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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 649 records · Page 36Linked to original sources

Roles of active oxygen species in glomerular epithelial cell injury in vitro caused by puromycin aminonucleoside.

The mechanism of puromycin aminonucleoside (PAN)-induced nephrosis has not yet been well defined. In the present study, we examined the protective effect of active oxygen scavengers on the PAN-induced injury of cultured rat glomerular epithelial cells (GECs) and the generation of active oxygen species in PAN-treated GECs. When exposed to PAN (greater than or equal to 25 micrograms/ml), cellular damage occurred in a time- and dose-dependent manner as evaluated by both the LDH release and MTT colorimetric assays. Concomitant addition of either the hydrogen peroxide (H2O2) scavenger, catalase, or the iron chelating agent, deferoxamine, to the culture medium caused a striking reduction of cellular injury. This suggested a role for H2O2 and for hydroxyl radicals (OH.) generated via the iron-catalyzed breakdown of H2O2 in PAN nephrosis. Using the scopoletin fluorescence assay, the release of H2O2 into the culture medium by GECs exposed to PAN (greater than or equal to 50 micrograms/ml) was shown to increase dose-dependently (greater than or equal to 57 +/- 11 pmol/4.4 x 10(6) cells per h, P less than 0.01) as compared with control cells (14 +/- 2 pmol/4.4 x 10(6) cells per h). These results strongly suggested that active oxygen species, especially H2O2 and OH., might play an important role in PAN-induced GEC injury in vitro as well as in vivo.

Animals↗

Omentopexy for revascularization of free tracheal grafts in rats.

In rats, we examined the effect of an omentum wrapping on the vascularization of the trachea and on regeneration of the mucosal epithelium in the very early stage after free tracheal grafting. Two pieces of trachea were obtained from each donor rat. One piece was transplanted into the peritoneal cavity of the recipient rat and wrapped with omentum. The other piece was transplanted subcutaneously into the abdominal wall, without omentopexy. Recipients were sacrificed at random on days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels rose significantly earlier in the omentopexy tracheas than in those without omentopexy (p less than 0.01), with all the former showing a normal ciliated, columnar epithelium in the membranous region of the trachea on day 4, accompanied by excellent epithelial regeneration in the cartilaginous region. These results suggest that omentopexy causes revascularization to occur earlier and to be completed in a shorter time, and that it also promotes epithelial regeneration following free tracheal grafting.

Animals↗

Laser Doppler velocimetry measurement of canine mucosal circulation response to bronchial artery reperfusion after lung transplantation.

Left lung transplantation accompanied by reestablishment of the circulation of the bronchial arteries by simultaneous transplantation of part of the aorta was performed on seven dogs. Mucosal circulation of the bronchi at the anastomosis was evaluated using laser Doppler velocimetry (LDV). Since the donor lung must maintain blood supply through the bronchial arteries, the donor aorta from its ascending portion to the descending portion below the outlet for the last bronchial artery was retained with the lung graft. The distal end of the left brachiocephalic artery was sutured to the side of the recipient aorta when the blood supply to the bronchial arteries was to be restored. The LDV values before reperfusion of the bronchial arteries were 20 to 65% (mean: 42.8%) of the preoperative value. Since the LDV values increased to 36 to 125% (mean: 79.9%) of the control, blood flow to the bronchial mucosa increased evidently. Four out of seven dogs died one to two days after the operation due to bleeding and operative stress. One dog was sacrificed on the 4th postoperative day and another on the 16th. The last dog died 40 days after surgery. The unfavorable course of the LDV values in these three dogs suggest that the method used does not ensure an adequate blood supply to the bronchial arteries in the long term.

Animals↗

Neovascularization effect with He-Ne laser in the rat trachea.

The tracheal tissue of a rat was heterotopically transplanted beneath the abdominal skin of a syngenetic rat, and the transplanted graft was irradiated with a He-Ne laser (2.41 J/cm2). Four or seven days following transplantation, Chinese ink staining was used to ascertain the number of newly generated vessels. Rats sacrificed on day 4 were divided into 3 groups, according to the number of laser irradiation treatments: A0, A2, and A4. Similarly, rats sacrificed on day 7 were divided into groups B0, B2, and B4. Among the A groups, vascular counts were 49.5 +/- 31.1 in group A0 (n = 6), 108.9 +/- 34.7 in group A2 (n = 7), and 90.9 +/- 24.6 in group A4 (n = 4). Neovascularization was significantly more pronounced in the irradiated groups that in the non-irradiated group. In the B groups, vascular counts were 148 +/- 58 in group B0 (n = 6), 146 +/- 56 in group B2 (n = 5), and 147 +/- 49 in group B4 (n = 5). There was no significant difference between the irradiated and non-irradiated B groups. Laser irradiation was determined to stimulate neovascularization, and the possibility of a clinical application for this procedure was suggested.

Animals↗

Effects of milrinone on systemic capacitance vessels in relation to venous return and right ventricular pump function.

To investigate the effect of milrinone (MIL) on systemic capacitance vessels, we measured the mean circulatory filling pressure (MCP) in anesthetized open chest dogs. We measured hemodynamic parameters (a) at baseline blood volume (BV), (b) immediately after bloodletting (5 ml/kg), and (c) immediately after dextran injection (5 ml/kg). These measurements were taken in a control group (n = 8) and in a MIL group (n = 8), where MIL (100 + 2.5 micrograms/kg/min) was administered i.v. The extra volume (EV) was obtained by extrapolating the straight line that was fit to the MCP-BV plot. MIL significantly decreased the EV, from 22.8 +/- 1.0 to 19.1 +/- 0.4 ml/kg, indicating that MIL dilates the systemic capacitance vessels. MIL shifted the right ventricular output curve to the left and upward and shifted the venous return curve to the left and rotated it clockwise. Thus, venous return was increased by decreasing the resistance to venous return and by improving right ventricular pump function. Next we evaluated the effects of MIL (100 micrograms/kg) on systemic capacitance and resistance vessels from changes seen in the MCP and the total peripheral resistance (TPR), respectively. In the untreated dogs, MIL decreased TPR significantly without affecting MCP. In dogs pretreated with total spinal anesthesia or phenoxybenzamine, MIL significantly decreased both MCP and TPR. This suggests that the intrinsic venodilator action of MIL is modified by the baroreflex in untreated animals. MIL decreased the MCP and TPR elevated previously by norepinephrine. One would, therefore, predict that MIL would dilate the systemic capacitance vessels in patients with congestive heart failure.

Anesthesia, Spinal↗

[A case of chronic myelogenous leukemia with pulmonary aspergillosis diagnosed by the detection of circulating Aspergillus antigen].

Immunocompromised hosts usually develop invasive mycotic disease. Among many pathogenic fungi. Aspergillus spp, is the most common pathogen of respiratory infection. Early diagnosis of invasive type pulmonary aspergillosis is still difficult, and the treatment is usually difficult. Many investigations have recently suggested that detection of Aspergillus antigen from sera of the patients is useful for early diagnosis to save their lives. We have experienced a case diagnosed by the detection of circulating Aspergillus antigen by Pastorex Aspergillus, who was a 64-year-old female with the blastic crisis chronic myelogenous leukemia. After anti-leukemic chemotherapy, she suffered from pneumoniae with pleural effusions and severe hypoxia, which did not respond to antibiotics. At this point, her serum sample showed positive Aspergillus antigen by Pastorex Aspergillus. She was treated by intensive antifungal chemotherapy, and thereafter improved quickly. Titers of Pastorex Aspergillus were well correlated with her clinical course. The sensitivity of the test requires further improvement, but the specificity of the test is considered to be high enough for clinical use.

Antigens, Fungal↗

Analysis of dynamic behavior of human middle ear using a finite-element method.

Applying the general-purpose finite-element package program (ISAP), a three-dimensional finite-element method (FEM) model of a human right middle ear, which included ossicles, was made and the mechanical properties and boundary conditions of the middle ear were determined by a comparison between the numerical results obtained from the FEM analysis and the measurement results of the fresh cadavers, normal subjects and patients, which were obtained by our developed sweep frequency middle ear analyzer (MEA). The "Elastic" boundary condition consisting of linear and torsional springs at the eardrum attachments to the annular ligament was more appropriate for the actual condition than "fully clamped" one. Rotational axis of the ossicular chain was assumed to be a fixed straight line from the anterior process of the malleus to the short process of the incus, and a load of the ossicular chain and cochlea was simplified to be expressed by the stiffness of the cochlea. Vibration patterns of the eardrum and ossicles at the first resonance frequency, obtained under these assumptions, were in agreement with the experimental results obtained by means of time-averaged holography and by using a video measuring system, except for the relatively large displacements at the tympanic ring.

Auditory Perception↗

Histamine and histidine decarboxylase are correlated with mucosal repair in rat small intestine after ischemia-reperfusion.

The aim of this experiment was to demonstrate whether histamine and histidine decarboxylase (HDC) contribute to mucosal repair in small intestine subjected to ischemia-reperfusion (I/R). The superior mesenteric artery was occluded for 15 min followed by reperfusion. In jejunal mucosa, histamine content and HDC activity increased after I/R. Histamine output in mesenteric lymph was also elevated after I/R. These increases in HDC activity, and mucosal and lymph histamine levels were suppressed by pretreatment of alpha-fluoromethylhistidine (alpha-FMH), a suicide inhibitor of HDC. alpha-FMH also attenuated the increase of ornithine decarboxylase (ODC) activity normally observed after I/R. Transport of dietary lipid into lymph markedly decreased at 24 h after I/R, yet it was restored to normal at 48 h after I/R. alpha-FMH inhibitor led to a sustained deficit in lipid transport at 48 h after I/R. This sustained functional impairment in alpha-FMH treated animals was associated with blunted responses of HDC activity and histamine content to I/R. Our results suggest that histamine and HDC contribute to the restoration in mucosal function observed at 48 h after I/R. This response may be related, at least in part, to stimulation of ODC activity by histamine.

Amine Oxidase (Copper-Containing)↗

Differing actions of endothelin-1 on canine systemic resistance and capacitance vessels.

In anesthetized open-chest dogs, an intravenous bolus injection of endothelin-1 (ET-1, 400 pmol/kg) caused transient hypotension (initial hypotensive phase; phase 1), followed by a continuous elevation of blood pressure (late hypertensive phase; phase 2). The constriction and dilation of the systemic capacitance and resistance vessels were evaluated from the change in mean circulatory pressure (MCP) and in total peripheral resistance (TPR) in phases 1 and 2. To examine the modification of the action of ET-1 on the blood vessels by the baroceptor reflex or by the endothelium-derived relaxing factor (EDRF) released by ET-1 in phase 1, we performed experiments in dogs under total spinal anesthesia (TSA group), methylene blue-treated dogs (MB group) as well as in the untreated dogs (control group). ET-1 decreased the TPR significantly, and increased the MCP significantly in phase 1 in the control (n = 8) and TSA (n = 8) groups; there was no difference between the groups. ET-1 had no significant effect on TPR but increased the MCP significantly in MB group (n = 8) during phase 1. The percentage increase of MCP in the MB group significantly exceeded that of the control group. ET-1 increased both the TPR and MCP significantly in phase 2 in the control group (n = 8). This study indicated that the vasoconstrictor action of ET-1 on the systemic capacitance vessels in phase 1 did not result from a baroceptor reflex, and that the vasodilator action of ET-1 on the systemic resistance vessels may be at least in part mediated via EDRF released by ET-1. We suggest that the vasoconstrictor action of ET-1 on the systemic capacitance vessels is strong, but the vasodilator action of EDRF on the systemic capacitance vessels is weak.

Animals↗

[From biochemistry to pharmacology: the histaminergic neuron system in the brain].

The histaminergic neuron system in the brain has been well-characterized in the last twenty years. This article describes the studies performed by our research groups and discusses the physiological functions of the histaminergic neurons. To demonstrate the distribution of neuronal antibodies against histidine decarboxylase (HDC), the sole enzyme responsible for histamine formation, was used, although the purification of the HDC from fetal rat liver was a difficult task. It took five years to purify the enzyme and another five years to obtain specific antibody suitable for immunohistochemistry. The cell bodies were located in the tuberomammillary nucleus of the posterior hypothalamus. The clusters of cell bodies were designated as E1-5 groups. The fibers that projected from the neurons were distributed in almost all parts of the brain, especially densely in the anterior hypothalamus. alpha-Fluoromethylhistidine, a specific inhibitor of HDC, is a powerful tool for reducing the neuronal histamine in the brain. Administration of alpha-fluoromethylhistidine led to changes in various activities of the brain such as arousal state, circadian rhythm, neuroendocrine functions, feeding behavior, body temperature, and vestibular function. These results indicate that the histaminergic neuron system regulates a wide range of physiological functions in the brain by targeting both neurons and glial cells, on which we found histamine H1 and H2 receptors. The molecular structure of the H1-receptor was also discussed.

Amino Acid Sequence↗

Thyrotropin-secreting pituitary adenoma: a case report.

We report a 44-year-old male with a thyrotropin (TSH)-secreting pituitary adenoma. Based serum free triiodothyronine (FT3, 12.1 pmol/l) and free thyroxine (FT4, 28 pmol/l) were increased with normal basal TSH (3.1 mU/l). There was impaired TSH response to thyrotropin releasing hormone (TRH) test. Serum TSH was suppressed to 59% of the basal level after oral administration of 1.4 mg 3,3'-5-triiodothyroacetic acid (triac), whereas no suppression was observed after 75 micrograms daily administration of triiodothyronine (T3). Serum concentrations of alpha-subunit of TSH (TSH-alpha) and TSH-alpha/TSH molar ratio were high, being 1.95 micrograms/l, and 4.4, respectively. Pituitary CT and MRI scan showed the presence of a macroadenoma in the anterior lobe of the pituitary gland. Histopathology of the excised pituitary confirmed the diagnosis of a TSH-producing adenoma. A positive correlation between TSH and FT3 (r = 0.66, P less than 0.01) or FT4 (r = 0.54, P less than 0.01) was observed in serial sera obtained before and after operation.

Adult↗

Late-onset homozygous protein C deficiency manifesting cerebral infarction as the first symptom at age 27.

We report a 31-year-old female who had repeated thrombosis and was diagnosed as having congenital homozygous protein C deficiency based on decreased protein C antigen and activity, and the findings of family history. This patient had shown no symptom of thrombosis until the age of 27 years, when she had cerebral infarction as the first symptom. Low molecular weight heparin was useful for disseminated intravascular coagulation (DIC) that complicated protein C deficiency in this patient.

Adult↗

Effects of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs.

Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like symptoms of sneezing and watery rhinorrhea and decreased the histamine content of the nasal mucosa in guinea pigs. However, in the animals pretreated with capsaicin (capsaicin desensitization) before sensitization with TDI, nasal allergy-like symptoms were not induced. Capsaicin desensitization also inhibited histamine release in the nasal mucosa induced by TDI. These findings suggest that antidromic impulses of capsaicin-sensitive sensory nerves stimulated by TDI cause histamine release from mast cells in the nasal mucosa, resulting in nasal discharge and sneezing in guinea pigs. Thus neurogenic inflammation via an axon reflex in the nose may contribute to the pathogenesis of vasomotor rhinitis.

Animals↗

Diagnosis of middle ear disease with eardrum perforation by a newly developed sweep frequency measuring apparatus.

Dynamic characteristics of an artificial middle ear model with and without eardrum perforations were measured with our newly developed sweep frequency measuring apparatus. Then, the dynamic characteristics of patients with chronic otitis media having eardrum perforations and with traumatic perforations were measured with this apparatus, and the results were compared with those of the artificial middle ear model with an eardrum perforation. The comparison leads to the conclusion that the middle ear condition of patients with eardrum perforations can be distinguished on the basis of their measurement results. Furthermore, the ossicular chain conditions of patients with eardrum perforations can be diagnosed after putting a paper patch on the eardrum perforation. Therefore, this apparatus seems to be highly useful in the diagnosis of both ossicular chain disorders and eardrum perforations.

Acoustic Impedance Tests↗

[Comprehensive activities of daily living (ADL) index for the elderly].

In order to measure disability in the elderly with a variety of handicaps a comprehensive activities of daily living (ADL) index is described. This instrument, named the ADL-20, consists of 20 items from four major categories of daily activities: (1) 5 items from basic ADL for mobility (BADLm), (2) 6 items from basic ADL for self-care (BADLs), (3) 7 items from instrumental ADL (IADL), and (4) 2 items from communication ADL (CADL). Each activity is scored on a four point scale with values from 0 (total dependency) to 3 (independency). In order to study the interrater reliability of the instrument 40 subjects were examined by a physician and physiotherapist independently at the University of Tokyo Hospital on the same day. Perfect agreement rates on the assignment of the disability score ranged from 70.0% to 97.5% with 85.6% in 800 paired examinations. The kappa values for perfect agreement ranged from 0.52 to 0.88. These results may guarantee a moderate or greater degree of interrater reliability. The correlation coefficients of the Spearman test on the rating scores by the physician and physiotherapist ranged from 0.66 to 0.99 in each activity with 0.97 in total score of 20 items. This scale was employed in 110 patients at the University Hospital and 106 patients staying in the nursing home or long-stay geriatric hospital in order to study its validity. The average age of those 216 patients, 77 males and 139 females, was 76.2 years old. The Cronbach alpha value concerning the consistency of each item as ADL assessment scale was 0.97.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Combination use of suboptimal dose of FK 506 and cyclosporine in canine lung transplantation.

The immunosuppressive potency and the side effects of combination therapy with FK 506 and cyclosporine A were studied in dogs that had undergone lung transplantation. The animals were divided into four groups: group A (one third optimal FK 506 dose: FK 506, 0.03 mg/kg intramuscularly) (n = 5), group B (one third optimal cyclosporine dose: cyclosporine 6 mg/kg orally) (n = 5), group C (one third FK 506 and one third cyclosporine optimal doses): FK 506, 0.03 mg/kg intramuscularly plus cyclosporine 6 mg/kg orally) (n = 5), and group D (half FK 506 plus half cyclosporine optimal doses: FK 506, 0.05 mg/kg intramuscularly, plus cyclosporine, 10 mg/kg orally) (n = 10). Assessments including chest x-ray film, fiberoptic bronchoscopy, hematologic and biochemical tests, FK 506 and cyclosporine blood trough level measurement, right pulmonary artery occlusion test, and histopathologic observations were performed. In group A two of five dogs survived 28 days and three died on postoperative days 7, 14, and 21. In group B one dog survived 28 days and four died on postoperative days 9 (two dogs), 14, and 21. Histologic examination showed severe rejection in both group A and group B. In group C all five dogs survived 28 days but showed mild rejection. In group D one dog died of intestinal bleeding on postoperative day 7 and nine survived 28 days. No pathologic changes were observed except in one case of mild rejection. The ventilation function of the transplanted lung was poor in groups A, B, and C but good in group D. No abnormal rise of FK 506 and cyclosporine trough levels was observed. There were no significant side effects and abnormal hematologic and biochemical data except in one dog in group D. We concluded (1) the combination of FK 506, 0.03 mg/kg, and cyclosporine, 6 mg/kg, is much more effective than either drug used singly, (2) the combination of FK 506, 0.05 mg/kg, and cyclosporine, 10 mg/kg, prevents rejection with tolerable side effects, and (3) no worse side effects are caused by combination therapy with FK 506 and cyclosporine than by either one used singly.

Animals↗