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Biomedical subjects

T Tagawa

Publications and source records attributed to T Tagawa.

At least 55 records · Page 3Linked to original sources

Ultrastructural study of direct bone formation induced by BMPs-collagen complex implanted into an ectopic site.

OBJECTIVE: Some authors have reported that direct bone formation is ectopically induced by bone morphogenetic proteins (BMPs) independently of cartilage formation when type I collagen is used as a carrier. This study ultrastructurally investigated the mechanism of direct bone formation by BMPs-collagen complex. MATERIALS AND METHODS: Partially purified BMPs were combined with atelopeptide type I collagen (AC) and were implanted into the calf muscles of rats (n = 20). Tissue specimens were removed on days 7, 10, 14, and 21 after implantation. RESULTS: Ultrastructurally, several regions near the pellet rim showed evidence of early calcification on day 10. In the uncalcified regions, mitochondrial calcification was seen in mesenchymal cells near AC fibers. The initially calcified regions contained numerous calcified granules deposited in the AC fibers. Some of these granules adhered to the cell membrane of osteogenic cells. In the highly calcified regions, some osteogenic cells secreted uncalcified matrix and deposited needle-like crystals and calcified collagen microfibrils on the AC fibers. CONCLUSION: This study suggests that the mesenchymal cells invading BMPs-AC complex closely contacted the AC fibers, differentiated into osteogenic cells, and deposited calcified matrix on the AC fibers, resulting in direct osteoinduction without cartilage formation.

Animals↗

The physiological role of AT1 receptors in the ventrolateral medulla.

Neurons in the rostral and caudal parts of the ventrolateral medulla (VLM) play a pivotal role in the regulation of sympathetic vasomotor activity and blood pressure. Studies in several species, including humans, have shown that these regions contain a high density of AT1 receptors specifically associated with neurons that regulate the sympathetic vasomotor outflow, or the secretion of vasopressin from the hypothalamus. It is well established that specific activation of AT1 receptors by application of exogenous angiotensin II in the rostral and caudal VLM excites sympathoexcitatory and sympathoinhibitory neurons, respectively, but the physiological role of these receptors in the normal synaptic regulation of VLM neurons is not known. In this paper we review studies which have defined the effects of specific activation or blockade of these receptors on cardiovascular function, and discuss what these findings tell us with regard to the physiological role of AT1 receptors in the VLM in the tonic and phasic regulation of sympathetic vasomotor activity and blood pressure.

Angiotensin I↗

Identification of oxidative stress-regulated genes in rat aortic smooth muscle cells by suppression subtractive hybridization.

A suppression subtractive hybridization technique was used to identify reactive oxygen species (ROS)-regulated genes in rat vascular smooth muscle cells. Three genes out of 89 clones, identified as fibronectin, p105 coactivator and ECA39, showed increased expression after treatment with H(2)O(2). The mRNA expressions of these three genes were induced in a time- and dose-dependent manner, independent of protein kinase C activation. Immunohistochemical staining showed that the p105 coactivator expression was markedly induced in the neointima of balloon-injured rat carotid arteries. These results suggest that ROS may play an important role in the development of atherosclerosis by regulating the gene expressions we identified in this study.

Animals↗

Sympathoinhibition after angiotensin receptor blockade in the rostral ventrolateral medulla is independent of glutamate and gamma-aminobutyric acid receptors.

Bilateral blockade of angiotensin (Ang) receptors in the rostral ventrolateral medulla (RVLM) causes a profound fall in arterial pressure. In this study, we tested whether this effect is due to an interaction between Ang receptors and either glutamatergic or gamma-aminobutyric acidergic (GABAergic) synaptic inputs to RVLM sympathoexcitatory neurons. In urethane-anaesthetised rats, bilateral microinjections of the Ang receptor antagonists [Sar1,Thr8]Ang II or [Sar1,Ile8]Ang II into the RVLM pressor region caused large decreases in arterial pressure, heart rate and renal sympathetic nerve activity (RSNA). These responses were not significantly altered following bilateral microinjections into the RVLM of the glutamate receptor antagonist kynurenic acid (4.5 nmol). Furthermore, bilateral injections of kynurenic acid plus the GABA(A) receptor antagonist bicuculline (200 pmol) into the RVLM increased the baseline arterial pressure and RSNA, but did not alter the percentage decreases in these variables evoked by bilateral microinjections of [Sar1,Ile8]Ang II. However, the level of arterial pressure and RSNA following bilateral injections of kynurenic acid, bicuculline and [Sar1,Ile8]Ang II were similar to the levels before injection of any of these compounds. The effectiveness of the microinjections of kynurenic acid and bicuculline into the RVLM was demonstrated by the observation that they virtually abolished the somato-sympathoexcitatory and baroreceptor-sympathoinhibitory reflexes, which are mediated by glutamatergic and GABAergic synapses, respectively, in the RVLM. These results indicate that (1) blockade of Ang receptors greatly reduces the firing rate of RVLM sympathoexcitatory neurons via a mechanism that is independent of glutamatergic or GABAergic neurotransmission, and (2) in the absence of inputs mediated by ionotropic glutamate, GABA(A) and Ang receptors, there are other mechanisms which generate a level of tonic activity in RVLM sympathoexcitatory neurons sufficient to maintain a normal level of sympathetic vasomotor activity.

Angiotensin Receptor Antagonists↗

Effects of activation and blockade of P2x receptors in the ventrolateral medulla on arterial pressure and sympathetic activity.

Sympathoexcitatory and sympathoinhibitory neurons in the rostral and caudal ventrolateral medulla (VLM) play a crucial role in the tonic and reflex control of sympathetic vasomotor activity. Recent evidence also indicates that the VLM contains a high density of P2x purinoceptors. In this study, we investigated the cardiovascular effects of selective activation of P2x purinoceptors in the rostral and caudal VLM, and the effects of blockade of P2x purinoceptors in the rostral VLM on the tonic and reflex control of sympathetic vasomotor activity. In anesthetized barodenervated rabbits, microinjection into the rostral and caudal VLM of the P2x purinoceptor agonist, alpha,beta-methylene adenosine triphosphate (alpha,beta-meATP) (4-400 pmol) elicited dose-dependent increases and decreases, respectively, in arterial pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA). The response evoked by alpha,beta-meATP in the rostral VLM was blocked by prior injection into the same site of the P2 purinoceptor antagonist suramin but not by the ionotropic glutamate receptor antagonist kynurenic acid. Bilateral injections of suramin into the rostral VLM sympathoexcitatory region had no significant effect on resting cardiovascular variables, nor on the reflex increase in RSNA evoked by sciatic nerve stimulation (which is known to be mediated by the rostral VLM sympathoexcitatory neurons). The results demonstrate that: (1) activation of P2x purinoceptors in the VLM are capable of producing marked excitation of both sympathoexcitatory and sympathoinhibitory neurons; (2) these effects are not due to modulation of glutamatergic inputs to these neurons; and (3) P2x purinoceptors do not play a significant role in maintaining the tonic activity of rostral VLM sympathoexcitatory neurons or in modulating their responses to excitatory synaptic inputs evoked by stimulation of sciatic nerve afferents.

Adenosine Triphosphate↗

Usefulness of the assessment of urinary enzyme leakage in monitoring acute fluoride nephrotoxicity.

A single oral dose of sodium fluoride (NaF) in aqueous solution was given to male Wistar rats. Twenty-four-hour urine samples were collected and examined to evaluate fluoride-induced acute renal damage. The following parameters were measured in 24-h urine: urine volume and urinary excretion of fluoride, N-acetyl-beta-d-glucosaminidase (NAG), alpha-glutathione-S-transferase (alpha-GST), and creatinine (CR). Fluoride exposure produced specific, dose-dependent changes of these parameters. Significant increases of fluoride and fluoride-induced polyuria were observed. NAG as specific marker of proximal convoluted tubule (PCT) function showed a significant increase when the lowest dose of fluoride was administered. At this minimal dose, alpha-GST, a specific marker for the S3 segment, did not show a significant increase but presented the strongest relationship (r = 0. 83) to fluoride dose. No significant changes were measured for CR excretion, which showed a low correlation coefficient (r = 0.36) to administered fluoride. The specific differences in the increase pattern of these parameters show that the PCT is more susceptible to damage by low-dose fluoride than the S3 segment or the glomerulus. We concluded that both NAG and alpha-GST are useful for the diagnosis of fluoride-induced acute nephrotoxicity. Proper evaluation of these urinary indices may be of help to establish the site and extent of kidney injury in acute fluoride toxicity.

Acetylglucosaminidase↗

Nonconvulsive status epilepticus in a child with congenital bilateral perisylvian syndrome.

A 9-year-old male with congenital bilateral perisylvian syndrome is described. He had pseudobulbar palsy, mental retardation, and intractable epilepsy. Computed tomography and magnetic resonance images of the brain demonstrated bilateral perisylvian malformations and a diffuse pachygyric appearance. At 8 years of age, he had episodes of excessive drooling, fluctuating impairment of consciousness, unsteady sitting, and frequent head drop that lasted several days. The electroencephalogram demonstrated continuous diffuse slow spike and waves. These findings suggested atypical absence status epilepticus. Intravenous administration of diazepam resulted in transient improvement of clinical and electroencephalographic findings. Status epilepticus recurred within several minutes after diazepam administration. Although no patient has been reported to have a history of status epilepticus among those affected by this syndrome, it seems that atypical absence status can occur more frequently than expected, as seen in Lennox-Gastaut syndrome. After recognition and confirmation of nonconvulsive status epilepticus, immediate treatment must be attempted.

Anticonvulsants↗

Long-term treatment with eicosapentaenoic acid augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilatation in patients with coronary artery disease.

Long-term treatment with eicosapentaenoic acid (EPA) is known to improve impaired endothelium-dependent relaxations of atherosclerotic blood vessels in animals and humans. However, it remains to be determined which mechanisms are involved in this beneficial effect of EPA. In this study, we investigated our hypothesis that EPA improves both nitric oxide (NO)-mediated and non-NO-mediated endothelium-dependent vasodilatation in patients with coronary artery disease. The study included eight patients with documented coronary artery disease. The forearm vascular responses to the endothelium-dependent vasodilator acetylcholine and substance P were examined before and after intraarterial infusion of NG-monomethyl-L-arginine (L-NMMA). Same measurements were repeated after the treatment with EPA (1,800 mg/day) for 6 weeks. The long-term treatment with EPA augmented forearm blood-flow response to both acetylcholine and substance P. Furthermore, acute administration of L-NMMA significantly inhibited the EPA-induced augmented response to acetylcholine but not that to substance P. The forearm vascular response to sodium nitroprusside was unchanged by the EPA treatment. These results indicate that long-term treatment with EPA augments both NO-dependent and non-NO-dependent endothelium-dependent forearm vasodilatation in patients with coronary artery disease. Thus the beneficial effects of EPA appear to extend to non-NO-dependent mechanism(s).

Acetylcholine↗

AT(1) receptors mediate excitatory inputs to rostral ventrolateral medulla pressor neurons from hypothalamus.

Angiotensin II type 1 (AT(1)) receptors are located on pressor neurons in the rostral ventrolateral medulla, and their activation results in an increase in arterial pressure. However, the normal role of these AT(1) receptors in cardiovascular regulation is unknown. In this study, we tested the hypothesis that these receptors mediate synaptic excitation of rostral ventrolateral medullary pressor neurons in response to activation of the hypothalamic paraventricular nucleus. In anesthetized rats, microinjections of the gamma-aminobutyric acid receptor antagonist bicuculline were made into the paraventricular nucleus; this injection causes activation of the nucleus as a consequence of disinhibition. The pressor and sympathoexcitatory responses evoked by paraventricular nucleus activation were significantly reduced (by approximately 40% to 50%) after microinjection of the specific AT(1) receptor antagonists losartan or L-158,809 into the rostral ventrolateral medulla on the ipsilateral, but not contralateral, side. These responses were reduced to a similar degree after microinjections of the neuroinhibitory compound muscimol into the ipsilateral, but not contralateral, rostral ventrolateral medulla. However, bilateral microinjections of the glutamate receptor antagonist kynurenic acid into the rostral ventrolateral medulla had no effect on the responses evoked from the paraventricular nucleus. Conversely, bilateral microinjections of kynurenic acid into the rostral ventrolateral medulla virtually abolished the somatosympathoexcitatory reflex, whereas bilateral microinjections of losartan or L-158,809 had no effect on this reflex. The results indicate that excitatory synaptic inputs to pressor neurons in the rostral ventrolateral medulla arising from activation of the paraventricular nucleus are mediated predominantly by AT(1) receptors.

Animals↗

[Surgical treatment of lung cancer with combined resection of the aorta or superior vena cava].

Until December 1997, 699 cases of lung cancer were resected in our institute. Four cases of invasion into the aorta and seven cases of invasion into the superior vena cava were also operated and each vessels were reconstructed. Two pneumonectomies and nine lobectomies were performed. Four cases of squamous cell carcinoma, three of adenocarcinoma, three of large cell carcinoma and one of adenosquamous carcinoma were found on pathological examination. Four cases of N0, four of N2 and two of N3 were also detected on pathological lymph node evaluation. One case was stage IV with metastasis of ipsilateral axillar lymph nodes and the others were stage IIIB. With respect to pathological curability, absolutely noncurative operation was performed in all cases involving the aorta and absolutely noncurative in four and relatively curative three in cases involving the superior vena cava. During resection and reconstruction of the aorta, three cases received temporary blood supplying bypass and one case was underwent temporary clamping. Two cases developed bilateral lower extremity paralysis. During resection and reconstruction of the superior vena cava, one case underwent intraluminal temporary blood supplying bypass, two received sideclamping and four were reconstructed with double artificial grafts for bilateral innominate veins. Two cases who underwent resection of the aorta died within one year and one is alive after nine months of operation. Five cases who underwent resection of the superior vena cava died due to cancer. One case of N0 and relatively curative is alive in free of recurrence after seven years and six months of operation and another case who had brain metastasis resected is alive after two years and two months of pulmonary operation. Careful selection should be made for resection of the aorta because the prognosis is usually poor. In the resection of the superior vena cava, good prognosis is expected in some cases (N0, relatively curative) and quality of life is expected to improve with the prevention of the superior vena cava syndrome. Aggressive resection should be considered for lung cancer invasion into the superior vena cava.

Adult↗

Measuring respiration of cultured cell with oxygen electrode as a metabolic indicator for drug screening.

New trend in methods for assessing pharmacological action to bacteria and cell is to measure their metabolic activities induced, while the conventional methods used population growth. We focused on respiration volume as an indicator of cell metabolism, and developed inexpensive disposable oxygen electrode sensor and multi-channel dissolved oxygen meters (DOX-10 and DOX-96KB). Using these instruments, cytotoxicity was measured for 48 hrs and the method showed superior features to conventional methods in its handiness of one step assay, and excellent adaptability to automated systems. Total usability of this oxygen electrode method is being evaluated in bacterial drug susceptibility test, anticancer drug susceptibility test, and alternatives to animal experiment.

Antineoplastic Agents↗

[Repair of intrathoracic visceral damage using video-assisted thoracoscopic surgery for blunt chest trauma and rib fixation at the site of mini-thoracotomy].

We treated three patients with intrathoracic visceral damage caused by severely dislocated fractured ribs resulting from blunt trauma by using video-assisted thoracoscopic surgery (VATS) and rib fixation through a mini-thoracotomy. Under general anesthesia and unilateral respiration, the thoracic cavity was inspected with a thoracic video scope through the port inserted through the thoracic drainage opening which was made upon arrival at hospital. As the visceral damage seemed restorable under VATS, a mini-thoracotomy was positioned just above the rib fracture. Two thoracic ports were inserted through the site of rib fracture or through the intercostal space and then VATS was performed using three ports. After the restoration of intrathoracic visceral damage, the fractured rib was fixated using a bioabsorbable poly-L-lactide rib fixation pin or a marlex mesh. Lung injuries were sutured and ligated under VATS in two of our cases and a spur of the fractured rib was shaved in one case. Only severely dislocated ribs were fixated through the mini-thoracotomy in all cases. Air leakage stopped just after this procedure and there were no complications. The rib fixation and bone regeneration were excellent after this procedure. The advantages of this method are the visceral restoration under VATS through a mini-thoracotomy and the ability to perform rib fixation without injuries to the intercostal muscle, artery, vein or nerve. This operative procedure is recommended for intrathoracic visceral damage caused by severely dislocated rib fracture.

Adult↗

Experience with thoracoscopic surgery for primary bronchial stump fistula after pneumonectomy.

UNLABELLED: After a left pneumonectomy, thoracoscopic closure with fibrin glue was performed for a fistula on the bronchial stump and the postoperative state progressed favorably thereafter. In this paper, we report on this successful case. CASE: A 61 year-old male, who underwent a left pneumonectomy on January 17, 1996 for pulmonary carcinoma (T 3 N 1M 0 stage III A). The bronchial stump was covered with anterior serratus muscle flap. On April 1 (the 76th postoperative day), after two courses of Carboplatin and Vindesine treatment, the patient suddenly developed a fistula on the bronchial stump. Bronchofiberscopic closure with fibrin glue was attempted, but failed to close the fistula. Thoracoscopic surgery was then performed on May 15 (the 45th day after the onset of the fistula). After the intrathoracic opening of the fistula was found with a contrast medium, fibrin glue was injected to fill up to the bronchial stump, and communication with the thoracic cavity was blocked. Owing to coverage with a myocutaneous flap, the patient's general postoperative state remained relatively stable. Thoracoscopic surgery is useful as a treatment for some cases of bronchial stump fistula after pneumonectomy.

Bronchial Fistula↗

Clear cell odontogenic carcinoma: A case report and literature review of odontogenic tumors with clear cells.

Clear cell odontogenic carcinomas are uncommon epithelial neoplasms that have metastatic potential. We describe such a tumor in a 67-year-old Japanese man with a well-defined, unilocular radiolucent area in the mandible. The tumor was enucleated and has not recurred or metastasized 3 years after surgery. Histologically, the tumor was composed of a predominant clear cell area and a plexiform ameloblastic pattern. The latter was located at the periphery of the tumor. In the English literature, 19 cases of clear cell odontogenic carcinoma, clear cell odontogenic tumor, and clear cell ameloblastoma have been reported. The mean age of the patients at diagnosis was 56.4 years and the gender ratio (M:F) was 8:11. Fourteen tumors were located in the mandible and 5 in the maxilla. Recurrence or metastasis occurred in approximately one half of these patients, and five of the patients died of their disease. More than one half recurrent or metastatic tumors contained palisading clear cells.

Aged↗

Endothelin-1 increases the neuronal activity and augments the responses to glutamate in the NTS.

The aims of this study were to determine 1) whether endothelin (ET)-1 affects the neuronal activity of the NTS neurons, 2) whether specific ET receptor antagonists affect the neuronal activity of the NTS neurons, and 3) whether ET-1 or ET receptor antagonists modulate the responses of the nucleus of the solitary tract (NTS) neurons to L-glutamate (Glu). The single-unit discharge was extracellularly recorded with a fine electrode from medulla brain slice preparations of rats. ET-1 and Glu were iontophoretically applied to the recorded neuron. Both ET-1 and Glu increased the neuronal activity. The ETA receptor antagonist BQ-123 attenuated the basal neuronal activity. ET-1 augmented the magnitude of the increases in the neuronal activity evoked by Glu, and these responses were antagonized by BQ-123. These studies suggest the following conclusions: 1) ET-1 increases the neuronal activity of the NTS neurons via ETA receptors, 2) endogenous ET plays a controlling role of the neuronal activity of NTS neurons, and 3) ET-1 augments the responses evoked by Glu, believed to be the neurotransmitter from the solitary tract, via ETA receptors. These results suggest that ET-1 facilitates synaptic transmission in the NTS.

Animals↗