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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 595 records · Page 33Linked to original sources

Effects of trehalose in preservation of canine lung for transplants.

The effect of trehalose, a non-reducing disaccharide which stabilizes and protects membranes, in the preservation of canine lungs was examined when Euro-Collins solution was basically used as a preservant. In group I, five lungs were perfused and preserved in an Euro-Collins solution modified by replacing the glucose with 35.0 g/L of trehalose. Five control lungs (group II) were perfused and preserved with Euro-Collins solution containing 35.0 g/L glucose. In both groups, no vasodilators were used. After preservation for 12 hours, left lung allotransplantation was performed. At 10, 40, 70, and 130 minutes after reperfusion, the right pulmonary artery was clamped for 10 minutes and four parameters were measured: arterial oxygen tension, mean pulmonary arterial pressure, peak inspiratory pressure, and wet/dry weight ratios. The transplanted lung was also examined histologically. At 10, 40, 70, and 130 minutes after reperfusion, oxygen-tension levels from group I were 263.2 +/- 19.2, 283.4 +/- 14.0, 277.5 +/- 19.9 and 264.9 +/- 26.2 mmHg, respectively. In group II, the corresponding values were 191.2 +/- 33.9, 188.0 +/- 40.3, 153.4 +/- 40.0 and 134.7 +/- 49.4 mmHg, respectively. At 70 and 130 minutes the difference were significant (p < 0.05). All transplanted lungs from group I showed normal histology, whereas four dogs in group II developed severe pulmonary edema and one had a partially edematous lung. These findings suggest that simple substitution of trehalose for glucose has a beneficial effect on preservation of canine lung for 12 hours.

Anesthesia↗

Preparation of in-vivo rat lung model for ischemia-reperfusion injury.

An in-vivo rat lung model for ischemia-reperfusion injury was prepared. The left lung was collapsed after hilar stripping, and the left main pulmonary artery and bronchus were clamped. After the determined period of clamping the left main pulmonary artery and bronchus were declamped and the right main pulmonary artery was clamped. Arterial gas analyses were performed, 1, 10, and 20 minutes after reperfusion. The wet/dry lung eight ratio was calculated and lungs were histologically examined. Before clamping, PaO2 was 102-155 mmHg in all animals. The experimental animals were divided into 4 groups; Group I: temperature 19 degrees C, humidity 55% and duration of clamping 120 minutes (n = 2); Group II: 23 degrees C, 55% and 120 minutes (n = 4); Group III: 23 degrees C, 55% and 90 minutes (n = 5); Group IV: 23 degrees C, 65% and 75 minutes (n = 9). In Group IV, PaO2 decreased significantly in all 9 animals immediately after reperfusion, and at 1, 10, and 20 minutes it was 53.2 +/- 6.1 mmHg, 53.4 +/- 10.2 mmHg, and 67.0 +/- 10.2 mmHg, respectively. Pulmonary edema was observed histologically in 7 of the 9 animals. In-vivo rat lung models for ischemia-reperfusion injury are affected by the surrounding conditions. We established a stable model by setting ischemic time, temperature, and humidity at 75 minutes, 23 degrees C, and 65%, respectively.

Animals↗

Increased plasma level of interleukin-6 in disseminated intravascular coagulation.

Plasma interleukin-6 (IL-6) was higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC. Levels of IL-1 beta and TNF alpha were also significantly higher in patients with DIC. Plasma IL-6 was highest in patients with underlying sepsis and was also high in those with advanced solid cancer. Levels were high in some patients with acute promyelocytic leukaemia and were significantly higher in patients with organ failure than in those without this complication. Plasma IL-6 was higher in DIC patients showing a poor response to therapy than in those with a good response. Incubation with IL-6 caused significant increases in tissue factor activity in mononuclear cells and release of plasminogen activator-1 antigen from human umbilical vein endothelial cells. As increases in IL-6 might give rise to hypercoagulable and hypofibrinolytic states, this may be a cause of DIC and be related to prognosis and organ failure.

Disseminated Intravascular Coagulation↗

Stimulation of tissue type plasminogen activator by leukaemic cell homogenates.

In patients with disseminated intravascular coagulation (DIC), hyperfibrinolysis was observed in patients with leukaemia, but hypofibrinolysis was seen in those with sepsis. Although the plasma tissue plasminogen activator (t-PA) level was higher in patients with DIC than in those without DIC, there was no significant difference in t-PA level between the patients with leukaemia and sepsis. Hyperfibrinolysis might not be caused by t-PA derived from leukaemic cells, although the PA antigen level in leukaemic cell homogenates was significantly higher in patients with DIC than in those without DIC. The activation of t-PA by leukaemic cell homogenates in the absence of bromocyan fibrinogen fragments suggested that leukaemic cell homogenates had t-PA stimulator activity. The t-PA stimulator activity was high in both acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL), especially in DIC, but this activity was not detected in chronic myelocytic leukaemia (CML) or normal cells. Since fibrinogen and soluble fibrin monomer complex levels in leukaemic cells were also high in patients with DIC, fibrinogen degradation products might be the major t-PA stimulator in leukaemic cells. This might be one of the causes of hyperfibrinolysis in leukaemia.

Biomarkers, Tumor↗

Histamine content, synthesis and degradation in human nasal mucosa.

Histamine content and enzyme activities of histamine metabolism, histidine decarboxylase (HDC), histamine N-methyltransferase (HMT) and histaminase (diamine oxidase, DAO) in human nasal mucosa were determined with a highly sensitive and specific fluorescent method which was combined with high performance liquid chromatography. Histamine content and HDC activity were determined in 10 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate. HMT and histaminase activities were determined in 15 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate obtained during surgical therapy. Histamine and activities of HDC, HMT and histaminase were detected in all specimens except the case of histaminase activity in one specimen of nasal polyp. The mean values of histamine content and activities of HDC, HMT and histaminase of human nasal mucosa were 137.3 nmol/g wet weight, 26.3 fmol/min/mg protein, 26.4 pmol/min/mg protein and 0.5 pmol/min/mg protein, respectively. Histamine content in the mucosal tissue of the maxillary sinuses was significantly higher than that of nasal polyps or inferior turbinates. There were no significant differences in HDC activities among three kinds of nasal mucosa. Activities of HMT and histaminase, including their kinetic constants (Km and Vmax values for histamine) indicated that HMT has a greater potential than histaminase for histamine degradation in the human nasal mucosa. The presence of these enzymes suggests that these activities constitute an important modulating factor in histamine mediated allergic and inflammatory reactions in human nasal mucosa.

Adolescent↗

[Rapid diagnosis of cytomegalovirus interstitial pneumonitis by the polymerase chain reaction method--comparison of four diagnostic procedures].

The authors conducted a comparative study on the rapid diagnosis of cytomegalovirus (CMV) interstitial pneumonitis by 4 different methods. Among them, the polymerase chain reaction (PCR) method was found to achieve the most rapid diagnosis of CMV infection. The clinical usefulness of making a diagnosis from the serum antibody titer and viral isolation was questionable as compared with the PCR method. Therefore, early diagnosis of CMV infection by PCR may be promising especially for the compromised patients with hematological diseases.

Base Sequence↗

Effect of unilateral vestibular stimulation on histamine release from the hypothalamus of rats in vivo.

1. We investigated the effect of unilateral vestibular stimulation on histamine release from the anterior hypothalamic area of urethan-anesthetized rats in vivo, using a brain microdialysis method coupled with high-performance liquid chromatography fluorometry. 2. The histamine release was increased to approximately 180% of the basal release by the electrical stimulation of the inner ear with 1 Hz, 500 microA, and 200 ms for 20 min. This effect was dependent on the current intensity. 3. Activation of the unilateral horizontal semicircular canal by middle ear irrigation for 15 min with 45 degrees C water increased the histamine release to approximately 200% of the basal release. 4. Irrigation of the middle ear with ice water for 15 min increased the histamine release to approximately 190% of the basal release. 5. The histamine release was not changed by the irrigation of the middle ear with 37 degrees C water and the irrigation of the auricle with ice water, which suggests that neither somatosensory stimulation to the middle ear nor nonspecific cold stress affects the histamine release. 6. All these findings suggest that the sensory mismatch signals induced by caloric stimulation and unilateral electrical vestibular stimulation activate the histaminergic neuron system in the brain.

Afferent Pathways↗

Direct injection analysis of atenolol enantiomers in plasma using an achiral/chiral coupled column HPLC system.

A novel HPLC system was developed with an achiral/chiral coupled column for the direct injection analysis of atenolol (AT) enantiomers in plasma. The system consists of a size-exclusion column, an ODS silica column and a newly developed beta-cyclodextrin perphenylcarbamate(ph-beta-CD)-bonded silica column connected in a series via two switching valves. The neat plasma sample was directly injected onto the size-exclusion column, and the deproteinized fraction of AT enantiomers was concentrated on the ODS silica column. The enantiomers were then transferred and separated mutually on the ph-beta-CD silica column. The calibration line for each of the AT enantiomers was linear in the range of plasma concentration of 10-200 ng/ml (r > 0.9997) with good reproducibility (CV < 9.7%, n = 20). The recoveries from plasma were almost complete (> 97.4%) for both enantiomers. One analysis finished within 30 min. The developed system was applied to the enantioselective determination of plasma concentration-time curve of AT after the oral administration of racemic AT to a healthy volunteer.

Atenolol↗

[Antigenicity study of trandolapril (RU44570)].

Antigenicity of trandolapril (RU44570) was evaluated using the following six standpoints: 1. active systemic anaphylaxis (ASA) in guinea pigs; 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum of sensitized guinea pigs; 3. histamine release from lung tissue of sensitized guinea pigs; 4. Schultz-Dale reaction with isolated ileum of sensitized guinea pigs; 5. passive cutaneous anaphylaxis (PCA) in rats with serum of sensitized mice; and 6. delayed type skin reaction by Maximization test in guinea pigs. In the test of immediate type reactions, guinea pigs were sensitized by RU44570 (p.o.), an FCA emulsion of RU44570 (s.c.) or an FCA emulsion of incubate solution of RU44570 and normal guinea pig's serum, and mice were sensitized by a mixture of RU44570 and alum (i.p.). In the test of delayed type reaction, guinea pigs were sensitized by intradermal injection and patch application. 1. ASA in guinea pigs: No anaphylaxis symptoms were observed in any of the sensitized guinea pigs. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than 1. 3. Histamine release from lung tissue: No histamine release was observed in any of the isolated lung tissue. 4. Schultz-Dale reaction: No contraction was observed in any of the isolated ileums. 5. PCA in rats: PCA titer of sera from sensitized BALB/c and C3H/He mice was less than 5. 6. Delayed type skin reaction test: No skin reactions were observed in any of the sensitized guinea pigs. From these results, it is concluded that RU44570 has no antigenicity under the conditions of the present study.

Anaphylaxis↗

Spa bathing activates fibrinolysis in patients with cerebral infarction.

The effects of spa bathing on blood coagulation and fibrinolysis were studied in 20 patients with chronic cerebral infarction. Blood was obtained before and after a 10-minute period of spa bathing at 41 degrees C. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII activity, von Willebrand factor activity, and antithrombin III activity did not show significant changes after bathing, but euglobulin lysis time was significantly reduced (p < 0.01) and fibrin lysis activity was increased (p < 0.05). These findings suggest that spa bathing activates fibrinolysis without markedly changing blood coagulation in patients with chronic cerebral infarction. It is thought that the activation of fibrinolysis without the activation of coagulation has a favorable effect on blood circulation. The results of fibrin-plate assays using C1 inactivator indicated that tissue-type plasminogen activator was the major contributor to the activation of fibrinolysis during spa bathing.

Aged↗

[Concentrations of multiple neurochemicals in the cerebrospinal fluid of patients with senile dementia and the relationship to alpha 1-antichymotrypsin].

The authors investigated the concentrations of multiple neurochemicals (6 kinds of catecholaminergic and 5 kinds of indolaminergic substances) in the lumbar cerebrospinal fluid (CSF) of patients with and without senile dementia (13 Alzheimer type (AD), 7 vascular type (VD), 11 Parkinson's disease (PD) and 9 non-demented controls (C)) by means of a neurochemical analyzing system (Neurochem, ESA). By means of the enzyme-linked immunosorbent assay (ELISA), we also determined the concentration of alpha 1-antichymotrypsin (ACT) in the CSF, which may be a possible diagnostic biochemical marker of the senile dementia of Alzheimer type. ACT in CSF was significantly higher in the AD group. It correlated negatively with Hasegawa's dementia scale (HDS) significantly. It also correlated negatively with the concentration of HVA significantly and showed tendency to correlate with the concentrations of dopamine and the ratio of kynurenine and tryptophan (KYN/TRP). Each dementia group showed characteristic concentration patterns of neurochemicals (DA, HVA, MHPG/NE, KYN/TRP, and 5-HIAA/5-HT). Our approach may provide a new quantitative method to diagnose geriatric neuropsychological diseases as well as senile dementia.

Aged↗

[A case report of pseudolymphoma of the kidney and orbit].

Pseudolymphoma is reactive extranodal lymphocytosis, and it's lymphocytes are so minimally atypical that it is basically benign. The patient was a 68-year-old female with pain in the left back and lower abdomen. Plain CT (computerized tomogram) of the kidney revealed a mass in the left kidney. It had a smooth surface and higher density than parenchyma. Similarly a left orbital mass was revealed by CT. We could not deny the mass to be a malignant tumor, so we took specimens from these lesions by an open biopsy. Histological examination of these specimens showed pseudolymphoma. Pseudolymphoma of the left kidney was reduced in its size by treatment with prednisolone. The patient is continuously followed up to date.

Aged↗

Prolonged lung allograft survival with a short course of FK 506.

We examined the hypothesis that FK 506 would induce graft acceptance after lung transplantation. Left lung allotransplantation was performed in size-matched mongrel dogs allocated to control (no immunosuppression, n = 3) and FK 506 (n = 5) groups. FK 506 (1.2 mg/kg intramuscularly every day) was given on posttransplantation days 0, 1, and 2. No other immunosuppressive agents were administered to either group. Chest x-ray and transplant lung physiologic assessments were performed on the fifth day and weekly thereafter. On day 29 an open lung biopsy and a third-party skin graft were performed. Lymphocytes were harvested and frozen from the recipient peripheral blood before transplantation and on days 8 and 29 afterwards for assessment in mixed lymphocyte reaction. Dogs were killed when their chest x-ray films showed allograft opacification or when the skin graft was rejected. Control lungs were all rejected after a median of 5 days. In the FK 506 group, one of five dogs aspirated during the fifteenth-day assessment and was killed, on the twenty-ninth day, because of severe rejection. At day 29, in the other four dogs, the transplanted lung yielded an arterial oxygen tension of 613 +/- 25 mm Hg (mean +/- standard deviation) and lung biopsy specimens showed no abnormalities histologically. These four dogs rejected third-party skin grafts after a median of 10 days. In two FK 506 dogs, mixed lymphocyte reaction at day 8 showed suppression of proliferation responses against donor and third-party lymphocytes. By day 29 responses against third-party lymphocytes had returned to almost preoperative levels, whereas antidonor responses were still suppressed. After skin graft rejection and killing, one of four dogs showed no sign of rejection, and the other three showed minimal to mild lung rejection at the time they were killed. We conclude that a 3-day course of 1.2 mg/kg of FK 506 induced prolonged graft acceptance after lung transplantation in dogs.

Animals↗

[Cytokine levels in patients with thrombotic thrombocytopenic purpura].

Plasma cytokine levels were examined in 13 patients with thrombotic thrombocytopenic purpura (TTP). Complete remission (CR) was attained in 7 of the 13 patients, but 6 died. Tumor necrosis factor (TNF), Interleukin (IL)-1, IL-6 and soluble IL-2 receptor showed marked increases at onset and decreased at CR. The prognosis tended to be poor in patients with increased IL-6 and soluble IL-2 receptor levels. Tissue factor production in human umbilical vein endothelial cell (HUVEC) cultured with TTP plasma was significantly increased, but the migration of HUVEC to TTP plasma was significantly lower. These findings suggest that immunological mechanisms and vascular endothelial cell damages are involved in the pathogenesis of TTP and are reflected in the plasma cytokine levels.

Adolescent↗