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Biomedical subjects

N Kita

Publications and source records attributed to N Kita.

At least 19 recordsLinked to original sources

Distribution of quinidine in rats with carbon tetrachloride-intoxicated hepatic disease.

The disposition of quinidine was investigated in rats with experimental hepatic disease caused by an intraperitoneal injection of CCl4. The plasma disappearance of quinidine after a 12.5 mg/kg i.v. bolus injection was analyzed by a two-compartment open model in both control and CCl4-intoxicated rats. In the CCl4-intoxicated rats, plasma total body clearance (CLtot), elimination rate constant of the central compartment (kel) and the volume of distribution (Vdss) of quinidine were decreased by 73, 51 and 36%, respectively, compared to those in the control rats. At a steady state of quinidine plasma concentration of 1 micrograms/ml, tissue-to-plasma partition coefficient (Kp,vivo) of the drug in the lung, spleen, heart, kidney and liver in the CCl4-intoxicated rats were decreased ranging from 32 to 42% compared to those in the control rats. The plasma free fraction of quinidine in the intoxicated rats was decreased by 34% of that in the control rats. Neither tissue binding of quinidien in vitro, nor plasma pH was altered in the intoxicated rats. Thus, the decrease in Vdss and Kp,vivo for quinidine in the intoxicated rats seems likely to be due to an increase in plasma protein binding of the drug. Metabolic activity in the liver, the hepatic extraction ratio for quinidine, and the hepatic blood flow in the CCl4-intoxicated rats were decreased by 84, 57 and 47%, respectively, compared to those in the control rats. The decrease in CLtot and kel in the intoxicated rats is considered to be attributed to both the reduction of liver functions and the increase in the plasma protein binding of the drug.

Animals

Accumulation of propranolol in cultured rat fibroblasts.

In order to clarify the involvement of phosphatidylserine (PhS) in the cellular accumulation of propranolol, we have characterized the binding of 3H-propranolol to cultured rat fibroblasts and to liposomes containing PhS. The properties of propranolol binding to the cells and liposomes were analyzed by means of a Scatchard plot. The cells contained at least two classes of propranolol binding sites, one site of high affinity/low capacity and the second site of lower affinity/higher capacity, while the liposomes contained only one class of binding site. The values of the association constant (K) and number of binding sites (n), given on a PhS basis for the propranolol binding site in the liposomes, were both very close to those of corresponding binding parameters for the high affinity/low capacity binding site in the cells. Cell death, caused by various toxic reagents, resulted in a marked decrease in propranolol accumulation in the cells. Kinetic analysis of the drug binding to dead cells showed one binding site with binding parameters comparable to those of the low affinity/high capacity binding site in the intact cells. Polar cations, methylamine and NH4Cl, completely inhibited propranolol binding to the liposomes. On the other hand, these cations partially inhibited propranolol accumulation in intact cells and failed to inhibit the drug binding to dead cells. These results suggest that PhS in cytomembranes represents the high affinity/low capacity propranolol binding site in cultured rat fibroblasts.

Ammonium Chloride

Plasma alpha 1-acid glycoprotein concentration in rats with chemical liver injury.

The influence of liver injury on the plasma concentrations of alpha 1-acid glycoprotein (AGP) and albumin was examined in several different models of chemically-induced liver injury. The plasma AGP concentration in carbon tetrachloride (CCl4), allyl alcohol, bromobenzene, acetaminophen or N-nitrosodimethylamine-induced liver injury was increased to 2-3.5 times the normal level at 24 h after the intoxication. The plasma AGP concentration was unchanged in ethionine-induced liver injury and was markedly decreased in galactosamine-induced injury. The plasma albumin concentration was significantly decreased by the damage due to galactosamine, allyl alcohol or N-nitrosodimethylamine-induced liver injury, while no influence was observed by other hepatotoxin-induced liver injury. The plasma protein binding of propranolol was also determined in relation to the plasma concentrations of AGP and albumin in all the experimental models. Propranolol binding, expressed as bound to free ratio, showed a good correlation with the AGP concentration (r = 0.940; p < 0.001), but not with the albumin concentration.

Animals

Summer-type hypersensitivity pneumonitis: comparison of high-resolution CT and plain radiographic findings.

Summer-type hypersensitivity pneumonitis is an immunologic disease that occurs only in Japan. It is a form of hypersensitivity pneumonitis in which the clinical symptoms appear in the summer and subside spontaneously in mid autumn. The purpose of our study was to determine the CT findings in this condition, to compare the CT findings with those on chest radiographs, and to assess the variations in the CT findings over time. Accordingly, high-resolution CT scans and chest radiographs of 15 patients with summer-type hypersensitivity pneumonitis were retrospectively studied. Seven patients had sequential CT examinations 18-37 days apart. The CT scans and chest radiographs were reviewed by two observers independently. CT findings included diffuse micronodules (n = 15), slightly elevated lung density (n = 13), and patchy air-space consolidation (n = 13). In one patient, the findings on a chest radiograph were normal, while CT showed parenchymal abnormalities. In two cases, follow-up CT showed micronodular abnormalities after findings on the chest radiograph had returned to normal. Our results show that high-resolution CT findings of summer-type hypersensitivity pneumonitis include pulmonary micronodules, increased lung density, and air-space consolidation. High-resolution CT appears to be more useful than plain chest radiographs in the evaluation of pulmonary parenchymal abnormalities in this condition.

Adult

Early asbestosis: evaluation with high-resolution CT.

To determine the earliest stage at which lesions in asbestosis can be diagnosed and to assess their progression, 23 asbestos-exposed patients with minimal or no abnormalities at plain radiography were examined with high-resolution computed tomography (HRCT) twice, with an interval of 12-37 months between examinations. In 21 of the patients, parenchymal abnormalities were found. Major parenchymal features seen at CT included thickened intralobular and interlobular lines, subpleural curvilinear lines, pleural-based nodular irregularities, hazy patches of increased attenuation, small cystic spaces, and small areas of low attenuation. At paired serial CT, subpleural isolated dots or branching structures connected with the most peripheral branch of the pulmonary artery started to appear in lower subpleural zones and then became confluent to create pleural-based nodular irregularities. CT-pathologic correlation led to the conclusion that the confluence of subpleural peribronchiolar fibrosis creates subpleural fibrosis.

Adult

Increase in the plasma protein binding of weakly basic drugs in carbon tetrachloride-intoxicated rats.

Plasma protein binding of weakly basic drugs such as propranolol and quinidine was determined in rats with carbon tetrachloride (CCl4)-induced hepatic disease. Free fractions of propranolol and quinidine in the plasma of rats at 24 h after CCl4-intoxication were decreased by 41 and 30%, respectively, compared to those of control rats. An addition of Tris (butoxyethyl) phosphate (TBEP), a specific displacer for basic drugs from alpha 1-acid glycoprotein (AGP), to the plasma increased the free fractions of the basic drugs, resulting in no difference in the extent of the plasma free fraction of each drug between control and CCl4-intoxicated rats. Plasma concentration of AGP in CCl4-intoxicated rats was elevated 2.7-fold of that in control rats at 24 h after the CCl4 intoxication and reached a peak of 4.8-fold elevation at 48 h. A regression analysis revealed a high degree of positive correlation between ratios of bound to free fraction of propranolol and plasma concentrations of AGP. These results suggest that the plasma protein binding of the basic drugs was increased mainly due to the rise in the plasma AGP concentration in CCl4-intoxicated rats.

Animals

[Therapeutic effect of ofloxacin on intractable pulmonary tuberculosis and ofloxacin resistance of tubercle bacilli isolated from the patients. Chest DIsease Cooperative Study Unit of National Sanatoriums in Kinki District].

Ofloxacin, a synthetic antibacterial pyridone-carboxylic acid derivative, was used in the treatment of intractable pulmonary tuberculosis. In this study, the therapeutic effect of Ofloxacin on pulmonary tuberculosis and Ofloxacin resistance were analyzed. All patients had been hospitalized in eight national sanatoria in Kinki district, and were excreting tubercle bacilli resistant to various anti-tuberculosis drugs agents. Ofloxacin was given to 118 patients orally at a daily dose of 300 mg to 600 mg for more than 3 months. A few anti-tuberculosis drugs, which had failed in the negative conversion of bacilli previously, were used in combination. By Ofloxacin, 23 patients (19.5%) showed negative conversion of tubercle bacilli in sputum culture within 5 months, and they remained culture-negative for at least 6 months after conversion. Side-effects were observed in 2 patients. One complained of arthralgia and the other felt abdominal fullness. But both were not serious. From these results, it was concluded that Ofloxacin was effective for intractable pulmonary tuberculosis. The resistance of tubercle bacilli to Ofloxacin increased significantly after it was used.

Adult

[Studies on the nontuberculous lung mycobacteriosis in Japan. (Report of the study in the year 1987 and 1988 of the Mycobacteriosis Research Group of the Japanese National Chest Hospitals)--pulmonary infection caused by Mycobacterium kansasii has begun to appear in all over Japan including north Japan Hokkaido].

UNLABELLED: In this study, the Mycobacteriosis Research Group of the Japanese National Chest Hospitals (MRG) presents the reports of study years 1987 and 1988. As reported previously**, pulmonary infection caused by Mycobacterium kansasii occurred principally in South-West Japan (prefectures South-West of Tokyo) and did not appear in North Japan. However, this disease appeared in 1987 and 1988 in Hokkaido (Sapporo Hospital). Accordingly, we may say the disease occurs all over Japan. This is a noteworthy finding newly recognized in the study years. The prevalence rate of nontuberculous lung mycobacteriosis was determined as 2.92 or 2.78 in 1987 and as 2.02 or 1.91 in 1988 per 100,000 population per year. The estimated rates based on the ratio of nontuberculous lung mycobacteriosis against active lung tuberculosis and based on the ratio of nontuberculous lung mycobacteriosis against culture-positive lung tuberculosis well agreed with each other. COMMENT: In this country, chest physicians customarily report their cases of nontuberculous mycobacteriosis including lung tuberculosis, because the payment of treatment for patients with tuberculosis is free. Because of this custom, tuberculosis statistics surely contain cases of nontuberculous mycobacteriosis. Caution about this has been paid in calculating the prevalence rate. From the study year 1987, the MRG chairman moved from Michio Tsukamura, The National Chubu Hospital, to Nobuhiko Kita, The National Kinki Chuo Hospital.

Humans

Asbestosis: high-resolution CT-pathologic correlation.

High-resolution computed tomography (HRCT) was performed in seven inflated and fixed postmortem lungs from seven asbestos-exposed patients with pathologically proved asbestosis. The parenchymal abnormalities seen at in vitro HRCT included thickened intralobular lines (n = 7), thickened interlobular lines (n = 7), pleural-based opacities (n = 7), parenchymal fibrous bands (n = 5), subpleural curvilinear shadows (n = 4), ground-glass appearance (n = 4), traction bronchiectasis (n = 4), and honeycombing (n = 2). The thickened intralobular lines were shown histologically to be due to peribronchiolar fibrosis. Thickened interlobular lines were due mainly to interlobular fibrotic thickening in four lungs and edema in three. The peribronchiolar fibrosis was most severe in the subpleural lung regions, creating curvilinear line shadows and pleural-based areas of opacity. Some subpleural fibrosis extended proximally along the bronchovascular sheath to create bandlike lesions. Areas of ground-glass appearance on HRCT scans were shown to be the result of mild alveolar wall and interlobular septal thickening due to fibrosis or edema. Postmortem HRCT findings were similar to premortem HRCT findings and correlated well with the pathologic findings of asbestosis.

Aged

Radiographic type p pneumoconiosis: high-resolution CT.

High-resolution computed tomography (CT) was performed in 90 patients with pneumoconiosis who had small rounded opacities on radiographs. The CT appearances of radiographic type p small rounded opacities in 55 patients were compared with the appearances of type q and r opacities. Radiographic type p pneumoconiosis on high-resolution CT scans was characterized by tiny binary branching structures or a gathering of a few dots. In 21 of the 55 patients, nonperipheral, small areas of low attenuation with a central dot were found. On the basis of CT-pathologic correlation in two postmortem specimens, these tiny opacities and areas of low attenuation corresponded to irregular fibrosis around and along the respiratory bronchioles and to focal-dust emphysema, respectively. Focal emphysema was most commonly found in pneumoconiosis with p-type changes and can be identified with high-resolution CT scanning. The addition of high-resolution CT to chest radiography is useful in achieving more accurate categorization of the lesions.

Humans

Diffuse panbronchiolitis: evaluation with high-resolution CT.

High-resolution computed tomography (CT) was performed in 20 patients with diffuse panbronchiolitis. Images of abnormal peripheral lung were classified into four types: small nodules around the end of bronchovascular branchings (CT type I), small nodules in the centrilobular area connected with small branching linear opacities (CT type II), nodules accompanied by ring-shaped or small ductal opacities connected to proximal bronchovascular bundles (CT type III), large cystic opacities accompanied by dilated proximal bronchi (CT type IV). CT classifications were compared with radiographic classifications and clinical stages of the disease. The comparison revealed that the classification based on CT findings reflected the clinical stages and pathologic process of diffuse panbronchiolitis. The authors conclude that high-resolution CT is useful in the evaluation of both the location and severity of the lesions.

Adult

Studies on the epidemiology of nontuberculous mycobacteriosis in Japan.

The epidemiology of mycobacterial disease in Japan changed considerably over the period 1971 to 1984. During this time, the incidence of pulmonary disease caused by Mycobacterium tuberculosis has steadily declined; disease caused by M. avium complex has remained stable; disease caused by M. kansasii has increased considerably; and, for the first time, substantial numbers of cases caused by M. szulgai, M. fortuitum, M. chelonae, and M. nonchromogenicum have been reported. From 1981 to 1984 the incidence of pulmonary nontuberculous mycobacterioses (NTM) was estimated at 1.73 +/- 0.25 cases per 100,000 population per year; of these, M. avium complex constituted 1.29 +/- 0.24 and M. kansasii 0.34 +/- 0.11 per 100,000 per year. The prevalence of the NTM was relatively high in southwestern Japan (industrialized, warm climate) and low in northern Japan (rural, cold).

Age Factors