Scanning-tunneling-microscopy study of Ge/GaAs(110). II. Coalescence and layer-by-layer growth.
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Biomedical subjects
Publications and source records attributed to Y Yang.
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The finding that two subunits of the proteasome, LMP2 and LMP7, are encoded in the major histocompatibility complex (MHC) has linked the proteasome which represents a major extralysosomal proteolytic system to the processing of intracellular antigens. Here we describe a second form of the human LMP7 cDNA, LMP7-E2, which has been identified during the characterization of novel genes in the MHC. The analysis of the genome organization of LMP7 revealed that LMP7-E1 and LMP7-E2 arise by alternative exon usage. Using specific antibodies against LMP2 and LMP7, we show that they are co-expressed with class I MHC molecules as well as a putative peptide transporter. The polypeptides encoded by LMP7 and LMP2 undergo proteolytic processing when incorporated into proteasomes, and the LMP7 precursor is derived mainly from LMP7-E2. Furthermore, our data suggest that LMP7 and LMP2 are mutually dependent for their incorporation into the proteasomal complex.
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The effect of hypoxia on the neurotransmitter phenotype of rat forebrain cholinergic neurons was analyzed using a dissociated fetal rat culture system. The aims of this study were to examine the feasibility of using choline acetyltransferase (ChAT) activity as a measure of cell injury and/or recovery, to measure the time course of hypoxic effects on ChAT activity, to determine how changes in ChAT activity at 48 h post-injury relate to microscopic changes and LDH release into the medium during that time, and finally to explore the possible mechanisms of hypoxic injury in this model. At exposure to 0.5-1.5% O2 there was a time-dependent decrease in ChAT activity when cells were harvested 48 h after exposure. Forty-eight hours after 8-9 h hypoxic exposure ChAT activity was 50-60% that of controls without any alteration in morphology of neurons. An 8 h exposure to hypoxic conditions caused a post-exposure time-dependent decrease in ChAT activity to 20% of control level at 72 h. Thereafter there was spontaneous recovery of phenotype to 60% of control which remained stable between 5 and 7 days post-exposure. Loss of neurotransmitter phenotype was not well correlated with other measures of cytotoxicity including morphological changes and LDH release. The loss of phenotype observed with hypoxia was mimicked by glutamate and kainate but not by NMDA. Consistent with these observations, neither APV nor AP3 significantly altered the effect of hypoxia on forebrain cholinergic neurons, while the addition of APV and CNQX in combination protected the phenotype of these neurons only if there was 50% or less loss of phenotype following hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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The mutant murine lymphoma cell line RMA-S is unable to present endogenous antigens due to its inability to efficiently assemble class I major histocompatibility complex molecules and antigenic peptides. Therefore, it has been suggested that RMA-S cells are defective either in peptide generation or in peptide transport into the endoplasmic reticulum, where class I major histocompatibility complex molecule assembly is believed to occur. As proteasomes and the putative peptide transporters HAM1 and HAM2 have been implicated in class I antigen processing, we have investigated their expression in RMA-S and its wild-type counterpart RMA. Both proteasomes and HAM1 proteins are expressed at similar levels and show identical subcellular distributions in the two cell lines. However, only one copy of the HAM2 gene is present in RMA-S cells, and it contains a point mutation that leads to a premature stop codon. Thus, the HAM2 protein is absent from RMA-S cells. These data demonstrate that HAM2 is essential for peptide loading onto class I molecules.
Class I major histocompatibility complex (MHC) molecules present antigenic peptides of cytoplasmic origin to T cells. As the lengths of these peptides seem restricted to eight or nine amino acids, an unusual proteolytic system must play a role in antigen processing. Proteasomes, a major extralysosomal proteolytic system, are responsible for the degradation of cytoplasmic proteins. We demonstrate that several proteasomal subunits, including MHC-encoded subunits, are regulated by interferon gamma. These data and the finding that MHC-encoded and other interferon gamma-regulated proteasomal subunits are uniquely associated with proteasomes strongly suggest that the immune system has recruited proteasomes for antigen processing.
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We report the cloning of a human gene encoding the 5-hydroxytryptamine1B receptor. The receptor has the characteristics of a G-protein-linked receptor and is most homologous to the human 5-HT1D receptor. This human 5-HT receptor gene, most abundantly expressed in striatum, is localized on chromosome 6, at 6q13, and the gene encoding the 5-HT1D receptor is localized on chromosome 1. Radioligand studies indicate that the affinity of [3H]5-HT is 16 +/- 2 nM. Drug competition studies indicate that the receptor displays high affinity (i.e. less than 40 nM) for 5-HT, 5-carboxyamidotryptamine, methiothepin, and metergoline.
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In view of the limitations associated with the present tumor markers for prostate cancer, we have examined the potential expression of two further markers, Cathepsin-D and pS2, in human prostate and attempted to link their concentrations with the histopathology of the tissue, the PSA levels and the androgenic status of the gland. Cathepsin-D and pS2 were measured in cytosol fractions obtained from 22 patients with benign prostatic hyperplasia (BPH) and 20 patients with prostate cancer (CaP) employing immunoassays specific for these markers. The concentrations of Cathepsin-D (BPH: mean +/- SEM = 18.50 +/- 1.88 nmol/g protein; CaP = 19.75 +/- 2.49 nmol/g protein) and pS2 (BPH = 1,024.7 +/- 348.06 ng/g protein; CaP = 1,513.88 +/- 268.60 ng/g protein) were not different in the two tissue types, whereas PSA in BPH tissue (1,952.27 +/- 249.93 micrograms/g protein) was significantly higher than the measurements in CaP (583.75 +/- 104.33 micrograms/g protein). However, none of the tumor marker concentrations correlated with the degree of differentiation of the tumors, and we were unable to establish any correlation with the levels of testosterone and dihydrotestosterone in the tissue. In conclusion, although Cathepsin-D and pS2 are expressed in prostate tissue, it is doubtful whether they will have an active role in the management of prostate cancer.
In 427 subjects TEE was performed with either a uniplane or biplane transducer; in seven cadavers the cardiac anatomic segments were observed in several levels and directions. Nine transverse and six longitudinal views were compared with the corresponding cardiac anatomic segments. Based on this correlative study, the levels of segments, insertion depth, anatomic structure identification, image characteristics, clinical applications, and the advantages as well as the limitations of biplane TEE are discussed.
Interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) were identified in samples of first trimester and term placentas by immunocytochemistry using two sets of polyclonal antibodies to recombinant IL-1. All samples contained the two species of IL-1, which predominated in different types of cells: IL-1 alpha was contained primarily in placental villous trophoblastic and stromal cells whereas IL-1 beta was localized to cells in fetal and maternal blood. With respect to the cellular localization of the two proteins, early and late gestation tissues were similar. Although these results were generally consistent for the two sets of antibodies, differences were noted in the binding patterns of the individual reagents. The findings in this study provide strong support for the postulate that IL-1 modulates placental development and suggest that IL-1 alpha may be the preferred species in extraembryonic tissues.
We have used in situ hybridization and immunocytochemistry to characterize the cellular distribution of cystic fibrosis (CF) gene expression in human bronchus. The cystic fibrosis transmembrane conductance regular (CFTR) was primarily localized to cells of submucosal glands in bronchial tissues from non-CF individuals notably in the serous component of the secretory tubules as well as a subpopulation of cells in ducts. Normal distribution of CFTR mRNA was found in CF tissues while expression of CFTR protein was genotype specific, with delta F508 homozygotes demonstrating no detectable protein and compound heterozygotes expressing decreased levels of normally distributed protein. Our data suggest mechanisms whereby defects in CFTR expression could lead to abnormal production of mucus in human lung.
The use of synthetic cuffs to simplify and hasten microvascular anastomoses is offered as an alternative to conventional methods. In this study, a soft, non-irritating, silicone rubber cuff was used to construct end-to-end and end-to-side cuff-sutured anastomoses in rats. This technique was as rapid as other non-sutured anastomoses, required no assistant, and provoked no foreign-body reactions.
Upon dichoptic viewing of dissimilar patterns, several distinct perceptual states may be experienced over time. One state is exclusive monocular dominance, wherein the view of only one eye is seen in its entirety for some period of time. Another state is characterized by a mosaic-like college consisting of portions of the view of each eye. Two other states involve simultaneous perception of both monocular images in their entirety. In one of these states, the two monocular stimuli appear to be superimposed without depth (a phenomenon we shall term 'superimposition'). In the other state, the two monocular stimuli appear to be located at different depth planes (which we shall term 'transparency'). This paper documents the stimulus conditions favoring these various perceptual states. Exclusive monocular dominance occurs most often when the two eyes view dissimilar patterns with the same spatial-frequency content, particularly when both patterns consist of low spatial frequencies. Superimposition also occurs most often when the two eyes view the same spatial frequencies, but predominantly when those spatial frequencies are high. Transparency is favored when the spatial-frequency difference between the eyes is great, particularly when the view of one eye consists of high spatial-frequency information.
Against a background of problems in delivering rural health care in the Jiujiang district of China, this paper outlines the development of a relevant 3-year SSO (Strengthening the training of clinical skills, Strengthening preventive medicine education, and Optimizing curricular structure) programme at Jiujiang Medical College (JMC). Some comparisons between JMC and the Southern Illinois University School of Medicine (SIUSM) are made, and the possibility of applying problem-based learning to JMC is discussed.
The methanol-soluble, heat-stable enterotoxin of Escherichia coli is a protease-resistant extracellular peptide which is synthesized as a 72-amino-acid precursor Pre-Pro-STA3. The specific roles of Pre (19 amino acids), Pro (34 amino acids) and STA3 (19 amino acids) in the secretion process were studied by functionally deleting each of the three domains. Deletion of the Pre signal sequence resulted in a short-lived cell-associated molecule with an M(r) equivalent to that of Pro-STA3. Deletion of Pro (i.e., Pre-STA3) resulted in the rapid extracellular accumulation of STA3; the periplasmic intermediate found in the secretion of the wild-type toxin was undetected. Deletion of the STA3 domain resulted in a cell-associated Pre-Pro peptide; with time this form converted to periplasmic Pro which later became extracellular. When DNA encoding either STA3, by itself, or Pro-STA3 (lacking the signal peptide) was expressed, these peptides were degraded intracellularly, with no periplasmic or extracellular forms detected. The results presented demonstrate that the signal peptide (Pre) is essential even for the export of small peptides to the periplasm, and that its absence causes the STA3 domain to become susceptible to intracellular proteases. The rapid degradation of intracellular STA3 indicates that its proteolytic resistance is acquired in a compartment other than the cytoplasm. The results also show that after the Pre domain is proteolytically cleaved from Pre-STA3 and Pre-Pro, the STA3 and Pro peptides can exit to the culture supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)