Biomedical subjects
Publications and source records attributed to Y Kaneko.
Polysomnography(PSG) is essential for the diagnosis of all pathophysiologic conditions due to both any types of sleep disordered breathing and to any types of sleep disturbance. Since this issue's objection is to describe the outline of PSG, we will explain here about when PSG is needed, what type of measurements are necessary for PSG, and how it should be interpreted from the result of the PSG tracing for the diagnosis for sleep apnea syndrome, etc.
We analyzed the prognostic significance of chromosomal findings in children with acute lymphoblastic leukemia (ALL), treated according to the Children's Cancer and Leukemia Study Group protocols between 1987 and 1993. Patients were classified into 5 groups according to chromosome number. The patients with a hyperdiploid(> 50) karyotype(13%) had the best prognosis [4-year event-free survival (EFS): 83 +/- 6%], while those with a pseudodiploid karyotype (24%) had the worst prognosis(4-year EFS: 52 +/- 6%) (log-rank, p = 0.03). However, multivariate analysis revealed that the ploidy classification had no prognostic significance in terms of EFS. When patients were classified according to chromosome abnormalities, those with any type of translocation had a worse outcome (4-year EFS: 33 +/- 9%) than those with hyperdiploidy(> 50), normal diploidy, and other abnormalities(log-rank, p < 0.0001). Multivariate analysis revealed that chromosome abnormalities were an independent prognostic factor (relative risk 3.98; p < 0.0001). Patients with t(1; 19) had an EFS similar to that of patients with chromosome abnormalities other than translocations or normal diploidy. We conclude that chromosomal findings have prognostic significance, although some chromosome abnormalities lost their statistical significance after modern intensified chemotherapy. Childhood ALL should be further stratified according to chromosome classification.
UNLABELLED: The need to draw regions of interest (ROIs) manually may reduce the convenience and reliability of estimating renal function from renal scintigraphy. We developed a semiautomated method to define ROIs for renal scintigraphy with 99mTc-mercaptoacetyltriglycine (MAG3) and evaluated the clinical applicability of the method to the estimation of renal function by camera-based methods. METHODS: Dynamic renal scintigraphy with 99mTc-MAG3 was performed on 21 patients. An operator placed a large rectangular ROI over each kidney, a circular ROI within the liver, and a rectangular ROI between the kidneys. Using these ROIs, semiautomated renal ROIs were determined on the basis of the temporal changes in counts, in addition to the absolute counts, and a subrenal background ROI was automatically assigned for each renal ROI. Background-subtracted renograms were generated using these renal and subrenal ROIs, and renogram parameters were derived from the slope of the renogram and the area under the renogram. Clearance was calculated using the renogram parameters and equations determined previously with manual ROIs and correlated with clearance measured by a single-sample method. The relative function of the right kidney determined by the semiautomated method was compared with that determined by the manual method. Data processing was performed independently by another operator to assess interoperator reproducibility. RESULTS: ROIs defined by the semiautomated method were visually judged to be acceptable for clinical use in all patients with a wide range of renal function. Clearance was successfully predicted with the semiautomated ROIs (r = 0.968 using the slope of the renogram; r = 0.934 using the area under the renogram), and relative function calculated with the semiautomated ROIs was almost identical to that calculated with manual ROIs. There was almost complete concordance in absolute and relative function between the two operators. CONCLUSION: The semiautomated method can define ROIs for 99mTc-MAG3 renal scintigraphy with limited operator intervention. Camera-based methods using the semiautomated ROIs allow estimation of renal function with high accuracy and little interoperator variability and are suggested to be suitable for clinical use.
CPAP treatments for sleep apnea syndrome (SAS) are being established; however, there is no established evaluation method to scale the long-lasting effectiveness of the treatment. The only available method is to judge the results from each patient's subjective symptoms. We therefore tested a self-contained microcomputer with an acceleration sensor (Lifecorder) in an attempt to evaluate the effectiveness of treatments objectively. Fifteen patients with OSAS were the subjects. We keep the records of Lifecorders that were worn by the subjects a month before and a month after nasal CPAP treatment. We also assessed their daily physical activity levels; the number of steps taken, calories consumed, intensity of each activity along with improvement in their subjective symptoms. The number of steps taken in a day increased as did the calories consumed after treatment in 9 subjects. Moderate and intensive activities also increased among those 9 subjects. Our results indicate that evaluation with a Lifecorder, which is simple and inexpensive, can provide objective indicators to assess the effectiveness of treatments in patients' daily activities.
It is important for dural arteriovenous fistula (DAVF) to evaluate venous ischemia in the brain related to venous hypertension, but only a few such studies have been performed. In this study, regional cerebral blood flow(rCBF) in DAVF was examined for venous ischemia by 123I-IMP SPECT. The subjects were eighteen patients with DAVF. Of the eighteen patients, nine had DAVF with low perfusion areas and venous ischemia. The factors affecting rCBF in DAVF are: 1) the presence of retrograde leptomeningeal venous drainage, 2) sinus occlusion, and 3) DAVF with high flow. The presence of retrograde leptomeningeal venous drainage was observed in nine patients, sinus occlusion in four patients, high flow in three patients. In two patients, pure leptomeningeal venous drainage was formed by patent sinus, and blood regurgitated from DAVF on the sinus wall to cortical vein. When DAVF was associated with LMVD, most patients had venous hypertension and concomitant venous congestion in the same areas due to reduced venous circulation, resulting in a decrease in rCBF and an increase in regional cerebral blood volume. These hemodynamics suggest venous ischemia in the brain. 123I-IMP SPECT was useful for evaluating rCBF and as a parameter of the treatment.
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The aim of the study was to investigate whether preemptive multimodal analgesia (diclofenac, butorphanol, and lidocaine) was obtained during sagittal split ramus osteotomy (SSRO). Following institutional approval and informed consent, 82 healthy patients (ASA-I) undergoing SSRO were randomly assigned to 1 of 2 groups, the preemptive multimodal analgesia group (group P, n = 41) and the control group (group C, n = 41). This study was conducted in a double-blind manner. Patients in group P received 50 mg rectal diclofenac sodium, 10 micrograms/kg intravenous 0.1% butorphanol tartrate, and 1% lidocaine solution containing 10 micrograms/mL epinephrine for regional anesthesia and for bilateral inferior alveolar nerve blocks before the start of surgery. Postoperative pain intensity at rest (POPI) was assessed on a numerical rating score (NRS) in the postanesthesia care unit (PACU) and on a visual analogue scale (VAS) at the first water intake (FWI) and at 24, 48, and 72 hours after extubation. POPI in the PACU was significantly lower in group P than in group C, whereas there were no significant differences at FWI, 24, 48, and 72 hours after extubation in both groups. Preemptive multimodal analgesia was not observed in this study.
The potency of 4 local anesthetics to dental pulp was compared. Drugs were 4% articaine with 12 microgram/mL epinephrine (A12), 4% articaine with 6 microgram/mL epinephrine (A6), 2% lidocaine with 12.5 microgram/mL epinephrine (L), and 3% propitocaine with 0.03 IU/mL felypressin (P). Local anesthetics were injected into the dental root of the mandibular incisor. Electromyogram (EMG) of the digastric muscle was measured during the jaw-opening reflex induced by electrical stimulation. The disappearance of the EMG wave was judged as positive evidence of anesthesia. The determination of ED50 of the anesthetic was made by probit analysis. The ED50 of the A12 was minimal in all the tested anesthetics throughout the entire course. The potency in the A6 was 2.8 times that of the L. The potency of the A12 at the 15-minute measurement was 3.8 times that of the A6. The ED50 of the P was higher compared with those of the other 3 groups. It was concluded that articaine showed quicker onset than lidocaine and propitocaine and that there was a need to increase the dosage to attain a quick onset or to extend the duration.
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The present study examined the occurrence of apoptosis, identified by an in situ technique for detecting DNA fragmentation, in the regenerating retina of adult newts following ablation of the retina. Apoptosis occurs in the initial phase of regeneration when retinal precursor cells are actively proliferating. In the late stage of regeneration, when two synaptic layers are forming, apoptosis occurs mainly in the ganglion cell layer and inner nuclear layer. We found that apoptosis occurred with proliferation, differentiation, formation of retinal layers and retinotectal projections during retinal regeneration. Our findings suggest that apoptosis is closely related to these phenomena.
In response to DNA damage, mammalian cells adopt checkpoint regulation, by phosphorylation and stabilization of p53, to delay cell cycle progression. However, most cancer cells that lack functional p53 retain an unknown checkpoint mechanism(s) by which cells are arrested at the G(2)/M phase. Here we demonstrate that a human homolog of Cds1/Rad53 kinase (hCds1) is rapidly phosphorylated and activated in response to DNA damage not only in normal cells but in cancer cells lacking functional p53. A survey of various cancer cell lines revealed that the expression level of hCds1 mRNA is inversely related to the presence of functional p53. In addition, transfection of normal human fibroblasts with SV40 T antigen or human papilloma viruses E6 or E7 causes a marked induction of hCds1 mRNA, and the introduction of functional p53 into SV40 T antigen- and E6-, but not E7-, transfected cells decreases the hCds1 level, suggesting that p53 negatively regulates the expression of hCds1. In cells without functional ataxia telangiectasia mutated (ATM) protein, phosphorylation and activation of hCds1 were observed in response to DNA damage induced by UV but not by ionizing irradiation. These results suggest that hCds1 is activated through an ATM-dependent as well as -independent pathway and that it may complement the function of p53 in DNA damage checkpoints in mammalian cells.
Human V alpha24 NKT cells bearing an invariant V alpha24J alphaQ antigen receptor, the counterpart of the murine V alpha14 NKT cells, are activated by the specific ligand, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Here, we demonstrate that the alpha-GalCer-activated V alpha24 NKT cells exert a potent perforin-dependent cytotoxic activity against a wide variety of human tumor cell lines. In addition, we demonstrate that V alpha24 NKT cells and dendritic cells (DCs) from melanoma patients are functionally normal, even in the tumor-bearing status. The potential use of alpha-GalCer-activated V alpha24 NKT cells and/or DCs from patients for cancer immunotherapy is discussed.
Dietary phosphate (P(i)) is a most important regulator for renal P(i) reabsorption. The type II sodium-dependent phosphate (Na/P(i)) cotransporters (NPT2) are located at the apical membranes of renal proximal tubular cells and major functional transporters associated with renal P(i) reabsorption. The consumption of a low-P(i) diet induces the synthesis of NPT2, whereas a high P(i) diet decreases it. The molecular mechanisms of regulation by dietary P(i) are not yet known. In this report, in weaning mice fed a low-P(i) diet for 4 days, the NPT2 mRNA level was increased 1.8-fold compared with mice fed a normal P(i) diet. This increase was due to an elevation of the transcriptional activity. In the NPT2 gene promoter, the DNA footprint analysis showed that six regions were masked by the binding protein, but at the position -1010 to -985 upstream of the transcription start site, the binding clearly responded to the levels of dietary P(i). The phosphate response element (PRE) of the NPT2 gene was found to consist of the motif related to the E box, 5'-CACGTG-3'. A yeast one-hybrid system was used to clone a transcription factor that binds to the PRE sequences in the proximal promoter of the NPT2 gene. Two cDNA clones that encoded protein of the mouse transcription factor muE3 (TFE3) were isolated. This is a DNA-binding protein that activates transcription through the muE3 site of the immunoglobulin heavy chain enhancer. TFE3 antibody completely inhibited the binding to the PRE. The coexpression of TFE3 in COS-7 cells transfected with the NPT2 gene promoter markedly stimulated the transcriptional activity. The feeding of a low P(i) diet significantly increased the amount of TFE3 mRNA in the kidney. These findings suggest that TFE3 may participate in the transcriptional regulation of the NPT2 gene by dietary P(i).
We recently reported that not only lymphoid cells, but cells of neuronal origin may harbor C5a receptors (C5aR) as suggested by results of RT-PCR testing and that an apoptotic pathway is associated with the C5aR. To determine whether C5aR is expressed as an integral membrane protein, we generated mono- and polyclonal anti-C5aR antibodies. Flow cytometry showed a low-level expression of C5aR in TGW neuroblastoma cells. Epitope mapping suggested that a conformation change in C5aR occurs when exposed to C5a. Although an aphysiologically high concentration of C5a is necessary for inducing a transient increase in the intracellular Ca2+ level, TGW cells do employ the signal transduction pathway associated with C5aR, suggesting that these cells may serve as putative model for C5aR-expressing neurons.
The p21CKI forms a physical complex with the retinoblastoma protein (pRb) both in vitro and in vivo. The A/B pocket region of pRb and the N-terminal region of p21 were indispensable for this interaction. Among p21 family members, p57, but not p27, associated with pRb. Overexpression of cyclin D1, Cdk4, and E2F1 in the cells expressing pRb and p21 did not perturb the interaction between p21 and pRb. Coexpression of p21 in cells expressing pRb, cyclin D1, and Cdk4 prevented pRb hyperphosphorylation by cyclin D1/Cdk4. On the other hand, hyperphosphorylation of pRb by an excess amount of cyclin/Cdk disrupted pRb/p21 complex formation in vitro. These findings suggest that pRb may be dynamically regulated by the relative binding and activities of p21 and Cdks.
In mice, the Hsp110/SSE family is composed of the heat shock protein (Hsp)110/105, Apg-1 and Apg-2. In humans, however, only the Hsp110/105 homolog has been identified as a member, and two cDNAs, Hsp70RY and HS24/p52, potentially encoding proteins structurally similar to, but smaller than, mouse Apg-2 have been reported. To clarify the membership of Hsp110 family in humans, we isolated Apg-1 and Apg-2 cDNAs from a human testis cDNA library. The human Apg-1 was 100% and 91.8% identical in length and amino acid (aa) sequence, respectively, to mouse Apg-1. Human Apg-2 was one aa shorter than and 95.5% identical in sequence to mouse Apg-2. In ECV304, human endothelial cells Apg-1 but not Apg-2 transcripts were induced in 2 h by a temperature shift from 32 degrees C to 39 degrees C. As found in mice, the response was stronger than that to a 37-42 degrees C shift. The human Apg-1 and Apg-2 genes were mapped to the chromosomal loci 4q28 and 5q23.3-q31.1, respectively, by fluorescence in-situ hybridization. We isolated cDNA and genomic clones encompassing the region critical for the difference between Apg-2 and HS24/p52. Although the primer sets used were derived from the sequences common to both cDNAs, all cDNA and genomic clones corresponded to Apg-2. Using a similar approach, the relationship between Apg-2 and Hsp70RY was assessed, and no clone corresponding to Hsp70RY was obtained. These results demonstrated that the Hsp110 family consists of at least three members, Apg-1, Apg-2 and Hsp110 in humans as well as in mice. The significance of HS24/p52 and Hsp70RY cDNAs previously reported remains to be determined.
Tektins are a class of proteins that form filamentous polymers in the walls of ciliary and flagellar microtubules. We report here the molecular cloning of a new member of the tektin family, tektin-t, identified from a mouse haploid germ cell-specific cDNA library. Tektin-t mRNA encodes a protein of 430 deduced amino acids possessing RSNVELCRD, the conserved sequence of tektin family proteins. Western blotting showed a single band having a molecular weight of 86 kDa in the mouse testis. Immunohistochemistry of the testis showed that tektin-t is localized in the flagella of elongating spermatids from developmental step 15 to maturity.
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