PubMed HealthSearch

Biomedical subjects

N Hasegawa

Publications and source records attributed to N Hasegawa.

At least 19 recordsLinked to original sources

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

The role of recombinant human tissue-type plasminogen activator in the treatment of acute pulmonary thromboembolism.

The effect of intravenous recombinant human tissue-type plasminogen activator (tPA) on arterial blood gases was compared with the effect of heparin treatment in acute pulmonary thromboembolism. Fifteen patients received heparin alone (group A), 5 cases were treated with 7.7 x 10(6) I.U. of tPA (group B) and 10 cases with 15 x 10(6) I.U. of tPA (group C) combined with heparin treatment. Arterial oxygen tension before treatment was not significantly different among the three groups. PaO2 was dramatically improved on the 1st day in group C. By the 7th day, PaO2 of group B had improved to the level of group C. However, the PaO2 of group A on the 7th day was not significantly different compared to the pre-treatment value. In group C, post-treatment perfusion lung scintigrams were improved compared to the pre-treatment images, but this was not the case in group B. Treatment with tPA is more effective for acute pulmonary thromboembolism than heparin alone and a high dose of tPA (15 x 10(6) I.U.) leads to rapid improvement in arterial blood gases and lung perfusion images.

Acute Disease

[Effects of exercise training on restoration of residual myocardial ischemia after percutaneous transluminal coronary angioplasty].

The effects of exercise training on the restoration of hibernating myocardium after percutaneous transluminal coronary angioplasty (PTCA) were evaluated. Symptom-limited treadmill exercise with thallium-201 myocardial single photon emission CT (SPECT) was performed at one and 13 weeks after PTCA in 15 patients with training and in 15 control patients without training who had no restenosis on repeat angiography. For quantitative analysis, counts for the regions of interest (ROI) were calculated in the hypoperfused area on the polar map. Percent T1 uptake was determined by dividing counts of the hypoperfused area by counts of a normal reference area on the initial image (%IU) and delayed image (%DU). The difference between %DU and %IU, defined as percent redistribution (%RD), was a parameter of residual ischemia in the hypoperfused area. %DU increased significantly in the trained group (65 +/- 11 to 73 +/- 9.3%, p < 0.01) and in the untrained group (66 +/- 14 to 70 +/- 15%, p < 0.05). %RD decreased significantly in the trained group (6.3 +/- 3.2 to 2.8 +/- 2.3%, p < 0.01); whereas, there was no significant change in the untrained group (6.1 +/- 2.8 to 5.2 +/- 3.8%). These findings suggest that, after successful PTCA, exercise training helps alleviate myocardial ischemia, probably by fostering the promoting effects which restore the hibernating myocardium.

Aged

Studies on antitumor effects and mechanism of action of l-hexylcarbamoyl-5-fluorouracil by DNA/BrdU double staining using flow cytometry.

An investigation was carried out to elucidate the mechanism of action of the oral antitumor agent 1-hexylcarbamoyl-5-fluorouracil (HCFU) by determining its effects on the growth and cell cycle of epipharyngeal carcinoma cells (KB cell) by DNA/BrdU double staining using flow cytometry (FCM). As a result, it was found that HCFU stimulates KB cells in the S phase to proliferate for the first 3 days of treatment in a low concentration (8 micrograms/ml) and caused cell accumulation in the later G2M phase. On the other hand, when administered in the concentration (20 micrograms/ml) that produces a 50 per cent cell kill, as determined from the cell growth curve, HCFU appeared to exhibit a cytocidal effect by blocking cells in S and G2M for the first 3 days after exposure. It was revealed by FCM for the first time that HCFU operates by a similar mechanism to that of 5-FU. This method seems to be of significance to therapeutic schemes that take into consideration the mechanism of action of antitumor drugs.

Antineoplastic Agents

[Measurements of plasmin-alpha 2 plasmin inhibitor complex and FDP.D dimer levels in the fibrinolytic therapy of acute pulmonary thromboembolism].

The key enzyme for fibrinolysis is plasmin, which is converted from plasminogen by plasminogen activator. Activated plasmin lyses fibrinogen and fibrin to make fibrin degradation products(FDPs) and plasmin is inactivated immediately by alpha 2 plasmin inhibitor. As FDP.D dimer is derived solely from insoluble fibrin, FDP.D dimer is thought of as an index for clot lysis. We measured plasmin-alpha 2 plasmin inhibitor complex(PIC) and FDP.D dimer plasma levels in 3 patients with acute pulmonary thromboembolism treated with recombinant tissue plasminogen activator(tPA). Fifteen million units of tPA(TD-2061) were infused in one hour on the first, second and third hospital days. PIC and FDP.D dimer before tPA infusion showed slightly elevated values as compared to normal ranges. They increased markedly after tPA infusion. These findings suggest that the fibrinolytic system is slightly activated in the acute phase of pulmonary thromboembolism and also strongly activated by tPA infusion. Increased FDP D dimer suggests that fibrin clots are dissolved by activated plasmin. Improvement of arterial oxygen tension was observed after tPA infusion. As sustained higher FDP.D dimer means the existence of fibrin clots, heparin treatment should be continued for prevention of clot formation as long as FDP.D dimer shows higher value. In conclusion, PIC and FDP.D dimer are useful indices not only to detect the activated state of the fibrinolytic system but also to know clot lysis in tPA treatment.

Acute Disease

Concentrations and molecular forms of C-type natriuretic peptide in brain and cerebrospinal fluid.

To develop a radioimmunoassay (RIA) specific for human C-type natriuretic peptide (hCNP), we used a highly specific antiserum raised in rabbits. Quantitative inhibition tests with various natriuretic peptides demonstrated that the 50% inhibitory dose of hCNP was 15 fmol, whereas those of other natriuretic peptides were 10(5)-fold higher, indicating a specificity satisfactory for determining concentrations of hCNP in tissues. Using this antiserum, we detected immunoreactive hCNP (ir-hCNP) in various regions of human brain and spinal cord, as well as in cerebrospinal fluid (CSF). The ir-hCNP concentrations in human neural tissues were approximately 10-fold higher than those of immunoreactive human atrial natriuretic peptide (ir-hANP). The mean (+/- SD) concentration of ir-hCNP (72.0 +/- 17.8 ng/L) in CSF also was 10-fold higher than that of ir-hANP (5.2 +/- 2.1 ng/L). Using gel-permeation chromatography, we identified two molecular forms of ir-hCNP in brain and CSF: a 2-kDa form corresponding to mature hCNP, which is composed of 22 amino acid residues (hCNP-22), and a 5- to 6-kDa form corresponding to an N-terminally extended molecule (hCNP-53). The latter form was predominant in brain; the former was the main constituent of hCNP in CSF. These results support the hypothesis that hCNP is a major natriuretic peptide, is synthesized in human brain, and functions in human central nervous tissues.

Aged

[Delayed sternal closure after cardiac surgery].

Following cardiac surgery, approximation of sternum will produce systemic hypotension or elevation of left atrial and central venous pressures. A new criteria for delayed sternal closure is proposed. Sternal closure has to be delayed when mean left atrial or central venous pressures increased over 2 mmHg at the tentative closure. In seven cases (3.5%) of consecutive 201 patients was delayed the sternal closure under the above mentioned state, all survived and received the successful closure later. One of them died of congestive heart failure four months after the operation and one died of the rupture of the ascending aortic pseudoaneurysm eleven months after the initial operation. Microbiological examination of the mediastinal and pericardial contents obtained at the final sternal closure were negative in all cases. Comparing the total cardiopulmonary bypass time, ventricular fibrillation time, and myocardial ischemic time between in the secondary closure group and in the primary closure group, the total bypass time and the ventricular fibrillation time of the former were significantly longer than the latter, but the ischemic time revealed no difference. In conclusions, persistent elevation of left atrial or central venous pressures after cardiac surgery at the tentative sternal closure seems the reliable predictor for the delayed closure of the sternum. Careful post-operative management prevents serious mediastinal infection. Delayed sternal closure is preferable procedure for the patient with brittle hemodynamics after open heart surgery.

Adult

[A case report: successful direct closure of atrial septal defect in isolated right ventricular hypoplasia].

We experienced a surgery for an isolated right ventricular hypoplasia with atrial septal defect (ASD). The patient, 3 1/2-year-old girl, underwent direct closure of ASD. Preoperatively right ventricular end diastolic volume was 18 ml or 22 ml including trabecular portion by angiocardiographic examination. It was almost a half of normal. We performed intraoperative ASD occlusion test using a Foley 12 F balloon catheter before surgical closure of ASD. Postoperatively, mild right pleural effusion was found, but it disappeared soon with a use of diuretics. ASD occlusion test was safe and useful for estimating surgical closure of ASD. Postoperative cardiac catheterization revealed slight increase of right atrial pressure. It is necessary to follow up her condition carefully.

Child, Preschool

[A case of middle lobar bulla associated with severe bronchial asthma].

We experienced a case of middle lobar bulla associated with severe bronchial asthma. Bulla occurs favoritely at apical area and S6, and middle lobar bulla which is very rare has been reported to cause higher ventilatory disorder compared with superior lobar bulla, when it becomes giant. The pathogenesis of the present middle lobar bulla remains unknown, but steroid administration to bronchial asthma may possibly have influenced pleura and/or lung parenchyma. We would like to make its further observation, paying attention to its possible recurrence and its occurrence at other sites.

Adult

[A case of intrathoracic chest wall type lipoma].

Intrathoracic lipoma is a comparatively rare disease. We have recently experienced a case of intrathoracic chest wall type lipoma associated with Charcot-Marie-Tooth disease. The case was a 16-year-old man, in whom preoperative examination of his foot-drop due to Charcot-Marie-Tooth disease pointed out an abnormal chest shadow. Image diagnosis led to intrathoracic chest wall type lipoma. The tumor was easily resectable and was lipoma pathohistologically as well. The literature presented us with 22 cases of such lipoma, which appeared to be predominant for age not more than 10 and age 41-60 and to occur favorably in postero-superior chest wall. Preoperative diagnosis of the present disease became possible to a certain extent by means of CT, MRI. However, in view of imperfect differentiation between lipoma and liposarcoma, surgical resection should be considered, if possibly. No case of intrathoracic lipoma associated with Charcot-Marie-Tooth disease had been reported in the literature, and the causal relationship there between also remains unknown, but to be further examined.

Adolescent

[Surgical analysis of mediastinal lymphangioma--analysis of 7 cases].

Mediastinal lymphangioma is a very rare disease. In this study, we evaluated 7 surgically treated cases of mediastinal lymphangioma. Four males and 3 females with ages ranging from 5 months to 74 years (average 31.4 years) were examined. Four patients were asymptomatic but had abnormal shadows on their chest X-ray. Of the remaining patients, one had hoarseness and another had superior vena cava syndrome and both had dyspnea. The other patient was discovered because of cervical tumor. Multiple lymphangiomas were found in only 2 patients. One patient had 4 tumors and the other had 2 tumors in the mediastinum. Of all lymphangiomas, 2 were found in the superior mediastinum, 2 in the anterior mediastinum, 3 in the median mediastinum and 3 in the posterior mediastinum. All patients had cystic lymphangioma including 1 with capillary lymphangioma and 1 with cavernous lymphangioma. Median sternotomy was performed in 3 of the patients and posterolateral thoracotomy was performed in the remainder. The cervical tumor was removed by local incision. Complete resection of the lymphangiomas was performed and no recurrence was observed after surgery.

Adult

Differential regulation of estrogen-dependent sexual development of rat brain by growth factors.

Intraventricular infusion of antiserum to nerve growth factor (ANGF), but not that to insulin, epidermal growth factor nor normal rabbit serum, resisted estrogen-induced behavioral defeminization in the female rat neonates. A significant number of the ANGF-treated rats showed lordosis as adults despite neonatal estrogen, but positive feedback of estrogen on serum luteinizing hormone was absent. Sexual phenotype in behavioral and gonadotropic functions may be under differential development regulation.

Animals