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Biomedical subjects

T Toyoda

Publications and source records attributed to T Toyoda.

At least 145 records · Page 8Linked to original sources

Influence of endothelin on human platelet aggregation and prostacyclin generation from human vascular endothelial cells in culture.

The effects of endothelin (ET) on the function of cultured human umbilical vein endothelial cells (HUVEC) and that of human platelets were investigated with reference to endothelium-derived relaxing factor (EDRF) and PGI2. Considering the platelets, ET had no effect on platelet-rich plasma (PRP) aggregation, the generation of thromboxane A2 ([TXA2]) from platelets, and cytosolic free calcium ion concentration ([Ca++]i), cAMP content ([cAMP]i) or cGMP content ([cGMP]i) in platelets. In contrast, the addition of the solution in which HUVEC had been incubated with ET to PRP produced a decrease in PRP aggregation, [TXA2], and [Ca++]i, and an increase not only in [cAMP]i but also in [cGMP]i in platelets. In the HUVEC pretreated with acetylsalicylic acid (aspirin), this increase of [cGMP]i was not affected, but the HUVEC-mediated decrease in PRP aggregation, [TXA2], and [Ca++]i induced by ET were not completely abolished. However, the pretreatment of HUVEC with a combination of aspirin and L-NG-monomethyl arginine (LNMMA) as an inhibitor of EDRF completely abolished the HUVEC-mediated decrease in PRP aggregation, [TXA2] and [Ca++]i induced by ET, and also abolished the enhancement of [cGMP]i and [cAMP]i in platelets. The PGI2 of HUVEC was enhanced by ET with no changes in [Ca++]i, [cAMP]i and [cGMP]i. The ET-induced enhancement was remarkably attenuated by pretreating the HUVEC with aspirin, but not with LNMMA. We conclude that ET attenuates the aggregation of platelets through a decrease in [TXA2] by an increase in [cAMP]i via the increase in PGI2 of HUVEC, and by an increase in [cGMP]i via EDRF.

Blood Platelets↗

[Polymerase chain reaction for identification of Mycobacterium in sputa].

Polymerase chain reaction was applied to the diagnosis of mycobacterial infections. This reaction could detect bacteria in clinical specimens within a few hours. Sensitivities of the five primer systems reported in 1990 were compared. It was proved that the primer system reported by Eisenach et al. was as sensitive as culture on Ogawa's medium for the detection of Mycobacterium tuberculosis in sputa. Other systems were found to be less sensitive than this system, and the nested PCR should be applied to make these systems highly sensitive. For the practical application of PCR method, we should improve the detection system to fit for the practice in clinical laboratory. High cost of PCR system could be another barrier for the practical application.

Base Sequence↗

[The giant cavernous hemangioma of the neck].

A 67-year-old female who had complains of dyspnea and giant mass in the right neck. The plain CT scan and selective angiography showed an giant mass in the neck and extended into antero-superior mediastinum which pressed intrathoracic trachea. The tumor was resected completely by oblique neck incision and partial median sternotomy. It was 15 x 9 x 5 cm in size. The histological diagnosis was cavernous hemangioma. The giant cavernous hemangioma in neck extended into mediastinum is rare.

Aged↗

[CT findings of six cases with intracranial tuberculosis in National Higashi-Saitama Hospital].

We have experienced 6 cases of intracranial tuberculosis since 1985. 2 cases were diagnosed as intracranial tuberculoma without tuberculous meningitis, and 4 cases were diagnosed as tuberculous meningitis. Brain CT showed intracranial tuberculomas in three of them, and showed cerebral infarcts in two cases, and showed hydrocephalus in two cases. Brain CT on intracranial tuberculosis showed various findings. In two cases with tuberculous meningitis, brain CT showed many tuberculomas with ringed or nodular enhancement appeared after adequate chemotherapy had been started. About 1 year later, a few tuberculomas were found with homogeneous enhancement and were enlarged while the chemotherapy was continued. But later they were reduced in size. The above facts may suggest that intracranial tuberculoma could appear and be enlarged on cranial CT in spite of adequate anti-tuberculous chemotherapy during a course of tuberculous meningitis. They also suggest that the continuation of adequate chemotherapy might be necessary to the treatment of intracranial tuberculomas.

Aged↗

[The appearance of "central core of respiratory muscle" in patients with respiratory failure].

We report the histological and histochemical features of core fibers present in respiratory muscles obtained from autopsy since 1980. Fifty autopsy cases of adults without neuromuscular disease were examined. "Central core" structure was present in 38 cases and absent in 12 cases. The duration of D.O.E. was greater than 1 month in 81.8% of core positive cases. In core negative cases, the duration of D.O.E. was less than 3 months. "Central core" structure were present in 80.0% of chronic respiratory failure cases and 41.7% of non-chronic cases. It is suggested that central core in respiratory muscles develops less than 3 months after the onset of D.O.E.

Adult↗

Comparative studies of angiotensin converting enzyme inhibitors with and without the SH-radical.

This study was conducted to evaluate the effects of an SH-radical in an angiotensin converting enzyme (ACE) inhibitor on PGI2 generation, intracellular cGMP, and Ca2+ kinetics in vascular endothelial cells. In the cultured human umbilical vein endothelial cells, the non-SH containing ACE inhibitors, delapril and enalapril, did not result in significant changes in cGMP concentrations. By comparison, captopril significantly (P less than .01) increased cGMP concentrations. Only captopril showed a significant (P less than .01) effect on 45Ca kinetics in cultured human vascular endothelial cells. Captopril also decreased PGI2 generation in vascular endothelial cells. These effects were not seen with delapril or enalapril. The significance of the SH moiety in ACE inhibitors remains controversial. However, these results suggest that there could be differences in the vascular actions of ACE inhibitors related to the presence or absence of SH radical.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of cyclic GMP and sulfhydryl on prostacyclin production by human vascular endothelial cells.

The relationship between sulfhydryls and cGMP has been observed in several biological processes. Captopril is a sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor, that decreases PGI2 production in cultured human vascular endothelial cells. Enalapril does not appear to have this property. The role of cyclic GMP (cGMP) and sulfhydryls in the regulatory mechanisms in captopril-induced PGI2 production and Ca++ kinetics was investigated. Bradykinin and Ca ionophore A23187 enhanced PGI2 production, and increased the cytosolic free Ca++ concentration ([Ca++]i). It was observed that 8-bromo cGMP increased intracellular cGMP concentration ([Ca++]i), and decreased PGI2 production without changing [Ca++]i. Sulfhydryl containing compounds such as captopril, N-acetylcysteine and glutathione decreased PGI2 production via increased [cGMP]i. Enalapril, an ACE inhibitor without sulfhydryls, has no effect on PGI2 production, [Ca++]i and [cGMP]i. These results suggested that the presence of sulfhydryl groups is an important factor in the ability of vasoactive substances to induce PGI2 production.

Acetylcysteine↗

An endoprotease homologous to the blood clotting factor X as a determinant of viral tropism in chick embryo.

Host cell proteases responsible for activation of viral fusion glycoproteins are an important determinant for spread and tropism of various animal viruses. Exemplifying such proteases for the first time, we isolated an endoprotease from chick embryo, that activates para- and orthomyxovirus fusion glycoproteins by cleaving their precursor proteins at a specific, single arginine site. The protease is a calcium dependent serine protease consisting of two subunits, the 33 kd catalytic chain and the 23 kd chain possibly required for Ca2+ binding, and was found to be highly homologous, if not identical, to the blood clotting factor X(FX), a member of the prothrombin family. Its high efficiency and specificity in cleavage reactions was attributable to the properties characteristic of FX. Its role in vivo was strongly supported by cleavage inhibition in ovo highly selective for this virus group with a specific peptide inhibitor against FX.

Amino Acid Sequence↗

Growth restriction of negative-strand-RNA viruses in a rat 3Y1 cell line.

A rat fibroblast cell line, 3Y1 is nonpermissive for infection by several negative-strand-RNA viruses including influenza virus A, Sendai virus, Newcastle disease virus and vesicular stomatitis virus (VSV), but not refractory to that of a positive-strand-RNA virus, Sindbis virus. To elucidate the mechanism of the restricted viral growth, we compared the replication pattern of VSV in 3Y1 cells and in baby hamster kidney cells, which are fully permissive for those viruses. The results indicated that the restriction was imposed predominantly on the transcription of the viral RNA. The subsequent steps such as protein synthesis and nucleocapsid assembly appeared to occur normally, although these levels remained low due to the restricted transcription. Virus attachment onto, and penetration into, 3Y1 cells were also not restricted.

Animals↗

Evaluation of the antiviral effect of synthetic oligopeptides whose sequences are derived from paramyxovirus F1 N termini.

We examined the antiviral effects of three oligopeptides, carbobenzoxy(Z)-D-Phe-Ile-Gly, Z-D-Leu-Ile-Gly and Z-D-Phe-Phe-Gly, which mimic the N-terminal regions of F1 glycoproteins of two Newcastle disease virus strains (Miyadera and D26) and Sendai virus, respectively. Only one of these peptides, Z-D-Phe-Phe-Gly, significantly and with a similar potency inhibited viruses of homologous and heterologous F1 N-terminal sequences, suggesting no strict sequence requirement for inhibition. Furthermore, the enveloped RNA viruses of several different families showed essentially the same sensitivity to the three peptides as the paramyxoviruses, while a non-enveloped RNA virus was not susceptible to any of them. In addition, the Z-D-Phe-Phe-Gly peptides was effective only when the virus particles had been pretreated before infection.

Amino Acid Sequence↗

Phosphatidylserine as a determinant for the tissue distribution of weakly basic drugs in rats.

Interogan variation in tissue distribution of weakly basic drugs such as quinidine, propranolol, and imipramine was investigated as a function of binding to phosphatidylserine (PhS) in tissues. Tissue distributions of these drugs were determined using 10 different tissues at a steady-state plasma concentration and were expressed as tissue-to-plasma partition coefficients (Kp values). The concentration of PhS in the tissue was determined by two-dimensional thin-layer chromatography. Plotting of Kp values, except for brain, against the tissue PhS concentrations showed a linear relationship, indicating that PhS is a determinant in the interorgan variation of these tissue distributions. Further, differences in tissue distribution among the drugs was considered to be due to the difference in binding potency to PhS. Drug binding parameters to individual standard phospholipid were determined using a hexane-pH 4.0 buffer partition system. Binding was highest to PhS, and a linear relationship was found between the log nK [product of the number of binding sites (n) and the association constant (K) for PhS binding] obtained in vitro and Kp values of drugs in tissues in vivo. The empirically derived equation, Kp = 14.3 x (log nK) x (PhS conc.) - 8.09, was found to predict Kp values in vivo of weakly basic drugs. Thus, a determinant of interorgan variation in the tissue distribution of the weakly basic drugs studied was the tissue concentration of PhS and the drug binding affinity to PhS.

Animals↗

Amelanotic malignant melanoma of the esophagus: case report and review of the literature.

A case of amelanotic malignant melanoma of the esophagus in a 76-year-old woman is reported. A whitish polypoid tumor, measuring 3 x 2 x 2.7 cm, surrounded by black pigmented mucosa, was detected in the middle intrathoracic esophagus. The tumor showed a lobulated surface lined by squamous cell layer, and had epithelioid and polyhedral cells forming alveolar clusters. Melanin pigments or stainability for the dihydroxyphenylalanine (DOPA) reaction were only observed in a few tumor cells. Junctional changes and mucosal melanosis, however, were found freely in the mucosa around the tumor. Many tumor cells showed a strongly positive immunohistochemical reaction for neuron specific enolase (NSE) and S100 protein. The patient died of widespread metastases six months after surgery. Further, a review of 106 reported cases of primary esophageal malignant melanoma, including 29 autopsies, was made; the melanomas were found to include 10 of amelanotic type, eight of which had been misdiagnosed at biopsy. Junctional changes could be found in the mucosa over or around the tumor, in four cases, and mucosal melanosis in one. Lymph node metastasis was the most frequently observed development at autopsy regardless of whether the tumor was amelanotic or melanotic. For correct diagnoses of melanomas of the amelanotic type, peripheral mucosal findings, such as junctional changes or melanosis, should be helpful; and, in order to obtain a good prognosis, a careful resection of the regional lymph nodes could prove valuable.

Aged↗

[Studies on the changes in clinical features of tuberculosis].

The epidemiological and clinical features of tuberculosis have largely changed in recent years owing to rapid improvement of social environments and therapeutics. For the determination of these changes, especially clinical ones, the author made comparative studies on all patients hospitalized in National Sanatorium Higashi Saitama Hospital during the periods from 1964 to 1966 and from 1985 to 1988. The 1964-66 group included 400 patients and the 1985-88 group included 508, making a total of 908. The results are as follows: 1. Primary treatment cases with positive bacteriology, atypical mycobacteriosis cases and those with complications increased in number, while re-treatment cases decreased. 2. Comparison was made for bacteriologically positive primary treatment cases between the two groups, namely 112 patients of 1964-66 group and 213 patients of 1985-88 group. The results were: (1) 1985-88 group included larger number of more aged patients and patients with complications. (2) The two groups showed no marked differences in radiological findings such as the size of affected areas or cavities and the rate of cavitation. The patients with radiologically fibrocaseous findings increased in number. (3) The incidence of lower lung field tuberculosis was almost doubled in the 1985-88 group, and this type of tuberculosis was more frequently observed among patients below 29 and over 70 years of age and among those complicated with diabetes mellitus. In chest CT, eight out of 10 patients with lower lung field tuberculosis showed some changes in their mediastinum and/or hilar lymph nodes. This may suggest that the primary mediastinum and/or hilar lymph nodes tuberculosis had perforated into the trachea or bronchi. (4) Although the two groups did not show difference in mortality, deaths due to complications were observed more in the 1985-88 group. However, 4 patients in this group died of tuberculosis itself, all within about 40 days after hospitalization.

Adolescent↗

[A case of coronary artery bypass grafting using bilateral mammary arteries in a patient with systemic lupus erythematosus].

A 40-year-old female who had been treated with steroid for 10 years because of systemic lupus erythematosus (SLE) was admitted to our department for triple-vessel disease with LMT lesion. She underwent bilateral internal mammary artery grafting to the right ventricular branch of RCA and the No. 7 segment of LAD. Intraoperative free flow was 70 ml/min in both bypass grafts. She dropped to severe shock with a high fever of 40 degrees C and decreased the white blood cell count of 900/mm3 on the 6th postoperative day. These clinical and laboratory findings were suggestive of rebound phenomenon of SLE or withdrawal syndrome of steroid therapy. She was treated with pulse therapy of methyl-prednisolone and her condition improved in two weeks. Histological findings of the right internal mammary artery revealed stenotic lesion of about 50%, but on June 24, 1988, postoperative angiography showed a good patency of both internal mammary arteries. Only a few reports of successful attempt of coronary artery bypass grafting for coronary lesion due to SLE are available in the literature. Some important problems concerning the surgical treatment as well as the therapy of steroid involved in this case were discussed.

Adult↗