The endocrine glands of the human foetus are active early in gestation, and various foetal and placental hormonal contributions are essential for growth and sexual differentiation. 1. The anterior pituitary gland has the ability to synthesize, store and secrete hormones early in gestation. The patterns of change in plasma concentrations of hGH (Fig. 1), ACTH, LH and FSH (Fig. 2) during gestation indicate that secretion is at a maximum at mid-gestation, followed by a progressive decrease towards term. The high levels at mid-gestation can be interpreted as due simultaneously to a high secretion rate, low peripheral catabolism and absence of feedback mechanism. In contrast, the secretions of PRL (Fig. 1) and TSH are moderate at mid-gestation and only increase in the last trimester of gestation. 2. Effective control by the central nervous system (CNS) of the pituitary secretions is still immature at mid-gestation. The presence in the foetal hypothalamus of releasing factors such as LRF (Fig. 5) and TRF, and of somatostatin (Fig. 6), a growth hormone release inhibiting factor (GIF), has been established. TRF and GIF, but not LRF, are also present in the cerebral cortex. It has been postulated that, early in life, relatively autonomous and unrestrained secretion of hypothalamic hypophysiotropic releasing factors occurs, and that, later in development, there is a maturation of inhibitory or restraining influences mediated via the CNS (feedback mechanisms) that modulates the secretion of the foetal adenohypophyseal hormones (Fig. 3 and 4). 3. Observations made with anencephalic newborn confirm that a functional hypothalamus is necessary during foetal life for the secretion of each of the hormones of the anterior pituitary gland with the exception of PRL, the secretion of which is normal in anencephaly. Although somatostatin probably participates in the regulation of hGH during foetal life, it appears evident from the anencephaly data that this regulation can only be fully understood by postulating the existence of a growth hormone releasing factor (GRF).

Background and objective: EUS has been shown in two small series to be capable of documenting increases in the total esophageal wall thickness (TWT) in children and adults with eosinophilic esophagitis (EoE). To apply EUS-derived TWT in clinical situations or in scientific investigations in pediatric EoE, measurements of esophageal TWT in children of differing ages and heights are required.

Materials and methods: Thirty patients (18M: 12F, 7 months to 20 years and 10 months) with a history of esophageal symptoms, but no endoscopic or histologic criteria of EoE were studied using a through the scope 20 MHZ Olympus Ultrasound miniprobe UM-3R (Olympus America, Center Valley Pa 18034) through a GIF Q180 or 160 (Olympus) standard pediatric upper endoscope. The mucosa, the mucosa plus submucosa, and the TWT were measured in the mid- and distal esophagus immediately before taking diagnostic biopsies.

Results: Measurements from both sites showed a statistically significant increase in TWT as a function of age (P < 0.001) and height (P < 0.001), as did the individual layers. The width of the mucosa and the submucosa were equivalent and together, they contributed more than half of the entire TWT. There were no significant differences between the means of the mid- and distal esophageal measurements. A multiple regression equation that can predict TWT based on age, with 95% confidence limits, is presented.

Conclusions: EUS has demonstrated that esophageal TWT in a cohort of control children correlates with height and with age and has provided insights into the organization of the esophageal wall. Esophageal TWT values obtained by EUS can now be interpreted to recognize esophageal wall thickening throughout childhood.

Keywords: EUS; esophagus; pediatrics.

Study objective. The study examined the peculiarities of upper gastrointestinal tract diseases in children suffering from a syndrome of heart connective tissue dysplasia (HCTDS) born from persons exposed to ionizing radiation in a childhood after the ChNPP accident. Materials and methods. The study included 120 children suffering from HCTDS (group I) and 75 persons having no signs of the syndrome (Group II). Diagnosis of HCTDS was obtained from echocardiography in Band M-modes and Doppler echocardiography. Esophagogastroduodenoscopy was performed using a flexible endoscope "OLYMPUS" model GIF-P3. Abdominal diagnostic ultrasound was used to assay the structure of abdominal parenchymal viscera. Results. Upper gastrointestinal tract diseases (UGITD) manifest earlier in children suffering the HCTDS (beginning from a preschool age). Along with age the systemic pattern of organ and system injury becomes evident i.e. there were 6.8 clinical/nosological entities per one child in Group I and 4.9 in Group II. Clinical presentation of chronic UGITD diseases in children suffering concomitant HCTDS were characterized by more frequent exacerbation after the psychoemotional and physical strain, more frequent intestinal motor dysfunction, nervous system disorders (80 %), and chronic infections (62.2 %). Endoscopic pattern of chronic UGITD with concomitant HCTDS featured a combination of mucosal inflammation (a range of various forms of esophagitis, erythematous and hypertrophic gastroduodenopathy) with abnormal gastrointestinal motor function i.e. gastroesophageal and duodenogastric reflux (73.34 %). Destructive lesions at most of duodenal zone were found in 20 %. Conclusions. UGITD namely chronic gastroduodenitis with typically concomitant involvement of several parts of digestive tract are most prevalent within all digestive system diseases in remote period upon the Chornobyl disaster in children born from persons exposed to ionizing radiation in a childhood. Presentation of UGITD occurs earlier in children suffering HCTDS with evident systemic pattern of organ and system injury along with an age. Refluxes of various nature and localization are the leading factors for UGITD onset in children suffering HCTDS. Thus a range of multidirectional tools of reflux disease prophylaxis is required for inclusion to the disease management.

Echocardiographic examination (EUS) gives a good overview of the structure of the whole oesophagus and the paraoesophageal space. To the EUS picture of reflux oesophagitis and normal EUS picture of paraoesophageal lymph nodes relatively few publications are devoted. The objective of the present work is to describe ultrasonographic (USG) signs of endoscopically and histologically confirmed oesophagitis (grade III and IV) and compare them with a control group, describe the USG picture of paraoesophageal lymph nodes in subjects with oesophagitis and in controls. The authors examined, using an Olympus GIF-UM20 instrument with a radial probe (7.5 ad 12MHz), 30 patients with endoscopically and histologically confirmed oesophagitis (m/f 15/15) and a control group of 40 subjects (m/f 21/19) with a negative endoscopic and histological finding of the oesophagus, cardia and stomach, a USG finding on the hepatobiliary system and X-ray of the lungs. They assessed the thickness of the oesophageal wall and evaluated its USG structure. The authors examined also the paraoesophageal lymph nodes (number, size, shape, structure) in both groups. In oesophagitis they found in all instances less distinct outlines of the three inner USG layers of the oesophageal wall. The oesophageal wall in oesophagitis was significantly thicker than in controls (6.9 +/- 1.7 mm and 3.2 +/- 0.7, alpha=0.05). The paraoesophageal nodes could be evaluated in 21, i.e. 70% patients with oesophagtis and in 23 of 40, i.e. 30% of the controls. The mean number of lymph nodes in patients with oesophagitis was 2.1, in controls 1.8. The percentage of triangular and oval lymph nodes was 52 in oesophagitis, i.e 48%, in controls 57, i.e. 43%. The central echo was apparent in triangular/oval lymph nodes in 91/40%, in controlsin 85 and 30%. The mean dimensiion of triangular/oval lymph nodes in oesophagitis and controls was 7.3 +/- 2.3/6.3 +/- 1.6 mm and 8.5 +/- 2.3/6.5 +/- 1.7 mm. The differences of parameters recorded in lymph nodes in the two groups are not statistically significant.

CONCLUSIONS

The oesophageal wall in portions with oesophagitis is significantly thicker. The outlines of the inner three USG layers are not sharp. There is an association between oesophagitis and the number, size, shape and structure of paraoesophageal lymph nodes. The majority of paraoesophageal lymph nodes in both groups is above the 5 mm borderline. When malignant infiltration of the lymph nodes is suspected, thin needle aspiration biopsy under EUS control is indicated.

OBJECTIVE

Stuttering is a fluency disorder with a worldwide prevalence of 1%. Reports on the epidemiology of stuttering in India are limited. Our primary goal was to examine the prevalence of the disorder among school children. The study also aimed to examine risk factors associated with severity and the impact of parental consanguinity in stuttering.

METHODS

Children from 97 schools in the State of Tamil Nadu, India were screened. Extensive speech characterization, epidemiological details and three-generational pedigrees were collected for 180 probands. The genetic basis of stuttering was examined using the analysis of genealogical index of families (GIF), kinship group and sibling recurrence risk (SRR) measures. Regression analysis and chi-square tests were performed to test the association of risk factors with severity of the disorder.

RESULTS

Among the 74,544 school children screened, the prevalence of stuttering was found to be 0.46%. Pedigree analysis revealed a positive family history in 101 (56%) probands; overall familial incidence was 11%. We observed an overall male-favored sex ratio (4:1). Familial aggregation (GIF = 442.60, p-value <0.001) and sibling recurrence risk ratio (Ks = 0.197, SD = 0.041) was high among consanguineous families. Severity of stuttering was strongly associated with gender and moderately associated with age at onset.

CONCLUSIONS

The prevalence of stuttering in Tamil Nadu is estimated for the first time in this study. High familial incidence, familial aggregation and sibling recurrence risk ratio point to the presence of a genetic basis. Familial aggregation was high among consanguineous families although consanguinity did not seem to play a role in severity.

Histological features of tuberculosis are caseation necrosis and epithelioid cell granuloma formation. Both phenomena are interpreted as expression of cellular immunity. Caseation necrosis is thought to be immunopathology and epithelioid cell granuloma formation is considered to be expression of protective immunity. Recently roles of cytokines for granuloma formation are gradually elucidated. In this symposium, mechanisms and functions of necrosis and granuloma formation Dr. Akagawa reported differentiation of two types of phenotypically different macrophages from human monocytes by GM (granulocyte-macrophage)-CSF or M (macrophage)-CSF. Interestingly such a basic differentiation induced by CSF was affected by IL-4 (interleukin-4). Langerhans-like dendritic cells were generated by cooperation of GM-CSF and IL-4, and multinucleated cells were generated by cooperation of IL-4 and M-CSF. Dr. Fukuda reported human Langerhans cell granulomatosis (LCG) from the pathological and immunohistochemical standpoints. In situ proliferation of LCs in the LCG was demonstrated by immunohistochemistry using antibody to PCNA (proliferating cell nuclear antigen) which is used to detect proliferating cells. In the course of granuloma formation, damage and disruption of lung structure such as alveolar basement membrane and elastic tissue framework, and reactive intraluminar fibrosis was observed. Mechanism of cystic dilation was also reported. Cytokines might play important roles in these events. Dr. Ina demonstrated experimental epithelioid cell granuloma formation. Extract (granuloma inducing factor, GIF) from Schistosoma mansoni Egg-induced granuloma, TNF -alpha, or IL-1 beta were coated, individually on the surface of beads, then these beads were inoculated to rat's skins or cultured with rat's monocytes. Four weeks later, epithelioid cell granuloma was demonstrated histologically and electronmicroscopically around beads in vitro and in vivo. GIF-induced granuloma was more organized than cytokine-induced ones. In vitro using human monocytes, activated macrophages accumulated around beads of which cytokines or GIF were coated. It was suspected that many cytokines or other factors are needed to make epithelioid cell granuloma. Dr. Sakamoto showed the presence of acid fast bacilli and various inflammatory cells including lymphocytes and macrophages in the tuberculous caseous necrosis after exudative reaction (E-necrosis) by immunohistochemistry. But no acid fast bacilli or inflammatory cells were found in the caseous necrosis after productive reaction (P-necrosis). TNF-alpha (tumor necrosis factor-alpha) and IL-4 were stained in the E-necrosis and IL-4 and ICAM-1 (intercellular adhesion molecule-1) were positively stained in the cytoplasm of epithelioid cells by immunohistochemistry. It was suspected that many cells and cytokines were involved in epithelioid cell granuloma formation and caseous necrosis formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Phenolphthalein (PTH), which has been used as the active ingredient in a number of prescription and over-the-counter laxative products, is a rodent chemical carcinogen in multiple organs in the NTP 2-year bioassay at doses of 291-2927 mg/kg. This paper describes the toxicokinetics and estimates the internal dose of PTH administered as a single iv or gavage dose, or ad libitum for 14 days in feed to F344 rats, B6C3F1 mice, p53 (+/-) mice, and C57BL mice at doses that bracketed those used in the bioassay. Plasma concentrations for free phenolphthalein (PTH-F) and phenolphthalein glucuronide (PTH-G) were obtained for each dose regimen. Total phenolphthalein (PTH-T) was calculated as the sum of the molar concentrations of PTH-F and PTH-G. Noncompartmental pharmacokinetic models were used to calculate the area under the curve (AUC) from 0 h to infinity (AUC(infinity)), clearance (Cl), and oral bioavailability (F) for PTH-F; and were used to calculate AUC(infinity), t((1/2)), and relative absorption (Q) for PTH-T. After iv administration, PTH-F rapidly declined in rats and mice; PTH-T rose rapidly to Cmax and slowly declined 6-8 h after dosing, with no sex-related differences for rats or mice. For feed studies, mean plasma concentration (f1.gif" BORDER="0">(infinity)) and 24-h area under the curve (AUC(24h)) values were calculated. Results from feed studies showed no dose response in rat plasma PTH-F above approximately 50 mg/kg. Rat PTH-T AUC(24h) and f1.gif" BORDER="0">(infinity) were linear with doses up to approximately 650 mg/kg. In B6C3F1 mice, PTH-F and PTH-T AUC(24h) increased nonlinearly with doses above approximately 165 mg/kg. PTH is well absorbed and readily converted to PTH-G when administered in feed to rats and mice, except at the highest bioassay doses, where PTH absorption may be saturated.

Transplantation of the EL-4 lymphoma to syngeneic recipients caused significant endocrine changes which occurred very early as well as late after transplantation. Among the hormonal changes induced were a biphasic increase in the level of serum corticosterone, a biphasic decrease in serum insulin levels, an early decrease in prolactin and a terminal severe deficiency in thyroxine. The mechanism by which corticosterone levels are increased immediately following tumor transplantation appears to involve post-thymic T cells. In addition, the corticosterone response after tumor transplantation seems to be restricted to syngeneic recipients and does not seem to occur with allogeneic tumor transplantation. Further, the phenomenon may require an immunogenic tumor since the relatively nonimmunogenic mammary tumor virus (MTV) induced adenocarcinoma did not increase corticosterone in syngeneic C3H/He mice. Such data are consistent with the proposition that recognition of tumor antigen by mature T cells occurs within hours of tumor transplantation. This recognition appears to be MHC restricted. Whereas mitogen stimulation of T cells produces a glucocorticoid increasing factor designated GIF (Besedovsky et al., 1985b), it is reasonable to suggest that GIF is produced in vivo as part of the T cell response to tumor antigen. GIF in turn stimulates hypophyseal release of ACTH with a subsequent release of corticosterone from the adrenal gland. The biological relevance of this physiological increase in serum levels of corticosterone was examined with respect to the anti-inflammatory phenomenon often observed after tumor transplantation. First, a concordance was noted following tumor transplantation between elevated corticosterone levels and anti-inflammation. Similarly, transplantation of the MTV induced mammary adenocarcinoma which failed to increase serum levels of corticosterone did not exhibit anti-inflammation. Consistent with the concept that corticosterone levels increase following T cell recognition of tumor antigens, it is known that anti-inflammation does not occur with weakly immunogenic tumors but does follow transplantation of moderately immunogenic tumors (Normann, 1985b; Normann et al., 1985a). Second, adrenalectomy prevented the corticosterone response to tumor transplantation and eliminated tumor associated anti-inflammation. Additional studies are necessary to determine if the increase in serum levels of corticosterone alters other parameters of the host response to tumors. Anti-inflammation was shown to occur following tumor transplantation via a corticosterone dependent pathway.(ABSTRACT TRUNCATED AT 400 WORDS)

Parapoxviruses cause nodular lesions on the skin and mucosal membranes of pinnipeds and infections by these viruses have been documented worldwide. Seal parapoxvirus is currently classified as a tentative species of the Parapoxvirus genus. Tissue or swab samples were analyzed from 11 pinnipeds of different host species undergoing rehabilitation on the east and west coasts of the United States of America (USA) that were positive for parapoxvirus. The aim of the study was to compare parapoxvirus sequences of fragments of the B2L, DNA polymerase, GIF and viral interleukin-10 ortholog (vIL-10) genes and to examine the evolutionary relationship between viruses detected in different pinniped species and at different locations with other members of the Parapoxvirus genus, such as Orf virus (ORFV), Bovine papular stomatitis virus (BPSV) and Pseudocowpox virus (PCPV). The sequence analysis showed that the parapoxvirus sequences from the pinnipeds differed significantly from those found in terrestrial hosts and that they formed a separate cluster within the genus. Our results suggest that transmission of the same parapoxvirus strain is possible between different species, including between members of different families (phocids and otariids). Animals belonging to the same species but living in distant geographic locations presented genetically distant parapoxviruses. The findings of this study demonstrate that sealpox lesions in pinnipeds of different species are caused by viruses that belong to the Parapoxvirus genus but have significant genetic differences compared to the established virus species in terrestrial hosts, thus strongly supporting the classification of pinniped parapoxvirus as a new species of the genus.

Keywords: parapoxvirus; pinniped; seal parapoxvirus; sealpox; skin lesion.

The origin of epigenetics has been traditionally traced back to Conrad Hal Waddington's foundational work in 1940s. The aim of the present paper is to reveal a hidden history of epigenetics, by means of a multicenter approach. Our analysis shows that genetics and embryology in early XX century--far from being non-communicating vessels--shared similar questions, as epitomized by Thomas Hunt Morgan's works. Such questions were rooted in the theory of epigenesis and set the scene for the development of epigenetics. Since the 1950s, the contribution of key scientists (Mary Lyon and Eduardo Scarano), as well as the discussions at the international conference of Gif-sur-Yvette (1957) paved the way for three fundamental shifts of focus: 1. From the whole embryo to the gene; 2. From the gene to the complex extranuclear processes of development; 3. From cytoplasmic inheritance to the epigenetics mechanisms.

Laboratory batch experiments were conducted to examine mechanisms of Hg(II) removal by reactive materials proposed for groundwater treatment. These materials included granular iron filings (GIF), 1:1 (w/w) mixtures of metallurgical granular Fe powder + elemental S (MGI+S) and elemental Cu + elemental S (Cu+S), granular activated carbon (GAC), attapulgite clay (ATP), ATP treated with 2-amino-5-thiol-1,3,4-thiadiazole (ATP-a), and ATP treated with 2,5-dimercapto-1,3,4-thiadiazole (ATP-d). Following treatment of simulated groundwater containing 4 mg L(-1) Hg for 8 or 16 days, the solution pH values ranged from 6.8 to 8.8 and Eh values ranged from +400 to -400 mV. Large decreases in aqueous Hg concentrations were observed for ATP-d (>99%), GIF (95%), MGI+S (94%), and Cu+S (90%). Treatment of Hg was less effective using ATP (29%), ATP-a (69%), and GAC (78%). Extended X-ray absorption fine structure (EXAFS) spectra of Hg on GIF, MGI+S, and GAC indicated the presence of an Hg-O bond at 2.04-2.07 Å, suggesting that Hg was bound to GIF corrosion products or to oxygen complexes associated with water sorbed to activated carbon. In contrast, bond lengths ranging from 2.35 to 2.48 Å were observed for Hg in Cu+S, ATP-a, and ATP-d treatments, suggesting the formation of Hg-S bonds.

Dose distribution images in radiation therapy play important roles in the management of cancer patients. To date, hard copies of these images have been stored for referral by radiation oncologists as needed. In most cases, these images are not available to medical personnel outside the radiation oncology department. We have developed a means to access these dose distribution images from the hospital via the World-Wide Web (WWW). A screen snapshot of a dose distribution image on the CRT of a treatment planning unit is copied to the WWW server and converted to a GIF (graphic interchange format) image. Similarly, we can register dose volume histograms and digitally reconstructed radiographs (DRR) on the WWW. Medical personnel can view these images through the WWW browser from anywhere in the hospital. As a result, radiation oncologists are given detailed information on target definition in treatment planning by expert physicians. The system also helps co-medical personnel in understanding dose distribution and predicting radiation injury. At the same time, it actualizes an electronic archive of dose distribution images, which is a database for quick and reliable review, evaluation, and comparison of treatment plans. This technique also fosters closer relationships among radiation oncologists, physicians, and co-medical personnel.

Objective: To evaluate the therapeutic effect of electroacupuncture on acute gastrointestinal injury (AGI) in patients with severe traumatic brain injury (sTBI).

Methods: A prospective randomized controlled trial was conducted. 126 consecutively hospitalized patients with AGI after sTBI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2018 to December 2019 were enrolled. The patients were divided into observation group and control group by random number table. All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days, including the treatments of primary diseases, indwelling nasogastric tube to extract gastric contents every 6 hours to determine gastric residual volume (GRV). When vital signs were basically stable, enteral nutrition (EN) was implemented and EN feeding amount and speed were adjusted according to GRV. On the basis of conventional western medicine treatment, the observation group was treated with electroacupuncture at Zusanli, Tianshu, Shangjuxu, Xiajuxu and Zhongwan, once in the morning and once in the evening, 30 minutes each time. The gastrointestinal function parameters including intra-abdominal pressure (IAP), serum diamine oxidase (DAO) and gastrointestinal failure (GIF) scores were observed before treatment and at day 3 and day 7 of treatment. The incidence of ICU hospital-acquired pneumonia (HAP-ICU), duration of mechanical ventilation (MV), length of ICU stay, 28-day mortality and adverse reactions of electroacupuncture were also observed in the two groups. Kaplan-Meier method was used for 28-day survival analysis.

Results: During the 7-day treatment and observation, 26 cases of 126 patients withdrew from the study, and 100 cases were actually enrolled, 50 cases in the observation group and 50 cases in the control group. IAP and DAO at day 3 of treatment in both groups were significantly lower than those before treatment [control group: IAP (cmH₂O, 1 cmH₂O = 0.098 kPa) was 13.75±2.76 vs. 18.11±3.97, DAO (U/L) was 129.88±24.81 vs. 158.01±22.64; observation group: IAP (cmH₂O) was 13.56±2.19 vs. 18.50±3.54, DAO (U/L) was 129.11±29.32 vs. 159.36±28.65; all P < 0.01]. The gastrointestinal function parameters of the two groups improved gradually with the extension of treatment time, and the IAP, DAO and GIF scores at day 7 of treatment in the observation group were significantly lower than those in the control group [IAP (cmH₂O): 11.28±3.61 vs. 12.68±3.23, DAO (U/L): 49.69±17.56 vs. 57.27±20.15, GIF score: 2.02±0.74 vs. 2.40±0.70, all P < 0.05). The duration of MV and the length of ICU stay in the observation group were significantly shorter than those in the control group [duration of MV (days): 15.72±4.60 vs. 18.08±4.54, length of ICU stay (days): 16.76±4.68 vs. 19.26±5.42, both P < 0.05], and the incidence of ICU-HAP and 28-day mortality were significantly lowered (12.0% vs. 30.0%, 22.0% vs. 32.0%, both P < 0.05). Survival analysis showed that the 28-day cumulative survival rate in the observation group was significantly higher than that in the control group (86.4% vs. 76.1%; Log-Rank test: χ² = 37.954, P < 0.001). The patients in the observation group had no significant adverse reaction of electroacupuncture treatment.

Conclusions: Electroacupuncture at corresponding acupoints can effectively improve gastrointestinal function in patients with AGI after sTBI, which is beneficial to shortening the length of ICU stay, promoting the recovery of the patients, and reducing the 28-day mortality.

Two adult-size endoscopes (Olympus GIF-K2 and ACMI TX-8) were compared for extent of duodenal intubation by the endoscopist's estimate of location and x-ray position in 55 patients. The endoscopes were not different in duodenal position when separately analyzed for the endoscopist's estimate or x-ray location. Combining the results for both endoscopes showed the endoscopist's estimate to differ significantly from x-ray location in 47% of patients (p = 0.02). When incorrect, the endoscopist overestimated 62% of the time and underestimated 38% of the time. X-ray evaluation of insertion depth confirmed that the second portion of the duodenum was reached in 96%, third portion in 51%, and fourth portion or beyond in 38% of patients. We conclude that fluoroscopic confirmation may be necessary when endoscopically assessing distal duodenal segments for pathology.

Interferons (IFNs) stimulate gene expression to mediate their biological actions. A multimeric transcription factor consisting of STAT1, STAT2 and p48, a DNA binding protein, regulates IFN-alpha/beta stimulated gene expression. Since the cellular level of p48 is also increased by pre-treatment of cells with IFN-gamma, it is also known as ISGF3gamma. To understand how IFN-gamma regulates the expression of the p48 gene, we have previously isolated and characterized the promoter of murine p48 gene and identified a novel gamma-IFN activated transcriptional element (GATE). In this study using several mutant constructs of p48 promoter we have determined that the same element responds to IFN-alpha/beta treatment. Relatively high doses of IFN-alpha/beta compared to IFN-gamma are required for the induction of p48 promoter. This ability of IFN-alpha/beta to regulate GATE dependent gene expression is linked to the activation of a factor induced by IFN-alpha. However, IFN-gamma induces the binding of two gamma-IFN inducible factors (GIFs) to GATE. The IFN-alpha inducible GATE binding factor is not recognized by specific antibodies raised against the known IFN-regulated factors. It is likely IFN-gamma is a stronger inducer of this gene because it activates two GIFs. GATE-like elements present in hither to undefined IFN-stimulated genes may control IFN-responses in a unique manner.

Meyer [Phys. Rev. E 50, 1485 (1994)] analyzed the filtering mechanism of polarizing a stored beam by scattering from an internal polarized target. We noticed in Meyer's derivation of Eq. (4) of that paper that he had added a new twist to an old argument [W. Brückner, Physics with Antiprotons at LEAR in the ACOL Era: Proceedings of the Third LEAR Workshop, Tignes, Savoie, France, January 19-26, 1985 (Editions Frontières, Gif-sur-Yvette, France, 1985), p. 245] by allowing some particles that are spin flipped to be kept in the beam. We show that this invalidates the old result and leads to a more complicated expression for the buildup of polarization.

The painting Rebecca and Eliezer at the Well, which hangs in the Fitzwilliam Museum, Cambridge, UK, is possibly one of the last figure painting executed by Nicolas Poussin at the very end of his life and is usually dated to the early 1660s. In this perspective special feature, Philippe Walter, Alain Brunelle and colleagues give new insights on the artist's working methods by a careful stateof-the-art imaging ToF-SIMS study of one sample taken on the edge of the painting. This approach allowed for the identification of the pigments used in the painting, their nature and components and those of the ground and preparatory layers, with the identification of the binder(s) and possible other additions of organic materials such as glue. This study paves the way to a wider use of ToF-SIMS for the analysis of ancient cultural heritage artefacts. Dr. Walter is the Director of the Molecular and Structural Archeology Laboratory (Université Pierre et Marie Curie, Paris, France). Dr. Brunelle is Head of the Mass Spectrometry Laboratory at the Institut de Chimie des Substances Naturelles (CNRS, Gif-sur-Yvette, France). Their long standing collaboration has led to several seminal publications on the analysis of ancient artefacts by mass spectrometry.

After the deprivation of gonad-inhibiting factor (GIF) from the brain in adult Nemertines of both sexes, the sexual characters appear and/or grow rapidly. Very early, RNA synthesis is promoted in young oocytes, DNA synthesis is increased in spermatogonia and primary spermatocytes and protein synthesis is significantly increased in germ cells and sexual somatic cells. The brain origin of GIF suggests a polypeptide nature whereas its effects are those of sex steroid hormones in Vertebrates. GIF could be a regulating hormone which would inhibit the secretion of tropic hormone(s) produced by unknown cells in proximity to the sexual targets.

Endocytoscopy (ECS) is a novel endoscopic technique that allows detailed diagnostic examination of the gastrointestinal tract at the cellular level. We previously reported that use of ECS at ×380 magnification (GIF-Y0002) allowed a pathologist to diagnose esophageal squamous cell carcinoma (ESCC) with high sensitivity (94.9%) but considerably low specificity (46.7%) because this low magnification did not reveal information about nuclear abnormality. In the present study, we used the same magnifying endoscope to observe various esophageal lesions, but employed digital 1.6-fold magnification to achieve an effective magnification of ×600, and evaluated whether this improved the diagnostic accuracy in distinguishing neoplastic from non-neoplastic lesions.We examined the morphology of surface cells using vital staining with toluidine blue and compared the histological features of 40 cases, including 19 case of ESCC and 21 non-neoplastic esophageal lesions (18 cases of esophagitis, 1 case of glycogenic acanthosis, 1 case of leiomyoma, and 1 case of normal squamous epithelium). One endoscopist classified the lesions using the type classification, and we consulted one pathologist for judgment of the ECS images as 'neoplastic', 'borderline', or 'non-neoplastic'. At ×600 magnification, the pathologist confirmed that nuclear abnormality became evident, in addition to the information about nuclear density provided by observation at ×380. The overall sensitivity and specificity with which the endoscopist was able to predict neoplastic lesions using the type classification was 100% (19/19) and 90.5% (19/21), respectively, in comparison with values of 94.7% (18/19 cases) and 76.2% (16/21), respectively, for the pathologist using a magnification of ×600. The pathologist diagnosed two non-neoplastic lesions and one case of ESCC showing an apparent increase of nuclear density with weak nuclear abnormality as 'borderline'. Among the 21 non-cancerous lesions, two cases of esophagitis that were misdiagnosed by the endoscopist were also misinterpreted as 'neoplastic' by the pathologist. We have shown, by consultation with a pathologist, that an ECS magnification of ×600 (on a 19-inch monitor) is adequate for recognition of nuclear abnormality. We consider that it is feasible to diagnose esophageal neoplasms on the basis of ECS images, and that biopsy histology can be omitted if a combination of increased nuclear density and nuclear abnormality is observed.

Dose distribution images play important roles in the management of cancer patients. To date hard copies of these images have been stored and referred to by radiation oncologists as needed. In most cases, these images were not available to medical personnel outside the radiation oncology department. We have developed a mechanism in the hospital to access these dose distribution images via WWW (World Wide Web). A screen snapshot of a dose distribution image on the CRT of a treatment planning machine is copied to the WWW server and converted to a GIF image. Similarly, we can register dose volume histograms and digitally reconstructed radiographs on the WWW. Medical personnel throughout the hospital can access the images through the WWW browser. As a result, radiation oncologists are given detailed information on target definition in treatment planning by expert physicians. The system also helps co-medical staff in understanding dose distributions and predicting radiation injuries. At the same time, it actualizes an electronic archive of dose distribution images, which is a database for quick and reliable review, evaluation and comparison of treatment plans. This technique also furthers a close relationship among radiation oncologists, physicians, and co-medical personnel.

The presentation of radiology exams can be enhanced through the use of dynamic images. Dynamic images differ from static images by the use of animation and are especially useful for depicting real-time activity such as the scrolling or the flow of contrast to enhance pathology. This is generally superior to a collection of static images as a representation of clinical workflow and provides a more robust appreciation of the case in question. Dynamic images can be shared electronically to facilitate teaching, case review, presentation, and sharing of interesting cases to be viewed in detail on a computer or mobile devices for education. The creation of movies or animated images from radiology data has traditionally been challenging based on technological limitations inherent in converting the Digital Imaging and Communications in Medicine (DICOM) standard to other formats or concerns related to the presence of protected health information (PHI). The solution presented here, named Cinebot, allows a simple "one-click" generation of anonymized dynamic movies or animated images within the picture archiving and communication system (PACS) workflow. This approach works across all imaging modalities, including stacked cross-sectional and multi-frame cine formats. Usage statistics over 2 years have shown this method to be well-received and useful throughout our enterprise.