Multicolor, time-gated, soft x-ray pinhole imaging of wire array and gas puff Z pinches on the Z and Saturn pulsed power generators.

A multicolor, time-gated, soft x-ray pinhole imaging instrument is fielded as part of the core diagnostic set on the 25 MA Z machine [M. E. Savage et al., in Proceedings of the Pulsed Power Plasma Sciences Conference (IEEE, New York, 2007), p. 979] for studying intense wire array and gas puff Z-pinch soft x-ray sources. Pinhole images are reflected from a planar multilayer mirror, passing 277 eV photons with <10 eV bandwidth. An adjacent pinhole camera uses filtration alone to view 1-10 keV photons simultaneously. Overlaying these data provides composite images that contain both spectral as well as spatial information, allowing for the study of radiation production in dense Z-pinch plasmas. Cu wire arrays at 20 MA on Z show the implosion of a colder cloud of material onto a hot dense core where K-shell photons are excited. A 528 eV imaging configuration has been developed on the 8 MA Saturn generator [R. B. Spielman et al., and A. I. P. Conf, Proc. 195, 3 (1989)] for imaging a bright Li-like Ar L-shell line. Ar gas puff Z pinches show an intense K-shell emission from a zippering stagnation front with L-shell emission dominating as the plasma cools.

Mechanical control of cyclic AMP signalling and gene transcription through integrins.

This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

Combination therapy of pentoxifylline and TNFalpha monoclonal antibody in dextran sulphate-induced mouse colitis.

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) has been suspected of playing an important role in the pathogenesis of inflammatory bowel diseases, and has become a target for the treatment of these diseases. Open-label, placebo controlled studies have shown that engineered CDP571 and chimeric anti-TNF antibody (cA2) provide a significant benefit in Crohn's disease. Since these antibodies have to be used repeatedly to maintain remission in inflammatory bowel disease, there is a concern that their use may compromise host defence and produce toxic side-effects. METHODS: We evaluated the combined use of mouse specific TNFalpha mab (25 microg/mouse, Endogen) and pentoxifylline (PF, 100 mg/kg/day, p.o., TNFalpha release inhibitor) in the DSS (3% dextran sulphate solution) model of mouse colitis. Colitis was induced by the feeding of 3% DSS for three cycles. The study groups were: Group I: single injection of rat anti-mouse IgG, Group II: single injection of TNFalpha mab, Group III: daily PF for three cycles, Group IV: single injection of TNFalpha mab + PF for three cycles, Group V: TNFalpha mab at the beginning of each cycle (three injections) and Group VI: TNFalpha mab (three injections) + daily PF for three cycles. Daily disease activity (DAI) was measured throughout the study. At the end of each cycle, colon tissue was processed for histology, myeloperoxidase (MPO) and plasma TNFalpha. RESULTS: Mice treated with a single injection of TNFalpha alone or TNFalpha mab + PF showed significantly lower DAI, inflammation scores and ulcer index compared with the IgG treated group. Mice treated with TNFalpha mab + PF had no ulcers. Multiple injections of TNFalpha mab or TNFalpha mab + PF showed greater inhibition in DAI and cytokines in the first two cycles. However, in the third cycle, multiple injections of TNFalpha mab showed adverse proinflammatory effects. CONCLUSION: The simultaneous administration of pentoxifylline and TNFalpha mab may enhance therapeutic outcomes in inflammatory bowel disease and reduce the side-effects associated with the repeated use of TNFalpha mab.

Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions.

The extracellular matrix (ECM) activates signalling pathways that control cell behaviour by binding to cell-surface integrin receptors and inducing the formation of focal adhesion complexes (FACs). In addition to clustered integrins, FACs contain proteins that mechanically couple the integrins to the cytoskeleton and to immobilized signal-transducing molecules. Cell adhesion to the ECM also induces a rapid increase in the translation of preexisting messenger RNAs. Gene expression can be controlled locally by targeting mRNAs to specialized cytoskeletal domains. Here we investigate whether cell binding to the ECM promotes formation of a cytoskeletal microcompartment specialized for translational control at the site of integrin binding. High-resolution in situ hybridization revealed that mRNA and ribosomes rapidly and specifically localized to FACs that form when cells bind to ECM-coated microbeads. Relocation of these protein synthesis components to the FAC depended on the ability of integrins to mechanically couple the ECM to the contractile cytoskeleton and on associated tension-moulding of the actin lattice. Our results suggest a new type of gene regulation by integrins and by mechanical stress which may involve translation of mRNAs into proteins near the sites of signal reception.

Observer agreement on interpreting colposcopic images of CIN.

The purpose of this work was to study intraobserver and interobserver variation in the interpretation of colposcopic images of cervical intraepithelial neoplasia (CIN). Twenty-three experienced colposcopists were asked to assess colposcopic images presented on slides and to select the biopsy site. Eleven cases were independently interpreted twice with an interval of 2-3 months by all observers. No information about the cytological classification was available. In each case the "majority assessment" was considered as the standard, being "no CIN" in 2 cases, CIN I in 4 cases, CIN II in 3 cases, and CIN III in 2 cases. Intraobserver concordance was 66.7%, the kappa value was 0.54. Interobserver agreement was found to be 52.4 and 51.0% in the first and second sessions, respectively, while the mean kappa values were 0.41 and 0.33, respectively. In selecting the site for biopsy, 77.4% of all observers agreed while the same site was selected in 85.3% of cases by the individual colposcopist in the two sessions. Overall, CIN I and II interpretations revealed lower levels of agreement than no CIN or CIN III interpretations. It is concluded that observer variability in interpreting colposcopic images and selecting the site for biopsy is in the same range as observer variation in other subjective diagnostic tests such as cytology and histopathology. This variation should be taken into account in the colposcopical management of patients with abnormal cytology.

Relationship between corneal edema and topography.

We found that corneal edema can occur without significant concomitant changes in central and peripheral corneal topography. We examined the relationship between corneal edema and corneal topography in 10 subjects with normal ocular examinations. Baseline pachymetry and topographic measurements for both eyes of each patient were obtained. The right eye of each subject was exposed to an anoxic environment for 2 hours using a nitrogen chamber goggle. The left eye served as control. Optical pachymetry and computerized corneal topographic measurements were taken for both eyes immediately after removal of the nitrogen chamber goggle. All corneas exposed to the nitrogen chamber were thickened in all areas after removal of goggles. Average percent thickening per area was: 16.4% centrally, 6.3% nasally, 6.0% temporally, 6.3% superiorly, and 9.2% inferiorly. Corneas exposed to the nitrogen chamber demonstrated no significant topographic changes, except in the nasal area where the corneal power lessened. Furthermore, there was no significant correlation between corneal thickening in any area measured and changes in corneal topography. Control corneas did not thicken or demonstrate significant topographic changes.

A distal tyrosinase upstream element stimulates gene expression in neural-crest-derived melanocytes of transgenic mice: position-independent and mosaic expression.

We have assessed the importance of a melanocyte-specific DNase I hypersensitive site and matrix attachment region situated 15 kb upstream of the mouse tyrosinase gene by analysis in transgenic mice. Transgenes containing all, part, or none of this region linked to the tyrosinase promoter and human tyrosinase cDNA were introduced into genetically albino mice, and pigmentation and transgene message levels were analyzed in the resulting transgenic lines. The effect of the upstream region was to enhance significantly gene expression in melanocytes, and to provide position-independent expression of the transgene. Two exceptions to complete position independence were seen; these lines displayed a mosaic expression pattern in which the transgene was expressed fully in some melanocyte clones but less so in others, resulting in transverse stripes of colours ranging from near white to dark grey. Unexpectedly, pigmentation in the eye of all transgenic lines containing the upstream region was nonuniform, in that the neural-crest-derived melanocytes of the choroid and anterior iris contained significantly more pigment than those derived from the optic cup (retinal pigment epithelium and posterior iris). Transgenes containing a small part or none of the upstream region were expressed poorly and in a position-dependent manner; of those lines that were visibly pigmented, expression was equal in the neural crest and optic-cup-derived cells of the eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Human papillomavirus DNA and genotypes: prognostic factors for progression of cervical intraepithelial neoplasia.

A retrospective study of 227 patients presenting with abnormal cervical cytology was conducted to investigate the relationship between human papillomavirus (HPV) and progression of untreated cervical intraepithelial neoplasia (CIN) lesions. All patients had colposcopically directed biopsies for histologic diagnosis. The patients were followed cytologically and colposcopically for a mean of 19 months (range 6-42 months). Progression of a cervical lesion was defined as progression to a higher CIN grade confirmed histologically by directed biopsy. HPV DNA detection was done on material remaining from the cervical swabs by the general primer polymerase chain reaction (PCR) and type-specific PCR method, which made the detection of HPV types 6, 11, 16, 18, 31, 33 and not yet sequenced DNA types (X) possible. The presence of HPV DNA increased with the severity of the lesion (P < 0.001). In CIN III, a 100% HPV DNA prevalence was found, with HPV type 16 being the most prevalent type in 75%. Progression was significantly related to the presence of HPV DNA, in particular HPV type 16. The percentage of progressive disease was 21% in the case of HPV DNA positive lesions (n = 130) and 29% in the presence of HPV type 16, whereas HPV DNA negative lesions (n = 97) showed no progression. The detection of HPV DNA and HPV genotype can be used to identify patients with high-risk cervical lesions, since the presence of HPV DNA and genotype 16 in particular are closely related to CIN progression.

Post-discharge follow-up of stroke patients at Groote Schuur Hospital--a prospective study.

A survey of 59 stroke patients was undertaken between 3 and 6 months after the event to determine whether a weekly stroke round would improve the rate of referral for rehabilitation. Comparison with a previous survey at Groote Schuur Hospital showed a marked improvement (40% for physiotherapy and 10% for occupational therapy v. 76% and 50% respectively). A comparison of referral rates between younger (< 65 years old) and older patients (> 65 years old) revealed a significantly higher rate of referral among the younger patients. Attendance for both groups was low (approx. 7 sessions per 3 months). Social work was an important requirement and 60% of all patients expressed a need for more help. Social needs of older and younger patients differ. Despite the improved referral rate the rehabilitation of stroke patients is unsatisfactory, mainly because of transport difficulties. Methods should be investigated to establish rehabilitation centres in the community to overcome this impasse.

[The clinical diagnostic value of studies using magnetic stimulation]. / De klinisch-diagnostische betekenis van magnetostimulatie-onderzoek.

OBJECTIVE: To assess the clinical value of magnetic stimulation in various neurological disorders. DESIGN: A retrospective, descriptive study. SETTING: Department of Neurology and Clinical Neurophysiology, Medisch Spectrum Twente, Enschede. METHOD: Evaluation of motor pathways by magnetic stimulation of the human brain and peripheral nervous system is a new, noninvasive technique. A magnetic field pulse, produced by a wire coil, induces a small stimulating current applied to the motor cortex, cervical or lumbar spine or peripheral nerves. Muscle responses can be recorded by EMG recording systems in upper and lower extremities. Central conduction times can be obtained by computing latency differences between cortical and cervical or lumbar stimulation respectively. Magnetic motor evoked potentials were recorded in 60 patients with various neurological disorders, including multiple sclerosis, motor neuron disease, spinal and peripheral disorders. RESULTS: Abnormal motor evoked potentials were recorded in 5 of 8 patients with multiple sclerosis, 5 of 5 with motor neuron disorder, 5 of 6 with hereditary spastic paraplegia, 12 of 16 with various spinal disorders, 6 of 11 with lower motor neuron disorders, 0 of 4 with hysterical paralyses and 7 of the 10 remaining patients. However, these abnormalities were non-specific and could be suspected in most cases after physical examination. CONCLUSION: Magnetic stimulation is a painless and safe technique of which the clinical usefulness is still limited. It is likely that it will gain an important place in diagnosing neurological disorders, especially with involvement of motor pathways.

Mannose-resistant haemagglutination (MRHA) and haemolysin (Hly) production of strains of Escherichia coli isolated from children with diarrhoea: effect of breastfeeding.

Haemolysin production (Hly) and mannose-resistant haemagglutination induction (MRHA) of human (H), bovine (B), and both (HB) erythrocytes was investigated in strains of E. coli isolated from 142 cases of children with diarrhoea aged 0-36 months. Haemolysin production was more frequent in strains isolated from children under 1 year and this characteristic was strongly associated with HB+ haemagglutination (P < 0.005). Isolation frequency of MRHA strains was compared in 53 breastfed and 50 non-breastfed children under 1 year of age. HB+ strains were significantly more frequent in non-breastfed infants (P < 0.025). Severity of diarrhoea evaluated by the number of watery stools per day, was significantly reduced in the breastfed group (P < 0.05). The results suggests that breastfeeding may protect infants against the establishment of HB+ strains which might be acting either as a main pathogen or as an opportunistic strain.

Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastases: a prospective comparative study.

Although palpation has proved to be an unreliable staging procedure, the indications for and the implications of more reliable radiologic staging methods for the neck in patients with a primary squamous cell carcinoma of the head and neck remain controversial. Only a very accurate imaging technique can replace neck dissection in clinical NO disease. This study compares the value of palpation with computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US) with or without guided aspiration cytology for neck node staging. One hundred and thirty-two patients with squamous cell carcinoma of the head and neck were examined radiologically before undergoing a total of 180 neck dissections as part of their treatment. CT, US and MRI proved to be significantly more accurate than palpation for cervical lymph node staging. The accuracy of US-guided aspiration cytology was significantly better than of any other technique used in this study. Modern imaging techniques are essential for appropriate assessment of neck node metastases. In view of advances in the accuracy of contemporary imaging, the need for elective treatment of the neck requires reappraisal.

Micrometastases from squamous cell carcinoma in neck dissection specimens.

The incidence of micrometastases in cervical lymph nodes from squamous cell carcinomas of the head and neck was studied using routine histopathological examination. Micrometastases were found in 66 lymph nodes in 41 of the 92 tumor-positive neck dissection specimens. The detection of these micrometastases influenced postoperative treatment in 3 of the 77 patients with neck node metastases. The value of additional sectioning for detecting micrometastases was thus assessed. Sectioning at a deeper level in 600 originally histopathologically negative lymph nodes from 64 patients revealed 7 additional micrometastases in 5 patients. Antikeratin staining with a mixture of two monoclonal antibodies (AE1 and AE3) revealed 4 micrometastases in 739 originally histopathologically negative lymph nodes in 3 of 13 patients studied. Because of the unknown prognostic significance of micrometastases and the consequent arbitrary consequences for postoperative treatment, present findings show that the extra workload of immunostaining and deeper sectioning does not warrant their routine use in clinical practise.

Magnetic resonance imaging vs palpation of cervical lymph node metastasis.

In a series of 100 patients with head and neck carcinoma, the preoperative histopathologic findings of palpation and magnetic resonance imaging were compared with regard to both laterality and lymph node level (I through V). The overall error for palpation in detecting affected sides was 32%. Gadolinium-enhanced magnetic resonance images reliably upgraded 60% of the clinically negative necks, the overall error of magnetic resonance imaging being 16%. However, for both modalities, the sensitivity per level was too low to allow for selective neck dissections in case of only one positive level. These findings show that apart from primary tumor grading, magnetic resonance imaging can improve the preoperative grading of cervical lymph nodes. In selected cases, this may change the treatment plan to a "wait-and-see" policy or a more conservative type of neck dissection.

Differentiation dependent expression of P-glycoprotein in the normal and neoplastic human kidney.

Adult renal cell carcinoma (RCC) is clinically resistant to chemotherapy. However, in nephroblastoma (NBL) chemotherapy has increased survival dramatically. We studied the P-glycoprotein (P-gp) expression of 18 RCC and 9 NBL as well as 1 benign renal adenoma and fetal renal tissue using three different monoclonal antibodies (MRK-16, C-219, JSB-1). P-gp was found positive with all three antibodies in 12/18 RCC, while only 2 tumors were completely negative. Staining varied with respect to intensity and number of positive cells [5%-90%]. Intense staining was seen at the apical side of malignant tubules in well differentiated parts of RCC and in tubular structures of the benign renal adenoma. Poorly differentiated parts of the tumors showed less staining. In NBL blastemal parts were negative. In 4/8 specimens showing focal epithelial differentiation, however, the luminal side of more differentiated tubular structures did stain, strongly resembling P-gp staining in the developing fetal human kidney. These results indicate that P-gp expression in normal (fetal) human kidney as well as in benign and malignant tumors derived from this organ depends on the degree of differentiation of tubules, which may have implications for chemotherapy sensitivity in both malignant tumors.

Sinonasal non-Hodgkin's lymphomas and Wegener's granulomatosis: a clinicopathological study.

Reports of sinonasal non-Hodgkin's lymphomas, analysed with monoclonal antibodies, are scarce, and differentiation of these lymphomas from Wegener's granulomatosis can be difficult. In this study, we investigated histopathologically and immunohistologically 20 cases of non-Hodgkin's lymphoma, primary in the sinonasal region, and sinonasal biopsies from 11 patients with Wegener's granulomatosis. All T-cell lymphomas (n = 7) and plasmacytomas (n = 4) were stage I at clinical presentation, while all B-cell lymphomas (n = 9) presented at higher stages. T-cell lymphomas tended to be more frequent in the nasal cavity and paranasal sinuses; B-cell lymphomas more often presented in the nasopharynx. Remarkably, 1 B-cell lymphoma expressed MT1, and 1 T-cell lymphoma expressed L26 (CD 20). The follow-up of 2 patients with a clinical diagnosis of Wegener's granulomatosis was suggestive of non-Hodgkin's lymphoma. Retrospective immunohistochemical analysis revealed that the original histological diagnosis of non-specific inflammation had to be changed to T-cell lymphoma, pleomorphic small cell type. We conclude that a biopsy from the sinonasal region with a dense inflammatory infiltrate, consisting predominantly of T-lymphocytes, renders a diagnosis of Wegener's granulomatosis unlikely and is at least suspicious of T-cell lymphoma. Immunohistochemical analysis is warranted for this type of biopsy.

Triggering of the CD44 antigen on T lymphocytes promotes T cell adhesion through the LFA-1 pathway.

The CD44 molecule, a molecule which has been previously known as Hermes, Pgp-1, extracellular matrix receptor III, and In(Lu)-related p80, is currently thought to be involved in several steps of normal immune cell function, including lymphocyte adhesion to high endothelial venules and to the extracellular matrix and T cell activation. We now demonstrate that triggering of CD44 on T lymphocytes by anti-CD44 mAb promotes cell adhesion. The induced homotypic adhesion is mediated by lymphocyte function-associated antigen-1 (LFA-1), because it was inhibited by anti-LFA-1 antibodies and not by anti-LFA-3 antibodies. This notion is supported by the temperature and Mg2+ dependence which is characteristic of LFA-1-mediated adhesion. Moreover, the sensitivity of CD44-induced adhesion to AMG and H7, which both prevent the activation of protein kinase C, and to cytochalasin B, which inhibits microfilament formation, suggests that the activation of the LFA-1 pathway via CD44 involves protein kinase C activation and requires an intact cytoskeleton.

Cervical lymph node metastasis: assessment of radiologic criteria.

To estimate the accuracy of different radiologic criteria used to detect cervical lymph node metastasis in patients with head and neck carcinoma, seven different characteristics of 2,719 lymph nodes in 71 neck dissection specimens from 55 patients were assessed. Three lymph node diameters, their location, their number, the presence of a tumor, and the amount of necrosis and fatty metaplasia were recorded. The minimal diameter in the axial plane was found to be the most accurate size criterion for predicting lymph node metastasis. A minimal axial diameter of 10 mm was determined to be the most effective size criterion. The size criterion for lymph nodes in the subdigastric region was 1 mm larger (11 mm). Groups of three or more borderline nodes were proved to increase the sensitivity but did not significantly decrease the specificity. Radiologically detectable necrosis (3 mm or larger) was found only in tumorous nodes and was present in 74% of the positive neck dissection specimens. Shape was not a valuable criterion for the radiologic assessment of the cervical lymph node status.

Detection and characterization of metastatic cervical adenopathy by MR imaging: comparison of different MR techniques.

Thirty-five patients scheduled to undergo a neck dissection for squamous cell carcinoma of the head and neck were evaluated preoperatively by magnetic resonance (MR) imaging. Axial and occasionally sagittal and coronal images were obtained. To define the most reliable technique to detect cervical lymph node metastasis, we compared several MR pulse sequences with and without Gd-DTPA administration to histopathologic findings in the neck dissection specimens. T1-weighted spin echo combined with T2-weighted gradient recalled echo (GE) sequences were found to be more useful than any other combination of pulse sequences in localizing lymph nodes. On T2-weighted GE images, lymph nodes were depicted with intermediate to high signal intensity in contrast to low signal muscular and fatty tissue. Gadolinium DTPA enhanced T1-weighted GE images reliably depict central lymph node necrosis, the most specific criterion for lymph node metastasis.