[Organ lesions and progress in diagnosis of collagen diseases. (5) Cardiovascular lesions].
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Cardiovascular Diseases↗
Biomedical subjects
T Tojo
Publications and source records attributed to T Tojo.
Survivorship analysis of total knee arthroplasty with the kinematic prosthesis in patients who have rheumatoid arthritis.
Eighty-eight primary total knee arthroplasty procedures in 61 patients with rheumatoid arthritis were performed using the Kinematic total knee prosthesis (Howmedica, Rutherford, NJ) with cement between 1980 and 1985. No patients were lost to follow-up evaluation. Thirty-one of 61 patients died during the study period. Survivorship for all patients by life-table method was estimated as 56% at 10 years. This was shorter than the expected survival rate of a sex- and age-matched control group. Fifty procedure outcomes in 34 patients (27 women, 7 men) who were followed for more than 10 years were available for clinical evaluation. Complications occurred in 11 cases; in 4 of these, revision surgery was required. With revision as the endpoint, the survival rate of the prostheses was estimated as 93% at 10 years.
Adult↗
Probable participation of phospholipase A2 reaction in the process of fertilization-induced activation of sea urchin eggs.
In sea urchin eggs activated by sperm, A23187 or melittin, BPB (4-bromophenacyl bromide, a phospholipase A2 inhibitor) blocked fertilization envelope formation and transient CN(-)-insensitive respiration in a concentration-dependent manner. BPB had virtually no effect on the increase in [Ca2+]i (cytosolic Ca2+ level), the activity of phosphorylase a and the rate of protein synthesis, as well as acid production and augmentation of CN(-)-sensitive respiration. BPB also inhibited fertilization envelope formation and augmentation of CN(-)-insensitive respiration induced by melittin. Melittin, known to be an activator of phospholipase A2, induced the envelope formation, acid production, augmentation of CN(-)-insensitive and sensitive respiration, but did not cause any increase in [Ca2+]i, the phosphorylase a activity and the rate of protein synthesis. An activation of phospholipase A2 induced by Ca2+ or melittin seems to result in cortical vesicle discharge and production of fatty acids, which are to be utilized in CN(-)-insensitive lipid peroxidase reactions. Activation of other examined cell functions in eggs activated by sperm or A23187, probably results from Ca(2+)-triggered sequential reactions other than Ca(2+)-caused activation of phospholipase A2.
Acetophenones↗
Studies on anti-inflammatory agents. V. Synthesis and pharmacological properties of 3-(difluoromethyl)-1-(4-methoxyphenyl)-5- [4-(methylsulfinyl)phenyl]pyrazole and related compounds.
A series of novel 1,5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyraz ole (10) with oral ED50 values of 0.31 and 2.6 mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED30 = 0.55 and 1.8 mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED50 = 21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported.
Animals↗
Studies on anti-inflammatory agents. IV. Synthesis and pharmacological properties of 1,5-diarylpyrazoles and related derivatives.
A series of novel 1,5-diarylpyrazole derivatives was synthesized and tested for anti-inflammatory and analgesic activities to develop anti-inflammatory agents with fewer side effects than existing nonsteroidal anti-inflammatory drugs. The structure-activity relationships in this series were extensively studied. Electron-withdrawing substituents such as CN and CF3 were optimal at the 3-position of the pyrazole ring. Replacement of these substituents with bulky ones gave less active compounds. The 4-(methylsulfonyl)phenyl group seemed to be the optimal group at the 5-position of the pyrazole ring. The most potent compound was 1-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-pyrazole-3-carbonitrile (19a), with oral ED50 value of 0.030 and 0.47 mg/kg on adjuvant-induced arthritis and collagen-induced arthritis, respectively, and an ED30 value of 7.4 mg/kg in the yeast-induced hyperalgesia (Randall-Selitto) assay. Compound 19a also showed potent inducible cyclooxygenase (COX-2)-inhibitory activity (IC50 = 0.24 microM) with no COX-1 inhibition even at 100 microM.
Anilides↗
Thoracoscopic wedge resection of blebs under local anesthesia with sedation for treatment of a spontaneous pneumothorax.
We performed thoracoscopic wedge resections of blebs with a stapling device under local anesthesia with sedation in 34 consecutive patients who presented with spontaneous pneumothoraces. The indications for surgery included the absence of parietal pleural adhesions and knowledge of the precise bleb location prior to the procedure. Prior to surgery, 0.5% lidocaine was administered into the pleural space, and IV butorphanol tartrate and diazepam were administered to reduce pain and anxiety during the procedure. In our series, the thoracoscopic procedure resulted in favorable outcomes in all but two patients. There was no evidence of hemodynamic instability or arterial blood gas abnormalities encountered during the procedure. Minor postoperative complications were seen in only three patients (two with air leakage and one with transient atelectasis). One patient had a recurrence of his spontaneous pneumothorax 3 months following the procedure. Therefore, the overall success rate was 91%. We compared the results of this therapeutic modality (group 1) with those of 38 patients who underwent the procedure under general anesthesia (group 2) during the same period. The length of hospital stay was shorter in group 1 than in group 2 (4.5 +/- 1.3 vs 5.8 +/- 1.1 days; p < 0.01). Thoracoscopic wedge resections under local anesthesia are safe and offer the benefit of shorter hospital stays. We believe that this thoracoscopic technique will further simplify the surgical treatment of pneumothoraces without incremental risks.
Adolescent↗
Brasiliquinones A, B and C, new benz[alpha]anthraquinone antibiotics from Nocardia brasiliensis. I. Producing strain, isolation and biological activities of the antibiotics.
New benz[alpha]anthraquinone antibiotics (brasiliquinones A, B and C) with an ethyl group at C-3 were isolated. The producer was identified as Nocardia brasiliensis. The antibiotics were active against Gram-positive bacteria including Mycobacterium sp., but not active against Gram-negative bacteria or fungi. They were also active against multiple drug-resistant P388/ADR tumor cells.
Animals↗
[Clipping of the thoracic duct with video-assisted thoracic surgery in the treatment of chylothorax after pulmonary resection].
We describe a procedure for video-assisted thoracoscopic clipping of the thoracic duct to treat postoperative chylothorax. This technique was successfully performed on a 62-year-old man who developed chylothorax following right lower lobectomy and partial resection of the 11th and 12th vertebral bodies for squamous cell lung cancer. Because conservative therapy for 7 days failed to reduce the amount of pleural effusion, we performed thoracoscopic examination of the thoracic duct and found a site leaking chylous fluid. The thoracic duct was successfully and easily clipped resulting in complete elimination of the effusion in 2 days. Generally, chylothorax complicating pulmonary resection has been managed by medical treatment first, followed by surgical intervention in case that fail to respond to initial therapy. The newly designed video-assisted thoracic surgery procedure reduces the trauma, shortens the drainage period and hospital stay, and provides better exposure of the thoracic duct. We believe that this procedure can be carried out shortly after the occurrence of chylothorax.
Chylothorax↗
Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region.
CD40 signalings play crucial roles in B-cell function. To identify molecules which transduce CD40 signalings, we have utilized the yeast two-hybrid system to clone cDNAs encoding proteins that bind the cytoplasmic tail of CD40. A cDNA encoding a putative signal transducer, designated TRAF6, has been molecularly cloned. TRAF6 has a tumor necrosis factor receptor (TNFR)-associated factor (TRAF) domain in its carboxyl terminus and has a RING finger domain, a cluster of zinc fingers and a coiled-coil domain, which are also present in other TRAF family proteins. TRAF6 does not associate with the cytoplasmic tails of TNFR2, CD30, lymphotoxin-beta receptor, and LMP1 of Epstein-Barr virus. Deletion analysis showed that residues 246-269 of CD40 which are required for its association with TRAF2, TRAF3, and TRAF5 are dispensable for its interaction with TRAF6, whereas residues 230-245 were required. Overexpression of TRAF6 activates transcription factor NFkappaB, and its TRAF-C domain suppresses NFkappaB activation triggered by CD40 lacking residues 246-277. These results suggest that TRAF6 could mediate the CD40 signal that is transduced by the amino-terminal domain (230-245) of the CD40 cytoplasmic region and appears to be independent of other known TRAF family proteins.
Amino Acid Sequence↗
TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling.
Signals emanating from CD40 play crucial roles in B-cell function. To identify molecules that transduce CD40 signalings, we have used the yeast two-hybrid system to done cDNAs encoding proteins that bind the cytoplasmic tail of CD40. A cDNA encoding a putative signal transducer protein, designated TRAF5, has been molecularly cloned. TRAF5 has a tumor necrosis factor receptor-associated factor (TRAF) domain in its carboxyl terminus and is most homologous to TRAF3, also known as CRAF1, CD40bp, or LAP-1, a previously identified CD40-associated factor. The amino terminus has a RING finger domain, a cluster of zinc fingers and a coiled-coil domain, which are also present in other members of the TRAF family protein except for TRAF1. In vitro binding assays revealed that TRAF5 associates with the cytoplasmic tail of CD40, but not with the cytoplasmic tail of tumor receptor factor receptor type 2, which associates with TRAF2. Based on analysis of the association between TRAF5 and various CD40 mutants, residues 230-269 of CD40 are required for the association with TRAF5. In contrast to TRAF3, overexpression of TRAF5 activates transcription factor nuclear factor kappa B. Furthermore, amino-terminally truncated forms of TRAF5 suppress the CD40-mediated induction of CD23 expression, as is the case with TRAF3. These results suggest that TRAF5 and TRAF3 could be involved in both common and distinct signaling pathways emanating from CD40.
Amino Acid Sequence↗
Differential display and cloning of shear stress-responsive messenger RNAs in human endothelial cells.
To investigate the effect of shear stress on endothelial gene expression, we performed differential display of mRNAs from cultured human umbilical vein endothelial cells either incubated under static conditions or exposed to shear stress (15 dynes/cm2) for 6 h in a flow-chamber. Around 4% of the total number of mRNAs detected were either up- or down-regulated by shear stress. DNA sequencing of some of these shear stress-responsive mRNAs revealed homology of several clones to known gene sequences and many other clones for unknown genes. Known genes, including those for human laminin B1 chain, H(+)-ATP synthase coupling factor 6, lysyl oxidase, myosin light chain kinase, and interleukin-8 receptor, were upregulated by shear stress, while the gene encoding NADH dehydrogenase was down-regulated. The present results suggest that shear stress can change the expression of numerous genes in endothelial cells, far more than reported to date, and that mRNA differential display is quite useful for cloning known and unknown shear stress-responsive genes.
Antigens, CD↗
[Current trends in the study of mixed connective tissue disease].
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Humans↗
Nodular regenerative hyperplasia of the liver in a patient with systemic sclerosis.
We report on a 33-year-old female patient with systemic sclerosis and nodular regenerative hyperplasia of the liver (NRHL). A needle biopsy of the patient's liver did not reveal the histology of NRHL or liver cirrhosis at her first visit to our hospital, when portal hypertension was demonstrated by percutaneous transhepatic portography. After 11 years, the patient died of hepatic and renal failure. At the time of autopsy, multiple nodules were found in the liver, and a microscopic examination showed a histology compatible with NRHL. It is suggested that the immunological disturbance was related to the patient's portal hypertension and NRHL.
Adult↗
In vitro study of ablated lung tissue in Nd:YAG laser irradiation.
BACKGROUND: Neodymium:yttrium-aluminum garnet lasers are used to reduce lung volume. An assessment of the relationship between the histologic and gross findings in the lung irradiated by a laser would be helpful in laser-assisted pneumoplastic procedures. METHODS: In vitro lung lobes surgically resected for pulmonary carcinomas were irradiated with a neodymium:yttrium-aluminum garnet laser at three energy levels in three modes: contact rubbing, contact pointing, and noncontact. Pleural degeneration in 216 samples from 24 lobes was classified as coagulative, amorphous, or destructive. At all energy levels, the laser was applied for 1.5 seconds. RESULTS: Noncontact mode at 7.5 W or 15 W and contact rubbing at 5 W caused coagulative or amorphous degeneration but no destructive degeneration. The energy level correlated with the color of the degenerated pleura. The incidence of destructive pleural degeneration, which led to air leaks as revealed by an air inflation test, was 0% in pink and white samples, 59% in brown samples, and 100% in black samples (p < 0.0001, white versus brown samples). CONCLUSIONS: In neodymium:yttrium-aluminum garnet laser ablation of lung tissue, the color of the degenerated pleura correlates with the intensity of the applied laser energy and the degree of pleural degeneration.
Aged↗
Management of malignant tracheobronchial stenosis with metal stents and Dumon stents.
BACKGROUND: Tracheobronchial stenosis caused by malignancy is a life- threatening problem. Stenting is one of the treatment modalities and recently has been used widely for the management of such stenosis, but we do not have a clear guide as to which stent should be selected. METHODS: We evaluated 25 patients (19 men, 6 women; mean age, 60.7 years; range, 34 to 77 years) received 24 metal stents (four covered with silicone rubber) and three Dumon stents. All 25 patients had severe dyspnea because of airway stenosis caused by malignant tumors. RESULTS: Among the 25 patients, airway obstruction due to extrinsic compression by tumor developed in 11 and was treated with a bare metal stent. The airway remained patent in 10 patients. In 16 patients with intraluminal tumor invasion, nine lesions were treated with a bare metal stent, four lesions with a covered metal stent, and the remaining three lesions with a Dumon stent. Recurrent stenosis did not occur in any patient with a covered metal stent or a Dumon stent. However, restenosis occurred in 4 patients with a bare metal stent, all of whom received laser therapy. In all patients, stenting immediately relieved dyspnea. Six patients lived for 32 days to 53 months after stenting, and 19 patients died of primary malignancies with a mean survival of 131.9 days. CONCLUSIONS: Metal stents are effective in treating malignant extrinsic tracheobronchial compression. The use of covered metal stents or Dumon stents is preferable for intraluminal stenosis due to malignant growth.
Adult↗
In vitro comparison between Argon Beam Coagulator and Nd:YAG laser in lung contraction therapy.
BACKGROUND: The Argon Beam Coagulator (ABC) and neodymium:yttrium-aluminum garnet (Nd:YAG) laser are used for lung tissue contraction. Assessing the damage of treated lung tissue is helpful in choosing devices for pulmonary volume reduction by pneumoplastic procedures. METHODS: We assessed the damage of in vitro lung lobes resected at operation for pulmonary carcinoma. Samples were irradiated with noncontact Nd:YAG laser and ABC. One hundred forty-four samples obtained from 24 lobes were examined by light microscopy. The lung tissue showing destructive degeneration at the pleura and slight coagulation at the residual parenchyma was defined as showing "air leak pattern" based on a previously reported experiment of the air inflation test. RESULTS: At the power of clinical use (Nd:YAG, 15 W; ABC, 80 W), most of the visceral pleura treated with the Nd:YAG laser was classified as presenting amorphous degeneration, and that treated with ABC showed destructive degeneration. Air leak pattern occurred in all samples treated with ABC. At the power of 40 W, ten (42%) of 24 visceral pleuras irradiated with the Nd:YAG laser were classified as presenting destructive degeneration, and of those irradiated with the ABC, 18 (75%) showed destructive degeneration (p < 0.05). Air leak patterns were found in 3 (13%) of the samples treated with the Nd:YAG laser and in 16 (63%) of those treated with the ABC (p < 0.05). CONCLUSIONS: The ABC had more potential to damage the pleura and less potential to produce underlying parenchymal coagulation in the lung tissue than did the Nd:YAG laser. This information may be useful in the selection of devices for pulmonary volume reduction by pneumoplastic procedures.
Aged↗
'Seronegative' Sjögren's syndrome manifested as a subset of chronic fatigue syndrome.
We determined the extent to which chronic fatigue syndrome (CFS) patients with sicca symptoms fulfil the diagnostic criteria for Sjögren's syndrome (SS). Three sets of diagnostic criteria for SS, formulated by the Japanese, Europeans and Fox, were used. One-third of the CFS patients with sicca symptoms fulfilled the diagnostic criteria for SS. However, they were 'seronegative', differing from the ordinary primary SS.
Adult↗
Abnormal prostanoid metabolism in lupus nephritis and the effects of a thromboxane A2 synthetase inhibitor, DP-1904.
Abnormalities of prostanoid metabolism, which may affect renal function, were studied in lupus nephritis. The subjects were 31 patients with lupus nephritis, ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-PGF1 alpha,2,3-dinor-6-keto-PGF1 alpha and PGE2, and plasma level of 11-dehydro-TXB2, were determined. The effects of four days' dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904 (DP), on prostanoid metabolism, were also studied. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis as compared with non-renal SLE (p < 0.05). The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01), indicating a prostanoid imbalance, which may lead to impaired renal function and subsequent pathology. The urinary TXB2/6-keto-PGF1 alpha ratio in these lupus nephritis patients showed negative correlations with Ccr and positive correlations with anti-DNA antibody titer (p < 0.001). DP was administered orally (400 mg/day, given in two divided doses) for four days to eight lupus nephritis patients. The urinary excretion of TXB2 and urinary TXB2/6-keto-PGF1 alpha ratio were decreased after one to two days of treatment in all patients. An increase in creatinine clearance used as a measure of renal function was observed in four of eight patients. Furthermore, no side effects were elicited during the four days of treatment. The conclusion reached were that the abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function through hemodynamic mediation, and that the deviated metabolism was reversible and, at least partially, corrected by a TXA2 synthetase inhibitor.
6-Ketoprostaglandin F1 alpha↗