Genesis, goals and achievements of Long-Term Ecological Research at the global scale: A critical review of ILTER and future directions.

Since its founding in 1993 the International Long-term Ecological Research Network (ILTER) has gone through pronounced development phases. The current network comprises 44 active member LTER networks representing 700 LTER Sites and ~80 LTSER Platforms across all continents, active in the fields of ecosystem, critical zone and socio-ecological research. The critical challenges and most important achievements of the initial phase have now become state-of-the-art in networking for excellent science. At the same time increasing integration, accelerating technology, networking of resources and a strong pull for more socially relevant scientific information have been modifying the mission and goals of ILTER. This article provides a critical review of ILTER's mission, goals, development and impacts. Major characteristics, tools, services, partnerships and selected examples of relative strengths relevant for advancing ILTER are presented. We elaborate on the tradeoffs between the needs of the scientific community and stakeholder expectations. The embedding of ILTER in an increasingly collaborative landscape of global environmental observation and ecological research networks and infrastructures is also reflected by developments of pioneering regional and national LTER networks such as SAEON in South Africa, CERN/CEOBEX in China, TERN in Australia or eLTER RI in Europe. The primary role of ILTER is currently seen as a mechanism to investigate ecosystem structure, function, and services in response to a wide range of environmental forcings using long-term, place-based research. We suggest four main fields of activities and advancements for the next decade through development/delivery of a: (1) Global multi-disciplinary community of researchers and research institutes; (2) Strategic global framework and strong partnerships in ecosystem observation and research; (3) Global Research Infrastructure (GRI); and (4) a scientific knowledge factory for societally relevant information on sustainable use of natural resources.

The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii.

BACKGROUND AND PURPOSE: L-DOPA is generally considered to alleviate the symptoms of Parkinson's disease by its conversion to dopamine. We have proposed that DOPA is itself a neurotransmitter in the CNS. However, specific receptors for DOPA have not been identified. Recently, the gene product of ocular albinism 1 (OA1) was found to exhibit DOPA-binding activity. Here, we have investigated whether OA1 is a functional receptor of DOPA in the nucleus tractus solitarii (NTS). EXPERIMENTAL APPROACH: We examined immunohistochemical expression of OA1 in the NTS, and the effects of DOPA microinjected into the depressor sites of NTS on blood pressure and heart rate in anaesthetized rats, with or without prior knock-down of OA1 in the NTS, using shRNA against OA1. KEY RESULTS: Using a specific OA1 antibody, OA1-positive cells and nerve fibres were found in the depressor sites of the NTS. OA1 expression in the NTS was markedly suppressed by microinjection into the NTS of adenovirus vectors carrying the relevant shRNA sequences against OA1. In animals treated with OA1 shRNA, depressor and bradycardic responses to DOPA, but not those to glutamate, microinjected into the NTS were blocked. Bilateral injections into the NTS of DOPA cyclohexyl ester, a competitive antagonist against OA1, suppressed phenylephrine-induced bradycardic responses without affecting blood pressure responses. CONCLUSION AND IMPLICATIONS: OA1 acted as a functional receptor for DOPA in the NTS, mediating depressor and bradycardic responses. Our results add to the evidence for a central neurotransmitter role for DOPA, without conversion to dopamine.

Plasma orexin-A is lower in patients with narcolepsy.

Recently identified hypothalamic peptides called orexins (or hypocretins) have been implicated in the sleep-wake cycle and in sleep disorder narcolepsy. Neuropathological studies have shown that in patients with narcolepsy, global reduction in the expression of orexins occurs due to the loss of orexin neurons in the hypothalamus. Cerebrospinal fluid analysis has confirmed a reduced or undetectable level of orexin-A in most narcolepsy patients. In this study, measurement of plasma orexin showed significantly lower concentrations in patients with narcolepsy than in age- and gender-matched normal controls. These data suggest that low levels of orexin-A in plasma could serve as a biological marker for narcolepsy.

Cross-sectional shapes of the internal auditory canal in patients with acoustic neuromas.

Cross-sectional images of the internal auditory canal (IAC) were investigated in 23 patients with acoustic neuroma in order to clarify the widening of the IAC. The area of the IAC and the ratio of areas (neuroma side:normal side) were calculated. The shape of the IAC was fitted by an ellipse to obtain the length of the axes and the direction of the long axis. The area of the IAC was 34.2+/-12.2 mm2 in the neuroma side and 18.1+/-4.8 mm2 in the normal side. The neuroma side was larger than the normal side in all patients, and the mean ratio of areas was 1.9. However, the degrees of cochlear and vestibular damage did not correlate with the ratio of areas. The mean ratio of axes of the approximated ellipse was 1.17+/-0.09 in the neuroma side and 1.14+/-0.10 in the normal side; however, no significant difference was seen between the ratio of axes. The directions of the long axes were not always consistent with the positions of the originating nerves of the tumour. Referring to hypothetical models of enlargement of the IAC, our data suggest that the widening of the IAC in the acoustic neuroma was expansive. The data also indicated that symptoms of the acoustic neuroma were caused not only by compression of the nerves but also by other mechanisms, such as vascular insufficiency to the inner ear.

Antimicrobial susceptibilities of Helicobacter pylori isolates under microaerophilic atmospheres established by two different methods.

The MICs of clarithromycin, amoxicillin, and metronidazole for 150 Helicobacter pylori isolates were determined using the AnaeroPack system and were compared with those determined using a microaerophilic incubator. The MICs of clarithromycin, amoxicillin, and metronidazole determined under both microaerophilic atmospheres were mostly within one twofold dilution for 146 (97.3%), 150 (100%), and 149 (99.3%) of the isolates, respectively.

Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein.

Transport of quinolone antimicrobials and the contribution of the secretory transporter P-glycoprotein were studied in-vivo and in-vitro. In rat intestinal tissue (Ussing chambers method) and human Caco-2 cells (Transwell method), grepafloxacin showed secretory-directed transport. In both experimental systems, the secretory-directed transport was decreased by ciclosporin A, an inhibitor of P-glycoprotein, and probenecid, an inhibitor of anion transport systems. This suggested the contribution of P-glycoprotein and anion-sensitive transporter(s). The involvement of P-glycoprotein was investigated by using a P-glycoprotein over-expressing cell line, LLC-GA5-COL150, and P-glycoprotein-gene-deficient mice (mdr1a(-/-)/1b(-/-) mice). LLC-GA5-COL150 cells showed secretory-directed transport of grepafloxacin, while the parent cell line, LLC-PK1, did not. The secretory-directed transport of sparfloxacin and levofloxacin was also detected in LLC-GA5-COL150 cells. In the mdr1a(-/-)/1b(-/-) mice, the intestinal secretory clearance was smaller than that in wild-type mice after intravenous administration of grepafloxacin. Moreover, the absorption from an intestinal loop in mdr1a(-/-)/1b(-/-) mice was larger than that in wild-type mice. Accordingly, it appears that some quinolones are transported by secretory transporters, including P-glycoprotein. The involved transporters function in-vivo not only to transport grepafloxacin from blood to intestine but also to limit its intestinal absorption.

Fibrous dysplasia with cystic appearance in maxillary sinus.

Fibrous dysplasia (FD) in the paranasal sinuses is uncommon, and its management may be difficult. We report the case of a 25-year-old female with FD exhibiting a cystic appearance in the maxillary sinus. The patient had been complaining of facial swelling for few years. Imagery study showed a cystic lesion and dense bone changes in the maxillary bone. Inferior meatal antrostomy with a nasal endoscope failed to confirm a histological diagnosis. After a 3-year follow-up, the degree of facial swelling was unchanged, and the patient underwent middle meatal antrostomy and was diagnosed with FD.

[Imaging studies and surgical approach to postoperative maxillary cysts].

Surgical treatment for postoperative maxillary cysts (POMC) can be performed using the peroral method, or the endonasal method which is less invasive. Recently, the percentage of cases in which the endonasal method is employed has increased with the widespread use of endoscopy and advancement in imaging techniques. However, the peroral method is still necessary in some cases. During the 5-year period from July 1994 to June 1999, we operated on 29 patients (31 sides) for POMC. The endonasal method was used for 22 sides, and the peroral method was needed for the remaining 9 sides. Following analysis of the CT scans and MR images, we concluded that it is difficult to employ the endonasal method in the following cases; 1) Cysts located in the lateral or anteroinferior portion of the maxillary sinus 2) Small cysts 3) Cysts with a bony wall.

Three-dimensional imaging of the internal auditory canal in patients with acoustic neuroma.

Three-dimensional imaging of the internal auditory canal (IAC) was carried out in 21 patients with acoustic neuromas using helical computed tomography. The IAC was widened in 20 patients, but no irregularities of the canal walls were seen. In addition, the shape of the enlarged IAC corresponded to that of the tumor on magnetic resonance imaging. The data suggest that widening of the IAC in acoustic neuroma patients is due to enlargement of the tumor. Other mechanisms, for example, tumor invasion or destruction caused by release of a specific mediator from the tumor, are unlikely to explain these findings; however, further investigation is needed.

The effects of water extracts of CagA positive or negative Helicobacter pylori on proliferation, apoptosis and connexin formation in acetic acid-induced gastric ulcer of rats.

AIM: To investigate the influence of water extracts of CagA-positive or -negative Helicobacter pylori on healing of chronic gastric ulcers and on connexin formation, proliferation and apoptosis, in acetic acid-induced chronic gastric ulcers in rats. METHODS: Acetic acid was used to induce chronic gastric ulcers in rats, and a water extract of H. pylori was given by mouth every day. Connexin 32 formation was assessed using Western blotting as previously described. The frequencies of proliferating cell nuclear antigen staining and of TdT-mediated dUTP-biotin nick end labelling were examined. RESULTS: In untreated rats, acetic acid-induced gastric ulcers healed after 14 days and the electrophoretic band corresponding to connexin 32 appeared 4 days after ulcer induction. Treatment with a water extract of H. pylori delayed ulcer healing, with the ulcers remaining unhealed even on the 14th day; healing was delayed more when treatment was with an extract of CagA-positive rather than CagA-negative H. pylori. Connexin 32 appeared earlier when treatment was with a CagA-negative rather than a CagA-positive extract, but in both cases later than in the untreated control group. Proliferating cell nuclear antigen labelling on the fourth day was seen in 14.5% +/- 1.6% of mucosal cells of control group, but in 35.9% +/- 1.4% and 36.5% +/- 1.4% of mucosal cells treated with either VacA(+)CagA(-) and VacA(+)CagA(+) H. pylori extract, respectively. Furthermore, extracts of both H. pylori strains, especially VacA(+)Cag(+) H. pylori promoted apoptosis. CONCLUSIONS: A water extract of H. pylori increased both proliferation and apoptosis, which are related to exacerbation and healing of ulcer as well as appearance of connexin 32.

Transport of 1,5-anhydro-D-glucitol into insulinoma cells by a glucose-sensitive transport system.

The uptake of 1,5-anhydro-D-glucitol (1,5-AG) occurs by passive mechanisms in cells or tissues that have passive glucose transporters. It is known that serum 1,5-AG concentrations are reduced in patients with diabetes mellitus. To elucidate the metabolism of this substance and its physiological role in pancreatic beta-cells, we assayed 1,5-AG transport in the insulinoma-derived cell lines, RINr and MIN6. Both cell lines showed an insulin-insensitive, concentration-dependent uptake of 1,5-AG with a saturation time of approximately 120 min, and most of the 1,5-AG in the cytoplasm was in the free form. A biphasic saturation curve was obtained using a wide range of 1,5-AG concentrations, suggesting that accumulation was mediated by a high affinity and a low affinity transporter. The high affinity transporter had a K(m) of 10.4 in RINr cells and 13.0 mM in MIN6 cells, and the low affinity transporter had a K(m)100 times, being much higher than the physiological concentrations of 1,5-AG. These results indicate that the 1,5-AG carrier system in insulinoma cells is distinct from that in either the somatic cells or renal tubular cells. These findings also suggest that a unique 1,5-AG transport system is present in pancreatic beta-cells.

Rare incidence of interspousal transmission of Helicobacter pylori in asymptomatic individuals in Japan.

PCR-restriction fragment length polymorphism electrophoretic patterns of amplified ureB and ureC of Helicobacter pylori were compared between spouses after digestion with restriction endonucleases. Twenty of 21 couples, both members of which were positive for H. pylori, showed ureB and ureC patterns that differed between spouses. We concluded that in Japan, interspousal transmission of H. pylori occurs rarely.

Glutathione reductase activity and flavin concentration in guinea-pig tissues.

Glutathione reductase (GR) activity and flavin concentration were studied in systemic tissues (brain, heart, lung, liver, spleen, stomach, pancreas, muscle, kidney, testis) and blood components (erythrocytes and plasma) from male guinea-pigs. GR activity and the flavin concentration were high in kidney and liver, and low in muscle. GR activity in erythrocytes was found in a range of tissues, but flavin concentration in erythrocytes was lower than in any tissues. GR was saturated with flavin adenine dinucleotide (FAD) in almost all tissues, but not in muscle or erythrocytes.

Epidemiological study on sleep habits and insomnia of new outpatients visiting general hospitals in Japan.

A large scale epidemiological survey of sleep habits, specifically for insomnia, was conducted using 6277 new outpatients from 11 general hospitals in Japan. They were requested to answer a questionnaire newly designed for this study, which consisted of 34 questions concerning sociodemographic characteristics, current medical conditions, sleep habits, current or past sleep complaints, symptoms of parasomnia, use of hypnotics/anxiolytics and other aspects of daily life. Insomnia was the focus of analysis using chi2 statistics and, additionally, logistic regression to explore the predictors of insomnia. Bedtime was 23:30 and wake-up time was 6:35 on average, with a mean sleep time of 6.77 h on weekdays. The number of subjects with current sleep complaints was 1276, of which 735 (11.7% of the total sample) had insomnia lasting for 1 month or more. Only 37.6% of those were taking hypnotics and/or anxiolytics. Old age, female sex, neurology, psychiatry, early bedtime, late wake-up time, living alone and dissatisfaction with the bedroom environment for sleep were found to be associated with long-term insomnia. This study helps to provide a framework for further studies using the general population.

[Effect of antibiotics and antibody on phagocytic bactericidal activity of polymorphonuclear neutrophils of Bordetella pertussis].

The phagocytic bactericidal activity of the polymononucler neutrophils (PMNs) that were collected from healthy volunteer with and without antibody against Bordetella pertussis was investigated. Furthermore, these activity against B. pertussis under observing penicillins or macrolides antibiotics was investigated. Although no efficacy to B. pertussis strain by the PMNs in serum without antibody, but the viable cells of B. pertussis decreased to 1/1,000 1 hr after incubation and was not detected after 4 hrs. In particular, the viable cells of B. pertussis by the PMNs in serum with antibody was markedly reduced when azithromycin was present. These results suggests that the synergistic action of macrolide antibiotics and antibody-mediated phagocytic bactericidal activity on B. pertussis may have clinical relevance.

Three-dimensional reconstruction of the incudostapedial joint with helical computed tomography.

Three-dimensional images of the incudostapedial joint (I-S joint) were reconstructed using helical computed tomography (CT). The images of the joint were most often reconstructed when threshold values were selected at -500 to -700 Hounsfield Units. These shapes were changed by choosing various threshold values. Histological examinations of the cadaver specimen indicate that these changes are due to structure of the I-S joints. We conclude that these 3-D images may be useful in assessing pathology of the I-S joint.

Two cases of adult varicella accompanied by hepatic dysfunction.

Varicella is a typical acute exanthematous viral infection caused by varicella-zoster virus (VZV). In recently years, as far as hepatic dysfunction caused by viruses other than the hepatitis virus is concerned, there have been a few reports on hepatic dysfunction accompanying varicella following organ transplantation of Europe and America and another report on an immunocompromized adult following treatment for Systemic lupus erythematosis (SLE) in Japan. Nonetheless, we searched the MEDLINE and J MEDICINE listing the publications between 1986 and 1996 and found one report on healthy adults with varicella accompanied by hepatic dysfunction in Europe and America and two reports in Japan. Only Noguchi et al. dealt with the findings of liver biopsy. We examined two healthy adults with varicella and mild-to-moderate hepatic dysfunction, and referred to the results of their liver biopsies. The present paper discusses this issue, citing some references.

[Study of diarrhea-inducing strains of Escherichia coli mainly isolated in Kanto area between June and September 1996].

A total of 21,609 faecal specimens obtained from patients with diarrhea mainly in Kanto area between June and September 1996 were investigated to identify the causative pathogens for diarrhea. One-hundred fifty-seven strains of Escherichia coli of 29 different O-serotypes were isolated as the causative pathogens, which were previously recognized to induce severe abdominal cramps and diarrhea. Of these, 114 strains, in which the possibility of enterohemorrhagic E. coli due to their O-serotypes was predicted, were examined for the producibility of Vero toxins. Twenty-six (76.5%) of the 34 strains of E. coli O157 produced the Vero toxins, and other 8 strains were the non-producers. Twenty of the 26 producers produced both VT1 and VT2, whereas the other 6 strains produced VT2 only. Furthermore, 4 strains of E. coli O26, and 1 strain each of E. coli O125 and O126 produced Vero toxins. Thirty-two of the 114 strains, isolated from the patients with diarrhea and selected as the enterohemorrhagic E. coli according to the specific O-serotypes, were actually confirmed produce Vero toxins. Thirty-four strains of E. coli O157 tested were susceptible to all antibiotics such as ampicillin, doxycylin, levofloxacin, fosfomycin, chloramphenicol and polymyxin B, and no strains resistant to levofloxacin, polymyxin B and fosfomycin were found.

[Clinical study in vertiginuous patients suspected of having neurovascular compression syndrome of the eighth cranial nerve].

Neurovascular compression syndrome of the 5th and 7th cranial nerves has been recognized as the cause of trigeminal neuralgia and hemifacial spasm. On the other hand, it is still difficult to diagnose vertigo as neurovascular compression syndrome of the 8th cranial nerve. To detect some specific finding in this syndrome of the 8th cranial nerve, 5 patients with vertigo with hemifacial spasm were examined for the clinical course and neuro-otological features. In all patients MRI and/or angiography suggested vascular compression against the 8th cranial nerve. The clinical courses of these patients revealed various symptoms resembling benign paroxysmal positional vertigo, vestibular neuronitis and Meniere's disease. Audiograms showed two normal hearing patterns, bilateral high frequency hearing loss probably due to aging in one case, bilateral C5-dip in one and fluctuating unilateral hearing loss like Meniere's disease in one. The prolongation of IPL I-III on auditory brainstem response proposed as a criterion by Møller was detected in one case. No response in the caloric test was found in two cases. These abnormalities in the auditory brainstem response and caloric test appeared to be useful for diagnosis but were uncommon findings in all cases. Electronystagmographic examinations including the eye tracking test, optokinetic nystagmus and optokinetic pattern were all normal. We could not find any specific clinical findings valuable for diagnosis of neurovascular compression syndrome of the 8th cranial nerve. It is proposed that the indication of microvascular decompression should be decided carefully.