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Biomedical subjects

K Takano

Publications and source records attributed to K Takano.

At least 217 records · Page 12Linked to original sources
PubMed1996

Cytokine-induced neutrophil chemoattractant (CINC)-2 alpha, a novel member of rat GRO/CINCs, is a predominant chemokine produced by lipopolysaccharide-stimulated rat macrophages in culture.

Neutrophil chemotactic factors (chemokines) have been purified from conditioned medium of lipopolysaccharide (LPS)-stimulated rat macrophages in culture. The LPS-stimulated macrophages produced one acidic chemokine, rat macrophage inflammatory protein (MIP)-1alpha, and four basic chemokines, cytokine-induced neutrophil chemoattractant (CINC)-1. CINC-2alpha, CINC-2beta and CINC-3/rat MIP-2. CINC-2alpha, a novel chemokine recently isolated from conditioned medium of rat granulation-tissue culture, was the major chemoattractant among these four basic chemokines. The results suggest that CINC-2alpha is produced by activated macrophages in vivo and plays an important role in the infiltration of neutrophils into inflammatory sites in rats

Amino Acid Sequence↗
PubMed1996

The role of spreading depression in focal ischemia evaluated by diffusion mapping.

This study investigated the role of spontaneous and induced spreading depression (SD) on the evolution of focal ischemia in vivo. We induced focal ischemia in 12 rats using the middle cerebral artery suture occlusion (MCAO) method. Chemical stimulation of nonischemic ipsilateral cortex by potassium chloride application (KCl group; n = 7) and saline (NaCl group; n = 5) was performed at 15, 30, 45, and 60 minutes following MCAO, and SD was detected electrophysiologically. Ischemic lesion volumes assessed over 15-minute intervals, evaluated by continuous apparent diffusion coefficient (ADC) of water mapping, demonstrated that the ischemic region increased significantly during 15-minute time epochs with a single SD episode (36.5 +/- 12.9 mm3, mean +/- SD) or multiple SD episodes (39.8 +/- 22.3) compared with those without SD (13.9 +/- 11.5) (p = 0.0009). Infarct volume at postmortem 24 hours after MCAO was significantly larger in the KCl group, with more total SDs (237.8 +/- 13.8) than the NaCl group (190.5 +/- 12.6) (p = 0.0001). This study demonstrates that ischemia-related and induced SDs increase significantly ischemic lesion volume in vivo, supporting the hypothesis for a causative role of SD in extending focal ischemic injury.

Animals↗
PubMed1996

The effects of prolonged treatment with citicoline in temporary experimental focal ischemia.

Potential therapeutic effects of cytidine 5-diphosphocholine (citicoline), a key intermediary in the biosynthesis of the membrane phospholipid, phosphatidylcholine, are presumably related to enhanced phospholipid synthesis in the ischemic brain. We evaluated prolonged citicoline treatment in a temporary focal ischemia model. Using the suture occlusion model, we induced 2 hours of temporary ischemia in 30 Sprague-Dawley rats. The rats were randomly and blindly assigned to receive intraperitoneally 500 mg/kg citicoline (HD), 100 mg/kg citicoline (LD) or physiologic saline as the control group once daily for 7 days (n = 10 per group) beginning at the time of reperfusion. Neurological scoring (0-5 scale) was performed daily. After elective sacrifice on day 7, or earlier if death occurred prematurely, the brains underwent 2,3,5-triphenyltetrazolium chloride (TTC) staining for calculation of corrected infarct and edema volume. The mean corrected infarct volume in the HD group was 125 +/- 45.2 mm3 (mean +/- SD), significantly smaller than controls, 243.5 +/- 88.6 mm3 (p < 0.01, Scheffe's-test). The LD group infarct volume was 200.2 +/- 62.8 mm3 (N.S.). The mean amount of brain edema in the HD group was 46.4 +/- 45.6 mm3 was smaller than the controls, 92.3 +/- 54.4 mm3 and the LD group, 84.9 +/- 71.7 mm3 (N.S.). Mortality before day 7 in the HD was 30% while it was 50% in the two other groups. The neurologic score on day 7 was 2.5 +/- 1.8 in the HD group, 3.3 +/- 1.8 in the LD group and 3.4 +/- 1.7 in controls (N.S.). These results demonstrate that extended high dose citicoline treatment significantly reduced infarct volume in this temporary focal ischemia model and that there was a trend toward reducing brain edema and mortality. These effects may be related to membrane stabilization and inhibition of free fatty acid release.

Animals↗
PubMed1996

Development in vitro of preimplantation embryos from 55 mouse strains.

Mouse pronuclear embryos were obtained by in vitro fertilization with oocytes of 55 strains of immature females by gonadotrophin-induced ovulation and epididymal sperm of Slc:ICR strain. The number of oocytes ovulated with hormones (5.3-49.4 oocytes per head; average, 22.6), rates of in vitro fertilization (12.2-95.3%; average, 70.7%) and subsequent preimplantation development in Whitten's medium (WM) varied greatly among strains. F1 hybrids developed significantly better than other strains of mice and outbred animals did not develop as well as inbred animals. Within inbred mice, coat colour had no significant effect. In addition, the observation of preimplantation development in WM supplemented with ethylenediamine tetraacetic acid (EDTA) showed that the beneficial effect of the chelator was not universal to mouse embryos; EDTA had a good effect on ICR and PW/aSlc embryos but not on AKR or ddY embryos. The results indicate that strain differences should be considered when interpreting reproductive experiments using mouse embryos.

Analysis of Variance↗
PubMed1996

Secretory granule formation and synthesis pathway of secretory proteins in parotid gland cells.

The cytochemical technique for endogenous peroxidase and an immunocytochemical method with protein A-gold were used to investigate the formation of the secretory granule substructure in acinar cells of the gerbil parotid glands in normal conditions and after treatment with the ionophore monensin. In untreated animals and 90 min after treatment with monensin, peroxidase activity was seen in rER, in transport vesicles close to the condensing vacuoles, and in the dense core of condensing vacuoles and secretory granules, whereas the Golgi cisternae remain unreactive. At 45 or 60 min after stimulation with monensin, the condensing vacuoles and the immature granules in the trans Golgi area did not exhibit dense cores and their content appeared similar to the peripheral portion of the mature secretory granules. These observations suggest that, in Mongolian gerbil parotid acinar cells, some substances such as peroxidase may be transported from the rER directly to the condensing vacuoles.

Animals↗
PubMed1996

The structure, stability, and folding process of amyloidogenic mutant human lysozyme.

The physicochemical properties of an amyloidogenic mutant human lysozyme (Ile56Thr) were examined in order to elucidate the mechanism of amyloid formation. The crystal structure of the mutant protein was the same as the wild-type structure, except that the hydroxyl group of the introduced Thr56 formed a hydrogen bond with a water molecule in the interior of the protein. The other physicochemical properties of the mutant protein in the native state were not different from those of the wild-type protein. However, the equilibrium and kinetic stabilities of the mutant protein were remarkably decreased due to the introduction of a polar residue (Thr) in the interior of the molecule. It can be concluded that the amyloid formation of the mutant human lysozyme is due to a tendency to favor (partly or/and completely) denatured structures.

Amyloidosis↗
PubMed1996

Superimposition of In-111 platelet SPECT and CT/MR imaging in intracardiac thrombus.

An initial attempt to superimpose in-111-labeled platelet SPECT over CT/MRI in two patients with intracardiac thrombus is presented. One patient was a 65-year-old woman with a history of mitral and tricuspid valve replacement. This patient had a large thrombus measuring 74 x 43 x 34 mm in the right atrium. Fusion imaging with CT showed increased in-111 activity on the surface of the thrombus, which was visualized as circular activity on a planar image. The other patient was a 72-year-old woman who had a thrombus measuring 17 x 14 x 12 mm at the cardiac apex. Planar imaging showed two discrete areas of abnormal in-111 activity. Superimposition of the SPECT image over MR revealed that one of these areas corresponded to the small thrombus, whereas the other related to a previous subendomyocardial biopsy. In both patients, the activity ratio of the abnormal in-111 accumulation versus the cardiac chamber on SPECT was greater than that on planar images. The correlation of in-111 platelet SPECT and CT/MRI was useful in accurately localizing the intracardiac thrombus.

Aged↗
PubMed1996

GHRH activates a nonselective cation current in human GH-secreting adenoma cells.

Electrophysiological responses induced by human (h) growth hormone-releasing hormone (GHRH) were analyzed using the perforated whole cell clamp technique in human growth hormone (GH)-secreting adenoma cells. Application of hGHRH depolarized the membrane by increasing Na+ conductance. The reversal potential of the hGHRH-induced current was -20 to 0 mV. The channel was permeable to Na+, Li+ and K+ but not to TMA+. These properties were compatible with those of nonselective cation channels. Similar nonselective cation current was activated by 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin, and the activation of the hGHRH-induced current was inhibited by protein kinase A (PKA) inhibitors, (R)-p-adenosine 3',5'-cyclic monophosphate and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoleinsulfonamide, and PKA inhibitor peptide PKI-(5-24), indicating that hGHRH-induced current was activated by PKA. Cholera toxin pretreatment eliminated the hGHRH-induced current, suggesting that Gs is involved in the activation of this current. This current became irreversible when the cells were pretreated with okadaic acid, suggesting that the recovery of the hGHRH-induced current was mediated by a serine/threonine protein phosphatase. GHRH-induced GH secretion was inhibited in Na+-free medium, suggesting the importance of the nonselective cation current on hGHRH-induced GH secretion. In human GH-secreting nonadenoma cells, hGHRH increased Na+ conductance, as was the case in GH-secreting adenoma cells.

Adenoma↗
PubMed1996

Enhancement of Ca2+ currents by GHRH and its relation to PKA and [Ca2+]i in human GH-secreting adenoma cells.

The effects of human growth hormone-releasing hormone (hGHRH) on Ca2+ channels were examined in human growth hormone-producing adenoma cells using the perforated whole cell clamp technique. These cells exhibited T- and L-type Ca2+ channel currents, and application of 10(-8) M hGHRH increased the amplitude of both currents. Application of 10(-5) M 8-bromoadenosine 3',5'-cyclic monophosphate also increased T- and L-type currents. Additional application of 10(-8) M hGHRH did not further increase the current amplitudes. Treatment with the Rp diastereomer of adenosine 3',5'-cyclic monophosphothioate (10(-5) M) or H-89 (10(-5) M) inhibited the enhancement of Ca2+ channel currents by hGHRH, as did intracellular injection of protein kinase A (PKA) inhibitor peptide [PKI-(5-24)], indicating that hGHRH increased the amplitude of Ca2+ channel currents through the activation of the adenosine 3',5'-cyclic monophosphate (cAMP)-PKA system. When intracellular Ca2+ concentration ([Ca2+]i) was chelated to < 30 nM with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTAAM), hGHRH failed to increase the Ca2+ channel currents. In this condition, hGHRH activated nonselective cation channels, which revealed that the cAMP-PKA system operated after treatment with BAPTA-AM and that the site of low [Ca2+]i-induced inhibition of hGHRH effects on Ca2+ channels was at a step after PKA activation.

Adenoma↗
PubMed1996

Gq/11 and PLC-beta 1 mediate the substance P-induced inhibition of an inward rectifier K+ channel in brain neurons.

1. Substance P (SP) induces a slow neuronal excitation in cholinergic neurons from the nucleus basalis by suppressing an inwardly rectifying K+ current (Kir). We have determined which G protein alpha-subunit mediates this SP effect. 2. After intracellularly injecting antibody against each alpha-subunit of G proteins (Gq alpha/11 alpha, G12 alpha, and G13 alpha) with an Eppendorf microinjector, we examined, by using the whole cell patch-clamp and the ON-cell mode of single-channel recording, the effect of SP on Kir in cultured neurons of the nucleus basalis. The effect of SP on Kir was substantially reduced in neurons injected with antibodies to Gq alpha/11 alpha but not with antibodies to G12 alpha or G13 alpha. 3. The effects of antibodies against three isozymes of phospholipase C (PLC-beta 1, PLC-beta 2, and PLC-beta 3) were tested. The SP-induced suppression of Kir was reduced by antibody against PLC-beta 1 but not by antibodies against PLC-beta 2 or PLC-beta 3. 4. We conclude that the SP-induced inhibition of Kir in nucleus basalis neurons is mediated by Gq/11 and PLC-beta 1.

Animals↗
PubMed1996

Serum albumin for estimating creatinine clearance in the elderly with muscle atrophy.

The present study was conducted to develop a special formula to predict creatinine clearance (CCr, ml/min) in the elderly with chronic muscle atrophy using serum albumin (Alb, g/dl). We obtained 90 data sets including actual body weight (BW, kg), urinary creatinine excretion (UCr, mg/24 h), serum creatinine (SCr, mg/dl), and Alb from 90 inpatients aged 60-92 years. Regression equations were determined between the dependent variable of UCr/BW and the explanatory variable of Alb as follows: For males Ucr/BW = 2.695 Alb + 4.665 For females Ucr/BW = 1.827 Alb + 4.146. Then, the new predictive formula was derived from the equations: For males CCr = (19Alb + 32)BW/(100 x SCr) For females CCr = (13Alb + 29)BW/(100 x SCr). Evaluations for the predictive error (predicted CCr- measured CCr) showed that the new formula could provide more accurate and less biased estimates of CCr than the Cockcroft and Gault formula could, even in patients with renal insufficiency and in those with Alb < or = 2.8 g/dl.

Aged↗
PubMed1996

Effect of basic fibroblast growth factor on experimental focal ischemia studied by diffusion-weighted and perfusion imaging.

BACKGROUND AND PURPOSE: Basic fibroblast growth factor (bFGF) has documented neuroprotective properties. This study was performed to evaluate the effects of bFGF on infarct size when administered 30 minutes after induction of focal cerebral ischemia in rats. Diffusion-weighted and perfusion MRI were used during the drug infusion. METHODS: We blindly randomized 20 Sprague-Dawley rats to receive either drug (n = 10) or vehicle (n = 10). The animals underwent middle cerebral artery (MCA) occlusion using the suture model. Diffusion-weighted MRI was initiated 30 minutes after induction of ischemia and repeated frequently for 3.5 hours. Drug (45 micrograms/kg per hour) or vehicle (saline) infusion began 30 minutes after MCA occlusion and continued for 3 hours. Perfusion images were made at 25, 90, and 150 minutes after MCA occlusion. The animals were killed after 24 hours of permanent MCA occlusion, and brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). RESULTS: The TTC-derived, corrected infarct volume postmortem in the bFGF-treated group was significantly smaller than that in controls (126.6 +/- 51.9 versus 180.2 +/- 54.9 mm3, mean +/- SD, P = .038). Diffusion imaging showed essentially equal lesion volumes 3 hours after MCA occlusion (195.4 +/- 61 mm3 in the drug-treated group and 194.4 +/- 65 mm3 in controls). At 4 hours, ischemic lesion size was 182.1 +/- 56.9 mm3 in treated animals and 222.9 +/- 88.7 mm3 in the controls (P = .24, NS). Perfusion imaging did not show a change of cerebral perfusion within ischemic brain regions in the bFGF group during the infusion. No behavioral or physiological side effects were observed. CONCLUSIONS: bFGF is a safe and effective treatment for focal cerebral ischemia in rats. We observed a modest delayed difference of ischemic lesion size in vivo with diffusion MRI. The diffusion-weighted MRI findings suggest a potential delayed therapeutic effect of bFGF, and the perfusion imaging findings imply that the effect is not due to increased blood flow to the ischemic region.

Animals↗
PubMed1996

Location and behavior of dorsal determinants during first cell cycle in Xenopus eggs.

In Xenopus eggs, removal of small volumes of cytoplasm along with the surface (2-10% of the entire egg volume) causes very severe dorsal reduction (average DAI=1.4) when made at a site ventrally 30 degrees off the vegetal pole at 20% time of first cell cycle (0.2 NT). The greatest dorsal reduction (average DAI=1.1) occurs when removal is done at the vegetal pole at 0.3 NT, and intermediate reductions (average DAI=2.2-2.6) when done at sites dorsally, dorsolaterally or laterally 30 degrees off the vegetal pole at 0.4 NT. Removal at sites dorsally, dorsolaterally or laterally 60 degrees off the vegetal pole provokes slight dorsal reduction (average DAI=3.5-3.9) when made at 0.4-0.5 NT. Removal at all sites after 0.4 NT causes a steady decrease in the extent of dorsal reduction. By contrast, removal of larger volumes of dorsal cytoplasm (16-50% of the entire egg volume) causes a steady increase in the extent of dorsal reduction during first cell cycle with its maximum effect at 1.0 NT (average DAI=3.1). The surgery for the cytoplasmic removal does not affect cortical rotation. We conclude from these results that dorsal determinants are concentrated first in a small region ventrally 30 degrees off the vegetal pole by 0.2 NT, then move toward the vegetal pole during the period 0.2-0.3 NT and disperse to a broad region spanning over both the presumptive dorsal and ventral, but mainly the dorsal, hemispheres during the period 0.3-0.8 NT.

Animals↗
PubMed1996

Growth response to growth hormone therapy in patients with different degrees of growth hormone deficiency.

Growth response to GH therapy in prepubertal patients with idiopathic GH deficiency (GHD) was analyzed in terms of the chronological age at the start of GH treatment and the GH secretory capacity, by using the large database provided by the International Cooperative Growth Study (ICGS) Japan. 1192 patients, aged from 3 to 10 years were divided into three groups with the following maximum GH values in GH stimulation tests: Group A: both < or = 5 ng/ml, group B: both 5-10 ng/ml, group C: one > 10 ng/ml. Analysis of age-related growth response using with delta height SDS (delta height SDS) as a response variable revealed that the group A patients responded better to GH, while there was no differences between the other groups. Simple and multiple regression analysis showed that IGF-I and chronological age (CA) negatively correlated with growth response, and target height SDS-height SDS positively correlated. These three most important predictors accounted for 49% of the variation in the growth response in group A, whereas six variables such as CA, frequency of GH injection, % overweight, GH dose, target height-height SDS, and pretreatment height velocity SDS accounted for only 28% of those in groups of B and C. These results lead us to conclude that growth response to GH is related to the degree of GH impairment with its cut-off level of 5 ng/ml. From these findings it might be suggested that treatment regimen should be tailored to individual requirements according to the degree of GHD.

Aging↗
PubMed1996

[Small cell lung cancer associated with ectopic ACTH syndrome].

A 70-year-old woman was referred to our hospital for diagnosis and treatment of a pulmonary mass detected on a chest X-ray film. Small cell lung cancer was diagnosed from pathological examination of a specimen of the tumor obtained by transbronchial biopsy. Paraneoplastic Cushing's syndrome was diagnosed on the basis of an elevated serum ACTH level (2000 pg/ml), the serum cortisol level (171.9 micrograms/dl), elevated excretion of urinary 17-OHCS (67 mg/day), persistent hypokalemia, metabolic alkalosis, hyperglycemia, central obesity, hypertension, systemic pigmentation, and the lack of a history of diabetes mellitus. Immunohistochemical staining with a polyclonal anti-ACTH antibody of a biopsy specimen from a lymph node with metastasis showed that tumor cells were weakly positive. The patient responded well to intensive chemotherapy with VP-16 (100 mg/m2 day 103), CBDCA (100 mg/m2 day 1-3), and CDDP (80 mg/m2 day 1). Complete response was obtained after 6 courses of chemotherapy. The serum ACTH level decreased rapidly as the tumor shrank. The primary tumor, however, relapsed after 3 months and the patient died of progressive disease, 11 months after diagnosis.

ACTH Syndrome, Ectopic↗
PubMed1996

[Attempt of helical CT densitometry for assessing regional pulmonary ventilation].

Pulmonary dynamic CT densitometry during steady-state breathing was recorded and analyzed using helical CT scan in 14 patients with obstructive disorders involving small and large airways, and 2 with restrictive lung disease. The data set of 7-second, continuous helical scan at constant table position were reconstructed as 35 one-second temporarily overlapping images at 0.2- second intervals over 2-3 respiratory cycles, and regional CT densitometry was displayed. Normal lungs (5 volunteers) showed a regular sinusoidal curve, and maximal lung density change (LDC) was greater independent lungs than in independent lungs, with an average difference of 29.5 HU, indicating the gravitational effect In contrast, a regular sinusoidal curve was not shown in obstructive disorders, and a significant reduction in maximal LDC (33.7 +/- 22.6 HU) compared with the normal lungs (60.8 +/- 25.9 HU) (P < 0.001) was indicated. In contrast, no marked reduction in maximal LDC (53.7 +/- 28.6 HU) was shown in restrictive disorders. This method is fast and easy, and appears useful for the detection of ventilation abnormalities in obstructive lung disorders.

Absorptiometry, Photon↗