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Biomedical subjects

Y Kitagawa

Publications and source records attributed to Y Kitagawa.

At least 73 records · Page 4Linked to original sources
PubMed2001

Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a novel and minimally invasive approach.

Although the sentinel node (SN) concept has been validated in malignant melanoma and breast cancer, the application of this concept for other solid tumors, including gastrointestinal (GI) cancer, is still controversial. We have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric, and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastasis from the primary lesion were detectable using this method. More recently, we have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimized the identification of SNs that drained GI cancers. Our preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis, and we believe that it will become an important component of a minimally invasive approach to early-stage GI cancers.

Colonic Neoplasms↗
PubMed2001

[Clinical significance of sentinel node navigation surgery in the treatment of early gastric cancer].

Radical lymphadenectomy is the standard surgical approach even for early-stage gastric cancer with a relatively low incidence of lymph node metastasis because of the limited sensitivity of diagnostic imaging to detect micrometastasis in regional lymph nodes. The sentinel node (SN) concept is one topic among novel diagnostic procedures for micrometastasis. The SN is defined as the first draining node from the primary lesion and it would be the first site of micrometastasis. SN biopsy has been clinically validated and applied for the surgical treatment of malignant melanoma and breast cancer. Although the feasibility of this technique in other solid tumors including gastric cancer is still controversial, there are several reports demonstrating the diagnostic significance of SN mapping in early gastric cancer. We have established radio-guided SN mapping for early gastric cancer, and the diagnostic accuracy using this procedure in cT1N0 cases reached 98%. The radio-guided method allows us to detect the SN in endoscopic surgery quantitatively and reproducibly. Validation of the SN concept in gastric cancer in a multi-centric clinical trial is essential for clinical application of this procedure, including the establishment of a novel, minimally invasive approach for early-stage gastric cancer.

Humans↗
PubMed2001

[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of paclitaxel].

A 57-year-old woman underwent modified radical mastectomy for left breast cancer (T4bN1M1: stage IV) in September 1999. Four-cycle CAF therapy had been administered as adjuvant therapy, but multiple recurrent tumors in the liver had grown bigger and the tumor marker (CEA) increased in value. Because CAF therapy was not effective, we tried to treat the patient with systemic and intra-arterial chemotherapy using paclitaxel. The side effects of this treatment were mild nausea and appetite loss, which required no treatments. This treatment reduced the multiple liver metastases on an abdominal CT and was thought to produce a partial response (PR). The time to response was the 101st day and PR has been continued.

Antineoplastic Agents, Phytogenic↗
PubMed2000

High and low affinity heparin-binding sites in the G domain of the mouse laminin alpha 4 chain.

G domains of the mouse laminin alpha 1 and alpha 4 chains consisting of its five subdomains LG1-LG5 were overexpressed in Chinese hamster ovary cells and purified by heparin chromatography. alpha 1LG1-LG5 and alpha 4LG1-LG5 eluted at NaCl concentrations of 0.30 and 0.47 m, respectively. In solid phase binding assays with immobilized heparin, half-maximal concentrations of 14 (alpha 1LG1-LG5) and 1.4 nm (alpha 4LG1-LG5) were observed. N-Glycan cleavage of alpha 4LG1-LG5 did not affect affinity to heparin. The affinity of alpha 4LG1-LG5 was significantly reduced upon denaturation with 8 m urea but could be recovered by removing urea. Chymotrypsin digestion of alpha 4LG1-LG5 yielded high and low heparin affinity fragments containing either the alpha 4LG4-LG5 or alpha 4LG2-LG3 modules, respectively. Trypsin digestion of heparin-bound alpha 4LG1-LG5 yielded a high affinity fragment of about 190 residues corresponding to the alpha 4LG4 module indicating that the high affinity binding site is contained within alpha 4LG4. Competition for heparin binding of synthetic peptides covering the alpha 4LG4 region with complete alpha 4LG1-LG5 suggests that the sequence AHGRL1521 is crucial for high affinity binding. Introduction of mutation of H1518A or R1520A in glutathione S-transferase fusion protein of the alpha 4LG4 module produced in Escherichia coli markedly reduced heparin binding activity of the wild type. When compared with the known structure of alpha 2LG5, this sequence corresponds to the turn connecting strands E and F of the 14-stranded beta-sheet sandwich, which is opposite to the proposed binding sites for calcium ion, alpha-dystroglycan, and heparan sulfate.

Animals↗
PubMed2000

Antitumor promoting activities of 3-O-acyl-(-)epigallocatechins.

As an exploratory investigation of antitumor promoting compounds, 3-O-acyl-(-)-epigallocatechins possessing a straight-, branched-, phenyl-inserted- or 1,4-phenylene-inserted-acyl chain of varying length from C4 to C18 were synthesized and evaluated their inhibitory effects against the activation of the Epstein-Barr virus early antigen (EBV-EA). It was indicated that the epigallocatechin derivatives having the straight- or branched-acyl chain of C8 to C11 carbon atoms achieve marked effects.

Anticarcinogenic Agents↗
PubMed2000

Induction of aldose reductase in cultured human microvascular endothelial cells by advanced glycation end products.

Accelerated formation and accumulation of advanced glycation end products, as well as increased flux of glucose through polyol pathway, have been implicated in the pathogenesis of diabetic vascular complications. We investigated effects of advanced glycation end products on the levels of aldose reductase mRNA, protein, and activity in human microvascular endothelial cells. When endothelial cells were cultured with highly glycated bovine serum albumin, aldose reductase mRNA in endothelial cells demonstrated concentration-dependent elevation. The increase in aldose reductase mRNA was accompanied by elevated protein expression and enzyme activity. Significant increase in the enzyme expression was also observed when endothelial cells were cultured with serum obtained from diabetic patients with end-stage renal disease. Pretreatment of the endothelial cells with probucol or vitamin E prevented the advanced glycation end products-induced increases in aldose reductase mRNA and protein. Electrophoretic mobility shift assays using the nuclear extracts of the endothelial cells treated with advanced glycation end products showed enhancement of specific DNA binding activity for AP-1 consensus sequence. These results indicate that accelerated formation of advanced glycation end products in vivo may elicit activation of the polyol pathway, possibly via augmented oxidative stress, and amplify endothelial cell damage leading to diabetic microvascular dysfunction.

Aldehyde Reductase↗
PubMed2000

Identification and characterization of negative regulatory elements of the human telomerase catalytic subunit (hTERT) gene promoter: possible role of MZF-2 in transcriptional repression of hTERT.

Human telomerase reverse transcriptase (hTERT) is a catalytic subunit of human telomerase and is a critical determinant of the enzymatic activity of telomerase. Expression of hTERT is known to be regulated mainly at the transcriptional level. In the present study, using transient expression assays, we identified a 400 bp silencer of the hTERT promoter between -776 and -378 upstream of the proximal core promoter. The inhibitory effects of this silencer were enhanced with cellular differentiation. A computer-assisted homology search identified multiple binding motifs for myeloid-specific zinc finger protein 2 (MZF-2) within this region. Mutation introduced in these sites resulted in significant activation of hTERT transcription. Gel shift assays demonstrated that MZF-2 proteins specifically bound to these sites. Overexpression of MZF-2 in cells led to down-regulation of hTERT transcription as well as telomerase activity. These findings suggest that the 400 bp region upstream of the hTERT core promoter that we identified functions as a negative regulatory region and that MZF-2 may be an effector of negative regulation of hTERT.

Base Sequence↗
PubMed2000

Molecular cloning of a novel water channel from rice: its products expression in Xenopus oocytes and involvement in chilling tolerance.

Water channel proteins, aquaporins, play a fundamental role in transmembrane water movements in plants. We isolated rice cDNA, rwc1, by screening a rice (Oryza sativa cv. Josaeng Tongil) cDNA library using a conserved motif of aquaporins. Like other aquaporin genes, rwc1 encodes a 290-residue protein with six putative transmembrane domains. The derived amino acid sequence of RWC1 shows high homology with PIP1 (plasma membrane intrinsic protein 1) subfamily members, which suggest it is localized in the plasma membrane. Injection of its cRNA into Xenopus oocytes increased the osmotic water permeability of the oocytes 2-3 times. Northern analysis showed that rice aquaporin genes are expressed in rice seedling leaves and roots, but that it disappeared from the root 6 h after osmotic stress began and that the transcript level remained low for about 24 h, then recovered. The time course of rice aquaporin gene-expression under osmotic stress was correlated with time course of turgor transition in plant. On the other hand, the levels of rice aquaporin gene-transcripts in leaves under chilling and recovery temperature depend on the pretreatment of mannitol for short time. This variation of the transcripts shown that rice aquaporin genes may play an important role in response to water stress-induced chilling tolerance.

Journal Article↗
PubMed2000

Telomerase activity as an indicator of malignant potential in iodine-nonreactive lesions of the esophagus.

BACKGROUND: Iodine-nonreactive lesions of esophageal epithelium often are associated with dysplasia and carcinoma. The authors examined the usefulness of telomerase activity as an indicator for esophageal carcinogenesis in such lesions. METHODS: Telomerase activity was measured using the telomeric repeat amplification protocol assay in 18 samples of iodine-nonreactive lesions apart from the primary tumor in surgically resected specimens obtained from patients with esophageal squamous cell carcinoma (ESCC) and 55 endoscopic punch biopsies of iodine-nonreactive lesions obtained from 25 patients with ESCC and 30 patients who had undergone endoscopic examination for other reasons. RESULTS: Ten of 18 iodine-nonreactive samples (56%) obtained from surgically resected specimens showed telomerase activity. In all ten telomerase positive samples, carcinoma in situ (CIS) was observed in iodine-nonreactive mucosa by light microscopy. In eight telomerase negative samples, no tumor tissue was observed in iodine-nonreactive lesions. In a parallel study, telomerase activity was detected in 28 of 55 endoscopic punch biopsy specimens (51%). CIS was observed in 25 of 28 iodine-nonreactive lesions with positive telomerase activity (89%), and tumor tissue was not observed in the other 3 samples (11%), which included 2 cases of severe dysplasia and 1 case of moderate dysplasia. No tumor tissue was observed in any of the 27 telomerase negative samples. CONCLUSIONS: Positive and negative telomerase activity was found to be correlated with the presence and absence, respectively, of immortalized tumor cells in iodine-nonreactive lesions. The measurement of telomerase activity in iodine-nonreactive lesions independently contributes to the selection of an appropriate therapeutic strategy.

Adult↗
PubMed2000

A new predictive factor for hepatocellular carcinoma based on two-dimensional electrophoresis of genomic DNA.

Molecular genetic analyses have clarified that accumulation of genomic changes provides important steps in carcinogenesis and have identified a number of valuable genetic markers for certain cancers. To date, however, no prognostic markers have been identified for hepatocellular carcinoma (HCC). In this study, we used restriction landmark genomic scanning (RLGS), a new high-speed screening method for multiple genomic changes, to detect unknown genetic alterations in HCC. Thirty-one HCC samples and their normal counterparts were examined by RLGS. Eight spot changes were common in several cases, and all were seen only on the HCC profile. Five of these spots were detected in more than 12 of 31 cases (38.7%). Viral infection had no influence on changes in the RLGS spots. The disease-free survival rate for patients with > or =16 changed RLGS spots was significantly lower than that for patients with fewer changed RLGS spots (< or =15 spots) (P<0.001). In multivariate analysis, the number of changed spots was proven to retain an independent prognostic value (relative risk 1.095: P = 0.0031). These results suggest that the number of changed RLGS spots may be a useful biological marker for recurrence of HCC.

Adult↗
PubMed2000

Long-scale jet formation with specularly reflected light in ultraintense laser-plasma interactions

Long-scale jetlike x-ray emission was observed in a 100-TW laser-plasma interaction. The jet was well collimated with a divergence of 30-40 mrad and continued from the target surface into underdense regions for a distance over 4 mm in the specular direction of the laser light. A two-dimensional particle-in-cell simulation shows an electron acceleration with the specularly reflected laser light and collimation of the electron stream by a self-generated magnetic field, resulting in the electron jet to the direction of the specularly reflected light.

Journal Article↗
PubMed2000

Sentinel lymph node biopsy using tin colloid RI and blue dye method.

Axillary dissection has been considered essential for breast cancer staging because nodal metastasis is the most powerful predictive factor for recurrence. On the other hand, morbidity, such as lymphedema and shoulder dysfunction, may occur. Sentinel node biopsy is a good way to avoid unnecessary axillary dissection. We used tin colloid as a carrier of Tc99m tracer together with the blue dye method. The detection rate of the sentinel node was 27 cases out of 29 (90%) for the blue dye method, 10 cases out of 19 (53%) for the RI method, and 27 out of 33 (82%) for the combined method. The detection rate of the RI method was improved after adding the subcutaneous injection over the tumor from 45% before adding the subcutaneous injection to 82% after adding it. The false negative rate was 11% for the blue dye method, 0% for the RI method, and 10% for the combined method. This yields a sensitivity of 89% for the blue dye method, 100% for the RI method, and 90% for the combined method. Specificity was 100% for all three methods. Accuracy was 96% for the blue dye method, 100% for the RI method, and 96% for the combined method. There were two false negative cases. The average number of sentinel lymph nodes was 2.12 for the dye method, 1.66 for the RI method, and 1.95 for the combined method. There were three of 49 cases with identified parasternal lymph nodes by RI imaging. Lymphatic mapping using tin colloid may be useful for detecting sentinel nodes.

Adult↗
PubMed2000

Outlining the body contours with scattered photons in lymphoscintigraphy for sentinel nodes.

Although lymphoscintigraphy is a useful method of detecting the sentinel nodes of malignancy, conventional lymphoscintigraphy images only the sentinel nodes without revealing their anatomical location. We, therefore, used scattered photons to attempt to outline the body contours of patients with either breast or esophageal cancer. Lymphoscintigraphy was performed 3 to 4 hours after the injection of 111 MBq of 99mTc tin colloid into the peritumoral region. Images were obtained with dual-energy windows of 130 to 150 keV for the primary photons and 70 to 110 keV for the scattered photons. The images constructed from the scattered photons clearly showed the contours of the body, and the fusion images constructed from the primary and scattered photons allowed for easy identification of the location of the sentinel nodes. The results of this study confirm that images obtained from scattered photons on lymphoscintigraphy are helpful in identifying the anatomical location of sentinel nodes.

Adult↗
PubMed2000

The role of the sentinel lymph node in gastrointestinal cancer.

Evaluation of the clinical significance of the sentinel node concept in GI cancer has just begun. The authors' preliminary data, using intraoperative radiation techniques and the gamma probe, suggest that it is worthwhile to continue the evaluation of this procedure to determine its role in an accurate staging and a minimally invasive approach to GI cancers.

Feasibility Studies↗
PubMed2000

Association between type 1 diabetes age-at-onset and intercellular adhesion molecule-1 (ICAM-1) gene polymorphism.

We investigated the intercellular adhesion molecule-1 (ICAM-1) gene polymorphism in 90 patients with young-onset type 1 diabetes, 74 with adult-onset type 1 diabetes, and 171 control subjects. The distribution of C-T genotypes and allele frequencies in exon 6 of the ICAM-1 gene was significantly different between adult-onset type 1 diabetes patients and controls (chi(2) = 9.76, p = 0.0076), and between patients with adult-onset and young-onset type 1 diabetes (chi(2) = 11.28, p = 0.0036). In contrast, we failed to detect any association between patients with young-onset type 1 diabetes and controls. Our data suggest that ICAM-1 exon 6 gene polymorphism affects the age-at-onset of type 1 diabetes and that different pathogenetic mechanisms may exist between young-onset and adult-onset type 1 diabetes.

Adolescent↗
PubMed2000

Enlargement of mandibular canal without hypesthesia caused by extranodal non-Hodgkin's lymphoma: a case report.

A rare condition of enlargement of the mandibular canal caused by an extra-nodal non-Hodgkin's lymphoma in a 59-year-old Japanese woman was reported. The patient had a swelling of the hard palate and protrusion of both ocular bulbs, which had been present for 10 years. A panoramic radiograph revealed that the right mandibular canal was widely enlarged, extending from the mandibular foramen to the mental foramen, without bone destruction. The continuous dilation of the mandibular canal to an approximate 15-mm width was associated with peripheral bony sclerosis. Computed tomography and magnetic resonance imaging showed a soft tissue tumor inside the mandibular canal. The lesion demonstrated expansive growth in the orbits, extending to the skull base through the superior orbital fissures and cavernous sinus. The lymphoma was suspected to have grown so slowly that the adjacent mandibular canal and ocular bulbs enlarged without destroying the normal bone and nervous tissue.

Dilatation, Pathologic↗