Gastrointestinal involvement of primary skin diseases.

Less is known about gastrointestinal (GI) involvement of primary skin diseases due to the difference in embryology, histology, microbiology and physiology between integument and alimentary tract. Oesophagus, following the oropharyngeal mucosa, is the most common GI segment affected by primary skin diseases, especially by eosinophilic oesophagitis, lichen planus and autoimmune bullous dermatoses like pemphigus vulgaris, mucosal membrane pemphigoid and epidermolysis bullosa acquisita. Eosinophilic oesophagitis is an emerging chronic atopic disease with oesophageal dysfunction as the typical presentation, and oesophageal narrowing, rings and stricture as late complications. Oesophageal lichen planus mainly involves the proximal to mid-oesophagus in elderly aged women with long-term oral mucosal lesions. In acute attack of pemphigus vulgaris, oesophageal involvement is not uncommon but often neglected and may cause sloughing oesophagitis (oesophagitis dissecans superficialis) with acute GI bleeding in rare cases. GI manifestation of hereditary bradykininergic angio-oedema with colicky acute abdomen mostly affects small intestine, usually in the absence of pruritus or urticaria, and is more severe and long-lasting than the acquired histaminergic form. Strong evidence supports association between inflammatory bowel disease, especially Crohn disease, and hidradenitis suppurativa/acne inversa. Patients with vitiligo need surveillance of autoimmune liver disease, autoimmune atrophic gastritis or coeliac disease when corresponding symptoms become suspect. Melanoma is the most common primary tumour metastatic to the GI tract, with small intestine predominantly targeted. Gastrointestinal involvement is not uncommon in disseminated mycosis fungoides. Extramammary Paget's disease is an intraepidermal adenocarcinoma of controversial origin, and a high association between the anogenital occurrence and colorectal adenocarcinoma has been reported. As GI tract is the largest organ system with multidimensional functions, dermatologists in daily practice should be aware of the gastrointestinal morbidities related to primary skin diseases for an early diagnosis and treatment.

Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish.

The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. In the current study, we found that AML patients with low bone marrow (BM) SOX4 expression had higher remission rates and longer overall survival than those with high SOX4 expression, regardless of age, white blood cell count at diagnosis, karyotype profile and NPM1/FLT3-ITD status. To elucidate the role of SOX4 in leukemogenesis, we generated a transgenic zebrafish model that overexpressed human SOX4 in the myeloid lineage Tg(spi1-SOX4-EGFP). These transgenic zebrafish showed, at 5 months of age, increased myelopoiesis with dedifferentiation in kidney marrow. At 9 months of age, their kidney structure was significantly effaced and distorted by increased infiltration of myeloid progenitor cells. These results suggest that SOX4 is not only an independent prognostic factor of AML, but also an important molecular factor in leukemogenesis.

Infrared thermography to mass-screen suspected SARS patients with fever.

Fever greater than 38 degrees C is a cardinal sign of patients with the severe acute respiratory syndromes (SARS). To reduce the risk of nosocomial cross infections, screening all patients and visitors who visit hospitals and clinics for fever at the entrance of every hospital building has become a standard protocol in Taiwan during the SARS epidemic from mid-April to mid-June 2003. We used a digital infrared thermal imaging (DITI) system (Telesis Spectrum 9000 MB) to conduct mass screening of patients and visitors who entered the hospital to identify those with fever. The DITI system has two components: a sensor head and a PC imaging workstation. The sensor head is an optic-mechanical device which consists of imagining optics for focusing the infrared source information on the infrared detector. The infrared images are further converted into electrical signals, which are then processed for real-time display on the monitor. During the period from April 13 to May 12 2003, 72,327 outpatients and visitors entered Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan. A total of 305 febrile patients (0.42%) was detected by infrared thermography. Among them, three probable SARS patients were identified after thorough studies including contact history, laboratory tests and radiology examinations. The findings suggests that infrared thermography was an effective and reliable tool ideal for mass-screening patients with fever in the initial phase of screening for SARS patients at a busy hospital which sees approximately 3,000 outpatients every weekday during the SARS epidemic.

Virtual reality orthopedic surgery simulator.

This paper describes a highly interactive virtual reality orthopedic surgery simulator. The simulator allows surgeons to use various surgical instruments to operate on virtual rigid anatomic structures, such bones, prostheses and bone grafts, to simulate every procedure on the rigid structures for complex orthopedic surgeries, including arthroplasty, corrective or open osteotomy, open reduction of fractures and amputation. A comparative study of the simulator with paper simulation was performed and showed that interns and residents found the simulator to be a useful learning tool, and that visiting doctors could use it effectively for planning verification and rehearsal of operations.

Suppression of Fas ligand expression on endothelial cells by arsenite through reactive oxygen species.

Chronic exposure to arsenite is associated with vascular disease, such as arteriosclerosis. However, the cellular mechanisms for vascular disease in response to arsenic are not well known. The present study has demonstrated that arsenite not arsenate decreased the Fas ligand (FasL) expression on ECV304 cells through reactive oxygen species. Incubation of ECV304 cells with arsenite decreased the FasL expression and increased the intracellular peroxide levels. In addition, hydrogen peroxide was found to suppress FasL expression in a dose-dependent manner. The antioxidant, N-acetyl-cysteine, blocked the suppression of FasL expression in response to arsenite. These data suggested that arsenite initiates endothelium dysfunction, at least partly, by suppressing the FasL expression through activating reactive oxygen species sensitive endothelial cell signaling.

Diagnosis of herniated intervertebral disc assisted by 3-dimensional, multiaxial, magnetic resonance imaging.

Magnetic resonance (MR) imaging with multiaxial cross sections has been used to improve the resolution of small, fine, and slender spinal roots to more precisely diagnose herniated intervertebral disc (HIVD), especially in cases of far lateral disc (FLD) herniation. However, false-negative results remain a problem because of the unsatisfactory resolution of these methods. We report the use of a volume visualization technique to generate three-dimensional (3D) images from multiaxial sections. In our study, 10 patients with FLD herniation each underwent MR imaging (method 1), 3D MR image reconstruction with single-axis cross-sections (method 2), and 3D MR image reconstruction with multiaxial cross sections (method 3). Final diagnoses were confirmed at surgery. The preoperative diagnosis matched the operative findings in five patients using method 1, six patients using method 2, and nine patients using method 3. In addition, the software developed for this application includes functions which simulate decompression of the spinal cord and roots. Therefore, this computer-aided diagnosis system using multiaxial cross sections is a useful tool for diagnosing HIVD and for training medical residents and students. This technique has three main advantages over conventional imaging modalities: 1) resolution of small, fine, or slender anatomic structures, which reduces the possibility of false-positive and false-negative image findings; 2) segmentation (disarticulation) of images; and 3) simulation of surgery.

The characterization of adenyl cyclase activity in FRTL-5 cell line.

The purpose of this study is to characterize the adenyl cyclase (AC) activity in Fisher rat thyroid cell line when stimulated with several agonists, such as: forskolin, sodium fluoride, Gpp(NH)p (guanosine-5'-(beta, gamma -imino) triphosphate or thyrotropin. The following studies such as: dose-response, pH, temperature, time-response, millieu concentration, 3H-thymidine uptake, Km and Vm study were also performed. Adenyl cyclase activity was measured as adenosine 3', 5'-cyclic monophosphate generated by cell cultures in 120- minutes incubation at 37 degrees C. The basal AC activity was 15.0 +/- 7.0 (mean +/- SEM, n = 6) pmol/100,000 cells/120 minutes. Forskolin at 0.1 mM increased the AC activity to 10 folds of basal AC activity. Thyroid stimulating hormone at 1 mU/ml and 10 mU/ml increased the AC activity 2 and 15 folds, respectively. Sodium fluoride stimulation study demonstrated dual actions of fluoride on adenylate cyclase; when the cells were assayed with increasing concentration of NaF, the AC activity increased as the concentration of NaF increased from 0.01 to 1 mM, but decreased strikingly as that concentration increased from 1 mM to 100 mM. When the concentration of nonhydrolyzable guanine nucleotide analogs increased in the presence of TSH, there was first an increase in adenylate cyclase activity, followed by a decrease at higher concentration. The amount of cAMP generation was much higher (P < 0.05) in hypotonic than in isotonic millieu. When the incubation temperature raised to 56 degrees C, all the AC activity was diminished. The optimal pH for AC activity was in the range of 7.4 and 8.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid quantification of adenosine cyclic 3',5'-monophosphate by competitive enzyme-linked immunosorbent assay.

A reliable and rapid enzyme-linked immunosorbent assay (ELISA) for cyclic AMP determination is described. Succinyl cyclic AMP, coupled to human albumin, was injected into rabbit to elicit antibodies to cyclic nucleotide hapten. Succinyl cyclic nucleotide to human albumin as immunogen or the cyclic AMP to porcine thyroglobulin as coating antigen was conjugated by a carbodiimide coupling procedure. The latter conjugate, captured to microplate with coating buffer and blocked with 0.8% gelatin for 30 minutes, was bound to antibody in inverse proportion to free cyclic AMP in a sample or standard. Bound antibody was then quantified with horseradish peroxidase-labelled goat antirabbit immunoglobulin and ABTS (2, 2'-Azinobis (3-ethylbenzthiazolinesulfonic Acid). Our results showed that concentration of both standard and sample cyclic AMP could be measured as low as 2.5 fmol/well (0.05 pmol/ml). The intra- and inter-assay coefficients of variation for samples were 6.0-8.0% and 8.9-9.5%, respectively. In addition, there was no cross-reaction of the antisera with ADP, ATP, 5'-AMP or cyclic GMP. Short period of incubation at room temperature seems as good as long period of incubation at 4 degrees C. The biological study demonstrated a consistency between increase in platelet-cyclic AMP generation after prostaglandin E1 stimulation and its biological effects. Our approach to ELISA is validated by showing agreement in levels, obtained in parallel by ELISA and RIA, of cyclic AMP content in extracts of prostaglandin E1-stimulated platelet cells.

The establishment of radioimmunoassay of cyclic AMP.

Succinyl cyclic AMP, coupled with human albumin, was injected into rabbit to elicit antibodies to the cyclic nucleotide hapten. The succinyl cyclic nucleotides were conjugated to human albumin through a carbodiimide coupling procedure. The radioligand was prepared essentially by the modified method of Hunter and Greenwood. The resulting radiolabeled 125-ScAMP-TME was subsequently purified by reverse phase chromatography on Seppak C18 cartridge and used as tracers. Free and bound form of labeled antigens in the assay system were separated according to their differences in adsorption to solid material, i.e., charcoal. The antisera in routine use had 8% cross-reactivity with cyclic GMP, but had no cross-reactivity with ADP, 5'-AMP or ATP. The sensitivity of the assay in standard was around 0.05 pmol/ml. The sequential saturation analysis system was superior to the equilibrium study in terms of its sensitivity in standard curve determination. The media dilution and recovery studies showed good parallelism with the standard curve. The intra-assay and inter-assay coefficient variations were 5% and 7%, respectively. It showed that a significant increase in tracer binding to the antibodies in equilibrium incubating system was obtained when they were incubated at 4 degrees C for up to 72 hours. When the standard curve was derived for Scatchard plot analysis, Kd of the curve decreased inversely with the increase of the antibodies diluted, the total binding capacity of the antibody would not alter. A thyroid-stimulating hormone produced a normal response of cyclic AMP concentrations in FRTL-5 tissue cultures.