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Biomedical subjects

K Ito

Publications and source records attributed to K Ito.

At least 91 records · Page 5Linked to original sources
PubMed2004

Expression of cholesteryl ester transfer protein (CETP) in germinal centre B cells and their neoplastic counterparts.

AIMS: Cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of lipids between plasma lipoproteins. Previous studies on human tissues have determined that the spleen contains large amounts of CETP mRNA, while the exact location of CETP in such organs remains unknown. In the present study, our aim was to locate CETP protein expression at the cellular level in human normal and neoplastic lymphoid organs. METHODS AND RESULTS: In-situ hybridization (ISH) and immunohistochemistry were applied to pathology specimens. A specific rabbit anti-CETP antibody was used for immunohistochemical analysis, together with another CETP-specific monoclonal antibody. A riboprobe for ISH was derived from CETP cDNA. Immunohistochemically, CETP was localized in germinal centre B cells and a proportion of marginal zone B cells. ISH showed that CETP mRNA was located mostly in the same areas. When 141 malignant lymphomas of various subtypes were studied, high expression of CETP, equivalent to that found in normal germinal centre B cells, was demonstrated in lymphoma subtypes that are currently regarded as the neoplastic counterparts of primarily germinal centre B cells. CONCLUSION: CETP localizes B cells in germinal centres, a proportion of post-germinal centre B cells and their neoplastic counterparts.

Animals↗
PubMed2004

Detection of Epstein-Barr virus in saliva by real-time PCR.

The purpose of this investigation was to assess the salivary levels of Epstein-Barr virus (EBV) in patients with periodontitis using real-time PCR. EBV was detected in 16 out of 33 (48.5%) periodontitis patients and in 3 out of 20(15%) healthy subjects. The baseline mean values for bleeding on probing in EBV-positive patients were significantly higher than those in EBV-negative patients. A significant decrease in EBV levels was observed after initial periodontal treatment. Our findings indicate that levels of EBV in saliva may reflect the status of periodontal inflammation.

Adult↗
PubMed2004

Treatment strategy for Boerhaave's syndrome.

Esophageal rupture is a potentially mortal condition. Rapid and correct diagnosis, and urgent surgical treatment with esophagectomy is indicated, but conservative and other surgical treatments have also been reported recently. The treatment strategies for esophageal rupture are discussed here, based on our experiences with four cases during the last 10 years. They were admitted urgently and each was treated by a different method. Three of them underwent emergency operations, one undergoing primary closure of the ruptured esophagus, another received a T-tube insertion from the ruptured site with omental flap, and the third an esophagogastrectomy. The fourth case was treated conservatively. All patients survived and were discharged 36-144 days post treatment. One of them was readmitted for debridement of necrotic rib. In conclusion, the prompt and accurate diagnosis of esophageal rupture is crucial for a subsequent successful treatment. Conservative treatment or operation including esophagectomy will be determined by the severity of the condition.

Adult↗
PubMed2004

Increased adrenomedullin immunoreactivity and mRNA expression in coronary plaques obtained from patients with unstable angina.

OBJECTIVE: To examine the expression and localisation of adrenomedullin in human coronary atherosclerotic lesions from patients with unstable angina (UAP) and stable angina (SAP), and to study the relation between adrenomedullin expression and plaque instability. DESIGN: A retrospective observational study. PATIENTS: Directional coronary atherectomy samples were obtained from 15 patients with UAP and 12 with SAP. METHODS: The localisation of adrenomedullin was examined by immunohistochemistry, and adreno-medullin mRNA expression was measured by quantitative polymerase chain reaction. RESULTS: Adrenomedullin immunoreactivity was preferentially localised in macrophages, intimal smooth muscle cells, and proliferated microvessels. The mean number of adrenomedullin positive cells in five high power fields (x 400) per specimen was higher in patients with UAP than in those with SAP (mean (SEM), 110 (13) v 76 (7); p < 0.05); and the ratio of adrenomedullin positive to total cells was higher in patients with UAP (43.0 (2.2)% v 34.2 (2.0)%; p < 0.01). More adrenomedullin mRNA was expressed in the plaque of patients with UAP than in those with SAP (60.4 (16.9)% v 9.7 (3.3)%; p < 0.01). CONCLUSIONS: The findings suggest that adrenomedullin is involved in the development of atherosclerosis and plaque instability in human coronary arteries, in an autocrine or paracrine manner.

Adrenomedullin↗
PubMed2004

Primary lateral sclerosis presenting parkinsonian symptoms without nigrostriatal involvement.

We encountered three patients with primary lateral sclerosis (PLS) showing bradykinesia, frozen gait, and severe postural instability, as well as slowly progressive spinobulbar spasticity. Cranial magnetic resonance (MR) imaging showed precentral gyrus atrophy. Central motor conduction was markedly prolonged or failed to evoke a response. Positron emission tomography (PET) showed significant reduction of [18F]fluoro-2-deoxy-D-glucose uptake in the area of the precentral gyrus extending to the prefrontal, medial frontal, and cingulate areas. No abnormalities were seen in the nigrostriatal system with PET using [18F]fluorodopa or [11C]raclopride or with proton MR spectroscopy. Thus, widespread prefrontal, medial, and cingulate frontal lobe involvement can be associated with the parkinsonian symptoms in PLS.

Adult↗
PubMed2004

Operative treatment of hip fracture in haemodialysed patients.

PURPOSE: To study operative treatment and postoperative clinical outcomes of hip fracture in haemodialysed patients. METHODS: In 12 patients (8 men and 4 women) undergoing haemodialysis, 14 hip fractures were treated. Of these, 8 hips were treated with bipolar hip arthroplasty, one hip with total hip arthroplasty, 4 hips with a compression hip screw, and one hip with a gamma nail. The mean duration of dialysis treatment until fracture was 7 years. During a mean postoperative follow-up period of 17 months (range, 1-44 months), the patients' renal condition, type of fracture, and level of activities of daily living before and after surgery were assessed. RESULTS: Of the 7 patients who died during a mean follow-up period of 17 months, 2 died from myocardial infarction, 2 from sepsis, and one each from gastric cancer, pulmonary oedema, and liver failure. Five of the 8 patients with diabetic nephropathy died, whereas 6 of the 8 patients who underwent bipolar hip arthroplasty or total hip arthroplasty died. Most of the patients had declined level of activities of daily living postoperatively. CONCLUSION: For haemodialysed patients with fractures, it is essential to select the most suitable operating method and to conduct vigilant management before and after the operation.

Aged↗
PubMed2004

Circulating free insulin-like growth factor (IGF)-I, total IGF-I, and IGF binding protein-3 levels do not predict the future risk to develop prostate cancer: results of a case-control study involving 201 patients within a population-based screening with a 4-year interval.

Recent studies have reported that serum IGF-I levels in the highest quartile of the normal range and IGF binding protein-3 (IGFBP-3) in the lowest quartile of the normal range are associated with an increased risk of future prostate cancer and/or presence of prostate cancer. It has also been suggested that the measurement of circulating total IGF-I concentrations might be a useful tool for the early detection of prostate cancer in men with moderately increased prostate-specific antigen (PSA) levels. To determine whether circulating free IGF-I, total IGF-I, and IGFBP-3 levels can predict future prostate cancer risk, we prospectively studied prostate cancer characteristics in a cohort of men during two rounds (mean interval, 4 yr) of a population-based screening study for prostate cancer. Two hundred one prostate cancer cases were detected at the second-round screening (aged 55-70 yr), and all these subjects were enrolled in the case group for the present study. Prostate cancer had been confirmed by biopsy in all cases. These 201 subjects were matched with the 201 nonprostate cancer cases by age, serum PSA range at the first-round screening (PSA < 2 ng/ml, n = 67; PSA = 2-3 ng/ml, n = 67; and PSA = 3-4 ng/ml, n = 67), and residence area. At baseline, total IGF-I, free IGF-I, and IGFBP-3 levels and prostate volume of cases with prostate cancer were not different from those of healthy controls. PSA velocity was significantly different between cases and controls (P < 0.001).Stepwise forward logistic regression analysis showed that only PSA levels at baseline and PSA at round 2 after 4 yr are good predictors of prostate cancer, whereas total IGF-I, free IGF-I, and IGFBP-3 did not predict the development of prostate cancer. Only one of the 201 subjects with prostate cancer had metastases. Within the subjects with prostate cancer, there were no differences of IGF-I parameters with different tumor node metastasis categories and/or Gleason scores. Our study suggests that the measurement of serum IGF-I and/or IGFBP-3 concentrations in addition to PSA does not improve the identification of men at high risk to develop early stages of prostate cancer. In addition, our results indicate that the endocrine IGF-I system is not directly involved in the growth of the early stages of prostate cancer.

Aged↗
PubMed2004

Quantitative measurement of hepatic portal perfusion by multidetector row CT with compensation for respiratory misregistration.

Our purpose was to determine whether hepatic portal perfusion assessed by multidetector row CT using compensation for respiratory misregistration can predict the severity of chronic liver disease. We carried out dynamic CT in 43 patients (chronic hepatitis: n=9; cirrhosis: n=24; normal liver: n=10). In this series, 20 patients had liver tumours. The CT protocol was designed to avoid respiratory artefacts and included two interscan breathing periods during the study. To compensate for respiratory misregistration, image sets in the same z-axis position were acquired from four-slice data on each scan, and the portal perfusion calculations were made according to the maximum slope method. Portal perfusion was compared with and without compensation for respiratory misregistration, and the different types of hepatic disease. In the liver tumour patients in particular, portal perfusion was compared with the degree of hepatic fibrosis in the liver sections. Portal perfusion in the patients without compensation for respiratory misregistration (1.10 ml min(-1)ml(-1)) was higher than that of those with compensation (0.99 ml min(-1)ml(-1); p=0.036). Hepatic portal perfusion of patients with chronic hepatitis (0.97 ml min(-1)ml(-1)) and liver cirrhosis (0.88 ml min(-1)ml(-1)) was less than that of patients with normal liver (1.32 ml min(-1)ml(-1); p=0.03, 0.001). Moderate correlation was seen between portal perfusion and the percentage of fibrosis in patients with liver tumours (r=0.55). Hepatic portal perfusion obtained by multidetector row dynamic CT using compensation for respiratory misregistration has the potential to improve non-invasive assessment of the degree of chronic liver disease.

Aged↗
PubMed2004

Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes.

Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). This is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. To identify a set of genes involved in the development of ATC, we investigated expression profiles of 11 cell lines derived from ATC using a cDNA microarray representing 25 344 genes. Semi-quantitative RT-PCR experiments carried out for some genes that had shown altered expression on the microarray verified frequent over-expression of destrin, HSPA8, stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATCs. In addition to mRNA expression studies, up-regulation of GDI2, destrin and stathmin were confirmed with immunohistochemical analysis. The extensive list of genes identified provides valuable information towards understanding the development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for the development of novel drugs to treat ATC.

Biomarkers, Tumor↗
PubMed2004

Absence of mutations in the Wilms' tumor gene wt1 in de novo non-small cell lung cancers.

We recently demonstrated that the WT1 gene was overexpressed in the majority of de novo lung cancers regardless of cancer subtypes. Here, we examined WT1 genomic DNA in 38 cases of de novo non-small cell lung cancers (NSCLC) for mutations using direct sequencing. The sequencing analysis showed no mutations of WT1 genomic DNA in any of 38 de novo non-small cell lung cancers examined. These results indicated that the non-mutated, wild-type WT1 gene played an important role in de novo NSCLC.

Adult↗
PubMed2004

Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB.

SETTING: Zomba Central Hospital, Malawi. OBJECTIVES: To determine the outcome of all adult patients who were registered for tuberculosis (TB) treatment 7 years previously according to initial human immunodeficiency virus (HIV) status and type of TB. DESIGN: A retrospective cohort study of adult patients registered for TB treatment between July and December 1995. Follow-up at patients' homes was performed at the end of treatment, at 32 months and at 84 months (7 years) from the time of TB registration. FINDINGS: Eight hundred and twenty-seven TB patients were registered: 793 had concordant HIV test results, of whom 612 (77%) were HIV-positive. At 7 years, 136 (17%) patients were alive, 539 (65%) had died and 152 (18%) were lost to follow-up. The death rate for all TB patients was 23.7 per 100 person-years of observation. HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.2, 95% confidence interval [95%CI] 1.7-2.8). Death rates in smear-negative pulmonary TB patients (HR 2.1, 95%CI 1.7-2.6) and in patients with extra-pulmonary TB (HR 1.7, 95% CI 1.3-2.0) were higher than in patients with smear-positive PTB. CONCLUSIONS: There was a high mortality rate in TB patients during and after anti-tuberculosis treatment. Adjunctive treatments to reduce death rates are urgently needed.

Adult↗
PubMed2004

Auditing the new decentralised oral treatment regimens in Malawi.

SETTING: All 44 non-private hospitals in Malawi treating tuberculosis (TB) cases in which oral regimens were used allowing patients during the initial phase to receive directly observed treatment (DOT) from health centres or guardians at home. OBJECTIVES: A country-wide audit of the oral regimens to determine: 1) TB ward bed occupancy rates, 2) patient DOT options, 3) patients' knowledge of treatment and 4) treatment outcomes compared to those obtained with previous treatment regimens. DESIGN: Retrospective data collection using registers and treatment cards. Prospective interviews with patients. Inspections of TB wards. RESULTS: There were 1513 TB beds occupied by 807 (53%) TB patients. Over 50% of 4793 patients registered with different types of TB chose guardian-based DOT. For 266 patients with pulmonary TB the correct knowledge about total duration of treatment (45%), all three DOT options (62%) and the months for giving follow-up sputum (16%), was poor. There were differences in treatment outcomes between TB patients on oral compared with previous regimens. With oral regimens, rates of unknown outcome were high. CONCLUSION: Oral treatment regimens are associated with reduced bed occupancy rates on TB wards. However, rates of unknown outcome are increased, and TB control is therefore weakened.

Administration, Oral↗
PubMed2003

Phase I/II study of daily carboplatin, 5-fluorouracil and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities and the response rate of carboplatin and 5-fluorouracil administered daily with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, unresectable stage IIIA or IIIB non-small-cell lung cancer (NSCLC) were enrolled. Carboplatin (20-40 mg m(-2) 2-h infusion, daily) and 5-fluorouracil (200 mg m(-2) 24-h continuous infusion, daily) were administered concurrently with radiotherapy on days 1-33. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions on days 1-40. In the phase I portion, the daily dose of carboplatin was escalated from 20 to 40 mg m(-2). Once the maximum tolerated dose (MTD) and recommended dose (RD) of carboplatin was determined, the study entered the phase II portion. In the phase I portion, the daily MTD and RD of carboplatin were 40 and 35 mg m(-2), respectively. The dose-limiting toxicity was neutropenia. In the following phase II study, 30 patients were entered and the objective response rate was 76.7% (95% CI, 62-92%) and the local control rate was 85.7%. The median survival time was 19.8 months, with a survival rate of 70% at 1 year, 36.7% at 2 years. The major toxicities of treatment were neutropenia (>or=grade 3, 87.9%) and thrombocytopenia (>or=grade 3, 23.3%). This combined therapy for locally advanced non-small-cell lung cancer is promising and shows acceptable toxicity.

Adult↗
PubMed2003

Effects of NRA0045, a novel potent antagonist at dopamine D4, 5-HT2A, and alpha1 adrenaline receptors, and NRA0160, a selective D4 receptor antagonist, on phencyclidine-induced behavior and glutamate release in rats.

RATIONALE: Administration of phencyclidine (PCP) to animals produces abnormal behavior such as hyperlocomotion, stereotyped behavior, and ataxia; this abnormal behavior is only weakly blocked by dopamine D(2) receptor antagonists. This study examined the effects of a novel thiazole derivative, NRA0045 which potently antagonizes not only dopamine D(4) receptors but also 5-HT(2A) and alpha(1) adrenaline receptors, and NRA0160, a selective dopamine D(4) receptor antagonist, on PCP-induced abnormal behavior, and accompanying increases in extracellular levels of glutamate in the medial prefrontal cortex. Furthermore, this study compared the effects of these drugs with those of clozapine and haloperidol. METHODS: To study the effects of NRA-drugs, atypical and typical antipsychotics, we measured locomotor activity with an infra-red sensor, and stereotypy and ataxia on a rating scale. Extracellular glutamate levels were measured by in vivo microdialysis. RESULTS: NRA0045 (1 or 3 mg/kg) or clozapine (1 mg/kg) attenuated hyperlocomotion, stereotypy, and ataxia induced by PCP (7.5 mg/kg) without affecting behavior after saline injection. Although haloperidol (0.1 or 1 mg/kg) attenuated or inhibited PCP-induced behavior, this drug also affected behavior after saline injection. NRA0160 (0.1, 1, or 3 mg/kg) had no effect on behavior induced by PCP or saline. NRA0045 (3 mg/kg), but not NRA0160, inhibited PCP-induced increases in glutamate levels in the medial prefrontal cortex. PCP-induced hyperlocomotion correlated with the PCP-induced increases in glutamate levels in this brain region. CONCLUSIONS: These results suggest that the effects of NRA0045 on PCP-induced abnormal behavior are similar to those of the atypical antipsychotic clozapine. NRA0045 probably attenuates PCP-induced abnormal behavior by inhibiting the PCP-induced increase in glutamate levels in the medial prefrontal cortex; this inhibition may be mediated via the blockade of 5-HT(2A) receptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2003

Formation of a vortex crystal cell assisted by a background vorticity distribution.

A vortex crystal is a quasistationary, symmetric array of intense vortices (clumps). A low level of background vorticity is experimentally observed to assist three clumps in forming an equilateral triangle starting from initial positions on a linear array. The triangle constitutes a unit cell of a crystal in a many-vortex system. The background vortex curbs the orbital motion of the clumps with unequal strengths to arrest them at the vertices of an equilateral triangle by wrapping them with different sized belts of depleted vorticity (ring holes). We characterize the contributions of a low-level background vorticity distribution on the formation of ordered states of clumps in light of the experimental results and existing theories.

Journal Article↗
PubMed2003

Expression of an artificial Cl- channel in microperfused renal proximal tubules.

To better understand the process of fluid movement driven by Cl- conductance, a Cl- channel-forming peptide was delivered to the luminal membrane of microperfused rabbit renal proximal tubules. When the peptide (NK4-M2GlyR) was perfused, a significant new conductance was observed within 3 min and stabilized at 10 min. Alteration of the ion composition revealed it to be a Cl(-)-specific conductance. Reabsorption of Cl- (JCl) was increased by NK4-M2GlyR, but not by a scramble NK4-M2GlyR sequence, suggesting that the active peptide formed de novo Cl- channels in the luminal membrane of the perfused tubules. In the presence of the peptide, reabsorption of fluid (Jv) was dramatically increased and JNa and JCa were concomitantly increased. We propose that introduction of the new Cl- conductance in the luminal membrane leads to a coordinated efflux of water across the membrane and an increase in cation translocation via the paracellular pathway, resulting in an increase in Jv. This novel method could prove useful in characterizing mechanisms of fluid transport driven by Cl- gradients.

Animals↗
PubMed2003

Interfering mutations provide in vivo evidence that Escherichia coli SecE functions in multimeric states.

SecY, SecE and SecG form a heterotrimer, which functions as a protein translocation channel in Escherichia coli. The cytosolic loop of SecE contains a segment that is conserved among different organisms. Here we show that mutational alterations in this segment not only inactivate the SecE function but confer dominant interfering properties on the altered SecE molecule. Such effects were especially evident in mutant cells in which the requirement for SecE function was increased. Overproduction of SecE, but not of SecY, alleviated the dominant negative effects. These results suggest that the inactive SecE molecule sequesters wild-type SecE. It was also found that an amino acid substitution, D112P, in the C-terminal periplasmic region intragenically suppressed the dominant interference. These results are consistent with a notion that there is significant SecE-SecE interaction in vivo, in which the C-terminal region has an important role. The data hence suggest that dimeric SecE participates in the formation of the functional translocation channel.

Amino Acid Sequence↗