Gastric adenocarcinoma of fundic gland type (chief cell predominant type) with unique endoscopic appearance curatively treated by endoscopic submucosal resection.

Gastric adenocarcinoma of fundic gland type [chief cell predominant type; (GA-FD-CCP)] is a rare gastric cancer variant arising from non-atrophic mucosa without Helicobacter pylori infection in the upper third portion of the stomach. GA-FD-CCP originates deep in the mucosal layer; hence, endoscopic lesion detection is often difficult at an early stage because of a minimal change in the mucosal surface. Here we present a 66-year-old man with an early stage of GA-FD-CCP showing characteristic endoscopic features. Esophagogastroduodenoscopy demonstrated a flat, slightly reddish area with black pigment dispersion and irregular micro-surface structure at the gastric fornix. The tumor was resected by endoscopic submucosal dissection and was pathologically diagnosed as GA-FD-CCP. Prussian blue staining revealed that the black pigment was a hemosiderin deposition. We reported a rare case of successfully treated GA-FD-CCP with black pigmentation that aided in early lesion detection.

Circadian variation of basal total vascular tone and chronotherapy in patients with vasospastic angina pectoris.

Vasospastic angina pectoris (VSA) is an anginal attack which occurs characteristically between night and early morning. The aim of this study was to clarify the cause of VSA. The subjects consisted of 16 patients with VSA, 18 patients with effort angina (EAP) and 15 healthy individuals, who were used as the control group. Subjects were attached to an ambulatory blood pressure monitor and a non-invasive continuous cardiac output monitor concurrently, over a 24-hour period. Mean blood pressure (MBP), and cardiac index (CI) were measured. Then basal total vascular tone (TVT) was calculated as follows: basal TVT = (MBP/CI) x 1,332 dyne/sec/cm5. The decrement of CO was greater during sleeping hours as compared with the decrement of the MBP in the VSA group. Nocturnal basal TVT was significantly greater in the VSA group than in the EAP group or the control group. The increased nocturnal basal TVT was significantly suppressed by long acting calcium antagonists to the level of the EAP and the control groups. The treatment also decreased the frequency of ischemic attacks.

The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment.

Human beta-defensin-2 (HBD-2) is a member of the defensin family of antimicrobial peptides. HBD-2 was first isolated from inflamed skin where it is posited to participate in the killing of invasive bacteria and in the recruitment of cells of the adaptive immune response. Static light scattering and two-dimensional proton nuclear magnetic resonance spectroscopy have been used to assess the physical state and structure of HBD-2 in solution. At concentrations of < or = 2.4 mM, HBD-2 is monomeric. The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta-sheet with strands 2 and 3 in a beta-hairpin conformation. A beta-bulge in the second strand occurs at Gly28, a position conserved in the entire defensin family. In solution, HBD-2 exhibits an alpha-helical segment near the N-terminus that has not been previously ascribed to solution structures of alpha-defensins or to the beta-defensin BNBD-12. This novel structural element may be a factor contributing to the specific microbicidal or chemokine-like properties of HBD-2.

Experimental observation of vertically polarized transverse dust-lattice wave propagating in a one-dimensional strongly coupled dust chain.

Externally driven, vertically polarized transverse dust-lattice waves were observed in a one-dimensional strongly coupled dust chain levitated in the plasma-sheath boundary of a dc argon plasma at low gas pressure around 5 mtorr. Real and imaginary parts of the complex wave number were measured in the experiments. The experimental result clearly shows that the observed transverse dust-lattice wave propagates as a backward wave, which is in good agreement with the theoretical prediction.

Cell cycle-dependent switch of up-and down-regulation of human hsp70 gene expression by interaction between c-Myc and CBF/NF-Y.

A CCAAT box-binding protein subunit, CBF-C/NF-YC, was cloned as a protein involved in the c-Myc complex formed on the G(1)-specific enhancer in the human hsp70 gene. CBF-C/NF-YC directly bound to c-Myc in vitro and in vivo in cultured cells. The CBF/NF-Y.c-Myc complex required the HSP-MYC-B element as well as CCAAT in the hsp70 G(1)-enhancer, while the purified CBF subunits recognized only CCAAT even in the presence of c-Myc. Both the HSP-MYC-B and CCAAT elements were also required for the enhancer activity. In transient transfection experiments, the CBF/NF-Y.c-Myc complex, as well as transcription due to the G(1)-enhancer, was increased by the introduction of c-Myc at low doses but decreased at high doses. The repression of both complex formation and transcription by c-Myc at high doses was abrogated by the introduction of CBF/NF-Y in a dose-dependent manner. Furthermore, the CBF/NF-Y.c-Myc complex bound to the G(1)-enhancer appeared in the early G(1) phase of the cell cycle when c-Myc was not higly expressed and gradually disappeared after the c-Myc expression reached its maximum. The results indicate that the cell cycle-dependent expression of the hsp70 gene is regulated by the intracellular amount of c-Myc through the complex formation states between CBF/NF-Y and c-Myc.

Expression of the Bombyx mori beta-tubulin-encoding gene in testis.

We have isolated a beta-tubulin-encoding cDNA clone of Bombyx mori from testes and determined the nucleotide sequence. Northern analyses showed that its expression is testis-specific and most active in the pupal stage.

Isolation and characterization of activin receptor from mouse embryonal carcinoma cells. Identification of its serine/threonine/tyrosine protein kinase activity.

The activin receptor protein was isolated from the mouse embryonal carcinoma (EC) cell line P19 by three cycles of affinity chromatography on an activin A-immobilized column. The purified receptor had a specific and high affinity for activins A, AB, and B (Kd = 345 pM), but not for transforming growth factor beta. The purified activin receptor was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ligand blotting analysis as a single protein of 70 kDa. The amino acid sequence of the first 18 NH2-terminal residues revealed that the receptor is a member of the activin receptor family. The purified receptor phosphorylated itself and exogenous substrate proteins on serine, threonine, and tyrosine residues, indicating that the activin receptor is a transmembrane serine/threonine/tyrosine protein kinase. These results suggest that signal transduction of activin employs a novel pathway via a new class of cellular receptor in EC P19 cells.

Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines: kinetics of the arrest and expression of the cell cycle marker proliferating cell nuclear antigen in Raji cells.

In order to elucidate further the mechanism of reversible cell cycle arrest induced by treatment of Raji cells with 1.5% dimethyl sulfoxide (DMSO), we have performed a detailed analysis of the kinetics of arrest and of reentry into the cell cycle after removal of DMSO and have correlated cell cycle progression with expression of proliferating cell nuclear antigen (PCNA). No significant effect of DMSO on cell cycle patterns, assessed by flow cytometric analysis of bromodeoxyuridine-prelabeled cells, was seen for the first 19 h of treatment. A clear reduction of entry into S phase was detected by about 25 h of treatment; essentially all cells were arrested with a G1 content of DNA after 96 h of treatment. When DMSO-arrested cells were released from the block, entry into S phase began at 12 h after release and continued in a fairly asynchronous manner for a further 12-14 h. In arrested cells, the content of PCNA was reduced to about 25% of the amount present in logarithmically growing G1 phase cells. Six h after release from DMSO, PCNA RNA transcripts were first detected by Northern blotting. The increase of PCNA protein, detected by Western blotting, was seen by 9 h after release. The kinetics of entry into the cell cycle and restoration of PCNA protein are similar to that seen in serum stimulation of quiescent cells. These results suggest that DMSO reversibly arrests proliferation of Raji cells at G0 or at an early point in G1 phase and that progression through late G1 phase and entry into S phase are correlated with synthesis of the PCNA gene product.

[Evaluation of myocardial oxygen extraction dynamics in syndrome X by continuous measurement of coronary sinus oxygen saturation and its relation to clinical features].

We investigated the relation of myocardial oxygen extraction dynamics to pathophysiology and clinical features in syndrome X. In patients with syndrome X who underwent cardiac catheterization, coronary sinus oxygen saturation (n = 21) during rapid atrial pacing loading was continuously measured using a fiberoptic catheter system, and global and regional left ventricular function (n = 14) was evaluated before and immediately after pacing loading. Results were as follows: 1) In 5 of 21 patients with syndrome X, coronary sinus oxygen saturation during pacing loading fell less than 5% below the baseline without any impairments of global and regional left ventricular function. 2) In 16 patients with syndrome X, coronary sinus oxygen saturation during the pacing loading continuously fell over 5% below the baseline accompanied by impairment of both global and regional left ventricular function. The decrease in regional wall motion of the left ventricle was mainly observed in the apical area. These findings imply that changes in myocardial oxygen extraction dynamics in syndrome X during rapid atrial pacing may show the extent of a patchy area where myocardial oxygen demand-supply imbalance occurs due to coronary microcirculatory disturbances.

DNA ligase I mRNA and enzyme levels in human hematopoietic cells under dimethyl sulfoxide-induced growth-arrest and differentiation.

About half the activity level of DNA ligase I in cycling human lymphoblastoid cells (Raji and Akata) remained in the cells arrested at G1 by a 4-day treatment with 1.5% dimethyl sulfoxide (DMSO), and one-third the enzyme activity in actively growing promyelocytic leukemia cells HL-60 was detected in the terminally differentiated cells after DMSO-treatment. In contrast, DNA ligase I mRNA was negligible in the G1-arrested Raji and differentiated HL-60 cells. The steady-state mRNA level was increased 9 h after release from DMSO in the G1-arrested Raji cells and reached a maximum at 18 h. These results indicate that gene expression of human DNA ligase I, but not activity level of the enzyme, is closely correlated with activity of cell proliferation.

[A case of adult type of anomalous origin of left coronary artery from pulmonary artery--with a referential consideration to the disease in Japan].

A case of a 33-year-old man with anomalous origin of the left coronary artery from the pulmonary artery (ALCP) was reported with a referential consideration to the adult type of ALCP previously reported in Japan. The patient visited our hospital for further examination of cardiac murmur detected on a mass physical checkup. He was found to have a continuous murmur, the loudest in the left sternal border of 3rd intercostal space, and developed evidence of ischemia during the exercise stress test in the ECG leads of L2, L3, aVF, and V2 through V6. In addition, studies using echocardiography and color Doppler-echocardiography detected a hypertrophied intraventricular septum and a pattern of turbulent blood flow in the proximal pulmonary artery. Cardiac catheterization and aortography proved the existence of ALCP with a markedly developed collateral circulation from the right coronary artery to the left coronary artery. After surgical restoration by ligating the anomalous opening of the left coronary artery, and by bypass grafting to the left coronary artery, it was clear that dilation and kinking of the right coronary artery was lessened and hypoperfusion in the anterior left ventricular wall was improved. As far as we know, this case is the 35th of adult type ALCP reported in our country. Results from this case and others suggest that early detection and therapy for adult type ALCP is important from the point of view preventing ischemic progression, and indicate that restoration by ligation and bypass grafting may be one of the effective surgical procedures for ALCP.

Expression of c-fos and c-myc in Raji Burkitt's lymphoma cells during the progression of DMSO-induced G1 cells into S phase.

Using flow cytometry, we have recently found that dimethyl sulfoxide (DMSO) reversibly induces G1-arrest in the cell cycle of human lymphoid cell lines such as Raji, Akata, and Molt-4. Here we investigated c-fos and c-myc expression in Raji Burkitt's lymphoma cells at DMSO-induced G1 arrest and after release from DMSO. A small but significant accumulation of c-fos mRNA was observed in G1-arrested Raji cells after treatment with 1.5% DMSO for 96 h. When G1-arrested Raji cells were transferred to DMSO-free medium, a transient increase in c-fos transcripts was detected 30-60 min after the release. The steady state level of c-myc transcripts in G1-arrested Raji cells was found to be one-third that in the log-phase cells. After removal of DMSO, the level of c-myc mRNA was restored and reached a maximum at 4.5-6 h. Immunoblot analysis with a monoclonal antibody against human c-myc protein indicated that c-myc protein in the G1-arrested cells was decreased less than one-tenth that in the log-phase cells. The level of c-myc protein gradually increased after the release from DMSO and reached a maximum at 6-9 h.

[Coronary venous oxygen saturation dynamics during intracoronary infusion of ergonovine or acetylcholine in vasospastic angina].

We investigated changes in coronary venous oxygen saturation (CSO2-Sat) dynamics during intracoronary infusion of ergonovine (ERG) or acetylcholine (ACh) in patients with vasospastic angina. In 16 patients with suspected vasospasm in the left coronary artery, intracoronary ERG injection provoked vasospasm in 4 out of 6 patients, and intracoronary ACh in 6 out of 11 patients. A gradual decrease in CSO2-Sat, anteceding angina and ischemic ECG evidence, was characteristic in ERG-induced vasospastic patients, while no significant change of CSO2-Sat was observed in non ERG-induced patients. Intracoronary infusion of ACh was followed in all 11 patients by a transient increase in CSO2-Sat, suggesting decreased myocardial oxygen extraction due to increased coronary blood flow with ACh. However, earlier and sudden decreases in CSO2-Sat below the control levels were characteristic in 6 patients with ACh-induced vasospastic angina. These findings suggest that effects of ERG and ACh on coronary flow dynamics are essentially different although both drugs can provoke vasospasm.

[Correlations between redistribution areas observed on exercise thallium-201 myocardial SPECT images and the coronary collateral circulations in patients with myocardial infarction].

The significance of coronary collateral circulation for redistribution in the infarcted zone was evaluated in 16 patients with history of myocardial infarction and severe stenosis (> or = 90%) of the coronary artery. Redistribution areas were quantitatively measured using the redistribution ratios and redistribution indices on the infarction-redistribution map obtained by thallium-201 scintigraphy with single photon emission computed tomography. Coronary collateral findings were categorized in 4 classes according to the Rentrop's grading. There was good, positive linear correlation between the redistribution ratio (Y) and collateral grading (X) (Y = 0.21X + 0.10, r = 0.92, p < 0.01). The redistribution index (X) also correlated well with the collateral grading (Y) using a good, positive quadratic equation (Y = 0.32X2 + 0.24X + 0.04, r = 0.89, p < 0.01). These results suggest that the measurements of the redistribution areas in the ischemic zone in myocardial infarction correlated well with collateral perfusion. Collateral perfusion severer than Rentrop's grade 2 markedly reduces the severity of ischemia and increases redistribution areas.

[Continuous measurement of coronary sinus oxygen saturation in patients with effort angina and vasospastic angina].

Coronary sinus oxygen saturation (CSO2-Sat) was measured continuously using a fiberoptic catheter system during interventional catheterization, i.e., pacing stress test and ergonovine provocation test to determine whether such measurement can detect myocardial ischemia. Subjects consisted of 24 patients who underwent routine cardiac catheterization; 14 patients with effort angina, 3 with old myocardial infarction and 3 with valvular heart disease were assigned to pacing stress test, and 4 with vasospastic angina were assigned to ergonovine provocation test. The results were as follows: 1. Among 14 patients with effort angina, ischemic electrocardiographic changes occurred in 10 patients during pacing stress test. Of these 10 patients, CSO2-Sat decreased in 8 with ischemic electrocardiographic changes. All patients with decrease in CSO2-Sat had significant left coronary artery stenosis. CSO2-Sat continued to decrease throughout intervention and never came back to the baseline. Decrease in CSO2-Sat was more than 5% in most of the cases. 2. In all patients with vasospastic angina, coronary vasospasm was induced by the ergonovine provocation test. CSO2-Sat declined (> 5%) gradually, preceding anginal pain and ischemic ST segment changes. The present study suggests that continuous monitoring of coronary sinus oxygen saturation may be useful in detecting myocardial ischemia at its early stage, except for patients with right coronary artery disease.

Measurement of bronchial hyperreactivity in infants and preschool children using a new method.

We report a new method for examination of bronchial reactivity by measuring transcutaneous oxygen pressure (tcPO2) during the inhalation of histamine in stepwise incremental concentrations. The correlation between changes in tcPO2 and those in PEFR or FEV1 was high (P less than .001). When the fall in PEFR or FEV1 was more than 20% compared with baseline, the fall in tcPO2 was more than 10%. We also measured the dose of radiolabeled aerosol (99mTc-DTPA) inhaled into the lung using a scintillation camera. When aerosol is inhaled during tidal breathing, there are adequate correlations between the dose of aerosol in the lung and both the age and height of the patients (P less than .001). When aerosol was inhaled during crying, little deposit within the lung was shown. When the inhalation challenge test was done during a sleeping period for children aged under 2 years, the loading dose of aerosol in the lung was sufficient. The geometrical means of respiratory threshold of histamine (RT-Hist) among 106 asthmatic and 11 control children, aged 2 to 6 years, were 1182 and 4414 micrograms/mL, respectively. The means of RT-Hist in 17 children with bronchial asthma, nine with atopic dermatitis, five with respiratory disease, and nine controls, aged under 2 years, were 1152, 964, 544, and 3402 micrograms/mL, respectively.

Reversible G1 arrest in the cell cycle of human lymphoid cell lines by dimethyl sulfoxide.

Proliferation of human B- and T-lymphoid cell lines including Raji and Akata cells was found to be arrested at the G1 stage in the cell cycle by dimethyl sulfoxide (DMSO). The G1 arrest by DMSO occurred gradually and was completed within 96 h after addition of 1.5% DMSO concomitantly with a decrease in growth rate. Progression of G1-phase cells containing a larger amount of RNA into S-phase began 9-12 h after removal of DMSO. At 24 h, the DNA pattern of the cell cycle was similar to that of nontreated log-phase cells. The expression of six differentiation markers on the lymphoid cells was not appreciably changed by treatment with DMSO. On the other hand, the expression of transferrin receptor (one of the growth-related markers) on G1-phase cells 96 h after addition of DMSO was decreased to one-fourth that on log-phase cells and was completely restored 24 h after removal of DMSO. These results indicate that DMSO, known as an inducer of differentiation in several myeloid cell lines, acts as an agent inducing G1 arrest in the cell cycle of the lymphoid cells.