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Biomedical subjects

K Nakajima

Publications and source records attributed to K Nakajima.

At least 109 records · Page 6Linked to original sources

Serum p53 antibody as a useful marker for monitoring of treatment of superficial colorectal adenocarcinoma after endoscopic resection.

BACKGROUND: Mutation of the p53 gene is a genetic alteration found in human cancers. Overexpression of p53 has been found to induce antibody production in serum, and, recently, the simple detection of serum antibody has been made possible. The aim of this study was to evaluate the potential role of serum p53 antibody in the early diagnosis of superficial colorectal cancer and in the monitoring of its treatment after endoscopic resection. METHODS: In a prospective study, our subjects were 27 patients with superficial colorectal adenocarcinomas, whose results were compared with those in 38 patients with benign adenomas; all patients were treated by endoscopic resection. The correlation between serum p53 antibody levels before and within 3 weeks after resection was determined, using an immunoassay. Immunohistological staining for p53 was also performed, and its sensitivity was compared with that of two other tumor markers. RESULTS: Preoperatively, serum p53 antibody was detected in 63.0% (17/27) patients with adenocarcinoma and in 2.6% (1/38) patients with adenoma, showing a significant difference (P < 0.001). However, the two other markers carcinoembryonic antigen (CEA) and carbohydrate antigen CA19-9, showed no significant difference between superficial colorectal adenocarcinoma and adenoma. The serum p53 antibody status was strongly correlated with p53 immunostaining in adenocarcinoma (P = 0.0065), but there was no significant correlation in adenoma (P = 0.973). Sixteen (94.1%) of 17 seropositive adenocarcinoma patients, showed negative conversion after complete tumor resection, and all these 16 patients remained seronegative. CONCLUSION: The detection of serum p53 antibody is expected to serve as a new genetic marker, determined by serological analyses, for aiding in the early diagnosis of superficial colorectal cancer and indicating its local curability after endoscopic treatment.

Adenocarcinoma↗

Assessment of left ventricular systolic and diastolic function based on the edge detection method with myocardial ECG-gated SPET.

The aim of this study was to determine the feasibility of assessing left ventricular systolic ejection and diastolic filling by the edge detection method with ECG-gated single-photon emission tomography (G-SPET) data. Fifty-two patients who had undergone both G-SPET and gated equilibrium blood pool scintigraphy (GBP) within an interval of 2 weeks were enrolled. For G-SPET, 740 MBq of technetium-99m methoxyisobutylisonitrile (MIBI) was injected at rest, and myocardial SPET was performed 60 min later using 360 degrees acquisition and 12 frames per cardiac cycle. In each frame, left ventricular volume was determined with automatic edge detection using a quantitative gated SPET program, and the time-volume curve was fitted by Fourier transform of the first to fourth harmonics. Ejection fraction (EF, %), peak ejection rate (PER, /s), peak filling rate (PFR, /s) and mean filling rate during the first third of diastolic time (1/3FRm, /s) were calculated from the fitted curve. These parameters were also calculated by means of GBP performed with 24 frames per cardiac cycle. Correlation coefficients in respect of EF, PER, PFR and 1/3FRm between G-SPET and GBP were 0.90 (P<0.001), 0.88 (P<0.001), 0.80 (P<0.001) and 0.82 (P<0.001), respectively. The correlations were good for EF, PER and 1/3FRm. Gated SPET dV/dt parameters were slightly lower compared with GBP values owing to the limited number of frames per cardiac cycle. It is concluded that left ventricular ejection and filling rates can be calculated using G-SPET with edge detection software, and in this study these parameters were significantly correlated with those derived using GBP. Diastolic abnormality on gated SPET study should be recognised as a positive finding, and appropriate gated SPET parameters should be further investigated.

Adult↗

Three-dimensional pressure imaging: a novel method for intraoperative manometry during laparoscopic esophagomyotomy for esophageal achalasia.

With the introduction of computerized manometry, the creation of the three-dimensional (3-D) pressure image with measurement of pressure vector volume (PVV) has become available to assess the pressure structure of the high-pressure zone (HPZ) of the distal esophagus. We have applied this technique to intraoperative manometry during laparoscopic surgery for esophageal achalasia (EA). A laparoscopic esophagomyotomy with anterior fundoplication was performed in a 12-year-old boy with EA. Computerized 3-D images were obtained by a stepwise pullback of a manometric assembly with eight radial side-holes to quantitate the PVV of the HPZ of the distal esophagus in each stage of the operation for EA. Virtual abolishment of the peak pressure image and a marked reduction in the PVV after esophagomyotomy suggested appropriate decompression of the HPZ. Intraoperative manometry using computerized 3-D pressure imaging with measurement of the PVV is thus useful to assess the HPZ during laparoscopic surgery for EA.

Child↗

Effect of a low-fat diet enriched with oleic acid on postprandial lipemia in patients with type 2 diabetes mellitus.

The aim of the present study was to compare the effects of a low-fat diet enriched with oleic acid to those of a low-fat diet enriched with linoleic acid on fasting lipids, postprandial lipemia, and oxidative susceptibility of low-density lipoprotein (LDL) in patients with type 2 diabetes mellitus (DM). In a 3-wk randomized crossover study, eight patients with type 2 DM were given an experimental low-fat diet enriched with either oleic acid or linoleic acid. The oleic-acid-enriched diet contained 5, 15, and 5%, energy from saturated, monounsaturated, and polyunsaturated fatty acids, and the linoleic-acid-enriched diet contained 5, 5, and 15% energy from saturated, monounsaturated, and polyunsaturated fatty acids, respectively. In addition to evaluating the fasting lipids and oxidative susceptibility of LDL, we evaluated postprandial lipemia using an oral fat load at the end of each 3-wk dietary phase. There were no significant differences in fasting lipid profile or lag time of LDL oxidation between the two experimental dietary phases. The average and maximal increments of remnant-like particle (RLP) cholesterol levels during oral fat load were significantly higher after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. The area under the curve of RLP cholesterol was also significantly larger after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. These results suggest that the oleic-acid-enriched diet was associated with increased formation of postprandial chylomicron remnants compared with the linoleic-acid-enriched diet.

Aged↗

Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study.

Remnants of triglyceride-rich lipoproteins (TRL) of both intestinal and liver origin are considered to be atherogenic, but separation of remnant lipoproteins from other TRL is difficult. An assay has been developed that allows immunoseparation of remnant-like particles (RLP) and measurement of cholesterol (RLP-C) and triglyceride (RLP-TG). We measured RLP-C and RLP-TG in fast plasma samples obtained from 1567 women participating in cycle 4 of the Framingham heart study (FHS). When values from 83 women with cardiovascular disease (CVD) were compared with the values from 1484 women without disease, concentrations in women with CVD were found to be significantly higher for both RLP-C (0.215+/-0.102 vs. 0.186+/-0.162 mmol/l; +15.6%; P<0.0001) and RLP-TG (0.319+/-0.352 vs. 0.251+/-0. 716 mmol/l; +27.0%; P<0.0002). Logistic regression analysis revealed that RLP-C was significantly associated with prevalent CVD in women (P<0.002) after adjustment with other major risk factors. In conclusion, we have documented that RLP-C is an independent risk factor for CVD in women, and provides significantly more information than do triglycerides.

Adult↗

The distribution and production of cholesteryl ester transfer protein in the human aortic wall.

Cholesteryl ester transfer protein (CETP) has been considered to mediate the transfer of cholesteryl ester from arterial wall, however, the distribution and production of CETP in human arterial wall remains unclear. Present study histopathologically demonstrated the distribution of CETP and CETP mRNA in the human aortic wall by immunohistochemistry and in situ hybridization. While CETP was constantly distributed in the media, the protein was recognized within the intima with fibrocellular thickening and atherosclerotic intima. Double immunostaining methods demonstrated CETP expression in smooth muscle cells in the intima and media. CETP mRNA was detected not only in intimal cells but medial smooth muscle cells. Intimal cells expressing CETP mRNA were considered to be monocyte-derived macrophages and smooth muscle cells by immunohistochemistries using two antibodies against smooth muscle actin and human macrophage on the subserial sections. Our in vivo study provides that CETP is produced by smooth muscle cells in the intima and media of human aorta, and it is suggested that arterial smooth muscle cells positively participate in the removal of excessive cholesteryl ester from the arterial wall by CETP production.

Aorta↗

Isolation of remnant particles by immunoseparation: a new approach for investigation of postprandial lipoprotein metabolism in normolipidemic subjects.

Abnormal postprandial lipoproteins are associated with an increased risk for cardiovascular disease. Postprandial remnant lipoproteins were usually analyzed indirectly using retinyl esters (RE) as a chylomicron core label during an oral fat loading test. Apo B-100 containing VLDL remnants in addition to apo B-48 containing chylomicron remnants can also be directly quantified using the RLP-Cholesterol Immunoseparation Assay. This recently available method uses monoclonal antibodies to apo A-I and apo B-100 to remove non-remnant lipoproteins and quantifies cholesterol in the remaining apo E-rich remnant fraction. In the present study we compared the analysis of retinyl ester with the immuno-based RLP-Cholesterol (RLP-C) analysis in measuring postprandial remnant lipoproteins in healthy normolipidemic subjects. Sixteen healthy normolipidemic subjects were selected for this study. Postprandial plasma retinyl esters peaked at 5.0+/-1.2 h, whereas plasma RLP-C showed a peak significantly earlier (P<0.001) at 3.5+/-0.6 h. In comparison, postprandial plasma TG and FFA peaked at 3.3+/-1.1 h (P<0.005 compared to retinyl esters). In conclusion, levels of RLP-C changed, during the postprandial phase, in parallel with plasma TG and FFA concentrations and peaked significantly earlier than retinyl esters. Postprandial measurements of RLP-C can be considered as a fast alternative method for the more laborious retinyl-ester analysis in clinical studies.

Adult↗

Intact microglia are cultured and non-invasively harvested without pathological activation using a novel cultured cell recovery method.

Because spontaneous host regeneration of damaged tissues is limited, novel therapeutics utilizing cultured cells with the aid of tissue engineering methods are promising alternatives for tissue replacement. One critical shortcoming is current requirement for invasive cell harvest from culture to fabricate cell-based devices. Although microglia that secrete neurotrophic factors are attractive candidates for novel cell transplantation therapy for damaged central nervous system tissue, the intact harvest of cultured microglia is presently not achievable. Therefore, primary microglia were plated onto culture surfaces grafted with the temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm). This surface undergoes rapid, reversible temperature-dependent changes in its hydration state and surface hydrophilicity. Microglia attached and proliferated on PIPAAm-grafted dishes at 37 degrees C. By reducing culture temperature, more than 90% of the cells spontaneously detached from the dishes within several minutes without trypsin or EDTA treatment. Recovered and replated microglia exhibited phenotypic properties comparable to those of primary microglia freshly isolated from brain. By contrast, less than 60% of the cells were harvested by trypsin digestion, and exhibited significant alteration of characteristic cellular properties as monitored by pathological states in vivo. This new technology exhibits utility for the preparation of cell sources required for cell transplantation as well as microglial function analysis.

Animals↗

Efficient in utero gene transfer system to the developing mouse brain using electroporation: visualization of neuronal migration in the developing cortex.

We report a novel gene transfer system using electroporation. We used this technique to introduce a marker gene plasmid containing enhanced green fluorescent protein into mouse brains at embryonic day 12-17 without removing the embryos from the uterus. The embryos were allowed to continue to develop in utero, and more than 80% were born normally expressing the exogenous gene. Enhanced green fluorescent protein driven by the cytomegalovirus promoter was strongly expressed in the ventricular zone, radial fibers and migrating neuroblasts, but not in mature neurons, suggesting that the cytomegalovirus promoter is silenced after the cells differentiate into mature neurons. Since there is still no convenient way of visualizing the migrating neuroblasts, especially of distinguishing them from the surrounding mature neurons in the cortical plate, this system should provide a good tool for analysing neuronal migration. In the postnatal lateral cortex, neuroblasts migrated almost "tangentially" along the obliquely running "radial" fibers beneath the cortical plate, and after entering the cortical plate, turned towards the marginal zone and migrated radially. Neurons with primitive dendrites were observed only along the border between the marginal zone and the cortical plate, and never at other sites, such as in the middle of the cortical plate. These results imply that the neuroblasts do terminate migration and start differentiation to mature neurons when they encounter the marginal zone, as has long been suggested. By contrast, when elongation factor 1alpha promoter was used, prominent fluorescence allowed visualization of the entire mature neurons as well. The labeled neurons were observed to send axons to the contralateral cortex where they arborized extensively.Thus, this system is much easier and more efficient than virus-mediated gene transfer, and is useful for gain-of-function analysis of neural cell fate determination, migration, positioning and axon path-finding in mouse embryos.

Animals↗

Impact of coronary artery remodeling on clinical presentation of coronary artery disease: an intravascular ultrasound study.

OBJECTIVES: We examined the association between the features of the culprit lesion in coronary artery disease (CAD) and clinical presentation as shown by intravascular ultrasound (IVUS). BACKGROUND: The association between coronary remodeling pattern and clinical presentation of CAD is unclear. METHODS: We analyzed 125 selected patients who underwent preintervention IVUS. Acute myocardial infarction (AMI) and unstable angina pectoris (UAP) were categorized as an acute coronary syndrome (ACS), and stable angina pectoris (SAP) and old myocardial infarction (OMI) as stable CAD. Coronary remodeling patterns and plaque morphology of the culprit lesion obtained by IVUS were analyzed in terms of their association with clinical presentation or angiographic morphology. RESULTS: Angiographically complex lesions were associated with ACS and OMI. In patients with a complex lesion, positive remodeling was observed more frequently than in those with a simple lesion. In AMI and UAP, positive remodeling was observed more frequently than in SAP and OMI (82% vs. 78% vs. 33% vs. 40%, respectively, p < 0.0001). The remodeling ratio was greater in AMI and UAP than in SAP and OMI (1.26 +/- 0.15 vs. 1.11 +/- 0.10 vs. 0.94 +/- 0.11 vs. 0.96 +/- 0.13, respectively, p < 0.0001). Furthermore, within ACS, the remodeling ratio was greater in AMI than in UAP (1.26 +/- 0.15 vs. 1.11 +/- 0.10, respectively, p < 0.05), whereas the frequency of positive remodeling was not different. CONCLUSIONS: Positive remodeling was more frequently observed in ACS than in stable CAD. Moreover, the degree of positive remodeling was greater in AMI than in UAP. These results may reflect the impact of remodeling types and its degree in the culprit lesion of CAD on clinical presentation.

Adult↗

Suppression of fibrous adhesion by proteoglycan decorin.

Small proteoglycan decorin is known to suppress the bioactivity of TGF-beta through a competitive binding with the cell surface receptors for the cytokine. Based on this knowledge, we hypothesized that decorin could reduce the formation of fibrous adhesion, because our previous study showed the neutralizing antibody to TGF-beta1 has that effect. An intra-articular adhesion model in the rabbit knee joint was employed in this study, and decorin was administered into the joint cavity continuously during the 4 weeks of the experiment. The results of the dose-response study demonstrated that decorin suppresses formation of fibrous adhesion in a dose-dependent manner. When the administration of decorin was limited to shorter periods, this effect was considerably impaired and the necessity of long-term administration was demonstrated. On the other hand, when administered together with TGF-beta1, decorin still suppressed adhesion but to a lesser extent, and it was suggested that this proteoglycan could have other significant mechanism(s) to suppress adhesion besides the neutralization of TGF-beta. Thus, the present study showed that decorin could inhibit adhesion formation by both TGF-beta dependent and independent mechanisms. Considering that decorin exists ubiquitously in the body, its administration might be a promising approach to suppress adhesion.

Animals↗

Plasma triglyceride-rich lipoprotein remnants as a risk factor of 'Pokkuri disease'.

In our recent report, it remained unclear whether or not triglyceride-rich lipoprotein remnants (RLP) were associated with the risk of sudden coronary death in younger cases without coronary atherosclerosis that were detected in about 10% of all sudden coronary death cases in Japan. These cases were categorized as 'origin unknown, but suspected to be due to coronary spasm', the so called 'pokkuri disease' in Japan. The present study population consisted of 108 sudden death cases without coronary atherosclerosis [(pokkuri disease n=57) and non-cardiac sudden death (control n=51)] aged 20-69 years from Kanagawa prefecture in Japan. All individuals had died suddenly and unexpectedly, most had no significant history of medical conditions including cardiac symptoms and had not taken medications prior to death according to their medical records. All the autopsies were performed within 12 h after death. Plasma total cholesterol (TC), triglycerides (TG), phospholipids, RLP-C and RLP-TG, VLDL-C, LDL-C, HDL-C, apolipoproteins A-I, A-II, B, C-II, C-III, E, Lp (a) and homocysteine were measured in postmortem plasma samples. The TG-rich lipoprotein remnants measured as RLP-C and RLP-TG were significantly higher in pokkuri disease compared with controls both in fasting and postprandial states (P<0.05 and P<0.001), indicating that RLP-C and RLP-TG were the most significant risk factor in pokkuri disease among the parameters tested in this study. In conclusion the TG level in RLP (RLP-TG) appeared to be strongly associated with the risk of sudden death in the absence of coronary atherosclerosis (pokkuri disease).

Journal Article↗

New polymorphic microsatellite markers in the human MHC class III region.

The human major histocompatibility complex (MHC) class III region spanning approximately 760 kb is characterized by a remarkably high gene density with 59 expressed genes (one gene every 12.9 kb). Recently, susceptibility loci to numerous diseases, such as Graves disease, Crohn disease, and SLE have been suggested to be localized to this region, as assessed by associations mainly with genetic polymorphisms of TNF and TNF-linked microsatellite loci. However, it has been difficult to precisely localize these susceptibility loci to a single gene due to a paucity to date of polymorphic markers in the HLA class III region. To facilitate disease mapping within this region, we have analyzed 2 approximately 5 bases short tandem repeats (microsatellites) in this region. A total of 297 microsatellites were identified from the genomic sequence, consisting of 69 di-, 62 tri-, 107 tetra-, and 59 penta-nucleotide repeats. It was noted that among them as many as 17 microsatellites were located within the coding sequence of expressed genes (NOTCH4, PBX2, RAGE, G16, LPAAT, PPT2, TNXB, P450-CYP21B, G9a, HSP70-2, HSP70-1, HSP-hom, MuTSH5 and BAT2). Eight microsatellite repeats were collected as polymorphic markers due to their high number of alleles (11.9 on average) as well as their high polymorphic content value (PIC) (0.63). By combining the 38 and the 22 polymorphic microsatellites we have previously collected in the HLA class I and class II regions, respectively, we have now established a total of 68 novel genetic markers which are uniformly interspersed with a high density of one every 63.3 kb throughout the HLA region. This collection of polymorphic microsatellites will enable us to search for the location of any disease susceptible loci within the HLA region by association analysis.

Chromosome Mapping↗

Microfabricated silicon dioxide cantilever with subwavelength aperture.

We have developed a microfabricated SiO2 cantilever with subwavelength aperture for scanning near-field optical microscopy (SNOM), to overcome the disadvantages of conventional optical fibre probes such as low reproducibility and low optical throughput. The microcantilever, which has a SiO2 cantilever and an aperture tip near the end of the cantilever, is fabricated in a reproducible batch process. The circular aperture with a diameter of 100-150 nm is formed by a focused ion-beam technique. Incident light is directly focused on the aperture from the rear side of the cantilever using a focusing objective, and high optical throughput (10(-2) to 10(-3)) is obtained. The microcantilever can be operated as a SNOM probe in contact mode or in dynamic mode.

Journal Article↗

Endoscopic management of a traumatic disruption of the bulbous urethra using a thin trocar puncture.

A case is reported in which complete disruption of the bulbous urethra resulted in a straddled-type injury, which was managed by endoscopic realignment with a thin trocar needle. The endoscopic urethroplasty consisted of: (i) direct observation of the proximal end of the obliterated urethra by an antegrade flexible cystoscope; (ii) adjustment of the direction of trocar penetration under fluoroscopy and direct vision; (iii) confirmation of the exact trocar position and penetration by antegrade flexible cystoscope; and (iv) placement of the guidewire following the trocar penetration as guidance for urethrotomy. A Foley catheter was left in place for 6 weeks. To date, no further endoscopic revision has been required. Although long-term follow up and more experience are required, this technique is reported because it appears to be safe, reproducible, simple and minimally invasive.

Cystoscopy↗

Remnant-like particles cholesterol is higher in diabetic patients with coronary artery disease.

Diabetes mellitus (DM) has been well known to be one of the risk factors of coronary artery disease (CAD). Recently, remnant-like particles cholesterol (RLP-C) has been reported to be associated with CAD. However, few studies reported the association of RLP-C level with CAD in subjects with DM. To investigate the effects of presence or absence of DM on the association between RLP-C and CAD, we compared the RLP-C level in 142 male patients with CAD and 123 male subjects without CAD (non-CAD), including 44 and 38 DM patients, respectively. RLP-C was significantly higher in CAD than non-CAD (P <.05). RLP-C and RLP-C/plasma-triglyceride (TG) ratio in CAD with DM were higher than CAD without DM (P <.01, P <.05), and non-CAD with DM (P <.001, P <.05). There was positive correlation between RLP-C and plasma-TG in non-CAD without DM (r =.44, P <.01), non-CAD with DM (r =.56, P <.001), CAD without DM (r =.81, P <.0001), and CAD with DM (r =.75, P <.001). After excluding the hypertriglyceridemic patients (>200mg/dL), RLP-C/plasma-TG ratio was significantly higher in CAD with DM than CAD without DM (P <.001) and non-CAD with DM (P <.05). These results suggest that increased RLP-C to plasma-TG may be associated with CAD in middle-aged diabetic male subjects.

Blood Glucose↗