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Biomedical subjects

Y Kameda

Publications and source records attributed to Y Kameda.

At least 19 recordsLinked to original sources

Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer.

We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.

Adult↗

Prognosis and morphometrical features of non-bronchioloalveolar cell adenocarcinoma: an assessment of the non-alveolar replacing area and high grade atypical area.

AIM: It has become obvious that the prognosis of bronchioloalveolar cell carcinoma (BAC) in small peripheral adenocarcinoma of the lung is good, but most cases actually treated as pulmonary adenocarcinoma in hospitals tend to be non-bronchioloalveolar cell carcinoma (non-BAC). The prognoses of non-BAC are greatly varied. We studied the relationships between the morphometrical features and the prognoses of non-BAC. METHODS: In total, 69 cases of non-BAC measuring <or=20 mm in diameter across their greatest dimension were evaluated. We considered that the non-alveolar replacing area and the high grade atypical area were related to the prognosis, and therefore defined the ratio of both areas to the total area at the maximum face of the tumours as the non-alveolar replacing area ratio (NAAR) and the high grade atypical area ratio (HAAR), respectively. We thereafter analysed the relationships between both ratios and the prognosis. RESULTS: The NAAR and HAAR were significantly higher in the recurrent cases than in the recurrence free cases. We divided the non-BAC cases at the centre of both ratios into two groups, high and low. The 5 year survival rate of the high NAAR and high HAAR group was 48.3%, while that of the low NAAR and low HAAR group was 72.2%. The groups showing high rates for both ratios had significantly worse prognoses. A multivariate analysis indicated that the HAAR contributes most to the prognosis. CONCLUSIONS: These results suggest that the NAAR and HAAR are closely associated with the prognosis of non-BAC.

Adenocarcinoma↗

Pilomatrix carcinoma of the axilla: CT and MRI features.

Pilomatrix carcinoma, a rare malignant soft tissue tumour, is the malignant variant of pilomatricoma. We report a case of pilomatrix carcinoma of the axilla. CT demonstrated a well-circumscribed, sand-like calcified mass. MRI showed diffusely inhomogeneous, mixed signal intensities with inhomogeneous enhancements. The MRI findings were different from those previously reported for pilomatricoma.

Axilla↗

[Liposarcoma of the pleural cavity; report of a case].

A 43-year-old-woman who had sever anterior chest pain visited our hospital on April 3, 2000. A well-defined abnormal shadow was seen in the middle and lower field of the right lung on chest X-ray. Computed tomography showed a large fat density mass in the right pleural cavity with a septum enhanced by contrast medium. Percutaneous needle biopsy revealed lipoma or liposarcoma. Complete resection could be done with combined resection of right lung, lpericardium, parietal pleura and diaphragm. Final histologic diagnosis was well differentiated liposarcoma. There are few reports of liposarcoma arising in the thoracic cavity, we present our case and review the 23 cases reported from the Japanese literatures.

Adult↗

Hoxa3 regulates integration of glossopharyngeal nerve precursor cells.

In vertebrates, certain Hox genes are known to control cellular identities along the anterior-posterior (A-P) axis in the developing hindbrain. In mouse Hoxa3 mutants, truncation of the glossopharyngeal (IXth) nerve or the fusion of the IXth and vagus (Xth) nerves was reported, although its underlying mechanism is largely unknown. To elucidate the mechanism of the IXth nerve defects, we reexamined the phenotype of Hoxa3 mutant embryos. In Hoxa3 mutants, we observed an abnormal caudal stream of the migrating Hoxa3-expressing neural crest cells at the prospective IXth nerve-forming area. Dorsomedial migration of the placode-derived neuronal precursor cells of the IXth nerve was also affected. Motor neurons at rhombomere 6 (r6), where those of the IXth nerve were positioned, often projected axons to the Xth nerve. In summary, the Hoxa3 gene has crucial roles in ensuring the correct axon projection pattern of all three components of the IXth nerve, i.e., motor neurons and sensory neurons of the proximal and distal ganglia.

Animals↗

Differential osteopontin expression in lung cancer.

Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. Its expression is induced by a variety of stimuli such as TNF-alpha and Ras proto-oncogene. However, differential OPN expression and its regulation in each histologic type of lung cancer are not well established. In this study, we assessed expression of OPN in lung cancer tissues with immunohistochemical analysis. OPN was predominantly expressed in tumor cells of non-small cell lung cancer (NSCLC) tissues: 11 of 16 cases (68.8%) of squamous cell carcinoma (SCC), five of 24 cases (20.8%) of adenocarcinoma (AD), but only two of 18 cases (11%) of small cell lung cancer (SCLC). Expectedly, OPN was principally expressed in NSCLC cell lines (H322 cells and HL460 cells) but not in SCLC cell line (H69 cells) by Western blotting and Northern blotting. Interestingly, Ras-p21 was specifically co-expressed with OPN staining in eight of eight cases with SCC (100%), whereas it was demonstrated in three of ten cases (30%) with AD and only one of 18 cases (5%) with SCLC. Collectively, these results suggest that OPN is mainly expressed in NSCLC, especially among SCC. OPN expression may be tightly regulated by Ras oncogene, and its concomitant induction with Ras activation may play a crucial role in the development of SCC.

Adenocarcinoma↗

Localization of neuropeptide Y mRNA and peptide in the chicken hypothalamus and their alterations after food deprivation, dehydration, and castration.

Localization of neuropeptide Y (NPY) mRNA in the hypothalamus of chickens was studied by in situ hybridization with digoxigenin-labeled chicken NPY cRNA probe. The largest number of perikarya-expressing NPY mRNA was found within the mediobasal hypothalamus, including the infundibular nucleus, inferior hypothalamic nucleus, and median eminence. Many NPY perikarya were noted to surround the nucleus rotundus and to be present in the supraoptic nucleus. Moreover, some perikarya were detected in the nucleus of basal optic root, bed nucleus pallial commissure, and nucleus striae terminalis close to the lateral forebrain bundle. NPY-immunoreactive nerve fibers were densely distributed in these regions containing the NPY mRNA-expressing perikarya. Following food deprivation for four days, perikarya-expressing NPY mRNA and peptide were markedly increased in the mediobasal hypothalamus and particularly so in the infundibular nucleus. No changes, however, were detected in other regions containing NPY-positive perikarya. Water deprivation induced less increase in NPY-positive perikarya in the mediobasal hypothalamus compared to food deprivation. After gonadectomy, the number of NPY-positive perikarya in the mediobasal hypothalamus was unaltered. Northern blot analysis with (32)P-labeled chicken NPY cDNA probe demonstrated that a 2.7-fold increase of NPY mRNA was induced by starvation and a 1.5-fold increase was induced by dehydration, whereas the NPY mRNA band remained unchanged after gonadectomy. Thus, it seems that NPY neurons located in the mediobasal hypothalamus are involved in feeding behavior but not reproductive activity.

Animals↗

Neuronal properties in cultured ultimobranchial C cells of chick embryos: process outgrowth and expression of TuJ1 and enkephalin.

We have analyzed the neuronal properties in cultured ultimobranchial C cells isolated from embryonic chicks at different developmental stages (12--16 days of incubation) by immunohistochemistry and electron microscopy. The ultimobranchial glands mostly consist of C cell solids. In 13-day-old embryos, many C cells cultured for 7 days on laminin-coated slides extended long neurite-like processes, reaching 300 microm in length. Neuritic outgrowth of C cells was regulated developmentally and virtually unaffected by nerve growth factor (NGF). The cultured C cells expressed intense immunoreactivity for calcitonin and enkephalin. It was also confirmed by confocal laser-scanning microscopy that almost all C cells were intensely immunostained by both the calcitonin antiserum and the monoclonal antibody TuJ1, a neuron-specific marker. Scanning electron microscopy identified the outgrowth of long, branching neuritic processes emerging from C cell soma. The processes had numerous varicosities along their course and ended in growth cones. The C cells with processes were usually monopolar and less frequently bipolar or multipolar. Transmission electron microscopy revealed the presence of membrane-bounded secretory granules in the cultured C cells. The neuritic processes of C cells contained aggregations of microfilaments, intermediate filaments and microtubules arranged in parallel to the long axis. In addition, synaptic-like contacts showing desmosome-like membrane-thickenings and accumulations of small clear vesicles and dense-cored vesicles were formed between the endings of the processes and the surface of C cells. These results indicate that the C cells cultured from early chick embryos (12- and 13-day-old) maintain the neuronal characteristics for long periods in vitro.

Animals↗

Effect of different photoperiods on the ultrastructure of the specific secretory cells and alpha-subunit mRNA level in the chicken pars tuberalis.

The effect of different photoperiods on the specific secretory cells of the pars tuberalis was examined in male chicks. Animals were placed in one of three different photoperiod regimens: (1) normal control (light:dark = 12 h:12 h), (2) continuous light (L:D = 24 h:0), and (3) extended darkness (L:D = 1 h:23 h). The levels of common alpha-subunit mRNA in the pars tuberalis were examined by Northern blot analysis and compared with those in the pars distalis. In chicks exposed to continuous light for 1 week, alpha-subunit mRNA level in the pars tuberalis was decreased, although the level in the pars distalis was increased. Exposure to continuous light for 30 days also induced a decrease in alpha-subunit mRNA level in the pars tuberalis. On the other hand, in chicks exposed to extended darkness for 1 week, the alpha-subunit mRNA level of the pars tuberalis was markedly increased. In situ hybridization with digoxigenin-labeled common alpha-subunit cRNA probe also showed that the hybridization signals for alpha-subunit mRNA in the pars tuberalis cells become weak under continuous light for 30 days but they are very intense under extended darkness. Thus, the synthesis of alpha-subunits in the chick pars tuberalis was inhibited by continuous light but stimulated by extended darkness. These results were confirmed by semiquantitative electron-microscopic analyses. After exposure to continuous light for 30 days, many pars tuberalis (PT)-specific cells were filled with enlarged secretory granules, showing the reduction of secretory activity. On the contrary, extended darkness for 30 days induced hypertrophy of the PT-specific cells; the areas of cytoplasm and nucleus were significantly increased. In addition, secretory granules became small in size and exocytotic features were more frequent. Mitochondria and lysosomes were also increased in number. Thus, the synthetic and secretory activities of the PT-specific cells were increased under extended darkness. The data indicate that the specific cells of the pars tuberalis are responsive to photoperiodic changes in the chick.

Animals↗

Polyhydroxylated alkaloids isolated from mulberry trees (Morusalba L.) and silkworms (Bombyx mori L.).

New polyhydroxylated alkaloids, (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine-N-propionamide from the root bark of Morus alba L., and 4-O-alpha-D-galactopyranosyl-calystegine B(2) and 3 beta,6 beta-dihydroxynortropane from the fruits, were isolated by column chromatography using a variety of ion-exchange resins. Fifteen other polyhydroxylated alkaloids were also isolated. 1-Deoxynojirimycin, a potent alpha-glucosidase inhibitor, was concentrated 2.7-fold by silkworms feeding on mulberry leaves. Some alkaloids contained in mulberry leaves were potent inhibitors of mammalian digestive glycosidases but not inhibitors of silkworm midgut glycosidases, suggesting that the silkworm has enzymes specially adapted to enable it to feed on mulberry leaves. The possibility of preventing the onset of diabetes and obesity using natural dietary supplements containing 1-deoxynojirimycin and other alpha-glucosidase inhibitors in high concentration is of great potential interest.

Alkaloids↗

A case of lung metastasis from endometrial adenoacanthoma 17 years after initial treatment.

In March 1982, a 60-old woman presented with an International Federation of Gynecology and Obstetrics grade 1, stage Ib endometrial adenoacanthoma, histological subtype of endometrial carcinoma. The patient underwent radical hysterectomy and was followed up for 10 years, without disease. In August 1998, an abnormal shadow in the right lung was suggested on a chest X-ray film at her routine health check-up and she came to our hospital for further evaluation. A thin-section computed tomographic scan of the chest suggested a malignant lung tumor, but the diagnosis remained tentative. Open biopsy was recommended, but the patient refused and was followed up on an outpatient basis. In November 1999, a thin-section computed tomographic scan of the chest revealed a slightly enlarged tumor and laboratory examination showed a high serum progastrin-releasing peptide concentration of 90.7 pg/ml. We performed partial resection of right upper lobe with video-assisted thoracic surgery. Pathological examination confirmed the lung tumor had metastasized from endometrial adenoacanthoma. Immunohistochemical stainings of estrogen receptor and progesterone receptor were positive both in the primary and lung tumor, only in the component of adenocarcinoma. After surgery, the serum progastrin-releasing peptide concentration remained unchanged. The patient is currently alive and free of disease.

Adenocarcinoma↗

Differences in adaptation to growth of children between internal thoracic artery and saphenous vein coronary bypass grafts.

BACKGROUND: It is not known how the internal thoracic artery (ITA) and saphenous vein graft (SVG) adapts to somatic growth of pediatric patients who underwent coronary artery bypass grafting (CABG). METHODS: Twenty-two ITAs and 6 SVGs in 17 patients who underwent at least three postoperative catheterizations with biplanar cineangiography and followed for a minimum of 5 years were evaluated. We evaluated the length, diameter and curvature of the grafts by cineangiographies which were performed at 1 month, 1 year, 5 years and more than 5 years postoperatively. RESULTS: The length of the ITA (1-month: 117+/-31 mm, 1-year: 134+/-32 mm, 5-years: 146+/-28 mm, and >5-years: 155+/-34 mm, p=0.032) and diameter of the ITA (1.4+/-0.4 mm, 2.0+/-0.7 mm, 2.3+/-0.6 mm and 2.6+/-0.6 mm, p<0.0001) significantly increased over time, but neither the length nor diameter of the SVG length: 121+/-33 mm, 119+/-29 mm, 119+/-25 mm and 126+/-1 mm, p=0.9907; diameter: 4.1+/-1.0 mm, 3.9+/-0.7 mm, 4.0+/-0.8 mm and 3.3+/-0.4 mm, p=0.5784) increased. Although the ITA exhibited no change in curvature over time (1 month: 1.15+/-0.07, late: 1.15+/-0.07, p=0.8490), the curvature of the SVG significantly decreased over time (1 month: 1.42+/-0.19 and late: 1.25+/-0.16, p=0.0277). The percent segmental length of ITAs were changed little from early to late after CABG (1 month: proximal: 33.7+/-7.0%, middle: 33.3+/-7.9% and distal: 32.9+/-7.9%, vs late: 34.3+/-7.2%, 33.2+/-7.9% and 32.5+/-7.9%, p=0.937). CONCLUSIONS: ITAs grow in proportion to somatic growth, while SVGs course in a more linear fashion in adapting to patient growth.

Adaptation, Physiological↗

[Off-pump coronary artery bypass using bilateral in situ internal thoracic artery grafts for left coronary artery system: a case report].

A 63-year-old man with triple vessel disease in the coronary artery and multiple arterial stenoses in intra-cranial vessels underwent off-pump coronary artery bypass (OPCAB). We were able to perform three coronary artery bypass grafting (in situ left internal thoracic artery (left ITA)--left anterior descending artery, in situ right ITA--circumflex artery through the transverse sinus, and saphenous vein graft--right coronary artery) using octopus 2 and "Lima" suture technique without cardio-pulmonary bypass. Operation time was 355 minutes and established blood loss was 440 ml. Postoperative course was uneventful. Postoperative angiogram revealed well patent three grafts. Using bilateral in situ ITAs OPCAB could achieve high quality.

Coronary Artery Bypass↗

Functional and perfusional assessment with electrocardiograph-gated single photon emission computed tomography after minimally invasive direct coronary artery bypass grafting.

BACKGROUND: Because of limited surgical field, minimally invasive coronary artery bypass grafting (MIDCAB) requires anastomosis to the distal portion of the left anterior descending artery (LAD) of the left internal thoracic artery (LITA) with the heart beating. Though the diameters of these arteries are very small, it is unknown whether blood flow sufficient for the LAD territory is obtained by bypass grafting. METHOD: Eight patients with single-vessel disease of the LAD underwent MIDCAB with the LITA to the LAD and we evaluate the perfusion and function in the LAD territory by quantitative ECG-gated SPECT (QGS) with 99m-technetium sestamibi (MIBI) before and after operation. RESULT: The intraoperatively measured diameters of the LITA and LAD at the site of anastomosis were 1.1+/-0.2 mm and 1.3+/-0.4 mm, respectively. The percentage increases in end-diastolic perfusion, regional ejection fraction and regional wall thickening in the anteroseptal area after MIDCAB were 136.3+/-11.7(p=0.071), 148.4+/-6.6(p=0.007) and 133.0+/-5.6(p=0.029), respectively (paired t-test, mean +/- SD %). Stress-rest MIBI SPECT indicated no ischemia in anteroseptal wall. CONCLUSION: The MIDCAB technique thus appeared to improve perfusion and function in the LAD territory despite bypass to the distal LAD, and ECG-gated MIBI SPECT using QGS software was very useful for evaluating the quality of anastomosis after MIDCAB.

Aged↗

[Edge to edge repair for mitral regurgitation in a patient with chronic hemodialysis: report of a case].

In a patient with chronic hemodialysis, the high risk of calcific degeneration of biological prosthetic valve and anticoagulant related complications after valve replacement have been reported. A 71-year-old woman with hemodialysis underwent the edge to edge repair combined with ring-annuloplasty for mitral regurgitation caused by the anterior leaflet prolapse without any torn chordae. Postoperative course was uneventful. There was no significant mitral regurgitation. Double mitral orifices were confirmed by the postoperative echocardiography. A calculated functional mitral valve area was 3.06 cm2. The edge to edge repair is a simplified technique and carried out in a short time. We believe the edge to edge repair is a useful technique for anterior mitral valve prolapse in a patient with chronic hemodialysis.

Aged↗

Immunological detection of a novel advanced glycation end-product.

BACKGROUND: The advanced stage of the Maillard reaction that leads to the formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients and in the aging process. Recently, it has been proposed that the intermediates contributing to AGE formation include dicarbonyl intermediates such as glyoxal, methylglyoxal, and 3-deoxyglucosone (3-DG). In the present study, we developed a novel, non-carboxymethyllysine (CML) anti-AGE antibody that recognizes serum proteins and peptides modified by 3-DG in vivo. MATERIALS AND METHODS: AGE-modified serum albumins were prepared by incubation of rabbit serum albumin with 3-DG or D-glucose. After immunization of rabbits, anti-AGE antisera were subjected to affinity chromatography on a Sepharose 4B column coupled with CML-BSA, or AGE-BSA created by incubation with 3-DG (AGE-6) or D-glucose (AGE-1). The AGE-Ab-6 and AGE-Ab-1 thus obtained was used to investigate AGEs in serum from diabetic patients on hemodialysis. RESULTS: Characterization of the novel AGE-Ab-6 obtained by immunoaffinity chromatography was performed with a competitive ELISA and immunoblot analysis. This antibody specifically cross-reacted with proteins modified by 3-DG. AGE-6 was detected in diabetic serum as three peaks with apparent molecular weights of 200, 1.15, and 0.85 kD, while AGE-1 was detected as four peaks with apparent molecular weights of 200, 65, 1.15, and 0.85 kD. CONCLUSION: This study provides new data on the pathways of AGE formation from 3-DG and methods for the immunochemical detection of AGEs. We also provide immunochemical evidence for the existence of six distinct AGEs in vivo among the AGE-modified proteins and peptides in the serum of diabetic patients on hemodialysis.

Animals↗

Molecular cloning and characterization of a novel human STE20-like kinase, hSLK.

We have cloned a human counterpart to a guinea pig STE20-like kinase cDNA, designated human SLK (hSLK), from a human lung carcinomatous cell line A549 cDNA library. hSLK cDNA encodes a novel 1204 amino acid serine/threonine kinase for which the kinase domain located at the N-terminus shares considerable homology to that of the STE20-like kinase family. The C-terminal domain of hSLK includes both the coiled-coil structure and four Pro/Glu/Ser/Thr-rich (PEST) sequences, but not the GTPase-binding domain (GBD) that is characteristic of the p21-activated kinase (PAK) family, polyproline consensus binding sites, or the Leu-rich domain seen in the group I germinal center kinases (GCKs). Northern blot analysis indicated that hSLK was ubiquitously expressed. hSLK overexpressed in COS-7 cells phosphorylates itself as well as myelin basic protein used as a substrate. On the other hand, hSLK cannot activate any of the three well-characterized mitogen-activated protein kinase MAPK (ERK, JNK/SAPK and p38) pathways. Moreover, hSLK kinase activity is not upregulated by constitutive active forms of GTPases (RasV12, RacV12 and Cdc42V12). These structural and functional properties indicate that hSLK should be considered to be a new member of group II GCKs.

Amino Acid Sequence↗

Homonojirimycin analogues and their glucosides from Lobelia sessilifolia and Adenophora spp. (Campanulaceae).

2,6-Dideoxy-7-O-(beta-D-glucopyranosyl) 2,6-imino-D-glycero-L-gulo- heptitol (7-O-beta-D-glucopyranosyl-alpha-homonojirimycin, 1) was isolated from the 50% methanol extract of the whole plant of Lobelia sessilifolia (Campanulaceae), which was found to potently inhibit rice alpha-glucosidase. Adenophorae radix, roots of Adenophora spp. (Campanulaceae), yielded new homonojirimycin derivatives, adenophorine (2), 1-deoxyadenophorine (3), 5-deoxyadenophorine (4), 1-C-(5-amino-5-deoxy-beta-D-galactopyranosyl)butane (beta-1-C-butyl-deoxygalactonojirimycin, 5), and the 1-O-beta-D-glucosides of 2 (6) and 4 (7), in addition to the recently discovered alpha-1-C-ethylfagomine (8) and the known 1-deoxymannojirimycin (9) and 2R,5R-bis(hydroxymethyl)-3R,4R- dihydroxypyrrolidine (DMDP, 10). Compound 4 is a potent inhibitor of coffee bean alpha-galactosidase (IC50 = 6.4 microM) and a reasonably good inhibitor of bovine liver beta-galactosidase (IC50 = 34 microM). Compound 5 is a very specific and potent inhibitor of coffee bean alpha-galactosidase (IC50 = 0.71 microM). The glucosides 1 and 7 were potent inhibitors of various alpha-glucosidases, with IC50 values ranging from 1 to 0.1 microM. Furthermore, 1 potently inhibited porcine kidney trehalase (IC50 = 0.013 microM) but failed to inhibit alpha-galactosidase, whereas 7 was a potent inhibitor of alpha-galactosidase (IC50 = 1.7 microM) without trehalase inhibitory activity.

1-Deoxynojirimycin↗