Electrochemistry on Mars.
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Biosensing Techniques↗
Biomedical subjects
W Schubert
Publications and source records attributed to W Schubert.
The use of the Naugle orbitometer in maxillofacial trauma.
BACKGROUND AND OBJECTIVES: Objective measuring of globe position is not a universal practice in the management of orbital trauma. Few studies in the literature advocate its routine use. METHODS AND MATERIALS: The Hertel exophthalmometer is the most widely used instrument; however, in trauma involving the lateral orbital rim (e.g., in zygoma fractures), the results are inaccurate because the displacement of the zygomatic bone interferes with its reference point on the lateral orbital rim. A more recent measuring device, the Naugle orbitometer, was introduced in 1992. It uses the superior orbital rim (frontal bar) and inferior orbital rim (malar eminence) as reference points. RESULTS AND/OR CONCLUSIONS: This article reports experience with this instrument in objective measuring the position of the globe in orbital trauma. These measurements are used 1) to monitor fractures that may not require repair but should be followed and observed for dystopia or enophthalmos, 2) to determine the adequacy of fracture repair, and 3) to determine the volume adjustment required for correcting enophthalmos. Future studies will be directed to compare the accuracy of Naugle and Hertel exophthalmometers.
Adult↗
Functional imaging of mitochondria in saponin-permeabilized mice muscle fibers.
Confocal laser-scanning and digital fluorescence imaging microscopy were used to quantify the mitochondrial autofluorescence changes of NAD(P)H and flavoproteins in unfixed saponin-permeabilized myofibers from mice quadriceps muscle tissue. Addition of mitochondrial substrates, ADP, or cyanide led to redox state changes of the mitochondrial NAD system. These changes were detected by ratio imaging of the autofluorescence intensities of fluorescent flavoproteins and NAD(P)H, showing inverse fluorescence behavior. The flavoprotein signal was colocalized with the potentiometric mitochondria-specific dye dimethylaminostyryl pyridyl methyl iodide (DASPMI), or with MitoTrackerTM Green FM, a constitutive marker for mitochondria. Within individual myofibers we detected topological mitochondrial subsets with distinct flavoprotein autofluorescence levels, equally responding to induced rate changes of the oxidative phosphorylation. The flavoprotein autofluorescence levels of these subsets differed by a factor of four. This heterogeneity was substantiated by flow-cytometric analysis of flavoprotein and DASPMI fluorescence changes of individual mitochondria isolated from mice skeletal muscle. Our data provide direct evidence that mitochondria in single myofibers are distinct subsets at the level of an intrinsic fluorescent marker of the mitochondrial NAD-redox system. Under the present experimental conditions these subsets show similar functional responses.
Animals↗
Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+CD18+ cells and CD8+CD103+ cells by multi-epitope imaging.
Pancreatic cancer is characterized by an increasing incidence and an extremely poor prognosis. It is resistant to most of the conventional treatment modalities. Histomorphologically, it presents with a strong desmoplastic reaction around cancer cells, and lymphocytes are typically localized as aggregates in the fibrotic interstitial tissue. Using the method of multi-epitope imaging with fluorochrome-tagged specific MoAbs which allows the simultaneous localization and characterization of T cells in tissues, we studied phenotypes and distribution of tumour-infiltrating lymphocytes (TIL) in pancreatic cancer. CD3+ T cells comprised up to 90% of the tumour-infiltrating cells which were either CD4+ or CD8+, most of them being memory cells (CD45RO+). In decreasing order of frequency, T lymphocytes carried the markers for CD45RO, CD18, CD103 and TCR gammadelta. Very few natural killer cells (CD56+) were observed. Twenty percent of CD8+ were labelled with CD103. These CD8+CD103+ T cells, analogous to the gut intraepithelial lymphocytes (IEL), were found in the fibrous interstitial tissue. Furthermore, an inverse correlation was found between the expression of CD18, the beta2-integrin, which mediates adhesion of activated lymphocytes, and CD45RO in the CD8+ subset of TIL (P = 0.046). In conclusion, phenotyping of T lymphocytes in pancreatic cancer raises the possibility that pancreatic cancer cells develop several strategies to escape the T cell-induced cytolysis by (i) the aggregation of cytotoxic CD8+CD103+ T cells in the fibrous tissue distant from the tumour cells, and (ii) the presence of CD18-bearing cells which lack the expression of the activation marker CD45RO.
Adolescent↗
T-cell receptor Valpha gene expression of infiltrating T cells in pancreatic cancer.
BACKGROUND: T lymphocytes play a central role in the immune response to cancer, with specific T-cell reactivity provided by the T-cell receptor (TCR) alphabeta-chain heterodimer. Whereas human pancreatic adenocarcinoma is characterized by a massive infiltration of T lymphocytes, to date no analysis of the TCR Valpha-gene expression of the tumor-infiltrating lymphocytes in pancreatic cancer has been performed. METHODS: Using reverse transcriptase polymerase chain reaction (RT-PCR) followed by dot blot hybridization, we determined the TCR alpha-chain repertoire at the mRNA level in pancreatic carcinoma and compared our findings with the TCR Valpha repertoire in the normal pancreas and chronic pancreatitis. RESULTS: A heterogeneous lowly restricted TCR Valpha repertoire was observed in pancreatic carcinomas, different from the TCR Valpha repertoire in chronic pancreatitis. CONCLUSIONS: Pancreas-infiltrating T cells show a distinct TCR Valpha gene expression profile in normal pancreas, chronic pancreatitis, and pancreatic cancer.
Adenocarcinoma↗
Portable fluoroscopy in the management of zygomatic arch fractures.
Operative methods that do not allow intraoperative visualization of the fracture fragments in patients with isolated zygomatic arch fractures often result in inadequate reduction. This article describes a technique using a portable, surgeon-operated fluoroscopic machine that can be used preoperatively, intraoperatively, and postoperatively in patients with isolated zygomatic arch fractures. Using the portable fluoroscopic unit, reduction of isolated zygomatic arch fractures was performed in 9 consecutive patients over a period of 1.5 years. Postoperative alignment was confirmed using computed tomography (CT). These CT images were compared with the fluoroscopic images in several of the patients. Eight of the nine fractures were reduced via an intraoral approach and one through a Gillies approach. All nine fractures were easily visualized and their reductions were confirmed with intraoperative dynamic visualization using a portable fluoroscopic unit. Postoperative CT revealed images of the reduction that were comparable with intraoperative and postoperative fluoroscopic images. The use of portable fluoroscopy intraoperatively allows for dynamic visualization of instrumentation and the immediate confirmation of the adequacy of fracture reduction. Moreover, this technique may eliminate the need for postoperative CT in isolated zygomatic arch fractures. Portable fluoroscopy may also have a place in the management of certain zygomatic complex fractures.
Cost-Benefit Analysis↗
CD8+CD103+ T cells analogous to intestinal intraepithelial lymphocytes infiltrate the pancreas in chronic pancreatitis.
OBJECTIVE: Chronic pancreatitis is a painful chronic inflammatory disease of the exocrine pancreas that is associated with the replacement of functional parenchyma by extended fibrosis and with a massive infiltration of T lymphocytes. However, to date further characterization of infiltrating T cells in chronic pancreatitis has not been undertaken. METHODS: Using the novel method of multiepitope imaging with fluorochrome-tagged specific monoclonal antibodies, which allows the simultaneous localization and characterization of T cells in tissues, we analyzed the distribution and phenotypes of T cells infiltrating the pancreas in chronic pancreatitis. RESULTS: The mean CD4:CD8 ratio in 10 cases of chronic pancreatitis was 2.4:1. In order of decreasing frequency, the following markers were observed: CD45RO, CD18, TCRgammadelta, and CD103. The lymphocytes, especially of the CD4+ subset, were found mainly in the fibrous stroma, but T cells were also observed periductally. A T-cell subset bearing the phenotype CD8+CD103+, analogous to intestinal intraepithelial lymphocytes, was found intracalating between the cells of the ductal epithelium. CONCLUSIONS: Phenotyping of the T lymphocytes in chronic pancreatitis supports the concept of the involvement of cell-mediated cytotoxicity in the pathogenesis of this disease. In addition, intraepithelial lymphocytes were found interspersed between the ductal epithelial cells, pointing to a role of this T-cell subset as a first-line defense against deleterious epithelial events in chronic pancreatitis.
Adolescent↗
Constitution and solution conformation of the antibiotic mersacidin determined by NMR and molecular dynamics.
The solution structure of the tetracyclic lantibiotic mersacidin in methanol (CD3OH) has been determined by NMR followed by distance bound driven dynamics and subsequent restrained molecular dynamics simulations combined with an iterative relaxation matrix approach and alternatively by a simulated annealing protocol. The molecular dynamics simulations were performed with the AMBER program system and with the INSIGHT program package. The distance bound driven dynamics calculation was conducted using a modified version of the DISGEO II program. The interproton distance restraints were derived from jump symmetrized rotating-frame Overhauser enhancement and exchange (JS-ROESY) spectra, which yield optimum sensitivity for medium-sized molecules like mersacidin. The connectivities via the sulfide bridges were unambiguously confirmed by heteronuclear NMR techniques (heteronuclear single quantum coherence and heteronuclear multiple bond correlation methods). Due to the tetracyclic structure, mersacidin exhibits a rather rigid globular shape, which neither belongs to the duramycin nor to the nisin structure type lantibiotics. The resulting structures for the simulated annealing protocol of restrained and subsequent free molecular dynamics were compared and found to be very similar.
Amino Acid Sequence↗
Dipeptidyl peptidase IV (CD26) and Alzheimer amyloid protein precursor (APP) in polymyositis.
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Amyloid beta-Protein Precursor↗
Rapid mitogen-induced aminopeptidase N surface expression in human T cells is dominated by mechanisms independent of de novo protein biosynthesis.
The membrane bound metalloprotease aminopeptidase N (APN, CD13, EC 3.4.11.2) is a well established marker of normal and malignant cells of the myelo-monocytic lineage. It is also expressed by leukaemic blasts of a small group of patients suffering from acute or chronic lymphoid leukaemia. Recently, the expression of the APN gene in T cell lines as well as the induction of APN gene and surface expression in human peripheral T cells by mitogenic activation have been demonstrated. Here, by means of cytofluorimetric analysis evidence is provided, that the induction of APN surface expression is partially resistent to the action of the inhibitors of protein biosynthesis, puromycin and cycloheximide, and is not prevented by tunicamycin, an inhibitor of glycosylation. These data suggest that the rapid mitogen-induced surface expression of APN, detectable 20 hours after stimulation is dominated by mechanisms not dependent on de novo protein biosynthesis or glycosylation. As shown by simultaneous analyses, the inhibitors used did also differently modify the induction of surface expression of other inducible glycosylated leukocyte surface antigens, namely CD25, CD69 and CD95.
CD13 Antigens↗
Cross-sectional area of the mandible.
PURPOSE: The anatomy of the mandible was examined by measuring the cross-sectional area (CSA) of multiple regions of 10 fully dentulous hemimandibles to provide a better understanding of regional structural differences that may have implications regarding biomechanical strength, surgical reconstruction, and fracture site frequency. MATERIALS AND METHODS: Fifteen cuts from the condyle to the symphysis were made of each hemimandible (n = 150 cuts). A Zeiss Videoplan digitizer was used to determine the CSA. RESULTS: The total CSA through the condyle was greater than the CSA through the condylar neck. The CSA through the ramus exceeded that of the condylar neck. The total CSA of the midramus was significantly greater than that of the upper ramus. The total CSA at the body, parasymphysis, and symphysis was significantly greater than at the mid-angle. The total CSA of the cortex increased anteriorly; these differences become significant between the condylar neck and the body, parasymphysis, and symphysis. The total CSA, and the CSA of the cortex and spongiosa, remained relatively constant from the inferior angle anteriorly. CONCLUSIONS: Significant differences exist in the CSA at different points, with an increase in the total, cortical, and spongiosal CSA anteriorly from the condylar neck to the angle. The total CSA and the CSA of the cortex and spongiosa remain relatively constant anterior to the inferior angle. These data suggest that bony CSA alone is not the sole factor in determining fracture site frequency.
Adult↗
Gallium scans in the management of patients with Hodgkin's disease: a study of 101 patients.
PURPOSE: To evaluate the utility of periodic gallium (67Ga) scans in the management of patients with Hodgkin's disease. PATIENTS AND METHODS: From 1990 to 1994, 101 patients treated for Hodgkin's disease (stage I to II, n = 67; stage III to IV, n = 34) had a positive 67Ga scan at the time of diagnosis. Treatment included chemotherapy in 27 patients, radiation therapy in 28, and combined modality therapy in 46. All patients underwent 67Ga scans at the time of diagnosis, near the end or just after treatment, and at periodic follow-up evaluation. RESULTS: After treatment, the 67Ga scan remained positive in four patients and was interpreted as negative in 97. Among the four patients with positive scans, two died of progressive disease and two relapsed. Among the remaining 97 patients with negative 67Ga scans, 16 patients relapsed, including five with stage I to II (7.5%) and 11 with stage III to IV (34.4%) disease. The negative predictive value of posttherapy 67Ga scan was 83.5% for all patients; however, when calculated according to stage, it was 92.4% for patients with stage I to II disease and 64.5% for patients with stage III to IV disease (P < .01). CONCLUSION: A positive 67Ga scan at the end of therapy is rarely seen in patients with Hodgkin's disease and should be considered a manifestation of gross residual disease. However, a negative 67Ga scan after therapy had a significantly lower predictive value in patients with stage III to IV disease compared with stage I to II disease. The predictive value of 67Ga scans, as well as newer imaging studies, should be analyzed according to pretreatment stage.
Adolescent↗
Preexpanded radial forearm free flap to the scalp.
The radial forearm flap is a versatile tool for the reconstructive surgeon because of its thinness, durable skin quality, aesthetic match, and relative ease of dissection. This flap is an ideal candidate for reconstruction of head and neck defects. One of the drawbacks is its relative small size, which may limit its use in certain applications. We describe the preexpansion of the radial forearm flap for its use in covering a large scalp defect. Preexpansion of the radial forearm free flap enables the reconstructive surgeon to increase the size of the flap markedly without altering its neurovascular anatomic relationships. Also described is the unexpected benefit of a periprosthetic capsule that covers the flexor tendons of the forearm and acts as an excellent bed for a skin graft.
Burns↗
Second solid tumors in patients with Hodgkin's disease cured after radiation or chemotherapy plus adjuvant low-dose radiation.
PURPOSE: Late solid tumors (STs) are a significant cause of morbidity and mortality in long-term survivors of Hodgkin's disease. To investigate the carcinogenic potential of two different therapeutic approaches, we measured the relative risk (RR) of STs in patients with early-stage disease cured after primary full-dose (approximately 40 Gy) radiation therapy (RT) and in patients with advanced disease who were treated with chemotherapy followed by low-dose (15 to 30 Gy) involved-field radiation (CMT). PATIENTS AND METHODS: Because therapy-induced STs generally begin after a latency period of 5 to 10 years, we restricted our analysis to patients treated before 1986 who achieved durable remissions. Patients who required salvage chemotherapy or who died of Hodgkin's disease were excluded from analysis. The RR of STs was calculated by dividing the observed number of cases by the expected number in a matched population from the Connecticut Tumor Registry. The actuarial incidence of STs was also measured. RESULTS: A total of 197 patients formed the RT group and 116 the CMT group. The median follow-up period in the RT group was 12.8 years, versus 13.5 years in the CMT group. The overall RR of STs in the CMT group was 1.5 (95% confidence interval [CI], 0.6 to 3.5; P = .122). There were no cases of lung or breast cancer. In the RT group, the overall RR of STs was 3.3 (95% CI, 2.0 to 5.3; P < .001). There were seven cases of lung cancer (RR = 10.8; 95% CI, 5.3 to 22.2; P < .001) and two cases of breast cancer (RR = 2; 95% CI, 0.6 to 7.4; P = .07). All six benign tumors occurred in the RT group. CONCLUSION: In patients cured by initial treatment for Hodgkin's disease, RT was associated with a statistically significant increase in STs, particularly lung cancer. CMT was not associated with a significant increase in STs. These data may have important implications for the design of newer therapies for early-stage Hodgkin's disease.
Actuarial Analysis↗
Detection by 4-parameter microscopic imaging and increase of rare mononuclear blood leukocyte types expressing the Fc gamma RIII receptor (CD16) for immunoglobulin G in human sporadic amyotrophic lateral sclerosis (ALS).
By using quantitative multiparameter microscopic imaging we demonstrate concentration of two peripheral mononuclear blood leukocyte types expressing the Fc gamma RIII receptor for immunoglobulin G in a clinical subgroup of amyotrophic lateral sclerosis (ALS, n = 9) showing bulbar palsy (ALSBP) and/or predominant involvement of the upper motor neuron (ALSC). Triple fluorescence staining and overlay with phase contrast images (4 parameters) reveals that cell type 1 co-expresses Fc gamma RIII (CD16), CD8 and CD57 surface antigens (ALSC 50 +/- 33.6 cells/microliters, P = 0.0012; ALSBP 16.5 +/- 32.4, P = 0.029). This cell type is not observed in healthy individuals (n = 8) and is only insignificantly increased (P > 0.05) in neurological disease controls (stroke, n = 3, 2.1 +/- 3.7; polymyositis, n = 6, 1.5 +/- 4.0 cells/microliters) and in ALS cases with peripheral symptoms (ALSP n = 12: 7.6 +/- 8.7). Cell type 2 co-expresses Fc gamma RIII (CD16) and CD8, but is negative for CD57 (ALSC 60.1 +/- 19.3; ALSBP 24.2 +/- 28.0 cells/microliters). These findings are consistent with previous reports on IgG isotype changes and immune-cell invasion of the motor system in ALS.
Amyotrophic Lateral Sclerosis↗
Water channel-carrying vesicles in the rat IMCD contain cellubrevin.
Antidiuretic hormone (arginine vasopressin) induces a cyclic process of docking, fusion, and endocytosis of water channel-containing vesicles in the collecting duct. There is now evidence that docking and endocytosis are mediated by an array of proteins associated with vesicles and target membranes. In recent studies, we have shown that cellubrevin, a member of the vesicle-associated membrane protein family, as well as other docking proteins, are expressed in the rat inner medullary collecting duct. We now show by immunogold electron microscopy that cellubrevin is present on vesicles containing water channels, that it is associated with both coated and uncoated vesicles, and that it is present on the apical membrane. Cellubrevin, therefore, is in a position to mediate one or more steps in arginine vasopressin-induced water channel cycling.
Animals↗
Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women.
In an open, randomized, cross-over study the concentrations of 17 beta-estradiol and estrone in serum were measured over 192 hours in 8 ovariectomized women after a single oral dose intake of 2 mg micronized 17 beta-estradiol. The subjects were studied with and without grapefruit juice intake containing the three natural flavonoids, naringenin, quercetin and kaempherol, which are found as glycosides in citrus fruit. These flavonoids interact with the metabolism of drugs such as 17 beta-estradiol and other steroids that are extensively metabolised through the P-450NF (P-450 IIIA4) enzyme or closely related P-450 systems. After administration of grapefruit juice, peak estrone (between 2-6 hours after tablet intake) concentrations increased significantly. The AUC0-48 and AUC0-192 for estrone but not 17 beta-estradiol, resulting from a single administration of micronized 17 beta-estradiol, were significantly altered. Combined measured estrogens (i.e. 17 beta-estradiol and estrone) also increased significantly. The relationship between the AUCs for 17 beta-estradiol and estrone was not altered by juice intake indicating that a metabolic step after estrone, i.e. further A and/or D ring conversion was inhibited. This study demonstrates that grapefruit juice may alter the metabolic degradation of estrogens, and increase the bioavailable amounts of 17 beta-estradiol and its metabolite estrone, presumably by affecting the oxidative degradation of estrogens. This food interaction may be one factor behind the interindividual variability in 17 beta-estradiol, estrone and estriol serum concentrations after exogenous administration of 17 beta-estradiol to patients.
Beverages↗
Regulation and expression of the Alzheimer's beta/A4 amyloid protein precursor in health, disease, and Down's syndrome.
A four- to fivefold overexpression of the gene for the Alzheimer beta/A4 amyloid precursor protein (APP) in individuals with Down's Syndrome (DS) appears to be responsible for the fifty year earlier onset of Alzheimer's disease (AD) pathology in DS compared to the normal population. It is therefore likely that a deregulated overexpression of the APP gene is a risk factor for the beta/A4 amyloid formation. To test this hypothesis and to get a better understanding of how APP expression is regulated, we studied the 5' control region of the human APP gene, alternative splicing of the 19 APP exons, and APP biogenesis, metabolism and function. The analysis of the APP promoter revealed its similarity with those of housekeeping genes by the presence of a GC-rich region around the transcription start site and the lack of a TATA box. Gene transfer experiments showed this GC-rich region to contain overlapping binding sites for different transcription factors whose binding is mutually excluded. An imbalance between these factors may cause APP overexpression and predispose to AD pathology. Another putative risk factor for AD is regulation of splicing of exon 7 in APP mRNA's which changes in brain during aging. This is relevant for APP processing since exon 7 codes for a Kunitz protease inhibitory domain. Investigation of further splicing adjacent to the beta/A4 exons 16 and 17 which might also interfere with APP processing led to the identification of the leukocyte-derived (L-APP) splice forms which lack exon 15. In brain this splicing occurs in activated astrocytes and microglia. The localization of APP at synaptic sites in brain suggests that APP regulation and expression are critical determinants of a potential and early impairment of central synapses. This may be the case during pathological evolution of AD and DS when beta/A4 derived from synaptic APP is converted to beta/A4 amyloid by radical generation.
Aging↗