ATG16L1 deficiency in macrophages drives clearance of uropathogenic E. coli in an IL-1ß-dependent manner.

Urinary tract infections (UTIs) are frequent, commonly recurrent, and costly. Deficiency in a key autophagy protein, ATG16L1, protects mice from infection with the predominant bacterial cause of UTIs, Uropathogenic E. coli (UPEC). Here, we report that loss of ATG16L1 in macrophages accounts for this protective phenotype. Compared with wild-type macrophages, macrophages deficient in ATG16L1 exhibit increased uptake of UPEC and enhanced secretion of interleukin-1ß (IL-1ß). The increased IL-1ß production is dependent upon activation of the NLRP3 inflammasome and caspase-1. IL-1ß secretion was also enhanced during UPEC infection of ATG16L1-deficient mice in vivo, and inhibition of IL-1ß signaling abrogates the ATG16L1-dependent protection from UTIs. Our results argue that ATG16L1 normally suppresses a host-protective IL-1ß response to UPEC by macrophages.

Thermal activation between Landau levels in the organic superconductor beta(")-(BEDT-TTF)2SF5CH2CF2SO3.

We show that Shubnikov-de Haas oscillations in the interlayer resistivity of the organic superconductor beta(")-(BEDT-TTF)2SF5CH2CF2SO3 become very pronounced in magnetic fields approximately 60 T. The conductivity minima exhibit thermally activated behavior that can be explained simply by the presence of a Landau gap, with the quasi-one-dimensional Fermi surface sheets contributing negligibly to the conductivity. This observation, together with complete suppression of chemical potential oscillations, is consistent with an incommensurate nesting instability of the quasi-one-dimensional sheets.

Botulinum toxin: new treatment for temporomandibular disorders.

BACKGROUND: Temporomandibular disorders (TMDs) affect the face and jaws, and cause chronic pain and dysfunction in many people. As in other conditions involving the musculoskeletal system, controlling the myogenous component is an integral part of treatment. In this study, we evaluated subjective and objective responses to treatment with botulinum toxin A (BTX-A) in a group of 46 patients with TMDs. METHODS: 46 subjects with TMD were enrolled in this uncontrolled study and treated with BTX-A 150U. Both masseter muscles were injected with 50 U each and both temporalis muscles with 25 U each under electromyographic guidance. Subjects were assessed at two-week intervals for eight weeks. Outcome measures included subjective assessment of pain by visual analogue scale (VAS), measurement of mean maximum voluntary contraction (MVC), interincisal oral opening, tenderness to palpation, and a functional index based on multiple VAS. Medians of the data were taken for each outcome measure at each time point and subjected to Duncan's multiple range test. RESULTS: There were significant (P<0.05) differences in all median outcome measures between the pre-treatment assessment and the four follow-up assessments except for MVC. Although MVC was significantly reduced midway through the study, it had returned to pretreatment values by the final two assessments. All other outcome measures remained significantly different from the pretreatment findings. Paired correlation of variables including age, sex, diagnosis, depression index, and time of onset showed no significant differences. CONCLUSIONS: BTX-A injections produced significant improvements in pain, function, mouth opening, and tenderness to palpation. MVC initially diminished then returned to the initial values. Although the study was uncontrolled, the results strongly suggest that BTX-A reduces severity of symptoms and improves functional abilities for patients with TMD and that these extend beyond its muscle-relaxing effects.

Experimental study of bone growth around a dental implant after Surgibone grafting.

Histologic and histomorphometric results of bone growth around titanium alloy screw-type implants after Surgibone grafting in New Zealand white rabbits are presented. At 21 days, new bone was formed along the surface of the implant. At 84 days, newly formed bone replaced almost all of the trabecular bone of the graft and reached the shoulder level of the implant. There was a higher percentage of host bone area at 84 days than at any of the earlier experimental periods (P < .01). The average mineral apposition rates ranged from 1.82 to 2.35 microns/day in original bone and 2.55 to 2.80 microns/day in newly formed bone. The results suggest that Surgibone grafting in combination with dental implants can be used to increase the height of the recipient bone and therefore aid in the fixation of the implant in this animal model.

The use of botulinum toxin for the treatment of temporomandibular disorders: preliminary findings.

PURPOSE: The aim of this study was to evaluate the response of patients with temporomandibular disorders to Botulinum toxin A (BTX-A) therapy. METHODS: The 15 subjects enrolled in this uncontrolled study were diagnostically categorized and treated with 150 units of BTX-A. Both masseter muscles received 50 units each under eletromyographic (EMG) guidance. Similarly, both temporalis muscles were injected with 25 units each. Subjects were assessed at 2-week intervals for 8 weeks. Outcome measures included subjective pain by visual analog scale (VAS), measurement of bite force, interincisal opening, tenderness to palpation, and a functional index based on multiple VAS. RESULTS: All mean outcome measures, with the exception of bite force, showed a significant (P = .05) difference between the preinjection assessment and the four follow-up assessments. No side effects were reported. CONCLUSIONS: BTX-A injections produced a statistically significant improvement in four of five measured outcomes, specifically pain, function, mouth opening, and tenderness. No statistically significant changes were found in mean maximum voluntary contraction or in paired correlation of factors such as age, sex, diagnosis, depression index, or time of onset.

[Experimental study of cattle bone grafting in combination with implant insertion].

OBJECTIVE: To study the effect of cattle bone grafting in combination with implant insertion. METHODS: Twenty cattle bone blocks were onlayed on the rabbit tibial metaphysis, which were fixed by dental implants. Triple fluorochromes were sequentially given to animals following the operation. New bone formation was histologically and histomorphometrically evaluated. RESULTS: The fluorochrome-labelled new bone gradually replaced almost all the spongy bone and the partial cortical bone of the graft at the end of the experiment. There was a significant higher percentage of bone area at the first four thread levels at 84 days than at 21 days. The average mineral apposition rates ranged from 1.90 microns/d to 2.75 microns/d. CONCLUSION: The onlay cattle bone grafting in conjunction with screw-type dental implants can be used to increase the volume of the recipient bone.

A clinical trial of a new dental implant.

This paper presents the results of a clinical trial of a new dental implant after two years of loading. The design and the technical details of the surgical and prosthodontic phases of treatment are discussed. The implant's success was measured using Health Canada (Health Protection Branch) criteria. Patients with less than optimal clinical situations were not excluded from the study. The study shows survival rates in the lower jaw of 85.6 per cent and in the upper jaw of 86.7 per cent. Bleeding and oral hygiene indices and bone loss (less than 0.2 mm/yr) all fall within generally accepted limits.

Effect of drill speed on bone temperature.

Measurements of bone temperature rise were recorded during drilling of bovine cortical bone specimens. A surgical drill (Stryker-100) was fitted with a custom-designed speedometer for monitoring the rotational speed during the drilling, and the drill was mounted on a specially constructed drill press. The tests were conducted in 36 specimens at variable speeds (20000-100000 rpm) and at different constant forces (1.5-9.0 N) which were applied by placing weights on the drill platform. The results revealed that the temperature rise and the duration of temperature elevation decreased with speed and force, suggesting that drilling at high speed and with large load is much more desirable than previously thought.

Transcriptional repression by human adenovirus E1A N terminus/conserved domain 1 polypeptides in vivo and in vitro in the absence of protein synthesis.

The human adenovirus E1A 243R protein (243 residues) transcriptionally represses a set of cellular genes that regulate cellular growth and differentiation. We describe two lines of evidence that E1A repression does not require cellular protein synthesis but instead involves direct interaction with a cellular protein(s). First, E1A 243R protein represses an E1A-repressible promoter in the presence of inhibitors of protein synthesis, as shown by cell microinjection-in situ hybridization. Second, E1A 243R protein strongly represses transcription in vitro from promoters of the E1A-repressible genes, human collagenase, and rat insulin type II. Repression in vitro is promoter-specific, and an E1A polypeptide containing only the N-terminal 80 residues is sufficient for strong repression both in vivo and in vitro. By use of a series of E1A 1-80 deletion proteins, the E1A repression function was found to require two E1A sequence elements, one within the nonconserved E1A N terminus, and the second within a portion of conserved region 1 (40-80). These domains have been reported to possess binding sites for several cellular transcription regulators, including p300, Dr1, YY1, and the TBP subunit of TFIID. The in vitro transcription-repression system described here provides a powerful tool for the further analysis of molecular mechanism and the possible role of these cellular factors.

Mycobacterium kansasii bacteremia in patients infected with human immunodeficiency virus.

In a retrospective review of microbiology records at the George Washington University Hospital from 1980 through 1990, Mycobacterium kansasii bacteremia was identified in 10 patients; this finding represented 4.5% of nontuberculous mycobacterial blood cultures. M. kansasii was isolated from respiratory specimens from all 10 patients, and pulmonary parenchymal changes were noted in five patients. The median survival time was 14 weeks; however, only five patients received therapy with two or more drugs active against M. kansasii.

Molecular cloning and characterization of a cellular protein that interacts with the human immunodeficiency virus type 1 Tat transactivator and encodes a strong transcriptional activation domain.

The mechanism by which human immunodeficiency virus type 1 Tat transactivates the long terminal repeat promoter is not understood. It is generally believed that Tat has one or more transcription factors as its cellular target. One might expect a cellular target for Tat to possess several properties, including (i) the ability to bind to the Tat activation region, (ii) the possession of a transcriptional activation domain, and (iii) the ability to contact the cellular transcription machinery. Here we describe the cloning, expression, and characterization of a human protein, termed TAP (Tat-associated protein), which possesses some of these properties. TAP is highly conserved in eukaryotes and is expressed in a variety of human tissues. The major intracellular species of TAP is a highly acidic 209-amino-acid protein that likely is formed by removal of a highly basic 70-amino-acid N-terminal segment from a primary translation product. By deletion analysis, we have identified a TAP C-terminal region rich in acidic amino acids and leucine residues which acts as a strong transcriptional activator when bound through GAL4 sites upstream of the core long terminal repeat promoter, as well as flanking sequences that mask the activation function. Amino acid substitution of two leucine residues within the core activation region results in loss of the TAP activation function. Two lines of evidence suggest that Tat interacts with TAP in vivo. First, promoter-bound Tat can recruit a TAP/VP16 fusion protein to the promoter. Second, transiently expressed Tat is found associated with endogenous TAP, as demonstrated by coimmuno-precipitation analysis. As shown in an accompanying report, the TAP activation region binds the Tat core activation region and general transcription factor TFIIB (L. Yu, P.M. Loewenstein, Z. Zhang, and M. Green, J. Virol. 69:3017-3023, 1995). These combined results suggest the hypothesis that TAP may function as a coactivator that bridges Tat to the general transcription machinery of the cell via TFIIB.

Differential antagonism of platelet activating factor-induced neutrophilia and gastric hemorrhage in the rat.

Intravenous injection of platelet activating factor (PAF) in rats produced hypotension, neutrophilia, gastric congestion, and sloughing of the gastric epithelium. The congestion was quantified by measuring hemoglobin in the gastric mucosa. Other lesions were quantified by scores of gross pathology and histopathology. PAF-induced changes in neutrophil levels were prevented by pretreatment with the PAF-antagonist Ro24-4736, but not by the PAF-antagonist CV-3988. Both PAF antagonists reduced the hypotension, the amount of hemoglobin in the gastric mucosa, and the PAF-induced gastric pathology. These results suggest that PAF receptors involved in PAF-induced neutrophil mobilization respond differently from PAF receptors in the gastrointestinal and cardiovascular systems.

Clinical prosthodontic management of a new implant system.

Just prior to the advent of the branemark implant, the Harvard consensus on implantology condemned all maxillary implants. While implant utilization has skyrocketed in the last few years integration of implants in the maxilla is a persistent problem and even the branemark implant enjoys a lower success rate in this bone. These observations underscore the higher failure rate of the maxillary implant and suggest the need for development of a new implant design configuration that would favour long term successful integration despite the attenuated maxillary attributes. Such is the intent of the ostial implant. The basic considerations concerning this device, its bioengineering, experimental performance and clinical trials are discussed elsewhere. The purpose of this paper is to describe clinical prosthodontic applications of this implant system.

Postoperative computed tomography study of pterygomaxillary separation during the Le Fort I osteotomy.

Computed tomography (CT) was used postoperatively to assess the pterygomaxillary region in 12 orthognathic surgery patients who had had a Le Fort I osteotomy. Although pterygomaxillary separation was successful in all cases, in only 41.6% of the sides did fractures of the plate not occur. The incidence of low pterygoid plate fracture was 37.5% and that of high pterygoid plate fracture was 25%; 4.2% of sides showed a maxillary tuberosity fracture. Multiple fractures were observed in 8.3% of separated plates. Of 17 pterygoid plates judged clinically to be intact, only 10 were intact as assessed by CT. The significance of these findings and application of CT to evaluation of modifications to the Le Fort I osteotomy is discussed.

Evaluation of an interleukin-1 receptor antagonist in the rat acetic acid-induced colitis model.

The anti-inflammatory activity of the IL-1 receptor antagonist, IL-1ra, was evaluated in the acetic acid (HOAc)-induced model of colitis in rats. Animals treated with 10 mg/kg IL-1ra or vehicle were evaluated for general health, acute phase response, and colonic in flammation 24 hours after the initiation of inflammation. A significant decrease in the accumulation of neutrophils in the colonic mucosa as measured by myeloperoxidase activity was seen in animals with HOAc induced colitis that were treated intraperitoneally with IL-1ra when compared to animals with colitis that had been treated with vehicle. IL-1ra also reduced colonic necrosis measured grossly, although there was no effect on the histology IL-1ra had a modest effect on the HOAc-induced acute phase response, as indicated by changes in the serum iron, albumin and transferrin, but the results were not statistically significant. The number of circulating erythrocytes and neutrophils was significantly increased in animals with HOAc-induced colitis and treated with IL-1ra, suggesting that IL-1ra under these experimental conditions inhibited the migration of neutrophils to the injured colon and also the overall intestinal necrosis in the colon as assessed by gross pathology. IL-1ra may be useful as an intestinal anti-inflammatory agent.

Rhabdomyosarcoma of the maxillary sinus: review of the literature and report of a case.

A case of rhabdomyosarcoma of the maxillary sinus is reported. A brief review of the origin, histomorphology, classification, clinical presentation, behavior, prognosis, and treatment is given relative to occurrence in the maxillary antrum. Misinterpretation of the microscopic findings can delay the histologic diagnosis. An error in tissue diagnosis may be minimized by awareness of a chance encounter with this lesion.