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Cryptogenic stroke might relate to paradoxical embolism stemming from right-to-left shunt caused by patent foramen ovale (PFO). We performed radionuclide venography using the Valsalva maneuver, followed by (99m)Tc-macroaggregated albumin (MAA) brain SPECT to investigate the fate of emboli originating from the lower extremities.Ten patients (9 men, 1 woman; mean age, 61 +/- 17 y) with PFO underwent radionuclide venography with and without the Valsalva maneuver on the whole-body image, followed by brain SPECT with (99m)Tc-MAA to determine the cortical uptake that would detect right-to-left shunt. After counts in each region of interest (ROI) were normalized by comparison with the averaged count, the distribution of MAA was compared with that of (99m)Tc-hexamethyl-propyleneamine oxime (HMPAO) brain SPECT by drawing ROIs on frontal, temporoparietal (anterior circulation territory), occipital, and cerebellar areas (posterior circulation territory).The thyroid on the whole-body scan was visualized after the Valsalva maneuver in 2 of the 10 patients. In 7 of 10 patients, 56 ROIs in the visualized cortical uptake showed that the distribution of MAA correlated well with that of HMPAO according to the equation: HMPAO = -71.21 + 1.71 x MAA, (r = 0.575, P0.01). The excess difference in the relative counts in the posterior over anterior circulation territory was 5.6% and 16.1% of the HMPAO and MAA values, respectively.Brain SPECT with (99m)Tc-MAA was more sensitive than thyroid visualization in detecting right-to-left shunt. The excess flow in the posterior cerebral circulation indicated an increased likelihood of cerebral emboli originating from the lower extremities and indicated that the flow difference between HMPAO and MAA probably resulted from poor linearization of HMPAO in the high-flow area.

A retrospective follow-up study was conducted on patients with subacutely progressive interstitial pneumonia who underwent surgical biopsy. Pathologically, they were subclassified into subacute interstitial pneumonia (SIP) and SIP + F, which consisted of an SIP lesion and a focal usual interstitial pneumonia. The SIP group consisted of 35 cases and the SIP + F group, of 15 cases. The majority of patients in both groups were female and complained of dyspnea. Both groups showed increased neutrophil counts (8.8%, 6.3%), eosinophils (6%, 5.6%), and lymphocytes (43.1%, 42.3%) in bronchoalveolar lavage. Chest radiography generally demonstrated predominant lower lobe involvement together with shrinkage in both groups, and differentiation of the two was difficult before biopsy. All but one improved temporarily with steroid therapy, or spontaneously, in both groups. On further observation after temporary improvement, 27 cases (82%), did not show any worsening and 6 cases (18%) showed worsening (including death) in the SIP group, while 6 cases (43%) showed no worsening, though 8 cases (57%) worsened in the SIP + F group. Deaths in either group that were not related to the original diseases were excluded from the statistical analysis. We concluded that the presence of focal usual interstitial pneumonia in SIP lesions affects prognosis in patients with subacutely progressive interstitial pneumonia.

In hemophagocytic lymphohistiocytosis (HLH), cytokine-induced pancytopenia is a common finding and is associated with hypoplastic and hypocellular bone marrow and abundant hemophagocytosis. To date, neutrophil nuclear segmentation abnormalities have not been clarified in HLH patients. We report a study of bone marrow from 6 cases of HLH that showed abnormal granulocytes, dyserythropoietic changes, and micromegakaryocytes mimicking the findings in myelodysplasia at the onset of disease. Pelger-Huët anomalies were particularly noted in all cases. The increased levels of cytokines in these cases may have caused cellular damage leading to the morphological changes in the bone marrow of these HLH patients. The impact of these findings on pathophysiology and prognosis in HLH patients remains to be determined.

The effects of TS-951, a novel gastrointestinal prokinetic agent with 5-HT(4) receptor agonistic action, on the action potential parameters of isolated rabbit Purkinje fiber, ventricular muscle and sinoatrial node, and on the spontaneously beating rates of isolated rabbit right atria were compared with those of cisapride. TS-951 had no effect on the action potential parameters in both rabbit Purkinje fiber and ventricular muscle preparations. However, cisapride significantly prolonged action potential duration (APD) in both preparations. Both TS-951 and cisapride produced a negative chronotropic effect in rabbit right atria; TS-951 and cisapride at 3 x 10(-5) mol/l reduced the beating rate by about 20 and 40%, respectively. In the sinoatrial node preparations, TS-951 (3 x 10(-5) mol/l) as well as cisapride (10(-6) mol/l) prolonged cycle length and APD and reduced the diastolic depolarization rate. These results indicate that TS-951 does not appear to possess electrophysiological features leading to cardiotoxicity such as QT prolongation and, thus, torsades de pointes in common with cisapride.

Extracellular signal-regulated kinase (ERK) belongs to the family of mitogen-activated protein kinases (MAPKs), which are serine-threonine kinases activated by phosphorylation in response to a variety of mitogenic signals. We previously reported that 17 beta-estradiol rapidly activates ERK in the rat hippocampus. However, the physiological role of this rapid activation of ERK by estrogen in vivo has not yet been elucidated. This study investigated whether ERK may participate in mediating the neuroprotective effects of estrogen against quinolinic acid (QA) toxicity in the rat hippocampus in vivo. Injection of QA into the hippocampi of male rats produced a loss of Nissl-stained neurons in the CA1 after 24 h. Prior administration of 17 beta-estradiol (50 pmol/animal) to the ventricles prevented the QA-induced decrease in Nissl-stained neurons. Pretreatment with U0126, an inhibitor of MAPK/ERK kinase, inhibited the rapid activation of ERK by 17 beta-estradiol in the rat hippocampus. Moreover, the neuroprotective effects of 17beta-estradiol against QA toxicity were blocked by the pretreatment with U0126. U0126 alone did not produce a loss of neurons. These results indicate that ERK mediates estrogen neuroprotection after QA toxicity in the rat hippocampus.

We describe a boy with a deletion of the short arm of chromosome 3; (46, XY, del (3) (p25-pter) who presented several minor craniofacial anomalies at birth. Only 34 cases of small distal 3p deletion have been described in the literature, seven of them showed hearing loss and four of the 34 cases had brain anomalies. But in none of the 34 cases the middle and internal ear were radiographically examined. Despite the severe hearing loss detected by auditory brainstem evoked responses (ABR), computerized tomographic scanning (CT-scan) of the ear showed a normal anatomy in this patient. The head CT-scan and magnetic resonance imaging (MRI) disclosed a hypoplastic corpus callosum and an enlargement of the lateral ventricles.

We examined CK19 mRNA expression in the peripheral blood mononuclear cells (PBMC) from patients with ovarian tumor by reverse transcriptase-polymerase chain reaction (RT-PCR) using primers which did not cross-amplify pseudogenes of CK19 gene. The incidence of positive CK19 mRNA expression in healthy individuals, benign ovarian tumor patients and ovarian cancer patients were 60% (12/20), 71% (10/14) and 84% (21/25), respectively. Although the frequency of positive CK19 mRNA expression in PBMC from ovarian tumor patients was higher than that from healthy individuals, there was no statistically significant difference between the frequencies. Moreover, one healthy control showed CK19 mRNA expression only in her menstrual period, not in her proliferative phase or secretory phase. These results suggested that CK19 is not a suitable target to detect the presence of tumor cells in the PBMC from patients with ovarian tumors.

This study was designed to elucidate the usefulness of crosstalk correction for dual-isotope simultaneous acquisition (DISA) with 99mTc-tetrofosmin and FDG in estimating myocardial perfusion and viability.Eighteen patients with coronary artery disease were studied. First, SPECT was performed with a low-energy high-resolution collimator after a single injection of 99mTc-tetrofosmin (single 99mTc-tetrofosmin). Second, PET and DISA with an ultra-high-energy collimator were performed after glucose loading and an injection of FDG. DISA was designed to operate with simultaneous 3-channel acquisition, and weighted scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak was performed by modification of an existing dual-window technique. The FDG SPECT images were compared with the images obtained by PET. Both crosstalk-corrected and uncorrected 99mTc-tetrofosmin images were generated and compared with the single 99mTc-tetrofosmin images.Regional percentage uptake of FDG agreed well between DISA and PET. However, regional percentage uptake of 99mTc-tetrofosmin was generally higher on the uncorrected 99mTc-tetrofosmin images than on the single 99mTc-tetrofosmin images, especially in areas of low flow (percentage count of 99mTc-tetrofosminor = 50%). The crosstalk correction contributed to improving the agreement between regional percentage uptakes and significantly improved the detectability of myocardial perfusion-metabolism mismatching.With 3-channel acquisition and weighted-scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak, DISA with 99mTc-tetrofosmin and FDG is feasible for assessing regional myocardial perfusion and viability.

We characterized the genomic structure of the human ING1 gene, a candidate tumor suppressor gene, and found that the gene has three exons. We also demonstrated that four mRNA variants were transcribed from three different promoter regions. Of 34 informative cases of head and neck squamous cell carcinoma, 68% of tumors showed loss of heterozygosity at chromosome 13q33-34, where the ING1 gene is located. Here we present the first report that three missense mutations and three silent changes were detected in the ING1 gene in 6 of 23 tumors with allelic loss at the 13q33-34 region. These missense mutations were found within the PHD finger domain and nuclear localization motif in ING1 protein, probably abrogating the normal function.

To investigate the development of the voluntary control of saccadic eye movement, we examined eye movements in 99 normal children (4-13 years of age). Subjects were asked to fixate a central light for 3-5 s. A target was then presented, either to its right or left. In visually guided saccades, the mean latencies of the child group were longer than those of the adults, and decreased with age until the age of 12 where they reached adult levels. On the other hand, their peak saccadic velocities were not different from those of the adults. In the antisaccade task, they showed a higher rate of directional errors, indicating an inability to suppress reflexive saccades to the target. Mean latencies of correct antisaccades were significantly longer in the children than in the adults. Error rates and antisaccadic latency tended to decrease with age. We also examined the effects of an auditory warning signal during the fixation period and compared the results with those without. The warning stimulus was less effective in children than in adults in both tasks. Similar peak saccadic velocities between children and adults suggest the earlier development of the saccadic burst generator in the brainstem. In contrast, the delayed development of latency of saccades and antisaccades and the error rates of antisaccades suggest delayed maturation of the cerebral cortex, particularly the frontal association areas that are involved in both eye movement control and attentional processes.

The diagnostic accuracy of cardiac FDG imaging obtained with the dual-head coincidence gamma camera (DHC) is impaired by artifacts induced by nonuniform attenuation. This study proposed a new method (registration and segmentation method for attenuation correction [AC-RS]) to correct these attenuations in the chest region without the need for additional hardware or expensive transmission scanning equipment.Before DHC imaging, 99mTc-tetrofosmin SPECT was performed using dual-energy acquisition from both the photopeak and Compton scatter windows. The scatter window images of the 99mTc-tetrofosmin were then registered 3-dimensionally with the cardiac DHC images and segmented into anatomic regions to obtain body and lung contours by applying the optimal threshold method on localized histograms. Theoretic attenuation coefficient values were assigned to the corresponding anatomic regions, and the DHC emission images were reconstructed using these attenuation correction factors. The results were quantitatively evaluated by imaging a cardiac phantom filled with a uniform solution and placed in a chest phantom. Eight nondiabetic subjects were also examined using this technique, and the results were compared with those of measured attenuation-corrected PET images.Use of this technique in phantom and clinical studies decreased the degree of artifacts seen in the inferior wall activity and corrected the emission images. When the results were compared with those of PET scans, the regional relative counts of the uncorrected DHC scan did not correlate with the results of the PET scan. However, the regional relative counts of the AC-RS-corrected DHC scan exhibited a linear correlation with the results of the PET scan (r = 0.73; P0.001).Reasonably accurate attenuation-corrected cardiac DHC images can be obtained using AC-RS without the need for transmission scanning.

An indole derivative, schizocommunin, was isolated along with indigotin (indigo), indirubin, isatin, and tryptanthrin, from the liquid culture medium in which a culture of Schizophyllum commune, isolated from the bronchus of a human patient with allergic bronchopulmonary mycosis, had been grown. The structure of schizocommunin was established by spectroscopic investigation. Schizocommunin showed the strong cytotoxicity against murine lymphoma cells. The assignments of the 1H- and 13C-NMR signals of indigotin were also listed.

In mineralocorticoid target organs, 11beta-hydroxysteroid dehydrogenase type II (11beta-HSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive metabolites. Placental 11beta-HSD2 is also thought to protect the fetus from high levels of circulating maternal glucocorticoid. In this study, we examined the immunoreactivity of 11beta-HSD2 and MR in human placenta from 5 weeks gestation to full term using immunohistochemistry, 11beta-HSD2 messenger RNA (mRNA) expression using Northern blot analysis, and MR mRNA expression using RT-PCR analysis. Marked 11beta-HSD2 immunoreactivity was detected in placental syncytiotrophoblasts at all gestational stages. MR immunoreactivity was moderately detected in syncytiotrophoblasts, some cytotrophoblasts, and interstitial cells of the villous core. Marked mRNA expression of 11beta-HSD2 was detected in placenta by Northern analysis. RT-PCR analysis of MR in placental tissues showed an amplified product consistent in length with the primers selected. These results suggest that placental 11beta-HSD2 is involved in not only regulating the passage of maternal active glucocorticoids into the fetal circulation but also in regulation of maternal-fetal electrolyte and water transport in the placenta, as in other mineralocorticoid target organs.

BACKGROUND AND PURPOSE: Dual-head coincidence gamma camera (DHC) imaging has been proposed as an alternative to dedicated ring-detector positron emission tomography (dr-PET) for clinical fluorodeoxyglucose (FDG) studies. The purpose of this investigation was to assess the quality of DHC images in FDG studies of the human brain. METHODS: Seven healthy volunteers and 12 patients with various cerebral disorders underwent consecutive brain dr-PET and DHC with FDG. All sets of images were compared semiquantitatively using regions of interest. RESULTS: Cortical count ratios to the cerebellum on DHC and dr-PET images did not differ significantly among the volunteers, except in the superior frontal cortex and thalamus. In all studies including those of cerebral disorders, the mean cortical-to-cerebellar ratios of DHC and dr-PET images correlated closely. CONCLUSION: FDG imaging with DHC delineated the metabolic distribution of glucose in the brain as well as dr-PET did, except in the superior frontal cortex and thalamus. Therefore, DHC may be a dedicated cost-effective means of detecting metabolic abnormalities in the brain.

Type IIbeta-hydroxysteroid dehydrogenase endows specificity on the mineralocorticoid receptor by metabolizing cortisol and regulates sodium absorption in renal and colonic epithelium. Altered expression of this enzyme may be associated with impaired sodium absorption often seen in colonic mucosa of inflammatory bowel disease. The aim of this study was to investigate possible abnormality of 11beta-hydroxysteroid dehydrogenase protein and mRNA expression in inflammatory bowel disease. In Crohn's disease, the colonic epithelium showed comparable levels of immunoreactivity and mRNA expression to those of control, except for the decreased immunoreactivity in severe inflamed lesions with deep ulcer. In contrary, a lack or decrease of immunoreactivity was relevant in ulcerative colitis regardless of the histological degree of inflammation. The mRNA expression was also significantly decreased in ulcerative colitis. This study demonstrates that abnormality of epithelial cells in ulcerative colitis includes the enzyme that regulates water and sodium absorption, which are physiologically essential.

To clarify the features of the coexistence of active pulmonary tuberculosis in patients with lung cancer, we analyzed clinical data on 25 cases with coexisting lung cancer and active pulmonary tuberculosis encountered at Tokyo National Chest Hospital during the period from 1991 to 1998. There were 23 men and 2 women, with a mean age of 70 years. The incidence of lung cancer among patients with active pulmonary tuberculosis at our hospital was 0.7 per cent, while the incidence of active pulmonary tuberculosis in untreated lung cancer patients at our hospital was 1.9 per cent. We classified the 25 cases into 2 groups as follows: (1) tuberculosis sequential to lung cancer (11 cases) and (2) tuberculosis concurrently detected with lung cancer (14 cases). All patients in the former group were transferred from other hospitals after diagnosing the coexistence of pulmonary tuberculosis during the management of lung cancer. Histological types of lung cancer were squamous cell carcinoma in 12, adenocarcinoma in 9, and small cell carcinoma in 4, and as to the disease stage, stages III to IV were predominant. Analysis on relationship of chest X-ray findings between lung cancer and pulmonary tuberculosis revealed that in general, the location of lung cancer and tuberculosis seemed to be independent. Tuberculosis in the sequential group was more extensive and severer than in the concurrent group. In the concurrent group, treatment for tuberculosis was successful except for one case, and coexisting tuberculosis did not seem to affect the course of lung cancer among this group. However, in the sequential group, 5 patients died within 3 months, 2 of them died of tuberculosis. We consider that in the management of lung cancer, physicians should consider the possibility of coexistent active pulmonary tuberculosis and should not make delay in the diagnosis of active pulmonary tuberculosis.

We have shown recently in alert monkeys that repeated interaction between the pursuit and vestibular systems in the orthogonal plane induces adaptive changes in the VOR. To examine further properties of adaptive cross axis VOR induced by pursuit training, sinusoidal whole body rotation was applied either in the pitch or yaw plane while presenting a target spot that moved orthogonally to the rotation plane with either 90 degrees phase-lead or 90 degrees phase-lag to the chair signal. After one hour of training at 0.5 Hz (+/- 10 degrees), considerable phase-shift was observed in orthogonal eye movement responses consistent with the training paradigms by identical chair rotation in complete darkness, with further lead at lower frequencies and lag at higher frequencies. However, gains (eye/chair) induced by phase- shift pursuit training was different during pitch and yaw rotation. Although frequency tuning was maintained during pitch in the phase-shift paradigms, it was not maintained during yaw, resulting in higher gains at lower stimulus frequencies compared to the gains during yaw. This difference may reflect otolith contribution during pitch rotation. To understand further the nature of signals that induce adaptive cross axis VOR, we examined interaction of pursuit, whole field-visual pattern and vestibular stimuli. Magnitudes of the cross axis VOR with a spot alone on one hand and with a spot and pattern moving together in the same plane on the other during chair rotation were similar, and when one of the two visual stimuli was stationary during chair rotation, our well trained monkeys did not induce the cross axis VOR. These results suggest that the cross axis VOR induced by pursuit training shares common mechanisms with the cross axis VOR induced by whole field-slip stimuli and that if conflicting information is given between the two visual stimuli, adaptive changes are inhibited. Horizontal GVPs were recorded in the cerebellar floccular lobe during pitch rotation coupled with horizontal pursuit stimuli. These GVPs did not respond to pitch in the dark before training, but responded after 60 min of pursuit training with eye velocity sensitivities similar to those before training. Adaptive change in the VOR was specific to smooth eye movements but not to saccades in our paradigms.

To clarify the changes in vascular resistance in Crohn's disease, we studied changes in the thickness of arterial media histometrically. The resected specimens of mesenterium and intestine from 18 patients with Crohn's disease were used. Each intestinal lesion was classified into three grades: no inflammation, exudative change, and fibrosing change. In the ileum, significant atrophy in the media of the submucosal peripheral arteries was noted during exudative and fibrosing changes, while in the submucosal larger vessels or in the mesenterium, the thickness of the arterial media did not change. In the colon, atrophy in the media of the submucosal arteries was noted in all stages except in the larger vessel during exudative change, while no significant changes were noted in the mesenterium. In conclusion, it is suggested that circulatory disturbance occurs even in the early stage in Crohn's disease, and there seems to be increased vascular resistance in the area between the deep submucosal and the distal mesenteric arteries.

Isoforms of cytochrome P-450 (CYP) involved in the metabolism of gallopamil enantiomers were identified by measuring the disappearance rate of parent drug from an incubation mixture with human liver microsomes and recombinant human CYPs. Mean (+/- S.D.) intrinsic clearances (CL(int)) of R(+)- and S(-)-gallopamil in human liver microsomes were 0.320 +/- 0.165 and 0.205 +/- 0.107 ml/min/mg protein, respectively. These values were highly correlated with the 6beta-hydroxylation activity of testosterone, a marker substrate of CYP3A4 (r = 0.977 and 0.900 for R(+)- and S(-)-gallopamil, respectively, p.001). Ketoconazole and troleandomycin, selective inhibitors of CYP3A4, and polyclonal antibodies raised against CYP3A4/5 markedly reduced the CL(int) of gallopamil enantiomers in human liver microsomes. Among the 10 recombinant human CYP isoforms, CYP3A4 exhibited the highest CL(int) of gallopamil enantiomers, and CYP2C8 and CYP2D6 also exhibited appreciable activity. When the contribution of CYP3A4 to the total metabolic clearance of gallopamil enantiomers in human liver microsomes was estimated by relative activity factor, the mean (+/- S.D.) contributions were 92 +/- 18 and 68 +/- 19% for R(+)- and S(-)-gallopamil, respectively. These values were comparable to the rates of immunoinhibition by antibodies raised against CYP3A4/5 observed in human liver microsomes. The present study suggests that CYP3A4 is a major isoform involved in the overall metabolic clearance of gallopamil enantiomers in the human liver, and that the present approach based on disappearance rate may be applicable to identify major isoforms of CYP involved in the metabolism of a drug in human liver microsomes.

Mineralocorticoid action is essential for colonic sodium and water absorption and is mediated via mineralocorticoid receptors in the upper half of colonic crypts. On the other hand, it has been established that sodium butyrate induces differentiation-like phenomenon in vitro. The aim of this study is to investigate whether this bacterial product participates in the regulation of gene and protein expression of mineralocorticoid receptor in vitro. IEC6 and T84 cells were stimulated by sodium butyrate and RNAs extracted. Gene expression of mineralocorticoid receptor was evaluated by northern blotting or semiquantitative RT-PCR. Protein expression was determined in T84 cells using immunohistochemistry. To investigate whether MR induction was associated with cellular differentiation, we also measured alkaline phosphatase in situ. The mineralocorticoid receptor gene was induced by sodium butyrate in both IEC6 and T84 cells. Immunoreactivity increased in butyrate-treated T84 cells, but receptor-containing cells were not uniformly distributed and often formed clusters. Induction of alkaline phosphate activity was also demonstrated in both IEC6 and T84 cells. Double staining by immunoreactivity and alkaline phosphatase activity clearly demonstrated the colocalization of both after butyrate treatment. In conclusion, sodium butyrate up-regulates gene and protein expression of the functionally important mineralocorticoid receptor in epithelial cells, after induction by differentiation-like condition in vitro.

Crohn's disease (CD) is a condition characterized by excessive numbers of activated T cells in the mucosa. We investigated whether a defect in apoptosis could prolong T cell survival and contribute to their accumulation in the mucosa. Apoptotic, Bcl-2+, and Bax+ cells in tissue sections were detected by the TUNEL method and immunohistochemistry. T cell apoptosis was induced by IL-2 deprivation, Fas Ag ligation, and exposure to TNF-alpha and nitric oxide. TUNEL+ leukocytes were few in control, CD, and ulcerative colitis (UC) mucosa, with occasional CD68+ and myeloperoxidase+, but no CD45RO+, apoptotic cells. Compared with control and UC, CD T cells grew remarkably more in response to IL-2 and were significantly more resistant to IL-2 deprivation-induced apoptosis. CD T cells were also more resistant to Fas- and nitric oxide-mediated apoptosis, whereas TNF-alpha failed to induce cell death in all groups. Compared with control, CD mucosa contained similar numbers of Bcl-2+, but fewer Bax+, cells, while UC mucosa contained fewer Bcl-2+, but more Bax+, cells. Hence, the Bcl-2/Bax ratio was significantly higher in CD and lower in UC. These results indicate that CD may represent a disorder where the rate of T cell proliferation exceeds that of cell death. Insufficient T cell apoptosis may interfere with clonal deletion and maintenance of tolerance, and result in inappropriate T cell accumulation contributing to chronic inflammation.

Glucosyltransferase (GTF) plays an important role in the development of dental caries. We examined the possible presence of self-inhibitory segments within the enzyme molecule for the purpose of developing anticaries measures through GTF inhibition. Twenty-two synthetic peptides derived from various regions presumably responsible for insoluble-glucan synthesis were studied with respect to their effects on catalytic activity. One of them, which is identical in amino acid sequence to residues 1176-1194, significantly and specifically inhibited both sucrose hydrolysis and glucosyl transfer to glucan by GTF-I. Double-reciprocal analysis revealed that the inhibition is noncompetitive. Scramble peptides, composed of the identical amino acids in randomized sequence, had no effect on GTF-I activity. Furthermore, the peptide is tightly bound to the enzyme once complexed, even in the presence of sodium dodecyl sulfate (SDS). Kinetic analysis using an optical evanescent resonant mirror cuvette system demonstrated that the enzyme-peptide interaction was biphasic. These results indicate that the peptide directly interacts with the enzyme with high affinity and inhibits its activity in a sequence-specific manner. This peptide itself could possibly be an effective agent for prevention of dental caries, although its effectiveness may be improved by further modification.

We applied the QGS program for LV function analysis (described by Germano, 1995) to a 201Tl SPECT study at rest, and estimated its accuracy. We performed 201Tl ECG-gated myocardial SPECT in 25 patients with ischemic heart disease under an acquisition time used in the routine 99mTc ECG-gated SPECT study. The quality of the gated images was visually assessed with a 4-point grading system. LVEDV, LVESV, LVEF determined by the QGS program were compared with those by Simpson's method on biplane LVG in 25 patients. Regional wall motion scores in 7 myocardial segments were assessed on the three-dimensional display created by the QGS program and the cine display of biplane LVG with a 5-point grading system. Wall motion scores obtained by the QGS program were compared with those by LVG. Although 72.0% of 201Tl ECG-gated SPECT images were fair or poor in image quality, there were good correlations between the values obtained by the QGS program and LVG (LVEDV: r = 0.82, LVESV: r = 0.88, LVEF: r = 0.89). In addition, wall motion scores by the QGS program were correspondent to those by LVG in 77.1% of all 175 myocardial segments. We conclude that the QGS program provides high accuracy in evaluating left ventricular function even from 201Tl ECG-gated myocardial SPECT data.

A modulator-integrated DFB-laser transmitter module with a driver IC and a planar superlattice-APD receiver module with a preamplifier IC were developed for 10-Gbps optical transmission systems. High-speed modulation and high receiver sensitivity were successfully demonstrated by these modules.

The colon plays an important role in water and electrolyte homeostasis and is a major target tissue for aldosterone. 11 beta-Hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) confers specificity to the non-selective mineralocorticoid receptor by inactivating glucocorticoids, thus allowing binding by mineralocorticoids. Using immunohisto/cytochemistry and Northern blot analysis, we examined 11 beta-HSD2 expression in human fetal colon (23 cases ranging in age from 15 to 40 weeks gestation), neonatal colon (2 cases, 6 and 12 months old), normal adult colon (15), adenoma (35), adenocarcinoma (34) and the human colonic epithelial cell line T84, in the presence or absence of sodium butyrate, to study the correlation between enzyme expression and cellular or neoplastic differentiation. In fetal colon, weak 11 beta-HSD2 immunoreactivity was detectable in superficial epithelium from 25 weeks gestation, but normal adult levels were apparent only after 40 weeks gestation, suggesting that fully developed aldosterone induced electrolyte transport can occur only at late gestational stages. In adult normal colon, superficial absorptive cells at the top of crypts were strongly positive for 11 beta-HSD2, whereas immunoreactivity was weak in adenomas and carcinomas, and the pattern of localization varied among patients. Northern blot analysis performed on 4 cases of adenocarcinoma also demonstrated lower levels of mRNA than autologous non-neoplastic colonic mucosa. In carcinomas, 11 beta-HSD2 immunoreactivity was more frequently detected in differentiated structures, such as those forming glandular or tubular structures. Studies with T84 cells showed that expression of 11 beta-HSD2 was markedly enhanced with the addition of sodium butyrate, a well known inducer of cell differentiation in colonic epithelia. These results suggest that the expression of 11 beta-HSD2 is associated with differentiation or maturation in human colonic epithelia and that the enzyme may serve as a useful marker in development and disease.

The N-linked sugar chain structures of human hepatic, intestinal, and placental alkaline phosphatases (ALPs) were studied comparatively by chromatography on various lectin columns in combination with digestion by several kinds of exoglycosidases. The sugar chain structures were organ specific. On the basis of these organ-specific structures, we investigated serum ALP using a Neu5Ac(alpha)2--6Gal(beta)1--4 GlcNAc-specific Trichosanthes japonica agglutinin-I (TJA-I)-Sepharose column to clarify whether the level of TJA-I-binding serum ALP activity can be used as an indicator to discriminate one form of chronic liver disease from another. Levels of TJA-I-binding ALP in serum were higher in cases of liver cirrhosis and hepatocellular carcinoma than in chronic hepatitis (P0.01). The levels of TJA-I-binding ALP in serum did not change significantly after transcatheter arterial embolization, and the amounts of TJA-I-binding ALP activity in noncancerous cirrhotic liver tissues were higher than those in cancerous liver tissues derived from hepatocellular carcinoma patients, indicating that the TJA-I-binding ALP is mainly derived from cirrhotic liver tissues rather than cancerous liver tissues. These results indicate that analysis of the levels of TJA-I-binding ALP in serum is clinically useful for differentiating liver cirrhosis from chronic hepatitis and that altered sugar chain expression in ALP occurs mainly in liver cirrhosis.

Structures of N-linked sugar chains are species and tissue specific and change in the course of tumorigenesis. Sialyl linkages of human placental glycoproteins are exclusively Neu5Ac alpha2--3Gal, whereas Fuc alpha1--2Gal and Neu5Ac alpha2--6Gal residues are expressed in human chorionic gonadotropin and alkaline phosphatase, which are produced in human choriocarcinoma JEG-3 and BeWo cells. In the present study, to elucidate the enzymological and molecular biological basis of the structural changes that occur in the course of tumorigenesis, alpha1--2 fucosyltransferase, alpha2--3 and alpha2--6 sialyltransferase activities, and the expression levels of the corresponding mRNAs were measured. The alpha2--3 sialyltransferase activity did not change as a result of tumorigenesis; however, the alpha2--6 siayltransferase activity and alpha1--2 fucosyltransferase activity in JEG-3 and BeWo cells increased to levels several times higher than those in placenta Competitive PCR analysis showed that the expression levels of mRNA encoding alpha1--2 fucosyltransferase and mRNA encoding alpha2--6 sialyltransferase increased significantly as a result of tumorigenesis, indicating that such structural changes are regulated at the level of transcription of these glycosyltransferase genes.

To examine the effects of smooth-pursuit eye movements on the initiation of saccades, their latency was measured when subjects initially fixated or pursued a target. In half of the block of trials, the fixation or pursuit target was extinguished 200 ms before the saccade target was illuminated (gap trials). Reduction of the mean saccade latency in the gap trials (the "gap effect") was evident even when the subjects were pursuing a moving target, consistent with previous observations. The effect of pursuit direction on saccade latency was also examined. Saccades in the same direction as the preceding pursuit (forward saccades) had shorter latencies than those in the opposite direction (backward saccades). This asymmetry was observed in both the gap and nongap trials. Although the forward-backward asymmetry was much smaller than the "gap effect", it was statistically significant in six of eight cases. These results suggest that the preparation of saccades is affected by smooth-pursuit eye movements.

A 56-year-old man with pure red cell aplasia (PRCA), hypogammaglobulinemia and mediastinal tumor was admitted to our hospital with of dyspnea, high fever and general fatigue. Chest X-ray showed a large cavity with a niveau in the left lung. Biopsy of the mediastinal tumor revealed an epithelial cell-type thymoma. Lung abscess with Good's syndrome and PRCA was diagnosed. Antibiotics was administered, and percutaneous catheter drainage of the lung abscess was performed. He recovered and was discharged. Hypogammaglobulinemia in the case may have resulted from reduced production of gammaglobulin associated with a quantitative B-cell defect.

Sodium butyrate is a well-recognized differentiating agent inducing alkaline phosphatase activity, one of the epithelial differentiation markers. When IEC6 cells, a nontransformed, small intestinal epithelial cell line, were cultured with butyrate, this substrate induced alkaline phosphate activity in a time- and dose-dependent fashion. However, the type of isoenzyme involved was a liver-type, not an intestinal-type. Electron microscopy revealed that the induced activity was strictly localized in the cytosol and not on the plasma membrane. However, disaccharidase activities, another kind of differentiation marker, were also enhanced by sodium butyrate. In addition, the positive cells demonstrating the presence of alkaline phosphatase activity were preferentially observed in tubular structures. These data show that butyrate-induced alkaline phosphatase activity is closely associated with differentiation-like phenomena in IEC6 cells, although the type of isoenzyme and cellular localization of the activity are different from those observed in mucosa.

P193 Long-term incidence and characteristics of intestinal failure in Crohn’s disease: A Japanese multicentre study K. Watanabe1 *, I. Sasaki1, K. Fukushima2, K. Futami3, H. Ikeuchi4, A. Sugita5, R. Nezu6, T. Mizushima7, S. Kameoka8, M. Kusunoki9, K. Yoshioka10, Y. Funayama11, T. Watanabe12, H. Fujii13, M. Watanabe14. 1Tohoku University Graduate School of Medicine, Surgery, Sendai, Japan, 2Tohoku University Graduate School of Medicine, Laboratory of GI tract reconstruction, Sendai, Japan, 3Fukuoka University Chikushi Hospital, Surgery, Fukuoka, Japan, 4Hyogo College of Medicine, Inflammatory Bowel Disease Center, Nishinomiya, Japan, 5Yokohama Municipal Citizen’s Hospital, Surgery, Yokohama, Japan, 6Nishinomiya Municipal Central Hospital, Surgery, Nishinomiya, Japan, 7Osaka University Hospital, Gastroenterological Surgery, Suita, Japan, 8Tokyo Women’s Medical University, Surgery II, Tokyo, Japan, 9Mie University Hospital, Gastrointestinal and Pediatric Surgery, Tsu, Japan, 10Kansai Medical University Takii Hospital, Surgery, Moriguchi, Japan, 11Tohoku Rosai Hospital, Surgery, Sendai, Japan, 12The University of Tokyo, Surgical Oncology, Tokyo, Japan, 13Nara Medical University Hospital, Endoscopy, Kashihara, Japan, 14Tokyo Medical and Dental University, Gastroenterology, Tokyo, Japan

Experimental Penicillium marneffei infection in mice was investigated histopathologically and by electron microscopy. Viable conidia (5 x 10(6) cells) of P. marneffei were inoculated into each mouse of group A (BALB/c mice) and group B (BALB/c-nu/nu-SIc mice) through the tail vein. All the mice were sacrificed at intervals and the livers were examined. In group A, the conidia were phagocytosed by Kupffer cells soon after inoculation, and proliferated by fission in the cytoplasm. Marked proliferation of yeast cells was observed 7 and 14 days after inoculation. With proliferation of the fungus, the number of lysosomes in Kupffer cells increased, and numerous granulomas were formed in the liver. These granulomas consisted mainly of macrophages with yeast cells, together with a few polymorphonuclear leukocytes, lymphocytes and giant cells. From 28 days on yeast cells were gradually cleared from the granulomas, and 56 days after inoculation almost all the granulomas disappeared. In group B, at an early stage of infection, similar pathological changes to those seen in mice of group A were observed. However, as the infection progressed, the number of granulomas continued to increase and yeast cells continued to proliferate although lymphocytes did not infiltrate these granulomas. With proliferation of yeast cells the liver tissue was replaced with both yeast cells engulfed by macrophages and extracellular yeasts, and dissemination occurred.

To investigate whether habituation occurs in ocular counterrolling (OCR), how stable shifted Listing's plane is, and what effects visual stimulation and alertness exert on the OCR and on Listing's plane.Two monkeys (Macaca fuscata) were engaged in this experiment. A dual scleral search coil method was used for recording three-dimensional eye movements. Spontaneous eye movements were recorded for 2 hours in dark and light, while each monkey was held in different static roll positions (up to +/-34 degrees) with its head fixed. Eye movements were also recorded during the monkeys' drowsy periods in the dark.In alert conditions, OCR gains showed some fluctuations but did not change consistently for 2 hours in seven of seven sessions in the dark and in seven of nine sessions in the light. The OCR gains in the light did not differ from those in the dark. The thickness of shifted Listing's plane during the static roll-tilt was also stable for 2 hours and was within the range of the thickness of Listing's plane in the upright position in the light. During drowsy periods, the thickness of Listing's plane increased, and the gain in OCR decreased.Ocular counterrolling shows no habituation for 2 hours of static roll-tilts in the alert monkey. In the same condition, Listing's plane consistently maintains its precision. Visual input does not affect OCR, but alertness is necessary to keep the stability of OCR and Listing's plane.

A 46-year-old man was admitted to the hospital for evaluation of a dense infiltrative shadow in the right middle lung field. Bronchoscopic examination revealed a polypoid lesion in the right middle-lobe bronchus (Bb11(5)). Examination of a biopsy specimen showed a lump with many Nocardia asteroides bacteria. The response to chemotherapy, which included sulfomethoxazole, was poor, and therefore a right middle lobectomy was done. Three mycetomas were found inside the ectatic bronchi in the S5 area. Pulmonary Nocardia mycetoma is rare.

Acceleration of heart rate simultaneously with excitatory movements was observed during anesthesia with propofol in four patients. Anesthesia was induced with propofol 2.5 mg.kg-1 i.v. and maintained with propofol 10 mg.kg-1.hr-1 i.v. About ten minutes after the induction, the patients showed jerking movements such as pronation or flexion of their arms, and/or plantar flexion. These movements lasted one or two seconds and appeared two or three times a minute. Three patients received vecuronium 0.1 mg.kg-1 and even after muscular relaxation acceleration of heart rate persisted. In one of two patients who had received midazolam 0.8 mg.kg-1, heart rate acceleration ceased. In one patient acceleration of heart rate and excitatory movements stopped after reducing the infusion rate of propofol from 10 mg.kg-1.hr-1 to 3 mg.kg-1.hr-1. Another patient with no involuntary movements showed no heart rate changes. These results suggest that heart rate acceleration in four patients was closely related to excitatory movements caused by propofol. As it was not influenced by muscular relaxation, heart rate monitoring would be useful to detect latent excitatory movements under muscular relaxation.