The number of neutrophils in the blood and tissues is controlled by constitutive apoptotic programmed cell death and clearance by phagocytes such as macrophages. Here, we found that calpains cleave the X-linked inhibitor of apoptosis (XIAP) in vitro, producing fragments that are unable to inhibit caspase-3. These fragments were detected in normal neutrophils but were unstable and rapidly degraded. Calpain inhibition delayed tumor necrosis factor-␣-induced apoptosis of normal neutrophils, consistent with a role for calpains in regulating the onset of apoptosis. Interestingly, neutrophils from three patients with chronic neutrophilic leukemia, a rare syndrome characterized by accumulation of mature neutrophils, exhibited decreased -calpain expression, diminished calpain activity, and impaired XIAP degradation. Neutrophils from these patients displayed a delay in spontaneous, Fas-stimulated, and tumor necrosis factor-␣-induced apoptosis. These observations suggest that calpain-mediated XIAP degradation contributes to initiation of apoptosis in normal neutrophils and dysfunction of this regulatory pathway can lead to pathological neutrophil accumulation.
An aromatase-containing neural system was examined in the rat forebrain, using a polyclonal antibody against aromatase-associated human placental antigen X-P2 (hPAX-P2). Numerous dot-like structures, which we have called stigmoid bodies, were immunostained in the preoptico-hypothalamic region, the bed nucleus of the stria terminalis, the medial amygdala, the arcuate nucleus, the subfornical organ, and the area extending from the hypothalamic area to the central gray through the medial forebrain bundle and the periventricular fiber system of the posterior diencephalon. The stigmoid bodies were always found as inclusions in the neuronal cytoplasm. Their diameter was usually 1-3 microns, but exceptionally large forms, over 3 microns, were found in some brain regions, including the area extending from the median preoptic nucleus surrounding the organosum vasculosum laminae terminalis to the anterior medial preoptic nucleus, the periventricular nucleus of the preoptic area, and some parts of the medial preoptic nucleus. Most of these nuclei show sexual dimorphism. The distribution pattern of the hPAX-P2 immunoreactive stigmoid bodies agreed well with that of aromatase activity previously reported in many biochemical studies. Brain regions where the stigmoid bodies were prominent largely coincide with steroid binding locations common to both androgen and estrogen, or regions where both sex steroid receptors are present. Although it still remains to be determined whether aromatase is localized within these stigmoid bodies, it appears likely that they are closely associated with the function of sex steroids at their target sites in the brain.
Spectroscopic properties of Er3+ in Ga2S3–GeS2–La2S3 glasses are investigated on the basis of the spontaneous emission probabilities calculated by the use of the Judd–Ofelt theory and lifetime data. Frequency upconversion spectra are also measured with excitation at 800 and 980 nm. The spontaneous emission probabilities are much larger than those of the other glass systems such as oxides and fluorides. This is mainly attributed to the large refractive indices of the sulfide glasses. The quantum efficiencies of I11/24 and F9/24 levels are comparable or larger than the typical values of Er3+ in a fluoride glass. This is a consequence of the large spontaneous emission probabilities and low phonon energies of the sulfide glasses. However, the quantum efficiency of the S3/24 level is less than one-half of the value in the fluoride glass. The nonradiative transition probability of the S3/24 level is much larger than the value which is evaluated from the multiphonon relaxation theory. This suggests the presence of the other nonradiative relaxation process in addition to the multiphonon relaxation. This process is considered to be the energy transfer from the excited Er3+ to the band-gap excitation of the matrix glass. In upconversion spectra, the 497 nm emission from the F7/24 level is observed in addition to the red (665 nm) and the green (533 and 552 nm) emission bands.
We have investigated the decay processes of the Er:4S3/2 and F39/2 states and the mechanisms of frequency upconversion under 800 nm excitation of Er3+ in ternary ZrF4–BaF2–LaF3 glasses. The decay processes of the Er:4S3/2 and F49/2 states are discussed on the basis of the Er concentration dependence of the fluorescence lifetime. The quantum efficiencies of emission of the S43/2 and F49/2 states are 73% and 25%, respectively. The difference in the quantum efficiencies between these states can be explained from the difference in the multiphonon decay rates: the multiphonon decay rate of the S43/2 state is much smaller than that of the F49/2 state. The multiphonon relaxation is a dominant nonradiative decay process of the F49/2 state. A dominant nonradiative decay process of the S43/2 state is self-quenching at high Er concentrations. The upconversion mechanisms under 800 nm excitation are also investigated from the dependence of upconversion luminescence on excitation wavelengths (800 and 980 nm), excitation laser power, and Er concentration. The mechanism of upconversion from 800 to 660 nm is mainly due to the energy transfer between the I49/2→4I13/2 and F49/2←4I11/2 transitions. We also show that the upconversion from 800 to 550 nm is due to excited-state absorption.
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