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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 415 records · Page 23Linked to original sources

Exercise-induced ST-segment elevation and hemodynamic responses one month after myocardial infarction.

Changes in hemodynamics and plasma norepinephrine levels during supine bicycle exercise after myocardial infarction were measured to investigate the mechanism of exercise-induced ST-segment elevation. Seventy-eight patients were divided into groups which showed either ST elevation (STE), ST depression (STD), or no ST changes (STU). Most of the STE group had anterior myocardial infarction (90.6%) and single-vessel disease (76.7%). The STE group achieved a significantly higher workload (119.5 +/- 4.0 watts, mean +/- SEM) than the STD group (82.3 +/- 2.8, p < 0.01). Heart rate and cardiac output at maximal workload were significantly higher in the STE group (136.6 +/- 3.4 beats/min, 7.44 +/- 0.28 l/min/m2) than in the STD group (110.0 +/- 3.9, 4.83 +/- 0.36, p < 0.01). Pulmonary artery pressures were less elevated in STE than STD patients. Plasma norepinephrine levels increased significantly at maximal workload in STE patients, as compared to the other groups. In conclusion, the STE group achieved a higher exercise level associated with augmented sympathetic activity, which may be a possible mechanism of exercise-induced ST elevation after myocardial infarction.

Cardiac Output↗

[The prevalence and significance of abnormal thyroid hormone metabolism in acute myocardial infarction].

In order to clarify the relationship between thyroid function and left ventricular function in acute myocardial infarction (AMI), 52 patients (63.3 +/- 11.0 years old) admitted to the coronary care unit within 24 hours after the onset were studied. Both FT3 and FT4 levels measured at 48-72 h after the onset (1.66 +/- 0.59 pg/ml, 1.02 +/- 0.37 ng/dl) were significantly lower than those on admission (2.99 +/- 0.76 pg/ml; p < 0.01, 1.14 +/- 0.25 ng/dl; p < 0.05) and controls (3.27 +/- 0.66 pg/ml; p < 0.01, 1.22 +/- 0.23 ng/dl; p < 0.05). The decline of these thyroid hormone levels correlated well with the severity of AMI (Killip's classification), hemodynamic deterioration and liver function (low levels of albumin and cholinesterase). Low thyroid hormone levels were also associated with the elevation of catecholamine and alpha-hANP levels on admission. Low cortisol and impaired renal function were recognized as factors which might prolong the condition of low thyroid hormones. Non-survivors showed significantly lower levels of FT3 and FT4 48 hours after onset, and a lower level of FT4 in aged patients was consistent with a poor prognosis. In conclusion, the measurement of thyroid hormones in AMI is important in evaluating the severity of the condition and waking a prognosis.

Aged↗

Antiphospholipid antibodies. A prognostic factor in sarcoidosis?

Serum antibodies against five types of phospholipids, antiphospholipid antibodies (aPL), were determined by an enzyme-linked immunosorbent assay in 55 patients with sarcoidosis. Either IgG or IgM aPL were detected in 21 patients (38 percent). This positive rate was significantly higher than that (7 percent) of healthy control subjects (p < 0.001). In terms of immunoglobulin classes, 5 cases had IgG aPL only, 11 cases had IgM aPL only, and 5 cases had both classes of aPL. No correlation was observed between the occurrence of aPL and disease activity of sarcoidosis. A significant correlation was noted between the occurrence of aPL and many extrathoracic organ lesions or the persistence of abnormal chest x-ray film findings for periods of 2 and 5 years. Taken together, the presence of aPL in sarcoidosis is a useful index to judge the prolongation of the disease.

Adult↗

Significance of interleukin 6 in patients with sarcoidosis.

Interleukin 6 (IL-6) levels in various materials from patients with sarcoidosis were determined. The subjects of the study were 38 patients with sarcoidosis and 28 healthy controls. For detection of IL-6, an enzyme-linked immunosorbent assay method was used. Interleukin 6 activity in serum was detected in 4 of 30 patients, but not in 19 controls. In bronchoalveolar lavage (BAL) fluid, following 20-fold concentration, IL-6 activity was detected in four of ten patients (nonsmokers) and three of seven controls (two of two smokers and one of five nonsmokers). Interleukin 6 levels in the supernatants of cultured monocytes and alveolar macrophages (AMs) were significantly higher (p < 0.01 and p < 0.01, respectively) in patients with sarcoidosis than in controls. Interleukin 6 production from monocytes tended to correlate with that from AMs. A significant correlation (r = 0.70, p < 0.05) was found between IL-6 production from AMs and the ratio of CD4+/CD8+ in BAL fluid, although no correlation was observed between that from monocytes and CD4+/CD8+ ratio in BAL fluid. Taken together, IL-6 may be involved in the initiation and maintenance of alveolitis by activating and causing the proliferation of T cells.

Adult↗

Genistein but not staurosporine can inhibit the mitogenic signal evoked by lithium in rat thyroid cells (FRTL-5).

Long-term administration of lithium is one of the well-known causes of goiter. It can stimulate DNA synthesis in rat thyroid cells (FRTL-5) treated with thyroid-stimulating hormone (TSH). To investigate the mitogenic signal transduction system activated by lithium, lithium-induced DNA synthesis and Ca2+ influx were studied using two protein kinase inhibitors, genistein as a specific tyrosine kinase inhibitor and staurosporine as a potent inhibitor of protein kinase C. Genistein but not staurosporine blocked the DNA synthesis induced by lithium in TSH-primed cells but neither compound had any effect on the Ca2+ entry stimulated by lithium. Genistein clearly attenuated the phosphotyrosine content of the 175 kDa substrate in the presence of lithium but staurosporine failed to do so. Moreover, lithium could also stimulate DNA synthesis in protein kinase C down-regulated cells. These data demonstrate that lithium may require the activation of a particular genistein-sensitive kinase, possibly a tyrosine kinase, to induce cell proliferation. It is suggested that the phorbol ester-sensitive protein kinase C family might not participate in the mitogenic signal transduction pathway activated by lithium.

Alkaloids↗

Acute, subchronic and chronic toxicity studies of a synthetic antioxidant, 2,2'-methylenebis(4-methyl-6-tert-butylphenol) in rats.

General toxicity studies on 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (MBMBP) were conducted using male and female Wistar rats. LD50 values were greater than 5 g/kg BW by oral administration for both sexes. Diarrhea was observed until 5 days. In the subchronic test, rats were fed diet containing MBMBP at 0, 0.12, 0.6 or 3.0% for 12 weeks. Severe suppression of body weight gain was observed in both sexes of 0.6 and 3.0% groups. Death accompanied by hemorrhage from nasal cavity was observed in 0.6 and 3.0% males and 3.0% females. Dose-dependent toxicity to the liver in both sexes was observed in blood chemical analysis. Histopathologically, testicular atrophy and decrease of spermatogenesis were dose- and time-dependently observed in all treated males. Atrophy of ovaries was evident in 0.6 and 3.0% females. Thymus atrophy and bone marrow hypoplasia were observed in both sexes of 0.6 and 3.0% groups. In the chronic test, rats were fed diet containing MBMBP at 0, 0.01, 0.03 and 0.1% for 18 months. Body weight gain was only suppressed in both sexes receiving 0.1%. Histopathologically, testicular atrophy and decrease of spermatogenesis were apparent in 0.1% males. No neoplastic response by MBMBP administration was noted. NOAEL was concluded to be 0.03% in the diet (12.7 mg/kg BW/day for male rats and 15.1 mg/kg BW/day for female rats).

Administration, Oral↗

Confirmation study, using nitrobenzene, of the Combined Repeat Dose and Reproductive/Developmental Toxicity Test protocol proposed by the Organization for Economic Cooperation and Development (OECD).

A confirmatory familiarization study of the Combined Repeat Dose and Reproductive/Developmental Toxicity Screening (ReproTox) test protocol proposed by the Organization for Economic Cooperation and Development (OECD) was performed using nitrobenzene, a testicular toxicant. The agent was given daily by gavage to groups of 10 male and 10 female Sprague-Dawley rats at doses of 100, 60, 20 and 0 mg/kg body weight. Some of the high dose animals exhibited neurological signs, and two males and 9 females died. Hemolytic anemia due to methemoglobin formation was evident in treated males. Histopathologically, treated males showed atrophy of seminiferous tubules of the testis, reactive changes secondary to hemolytic anemia in the hematopoietic organs, and hepatocellular swelling. Cerebral gliosis was observed in middle and high dose males. Male fertility was not affected. The body weights of pups from treated dams were lowered, and their postnatal loss was increased. Most of the known toxicological properties of this chemical was demonstrated in the present study, with the exception of reduced fertility. Therefore, the ReproTox protocol was concluded as being useful as a screening test of existing high production volume chemicals. It should be noted that while the reproductive toxicity test alone is insensitive for detection of male fertility disturbances associated with testicular toxicity, the latter easily be distinguished on morphological grounds.

Animals↗

Abundant existence of 40kD-cdc2-related protein in rat thyroid cells.

The cdc2 kinase family is known to be one of the important factors for cell proliferation in both yeast and mammalian cells. By using polyclonal antibodies against PSTAIRE region of cdc2HS, we studied the amount of cdc2-related kinases in the rat thyroid cell line, FRTL-5, during the cell cycle. The immunoreactive protein with molecular weight 34kD was hardly detectable, instead, 40kD protein exists constantly in amount through G0 phase to S phase. Further, it did not decrease when the cells were cultured in serum- and hormone-free medium. Moreover, we observed an increase of this protein in the nuclear fraction as the cells enter S phase. On the contrary, we could not detect any immunoreactive 40kD protein in primary cultures of rat thyroid cells. These results may indicate abundant existence of this protein might concern cell cycle regulation of FRTL-5 or its immortal feature.

Animals↗

Phorbol ester inhibits DNA synthesis induced by interleukin-6 in TSH-pretreated FRTL-5 cells.

Combination of TSH and Interleukin-6 (IL-6) can stimulate DNA synthesis in FRTL-5 cells. Phorbol 12-myristate 13-acetate (PMA) stimulates G0 to G1 transition but inhibits G1 to S transition in these cells. We studied the effect of IL-6 on DNA synthesis in TSH-pretreated FRTL-5 cells in the presence or absence of PMA. IL-6 induced DNA synthesis when it was added to TSH-pretreated cells. Further, PMA inhibited the DNA synthesis induced by IL-6. These data might suggest that in FRTL-5 cells IL-6 can show its mitogenic effect in G1 phase of their cell cycle progression.

Animals↗

[Disseminated intravascular coagulation (DIC) and pre-DIC due to severe infection in the elderly].

Because of pre-thrombotic state frequently present in the elderly, sepsis easily progresses to pre-DIC and DIC, sometimes with a fatal outcome. We assessed 31 elderly patients who developed pre-DIC and DIC due to severe infection. They were divided into two groups, early death group: 14 elderly patients with poor prognosis died within 14 days, and long survival group: 17 patients with good prognosis lived 15 days or more. Controls consisted of 31 elderly thrombotic disease cases and 25 healthy elderly cases. The DIC score was significantly higher in the early death group than in the long survival group, and there was a correlation between DIC score and survival. Moreover, many of the early death group were long-termed bed-ridden patients, serum BUN and Cre levels were significantly increased in the early death group compared to the long survival group. While plasma TAT, PIC and D-dimer levels were increased in thrombotic disease group compared to the healthy control group, TAT and D-dimer were also increased in the pre-DIC and DIC state than in the thrombotic state. In the early death group, D-dimer was higher than in the long survival group. We suggest that early diagnosis by molecular marker is important in the DIC stage, and a high D-dimer level may be a poor prognostic factor.

Aged↗

Lysozyme regulates LPS-induced interleukin-6 release in mice.

Bacterial lipopolysaccharide (LPS) stimulates the production and release of endogenous mediators [e.g., tumor necrosis factor (TNF), interleukins-1 and -6 (IL-1 and IL-6), and Platelet Activating Factor [PAF] responsible for the pathophysiologic changes and the mortality associated with sepsis. We recently demonstrated that lysozyme (LZM) bound to LPS (LZM-LPS complex) suppresses LPS-induced tumor necrosis factor-alpha (TNF-alpha) production in vivo. In the present study, we investigated the effect of LZM-LPS complex formation on LPS-induced IL-6 production, both in vitro and in vivo. With the addition of LZM-LPS complex, TNF-alpha and IL-6 release was significantly reduced compared with that by LPS in a dose-dependent manner in mouse macrophage-like cells, RAW264.7. IL-6 production in serum by LPS in carrageenan (CAR)-primed mice peaked at 2 hr following injection. LZM-LPS and LZM-Escherichia coli cell complex (as 1 microgram of LPS per mouse) released significantly reduced concentrations of IL-6 in serum (P < 0.01 and P < 0.001 versus CAR-pretreated LPS- or cell-injected mice). These results emphasize the important role of LZM in vivo in the neutralization of endotoxin. However, in the case of IL-6, by administration of a lethal dose of LPS (as 100 micrograms of LPS per mouse), the IL-6 level was reduced by LZM, but a significant concentration of IL-6 was still released; although the TNF- alpha concentration was negligible in this experimental condition. Thus, it is suggested that LZM might regulate the systemic inflammation induced during Gram-negative bacterial infections by inhibiting the release of cytokines in serum.

Animals↗

Prognosis after pacemaker implantation in cardiac sarcoidosis in Japan. Clinical evaluation of corticosteroid therapy.

Corticosteroids (CS) are useful drugs for the treatment of cardiac sarcoidosis with severe conducting defects due to sarcoid granuloma. Despite the continuous administration of CS, many patients with severe cardiac involvement may eventually die of congestive heart failure. The purpose of this study was to evaluate the efficacy of CS in patients who had a pacemaker implanted. Questionnaires were obtained from 29 institutes, and 34 cardiac sarcoidosis patients (8 males and 26 females) with pacemaker implantation were enrolled in this survey. We analyzed the survival period in these patients by the Kaplan-Meier method. There was no statistically significant difference in the survival of these patients in terms of their age, sex or disease duration (time from the onset of sarcoidosis to cardiac involvement). However, their survival was affected by the grade of dyspnea, the presence of heart failure, and certain abnormal findings on a myocardial scintigram and echocardiogram. In order to evaluate the effect of CS on the prolongation of survival, we measured the survival of the patients treated with CS and those not treated with CS. However, because of the small number of patients not treated with CS, we were unable to detect any statistically significant difference in survival. Therefore, we analyzed 104 cases in order to evaluate CS therapy: the 34 cases from the questionnaires and 70 cases reported in the literature over the last 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathies↗

[Anemia and neutropenia in elderly patients caused by copper deficiency for long-term enteral nutrition].

Anemia and neutropenia caused by copper deficiency is a well-known consequence of long term total parenteral nutrition in the literature. We present 6 bed-ridden elderly patients who developed anemia and neutropenia after receiving enteral nutrition for a long time (mean: 3.3 years) In all 6 patients, serum copper and ceruloplasmin level were very low, and the mean of their hematological data were as follows: WBC 2,200/microliters, neutrophil 554/microliters, hemoglobin 8.1 g/dl, platelet 260 x 10(3)/microliters, respectively. The bone marrow examination showed cytoplasmic vacuolization of both myeloid and erythroid precursors, and maturation arrest of granulopoiesis. Then, copper sulfate was administrated by enteral tube to 6 patients, and the improvement of anemia and neutropenia was observed within a month. A 82-year-old woman who received enteral nutrition for 3.5 years with sever anemia (Hb 3.7 g/dl) and neutropenia (neutrophil 350/microliters), showed a marked improvement in hematological data (Hb 8.0 g/dl, neutrophil 4, 092/microliters, respectively) after two months by administering the copper supplementation. The exact cause of the anemia and neutropenia in copper deficiency is unclear, but it is suggested that the decreased activity of enzyme containing copper may be related. Hematological abnormalities due to copper deficiency should be cared during long term enteral nutrition with long termed bed-ridden elderly patients.

Aged↗

Cerebellar MR in Fukuyama congenital muscular dystrophy: polymicrogyria with cystic lesions.

PURPOSE: To determine the MR appearance of cerebellar abnormalities in Fukuyama congenital muscular dystrophy. METHODS: We reviewed brain MR images of 25 patients with Fukuyama congenital muscular dystrophy and examined the autopsy specimens of a 23-month-old girl with the disease to determine the pathologic nature of the MR findings. RESULTS: MR studies revealed two characteristic cerebellar abnormalities: (a) disorganized cerebellar folia (16 cases) that were recognized as unusual distortions of the cortex; and (b) clusters of intraparenchymal cysts (23 cases). The two lesions were located close to each other, and milder lesions tended to affect only the superior semilunar lobule. The autopsy specimen revealed small cerebellar cysts, which consisted of dilated subarachnoid spaces buried beneath the malformed cortex. CONCLUSION: The disorganized folia represent cerebellar polymicrogyria, and the presence of cerebellar cysts is related to the polymicrogyria. These two MR changes are often present in Fukuyama congenital muscular dystrophy and are distinct enough to suggest the radiologic diagnosis.

Adolescent↗