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Biomedical subjects

K Yoshikawa

Publications and source records attributed to K Yoshikawa.

At least 55 records · Page 3Linked to original sources
PubMed2001

Dorsal root ganglia morphologic features in patients with herniation of the nucleus pulposus: assessment using magnetic resonance myelography and clinical correlation.

STUDY DESIGN: Morphologic features of the dorsal root ganglia were investigated in patients with herniation of the nucleus pulposus by means of magnetic resonance myelography. OBJECTIVES: This study was undertaken to assess morphologic changes of the dorsal root ganglia in patients with herniation of the nucleus pulposus and to determine the relations between the morphologic features of the dorsal root ganglia and clinical features. SUMMARY OF BACKGROUND DATA: It has recently been reported that application of the nucleus pulposus to a nerve root induces edema in the rat dorsal root ganglion. Edema in the human dorsal root ganglion resulting from lumbar disc herniation has not been discussed in the literature, to the authors' knowledge. METHODS: Eighty-three consecutive patients (average age 42.1 years; range 17 to 77 years) with monoradicular symptoms were examined. Dorsal root ganglion morphologic features, i.e., indentations and swelling, were evaluated by magnetic resonance myelography. The dorsal root ganglion swelling at each level was quantitatively expressed as a ratio of the dorsal root ganglion width on the involved side to that of the contralateral side and was termed dorsal root ganglion ratio. Eighty-three uninvolved levels were chosen as controls in a randomized manner. Factors possibly contributing to the morphologic changes in the dorsal root ganglion were investigated. Neurologic symptoms, evaluated by the Japan Orthopaedic Association scoring system, were correlated to the morphologic changes. The morphologic features were followed up for 1 year after treatment in a small group of patients. RESULTS: Dorsal root ganglion indentations were always found in the narrowed intervertebral foramens. The incidence of indentations was significantly higher at the involved nerve roots (10.8%) than at the uninvolved nerve roots (4.0%) (P = 0.026). Patients with dorsal root ganglion indentations were significantly older (P = 0.0008). Leg pain scores in patients with indentations were significantly poor (P = 0.007). The dorsal root ganglion ratios were significantly higher at the involved levels than at the uninvolved levels (P = 0.001); the means +/- SD were 1.19 +/- 0.25 and 1.08 +/- 0.13, respectively. Patients with lateral herniated nucleus pulposus had significantly higher dorsal root ganglion ratios than those with central herniated nucleus pulposus (P = 0.0001); the mean ratios +/- SD were 1.48 +/- 0.32 and 1.10 +/- 0.12, respectively. A moderate positive correlation was found between dorsal root ganglion ratio and age (Pearson's correlation coefficient = 0.313). There was moderate negative correlation between the dorsal root ganglion ratio and leg pain, gait, motor, and total Japan Orthopaedic Association score (correlation coefficients were = -0.385, -0.350, -0.422, and -0.358, respectively). The dorsal root ganglion ratios were significantly diminished at 1-year follow-up (P = 0.001); the means +/- SD were 1.22 +/- 0.22 and 1.09 +/- 0.07, respectively. Indentations observed before treatment disappeared after treatment. CONCLUSIONS: Swelling and impingement in the involved dorsal root ganglion were clearly visualized by magnetic resonance myelography. The swelling and indentations were well correlated with severity of leg pain. These findings have important value in understanding the pathophysiology of the nerve roots in herniated nucleus pulposus.

Adolescent↗
PubMed2001

A new IFN-like cytokine, limitin, modulates the immune response without influencing thymocyte development.

A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN-alphabeta receptor, although it lacked growth suppression on myeloid and erythroid progenitors. Here we have studied diverse effects of limitin on T lymphocytes and compared limitin with previously known IFNs. Like IFN-alpha and -beta, limitin modified immunity in the following responses. It suppressed mitogen- and Ag-induced T cell proliferation through inhibiting the responsiveness to exogenous IL-2 rather than suppressing the production of IL-2. In contrast, limitin enhanced cytotoxic T lymphocyte activity associated with the perforin-granzyme pathway. To evaluate the effect of limitin in vivo, a lethal graft-versus-host disease assay was established. Limitin-treatment of host mice resulted in the enhancement of graft-versus-host disease. Limitin did not influence thymocyte development either in fetal thymus organ cultures or in newborn mice injected with limitin-Ig, suggesting that limitin is distinguishable from IFN-alpha and -beta. From these findings, it can be speculated that the human homolog of limitin may be applicable for clinical usage because of its IFN-like activities with low adverse effects on, for example, T lymphopoiesis, erythropoiesis, and myelopoiesis.

Adjuvants, Immunologic↗
PubMed2001

Intercalating fluorescence dye YOYO-1 prevents the folding transition in giant duplex DNA.

Recently, it has become clear that with the addition of polyamines, giant DNA molecules of size greater than 10 kbp exhibit all-or-none switching between elongated coil and folded compact states. Here the effects of the intercalating fluorescent labeling dye, YOYO-1, and the minor-groove binding fluorescent labeling dye, DAPI, on the folding transition of single giant T4 DNA (166 kbp) induced by spermidine(3+) were examined, by use of the experimental technique of single molecular chain observation with fluorescence microscopy. It is found that the intercalating dye, YOYO-1, markedly prevents the folding transition, whereas the minor-groove binding dye, DAPI, exhibits negligible effect on the folding transition. This action of YOYO-1 is discussed in relation to the biological effect of intercalators.

Benzoxazoles↗
PubMed2001

Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma.

MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9 -positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at -74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at -74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at -74 bp. These findings suggest that hypomethylation of the CpG at -74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC.

Carcinoma, Renal Cell↗
PubMed2001

Histone core slips along DNA and prefers positioning at the chain end.

We studied the stability and dynamics of a model of a nucleosome, the fundamental unit for the packing of long DNA in eukaryotes, using a Brownian dynamics simulation. For the proper folding of a stiff polymer on a core particle, moderate attractive interaction is shown to be essentially important, which explains the empirical experimental protocol for the reconstitution of nucleosomes. The effect of the chain end on the positioning of the core particle is examined and compared with the experimental data by atomic force microscopy measurement. It is also suggested that the core particle exhibits sliding motion along the chain as a manifestation of Brownian motion.

DNA↗
PubMed2001

Age-related reduction of extrastriatal dopamine D2 receptor measured by PET.

Although the aging effect of dopamine D2 receptor in the striatum is well-documented, the effect of age on the extrastriatal dopamine D2 receptor has not been fully examined. Since the density of extrastriatal dopamine D2 receptor is very low, suitable ligands are limited. In this study, we used [11C]FLB 457 to quantify the extrastriatal dopamine D2 receptor in the living human brain. Twenty-seven healthy male subjects aged from 21 to 82 years participated in the positron emission tomography study. Extrastriatal [11C]FLB 457 binding was quantified with a reference tissue model using cerebellum as a reference region. Binding potentials corresponding to Bmax/Kd were used to evaluate age-related change. We found age-related decreases of D2 receptor binding in all measured extrastriatal regions. The decrease of D2 receptor binding was 13.8% per decade in frontal cortex, 12.0% in temporal cortex, 13.4% in parietal cortex, 12.4% in occipital cortex, 12.2% in hippocampus, and 4.8% in thalamus. These findings suggest that the amounts of D2 receptor declines in all brain regions as part of the normal aging process.

Adult↗
PubMed2001

The binding of thymus leukemia (TL) antigen tetramers to normal intestinal intraepithelial lymphocytes and thymocytes.

Thymus leukemia (TL) Ags belong to the family of nonclassical MHC class I Ags and can be recognized by both TCRalphabeta and TCRgammadelta CTL with TL, but not H-2 restriction. We previously reported that the CTL epitope is TAP independent, but the antigenic molecule(s) presented by TL has yet to be determined. In the present study, TL tetramers were prepared with T3(b)-TL and murine beta(2)-microglobulin, not including antigenic peptides, and binding specificity was studied. CTL clones against TL Ags were stained with the T3(b)-TL tetramer, and the binding shown to be CD3 and CD8 dependent. Normal lymphocytes from various origins were also studied. Surprisingly, most CD8(+) intraepithelial lymphocytes derived from the small intestines (iIEL), as well as CD8(+) and CD4(+)CD8(+) thymocytes, were stained, while only very minor populations of CD8(+) cells derived from other peripheral lymphoid tissues, such as spleen and lymph nodes, were positive. The binding of T3(b)-TL tetramers to CD8(+) iIEL and thymocytes was CD8 dependent, but CD3 independent, in contrast to that to TL-restricted CTL. These results altogether showed that TL-restricted CTL can be monitored by CD3-dependent binding of T3(b)-TL tetramers. In addition, CD3-independent T3(b)-TL tetramer binding to iIEL and thymocytes may imply that TL expressed on intestinal epithelium and cortical thymocytes has a physiological function interacting with these tetramer(+)CD8(+) T lymphocytes.

Animals↗
PubMed2001

Necdin acts as a transcriptional repressor that interacts with multiple guanosine clusters.

Necdin is a growth suppressor expressed predominantly in postmitotic neurons, and ectopic expression of this protein suppresses cell growth. Here we report that Necdin directly binds to specific DNA sequences and serves as a transcriptional repressor. Polyhistidine-tagged Necdin was used for selection of random-sequence oligonucleotides by polymerase chain reaction-based amplification. Necdin recognized guanosine (G)-rich sequences that encompass multiple G clusters and intervening mono- or di-nucleotides of A, T and C. These sequences, termed GN boxes, resemble multiply aligned forms of the canonical GC box which is recognized by Sp family members. Necdin directly bound to a GN box consisting of contiguous two GC boxes with four G clusters, but not to a single GC box with two G clusters, whereas Sp1 bound to both. In a reporter system using Drosophila Schneider Line 2 cells, Necdin repressed Sp1-dependent activity of mouse c-myc P1 promoter that contains a typical GN box. Deletion of the GN box from the c-myc P1 promoter or its conversion to the single GC box abolished the Necdin-dependent repression. These results suggest that Necdin modulates gene transcription via the GN box that is potentially recognized by GC box-targeting Sp family members.

Animals↗
PubMed2001

Co-administration of adenovirus vector expressing CTLA4-Ig prolongs transgene expression in the brain of mice sensitized with adenovirus.

The duration of transgene expression in the brain is known to be shortened by previous sensitization to adenovirus. In order to prolong transgene expression, adenovirus vectors expressing CTLA4-Ig (AdCTLA), which blocks the B7-CD28 co-stimulatory signals required for T-cell activation, were used. Local administration of AdCTLA into the brain suppressed both the cellular and humoral immune responses to adenovirus vectors, and prolonged the duration of transgene expression. AdCTLA may be an effective tool for repeated gene transfer.

Abatacept↗
PubMed2001

Protein determination by high-performance gel-permeation chromatography: applications to human pancreatic juice, human bile and tissue homogenate.

A high-performance gel-permeation chromatography (HPGPC) method to determine the proteins of human pancreatic juice, bile, and tissue homogenate has been developed. A diol-type silica gel column (35 x 8 mm I.D., 5 nm average pore diameter) was used under a column temperature of 8 degrees C. The eluent was acidic phosphate buffer with a high concentration of sodium chloride, nonionic detergent of polyoxyethylene (20) cetyl ether (Brij 58), glycerol and 2-propanol. The UV wavelength used for the protein detection was 210 nm. Analytical time was within 3.5 min. Good correlation coefficients were obtained with this HPLC method at a column temperature of 8 degrees C and a spectrophotometric bicinchoninic acid (BCA) method. A photometric pyrogallol-red molybdate complex method was found to correlate well with this HPLC method and with the BCA method only for tissue homogenate. Since this HPGPC protein assay method is simple, convenient, rapid, reproducible, and reliable, it is expected to be generally applicable to clinical and also to biochemical research.

Animals↗
PubMed2001

Real-time memory on an excitable field.

Recently, we proposed a novel method for computing logic operations based on the time-sequential information in a geometrically arranged excitable field. As an extension of this study, in the present article we describe a strategy for creating real-time memory. Using a numerical simulation, we show that input pulse trains can be stored as a sequence of rotating traveling waves in a circular excitable field, by using its characteristics as a diode due to spatially asymmetric arrangement. Furthermore, through an experiment on an excitable chemical reaction, we demonstrate that this real-time memory actually works in the real world.

Journal Article↗
PubMed2001

A functional MRI study on the neural substrates for writing.

Functional neuroanatomy of writing is relatively unknown compared to that of other linguistic processes. This study aimed at identifying brain regions crucial to the process of writing. Using functional magnetic resonance imaging (fMRI), brain hemodynamic activity was examined during three conditions that differentially engaged visual, linguistic, and/or motor functions: (1) writing names of pictures with the right index finger, (2) naming pictures silently, and (3) visually cued finger tapping. A writing minus naming comparison and a writing minus tapping comparison were performed, and brain regions commonly activated in these two contrasts were detected. Our main finding was that such common activation was observed in the anterior part of the left superior parietal lobule, the posterior part of the middle and superior frontal gyri, and the right cerebellum. The parietal and frontal regions were considered to subserve the process of writing as separated from that of naming and finger movements, which is consistent with the classical notion mainly proposed by studies of selective writing deficits called pure agraphia. The right cerebellar activation, on the other hand, was interpreted as the reflection of the execution of complex finger movements required for writing.

Adult↗
PubMed2001

Cells derived from tuberous sclerosis show a prolonged S phase of the cell cycle and increased apoptosis.

Tuberous sclerosis complex (TSC) is a multisystemic disorder characterized by systemic hamartomas. Although the disease-determining genes TSC1 and TSC2 have been isolated, the molecular pathogenesis of the disease is not understood. We examined cell cycle abnormalities in skin specimens and cultured cells derived from specific lesions of TSC patients with confirmed TSC1 or TSC2 mutations. None of the specimens used in this study showed loss of heterozygosity (LOH). We detected more cells positive for PCNA and fewer cells positive for MPP2 in the epidermis of TSC patients than in the epidermis of control patients without TSC. Incorporation of 5-bromo-2-deoxyuridine (BrdU) was similar in fibroblasts derived from TSC lesions and in normal human fibroblasts. These results suggest that the cell cycle of TSC cells shows a prolonged S phase. Flow cytometric analysis confirmed S phase prolongation in TSC cells. Many apoptotic cells were detected by a nick end labeling assay in both skin tissue and cultured fibroblasts derived from specific TSC lesions. Examination of cyclin levels showed increased nuclear cyclin A and cytoplasmic cyclin B and decreased nuclear cdc2 levels. We conclude that suppression of either TSC1 or TSC2 may change cyclin levels, prolong S phase and induce apoptotic cell death.

Adult↗
PubMed2001

Increased expression of a nucleolar Nop5/Sik family member in metastatic melanoma cells: evidence for its role in nucleolar sizing and function.

F10 and BL6 cells of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells can metastasize to lungs after subcutaneous injection. Differences in gene expression between the two cell lines were examined, and a greater expression of the Sik-similar protein (Sik-SP) gene was found in BL6 cells. Structurally, Sik-SP belongs to the nucleolar Nop5/Sik family whose members play central roles in ribosome biogenesis; however, the function of Sik-SP has not been examined. Cytology with green fluorescent protein-fused proteins showed that Sik-SP was localized to the nucleolus. To examine whether Sik-SP is involved in ribosome biogenesis, two parameters were measured: magnitude of ribosomal RNA synthesis per nucleus and magnitude of protein production from the same amount of mRNA of an exogenous luciferase gene. Both values and, in addition, nucleolar size were larger in COS-7 monkey kidney cells overexpressing Sik-SP and BL6 cells than in mock-transfected COS-7 and F10 cells, respectively. Sik-SP seemed to promote ribosome biogenesis in the nucleolus. Furthermore, the expression of Sik-SP seemed to confer a greater cell growth response to serum, because such a response was greater in BL6 cells and F10 cells overexpressing Sik-SP than in untreated and mock-transfected F10 cells. Sik-SP may render melanoma cells more competent to survive through augmenting the activity of nucleolus.

Animals↗
PubMed2001

Is segmentectomy with lymph node assessment an alternative to lobectomy for non-small cell lung cancer of 2 cm or smaller?

BACKGROUND: Lesser resection than the standard lobectomy for small-sized cT1N0M0 non-small cell lung cancers continues to be debated. METHODS: We reviewed specimens of 139 patients after lobectomy for cT1N0M0 cancer of 2 cm or less. In addition, we prospectively enrolled 70 patients able to tolerate a lobectomy, in a trial of lesser resection for these lesions. The limited procedure consisted of segmentectomy in which the resection line was delivered beyond the burdened segment, plus exploration of lymph nodes by frozen sectioning. This procedure was modified if the result was positive; this modified procedure was called extended segmentectomy. RESULTS: The nodal status after lobectomy was pN0, 107 patients; pN1, 12 patients; and pN2, 20 patients. Of the pN1 patients, 2 had only intralobar nodal involvement within the same segment of the main tumor. In the remaining 30 patients with nodal involvement, we ascertained the nodal involvement during the operation. Regarding intrapulmonary metastasis, 1 of 8 patients having this metastasis had the lesion at the segment where the main tumor was not located and had N2 disease, which was detected intraoperatively. If extended segmentectomy had been performed instead of lobectomy, the lesion could have been removed completely. The 5-year survival of patients with cT1N0M0 cancer of 2 cm or less was 87.3% after extended segmentectomy. There were no local recurrences and three noncancer-related deaths. Among patients with pT1N0M0 cancer of 2 cm or less, the 5-year survival was 87.1% in the extended segmentectomy group and 87.7% in the lobectomy group (p = 0.8008). CONCLUSIONS: Extended segmentectomy should be considered as an alternative for patients with cT1N0M0 non-small cell lung cancer of 2 cm or smaller.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Disappearance of the negative charge in giant DNA with a folding transition.

In the present study we measure the electrophoretic mobility of giant T4 DNA (166 kbp) by electrophoretic light scattering for the elongated and folded compact states at different spermidine (trivalent cation) concentrations in 50 mM sodium maleate buffer (pH 6.0). It is found that the electrophoretic mobility of elongated DNA in the absence of the multivalent cation is seven times greater than that of fully folded compact DNA, where, with the increase of the concentration of spermidine, an abrupt transition is generated after a gradual decrease of the mobility. An analysis of the electrophoretic mobility suggests that the folded compact DNA chains almost completely lose their negative charges, by taking into account the difference of friction mechanism between an elongated and folded compact state. From the single chain observation by use of fluorescence microscopy, it is found that a phase-segregated structure is generated at intermediate concentrations of spermidine. The gradual decrease of the electrophoretic mobility in the transition region is, thus, attributed to the formation of the segregated state, exhibiting partial electroneutralization in the folded part. Disappearance of the negative charges in the completely folded compact DNAs is discussed in relation to the mechanism of transition, in terms of a first-order phase transition.

Anions↗
PubMed2001

Potential anti-androgenic activity of roxithromycin in skin.

Since acne formation is a multistep process accelerated by androgens, we examined whether a new anti-acne antibiotic roxithromycin (RXM) may act as anti-androgen using transient transfection assays in human skin fibroblasts. The result showed no significant effect of 0.5, 1 and 5 microg/ml RXM on 10(-9) M R1881-induced androgen receptor (AR) transcriptional activity. While the cotransfection of exogenous ARA55, a novel AR coactivator, increased AR transactivation up to 2.59-fold, this increase was attenuated by 5 microg/ml RXM to 64.7%. Semiquantitative RT-PCR results showed that 0.1 mM H(2)O(2) treatment increased ARA55 mRNA expression level, indicating that reactive oxygen species increase the expression of ARA55 in skin. These results suggest that RXM may serve as anti-androgen only in the hypersensitive state to androgen, but not in the physiological state, through modulating end-organ hypersensitive condition to androgen possibly involving the pathway from reactive oxygen species to ARA55.

Androgen Antagonists↗