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Allergic and chronic inflammation of the airway is regarded as the main pathogenesis of bronchial asthma, in which adhesion of inflammatory cells requires the expression of adhesion molecules. Thus, to clarify the role of fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were determined. FN concentrations in plasma and BALF were measured by enzyme-linked immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb) level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was significantly higher than that of healthy controls (0.727 microgram/mg). Non-atopic asthmatics showed a significantly higher level of FN in their BALF in comparison with atopic asthmatics, although the ratio of FN to albumin showed no significant difference. FN levels in BALF correlated significantly with total cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P < 0.05). FN levels in plasma did not correlate with those in BALF. In conclusion, increased FN in BALF, which was produced locally in the airways of asthmatic patients, is actively involved in the regulation of allergic inflammation.

Hepatic encephalopathy is one of the major complications in decompensated liver cirrhosis. The current study was conducted to clarify the mechanisms of zinc deficiency in liver cirrhosis and its involvement in hepatic encephalopathy via ammonia metabolism. Ten patients each with compensated or decompensated liver cirrhosis and 11 healthy volunteers were enrolled in the study. Serum zinc levels and its daily urinary excretion were measured, an oral zinc-tolerance test was performed to examine zinc malabsorption, and the effects of diuretics on zinc excretion and of zinc supplementation on ammonia metabolism in the skeletal muscle were studied. The mean serum zinc levels in patients with decompensated liver cirrhosis were found to be significantly lower than the levels in controls and patients with compensated liver cirrhosis. The serum zinc levels were inversely correlated with blood ammonia in the fasting state. In the oral zinc-tolerance test, the percent increase in serum zinc levels 120 and 180 min after ingestion was less in cirrhotic patients than in controls. A diuretic administration resulted in a significant reduction in serum zinc levels. An increased uptake of ammonia by and an increased release of glutamine from leg skeletal muscle after oral supplementation of zinc sulfate were evident. Taken together, zinc deficiency in decompensated cirrhotic patients appears to be due to low absorption and to high urinary excretion, for which excessive diuretic administration is, in part, responsible, and zinc supplementation might play an important role in the prevention of hepatic encephalopathy by activating glutamine synthetase.

To clarify the involvement of the caspase family in the pathway of NO-induced chondrocyte apoptosis, osteoarthritis (OA) cartilage obtained from 8 patients undergoing total hip arthroplasty were used for histopathological study. Cartilage samples taken from non-fibrillated areas of femoral head resected during surgery for femoral neck fracture were used for comparison. DNA fragmentation of chondrocytes was detected by the nick end-labeling (TUNEL) method. Apoptosis was further confirmed by transmission electron microscopy. The distributions of nitrotyrosine (NT), caspase-3, and -9 were examined immunohistochemically. The populations of apoptotic as well as NT-, caspase-3-, and -9-positive cells were quantified by counting the number of cells in the superficial, middle, and deep layers, respectively. The TUNEL-positive cells were observed primarily in superficial proliferating chondrocytes, clustering chondrocytes, and deep-layer chondrocytes of OA cartilage. Few positive cells were seen in the proliferating chondrocytes in the middle layer. Positive reactions for caspase-3 and -9 were observed in chondrocytes in similar areas. Histological OA grade showed significant correlations with the mean populations of apoptotic chondrocytes (% apoptosis) over the 3 areas. The populations of NT-positive cells (% NT) over the same areas also showed significant correlation with OA grade. Positivity for caspase-3 closely correlated with the OA grade, % apoptosis and %NT. It was concluded that caspase-3 and -9 could play a role in NO-induced chondrocyte apoptosis in OA cartilage.

We studied total nitric oxide (nitrite + nitrate) (NO) levels in cerebrospinal fluid (CSF) of chronic spinal diseases in nonsmokers (133 patients: 76 men and 57 women; mean age, 63 years; range, 15-92 years) by the Griess method to clarify the role of NO in different spinal diseases. The extent of compression in terms of numbers of disc level at the compressed spinal nerve and neurological evaluation were also assessed according to the Japanese Orthopaedic Association scores. The spinal diseases included cervical myelopathy and radiculopathy (cervical disease group), ossification of yellow ligament (thoracic disease group), and lumbar disc herniation, lumbar canal stenosis and lumbar spondylolisthesis (lumbar disease group). NO levels in the spinal disease groups (4.98+/-2.28 micromol/l: mean +/- SD) were significantly higher than that in the control group (2.53+/-0.94 micromol/l). An inverse correlation was detected between the elevated levels of NO and the grade of clinical symptoms in the cervical disorders. The number of disc level at the compressed spinal nerve was positively correlated with elevated NO levels in CSF in the cervical and lumbar disorder groups. These results indicate that nerve compression may elevate NO levels in CSF, and that NO concentration in the CSF might be a useful marker of damage to nervous system in spinal disorders.

The mechanisms of arterial hypotension following intravenous anesthetic induction agents are multifactorial. The purpose of this study was to evaluate and compare the effects of thiopental, propofol and etomidate on hemodynamics, sympathetic outflow and arterial baroreflex sensitivity using not only neuraxis-intact but also totally baro-denervated rabbits. A total of 60 rabbits was anesthetized with urethane, tracheotomized, and mechanically ventilated with oxygen in nitrogen (FiO2 0.5). The left renal sympathetic nerve was isolated and placed on a bipolar electrode to record renal sympathetic nerve activity (RSNA). Thirty animals underwent a surgical preparation of total baroreceptor denervation. Bolus injections of an anesthesia induction dose of thiopental 4 mg/kg and twice the induction dose of propofol 4 mg/kg significantly decreased RSNA to the same extent (19.4+/-6.7 and 19.7+/-5.2% reduction, mean +/- SEM) and mean arterial pressure (MAP) also to the same extent (19.5+/-4.6 and 22.1+/-3.1% reduction) in the neuraxis-intact animals. RSNA was increased (34.5+/-6%) without reduction of MAP by an induction dose of etomidate, 0.3 mg/kg. Sympathetic barosensitivity was attenuated even 10 min after thiopental at 4 mg/kg or propofol at 4 mg/kg (68% and 54% of control, respectively). Propofol at 2 mg/kg (induction dose) and etomidate at 0.6 mg/kg decreased RSNA and MAP only in the baro-denervated animals. It was found from the barosensitivity study that patients can be hemodynamically unstable even though blood pressure has returned to normal after thiopental and propofol administration. Data suggest that etomidate can even stimulate the sympathetic nervous system and increase sympathetic outflow. It was also clearly found from the baro-denervated animal study that thiopental was stronger than propofol in directly suppressing sympathetic outflow at the induction dose.

Postnatal adaptations of cardiac hemodynamics in infants born vaginally or by caesarean section may be different. These cardiac functions were evaluated by Doppler echocardiography to assess adaptation differences. Cardiac output, heart rate, stroke volume, mean arterial pressure, total systemic vascular resistance, ejection fraction, and ductus arteriosus diameter were determined and compared at 1, 24 and 72 h of life in 22 infants born vaginally (group 1) and 23 born by caesarean section (group 2). One hour after delivery, heart rate, mean blood pressure, and total systemic resistance were found to be higher in group 1 infants (P < 0.01, P < 0.05, P < 0.05 respectively). Stroke-volume measurements were significantly higher in group 2 (P < 0.05). The ejection fraction and cardiac output values were similar in both groups. At 24 and 72 h, no significant differences were observed in measurements of infants born vaginally or by caesarean section. We did not find a parameter negatively affecting healthy newborns in either mode of delivery. However, under pathological conditions affecting the cardiovascular system at 1 h of life, including perinatal infections and hypoxemia, a lower stroke volume, higher heart rate, higher mean blood pressure, and higher peripheral resistance may cause additional work load to the cardiovascular system in infants born vaginally.

We used a regression tree method (RTM) to determine risks of depression in children/adolescents. The survey records of 4,143 children/adolescents in a study based in Mersin, Turkey served as data in this study, and multi-step, stratified, and cluster sampling were used. Effects of 24 variables (sex, smoking, parental problems, etc.) were evaluated on depression scores. The Child Beck Depression Inventory (CBDI) was used to determine the level of depression. Subjects were into 12 different groups based on magnitudes of mean depression scores. The interactions among 7 variables determined to be risk factors are shown on a schema. The STATISTICA (ver.6.0) package program was used for all computations. Although traditional statistical methods have often been used for analysis in this field, such approaches are associated with certain disadvantages such as missing values, ignorance of interaction effects, or restriction of the shape of the distribution. To avoid such disadvantages, we therefore suggest the use of the RTM in studies involving numerical-based outcome variables and for the investigation of a large number of variables and it may be more effective than traditional statistical methods in epidemiological studies which determine risk factors.

The metabolism of L-cysteine in guinea pig liver was studied. Guinea pig liver contained 0.45 +/- 0.05 (mean +/- SD) mumol of cysteine, 0.180 +/- 0.080 mumol of 3-mercaptolactate-cysteine disulfide [S-(2-hydroxy-2-carboxyethylthio)cysteine, HCETC], and 8.082 +/- 0.516 mumol of reduced glutathione per g of fresh tissue. The taurine content was 0.912 +/- 0.158 mumol per g of fresh liver. Cysteine dioxygenase (EC 1.13.11.20) activity was several-fold lower than cysteine aminotransferase (EC 2.6.1.3) activity. Lactate dehydrogenase (EC 1.1.1.27) activity was about 10-fold higher than 3-mercaptopyruvate sulfurtransferase (EC 2.8.1.2) activity. These results indicate that the oxidative metabolism of L-cysteine in the guinea pig liver is not as active as in the rat liver and that L-cysteine, at least in part, is metabolized via the transaminative pathway, in which 3-mercaptopyruvate is partly reduced to 3-mercaptolactate and is utilized to form HCETC.

In an attempt to evaluate high density lipoprotein (HDL) subfraction levels in liver diseases, HDL was separated by a precipitation method with dextran sulfate-Mg2+ from sera of 289 healthy adults and 50 patients with liver diseases. The HDL was subdivided into HDL2e and HDL3e by Utermann's polyacrylamide gel electrophoresis with lauric acid. Ultracentrifugally separated HDL2 and HDL3 roughly corresponded to HDL2e and HDL3e, respectively. Male and female groups had different distributions of HDL2e/HDL3e ratios. Among healthy males, 121 cases had ratios less than 1.0 (mean +/- SD = 0.72 +/- 0.39, n = 150), while among healthy females, the ratios were generally larger than those of males and varied widely from 0.2 to 6.6 (mean +/- SD = 1.77 +/- 1.05, n = 139). Low levels of HDL-cholesterol were found in patients with liver diseases, except those with mild alcoholic liver injury and intrahepatic cholestasis. Apparent decreases in HDL3e, but not in HDL2e, were found in all cases with liver diseases investigated, even in those who did not show decreases in the total HDL level, when male and female patients were analyzed separately. The analysis of HDL subfractions by the present method is simple and useful for the study on altered lipid metabolism in liver diseases.

The proliferation of lymphocytes induced by Propionibacterium acnes (P. acnes) was measured by the in vitro incorporation of 3H-thymidine. The mean response rate of alveolar lymphocytes obtained by bronchoalveolar lavage was 2.23 +/- 0.89 in nine untreated sarcoidosis patients, 0.85 +/- 0.17 in five sarcoidosis patients given corticosteroids and 0.78 +/- 0.29 in 11 controls. The proliferation was significantly enhanced in the untreated patients compared to both the treated patients (p less than 0.01) and controls (p less than 0.001), but there was no significant difference in response rates between the treated patients and controls. The response rate of alveolar lymphocytes was significantly higher in four active patients (3.05 +/- 0.61) than in four inactive patients (1.77 +/- 0.44) (p less than 0.05) and in the controls (p less than 0.001). In sarcoidosis patients, the response rates showed a good correlation with activities of serum lysozyme (r = 0.695, p less than 0.01), and with percentages of lymphocytes in bronchoalveolar lavage fluid (r = 0.591, p less than 0.05). There was a low correlation between angiotensin-converting enzyme activities and the response rates (r = 0.508, p less than 0.1). Neither peripheral blood lymphocytes in sarcoidosis patients nor in controls showed any response to P. acnes, but alveolar lymphocytes of the untreated active sarcoidosis patients were sensitive to P. acnes. The lymphocytes activated by P. acnes may play a central role in the induction of alveolitis in sarcoidosis patients.

Using a cell line (SBC-3/ADM) of human small cell lung cancer, which is 30-fold more resistant to adriamycin than the parent cell line (SBC-3), the activity of a variety of anticancer agents was analyzed by soft agar clonogenic assay to search for a means of circumventing drug resistance. The SBC-3/ADM cells were markedly resistant to some anthracycline antibiotics in comparison with the SBC-3 cells: 28-fold for daunomycin, 26-fold for 4'-epiadriamycin, 18-fold for THP-adriamycin, and 8.4-fold for aclarubicin. However, the cells were as sensitive to mitoxantrone, one of the anthraquinone derivatives, as the parent cells. The cells were resistant to structurally or pharmacodynamically unrelated compounds such as vincristine, mitomycin C, and an active form of ifosfamide, whereas they were susceptible to cisplatin to some extent. The in vitro radiosensitivity of both cell lines was also evaluated, and they were found to be equally sensitive to X-ray. These results suggest that mitoxantrone and cisplatin may exert sufficient activity for small cell lung cancer which has acquired resistance to adriamycin, and that consolidative chest irradiation may be clinically useful after combination chemotherapy including adriamycin.

Primary cultures of surgically obtained noncancerous portions of human liver tissues were made. Liver tissues were poorly dissociated with collagenase, but well dissociated with dispase. The yield and viability of cells were improved somewhat when dissociated with collagenase followed by dispase. The mean cell yield was 1.1 X 10(6) cells/g liver. The epithelial-like morphology of the dissociated liver cells was maintained for about one week, but thereafter degenerative alteration of cells was observed. In liver explant culture, an active outgrowth of cells was observed for more than one month. Albumin production in culture fluids from dissociated livers was detectable for about 2 weeks, but later became undetectable, while that from explant culture was detectable for at least one month. These data demonstrate that adult human hepatocytes can be isolated from noncancerous portions of livers with relatively high yield, and that albumin production of the dissociated cells is detectable for several days.

Maximal expiratory volume-time and flow-volume (MEVT and MEFV) curves were drawn for young male nonsmoking healthy adults and for young male nonsmoking asthmatic patients. Eleven parameters, two MEVT (%FVC and FEV1.0%), six MEFV (PFR, V75, V50, V25, V10 and V50/V25), and three MTC parameters (MTC75-50, MTC50-25 and MTC25-RV) were used for the multivariate analysis. The multivariate analysis in this study consisted of correlation coefficient matrix computation, the test for mean values in the multivariates, and the linear discriminant analysis using the all possible selection procedure (APSP). Correlation coefficients among flow rate parameters and flow rate related parameters in high lung volumes were different between the two groups. In the eleven-parameter discriminant analysis by APSP using single parameters, PFR, V75 (flow rate at 75% of forced vital capacity), and FEV1.0% were considered to be the effective parameters. In the seven-parameter discriminant analysis using the parameter groups, the group of all parameters and the %FVC and flow rate-related parameter group were considered to be the effective numerical alternatives to MEFV curves discriminating between healthy adults and asthmatic patients.

Vital observation on the cellular morphology of the normal human blood cells was conducted by means of bone marrow culture successfully in conjunction with vital staining with Janus green B and neutral red. A special attention was paid for the alterations of the cellular structures in the course of the culture. The findings are summarized as follows : 1) Intracellular particles with affinity to Janus green B or neutral red were classified into minute granules, granules, vacuoles, and mitochondria. Morphologic features of each type of the particles were studied in detail. 2) Two types of granules are present in neutrophilic and eosinophilic blood cells, whereas one type of granules is present in basophilic blood cells. Eosinophilic and basophilic granules show characteristic pole formation in them at the terminal stage of the staining. 3) The rosette formation in the mature monocyte and the aggregations of neutral red vacuoles in the mature neutrophil and the mature lymphocyte were characterized. 4) The cluster of neutral red vacuoles is characteristic of the erythroblast. 5) The mitochondria of the mature neutrophil and the mature monocyte participate in producing neutral red vacuoles.

Within the range of our investigations the most important biochemical characteristics in the brain of idiopathic epileptic patients seem to be defect in the production of and the attendant decrease in free amino acids of the brain. On account of these phenomena there seem to occur the acceleration of the ChE activity and a poor utilization of glucose. Of the free amino acids in the brain the combined amount of glutamic acid, glutamine and γ-aminobutyric acid (GABA) will occupy the major portion of the total free amino acids found in brain, and thus diminution in the contents of glutamic acid and GABA in the brain of idopathic epileptic patients has quite an important meaning. At the present stage it is not yet possible to give any definitive answer to the question why such decrease occurs but it is believed that the most urgent problem facing us today is the amino acid metabolism that is associated with glutamic acid and the comparative studies of the amino acid metabolism in the epileptic brain to that in the non-epileptic brain are required. The fact that γ-amino-β-hydroxybutyric acid (GABOB), the substance that suppresses the central excitation, is decreased seems to indicate biochemically the existence of a defect in the processes of excitation in the brain of idiopathic epleptic patients.

1. Adrenalin, when acting directly on eosinophils, brings about a diminution in the wandering velocity of eosinophils but it has no influence on the number of the cells. Judging from the movement patterns of eosinophils this drug acts as to impede the motive function. 2. Acting directly on eosinophils, cortisone markedly decreases the wandering velocity of these cells and also brings about the diminution in the number of the cells. Likewise from the movement patterns of eosinophils, this drug markedly impedes the motive function of the cells. 3. ACTH (adrenocorticotropic hormone), when acting directly on eosinophils, enhances the wandering velocity of eosinophils but it in no way affects the number of eosinophils. Judging from the eosinophil movement patterns, this drug markedly promotes the motive function. 4. Although adrenalin brings about a decrease in the number of peripheral eosinophils in hypophysectomized dogs, the rate of the decrease is less than that observable in the case of normal dogs. 5. Cortisone brings about no significant change in the number of peripheral eosinophils in hypophysectomized dogs, but is induces a decrease in peripheral eosinophils of normal dogs. 6. ACTH acts as to decrease the number of peripheral eosinophils to an equal. degree in both hypophysectomized and normal dogs. 7. When cortisone is administered simultaneously with Adrex, a marked decrease in peripheral eosinophils is brought about in hypophysectomized dogs. 8. By means of the bone-marrow tissue culture of hypophysectomized dogs it has been confirmed that the blood plasma of hypophysectomized dogs lacks an essential factor for cortisone to induce eosinopenia in perpheral blood. 9. The decrease in eosinophils of peripheral blood induced by cortisone has been proved to be dependent upon the presence or absence of the pituitary body. 10. Taking the decrease in peripheral eosinophils by cortisone administration as the criterion, the author has carried out clinical observations with this method and obtained anticipated results.

The vector electrocardiographic method was applied on 126 healthy young Korean adults without any evidence of cardiac diseases. The range of the age of the subjects were between 19 and 34. The normal values of the magnitude and direction of the mean QRS, T, P vectors, ventricular gradient and QRS-T angle in frontal plane were presented and discussed in comparison with those previously reported in the literature. Considering the age of the subjects under study, our results were in general agreement with those previously reported by other authors.

1) I designed a new micro-method for complement fixation test by means of a capillary pipette. 2) By this method, the complement-fixing antibodies in an individual mouse could be tested without taking its life. 3} The complement fixation titers in mice immunized with Japanese B encephalitis had a considerable individuality. 4) An adjuvant containing anhydrous lanoline and paraffin-oil, when mixed with Japanese B encephalitis vaccine, was effective to potent complement-fixing antibody productions in mice to this antigen.

In such animals not having any organic changes in their brains during the initial stage showed a descendence of convulsive threshold. abnormal findings in their electroencephalogram and ascending activity of ChE. But what is the cause of these functional changes? First, from the fact that though there was no organic changes, they were sensitized and reiniected by a known antigen, which is obviously an antigen-antibody reaction. Second, from the fact that we got a histological.change, which was acknowledged as C.L.A. changes by increasing the concentration of these solution and the number of injections, it could be thought that these functional changes were caused by what I called latent C.L.A.. That is, it seems it could be thought that it would give functionally a permanent hypersensitivity, which is called convulsive arrangement. Furthermore, a similar histological findings as seen in old epileptics were made experimentally after prolonged and repeated injections of very diluted antigens. I believe it can be said, also from this histological point that they are experimental epileptics. But I am not trying to say that idiopathic epilepsy is the same allergic disease as asthma. If it was so, it should offer clinically a problem of eosinophilia in the blood of epileptics. But actually there is no eosinophilia in epileptics. Also, in adult epileptics, convulsive attacks is not often seen soon after introduction of antigens. Consequently, my theory that epilepsy is allergic, does not mean that allergy is the direct cause of epileptic attacks. What I mean is, the causal genesis of idiopathic epilepsy is hypersensitivity of nerve cells in the brain. This hypersensitivity was attained as a tissue reaction by some allergic mechanism without any organic changes. This functional change gives the nerve cell a hypersensitive state, which becomes the base of the beginnihg of convulsion. Its inducement of attack could be water stagnation in the body, anemic state of the brain, alkalosis, or introduction of allergens. In short, the cause of attack does not always come from allergic reactions.