Biomedical subjects

S Koike

Publications and source records attributed to S Koike.

At least 19 recordsLinked to original sources

PubMed2006

ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-beta/Smad-induced growth arrest of prostate cells.

Transforming growth factor-beta (TGF-beta) elicits a potent growth inhibitory effect on many normal cells by binding to specific serine/threonine kinase receptors and activating specific Smad proteins, which regulate the expression of cell cycle genes, including the p21 cyclin-dependent kinase (CDK) inhibitor gene. Interestingly, cancer cells are often insensitive to the anti-mitogenic effects of TGF-beta for which the molecular mechanisms are not well understood. In this study, we found that the candidate prostate cancer susceptibility gene ELAC2 potentiates TGF-beta/Smad-induced transcriptional responses. ELAC2 associates with activated Smad2; the C-terminal MH2 domain of Smad2 interacts with the N-terminal region of ELAC2. Small interfering siRNA-mediated knock-down of ELAC2 in prostate cells suppressed TGF-beta-induced growth arrest. Moreover, ELAC2 was shown to specifically associate with the nuclear Smad2 partner, FAST-1 and to potentiate the interaction of activated Smad2 with transcription factor Sp1. Furthermore, activation of the p21 CDK inhibitor promoter by TGF-beta is potentiated by ELAC2. Taken together our data indicate an important transcriptional scaffold function for ELAC2 in TGF-beta/Smad signaling mediated growth arrest.

Animals↗

PubMed2005

Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry.

OBJECTIVE: To assess the production mechanism of anti-GQ1b autoantibody in Fisher syndrome (FS). METHODS: The authors conducted a prospective case-control serologic study of five antecedent infections (Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae) in 73 patients with FS and 73 sex- and age-matched hospital controls (HCs). Serologic evidence in FS patients of C. jejuni (21%) and H. influenzae (8%) infections was present significantly more often than in the HCs. None of the five pathogens examined was found in the 49 (67%) patients with FS. Anti-GQ1b IgG antibody was detected in most FS patients infected with C. jejuni or H. influenzae. Mass spectrometry analysis identified a C. jejuni strain (CF93-6) carrying a GT1a-like lipo-oligosaccharide (LOS) that had been isolated from an FS patient. Immunization of complex ganglioside-lacking knockout mice with the GT1a-like LOS generated IgG class monoclonal antibodies (mAbs) that reacted with GQ1b and GT1a. Thin-layer chromatography with immunostaining showed that anti-GQ1b mAb bound to the C. jejuni LOS (50% of the 20 FS-related strains) more commonly than in the Guillain-Barré syndrome (GBS)-related (7% of 70) or enteritis-related (20% of 65) strains. Anti-GM1 and anti-GD1a mAbs also reacted with the LOS from some FS-related strains (both 20%), but binding frequencies were higher in the GBS-related strains (74 and 57%). The GQ1b epitope was detected in 4 (40%) of the 10 FS-related H. influenzae strains but was absent in strains from patients with GBS (n = 4) and uncomplicated respiratory infections (n = 10). CONCLUSIONS: C. jejuni and H. influenzae are related to Fisher syndrome (FS) development, and production of anti-GQ1b autoantibody is mediated by the GQ1b-mimicking lipo-oligosaccharides on those bacteria. The causative agents remain unclear in the majority of patients with FS.

Adult↗

PubMed2005

Ambiguous value of Haemophilus influenzae isolation in Guillain-Barre and Fisher syndromes.

BACKGROUND: Haemophilus influenzae is considered a causative agent of Guillain-Barré syndrome (GBS) and Fisher syndrome, but the frequency of this infection in GBS is controversial. OBJECTIVE: To determine whether isolation of H influenzae indicates it is a causative agent in GBS and Fisher syndrome. RESULTS: Four (15%) of 27 patients with GBS and Fisher syndrome in whom H influenzae was isolated were also seropositive for Campylobacter jejuni. Antiganglioside IgG antibodies in these four patients did not cross react with their H influenzae lipo-oligosaccharides, whereas antiganglioside antibodies in the four patients with positive serology for H influenzae did. CONCLUSIONS: The findings suggest that H influenzae isolation is not always indicative of the causative agent in these syndromes and that tests for other infections should be made, even in cases of positive culture.

Adult↗

PubMed2004

Evidence from mucin core protein expression that some Paget's disease on areola can be of extramammary-like histogenesis and part of multisite disease.

Triple extramammary Paget's disease, which consists ordinarily of bilateral axillary and genital lesions, is uncommon. Triple extramammary Paget's disease involving other sites has never been reported, although solitary extramammary Paget's disease can occur at various sites around the body. Erythematous plaques on the areola, axilla and genitalia of a 91-year-old man were surgically removed under the clinical diagnosis of multiple extramammary Paget's disease. Histology revealed that all three lesions consisted of intraepidermal nests of Paget cells and other isolated Paget cells scattered in the epidermis. Although adnexal invasion was observed in the genital lesion, neither intraductal invasion nor underlying breast carcinoma was detected in the areolar lesion. Immunohistochemically, the Paget cells in all lesions expressed simple epithelial cytokeratins (CK8, 18 and 19), mucin (MUC)1 and MUC5AC, but neither CK20 nor MUC2. From the histological findings, the present case was interpreted as triple extramammary Paget's disease rather than synchronous mammary and extramammary Paget's disease. Furthermore, the mucin core protein expression pattern, which was identical to that observed in extramammary Paget's disease, supported the above interpretation.

Aged↗

PubMed2003

Host range of poliovirus is restricted to simians because of a rapid sequence change of the poliovirus receptor gene during evolution.

The host range of most poliovirus (PV) strains is restricted to simians. This host range specificity is believed to be determined by the interaction between PV and its receptor molecule. To elucidate the molecular basis of this species-specific infection of PV, we cloned orthologs of the PV receptor (PVR) gene ( pvr) as well as those of PV receptor-related genes 1 and 2 ( prr1 and prr2) from various mammalian species. These three genes are widely present in mammalian genomes including those of non-susceptible species. Comparison of the deduced amino acid sequences of PVR orthologs revealed that the NH(2)-terminal immunoglobulin-like domain (domain 1), which is the virus binding site in the human PVR, is highly variable among species, whereas that of PRR1 is highly conserved. Domain 1 of the PVR orthologs for the ring-tailed lemur and rabbit, which are not susceptible to PV, show only 51 and 61% amino acid sequence identity to that of human PVR, respectively. Chimeric PVR proteins that have the domain 1 of the ring-tailed lemur and rabbit PVRs failed to serve as receptors for PV. These results suggest that rapid changes in the domain 1 sequence during mammalian evolution determined the host range restriction of PV.

Amino Acid Sequence↗

PubMed2003

Kinetics of in sacco fiber-attachment of representative ruminal cellulolytic bacteria monitored by competitive PCR.

Stems of orchardgrass hay in nylon bags were incubated in the rumens of three ruminally fistulated sheep to monitor the rate and extent of fiber attachment by the representative ruminal cellulolytic bacteria via competitive polymerase chain reaction. After incubation for 5 min, the numbers of Fibrobacter succinogenes and the two ruminococcal species attached to stems were 10(5) and 10(4)/g dry matter (DM) of stem, respectively. At 10 min, the numbers of all three species attached to stems increased 10-fold. Thereafter, attached cell numbers of the three species gradually increased and peaked at 24 h (10(9)/g DM for F. succinogenes and 10(7)/g DM for Ruminococcus flavefaciens) or 48 h (10(6)/g DM for Ruminococcus albus). On the other hand, cell numbers of all three species in the whole digesta were constant over 24 h. Changes in the rate of in sacco neutral detergent fiber disappearance of hay stem, which showed a linear increase up to 96 h, were not synchronized with changes in cellulolytic bacterial mass. These results suggest that sufficient numbers of cells of the three cellulolytic species to move to new plant fragments are present at the start of incubation, the initial attachment to new plant matter is mostly accomplished within 10 min and then bacterial growth and fibrolytic action follow. F. succinogenes was most dominant, both in the whole rumen digesta and on the suspended hay stems, demonstrating the ecological and functional significance of this species in ruminal fiber digestion.

Animals↗

PubMed2002

Pharmacokinetics, toxicokinetics, distribution, metabolism and excretion of linezolid in mouse, rat and dog.

1. Linezolid (ZYVOX), the first of a new class of antibiotics, the oxazolidinones, is approved for treatment of Gram-positive bacterial infections. 2. The aim was to determine the absorption, distribution, metabolism and excretion (ADME) of linezolid in mouse, rat and dog in support of preclinical safety studies and clinical development. 3. Conventional replicate study designs were employed in animal experiments, and biofluids were assayed by HPLC or HPLC-MS. 4. Linezolid was rapidly absorbed after p.o. dosing with an p.o. bioavailability of > 95% in rat and dog, and > 70% in mouse. Twenty-eight-day i.v./p.o. toxicokinetic studies in rat (20-200mg kg(-1) day(-1)) and dog (10-80 mg kg(-1) day(-1)) revealed neither a meaningful increase in clearance nor accumulation upon multiple dosing. 5. Linezolid had limited protein binding (<35%) and was very well distributed to most extravascular sites, with a volume of distribution at steady-state (V(ss)) approximately equal to total body water. 6. Linezolid circulated mainly as parent drug and was excreted mainly as parent drug and two inactive carboxylic acids, PNU-142586 and PNU-142300. Minor secondary metabolites were also characterized. In all species, the clearance rate was determined by metabolism. 7. Radioactivity recovery was essentially complete within 24-48 h. Renal excretion of parent drug and metabolites was a major elimination route. Parent drug underwent renal tubular reabsorption, significantly slowing parent drug excretion and allowing a slow metabolic process to become rate-limiting in overall clearance. 8. It is concluded that ADME data were relatively consistent across species and supported the rat and dog as the principal non-clinical safety species.

Acetamides↗

PubMed2002

Significance of fractionated irradiation for the biological therapeutic gain of carbon ions.

It is well established that the RBE (relative biological effectiveness) for cell killing depends on LET (linear energy transfer), and that a maximum RBE is observed at approximately 150 keV.micron-1. However, the therapeutic gain depends on the ratio of the RBEs for the effects on the cancer cell population and the effects on normal tissues. The RBE of a given radiation quality depends not only on LET but also on dose, biological system and effect, and irradiation conditions. There is no data available to answer the question: which LET is suitable to improve the biological therapeutic gain of carbon ions? Here, three different LET values of 290 MeV/u carbon ions were selected, and the relative biological effectiveness was compared between tumour-growth retardation and skin damage using a murine transplantable tumour. Larger RBE values for tumours after than the skin type were obtained when carbon ions of intermediate LET were delivered daily for 2 to 5 fractions. The biological therapeutic gain would be high for the carbon ion SOBP if the number of fractions were correctly selected in clinical trials.

Animals↗

PubMed2001

Development and use of competitive PCR assays for the rumen cellulolytic bacteria: Fibrobacter succinogenes, Ruminococcus albus and Ruminococcus flavefaciens.

Competitive PCR assays were developed for the enumeration of the rumen cellulolytic bacterial species: Fibrobacter succinogenes, Ruminococcus albus and Ruminococcus flavefaciens. The assays, targeting species-specific regions of 16S rDNA, were evaluated using DNA from pure culture and rumen digesta spiked with the relevant cellulolytic species. Minimum detection levels for F. succinogenes, R. albus and R. flavefaciens were 1-10 cells in pure culture and 10(3-4) cells per ml in mixed culture. The assays were reproducible and 11-13% inter- and intra-assay variations were observed. Enumeration of the cellulolytic species in the rumen and alimentary tract of sheep found F. succinogenes dominant (10(7) per ml of rumen digesta) compared to the Ruminococcus spp. (10(4-6) per ml). The population size of the three species did not change after the proportion of dietary alfalfa hay was increased. All three species were detected in the rumen, omasum, caecum, colon and rectum. Numbers of the cellulolytic species at these sites varied within and between animals.

Animals↗

PubMed2001

Electroretinogram analysis of relative spectral sensitivity in genetically identified dichromatic macaques.

The retinas of macaque monkeys usually contain three types of photopigment, providing them with trichromatic color vision homologous to that of humans. However, we recently used molecular genetic analysis to identify several macaques with a dichromatic genotype. The affected X chromosome of these animals contains a hybrid gene of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) photopigments instead of separate genes encoding L and M photopigments. The product of the hybrid gene exhibits a spectral sensitivity close to that of M photopigment; consequently, male monkeys carrying the hybrid gene are genetic protanopes, effectively lacking L photopigment. In the present study, we assessed retinal expression of L photopigment in monkeys carrying the hybrid gene. The relative sensitivities to middle-wavelength (green) and long-wavelength (red) light were measured by electroretinogram flicker photometry. We found the sensitivity to red light to be extremely low in protanopic male monkeys compared with monkeys with the normal genotype. In female heterozygotes, sensitivity to red light was intermediate between the genetic protanopes and normal monkeys. Decreased sensitivity to long wavelengths was thus consistent with genetic loss of L photopigment.

Animals↗

PubMed2001

MR imaging of pancreatic diseases.

This article presents current MR imaging techniques for the pancreas, and review a spectrum of MR imaging features of various pancreatic diseases. These include: 1) congenital anomalies such as anomalous union of pancreatobiliary ducts, divisum, and annular pancreas, 2) inflammatory diseases, including acute or chronic pancreatitis with complications, groove pancreatitis, and autoimmune pancreatitis, tumor-forming pancreatitis, 3) pancreatic neoplasms, including adenocarcinoma, islet cell tumors, and cystic neoplasms (microcystic adenoma, mucinous cystic neoplasms, and intraductal mucin-producing pancreatic tumor). Particular attention is paid to technical advances in MR imaging of the pancreas such as fat-suppression, MR pancreatography (single- or multi-slice HASTE), and thin-section 3D multiphasic contrast-enhanced dynamic sequences. Imaging characteristics that may lead to a specific diagnosis or narrow the differential diagnosis are also discussed.

Acute Disease↗

PubMed2001

Localization of heme oxygenase-2 in the canine larynx.

The localization of heme oxygenase-2 (HO-2) in the larynx of the dog was investigated using immunohistochemistry. HO-2-positive cells were seen among neurons in intralaryngeal ganglia. Nerve fibers positive to HO-2 immunohistochemistry were seen surrounding laryngeal glands and arterioles and also in the adventitia of arterioles. HO-2-positive fibers were also seen running parallel to the mucosa in the lamina propria but no positive fibers were seen in the epithelium. Some of the intramuscular neurons found in the intrinsic laryngeal muscles were HO-2-positive, although no positive motor fibers were seen, and the neuromuscular junctions were also HO-2-negative. The results implicate the participation of HO-2-in the parasympathetic innervation of the larynx.

Animals↗

PubMed2001

Endovascular stent grafting for the treatment of blunt thoracic aortic injury.

OBJECTIVE: Recent advances of endovascular stent-grafting (ESG) provide a new therapeutic option with minimum surgical damage for blunt aortic injury (BAI) during its acute phase. To clarify the effectiveness of ESG for BAI, a prospective clinical study at a university hospital was conducted. METHODS: All patients with blunt thoracic injury underwent thoracic contrast-enhanced computed tomographic (CT) scan. Six patients age 48.8 +/- 19.8 years, with Injury Severity Scores of 35.8 +/- 8.1, and with BAI were treated according to our protocol. The stent-graft covered by woven Dacron was placed at the injury site. Endoleakage was then checked by aortography and CT scan was again performed once a day on days 7 through 14. RESULTS: All patients had injury of the aortic isthmus. ESG placement was performed within 8 hours after injury except in one (48 hours). The operating time was 159.5 +/- 21.1 minutes and bleeding volume was 105 +/- 26.6 mL. No endoleakage was found. Repeat CT scan revealed disappearance of hematoma. All patients except one had an event-free clinical course. One patient died because of rupture of the ascending aorta on day 6; however, autopsy revealed evidence of the healing process at the injury site sealed by ESG. CONCLUSION: An ESG is a valid therapeutic option with minimal surgical invasion for patients with acute-phase aortic injury.

Adult↗

PubMed2001

Time course of reoxygenation in experimental murine tumors after carbon-beam and X-ray irradiation.

We compared the tumor reoxygenation patterns in three different murine tumor cell lines after X-irradiation with those after carbon-beam irradiation using a heavy-ion medical accelerator (HIMAC) system. The tumors of the cell lines SCCVII, SCCVII-variant-1 and EMT6 on the hind legs of mice received local priming irradiation with a carbon-beam (8 Gy, 73 keV/microm in LET, 290 MeV/u, 6 cm SOBP) or X-rays (13 Gy, 250 kVp). After various intervals, the mice were given whole-body test irradiation (16 Gy. 250 kVp X-ray) either in air or after they were killed. The hypoxic fractions were estimated as the proportions of the surviving fractions of the tumors in killed mice to those in air-breathing mice. In the SCCVII tumors, the hypoxic fractions at 0.5 h were 50% and 21% (p < 0.05) after the priming X-irradiation and carbon-beam irradiation, respectively. In the SCCVII-variant-1 tumors, the hypoxic fractions were 85% and 82% at 0.5 h, 84% and 20% at 12 h (p < 0.01), and 21% and 31% at 24 h after X-ray and after carbon-beam irradiation, respectively. In the EMT6 tumors, the reoxygenation patterns after X-irradiation and carbon-beam irradiation were quite similar. We concluded that the reoxygenation pattern differed among the three tumor cell lines, and that reoxygenation tended to occur more rapidly after carbon-beam irradiation than after X-irradiation for SCCVII and SCCVII-variant-1 tumors.

Animals↗

PubMed2001

Relative biological effectiveness of the 235 MeV proton beams at the National Cancer Center Hospital East.

A therapy-dedicated cyclotron was installed in the National Cancer Center Hospital East (NCCHE) at Kashiwa in 1997. Prior to the start of clinical use, we investigated the biological effectiveness of therapeutic proton beams for cell lethality. The proton beams accelerated up to 235 MeV were horizontally extracted from the cyclotron, and scattered by a bar-ridge filter to produce a Spread-Out-Bragg-Peak (SOBP) of 10-cm width. The biological systems used here were mouse intestinal crypt cells and three in vitro cell lines, including SCC61 human squamous cell carcinoma, NB1RGB human fibroblasts and V79 Chinese hamster cells. The dose responses after irradiation at either the entrance plateau or the middle portion of SOBP were compared with those after linac 6 MV X-ray irradiation. The fit of a linear quadratic model to survival curves showed that proton irradiation increased the alpha value of SCC61 and the beta value of V79 cells with a least change for alpha/beta ratio of NB1RGB cells. The isoeffect dose that reduces either cell survivals to 10% or mouse jejunum crypts to 10 per circumference was termed D10. The relative biological effectiveness (RBE) of protons obtained by comparing the D10 values between protons and X-rays ranged from 0.9 to 1.2. The depth distribution of cell lethality was measured by replating V79 cells after irradiation from a "cell stack chamber" that received a single dose of 7 Gy at the middle position of SOBP. The thus-obtained cell survivals at various depths coincided well with the estimated survivals, but tended to decrease at the distal end of SOBP. We conclude that an RBE of 1.1 would be appropriate for 235 MeV proton beams at the NCCHE.

Animals↗

PubMed2000

Gastric seromuscular and omental pedicle flap for bronchopleural fistula after pneumonectomy.

We report a case of postpneumonectomy bronchopleural fistula treated using a gastric seromuscular and omental pedicle flap and maintaining good postoperative respiratory function. A 76-year-old man underwent right pneumonectomy with regional lymph node dissection for squamous cell carcimoma of the lung. Five weeks later, a bronchopleural fistula occurred. Empyema with the bronchopleural fistula was diagnosed and chest tube drainage implemented immediately. Despite the drainage, signs of inflammation persisted and the patient's nutrition did not improve leading to surgery, on August 18, 1997. The bronchopleural fistula was closed by horizontal suture proximal to the stapling sutured line. A gastric seromuscular and omental pedicle flap was sutured as a cover over the bronchial stump. Postoperative analysis of respiratory function and arterial blood gas showed good results.

Aged↗

PubMed2000

Changes in cardiopulmonary parameters during upper gastrointestinal endoscopy in patients with heart disease: towards safer endoscopy.

BACKGROUND AND STUDY AIMS: Gastrointestinal endoscopy is an invasive examination. The aims of this study were to elucidate the effects and risks of upper gastrointestinal endoscopy with regard to cardiopulmonary functions in patients with heart disease, and to establish safety guidelines for use during endoscopy in this particular group of patients. PATIENTS AND METHODS: The patients involved were 53 inpatients in whom upper gastrointestinal endoscopy was carried out before cardiac surgery. Their cardiac functions had been evaluated previously. Electrocardiography with two leads (II, V5) was used, and blood pressure and peripheral oxygen saturation (SpO2) were monitored throughout the procedure. The relationship between the changes in cardiopulmonary parameters during endoscopy and the cardiac functions was analyzed. RESULTS: Heart rate increased immediately after insertion of the endoscope (P < 0.01). There was a significantly higher incidence of ventricular and supraventricular extrasystoles during observation of the second portion of the duodenum (P < 0.05). A lower cardiac index (P < 0.05) and a higher New York Heart Association (NYHA) functional classification (P < 0.05) were found in patients with oxygen desaturation than in patients without it. Two patients with severe coronary artery lesions showed marked ST-T depression, and these ischemic changes were thought to be due to increase in cardiac work during endoscopy. CONCLUSIONS: Upper gastrointestinal endoscopy has many adverse effects on cardiopulmonary functions in patients with heart disease. In our study, the clinical value of very close monitoring and administration of oxygen for patients with heart disease was confirmed by objective data.

Aged↗

PubMed2000

Induction of nitric oxide synthase activity in nucleus ambiguus motoneurons after injury to the rat recurrent laryngeal nerve.

Recent studies have implicated nitric oxide (NO) in neuronal degeneration and plasticity in the motor nervous system. In the present study, we investigated the induction of nitric oxide synthase (NOS) in the motoneurons in the nucleus ambiguus (NA) after injury to the rat recurrent laryngeal nerve (RLN) using nicotinamide-adenine-dinucleotide-phosphate-diaphorase (NADPH-d) histochemistry. NADPH-d reactivity was clearly induced in motoneurons in the ipsilateral NA after transection or avulsion of the RLN, compared with control animals. This finding suggests that NO may play an important role in the pathogenesis of RLN paralysis. Another interesting finding in the present study was the induction of NADPH-d reactivity in nerve terminals of the NA after RLN injury. This finding suggests that RLN injury has some effect on nitrergic input to the NA and a direct effect on the motoneurons.

Animals↗