-1a may represent a less mature hematopoietic cell than TF-1. In conclusion, TF-1a is different from TF-1 in many important aspects which are associated with neoplastic transformation. The variant appears to be an excellent model for studying the process of progressive malignant transformation of myeloid cells and for studying signal pathways involved in the spontaneous and factor-induced growth of the cells.

Animals↗

PubMed1998

Morphology of the unfixed cochlea.

Our knowledge of cochlear geometry is based largely upon anatomical observations derived from fixed, dehydrated, embedded and/or sputter-coated material. We have now developed a novel preparation, the hemicochlea, where for the first time living cochlear structures can be observed in situ and from a radial perspective. The experiments were performed on the Mongolian gerbil. Ion substitution experiments suggest that no significant swelling or shrinkage occurs when the preparation is bathed in normal culture medium, so long as calcium concentration is kept at endolymph-like (20 microM) levels. The tectorial membrane-reticular lamina relationship appears to remain well preserved. Hensen's stripe maintains a close relationship with the inner hair cell stereociliary bundle, unless the mechanical coupling becomes disturbed. In addition, standard fixation and/or dehydration procedures are used to quantify changes due to shrinkage artifacts. Various morphometric gradients are examined in unfixed specimens from apical, middle, and basal turns.

Animals↗

PubMed1998

Effects of increased solar ultraviolet radiation on materials.

Synthetic polymers such as plastics, as well as naturally occurring polymer materials such as wood, are extensively used in building construction and other outdoor applications where they are routinely exposed to sunlight. The UV-B content in sunlight is well known to affect adversely the mechanical properties of these materials, limiting their useful life. Presently their outdoor lifetimes depend on the use of photostabilizers in the case of plastics and on protective surface coatings in the case of wood. Any increase in the solar UV-B content due to a partial ozone depletion would therefore tend to decrease the outdoor service life of these materials. It is the synergistic effect of increased UV radiation with other factors such as the temperature that would determine the extent of such reduction in service life. The increased cost associated with such a change would be felt unevenly across the globe. Those developing countries that depend on plastics as a prime material of construction and experience high ambient temperatures are likely to be particularly affected in spite of the relatively small fractional decrease in ozone at those locations. Assessment of the damage to materials, associated with ozone depletion, requires a knowledge of the wavelength dependence as well as the dose-response characteristics of the polymer degradation processes of interest. While the recent literature includes some reliable spectral sensitivity data, little dose-response information has been reported, so it is difficult to make such assessments reliably at the present time. This is particularly true for the naturally occurring materials popularly used in construction applications. To maintain polymers at the same useful lifetime in spite of increased solar UV-B content, the amount of photostabilizers used in the formulations might be increased. This strategy assumes that conventional stabilizers will continue to be effective with the spectrally altered UV-B-enhanced solar radiation. While the present understanding of the degradation chemistry suggests the strategy to have merit, its effectiveness, in an altered solar radiation environment, has not been demonstrated for common polymers. The availability of these data is crucial for reliably estimating the cost of mitigating the increased damage to materials as a result of a possible partial depletion of the ozone layer using this approach.

Atmosphere↗

PubMed1998

Effect of chronic hypoxia on adrenoceptor responses of ovine foetal umbilical vessels.

1. The effects of chronic hypoxia on alpha1-adrenoceptor-mediated contractions were investigated in foetal umbilical vessels obtained from near-term (approximately 140 day gestation) pregnant sheep maintained near sea level ( 300 m) and at high altitude (3820 m) from 30 day gestation. 2. Chronic hypoxia significantly decreased contractile sensitivity of the umbilical vein to noradrenaline (pD2: 6.22+/-0.19 vs 5.67+/-0.09) and reduced the maximum response by 43%. Noradrenaline-induced contraction of the umbilical artery was abolished. In contrast, contractions to KCI were not affected by chronic hypoxia. 3. In umbilical vein, the apparent dissociation constant (KA) of noradrenaline to alpha1-adrenoceptors was increased from 0.54+/-0.06 microM in control animals to 1.35+/-0.14 microM in chronically hypoxic animals. In accordance, radioligand binding of agonist showed high and low affinity binding sites for noradrenaline in both normoxic and chronically hypoxic tissues. Addition of GTPgammaS (100 microM) abolished apparent high affinity binding sites. Whereas proportional binding sites were not changed by chronic hypoxia, the apparent high affinity of noradrenaline was significantly decreased (pKi: 7.80+/-0.17 vs 7.20+/-0.16). 4. Chronic hypoxia significantly decreased alpha1-adrenoceptor density (fmol mg protein(-1)) in umbilical vein (24.6+/-3.2 vs 12.3+/-3.1) and the artery (7.1+/-0.4 vs 3.1+/-0.9) with no change in [3H]-prazosin binding affinity. There was a linear correlation of the maximum contractions to noradrenaline and alpha1-adrenoceptor density. 5. We conclude that chronically hypoxic-induced depression in contractions of ovine foetal umbilical vessels to noradrenaline is mediated predominantly by decreases in alpha1-adrenoceptor density and the agonist binding affinity.

Adrenergic alpha-1 Receptor Antagonists↗