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Biomedical subjects

K Ikegami

Publications and source records attributed to K Ikegami.

At least 19 recordsLinked to original sources
PubMed2006

Homer1c interacts with Hippi and protects striatal neurons from apoptosis.

By the two hybrid screening of mouse brain cDNA library, we identified Hppi, a cell death-promoting protein, as a binding partner of postsynaptic scaffold protein Homer1c. Hippi interacted specifically with Homer1c but not with its homologue Homer2. It was reported that Hippi, when complexed with Hip1, induces the apoptosis in striatal neurons and may cause Huntington's disease. We found that this apoptotic effect of Hippi was specific to the striatum and was not observed in hippocampal neurons. Furthermore, the apoptotic effect of Hippi was prevented when Homer1c was co-expressed in cultured striatal neurons. The protective effect of Homer1c was diminished when Hippi binding domain was deleted. These results suggest that Homer1c may play an important role in the mechanisms of neuronal death in the striatum.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Ultrafast photoinduced melting of a spin-Peierls phase in an organic charge-transfer compound, K-tetracyanoquinodimethane.

Ultrafast photoinduced phase transition in a spin-Peierls (SP) system of K-tetracyanoquinodimethane (K-TCNQ) was studied by femtosecond (fs) reflection spectroscopy. Photocarriers destabilize the SP phase, resulting in a decrease in molecular dimerization within 400 fs. Such a melting of the SP phase drives three kinds of coherent oscillations. By comparing the oscillations with the Raman bands activated by the dimerization, we show that the oscillation of 20 cm-1 is due to an LO phonon, and it plays an important role for the stabilization of the SP phase.

Journal Article↗
PubMed2005

The validity of the mangled extremity severity score in the assessment of upper limb injuries.

The Mangled Extremity Severity Score (MESS) may be used to decide whether to perform amputation in patients with injuries involving a limb. A score of 7 points or higher indicates the need for amputation. We have treated three patients with a MESS of 7 points or higher, in two of which the injured limb was salvaged. This scoring system was originally devised to assess injuries to the lower limb. However, a MESS of 7 points as a justification for amputation does not appear appropriate when assessing injuries to the major vessels in the upper limb.

Adult↗
PubMed2003

Non-apoptotic neurite degeneration in apoptotic neuronal death: pivotal role of mitochondrial function in neurites.

The length and thinness of neurites render them greatly susceptible to a variety of insults. Accumulating evidence suggests that neurite degeneration is not a passive, but an active and causative, event in some neurodegenerative diseases. Nonetheless, the mechanisms underlying neurite degeneration remain largely unknown. To elucidate the relevant mechanisms, we employed a mutant C57BL/Wld mouse with a unique phenotype of resistance to Wallerian degeneration, and separately analyzed the destruction of cell soma and neurites following treatment with vinblastine, a microtubule-disrupting agent, in superior cervical ganglion neurons. Vinblastine induced macromolecular synthesis-dependent cell death, which was indistinguishable between the wild-type and mutant mice. Evidence for a loss of mitochondrial cytochrome c, caspase activation, and nuclear fragmentation, has indicated that this type of cell death is entirely apoptotic. Consistent with this, the ATP level in the cell soma was well maintained and indistinguishable between wild-type and mutant mice. In neurites of wild-type neurons, vinblastine induced an early loss of mitochondrial membrane potential (MMP) and ATP depletion preceding caspase-independent degeneration, suggesting that this type of neurite degeneration is principally non-apoptotic. In contrast, neurites of mutant neurons were markedly resistant to vinblastine-induced degeneration, and both the MMP and the ATP content in the neurites were well maintained. Exposure of mutant neurons to carbonyl cyanide m-chlorophenyl-hydrazone, an uncoupler, caused extreme neurite degeneration following rapid MMP loss. Collectively, our findings suggest that: 1) neurite degeneration is regulated through a non-apoptotic process achieved by mitochondrial dysfunction in neurites; 2) the mitochondrial functional status is controlled separately in neurites and in the neuronal soma.

Adenosine Triphosphate↗
PubMed2000

Membrane depolarization-mediated survival of sympathetic neurons occurs through both phosphatidylinositol 3-kinase- and CaM kinase II-dependent pathways.

It has been well established that the NGF-mediated survival of sympathetic neurons in culture occurs through the phosphatidylinositol (PI) 3-kinase/Akt-dependent pathway. In contrast, the mechanism by which membrane depolarization promotes neuronal survival independently of NGF remains unresolved. Here we show that LY294002, a specific inhibitor of PI 3-kinase, induced cell death of sympathetic neurons under depolarizing conditions with elevated K(+) (IC(50)= approximately 30 microM). Interestingly, lower concentrations of this agent (< or =10 microM) were sufficient to suppress Akt phosphorylation at Ser-473, a putative downstream target of PI 3-kinase, under these conditions. We also show that KN-62, a specific inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) suppressed depolarization-mediated survival in a does-dependent manner (IC(50)= approximately 2 microM) that paralleled attenuation of sustained levels of intracellular Ca(2+) evoked by depolarization. This IC(50) value is greater than that for CaMKII ( approximately 0.8 microM). These findings led us to hypothesize that depolarization-mediated survival occurs through both the PI 3-kinase/Akt and the CaMKII pathways. Indeed, combined treatment with LY294002 (25 microM) and KN-62 (0.5 microM) dramatically abolished depolarization-mediated survival, whereas each alone did not significantly attenuate it. Under these conditions, KN-62 neither impaired sustained levels of intracellular Ca(2+), nor inhibited the phosphorylation of Akt. It is thus likely that PI 3-kinase and CaMKII independently promote the membrane depolarization-mediated survival of sympathetic neurons in culture.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Late onset X-linked hydrocephalus with normal cerebrospinal fluid pressure.

A family with X-linked hydrocephalus with normal cerebrospinal fluid (CSF) pressure and in which three brothers and a grandson of case 1, a proband, were affected is reported. The symptoms at onset were epileptic attacks that started in adulthood in the three brothers and at the age of 6 years in the grandson. In the three brothers, from 10 to 27 years after the onset of epileptic episodes, disorganization of intelligence and psychiatric deterioration were gradually noticed by their families. At the same time, they showed occasional urinary incontinence. Brain computed tomography (CT) scans revealed dilatation of the ventricular systems. Based on the results of the measurement of CSF pressure and radioactive-iodinated human serum albumin (RISA)-cysternography, two of the brothers were diagnosed as having normal pressure hydrocephalus (NPH), and they were treated neurosurgically. However, no obvious improvement in clinical symptoms was observed. Although the grandson had shown normal psychomotor development during his early childhood, temporal epilepsy and temper tantrums started at the age of 6 years. Computed tomography-scanning revealed dilatation of the ventricular system similar to the other three cases at the age of 8 years. With the diagnosis of NPH, the patient underwent a shunt operation, which resulted in no obvious effects. As it is reasonable to surmise that the pathological gene would have been transferred via the daughter of the proband to the grandson, it is suggested that the inheritance manner might be X-linked recessive. The cases presented here are different from the cases of hydrocephalus due to stenosis of the aqueduct Sylvius (HSAS) and other types of X-linked hydrocephalus reported previously in terms of the age of onset, course, symptoms, and CT findings. Thus, it is suggested that the present cases might be a new type of X-linked hydrocephalus.

Adolescent↗
PubMed2000

Effect of tranilast oily gel on carrageenin-induced granulation in rats.

Tranilast (TL) oily gels consisting of hydrogenated soybean phospholipid and fatty-acid ester were prepared, and the inhibitory effect of the gels on the growth of granulation tissue were evaluated in a carrageenin-induced rat granulation model. By the application of 0.1 and 0.2% TL oily gel, the weight of granulation tissue was significantly reduced to 64 and 55%, respectively, of control value. Furthermore, these gels reduced their respective hydroxyproline content to 64 and 51% of the control. On the other hand, the inhibitory effect of 10% TL ointments, which are clinically used for the treatment of keloids and hypertrophic scars as hospital preparations, was much lower than that of the oily gels. In addition, the application of 0.1 and 0.2% oily gel led to high concentration (0.1% gel, 168+/-18 microg/g; 0.2% gel, 221+/-16 microg/g) of TL in the dermis as compared with the 10% TL ointments. These results suggest that TL oily gels may be a useful topical formulation for the treatment of keloids and hypertrophic scars.

Administration, Topical↗
PubMed2000

Rapid, sensitive and simple detection of candida deep mycosis by amplification of 18S ribosomal RNA gene; comparison with assay of serum beta-D-glucan level in clinical samples.

We evaluated the clinical usefulness of a polymerase chain reaction (PCR) assay amplifying the 18S ribosomal RNA gene of fungi for the diagnosis of deep candidiasis, compared with that of the beta-glucan test or Cand-Tec test. Thirty critically ill patients who had received prolonged care with intravenous hyperalimentation and endotracheal intubation in the intensive care unit and were suspected of having deep fungal infections were examined. Twenty-one were fungi positive in the PCR assay (70%). Among 24 samples in which the PCR assay, beta-glucan test and Cand-Tec test were performed simultaneously, 75% of the samples (18/24) were fungi positive in the PCR assay, whereas only 54% (13/24) had positive reactions in the beta-glucan test and 21% (5/24) in the Cand-Tec test. The results of the Cand-Tec test showed no relationship with those of the PCR or beta-glucan test. The lower limit of detection in the PCR assay was 4-5 CFU/ml of C. albicans in blood. No fungal organism was amplified from the serum of 20 healthy individuals. The results of the PCR assay and beta-glucan test showed a significant correlation in this study, but the PCR assay proved to be more sensitive than the beta-glucan test (p < 0.05), and to be more useful for the clinical diagnosis and monitoring of deep Candidiasis.

Candida↗
PubMed1999

Effects of terfenadine, astemizole and epinastine on electrocardiogram in conscious cynomolgus monkeys.

We examined the effects of non-sedative histamine H1 receptor antagonists on the electrocardiogram (ECG) in conscious cynomolgus monkeys. Terfenadine (3 mg kg(-1) h(-1), i.v.) and astemizole (0.3 and 1 mg kg(-1) h(-1), i.v.) caused significant time-dependent increases in the QT interval and QTc Bazett (QTc). However, normal ECG forms were found during a 60-min infusion of epinastine (3 mg kg(-1) h(-1) i.v.). A higher dose of epinastine (10 mg kg(-1) h(-1), i.v.) increased the QTc and PR interval only 5 min after the start of the infusion. The minimum plasma concentrations of terfenadine, astemizole and epinastine which caused QTc prolongation were 85, 35 and over than 3600 ng/ml, respectively. These drugs did not alter the PQ and QRS intervals and did not cause arrhythmia or atrioventricular block. Our results are consistent with the clinical observation that prolongation of QTc is caused by terfenadine and astemizole but not by epinastine. Thus, measurement of QTc in cynomolgus monkey appears to be a useful approach for evaluating the potential cardiotoxicity of histamine H1 receptor antagonists.

Animals↗
PubMed1999

Evaluation of colonic absorbability of drugs in dogs using a novel colon-targeted delivery capsule (CTDC).

A series of dog studies were performed to examine the in vitro/in vivo relationship of drug release behavior of the newly developed colon-targeted delivery capsule (CTDC). The four kinds of CTDCs containing theophylline, each of which has a different in vitro dissolution lag time, were orally administered to four beagle dogs under fasted condition, and the onset times of drug absorption were compared. The CTDC with longer in vitro lag time had a later onset of drug absorption. It was also found that the time difference between the gastric emptying and the onset of drug absorption was almost equal to the in vitro dissolution lag time of the capsule, suggesting a similar performance of CTDC in the gastrointestinal tract. From the comparison to the absorption behavior of the colon arrival marker, i.e. sulfasalazine, it was proved that the CTDC with the lag time of 3 h can deliver the drug directly to the colon. This result implied that the CTDC can be used as a non-invasive means for assessing the regional absorbability of drugs in the gastrointestinal tract. To evaluate the absorbability of drugs in the colon, three model drugs, theophylline (THEO), acetaminophen (ACET), and phenylpropanolamine hydrochloride (PPA) were directly delivered to the colons of beagle dogs using the CTDC with the lag time of about 3 h. The obtained relative bioavailabilities to the solution form were as high as 94.2%, 71.0%, and 91.5% for THEO, ACET and PPA, respectively, suggesting that the colonic absorbability of those drugs is essentially good.

Absorption↗
PubMed1999

Molecular weight independence of the effect of additive hyaluronic acid on the lubricating characteristics in synovial joints with experimental deterioration.

OBJECTIVE: To assess the molecular weight dependence of the lubricating characteristics of additive hyaluronic acid in animal joints with experimental deterioration. DESIGN: An experimental study in rabbits stifles in vitro. BACKGROUND: Hyaluronic acid is used as a drug for osteoarthritis. However, the molecular weight dependence of the effect of hyaluronic acid has been unclear. METHODS: Using a robotic arm under force-control, frictional coefficients were measured in fourteen rabbit stifles. The experimental conditions examined were: (1) intact joint surfaces; (2) after the joint surfaces were washed with physiological saline; (3) after the addition of 1% hyaluronic acid solution with a molecular weight of one million daltons and two million daltons, respectively. RESULTS: The increased frictional coefficient produced by washing with saline was decreased significantly by the addition of hyaluronic acid to the joint surfaces. This effect was observed regardless of the molecular weight of the hyaluronic acid. CONCLUSION: The lubricating characteristics of hyaluronic acid in synovial joints do not change with molecular weight. RELEVANCE: Hyaluronic acid solution is used clinically for the treatment of osteoarthritis. In the present study, the molecular weight dependency of the lubricating characteristics of hyaluronic acid was tested using the friction in synovial joints.

Animals↗
PubMed1999

Analysis of glycosaminoglycans in rabbit cornea after excimer laser keratectomy.

BACKGROUND/AIMS: The biochemical basis for the development of subepithelial opacity of the cornea after excimer laser keratectomy has yet to be fully defined. The aim of this study was to evaluate the alterations of glycosaminoglycans (GAGs) after excimer laser keratectomy. METHODS: Rabbit corneas were harvested on days 5, 10, 20, and 30 after excimer laser photoablation. The amount of main disaccharide units was determined by high performance liquid chromatography (HPLC). In addition, immunohistochemical studies were performed on corneal sections 20 days after the ablation. RESULTS: The concentrations of DeltaDi-0S at 5 and 10 days were significantly lower than before the ablation. DeltaDi-6S showed a significant increase 5 days after the ablation but DeltaDi-4S did not show any significant change. There was a significant increase in DeltaDi-HA at 20 and 30 days after ablation. In immunohistochemistry, the positive staining for DeltaDi-6S and hyaluronic acid was observed in the subepithelial region. These immunohistochemical results were well correlated with the HPLC findings. CONCLUSIONS: The increase in chondroitin-6 sulphate and hyaluronic acid may be related to corneal subepithelial opacity after excimer laser keratectomy.

Animals↗
PubMed1999

Effect of UV-absorbing agents on photodegradation of tranilast in oily gels.

Tranilast (TL) oily gels containing UV-absorbing agents (UV absorber) were prepared, and the effect of the agents against photodegradation of TL was investigated. When 0.1% TL oily gel without UV absorber was exposed to light, TL was photochemically decomposed to the extent of 74.1% of its initial content at the end of the first hour. Although there were differences in the preventive effect on photodegradation of TL depending on the UV absorbers employed, 2-(2-benzotriazolyl)-p-cresol (BTPC) was the most effective absorber. The addition of UV absorbers to the oily gel did not affect the release of TL from the gel, the skin permeation, or the skin concentration of TL following topical application. UV absorbers added to TL oily gel penetrated into skin; however, their concentration in skin was similar to that following application of commercial sunscreen. These results suggest that the addition of UV absorbers to the oily gel of TL may be useful in preventing photodegradation of TL in the gel.

Animals↗
PubMed1999

[Damage control surgery].

Trauma patients who receive exsanguinating torso injuries often develop hypothermia, metabolic acidosis, and coagulopathy before death. A new strategy for trauma surgery has been developed to avoid the occurrence of these events and hence prevent trauma deaths. The strategy is called "damage control surgery" and consists of three maneuvers: a) damage control; b) restoration of physiologic stability; and c) definitive surgery. The goals of damage control are to: a) identify injuries; b) control ongoing hemorrhage; and c) control intestinal spillage. Damage control is followed by intensive care to restore the physiologic reserve. Once secondary resuscitation in the ICU is accomplished, planned reoperation should be performed to repair anatomic injuries. Planned reoperation is usually possible within 36 hours after the initiation of intensive care. Some patients who undergo damage control develop abdominal compartment syndrome characterized by increased intraabdominal pressure, increased peak airway pressure, decreased urine output, and decreased cardiac output. Early decompression surgery should be considered in such patients.

Critical Care↗
PubMed1998

Outbreak of severe infection due to adenovirus type 7 in a paediatric ward in Japan.

Between November 1996 and January 1997, 14 patients were diagnosed as having infection caused by adenovirus type 7 in a paediatric ward of Asahikawa Kosei Hospital. The age range of the patients was from two months to five years. Their diseases and abnormal laboratory findings were pneumonia in all 14, leukocytopenia in 10, myositis in nine, gastroenteritis in eight, encephalitis in five, liver dysfunction in three, pleuritis in two, inappropriate secretion of antidiuretic hormone syndrome in two, and thrombocytopenia in two. The infected patients, except for the first had been hospitalized in the paediatric ward for treatment of another disease and re-admitted because of high fever and coughing a few days after improvement or discharge. It is thought that the cause of the outbreak was hospital-acquired infection.

Adenovirus Infections, Human↗
PubMed1998

Hyperechoic appearance of hepatic parenchyma on ultrasound examination of patients with blunt hepatic injury.

OBJECTIVE: To study the significance of a geographic hyperechoic liver parenchyma pattern on ultrasound (US) examination of patients with blunt abdominal injury. DESIGN: Prospective clinical study with double-blind evaluation of images and clinical data. METHODS AND MAIN RESULTS: We performed US examinations in 831 consecutive patients admitted to our hospital for blunt abdominal trauma and identified 33 with a geographic hyperechoic pattern in the liver. We correlated the appearance with computed tomographic images and with clinical, angiographic, and scintigraphic data. All patients with a geographic hyperechoic pattern showed mild computed tomographic evidence of hepatic injury (Mirvis grade 2, 69%; Mirvis grade 3, 31%). Excluding patients who required urgent surgery for other reasons and patients in shock, patients with the geographic hyperechoic pattern were managed conservatively with no complications. CONCLUSION: The geographic hyperechoic pattern of liver parenchyma on US examination of trauma patients is a mild injury that, of itself, does not require surgical therapy.

Adolescent↗