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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 415 records · Page 23Linked to original sources

Prognostic values of preoperative and postoperative CEA and CA19.9 levels in pancreatic cancer.

Preoperative serum levels of carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19.9 (CA19.9) were measured in 90 patients with advanced pancreatic cancer. CEA antigen was above the cutoff levels of 5.0 ng/ml in 51% of patients and CA19.9 was above the cutoff limit of 37 U/ml in 87% of patients. High preoperative CEA and CA19.9 levels were related to a poor prognosis of the patients. In multivariate analysis, the hazard rate was significantly higher in the high-CEA group (> 2.5 ng/ml) compared to the low-CEA group (< 2.4 ng/ml). An increase in CEA and/or CA19.9 within 1 month after the operation was also significantly related to the hazard rate. This study reconfirms the prognostic importance of preoperative and postoperative CEA and CA19.9.

CA-19-9 Antigen↗

A multicenter, randomized, controlled trial of intravenous gamma globulin therapy in children with acute Kawasaki disease.

We studied the effect of intravenous, polyethyleneglycol-treated, human immunoglobulin, administered at 200 mg/kg per day (group A: n = 147; male 86, female 61; age < 1 year, 50) or 400 mg/kg per day (group B: n = 152; male 87, female 65; age < 1 year, 52) for five consecutive days and compared it with freeze-dried, sulfonated human immunoglobulin [group C: n = 152; male 87, female 65; age < 1 year, 51), administered at 200 mg/kg per day for five consecutive days, on the prevention of coronary artery abnormalities in Kawasaki disease. Echocardiograms were interpreted blindly and independently. Proportions of 87.1%, 95.4%, and 82.3% in groups A, B, and C, respectively, had no coronary artery abnormalities. The confidence limits of difference between the proportions of groups A and C, groups B and C, and groups B and A were -4.4% and 10.4%, 7.8% and 15.9%, and 4.0% and 10.8%, respectively. Duration of fever and serum immunoglobulin G (IgG) levels were correlated with the prevalence of coronary artery abnormalities. We concluded that intravenous, polyethyleneglycol-treated, human immunoglobulin and freeze-dried, sulfonated human immunoglobulin had clinically equivalent effects on coronary artery abnormalities, and that five daily doses of 400 mg/kg of intravenous, polyethyleneglycol-treated, human immunoglobulin is more effective than that of 200 mg/kg gamma globulin.

Acute Disease↗

Modulating the potency of an activator in a yeast in vitro transcription system.

The intrinsic stimulatory potential or potency of a eukaryotic gene activator is controlled by the interaction between the activation domain and the transcriptional machinery. To further understand this interaction, we undertook a biochemical study to identify parameters that could be used to modulate activator potency. We considered how varying the number of activation domains, their flexibility, and the number of promoter sites affects potency in a yeast nuclear extract. The effects of GAL4 derivatives bearing either one, two, or four herpes simplex virus VP16 activation domains (amino acids 413 to 454) were measured on DNA templates containing one or two GAL4 sites in a Saccharomyces cerevisiae nuclear extract. We found that multimerized VP16 activation domains acted synergistically to increase the potency of the activators. The spacing between the activation domains was critical, such that the increased flexibility imparted by a protein linker contributed to increased activator potency. With highly potent activators, the levels of transcription stimulated on a single site were saturating, whereas the stimulatory effect of weaker activators increased with the number of sites. We discuss how these biochemical studies relate to the mechanism of gene activation and synergy in a yeast in vitro system.

Cell Nucleus↗

Presence of bronchoalveolar lavage fluid necessary for platelet activating factor-induced ciliary depression.

Many different mediators have been implicated in allergic responses and allergic diseases of the respiratory tract. The influence of several allergic inflammatory mediators on the ciliary activity has been well studied. However, ciliary responsiveness to platelet-activating factor (PAF) is yet to be established conclusively. Our study concerns the response of normal tracheal cilia from the guinea pig during an in vitro contact with PAF. PAF at concentrations between 10(-10) and 10(-8) M never affected the ciliary activity. On the other hand, such concentrations of PAF inhibited the ciliary activity in a dose-response fashion within 5 min in the presence of alveolar macrophages. Such a ciliary dysfunction should allow allergens and other molecules to easily invade epithelium and submucosa of the airway, resulting in an increased epithelial permeability which might be a mild manifestation of airway hyperresponsiveness and make a significant contribution to further airway hyperresponsiveness.

Animals↗

Pseudo-acylceramide with linoleic acid produces selective recovery of diminished cutaneous barrier function in essential fatty acid-deficient rats and has an inhibitory effect on epidermal hyperplasia.

Pseudo-acylceramides with different acyl properties were investigated for their capacity to restore diminished barrier function in essential fatty acid-deficient rats. Daily topical applications of synthetic pseudo-acylceramides containing ester-linked linoleic acid caused a dose-dependent, significant reduction of transepidermal water loss (TEWL). Both other pseudo-acylceramides with ester-linked oleic acid or saturated alkyl chains and ordinary ceramides exhibited a poor effect on recovery of TEWL. Furthermore, pseudoceramide containing ether-linked linoleic acid, which is biologically inactive in terms of degradation by hydrolytic enzymes, also induced a significant and similar increase in the barrier function. This restoration of barrier function by pseudo-acylceramides with linoleic acid was accompanied by suppressed DNA synthesis in the EFAD rat epidermis. In UVB-irradiated guinea pig skin, topical applications of the pseudo-acylceramides with linoleic acid immediately after the exposure significantly reduced epidermal hyperplasia, secondary to markedly diminished barrier disruption, whereas linoleic acid itself did not. A comparison of both the anti-hyperplasia and the barrier recovery effects in the series of pseudo-ceramide derivatives examined revealed that the suppressive effect on the induced epidermal hyperplasia was paralleled by the recovery of the barrier defect in EFAD rats. These findings directly suggest that acylceramide with an ester-linked linoleic acid has an essential role in the epidermal permeability barrier.

Animals↗

[Baroreceptor reflex function in young normotensive men with a family history of hypertension].

The purpose of this study is to evaluate the baroreflex function using lower body negative pressure (LBNP) and neck suction in young normotensive men with or without a family history of hypertension. Twenty-two young normotensive men with a family history of hypertension (FH+) and eight young normotensive men who had no family history of hypertension (FH-) were studied. FH(+) consisted of men who had a family history of hypertension within second degree relatives. We studied cardiopulmonary baroreflex function using LBNP and carotid sinus baroreflex function using neck suction and evaluated the reflex function under stimulated conditions using both LBNP and neck suction at the same time. Systolic arterial pressure (SAP)(F = 5.42, p < 0.0001) and pulse pressure (PP)(F = 15.57, p < 0.0001) decreased similarly in both groups in response to LBNP. SAP and PP responses to LBNP were not significantly affected by the family history of hypertension. Diastolic arterial pressure (DAP) increased (F = 2.89, p < 0.005) in both groups. There was a relationship between the LBNP level and family history of hypertension (F = 2.53, p < 0.013), and the increment in DAP during LBNP -30, -40 mmHg was larger in the FH(+) group. Through mean arterial pressure (MAP) was not effected by LBNP, there LBNP level was related to the family history of hypertension (F = 2.23, p < 0.02). Heart rate increased progressively (F = 25.7, p < 0.0001) with increasing levels of LBNP; however, these changes did not differ significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Alterations in vascular pattern of the developing palate in normal and spontaneous cleft palate mouse embryos.

The alterations in the vascularization of the developing palate were studied through the use of resin cast images of vascular networks in normal and spontaneous cleft lip and palate (CL/Fr) mouse embryos (crown rump [CR] Length 9-18 mm, body wt. 0.11-0.65 g). A more dense vascular plexus was observed in the oral side than in the nasal side before the reorientation of the palatal shelves. Prominent terminal dilatations of the vascular plexus were observed in the extreme medial edge of the elevating palatal shelves which may exert significant force for palatal shelf elevation. The vascular plexus showed a lateral extension. Many small spherical masses of resin were observed in the medial edge of the palatal shelves at the time of medial extension and during fusion, indicating some changes occurring in the capillary wall leading to the resin leakage. In the spontaneous cleft group, a similar vascular pattern was observed, but the greater palatine artery showed discontinuity in the premaxillary region at an early stage. At the same time, terminal dilatations were delayed and frequently absent in the contralateral shelf. After the reorientation of the palatal shelves, the vascular plexus formed an irregular lattice pattern. Dilated vasculature was apparent in the anterior nasopalatine region, indicating the persistence of a more primitive vascular structure in the spontaneous cleft embryos. However, the area where capillary dilatation occurred was different between unilateral and bilateral cleft embryos. In conclusion, blood vessels in the palatal shelves are underdeveloped and remained immature in cleft lip and palate embryos and showed different patterns in the anterior nasopalatine region between unilateral and bilateral cleft embryos. These variant vascular patterns may be due to the inadequate blood supply to the nasopalatine region from the early embryonic stages possibly resulting from the discontinuity of the greater palatine artery.

Animals↗

Increased risk factors for coronary artery disease in Japanese subjects with hyperinsulinemia or glucose intolerance.

OBJECTIVE: To understand the interrelationship of coronary artery disease (CAD) risk factors including hyperlipidemia, hypertension, and glucose intolerance to prevent and better manage this disease. RESEARCH DESIGN AND METHODS: We performed a 100-g oral glucose tolerance test in 2,113 subjects, and we evaluated their plasma lipid levels, blood pressure (BP), and plasma glucose and plasma insulin responses. RESULTS: Multiple regression analysis demonstrated a significant relationship of either BP, plasma triglyceride (TG), or high-density lipoprotein (HDL) cholesterol levels to plasma insulin and glucose response after the glucose load. Plasma cholesterol levels were related only to the plasma glucose response. In subjects matched for age, sex, and body mass index (BMI) with hyperinsulinemia or normoinsulinemia, the hyperinsulinemic subjects had a significantly higher mean BP and plasma TG level than the normoinsulinemic subjects (128.8/82.3 vs. 122.9/79.3 mmHg and 172.1 vs. 119.4 mg/dl), and the HDL-cholesterol level was significantly lower (43.9 vs. 47.8 mg/dl). Furthermore, subjects matched for age, sex, and BMI with glucose intolerance had a higher mean BP (128.4/81.8 vs. 123.5/78.7 mmHg) and higher plasma TG level (154.2 vs. 123.0 mg/dl) than those without glucose intolerance. CONCLUSIONS: Based on these findings, subjects with hyperinsulinemia or glucose intolerance should be carefully managed to prevent CAD, because they have more numerous and more severe risk factors than subjects with normal plasma insulin levels or subjects without glucose intolerance.

Blood Glucose↗

Coronary heart disease mortality is actually low in diabetic Japanese by direct comparison with the Joslin cohort.

OBJECTIVE: To identify the mortality rate from coronary heart disease (CHD) in diabetic Japanese by directly comparing the Tokyo University Hospital cohort and the Joslin cohort using identical protocols. RESEARCH DESIGN AND METHODS: Five hundred thirty-eight diabetic patients who were treated at Tokyo University Hospital with a 35- to 62-year age range at entry and with a diabetes duration of < 5 years were followed retrospectively for more than 24 years. RESULTS: The percentage of patients who survived at the end of the 24-year period was higher in the Tokyo University cohort (42%) than in the Joslin cohort (12%). The percentage of patients who died from CHD was remarkably lower in the Tokyo University cohort (11%) than in the Joslin cohort (39%). The CHD mortality rate was lower in the Tokyo University cohort than in the Joslin cohort, regardless of the duration of diabetes. CONCLUSIONS: Our study confirmed the previous finding that the CHD mortality is lower in diabetic Japanese than in diabetic Caucasians.

Adult↗

Nitrogen dioxide-induced eosinophilia and mucosal injury in the nose of the guinea pig.

Nitrogen dioxide exposure-induced mucosal pathology of the guinea pig nose was studied. Guinea pigs were exposed to 3 ppm or 9 ppm of nitrogen dioxide for 6 h a day, 6 times weekly for 2 weeks, and sacrificed 24 h after the final exposure. Exposure to 3 ppm of nitrogen dioxide resulted in decreased ciliary activity and slight eosinophil accumulation on the epithelium and submucosal layer. More serious pathologies were observed in the nose of guinea pigs exposed to 9 ppm of nitrogen dioxide, including a more prominent eosinophil influx to the epithelium and epithelial injury due to activation of eosinophils. Epithelial damage induced by nitrogen dioxide could lead to hyperresponsiveness and may result in a prolonged allergic inflammation. Our study suggests that environmental nitrogen dioxide may contribute to hyperresponsiveness and thus be involved in the increased morbidity of allergic rhinitis.

Animals↗

Epithelial wound healing in the denervated cornea.

We studied the epithelial healing of denervated corneas in New Zealand albino rabbits with their left trigeminal ganglia surgically amputated. On the 14th day after amputation, the corneas were keratectomized (in 8.5 mm diameter) and documentation of the healing process began. We calculated the epithelial healing rate using simple regression analysis. We observed a mean healing rate of 0.463 +/- 0.059 mm2/hr (mean +/- SE) in the denervated corneas, compared to 0.609 +/- 0.031 mm2/hr in the control corneas; a statistically significant difference of P < 0.001. We performed scanning electron microscopic observation (SEM) at three points; before keratectomy, 48 hrs after keratectomy, and 14 days after keratectomy. SEM observation revealed that, in contrast to the control corneas, the surface of the epithelial cells in denervated corneas appeared rough with numerous exfoliating cells observed. This indicates that the epithelial cells might attach only weakly to the floor in denervated corneas. Transmission electron microscopic observation (TEM) performed at 48 hrs and 14 days after keratectomy also supports this finding. For example, the intercellular space is widened and fewer desmosomes are observed in denervated corneas. Using immunohistochemistry, the surface of the wound bed was covered with fibronectin in a similar fashion to the control. In the late stage, the denervated corneas demonstrated spontaneous epithelial breakdown with 83% of them having persistent epithelial defects. Epithelial healing in the control corneas displayed no abnormal signs. On the 14th day after keratectomy, these eyes were enucleated for immunohistochemistry using bromodeoxyuridine (Brd U) to observe dividing cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The influence of intertrial interval on learning of an isometric contractile task].

The present study involved three motor learning experiments; Experiments 1 and 2 measured regulating grasping power and isometric elbow flexion power, respectively. Knowledge of Results (KR) was given after completion of a task of short duration. Experiment 3 was similar to Experiment 2, but procedurally, KR was given concurrently with the task. Accordingly, KR processing takes place within the intertrial interval and parallel to taking task in Experiments 2 and 3, respectively. In these experiments, influences of varying intertrial intervals on the learning process were examined. The results were as follows; 1) In Experiments 1 and 2, shortening of the intertrial interval caused a delay in learning, however this was not the case for Experiment 3. Insufficient KR processing time is considered to be partially responsible for the above delay, 2) In Experiment 3, lengthening of the intertrial interval caused the above delay. These results suggest motor information processing to involve a property of natural decay with the course of time.

Adult↗

[Immortalization of rat corneal epithelial cells by SV40-adenovirus recombinant vector].

Using a SV40-adenovirus recombinant vector, we have successfully established a rat corneal epithelial cell line (RatCE) and studied its biological characteristics. RatCE continued to grow for more than 400 generations. It proliferated centrifugally in the early phase of the culture (1-3 days in culture) and had a cobblestone-like appearance in confluency. Desmosomes and microvilli were clearly seen under a transmission electron microscope. RatCE could be stored in liquid nitrogen and its biological characteristics were: doubling time, 18.3 hrs, colony forming ability, 36%, and growth ability in soft agar, 2%. When the insoluble extract from RatCE was electrophoresed, insoluble proteins were seen at 36 kD, 40 kD, 44 kD, 48 kD, 56 kD, and 64 kD. Anti-64 kD cytokeratin antibody strongly reacted with numerous filaments in the cytoplasm of RatCE. Hence, RatCE possessed 64 kD corneal specific keratin. A large amount of fibronectin was also assessed at focal contact by immunohistochemistry. Thus, RatCE retains several kinds of epithelial characteristics, is derived from one clone, and is immortalized. RatCE will be a useful tool in studies of the corneal epithelium.

Animals↗

Suppression of graft rejection in rat keratoepithelioplasty by anterior chamber inoculation of donor lymphocytes.

A newly developed model of keratoepithelioplasty (KEP) in the rat was used to analyze the effect of anterior chamber-associated immune deviation on the suppression of corneal allograft rejection. The right eyes of Fisher rats received an anterior chamber (AC) injection of lymphocyte suspension from Dark Agouti (DA) rats (DAL group) or phosphate-buffered saline (positive control group). Seven days later, DA corneal lenticules were grafted onto both eyes of the recipients. Delayed type hypersensitivity (DTH) was also assessed in another group of Fisher rats receiving an AC injection of DA lymphocytes in the right eye. Within 15 days, 88% of the eyes in the positive control group demonstrated vigorous epithelial edema, a large area of epithelial defect, and vascularization. By contrast, in the DAL group, only 37% of the eyes showed slight epithelial edema, a small area of epithelial defect, and rare vascularization; suppression of graft rejection was observed in both eyes. DTH assay demonstrated significant suppression in the recipients of the AC injection of donor-type lymphocytes. This study indicates that the AC injection of donor-type lymphocytes prior to corneal grafting suppresses allograft rejection in the rat KEP model, correlative with the suppression of DTH reaction.

Animals↗

[The baseline EEG traits and the induced EEG changes by chronic antidepressant medication in patients with major depression. Early prediction of clinical outcomes solely based on quantification and mapping of EEG].

Forty patients of typical major depression (DSM-III-R) have been adopted for the present study. Hamilton Rating Scale for Depression (HAM-D) was used for the clinical assessment of depressive symptoms, and the patients were followed up at least for four weeks. All the patients were confirmed to be right-handed. The baseline EEGs were compared with age-matched normal subjects (N = 38; all right handed). The differences between depressive patients and normal subjects were less theta activity, more fast activity in anterior part of both hemispheres and in posterior part of the right hemisphere in the depressive patients than in the normal subjects. As a preliminary study, amitriptyline 25 mg was single dose administered and EEGs were recorded before and 1, 3 and 6 hours after the first drug administration in normal male volunteers (N = 6; right-handed). EEG changes of after the medication from the baseline were significant increase of theta and decrease of alpha activity, increase of beta activity was not significant changes. Particularly EEG changes of after 3 hour's administration showed the typical thymoleptic reaction type. EEG changes in patients from the baseline EEG after the first medication were similar to normal subjects. The patients (N = 21) were divided into two groups based on the changes of HAM-D score during four-weeks' treatment; therapy-responsive and therapy-resistant groups. EEG changes after the first single dose administrations in the former were compared with the latter of two patients' groups. Both groups have shown an increase of theta and a decrease of alpha activity. There was more evident alpha increase in therapy-responsive patients than in therapy-resistant ones. However, there were significant differences in amitriptyline-induced EEG changes particularly in beta frequency band; therapy-responsive group showed an increase of beta activity, while therapy-resistant showed no or little change. Using discriminant analysis, the overall hitting ratio of the EEG prediction for therapy-responsive and therapy-resistant group was calculated as 85% at 3 hours after the initiation of antidepressant medication. If EEG mapping, particularly the mapping of differences between pre- and post-drug EEGs, is used to illustrate the EEG responses against antidepressant medication, it will be quite useful to discriminate therapy-resistant patients from therapy-responsive ones in very early stage of the drug treatment.

Adult↗

[Recent proposals for early stage clinical trials of cancer].

Statistical designs for early stage cancer clinical trials, which include continual reassessment method for phase I and I-II studies, early stopping of phase II studies, randomized phase II and multi-stage phase II studies, are shortly reviewed. These recent proposals should be examined further as regards to their statistical characteristics as well as their ethical implication.

Antineoplastic Agents↗

[FIO2 and SpO2 during cardiac surgery in neonates and infants].

Fractional inspired oxygen (FIO2) applied before and after a repair or palliative procedure for cardiac defects along with SpO2 measured by pulse oximeter were reviewed from anesthetic records of 62 neonates and infants. Fentanyl was used for anesthesia, except in cases without i.v. route in which sevoflurane with nitrous oxide in oxygen was used for induction of anesthesia. FIO2 was adjusted using air and oxygen. The lower FIO2 was applied to the patients for a closure of ventricular septal defect, a reconstruction of coarctation or interrupted aortic arch, and pulmonary artery banding, while the higher FIO2 was used for systemic-to-pulmonary artery shunts and the repair of tetralogy of Fallot. In the congenital heart disease with the intracardiac shunt, the magnitude of the shunt flow and hemodynamics can be altered by changing systemic and pulmonary vascular resistance which could be induced by various ways. Since alveolar oxygen tension is a known determinant of pulmonary vascular resistance, an appropriate FIO2 should be applied to each patient with different pathophysiology. A low FIO2 should be set for the cases with nonrestrictive left-to-right shunting, since a high FIO2 may cause a torrential pulmonary blood flow. A high FIO2 is preferable for the cases with right-to-left shunting and a concomitant decreased pulmonary blood flow.

Anesthesia↗

[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies].

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.

Adolescent↗