Spread of murine cytomegalovirus to inner ocular structures following disruption of the blood-retina barrier in immunosuppressed BALB/c mice

PURPOSE: The aims of this study were to determine whether disruption of the blood-retina barrier (BRB) increases spread of murine cytomegalovirus (MCMV) to the eye after intraperitoneal inoculation and whether systemic immunosuppression influences the location of MCMV in the ocular compartment. METHODS: The BRB of the left eye of normal and immunosuppressed mice was disrupted by supraciliary inoculation of tissue culture medium followed 2 hours later by intraperitoneal injection of MCMV. Plaque assay of homogenized ocular tissue was used to determine the frequency of virus-positive eyes and the titer of virus in the eyes. Beta-galactosidase staining of frozen sections was used to locate virus in the eyes. RESULTS: In nonimmunosuppressed mice, the frequency of virus isolation, as well as the titer of virus, were significantly higher in eyes in which the BRB had been disrupted. Although the frequency of virus isolation was the same in both eyes of immunosuppressed mice, the titer of virus was significantly higher in the eye in which the BRB had been disrupted. The most striking result was that the location of virus was different in the nondisrupted eyes of immunosuppressed mice than it was in the disrupted eyes of immunosuppressed mice. In the former, virus was seen only in the outer ocular structures (conjunctiva, sclera, lacrimal gland), whereas in the latter, virus was observed in the retina and anterior segment (iris, ciliary body) as well as the outer ocular structures. CONCLUSIONS: The results of these studies suggest that ocular damage followed by increased spread of virus to and within the eye during systemic infection with CMV may be one mechanism by which development of CMV retinitis is facilitated in patients with acquired immune deficiency syndrome.     

Autoregulation during pressor response elevates wall shear rate in arterioles

Autoregulation of blood flow implies reciprocal changes in vessel diameter and red blood cell velocity (VRBC) when perfusion pressure is altered. We tested two hypotheses: 1) blood flow will be autoregulated throughout arteriolar networks during a pressor response, and 2) wall shear rate (WSR; proportional to VRBC/diameter) will increase during autoregulation. Male hamsters (109 +/- 3 g; n = 22) were anesthetized (pentobarbital sodium 60 mg/kg), and the cremaster muscle was prepared for intravital videomicroscopy. Internal diameter and VRBC were monitored in first (1A)- through fourth (4A)-order arterioles; WSR and blood flow were calculated. Data were acquired at rest and at the peak of diameter responses to bilateral carotid artery occlusion (CAO). At rest, 1) mean arterial and 1A transmural pressures were 100 +/- 5 and 59 +/- 4 mmHg, respectively; 2) as branch order increased, arteriolar diameter, VRBC, and blood flow decreased (P < 0.05); and 3) WSR and resting tone increased with branch order (P < 0.05). During pressor responses to CAO, 1) arterial and 1A pressures increased to 145 +/- 7 and 89 +/- 5 mmHg, respectively (P < 0.05); 2) 1A branches dilated while 2A, 3A, and 4A branches constricted (P < 0.05); 3) VRBC and WSR increased in all branches (P<0.05); and 4) blood flow increased in 1A and 2A branches (P < 0.05), yet was unchanged (i.e., was autoregulated) in 3A and 4A branches. Arteriolar constrictions during CAO were not affected by alpha-adrenoceptor blockade with phentolamine (10(-6) M). We conclude that autoregulation of muscle blood flow during a pressor response involves myogenic constriction of arterioles with concomitant elevation of WSR.     

Opioid therapy for chronic noncancer back pain. A randomized prospective study

STUDY DESIGN: A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain. OBJECTIVES: To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain. METHODS: All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finally, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance. RESULTS: Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P < 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior. CONCLUSIONS: The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep. Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.     

Radiation effects in high-temperature superconductors: A brief review

A brief review of the published results on radiation effects in high-temperature superconductors is given. The focus is on six observations: lack of ionization damage, displacement damage, displacement thresholds near 20 eV, effects on transition temperature and critical current, amorphization, and atomic site- and sublattice-specific damage processes. It is concluded that these new ceramic superconductors have a very complex interaction with radiation fields. For ambient-temperature, fast-neutron irradiation, they show effects similar to those observed for A-15 superconductors. However, their total response is far more complex. This paper is based on a presentation made in the symposium “Irradiation-Enhanced Materials Science and Engineering” presented as part of the ASM INTERNATIONAL 75th Anniversary celebration at the 1988 World Materials Congress in Chicago, IL, September 25–29, 1988, under the auspices of the Nuclear Materials Committee of TMS-AIME and ASM-MSD.     

Co-ordinate transformations of screws with applications to screw systems and finite twists

A simple form of expression for writing down a screw which has undergone a transformation of reference frame is established. The simplifications it brings to the standard problems of identifying the principal axes of a screw system and of identifying the axis line of a finite twisting motion is demonstrated.     

Intramolecular inhibition of human defensin HNP-1 by its propiece

We examined mechanisms that protect host defense cells from their cytotoxic effector molecules. Human neutrophil peptides (HNP) 1-3 are microbicidal and cytotoxic defensins, initially synthesized as 94-amino acid preproHNP(1-94), cotranslationally proteolyzed to proHNP(20-94), then converted by removal of the anionic propiece to mature HNP(65-94)(HNP-1 and -3) and HNP(66-94) (HNP-2). We hypothesized that during synthesis and subcellular sorting the anionic propiece inhibits the cytotoxicity of the cationic defensin. We expressed preproHNP-1 cDNA in recombinant baculovirus-infected insect cells that secreted the normally transient proHNP-1(20-94) into the medium. Cyanogen bromide cleaved proHNP-1(20-94) at the fortuitously located Met64 to yield mature recombinant HNP-1(65-94) and unlinked propiece. Recombinant and native HNP-1 purified from PMN were identical as judged by mass spectrometry, retention time in reverse-phase high performance liquid chromatography, migration on acid-urea polyacrylamide gels, and reaction with a conformation-specific antibody. Recombinant and native HNP-1 had comparable microbicidal activity towards Listeria monocytogenes and were similarly potent in permeabilizing K562 leukemia cells, but proHNP-1(20-94) was virtually inactive in both assays. Addition of unlinked propiece (proHNP-1(20-64) with Met64-->homoserine) inhibited the bactericidal and cell-permeabilizing activity of mature HNP-1 in a dose-dependent manner. Linked, and to a lesser extent unlinked, propiece interfered with the binding of HNP-1 to target cells. The propiece thus acts as an efficient intramolecular inhibitor of defensin HNP-1 cytotoxicity.     

Characterization of the oviductal sperm reservoir in cattle

A reservoir for sperm has been found in the oviductal isthmus in several species. Sperm are apparently trapped in the reservoir by binding to the oviductal epithelium, although other factors may be involved. We hypothesized that binding sites for bovine sperm are limited to the isthmus and are regulated by the hormonal state of the cow. Ipsilateral oviducts were obtained from heifers that were preovulatory (in estrus), had ovulated recently (within 12 h), or were in diestrus (Day 10). The isthmic and the ampullar epithelium were milked out and incubated separately in serum-free (SFRE-199-2) medium, at 39 degrees C in 5% CO2. Frozen-thawed sperm from bulls were added to the epithelium and coincubated for 15 min. The number of spermatozoa that bound to explants was not affected by stage of cycle or by anatomic origin of the explants (p > 0.05). In an additional experiment, oviducts were infused with sperm in vivo and then prepared for scanning electron microscopy, which revealed that sperm were associated with ciliated epithelium in both the isthmus and ampulla. Thus, bovine sperm may form a reservoir in the isthmic end of the oviduct because it is the first oviductal region that they encounter.