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K Fukuda

Publications and source records attributed to K Fukuda.

At least 181 records · Page 10Linked to original sources
PubMed2000

Thiopental induces contraction of rat aortic smooth muscle through Ca(2+) release from the sarcoplasmic reticulum.

UNLABELLED: Little is known about the mechanism of thiopental-induced contraction in vascular smooth muscle. This study aimed to clarify this question by conducting isometric tension experiments and (45)Ca(2+) flux measurements in endothelium-denuded rat aortic rings. Thiopental induced a concentration-dependent contraction under basal tension. This contraction was enhanced when rings were precontracted with phenylephrine in the presence of verapamil. In Ca(2+)-free solution, thiopental-induced contraction was reduced but not abolished with high concentrations. Ca(2+) store depletion with a maximum dose of caffeine in Ca(2+)-free solution further reduced the contraction by subsequent thiopental. Ca(2+) store depletion with thapsigargin completely abolished contraction by thiopental. (45)Ca(2+) influx experiment in the presence of verapamil showed that thiopental could not induce any Ca(2+) influx with or without phenylephrine prestimulation. The (45)Ca(2+) efflux experiment showed more evidence of thiopental-induced Ca(2+) release, which was abolished by thapsigargin. In conclusion, thiopental induces contraction in rat aortic smooth muscle by releasing Ca(2+) from the sarcoplasmic reticulum without Ca(2+) influx. IMPLICATIONS: This is the first study providing evidence that thiopental-induced vascular contraction is caused by Ca(2+) release from the sarcoplasmic reticulum of the smooth muscle.

Animals↗
PubMed2000

Comparative contractile effects of halothane and sevoflurane in rat aorta.

BACKGROUND: Volatile anesthetic agents have been shown to have contractile effects in vascular tissues during specific conditions. This study compared contractile effects of halothane and sevoflurane in rat aorta treated with verapamil. This study also tried to elucidate the mechanism of the contraction. METHODS: Endothelium-denuded rat thoracic aorta was used for recording of isometric tension and measurement of influx of 45Ca2+. All experiments were performed in the presence of verapamil. In recording of tension, rings were precontracted with a submaximum dose of phenylephrine, followed by exposure to halothane or sevoflurane. For measurement of influx of 45Ca2+, rat aortic strips were exposed to phenylephrine and then to additional halothane or sevoflurane. Influx of Ca2+ was estimated by incubating the strips in 45Ca2+-labeled solution for 2 min. RESULTS: Halothane (0.5-4.0%) induced contraction in a dose-dependent manner, whereas sevoflurane (1-4%) had no effect on tension. Influx of 45Ca2+ was strongly enhanced by halothane at 1% and 2%, but only slightly at 4%, and was not affected by 1-4% sevoflurane. SK&F 96365, a blocker of voltage-independent Ca2+ channels, abolished contraction and influx of 45Ca2+ by 1% halothane. Depletion of Ca2+ from the sarcoplasmic reticulum with ryanodine or thapsigargin reduced the contraction induced by halothane at 4% but not that at 1% and 2%. CONCLUSION: Halothane is suggested to cause contraction by enhancing influx of Ca2+ via voltage-independent Ca2+ channels at concentrations up to 2% and by inducing release of Ca2+ at 4%. Sevoflurane (1-4%) is devoid of these contractile effects.

Anesthetics, Inhalation↗
PubMed2000

Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship.

Cyclooxygenase-2 (COX-2) plays an important role in carcinogenesis. Investigation of the suppressive action of twelve flavonoids of different chemical classes on the transcriptional activity of the COX-2 gene in human colon cancer DLD-1 cells using a reporter gene assay have revealed quercetin to be the most potent suppressor of COX-2 transcription (IC50 = 10.5 microM), while catechin and epicatechin showed weak activity (IC50 = 415.3 microM). Flavonoids have three heterocyclic rings as a common structure. A structure-activity study indicated that the number of hydroxyl groups on the B ring and an oxo group at the 4-position of the C ring are important in the suppression of COX-2 transcriptional activity. A low electron density of the oxygen atom in the hydroxyl group of the A ring was also important. Further examination of the role of the hydroxyl group in the A ring showed that bromination of resacetophenone to give 3,5-dibromo-2,4-dihydroxyacetophenone resulted in a 6.8-fold increase in potency for suppressing COX-2 promoter activity. These results provide a basis for the design of improved suppressors of COX-2 transcriptional activity.

Acetophenones↗
PubMed2000

Influenza outbreak detection and control measures in nursing homes in the United States.

OBJECTIVE: To evaluate the use of influenza vaccine, rapid influenza testing, and influenza antiviral medication in nursing homes in the US to prevent and control outbreaks. METHODS: Survey questionnaires were sent to 1017 randomly selected nursing homes in nine states. Information was collected on influenza prevention, detection and control practices, and on outbreaks during three influenza seasons (1995-1998). RESULTS: The survey response rate was 78%. Influenza vaccine was offered to residents and staff by 99% and 86%, respectively, of nursing homes. Among nursing homes offering the influenza vaccine, the average vaccination rate was 83% for residents and 46% for staff. Sixty-seven percent of the nursing homes reported having access to laboratories with rapid antigen testing capabilities, and 19% reported having a written policy for the use of influenza antiviral medications for outbreak control. Nursing homes from New York, where organized education programs on influenza detection and control have been conducted for many years, were more likely to have reported a suspected or laboratory-confirmed influenza outbreak (51% vs 10%, P = .01), to have access to rapid antigen testing for influenza (92% vs 63%, P = .01), and to use antivirals for prophylaxis and treatment of influenza A for their nursing home residents (94% vs 55%, P = .01) compared with nursing homes from the other eight states. CONCLUSIONS: Influenza outbreaks among nursing home residents can lead to substantial morbidity and mortality when prevention measures are not rapidly instituted. However, many nursing homes in this survey were neither prepared to detect nor to control influenza A outbreaks. Targeted, sustained educational efforts can improve the detection and control of outbreaks in nursing homes.

Antiviral Agents↗
PubMed2000

Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart.

Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily of cytokines, possesses hypertrophic actions and atrial natriuretic peptide (ANP)-producing activity in vitro. The goal of our study is to elucidate whether CT-1 affects the cardiovascular system in vivo. Intravenous injection of CT-1 (4-100 microg/kg) in conscious rats evoked significant declines in blood pressure and reflex increases in heart rate (HR) in a dose-dependent manner. CT-1 induced no significant change in cardiac output (from 260.7 +/- 11.0 to 264.7 +/- 26.6 ml. min(-1). kg(-1), P = not significant), which was compatible with the results from isolated perfused rat hearts; HR, change in pressure over time, left ventricular developed pressure, and perfusion pressure were unaffected. Northern blot and RT-PCR analyses revealed that CT-1 increased expression of inducible nitric oxide synthase (iNOS) in lung and aorta but not in heart or liver. Pretreatment with aminoguanidine, a specific iNOS inhibitor, inhibited both iNOS mRNA production and the depressor effect of CT-1. Interestingly, CT-1 increased ventricular expression of ANP and brain natriuretic peptide (BNP). The data demonstrate that CT-1 elicits its hypotensive effect via a nitric oxide-dependent mechanism and that CT-1 induces ANP and BNP mRNA expression in vivo.

Animals↗
PubMed2000

Significance of ERK cascade compared with JAK/STAT and PI3-K pathway in gp130-mediated cardiac hypertrophy.

We compared the role of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MEK)/extracellular signal-regulated protein kinase (ERK)/p90(RSK) cascade in gp130-mediated cardiac hypertrophy with the contribution of the Janus kinase (JAK)/signal transduction and activation of transcription (STAT) and phosphatidylinositide 3-kinase (PI3-K) pathways. Primary cultured neonatal rat cardiomyocytes were stimulated with leukemia inhibitory factor (LIF). LIF sequentially activated Raf-1, MEK1/2, ERK1/2, and p90(RSK). We used PD-98059 (a specific MEK inhibitor), AG-490 (a JAK2 inhibitor), and wortmannin (a PI3-K inhibitor) to confirm that this cascade was independent of the JAK/STAT and PI3-K/p70 S6 kinase (S6K) pathways. PD-98059, AG-490, and wortmannin suppressed the LIF-induced increase in [(3)H]phenylalanine uptake by 54.7, 21.5, and 25.6%, respectively, and inhibited the increase in cell area by 61.2, 42.8, and 39.2%, respectively. Reorganization of myofilaments was predominantly suppressed by AG-490. LIF-induced expression of c-fos, brain natriuretic peptide, and skeletal alpha-actin mRNA was markedly suppressed by PD-98059 and moderately suppressed by wortmannin and AG-490. Atrial natriuretic peptide was significantly suppressed by AG-490. These findings indicate that this pathway is critically involved in protein synthesis, induction of c-fos, brain natriuretic peptide, and skeletal alpha-actin expression and is partially involved in myofilament reorganization and atrial natriuretic peptide induction in gp130-mediated cardiac hypertrophy.

Androstadienes↗
PubMed2000

Ovariectomy exacerbates and estrogen replacement attenuates photothrombotic focal ischemic brain injury in rats.

BACKGROUND AND PURPOSE: We previously reported the infarct volumes in female spontaneously hypertensive rats (SHR) to be significantly smaller than those in male SHR. The purpose of the present study was to determine whether estrogen is responsible for the sex difference in ischemic vulnerability in SHR. METHODS: In experiment 1, 1 week (short-term) or 4 weeks (long-term) after the ovariectomy (OVX), female SHR (5 months old) were randomly subjected to photothrombotic occlusion of the middle cerebral artery, and the infarct volumes were determined. In experiment 2, the rats were randomly assigned to 3 groups (ie, the sham-ovariectomized, ovariectomized, and estrogen replacement groups). In the replacement group, estradiol valerate (200 microgram/kg) was subcutaneously injected once a week after the OVX. Four weeks after the OVX or sham-OVX, all rats were subjected to middle cerebral artery occlusion. Changes in regional cerebral blood flow were determined by laser-Doppler flowmetry. RESULTS: In experiment 1, the infarct volume produced 1 week after the OVX was not different from that of the sham-ovariectomized group. In contrast, the infarct volume produced 4 weeks after the OVX was significantly larger than that of the sham-ovariectomized group (82.4+/-11.6 versus 54.5+/-16.0 mm(3), P=0.0058). In experiment 2, estradiol replacement after the OVX was observed to attenuate the infarct volume compared with the ovariectomized group (55.6+/-18.8 versus 78.5+/-21.0 mm(3), P=0.0321). The degrees of regional cerebral blood flow reduction did not differ among the sham-ovariectomized, ovariectomized, and estrogen replacement groups. CONCLUSIONS: Chronic estrogen depletion was thus found to increase the infarct size, which was attenuated by estradiol replacement. These findings indicate that estrogen contributes to the sex difference in ischemic vulnerability and that endogenous estrogen also has a neuroprotective effect against ischemic brain damage.

Animals↗
PubMed2000

The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium.

The embryonic gut of vertebrates consists of endodermal epithelium, surrounding mesenchyme derived from splanchnic mesoderm and enteric neuronal components derived from neural crest cells. During gut organogenesis, the mesenchyme differentiates into distinct concentric layers around the endodermal epithelium forming the lamina propria, muscularis mucosae, submucosa and lamina muscularis (the smooth muscle layer). The smooth muscle layer and enteric plexus are formed at the outermost part of the gut, always some distance away from the epithelium. How this topographical organization of gut mesenchyme is established is largely unknown. Here we show the following: (1) Endodermal epithelium inhibits differentiation of smooth muscle and enteric neurons in adjacent mesenchyme. (2) Endodermal epithelium activates expression of patched and BMP4 in adjacent non-smooth muscle mesenchyme, which later differentiates into the lamina propria and submucosa. (3) Sonic hedgehog (Shh) is expressed in endodermal epithelium and disruption of Shh-signaling by cyclopamine induces differentiation of smooth muscle and a large number of neurons even in the area adjacent to epithelium. (4) Shh can mimic the effect of endodermal epithelium on the concentric stratification of the gut. Taken together, these data suggest that endoderm-derived Shh is responsible for the patterning across the radial axis of the gut through induction of inner components and inhibition of outer components, such as smooth muscle and enteric neurons.

Animals↗
PubMed2000

Potentially distinctive features of sinonasal inverted papilloma on MR imaging.

OBJECTIVE: The objective of this study is to describe potentially distinctive MR features of sinonasal inverted papilloma and those of coexisting squamous cell carcinoma. CONCLUSION: A sinonasal mass with a convoluted cerebriform pattern on T2- or enhanced T1-weighted images suggests inverted papilloma as a histologic diagnosis. Necrosis in a mass with such an appearance strongly suggests coexistent carcinoma.

Adult↗
PubMed2000

Necessity of monitoring HPLC by a X-R control chart on measurement of serum fat-soluble vitamins.

In epidemiologic studies, many serum samples obtained from a large population have to be processed for measurement of fat-soluble vitamins. Quantification results by a high performance liquid chromatography (HPLC) should be stable in both intra- and inter-run, and a quality control may be performed by a X-R control chart. The present study shows that serum retinol, alpha-tocopherol, alpha-carotene, beta-carotene, and lycopene could be measured simultaneously, by 1) use of photodiode-array (POD) detector, 2) selection of some optimal analytical conditions (e.g. column, mobile phase, column temperature), 3) applying 2 internal standards, and 4) monitoring by a X-R control chart. The present procedure yielded relatively low coefficients of variations (CVs) compared to some reported figures. However, determination of CVs only does not ensure the accuracy and precision of an assay system, and application of a X-R control chart may be necessary for a good quality control of measurement, such as serum fat-soluble vitamins.

Chromatography, High Pressure Liquid↗
PubMed2000

The effects of alcoholic compounds on the stability of type I collagen studied by differential scanning calorimetry.

The interaction between bovine tendon collagen and a series of homologous alcohols were investigated using a differential scanning calorimetry. For all alcoholic substances, as well as 2-hydroxyethyl methacrylate (HEMA), the concentration dependence of the denaturation temperature of collagen was observed, which showed a minimum at 30%. Clearly there are two opposing actions on the stabilization of the collagen structure; destabilization dominates over stabilization at lower concentrations, and vice versa at higher concentrations. The concentration dependence became greater for longer chain alcohols, while it was suppressed by the increased number of OH groups. The chain length-dependent surface tension may be related, which controls the permeation of the additives through the collagen fibers. Overall hydrophobicity, indicated by the hydrophile-lipophile balance (HLB) numbers, suggests the importance of the hydrophobic effect in the interaction of collagen and alcoholic substances, including adhesive monomers such as HEMA.

Alcohols↗
PubMed2000

Power Doppler sonography of breast masses: correlation of Doppler spectral parameters with tumor angiogenesis and histologic growth pattern.

The purpose of this study was to examine the relationship between spectral analysis on power Doppler sonography and microvessel density. Power Doppler sonography was performed in 71 patients with breast masses (36 invasive carcinomas and 35 benign lesions). Microvessel density was measured in surgical specimens from all breast carcinomas using anti-factor VIII-related antibody. Invasive carcinomas were divided into two groups according to their growth pattern (solid type, scirrhous type). The pulsatility index and resistive index were high in malignant tumors compared with those in benign lesions (P < 0.001). The maximum velocity had weak statistical significance (P < 0.05). Although the correlation of maximum velocity with microvessel density was strong in solid tumors (P < 0.001), the maximum intensity in scirrhous tumors had no correlation with microvessel density. In conclusion, solid tumors showed a tendency toward correlation of maximum velocity with microvessel density. High maximum velocity with high microvessel density suggests breast carcinoma and could be predictive of a poor prognosis in invasive breast carcinoma.

Adult↗
PubMed2000

[Hospitalization reduction by an asthma tele-medicine system].

We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site randomized control study. In this program, a nurse under physician supervision monitors the patient's airway status at home and provides instructions to individuals via the telephone, helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan. Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and randomly assigned to either the telemedicine or control group. After a six-month study period, an 83% reduction in hospitalization was demonstrated in the telemedicine group versus the control group, with a P value of 0.01. Improvement of peak expiratory flow and symptoms were also shown in the study group. We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring, compliance with prescribed daily prophylactic anti-inflammatory steroid medications, and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration.

Aged↗
PubMed2000

Synergistic induction of eotaxin expression in human keratocytes by TNF-alpha and IL-4 or IL-13.

PURPOSE: To investigate the effects of tumor necrosis factor (TNF)-alpha, interleukin (IL)4, and IL-13 on expression of the chemokine eotaxin by cultured human keratocytes. METHODS: Cultured human keratocytes were incubated with various combinations and concentrations of TNF-alpha, IL-4, and IL-13. The concentration of eotaxin in the culture supernatant was subsequently measured by enzyme-linked immunosorbent assay, and the amount of eotaxin mRNA in cell lysates was determined by reverse transcription-polymerase chain reaction analysis. RESULTS: Keratocytes incubated in the absence of cytokines did not release detectable amounts of eotaxin into the culture medium. Whereas incubation of keratocytes with TNF-alpha, IL-4, or IL-13 alone or with the combination of IL-4 and IL-13 had only a small effect on eotaxin release, exposure of the cells to TNF-alpha in combination with either IL-4 or IL-13 resulted in a marked increase in eotaxin production that was both time and dose dependent. The abundance of eotaxin mRNA in keratocytes was also increased in a synergistic manner by incubation of cells with TNF-alpha together with either IL-4 or IL-13. CONCLUSIONS: Stimulation of human keratocytes with the combination of TNF-alpha and either IL-4 or IL-13 resulted in synergistic increases in both the abundance of eotaxin mRNA and the release of eotaxin protein. This cytokine-induced increase in eotaxin production by keratocytes may contribute to eosinophil infiltration in inflammatory ocular diseases such as vernal keratoconjunctivitis.

Adolescent↗
PubMed2000

Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity.

With juices of grapefruit and related fruits, possible relationships between contents of six different furanocoumarins and extents of inhibition of microsomal CYP3A activity have been studied in vitro. Microsomal CYP3A-mediated testosterone 6beta-hydroxylation was inhibited by the addition of a fruit juice (2.5%, v/v) from eight different grapefruit sources, two sweeties, three pomelos, and one sour orange, whereas no clear inhibition was observed with two sweet orange juices. The inhibitory component in grapefruit juice resides mainly in the precipitate rather than in the supernatant after centrifugation. Higher amounts of (R)-6',7'-dihydroxybergamottin (DHB) were distributed in the supernatant, whereas GF-I-1, GF-I-2, GF-I-4, and the newly isolated GF-I-5 and GF-I-6 were detected predominantly in the precipitate. Mixing of five representative furanocoumarins at their detectable levels in grapefruit juice reproduced roughly the inhibitory potencies of grapefruit juice, but omission of any of the components resulted in decreased potencies. These results suggested that all the major furanocoumarins contributed to the CYP3A inhibitory properties of grapefruit juice. Furthermore, all six furanocoumarins showed stronger CYP3A inhibitory potencies after preincubation in the presence of NADPH, suggesting that both competitive and mechanism-based inhibition occur in a grapefruit juices-drug interaction.

Aryl Hydrocarbon Hydroxylases↗
PubMed2000

[Intraoperative autologous blood transfusion was effective in a massive blood loss during living-related donor liver transplantation].

We have experienced massive blood loss (> 80,000 g) during living-related donor liver transplantation (LRDLT) of a 14-year old girl with biliary atresia. As available homologous blood was not sufficient, we transfused autologous blood (13,400 ml) during operation. Although immunosuppressant was administered to the patient, severe infection did not occur for 10 days after the operation. Cold ischemia time of the graft liver was about 16 hr, but her postoperative liver function was well-maintained. The case suggests that intraoperative autologus blood transfusion is effective if homologous blood is insufficient during LRDLT.

Adolescent↗
PubMed2000

[A case of effective bisphosphonate therapy of sequential pamidronate and incadronate for bone metastases from breast cancer].

A 55-year-old woman complained of neck pain ten years after undergoing surgery. She was diagnosed as having bone metastases and treated using pamidronate therapy with doxifluridine, tamoxifen and fadrozole, which was assessed as effective. She complained of neck pain 32 months after pamidronate infusion. CT revealed that the sclerosis had continued but new lytic lesions were detected in the cervical vertebra. Thus, we attempted incadronate and medroxyprogesterone acetate (MPA) administration. After 2 months, incadronate therapy with MPA relieved her neck pain. CT revealed lytic lesions of cervical vertebra showing sclerosis 3 months after this treatment and the sclerosis has continued. Bisphosphonate therapy of sequential pamidronate and incadronate with MPA administration is a useful treatment for bone metastasis from breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗