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Biomedical subjects

N Hasegawa

Publications and source records attributed to N Hasegawa.

At least 19 recordsLinked to original sources

Elevated promotion of prostacyclin production by synthetic lipid A analogs in aged human endothelial cells in culture.

We examined the effects of E. coli lipopolysaccharide (LPS) and synthetic analogs of lipid A, a bioactive moiety of LPS, on the prostacyclin (PGI2) production by young and old human endothelial cells in vitro. PGI2 production by endothelial cells has been shown to decrease during in vitro cellular senescence as well as in vivo. LPS and all the analogs tested in this study did not stimulate PGI2 production by young endothelial cells more than twofold. However, LPS and the majority of the lipid A analogs examined stimulated the PGI2 production by old cells more than twofold (approximately two- to sixfold). These results indicate that the responses to certain stimuli sometimes differ markedly between young and old cells, and this should be carefully considered when evaluating the biological effects of various compounds. Furthermore, these results suggest that certain synthetic lipid A analogs can be used as drugs to prevent some age-related vascular diseases.

Age Factors

Hemangioma of the esophagus: endosonographic imaging and endoscopic resection.

A 49-year-old Japanese man was seen to have an esophageal tumor on a routine barium swallow examination. Endoscopy revealed a sessile polyp covered by an almost normal esophageal mucosa, and the bioptic histology was non-diagnostic. Endoscopic ultrasonography showed a hypoechoic tumor with a diameter of 12 mm, confined to the submucosal layer, with the underlying muscularis propria layer being intact. On the basis of this finding, endoscopic resection was chosen and the tumor was resected using a two-channel endoscope, with prior hypertonic saline and epinephrine injection. The pathologic diagnosis was a cavernous hemangioma of the esophagus.

Esophageal Neoplasms

Primary malignant melanoma of the esophagus presenting with massive hematemesis.

A 66-year-old Japanese man was admitted to our hospital, presenting with massive hematemesis. Emergency endoscopy revealed a bleeding tumor at the esophagogastric junction. The endoscopic appearance of the tumor was that of a Borrmann 2-like tumor, with a brownish-black discoloration. Bioptic histology confirmed the diagnosis of malignant melanoma. Atypical melanocytes with junctional changes were also found at a small pigmented patch in the lower esophagus, separate from the gross tumor. Melanocytosis was noted in the adjacent esophageal epithelium in the resection specimen following surgery. No primary lesion was found elsewhere, even in the patient's skin. These pathologic findings support the possibility of multicentric occurrence of malignant melanoma in esophageal melanocytosis. The patient is alive 11 months later, with multiple liver metastases. Massive hematemesis is an unusual presentation of primary malignant melanoma of the esophagus.

Aged

Clinical value of a new serum tumor marker, CA125II, in gynecologic disease: comparison with CA125.

CA125 II, an improved version of the conventional CA125 was compared with CA125 as to which was more useful in gynecologic disease. In the diagnosis of tumors around the adnexal field (primary epithelial ovarian cancer, metastatic ovarian cancer, benign ovarian tumor and endometrial cyst), CA125 II showed the same sensitivity and specificity as CA125. CA125 II also has high simultaneous reproducibility in the low concentration area. The examination by the receiver operating characteristic curve revealed that CA125 II has higher precision than that of CA125 when it is used for the screening test. In conclusion, CA125 II is a better tumor marker than conventional CA125.

Biomarkers, Tumor

[Intraoperative hypoperfusion after coronary artery bypass grafting in a child with Kawasaki's disease: report of a case].

An 11-year-old boy with Kawasaki's disease who developed congestive heart failure due to acute myocardial infarction underwent coronary artery bypass grafting using the bilateral internal thoracic arteries. The surgical procedures were performed to the left anterior descending artery with the right internal thoracic artery and to the diagonal branch with the left internal thoracic artery with the aid of extracorporeal circulation and cardiac arrest with blood cardioplegia. About 30 minutes after the discontinuation of extracorporeal circulation, catastrophic ventricular fibrillation with acute left heart failure occurred because of coronary hypoperfusion. The cardiopulmonary bypass was reestablished after 20 minutes of resuscitation under cardiac massage. Additional saphenous vein graft bypass to the left anterior descending coronary artery that was already revascularized by the right internal thoracic artery was performed. Weaning from the cardiopulmonary bypass was then possible, and the patient were successfully treated using the delayed sternal closure technique. Use of the bilateral internal thoracic arteries appears to be beneficial in children with Kawasaki's disease to produce grafts in the growing heart, but the possibility of early catastrophic flow deterioration must be recognized because smaller arerial size provides inadequate nutritional support for the myocardium. The additional use of saphenous vein grafting might be beneficial in the case of severe coronary ischemia with small-sized internal thoracic arteries.

Child

Duodenal carcinoid tumor: endosonographic imaging and endoscopic resection.

A 75-yr-old Japanese woman was shown by endoscopy to have a sessile polyp in the duodenal bulb. Endoscopic biopsy confirmed the diagnosis of carcinoid tumor. The endoscopic ultrasound probe showed a 6-mm hypoechoic tumor that was confined to the submucosal layer; the underlying muscularis propria layer was intact. On the basis of these findings, endoscopic resection was chosen, and the tumor was completely resected by the strip biopsy technique with prior hypertonic saline and epinephrine injection; there were no complications.

Aged

Lymphoma syndrome leukemia revealed interesting finding on brain CT and ultrasound scan of abdomen at the initial presentation.

This paper reports on a patient with lymphoma syndrome leukemia (LSL) who showed interesting findings on brain computed tomography (CT) and ultrasound scans of the abdomen at the initial presentation. The patient was a 5 year old girl. When she was admitted to our hospital, there were many lymph nodes palpable. The abdomen was distended and the liver and spleen were palpable below the umbilicus. Hematologic examinations revealed a leukocyte count of 275,800/microL with 98% lymphoblasts. Chest X-ray film revealed a mediastinal mass. The diagnosis of LSL was made. Her brain CT scan showed a low density area in the right thalamic region without contrast enhancement; infarction was suspected. Furthermore, her abdominal ultrasound scan showed hepatosplenomegaly, kidney swelling with increasing echogenicity and hydronephrosis and stones in the renal pelvis and bladder. These findings are unprecedentedly rare in cases of childhood acute lymphoblastic leukemia (ALL), much less in LSL.

Abdomen

Effects of ONO-1078, a peptide leukotriene antagonist, on endotoxin-induced acute lung injury.

The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS group (n = 9) injected intravenously with 2 mg E. coli LPS, an ONO group (n = 8) receiving 30 mg/kg of intraperitoneal ONO, and an LPS+ONO group (n = 6) receiving 30 mg/kg of ONO intraperitoneally 10 min before the LPS injection. The [125I]albumin lung plasma ratio, which is a parameter of acute lung injury, was significantly increased (p < 0.01) in the LPS group compared with the saline, ONO, and LPS+ONO groups. The [125I]albumin BAL fluid plasma ratio was also increased (p < 0.01) in the LPS group compared with the other groups. ONO pretreatment attenuated the LPS-induced increases in neutrophil counts in the BAL fluid. In vitro studies showed that ONO suppresses the neutrophil chemotaxis induced by LTB4, zymosan-activated serum, and FMLP. We conclude that (1) ONO-1078 attenuates LPS-induced acute lung injury; and (2) this effect appears mainly a result of its potent antagonistic actions against peptide leukotrienes and also, in part, the suppression of neutrophil chemotaxis.

Albumins

Clinical significance of measuring myeloperoxidase, thiobarbituric acid reactive material and 7S collagen in plasma of patients with adult respiratory distress syndrome.

We measured myeloperoxidase (MPO), thiobarbituric acid reactive material (TBARM), and Type IV collagen 7S domain (7S collagen) in the plasma of 21 patients with acute lung injury (ALI). Sixteen healthy subjects served as a control group. There was no significant difference in MPO between the control and ALI groups. The TBARM and 7S collagen concentrations in ALI (TBARM; 3.05 +/- 0.65 nMol/ml, 7S collagen 9.06 +/- 5.96 ng/ml: Mean +/- SD) were significantly higher than those in the control group (2.54 +/- 0.33 and 3.43 +/- 1.05, p < 0.05). TBARM and 7S collagen levels of deceased ALI patients were higher than those of surviving ALI patients (p < 0.05). There were significant correlations between the plasma levels of these two parameters and the lung injury scores. Our findings suggest that plasma TBARM and 7S collagen are useful markers for the assessment of the severity of ARDS.

Adolescent

[Concomitant graft replacement of the total aortic root and the transverse aortic arch for type A aortic dissection associated with Marfan syndrome: report of a case].

A 25-year-old man of Marfan syndrome with chronic stage aortic dissection of Stanford type A underwent concomitant graft replacement of the total aortic root and transverse aortic arch. The surgical procedure were performed with an aid of extracorporeal circulation, blood cardioplegia, using the techniques of "open distal anastomosis" under the deep hypothermic circulatory arrest and continuous retrograde cerebral perfusion for cerebral protection during circulatory arrest. The operative techniques consisted of total aortic root replacement using a composite graft with Piehler's and Carrel patch technique for left and right coronary artery, and total arch replacement using en bloc distal arch reconstruction and a composite graft replacement for innominate artery. There were no neurological complications. In the case of Marfan syndrome, type A aortic dissection involving aortic arch should be treated by concomitant graft replacement of the total aortic root and the transverse aortic arch in order to reduce the late risk of aortic dissection or annular dilatation.

Adult

Epidermal growth factor suppresses in vitro senescence in the ability of human umbilical vein endothelial cells to proliferate, but not in the ability to produce prostacyclin.

Addition of epidermal growth factor (EGF) to culture medium extended the replicative life span of human umbilical vein endothelial (HUVE) cells in culture. In brief, EGF suppresses the age-related decrease (in vitro senescence) in cell proliferative ability. However, the addition of EGF did not extend the culture period in which prostacyclin (PGI2) is actively produced by the cells. Therefore, EGF does not suppress the age-related decrease (in vitro senescence) in the ability of cultured HUVE cells to produce PGI2. These results suggest that the process of in vitro senescence in the cell proliferative ability is not necessarily correlated with that of in vitro senescence in the ability to produce PGI2.

Cell Division

Influence of chest background on pulmonary 99mTc-DTPA clearance in interstitial lung disease.

We examined the effect of chest extracellular 99mTc-diethylenetriamine pentaacetate (DTPA) as a background in the measurement of pulmonary 99mTc-DTPA clearance in patients with interstitial lung disease (ILD). Eight healthy nonsmokers (HN) and eight patients with ILD were studied. We monitored changes in gamma counts after the inhalation of 99mTc-DTPA aerosol by using a gamma camera placed over the anterior chest. The rate constant of pulmonary 99mTc-DTPA clearance (k; %/min) was assessed by calculating the slope of the decrease in the gamma counts. The chest background, estimated by 99mTc-DTPA intravenous injection, was subtracted from the original data to obtain the corrected DTPA clearance (kc; %/min). In patients with ILD, k was significantly greater [2.19 +/- 1.03 (SD) %/min; n = 8] compared with HN (0.86 +/- 0.17%/min; n = 8; P < 0.01). In patients with ILD, kc was also greater (2.80 +/- 1.15%/min; n = 8; P < 0.01) compared with HN (1.20 +/- 0.12%/min; n = 8). There was no difference in percent underestimation of k between the two groups (29.1 +/- 8.8% for HN, 22.5 +/- 7.9% for patients with ILD). There was a significant correlation between k and kc among all subjects (r = 0.987, P < 0.01). We conclude that background causes significant underestimation of pulmonary 99mTc-DTPA clearance.

Adult

Granulocyte colony-stimulating factor does not enhance endotoxin-induced acute lung injury in guinea pigs.

We studied recombinant human granulocyte colony-stimulating factor (G-CSF) in terms of its hematopoietic and neutrophil-activating effects on acute lung injury induced by endotoxin. Guinea pigs were divided into four groups: (1) saline control animals, (2) endotoxin alone, (3) cyclophosphamide (CPA)+endotoxin, and (4) G-CSF+endotoxin. A G-CSF dose of 20 micrograms/kg was given subcutaneously twice a day for 5 days. Animals were observed for 4 h after intravenously administered endotoxin (0.02 and 2.0 mg/kg) with serial measurements of complete blood counts and hemodynamics. Lung extravascular water, [125I]albumin leakage in lung tissue, and histopathologic features were examined at death. The endotoxin-alone group showed peripheral leukopenia, transient hypotension, excess lung water, increased albumin leakage, PMN accumulation in lung tissue, and gross histopathologic edema. G-CSF-treated animals showed attenuated responses in peripheral leukopenia, excess lung water, and albumin leakage in comparison with the endotoxin-alone group. No augmented responses were seen in the G-CSF group. The CPA+endotoxin group also had attenuated lung injury, which was similar to that in the G-CSF group. In conclusion, pretreatment with G-CSF tended to attenuate rather than enhance neutrophil-dependent acute lung responses to endotoxin.

Animals

Degradation and distribution of brain natriuretic peptide in porcine tissues.

Brain natriuretic peptide (BNP) is a novel peptide that has actions similar to atrial natriuretic peptide (ANP). The present study investigated BNP localization in the heart, ANP and BNP contents in several organs, and ANP and BNP clearance through these organs. In the morphological study, it was shown that porcine BNP-like immunoreactivity was mainly distributed in the granules of the atrium. The content of porcine BNP-like immunoreactivity in the atrium was extremely high, about 100-fold greater than in the ventricle. From the determination of porcine BNP and ANP contents of such organs as the heart, kidney and liver and also plasma, it was shown that porcine BNP concentration was approximately one order of magnitude lower than that of ANP, and clearance rates of ANP and porcine BNP from these organs were similar and not significantly different between the organs. These results suggest that the modes of secretion and degradation of porcine BNP are not the same as those of ANP.

Animals

[Reproductive and developmental toxicity study of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187). (II)--Oral administration to rats during the period of fetal organogenesis (prenatal examination)

6-Amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187) was given orally to pregnant Crj : CD (Sprague-Dawley) rats from days 7 through 17 of gestation at dose levels of 50, 200 and 800 mg/kg/day. In the 800 mg/kg/day group, salivation just after dosing, suppression in body weight gain and decreased food consumption were observed. No external, visceral and skeletal anomalies attributable to FUT-187 were observed in fetuses. From the present result, it is considered that the no-effect dose level of FUT-187 for dams and fetuses are 200 mg/kg/day and 800 mg/kg/day respectively.

Administration, Oral

[Reproductive and developmental toxicity studies of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187). (IV)--Oral administration to New Zealand white rabbits during the period of fetal organogenesis.

Oral administration of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) at doses of 10, 30 and 100 mg/kg was given to New Zealand White rabbits on days 6 to 18 of gestation. The following results were obtained. Decreased food consumption and suppression of body weight gain in dams were observed and these changes contributed to the increase in aborted or prematured births and increased fetal mortality at the 100 mg/kg group. There were changes attributable to FUT-187 on external, skeletal and visceral examinations of fetuses. Based on the above, the no-effect dose level in dams and fetuses in the present study is 30 mg/kg/day.

Administration, Oral