Involvement of CD14 and complement receptors CR3 and CR4 in nuclear factor-kappaB activation and TNF production induced by lipopolysaccharide and group B streptococcal cell walls

This study was undertaken to evaluate the role of CD14 and complement receptors type 3 (CR3) and 4 (CR4) in mediating TNF release and NF-kappaB activation induced by LPS and cell wall preparations from group B streptococci type III (GBS). LPS and GBS caused TNF secretion from human monocytes in a CD14-dependent manner, and soluble CD14, LPS binding protein, or their combination potentiated both LPS- and GBS-induced activities. Blocking of either CD14 or CD18, the common beta-subunit of CR3 and CR4, decreased GBS-induced TNF release, while LPS-mediated TNF production was inhibited by anti-CD14 mAb only. Chinese hamster ovary cell transfectants (CHO) that express human CD14 (CHO/CD14) responded to both LPS and GBS with NF-kappaB translocation, which was inhibited by anti-CD14 mAb and enhanced by LPS binding protein. While LPS showed fast kinetics of NF-kappaB activation in CHO/CD14 cells, a slower NF-kappaB response was induced by GBS. LPS also activated NF-kappaB in CHO cells transfected with either human CR3 or CR4 cDNA, although responses were delayed and weaker than those of CHO/CD14 cells. In contrast to LPS, GBS failed to induce NF-kappaB in CHO/CR3 or CHO/CR4 cells. Both C3H/OuJ (Lps[n]) and C3H/HeJ (Lps[d]) mouse peritoneal macrophages responded to GBS with TNF production and NF-kappaB translocation, whereas LPS was active only in C3H/OuJ macrophages. Thus, LPS and GBS differentially involve CD14 and CR3 or CR4 for signaling NF-kappaB activation in CHO cells and TNF release in human monocytes, and engage a different set of receptors and/or intracellular signaling pathways in mouse macrophages.     

Transurethral cystotomy repair

We present a novel transurethral technique for cystotomy repair. This method can be used for immediate bladder repair following limited bladder injury and avoids the morbidity associated with laparotomy.     

Laser in situ keratomileusis: literature review of a developing technique

We reviewed papers published in peer-reviewed journals describing techniques and results of laser in situ keratomileusis (LASIK) and summarized the instruments used, nomograms, preoperative and postoperative refractions, predictability, outcome, safety, and complications. We performed a similar review of abstracts published in the abstract books of the 1996 meeting of the International Society of Refractive Surgery, the 1997 meeting of the Association for Research in Vision and Ophthalmology, and the 1997 meeting of the American Society of Cataract and Refractive Surgery. The number of LASIK and photorefractive keratectomy (PRK) patients described in the abstracts were sorted by city. Mean weighted latitudes were calculated and compared for each procedure. The mean preoperative refraction in the papers was -12.59 diopters (D), which was statistically higher than that in the abstracts, -8.71 D (P < .001), and the mean postoperative refraction, -1.10 and + 0.93 D, respectively. The mean percentage of cases within +/- 1.00 D was 67.0% in the papers and 82.5% in the abstracts. Uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 49.2% of eyes in the papers and 83.2% of those in the abstracts; a UCVA of 20/20 or better was achieved in 22.0 and 56.6%, respectively. The portion of eyes that lost two or more lines of best corrected visual was 8.0% in the papers and 0.9% in the abstracts. Complications in the papers included irregular flap (4.0%), incomplete cut (2.5%), free cap (4.9%), perforated lenticule (2.6%), short flap (3.0%), sliding flap (1.4%), interface debris (6.8%), central island (5.3%), decentration (4.7%), epithelial ingrowth (4.3%), induced astigmatism (5.1%), wrinkles (5.9%), haze (8.7%), night vision problems (14.0%), and reoperation (8.2%), Mean latitude for LASIK cases (27.00 degrees +/- 13.73 [SD] was significantly lower than that for PRK cases (42.85 +/- 11.7 degrees). Visual outcomes of LASIK surgery show significant improvements when recent abstracts are compared with published papers. This may reflect continued improvement in the surgical techniques, surgeons' skills, and visual outcomes.     

Gene therapy strategies for AIDS-related malignancies

AIDS-related malignancies (ARM) include AIDS-defining cancers such as Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical carcinoma. In addition, certain other malignancies are also increased with human immunodeficiency virus (HIV) infection. New antiretroviral agents and better prophylaxis and treatment of HIV-related opportunistic infections are prolonging the lives of HIV-infected individuals. There will thus likely be a continued rise in the incidence and prevalence of ARM in the long term, even if effective antiretroviral and other AIDS-related therapies reduce their appearance in the short term. There are presently no curative regimens for the common ARM, with the possible exception of some lymphomas. Survival is shortened by most, and treatment is often toxic and poorly tolerated. Gene therapies may thus offer a useful adjunct to conventional treatment strategies for selected ARM. Although some gene therapy strategies may work well in the HIV setting, the chronic viral infection, immunodeficient status of the host, the tendency for HIV-infected individuals to have altered drug metabolism and an increased rate of adverse drug reactions will likely present special challenges. This review summarizes the state-of-the-art in the fledgling field of gene therapy for ARM, and explores areas for future research.     

Foreign serum-induced pancreatitis in mice. II. Secretory disturbances of acinar cells

As previously reported, pancreatic acinar cell necrosis and inflammation develop in mice a few hours after one intraperitoneal injection of foreign serum. However, sublethally injured acinar cells exhibited notable increases in both zymogen granule numbers and amylase activity, observed within 3 hours and increasing with time. These two changes were coupled with a progressive decrease in the secretory response to pilocarpine and were preceded by significant disturbances in pancreatic tissue concentrations of sodium and potassium. We conclude that (1) the granule increase results from an induced disturbance of the granule exocytosis mechanism while granule formation continues and, therefore, (2) the granule secretory process is more sensitive to the serum injury mechanism than is the zymogen synthesis process. Although the granule increases developed in acinar cells throughout most of the nonnecrotic gland and persisted for at least 24 hours, acinar cell necrosis was maximal in extent--approximately 25% of the gland in severest form--by 12 to 15 hours. We conclude, therefore, that the increase in granules is neither the primary determinant nor initiator of acinar cell death. The latter is likely caused by disturbed plasma membrane functions, sufficient in some cells to result in lethal changes in ion and fluid composition. The injury mechanism, which permits granule formation to go on in the face of impaired granule exocytosis, is yet to be worked out. The possibilities are discussed in relationship to the reactivity of foreign sera for target cell plasma membranes.     

The role of dorsal hippocampus and basolateral amygdala NMDA receptors in the acquisition and retrieval of context and contextual fear memories.

The authors used 3-phase context preexposure facilitation methodology to study the contribution of N-methyl-D-aspartate (NMDA) receptors in dorsal hippocampus (DH) and the basal lateral region of the amygdala (BLA) to (a) acquisition of the context memory, (b) retrieval of the context memory, (c) acquisition of context-shock association, and (d) retrieval of the context-shock association. The NMDA receptor antagonist D-2-amino-5 phosphonopentanoic acid (D-AP5) was injected into either the DH or BLA prior to (a) the context preexposure phase, (b) the immediate shock phase, or (c) the test for contextual fear. Antagonizing NMDA receptors in the DH impaired the acquisition of the context memory but did not affect its retrieval or retrieval of the fear memory. Antagonizing NMDA receptors with D-AP5 in the BLA impaired acquisition of the context-shock association but had no effect on the expression of fear. However, both DL-AP5 and L-AP5 reduced the expression of fear when they were injected into the amygdala prior to testing for contextual fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proadrenomedullin N-terminal 20 peptide: minimal active region to regulate nicotinic receptors

Proadrenomedullin N-terminal 20 peptide (PAMP-[1-20]; ARLDVASEFRKKWNKWALSR-amide) is a potent hypotensive and catecholamine release-inhibitory peptide released from chromaffin cells. We studied the mechanism of PAMP action and how its function is linked to structure. We tested human PAMP-[1-20] on catecholamine secretion in PC12 pheochromocytoma cells and found it to be a potent, dose-dependent (IC50 approximately 350 nmol/L) secretory inhibitor. Inhibition was specific for nicotinic cholinergic stimulation since PAMP-[1-20] failed to inhibit release by agents that bypass the nicotinic receptor. Nicotinic cationic (22Na+,45Ca2+) signal transduction was disrupted by this peptide, and potencies for inhibition of 22Na+ uptake and catecholamine secretion were comparable. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. N- and C-terminal PAMP truncation peptides indicated a role for the C-terminal amide and refined the minimal active region to the C-terminal 8 amino acids (WNKWALSR-amide), a region likely to be alpha-helical. PAMP also blocked (EC50 approximately 270 nmol/L) nicotinic cholinergic agonist desensitization of catecholamine release, as well as desensitization of nicotinic signal transduction (22Na+ uptake). Thus, PAMP may exert both inhibitory and facilitatory effects on nicotinic signaling, depending on the prior state of nicotinic stimulation. PAMP may therefore contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release.     

Acute hemodynamic effects of estrogen administration in postmenopausal women

The hemodynamic effects of estrogens in replacement doses have not been fully clarified; therefore, we studied the acute hemodynamic changes after 0.625 and 1.25 mg of conjugated estrogens, administered intravenously, using a thermodilution catheter, in postmenopausal women without structural heart disease. Pulmonary and systemic pressures and resistances and stroke volume did not change compared with baseline, but heart rate and cardiac output decreased significantly, which may be associated with estrogen's previously described calcium-blocking effect or with a more recently contemplated beta-blocking action.