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Biomedical subjects

T Tagawa

Publications and source records attributed to T Tagawa.

At least 37 records · Page 2Linked to original sources

Expression of phosphodiesterase 3 in rat submandibular gland cell lines.

A recent preliminary (unpublished) study showed that phosphodiesterase (PDE) 3A and 3B are expressed in rat submandibular glands. Here, PDE3 activity was detected in homogenates of rat submandibular gland acinar epithelial (SMIE) cells, but not rat A5 (epithelial duct) cells. Most of the PDE3 activity in SMIE cells was recovered in the particulate fraction. Only PDE3B mRNA was detected by reverse transcription-polymerase chain reaction in RNA from SMIE cells. The nucleotide sequence of the fragment was identical to the sequence of rat PDE3B. The PDE3 specific inhibitor, OPC3689 (10 and 50 microM), inhibited the growth of SMIE cells (19 and 63%), but not A5 cells. As the submandibular gland contains many types of cells, these results indicate that PDE3B may regulate a cAMP pool that is important in submandibular gland acinar epithelial cell function.

3',5'-Cyclic-AMP Phosphodiesterases↗

An immuno-light- and electron-microscopic study of the expression of bone morphogenetic protein-2 during the process of ectopic bone formation in the rat.

Immunolocalization of endogenous bone morphogenetic protein-2 (BMP-2) was investigated during the process of ectopic bone formation induced by recombinant human BMP-2 (rhBMP-2). Pellets consisting of 5 microg of rhBMP-2 and 6 mg of atelopeptide type I collagen (AC) were implanted into the calf muscles of 6-week-old rats. On days 7, 10, 14, 21 and 28 after implantation, tissue specimens were removed and examined immunohistochemically by light and electron microscopy after incubation with anti-BMP-2 monoclonal antibodies. Immunolocalization by light microscopy showed BMP-2 in chondrocytes at the pellet rim on days 7 and 10, in osteocyte-like cells in the chondroid matrix on day 14, and in osteocytes in the newly formed bone on days 21 and 28 after implantation. Ultrastructurally, on days 7 and 10 after implantation, immunolabelling for BMP-2 was aggregated in vesicle-like matrices released from mature chondrocytes in the chondroid matrix. On day 14, immunolabelling against BMP-2 had accumulated in vesicle-like matrices embedded in the calcified cartilage, in the cytoplasmic vacuoles of chondroclasts absorbing the matrix, and at the resorption surface of the calcified cartilage. On days 21 and 28, BMP-2 immunolabelling was seen in the osteoid layer and osteocyte lacunae. These results suggest that the chondrocytes and osteocytes induced by rhBMP-2 produce endogenous BMP-2. It seems that part of the endogenous BMP-2 that accumulated in the chondroid matrix was absorbed by chondroclasts and then participated in the osteoblastic differentiation of immature mesenchymal cells. This study indicates that, in addition to the implanted exogenous rhBMP-2, endogenous BMP-2 plays an important part in the maintenance of the bone-formation cascade during ectopic osteoinduction.

Animals↗

Characterization of four cell lines derived from a human malignant fibrous histiocytoma of the maxillary sinus.

We have established four cell lines from a human malignant fibrous histiocytoma. Each cell line had human aneuploid karyotype and DNA aneuploidy. Cells in all lines expressed CD13, CD68 and vimentin but lacked CD11, CD14, CD15, CD16, CD45, HLA class II and other mesenchymal and epithelial markers such as desmin, alpha-smooth muscle, myoglobin, S-100 protein, and cytokeratin. None of the cells expressed surface IgG or C3 receptor, nor did any of them phagocytose latex particles. The cells reacted with an antibody for prolyl-4-hydroxylase, but no collagen (types I, II, III, or IV) was detected in any of the cell lines. The homogenates of all cell lines had cyclic nucleotide phosphodiesterase 3 activity. Two cell lines produced granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1alpha, IL-6 and tumor necrosis factor alpha, another line produced G-CSF, IL-1alpha, IL-6 and platelet-derived growth factor (PDGF)-AB, and the remaining cell line produced only PDGF-AB. None of the cells produced transforming growth factor-alpha. The results indicated that the cell lines were immunophenotypically similar to primitive mesenchymal cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Phosphodiesterase 3 as a potential target for therapy of malignant tumors in the submandibular gland.

Phosphodiesterase (PDE) 3s have been characterized in human neoplastic submandibular gland intercalated duct HSG cells. There have been no reports on PDE3 in malignant salivary gland cells. PDE3 activity was detected in homogenates of HSG cells. About 75% of PDE3 activity in HSG cells was recovered in supernatant fractions and 25% in particulate fractions. PDE3A and 3B mRNAs were detected by reverse transcription-polymerase chain reaction in RNA from HSG cells. The nucleotide sequences of the fragments were identical to those of human PDE3A and 3B. The PDE3-specific inhibitor, cilostamide, inhibited the growth of HSG cells. Our results indicate that PDE3s may be important in the growth of HSG cells. PDE3 thus appears to be a potential new target for antiproliferative therapies.

3',5'-Cyclic-AMP Phosphodiesterases↗

Descending pathways mediating cardiovascular response from dorsomedial hypothalamic nucleus.

Physiological and anatomic methods were used to determine whether neurons in the rostral ventrolateral medulla (RVLM), nucleus tractus solitarius (NTS), or hypothalamic paraventricular nucleus (PVN) mediate the cardiovascular response evoked from the dorsomedial hypothalamic nucleus (DMH), which is believed to play a key role in mediating responses to stress. In urethane-anesthetized rats, activation of neurons in the DMH by microinjection of bicuculline resulted in a large increase in arterial pressure, heart rate, and renal sympathetic nerve activity. The pressor and sympathoexcitatory responses, but not the tachycardic response, were greatly reduced after bilateral muscimol injections into the RVLM even when baseline arterial pressure was maintained at a constant level. These responses were not reduced by muscimol injections into the PVN or NTS. Retrograde tracing experiments identified many neurons in the DMH that projected directly to the RVLM. The results indicate that the vasomotor and cardiac components of the response evoked from the DMH are mediated by pathways that are dependent and independent, respectively, of neurons in the RVLM.

Adrenergic beta-Antagonists↗

Endogenous angiotensin II in the NTS contributes to sympathetic activation in rats with aortocaval shunt.

Recent studies have suggested that the central nervous system is responsible for activation of sympathetic nerve activity (SNA) and the renin-angiotensin system in heart failure (HF). The aim of this study was to determine whether activation of the renin-angiotensin system within the nucleus of the solitary tract (NTS) plays a role in enhanced SNA in HF. High-output HF was induced by an aortocaval (A-V) shunt with some modifications in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of high-output HF. Urinary catecholamine excretion and maximal renal SNA (RSNA) were greater in the A-V shunted rats than in the control rats. Microinjection of an angiotensin II type 1-receptor antagonist, CV11974, into the NTS was performed. The arterial pressure and RSNA were reduced by CV11974 to a greater degree in the A-V shunted rats than in the control rats. The expression of angiotensin-converting enzyme mRNA in the medulla was greater in the A-V shunted rats than in the control rats. These results suggest that activation of the renin-angiotensin system within the NTS contributes to an enhanced SNA in this model.

Angiotensin II↗

Sotos syndrome with enamel hypoplasia: a case report.

A rare case of Sotos syndrome with enamel hypoplasia is described. Dental abnormalities include enamel hypoplasia, expansion of the pulp cavity, high arched palate, and absence of the bilateral pre-molar teeth of the mandible.

Abnormalities, Multiple↗

Video-assisted mediastinoscopic resection of a thymic cyst by sternum lifting.

We performed mediastinoscopic surgery on two patients with a thymic cyst using a new instrument by sternum-lifting with tape. The merits of this technique are that a resection of the thymus and cyst can be achieved without a midline sternotomy, and under bilateral ventilation, and in cases with pleural adhesion. This technique can be applicable to most benign thymic lesions including thymectomy for myasthenia gravis and to selected cases with a malignant thymic tumor.

Aged↗

Toxicokinetics of intravenous fluoride in rats with renal damage caused by high-dose fluoride exposure.

Fluoride (F) complexes are used in some fields of industry and medicine. F excretion mainly depends on kidney function. Urinary F concentration is measured to monitor the health of workers exposed to F. The toxicokinetics of F were studied by analyzing plasma concentration of F after intravenous injection of 2.86, 5.71 and 8.57 mg/kg into male Wistar rats. A dose-response relationship was recognized between these F doses and renal tissue injury. Blood samples were removed at 0, 10, 20, and 30 min, and after 1, 2, 3, 4, 5, and 6 h after injection. Plasma concentration-vs-time profiles were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Results indicated that a two-compartment model could describe the elimination of F from plasma. The beta rate constant, total plasma clearance (C1) and first-order rate constants (K21, Kel) decreased, and the half-time of the beta-phase (t1/2beta) was significantly prolonged with increasing dose. The kidney is the main target organ for F toxicity. Acute exposure to high doses of F damages renal tissue and causes renal dysfunction. The C1 of F is mainly dependent on renal F excretion. Since severe kidney damage markedly affected the toxicokinetics of F and decreased its elimination, other nephrotoxic indicators and measurement of plasma F concentration are necessary for monitoring high-dose F exposure.

Analysis of Variance↗

Successful treatments of lung injury and skin burn due to hydrofluoric acid exposure.

Recent growth in the electronics and chemical industries has brought about a progressive increase in the use of hydrofluoric acid (HF), along with the concomitant risk of acute poisoning among HF workers. We report severe cases of inhalation exposure and skin injury which were successfully treated by administering a 5% calcium gluconate solution with a nebulizer and applying 2.5% calcium gluconate jelly, respectively. Case 1: A 52-year old worker used HF for surface treatment after welding stainless steel, and was hospitalized with rapid onset of severe dyspnea. On admission to the critical care medical center he had widespread wheezing and crackles in his lungs. Chest radiograph showed a fine diffuse veiling over both lower pulmonary fields. Severe hypocalcemia with high concentrations of F in serum and urine were disclosed. He was immediately given 5% calcium gluconate solution by intermittent positive-pressure breathing (IPPB), utilizing a nebulizer. On the 21st hospital day, chest film and CT scan did not demonstrate any abnormality. He was discharged very much improved on the 22nd hospital day. Case 2: A 35-year old worker at an electronics factory was admitted to his local hospital with severe skin burn on his face and neck after exposure to 100% HF. Treatment began with immediate copious washing with water for 20 min. Calcium gluconate 2.5% gel (HF burn jelly) was applied to the area as a first-aid measure. Persistent high concentrations of serum and urinary F were disclosed for 2 weeks. After treatment with applications of HF burn jelly, he was confirmed as being completely recovered. The present cases and a review of published data suggest that an adequate method of emergency treatment for accidental HF poisoning is necessary.

Administration, Topical↗

Pharmacokinetics and effects after intravenous administration of high-dose boron to rat.

Boron (B) compounds have been widely used in the chemical industry, agriculture, and environmental science. The kinetics and toxicity of B were studied by analyzing several serum and urine parameters after a single intravenous injection of sodium tetraborate solution (B: 85.7 mg/kg) in Wistar male rats. Blood samples were removed at 0, 1, 2, 4, and 6 h after injection. The serum parameters studied included: B, Na, Ca, K, P, Mg, gamma-GTP, AST, ALT, BUN, Cr, CK, LDH and ALD. Plasma concentration-time profiles of B were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Urine samples were collected from the bladder following infusion. The urinary parameters that were studied included urine volume and excretion of B, Cr and NAG. Results indicated that a two-compartment model could describe the elimination of B from plasma after intravenous administration. Urine volume significantly increased. A diuretic effect of B was noted.

Analysis of Variance↗

Expression of phosphodiesterase 3 in rat submandibular gland.

The expression of phosphodiesterase (PDE) 3 isoforms was investigated in extracts of rat submandibular gland by reverse transcription-polymerase chain reaction (RT-PCR) and the PCR fragments were then sequenced. PDE3 activity was detected in gland homogenates; about 90% of the activity was in the supernatant fraction and about 10% in the particulate fraction. PDE3A and 3B mRNA was detected by RT-PCR in RNA from the gland. The nucleotide sequences of the fragments were identical to those of rat PDE3A and 3B. The results indicate that two PDE3 isoforms are present in rat submandibular gland and may regulate an important cAMP pool.

3',5'-Cyclic-AMP Phosphodiesterases↗

What drives the tonic activity of presympathetic neurons in the rostral ventrolateral medulla?

1. The present review discusses the mechanisms that maintain the tonic activity of presympathetic cardiovascular neurons in the rostral part of the ventrolateral medulla. 2. Experimental evidence is reviewed that indicates that these neurons receive both tonic excitatory and tonic inhibitory synaptic inputs. The former appear to be mediated, at least in part, by glutamate receptors and the latter appear to be mediated by GABA receptors. 3. There is also evidence that these neurons have the capacity to generate action potentials in the absence of synaptic inputs. However, at present, there is not clear evidence that such an intrinsic pacemaker-like mechanism contributes to the tonic activity of these neurons under normal resting conditions. 4. These neurons are also chemosensitive and this may contribute to their tonic activation under conditions of hypoxia or hypercapnia.

Action Potentials↗