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Biomedical subjects

N Hirata

Publications and source records attributed to N Hirata.

At least 73 records · Page 4Linked to original sources

Allergen exposure induces the expression of endothelial adhesion molecules in passively sensitized human bronchus: time course and the role of cytokines.

To study the mechanisms contributing to the recruitment of a selective leukocyte subset in allergic inflammation involving the airways as may occur in asthma, we examined whether allergic exposure induces the expression of cell adhesion molecules (CAMs) on the bronchial endothelium of passively sensitized human bronchi. Human bronchial tissue obtained from patients undergoing lung cancer surgery was passively sensitized with serum from patients with atopic asthma who were sensitive to house dust mite. We incubated the tissues for 30, 120, 240, and 480 min in the presence or absence of the dust mite allergen. The tissues were stained immunohistochemically for intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1). ICAM-1 was constitutively expressed in both the epithelium and endothelium in all tissues but after allergen stimulation significantly increased at 240 and 480 min. E-selectin expression also existed constitutively and increased significantly at 120 and 240 min with allergen exposure. The constitutive expression of VCAM-1 was less than that of ICAM-1 and E-selectin. Following allergen exposure, VCAM-1 expression increased significantly at 30, 120, 240, and 480 min, and at 480 min reached an almost 3.5-fold increase from baseline expression. The TNF-alpha level in the supernatants significantly increased at 120 min after allergen stimulation, and the interleukin (IL)-1beta level increased in 4 of 15 samples. We also examined the induction of CAMs by TNF-alpha, IL-1beta, and IL-4 on human bronchial tissue. TNF-alpha and IL-1beta increased the expression of ICAM-1, E-selectin, and VCAM-1, whereas IL-4 induced only that of VCAM-1. In addition, neutralizing antibody against TNF-alpha and IL-1beta partially blocked the upregulation of CAMs on passively sensitized bronchial tissue after allergen exposure. Thus, both an IgE-dependent allergic response and selected cytokines are able to upregulate endothelial CAMs in human bronchial tissue. These observations provide further evidence that leukocyte infiltration into the site of allergic inflammation as occurs in atopic asthma is in part regulated by the expression of ICAM-1, VCAM-1, and E-selectin.

Adult↗

Sulfoquinovosyldiacylglycerol, KM043, a new potent inhibitor of eukaryotic DNA polymerases and HIV-reverse transcriptase type 1 from a marine red alga, Gigartina tenella.

A new sulfolipid, KM043, which belongs to the 6-sulfo-alpha-D-quinovopyranosyl-(1-->3')-1',2'-diacylglycerol (SQDG) class of compounds, has been isolated from a marine red alga, Gigartina tenella, as a potent inhibitor of eukaryotic DNA polymerases and HIV-reverse transcriptase type 1. Its structure was determined on the basis of spectroscopic and gas chromatographic analyses. The inhibition was dose-dependent, and complete (more than 90%) inhibition of DNA polymerase alpha (pol. alpha), DNA polymerase beta (pol. beta) and HIV-reverse transcriptase type 1 (HIV-RT) was observed at concentrations of 5, 10, and 30 microM, respectively.

Chromatography, Gas↗

Efficacy of coronary artery bypass grafting in patients with a dilated left ventricle due to myocardial infarction.

This study was designed to clarify the efficacy of coronary artery bypass grafting (CABG) on left ventricular (LV) function in 16 patients with a dilated LV due to myocardial infarction (LV end-systolic volume index: LVESVI >60 ml/m2). All had attained complete revascularization. To estimate the LV wall motion quantitatively using echocardiography, a wall motion score (WMS) was used (LV was divided into 17 segments with a four-point scale: akinesis=3, severe hypokinesis=2, hypokinesis=1, normal=0 and then summed). Exercise stress tests were performed after surgery, revealing that anginal symptoms had vanished in all the patients. In 5 patients with a preoperative end-systolic volume index (ESVI) >100 ml/m2, the ejection fraction (EF) did not change, and both were under 30% (before to after: 26+/-4 to 26+/-4%). Neither the ESVI (148+/-50 to 133+/-39 ml/m2) nor the end-diastolic volume index (end-diastolic volume index (EDVI): 198+/-62 to 180+/-37 ml/m2) changed; the WMS did not change (33+/-2 to 33+/-3). During exercise, in spite of the increase in heart rate (HR) (at rest, 81+/-20; HR during exercise, 111+/-21 beats/min, p<0.005) and LV end-diastolic pressure (EDP) (22+/-9; 35+/-13 mmHg, p<0.02), both cardiac index (CI) (2.4+/-0.3; 2.6+/-0.4 L/min x m2) and minute work (MW: 4.0+/-1.1; 4.1+/-0.4 kg x M/min) did not increase. In 11 patients with a preoperative ESVI <100 ml/m2, EF was extremely increased in 5 patients (more than 10%, 35+/-4 to 60+/-6%, p<0.005=improved subgroup) in whom the EDVI (130+/-16 to 120+/-13 ml/m2) did not change whereas the ESVI (82+/-14 to 48+/-7 ml/m2) was reduced. However, in the 6 remaining patients (ie nonimproved subgroup), neither ESVI (78+/-8 to 74+/-12 ml/m2), EDVI (115+/-10 to 115+/-20 ml/m2) nor EF (31+/-7 to 35+/-3%) changed. During exercise, HR (at rest, 88+/-13; during exercise, 108+/-11 beats/min, p<0.005), LVEDP (20+/-6; 29+/-7 mmHg, p<0.01), CI (2.5+/-0.6; 3.3+/-0.5 L/min x m2, p<0.05), MW (4.6+/-1.0; 6.5+/-1.5 kg x M/min, p<0.05) increased. The WMS in the nonimproved subgroup did not change (29+/-6 to 27+/-2), but in the improved subgroup it reduced after surgery (27+/-3 to 19+/-4, p<0.01). These data suggested that CABG in patients with a dilated LV was effective against anginal symptoms, but was restricted to left ventricular function. It may be possible to estimate postoperative LV function, including exercise tolerance, from the preoperative LVESVI.

Aged↗

Novel phosphodiesterase 4 inhibitor T-440 reverses and prevents human bronchial contraction induced by allergen.

To study the roles of phosphodiesterase (PDE) 4 in the human airways, we examined the effect of the novel PDE4 inhibitor T-440 in the isolated human bronchus. T-440 inhibited PDE4 extracted from human bronchial smooth muscle. IC50 values for the effect of T-440, rolipram (a PDE4 inhibitor) and theophylline on PDE4 activity of the bronchial tissues were 0.08 microM, 2 microM and > 100 microM, respectively. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-5) M histamine-induced contraction, the efficacy of 10(-6) M T-440 being almost the same as that of 3.3 x 10(-5) M aminophylline. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-4) M ACh-induced contraction. But their reversal effects on the ACh-induced contraction were weaker than those on the histamine-induced contraction. T-440 (10(-5) M) significantly reversed the contraction induced by allergen in passively sensitized bronchi. The efficacy of the reversal effect of T-440 (10(-5) M) was significantly higher than that of aminophylline (10(-5) M). T-440 and aminophylline significantly relaxed the basal tension, but pretreatment with T-440 or aminophylline did not significantly prevent histamine- or ACh-induced contraction. In contrast, both T-440 (10(-5) M) and aminophylline (3.3 x 10(-5) M) prevented the contraction induced by allergen, which suggests that PDE4 inhibitor inhibits the release of chemical mediators probably from bronchial mast cells in the allergic response. T-440 (10(-6) M to 10(-5) M) caused the accumulation of cAMP at the concentration that relaxed histamine-induced contraction. Thus selective PDE4 inhibitor is a candidate for the treatment of asthma.

Acetylcholine↗

Precision of the gallbladder ejection fraction obtained with Tc-99m-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) hepatobiliary scintigraphy as compared with the contraction ratio in three-dimensional computed tomography.

UNLABELLED: The gallbladder ejection fraction (GBEF) obtained with Tc-99m-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) hepatobiliary scintigraphy has been used as a parameter of gallbladder function. To determine the accuracy of GBEF, the relationship with the contraction ratio of the gallbladder (GBCR) obtained with three-dimensional helical computed tomography (3D-CT) was studied. PATIENTS AND METHODS: A normal volunteer, 8 patients suffering from cholecystolithiasis and a patient with gallbladder dyskinesia were examined. The percent initial dose (%ID) for the gallbladder and GBEF with hepatobiliary scintigraphy were used to compare the volume of the gallbladder and GBCR which was measured by 3D-CT. RESULTS: The %ID of the gallbladder was correlated with the volume of the gallbladder by 3D-CT (Y = 1.000X - 1.818, r = 0.928). GBEF was correlated well with GBCR by 3D-CT (Y = 0.916X + 6.296, r = 0.975). CONCLUSIONS: The %ID of the gallbladder obtained with hepatobiliary scintigraphy may be a good indicator of the volume of the gallbladder. The accuracy of GBEF was confirmed by comparison with 3D-CT examination. GBEF is considered a useful parameter of pathophysiological gallbladder function.

Adult↗

Assessment of myocardial distribution of retrograde and antegrade cardioplegic solution in the same patients.

OBJECTIVE: In order to clarify intramyocardial delivery and distribution of retrograde cardioplegic solution in humans, we induced both ante- and retrograde methods in the same patients to compare their respective delivery and distribution using myocardial contrast echocardiography during surgery. METHODS: 15 patients consisting of nine patients with valvular heart diseases and six patients with coronary artery diseases (including two patients with myocardial infarcted areas and two patients with areas supplied by coronary collateral situation associated with totally occluded coronary arteries without myocardial infarction). Induction of cardioplegia was initially accomplished antegradely and thereafter retrogradely. RESULTS: In valvular heart disease, retrograde cardioplegic solution was distributed less homogeneously, and was not delivered to the midportion of the interventricular septum in two-thirds of the patients (6/9). The transmural myocardial distribution in the anterior, lateral, and posterior walls in the left ventricle were similar for both ante- and retrograde cardioplegic solution, while delivery to the endocardial halves was better than to the epicardial halves (endo-/epicardial intensity ration in antegrade versus retrograde: 1.31 +/- 0.24 versus 1.29 +/- 0.26; 1.19 +/- 0.05 versus 1.36 +/- 0.23; 1.33 +/- 0.28 versus 1.44 +/- 0.35, respectively (all NS)). For delivery to the right ventricle, the existence of small cardiac vein was important. In patients with small cardiac vein (34% in our study), the delivery to the right ventricular dorsal walls was shown. In coronary heart disease, retrograde cardioplegic solution was well delivered to the areas by coronary collateral situation associated with totally occluded coronary arteries, but antegrade solution was not. Neither ante- nor retro grade solution was delivered to myocardial infarcted areas. CONCLUSIONS: These results have important implications for planning strategies for myocardial protection. We think that it is necessary to fully grasp the coronary arterial and venous anatomy of individual patients and to know how to use either ante- or retrograde cardioplegia properly.

Aged↗

Tachykinin antagonist FK224 inhibits neurokinin A-, substance P- and capsaicin-induced human bronchial contraction.

To determine the roles of endogenously released tachykinins (substance P [SP] and neurokinin A [NKA]) in the human bronchial tissues, we studied the effects of tachykinin antagonist FK224 on bronchial smooth muscle contraction induced by SP, NKA and capsaicin in an organ bath. FK224 (10(-6) M and 10(-5) M, respectively) significantly inhibited NKA-induced contraction and 10(-5) M FK224 shifted the dose-response curve to more than one log unit higher concentration. Because SP- and capsaicin-induced contractions were small, we pretreated the tissues with the neutral endopeptidase inhibitor phosphoramidon (10(-5) M), which inhibits degradation of exogenous tachykinins in order to potentiate the contractions. FK224 (10(-5) M) significantly inhibited SP-induced contraction and it shifted the dose-response curves to about one log unit higher concentration. FK224 (10(-5) M) also significantly inhibited capsaicin-induced contraction and it shifted the dose-response curves to more than one log unit higher concentration. In contrast, FK224 (10(-5) M) did not affect on acetylcholine-, histamine-, and leukotriene D4-induced contraction. These results suggest that FK224 is a tachykinin receptor antagonist in the human bronchial smooth muscle, and that capsaicin-induced contraction is due to endogenously released tachykinin-like substances in the human bronchus.

Acetylcholine↗

Gastrointestinal submucosal tumors: evaluation with endoscopic US.

PURPOSE: To describe the endoscopic ultrasound (US) features of benign versus malignant submucosal tumors throughout the gastrointestinal tract. MATERIALS AND METHODS: One hundred nine patients aged 24-81 years suspected to have submucosal tumors (11 esophageal, 41 stomach, 24 duodenal, and 33 colorectal tumors) at barium studies or endoscopy underwent endoscopic US. The layer of origin, internal echo pattern, and lesion margin were analyzed by means of consensus and independent interpretation by three radiologists. RESULTS: Endoscopic US findings revealed several distinct patterns among various submucosal tumors. Sixteen (94%) of the 17 homogeneous lesions with histopathologic findings of malignancy were hypoechoic, although 29 (43%) of the 68 homogeneous lesions with histopathologic findings of benignity were similarly hypoechoic. Homogeneous lesions that were anechoic, of intermediate echogenicity, or hyperechoic were almost exclusively benign (39 [98%] of 40). In contrast, 23 (96%) of the 24 malignant lesions were heterogeneous (n = 7) or homogeneously hypoechoic (n = 16). The sizes of benign and malignant lesions were significantly different (P < .05). There was no significant difference in the echo pattern (i.e., homogeneous versus heterogeneous), but there was a significant difference in the proportion of hypoechoic versus nonhypoechoic lesions (anechoic, hyperechoic, or of intermediate echogenicity; P < .001). CONCLUSION: The differential diagnosis of gastrointestinal submucosal tumors is assisted with endoscopic US.

Diagnosis, Differential↗

Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs.

To investigate whether tachykinins are released in the airways in response to stimulation of the esophagus, we studied the airway plasma extravasation induced by intraesophageal HCl in the presence or absence of neutral endopeptidase inhibitor phosphoramidon and NK1-receptor antagonist FK-888 in anesthetized guinea pigs. The airway plasma leakage was evaluated by measuring extravasated Evans blue dye in the animals pretreated with propranolol and atropine. Infusion of 1 N HCl into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation in the trachea and main bronchi, whereas FK-888 significantly inhibited that extravasation in a dose-related manner. In the capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilateral vagotomized animals. These results suggest that 1) tachykinin-like substances are released to cause plasma extravasation in the airways as a result of intraesophageal HCl stimulation and 2) there are neural pathways communicating between the esophagus and airways, including the vagus nerve.

Animals↗

Tuberculosis in heart transplant recipients.

STUDY OBJECTIVES: To clarify the prevalence and factors associated with tuberculosis, as well as patient survival in heart transplant recipients. DESIGN: A retrospective review of case records of all heart transplant recipients from March 1989 to February 1996 during a 7-year period. SETTING AND PATIENTS: During the period reviewed, 727 orthotopic heart transplantations were performed in 716 patients at the Heart Center Northrhine-Westphalia, Germany. RESULTS: Tuberculosis was proved in seven (1%) patients (four men/three women; age, 33 to 71 years; two miliary lesions, three pulmonary lesions, and two urogenital lesions). None of them had primary history of tuberculosis. Tuberculin skin tests were not performed before transplantation because there were no lesions indicating primary infection of turberculosis. The immunosuppressive regimen was based on double-drug (cyclosporine + azathioprine) therapy. Immunosuppression had been intensified by methylprednisolone pulses at least three times in those seven patients, and prednisone had been used orally in six of seven patients. Tuberculosis developed from 2.5 to 41 months after transplantation. Tuberculosis was found by routine examinations in four of seven patients. Diagnoses were made with both direct microscopy and cultures in six patients, and by histologic study in one. Treatment consisted of isoniazid, rifampicin, ethambutol, and pyrazinamide. Two patients with miliary lesions were treated with four drugs, and the others were treated with three drugs. Isoniazid was used in all patients. Rifampicin, which decreases cyclosporine serum levels, was not used from the beginning in one patient and treatment with it was stopped halfway in another patient because low cyclosporine level had induced rejection. Six of the seven patients are doing well while receiving antituberculous therapy. One patient died with miliary tuberculosis as a cause of death. CONCLUSIONS: The prevalence of tuberculosis in heart transplant recipients was higher than that in the general population. We recommend that a high degree of clinical suspicion is maintained for tuberculosis in heart transplant recipients with meticulous follow-up, and that the treatment of tuberculosis has to be with meticulous care, especially during the use of rifampicin.

Adult↗

Using endosonography to assess the effects of neoadjuvant therapy in patients with advanced esophageal cancer.

OBJECTIVE: The aim of this study was to determine the usefulness of endosonography for evaluating the effect of neoadjuvant therapy for advanced esophageal carcinoma. MATERIALS AND METHODS: Thirty-four patients with esophageal carcinoma (stage II, 16 patients; stage III, 18 patients) underwent various preoperative treatment. In all patients, endosonography was performed before and after treatment, and the percentage reduction in tumor size was calculated from the maximum area of the tumor. In the 27 patients who underwent surgery, the percentage reduction was compared with the pathologic response. Also, the overall survival rates were compared with the percentage reduction in tumor area. RESULTS: Reduction in tumor area ranged from 0% to 47%. The patients were divided into three groups according to the percentage reduction in tumor area. Pathologic response was graded according to the number of viable cells in the entire lesion. Correlation between pathologic response and percentage reduction in tumor area was strong. We found a significant difference in survival rates among the three groups. CONCLUSION: The percentage reduction in tumor area estimated by means of endosonography reflects the histologic effectiveness of neoadjuvant therapy in patients with advanced esophageal carcinoma and may enable clinicians to predict the prognosis of the disease.

Aged↗

[Pregnancy and delivery in the patients with spina bifida--report of 5 cases].

BACKGROUND: Because of improvement in the management for life-threatening complications of spina bifida, quality of life in the patient has become better and pregnancy is becoming more common problem in adolescent and adult female patients. In this paper, we reported patients with spina bifida who became pregnant and delivered a baby. METHODS: There were 6 deliveries from 5 patients. Mean patient age at the first pregnancy was 27.6 years (ranged from 26 to 32 years). Four patients had undergone surgical managements before pregnancy, of whom 1 had augmentation cystoplasty. Urological and obstetrical conditions during the pregnancy were analyzed. RESULTS: Upper urinary tract deterioration which was transient, was observed in 3 pregnancies. Serum BUN and creatinine levels remained stable throughout pregnancy in 4 patients. Pyelonephritis complicated 3 of 6 pregnancies. Delivery was vaginal in 4 and by cesarean section in 2. There were 7 obstetrical complications, which consisted of premature labor (2), uterine inertia (2), cephalo pelvic disproportion (2) and hydramnios (1). There were no significant anomalies in the newborns of these patients. CONCLUSION: To achieve successful pregnancy and delivery in the patient with spina bifida, careful urological and obstetrical observation for the potential complications is needed.

Adult↗

[Electroejaculation and assisted reproductive techniques in the patients with spinal cord injury].

BACKGROUND: Most of the patients with spinal cord injury (SCI) have fertility problems by an ejaculation and a poor fertility of the ejaculate. The objective of this paper is to evaluate the clinical effectiveness of electroejaculation (EE) and combined use of EE and assisted reproductive techniques for the patients with SCI. PATIENTS AND METHODS: Using a Seager Model, EE was attempted on 69 patients with SCI. Of the 69 patients 14 (20%) had cervical, 49 (71%) thoracic and 6 (9%) lumbar paraplegia. Mean patient age was 30 years (range 19 to 47 years) and the mean interval from spinal injury to the first EE was 9 years (range 1 to 38 years). Artificial insemination of husband (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were used to achieve a pregnancy. RESULTS: Antegrade ejaculation was obtained in 60 patients (86.9%). Patients with under-active bladder showed low induction rate (58.3%). Volume of ejaculate was ranged from 0.05 to 5.2 ml (average 1.0 ml) and sperm concentration was ranged from 0 to 546 x 10(6)/ml (average 40.3 x 10(6)/ml), but sperm motility was poor (range 0 to 70%, average 9.4%). Assisted reproductive techniques was attempted on 87 occasions (AIH 80, IVF 2, ICSI 5) on 15 couples. To date, there have been 4 pregnancies (AIH 2, ICSI 2) resulting in 3 healthy live births. CONCLUSION: Combined use of EE and assisted reproductive techniques is excellent management for the patients with SCI who wish to father children.

Adult↗

[Long-term follow up of patients with spina bifida--a review of 228 cases].

BACKGROUND: The objective of this report is to evaluate the upper urinary tract changes of the patients with spina bifida who have been followed up for more than 10 years. METHODS: We analyzed 228 patients (97 males and 131 females) of spina bifida. Mean patient age was 18.7 years (10 to 51 years) and follow up period ranged from 10 to 27 years (mean 13.4 years). Upper urinary tract deterioration (Hydroureter and/or hydronephrosis), vesicoureteral reflux (VUR) and bladder deformity were investigated by excretory urography and voiding cystourethrography. We compared these 3 parameters in the initial and final examinations. RESULTS: In the initial examinations, upper urinary tract deterioration, VUR and bladder deformity were observed in 32.9%, 33.3% and 40.0%, respectively. During the follow up period, upper urinary tract was improved in 47.3% and VUR in 80.0%. Bladder deformity was disappeared in 14.4%. On the other hand, upper urinary tract was deteriorated in 9.3%. VUR and bladder deformity was newly developed or progressed in 8.0% and 29.3%, respectively. Finally, upper urinary tract deterioration, VUR and bladder deformity were observed in 31.3%, 18.2% and 52.0%, respectively. CONCLUSION: These results revealed that upper urinary tract and VUR were relatively controlled, however, bladder deformity was increased in its frequency. To prevent upper urinary tract deterioration, further analysis of sequential changes of urinary tract conditions should be demanded.

Adolescent↗

[Long-term follow-up of female tetraplegic patients with cutaneous vesicostomy].

Tetraplegic women who underwent a cutaneous vesicostomy in our institutions were studied to evaluate long-term urinary complications and their quality of life (QOL). A total of 5 patients (C4, C5 and C6 injuries in one patient each and C7 injury in 2) were followed for 98 to 125 months (mean 107 months). Autonomic hyperreflexia disappeared after surgery in all patients. None of the patients showed deterioration of the upper urinary tract. Urinary tract infections were noted in 3 of 5 patients, but not severe. Bladder stones developed in 2 patients and a stomal stricture in 1. A questionnaire survey showed the patients to be satisfied with the operation, which had improved their QOL. These findings suggest that a cutaneous vesicostomy is an excellent surgical procedure for tetraplegic women.

Adult↗

[Cardiovascular surgery in the patients with liver dysfunction].

Under the current situations we have increasing opportunities to manage the patients with posthepatitis and/or congestive liver dysfunction. In order to prevent postoperative hepatic failure we described perioperative management for those patients. For this purpose, the major point is the selection of appropriate operative methods which reduce operative invasions and have sure efficacy. In order to decide operative methods, we have to grasp the functional reserve of dysfunctional liver. We have no effective methods to estimate the functional reserve, but our data suggested that serum cholinesterase level at the preoperative states might demonstrate prognostic significance. The others are managements of postoperative cardiopulmonary distress and infection. It goes without saying that preoperative improvement of anemia and poor nutrition.

Adolescent↗