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S Soma

Publications and source records attributed to S Soma.

At least 19 recordsLinked to original sources

Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions.

Pulmonary veins show greater sensitivity to endothelin (ET)-1-induced vasoconstriction than pulmonary arteries, and remodeling was observed in pulmonary veins under hypoxic conditions. We examined, using an immunohistochemical method, the expression of Big ET-1, ET-converting enzyme (ECE), and ET(A) and ET(B) receptors in rat pulmonary veins under normoxic and hypoxic conditions. In control rats, Big ET-1 and ECE were coexpressed in the intima and media of the pulmonary veins, with an even distribution along the axial pathway. ET(A) and ET(B) receptors were expressed in the pulmonary veins, with a predominant distribution in the proximal segments. The expression of Big ET-1 was more abundant in the pulmonary veins than in the pulmonary arteries. After exposure to hypoxia for 7 or 14 days, the expression of Big ET-1, ECE, and ET receptors increased in small pulmonary veins. Increases in the medial thickness, wall thickness, and immunoreactivity for alpha-smooth muscle actin were also observed in the small pulmonary veins under hypoxic conditions. The upregulation of ET-1 and ET receptors in the small pulmonary veins is associated with vascular remodeling, which may lead to the development of hypoxic pulmonary hypertension.

Actins↗

Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery.

Since pulmonary vasculature is complex in terms of regional difference in structure and function, it is important to understand the site of endothelin (ET) synthesis and the distribution of the ET system along the axial pathways of pulmonary artery. The expression of big ET-1, ET converting enzyme (ECE) and ET(A) receptors were examined in rat pulmonary arteries under normal and hypoxic conditions using an immunohistochemical method and Northern blot analysis. In normal conditions, big ET-1 was expressed in the intima and media of pulmonary arteries with a predominant distribution in the distal segments and a preferential localization in the media, while ETA receptors were dominantly expressed in the proximal segments. ECE was constitutively expressed in the intima and media. Following exposure to hypoxia, messenger ribonucleic acid (mRNA) expression of ET-1 and ET(A) receptors were up-regulated by two-fold and immunoreactivities for big ET-1, ECE, and ET(A) receptors significantly increased by two to five-fold in the distal segments. Smooth muscle cells are an important source of endothelin-1 in the pulmonary artery. The distribution of big endothelin-1 and endothelin A receptors in pulmonary arteries was discrepant in normal conditions while their expression concomitantly increased in the distal segments in hypoxic conditions. This heterogeneity may play an important role in the regulation of pulmonary vascular tone.

Animals↗

Local and chronic application of PTH accelerates tooth movement in rats.

We previously reported that whereas systemic continuous infusion of parathyroid hormone (PTH) accelerated orthodontic tooth movement, systemic but intermittent injection of PTH did not increase the rate of tooth movement. Analysis of these data suggested that continuous administration of PTH could be applicable for orthodontic therapy. In the present study, we investigated whether local and chronic application of PTH(1-34) would accelerate orthodontic tooth movement. To increase the residence time of PTH in the injected area, we used methylcellulose (MC) gel (2% W/V) for a slow-release formulation of PTH. MC gel containing PTH (PTH-MC) continuously released biologically active PTH into the acceptor medium for more than 72 hrs in vitro. When male rats received a local injection of PTH-MC into the subperiosteum in the mesio-palatal region of the maxillary first molar (M1) every other day, M1 movement, which was mesially drawn by an orthodontic coil spring attached to the maxillary incisors, was accelerated in a dose-dependent manner. PTH-MC injection at 1 microg/400 g body weight caused a 1.6-fold increase in the rate of tooth movement. The acceleration of tooth movement by PTH-MC injection was marked on days 6, 9, and 12. Local injection of PTH dissolved in saline without MC did not significantly accelerate tooth movement on day 6 or later. Histological examination revealed active osteoclastic bone resorption and a widened periodontal space on the compression side of the periodontal tissue in the PTH-MC-injected rats. These results suggest that local injection of PTH in a slow-release formulation is applicable to orthodontic therapy.

Animals↗

Somatic mutation of the PTEN/MMAC1 gene in breast cancers with microsatellite instability.

The extent to which microsatellite instability (MI) contributes to the etiology of breast cancer has not been established in any large-scale studies. We examined 528 samples of tumor DNA from patients with primary breast cancer for MI, using 14 polymorphic CA-repeat markers. The frequency of MI in these tumors was unexpectedly low (10/528, 1.9%). The ten MI+ tumors were analyzed for mutations in five potential target genes that contain simple repeat sequences (TGFBIIR, IGF2R, hMSH6, BAX and PTEN/MMAC1). A somatic insertion of an extra adenine in the (A)6 region at codon 321-323 (exon 8) of the PTEN/MMAC1 gene, leading to a frame-shift, was identified in one tumor. This observation represented the first documented instance of PTEN/MMAC1 alteration in a MI+ primary breast cancer.

Breast Neoplasms↗

Comparison between observation policy and fractionated stereotactic radiotherapy (SRT) as an initial management for vestibular schwannoma.

PURPOSE: To compare the use of an observation policy with that of stereotactic radiotherapy (SRT) for treatment of vestibular schwannoma. METHODS AND MATERIALS: The study group consisted of 27 patients who underwent observation as an initial treatment (observation group) and 50 who received SRT (SRT group). The mean follow-up period was 35 months and 31 months, respectively. Stereotactic radiotherapy consisted of small-field fractionated radiotherapy (36-44 Gy in 20-22 fractions over 6 weeks) with or without a subsequent 4-Gy single irradiation boost. RESULTS: Actuarial tumor control rate of the SRT group was significantly better than that of the observation group (p < 0.0001). The mean growth was 3.87 mm/year in the observation group and -0.75 mm/year in the SRT group (p < 0.0001). Eleven patients (41 %) in the observation group and 1 (2 %) in the SRT group received salvage therapy (p < 0.001). There was no difference in the actuarial Gardner and Robertson's class preservation curves for 5 years after the initial presentation. CONCLUSION: Stereotactic radiotherapy using a fractionated schedule provides a better tumor control rate and a similar rate of deterioration for hearing levels compared to an observation policy. Initial SRT may be a reasonable alternative to a wait-and-see policy.

Adolescent↗

Chronic hypoxia augments endothelin-B receptor-mediated vasodilation in isolated perfused rat lungs.

To investigate whether chronic hypoxia affects endothelin-B (ETB) receptor-mediated pulmonary vasodilation, we compared the vasodilator responses to IRL-1620, a selective ETB-receptor agonist, in isolated perfused lungs from normoxic and chronically hypoxic adult male rats. IRL-1620 caused a dose-dependent vasodilation that was greater in the hypertensive lungs than in the normotensive lungs. In normotensive lungs, a nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine (L-NNA; 300 microM), and an ATP-sensitive potassium (KATP)-channel inhibitor, glibenclamide (Glib; 10 microM), each reduced the vasodilator response to IRL-1620 (1 nM), but the combination of L-NNA and Glib inhibited it more effectively than either drug alone. In contrast, L-NNA alone, but not Glib alone, completely blocked IRL-1620-induced vasodilation in hypertensive lungs. The vasodilator response to a KATP-channel opener, NIP-121 (1 microM), but not the response to sodium nitroprusside (1 microM), was enhanced in hypertensive lungs. We also found increased expression of mRNA for the ETB receptor in lung tissue after hypoxic exposure. In addition, semiquantitative immunohistochemistry demonstrated higher expression levels of ETB receptors in the endothelium of distal segments of the pulmonary artery in hypoxic than in normoxic rats. These results suggest that ETB receptor-mediated pulmonary vasodilation is augmented after chronic hypoxic exposure and that release of NO may be the sole mechanism of this vasodilation in hypertensive lungs, whereas both release of NO and activation of KATP channels are involved in normotensive lungs. We speculate that the underlying mechanism responsible for this augmentation may partly be related to upregulation of ETB receptors in the endothelium of pulmonary resistance arteries in hypertensive lungs.

Adenosine Triphosphate↗

Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia-exposed rats.

To clarify the roles of two different endothelin (ET) receptors in the pulmonary vasculature, the localization and distribution of endothelin-A (ETA) and ETB receptors were investigated in rat lung under normal and hypoxic conditions by an immunohistochemical method. We also carried out in situ hybridization for ETB receptor. In normal rats, ETA receptor is localized in the media of the pulmonary artery and vein with predominant distribution in such proximal segments as elastic arteries and large muscular arteries. ETB receptor is expressed in the intima and media of pulmonary vessels. The distribution of ETB receptor in the media predominates in the distal segments of the pulmonary artery, whereas its distribution in the intima is greater in the proximal segments. Immunoreactivity for ETA receptor increases in the media of the distal segments of the pulmonary artery after exposure to hypobaric hypoxia. Semiquantitative evaluation showed immunoreactivity for ETA receptor in the pulmonary arteries accompanying the terminal bronchioles, respiratory bronchioles, and alveolar ducts to be increased by 2.5-, 5-, and 20-fold after 14 d exposure to hypoxia, respectively. The messenger RNA and immunoreactivity for ETB receptor increased significantly in the intima of the distal segments of pulmonary artery after 7 and 14 d exposure to hypoxia. These results suggest that the vasoconstrictive effects of ET-1 are exerted mainly through ETA receptor in the proximal segments of the pulmonary artery and vein, whereas its effects in the distal segments are mediated by ETA and ETB receptors in normal rats. ETA receptors that increase in resistance arteries after exposure to hypoxia appear to play an important role in the vascular remodeling associated with hypoxic pulmonary hypertension. Because ETB receptors in the endothelium mediate ET-1-induced vasodilatory effects, the increase in endothelial ETB receptors may counteract the development of hypoxic pulmonary hypertension.

Animals↗

Effects of continuous infusion of PTH on experimental tooth movement in rats.

Development of new methods for accelerating orthodontic tooth movement has been strongly desired for shortening of the treatment period. The rate of orthodontic tooth movement is dependent on the rate of bone resorption occurring in the compressed periodontium in the direction of orthodontic force applied to the tooth. In the present study, we examined the effects of continuous infusion of parathyroid hormone (PTH) on tooth movement. Male rats weighing 350-400 g were treated with subcutaneous of vehicle or hPTH(1-84) at 1-10 micrograms/100 g of body weight/day. When the upper right first molar (M1) was moved mesially for 72 h by the insertion of an elastic band between the first and second molars, M1 movement was accelerated by PTH infusion at 10 micrograms. PTH infusion caused a 2- to 3-fold increase in the number of osteoclasts in the compressed periodontium of M1, indicating that such treatment accelerated tooth movement by enhancing bone resorptive activity induced in the compressed periodontium. When M1 was moved mesially by an orthodontic coil spring ligated between upper incisors and M1 for 12 days, PTH(1-84) infusion at 10 micrograms caused a 2-fold increase in the rate of M1 movement. PTH(1-34) infusion at 4 micrograms had an effect comparable to that of PTH(1-84). However, intermittent injection of PTH(1-34) did not accelerate M1 movement. PTH infusion for 13 days did not affect either bone mineral measurements or the serum calcium level. These findings suggest that continuous administration of PTH is applicable to accelerate orthodontic tooth movement.

Animals↗

Prevention of pulmonary embolization during excision of an infected venous thrombus.

We describe the case of a 64-year-old woman with an iatrogenic pseudoaneurysm, arteriovenous fistula, and thrombotic occlusion of the right femoral vein with Staphylococcus aureus infection resistant to methicillin as complications of femoral catheterization for hemodialysis access. A temporary caval filter was introduced just prior to operation and kept in place for 4 days. An infected thrombus was captured and removed with a filter-catheter device. The placement of a temporary caval filter should be considered for prevention of pulmonary embolism in patients with infected venous thrombosis which requires surgical thrombectomy.

Catheterization, Peripheral↗

Enhancement by conditioned medium of stretched calvarial bone cells of the osteoclast-like cell formation induced by parathyroid hormone in mouse bone marrow cultures.

To investigate whether mechanical deformation of osteoblasts exerts an influence upon parathyroid hormone (PTH)-induced bone resorption, the effect of medium conditioned by a statistically stretched, osteoblast-enriched, bone cell population on PTH-induced osteoclast-like cell formation in mouse bone marrow cultures was examined. The conditioned medium of stretched cultures stimulated bone marrow cells to differentiate into tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells in the presence of 10(-8) M PTH(1-34). The stimulatory effect of the conditioned medium was significant when the bone cells were stretched at 2 mm deflection in the 90% subconfluent state. Conditioned medium from cultures in the 50% subconfluent state failed to enhance osteoclast-like cell formation. PTH-induced, TRAP-positive multinuclear cells were decreased in number by the addition of stretch-conditioned medium in the postconfluent state. When 10(-6) M indomethacin was added to bone cell cultures during stretching, the resulting conditioned medium suppressed PTH-induced, TRAP-positive multinuclear cell formation. However, even if 10(-8) M prostaglandin E2 was added to the stretched bone cell cultures along with the indomethacin, the resulting conditioned medium did not reverse the suppression of the PTH-induced, osteoclast-like cell formation. These findings suggest that bone resorption in response to continuous mechanical deformation is regulated by cells of the osteoblast lineage such as preosteoblasts, osteoblasts, bone lining cells and osteocytes in vivo, and that prostaglandins, but not prostaglandins E2, are involved in the stretch-enhanced, osteoclast-like cell formation.

Acid Phosphatase↗

Altered vasoreactivity in lungs isolated from rats exposed to nitric oxide gas.

A rebound phenomenon (severe arterial desaturation and pulmonary vasoconstriction) has been observed in some patients with pulmonary hypertension after sudden discontinuation of nitric oxide (NO) inhalation therapy. The mechanism responsible for this phenomenon is unknown. It has recently been reported that NO synthase (NOS) can be inhibited by NO as a negative feedback mechanism. We therefore hypothesized that this rebound phenomenon might be attributable to reduced endogenous NO production due to inhibition of pulmonary endothelial NOS (eNOS) activity by inhaled NO. To test this hypothesis, vasoreactivities were compared in isolated perfused lungs from rats exposed to 40 ppm NO gas and room air for 2 days. The pressor responses to angiotensin II and hypoxia of lungs from rats exposed to NO were markedly potentiated and their depressor response to bradykinin was considerably impaired, whereas that to sodium nitroprusside was preserved, compared with the responses of those exposed to room air. This altered pulmonary vasoreactivity was also induced by lower concentrations of inhaled NO (as low as 1 ppm) and was completely reversed by discontinuation of NO inhalation for several (< 8) hours. The expression of eNOS mRNA by lungs isolated from rats exposed to 40 ppm NO and room air for 2 days did not differ. These results suggest that pulmonary endogenous NO production is reversibly reduced after relatively short-term NO inhalation, which probably inhibits eNOS activity directly. We speculate that reduced production of pulmonary endogenous NO by exogenous (inhaled) NO could be the mechanism responsible for this rebound phenomenon.

Administration, Inhalation↗

Effects of salvia miltiorrhiza bunge (SMB) on MC3T3-E1 cells.

In previous research, we found that the Salvia Miltiorrhiza Bunge (SMB), a traditional Chinese medicinal herb, accelerates orthodontic tooth movement. In the present study, to characterize the actions of SMB on bone remodeling, we investigated the effect of SMB on DNA synthesis and alkaline phosphatase activity of murine osteoblast like cell-clone, MC3T3-E1 cells in vitro. Treatment of the cells with SMB for 72 hours caused significant increase in ALPase activity. It was found that SMB increased ALPase activity in a dose-dependent manner, and up to maximum at the concentration of 5.0 mg/ml. At that concentration, ALPase activity was about 135% greater than that of control. SMB at 5.0 mg/ml significantly stimulated ALPase activity of the cells in multilayer on day 8 or calcification stage on day 16, but inhibited it in the sparse stage on day 2 or subconfluency stage on day 4. SMB had no effect on DNA synthesis in any stage of culture. ALPase activity significantly increased at 48 hours and was up to 300% greater than that of control activity at 96 hours. These findings suggest that SMB directly stimulates ALPase activity of MC3T3-E1 cells in multilayer stage or calcification stage without any effect on proliferation. Locally administrated SMB may affect the differentiation of osteoblasts in vivo.

3T3 Cells↗

Differential effects of 1 alpha, 25-dihydroxycholecalciferol and 24R,25-dihydroxycholecalciferol on the proliferation and the differentiated phenotype of rabbit craniofacial chondrocytes in primary culture.

The response of chondrocytes from the craniofacial complex to vitamin D3 has been investigated in vitro. Chondrocytes were isolated from nasal septal cartilage (NSC), sphenooccipital synchondrosis (SOS) and mandibular condylar cartilage (MCC) of New Zealand rabbits weighing from 250-350 g. Treatment of NSC-chondrocytes with 1,25-(OH)2D3 or 24,25-(OH)2D3 for 6 days from days 4 to 10 in medium containing charcoal-treated FBS increased DNA synthesis dose-dependently at the concentrations of 10(-9) M to 10(-8) M, or 10(-11) M to 10(-9) M, respectively. 1,25-(OH)2D3 inhibited GAG synthesis dose dependently at the concentrations of 10(-11) M to 10(-8) M. 24,25-(OH)2D3 had no effect on GAG synthesis in NSC-chondrocytes. 1,25-(OH)2D3 increased DNA synthesis in SOS-chondrocytes at a concentration of 10(-10) M and inhibited GAG synthesis. 24,25-(OH)2D3 had no significant effect on DNA and GAG syntheses of SOS-chondrocytes. 1,25-(OH)2D3 slightly increased GAG synthesis at a concentration of 10(-10) M in MCC-chondrocytes but had no effect on DNA synthesis. 24,25-(OH)2D3 had no effect on DNA and GAG synthesis in MCC-chondrocytes at concentrations of 10(-11) M to 10(-9) M. These finding suggest that vitamin D3 metabolites, 1,25-(OH)2D3 and 24,25-(OH)2D3 play an important role in the growth of craniofacial cartilage by differently stimulating proliferation and expression of the differentiated phenotype of chondrocytes from NSC, SOS and MCC.

24,25-Dihydroxyvitamin D 3↗

Stimulation of alkaline phosphatase activity by ascorbic acid and suppression by 1,25-dihydroxycholecalciferol in rabbit craniofacial chondrocytes in culture.

To clarify the role of vitamins D and C in chondrocyte hypertrophy of craniofacial cartilage, we have studied cultured chondrocytes from rabbit mandibular condylar cartilage (MCC), sphenooccipital synchondrosis (SOS) and nasal septal cartilage (NSC) under conditions in which these cells mature into hypertrophic chondrocytes. In cultures of MCC- and SOS-chondrocytes, alkaline phosphatase (ALPase) activity started to increase on day 9 at confluence and the cessation of cell division, and reached a maximum on day 18. The degree of the increase of ALPase activity on day 18 was higher in MCC-chondrocytes than in SOS-chondrocytes. ALPase activity was very low level in NSC- and CGC-chondrocytes. Ascorbic acid induced a marked increase in ALPase activity in MCC-, SOS-, NSC- and CGC-chondrocytes. The ALPase activities in MCC- and SOS-chondrocytes with 50 micrograms/ml ascorbic acid were 2.5-times those in its absence. Those in NSC- and CGC-chondrocytes were 10 times and 20 times, respectively. When chondrocytes were cultured with 10% charcoal-treated serum, ALPase activity decreased less than that in cultures with 10% normal serum in MCC-, SOS-, NSC- and CGC-chondrocytes. Treatment of 1,25-(OH)2D3 for 9 days from days 4 to 13 in MCC-chondrocytes and for 14 days from days 4 to 18 in SOS-, NSC- and CGC-chondrocytes inhibited ALPase activity dose-dependently at the concentrations of 10(-12) M to 10(-8) M in MCC- chondrocytes, 10(-10) M to 10(-8) M in SOS- and CGC-chondrocytes, 10(-11) M to 10(-9) M in NSC-chondrocytes. These findings suggest that 1,25-(OH)2D3 and ascorbic acid may be involved in the control of cartilage growth and terminal differentiation.

Alkaline Phosphatase↗

Comparison of the effects of hydrostatic compressive force on glycosaminoglycan synthesis and proliferation in rabbit chondrocytes from mandibular condylar cartilage, nasal septum, and spheno-occipital synchondrosis in vitro.

We have developed a simple in vitro model whereby precise quantities of compressive force can be applied to cultured chondrocytes from craniofacial cartilage: mandibular condylar cartilage (MCC), nasal septal cartilage (NSC), and spheno-occipital synchondrosis (SOS). Using this model, we found that hydrostatic compressive force stimulated glycosaminoglycan (GAG) synthesis, a cartilage phenotype, in MCC and SOS chondrocytes and DNA synthesis in MCC, NSC, and SOS chondrocytes. These stimulations were dependent on force magnitude and duration, reaching maximal GAG synthesis at 27 hours and maximal DNA synthesis at 20 hours after application of force. The maximal increase of GAG synthesis induced by compressive force was about 60% at 100 gm/cm2 for 5 minutes in nonstimulated MCC chondrocytes and 40% at 50 gm/cm2 for 1 minute in nonstimulated SOS chondrocytes. The maximal increase in DNA synthesis, produced by a compressive force of 50 gm/cm2 for 1 minute, was 50% in NSC chondrocytes, 50% in SOS chondrocytes, and 30% in MCC chondrocytes. There was no stimulation of GAG synthesis in NSC chondrocytes. These observations suggest that extrinsic force regulates craniofacial growth by controlling the differentiation and proliferation of chondrocytes in the craniofacial skeleton and that the difference in their responses to compressive force may reflect differences in the characteristics of these cells and their physiologic function in vivo.

Animals↗

[Effects of hydrostatic pressure on proliferation and expression of the differentiated phenotype of cultured chondrocytes derived from rabbit craniofacial complex].

To investigate the effects of mechanical forces on the growth of cartilages of the craniofacial complex, chondrocytes isolated from nasal septal cartilage (NSC), spheno-occipital synchondrosis (SOS), and mandibular condylar cartilage (MCC) were cultured and exposed to hydrostatic pressure in vitro. Following results were obtained. 1. By application of the pressure, DNA synthesis increased in NSC and SOS (150% of control by 50 g/cm2, 1 min), but not so much in MCC in the medium containing 10% fetal calf serum (FCS). On the other hand, GAG synthesis increased in SOS (140% of control by 50 g/cm2, 2 min.) and MCC (160% of control by 100 g/cm2, 5 min), but decreased slightly in NSC in the same condition. The stimulations in DNA and GAG syntheses reached maxima 20-22 hr and 24-27 hr respectively after the application of the pressure. These stimulatory effects of the hydrostatic pressure on DNA and GAG syntheses could be found when cultured chondrocytes were in a multilayer stage. 2. It has been reported that addition of FCS at a concentration of 10% increases DNA synthesis in these chondrocytes preincubated in medium containing 0.3% FCS. The application of the pressure 2 min before the addition of 10% FCS potentiated the increase by FCS of DNA synthesis in NSC (130% of control), but not so much that in SOS and little that in MCC. 3. When the pressure was applied on these cells 2 min before addition of parathyroid hormone (PTH; 10(-7) M), this mechanical stimulation potentiated the increase by PTH of GAG synthesis in MCC (130% of control), but not so much that in SOS, and little that in NSC. Moreover, the intracellular cAMP level which was increased just after the addition of PTH also became higher by the application of the pressure. 4. These potentiation by the hydrostatic pressure in the cases of the addition of FCS and PTH diminished when intervals between application of pressure and addition of these factors were more than 10 min. These findings suggested that mechanical forces have influences on the growth of cartilages in craniofacial complex and that these effects are mediated by factors contained in serum.

Animals↗