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To study whether circadian variation of bronchial caliber participates in causing late asthmatic response (LAR), house-dust inhalation was made at 10 AM and 6 PM on separate days in 6 house-dust-sensitive asthmatic children aged 8 to 13 years. Bronchial obstruction was assessed through measurements of FEV1 at 4-h intervals from 24 h before to 24 h after the inhalation. The LAR, which is a 15 percent or greater decrease in FEV1 from the value at the same hour of the previous day, occurred 4 h or later after the inhalation in all challenges. The mean (+/- SD) time to the occurrence of the lowest FEV1 (maximum LAR) following the morning inhalation was 14.7 +/- 2.1 h versus 10.0 +/- 2.2 h following the evening inhalation (p0.05). Regardless of the hour of inhalation, FEV1 after the inhalation was lowest or near-lowest at 2 AM in all. Therefore, the maximum LAR was indistinguishable from the trough of further amplified circadian variation in FEV1 following the inhalation. These findings suggest that the downward arm of circadian variation may partially participate in causing the LAR.

Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.

Background: Imatinib used to be the only effective treatment for advanced gastrointestinal stromal tumor. However, early clinical reports have shown that sunitinib has substantial anticancer activity in patients with advanced gastrointestinal stromal tumor after failure of imatinib. Methods: Eighteen Japanese patients with advanced gastrointestinal stromal tumor who were resistant or intolerant to previous treatment with imatinib were entered into this study. These patients were given sunitinib orally, once daily at a 50-mg starting dose, in 6-week cycles with 4 weeks on and 2 weeks off treatment. Tumor response and drug safety were then evaluated. Results: Median time-to-treatment failure was 207 days. Overall, 5.6% (1/18) of patients achieved partial response, 38.9% (7/18) had stable disease and 44.4% (8/18) had progressive disease. The common adverse events were hand-foot syndrome, liver dysfunction, fatigue, anorexia and hypertension. Mild anemia, leukocytopenia and neutropenia were also noted. Nine patients required dose reduction or cessation because of adverse events. Conclusions: This study demonstrates that sunitinib may be an effective agent for advanced gastrointestinal stromal tumor after failure of imatinib in clinical practice.

Colorectal cancer (CRC) was first recognized as a complication of ulcerative colitis (UC) in 1925, and the increased risk has since been confirmed in a multitude of epidemiological studies. To our knowledge, however, all of these studies have been conducted in Western countries. The aim of this study was to identify the clinicopathological features of ulcerative colitis-related CRC in a consecutive series of patients at a single hospital in central Japan.314 (170 males, 144 females, mean age 30) consecutive patients diagnosed with ulcerative colitis were enrolled and investigated for the development of CRC. 240 patients had relapsing-remitting disease, 54 had chronic continuous disease, 16 had experienced one attack only, 2 had the acute fulminating type, and 2 were unknown. With regard to disease extension, 181 cases were of the pan-colitis type, 84 were left-sided colitis, and 42 were proctitis. Two patients (1%) had a family history of colorectal cancer and 45 (14%) were past or current smokers.Colorectal cancer developed in seven patients (male to female ratio of 1:6), which was 2.2% of the total. Average age at the onset of ulcerative colitis was 28 years. Average age at the onset of cancer was 44 years, and average duration of UC at cancer onset was 192 months. Ulcerative colitis was of the pancolitis type in all cases. Three patients (43%) showed the relapse-remitting type and four (57%) the chronic continuing type. Three patients (43%) had a family history of cancer, in particular colorectal cancer in one patient (14%). None of the patients had a history of smoking. The histological type of cancer was well differentiated tubular adenocarcinoma in three patients (43%) and poorly differentiated adenocarcinoma in three patients (43%) each, and endocrine cell carcinoma in one (14%).In this group of Japanese patients, development of colorectal cancer was more likely to occur in patients with ulcerative colitis that was long-standing, and more extensive than left-sided colitis, particularly in those with a family history of colorectal cancer, inflammatory polyps, or dysplasia. CRCs in our patients with UC were often poorly differentiated and had a poor prognosis.

Workshop on research and development of JIEDI (JAXA Ion Engine Development Initiatives) tool for numerical evaluation of ion engine grid lifetime, The plasma parameters, electron number density and electron energy distribution function, in a miniature microwave discharge ion thruster were successfully measured by means of laser Thomson scattering without perturbations. A photon counting method and a double monochromator were used against small Thomson scattering signal and strong stray laser light. The result shows an electron energy distribution function is Maxwellian, since the scattered spectrum can be fitted by Gaussian at the temperature of 1.5 eV. An electron density is 2.3 x 10(sup 18) m(exp -3). The measured electron number density and electron temperature values were found to be reasonable compared with estimation deduced form extracted ion beam current., 資料番号: AA0064642006, レポート番号: JAXA-RR-09-004

We report the case of a 37-year-old woman with two synchronous solid-pseudopapillary neoplasms (SPNs) of the pancreas. The patient underwent abdominal echography as part of the screening for hepatitis C virus antibody positivity, and a pancreatic tail tumor was detected. She was referred to our hospital for further examination of the pancreatic tail tumor. There were two masses measuring 37 and 20 mm, in the pancreatic body and tail, respectively, which were slightly enhanced on abdominal computed tomography. On endoscopic ultrasonography (EUS), their surfaces were smooth, their margins were clear, anechoic spots were seen in the hypoechoic mass, and there were no lateral shadows. Magnetic resonance imaging showed a low- and high-intensity mass of the body and a low- and low-intensity mass of the tail on T1- and T2-weighted images, respectively. EUS-guided fine needle aspiration biopsy (EUS-FNA) suggested SPNs because the tumor cells showed an aberrant nuclear expression of β-catenin and loss of membranous staining of E-cadherin on immunohistochemical analysis. With a diagnosis of SPNs based on the EUS-FNA findings, a distal pancreatectomy was performed. On histopathologic examination of the resected specimen, the SPNs were arising synchronously.

To elucidate the criterion for amplitude of circadian FEV1 variation suitable for phase analysis, six FEV1 measurements within a day were made on 346 days in 125 stable asthmatic children aged 8 to 12 years. Since coefficient of variation (CV) of FEV1 within a day in nonasthmatic children in our laboratory is less than 5 percent, circadian FEV1 variations were divided into CV greater than or equal to 5 percent and CV less than 5 percent groups. Forty-two (12 percent) variations with significant fit of cosinor rhythm were CV greater than or equal to 5 percent. Troughs in 32 (76 percent) variations of the 42 were distributed between 12 PM and 6 AM, and the deviation was highly significant against a uniform distribution (p less than 0.001). This was consistent with nocturnal asthma. Thirty-five (10 percent) variations with significant fit of cosinor rhythm were CV less than 5 percent. Troughs in 12 (34 percent) variations of the 35 were distributed between 12 PM and 6 AM, and the deviation from a uniform distribution was nonsignificant. These suggest that 5 percent or more of CV of FEV1 may be clinically suitable for analysis of circadian FEV1 variation.

Background: The chronic inflammatory process in patients with Crohn's disease (CD) may affect any part of the gastrointestinal (GI) tract. The pathogenesis of CD involves immunological abnormalities, including deficient or excessive expression of cytokines. We examined Helicobacter pylori infection status, endoscopic and histopathological findings, and cytokine production in the duodenum of CD patients in comparison with controls. Methods: Thirty-eight CD patients underwent diagnostic upper GI endoscopy. Twelve age- and sex-matched health checkup examinees were used as controls. H. pylori infection status was assessed by the 13C-urea breath test. At the time of endoscopy, two biopsy specimens each were obtained from the second portion of the duodenum, one for hematoxylin-eosin staining and immunohistochemical analysis with anti-CD68 antibody, and one for in vitro organ culture. Interleukin (IL)-6 and -8 levels were measured in organ culture supernatant by enzyme-linked immunosorbent assay. Results: H. pylori infection was significantly (P

To study the time-course of influenza-induced asthma, we retrospectively examined FEV1 from five days before to ten days after the onset of illness in 20 asthmatic children aged 8 to 12 years with tolerable respiratory symptoms. Influenza infection was confirmed by a rise at least fourfold in serum complement fixation titers. Fifteen of 20 patients had decrease in FEV1 more than 20 percent from baseline during the acute stage. FEV1 began to decrease with the onset of illness in the 15 patients with the exception of one whose FEV1 decreased during the incubation period. It continuously decreased on the second day, when mean (± SD) decrease in FEV1 became maximum, 30.3 ± 10.9 percent. It began to improve on the third day, and returned within 10 percent difference on the seventh to tenth day. We conclude that influenza-induced asthma may continuously deteriorate during the first two days of illness and may require at least seven days for recovery.

We try to reevaluate the pathogenesis of epituberculosis in infants and children with tuberculosis, because most studies on epituberculosis were done more than 50 years ago.Nineteen children (less than 1 y/o: 12, 1 y/o: 2, 2 y/o: 3, and 4 y/o: 2) were studied by CT imaging and bronchofiberscopy in addition to gastric Mycobacterium tuberculosis examination and regular chest XP.In 13 of total 19 patients (68%), lobar or segmental epituberculosis occured after starting antituberculous chemotherapy, including a case in which epituberculosis of right upper lobe was recognized at the time of diagnosis of tuberculosis and after starting chemotherapy, epituberculosis of right middle lobe was observed. CT imaging revealed that all 19 patients had enlargement of mediastinal and/or hilar lymphonodes compressing neighboring bronchi, and 16 of total 19 patients (84%) demonstrated relevant parenchymal infiltration. Gastric Mycobacterium tuberculosis was positive in 15 out of 19 patients (79%). Bronchofiberscopy was done in 16 patients, and it demonstrated mass lesion of various size on the bronchial wall in 13 patients (81%).The present study demonstrated that epituberculosis predominantly occured in tuberculosis infants less than one year old, which was different from the previous reports. The CT imaging also makes clear that epituberculosis may be the atelectasis of lobe or segment which occurs mostly due to compression of bronchi by the enlargement of mediastinal and/or hilar lymphonodes and their early exacerbation after starting chemotherapy. Bronchofiberscopy also elucidated that bronchial wall mass lesion resulted from perforation of lynphonodes may partially contribute to the formation of epituberculosis.

We report three tuberculosis children aged seven-month-old to 11-year-old who had paradoxical worsening of tuberculosis of lung and lymph nodes, lymph nodes, and intracranial tuberculoma at different treatment stages. In these children, paradoxical worsening occurred at about 14 days after start of anti-tuberculosis treatment, about six months after the start, and about three months after the completion of treatment. No alteration was done in the method of anti-tuberculosis treatment against expanding lesions, and predonisolone was prescribed in two subjects. Expanded lesions then improved one- to five-months later. The mechanisms of paradoxical worsening is unclear. However, these cases suggest that paradoxical worsening may occur at any time after starting anti-tuberculosis treatment based on interaction between the microbial factors and host immunological factors in lung, lymph nodes, intracranial tuberculosis lesions.

Tuberculin skin test (TST) is a useful tool to find non-symptomatic infants with tuberculosis. In 2005, Japanese government starts direct BCG vaccination without prior TST, and we may miss one of the chances to find the above patients. In this study, we tried to find if there is any clinical examination to find non-symptomatic infants with tuberculosis instead of regular TST.We found out 20 non-symptomatic infants with tuberculosis among 131 infants who referred to our clinic because of positive TST prior to BCG vaccination from 1996 to 2003. We examined the data of gastric aspirate examination for Mycobacterium tuberculosis, complete blood counts, and serum chemistries in the 20 infants with tuberculosis. We also tried to find out the source of tuberculosis of these patients by the contact investigation.Induration of TST among 20 non-symptomatic infants with tuberculosis were 7 to 26 (median, 13.5) mm. Mycobacterium tuberculosis from gastric aspirates was positive in 13 infants (65%). The level of blood hemoglobin was more than 11 g/dl in all infants. The white blood cell count was increased in 6 infants (30%), and exaggerated lymphocyte predominance was recognized in 8 infants (40%). Serum CRP was normal, or subtly increased. Serum GOT (AST) was increased in 15 infants (75%), though the reason was unknown. Serum albumin was normal in all the infants. In the contact investigation, suspected sources were found in 11 infants (55%), and 6 out of 11 sources (55%) were their mothers. Nine sources did not belong to the risk groups for tuberculosis except two mothers coming from tuberculosis epidemic countries.In 20 non-symptomatic infants with tuberculosis, examination of gastric aspirate for Mycobacterium tuberculosis, TST, and chest imaging were useful tools to diagnose tuberculosis. However, these examinations are not done in non-symptomatic infants. Eleven family members who might infect the infants were found by the contact investigations, and none of them realized that they have tuberculosis. Our study suggests that there is no realistic clue to find non-symptomatic infants with tuberculosis instead of regular TST, and that the control of infant's tuberculosis still depends on the examination of close contacts of sporadic adult patients with tuberculosis.

We previously reported the presence of periportal hypodensity on CT image in two newborns and an early infant with congenital tuberculosis as an adjunct diagnostic option. The aim of this study was to determine the degree of treatment based on both periportal hypodensity and serum IgM presented in asymptomatic newborns born from tuberculosis mothers.Eight newborns born from mothers with untreated tuberculosis between 1996 and 2002 were retrospectively studied. Newborns who presented periportal hypodensity and high serum IgM were treated with anti-tuberculosis medicines, combination of isoniazid and rifampicin for nine to 12 months with streptomycin in the initial two months, and the outcomes of the treatment were followed for at least two years.All eight newborns had gastric aspirates negative for Mycobacterium tuberculosis. Three of eight newborns (38%) demonstrated periportal hypodensity, and they also demonstrate a tendency of high serum IgM. None of these three newborns treated with combination of isoniazid, rifampin, and streptomycin for 9 to 12 months developed tuberculosis during the observation period.These results suggest that presence of both periportal hypodensity and high serum IgM in asymptomatic newborns born from mothers with untreated tuberculosis may be one of risk factors of developing congenital tuberculosis, and that anti-tuberculosis treatment for nine to 12 months may prevent them from the disease development despite possible criticism of overdiagnosis and overtreatment.

We report a case of one-year and three-month old male infant with healed tuberculosis who was found by positive tuberculin skin test prior to scheduled BCG vaccination. Abdominal CT imaging revealed calcification in liver, spleen, and lymphnodes along pancreas and hepato-duodenal ligament, despite of normal chest imaging. A temporary intubated infant with congenital tuberculosis and/or his mother with untreated tuberculosis might infect him during his stay in the same NICU when he had digestive disease at three-month old. This report suggests that periodic contact investigation is needed for infants who had contact with the intubated infant with congenital tuberculosis in the same room, since cell-mediated immunity is not well developed in infants.

We treated three newborns and early infants with congenital tuberculosis between 1996 and 2001. We reported imaging presentations of the three cases born in and after 1996 when new CT equipment (CT-HAS-SGS, GE-Yokokawa, Tokyo) was introduced in our institute. These three cases of congenital tuberculosis showed periportal hypodensity, in addition to pulmonary infiltrate, mediastinal and abdominal lymphadenopathy on CT images. Early diagnosis of congenital tuberculosis is urgently needed, however, it is very difficult. Our findings suggested that clinical suspicion supplemented by careful imaging examinations may facilitate the early diagnosis of congenital tuberculosis, and the detection of periportal hypodensity may offer a new additive diagnostic option to congenital tuberculosis.

Reevaluating the important points in tuberculosis contacts investigation.We retrospectively examined the medical charts of 25 infants and children who developed tuberculosis following contacts investigation.In thirteen patients, diagnosis of infection was missed, and three of five infants less than one year old suffered from meningitis or military tuberculosis while they were waiting the next examination. Three patients were not indicated preventive treatment despite of induration of 5 mm or more in tuberculin skin test. Other twelve patients including five infants less than one year old were diagnosed to have tuberculosis infection and started preventive therapy, however, tuberculosis developed in 10 patients while taking the medicine, and in two patients probably because of defaulting from taking the medicine.These results suggest that the contacts investigation have to be done promptly and be flexible based on age of contacts, evaluation of tuberculin skin test results and radiographic findings in order to reduce the disease further.

Although large clinical trials reported in 1960s suggested that preventive therapy in subjects with tuberculosis (TB) infection reduces the risk of developing TB by 70-90%, the therapy in our TB clinic seems to be more effectiveness.We retrospectively evaluated the efficacy of the present contacts investigation, especially of preventive therapy for further improvement of TB control for children.We examined 273 asymptomatic infants and children younger than five years who had household contacts with active TB patients and visited our clinic for contact investigation. After the diagnosis at the first visit to our TB clinic, they were treated and/or observed for at least two years to assess whether contact investigations and following treatment are appropriate. Since infants less than a year are underdeveloped in cell-mediated immunity and their tuberculous lymphadenopathy can be overlooked on standard chest radiographs, chest CT scans were added.At their first visit, 60 (22%) out of 273 subjects were diagnosed as TB, and 37 (14%) were suspected as TB. We treated them by combinations of anti-TB medicines including isoniazid and rifampin for six to 12 months, and they did not relapse during the observation period. Twenty-six subjects (9%) were diagnosed uninfected. However, a three-year-old girl developed bilateral hilar lymphadenopathy two months later when the reexamination was done. A hundred and fifty subjects (55%) were diagnosed to have TB infection. They received preventive therapy with isoniazid (10 mg/kg/day) for six months. Among them, a four-month-old boy developed TB disease soon after starting to take isoniazid and was treated by the combination of anti-TB medicines. Other 149 subjects completed the therapy, and none of them developed disease during the observation period. There was no increase in serum GOT and/or GPT to100 IU/L within one month after starting to take isoniazid.The present contacts investigations and treatments in our TB clinic are useful ways to find out and control TB diseases and infections, and it might be suggested to start the six-months preventive therapy after active TB has been ruled out in all infants and children who had close contacts with active TB patients for preventing TB disease and latent TB infection in the future even their clinical and laboratory examinations do not suggest infection.

It is useful to know the distribution of pulmonary lesions in the diagnosis of tuberculosis on radiological examination. The aim of this study was to investigate if there is predominant lung segment or lobe for tuberculous lesions in infants aged less than one year using contrast enhanced CT. We studied 57 infants (40 boys, 17 girls) who were diagnosed as tuberculosis by isolation of Mycobacterium tuberculosis or combination of family contact, radiographic findings suggesting tuberculosis, and positive reaction of 5 mm or more induration to PPD tuberculin. All the infants had lesions in mediastinal and/or hilar lymphonodes, and 54 out of 57 infants had parenchymal lesions as well. In the study of the segmental predominance of tuberculous lesions, each infant had a share of 100 points. If an infant had a single focus, all the points were distributed to the corresponding segment. If he or she had multiple foci, the 100 points were equally divided into affected lung segments. There was no significant difference between right (3385 points/10 segments) and left (2005 points/8 segments) lungs. The points in upper lobes (2224 points/5 segments) were significantly higher than the combined points of middle and lingual (896 points/4 segments) and lower (2270 points/9 segments) lobes (p0.05). The points in posterior lung segments (2839 points/7 segments) were significantly higher than the combined points of middle (436 points/3 segments) and anterior (2115 points/8 segments) lung segments (p0.05). These results suggest that upper lobes and posterior segments are predominant parenchymal regions of tuberculosis among infants less than one year, although tuberculous lesions may locate in any lung segment.

We retrospectively evaluated the clinical and laboratory data of children with tuberculous meningitis (TBM) treated at our hospital from 1990 to 1999 to determine the optimal method of diagnosing TBM. The evaluated diagnostic criteria for TBM were as follows: (1) fever and malaise as symptoms of acute/subacute inflammation, (2) positive cerebrospinal fluid and/or gastric aspirate cultures for Mycobacterium tuberculosis, (3) pleocytosis of cerebrospinal fluid, and (4) a good response to anti-tuberculous therapy. The data for eleven patients (6 boys, 5 girls) with TBM (mean age, 10.7 months) were reviewed. Three patients (27%) were previously vaccinated with BCG. A known contact with tuberculosis was established at the time of admission in four patients (36%). Symptoms related to tuberculosis appeared on the average 14.8 days before the diagnosis. Three patients (27%) were diagnosed as clinical stage I, three (27%) as stage II, and five (46%) as stage III; all patients had fever (100%). With regard to the cerebrospinal fluid examinations, pleocytosis with mononuclear predominance was noted in all patients but one (91%), and mycobacterial staining was positive in three patients (27%). Tuberculin skin test was positive in four out of 10 patients (40%). Mycobacterial staining of gastric aspirate was positive in four patients (36%). Chest radiological examinations showed a swelling of the mediastinal lymphonodes and/or parenchymal infiltration in all patients (100%). A cranial CT examination demonstrated a basal meningeal enhancement in all patients (100%), hydrocephalus in nine patients (82%), and infarction in eight patients (73%). These results suggest that chest and cranial CT examinations are useful adjunct methods for diagnosis of TBM in infants and young children suffering from meningitis with pleocytosis of the cerebrospinal fluid and mononuclear predominance, in addition to conventional methods such as the tuberculin skin test, plain chest radiography, and staining for mycobacteria in body fluids.

Nowadays, methods of the diagnosis in infants with suspected tuberculosis and of the treatment are definitely established in Japan, where a number of childhood tuberculosis has been falling down (the incidence is less than 2 per 100,000). Still, infants less than one year are considered to be at high risk against tuberculosis. Actually, the number of tuberculosis among them is three times larger than those of one or two years old children. One of major reasons of difficulties in the treatment is the rapid progress of the disease because of underdeveloped cell-mediated immunity among them. Alveolar macrophage and lymphocyte and their cooperation in immunological functions do not develop enough to kill or confine Mycobacterium tuberculosis. As a result, the infection may progress to disease quickly, and then may spread systemically before the starting treatment. Anatomical underdevelopment of cranial arteries and narrow cerebrospinal passages easily cause cerebral infarction and hydrocephalus following meningeal inflammation due to tuberculosis. These neurological disorders may result in poor prognosis despite of administration of effective anti-tuberculosis medicines. Delay in the diagnosis also makes the treatment difficult in some infants whose tuberculin skin test shows false negative and radiographic manifestation of chest is not clear. During the treatment, systemic and enteric viral infections occur frequently among infants with tuberculosis, and liver functional disorders caused by these infections sometimes disturbs the treatment for tuberculosis. Recurrence of tuberculosis is very rare among infants who complete the full treatment at the age of more than one year. Finally, it is important for the early start of treatment for tuberculosis to recognize both susceptibility to tuberculosis and difficulties in the diagnosis in some infants less than one year.

4. Avgerinos D,Llaguna O, Lo A, et al. Management of endoscopic retrograde cholangiopancreatography: related duodenal perforations. Surg Endosc 2009;23:833-8. 5. von Renteln D, Hans-Ulrich R, Schmidt A, et al. Endoscopic closure of duodenal perforations by using an over-the-scope clip: a randomized, controlled porcine study. Gastrointest Endosc 2010;71: 131-8. 6. Parodi A, Repici A, Conio M, et al. Endoscopic management of GI perforations with a new over-the-scope clip device (with videos) Gastrointest Endosc 2010;72:881-6. d

Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) is shown to inhibit the growth of MKN-45 cells, a human gastric cancer cell line, which overexpresses c-Met tyrosine kinase. The aim of the present study was to investigate whether PPARgamma regulates the expression of c-Met. Two days after the activation of PPARgamma by troglitazone, a potent and selective PPARgamma ligand, a dramatic reduction of c-MET transcripts and the c-Met protein in MKN45 cells was observed. The luciferase assay showed that the activation of PPARgamma suppressed -249 to +330 c-MET promoter activity, driven by cotransfection of ETS-1 expression vector. These data demonstrate that PPARgamma activation is capable of suppressing Ets-induced c-MET gene transcription. Thus, it is possible that the growth inhibitory effect of PPARgamma on MKN-45 cells is related to the suppression of c-MET transcription.

This study was designed to clarify the role of endogenous Bcl-xL expression in modulating apoptosis of malignant cells. Administration of bcl-x-antisense oligonucleotides decreased Bcl-xL protein levels in the MKN-45 human gastric cancer cell line. The decrease in Bcl-xL protein content resulted in increased cell death induced by serum deprivation or Fas-antibody administration. Flow cytometric analysis revealed that the increased apoptotic cell death was more prominent in bcl-x-antisense-treated cells as compared to control cells, bcl-x-sense-treated cells, or bcl-x-nonsense-treated cells. To inhibit the effect of intrinsic Bcl-xL protein, we overexpressed Bak, which binds Bcl-xL and inhibits the anti-apoptotic effect of Bcl-xL, by transfection into MKN-45 cells. Bak-overexpressing cells showed increased apoptotic cell death induced by Fas-antibody when compared to parent cells and MKN-neo-transfected cells. Bak-overexpressing cells also showed greater sensitization to 5-fluorouracil and cisplatin than parent cells and MKN-neo-transfected cells. In conclusion, we demonstrated that administration of bcl-x-antisense oligonucleotides or overexpression of Bak protein induces sensitization to apoptosis in MKN-45 gastric cancer cells, suggesting that endogenous Bcl-xL expression in cancer cells is an important modulator of apoptosis.

The norspermidine-pyruvate reaction catalyzed by polyamine aminotransferase from Arthrobacter sp. TMP-1 formed N-3-aminopropyl-3-aminopropionaldehyde (APAPAL), L-alanine, 1,3-diaminopropane (DAP), allylamine, and acrolein, and the relative rates of formation of the latter four products were 24, 3.3, 2.3, and 1.2%, respectively, of the rate of the DAP-pyruvate transamination. The identification of APAPAL was done by 13C-NMR after it had been enzymatically oxidized to N-3-aminopropyl-beta-alanine followed by isolation of the oxidized product. The DAP was also isolated and identified by 13C-NMR. The allylamine and acrolein were identified by HPLC and a specific color reaction with m-aminophenol, respectively. In the absence of pyruvate, the enzyme catalyzed the elimination of DAP from norspermidine to yield allylamine, and the addition of DAP to allylamine to yield norspermidine with relative rates of 0.007 and 0.095%, respectively. When allylamine was incubated with the enzyme as the sole substrate, it was converted to N-allyl-1,3-diaminopropane and an unidentified product.

Earlier studies demonstrated a correlation between diurnal bronchial variability and bronchial responsiveness (BR) in asthmatic patients. However, since the most severe bronchial obstruction tends to occur from midnight to early morning, diurnal bronchial variability might underestimate within-day bronchial variability. This study was undertaken to reevaluate the correlation after assessing more precisely the within-day variability of bronchial caliber in 43 children with episodic asthma (23 boys, 20 girls), aged 8-12 years. Seven FEV1 measurements were made every 4 h between 10:00 and 10:00 for 2 consecutive days. The coefficient of variation (CV) of the last six FEV1 was defined as the amplitude. Just after measurement of FEV1 at 10:00 on day 2, measurements of BR to house-dust allergen, histamine, and 7-min free running were made in 14, 14, and 15 patients, respectively. The BR was expressed as the percent change in FEV1 from the baseline value in house-dust inhalation and running challenges, and as the provocative concentration causing a 20% fall in FEV1 (PC20), transformed into a logarithmic scale, in histamine challenge. There were significant correlations between CV [mean (SD), 8.1 (5.3)%] and BR to house-dust [mean (SD), -19.0 (11.8)%] (r = -0.663, p0.01), and between CV [mean (SD), 7.4 (5.5)%] and histamine PC20 (geometric mean, 0.38 mg/ml) (r = -0.661, p = 0.01). There was a marginally significant correlation between CV [mean (SD), 6.4 (3.7)%] and BR to running [mean (SD), 28.5 (16.6)%] (r = -0.496, 0.05p0.1). These results confirmed the reliability of earlier studies that suggested that the bronchial variability may be one of clinical indices of BR to various stimuli in asthmatic patients.

incomplete exam included intubated patients (2/14), inadequate sedation (9/14), and inability to see the entire hypopharynx (3/14). The mean time of the WLE was 20.2 seconds while the NBI evaluation took 15.6 seconds for a mean 35.8 seconds for the entire exam of the hypopharynx and larynx. All patients then had successful examination of the esophagus/stomach/duodenum. There were 6 patients who had hypopharyngeal abnormalities seen on both WLE and NBI (5.4%) and were subsequently referred to otolaryngology. Of the 6 referrals, one patient had a vocal cord biopsy showing leukoplakia while the others were deemed normal anatomic variants. Minor procedural complications occurred in 3/111 (2.7%) of the patients and included hypotension, tachycardia, and hypoxia. Conclusion: Evaluation of the hypopharynx can be accomplished by gastrointestinal endoscopists at the time of EGD in the majority of patients in a safe manner while adding only about 35 seconds to the overall exam time.

To study whether nocturnal bronchial obstruction changes during the year, we assessed the circadian FEV1 variation during four consecutive seasons in 20 children (12 boys; aged 9-12 years) with episodic asthma who were outgrowing their asthma. FEV1 was determined every 4 h between 10:00 and 10:00 during two consecutive days. The last six FEV1 values were submitted to cosinor and coefficient of variation (CV) analyses. The seasonal means (SD) in the group 24 h percent predicted FEV1 was 85.5 (11.4), 81.2 (10.6), 86.0 (11.6), and 82.2 (14.0)% during spring, summer, autumn, and winter, respectively. The difference between the summer and autumn FEV1 values was statistically significant (p0.05). The mean (SD) of the circadian amplitude values was 4.1 (4.3), 6.0 (3.8), 4.9 (3.4), and 7.2 (4.1)% during spring, summer, autumn, and winter, respectively. The difference in amplitude between the spring and winter and between the autumn and winter values was statistically significant (p0.05). CV values of 48 of the 80 (60%) circadian FEV1 time series exceeded the average CV of 5% observed in nonasthmatic children studied in our laboratory. There was an unequal distribution during the year in elevated CV values; 6, 17, 10, and 15 of the high CV values occurred, respectively, in the spring, summer, autumn, and winter. These results suggest that nocturnal bronchial obstruction may change seasonally in terms of severity and amplitude in children who have nearly outgrown their asthma.

Histidine decarboxylase (HDC) mRNA in various rat tissues were quantitated by using a reverse transcription-polymerase chain reaction (RT-PCR) in which a mouse mRNA was used as an internal standard. The stomach HDC mRNA level was the highest followed by the brain, skin, jejunum, spleen and liver. There was no measurable HDC mRNA in the kidney. The stomach HDC activity was also the highest followed by the brain, skin, spleen, jejunum, liver and kidney. A significant correlation (r = 0.940,p < 0.0001) was observed between the HDC mRNA levels and HDC activities in these tissues. We have also examined the HDC mRNA levels in fasting rats and found that HDC mRNA levels in the stomach were reduced after the 48-hr-fasting with the decrease in HDC activities. These observations indicate that there may exist a gene regulation, at least at the basal level, for the HDC activities in the rats.

Objective: No previous studies have described endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) only for intra-ampullary lesions of the papilla of Vater. We aimed to examine whether EUS-FNA can be used to diagnose such lesions. Methods: This study included a subset of 10 consecutive patients in whom EUS-FNA targeted the ampulla of Vater. All the patients underwent biopsy and/or brushing cytology under endoscopic retrograde cholangiopancreatography (ERCP) prior to EUS-FNA. The final diagnosis was based on pathological examinations of specimens obtained by surgical resection or clinical follow-up more than 1 year in case of evidence of benign lesions. Results: Tissues from the ampulla of Vater could be obtained by EUS-FNA for all 10 patients. The final diagnosis was papillitis (n = 7) and intra-ampullary carcinoma (n = 3). Carcinoma of the ampulla of Vater showed neither exposure on the duodenal mucosal surface nor invasion to the pancreas. The diagnostic accuracy of surface biopsy with duodenoscopy, and intra-ampullary biopsy and/or brush cytology with ERCP and/or intra-ampullary biopsy after endoscopic sphincterotomy (EST) in distinguishing between benign and malignancy was 70%. The diagnostic accuracy of EUS-FNA was 100%. No complications associated with EUS-FNA were encountered in this study. Conclusion: EUS-FNA for ampulla of Vater may be safely and accurately performed, and should be considered as a diagnostic modality before EST.

To study the time-course of infectious asthma, we retrospectively examined FEV 1 from 5 days before to 10 days after the onset of illness in 31 asthmatic children (20 boys and 11 girls), aged 8 to 12 years. Infections were confirmed by a rise of at least fourfold in serum compliment fixation titers (respiratory syncytial virus, adenovirus, and Mycoplasma pneumoniae ) and hemoaggulutination inhibition titers (parainfluenza virus types 1,2, and 3). All the patients had 20 percent or more fall in FEV 1 from baseline value during acute phase, but were clinically tolerable and required minimum or no bronchodilators. Regardless of infectious agent, FEV 1 began to fall on the first disease day or the previous day, and deteriorate for the first few days. Mean(SD) maximum fall in FEV 1 ranged from 39(12) percent to 45(20) percent. Thereafter, FEV 1 began to improve and returned to the preillness level by the seventh to tenth day. These results suggest that progressive bronchial obstruction may be inevitable during the acute stage of any infectious asthma.

Endoscopic ultrasonography (EUS) represents the combination of endoscopy and intraluminal ultrasonography. This allows use of a high-frequency transducer (5-20 MHz) that, due to the short distance to the target lesion, provides ultrasonographic images of higher resolution than those obtained from other imaging modalities, including multiple-detector-row-computed tomography, magnetic resonance imaging, and positron emission tomography. EUS is now a widely accepted modality for diagnosing pancreatic diseases. However, the most important limitation of EUS has been the lack of specificity in differentiating between benign and malignant changes. In 1992, EUS-guided fine needle aspiration (FNA) of lesions in the pancreas head was introduced into clinical practice, using a curved linear-array echoendoscope. Since then, EUS has evolved from EUS imaging to EUS-FNA and wider applications. Interventional EUS for pancreatic cancer includes EUS-FNA, EUS-guided fine needle injection, EUS-guided biliary drainage and anastomosis, EUS-guided celiac neurolysis, radiofrequency ablation, brachytherapy, and delivery of a growing number of anti-tumor agents. This review focuses on interventional EUS, including EUS-FNA and therapeutic EUS for pancreatic cancer.

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.