Search PubMed⌕ Search

Biomedical subjects

H Misawa

Publications and source records attributed to H Misawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Oxygen wasting for Ca2+ extrusion activated by partial inhibition of sarcoplasmic reticulum Ca2+ -atpase by cyclopiazonic acid in rat left ventricles.

In the excised Langendorff-perfused rat whole-heart preparation, a linear relation between left ventricular myocardial oxygen consumption per beat (Vo2) and systolic pressure-volume area (PVA, a total mechanical energy per beat) is obtained from a curved end-systolic pressure-volume relation as in the blood-perfused preparation. The ordinate Vo2 intercept of the Vo2-PVA relation is composed of Vo2 for total Ca2+ handling in the excitation-contraction coupling and basal metabolism. The Vo2 for total Ca2+ handling is mainly consumed by sarcoplasmic reticulum (SR) Ca2+ -ATPase. The aim of the present study was to investigate, in terms of left ventricular mechanoenergetics, how an inhibition of SR Ca2+ -ATPase by cyclopiazonic acid (CPA; 4 micromol/l) affects Ca2+ handling mechanisms in the excised Langendorff-perfused rat whole-heart preparation. The short-term (for 3 to 6 min after onset of the infusion) CPA infusion decreased Vo2 proportionally to the decrease in PVA. The long-term (for 9 to 12 min after the short-term CPA infusion) CPA infusion gradually increased Vo2 almost to the control level with an increase in PVA. The increases in both Vo2 and PVA during this infusion were completely abolished by a Na+/Ca2+ exchanger inhibitor, 3'9,4'9-dichlorobenzamil, indicating the contribution of Na+/Ca2+ exchanger to the increases in Vo2 and PVA. The O2 cost of left ventricular contractility during the long-term CPA infusion was significantly higher than during the short-term CPA infusion. All these results suggest the possibility of the contribution of greater energy-wasting Ca2+ extrusion processes (such as Na+/K+-ATPase coupled to the Na+/Ca2+ exchanger; its stoichiometry is 1 ATP : 1 Ca2+ to the larger oxygen cost of left ventricular contractility.

Animals↗
PubMed2001

Molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein in rat, mouse and human liver.

The molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein (RGPR) was investigated using rat, mouse and human liver cDNA library with a yeast one-hybrid system and a rapid amplification of cDNA ends (RACE) method. The clone coding an unknown protein was isolated, and a novel protein was identified. This protein was termed as RGPR-p117. RGPR-p117 in rat, mouse and human liver consisted of 1058, 1051 and 1060 amino acid residues with calculated molecular mass of 117, 115 and 117 kDa and estimated pI of 5.69, 5.70 and 5.71, respectively. The homologies of amino acids among rat, mouse and human RGPR-p117 were at least 70%. RGPR-p117 had a leucine zipper motif. The expression of RGPR-p117 mRNA was found in the liver, kidney, heart, spleen, and brain of rats. The database search of the human RGPR-p117 showed that its gene consisted of at least 26 exons spanning approximately 4.1 kbp and localized on human chromosome 1q25.2. Furthermore, we found a cDNA clone which was highly identical to a front half part of the human RGPR-p117 cDNA, using the BLAST search of human RGPR-p117. This cDNA clone was a splicing variant of human RGPR-p117, which derived from human placental choriocarcinoma. Our study demonstrates that a novel gene coding RGPR-p117 is present in rat, mouse and human.

Amino Acid Sequence↗
PubMed2001

Stimulatory effect of zinc on insulin-like growth factor-I and transforming growth factor-beta1 production with bone growth of newborn rats.

The effect of zinc, an essential trace element, on insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 production was investigated to determine the role of this metal in bone growth of newborn rats. Femoral-diaphyseal and metaphyseal tissues were obtained between 1 and 28 days after birth of newborn rats, and cultured for 24 h in a serum-free Dulbecco's modified Eagle's medium containing either vehicle or zinc sulfate (10(-6) - 10(-4) M). Protein concentration in the medium was significantly increased by culture with bone tissues of newborn rats with increasing age (14 and 21 days). Medium IGF-I and TGF-beta1 concentration was gradually reduced with increasing age after birth. The presence of zinc (10(-5) and 10(-4) M) caused a significant increase in protein, IGF-I, and TGF-beta1 concentrations in the medium cultured with the diaphyseal or metaphyseal tissues obtained at 7 and 14 days after birth. The expression of IGF-I and TGF-beta1 mRNA was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis in the diaphyseal and metaphyseal tissues cultured for 24 h using rat IGF-I or TGF-beta1-specific primers. These expressions were significantly raised in the presence of zinc (10(-4) M) in culture medium. The present study demonstrates that zinc has a stimulatory effect on IGF-I and TGF-beta1 production in the femoral tissues with bone growth of newborn rats.

Animals↗
PubMed2001

Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer.

Plasma transforming growth factor beta1 (TGF-beta1) has been reported to be correlated with the extent of disease in colorectal cancer, but it is not known whether measuring this cytokine can help predict liver metastasis after curative resection. We prospectively studied whether plasma TGF-beta1 levels could predict liver metastasis in 117 patients with colorectal cancer before and after curative resection. Blood samples were drawn before and 2 weeks after surgery to determine the cytokine levels. Abdominal ultrasonography or computed tomography was done every 3 months after surgery. The primary end point for follow-up was recurrence. Seventy-seven of 117 cases (66%) had preoperative levels of the cytokine higher than the borderline limit of 7.5 ng/ml. Postoperative levels were >7.5 ng/ml in 29 of 117 patients (25%). The median follow-up period was 42 months (range, 5--66 months), with follow-up of all 117 patients. No recurrence was observed in 13 patients with Dukes' stage A lesions. Liver metastasis occurred in 18 of 104 patients (17%) with Dukes' stage B or C disease. Fourteen of 18 patients (78%) who developed liver metastasis had shown a postoperative plasma TGF-beta1 level of >7.5 ng/ml. Cox proportional hazards regression analysis showed that the postoperative level was a significant predictive factor for liver metastasis (P < 0.001). A single point measurement of plasma TGF-beta1 levels at 2 weeks after curative resection seems to be able to predict liver metastasis in colorectal cancer. This finding suggests the value of a prospective trial of liver-targeted adjuvant therapy for patients with elevated postoperative plasma TGF-beta1 levels.

Aged↗
PubMed2000

A novel function of synapsin II in neurotransmitter release.

Although synapsin has been localized to presynaptic structures, its function remains poorly understood. In the present study, we investigated the presynaptic function of synapsin II using a synaptic vesicle recycling process using synapsin-II-overexpressing NG108-15 cells. Western blot analysis with antibodies for synaptic-vesicle-associated protein indicated that the number of synaptic vesicles was approximately doubled in synapsin II transfectants as reported previously. In differentiated synapsin-II-overexpressing and control cells, the application of high potassium induced strong intracellular calcium elevation along neurites and varicosities after differentiation and a weak calcium rise in the cell bodies. The uptake and release of the fluorescent dye FM1-43 revealed that synaptic vesicle recycling in synapsin-II-transfected cells occurred with the same kinetics in the cell body and neuritic varicosities. Furthermore, the area labeled with FM1-43 fluorescence in the synapsin-II-transfected cells was approximately twice as much as in control cells after stimulation, and ATP released after synaptic vesicle fusion with the plasma membrane in synapsin-II-expressing cells was significantly elevated relative to controls. The number of synaptic vesicles paralleled the amount of transmitter released from the cells leading to the conclusion that the number of releasable synaptic vesicles were increased by synapsin II transfection into NG108-15 cells, suggesting that synapsin II may have a role in the regulation of synaptic vesicle number in presynapse-like structures in NG108-15 cells.

Adenosine Triphosphate↗
PubMed2000

Intracellular signaling factors--enhanced hepatic nuclear protein binding to TTGGC sequence in the rat regucalcin gene promoter: involvement of protein phosphorylation.

The transcriptional mechanism of regucalcin gene expression was determined using gel mobility shift assay with TTGGC oligonucleotide (II-b) which is located between position -523 and -506 in the promoter region, containing a nuclear factor I (NF1) consensus motif TTGGC(N)(6)CC. The mutation analysis in this motif showed that TTGGC sequence was a specific binding region of the nuclear protein in rat liver and the cloned rat hepatoma cells (H4-II-E). When liver nuclei were incubated with ATP (1 mM), the nuclear protein binding to TTGGC sequence was increased. This binding was also increased in the nuclei of H4-II-E cells cultured with 10% FBS. Such an increase was also seen by culture with vanadate (100 microM), a potent inhibitor of protein tyrosine phosphatase. Serum-enhanced nuclear protein binding to TTGGC sequence was decreased in the presence of TFP (10 microM), staurosporine (100 nM), genistein (10 microM), PD98059 (10 microM), or wortmannin (10 nM), which are inhibitors of various protein kinases. Treatment of a monoclonal phosphotyrosine antibody (4G10) caused an alteration in the TTGGC oligonucleotide-nuclear protein complex formation, indicating that tyrosine phosphorylation of nuclear protein is partly involved in the binding to TTGGC sequence. Moreover, when H4-II-E cells were cultured with FBS (10%), Bay K 8644 (5 microM), PMA (1 microM), or insulin (20 nM), the protein binding to TTGGC sequence in the nuclei was increased, while it was reduced in the cytoplasm, indicating a nuclear localization of the TTGGC sequence-binding protein. This study demonstrates that hepatic nuclear protein can specifically bind to the TTGGC sequence in rat regucalcin gene promoter region, and that this binding is enhanced by intracellular signaling factors which are partly mediated through protein phosphorylation.

Animals↗
PubMed2000

Contrasting localizations of MALS/LIN-7 PDZ proteins in brain and molecular compensation in knockout mice.

Proteins containing PDZ (postsynaptic density-95, discs large, zonula occludens) domains play a general role in recruiting receptors and enzymes to specific synaptic sites. In Caenorhabditis elegans, a complex of three PDZ proteins, LIN-2/7/10, mediates basolateral targeting of a receptor tyrosine kinase. Homologs of these LIN proteins have also been identified in higher organisms, and here we analyze the MALS/Veli (mammalian LIN-7/vertebrate homolog of LIN-7) proteins in brain. Immunohistochemical staining and in situ hybridization show that MALS occur differentially in discrete populations of neurons throughout the brain. Most neurons express only one MALS protein, although some cells contain two or even all three MALS isoforms. At the subcellular level, MALS proteins are found in both dendritic and axonal locations, suggesting that they may regulate processes at both pre- and postsynaptic sites. Targeted disruption of MALS-1 and MALS-2 does not yield a detectable phenotype, and hippocampal synaptic function and plasticity are intact in the MALS-1/2 double knockouts. Interestingly, MALS-3 protein is dramatically induced in the MALS-1/2 double knockouts, implying that dynamic changes in protein expression may play an important regulatory role for this family of synaptic PDZ proteins.

Animals↗
PubMed2000

Reversible phase transitions in polymer gels induced by radiation forces.

Many polymer gels undergo reversible, discontinuous volume changes in response to changes in the balance between repulsive intermolecular forces that act to expand the polymer network and attractive forces that act to shrink it. Repulsive forces are usually electrostatic or hydrophobic in nature, whereas attraction is mediated by hydrogen bonding or van der Waals interactions. The competition between these counteracting forces, and hence the gel volume, can thus be controlled by subtle changes in parameters such as pH (ref. 4), temperature, solvent composition or gel composition. Here we describe a more direct influence on this balance of forces, by showing that the radiation force generated by a focused laser beam induces reversible shrinkage in polymer gels. Control experiments confirm that the laser-induced volume phase transitions are due to radiation forces, rather than local heating, modifying the weak interactions in the gels, in agreement with previous observations of light-induced chain association in polymer solutions. We find that, owing to shear-relaxation processes, gel shrinkage occurs up to several tens of micrometres away from the irradiation spot, raising the prospect that the combination of stimuli-responsive polymer gels and laser light might lead to new gel-based systems for applications such as actuating or sensing.

Journal Article↗
PubMed2000

Aberrant splicing of human Cu/Zn superoxide dismutase (SOD1) RNA transcripts.

Two abnormal SOD1 mRNAs, exon 2-skipping and exon 2 and 3-skipping species, were identified from occipital brain tissue of sporadic amyotrophic lateral sclerosis (ALS) patients carrying no mutations in the SOD1 gene. Both transcripts were ubiquitously expressed in non-neuronal as well as neuronal tissues from a subject without neurological diseases. The expression pattern did not show disease specificity or lesional selectivity associated with ALS. Transient expression studies revealed weak expression of the proteins derived from the exon 2-skipping SOD1 cDNA in a cell-free translation system but not in cells. The putative abnormal SOD1 protein may accumulate and exert toxic effects on motor neurons in ALS when the proteolytic system is disturbed by aging or some causal factors.

Adolescent↗
PubMed2000

Expression of Ca(2+)-binding protein regucalcin in rat brain neurons: inhibitory effect on protein phosphatase activity.

The expression of Ca(2+)-binding protein regucalcin and its role in the regulation of protein phosphatase activity in rat brain neuronal cells obtained with primary culture was investigated. The expression of regucalcin mRNA was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis in brain neuronal cells using rat regucalcin-specific primers. Moreover, regucalcin protein in brain neuronal cells was detected by Western blot analysis using a polyclonal rabbit anti-regucalcin antibody. The presence of anti-regucalcin monoclonal antibody (20 or 50 ng/ml) in the enzyme reaction mixture caused a significant increase in protein phosphatase activity toward phosphotyrosine, phosphoserine and phosphothreonine in the reaction mixture containing the cytosol of neuronal cell homogenates. This increase was completely prevented by the addition of regucalcin (10(-8) M). Protein phosphatase activity toward three phosphoaminoacids was significantly elevated by the addition of Ca(2+) (100 microM) and calmodulin (5 microg/ml). This elevation was completely blocked by the addition of regucalcin (10(-8) M). The present study demonstrates that regucalcin is expressed in rat brain neuronal cells, and that it has an inhibitory effect on protein phosphatase activity in the cells.

Animals↗
PubMed2000

Involvement of hepatic nuclear factor I binding motif in transcriptional regulation of Ca(2+)-binding protein regucalcin gene.

The characterization of the binding of nuclear protein on the 5'-flanking region of the rat regucalcin gene was investigated. Nuclear extracts from rat liver and H4-II-E hepatoma cells were used for oligonucleotide competition gel mobility shift assay. An oligonucleotide between position -523 and -506 in the 5'-flanking region of the rat regucalcin gene, which contains a nuclear factor I (NF1) consensus motif TTGGC(N)(6)CC, competed with the probe for the binding of the nuclear proteins from rat liver and H4-II-E cells. The mutation of TTGGC in the consensus sequence caused an inhibition of the binding of nuclear factors. The presence of Bay K 8644, insulin, and phorbol esters could stimulate the binding of the nuclear factors to the TTGGC region of the rat regucalcin gene in H4-II-E cells. The specific mutation introduced in this region, which was ligated to a luciferase reporter gene, reduced significantly the effects of Bay K 8644, insulin, and phorbol esters in stimulating the regucalcin gene transcriptional activity in H4-II-E cells. These results suggest that the specific nuclear factor binds to the NF1-like sequence, which can stimulate the transcriptional activity, in the promoter region of regucalcin gene in liver cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

Role of endogenous regucalcin in protein tyrosine phosphatase regulation in the cloned rat hepatoma cells (H4-II-E).

Regucalcin, a regulatory protein of Ca2+ signaling, is mainly present in liver cells. The role of regucalcin in hepatoma cells, however, has not been clarified. The role of endogenous regucalcin in the regulation of protein tyrosine phosphatase activity in the cloned rat hepatoma cells (H4-II-E) was investigated. Hepatoma cells were cultured for 3 days in a medium containing serum (10% fetal bovine serum). After subconfluency, the cells were used for the assay of protein phosphatase activity toward phosphotyrosine. The expression of regucalcin in hepatoma cells was detected by Western blotting using anti-regucalcin antibody. Protein tyrosine phosphatase activity was exhibited in the cytosol of hepatoma cells. The enzyme activity in the cytosol of hepatoma cells was significantly elevated by the addition of calcium chloride (10(-6)-10(-4) M) in the reaction mixture. This elevation was completely blocked by the addition of trifluoperazine (TFP: 2.5 x 10(-6) M), an antagonist of calmodulin. The addition of regucalcin (10(-7) M) caused a complete inhibition of the calcium (10(-4) M)-increased enzyme activity. The presence of anti-regucalcin monoclonal antibody (25, 50, and 100 ng/ml) in the enzyme reaction mixture produced a significant increase in protein tyrosine phosphatase activity in the cytosols of hepatoma cells and normal liver cells. This increase was completely prevented by regucalcin addition. The effect of antibody (50 ng/ml) in elevating the enzyme activity was partly inhibited by vanadate (10(-4) M). Protein tyrosine phosphatase activity was significantly elevated by the culture with Bay K 8644, a Ca2+-channel agonist. This increase was blocked by TFP addition in the enzyme reaction mixture, and it was enhanced in the presence of anti-regucalcin antibody. The present study demonstrates that regucalcin is expressed in hepatoma cells (H4-II-E), and that the protein may have an inhibitory effect on Ca2+/calmodulin-dependent protein tyrosine phosphatase activity in the cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

Echocardiographic evaluation of the ductal morphology in patients with refractoriness to lipo-prostaglandin E1 therapy.

BACKGROUND: Lipo-prostaglandin (PG)E1 is effective at lower doses and has fewer side effects than PGE1-cyclodextrin (CD). Previous studies, however, have suggested that some patients show refractoriness to lipo-PGE1 in the course of treatment. The present paper examines: (i) whether such cases can be predicted by examining the ductal morphology before and 24 h after the start of lipo-PGE1 infusion; and (ii) whether PGE1-CD dilates the ductus arteriosus in patients with refractoriness to lipo-PGE1. METHODS: The ductal morphology was evaluated with two echo indices, such as minimal and minimal plus maximal intraluminal diameters of the ductus. Two-dimensional echocardiography was performed in 24 patients with ductus-dependent congenital heart disease. The two echo indices were measured before and 24 h after lipo-PGE1 infusion and also at least twice per week until surgery. RESULTS: In 19 of 24 patients, ductal patency was maintained until surgical treatment (group A). The remaining five patients (21%) showed ductal closure during the course of the lipo-PGE1 therapy (group B). There were no significant differences between the two groups, in either the maximal or minimal diameters, which were examined before and 24 h after treatment. In the five patients of group B, lipo-PGE1 was replaced with a relatively high dosage of PGE1-CD (50-100 ng/kg per min), resulting in good ductal patency until surgery. CONCLUSIONS: Patients with refractoriness to lipo-PGE1 therapy could not be predicted from initial intraluminal diameters of the ductus using echocardiography. Therefore, serial echocardiographic examinations are important to detect early findings of ductal closure. In addition, PGE1-CD is still useful as back-up therapy in such patients.

Alprostadil↗
PubMed2000

Clinicoepidemiologic features of sudden deafness diagnosed and treated at university hospitals in Japan.

Nationwide epidemiologic surveys were done 3 times by the Research Committee of the Ministry of Health and Welfare in Japan to investigate the number of patients and clinical manifestations of idiopathic sudden sensorineural hearing loss (sudden deafness). The first, second, and third surveys were carried out during the 1970s, 1980s, and 1990s, respectively. For each patient, we have compiled data regarding age, sex, onset day, presence or absence of vertigo, and hearing ability, including initial and final audiograms, in a computer in the Nagoya University Computer Center. Regarding patients who visited university hospitals, complete data were collected for 421 subjects (age: 40.2+/-15.4 years, female: 203, male: 218) between July 1973 and June 1974, for 813 subjects (age: 45.1+/-15.4 years, female: 407, male: 406) in 1987, and for 1112 subjects (age: 49.1+/-16.0 years, female: 591, male: 521) in 1993. The number of patients with sudden deafness treated in university hospitals in Japan has increased, especially in the elderly population. This increase is associated with population increase and age-adjusted incidence rates per 100,000 in the elderly population. The initial and final hearing levels in the first survey were worse than those in the second and third surveys; there was no significant difference in hearing between the second and third surveys. The hearing levels were worse in children and elderly patients than in the other age groups.

Adolescent↗
PubMed2000

Transthoracic ultrasonic visualisation of coronary aneurysm, stenosis, and occlusion in Kawasaki disease.

OBJECTIVE: To determine the sensitivity and specificity of our transthoracic echocardiographic technique using high frequency (7.5 MHz) transducers for identification of the presence and type of coronary artery disease in patients with Kawasaki disease. DESIGN: The results of the prospective echocardiographic study in each of seven segments of the four major coronary arteries were compared with the selective coronary angiograms. SETTING: Kitasato University Hospital. SUBJECTS: 60 patients with Kawasaki disease, ranging in age from 8.0 months to 22 years (median, 6.0 years). RESULTS: Adequate echocardiographic images were obtained in 397 (95%) of 420 coronary segments. Coronary angiography showed the presence of coronary aneurysms in 87 segments and stenosis or occlusion in 28. The overall sensitivity and specificity of cross sectional echocardiography for correctly identifying coronary aneurysms were 95% and 99%, respectively; for correctly identifying coronary stenosis or occlusion the values were 85% and 98% for the right coronary artery, and 80% and 97% for the left anterior descending coronary artery. Agreement on the presence or absence of coronary aneurysms and obstructive lesions on echocardiograms between the two observers was 1.0 and 0.98, respectively. CONCLUSIONS: Echocardiography may provide a non-invasive means of identifying the presence and type of coronary artery disease in patients with Kawasaki disease.

Adolescent↗
PubMed2000

Very strong correlation between dominant negative activities of mutant thyroid hormone receptors and their binding avidity for corepressor SMRT.

The syndrome of resistance to thyroid hormone (RTH) is an inherited disorder involving a mutation of the thyroid hormone receptor (TR) gene. Mutant (m) TR inhibits wild-type (wt) TR functions in a dominant negative manner, and this dominant negative effect (DNE) is a crucial factor in RTH pathogenesis. The molecular mechanism of the DNE is still unclear, although several possibilities (including competition between wt- and mTRs at the T(3) response element (TRE), sequestration of TR-associated protein(s) and titration out of functional TR) have been considered. Here we report that the DNE of mTRs is strongly correlated with their binding avidity for the retinoid X receptor (RXR), and especially for corepressor SMRT (silencing mediator for retinoid and thyroid hormone receptor), but not for the nuclear receptor corepressor, NCoR. The DNE of six natural TRs and four artificially constructed mTRs was assayed using a TR reporter gene containing TRE-DR4 (DR=direct repeat), TRE-pal (pal=palindrome) or TRE-lap (lap=inverted palindrome) in CV1 cells treated with 10 nM T(3). Of the mTRs examined, F451X (with a carboxy-terminal 11-amino-acid truncation) identified in a patient with RTH exhibited the strongest DNE on all TREs. The binding affinities between mTRs and corepressors SMRT or NCoR were quantified using a two-hybrid interference assay system consisting of VP16-TR(LBD) (LBD=ligand binding domain) and Gal4(DBD)-SMRT (DBD=DNA binding domain), or Gal4(DBD)-NCoR respectively, together with the Gal4 reporter gene. In this assay, VP16-TR(LBD) and Gal4(DBD)-SMRT (or Gal4 (DBD)-NCoR) interact with each other and trans-activate the Gal4 reporter gene. When an equal amount of mTR is coexpressed, it reduces the transcriptional activity of the reporter gene, depending on its binding avidity for a corepressor. A very strong correlation was observed between the SMRT-binding activity and the potency of the DNE among six natural mTRs and also among all mTRs, including four artificially constructed ones. The relationship between NCoR and DNE, however, was not significant. When we assayed the binding avidity of mTRs for RXR by using a two-hybrid assay system consisting of Gal4(DBD)-RXR(LBD) and VP16-TR(LBD), a significant correlation between DNE and binding avidity for the RXR was also observed. These results suggest that a corepressor plays an important role in DNE pathogenesis.

Analysis of Variance↗
PubMed2000

Increase in O(2) delivery with hyperoxia does not increase O(2) uptake in tetanically contracting dog muscle.

We investigated the influence of hyperoxia on O(2) uptake in tetanically contracting canine gastrocnemius. Hyperoxia showed neither increase in O(2) uptake nor decrease in lactate release, irrespective of increased O(2) supply, venous Po(2) and vascular resistance, as compared to normoxia, suggesting that hyperoxia decreases O(2) diffusion conductance and/or effective O(2) supply probably due to arteriovenous O(2) diffusion shunt.

Anaerobic Threshold↗