PubMed Health⌕ Search

Biomedical subjects

Tsutomu Sakuma

Publications and source records attributed to Tsutomu Sakuma.

At least 19 recordsLinked to original sources
PubMed2006

Fluorodeoxyglucose uptake correlates with the growth pattern of small peripheral pulmonary adenocarcinoma.

PURPOSE: Noguchi and colleagues reported that the growth pattern of small-sized adenocarcinoma was related to the vascular involvement and the prognosis of the patient. Noguchi's type A/B tumors had no lymph node metastasis, rare vascular involvement, and an excellent prognosis, which meant that Noguchi's type A/B tumors were preinvasive tumors of the peripheral type. Although Noguchi's classification was usually determined based on resected specimens, it would be useful to make a decision about the therapeutic strategy if the classification could be determined preoperatively based on the fluorodeoxyglucose (FDG) uptake. METHODS: The FDG uptake in 61 pulmonary adenocarcinomas measuring 3 cm or smaller in diameter was compared with the mediastinal uptake and was classified into five grades. The relationship between the FDG uptake and Noguchi's classification (A to F) was analyzed. RESULTS: The FDG uptake was significantly lower in Noguchi's type A/B tumors than in type C or in type D/E/F. Eleven of 12 tumors (92%) with no increased or a weak FDG uptake were classified as type A/B, whereas 32 of 33 tumors (97%) with a strong or very strong FDG uptake were classified as type C-F. CONCLUSIONS: The FDG uptake is helpful for making an accurate diagnosis of Noguchi's classification preoperatively in patients with pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Kaposiform hemangioendothelioma of the mediastinum in a 7-month-old boy: a case report.

Kaposiform hemangioendothelioma is an aggressive vascular proliferation that has been recognized as a separate entity from other childhood vascular tumors. The authors present an unusual case of hemangioendothelioma arising in the mediastinum of a 7-month-old male infant with acute respiratory distress and Kasabach-Merritt syndrome. This patient with life-threatening lesion showed a dramatic response to interferon alfa-2a. This case had many histologic and clinical features consistent with kaposiform hemangioendothelioma.

Airway Obstruction↗
PubMed2006

Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine.

OBJECTIVES: Because several experimental studies have demonstrated that cyclic adenosine monophosphate generation following beta-adrenoceptor activation can markedly stimulate alveolar fluid clearance, we determined whether the endogenous levels of catecholamines that occur in the pulmonary edema fluid and plasma of patients with acute lung injury are high enough to stimulate alveolar fluid clearance in the human lung. DESIGN: Observational clinical study. SETTING: Academic university hospital and laboratory. PATIENTS: Twenty-one patients with acute pulmonary edema plus ex vivo human lungs. INTERVENTIONS: Measurements of catecholamine levels in patient samples and controlled laboratory studies of the effects of these catecholamine levels on the rates of alveolar fluid clearance in ex vivo human lungs. MEASUREMENTS AND MAIN RESULTS: The concentrations of both epinephrine and norepinephrine in the pulmonary edema fluid and plasma were approximately 10 M (range of 1-8x10 M) in hydrostatic pulmonary edema (n=6) and acute lung injury patients (n=15). We therefore tested whether 10 M epinephrine or norepinephrine stimulated alveolar fluid clearance in isolated human lungs and found that these epinephrine or norepinephrine concentrations did not stimulate alveolar fluid clearance. However, higher concentrations of epinephrine (10 M), but not norepinephrine (10 M), significantly stimulated alveolar fluid clearance by 84% above control. Glibenclamide (10 M) and CFTRinh-172 (10 M), cystic fibrosis transmembrane conductance regulator inhibitors, completely inhibited the epinephrine-induced stimulation of alveolar fluid clearance. CONCLUSIONS: These results indicate that endogenous catecholamine concentrations in pulmonary edema fluid are probably not sufficient to stimulate alveolar fluid clearance. In contrast, administration of exogenous catecholamines into the distal airspaces can stimulate alveolar fluid clearance in the human lung, an effect that is mediated in part by cystic fibrosis transmembrane conductance regulator. Therefore, exogenous cyclic adenosine monophosphate-dependent stimulation will probably be required to accelerate the resolution of alveolar edema in the lungs of patients with pulmonary edema.

Adrenergic beta-Agonists↗
PubMed2006

Denopamine stimulates alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator in rat lungs.

OBJECTIVE: The objective of this study was to test the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance. METHODS: Isotonic 5% albumin solutions containing different pharmacological agents were instilled into the alveolar spaces of the isolated rat lungs. The lungs were inflated with 100% oxygen at an airway pressure of 7 cm H(2)O and placed in a humidified incubator at 37 degrees C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1 h. To test the hypothesis, we determined whether CFTR Cl(-) channel inhibitors (glibenclamide and CFTR(inh)-172) inhibited the effect of denopamine, a beta(1)-adrenergic agonist, on stimulation of alveolar fluid clearance in the isolated rat lungs. RESULTS: Denopamine increased alveolar fluid clearance in a dose-dependent manner. Atenolol, a beta(1)-adrenergic antagonist, abolished the effects of denopamine on stimulation of alveolar fluid clearance. Although glibenclamide alone or CFTR(inh)-172 alone did not change basal alveolar fluid clearance, these CFTR inhibitors inhibited the effect of denopamine on alveolar fluid clearance. CONCLUSION: CFTR plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance in rat lungs.

Adrenergic beta-Agonists↗
PubMed2006

Extraskeletal mesenchymal chondrosarcoma of the kidney.

A 61-year-old woman was referred for evaluation of an incidental mass found on the right kidney. Abdominal ultrasonography and computed tomography showed a 3-cm tumor with calcification and peripheral enhancement. Under the diagnosis of renal cell carcinoma, a transabdominal right radical nephrectomy was performed. The pathological diagnosis was extraskeletal mesenchymal chondrosarcoma of the kidney. No recurrence or metastasis occurred during a 6-year follow up. Primary renal chondrosarcoma is extremely rare, this being only the fifth case reported in the English literature, and the patient's extended survival is attributed to the small size of the tumor, as well as early diagnosis and treatment.

Bone Neoplasms↗
PubMed2006

Regulation of mouse hepatic CYP2D9 mRNA expression by growth and adrenal hormones.

The constitutive expression of CYP2D9 is sexually dimorphic, namely, strong in males, but diminutive in females. Repetition of mimic growth hormone (GH) secretion pattern impressively returned the mRNA expression level to that in intact mice: the GH secretion pattern's regulation of CYP2D9 mRNA expression has been predominantly disrupted by exogenous GH-administration. The extensive decline of CYP2D9 mRNA expression becoming a sexually non-specific P450 in 9-week-old male mice exposed as neonates to monosodium L-glutamate (MSG) suggested that the male GH secretion pattern is a key to the regulation of male-specific CYP2D9 mRNA expression in adult mice. Dexamethasone (Dex) showed possibility to induce CYP2D9 mRNA expression in adult MSG-neonatally treated mice of either sex. However, the antagonism was observed by co-administration of Dex and GH in the males. Dex-administration in adrenalectomized mice significantly elevated CYP2D9 mRNA expression levels. These findings suggest that an adrenal hormone participates in the regulatory mechanism of CYP2D9 mRNA expression in association with GH.

Adrenal Cortex Hormones↗
PubMed2006

Microvessel density: correlation with 18F-FDG uptake and prognostic impact in lung adenocarcinomas.

UNLABELLED: Although researched for many years, the prognostic value of tumor angiogenesis reflected by microvessel density (MVD) is still controversial, and there have been no previous reports regarding the correlation with 18F-FDG uptake in lung adenocarcinomas. Therefore, in the present study, we investigated the correlation between MVD determined with different endothelial cell antibodies and 18F-FDG uptake and compared the prognostic impact of those factors in lung adenocarcinomas. METHODS: Forty-four patients with 45 lung adenocarcinomas underwent 18F-FDG PET before surgery. Consecutive paraffin-embedded sections obtained from each resected tumor were immunostained for CD31 (a panendothelial cell marker), CD105 (a proliferation-related endothelial cell marker), and CD34/alpha-SMA (for double labeling of endothelial cells and mural cells). Four high-power fields in the area with the highest MVD were selected for analysis. Computer-assisted image analysis was used to assess MVD. RESULTS: MVD staining results for panendothelial cell markers can be classified into 3 microvessel patterns: diffuse, alveolar, and mixed. The highly ordered alveolar pattern is believed to represent preexisting alveolar vessels trapped in lung adenocarcinomas and may have no significant meaning for the aggressiveness of tumors. Preexisting alveolar cells also do not contribute to 18F-FDG uptake. CD105 staining of MVD (CD105-MVD) showed a significantly positive correlation with 18F-FDG uptake (P < 0.0001), whereas CD31 staining of MVD (CD31-MVD) showed a marginally negative correlation with it (P = 0.057). Although CD105-MVD correlated negatively with prognosis, patients with low CD105-MVD, compared with those with high or moderate CD105-MVD, had a much better prognosis in both disease-free and overall survival analyses (P = 0.017 and P = 0.013, respectively). Patients with low CD31-MVD had the worst prognosis (P = 0.032 for disease-free survival analysis and P = 0.179 for overall survival analysis). CONCLUSION: There is no positive correlation between 18F-FDG uptake and MVD determined with panendothelial cell markers (CD31 and CD34); in contrast, there is a marginally negative correlation between them. MVD determined with CD105, which is a proliferation-related endothelial cell marker, reflects active angiogenesis, correlates positively with 18F-FDG uptake, and is a better indicator of prognosis in lung adenocarcinomas.

Adenocarcinoma↗
PubMed2005

Modified expression of cytochrome P450 mRNAs by growth hormone in mouse liver.

The expression of eight mouse hepatic cytochrome P450s (P450s) genes was investigated at the mRNA level in relation with the pattern of growth hormone (GH) administration. The constitutive expression of five sex-dependent P450s was sexually dimorphic, namely female>male for CYP2A4, CYP2B9, CYP2B10, and CYP3A41, and male>female for CYP2D9. In mice neonatally treated with monosodium L-glutamate to produce GH-deficiency, GH was found to be an essential factor with GH archetype as a determinant in the regulatory mechanism of hepatic CYP2D9 and CYP3A41 expression, and GH was shown to be a repressive factor for the constitutive expression in females. Implantation with micro-osmotic pump containing GH (to yield a constant release of GH to mimic the plasma GH profile in females) to male mice increased CYP2A4, CYP2B9, CYP2B10, and CYP3A41, but decreased CYP2D9, expression to female levels, while conversely, twice-daily administration of GH (to produce the so-called male pattern of plasma GH levels) to female mice resulted in the repression of female-specific, CYP2B9 and CYP3A41, as well as female-predominant, CYP2A4 and CYP2B10, expression, and induction of male-specific CYP2D9 expression. Thus, the sex-dependent plasma GH profile (referred to hereafter as the GH archetype) was a decisive factor for the expression of sex-specific P450 genes in adult mouse liver. On the other hand, the regulation of CYP1A2, CYP2C29, and CYP3A11 expression was either sex-independent or GH archetype-independent, considering the comparable levels between sexes of the constitutive expression and GH-inducible expression of these isoforms. Moreover, the observations suggested for the first time that the expression of CYP2B9 and CYP2A4 was not entirely GH-independent, but rather involved an imprinting GH-related factor that participated in the regulatory mechanism of P450 expression in females.

Animals↗
PubMed2005

Activation of CYP1A1 gene expression during primary culture of mouse hepatocytes.

Expression of CYP1A1 mRNA in mouse hepatocytes in primary culture was investigated. The expression was obvious on day 3 of culture without addition of any known ligands of the aryl hydrocarbon receptor and increased with culture period. Removal of insulin from and addition of hydrogen peroxide to the medium enhanced and suppressed the expression, respectively. The CYP1A1 mRNA expression was also enhanced in the presence of anti-oxidant, t-butylhydroquinone, in the medium. Several kinds of kinase inhibitors markedly increased the CYP1A1 mRNA expression. In contrast, the inhibitory expression was prolonged in the presence of okadaic acid, a potent inhibitor of serine/threonine phosphatase PP1 and PP2. These observations suggest that there might be a repressive pathway in the regulation of CYP1A1 mRNA expression and that the presently observed expression pathway differs at several points from those previously reported, such as ligand-activated aryl hydrocarbon receptor- or omeprazole-mediated expression. Modulation of CYP1A2 mRNA expression after exposing hepatocytes to agents affecting phosphorylation pathways differed from that of CYP1A1 mRNA. This implies that regulatory pathways for CYP1A1 and CYP1A2 expression may differ.

Animals↗
PubMed2005

Localized bronchioloalveolar carcinoma with small foci of active fibroblastic proliferation. A report of 2 cases.

Localized bronchioloalveolar carcinoma (LBAC) without foci of active fibroblastic proliferation has been reported to be a pN0 disease. Predominantly, these tumors have not been associated with cancer relapse or death subsequent to surgery. Based on these observations, LBAC cases have been considered candidates for limited lung resection without lymph node dissection. However, this surgical option requires careful validation, and an accurate diagnosis is indispensable. The absence of foci of active fibroblastic proliferation must be confirmed by a thorough investigation. Nonetheless, these foci may escape detection, and even currently accepted diagnostic modalities may not be sufficient to accurately determine their absence. We illustrate this point by reporting 2 cases of LBAC with small but distinct foci of active fibroblastic proliferation.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2005

Annual periodic increases in serum carcinoembryonic antigen concurrent with ground-glass opacity in the lung: report of a case.

A 63-year-old woman underwent a video-assisted thoracoscopic lobectomy for cancer of the right lung in 1999. The following year, a lesion with ground-glass opacity was found in the left lung, and pathological examination after a partial lung resection revealed atypical adenomatous hyperplasia with expression of carcinoembryonic antigen (CEA). During postoperative screening tests for tumor recurrence, there were periodic increases in the serum CEA level by twofold above the normal levels in 2002 and 2003. Clinical evaluations, including laboratory tests, radiographic imaging, and endoscopy examinations, showed no evidence of a CEA-producing tumor, except for a new ground-glass opacity in the left lung. To our knowledge, this is the first report of periodic increases in serum CEA levels in a patient with ground-glass opacity in the lung, not reflecting recurrence of the lung tumor.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2005

Pulmonary T2N0 adenocarcinoma with metastasis to a lymph node in the thoracic wall.

We experienced a rare case of lung cancer without hilar/mediastinal nodal involvement or direct invasion to the thoracic wall, but with metastasis to a lymph node in the thoracic wall. A 72-year-old woman with lung cancer was admitted to our hospital for the surgical therapy. She had suffered from right pleuritis in her childhood. During the dissection of the pleural adhesion around the whole lung, one small black lymph node was found in the thoracic wall and resected. Then, right middle and lower lobectomy and systematic nodal dissection were performed. The postoperative pathological examination revealed that nodal involvement was not observed in all samples except in the lymph node in the thoracic wall. In lung cancer patients with broad pleural adhesion, we should pay attention to lymph nodes in the thoracic wall. If we find them, the nodes should be resected for accurate staging.

Adenocarcinoma↗
PubMed2005

Expression and characterization of Rab38, a new member of the Rab small G protein family.

Rab38 is a new member of the Rab small G protein family that regulates intracellular vesicle trafficking. Rab38 is expressed in melanocytes and it has been clarified that a point mutation in the postulated GTP-binding domain of Rab38 is the gene responsible for oculocutaneous albinism in chocolate mice. However, basic information regarding recombinant protein production, intracellular location, and tissue-specific expression pattern has not yet been reported. We produced recombinant Rab38 using a baculovirus/insect cell-protein expression system. A combination of Triton X-114 phase separation and nickel-affinity chromatography yielded exclusively prenylated Rab38 that bound [alpha-32P]-GTP. The mRNA and the native protein were expressed in a tissue-specific manner, e.g., in the lung, skin, stomach, liver, and kidney. Freshly isolated rat alveolar type II cells were highly positive for the mRNA signal, but the signal was rapidly lost over time. Immunofluorescence staining demonstrated that expressed GST-tagged Rab38 was mainly co-localized with endoplasmic reticulum-resident protein and also partly with intermittent vesicles between the endoplasmic reticulum and the Golgi complex. These results indicate that Rab38 is expressed non-ubiquitously in specific tissues and regulates early vesicle transport relating to the endoplasmic reticulum, and hence suggest that Rab38 abnormality may cause multiple organ diseases as well as oculocutaneous albinism.

Animals↗
PubMed2005

18F-FDG uptake by primary tumor as a predictor of intratumoral lymphatic vessel invasion and lymph node involvement in non-small cell lung cancer: analysis of a multicenter study.

UNLABELLED: Intratumoral lymphatic vessel invasion and lymph node involvement are important factors in the planning of therapeutic strategies, particularly limited surgical resection in patients with non-small cell lung cancer. (18)F-FDG uptake within the primary lesion correlates with aggressiveness on PET studies. The more metabolically active the tumor, the more aggressive are the findings. The aim of this multicenter study was to determine whether (18)F-FDG uptake of the primary tumor is a predictor of intratumoral lymphatic vessel invasion and lymph node metastasis in patients with non-small cell lung cancer. METHODS: One hundred thirty-two patients with lung cancer were studied. All patients underwent a thoracotomy within 4 wk of the (18)F-FDG PET study. A 3-point visual scoring system (low, moderate, or high grade in comparison with mediastinal activity) was used to interpret (18)F-FDG uptake within the primary lesions. The degree of (18)F-FDG uptake in the primary tumor was correlated with the incidence of intratumoral lymphatic vessel invasion and lymph node involvement. Multivariate analysis was performed with logistic multivariate analysis to assess the joint effects and interactions of the variables (age, sex, tumor size, histology, and (18)F-FDG uptake) on intratumoral lymphatic vessel invasion and lymph node involvement. RESULTS: Intratumoral lymphatic vessel invasion and lymph node involvement were found in 7.1% and 5.9%, respectively, of the patients classified in the low-grade group, and in 14.3% and 10.0%, respectively, of the patients classified in the moderate-grade group. In contrast, of the patients classified in the group with high (18)F-FDG uptake, intratumoral lymphatic vessel invasion and lymph node involvement were found in 39.7% and 38.9%, respectively. Multivariate analysis showed that only (18)F-FDG uptake was a significant factor for intratumoral lymphatic vessel invasion and that tumor size and (18)F-FDG uptake were significant factors for lymph node involvement. Of the patients in the high-grade group whose tumors were classified as > or =3 cm in size, lymph node involvement was found in 51.5%. In contrast, of the patients in the low- to moderate-grade group whose tumors were classified as <3 cm in size, lymph node involvement was found in only 9.1% (P < 0.0001). CONCLUSION: Patients with a low to moderate (18)F-FDG uptake in the primary lesion had a significantly lower risk of concurrent intratumoral lymphatic vessel invasion and nodal involvement than did patients with a high (18)F-FDG uptake. In patients with non-small cell lung cancer, (18)F-FDG uptake by the primary tumor is a strong predictor of intratumoral lymphatic vessel invasion and lymph node metastasis.

Adult↗
PubMed2005

[Effects of beta-adrenergic agonists on alveolar fluid clearance in rat lungs].

OBJECTIVE: To study the effects of three selective beta-adrenergic agonists on alveolar fluid clearance (AFC) in the isolated rat lungs. METHODS: Isotonic 5% albumin solutions with different pharmacological agents were instilled into the distal airways in the isolated rat lungs. The lungs were inflated with 100% oxygen at 7 cm H2O (1 cm H2O = 0.098 kPa) and placed in a humid incubator at 37 degrees C. AFC was estimated by the progressive increase in the albumin concentration over 1 h. RESULTS: The baseline AFC was 6.9% +/- 2.2%. Beta(1)-adrenergic agonist denopamine, beta(2)-adrenergic agonist terbutaline and beta(3)-adrenergic agonist BRL-37344 increased AFC significantly (17.1% +/- 2.4%, 19.5% +/- 1.2% and 19.9% +/- 2.5%, respectively). Beta(1)-adrenergic antagonist atenolol abolished the effects of denopamine (AFC was 6.1% +/- 0.9%), but did not inhibit the effects of terbutaline and BRL-37344. Beta(2)-adrenergic antagonist ICI-118551 abolished the effects of terbutaline and BRL-37344 (AFC were 5.7% +/- 0.6% and 7.8% +/- 2.6%), and also partially inhibited the effects of denopamine (AFC was 12.7% +/- 1.8%). Beta(3)-adrenergic antagonist SR-59230A partially inhibited the effects of BRL-37344 and terbutaline (AFC were 13.8% +/- 3.1% and 14.5% +/- 3.5%), but did not change the effects of denopamine. CONCLUSIONS: Denopamine, terbutaline and BRL-37344 are potent stimulators of AFC in the rat lungs. The effects of denopamine and terbutaline are mediated via beta(1)- and beta(2)-adrenoceptors, respectively. The effects of BRL-37344 may be mediated via beta(2)-adrenoceptors. ICI-118551 and SR-59230A may have some beta(1)- and beta(2)-inhibitory effects, respectively.

Adrenergic beta-Agonists↗
PubMed2004

Suppression of female-specific murine Cyp2b9 gene expression by growth or glucocorticoid hormones.

CYP2B9 is a constitutively and female-specifically expressed P450 isoform in mouse livers. Hypophysectomy-induced CYP2B9 mRNA expression in males to a level similar to that in females, while the operation did not affect females. Twice-daily injection of growth hormone (GH), which mimics the male pattern of GH secretion, significantly repressed hypophysectomy-induced mRNA expression in males. The same treatment completely suppressed expression in intact females. Treatments with synthetic glucocorticoid dexamethasone (DEX) suppressed expression of CYP2B9 mRNA in intact females, but not in GH-treated and un-treated hypophysectomized females. In primary cultured mouse hepatocytes, CYP2B9 mRNA expression was concentration-dependently suppressed by natural glucocorticoids such as hydrocortisone and corticosterone as well as by DEX. Glucocorticoid-mediated suppression was partially inhibited by RU486, a potent antiglucocorticoid. In contrast, RU486 by itself suppressed expression of CYP2B9 mRNA. These observations suggest that the sexually dimorphic expression of CYP2B9 is partly due to suppression by the masculine plasma GH profile and by glucocorticoid hormones.

Animals↗