Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 37 records · Page 2Linked to original sources

PubMed2001

Pancreatic granular cell tumor combined with carcinoma in situ.

A 58-year-old man was treated for a granular cell tumor (GCT) of the pancreas; a very rarely occurring tumor. The patient, who had been followed for 6 years due to alcoholic hepatitis, chronic pancreatitis and elevated carcinoembryonic antigen (CEA) levels from smoking, was admitted to our hospital for evaluation of back pain, diarrhea and constipation. The patient was diagnosed as having pancreatic head cancer using clinical imaging studies, and a pylorus-preserving pancreatico-duodenectomy was done. In the resected specimen, a white tumor measuring 13 mm in diameter was observed at the pancreatic head, and there was marked fibrous change surrounding the tumor. The microscopic appearance of the pancreas showed atrophy of acinar cells, fibrosis, and dilatation of the main pancreatic duct (MPD). Within the tumor were oval cells with low-grade atypia and an increased number of diffuse eosinophilic granules. Neither mitosis nor invasive findings were observed. Periodic acid-Schiff staining and immunohistochemical staining for the S-100 protein were positive, thus the tumor was diagnosed as a benign GCT. In addition, carcinoma in situ was found at the dilated MPD. Therefore, this patient was diagnosed as having GCT with carcinoma in situ of the pancreas. To the best of our knowledge, this is only the fourth case of GCT of the pancreas to be reported.

Biomarkers, Tumor↗

PubMed2001

The interactive effects of endotoxin with prenatal glucocorticoids on short-term lung function in sheep.

OBJECTIVE: Previously we have shown that neonatal lung function in sheep after preterm birth is profoundly enhanced by intra-amniotic injection of endotoxin, with a magnitude at least equal to that induced by maternal betamethasone administration. This study investigated the effects of betamethasone on lung maturation and growth in the presence of inflammation by treating sheep with both maternal intramuscular betamethasone and intra-amniotic endotoxin injections. STUDY DESIGN: Time-mated pregnant ewes at 118 days' gestation were allocated at random to receive maternal intramuscular or intra-amniotic saline solution injection (n = 10), maternal intramuscular betamethasone injection (0.5 mg/kg; n = 7), intra-amniotic endotoxin injection (20 mg Escherichia coli B055;B5; n = 11) by ultrasonographic guidance, or both betamethasone and endotoxin injections (n = 7). The lambs were delivered abdominally at 125 days' gestation (term is 150 days' gestation), and the neonates were ventilated for 40 minutes before postmortem examination. RESULTS: Combined treatment with betamethasone and endotoxin resulted in significantly greater improvements in neonatal lung function than occurred after treatment with either agent alone, and this effect was not accompanied by a further increase in surfactant levels. The reduction in birth weight that is seen after maternal betamethasone treatment was not seen when this treatment was combined with endotoxin. Endotoxin treatment resulted in inflammatory responses in cord blood and alveolar wash, and these responses were not inhibited by betamethasone treatment. There were no pregnancy losses. CONCLUSION: Both intra-amniotic endotoxin injection and maternal intramuscular betamethasone injection promoted fetal lung maturation. When these treatments were combined, there were additive effects on short-term postnatal lung function but not on surfactant levels. Endotoxin negated the growth restriction in sheep caused by maternal betamethasone treatment. These findings provide evidence that the lung maturation induced by glucocorticoids and that induced by endotoxin are mediated by different mechanisms.

Acute-Phase Reaction↗

PubMed2001

Prevention of bronchopulmonary dysplasia.

The clinical syndrome of bronchopulmonary dysplasia (BPD) in preterm infants results primarily from an arrest of lung vascular and alveolar development. The most likely mediators are proinflammatory cytokines that are induced by antenatal exposure to infection, postnatal ventilation, and oxygen exposure. New epidemiologic data suggest that attempts to avoid intubation and ventilation are the best ways to avoid severe BPD. The claim that one ventilation technique is better than another remains unconvincing, and any strategy that maintains the lung open and minimizes tidal volumes probably will be helpful. More adverse effects of postnatal steroids are being recognized. New insights into the pathophysiology of BPD and a new emphasis on minimizing ventilation and ventilator-mediated injury should improve outcomes for very preterm infants.

Bronchopulmonary Dysplasia↗

PubMed2001

Intra-amniotic endotoxin increases pulmonary surfactant proteins and induces SP-B processing in fetal sheep.

Intra-amniotic (IA) endotoxin induces lung maturation within 6 days in fetal sheep of 125 days gestational age. To determine the early fetal lung response to IA endotoxin, the timing and characteristics of changes in surfactant components were evaluated. Fetal sheep were exposed to 20 mg of Escherichia coli 055:B5 endotoxin by IA injection from 1 to 15 days before preterm delivery at 125 days gestational age. Surfactant protein (SP) A, SP-B, and SP-C mRNAs were maximally induced at 2 days. SP-D mRNA was increased fourfold at 1 day and remained at peak levels for up to 7 days. Bronchoalveolar lavage fluid from control animals contained very little SP-B protein, 75% of which was a partially processed intermediate. The alveolar pool of SP-B was significantly increased between 4 and 7 days in conjunction with conversion to the fully processed active airway peptide. All SPs were significantly elevated in the bronchoalveolar lavage fluid by 7 days. IA endotoxin caused rapid and sustained increases in SP mRNAs that preceded the increase in alveolar saturated phosphatidylcholine processing of SP-B and improved lung compliance in prematurely delivered lambs.

Amniotic Fluid↗

PubMed2001

GM-CSF regulates protein and lipid catabolism by alveolar macrophages.

Metabolism of surfactant protein (SP) A and dipalmitoylphosphatidylcholine (DPPC) was assessed in alveolar macrophages isolated from granulocyte-macrophage colony-stimulated factor (GM-CSF) gene-targeted [GM(-/-)] mice, wild-type mice, and GM(-/-) mice expressing GM-CSF under control of the SP-C promoter element (SP-C-GM). Although binding and uptake of (125)I-SP-A were significantly increased in alveolar macrophages from GM(-/-) compared with wild type or SP-C-GM mice, catabolism of (125)I-SP-A was markedly decreased in GM(-/-) mice. Association of [(3)H]DPPC with alveolar macrophages from GM(-/-), wild-type, and SP-C-GM mice was similar; however, catabolism of DPPC was markedly reduced in cells from GM(-/-) mice. Fluorescence-activated cell sorter analysis demonstrated decreased catabolism of rhodamine-labeled dipalmitoylphosphatidylethanolamine by alveolar macrophages from GM(-/-) mice. GM-CSF deficiency was associated with increased SP-A uptake by alveolar macrophages but with impaired surfactant lipid and SP-A degradation. These findings demonstrate the important role of GM-CSF in the regulation of alveolar macrophage lipid and SP-A catabolism.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs.

The inflammatory and lung maturational effects of intra-amniotic exposure to endotoxin were assessed in fetal lambs. Five hours to 25 days after intra-amniotic injection of endotoxin, preterm lambs were delivered at 119-125 days gestation. Intra-amniotic endotoxin caused an inflammatory cell infiltration in amnion/chorion at 5 h, which persisted for 25 days. At 5-15 h after endotoxin, amnion/chorion cytokine mRNAs increased [12- to 26-fold for interleukin (IL)-1beta, IL-6, and IL-8 mRNA and 3-fold for tumor necrosis factor-alpha mRNA]. At 1-2 days after endotoxin, lung cytokine mRNAs increased 6- to 49-fold. Endotoxin caused modest changes in peripheral white blood cell counts and no significant cytokine mRNA responses in fetal liver, placenta, or jejunum. Lung maturation, as characterized by increased lung volumes and alveolar saturated phosphatidylcholine, occurred at 7 days and persisted for 25 days after endotoxin. We conclude that exposure to a single dose of intra-amniotic endotoxin causes inflammation and increases in cytokine mRNA in amnion/chorion and the fetal lung before lung maturation, consistent with the hypothesis that proinflammatory cytokines signal lung maturation.

Amnion↗

PubMed2001

Exogenous surfactant changes the phenotype of alveolar macrophages in mice.

Alveolar macrophages are essential for the maintenance of surfactant homeostasis. We asked whether surfactant treatment would change alveolar macrophage number and whether the alveolar macrophage phenotype would become activated or apoptotic when challenged in vivo with exogenous surfactant. Surfactant pool size in mice was increased by repetitive surfactant treatments containing 120 mg/kg (110 micromol/kg) saturated phosphatidylcholine. The number of alveolar macrophages recovered by alveolar lavage decreased after the first dose by 49% and slightly increased after the second and third doses. Up to 28.5% of the macrophages became large and foamy, and their appearance normalized within 12 h. Surfactant treatment did not increase the percent of apoptotic or necrotic cells. The alveolar macrophages were not activated as indicated by no change in expression of CD14, CD16, CD54, CD95, and scavenger receptor class A types I and II after surfactant treatment. Surfactant treatment in healthy mice transiently changed the phenotype of alveolar macrophages to large and foamy without indications of changes in the surface markers characteristic of activation.

Animals↗

PubMed2001

Macrophage and type II cell catabolism of SP-A and saturated phosphatidylcholine in mouse lungs.

Type II cells and macrophages are the major cells involved in the alveolar clearance and catabolism of surfactant. We measured type II cell and macrophage contributions to the catabolism of saturated phosphatidylcholine and surfactant protein A (SP-A) in mice. We used intratracheally administered SP-A labeled with residualizing (125)I-dilactitol-tyramine, radiolabeled dipalmitoylphosphatidylcholine ([(3)H]DPPC), and its degradation-resistant analog [(14)C]DPPC-ether. At 15 min and 7, 19, 29, and 48 h after intratracheal injection, the mice were killed; alveolar lavage was then performed to recover macrophages and surfactant. Type II cells and macrophages not recovered by the lavage were subsequently isolated by enzymatic digestion of the lung. Radioactivity was measured in total lung, lavage fluid macrophages, alveolar washes, type II cells, and lung digest macrophages. Approximately equal amounts of (125)I-dilactitol-tyramine-SP-A and [(14)C]DPPC-ether associated with the macrophages (lavage fluid plus lung digest) and type II cells when corrected for the efficiency of type II cell isolation. Eighty percent of the macrophage-associated radiolabel was recovered from lung digest macrophages. We conclude that macrophages and type II cells contribute equally to saturated phosphatidylcholine and SP-A catabolism in mice.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

SP-D and GM-CSF regulate surfactant homeostasis via distinct mechanisms.

Both surfactant protein (SP) D and granulocyte-macrophage colony-stimulating factor (GM-CSF) influence pulmonary surfactant homeostasis, with the deficiency of either protein causing marked accumulation of surfactant phospholipids in lung tissues and in the alveoli. To assess whether the effects of each gene were mediated by distinct or shared mechanisms, surfactant homeostasis and lung morphology were assessed in 1) double-transgenic mice in which both SP-D and GM-CSF genes were ablated [SP-D(-/-),GM(-/-)] and 2) transgenic mice deficient in both SP-D and GM-CSF in which the expression of GM-CSF was increased in the lung. Saturated phosphatidylcholine (Sat PC) pool sizes were markedly increased in SP-D(-/-),GM(-/-) mice, with the effects of each gene deletion on surfactant Sat PC pool sizes being approximately additive. Expression of GM-CSF in lungs of SP-D(-/-),GM(-/-) mice corrected GM-CSF-dependent abnormalities in surfactant catabolism but did not correct lung pathology characteristic of SP-D deletion. In contrast to findings in GM(-/-) mice, degradation of [(3)H]dipalmitoylphosphatidylcholine by alveolar macrophages from the SP-D(-/-) mice was normal. The emphysema and foamy macrophage infiltrates characteristic of SP-D(-/-) mice were similar in the presence or absence of GM-CSF. Taken together, these findings demonstrate the distinct roles of SP-D and GM-CSF in the regulation of surfactant homeostasis and lung structure.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

Dose-dependent lung remodeling in transgenic mice expressing transforming growth factor-alpha.

Transgenic mice overexpressing human transforming growth factor-alpha (TGF-alpha) develop emphysema and fibrosis during postnatal alveologenesis. To assess dose-related pulmonary alterations, four distinct transgenic lines expressing different amounts of TGF-alpha in the distal lung under control of the surfactant protein C (SP-C) promoter were characterized. Mean lung homogenate TGF-alpha levels ranged from 388 +/- 40 pg/ml in the lowest expressing line to 1,247 +/- 33 pg/ml in the highest expressing line. Histological assessment demonstrated progressive alveolar airspace size changes that were more severe in the higher expressing TGF-alpha lines. Pleural and parenchymal fibrosis were only detected in the highest expressing line (line 28), and increasing terminal airspace area was associated with increasing TGF-alpha expression. Hysteresis on pressure-volume curves was significantly reduced in line 28 mice compared with other lines of mice. There were no differences in bronchoalveolar lavage fluid cell count or differential that would indicate any evidence of lung inflammation among all transgenic lines. Proliferating cells were increased in line 28 without alterations of numbers of type II cells. We conclude that TGF-alpha lung remodeling in transgenic mice is dose dependent and is independent of pulmonary inflammation.

Analysis of Variance↗

PubMed2001

Overexpression of TGF-alpha increases lung tissue hysteresivity in transgenic mice.

Increased transforming growth factor (TGF)-alpha has been observed in neonatal chronic lung disease. Lungs of transgenic mice that overexpress TGF-alpha develop enlarged air spaces and pulmonary fibrosis compared with wild-type mice. We hypothesized that these pathological changes may alter the mechanical coupling of viscous and elastic forces within lung parenchyma. Respiratory impedance was measured in open-chested, tracheostomized adult wild-type and TGF-alpha mice by using the forced oscillation technique (0.25-19.63 Hz) delivered by flexiVent (Scireq, Montreal, PQ). Estimates of airway resistance (Raw), inertance (I), and the coefficients of tissue damping (G(L)) and tissue elastance (H(L)) were obtained by fitting a model to each impedance spectrum. Hysteresivity (eta) was calculated as G(L)/H(L). There was a significant increase in eta (P < 0.01) and a trend to a decrease in H(L) (P = 0.07) of TGF-alpha mice compared with the wild-type group. There was no significant change in Raw, I, or G(L). Structural abnormality present in the lungs of adult TGF-alpha mice alters viscoelastic coupling of the tissues, as evidenced by a change in eta.

Airway Resistance↗

PubMed2001

Complete nucleotide sequence and the genome organization of Patchouli mild mosaic virus RNA1.

The nucleotide sequence of the RNA1 of Patchouli mild mosaic virus (PatMMV) has been determined. It contains 5,957 nucleotides excluding the 3'-terminal poly(A) tail and contains a single long open reading frame (ORF) of 5,613 nucleotides extending from nucleotide 235 to 5847. The predicted polyprotein encoded by the long ORF is 1,870 amino acids in length with a molecular weight of 210 kD. The conserved residues of RNA-dependent RNA polymerase, cysteine protease, purine NTP-binding domain and a cofactor for viral protease are present in a 210-kD polyprotein. As PatMMV RNA showed high sequence identity (81-97%) with BBWV-2 RNA, PaMMV may be one strain of BBWV-2.

5' Untranslated Regions↗

PubMed2001

Surfactant protein A recruits neutrophils into the lungs of ventilated preterm lambs.

We tested the effects of surfactant protein A (SP-A) on inflammation and surfactant function in ventilated preterm lungs. Preterm lambs of 131 d gestation were ventilated for 15 min to initiate a mild inflammatory response, and were then treated with 100 mg/ kg recombinant human SP-C surfactant or with the same surfactant supplemented with 3 mg/kg ovine SP-A. Addition of SP-A to the SP-C surfactant did not change lung function. After 6 h of ventilation, cell numbers in the alveolar wash were 4.9 times higher in SP-A + SP-C-surfactant-treated animals. Cellular infiltrates consisted of neutrophils that produced less hydrogen peroxide than did cells from SP-C-surfactant-treated animals. Expression of adhesion molecules CD11b and CD44 was significantly greater after SP-A treatment, whereas the expression of CD14 was unchanged. Messenger RNAs (mRNAs) for the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-8, but not tumor necrosis factor-alpha, were increased in SP-A-treated lungs. Surfactant protein mRNAs and protein leakage into alveolar washes were not altered by SP-A, indicating that SP-A treatment produces no evidence of lung injury. The present study identifies an unanticipated role of SP-A in neutrophil recruitment in the lungs of preterm lambs.

Animals↗

PubMed2001

Lung morphometry after repetitive antenatal glucocorticoid treatment in preterm sheep.

Antenatal glucocorticoids are thought to be less effective when delivery occurs more than 7 d after initiation of treatment; therefore, repeat courses are often administered. We examined lung structure after single or repetitive antenatal glucocorticoid injections in fetal sheep. Pregnant ewes received single or repetitive doses of 0.5 mg/kg betamethasone at 7-d intervals by maternal or fetal injection, beginning at D104 or D114 with delivery at D125, D135, or D146 gestation (term = 150 d). Changes in lung structure were more pronounced after repetitive versus single injections. Repetitive fetal or maternal injections beginning at D104 (delivery at D125) resulted in comparable structural changes: alveolar volume increased by 50 to 80%, alveolar numerical density decreased by 30 to 40%, and pleural and interlobular septal volumes decreased by as much as 70%. Similar changes were seen in animals delivered at D135 after repetitive maternal injections beginning at D114. There were no structural differences between control and repetitive betamethasone animals when delivery was delayed until D146, indicating that betamethasone induced structural changes were reversible.

Analysis of Variance↗

PubMed2001

[Clinicopathological study with regard to ulcer in the cancer lesion of the depressed type intramucosal cancer of the stomach].

UNLABELLED: We histologically investigated 207 cases with the depressed type intramucosal cancer of the stomach, as to the risk factor of ulcer formation in the cancer (Ul.), tumor size of less than and not less than 10 mm, histological type of differentiated carcinoma (Diff.) and undifferentiated carcinoma (Undiff.), tumor location classified by the usually occurring region of the peptic ulcer (Usual portion and Unusual portion) and the intramucosal propagations of extensively vertical type (EV) and nonextensively vertical type (NV). RESULT: 1) Tumor size, histological type, tumor location and intramucosal propagation type were significantly related to Ul., as the result of multivariate analysis. 2) The frequency of Ul. at the lesions of these cases, regardless of histological type, was higher at the lesion of Usual portion than at Unusual portion. And the frequency of Ul., independently of tumor location, was higher in Undiff. than in Diff.. 3) The frequency of Ul. at the lesions of Unusual portion in Undiff. was higher in EV than in NV. CONCLUSION: We suggested that extensively vertical propagation type of intramucosa, as well as large tumor size, Undiff. and at the lesion of Usual portion, was a significant risk factor for Ul. of the depressed type intramucosal cancer of the stomach. 2) We concluded that the intramucosal propagation type of the cancer was particularly concerned with Ul. at the intramucosal lesion of Unusual portion in Undiff.

Adult↗

PubMed2001

[Alternations of p53 gene, microsatellite instability and proliferation associated antigen Ki-67 in the synchronous multiple colorectal cancers].

To evaluate the malignant potential of synchronous multiple colorectal cancers, we studied clinicopathologically 31 synchronous multiple colorectal cancers resected at our hospital. We also compared the p53 gene mutation rate, replication error (RER) rate, and Ki-67 antigen positivity rate between these cancers and 90 sporadic colorectal cancers. There was no significant difference in lymphoid and venous invasion, hepatic metastasis, or stage of colon cancer between the two types of cancers. The p53 gene mutation rate was lower in synchronous multiple colorectal cancers (p < 0.05). The RER rate and positivity rate for Ki-67 antigen was significantly higher in these cancers (p < 0.05). These results suggest that some synchronous multiple colorectal cancers result from carcinogenesis in which RER genes are involved, as HNPCC does. In the patients with synchronous multiple colorectal cancers, it is clinically important to follow them carefully focusing on multiple metachronous colorectal cancers and multiple organ cancers.

Aged↗

PubMed2001

[The effects of percutaneous endoscopic gastrostomy feeding in patients with swallowing disturbance].

BACKGROUND AND PURPOSE: Because the number of patients who need home healthcare has recently increased in Japan, Percutaneous endoscopic gastrostomy (PEG) will soon become more popular. This study aims to examine the effects of enteral alimentation via PEG. MATERIAL AND METHODS: The subjects were 18 patients who underwent PEG instead of receiving total parental nutrition (TPN) (TPN-to-PEG group), 13 patients who underwent PEG instead of receiving enteral nutrition through a naso gastric tube (NG-to-PEG group), and 11 healthy volunteers (control). Morphological changes of the small bowel mucosa and activities of daily life (ADL) after PEG were also investigated. RESULTS: In the TPN-to-PEG group, the serum level of total protein and albumin, length of duodenal villi, ration of positive proliferative cells, width of duodenal microvilli and ADL markedly increased. In the NG-to-PEG group, body weight and ADL were markedly improved after PEG. CONCLUSION: Nutrition via PEG is superior to TPN or enteral nutrition with an NG tube. I conclude that PEG will become the first choice for improving nutrition in patients with dysphasia and will contribute to continuous enteral nutrition for home care.

Activities of Daily Living↗

PubMed2000

Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice.

Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in the lungs of SP-D (-/-) mice. Although lung morphology was unperturbed during the first 2 weeks of life, airspace enlargement was observed by 3 weeks and progressed with advancing age. Inflammation consisted of hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated with increased activity of the matrix metalloproteinases, MMP2 and MMP9, and immunostaining for MMP9 and MMP12 in alveolar macrophages. Hydrogen peroxide production by isolated alveolar macrophages also was increased significantly (10-fold). SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema.

Animals↗