Biomedical subjects

Y Honda

Publications and source records attributed to Y Honda.

At least 343 records · Page 19Linked to original sources

PubMed1996

Insulin-like growth factor (IGF) system components in human prostatic cancer cell-lines: LNCaP, DU145, and PC-3 cells.

BACKGROUND: Evidence has been accumulating that in many tumors, insulin-like growth factors (IGFs) promote cancer cell growth in an autocrine/paracrine manner via the IGF-I receptor. In an effort to understand the role of IGFs in prostate cancer cell growth, we characterized the IGF system components produced by human prostatic cancer cell-lines, LNCaP, DU145, and PC-3, grown in serum-free medium. METHODS: IGFs, their receptors, and IGF binding proteins (IGFBPs) produced by the three human prostate cell lines were characterized by reverse transcriptase-polymerase chain reaction (RT-PCR), radioimmunoassay (RIA), Western ligand blot, Western immunoblot, and Northern blot analyses. RESULTS: mRNA for IGF-II and receptors for IGF-I and IGF-II were detected in all three cell-lines by RT-PCR. In contrast to the published study, only LNCaP cells expressed a trace amount of IGF-I mRNA. RIA on conditioned media collected from these cells revealed that all three cell-lines produced measurable IGF-II but not IGF-I. Western Ligand blot, Western immunoblot, and Northern blot analyses revealed that LNCaP, DU145, and PC-3 cells expressed IGFBP-2, IGFBP-2/-3/-4/-6, and IGFBP-2/-3/-4/-5/-6, respectively. IGF-II stimulated [3H]thymidine incorporation into DNA in DU145 and PC-3 cells significantly although the effect was small. DNA synthesis in PC-3 cells but not in LNCaP and DU145 cells was significantly inhibited by the IGF-I receptor-specific monoclonal antibody. CONCLUSION: Theses results suggest potentially important roles of IGFs and IGFBPs in prostate cancer cell growth, and that in particular, IGF-II may play a critical role in prostate cancer cell growth.

Antibodies, Monoclonal↗

PubMed1996

Use of intravascular ultrasound for in vivo assessment of changes in intimal thickness of angiographically normal saphenous vein grafts one year after aortocoronary bypass surgery.

OBJECTIVE: To use intravascular ultrasound in vivo to evaluate changes in the intimal thickness of angiographically normal saphenous vein grafts one year after implantation. DESIGN: Fifteen saphenous vein grafts in 12 patients were examined one month and 12 months after aortocoronary bypass graft surgery with intravascular ultrasound using a 30 MHz transducer. None of the grafts examined showed any angiographic abnormalities. The intimal thickness and intimal area of the graft in the proximal portion were measured on intravascular ultrasound images obtained one month and 12 months after operation. SETTING: General hospital. PATIENTS: Twelve patients who underwent aortocoronary bypass graft surgery. RESULTS: The ultrasound images showed a thin-walled graft with a thin intima one month after operation (mean (SD)) (0.31 (0.09) mm). The intimal thickness of the graft increased significantly to 0.65 (0.08) mm (P < 0.001) 12 months after operation. The intimal area of the graft was 0.90 (0.80) mm2 one month after operation. 12 months after operation the intimal area had increased significantly to 5.26 (1.38) mm2 (P < 0.001). CONCLUSION: Intravascular ultrasound in vivo showed that one year after implantation angiographically normal saphenous vein grafts had a thicker intima than one month after implantation.

Coronary Artery Bypass↗

PubMed1996

Effect of prior O2 breathing on ventilatory response to sustained isocapnic hypoxia in adult humans.

Sixteen healthy volunteers breathed 100% O2 or room air for 10 min in random order, then their ventilatory response to sustained normocapnic hypoxia (80% arterial O2 saturation, as measured with a pulse oximeter) was studied for 20 min. In addition, to detect agents possibly responsible for the respiratory changes, blood plasma of 10 of the 16 subjects was chemically analyzed. 1) Preliminary O2 breathing uniformly and substantially augmented hypoxic ventilatory responses. 2) However, the profile of ventilatory response in terms of relative magnitude, i.e., biphasic hypoxic ventilatory depression, remained nearly unchanged. 3) Augmented ventilatory increment by prior O2 breathing was significantly correlated with increment in the plasma glutamine level. We conclude that preliminary O2 administration enhances hypoxic ventilatory response without affecting the biphasic response pattern and speculate that the excitatory amino acid neurotransmitter glutamate, possibly derived from augmented glutamine, may, at least in part, play a role in this ventilatory enhancement.

Administration, Inhalation↗

PubMed1996

Morphological and histochemical study of nonhemiplegic muscle in acute stroke patients manifesting respiratory failure.

There is little information on skeletal muscle changes in patients with acute stroke. We performed morphological and histochemical examinations of nonhemiplegic sternothyroid muscles biopsied at the time of tracheostomy from 13 patients with acute stroke manifesting acute respiratory failure. Degenerating and regenerating fibers were observed in all 13 specimens. Following characteristic myopathic changes suggestive of mitochondrial abnormalities were also demonstrated in a majority of patients. Namely, ragged-red fibers, focal increase in NADH-TR activity in subsarcolemmal areas and increases in acid phosphate activity were found. The changes were similar but extremely slight in control patients with acute respiratory failure due to causes other than stroke and were absent in the other control patients with adenomatous thyroid tumor. The severity and extent of the histopathological changes in the muscle fibers in patients with acute stroke were closely correlated with the duration of hypoxemia but not with such items as type of stroke, site of cerebral lesion, consciousness level, days of biopsy after the stroke, clinical outcome, levels of serum creatine kinase, myoglobin and PaO2. This acute nonhemiplegic muscle involvement was considered to be a very common complication in severe stroke patients.

Acute Disease↗

PubMed1996

Development of osteopenia in the hemiplegic finger in patients with stroke.

Previous studies have demonstrated that hip fractures in stroke patients occurred almost exclusively on the hemiplegic side. We examined the bone changes in the second metacarpal of the hemiplegic side in terms of microdensitometric indices in 93 stroke patients with hemiplegia. All six indices indicated a significant decrease in bone mass on the hemiplegic side compared with the contralateral side. Differences in the indices between the hemiplegic and contralateral sides were correlated well with the duration of the illness and Brunstrom's stage for finger, arm, and leg. The same degree of osteopenia occurred in both small capsular and large hemispheric lesions. The same osteopenia was demonstrated in paralyzed and immobilized patients with myopathy. Thus a combination of weakness and immobilization is thought to be responsible for the osteopenia in the hemiplegic metacarpal bone. The osteopenia noted in the second metacarpal in the affected limb may account for the fact that hip fractures in stroke patients occur almost exclusively on the hemiplegic side.

Adult↗

PubMed1996

Lipid analysis and surfactant-associated protein expression in lung adenocarcinoma cells from pleural effusion.

Primary lung adenocarcinomas originate from the progenitor cells of peripheral airway cells. Alveolar type II cells and Clara cells are the major progenitor cells of peripheral airway cells. Alveolar type II cells produce a lipid-protein complex called surfactant, which contains surfactant proteins SP-A, SP-B, SP-C and SP-D. Phosphatidylcholine (PC) and phosphatidylglycerol (PG) are believed to be essential for the surfactant function. Clara cells also express SP-A, SP-B and SP-D but not SP-C. In this study we examined the properties of the cancer cells isolated from the pleural effusion of a patient with primary lung adenocarcinoma by analyzing lipids, proteins and mRNAs. The cancer cells, designated as LC117 cells, were isolated from the pleural effusion of a patient with primary lung adenocarcinoma. The percent distributions of [14C]-acetate incorporated into PC and PG in the cancer cells were 55.7 and 1.1%, respectively. The disaturated species in total PC was 46.2%. Immunoblotting analysis using anti-SP-D monoclonal antibody revealed that the pleural effusion from a patient with lung adenocarcinoma contained SP-D. We determined the concentrations of SP-A and SP-D by enzyme-linked immunosorbent assay. The pleural effusions from this patient and the media incubated with cancer cells exhibited significant levels of SP-D as well as SP-A. Reverse transcriptase-polymerase chain reaction demonstrated that the tumor cells expressed mRNAs for SP-C as well as the other surfactant proteins. The results demonstrate that tumor cells from lung adenocarcinoma express all of surfactant-associated proteins, indicating that LC117 cells originate from alveolar type II cells. This study indicates that the combination of analyses of lipids, proteins and mRNAs in the cancer cells isolated from pleural effusion is useful to understand the property of lung adenocarcinoma.

Adenocarcinoma↗

PubMed1996

Increased cytokine gene expression in rat retina following transient ischemia.

Tumor necrosis factor (TNF) gene expression in rat retina following transient ischemia was studied by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Gene expression for other cytokines was also studied by RT-PCR. Although very little expression for TNF gene was detected in normal retina, it was markedly increased 0.5-48 h after reperfusion, with peak expression at 12 h (20-fold of control). Gene expression for interleukin-6, interferon-gamma, and transforming growth factor-beta 1 was also increased. The results provide evidence that retinal ischemia can up-regulate cytokine gene expression in the retina.

Animals↗

PubMed1996

Tyrosine phosphorylation in desmosomes and hemidesmosomes of the corneal epithelium.

We examined the localization of phosphotyrosine (p-Tyr)-modified proteins in the normal corneal epithelium using affinity-purified rabbit anti-p-Tyr antibody. Normal rat cornea was fixed and semi-thin and ultra-thin frozen sections were prepared. Immunofluorescence microscopy showed that p-Tyr was distributed along the cell membrane of the corneal epithelium. Immunogold electron microscopy revealed that the labeling is exclusively localized in the desmosomes and hemidesmosomes. A fraction enriched with desmosomes was extracted from the bovine corneal epithelium and examined by Western blotting. Immunoblotting for p-Tyr showed eight prominent bands (290, 200, 190, 115, 85, 62, 50, and 47 kD) in the desmosomal fraction. The enrichment of p-Tyr in desmosomes and hemidesmosomes of the corneal epithelium suggests that these cell-to-cell and cell-to-substrate junctions are involved in signal transduction.

Animals↗

PubMed1996

Recombinant synthesis of insulin-like growth factor-binding protein-4 (IGFBP-4): Development, validation, and application of a radioimmunoassay for IGFBP-4 in human serum and other biological fluids.

Insulin-like growth factor-binding protein-4 (IGFBP-4), like the five other IGFBPs present in human serum, acts as a transport protein for insulin-like growth factor I (IGF-I) and IGF-II and modulates their biological effects. To investigate the role of IGFBP-4 in the physiology of the IGF system, we developed a sensitive RIA for IGFBP-4 employing, as antigen, tracer, and standard, recombinant human IGFBP-4 (rhIGFBP-4) expressed in Escherichia coli as a fusion protein with glutathione S-transferase and affinity purified with glutathione-derivatized resin. Antibody against the rhIGFBP-4 fusion protein was raised in guinea pigs; tracer and standard were provided by the rhIGFBP-4 moiety that had been cleaved from the rhIGFBP-4 fusion protein and repurified by reverse phase high pressure liquid chromatography. We report that both IGFBP-4 purified from PC3 human prostate cell-conditioned medium and rhIGFBP-4 bound IGF and migrated in electrophoresis gels in an identical manner; that in gel permeation chromatography, rhIGFBP-4 coeluted with the IGFBP-4 present in human serum; and that both are equally immunoreactive with the IGFBP-4 antiserum. Employing this IGFBP-4 RIA, we determined that no IGFBP other than IGFBP-4 reacted with the IGFBP-4 antiserum, and that recovery of IGFBP-4 from serum samples exceeded 90% when exogenous IGFBP-4 was added and was unaffected by the addition of IGFs or by repeated freezing and thawing of the sample. We employed this IGFBP-4 RIA to demonstrate an increase in IGFBP-4 in TE85 human osteosarcoma cell-conditioned medium after treatment with dibutyryl cAMP, PTH, and 1,25-dihydroxyvitamin D3, agents known to increase the IGFBP-4 messenger ribonucleic acid level. Application of this RIA to the measurement of IGFBP-4 in human serum revealed that the circulating level of IGFBP-4 in 41 individuals in the 61-87 yr age group (546 +/- 135 microgram/L) was 35% higher than that in 24 individuals in the 23-40 yr age group (404 +/- 156 microgram/L). The mean circulating level of PTH was also 20% higher in the 61-87 yr group compared to that in the 23-40 yr group (P < 0.01). In addition, serum IGFBP-4 amounts showed a significant positive correlation with age (r = 0.54; P < 0.001) and serum PTH (r = 0.26; P < 0.01). These data validate this IGFBP-4 RIA and illustrate its utility in illuminating the physiological mechanisms that regulate IGFBP-4 in vivo and influence its effects on the IGFs in both normal and abnormal pathology and in aging.

Adult↗

PubMed1996

Scintigraphic detection of regional disruption of the adrenergic nervous system in sarcoid heart disease.

The presence of defects on resting thallium (201Tl) myocardial scintigraphy has been previously demonstrated in myocardial sarcoidosis. To examine cardiac sympathetic nerve activity in patients with cardiac sarcoidosis, we performed 201Tl and I-123 MIBG (meta-iodobenzylguanidine) myocardial scintigraphy in patients with sarcoidosis. Sixteen patients with sarcoidosis were classified into 2 groups according to the presence or absence of defects on 201Tl scintigraphy. Myocardial images by both 201Tl and I-123 MIBG were then divided into 20 segments and scored using a 6-point scoring system. Defect Score was defined as a the sum of significant scores in each image. The mean Defect Score in I-123 MIBG images was higher in the 201Tl defect group (44.3 +/- 13.3) than in both the normal 201Tl group (25.1 +/- 10.5) and the control group (22.7 +/- 11.4). Moreover, the locations of defects on I-123 MIBG scans were consistent with those on 201Tl scans. This study suggests that cardiac adrenergic function may be impaired in cardiac sarcoidosis, and I-123 MIBG scintigraphy may be more sensitive in detecting cardiac sarcoidosis than 201Tl scintigraphy, although the clinical significance of these findings requires further study.

3-Iodobenzylguanidine↗

PubMed1996

Chitinous component of the cell wall of Fusarium oxysporum, its structure deduced from chitosanase digestion.

The cell of Fusarium oxysporum was digested with commercial Bacillus chitosanase. The chitosanase produced low molecular weight heterooligosaccharides consisting of GlcN and GlcNAc from the cell wall. A main component of the digestion products was identified as 2-amino-2-deoxy-beta-D-glucopyranosyl- (1-->4)-2-acetamido-2-deoxy-D-glucopyranose. The chitosanase appeared to be more effective than Streptomyces griseus chitinase for cell wall digestion. Moreover, maltose was unexpectedly found in the digestion products, indicating that the cell wall contains alpha-1,4-linked glucan chain as a polysaccharide component.

Acetylglucosamine↗

PubMed1996

Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers.

Hydrophilic surfactant proteins, surfactant protein A (SP-A) and surfactant protein D (SP-D), have important roles in modulating the host defense functions in the peripheral airways. It has been reported that cigarette smoke may alter the component and function of pulmonary surfactant. In this study, we determined the contents of SP-A and SP-D in BAL fluids of healthy smokers and nonsmokers by enzyme-linked immunosorbent assay using monoclonal antibodies against each protein. The contents of SP-A and SP-D in BAL fluids were significantly (p<0.05) decreased in smokers compared to those in nonsmokers, although there was no significant difference of total phospholipid content between smokers and nonsmokers. These results suggest that the decreased levels of SP-A and SP-D in smokers may impair the host defense functions of surfactant in the peripheral airways and might have a crucial roles in the development of chronic obstructive lung disease.

Adolescent↗

PubMed1996

Cephalometric comparison of craniofacial morphology between primary bone grafted and nongrafted complete unilateral cleft lip and palate adults.

The effect of primary bone grafts on craniofacial growth was evaluated in adult patients with complete unilateral cleft lip and palate (UCLP). The subjects were 18 UCLP patients with primary bone grafts and a control group of 36 UCLP patients without bone grafts. The former received primary transplantation of autogenous rib bone simultaneously with primary cheiloplasty by the same surgeon between 1963 and 1969. Frontal and lateral cephalograms taken after 16 years of age were traced. Skeletal landmarks were identified on them, and their x,y-coordinates were digitized. The effects of gender and/or primary bone graft on the craniofacial morphology were tested by ANOVA using 21 angles, 8 breadths, 13 distances, and 2 ratios. Nasal cavity breadth was wider in the primary bone grafted group. However, the anterior maxilla in that group was more upward and retruded than that in the nongrafted group. The primary bone grafted group was divided into two subgroups based on the overjet of the incisors: group N = normal overjet; group C = anterior cross-bite. There was no difference in the maxilla between groups N and C. However, the mandible in group C was more anterior and superior than in group N. In conclusion, primary bone graft may impede maxillary horizontal and vertical growth to a certain degree, and severe anterior cross-bite in primary bone grafted subjects may be brought about by mandibular closure.

Adult↗

PubMed1996

Contribution of peripheral chemoreceptor drive in exercise hyperpnea in humans.

The peripheral chemoreceptors play a dominant role in the respiratory compensation of lactic acidosis during heavy exercise of humans. Our object was to determine the contribution of peripheral chemoreceptors to exercise hyperpnea during mild to moderate and heavy exercise above the anaerobic threshold. We used a hyperoxic suppression test in six normal male subjects. Inspired gas was abruptly changed without the subject's knowledge from air to pure oxygen for 5 to 6 breaths. The maximal ventilatory depression after O2 breathing was 5.5 +/- 1.7 L/min (BTPS) at mild exercise, and the depression increased with increasing exercise intensity up to 12.8 +/- 4.1 L/min (BTPS). The relative contribution of the peripheral chemoreceptors to ventilation in terms of percentage of the maximal ventilatory depression was maintained, being 20% throughout the entire work ranges studied. The contribution of the peripheral chemoreceptors to total ventilation is hardly altered by lactic acidosis caused by heavy exercise above the anaerobic threshold according to our data. These results suggested that the peripheral chemoreceptors may not be solely responsible for excessive hyperventilation, or residual activities of peripheral chemoreceptors still exist after O2 breathing especially during heavy exercise above the anaerobic threshold.

Acidosis, Lactic↗

PubMed1996

Sleep oxygen desaturation in late sequelae of pulmonary tuberculosis.

Thirty-eight patients with late sequelae of pulmonary tuberculosis (TB seq.) were studied to clarify the characteristics of sleep desaturation in comparison with 40 patients with chronic obstructive pulmonary disease (COPD). While awake, the TB seq. group had a lower % VC and a higher PaCO2. In both groups, the sleep lowest SaO2 was positively correlated with the awake SaO2. The regression line between the sleep lowest SaO2 and the awake baseline SaO2 in the TB seq. group was located below that in the COPD group. Awake PaCO2 was negatively related to the sleep lowest SaO2 only in the TB seq. group. These results indicate that the sleep lowest SaO2 values were lower in TB seq. than in COPD patients with the same levels of SaO2 while awake. Sleep studies are necessary to reveal the indication for nocturnal oxygen therapy in TB seq. patients, especially when they are hypercapnic in spite of their good awake oxygenation.

Aged↗

PubMed1996

Lack of immunoreactivity for myoglobin in skeletal muscle of acute stroke patients.

Sternothyroid muscle biopsy specimens, obtained during tracheostomies from 15 patients with acute stroke and respiratory failure, were examined immunohistochemically to immunoreactivity to myoglobin (Mb). A marked decrease or lack of Mb immunoreactivity in association with hyaline degeneration was observed in 0.8 to 44.4% of the muscle fibers on both the paretic and non-paretic sides of all patients. The percentages of negative staining for Mb were less than 3.1% in 5 patients with acute respiratory failure due to causes other than stroke. The pattern and incidence of attenuated Mb immunoreactivity in the muscle fibers was found to be distinctively different in the two patients groups. In one group of 5 patients, a large number of muscle fibers (24.8 +/- 15.6%) had no Mb staining and were clearly bordered and grouped. In another 10-patient group, only a limited number of muscle fibers (3.3 +/- 2.5%) had no staining for Mb and these fibers were scattered. Four patients in the former group had catastrophic outcomes, while all the patients in the latter group survived. Ischemia, produced by an increase in catecholamines, and the consequent vasoconstriction, rather than hypoxemia seemed to be the cause of the negative immunoreactivity for Mb in the group pattern. In contrast, hypoxemia may have caused the scattered pattern of negative Mb immunoreactivity. It was concluded that negative immunostaining for Mb in muscle fibers represents a common and characteristic complication in acute stroke patients.

Acute Disease↗

PubMed1996

Evaluation of retinal microcirculatory alterations in the Goto-Kakizaki rat. A spontaneous model of non-insulin-dependent diabetes.

PURPOSE: To evaluate retinal microcirculation in the spontaneous diabetic GK (Goto-Kakizaki) rat over an extended time. METHODS: The dye-dilution technique with scanning laser ophthalmoscope-based fluorescein angiography was used to evaluate retinal circulation in GK rats with diabetes of 1, 3, and 5 months' duration and in age-matched controls. Scanning laser ophthalmoscope fluorescein angiograms were recorded after a 10-microliter bolus of 10% sodium fluorescein was injected into the tail vein, followed by a flush of 0.1 ml saline. Retinal mean circulation times (MCTs), vessel diameters, and retinal segmental blood flows (SBFs) were determined using computer-assisted image analysis on a frame-by-frame basis. RESULTS: The MCTs were significantly prolonged (P< 0.01) in the GK rat groups (2.60 +/- 0.31, 2.74 +/- 0.28, and 2.84 +/- 0.38 seconds at 1, 3, and 5 months' duration of diabetes, respectively) compared to the age-matched controls (1.94 +/- 0.20, 1.99 +/- 0.12, and 1.91 +/- 0.22 seconds, respectively). No significant differences were observed in the retinal arterial and venous diameters between groups at each time period. The SBFs were significantly reduced (P< 0.03) in the GK rat groups (12.0 +/- 1.5, 12.1 +/- 2.0, and 11.8 +/- 2.5 x 10(2) micrometer squared/second at 1, 3, and 5 months' duration of diabetes, respectively) compared to the controls (16.0 +/- 2.2, 16.7 +/- 1.8, and 17.2 +/- 2.5 x 10(2) micrometer squared/second, respectively). In either group, no significant changes with growth were observed in MCT, vessel diameters, or SBF, although the MCTs in the GK rat group tended to lengthen, and arterial and venous diameters in the GK rat group tended to increase with duration of diabetes. Goto-Kakizaki rats did not exhibit dense cataracts, the retinal circulation could be observed, and morphologic changes of diabetic retinopathy did not develop throughout the experimental period. CONCLUSIONS: A significant prolongation in MCT and a significant reduction in SBF appeared in GK rats at an early stage in diabetes. This tendency continued until 5 months' duration of diabetes. These results suggest that retinal circulatory abnormalities are found before observable retinopathy development in GK rats and that there may be some mechanism causing a reduction in SBF without changing major retinal vessel diameters at an early stage in non-insulin-dependent diabetes mellitus (NIDDM). In addition, this study demonstrates that the GK rat will be a useful model of non-insulin-dependent diabetes mellitus to evaluate retinal circulation over an extended time.

Animals↗

PubMed1996

In vivo quantitation of peroxides in the vitreous humor by fluorophotometry.

PURPOSE: To detect intravitreal peroxides in vivo by a new fluorophotometric method with a hydrogen peroxide (H2O2)-sensitive fluorescent dye. METHODS: The authors used a 2',7'-dichlorofluorescin (DCFH) assay to measure oxidative status in the rabbit vitreous. In the presence of H2O2 and lipid hydroperoxides, nonfluorescent DCFH in the vitreous is oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF; excitation, 495 nm; emission, 520 nm) that is detectable by fluorophotometry. Reactions of DCFH with various concentrations of H2O2 were investigated in vitro and in vivo. An inhibitory effect of catalase also was monitored. Vitreous fluorophotometry with DCFH was performed immediately and at 3, 7, and 28 days after constant light exposure to the retina (1800 lux, 24 hours) as an oxidative stress. RESULTS: In vitro study revealed that H2O2 oxidized DCFH to DCF in a dose-dependent manner, ranging from 0.1 to 100 mmol/1 in concentration. Catalase inhibited DCF production. Vitreous fluorophotometry demonstrated that H2O2 oxidized DCFH to DCF in vivo in a dose-dependent manner, ranging from 0.06 to 60 mmol/1 in concentration. DCF production in the vitreous significantly increased immediately (P = 0.03) and at 3 days (P = 0.01) and 7 days (P = 0.01) after light exposure, and it returned to the pretreatment level by day 28. CONCLUSIONS: The results suggest that this fluorophotometric method quantitatively can detect intravitreal peroxides in vivo. This method will be helpful to study the oxidative status in some experimental pathologic conditions.

Animals↗