OBJECTIVE

Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction.

RESULTS

Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-short-segment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern.

CONCLUSIONS

We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.

Human neuronal growth inhibitory factor (GIF) is a metallothionein-like protein specific to the central nervous system, which has been linked to Alzheimer's disease. In this article a short overview of the biological and structural properties of native Cu4,Zn3-GIF are described. Moreover, metal-thiolate clusters formed in the synthetic beta-domain (residues 1-32) and the alpha-domain (residues 32-68) both with native CuI and ZnII, and as a spectroscopic probe also with Cd(II) are discussed. The cluster formation was followed by electronic absorption, circular dichroism (CD), magnetic circular dichroism (MCD) and 113Cd NMR spectroscopy and, in the special case of Cu(I) complexes, by luminescence spectroscopy at 77 K. These structural features are compared with those of recombinant Zn7- and 113Cd7-GIF. The structural studies suggest the existence of distinct MeII4S11 and MeII3S9 clusters located in the mutually interacting alpha- and beta-domains, respectively, of Cd7-GIF. In addition, evidence for a highly dynamic and flexible structure of this protein is presented.

Deficiency of neuronal growth inhibitory factor (GIF) and abnormalities in zinc homeostasis have been suggested to play a role in the neuropathogenesis of Alzheimer's disease. We report here that embryonic chick cerebral cell cultures zinc and copper containing GIF in the presence of marmoset hippocampal extract reduces significantly and concentration dependently mitochondrial succinate dehydrogenase activity (MTT) and cell mass. In contrast, no indications could be found that GIF affected neural retina cell cultures. Our results suggest that the observed effects of GIF are not elicited by zinc.

Wild-type (wt) strains of vesicular stomatitis virus (VSV) strain Indiana are poor to non-inducers of interferon (IFN) which express IFN induction-suppressing activity. At non-permissive temperatures, temperature-sensitive (ts) mutants of this virus are either like their wt parents, or they are good to excellent inducers of IFN. IFN inducibility and IFN induction-suppressing activity are mutually exclusive phenotypes in VSV-Indiana. With one exception, all Orsay ts mutants derived by A. Flamand (CNRS, Gif-sur-Yvette, France), representing the five complementation groups, were poor to non-inducers of IFN and were also capable of suppressing IFN induction by other viruses. In contrast, all Glasgow ts mutants derived by C. R. Pringle (University of Warwick, Coventry, U.K.) were excellent inducers of IFN. We demonstrate that this difference in acquisition of IFN inducibility relates primarily to the origin of the mutations; spontaneous for Orsay, and mutagen-derived for Glasgow. Tests with newly generated spontaneous and mutagen-derived mutants, and temperature-stable revertants of IFN-inducing ts mutants indicate that IFN inducibility results from non-ts, multiple mutations rarely acquired spontaneously, but generated frequently upon mutagenesis with 5-fluorouracil. The capacity of VSV-Indiana to induce IFN is considered intrinsic to the virus, but is only manifested when the dominant IFN induction-suppressing phenotype is lost through mutagenesis. Thus, non-ts mutations appear to regulate the expression of the IFN induction-suppressing phenotype, and hence the IFN inducibility of VSV-Indiana.

BACKGROUND

The low incidence of sarcomas in the general population makes heritable contribution to disease risk difficult to discern beyond highly penetrant Mendelian syndromes.

METHODS

The Utah Cancer Registry (UCR) and Utah Population Database were interrogated for sarcoma diagnostic codes grouped by genetic type, either complex genotype/karyotype sarcoma or balanced translocation-associated sarcoma. The genealogic index of familiality (GIF) was calculated and relative risks (RR) of disease estimated for first-, second-, and third-degree relatives of sarcoma probands. Cancer patterns in pedigrees of sarcoma probands were examined to rule out known hereditary cancer syndromes.

RESULTS

A total of 229 balanced translocation type and 1,161 complex genotype type sarcomas with at least three generations of ancestral genealogy data were identified in the UCR. There was no evidence for excess relatedness for the balanced translocation group by using the GIF test (P = 0.657) and no significantly elevated RRs. In the complex genotype group, we observed significantly elevated GIF (P = 0.03). Modest RRs corroborated the GIF analysis, in which excess relatedness existed in distant relationships. No recognized cancer syndromes were identified among high-risk pedigrees.

CONCLUSIONS

We identified strong familiality among complex genotype sarcomas, independent from known cancer predisposition syndromes. In the absence of significantly elevated RRs for close relatives, the high GIF argues for a strong genetic-rather than environmental-component to complex genotype sarcoma risk. We observed no significant familial risk of developing balanced translocation-associated sarcomas, but the sample was small.

CONCLUSIONS

There exists yet to be deciphered heritable risk for developing complex genotype sarcomas.

Developmental biologists have been fascinated with the long-standing mystery of how multicellular organisms, such as plants and animals, sense and control their organ size. In plants, leaves are a suitable experimental system for elucidation of the mystery, because they, like animal organs, inherently exhibit a determinate growth pattern, meaning that they possess genetic information for the control of their final size. The cell proliferation and expansion processes are prerequisites for growth, so that the genetic controls should converge on the 2 cellular processes and decide their rate or duration during leaf growth. Plant scientists have found dozens of genes involved in the control of the cellular processes, including the Arabidopsis thaliana GRF-INTERACTING FACTOR (GIF) family. The GIF family consists of 3 members, GIFGIFGIF family genes have been shown to play an essential role in the control of cell proliferation of the leaf organ, understanding of the spatio-temporal behaviors of GIF expression, in both aspects of their promoters and proteins, has been limited to GIFgif leaf organs and present spatio-temporal expression patterns of all GIF genes, thus providing comprehensive insights into biological roles and expression behaviors of the whole GIF family members during leaf growth.

BACKGROUND

The American Heart Association has proposed an impact goal for the year 2020 to improve cardiovascular health by 20%. The objectives of the study were to assess the association between the proposed cardiovascular health metric score and incident myocardial infarction (MI) and to estimate the generalized impact fraction (GIF).

METHODS

The health metric score was derived from ideal levels of six cardiovascular risk factors from the population-based Tromsø Study of 22,121 residents of Tromsø, Norway aged 30 to 79 years, examined in 1994-95, 2001, and 2007-08. Incident events of MI were recorded from the date of enrollment in 1994-95 to the end of 2010. Adjudication of hospitalized and out-of hospital events was performed by an independent endpoints committee based on data from hospital and out-of hospital journals, autopsy records and death certificates. Cox proportional hazard regression was used to estimate hazard ratios (HR). GIF was calculated from age stratified analysis using a case-load weighted-sum method. Bootstrapping was used to estimate 95% simulation intervals.

RESULTS

A total of 1652 MIs accrued over an average of 14.7 person-years of follow-up. Few men (0.96%) and women (3.6%) had ideal levels in all 6 metrics. 64.7% (men) and 55.7% (women) had ideal levels in 2 or 3 metrics. The age-adjusted HR per point increase in health score was 0.65 (95% confidence interval: 0.61, 0.70) in men and 0.59 (0.54, 0.64) in women. A shift of 30% of subjects from low score levels ≤3 to scores ≥4 was estimated to prevent 13.7% (11.2, 16.2) of incident MI in men and 15.9% (12.1, 19.4) in women.

CONCLUSIONS

The association between the health metric score and MI indicate that close to 15% of incident MIs could be prevented by attainable and realistic improvements in the health metrics.

Growth inhibitory factor (GIF) is a small protein belonging to the metallothionein family that has the capacity to inhibit neuronal survival and neurite formation in vitro. This study was conducted to investigate the role of GIF in the brain afflicted with ischemic injury. We used the in situ hybridization technique and Northern blot analysis to study the changes in GIF messenger RNA (mRNA) expression in a rat focal ischemia model. On the first day, the expression tended to decrease in the hemisphere ipsilateral to the injury. It returned to normal levels on the second day except for the central area of the middle cerebral artery (MCA) territory. On the third and fourth day, the expression increased diffusely in the hemisphere of the affected side, including the subcortical area. Two weeks after ischemia, the GIF mRNA expression increased again but only in the peri-infarcted area. Down-regulation of GIF on the first day in the cortex ipsilateral to the infarction might promote neurite sprouting. The subsequent increase in GIF mRNA expression on the third and fourth day might be a symptom of neurons attempting to inhibit excessive neurite outgrowth, or to protect themselves against toxicity caused by oxygen radicals. The later increase in the limited area around the infarction may be related to astroglial reaction. Growth inhibitory factor may play an important role in regulating the central nervous system after ischemic insults.

The ontogenesis of immunoreactive somatostatin in the embryonic and fetal rat pancreas has been measured by radioimmunoassay following acid extraction. Somatostatin (GIF) is detectable at 14 days gestation at a concentration of 1.6 X 10(-3) ng/pancreas. At term the content is 3.8 ng/pancreas, by 2 days neonatally, 8.3 ng/pancreas, and in the adult rat, 71 ng/pancreas through the concentration (expressed per microgram DNA) is constant from 14-19 days of gestation and reaches a level characteristic of the fully differentiated pancreas by birth. The detection of GIF in cultured pancreatic explants in the absence of innervation indicates that synthesis can occur independent of neural influence.

OBJECTIVE

Direct retrograde cholangioscopy (DRC) may improve the diagnostic and therapeutic yield of endoscopic retrograde cholangiography (ERC) but safety, feasibility, and outcome are unknown.

METHODS

All consecutive patients who underwent DRC at three tertiary endoscopy centers for inconclusive findings at ERC were included in this retrospective analysis. Ultraslim endoscopes (FujiFilm EG 530NP; Olympus GIF XP180; GIF N180) were used by the peroral route for intubating all accessible bile ducts. Success rate, usefulness in diagnosis and therapy, and safety of DRC were assessed in terms of technical and clinical parameters and therapeutic vs. diagnostic indication.

RESULTS

DRC was performed in 130 cases (89 patients). CO2 insufflation and an anchoring balloon were used in 66.9% and 97.7% of cases, respectively. Intubation of the papilla was successful in 115 of 130 (88.5%) cases, and the aim of the DRC investigation was accomplished in 105 cases (80.8%). DRC-guided biopsies were taken in 53 cases (40.8%), and a therapeutic intervention was performed in 32 cases (24.6%). The initial diagnosis was revised by DRC in 18 of 69 patients (26.1%) with indeterminate biliary stricture. Complications were observed in 10 cases (7.7%), including cholangitis (n=2; 1.5%), bleeding (n=2; 1.5%), and pain, hypoxia, bradyarrhythmia, air embolism, and perforation of an intrahepatic and an extrahepatic bile duct (1 each; 0.8%). There was no mortality associated with DRC.

CONCLUSIONS

DRC was successfully performed for the diagnosis and treatment of biliary disease that had eluded diagnosis with conventional ERC. DRC impacted on clinical decision making. The complication rate was low and similar to other cholangioscopy techniques.

Long manipulation length is critical for optical fiber tweezers to enhance the flexibility of non-contact trapping. In this paper a long manipulation distance of more than 40 μm is demonstrated experimentally by the graded-index fiber (GIF) tweezers, which is fabricated by chemically etching a GIF taper with a large cone angle of 58°. The long manipulation distance is obtained by introducing an air cavity between the lead-in single mode fiber and the GIF as well as by adjusting the laser power in the existence of a constant background flow. The influence of the cavity length and the GIF length on the light distribution and the focusing length of the GIF taper is investigated numerically, which is helpful for optimizing the parameters to perform stable optical trapping. This kind of optical fiber tweezers has advantages including low-cost, easy-to-fabricate and easy-to-use.

New therapeutic strategies are needed to overcome drawbacks in treatment of infections with intracellular bacteria. Chlamydiaceae are Gram-negative bacteria implicated in acute and chronic diseases such as abortion in animals and trachoma in humans. Water-filtered infrared A (wIRA) is short wavelength infrared radiation with a spectrum ranging from 780 to 1400 nm. In clinical settings, wIRA alone and in combination with visible light (VIS) has proven its efficacy in acute and chronic wound healing processes. This is the first study to demonstrate that wIRA irradiation combined with VIS (wIRA/VIS) diminishes recovery of infectious elementary bodies (EBs) of both intra- and extracellular Chlamydia (C.) in two different cell lines (Vero, HeLa) regardless of the chlamydial strain (C. pecorum, C. trachomatis serovar E) as shown by indirect immunofluorescence and titration by subpassage. Moreover, a single exposure to wIRA/VIS at 40 hours post infection (hpi) led to a significant reduction of C. pecorum inclusion frequency in Vero cells and C. trachomatis in HeLa cells, respectively. A triple dose of irradiation (24, 36, 40 hpi) during the course of C. trachomatis infection further reduced chlamydial inclusion frequency in HeLa cells without inducing the chlamydial persistence/stress response, as ascertained by electron microscopy. Irradiation of host cells (HeLa, Vero) neither affected cell viability nor induced any molecular markers of cytotoxicity as investigated by Alamar blue assay and Western blot analysis. Chlamydial infection, irradiation, and the combination of both showed a similar release pattern of a subset of pro-inflammatory cytokines (MIF/GIF, Serpin E1, RANTES, IL-6, IL-8) and chemokines (IL-16, IP-10, ENA-78, MIG, MIP-1α/β) from host cells. Initial investigation into the mechanism indicated possible thermal effects on Chlamydia due to irradiation. In summary, we demonstrate a non-chemical reduction of chlamydial infection using the combination of water-filtered infrared A and visible light.

Two genes for human immune interferon (hIFN-gamma), synthetic (GIFs) and cDNA prepared from mRNA (GIFm), have been expressed in E. coli under the control of the trp promoter. The expression level of GIFs was 100-fold lower than that of GIFm. Secondary structure analysis of two genes' mRNA surrounding Shine-Dalgarno (SD) sequence showed the presence of a 8 base-pair stable stem structure preceding SD sequence in GIFs mRNA, but not in GIFm mRNA. Expression of a GIFs gene, in which the stem structure was rendered unstable by changing two bases, became 100 times greater than that of the original GIFs.

Normal human peripheral blood T cells were propagated in the presence of human interleukin 2, and activated cells were incubated with human IgE-dimer to induce IgE binding factor formation. The cells were then fused with a mutant of the human T cell line CEM. Five of the T cell hybridomas formed IgE binding factors upon incubation with human IgE-dimer. Because IgE binding factors formed by the human T cell hybridomas had affinity not only for human IgE but also for rat IgE, the biologic activities of the factors were evaluated by using antigen-primed rat mesenteric lymph node (MLN) cells. When parent T cells were propagated with crude IL 2, which contained glycosylation enhancing factor (GEF), IgE binding factors formed by all of the five hybridomas had affinity for Con A, but only a fraction of the factors bound to lentil lectin. The 60,000 and 15,000 IgE binding factors formed by two representative hybridomas, i.e., 166A2 and 166G11, selectively potentiated the IgE-forming cell response of rat MLN cells. When parent T cells were obtained by propagation with purified IL 2, which did not contain GEF, and the cells were incubated with IgE-dimer in the presence of glycosylation inhibiting factor (GIF), T cell hybridomas constructed from the cells formed IgE binding factors that lacked affinity for Con A but bound to peanut agglutinin (PNA). The 30,000 IgE binding factors formed by two of such hybridomas, 398A3 and 400G2, selectively suppressed the IgE response of rat MLN cells. It was also found that the biologic activities and carbohydrate moieties of human IgE binding factors could be switched by changing the culture conditions of the hybridomas. When the 166A2 hybridoma was cultured with human IgE in the presence of bradykinin, essentially all of the IgE binding factors that were formed by the cells bound to lentil lectin, and the factors that were formed in the presence of bradykinin exerted higher potentiating activity than those obtained in the absence of bradykinin. On the other hand, IgE binding factors formed by the same cells in the presence of GIF had affinity for PNA, and selectively suppressed the IgE response of rat MLN cells.

Accumulation of aluminum in human has been reported to be associated with dementia, Parkinson's disease, and Alzheimer's disease. The objectives of this study were to evaluate an edible biopolymer poly(γ-glutamic acid) (γ-PGA) for aluminum removal efficiency under in vitro conditions as affected by pH, contact time, aluminum concentration, temperature, ionic strength, and essential metals in both aqueous aluminum solution and simulated gastrointestinal fluid (GIF). A low aluminum adsorption occurred at pH 1.5-2.5, followed by a maximum adsorption at pH 3.0-4.0 and precipitating thereafter as aluminum hydroxide at pH>> 4. Adsorption was extremely fast with 81-96% of total adsorption being attained within 1 min, reaching equilibrium in 5-10 min. Kinetic data at low (10 mg/L) and high (50 mg/L) concentrations were well described by pseudo-first-order and pseudo-second-order models, respectively. Equilibrium adsorption isotherms at different temperatures were precisely fitted by both Langmuir and Redlich-Peterson models with the maximum adsorption capacities at 25, 37, and 50 °C being 35.85, 38.68, and 44.23 mg/g, respectively. Thermodynamic calculations suggested endothermic and spontaneous nature of aluminum adsorption by γ-PGA with increased randomness at the solid/solution interface. Variation in ionic strengths did not alter the adsorption capacity, however, the incorporation of essential metals significantly reduced the aluminum adsorption by following the order copper>> iron>> zinc>> calcium>> potassium. Compared to aqueous solution, the aluminum adsorption from simulated GIF was high at all studied pH (1-4) with Langmuir monolayer adsorption capacity being 49.43 mg/g at 37 °C and pH 4. The outcome of this study suggests that γ-PGA could be used as a safe detoxifying agent for aluminum.

Bifunctional dantrolene derivatives have been synthesized as probes for radioisotope-free photoaffinity labeling with the aim of elucidating the molecular mechanism of skeletal muscle contraction. GIF-0430 and GIF-0665 are aromatic azido-functionalized derivatives that were designed to selectively inhibit physiological Ca2+ release (PCR) from sarcoplasmic reticulum (SR) in mouse skeletal muscle without a strong effect on Ca2+-induced Ca2+ release (CICR). These photoaffinity probes consist of either an azidomethyl or an ethynyl group, respectively, which could function as a tag for introduction of an optional detectable marker unit by an appropriate chemoselective ligation method after the photo-cross-linking operation. Actually, the former probe worked to photolabel its target proteins specifically as confirmed by subsequent fluorescent visualization.

The neutrophil-specific NB antigen system has been serologically characterized with human alloantisera. Two alleles, NB1 and NB2, have been described. NB1 is expressed on a subpopulation of peripheral blood neutrophils in 97 percent of healthy donors. Human alloantibodies have been used to identify the 58- to 64-kDa glycoprotein (GP) on which NB1 is located. NB1 can usually be detected by both a granulocyte immunofluorescence (GIF) assay and a granulocyte agglutination (GA) assay, but neutrophils from some donors have been found to react with anti-NB1 in GIF but not in GA assays. To determine if the latter neutrophils express NB1 and the corresponding 58- to 64-kDa GP, these neutrophils were probed with rabbit and human sera specific for NB1. First, the proportion of neutrophils that express NB1 was quantitated. Neutrophils from donors that typed as NB1-positive in both GA and GIF assays were analyzed by flow cytometry with antisera to NB1. Human and rabbit anti-NB1 reacted with 71 +/- 17 percent and 70 +/- 17 percent of neutrophils, respectively. There was no difference in the expression of NB1 in NB1-homozygous and NB1-heterozygous individuals. In contrast, significantly fewer neutrophils from four donors that typed as NB1-positive in GIF assay but not GA assay reacted with human (27 +/- 12%; p < 0.001) and rabbit (26 +/- 12%; p < 0.001) anti-NB1. When neutrophils from these same four donors were probed with rabbit and human anti-NB1 by immunoblotting and immunoprecipitation, the 58- to 64-kDa GP was identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Tea plant (Camellia sinensis (L.) O. Kuntze) is an important leaf-type woody crop used for producing of non-alcoholic beverages worldwide. The GROWTH-REGULATING FACTOR (GRF) transcription factors cooperated with GRF-INTERACTING FACTOR (GIF) transcriptional coactivators positively regulate leaf development. In the present study, six GRF and two GIF genes were identified and characterized in the leaf transcriptome of C. sinensis, respectively. The alignment results showed that the feature structures of the predicted homologous GRF and GIF proteins of C. sinensis hold a high identity with Arabidopsis and rice. The presence of C. sinensis miR396 target sites suggested that these miR396 members are the potential post-transcriptional regulators of CsGRF genes. The expression profiles of CsGRF and CsGIFGIF genes in response to different hormonal stimuli revealed the possible multiple functions of these genes in hormonal regulation. This study provided the potential molecular basis of the CsGRF and CsGIF family genes for future functional research on leaf development and hormonal stimuli in C. sinensis.

We examined neuroprotective effects of growth inhibitory factor (GIF) on injured adult rat facial motoneurons. The right facial nerves of adult rats were avulsed and removed from the stylomastoid foramen, and an adenoviral vector encoding rat GIF and Myc epitope (AxCArGIFM) were injected into the facial canal. Animals treated with AxCArGIFM showed intense immunolabeling for GIF/Myc in injured facial motoneurons. Treatment with AxCArGIFM after avulsion significantly prevented the loss of injured facial motoneurons, improved choline acetyltransferase immunoreactivity and prevented the induction of nitric oxide synthase activity in these neurons. These results indicate that GIF may have therapeutic potential against degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.

We obtained human T-cell hybridomas that are specific for bee venom phospholipase A2 (PLA2) and constitutively secrete glycosylation inhibiting factor (GIF). Upon crosslinking of CD3, the hybridoma produced GIF having affinity for PLA2. When affinity-purified PLA2-binding GIF was used as an immunogen, monoclonal antibodies specific for the antigen-binding GIF were obtained. Monoclonal antibody 110BH3 bound the antigen-binding GIF but failed to bind the 13-kDa nonspecific GIF, as determined by both bioassay and ELISA. In contrast, 388F1, a monoclonal antibody against nonspecific GIF, gave ELISA signals with both the nonspecific GIF and the antigen-binding GIF. Gel filtration of affinity-purified antigen-binding GIF revealed the presence of a 72- to 80-kDa protein which gave ELISA signals with both 110BH3 and 388F1 and contained GIF bioactivity. Upon reduction and alkylation, the antigen-binding GIF dissociated into a 62- to 64-kDa protein which gave positive ELISA with antibody 110BH3 but no signal with antibody 388F1, and a 15-kDa protein, which gave ELISA signal with the 388F1 but not with 110BH3. Immunoblotting of a PLA2-binding GIF preparation revealed that under reducing conditions, the antigen-binding GIF dissociated a 13-kDa peptide which reacted with polyclonal antibodies against recombinant GIF. The results indicate that the 13-kDa nonspecific GIF is a subunit of antigen-binding GIF. The PLA2-binding GIF has affinity for an epitope, representing amino acid residues 19-28 in PLA2 which appears to be an external structure in the antigen.

Growth inhibitory factor (GIF) inhibits survival and neurite formation of cortical neurons in vitro and is found abundantly in the normal human brain. The role of GIF is still obscure, although it is reported to decrease in the brain in Alzheimer's disease. We examined changes in GIF mRNA expression in a rat cortical-ablation model with the aid of an in situ hybridization technique. In sham-operated animals, the GIF mRNA was expressed consistently in the cerebral cortex, hippocampus, and thalamus. One day after cortical ablation of the left somatosensory cortex, the expression tended to decrease in the cortex ipsilateral to the injury. Four days after surgery, it increased markedly in the affected cortex and thereafter returned to the level of the control animals except for the area surrounding the injury, where GIF mRNA again increased 2 to 3 weeks after ablation. The transient increase in GIF mRNA expression may reflect efforts to inhibit excessive sprouting of neurites. We also studied the effect of topically applied basic fibroblast growth factor (bFGF), which has a range of neurotrophic effects, on GIF mRNA expression. Topically applied bFGF enhanced the suppression of GIF at 1 day after surgery, though it did not affect the subsequent response. GIF can therefore be assumed to affect the outgrowth of injured neurites and might play a major role in maintenance of the neuronal network in cooperation with other trophic factors. Modification of these factors may be the key to improve neuronal damage after injury.

BACKGROUND

Chromogranin-A (Cg-A) is a 439-amino-acid protein contained in secretory granules of neuroendocrine cells, in addition to specific hormone peptides or neuropeptides. Since Cg-A is co-released with peptide hormones its serum concentration can be used as a marker of neuroendocrine tumors.

OBJECTIVE

Evaluation of the analytical performance of a new IRMA method for Cg-A assay and of the clinical value of serum Cg-A and neuron-specific enolase (NSE) in neuroendocrine tumors. In addition, we compared the diagnostic usefulness of both Cg-A and NSE serum levels and their relationship to tissue expression.

METHODS

Initially we evaluated the analytical performance (intra- and interassay imprecision, dilution test and detection limit) of the Cg-A RIACT method (CIS Bio-International, Gif-sur-Yvette, France). We selected 50 patients affected by various histologically confirmed neuroendocrine tumors (NETs): 111In-pentetreotide scan and helical computed tomography were employed to assess tumor extent. Cg-A and NSE were measured before surgery in serum samples of patients and 50 age-matched controls by IRMA methods. After surgery immunohistochemical stains for Cg-A and NSE were performed on surgical specimens of tumor tissue.

RESULTS

Cg-A levels were significantly higher (p < 0.0001) in patients with NETs than in healthy controls and we found a positive correlation between serum and tissue expression (p < 0.05). Serum levels of Cg-A were also related to tumor extent (p < 0.05) but in some cases we observed significant elevation of serum Cg-A in small, intensely immunoreactive NETs. ROC curve analysis showed better accuracy for serum Cg-A compared to NSE in the diagnosis of NETs, while no significant relationship was found between serum expression and immunostaining for NSE.

CONCLUSIONS

Our results confirmed the biological and clinical significance of circulating Cg-A as an expression of granular content in neuroendocrine tissues and supported the complementary usefulness of serum Cg-A in the diagnosis and evaluation of NETs together with imaging modalities.

OBJECTIVE

In Japan, an increase in the number of routine esophagogastroduodenoscopy procedures is expected because several studies have reported that endoscopy screening has reduced gastric cancer mortality. Magnifying narrow-band imaging has been reported to be effective for accurate diagnosis of gastric abnormalities such as cancers, adenomas, and intestinal metaplasia. However, the efficacy of this method in routine esophagogastroduodenoscopy has not been clarified.

METHODS

We divided 3763 patients into two groups. The non-magnification group included 1842 patients who underwent endoscopy screening using GIF-H260/LUCERA-SPECTRUM between October 2014 and February 2015, whereas the magnification group included 1921 patients who underwent screening using GIF-H290Z/LUCERA-ELITE between March 2015 and May 2015. In the magnification group, diagnosis of cancer was conducted using the VS classification system. We did not carry out a biopsy when results were confirmed as non-cancer using magnifying narrow-band imaging. If cancer was diagnosed, or when a cancer or non-cancer diagnosis was difficult, we carried out a biopsy. We analyzed and compared the diagnostic performance between the two groups.

RESULTS

Gastric biopsy rate was significantly lower in the magnification group (29%) than in the non-magnification group (41%) (P < 0.001). Positive predictive value (PPV) for gastric cancer was significantly higher in the magnification group (5.5%) than in the non-magnification group (2.5%) (P < 0.001). Furthermore, PPV for gastric epithelial neoplasia was significantly higher in the magnification group (7.9%) than in the non-magnification group (3.2%) (P < 0.001).

CONCLUSIONS

Magnifying narrow-band imaging improves the diagnostic performance of routine esophagogastroduodenoscopy.