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Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 91 records · Page 5Linked to original sources

Amplotyping of microdissected, methanol-fixed lung carcinoma by arbitrarily primed polymerase chain reaction.

The arbitrarily primed polymerase chain reaction (AP-PCR) was used to detect somatic genetic alterations in lung carcinomas. DNA fingerprints generated by a single arbitrary primer were compared between normal and tumor tissues of the same individuals. We adapted the technique to the use of tissue fixed with methanol, which allowed the analysis of small areas of tissue by microdissection. This improvement of the fingerprinting technique permitted the study of tumors at early stages of progression. Loss of sequences from chromosome 7 was detected in 41.7% of adenocarcinomas and from chromosome 22 in 84.6% of small-cell carcinomas. Gains of sequences from chromosomes 1, 8 and 13 were detected in more than 40% of adenocarcinomas and in chromosome 2 in 63.3% of squamous-cell carcinomas. Our results indicate that allelic imbalances at these chromosomal regions are common genetic abnormalities in lung carcinomas. Loss of sequences from chromosome 22q13.3, found in 11 of 13 small-cell carcinomas, were confirmed by microsatellite PCR analysis. We show that the use of our improved AP-PCR fingerprinting permits the detection of both losses and gains of novel chromosomal regions early during lung cancer development. Our results indicate that early-stage tumors tend to have more allelic imbalances than relatively advanced tumors, suggesting a high tumor genetic heterogeneity in the early stages of lung tumor progression.

Adenocarcinoma↗

Internal mammary chain sentinel lymph node identification in breast cancer.

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy is not usually performed with respect to the internal mammary lymph node chain. However, the SLN may be located in the internal mammary chain, particularly with medial lesions. We carried out this study to investigate whether lymphatic mapping and SLN biopsy can detect internal mammary involvement in patients with breast cancer. METHODS: A dye- and gamma probe-guided SLN biopsy was performed in a consecutive series of 41 patients with tumor in situ or clinical stage I or II breast cancer. After the biopsy, these patients underwent either a modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection. Biopsy of internal mammary lymph nodes was performed in 19 of these patients. RESULTS: No involvement of internal mammary lymph nodes was found histologically in 5 patients in whom lymphatic flow or a "hot nodule" in the internal mammary chain was found using lymphoscintigraphy. Nodal involvement was demonstrated histologically in only 1 of 5 cases where lymphatic vessels showed dye staining or faintly stained nodes. Internal mammary lymph node biopsy also was performed in 14 of 36 patients with neither stained lymphatic vessels or nodes, nor with lymphatic flow or a hot nodule by lymphoscintigraphy. Nodal involvement was found histologically in 1 of these patients. CONCLUSION: SLN biopsy guided by lymphatic mapping is unreliable for identifying metastases to internal mammary lymph nodes.

Adult↗

Control of ciliary orientation through cAMP-dependent phosphorylation of axonemal proteins in paramecium caudatum.

Ciliary reorientations in response to cAMP do not take place after a brief digestion with trypsin in ciliated cortical sheets from Triton-glycerol-extracted Paramecium. In this study, we examined the effects of tryptic digestion on the cAMP-dependent phosphorylation of axonemal proteins to clarify the relationship between phosphorylation and ciliary reorientation. As reported for Paramecium tetraurelia, cAMP stimulated phosphorylations of the 29 kDa and 65 kDa axonemal polypeptides also in Paramecium caudatum. After a brief digestion of axonemes by trypsin, none of the cAMP-dependent phosphorylations occurred. On the other hand, the 29 kDa polypeptide still remained to be labeled after a brief digestion of axonemes that had previously been labeled with (32)P in the presence of cAMP, which indicates that this brief digestion breaks down endogenous cAMP-dependent protein kinases but not phosphorylated proteins. This must be the reason that trypsin-treated cilia on the sheets cannot reorient towards the posterior part of the cell. Our results indicate that cAMP regulates not only the beat frequency but also the ciliary orientation via phosphorylation of dynein subunits in Paramecium.

Animals↗

Breast cancer in dense breast: detection with contrast-enhanced dynamic MR imaging.

The purpose of this study was to identify contrast enhancement patterns of dense breast parenchyma and to investigate the ability of dynamic magnetic resonance imaging (MRI) to detect cancer in the dense breast. Thirty-two patients with breast cancer in dense breast underwent gadolinium-enhanced dynamic MRI. The detectability of cancer by dynamic MRI, mammography, and physical examination was compared. Two parenchymal enhancement patterns could be identified. One was increasingly multiple patchy enhancement found predominantly in the periphery (type A), and the other was faint enhancement without any nodular opacification (type B). Type A was thought to reflect severe proliferative fibrocystic change (PFC). For both patterns, the detection rate of primary cancers by dynamic MRI was found to be superior to that by other modalities. Dynamic MRI also could detect multifocal cancers, which could not be found with other modalities, although the detectability of these small cancers might be reduced in patients with severe PFC.

Adenocarcinoma↗

Sentinel lymph node biopsy in breast cancer using blue dye with or without isotope localization.

BACKGROUND: The purpose of this study was to determine the feasibility of sentinel lymph node (SLN) biopsy using blue dye with or without isotope localization to predict the presence of axillary and internal mammary lymph node (IMN) metastases in patients with breast cancer. We also investigated whether multiple sectioning of the SLN could improve the accuracy of frozen section examination. METHOD: One-hundred twenty-six patients underwent dye-guided or dye- and gamma probe-guided SLN biopsy followed by complete axillary lymph node dissection (ALND). No ALND was performed in the 14 patients with small tumors and a negative SLN. In addition, 69 patients underwent IMN biopsy. RESULTS: The axillary SLN was identified in 123 of 140 (88%) patients. An accuracy rate of 90% was obtained by frozen section examination of the SLN, which increased to 100% in patients examined with a greater number of sections. Lymphatic flow to the IMN and/or a radioactive hot spot in the IMN was found in 9 of 102 (9%) patients, while a hot node was detected using a gamma probe in only 2 of these patients. No involvement of the IMNs was found histologically in these 9 patients. IMN involvement was found in 7 of 61 (11%) patients without lymphatic flow to the IMNs or a hot spot by lymphoscintigraphy or who did not undergo lymphoscintigraphy. CONCLUSION: ALND can be avoided in patients with small breast cancers and a negative SLN. SLN biopsy guided by lymphatic mapping is unreliable for identifying metastases to IMNs.

Adult↗

Dye- and gamma probe-guided sentinel lymph node biopsy in breast cancer patients: using patent blue dye and technetium-99m-labeled human serum albumin.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a promising method for the diagnosis of the axillary nodal status. We examined the availability of the SLN biopsy using two mapping procedures: the dye- and gamma probe-guided method, and preoperative lymphoscintigraphy by gamma camera imaging. METHODS: We enrolled 48 patients with breast cancer. Technetium-99m-labeled human serum albumin was injected into the subdermal tissue above the primary tumor or biopsy cavity, and preoperative gamma camera imaging was performed. After induction of general anesthesia, patent blue dye was injected into the peritumoral area prior to the surgical procedure. A handheld gamma-detection probe was used to assist in SLN detection. Careful dissection was performed to identify blue-stained afferent lymphatic vessels and nodes. An SLN was defined as any blue and/or radioactive node, and was excised. After SLN biopsy, axillary lymph node dissection of level I, II, and III was completed, in order to confirm the diagnostic ability of the SLN biopsy. RESULTS: Intraoperative SLN identification of axillary lesions was successful in 43 of 48 patients (90%). The dye- and gamma probe-guided method was successful in 25 patients (52%), the dye-guided method alone succeeded in 11 patients (23%), and the gamma probe-guided method alone succeeded in 7 patients (15%). Preoperative lymphoscintigraphy revealed axillary focal accumulations in 29 of 48 patients (60%). All patients who underwent successful preoperative SLN identification by lymphoscintigraphy had successful intraoperative SLN identification. A diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100% were achieved in the diagnosis of axillary metastasis. Internal mammary SLNs were identified in four patients intraoperatively, but we could not detect cancer metastasis in the internal mammary SLNs. CONCLUSIONS: The dye-guided and gamma probe-guided methods were complementary. Preoperative lymphoscintigraphy was useful to predict intraoperative SLN identification. Further study is necessary to assess the role of SLN biopsy of the internal mammary lymph nodes.

Adult↗

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer.

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.

Axilla↗

Successfully treated descending necrotizing mediastinitis through mediansternotomy using a pedicled omental flap.

A 21-year-old man with an oropharyngeal abscess admitted to our institution was initially treated with systemic antibiotics but was referred to our department when his condition rapidly deteriorated. His respiratory insufficiency required circulatory support. A computed tomographic scan showed a parapharyngeal abscess descending into the mediastinum with multiple right-side capsulized empyema and pericardial effusion. We conducted emergency surgery through a mediansternotomy using a pedicled omental flap. Postoperative clinical and radiologic assessment showed a normal chest X-ray and primary wound healing without sternal dehiscence. Mediansternotomy using a pedicled omental flap offers excellent exposure for a complete one-stage operation with debridement of all affected tissues of the subauricular region, the mediastinum, and both pleural cavities. We conclude that this method yields good results for patients with acute widespread descending necrotizing mediastinitis.

Adult↗

The in vitro differentiating capacity of nonparenchymal epithelial cells derived from adult porcine livers.

Specific nonparenchymal epithelial cell (NPEC) clusters derived from normal adult porcine livers demonstrate a characteristic developmental pattern in the presence of other types of nonparenchymal cells in vitro. This pattern includes scattering, colonial growth, and an emergence of duct-like structures (DLSs) in the colonies. It has been confirmed that 96% of the scattered cell clusters in these cultures develop into colonies containing DLSs. In this study, we examine the differentiation of NPEC clusters using the scattered formation as a marker of the DLS-emerged colonies. We report that the NPECs expressed albumin, alpha-fetoprotein, transferrin, cytokeratin (CK) 18, CK7, and c-met, but not alpha-1-antitrypsin (AAT), at the scattering stage. In addition, at the same stage, NPECs expressed oval-cell-related markers such as OV6, but not biliary epithelial cell (BEC) markers such as gamma-glutamyltransferase, CK19, and CK14. At the DLS emerging stage, hepatocyte markers, including AAT, were detectable in the cells either at the periphery of colonies or in the cells surrounded by the DLSs. On the other hand, the cells constituting DLSs expressed BEC markers, suggesting a bile duct nature of the DLSs. Furthermore, the cells in the colonies possessed an ultrastructural appearance of differentiated hepatocytes and BECs. These results suggest that certain NPECs are bipotent, and that, in culture, they mimic hepatoblast development in vivo.

Animals↗

Separation and identification of the regioisomers of verdoheme by reversed-phase ion-pair high-performance liquid chromatography, and characterization of their complexes with heme oxygenase.

We report an HPLC method for separating the four regioisomers of verdoheme formed in the coupled oxidation of hemin with oxygen and ascorbate in aqueous pyridine. The reversed-phase ion-pair system uses hexafluoroacetone and pyridine as ion-pair agents. The regiochemistry of the separated isomers was established both by HPLC of the corresponding biliverdin IX derivatives and by 1H NMR of each isomer. Optical spectra of the pyridine verdohemochrome isomers were similar to each other, but showed differences in the absorption maxima in the red region, which appear at 680, 663, 648 and 660 nm for the alpha, beta, gamma, and delta-isomers, respectively. Each of the four isomers was incorporated anaerobically into heme oxygenase-1, yielding the corresponding verdoheme-enzyme complex. The ferrous forms had absorption maxima at 690, 667, 655, and 663 nm, and their CO-bound forms had maxima at 638, 624, 616, and 626 nm for alpha, beta, gamma, and delta-isomer, respectively. Addition of ferricyanide to the alpha-verdoheme-heme oxygenase complex brought about a ferric low-spin heme-like signal, which is identical with the ferric alpha-verdoheme complexed with the heme oxygenase that was observed in the heme oxygenase reaction.

Ascorbic Acid↗

Role of the common cytokine receptor gamma chain (gammac) in thymocyte selection.

During thymocyte development, T-cell receptor (TCR) alphabeta-mediated intracellular signals can elicit two entirely different cellular responses: positive selection (resulting in rescue from death and maturation or differentiation) and negative selection (induction of apoptosis). Here, Hiroshi Nakajima and colleagues discuss how survival signals that are dependent on the common cytokine receptor gamma chain (gammac) might affect the TCR-driven selection process in thymocytes, underscoring the potential role of cytokines in this process.

Animals↗

Long-term prognosis of parathyroid function after successful percutaneous ethanol injection therapy (PEIT) guided by color Doppler flow mapping in chronic dialysis patients.

Secondary hyperparathyroidism (2 HPT) is a representative disease of dialysis osteopathy, with the lesion that makes fibrous osteitis and the parathyroid hyperplasia by the hyper secretion of parathyroid hormone (PTH). This research examines the usefulness of selective percutaneous ethanol injection therapy (PEIT) of parathyroid glands in order to treat and control for 2 HPT. PEIT was performed in 46 patients resistant to calcitriol pulse therapy and all glands larger than 5 mm in diameter were destroyed by ethanol guided by power Doppler flow mapping. Serum intact-PTH (iPTH) levels fell from 633.3 +/- 359.9 to 226.3 +/- 204.7 pg/mL at three weeks and were maintained at 289.9 +/- 222.4 pg/mL at one year after PEIT. Total alkaline phosphatase activity fell from 384.9 +/- 160.1 to 234.0 +/- 110.5 IU/L at one year after PEIT. In 19 patients, i-PTH levels fell into relative hypoparathyroidism (iPTH < 160 pg/mL) at three weeks after PEIT: however, they recovered at one year after PEIT (191.1 +/- 29.6 pg/mL). In total, parathyroid function was maintained at optimal range (160 < iPTH < 360 pg/mL) in 80.4% of patients at one year after PEIT with appropriate medical therapy. As for the complications, recurrent nerve palsy was observed in only one patient, but was reversible. In conclusion, selective PEIT appears to be able to control appropriate parathyroid function and to be the method of choice to treat 2 HPT prior to parathyroidectomy.

Adult↗

The protooncogene TCL1 is an Akt kinase coactivator.

Human T cell prolymphocytic leukemia can result from chromosomal translocations involving 14q32.1 or Xq28 regions. The regions encode a family of protooncogenes (TCL1, MTCP1, and TCL1b) of unknown function. In yeast two-hybrid screening, we found that TCL1 interacts with Akt. All TCL1 isoforms bind to the Akt pleckstrin homology domain. Both in vitro and in vivo TCL1 increases Akt kinase activity and as a consequence enhances substrate phosphorylation. In vivo, TCL1 stabilizes the mitochondrial transmembrane potential and enhances cell proliferation and survival. In vivo, TCL1 forms trimers, which associate with Akt. TCL1 facilitates the oligomerization and activation of Akt. Our data show that TCL1 is a novel Akt kinase coactivator, which promotes Akt-induced cell survival and proliferation.

Animals↗

A multicenter validation study of sentinel lymph node biopsy by the Japanese Breast Cancer Society.

Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 21 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6 cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (< or = 1.5 cm) breast cancers.

Adult↗

The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development.

BACKGROUND: Germline-specific differential DNA methylation that persists through fertilization and embryonic development is thought to be the 'imprint' distinguishing the parental alleles of imprinted genes. If such methylation is to work as the imprinting mechanism, however, it has to be reprogrammed following each passage through the germline. Previous studies on maternally methylated genes have shown that their methylation imprints are first erased in primordial germ cells (PGCs) and then re-established during oocyte growth. RESULTS: We have examined the timing of the reprogramming of the paternal methylation imprint of the mouse H19 gene during germ cell development. In both male and female PGCs, the paternal allele is partially methylated whereas the maternal allele is unmethylated. This partial methylation is completely erased in the female germline by entry into meiosis, establishing the oocyte methylation pattern. In the male germline, both alleles become methylated, mainly during the gonocyte stage, establishing the sperm methylation pattern. CONCLUSION: The paternal methylation imprint of H19 is established in the male germline and erased in the female germline at specific developmental stages. The identification of the timings of the methylation and demethylation should help to identify and characterize the biochemical basis of the reprogramming of imprinting.

Animals↗

Heme oxygenase1 (HSP-32) is induced in myelin-phagocytosing Schwann cells of injured sciatic nerves in the rat.

Schwann cells participate in myelin phagocytosis in the early stage of Wallerian degeneration, prior to the recruitment of macrophages. This is the first report that Schwann cells induce heme oxygenase-1 (HO-1), a 32-kDa heat shock protein, only when they have transformed into myelin-phagocytosing cells from myelinating cells (days 2-3) immediately after crush injury of rat sciatic nerves. Double immunofluorescent labelling for HO-1 and transferrin receptors revealed that HO-1-immunoreactive Schwann cells also expressed transferrin receptors suggesting activation of iron metabolism. The transient induction of HO-1 in Schwann cells may contribute to the adaptive function in an altered environment when the cells have lost contact with axons, and may play a crucial role in the ensuing regeneration.

Animals↗