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961.
Summary Histopathological, immunocytochemical, and electron microscopical investigations were carried out in a man with a protracted history of spastic paraparesis, adrenal insufficiency and hypogonadism. Pathological findings were identical with those of the few previously reported cases of adrenomyeloneuropathy (AMN) including cytoplasmic lamellar inclusions consisting of two parallel 2.5 nm leaflets separated by a clear space of variable extent, in the brain, spinal roots, adrenal gland, and interstitial cells of the testis. No inclusions could be found in oligodendrocytes. In brain macrophages they are thought to represent breakdown products of pathological myelin stored in lysosomes, whereas in other localizations they might be an expression of the primary metabolic defect of the cell.Special attention was paid to the pseudosystematic type of fiber tract degeneration in the spinal cord. The dying-back pattern of axonal destruction was interpreted as a possible result of the multisegmental demyelination observed in these tracts.All known hormones could be localized in the pituitary by immunocytochemistry. Corticotrophs and gonadotrophs were numerous. The structural damage of the adrenal cortex and the interstitial cells of the testis is, therefore, considered to result from the inborn error of metabolism on the one hand and from an enhanced stimulation exerted by ACTH and gonadotrophins on the other.This work was supported in part by Grant No. 3.419.78 of the Swiss National Science Fundation 相似文献
962.
268 patients with primary liver cancer have been autopsied: 81% had hepatomas, 14% cholangiocellular carcinomas, 5% mixed carcinomas (hepatocholangiocellular) and 1% had mixed tumors (hepatoma and angiosarcoma). In contrast to cholangiomas, hepatomas were found more often in males than in females. The age peak of primary liver cancer was between 61 and 70 years. 79% of hepatomas developed in a cirrhotic liver, 71% of cholangiomas were without cirrhosis of the liver. Metastases were found in 66-67% of hepatomas and cholangiocellular carcinomas, especially in blood vessels, lymph nodes, lungs and within the liver. 相似文献
963.
Schuster M Rosanowski F Schwarz R Eysholdt U Lohscheller J 《Archives of otolaryngology--head & neck surgery》2005,131(11):945-952
OBJECTIVE: To evaluate the vibration pattern of the substitute voice generator of patients who have undergone laryngectomy. For automatic quantification of the oscillations of the pharyngoesophageal (PE) segments, image processing of digital high-speed video sequences is applied. DESIGN: Physiologic analysis. SETTING: An acute care hospital. PATIENTS: Endoscopic recordings were taken of 10 men who underwent laryngectomy (mean +/- SD age, 61.5 +/- 5.2 years) during sustained phonation of a vowel using a 90 degree endoscope coupled to a high-speed camera. MAIN OUTCOME MEASURES: An image-processing algorithm was developed to automatically define the pseudoglottis in each recording and track its movements. RESULTS: The clinical assessment of the high-speed technique for the endoscopic examination of the substitute voice generator yields the following results. The forms and oscillation characteristics of the pseudoglottides varied considerably: 3 pseudoglottides were circular, 6 were split shaped, and 1 was triangle shaped. A quasi-periodic opening and closing were observed and automatically detected by the described algorithm in each recording independently from quality of the recording and from morphologic and oscillation characteristics of the PE segment. The frequencies of the extracted oscillations of the pseudoglottides correspond to the structure of the acoustic signals. CONCLUSIONS: Automatic image processing of PE segments derived from high-speed endoscopic recordings enables the detection and quantification of the substitute voice generator's oscillations in high temporal resolution. These data directly prove that the detected pseudoglottis is the source of the substitute voice. Close relations between substitute voice and functional properties of the PE segment exist. In the future, these data will be interpreted by applying biomechanical models of the PE segment. Presumably, results may help to optimize surgical and adaptive procedures for specific substitute voice restoration. 相似文献
964.
Majetschak M Krehmeier U Ostroverkh L Blömeke B Schäfer M 《Clinical and diagnostic laboratory immunology》2005,12(2):296-303
Endotoxin-stimulated blood cytokine responses have been widely used to describe compromised host defense mechanisms after trauma. We investigated whether blood cytokine production after endotoxin stimulation is able to define distinct trauma-induced alteration patterns and whether alteration patterns are associated with tumor necrosis factor (TNF) gene polymorphisms. In 48 patients undergoing joint replacement, the levels of TNF alpha (TNF-alpha), interleukin 6 (IL-6), and IL-8 production in blood after endotoxin stimulation were measured preoperatively on the day of surgery and 24 h thereafter. Patients were genotyped for the TNF-alpha position -308 G/A polymorphism and the TNF-beta NcoI polymorphism. Postoperative alterations, i.e., increases or decreases of cytokine levels (TNF-alpha versus IL-6, P = 0.013; TNF-alpha versus IL-8, P = 0.001; IL-6 versus IL-8, P = 0.007), and relative postoperative changes, i.e., percentages of preoperative cytokine levels (TNF-alpha versus IL-6, r(s) = 0.491, P < 0.001; TNF-alpha versus IL-8, r(s) = 0.591, P < 0.001; IL-6 versus IL-8, r(s) = 0.474, P < 0.001 [where r(s) is the Spearman rank correlation coefficient]), had significant positive correlations among the cytokines. Overall enhanced postoperative alteration patterns were found in 10 patients, attenuated patterns were found in 18 patients, and mixed patterns were found in 20 patients. Preoperative cytokine production levels differed significantly between these groups (those of the overall enhanced pattern group were less than those of the mixed pattern group, which were less than those of the overall attenuated pattern group). TNF polymorphisms were not associated with overall alteration patterns, but the A*TNFB1 haplotype was associated with a postoperative increase in TNF-alpha production (P = 0.042). Whole-blood cytokine responses to endotoxin define the following preexisting patterns in leukocyte function: low baseline production and overall enhanced alteration patterns after trauma (type 1), intermediate baseline production and mixed alteration patterns (type 2), and high baseline production and overall attenuated alteration patterns (type 3). TNF gene polymorphisms were associated with changes in TNF-alpha production but do not explain the overall reaction patterns of cytokine production after trauma. The clinical correlate of these newly defined reaction types remains to be determined. 相似文献
965.
Wiedenmann J Vallone B Renzi F Nienhaus K Ivanchenko S Röcker C Nienhaus GU 《Journal of biomedical optics》2005,10(1):14003
The red fluorescent protein (FP) eqFP611 from the sea anemone Entacmaea quadricolor shows favorable properties for applications as a molecular marker. Like other anthozoan FPs, it forms tetramers at physiological concentrations. The interactions among the monomers, however, are comparatively weak, as inferred from the dissociation into monomers in the presence of sodium dodecyl sulfate (SDS) or at high dilution. Analysis at the single-molecule level revealed that the monomers are highly fluorescent. For application as fusion markers, monomeric FPs are highly desirable. Therefore, we examine the monomer interfaces in the x-ray structure of eqFP611 to provide a basis for the rational design of monomeric variants. The arrangement of the four beta cans is very similar to that of other green fluorescent protein (GFP-like) proteins such as DsRed and RTMS5. A variety of structural features of the tetrameric interfaces explain the weak subunit interactions in eqFP611. We produce functional dimeric variants by introducing single point mutations in the A/B interface (Thr122Arg, Val124Thr). By contrast, structural manipulations in the A/C interface result in essentially complete loss of fluorescence, suggesting that A/C interfacial interactions play a crucial role in the folding of eqFP611 into its functional form. 相似文献
966.
Meykadeh N Mirmohammadsadegh A Wang Z Basner-Tschakarjan E Hengge UR 《Journal of molecular medicine (Berlin, Germany)》2005,83(11):897-903
Gene expression following direct injection of naked plasmid DNA into the skin has been demonstrated in the past. Topical application of plasmid DNA represents an attractive route of gene delivery. If successful, it would have great prospects in skin gene therapy since it is painless and easy to apply. In this study, we analyzed the expression of plasmid DNA in vivo and in vitro following topical application of plasmid DNA in various liposomal spray formulations. Therefore, different concentrations of plasmid DNA expressing enhanced green fluorescent protein (pEGFP-N1) were sprayed onto mouse or human skin once daily for three consecutive days and compared with direct injection. Gene expression was assessed 24 h after the final topical application of various liposomal DNA formulations. The results showed that EGFP mRNA and protein were detectable by RT-PCR and Western blot, respectively. However, epicutaneously applied EGFP plasmid DNA did not lead to microscopically detectable EGFP protein, when assessed by confocal laser microscopy or fluorescence-activated cell sorting in contrast to about 4% of fluorescent keratinocytes following intradermal injection. In an in vivo mouse model, the application of pEGFP-N1 DNA led to the generation of GFP-specific antibodies. These results indicate that topical spray application of pEGFP-N1 liposomal DNA formulations is a suitable method for plasmid DNA delivery to the skin, yielding limited gene expression. This spray method may thus be useful for DNA vaccination. To increase its attractiveness for skin gene therapy, the improvement of topical formulations with enhanced DNA absorption is desirable. 相似文献
967.
Antigen processing and recognition is a key feature of antibacterial immune responses to intracellular bacteria. In contrast to viruses, which are primarily controlled by conventional MHC II- and MHC I-restricted CD4+ or CD8+ T cells, respectively, unconventional T cells participate additionally in antibacterial protection. These unconventional T cells include glycolipid-specific CD1-restricted T cells and phospholigand-specific gammadelta T cells. We are just beginning to understand the broad spectrum of antigen recognition and stimulation of distinct T-cell populations by bacterial pathogens. From the host perspective, a broad spectrum of different T-cell populations that recognize proteins, lipids and carbohydrates strengthens protective immunity. From the perspective of the pathogen, antigen presentation represents a bottleneck that should be exploited for evasion from, or devastation of, acquired immunity. Although several such mechanisms have been described in viral systems, few have thus far been elucidated in bacterial infections. 相似文献
968.
969.
Ueberham U Ueberham E Brückner MK Seeger G Gärtner U Gruschka H Gebhardt R Arendt T 《The European journal of neuroscience》2005,22(1):50-64
Various chronic neurological diseases are associated with increased expression of transforming growth factor-beta1 (TGF-beta1) in the brain. TGF-beta1 has both neuroprotective and neurodegenerative functions, depending on conditions such as duration and the local and temporal pattern of its expression. Previous transgenic approaches did not enable control for these dynamic aspects. To overcome these limitations, we established a transgenic mouse model with inducible neuron-specific expression of TGF-beta1 based on the tetracycline-regulated gene expression system. TGF-beta1 expression was restricted to the brain where it was particularly pronounced in the neocortex, hippocampus and striatum. Transgene expression was highly sensitive to the presence of doxycycline and completely silenced within 6 days after doxycycline application. After long-term expression, perivascular thioflavin-positive depositions, formed by amyloid fibrils, developed. These depositions persisted even after prolonged silencing of the transgene, indicating an irreversible process. Similarly, strong perivascular apolipoprotein E (ApoE) depositions were found after TGF-beta1 expression and these remained despite TGF-beta1 removal. These in vivo observations suggests that the continuous presence of TGF-beta1 as initial trigger is not necessary for the persistence and development of chronic lesions. Neuroprotective effects were observed after short-term expression of TGF-beta1. Death of striatal neurons induced by 3-nitropropionic acid was markedly reduced after induced TGF-beta1 expression. 相似文献
970.