Clinical characteristics of lupus enteritis in Japanese patients: the large intestine-dominant type has features of intestinal pseudo-obstruction.

This study was performed to investigate the clinical characteristics of lupus enteritis in Japanese patients with systemic lupus erythematosus (SLE). A total of 481 patients with SLE admitted to our hospital between 2001 and 2015 were retrospectively reviewed. Diagnosis of lupus enteritis was based on the following three criteria: (1) abdominal symptoms, (2) diffuse long-segment bowel thickening and (3) a requirement for glucocorticoid therapy. Lupus enteritis was identified in 17 patients (3.5%) and there were two distinct types: small intestine-dominant and large intestine-dominant. Significant differences between the two types were noted with respect to the age, frequency of biopsy-proven lupus nephritis, frequency of rectal involvement, maximum bowel wall thickness, and requirement for steroid pulse therapy. Among patients with large intestine-dominant lupus enteritis, 60% had extra-intestinal symptoms (hydroureter, bladder wall thickening, and bile duct dilatation) that are known complications of intestinal pseudo-obstruction. Two patients with large intestine-dominant lupus enteritis developed intestinal pseudo-obstruction either before or after diagnosis of lupus enteritis. Five patients (29%) developed recurrence during a median observation period of 7.2 years (1.4-14.4 years). In conclusion, large intestine-dominant lupus enteritis resembles intestinal pseudo-obstruction and these two diseases may have a common pathogenesis.

Site Specificity of Changes in Cortical Oxyhaemoglobin Concentration Induced by Water Immersion.

Our previous studies have shown that water immersion (WI) changes sensorimotor processing and cortical excitability in the sensorimotor regions of the brain. The present study examined the site specificity of the brain activation during WI using functional near infrared spectroscopy (fNIRS). Cortical oxyhaemoglobin (O2Hb) levels in the anterior and posterior parts of the supplementary motor area (pre-SMA and SMA), primary motor cortex (M1), primary somatosensory cortex (S1), and posterior parietal cortex (PPC) were recorded using fNIRS (OMM-3000; Shimadzu Co.) before, during, and after WI in nine healthy participants. The cortical O2Hb levels in SMA, M1, S1, and PPC significantly increased during the WI and increased gradually along with the filling of the WI tank. These changes were not seen in the pre-SMA. The results show that WI-induced increases in cortical O2Hb levels are at least somewhat site specific: there was little brain activation in response to somatosensory input in the pre-SMA, but robust activation in other areas.

The effect of magmatic activity on hydrothermal venting along the superfast-spreading East pacific rise.

A survey of hydrothermal activity along the superfast-spreading (approximately 150 millimeters per year) East Pacific Rise shows that hydrothermal plumes overlay approximately 60 percent of the ridge crest between 13 degrees 50' and 18 degrees 40'S, a plume abundance nearly twice that known from any other rige portion of comparable length. Plumes were most abundant where the axial cross section is inflated and an axial magma chamber is present. Plumes with high ratios of volatile ((3)He, CH(4), and H(2)S) to nonvolatile (Mn and Fe) species marked where hydrothermal circulation has been perturbed by recent magmatic activity. The high proportion of volatile-rich plumes observed implies that such episodes are more frequent here than on slower spreading ridges.

16S rRNA gene sequence-based analysis of clostridia related to conversion of germfree mice to the normal state.

AIMS: To determine phylogenetic groups of clostridia inhabiting the mouse intestine that are essential for normalization of germfree (GF) mice. METHODS AND RESULTS: Using both the culture method and cloning, clostridia inhabiting the mouse intestine were isolated, and phylogenetic analysis based on 16S rRNA gene sequences was carried out. As a result, the isolates were found to have novel sequences, and no isolate was determined to be identical to previously known identified clostridia. Although the taxonomy of mouse intestinal clostridia was complex, many of them belonged to Clostridium clusters XIVa and IV in conventional (CV) and limited flora mice and ex-germfree mice administered chloroform-treated CV mouse faeces. The clostridia that belonged to cluster XIVa were most often present and showed the highest diversity. CONCLUSIONS: Clostridia belonging clusters XIVa and IV are dominant in the mouse intestine as in other gut ecosystems. The novel groups in these clusters are essential for normalization of GF mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study can be applied in the strict control of mouse intestinal microbiota and will provide important information for normalization of GF mice and also for research on microbiology of the mouse intestine.

pH-sensing nano-crystals of carbonate apatite: effects on intracellular delivery and release of DNA for efficient expression into mammalian cells.

Two unique and fascinating properties of carbonate apatite which are well-known in hard tissue engineering, have been unveiled, for the first time, for the development of the simplest, but most efficient non-viral gene delivery device - ability of preventing the growth of crystals needed for high frequency DNA transfer across a plasma membrane and a fast dissolution rate for effective release of DNA during endosomal acidification, leading to a remarkably high transgene expression (5 to 100-fold) in mammalian cells compared to the widely used transfecting agents. Moreover, by modulating the crystal dissolution rate of carbonate apatite through incorporation of fluoride or strontium into it, transfection activity could be dramatically controlled, thus shedding light on a new barrier in the non-viral route, which was overlooked so far. Thus we have developed an innovative technology with significant insights, that would come as a promising tool for both basic research laboratories and clinical settings.

Novel diglycosyldiacylglycerol from the gram-negative bacterium Deleya marina.

A glycosyldiacylglycerol was isolated from the marine bacterium Deleya marina (ATCC 25374). The structure was determined, mainly by spectral data, to be 1, 2-diacyl-3-O-[alpha-2-amino-2-deoxy-glucopyranose-(1-->4)-O-alpha-idu ronopyranuronic acid]-glycerol. This is, to our knowledge, the first isolation of diglycosyldiacylglycerol containing both iduronopyranuronic acid and 2-amino-2-deoxy-glucopyranose from Gram-negative bacteria.

Familial Bartter's syndrome.

Two sisters were found to have Bartter's syndrome. Both had hypokalemia, hyperreninemia, normal BPs, and decreased pressor responses to angiotensin II. During a water diuresis, patient 1 had an abnormally low distal tubular fractional reabsorption of chloride initially, but this normalized after hypokalemia was corrected for one year. Patient 2 had no demonstrable defect in chloride transport. Hypokalemia in Bartter's syndrome may be caused by some hereditary mechanisms other than defective reabsorption of chloride in the distal tubules.

Design of polymer materials enhancing nucleotide hybridization for anti-gene technology.

Stabilization of nucleotide hybridization is considered important for improving gene therapy using oligonucleotides. We have designed comb-type copolymer consisting of polycation backbone (polylysine) and hydrophilic side chains as a stabilizer for double and triple helical DNAs. The copolymer considerably increased the thermal stability of triple helical structure but did not affect the reversible transition between triple helical and single-stranded DNA. An in vitro electrophoretic mobility shift assay revealed that the copolymer remarkably increased association constants of both Hoogsteen and reverse Hoogsteen-type triple helix formation. Moreover the triple helix-stabilizing efficiency of the copolymer was significantly higher than that of other oligocations like spermine and spermidine. Not only being good DNA triple helix stabilizer, it has also been shown to accelerate DNA strand exchange reactions between double helical DNA and its complementary oligonucleotides. From these, we conclude that this copolymer is capable of either 'stabilizing' or 'activating' DNA hybrids, and may useful for gene targeting employing oligonucleotides.

Blood pressure response to an angiotensin II antagonist in patients with acromegaly.

The renin-angiotensin-aldosterone system in patients with acromegaly was evaluated by infusing [sarcosine1, isoleucine8]angiotensin II, a competitive angiotensin II antagonist, into five acromegalic patients with hypertension and three normotensive acromegalics. The drug was infused at a rate of 600 ng/kg . min for 30 min, 1 h after iv injection of 40 mg furosemide. In addition, before the infusion, plasma samples were obtained for determination of PRA and plasma aldosterone concentration. A significant pressor response to [sarcosine1, isoleucine8]angiotensin II was observed in all eight patients. Preinfusion PRA and plasma aldosterone concentration were significantly lower than in normal controls. It is concluded that in acromegaly, the renin-angiotensin-aldosterone system is suppressed and that this system is probably not involved in maintenance of the high blood pressure observed in some acromegalic patients.

The effect of aging on urinary kallikrein excretion in normotensive subjects and in patients with essential hypertension.

The effect of aging on urinary kallikrein excretion (UkalV) was investigated in 54 normal subjects, 11-88 yr old, and 37 patients with essential hypertension, 17-82 yr old. Urinary sodium, potassium, and aldosterone excretion (U(Ald)V) were also measured in these subjects. Urinary sodium and potassium excretion in both normal subjects and hypertensive patients did not significantly change with aging. In normal subjects, U(kal)V (r = 0.45; P less than 0.001) and U(Ald)V (r = 0.58; P less than 0.01) significantly decreased with increasing age. U(kal)V was positively correlated with U(Ald)V (r = 0.44; P less than 0.001). In contrast, the hypertensive patients had a significant decrease with age in U(Ald)V (r = -0.36; P less than 0.05), but no significant age-related change in U(kal)V. No significant correlation between U(kal)V and U(Ald)V was observed in the hypertensive patients. In individuals less than 60 yr old, there was no significant difference in U(kal)V values between normal subjects and hypertensive patients. Hypertensive patients more than 60 yr old excreted more urinary kallikrein than normal subjects of the same age group (P less than 0.05). In conclusion, the age-related decrease of U(kal)V in normal subjects may be due to the reduced activity of the renin-angiotensin-aldosterone system. It remains to be elucidated whether the absence of the age-related decrease in U(kal)V in hypertensive patients is related to the pathogenesis or pathophysiology of essential hypertension.

Long-term effects of captopril in hypertension.

Captopril was given for treatment of hypertension alone or in combination with diuretics to 32 patients for 1- to 4-mo periods. The decrement of mean blood pressure after 1 and 2 mo correlated with pretreatment plasma renin activity (PRA) and the response of blood pressure to infusion of an angiotensin II antagonist. These correlations were no longer apparent after 4 mo of treatment. When subjects with a decrement of mean blood pressure that exceeded 13 mm Hg were compared with nonresponders, responders not only had higher control PRA and higher PRA at 1 mo of treatment, but also had decreased plasma aldosterone levels, decreased urinary aldosterone excretion, and increased serum postassium levels that persisted over the 4 mo of observation. The reduction of plasma aldosterone correlated with the fall of mean blood pressure. Urinary kallikrein, catecholamines, electrolytes, and endogenous creatinine clearance did not change in response to treatment. These findings indicate that the antihypertenisve activity of captopril on long-term administration probably depends in part on the blockade of angiotensin II, but other mechanisms cannot be excluded.

Hormonal responses to long-term converting enzyme inhibition in hypertensive patients.

Captopril was given alone and in combination with diuretics to 49 patients with hypertension for 1 to 12 mol Within 2 mo blood pressure reduction correlated with pretreatment plasma renin activity and response to the infusion of angiotensin II antagonist, but these effects were not present at 4 mo. Plasma and urinary aldosterone were suppressed but serum converting enzyme activity, plasma bradykinin, kallikren, and prostaglandins (E and F) were in the normal range effect of captopril. Despite sustained reduction of blood pressure, plasma catecholamines were not elevated and urinary catecholamines were suppressed in patients on captopril alone. It is concluded that another mechanism, such as enhancement of renal or local kinin-prostaglandin system, as well as suppression of the renin-angiotensin-aldosterone system may be involved in the long-term efficacy of captopril. Sympathetic activity may also be depressed and contribute to the hypotensive effect.

Oxidized low-density lipoprotein induces the production of superoxide by neutrophils.

Exposure of guinea pig peritoneal neutrophils to ox-LDL led to the production of superoxide, which was measured by the formation of superoxide-dependent chemiluminescence. The cells exposed to unoxidized LDL, e.g. native LDL, acetyl-LDL, and self-aggregates of LDL showed no production of superoxide. The superoxide production was correlated with the levels of oxidative modification of LDL and reached a maximum between 10 and 30 min during incubation, but preincubating the cells with cytochalasin B decreased the superoxide production. These findings indicate that neutrophils rapidly take up ox-LDL by phagocytosis and generate superoxide which may cause superoxide-mediated lipid peroxidation in vivo.

Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones.

A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess dual activities of thromboxane A2 (TXA2) synthetase inhibition and bronchodilation was synthesized, and their pharmacological activities were evaluated. While the length and the bulk of 2-alkyl substituents had no influence on either activity, the 2-substituents with polar groups reduced bronchodilatory activity. Furthermore, we introduced heteroaromatic nuclei into the 4-position of the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c) derivatives were as active as the parent 3-pyridyl compound 5b. These findings suggest that heteroaromatic nuclei at the 4-position of phthalazinones play a critical role in TXA2 synthetase inhibition. Additionally, the hydrophobicity of the compounds was found to exert a marked influence on bronchodilatory activity. These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1(2H)-phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone (16b) (KK-562) for further studies. Although their precise mechanism of action remains unclear, this series of novel phthalazinone derivatives represents a new class of antiasthma agents with dual activities.

Synthesis and evaluation of antiinflammatory activities of a series of corticosteroid 17 alpha-esters containing a functional group.

A series of 21-desoxy-21-chlorocorticosteroids that contain a functionalized ester group at 17 alpha has been prepared and examined to separate their systemic activity from topical antiinflammatory activity. Introduction of the functionalized ester group at 17 alpha was carried out by an acid-catalyzed formation of cyclic ortho esters with 17 alpha,21-hydroxyl groups of corticosteroids and subsequent acid-catalyzed hydrolysis. As for the functional group, chloro, methoxy, acetoxy, cyano, cyclopropyl, or alkoxycarbonyl group was introduced at the terminal carbon atom of the 17 alpha-alkanoate group. The topical antiinflammatory activity and systemic activity of these compounds were examined and found to be significantly dependent on the functionalities in the 17 alpha-esters. Among these derivatives, a series of 17 alpha-(alkoxycarbonyl)alkanoates (17 alpha-OCO(CH2)nCOOR) showed an excellent separation of the systemic activity from topical activity. The effects of the number of methylene groups (n) and of the alkyl groups of the ester (R) on either topical or systemic activity of the corticosteroid derivatives were also investigated.

Brain-derived neurotrophic factor increases inhibitory synapses, revealed in solitary neurons cultured from rat visual cortex.

To elucidate chronic actions of brain-derived neurotrophic factor (BDNF) on GABAergic synapses, we examined effects of a long-term application of BDNF for 10-15 days on autapses (synapses) of solitary GABAergic neurons cultured from rat visual cortex. Solitary neuron preparations were used to exclude a possible contamination of BDNF actions on excitatory neurons in dissociated neuron culture or slice preparations. Neurons were confirmed to be GABAergic pharmacologically with bicuculline, a selective antagonist for GABAA receptors and immunocytochemically with antibody against glutamic acid decarboxylase 65, a GABA synthesizing enzyme. To evaluate GABAergic synaptic function, evoked and/or miniature inhibitory postsynaptic currents (IPSCs) were recorded in the whole-cell voltage-clamp mode. The treatment with BDNF at a concentration of 100 ng/ml enhanced the amplitude of evoked IPSCs and the frequency of miniature IPSCs. In contrast, BDNF did not have a detectable effect on the amplitude of miniature IPSCs and the paired pulse ratio of IPSCs evoked by two, successive activations. To evaluate morphological changes, neurons were immunocytochemically stained with antibodies against microtubule-associated protein 2, to visualize somatodendritic region and synapsin I, to visualize presynaptic sites. The quantitative analysis indicated that BDNF increased the area of soma, the numbers of primary dendrites and dendritic branching points, the total length of dendrites and the number of synaptic sites. Such an action of BDNF was seen in both subgroups of GABAergic neurons, parvalbumin-positive and -negative neurons. To visualize functionally active presynaptic sites, neurons were stained with a styryl dye, FM1-43. BDNF increased the number of stained sites that was correlated with the frequency of miniature IPSCs. These results suggest that the chronic treatment with BDNF promotes dendritic and synaptic development of GABAergic neurons in visual cortex.

Left ventricular volumes and ejection fraction calculated from quantitative electrocardiographic-gated 99mTc-tetrofosmin myocardial SPECT.

UNLABELLED: We compared the left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) as calculated by Cedars automated quantitative gated SPECT (QGS) to those determined by first-pass radionuclide angiography (FPRNA) and contrast left ventriculography (LVG) in a group of 21 patients (mean age 61.4 +/- 9.2 y). METHODS: A total of 740 MBq 99mTc-tetrofosmin was administered rapidly into the right cubital vein at rest, and FPRNA was performed using a multicrystal gamma camera. One hour after injection, QGS was performed with a temporal resolution of 10 frames per R-R interval. LVG was performed within 2 wk. RESULTS: The EDV, ESV and LVEF calculated by QGS were highly reproducible (intraobserver, r = 0.99, r = 0.99 and r = 0.99, respectively; interobserver, r = 0.99, r = 0.99 and r = 0.99, respectively; P < 0.01) and were more consistent than those determined by FPRNA (intraobserver, r = 0.97, r = 0.95 and r = 0.93, respectively; interobserver, r = 0.86, r = 0.96 and r = 0.91, respectively; P < 0.01). There was a good correlation between EDV, ESV and LVEF by FPRNA and those by LVG (r = 0.61, r = 0.72 and r = 0.91, respectively; P < 0.01), and there was an excellent correlation between QGS and LVG (r = 0.73, r = 0.83 and r = 0.87, respectively; P < 0.01). The mean EDV by QGS (100 +/- 11.3 mL) was significantly lower than by FPRNA (132 +/- 16.8 mL) or LVG (130 +/- 8.1 mL), and the mean ESV by QGS (53.8 +/- 9.3 mL) was lower than by FPRNA (73.0 +/- 13.3 mL). Ejection fraction values were highest by LVG (57.1% +/- 3.2%), then QGS (51.8% +/- 3.0%) and FPRNA (48.9% +/- 2.4%). CONCLUSION: QGS gave more reproducible results than FPRNA. LV volumes and LVEF calculated by QGS correlated well to those by LVG.

Quantitative evaluation of rat lymphocyte adsorption on microdomain structured surfaces of poly(2-hydroxyethyl methacrylate)/polyamine.

The adsorption behaviour of rat lymphocytes on poly(2-hydroxyethyl methacrylate)-graft-polyamine (HA) copolymers was evaluated using a newly developed chromatographic method. The quantity of lymphocyte adsorption can be varied by regulating the polyamine content in the HA copolymer. A remarkable depression in lymphocyte adsorption was observed on the surface of HA copolymer, consisting of 7 wt% of polyamine graft and 93 wt% of poly(2-hydroxyethyl methacrylate) (pHEMA) backbone. Further introduction of a polyamine graft on pHEMA resulted in the increase of lymphocyte retention on the copolymer surfaces. Lymphocytes adsorbed on HA copolymer surface retained their original round shape. Detailed analysis of the chromatogram showed that interaction of lymphocytes with HA copolymer was very much weaker than that with homopolymer of pHEMA or polyamine.

Preparation of nanoparticles bearing high density carbohydrate chains using carbohydrate-carrying polymers as emulsifier.

A novel method of preparing nanoparticles bearing high density carbohydrate chains on their surface is described. Carbohydrate-bearing nanoparticles of poly(lactic acid) or polystyrene were prepared by the solvent evaporation method using a carbohydrate-carrying polystyrene derivative which served as both an emulsifier and a surface coating. The diameter of the obtained nanoparticles ranged from 80 to 300 nm depending on the concentration of the polystyrene derivative. As the concentration of the polystyrene derivatives increased the nanoparticle diameter decreased, indicating that the polystyrene derivatives worked as an emulsifier. The obtained particles were specifically aggregated by carbohydrate-specific lectin, showing that the polystyrene derivative was retained on the particle surfaces and expressed carbohydrate residues. The density of carbohydrates on the particle surfaces was determined to be 3-5 molecules per square nanometre. The particles prepared by the present method were stably dispersed and hardly aggregated in aqueous media during storage and centrifugal treatment compared with the post-coated particles that were prepared by adsorbing polystyrene particles with the polystyrene derivative. In vitro study with isolated rat hepatocytes revealed that surface carbohydrate chains were recognized by hepatocytes.