Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As shown previously monocytes upon stimulation with bacterial lipopolysaccharides (LPS) release granulocyte-activating mediator(s) (M-GRAM) which induced a long-lasting chemiluminescence (CL) response in human granulocytes. M-GRAM could be separated from interleukin-1 alpha and beta, interleukin-2, interferon alpha and gamma, granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), since these cytokines are shown to be unable to induce a significant CL response. In contrast, granulocyte macrophage colony stimulating factor (GM-CSF) and particularly tumor necrosis factor (TNF) are important triggers of the oxidative burst and they are capable of inducing a CL response. TNF activity but not lymphotoxin (LT) activity could be demonstrated in M-GRAM samples. A polyclonal rabbit IgG as well as a monoclonal antibody to recombinant human TNF which neutralized the TNF activity in M-GRAM preparations did not substantially block the CL signal. Furthermore, M-GRAM-induced CL response was not significantly inhibited by a polyclonal calf antiserum to human recombinant GM-CSF. For further functional characterization of M-GRAM-induced granulocyte activation different assays were performed in order to compare GM-CSF and TNF: (a) SOD-inhibitable cytochrome C-reduction (.O2-); (b) horseradish peroxidase-mediated oxidation of phenol red (H2O2); (c) the release of peroxidase; (d) ultrastructural detection of hydrogen peroxide production; and (e) scanning and transmission electron microscopy (SEM and TEM). Significant release of .O2- was induced by M-GRAM, TNF, and GM-CSF, whereas H2O2 production was significantly stimulated only by M-GRAM and TNF, as shown by functional and ultrastructural assays.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Granulocyte-activating mediators (GRAM): III. Further functional characterization of monocyte-derived GRAM. 284 61

The anatomical organization of the tuberal area of th posterior hypothalamus in Salamandra was investigated by the Golgi methods, SEM and TEM techniques. The ependymal cells of this area are poor in cilia and often show morphological features of actively secreting or absorbing elements. Intermingled with ependymal cells, two kinds of CSF-contacting processes are seen, arising from neurons of the periventricular grey. Their contents and morphological characteristics allow them to be divided into two groups, A and B. In the neuropil different synaptic contacts are seen. The observation of unconventional synaptic contacts possibly of axo-axonic type suggests the occurrence of local circuits on the final neurosecretory pathway.
 ...
PMID:Ultrastructural analysis of the posterior hypothalamus of salamander. 617 21

The fine structure of supraependymal cell clusters of the median eminence was studied with TEM. The cluster cells were identified on the basis of ultrastructure and histochemical determination of glial fibrillar acidic protein (GFA). The phagocytic properties were also studied by means of intraventricular injections of HRP. Neurons, neuroglia cells and degenerating ependyma- and glial cells were found. The extrusion of degenerating infundibular elements into the ventricle is a constant phenomenon but its precise localization and intensity are variable. The close proximity of the clusters to capillary loops is stressed. Because of the broken ependyma at the neck of the cluster, the permeability of the infundibular lining for HRP is increased. Clusters may be seen as sites lacking a brain--CSF barrier.
 ...
PMID:Supraependymal cell clusters in the rat hypothalamus. 620 Oct 88

14C-5,6-DHT-Melanin was injected into the left lateral ventricle of adult rats and its fate followed by light and EM autoradiography and by TEM of structures identified as labeled in preceding light micrographs. Shortly after injection, melanin particles were seen ingested by supraependymal and epiplexus cells, by cells residing in the pia-arachnoid, i.e. free subarachnoidal cells and perivascular cells, and by subependymally located microglia-like cells with intraventricular processes. Up to day four, an increase in the number of labelled phagocytes in the CSF was noted which transformed into typical reactive macrophages. After this time, many intraventricular melanin-laden phagocytes formed rounded clusters; cells of such clusters were subsequently found to invade the brain parenchyma by penetrating the ependymal lining and to accumulate in the perivascular space of brain vessels. 14C-Melanin-storing macrophages were found in the marginal sinus of the deep jugular lymph nodes suggesting emigration of CNS-derived phagocytes via lymphatics or pre-lymphatics that contact the subarachnoidal space compartment. This does not exclude the possibility that some of the macrophages leave the brain via the systemic circulation by penetrating the vascular endothelium; these may be disposed of in peripheral organs other than the lymph nodes. The ability of supraependymal, epiplexus, free subarachnoidal and perivascular cells in the pia and of subependymal microglia cells to accumulate synthetic melanin by phagocytosis suggests that these cells are local variants of the same type of resting potential phagocytes of the mammalian brain. The present study shows that 14C-5,6-DHT-melanin is an ideal phagocytic stimulant and marker for phagocytosis.
 ...
PMID:The disposition of intraventricularly injected 14C-5,6-DHT-melanin in, and possible routes of elimination from the rat CNS. An autoradiographic study. 742 32

This study focused on the design, biometric simulation and optimization of an intracranial nano-enabled scaffold device (NESD) for the site-specific delivery of dopamine (DA) as a strategy to minimize the peripheral side-effects of conventional forms of Parkinson's disease therapy. The NESD was modulated through biometric simulation and computational prototyping to produce a binary crosslinked alginate scaffold embedding stable DA-loaded cellulose acetate phthalate (CAP) nanoparticles optimized in accordance with Box-Behnken statistical designs. The physicomechanical properties of the NESD were characterized and in vitro and in vivo release studies performed. Prototyping predicted a 3D NESD model with enhanced internal micro-architecture. SEM and TEM revealed spherical, uniform and non-aggregated DA-loaded nanoparticles with the presence of CAP (FTIR bands at 1070, 1242 and 2926 cm(-1)). An optimum nanoparticle size of 197 nm (PdI=0.03), a zeta potential of -34.00 mV and a DEE of 63% was obtained. The secondary crosslinker BaCl(2) imparted crystallinity resulting in significant thermal shifts between native CAP (T(g)=160-170 degrees C; T(m)=192 degrees C) and CAP nanoparticles (T(g)=260 degrees C; T(m)=268 degrees C). DA release displayed an initial lag phase of 24 h and peaked after 3 days, maintaining favorable CSF (10 microg/mL) versus systemic concentrations (1-2 microg/mL) over 30 days and above the inherent baseline concentration of DA (1 microg/mL) following implantation in the parenchyma of the frontal lobe of the Sprague-Dawley rat model. The strategy of coupling polymeric scaffold science and nanotechnology enhanced the site-specific delivery of DA from the NESD.
 ...
PMID:Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain. 1970 30

The aim of this study was identifying bacterial pathogens involved in meningitis, studying their antibiotic resistance profiles, investigating the antibiotic resistance genes as well as evaluating the use of various antibiotic combinations. Antibiotic susceptibility tests were evaluated according to CLSI guidelines. Antibiotic combinations were evaluated by calculating the Fractional Inhibitory Concentration (FIC) index. A total of 71 bacterial isolates were recovered from 68 culture positive CSF specimens. Sixty five of these isolates (91.5%) were recovered from single infection specimens, while 6 isolates (8.4%) were recovered from mixed infection specimens. Out of the 71 recovered isolates, 48 (67.6%) were Gram-positive, and 23 (32.4%) were Gram-negative. Thirty one of the Gram positive isolates were S. pneumoniae (64.6%, n = 48). Out of the recovered 71 isolates; 26 (36.6%) were multidrug-resistant (MDR) isolates of which, 18 (69.2%) were Gram-negative and 8 (30.8%) were Gram-positive. All MDR isolates (100%) showed resistance to penicillin and ampicillin, however, they showed lower resistance to meropenem (50%), levofloxacin (50%), amikacin (48%), pipercillin-tazobactam (45.8%). Most common antibiotic resistance genes were investigated including: tem (21.1%), shv (15.8%), ctx-m (15.8%) coding for TEM-, SHV, CTX-M extended-spectrum beta-lactamases (ESBLs), respectively; aac(6')-I b(26.3%) coding for aminoglycoside 6'-N-acetyltransferase type Ib ciprofloxacin resistant variant; and qnrA (5.3%) gene coding for quinolone resistance. The DNA sequences of the respective resistance genes of some selected isolates were PCR amplified, analyzed and submitted to the GenBank database under the accession numbers, KX214665, KX214664, KX214663, KX214662, respectively. The FIC values for ampicillin/sulbactam plus cefepime showed either additive or synergistic effect against ten tested Gram-negative MDR isolates, while doxycycline plus levofloxacin combination revealed synergism against two MDR Gram-positive isolates. The results indicate high prevalence of antibiotic resistance among MDR isolates. Therefore, new guidelines should be implemented in Egypt to rationalize the use and avoid the misuse and abuse of antimicrobial agents.
 ...
PMID:Prevalence of MDR pathogens of bacterial meningitis in Egypt and new synergistic antibiotic combinations. 2820 68

Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradation via mitophagy to maintain energy homeostasis. We hypothesize that LRRK2 (leucine-rich repeat kinase 2) mutation disrupts mitochondrial turnover causing accumulation of defective mitochondria in aging brain. We found more ubiquitinated mitochondria with aberrant morphology associated with impaired function in aged (but not young) LRRK2R1441G knockin mutant mouse striatum compared to wild-type (WT) controls. LRRK2R1441G mutant mouse embryonic fibroblasts (MEFs) exhibited reduced MAP1LC3/LC3 activation indicating impaired macroautophagy/autophagy. Mutant MEFs under FCCP-induced (mitochondrial uncoupler) stress showed increased LC3-aggregates demonstrating impaired mitophagy. Using a novel flow cytometry assay to quantify mitophagic rates in MEFs expressing photoactivatable mito-PAmCherry, we found significantly slower mitochondria clearance in mutant cells. Specific LRRK2 kinase inhibition using GNE-7915 did not alleviate impaired mitochondrial clearance suggesting a lack of direct relationship to increased kinase activity alone. DNM1L/Drp1 knockdown in MEFs slowed mitochondrial clearance indicating that DNM1L is a prerequisite for mitophagy. DNM1L knockdown in slowing mitochondrial clearance was less pronounced in mutant MEFs, indicating preexisting impaired DNM1L activation. DNM1L knockdown disrupted mitochondrial network which was more evident in mutant MEFs. DNM1L-Ser616 and MAPK/ERK phosphorylation which mediate mitochondrial fission and downstream mitophagic processes was apparent in WT using FCCP-induced stress but not mutant MEFs, despite similar total MAPK/ERK and DNM1L levels. In conclusion, aberrant mitochondria morphology and dysfunction associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in mutant LRRK2 MEFs and mouse brain. Abbreviations: ATP: adenosine triphosphate; BAX: BCL2-associated X protein; CDK1: cyclin-dependent kinase 1; CDK5: cyclin-dependent kinase 5; CQ: chloroquine; CSF: cerebrospinal fluid; DNM1L/DRP1: dynamin 1-like; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell sorting; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; LAMP2A: lysosomal-associated membrane protein 2A; LRRK2: leucine-rich repeat kinase 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK1/ERK2: mitogen-activated protein kinase 1; MEF: mouse embryonic fibroblast; MFN1: mitofusin 1; MMP: mitochondrial membrane potential; PAmCherry: photoactivatable-mCherry; PD: Parkinson disease; PINK1: PTEN induced putative kinase 1; PRKN/PARKIN: parkin RBR E3 ubiquitin protein ligase; RAB10: RAB10, member RAS oncogene family; RAF: v-raf-leukemia oncogene; SNCA: synuclein, alpha; TEM: transmission electron microscopy; VDAC: voltage-dependent anion channel; WT: wild type; SQSTM1/p62: sequestosome 1.
 ...
PMID:Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2R1441G mice. 3330 Apr 46