Pyrrolidine inhibitors of human cytosolic phospholipase A(2).
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Cell Line↗
Biomedical subjects
Y Fujii
Publications and source records attributed to Y Fujii.
Pulmonary hypertension associated with pulmonary occlusive vasculopathy after allogeneic bone marrow transplantation.
BACKGROUND: Pulmonary vasculature abnormalities, including pulmonary veno-occlusive disease, have been demonstrated in marrow allograft recipients. However, it is often difficult to make a correct diagnosis of pulmonary lesions. METHODS: An open lung biopsy was performed on a patient who developed severe pulmonary hypertension after bone marrow transplantation for T-cell lymphoma. RESULTS: An open lung biopsy specimen demonstrated pulmonary arterial occlusion due to intimal fibrosis and veno-occlusion. The most striking alteration was partial to complete occlusion of the small arteries by fibrous proliferation of the intima. CONCLUSION: High-dose preparative chemotherapy and radiation before transplantation are thought to have contributed to the development of vasculopathy in this patient, because arterial occlusion by intimal fibrosis and atypical veno-occlusion are often associated with lung injury due to chemoradiation. An open lung biopsy is essential for diagnosing pulmonary vascular disease presenting signs compatible with posttransplantation pulmonary hypertension.
Adult↗
Prolonged effect of leukocytosis on reperfusion injury of rat intestine: real-time ATP change studied using (31)P MRS.
BACKGROUND: The intestine is one of the most sensitive tissues to ischemia and reperfusion (I/R). Polymorphonuclear neutrophils (PMN) may play an important role in ischemic injury. (31)P magnetic resonance spectroscopy (MRS) has been used to continuously monitor the energy metabolism of an animal in situ. We have applied MRS to study the effect of PMN on the I/R injury of rat intestine. MATERIAL AND METHODS: In a rat model of 30 min of intestinal ischemia and reperfusion, the number of PMNs was manipulated: group A, control; group B, leukopenia induced by cyclophosphamide; group C, leukocytosis induced by granulocyte colony-stimulating factor (G-CSF). MRS was employed to measure the level of real-time intestinal ATP and pH in vivo. RESULTS: In group A, ATP rapidly recovered on reperfusion to 61.0 +/- 11.0% of the preischemia level and maintained that level during reperfusion. The other two groups showed similar recovery of ATP at the initial phase of the reperfusion (<10 min). ATP in group B continued to recover, reaching 74.0 +/- 10.0% of the preischemia level. After the initial recovery, ATP in group C deteriorated reaching 46.0 +/- 4.4% of the preischemic level at 150 min of reperfusion. In group A and group B tissue pH decreased on ischemia and recovered on reperfusion in a similar manner. In group C, tissue pH was significantly lower than in other groups during I/R. CONCLUSION: Leukocytosis induced by G-CSF exerts a prolonged effect on ATP during I/R and leukocyte depletion helps protect against the I/R injury.
Adenosine Triphosphate↗
Modifications of the hemodynamic consequences of theophylline intoxication with landiolol in halothane-anesthetized dogs.
PURPOSE: To examine the effect of landiolol (ONO-1101), a new ultra-short acting, highly selective beta1 blocker, on hemodynamic response to acute theophylline intoxication in anesthetized dogs. METHODS: Thirty-four dogs were studied during halothane anesthesia. Aminophylline (50 mg x kg(-1) over 20 min followed by infusion at 1.75 mg x kg(-1) x hr(-1)) was administered as a model of acute theophylline intoxication. Dogs were randomly enrolled into four landiolol groups (0, 1, 10, 100 microg x kg(-1) x min(-1)) to treat tachyarrhythmias. Hemodynamic variables, heart rate (HR), systemic blood pressure (SBP), pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output (CO) were measured along with plasma concentrations of theophylline, epinephrine, and norepinephrine. RESULTS: After 60 min, plasma concentration of theophylline reached 46.6+/-4.0 (mean +/- SD) microg x ml(-1), HR increased from 129+/-21 to 193+/-27 bpm (P<0.0001) and CO increased from 1.6+/-0.5 l x min(-1) to 2.1+/-0.4 l x min(-1) (P<0.0001), whereas SBP decreased from 139+/-25 to 121+/-25 mm Hg (P<0.0001), with decreasing systemic vascular resistance. After intoxication, plasma epinephrine concentration increased from 125 +/-112 to 325+/-239 pg x ml(-1) (P<0.0001), and norepinephrine concentration from 103+/-61 to 133+/-61 pg x ml(-1) (P<0.0011). Landiolol 10 microg x kg(-1) x min(-1) decreased HR to pre-intoxication level, whereas HR returned to the intoxication baseline by 30 min after cessation of landiolol infusion. CONCLUSIONS: Landiolol controlled tachyarrhythmias associated with theophylline toxicity. The optimal effective dose of landiolol was 10 microg x kg(-1) x min(-1).
Adrenergic Agonists↗
Effect of xenon on diaphragmatic contractility in dogs.
PURPOSE: This study was undertaken to examine the effect of xenon on diaphragmatic contractility in pentobarbitone- anesthetized, mechanically ventilated dogs. METHODS: Twenty-one dogs were randomly allocated to three groups (n=7 of each): Group I received oxygen 100%; Group II received xenon 30% in oxygen; Group III received xenon 60% in oxygen. Diaphragmatic contractility was assessed by measuring transdiaphragmatic pressure (Pdi) generated during supramaximal stimulation of phrenic nerves at the neck at low-frequency (20-Hz) and high-frequency (100-Hz) stimulation, after maintaining 60 min of stable condition. RESULTS: With inhalation of xenon at two different concentration (30% and 60%), no changes were observed in Pdi at either concentration. There was no difference in Pdi among the three groups. CONCLUSION: Increasing the concentration of xenon to 60% has no effect on diaphragmatic contractility in dogs. This suggests that xenon may be used safely as an anesthetic with respect to respiratory muscle function.
Anesthetics, Inhalation↗
Different effects of olprinone on contractility in nonfatigued and fatigued diaphragm in dogs.
PURPOSE: To evaluate the effects of low-dose olprinone, a phosphodiesterase III inhibitor, on contractility and its mechanism in nonfatigued and fatigued diaphragm in dogs. METHODS: Thirty six pentobarbitone-anesthetized dogs were studied. In Group Ia (n=6), animals without fatigue, received no study drug. In Group Ib (n=6), dogs were given a bolus injection (10 ug x kg(-1)) followed by continuous infusion (0.1 microg x kg(-1) x min(-1)) of olprinone. In Groups IIa, IIb, and IIc (n=8 each), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz applied for 30 min. After producing fatigue, Group IIa received no study drug; Group IIb was infused with olprinone (10 ug x kg(-1) loading dose plus 0.1 microg-kg(-1) min(-1) maintenance dose); Group IIc was infused with nicardipine (5 microg x kg(-1) x min(-1)) during olprinone administration. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). RESULTS: No difference in Pdi was observed between Groups Ia and Ib. After fatigue, in Groups IIa, IIb, and IIc, Pdi at low-frequency (20-Hz) stimulation decreased from prefatigued (baseline) values (P < 0.05), whereas there was no change in Pdi at high-frequency stimulation (100-Hz). In Group IIb, during olprinone administration, Pdi at both stimuli increased from fatigued values (P < 0.05). In Group IIc, the augmentation of Pdi to each stimulus in fatigued diaphragm by olprinone was abolished with an infusion of nicardipine. CONCLUSION: Low-dose olprinone does not affect contractility in nonfatigued diaphragm, but increases contractility in fatigued diaphragm via its effect on transmembrane calcium movement in dogs.
3',5'-Cyclic-AMP Phosphodiesterases↗
Evaluation of new TNM lung cancer classification.
OBJECTIVE: A new staging system for lung cancer was proposed by the Union Internationale Contre le Cancer in 1997, with Stages I and II subdivided and T3N0M0 assigned as stage IIB. We studied the usefulness of this new classification. METHODS: Subjects were 753 patients with non-small-cell lung cancer undergoing pulmonary resection and follow-up data were retrospectively reviewed. RESULTS: A significant difference was seen between stage IA and IB survival--70.4% vs 52%. No significant difference was seen between survival for T3N0M0, T1N1M0 and T2N1M0--35.3%, 42.3%, and 43.8%--at 5 years. We found, however, that the prognosis for T3N2M0 tumors--6.5% 5-year survival--is too poor to be grouped with other N2 diseases having a better prognosis--23.9% 5-year survival. Significant differences were also seen in the survival of T3N0 or T3N1 patients by organ and diseases involving the rib, diaphragm, or mediastinum may be classified as T4. CONCLUSION: The new staging system predicts patient outcome fairly well and the modification is well grounded. It appears, however, to be appropriate to subdivide T3 tumors by invaded organs and T3N2M0 disease may be better classified as stage IIIB. The classification of pulmonary metastasis appears to require further improvement.
Adult↗
Left diaphragmatic hernia complicated by perforation of an intrathoracic gastric ulcer into the aorta: report of a case.
We describe herein a rare but fatal complication of diaphragmatic hernia that occurred in a 51-year-old man 3 years after his diaphragm had been repaired by a polytetrafluoroethylene sheet following resection during pleuropneumonectomy for a left pleural mesothelioma. He was admitted to our hospital in shock status, and was found to have massive bleeding from the nasogastric tube. An emergency operation revealed that an ulcer of the stomach, which had been displaced into the left thorax, had perforated directly into the descending aorta.
Aorta, Thoracic↗
Effect of avicatonin (chicken carbocalcitonin) on galvanic skin response: a randomized, prospective, double-blind, controlled study for an objective assessment of pain.
In an attempt to objectively evaluate the analgesic effect of avicatonin (chicken carbocalcitonin), galvanic skin response (GSR) was recorded in 18 patients with osteoporosis or osteopenia and backache in a randomized, prospective, double-blind, controlled study. Backache on examination and in daily living was assessed weekly by scores utilizing a questionnaire. After two measurements 1 week apart on induction of backache with a maximum anterior flexion of the back from a supine position, either 20 units of avicatonin or inactive placebo was intramuscularly injected once a week for 4 consecutive weeks. In the avicatonin group but not in the placebo group, the area under the curve (AUC) of GSR tracing was decreased, giving a significant difference between the avicatonin and placebo groups after the second week. The pain score obtained by questionnaire decreased in both groups, suggesting a placebo effect. Galvanic skin response may provide a breakthrough to the objective and reliable evaluation of the biological response to pain which could not be accomplished by questionnaires based on subjective impression markedly influenced by emotional and psychological factors.
Aged↗
Significance of plasma thymosin alpha1 measurements in gastric cancer patients.
Thymosin alpha1 is a cleavage product of prothymosin alpha. Expression of prothymosin alpha increases during cell proliferation. Thymosin alpha1, measurable in plasma, may be an indicator of cell proliferation especially if a cancer is present. In this report we investigated the relation between the clinical behavior of gastric cancer and the plasma thymosin alpha1 level. Plasma thymosin alpha1 was measured in 52 gastric cancer patients using a newly developed radioimmunoassay. Twenty-one tumors and lymph nodes were examined for thymosin alpha1 using immunohistochemistry. The plasma thymosin alpha1 level was higher in gastric cancer patients than in normal volunteers; and it was higher in patients with lymph node involvement than in those with negative nodes. Immunohistochemical study of thymosin alpha1 showed positivity in 52% of gastric cancers and 100% of lymph node metastasis. We concluded that a high level of plasma thymosin alpha1 suggests aggressive behavior of a gastric cancer, such as lymph node involvement.
Biomarkers, Tumor↗
Appraisal of surgical resection of gallbladder cancer with special reference to lymph node dissection.
BACKGROUND: Radical lymph node dissection in surgery for advanced gallbladder cancer is controversial. The purpose of this study is to evaluate the role of lymph node dissection based on the clinico-pathologic results. PATIENTS: Seventy-three patients who underwent radical surgery including systematic dissection of the N1+N2 region lymph node plus some of the para-aortic nodes were reviewed. RESULTS: pT1 patients had no lymph node metastasis, but pT2 and pT3/pT4 patients had lymph node metastasis at a rate of 50.0% (13/26) and 83.3% (25/30), respectively. As infiltration of the hepatoduodenal ligament (Binf) became severe, the rate and extent of lymph node metastasis increased. There were four 5-year survivors with lymph node involvement. The 5-year survival rates are 77.0% in pN0 cases and 27.3% in pN1 cases (P<0.01). There was no difference in survival between pN1 and pN2 patients. However, significant differences in survival were observed between pN0/1 and pN2/3 patients when these patients were limited to Binf0/1. Examination of the recurrence pattern showed that most patients with pN0/1/2 had no regional lymph node recurrence, but there was para-aortic lymph node recurrence in patients with pN3 outside the dissected region. Significant prognostic factors influencing survival after surgery by multivariate analysis were pN2/3, pT, and residual tumor. CONCLUSION: Systematic lymph node dissection of N1, N2, and part of the para-aortic region improves survival in advanced gallbladder cancer patients, especially in those without either para-aortic lymph node metastases or Binf2/3.
Adult↗
Growth of incidental meningiomas.
The aim of this study was to assess the growth of incidental meningiomas, to establish a strategy for dealing with these tumours. The cases of 37 patients with a meningioma revealed incidentally by computerized tomography or magnetic resonance imaging, who were followed at least once by an additional imaging study, were reviewed. The tumour volume was calculated, to estimate the annual growth rate of the incidental meningiomas. Nine of the 37 patients (24.3%) showed a considerable increase (the annual growth rate > 1 cu cm/year) in their tumour volume (tumour growth). There was no significant difference in the follow-up period, age, or the volume of tumour between the patients with and without tumour growth. However, a multivariate analysis revealed that the likelihood of tumour growth independently and significantly increased according to a decrease in the age of the patients (Odds ratio 0.18 for one-standard-deviation change (ISD) 12.6 years, p = 0.042) and according to an increase in the volume of the tumour (Odds ratio 3.64 for ISD 4.46 cu cm, p = 0.042). The majority of patients with incidental meningioma can be apparently observed without any surgical intervention, because their annual growth rates are generally less than 1 cu cm/year. However, clinical and radiological observations would be advisable for these patients (especially young patients and patients with a large tumour), in view of the presence of rapidly growing tumours in some of the patients.
Adult↗
Increase of intestinal calcium absorption and bone mineral density by heated algal ingredient (HAI) in rats.
Active absorbable calcium (AAACa) produced by adding HAI (heated algal ingredient) to oyster shell calcium (AACa) is quite efficiently absorbed from the intestine and can increase bone mineral density in elderly osteoporotic patients. HAI was produced by heating the seaweed Cystophyllum fusiforme under reduced pressure, extracting with 6N HCL, and partially neutralizing it. Butanol-ethanol extraction then yielded active HAI fraction A, corresponding to about 1% in weight. The active HAI fraction increased intestinal Ca absorption as shown by a dose-dependent increase of plasma Ca in young male parathyroidectomized rats maintained on a low-Ca diet by administration through a stomach tube with a constant dose of AACa. The action of the active fraction A to maintain bone mass was then tested in young male rats kept on a low-Ca diet for 2 weeks. Bone weight, trabecular bone density, and strength-strain index as indices of bone strength measured by peripheral computed tomography (pQCT) tended to increase when the active HAI fraction was given along with Ca. HAI increased intestinal Ca absorption and prevented the decrease of bone density in rats kept on a low-Ca diet.
Animals↗
Peripheral computed tomography (pQCT) detected short-term effect of AAACa (heated oyster shell with heated algal ingredient HAI): a double-blind comparison with CaCO3 and placebo.
Trabecular bone density at the distal radius and cortical bone density at the midradius were measured in four randomized groups of women before and after 4 months administration of AAACa, oyster shell heated under reduced pressure with addition of heated algal ingredient (HAI) (group A); AACa, the same preparation without HAI (group B); CaCO3 (group C); and placebo (group D) in a double-blind system using peripheral quantitative computed tomography (pQCT) with lumbar spine density measurement by dual-energy X-ray absorptiometry (DXA). Groups A, B, and C received 900 mg/day elemental calcium and D received none. In subjects of group A, but not B, C, and D, radial trabecular bone density increased significantly, to 106.2% +/- 2.1% of the initial value (mean +/- SEM). The increase of trabecular bone density was significantly different from the placebo group (D) only in AAACa (group A) and not in AACa (group B) and the calcium carbonate (group C). Cortical bone density increase was also greater in group A (but not in B and C) than in D. Lumbar spine density did not change significantly. AAACa was apparently more effective, increasing trabecular bone density more than AACa and CaCO3 containing the same amount of elemental calcium.
Absorptiometry, Photon↗
Histological study of articular cartilage in experimental rat knee arthritis induced by intracapsular injection of cationic polyethyleneimine.
Degeneration of proteoglycans and abnormalities in their metabolism have been assumed to be critical at an early stage of osteoarthritis. To clarify a trigger mechanism of osteoarthritis, anionic sites of knee articular cartilage were blocked by intracapsular injection of cationic polyethyleneimine of 2000 or 70,000 molecular weight (MW) into rat knee joints. Experimental or normal rats were examined by gross observation, roentgenography, cytokine interleukin-1beta (IL-1beta) assay, and light or electron microscopy. In both groups with the polyethyleneimine injection, the rats showed temporarily limping and swelling of their knee joints. By light or electron microscopic studies, knee articular cartilage was found to be degenerated at an early stage, but IL-1beta was within normal levels. At 2, 4, or 6 months, the deformity of the knee joints was obvious by roentgenography. Degeneration and hypofunction of proteoglycans might be related to the ultrastructural changes of articular cartilage at an early stage, though the inflammatory cytokine was not involved. At later stages the pathophysiology of the knee joints advanced chronically to typical osteoarthritis, which was more radically induced by the large molecular polyethyleneimine (70,000 MW). The functional impairment of anionic sites is a key point for elucidating the mechanism of osteoarthritic development in this animal model.
Animals↗
Effect of n-3 fatty acid deficiency on fatty acid composition and metabolism of aminophospholipids in rat brain synaptosomes.
Docosahexaenoic acid (DHA, 22:6n-3) is one of the major polyunsaturated fatty acids esterified predominantly in aminophospholipids such as ethanolamine glycerophospholipid (EtnGpl) and serine glycerophospholipid (SerGpl) in the brain. Synaptosomes prepared from rats fed an n-3 fatty acid-deficient safflower oil (Saf) diet had significantly decreased 22:6n-3 content with a compensatory increased 22:5n-6 content when compared with rats fed an n-3 fatty acid-sufficient perilla oil (Per) diet. When the Saf group was shifted to a diet supplemented with safflower oil plus 22:6n-3 (Saf + DHA) after weaning, 22:6n-3 content was found to be restored to the level of the Per group. The uptake of [3H]ethanolamine and its conversion to [3H]EtnGpl did not differ significantly among the three dietary groups, whereas the formation of [3H]lysoEtnGpl from [3H]ethanolamine was significantly lower in the Saf group than in the other groups. The uptake of [3H]serine, its incorporation into [3H]SerGpl, and the conversion into [3H]EtnGpl by decarboxylation of [3H]SerGpl did not differ among the three dietary groups. The observed decrease in lysoEtnGpl formation associated with a reduction of 22:6n-3 content in rat brain synaptosomes by n-3 fatty acid deprivation may provide a clue to reveal biochemical bases for the dietary fatty acids-behavior link.
Animals↗
Granisetron, droperidol, and metoclopramide for the treatment of established postoperative nausea and vomiting in women undergoing gynecologic surgery.
OBJECTIVE: The aim of this study was to evaluate granisetron, droperidol, and metoclopramide for efficacy and safety in the treatment of established postoperative nausea and vomiting after major gynecologic surgery. STUDY DESIGN: One hundred twenty postoperative female patients were monitored for the first 3 hours after anesthesia in the postanesthesia care unit and for the next 24 hours after anesthesia in the ward. Patients who had postoperative nausea and vomiting within the first 3 hours after anesthesia received intravenously, in a randomized double-blind manner, 40 microg/kg granisetron, 20 microg/kg droperidol, or 0.2 mg/kg metoclopramide. Patients were then observed for 24 hours after drug administration. RESULTS: Complete control of established postoperative nausea and vomiting, defined as no emesis and no need for another rescue antiemetic medication, was more frequent among the patients who had received granisetron (88%) than among those who had received droperidol (55%) or metoclopramide (50%) (P <.05). The severity of nausea was less in patients who had received granisetron than in those who had received droperidol or metoclopramide (P <.05). No clinically adverse events were observed in any of the groups. CONCLUSION: Granisetron is more effective than droperidol or metoclopramide for the treatment of established postoperative nausea and vomiting during the first 3 hours after anesthesia in patients undergoing major gynecologic operations.
Adult↗
A study on the mechanism of the proton transport in bacteriorhodopsin: the importance of the water molecule.
The mechanism of proton transport around the Schiff base in bacteriorhodopsin was investigated by ab initio molecular orbital (MO) calculations. Computations were performed for the case where there is a water molecule between the Schiff base and the Asp residue and for the case where there is no water molecule. Changes in the atomic configuration and potential energy through the proton transport process were compared between two cases. In the absence of water, the protonated Schiff base was not stable, and a proton was spontaneously detached from the Schiff base. On the other hand, a stable structure of the protonated Schiff base was obtained in the presence of water. This suggests that the presence of a water molecule is required for stability in the formation of a protonated Schiff base.
Aspartic Acid↗