Evaluation of a microsphere-based flow cytometric assay for diagnosis of celiac disease

The multiplexed particle-based flow cytometric technology proposes a new approach for the diagnosis of autoimmune diseases combining the advantages of conventional methods with the ability to quantitatively determine multiple autoantibodies in the same sample, simultaneously and rapidly. Recently, a commercial kit (FIDIS Celiac, Biomedical Diagnostics, Mane la Vallé, France) was introduced for the simultaneous detection of IgA anti-tissue transglutaminase (anti-tTG), IgG, and IgA anti-gliadin antibodies (AGA). This study was undertaken to evaluate and compare the FIDIS Celiac kit with standardized commercial ELISAs (QUANTA Lite, INOVA Diagnostics Inc., San Diego, CA). A disease group consisted of 21 samples from untreated patients with biopsy confirmed celiac disease (CD), and two control groups of historical sera (207 from regular blood donors and 181 from chronically infected hepatitis patients) were studied. All control sera were negative for IgA anti-endomysial antibodies (EmA) and had an IgA concentration above the lower normal limit. Concerning the reproducibility, intra- and inter-assay coefficients of variation (CVs) ranging between 2% and 12%, and between 3% and 21%, respectively, were observed. Regarding the diagnostic quality, each assay was compared to the disease diagnosis using the McNemar test and the kappa (K) parameter, while ROC analysis was applied. Generally, the performance of FIDIS assay was proved almost equally adequate to that of ELISA in the detection of IgA anti-tTG antibodies, IgA and IgG AGA. However, the performance of FIDIS assay was found surmounting that of ELISA among hepatitis patients, possibly due to the avoidance of debris and unbound cross contaminants and, hence, the "noise" of such materials in samples under analysis. Taking our results together with the simplicity and the high throughput of FIDIS assay, its overall performance in the diagnosis of CD seems better than that of ELISA.     

Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development

FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.     

Management of Isolated Blunt Duodenal Injury

Five cases of duodenal injuries were treated in our hospital between January 1, 1975 and June 18, 1979. They belonged to the Class II and early Class III of duodenal injuries. They were treated with simple closure of the perforation in a single or double layer with external drainage. Only in one case were gastrojejunostomy and bilateral vagotomy added because the patient had a history of ulcer disease. The delay in operative treatment ranged between five and 48 hours. All responded well to the surgical treatment. In the instance of the longest operative delay, a purulent drainage occurred and it responded promptly to a selective antibiotic therapy. The average hospitalization stay was nine days for the patients operated upon early, whereas it was 15 days for the two delayed cases. No mortality was recorded.     

Interobserver variability in determining MIB-1 labeling indices in oligodendrogliomas

Several studies have shown that MIB-1 labeling indices correlate well with tumor grade and prognosis in a variety of tumor types. Several factors are responsible for some degree of variability in the determination of labeling indices. Interobserver variability is one of the factors often cited as responsible for this variability. A slide from each of 30 oligodendrogliomas, stained with MIB-1 antibody, was distributed to six pathologists. The same set of slides was reviewed by each individual. Each pathologist was instructed to determine a MIB-1 labeling index by evaluating 1,000 tumor cell nuclei from the area of the slide with the most staining. The labeling index record reflected a percentage of positive-staining tumor cells. Interobserver agreement was compared. MIB-1 labeling indices ranged from 0 to 45.7. Overall agreement was good (> or =0.75) with a concordance coefficient of 0.832 (confidence interval, 0.700 to 0.909). Variability was greater among tumors with higher labeling indices as compared with tumors with labeling indices closer to 0. The overall agreement of MIB-1 labeling indices, while not perfect, was good. The generally minor variability among observers may be related to differences in the area of the slide evaluated and in differing lower thresholds for interpreting positivity. Further improvement of concordance may theoretically be attainable by further training and discussion among observers.     

Chitinases and chitinase-like proteins in T(H)2 inflammation and asthma

Chitin is the second most abundant biopolymer in nature, where it protects crustaceans, parasites, fungi, and other pathogens from the adverse effects of their environments, hosts, or both. Because chitin does not exist in mammals, it had been assumed that the chitinases that degrade it are also restricted to lower life forms. However, chitinases and chitinase-like proteins have recently been noted in mice and human subjects. The prototypic chitinase, acidic mammalian chitinase, was also noted to be induced during T(H)2 inflammation through an IL-13-dependent mechanism. It was also shown to play an important role in the pathogenesis of T(H)2 inflammation and IL-13 effector pathway activation and demonstrated to be expressed in an exaggerated fashion in human asthmatic tissues. The finding that chitinases contribute to host anti-parasite responses and asthmatic T(H)2 inflammation support the concept that asthma might be a parasite-independent anti-parasite response.     

Dose-intensive therapy for extensive-stage small cell lung cancer and extrapulmonary small cell carcinoma: long-term outcome.

Treatment for extensive-stage small cell lung cancer (ES SCLC) or extrapulmonary small cell carcinoma (EPSC) is typically palliative. We set out to determine progression-free survival (PFS) and overall long-term survival of ES SCLC and EPSC patients, physiologically aged < or = 60 years, responding to first-line chemotherapy followed by high-dose combination alkylating agents with hematologic stem cell support. Patients in first-line chemotherapy response underwent stem cell collection (marrow, peripheral blood progenitor cells, or both) followed by high-dose therapy with 1 of 2 regimens: CBP (cyclophosphamide, cisplatin, and carmustine) or ICE (ifosfamide, carboplatin, and etoposide) with or without etanidazole. Involved-field radiotherapy was given to selected patients with oligometastatic disease distributed in sites allowing for reasonable radiation ports, and prophylactic cranial radiotherapy was given upon recovery to patients in complete response (CR) or near-CR. A total of 36 patients were treated. Of 29 patients with ES SCLC, 6 (21%) had achieved CR, 18 near-CR, and 5 partial response prior to high-dose therapy. Of 7 patients with EPSC, 3 (43%) had achieved CR, 3 had achieved near-CR, and 1 had progression of disease prior to high-dose therapy. Thirteen ES SCLC patients received high-dose CBP. Of the remaining 23 patients with SCLC or EPSC, 17 were treated with ICE and 6 with ICE plus etanidazole, a hypoxic cell sensitizer. Treatment-related mortality was 11% (4 of 36 patients). For all patients, the median event-free survival (EFS) was 5 months. The 2- and 5-year survivals after intensification were 12% (95% confidence interval [CI], 5%-31%) and 9% (95% CI, 3%-27%), respectively. Of the 30 patients in or near CR prior to high-dose therapy, 5 remain continuously progression-free (2 ES SCLC, 3 EPSC) for a median of 55 months (range, 1-96 months) after high-dose therapy. By multivariate analysis, factors associated with more favorable EFS were the use of a more aggressive induction regimen (ICE), and the EPSC histology. These factors were also associated with more favorable overall survival. Other factors associated with more favorable overall survival were the use of short induction therapy (< or = 4 cycles) and younger age (<50 years). Except for high-dose ICE with etanidazole, the use of high-dose systemic therapy in ES SCLC and EPSC was associated with low treatment-related morbidity and mortality over the past 5 years. Late complications were infrequent, and most patients returned to full-time work and activity, barring disease recurrence. Nonetheless, few patients with ES SCLC have progression-free long-term survival. We conclude that high-dose therapy is not indicated as an approach for ES SCLC, except as part of an investigative trial. Conversely, 3 of the 7 patients with EPSC remain relapse-free (range, 1-96 months), warranting further phase II evaluation of this approach in this population.     

Alteration in platelet count during early pregnancy in the mouse

Published reports of pregnancy associated thrombocytopenia in mice have utilized the Quackenbush strain. The inability of some laboratories to verify this observation in other mouse strains prompted us to report our findings by using Swiss Albino ICR mice. In Exp. 1, pregnant and pseudopregnant mice were bled prior to mating (time 0) and daily on day 1 (vaginal plug) through day 7. In Exp. 2, media from 24 hr cultures of 2-cell mouse embryos or media from unfertilized oocytes were injected into splenectomized mice. Animals were bled at time 0 (before injection) and at 30, 60, and 120 min after injection. In Exp. 3, splenectomized mice were treated with either media from 2-cell stage embryos or with media supplemented with synthetic platelet-activating factor (PAF: 0.05, 0.1 or 0.2 micrograms). Animals were bled as in Exp. 2. Platelet numbers were determined in duplicate from each blood sample by using a hemacytometer. In Exp. 4, antagonist (SRI 63-441) or vehicle was administered to mated mice on days 1 through 4 of pregnancy. Animals were examined on day 8 to determine number of developing conceptuses. In Exp. 1-3, data were analyzed by using ANOVA for repeated measures, and in Exp. 4 data were analyzed by chi-square analysis. In Exp. 1, there was a treatment x time interaction (P less than .06) due to transient thrombocytopenia in pregnant but not pseudopregnant mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Triazin-polymere. II. Polyphenylentriazine

Condensation of benzamidine hydrochloride with acetanhydride gives 2-methyl-4.6-diphenyl-s-triazine with yields of more than 90%. The corresponding reaction of terephthaldiamidine dihydrochloride leads to poly[(6-methyl-2.4-s-triazinediyl)-1.4-phenylene] of low degree of polymerization, soluble in conc. sulfuric acid. Benzamidine-N-carboxylic acid ethylester is converted to 2-hydroxy-4.6-diphenyl-s-triazine in a yield of 99% by heating. Terephthaldiamidine-di-N-carboxylic acid ethylester decomposes by heat treatment under loss of ethyl carbamate to the insoluble white poly[(6-hydroxy-2.4-s-triazinediyl)-1.4-phenylene].     

A comparison of genetic chromosomal loci for intracranial, thoracic aortic, and abdominal aortic aneurysms in search of common genetic risk factors.

BACKGROUND: Genetic factors are likely to be involved in the pathogenesis of intracranial, ascending thoracic aorta, and infrarenal aortic abdominal aneurysms. Common genetic risk factors for these three types of aneurysms have been suggested. This review describes the results of whole-genome linkage studies on intracranial, thoracic aorta, and aortic abdominal aneurysms, and compares the genomic loci identified in these studies in search of possible common genetic risk factors for the three aneurysmal types. METHODS: A literature search of all whole-genome linkage studies performed on intracranial, thoracic aorta, and aortic abdominal aneurysms was performed. The genomic loci identified in these studies were described and compared in search of similarities between them. RESULTS: Five chromosomal regions on 3p24-25, 4q32-34, 5q, 11q24, and 19q that may play a role in the pathogenesis of two or more aneurysmal types were identified: 3p24-25 for thoracic aorta and intracranial aneurysms; 4q32-34 for aortic abdominal and intracranial aneurysms; 5q for thoracic aorta and intracranial aneurysms; 11q24 for thoracic aorta, aortic abdominal, and intracranial aneurysms; and 19q for aortic abdominal and intracranial aneurysms. CONCLUSIONS: Five chromosomal regions that may include common genetic factors for intracranial, thoracic aorta, and aortic abdominal aneurysms were identified. Further studies are needed to explore these chromosomal regions in different aneurysm patient groups and may further help to unravel the disease pathogenesis of aneurysms in general.