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Biomedical subjects

Y Kitano

Publications and source records attributed to Y Kitano.

At least 37 records · Page 2Linked to original sources
PubMed2000

Lung growth induced by tracheal occlusion in the sheep is augmented by airway pressurization.

BACKGROUND/PURPOSE: Prenatal tracheal occlusion (TO) has been shown to accelerate lung growth, yet the mechanism for this effect is poorly understood. Increased intratracheal pressure (ITP) with accumulation of lung fluid and secondary airway distension (stretch) may provide a mechanical stimulus for growth. In this study, ITP after TO is measured continuously, and the effect of altering ITP on lung growth is examined. METHODS: Fetal lambs of 115 to 120 days of gestation (term, 145 days) underwent placement of an intratracheal catheter and an amniotic fluid reference catheter. First, ITP was monitored continuously in normal controls (n = 4) and in fetuses undergoing TO (n = 6). In a subsequent study, 2 groups of fetuses were compared. In the TO group (n = 5) ITP was monitored after TO. In the pressurized group (n = 5) ITP was maintained at 7 to 8 mm Hg by a continuous servo regulated pump that maintains a preset pressure by lactated Ringers infusion. The animals were killed after 4 days, and lung growth was compared. RESULTS: In the control animals, ITP remained constant at 0.4 to 1.5 mm Hg. In the TO animals, ITP increased gradually during the initial 24 hours and plateaued at 4 to 5 mm Hg. In the second set of animals, ITP in the pressurized group was maintained at approximately 8 mm Hg using the infusion system. Lung volume (135.7+/-17.4 v. 95.2+/-14.8 mL/kg; P<.01), lung weight to body weight (6.70+/-0.73 v. 5.33+/-0.77%; P<.05), whole right lung dry weight (3.10+/-0.22 v. 2.63+/-0.20 mg/kg; P<.05), and right lung DNA and protein contents (87.3+/-6.0 v. 74.6+/-8.1 mg/kg, 2,310+/-248 v. 1,860+/-196 mg/kg, respectively; P<.05) were increased significantly in the pressurized group compared with the TO group. Morphometry confirmed greater volume of respiratory region and increased alveolar surface area in the pressurized lung. CONCLUSIONS: TO results in a gradual increase in ITP over 15 to 24 hours, which plateaus at 4 to 5 mm Hg. Further increasing ITP by infusion of crystalloid significantly augments lung growth beyond that observed with TO alone. These data support the hypothesis that airway pressure and secondary mechanical stretch are the primary stimuli of TO induced lung growth.

Animals↗
PubMed2000

Radiofrequency thermal ablation: a potential treatment for hydropic fetuses with a large chest mass.

BACKGROUND/PURPOSE: Physiological changes secondary to a rapidly enlarging fetal chest mass can lead to nonimmune hydrops, which is a predictor of impending fetal demise. Currently, open fetal surgery is offered for specific patients with hydrops before 32 weeks' gestation. The authors asked if a less-invasive technique, radiofrequency thermal ablation (RTA), could be applied safely to the destruction of fetal lung tissue. METHODS: Time-dated pregnant ewes at 120 to 125 days' gestation (term, 140 to 145 days) underwent RTA through a hysterotomy (n = 3) or in a transuterine fashion under ultrasound guidance (n = 4). The probe is a 15-gauge needle with a maximal 2-cm deployment sphere at its tip. By varying the intensity and duration of treatment, the power settings were optimized to create a defined area of ablation with minimal surrounding tissue injury. Five of the 6 fetal lambs were killed acutely, and 1 was followed up for 1 week with frequent ultrasound examinations. RESULTS: Gross examination of the animals killed acutely showed a consistent area of ablation using 10 watts of applied power for 3 minutes. Direct coagulation necrosis lesions ranged from 1x1 cm to 2x2 cm in size depending on the extent of the probe deployment. One animal was followed up for 1 week and showed no major adverse physiological effects. CONCLUSION: Radiofrequency thermal ablation can be performed safely in this fetal sheep model to create a controlled area of lung tissue ablation.

Animals↗
PubMed2000

Selection, enrichment, and culture expansion of murine mesenchymal progenitor cells by retroviral transduction of cycling adherent bone marrow cells.

It has been difficult to characterize murine bone marrow (BM)-derived mesenchymal progenitor cells (MPCs) because of contamination with hematopoietic cells. We took advantage of the rapid proliferation of MPCs after replating to enrich murine MPCs by transfection with a retroviral vector carrying both LacZ and the selective neomycin resistance (neoR) gene. Freshly harvested BM cells from mice were incubated with BAG retroviral vector produced by amphotropic psi-CRIP or ecotropic psi-CRE producer cells for 48 hours and grown in the presence of G418.Cells incubated in psi-CRIP supernatant formed colonies composed of large homogeneous cells that were free of CD45(+) cells, but cells incubated in psi-CRE supernatant did not form stromal cell colonies. In the undifferentiated state, the cells displayed a fibroblast-like phenotype with low alkaline phosphatase activity. However, upon treatment with dexamethasone or 5-azacytidine, the retrovirally transduced cells differentiated into oil-red-O-positive adipocytic cells and osteogenic cells generating von Kossa-positive bone nodules. Osteogenic supplements composed of beta-glycerophosphate, dexamethasone, and ascorbic acid induced an increase in alkaline phosphatase activity and acute osteogenesis associated with early cell detachment. Subcutaneous injection with retrovirally transduced cells into day 1 newborn mice of the same strain produced ectopic calcium depositions surrounded by X-gal(+) cells. Retroviral selection of cycling adherent cells is an effective approach for enrichment of MPCs.

Adipocytes↗
PubMed2000

Immediate contact hypersensitivity induced by repeated hapten challenge in mice.

An immediate reaction was investigated during repeated challenge testing for contact hypersensitivity to dinitrofluorobenzene (DNFB) in BALB/c mice. The mice were sensitized to DNFB on back skin and repeatedly challenged with the same hapten on the left ear at 1 week intervals. The ear after the 5th challenge showed biphasic responses which consisted of an immediate and a delayed-type reaction. The reactions were hapten specific. Mast cell-deficient WBB6F1 W/WV mice did not show any immediate reaction, while congenic normal mice showed both immediate and delayed-type reactions. Histologically, numerous dermal mast cells were found in the left ear of repeatedly challenged BALB/c and WBB6F1 normal mice, while there were few mast cells in the ear of WBB6F1 W/WV mice. Anti-DNP IgE antibodies were detected in BALB/c, WBB6F1 normal and W/WV mice after repeated challenge with DNFB. Intradermal injection of anti-IgE antibodies in the repeatedly DNFB-challenged ear elicited an immediate reaction. These results suggest that immediate contact hypersensitivity develops through the production of anti-DNP IgE antibodies and an increase in dermal mast cells after repeated challenge with DNFB.

Animals↗
PubMed2000

Involvement of central opioid systems in human interferon-alpha induced immobility in the mouse forced swimming test.

1. We investigated the mechanism by which human interferon-alpha (IFN-alpha) increases the immobility time in a forced swimming test, an animal model of depression. 2. Central administration of IFN-alpha (0.05 - 50 IU per mouse, i.cist.) increased the immobility time in the forced swimming test in mice in a dose-dependent manner. 3. Neither IFN-beta nor -gamma possessed any effect under the same experimental conditions. 4. Pre-treatment with an opioid receptor antagonist, naloxone (1 mg kg(-1), s.c.) inhibited the prolonged immobility time induced by IFN-alpha (60 KIU kg(-1), i.v. or 50 IU per mouse. i.cist. ). 5. Peripheral administration of naloxone methiodide (1 mg kg(-1), s. c.), which does not pass the blood - brain barrier, failed to block the effect of IFN-alpha, while intracisternal administration of naloxone methiodide (1 nmol per mouse) completely blocked. 6. The effect of IFN-alpha was inhibited by a mu(1)-specific opioid receptor antagonist, naloxonazine (35 mg kg(-1), s.c.) and a mu(1)/mu(2) receptor antagonist, beta-FNA (40 mg kg(-1), s.c.). A selective delta-opioid receptor antagonist, naltrindole (3 mg kg(-1), s.c.) and a kappa-opioid receptor antagonist, nor-binaltorphimine (20 mg kg(-1), s.c.), both failed to inhibit the increasing effect of IFN-alpha. 7. These results suggest that the activator of the central opioid receptors of the mu(1)-subtype might be related to the prolonged immobility time of IFN-alpha, but delta and kappa-opioid receptors most likely are not involved.

Animals↗
PubMed2000

Transient appearance of antegrade conduction via an AV accessory pathway caused by atrial fibrillation in a patient with intermittent Wolff-Parkinson-White syndrome.

A 55 year old man with intermittent Wolff-Parkinson-White (WPW) syndrome had an episode of atrial fibrillation (AF) that lasted for 117 days. After interruption of the AF a Delta wave appeared that lasted for two days and then disappeared. Exercise stress and isoprenaline infusion could not reproduce the Delta wave, but after another episode of AF which lasted for seven days a persistent Delta wave appeared that lasted for six hours. In an electrophysiological study performed on a day without a Delta wave, neither antegrade nor retrograde conduction via an accessory pathway was seen, but after atrial burst pacing (at 250 ms cycle length) for 10 minutes, a Delta wave appeared lasting for 16 seconds. Atrial electrical remodelling-that is, the shortening of the atrial effective refractory period caused by AF, is a possible mechanism of the appearance of the Delta wave.

Administration, Oral↗
PubMed2000

Quantitative evaluation of a directly depolarized area induced by high-output pacing on the cardiac muscle.

Quantitative information is needed on the directly depolarized area (DDA) induced by high-output energy during a precise mapping procedure to detect the origin of a tachycardia. In the present study, a DDA caused by high-output energy was quantitatively evaluated in the exposed canine heart. In 8 dogs, the right atrial and ventricular surfaces were exposed through a right thoracotomy and pacing with various outputs was delivered from the epicardial surface. A comb-shaped 16 polar electrode array and/or a 224 polar mat electrode array were used for recording the epicardial electrograms. The local activation time was measured at each electrode site, and the relationship of the distance between the electrode location from the pacing site and the local activation time was plotted and fitted to a primary regression line. The intercept of the regression line on the horizontal axis was defined as the radius of the 'DDA' and this was evaluated at each pacing output. The radius of the DDA was 0.6+/-0.1 mm with a 2 V and 3.8+/-0.2 mm with a 10 V output when it was evaluated in a direction perpendicular to the fiber orientation of the pectinate muscle, 0.8+/-0.1 mm with a 2 V and 4.1+/-0.3 mm with a 10 V output in a direction parallel to the pectinate muscle fiber orientation, and 0.9+/-0.3 mm with a 2 V and 3.6+/-0.5 mm with a 10 V output in the right ventricle. The DDA extended according to the increase in stimulation outputs at all sites, and there was no significant difference in the pacing site or the direction of the stimulation propagation. The DDA caused by high-output energy is a purely physical phenomenon that depends only on stimulation output and tissue resistance. The diameter of the DDA exceeded 4 mm (ie, the size of a standard tip electrode for catheter ablation) when pacing was delivered with an output greater than 6 V.

Animals↗
PubMed2000

Comparative studies on the cysteine proteinase inhibitory capacity of mammalian blood.

The inhibition of cysteine proteinase (papain) by human, bovine, horse, rabbit, guinea pig, rat, hamster, and mouse plasma, and pig, sheep, goat, and dog sera was investigated. The rat and mouse plasma and the pig serum showed such high inhibitory capacity as 813, 380, and 508%, respectively, of the human plasma. On the other hand, the horse, guinea pig, and rabbit plasma indicated 36, 40, and 54%, respectively, of the human plasma. A cysteine proteinase inhibitor (s) was separated from alpha-macroglobulin by Sephacryl S-300, and the inhibitory activity of all of the mammalian plasma/sera except for the guinea pig plasma appeared at around the 50-150-kDa region. The guinea pig plasma exhibited well-resolved two peaks of 100 and 200 kDa.

Animals↗
PubMed2000

High frequency of tetraploidy detected in malignant melanoma of Japanese patients by fluorescence in situ hybridization.

Aneuploidy and hyperploidy are often detected in malignant melanoma by cytogenetic analysis and flow cytometric analysis of DNA content. To determine the ploidy of cells in surgical specimens of melanin-producing tumors of Japanese patients, we performed fluorescence in situ hybridization (FISH) using touch smear technique to count the number of chromosomes 18 and X + Y in interphase nuclei using alpha-satellite DNA probes, D18Z1, DXZ1 and DYZ3. A normal melanocyte strain showed two D18Z1 and two [DXZ1+DYZ3] signals per nucleus, indicating 2N, and a malignant melanoma cell line showed 4 per nucleus, indicating 4N, consistent with results of cytogenetic and flow cytometric analyses. Therefore we employed this FISH method to analyze ploidy of surgical specimens. Specimens obtained from 8 patients with nevus cell nevus showed 2 FISH signals per nucleus. On the other hand, in all specimens obtained from 8 patients with malignant melanoma (6 primary and 2 metastatic melanoma), 65-90% of cells exhibited 4 signals per nucleus, indicating 4N. Histopathologically, 50-70% of cells were identified as malignant melanoma cells, indicating that our FISH method is effective to detect melanoma cells in tissue. We also analyzed allelic loss of the p53 gene by FISH with a p53 locus-specific probe and mutation of the p53 gene by immunostaining since mutation and deletion of the p53 gene may cause hyperploidy. All specimens except one obtained from a case with young-onset metastatic melanoma exhibited no allelic losses or negative p53 staining, showing the p53 gene was intact. These results indicate that tetraploidy, not caused by p53 mutation or deletion, is commonly found in malignant melanoma of Japanese patients. It is also suggested that there is no positive relationship between tetraploidy and poorer prognosis, and mutation and allelic loss of the p53 gene might be markers of aggressive form of malignant melanoma.

Adult↗
PubMed1999

Na(+)influx via Na(+)/H(+)exchange activates protein kinase C isozymes delta and epsilon in cultured neonatal rat cardiac myocytes.

Protein kinase C (PKC) is one of the important signaling molecules in the development of the cardiac hypertrophic response, and activation of Na(+)/H(+)exchange is caused by PKC in myocytes. In this study we examined the contribution of Na(+)/H(+)exchange in cardiac hypertrophy induced by the activation of PKC and its mechanism using cultured neonatal rat cardiac myocytes. Phenylephrine (PE), endothelin-1 (ET-1) and phorbol 12-myristate 13-acetate (PMA) increased cytoplasmic pH in myocytes, and this effect was strongly inhibited by treatment with HOE694, an inhibitor of Na(+)/H(+)exchange. These substances increased the [(3)H]phenylalanine incorporation, total protein content and beta -myosin heavy chain protein content in myocytes. These hypertrophic responses were also attenuated by HOE694. To clarify the role of Na(+)influx through activation of Na(+)/H(+)exchange in cardiac hypertrophy, we next examined the hypertrophic responses to veratridine and ouabain, which increase the intracellular Na(+)content. Veratridine and ouabain increased the [(3)H]phenylalanine incorporation. Staurosporine, a PKC inhibitor, completely abolished veratridine-induced hypertrophic response, but did not affect increment of intracellular Na(+)concentration by veratridine. PMA caused increases of alpha -, delta -and epsilon -PKC in the particulate fraction, but PE, ET-1 and veratridine affected only those of delta - and epsilon -PKC. HOE694 significantly inhibited only increases of delta - and epsilon -PKC caused by PE, ET-1 or PMA, but not those by veratridine. These results demonstrate that Na(+)influx via activation of Na(+)/H(+)exchange reactivates PKC in myocytes. delta - and epsilon -PKC appear to be involved in the signal mechanism of the hypertrophic response induced by Na(+)influx through Na(+)/H(+)exchange in myocytes.

Animals↗
PubMed1999

Antibacterial action of bile acids against Helicobacter pylori and changes in its ultrastructural morphology: effect of unconjugated dihydroxy bile acid.

Although it has been shown that bile acids possess antibacterial activity against Helicobacter pylori, few reports on their activity have been published. We determined the minimum inhibitory concentration at 72 h of various unconjugated and conjugated bile acids against laboratory standard strains and clinical isolates of H. pylori, and studied morphologic changes of H. pylori under the scanning electron microscope during treatment with deoxycholic acid and ursodeoxycholic acid at the minimum inhibitory concentrations for 24 h. We found that only the unconjugated form of dihydroxy bile acid has antibacterial activity. The minimum inhibitory concentration of deoxycholic acid is 200-400 microg/ml, that of chenodeoxycholic acid is similar to that of deoxycholic acid, and that of ursodeoxycholic acid is 400-800 microg/ml. The morphology of H. pylori changed from its primary rodlike shape to a spherical shape with blebs on the cell surface, and was further degraded to an irregularly condensed mass, following an increase in bile acid. This morphologic change in H. pylori was different from the change to a spherical shape caused by amoxicillin. On the basis of these results, it seems that unconjugated dihydroxy bile acid might be a candidate drug for eradication of H. pylori, but further investigations of the clinical usefulness of bile acid for this purpose should be done.

Bile Acids and Salts↗
PubMed1999

TGF-beta2 is increased after fetal tracheal occlusion.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) accelerates lung growth in normal and hypoplastic fetal lung. The mechanism of accelerated lung growth remains unknown but may be a result of growth factor induction. Previous studies of growth factors induced by tracheal ligation have characterized mRNA rather than protein expression. Although the transforming growth factor-beta (TGF-beta) family participates in normal lung morphogenesis, its role in lung growth after TO is unclear. The authors hypothesize that TGF-beta expression is increased with TO and may contribute to the accelerated lung growth seen after TO. METHODS: Diaphragmatic hernia (DH) was created in 80-day-gestation sheep (n = 6; term, 145) by excising the left diaphragm. At 110 days, the trachea was occluded (n = 4) with a clip. DH controls (n = 2) were not occluded. Fetuses were killed at 139 days, and lung samples were snap frozen for tissue analysis. Non-DH control lungs were harvested from full-term animals (n = 2). TGF-beta mRNA was analyzed by semiquantitative reverse transcriptionase-polymerase chain reaction (RT-PCR). TGF-beta protein was assessed by Western blot analysis. RESULTS: TGF-beta1 mRNA and protein were not increased with tracheal ligation compared with either non-DH or DH controls. TGF-beta2, however, was markedly increased, at both the mRNA and protein level, in ligated lungs compared with nonligated controls. CONCLUSIONS: TGF-beta2 protein, but not TGF-beta1, is increased in the hypoplastic lungs of fetal sheep after tracheal occlusion. Increased TGF-beta2 expression appears to result from increased or prolonged expression of mRNA transcripts. This is the first study to document a change in growth factor protein levels after TO. Increased TGF-beta2 expression may contribute to accelerated lung growth and decreased surfactant production observed after tracheal occlusion.

Animals↗
PubMed1999

Open fetal surgery for life-threatening fetal malformations.

After more than two decades of experimental and clinical work, fetal surgery has become an accepted treatment modality for selected fetuses with life-threatening anomalies. Color Doppler ultrasound and ultrafast fetal magnetic resonance imaging have enhanced the accuracy of prenatal evaluation traditionally made by ultrasound alone. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunting may be effective in the setting of a single large predominant cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation with liver herniation and a sonographic right lung to head circumference ratio (LHR) of less than one may benefit from fetal tracheal occlusion. Fetal sacrococcygeal teratoma complicated with placentomegaly, hydrops, or progressive high output heart failure may benefit from in utero resection of the tumor. Although preterm labor still remains the Achilles heel of open fetal surgery, effective tocolysis may, in the future, expand the scope of fetal surgery.

Bronchopulmonary Sequestration↗
PubMed1999

New developments in fetal lung surgery.

After more than two decades of experimental and clinical work, fetal surgery has become a reasonable treatment modality for selected fetuses with life-threatening anomalies. We review the literature on anatomic anomalies of the fetal lung that are amenable to fetal surgical therapy. Ultrafast fetal magnetic resonance imaging has enhanced the accuracy of prenatal evaluation. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunting may be effective in the setting of a single large predominant cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation, who have liver herniation and a sonographic right lung-to-head circumference ratio of less than 1.0, may benefit from temporary fetal tracheal occlusion to enhance lung growth before birth.

Algorithms↗
PubMed1999

New developments in fetal lung surgery

After more than two decades of experimental and clinical work, fetal surgery has become a reasonable treatment modality for selected fetuses with life-threatening anomalies. We review the literature on anatomic anomalies of the fetal lung that are amenable to fetal surgical therapy. Ultrafast fetal magnetic resonance imaging has enhanced the accuracy of prenatal evaluation. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunting may be effective in the setting of a single large predominant cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation, who have liver herniation and a sonographic right lung-to-head circumference ratio of less than 1.0, may benefit from temporary fetal tracheal occlusion to enhance lung growth before birth.

Journal Article↗
PubMed1999

Influence of increased abdominal pressure on steady-state cardiac performance.

The effect of steady-state increases in abdominal pressure (Pab) on cardiac performance was studied in seven acutely instrumented swine with pneumoperitoneum (PP). The animal was placed on volume-preset ventilation, and PP was created by air insufflation. Cardiac output (CO), right atrial (Pra), left atrial (Pla), pericardial (Ppe), and abdominal inferior vena cava pressures (Pivc) were measured while Pab was increased from baseline to 7.5, 15, and 30 mmHg (PP7.5, PP15, and PP30, respectively). Cardiac function curves of the right and left ventricle (RV and LV, respectively) were compared between baseline and PP30. CO presented biphasic changes, with an inital slight increase at PP7.5 followed by a fall at PP30. A significant discrepancy was observed between Pra and Pivc at PP15 and PP30, consistent with development of a "vascular waterfall." Transmural Pla (Pla - Ppe) showed parallel changes with CO, whereas transmural Pra (Pra - Ppe) exhibited a sustained increase. The RV cardiac-function curve was more depressed than was that of the LV at PP30; this suggests an increased RV afterload produced by the elevated airway pressure. These results support the hypothesis that our previously proposed concept of abdominal vascular zone conditions (M. Takata, R. A. Wise, and J. L. Robotham. J. Appl. Physiol. 69: 1961-1972, 1990) is also applicable to steady-state hemodynamic analyses. The abdominal zones appear to play an important role in determining CO, with increases in Pab, by modulating systemic venous return and the LV preload. Simultaneous measurements of Pra and Pivc may provide useful information in the hemodynamic care of patients with elevated Pab.

Abdomen↗