Developmental mucin gene expression in the human respiratory tract

The epithelial surface of the respiratory tract is coated with a protective film of mucus secreted by epithelial goblet and submucosal gland cells. Histology of the airway mucosa and composition of secretions during the second trimester of fetal life are known to differ from the normal adult in that these secretions show similarities with those of hypersecretory disorders. To provide information regarding cell-specific expression of mucin genes and their relation to developmental patterns of epithelial cytodifferentiation, we studied the expression of eight different mucin genes (MUC1-MUC4, MUC5AC, MUC5B, MUC6, MUC7) in human embryonic and fetal respiratory tract using in situ hybridization. These investigations demonstrated that MUC4 is the earliest gene expressed in the foregut at 6.5 wk, followed by MUC1 and MUC2 from 9. 5 wk of gestation in trachea, bronchi, epithelial tubules, and terminal sacs before epithelial cytodifferentiation. In contrast, MUC5AC, MUC5B, and MUC7 are expressed at later gestational ages concomitant with epithelial cytodifferentiation. During this developmental stage, MUC1 and MUC4 mRNAs are located in goblet and ciliated cells, whereas MUC2 mRNAs are located in basal and goblet cells. MUC5AC expression is confined to goblet cells. In the submucosal glands, MUC2 mRNAs are located in both mucous and serous cells, whereas MUC5B and MUC7 mRNAs are expressed in mucous and in serous cells, respectively. These data suggest distinct developmental roles for MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7 in the elongation, branching, and epithelial cytodifferentiation of the respiratory tract during ontogenesis. Distinct patterns of mucin gene expression are also likely to play an important role in regulating appropriate epithelial cell proliferation and cytodifferentiation in adult airway mucosa as it is indicated by aberrant expression in hypersecretory disorders.     

A role for host phosphoinositide 3-kinase and cytoskeletal remodeling during Cryptosporidium parvum infection

Cryptosporidium parvum preferentially infects epithelial cells lining the intestinal mucosa of mammalian hosts. Parasite development and propagation occurs within a unique intracellular but extracytoplasmic parasitophorous vacuole at the apical surface of infected cells. Parasite-induced host cell signaling events and subsequent cytoskeletal remodeling were investigated by using cultured bovine fallopian tube epithelial (BFTE) cells inoculated with C. parvum sporozoites. Indirect-immunofluorescence microscopy detected host tyrosine phosphorylation within 30 s of inoculation. At >30 min postinoculation, actin aggregates were detected at the site of parasite attachment by fluorescein isothiocyanate-conjugated phalloidin staining as well as by indirect immunolabeling with monoclonal anti-actin. The actin-binding protein villin was also detected in focal aggregates at the site of attachment. Host cytoskeletal rearrangement persisted for the duration of the parasitophorous vacuole and contributed to the formation of long, branched microvilli clustered around the cryptosporidial vacuole. The phosphoinositide 3-kinase inhibitor wortmannin significantly inhibited (P < 0.05) C. parvum infection when BFTE cells were pretreated for 60 min at 37 degreesC prior to inoculation. Similarly, treatment of BFTE cells with the protein kinase inhibitors genistein and staurosporine and the cytoskeletally acting compounds 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazapine, cytochalasin D, and 2,3-butanedione monoxime significantly inhibited (P < 0.05) in vitro infection at 24 h postinoculation. These findings demonstrate a prominent role for phosphoinositide 3-kinase activity during the early C. parvum infection process and suggest that manipulation of host signaling pathways results in actin rearrangement at the site of sporozoite attachment.     

Chronic antidepressant administration increases the expression of cAMP-specific phosphodiesterase 4A and 4B isoforms

The influence of chronic antidepressant administration on expression of the three major phosphodiesterase (PDE) 4 subtypes found in brain (PDE4A, PDE4B, and PDE4D) was examined. The treatments tested included representatives of four major classes of antidepressants: selective reuptake inhibitors of serotonin (sertraline and fluoxetine) or norepinephrine (desipramine), a monoamine oxidase inhibitor (tranylcypromine), and electroconvulsive seizure. Expression of PDE4A and PDE4B, but not PDE4D, mRNA and immunoreactivity were significantly increased in rat frontal cortex by chronic administration of each of the four classes of antidepressants. We also found that antidepressant administration significantly increased the expression of PDE4B mRNA in the nucleus accumbens, a brain region thought to mediate pleasure and reward that could also contribute to the anhedonia often observed in depressed patients. In contrast, expression of PDE4A and PDE4B were not influenced by short-term treatment (1 or 7 d) and were not influenced by chronic administration of nonantidepressant psychotropic drugs (cocaine or haloperidol), demonstrating the time dependence and pharmacological specificity of these effects. Upregulation of PDE4A and PDE4B may represent a compensatory response to antidepressant treatment and activation of the cAMP system. The possibility that targeted inhibition of these PDE4 subtypes may produce an antidepressant effect is discussed.     

A high index of suspicion: the key to an early diagnosis of Wilson's disease in childhood

Implantation of peritoneal dialysis catheters by traditional laparotomy or trocar/guidewire techniques leaves the operator blind to the actual location and configuration of the peritoneal catheter tubing; it is associated with drainage dysfunction from catheter obstruction in 10-22% of catheter placements. This report presents a laparoscopic technique that allows accurate tube placement with complete visualization of the implant procedure. The peritoneal dialysis catheter was implanted through a port inserted in a paramedian location. Videoscopic monitoring was performed through a second port inserted in a pararectus location on the opposite side of the abdomen. Nitrous oxide gas was utilized for peritoneal insufflation thus permitting the procedure to be accomplished under local anesthesia. Follow-up of 相似文献   

Optical amplifier noise figure reduction for opticalsingle-sideband signals

This paper analyzes the amplification of optical single-sideband signals, highlighting the significance of the optical signal bandwidth in determining signal-amplified spontaneous emission (ASE) beat noise. It predicts that an electrical noise figure of one may be realized for single-sideband signals using appropriate optical filtering. It verifies noise figure reduction experimentally, demonstrating an electrical noise figure of 1.1× the spontaneous emission factor of the amplifier, which is 2.6 dB below the limit for conventional intensity modulated signals     

Experimental stability diagram of a diode laser subject to weakphase-conjugate feedback from a rubidium vapor cell

We report on a systematic experimental investigation of the dynamical behavior of a diode laser subject to delayed feedback from a phase-conjugating mirror based on nearly-degenerate four-wave mixing in rubidium vapor. We present the first experimental stability diagram for this system. In the weak feedback regime, with feedback levels up to -30 dB, me demonstrate locking to the pump frequency with a reduced linewidth smaller than 8 MHz. In contrast to a laser with external injection, and contrary to predictions made for phase-conjugate feedback, the extent of this locking region is found to be limited. For increased feedback rates, the laser leaves the locking region and enters an unstable region through a series of multiple sidebands spectra. This is associated with self-excitation of the relaxation oscillation, and the observed scenario suggests a series of period-doublings after an initial Hopf bifurcation     

Transplantation of islets of Langerhans in patients with insulin-requiring diabetes mellitus undergoing orthotopic liver transplantation--the Miami experience

Most patients with cirrhosis of the liver have detectable insulin resistance. In 60-80% of patients with cirrhosis, impaired glucose tolerance can be uncovered; approximately 20% of these patients eventually develop overt diabetes. Theoretically, insulin resistance and glucose intolerance could be improved or reversed by orthotopic liver transplantation alone or in association with a simultaneous transplant of pancreatic islet cells from the same donor. To investigate these possibilities we initiated a pilot study of simultaneous liver and pancreatic islet cell transplantation in seven patients with diabetes and liver cirrhosis. Donor bone marrow cells were also infused to enhance the acceptance of the grafts. Seven patients who received only orthotopic liver transplantation and donor bone marrow cells were used as historical controls. The preliminary results of this pilot trial suggest that islet cell transplantation in conjunction with orthotopic liver transplantation improves glucose metabolism in patients with liver cirrhosis in association with reduced insulin requirements and HbA1c levels. These results were evident in spite of pre- and post-transplant basal C-peptide levels that were unchanged. Further evaluation of the effects of orthotopic liver transplantation with or without islet cell transplantation will require a randomized prospective trial including accurate metabolic evaluation with the euglycemic insulin clamp technique.     

An overview of smart technology

In recent years there has been a seemingly ever-increasing use of the synonymous adjectives ‘smart’ and ‘intelligent’ to describe a diverse range of materials, structures, systems and technologies.^1-4 The origin of this terminology can be dated to the early 1980s when researchers working mainly in the US, and funded predominantly from defence budgets, began to examine the potential of combining advanced materials and sensors with powerful and compact computers to produce futuristic systems able to monitor their operating environment in real time and respond appropriately. Public awareness of this technology was given an enormous boost by the prominence given to use of ‘smart’ munitions during the Gulf war. Various articles appearing in popular science journals^5–7 and broadsheet newspapers in the months following the successful conclusion of this conflict served to maintain interest and it became fashionable to examine the use of ‘smart’ technology in industrial applications far removed from those originally envisaged in aerospace and defence. Various dedicated university research groups were formed at around this time (among the first in the UK being the Smart Structures Research Institute at Strathclyde University), often bringing together academics who had been working on ‘smart’ technologies for several years without realising it! Over the last five years researchers working in most of the major industrial sectors have given at least some thought to how they might apply ‘smart’ technology, important areas being in transport, building, civil infrastructure, biomedicine, sport and leisure, power generation and oil, gas and petrochemical. Packaging has not been left out of this process, with the prospects for ‘intelligent packaging’ being assessed most notably by CEST and Pira International in a report prepared in 1992 under DTI funding.⁸ Interest in ‘smart’ packaging has been sustained over the four years since this pioneering study, with the focus of attention gradually shifting from abstract conjecture to practical application. Notwithstanding the attention now being devoted to all things ‘smart’, the underlying concepts are still only poorly understood in many quarters and the word must warrant some sort of prize for the proportion of times that it is inaccurately applied. This paper presents a systematic definition of ‘smart’ technology and goes on to review very briefly some of the major advances being made under this technological umbrella. The UK's Defence Research Agency (DRA), like its American counterparts, has been active in ‘smart’ technology from its earliest days and has, for obvious reasons, concentrated mainly on aerospace and defence applications. However, with the launch in April 1994 of the DRA's Structural Materials Centre (SMC), committed explicitly to promoting wealth creation via the dual (i.e. military and civil) use of technology, there has been a conscious effort to identify wider opportunities for the exploitation of the contributing ‘smart’ technologies. Some ideas relevant to packaging which are currently being developed in conjunction with the DRA's Packaging Authority are outlined, together with an invitation for interested companies to participate in various DRA-led joint development programmes. © 1997 John Wiley & Sons, Ltd.