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Biomedical subjects

K Chida

Publications and source records attributed to K Chida.

At least 217 records · Page 12Linked to original sources

Regulation of creatine phosphokinase B activity by protein kinase C.

We previously reported that topical application of 12-o-tetradecanoylphorbol-13-acetate to mouse skin causes phosphorylation of epidermal proteins with molecular weights of 40,000 (p40) and 34,000 (p34). In the accompanying paper, p40 was identified as creatine phosphokinase B. Here we report that both in intact cells and in a cell-free system, phosphorylation of creatine hosphokinase B by protein kinase C resulted in an increase in its ability to catalyze the transfer of the high-energy phosphate of phosphocreatine to ADP, thereby producing ATP. H-7, a specific inhibitor of protein kinase C was found to abolish the increase in enzyme activity. Lineweaver-Burk plot analysis indicated that the increased activity was mostly due to a decreased Km for phosphocreatine. Phosphorylation and activation of creatine phosphokinase B may be a physiological response to maintain ATP balance when a protein kinase C pathway is stimulated.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Purification and identification of creatine phosphokinase B as a substrate of protein kinase C in mouse skin in vivo.

We previously described epidermal proteins with molecular weights of 40,000 (p40) and 34,000 (p34) as target proteins of protein kinase C in mouse skin carcinogenesis in vivo. In the present work, p40 was purified from mouse brain by the use of 32P-labeled p40 of BALB/MK-2 cells as a tracer. Following four lines of evidence indicate that p40 is creatine phosphokinase B. 1) The amino acid sequences of all peptide fragments of p40 from mouse brain were located in the primary structure of creatine phosphokinase B. 2) p40 of BALB/MK-2 cells was immunoprecipitated with goat antibody against human creatine phosphokinase B. 3) p40 of BALB/MK-2 cells was absorbed to and eluted from a creatine affinity column. 4) Purified creatine phosphokinase B was phosphorylated in vitro by purified protein kinase C, but not by cAMP-dependent kinase or casein kinase II.

Alkaline Phosphatase↗

Lesions of rostral ventrolateral medulla abolish some cardio- and cerebrovascular components of the cerebellar fastigial pressor and depressor responses.

We sought to establish whether the C1 area of the rostral ventrolateral reticular nucleus (RVL) of the medulla oblongata mediates: (1) the elevations in arterial pressure (AP), heart rate (HR) and regional cerebral blood flow (rCBF) elicited by electrical stimulation of the rostral cerebellar fastigial nucleus (FN), the fastigial pressor response (FPR); (2) the reductions in AP and HR elicited by chemical stimulation of intrinsic neurons of FN with excitatory amino acids, the fastigial depressor response (FDR). Studies were conducted on rats anesthetized (chloralose), paralyzed and artificially ventilated. The FN was stimulated electrically through microelectrodes and chemically by microinjection of D.L-homocysteic acid (100 nmol in 100 nl). rCBF was measured in homogenates of 11 brain regions by the 14C-iodoantipyrine technique. Bilateral electrolytic lesions restricted to the RVL abolished the elevations in AP, HR and rCBF elicited by electrical stimulation as well as the fall of AP and HR elicited by chemical stimulation of the FN. The disappearance of the responses was anatomically selective and could not be attributed to changes in resting AP, HR or rCBF, loss of reactivity of preganglionic sympathetic neurons, or variations in blood gases. Since the FN neither projects to nor receives afferents from the RVL the pathway to RVL is indirect. We conclude that: (1) the FPR results from excitation and the FDR inhibition of reticulospinal sympathoexcitatory axons of RVL; (2) the FPR is a consequence of excitation of axons arising from neurons in an as yet unidentified area of lower brainstem projecting to or through the FN and with collateral branches innervating RVL mono- or polysynaptically; (3) the FDR, in contrast, represents excitation of intrinsic FN neurons with a polysynaptic projection to RVL through unidentified regions of lower brainstem; (4) the RVL is a relay mediating the increase in rCBF associated with the FPR; and (5) the RVL plays a critical role in integrating actions on the systemic and cerebral circulation represented in cerebellum.

Animals↗

A quantitative evaluation of pontine volume by computed tomography in patients with cerebellar degeneration.

We used CT to make a quantitative evaluation of the pontine volumes of 55 patients with adult-onset cerebellar degeneration and compared the results with their clinical records. Patients with pontine atrophy showed significantly more autonomic dysfunction and extrapyramidal signs; their other clinical features did not differ from patients without pontine atrophy. After dividing the patients into 2 groups, those with and without autonomic dysfunction or extrapyramidal signs, we found that those with these manifestations also had pontine atrophy, a later onset and shorter duration of the disease, and impairment of higher brain functions. The group without these manifestations had relatively normal pontine volume, a greater familial tendency for cerebellar degeneration, and longer duration of the disease. Our results suggest that quantitative volume evaluation of the pons by CT is important for the clinical categorization of cerebellar degeneration.

Atrophy↗

[A clinical study of hypertrophic obstructive cardiomyopathy in the elderly].

Seven elderly patients with hypertrophic obstructive cardiomyopathy (HOCM), who had the three following characteristics on echocardiograms 1) extremely thickened septum, 2) systolic anterior motion of the mitral valve, 3) mid systolic semi-closure of the aortic valve, were clinically evaluated. Ages ranged from 73 to 86 years old (average 78.9% yr.) and all were women. None had not a family history of hypertrophic cardiomyopathy but they had mild hypertension. Six patients showed a significant high voltage on the ST-segment and T-wave abnormalities ("strain" pattern). The left ventricular posterior wall as well as the septum was thickened in 5 and the remaining 2 showed asymmetrical septal hypertrophy (ASH) on echocardiograms. The left ventricular cavity was narrowed due to left ventricular hypertrophy and the shape of the left ventricular cavity was ovoid in all patients. The aorto-septal angles in these 7 patients were 80 degrees to 120 degrees. In addition, proximal septal bulge in all and anterior displacement of the mitral posterior leaflet due to the mitral ring calcification (MRC) in some patients contributed to the narrowing of the left ventricular outflow tract, and the mitral valve was pulled up toward the septum because of the good left ventricular systolic function (ejection fraction: 70 to 94% by echocardiography) and blood was ejected at a high velocity through a narrowed outflow tract (Venturi effect). Pressure gradients in the left ventricular outflow tract was 38 to 146 mmHg in 5 examined by cardiac catheterization. Biopsy specimens were obtained from 2 patients, showing hypertrophic myocytes (diameter: 20 to 30 micron) in 2 and mild disarray in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Histochemical and immunohistochemical study on the expression of alkaline phosphatase, gamma-glutamyl transpeptidase and alpha-fetoprotein during the process of rat hepatocyte proliferation.

The changes in the activity and the localization of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP) and alpha-fetoprotein (AFP) were examined during cell regeneration in the galactosamine-injured rat liver. D-galactosamine was injected i.p. into rats at a single dose level of 400 mg/kg. The biochemical activities of ALP and gamma-GTP in rat liver homogenate increased significantly in comparison with those in the control rats 3 days and 4 days after administration of D-galactosamine. In the histochemical analysis, 3 days, 4 days and 5 days after the administration of the amino sugar, a high level of activity of both ALP and gamma-GTP was seen along the cell borders between adjacent hepatocytes. AFP was detected by the enzyme-labeled antibody technique in the cytoplasm of a few small hepatocytes around Glisson's sheath and epithelial cells of small tubules within Glisson's sheath which show morphological features similar to bile duct 3 days, 4 days and 5 days after the administration of the amino sugar. AFP was detected in serum by the western blotting method 3 days and 4 days after the administration of D-galactosamine, whereas serum albumin decreased significantly in the same period. In this study, it was shown that ALP, gamma-GTP and AFP were proper markers to justify the degree of the differentiation of hepatocytes during the state of proliferation.

Alkaline Phosphatase↗

[Improvement in alveolar macrophage function after therapeutic lung lavage in pulmonary alveolar proteinosis].

Alveolar macrophage (AM) function was investigated in 4 cases of pulmonary alveolar proteinosis (PAP). Therapeutic bronchoalveolar lavage (BAL) with a flexible bronchofiberscope was done 7-13 times during periods of 4-24 weeks. In the initial BAL, the total cell count was only 0.18-0.92 x 10(5)/ml. Also low AM, lymphocytosis and eosinophilia values were noted. The phagocytic activity of AM was only 3-14% and nitroblue tetrazonium (NBT) reduction of AM was under 5% before therapeutic BAL. However, the phagocytic activity was from 25-63% and NBT reduction from 15-35% after therapeutic BAL, AM function with periods of remission of PAP was normal but AM function decreased during relapse and exacerbation of PAP. After therapeutic BAL, two patients have been in remission for three years, one patient with incomplete restoration of AM function relapsed after one year, and one patient without restoration of AM function showed further deterioration after developing pulmonary tuberculosis. These findings indicate that the defect in AM function found in PAP is reversible with therapeutic BAL, and that the severity of PAP is closely associated with AM function.

Adult↗

[Analysis of immunoglobulin G subclasses in chronic respiratory tract infections].

To analyze the immunological aspects of chronic respiratory tract infections, immunoglobulin G (IgG) subclass patterns were investigated in 20 patients with diffuse panbronchiolitis (DPB) and 20 patients with cystic bronchiectasis (CBE). All IgG subclasses were increased in both diseases in comparison to the normal group. Increased levels of IgG1 and IgG2 were recognized more dominantly in DPB, whereas IgG4 level was elevated in CBE. Furthermore, analysis of the ratio of IgG subclass to total IgG showed increase of IgG1 and decrease of IgG2 in both diseases, and increase of IgG4 only in CBE. On the other hand, the increase of IgG1 correlated with infection by P. aeruginosa while increase of IgG4 was recognized in the group of non-P. aeruginosa infections. These results indicate that increased IgG1 and IgG2 levels are common characteristic phenomena in chronic respiratory tract infections such as DPB and CBE, reflecting the pathophysiological aspects based on respiratory tract defense mechanisms against microorganisms, and demonstrated that differences of IgG subclass patterns are observed among DPB and CBE, and also according to causative agents.

Adult↗

[A study of causes of death among patients with active pulmonary tuberculosis from the standpoint of host factors].

To clarify the clinical features of fatal cases of active pulmonary tuberculosis, 36 patients with sputum positive for tubercle bacilli on admission were examined retrospectively. They were divided into two groups, those who died of tuberculosis (Group I), and those who died of non-tuberculous diseases (Group II). The mean age of all the patients was 74.8 years, and the male: female ratio was 7 : 3. In Group I (n = 26), the direct causes of death were respiratory failure (35%), general weakness (27%) and acute progression of tuberculosis (31%), and in Group II (n = 10), about half of the patients died of neoplasms. In addition, a control group (Group III) (n = 27) of patients matched for age and sex with Group I, was examined. They were tuberculous patients who had improved and were subsequently discharged after chemotherapy. Compared with Group III, more patients in Group I showed poor oral feeding and had been bedridden on admission. Their nutritional status was significantly poorer, based on determination of total serum protein, albumin, total serum cholesterol, and hemoglobin. With respect to cell-mediated immunity, Group I patients showed significantly lower peripheral lymphocyte counts and a reduced PPD skin reaction. However, the disease was more serious in Group I than in the control. It was suggested that patients subsequently died of active pulmonary tuberculosis showed not only serious illness, but also malnutrition and depressed cell-mediated immunity.

Adult↗

[Pulmonary tuberculosis with chemotherapy related liver dysfunction].

A retrospective study of the hepatotoxicity of antituberculous drugs was undertaken to establish preventive measures for elevated transaminases by analyzing its clinical courses. Four hundred and forty six patients with normal liver function on admission were enrolled in this study. More than 50% of total 113 cases who showed abnormalities of transaminases were aggravated up to 4th week after administration of drugs, and 80% up to 8th week. The initial values of elevated transaminases did not relate to recovery rate, and could tolerate the additional administration of drugs. However, cases with higher peak values and exacerbation in transaminases showed a tendency of delayed normalization. These results indicate that the chronological observation of transaminases is useful to determine whether or not the antituberculous drugs should be discontinued when hepatic dysfunction occurs. Moreover, they suggest that patients with severe pulmonary tuberculosis may continue chemotherapy with the same regimen under careful observation of liver function even when their transaminase values exceed 100.

Adolescent↗

[Calcium metabolism in tuberculosis].

To investigate the role of Ca metabolism in granulomatous lung diseases, 187 patients with pulmonary tuberculosis 42 patients with sarcoidosis, and 47 patients with pneumonia were examined. The mean value of serum Ca on admission in tuberculosis patients was significantly lower than in patients with sarcoidosis. Of 183 patients with tuberculosis, 69 patients (38%) showed Ca level lower than normal range. The longitudinal observation of serum Ca level in 33 drug-responsive patients with tuberculosis disclosed that mean Ca level rose significantly at the third month of treatment, and maintained the similar level up to the sixth month. These findings suggest that the dynamics of Ca metabolism seen in tuberculosis were similar to that in pneumonia and differed from that in sarcoidosis, although both tuberculosis and sarcoidosis are characterized histologically by granuloma formation induced by cell-mediated immunity. To explain changes in Ca level, the chronological analysis of serum Vitamin D level was done, and it showed no correlation with serum Ca level. The lower serum Ca level on admission and their normalization according to the improvement of clinical course in tuberculosis have not been reported yet. It seems that there are responsible factors other than Vit D for Ca level fluctuation, and further studies are needed.

Adult↗

Global reduction in cerebral blood flow and metabolism elicited from intrinsic neurons of fastigial nucleus.

We sought to determine whether the global increase in regional cerebral blood flow (rCBF) produced by electrical stimulation of the rostral cerebellar fastigial nucleus (FN) is a consequence of excitation of intrinsic neurons of the FN or of axons of fibers passing through or projecting into it. Studies were conducted in rats anesthetized with chloralose, paralyzed and ventilated. rCBF was measured with [14C]iodoantipyrine as tracer and regional cerebral glucose utilization (rCGU) by [14C]2-deoxyglucose in homogenates of 11 brain regions. Neuronal perikarya in FN were excited chemically by local microinjection of the glutamate analogue kainic acid (KA) (5 nmol in 100 nl). KA elicited a transient and significant fall of arterial pressure and heart rate, the fastigial depressor response (FDR). Associated was a significant and symmetrical reduction in rCBF, to 44% of control in all regions except medulla. The response was site- and agent-specific and unrelated to the hypotension. KA also significantly and proportionally reduced, to 52% of control, rCGU in the same 10 areas of brain. In all regions the magnitudes of the reductions in rCBF and rCGU elicited by KA were linearly related. Intrinsic neurons of FN were chronically destroyed by local microinjection of the excitotoxin ibotenic acid (IBO) (10 micrograms/microliters in 0.4 microliter). Destruction of intrinsic FN neurons had no effect on resting rCBF nor on the global cerebrovascular vasodilation elicited by electrical stimulation of the FN. We conclude that: (a) excitation of intrinsic neurons of FN elicits a widespread reduction of cerebral metabolism and, secondarily, blood flow; (b) FN neurons do not exert a long-term tonic influence on brain blood flow nor metabolism; (c) the global increase in rCBF elicited by electrical stimulation of the FN is a consequence of excitation of axons projecting into or through the nucleus.

Animals↗

Levels of protein kinase C activity in human gastrointestinal cancers.

The protein kinase C (PKC) activities of tumor tissue and adjacent normal mucosa of human cancers of the esophagus (8 cases), stomach (1 case) and colon (3 cases) were measured. Considerable variations were found in the activity of PKC and in its subcellular distribution in these cancers. The PKC activities of the membrane and cytosolic fractions of the eight esophageal cancers were, however, similar to those of the adjacent normal mucosa: the average PKC activities of the tumor tissues and normal mucosa were 7.5 and 8.3 pmol/min/mg protein, respectively, in their membrane fractions and 7.9 and 7.8 pmol/min/mg protein, respectively, in their cytosolic fractions.

Cell Membrane↗

Alteration in autonomic function and cardiovascular regulation in amyotrophic lateral sclerosis.

Autonomic function mediating cardiovascular regulation was evaluated in amyotrophic lateral sclerosis (ALS) in comparison with Shy-Drager syndrome. The subjects were 14 normal controls and 9 patients each with ALS and Shy-Drager syndrome. To evaluate the autonomic function in detail, a new series of quantitative autonomic function tests was conducted, in conjunction with conventional tests. In patients with ALS, the data indicated subclinical sympathetic hyperfunction and parasympathetic (vagal) hypofunction, probably resulting in cardiovascular dysfunction.

Aged↗

Quantitative evaluation of pontine atrophy using computer tomography.

Pontine volume was measured and evaluated by computer tomography (CT) in 37 healthy adults and in 29 adult autopsied brains which did not have chronic neurologic diseases. The pons was cut serially into 5 mm slices in the autopsied brains. In the CT examinations both 5 mm and 2 mm slices were studied. Pontine areas in horizontal planes were measured using an image analyzer, then pontine volume was calculated by accumulation of the mean value of the areas and cranio-caudal length. Pontine volume was approximately 19 cm3 and pontine atrophy could be defined as less than 12 cm3 (i.e. the mean - 2 SD) in both methods, which heretofore have not been reported.

Adult↗

Use of human epidermal cells in the study of carcinogenesis.

Because of the importance of human cells, particularly human epithelial cells, in cancer research, we have studied certain phases or events of carcinogenesis using human epidermal cells in primary culture. 1) We found that human epidermal cells are capable of metabolizing benzo[a]pyrene. Large inter-individual variations are found in the basal and induced arylhydrocarbon-hydroxylase activities. 2) UV-induced unscheduled DNA synthesis was demonstrated in human epidermal cells on autoradiographs. We also found that DNA repair is defective in epidermal cells isolated from xeroderma pigmentosum by a new explant-outgrowth culture. 3) Human epidermal cells are unique in that there is a large number of binding sites to phorbol esters compared with mouse epidermal cells, but there is no down-regulation. Further, human epidermal cells show essentially negative responses to tumor promoters, i.e., no stimulation of DNA synthesis, sugar uptake, and no induction of ornithine decarboxylase activity. 4) Human epidermal cells contain 1.5 x 10(5) binding sites per cell for epidermal growth factor (EGF), whereas squamous cell carcinomas of skin and oral cavity have larger amounts of EGF receptors in the order of 10(6) per cell. 5) Based on the above results, we attempted to transform human epidermal cells by the treatment with chemical carcinogens, but until now no transformation was obtained.

Benzo(a)pyrene↗

Stenotic lesions and length of the left main coronary artery in the aged.

To evaluate lesions of the left main coronary artery (LM) in the aged, a pathologic study was performed on a total of 972 consecutive autopsy cases over 60 years of age. The study population consisted of 503 men and 469 women with an average age at death of 79.0 years. In this study the degree of narrowing and length of the LM were evaluated in all cases (T), and the 141 cases with normal hearts (N) were compared with the 202 cases with myocardial infarction (MI). The following results were obtained: (1) the average coronary stenotic index (CSI) was 9.1/15 in T, 5.8/15 in N and 11.2/15 in MI (N less than MI, p less than 0.001), (2) the grade of narrowing in the LM (LMG), when 100% obstruction of the LM is counted as 5, was 1.8 +/- 0.9 in T, 1.3 +/- 0.6 in N and 2.3 +/- 1.1 in MI (N less than MI, p less than 0.001). Cases showing more than 75% narrowing of the LM were found in 58 (6%), of which 35 cases belonged to MI, but development of MI directly due to lesions in the LM was found in only 9 patients (4.5% among MI), (3) the average length of the LM (LML) was 9.4 +/- 4.4 mm in T, 9.0 +/- 4.2 mm in N and 9.3 +/- 3.8 mm in MI (N vs MI; n.s.). Cases presenting left coronary artery dominance (n = 82) or a balanced type (n = 159) showed shorter LML than those with right coronary artery dominance (n = 729) (8.5 +/- 4.0 mm, 8.8 +/- 4.6 mm and 9.7 +/- 4.4 mm, respectively, p less than 0.05), (4) in T there was a correlation between the LMG and CSI, but not between the LML and CSI. In conclusion, lesions of the LM in the aged were generally mild and the LMG showed a positive correlation with CSI and the narrowing of each coronary branch, while no relationship was noted between the LML and CSI.

Aged↗

[Luminol-amplified chemiluminescence evaluation of the microbicidal property of alveolar macrophages in response to drugs].

The present study was designed to evaluate the validity of luminol-dependent chemiluminescence (CL) to evaluate the microbicidal properties of alveolar macrophages (AM) in response to drugs. It was observed that production of CL is associated with H2O2 as well as O2-, 1O2, .OH. Furthermore, our data revealed that CL is dependent not only upon the extracellular release of these oxygen radicals, but also upon intracellular metabolic events, which thus allows a complete analytical study in any given state. It should also be noted from our data that the effect of antibacterial agents on CL was greatly affected by the source of the target cells. The defect of amplified CL in AM obtained from young rabbits might be attributable to immaturity of AM.

Animals↗