Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells

Murine Lyme borreliosis is characterized by arthritis and carditis that are most severe at 2 to 3 wk, then regress during the course of persistent infection. Borrelia burgdorferi-specific Abs and CD4+ T cells have been implicated in the resolution phase of arthritis. Therefore, MHC class II transactivator (CIITA)-deficient mice that do not express conventional class II molecules and lack the normal CD4 repertoire were used to investigate the role of MHC class II-mediated responses in Lyme disease. The development of arthritis and carditis, and the resolution of arthritis, were similar in CIITA-deficient and control C57/BL6 mice. In contrast, the resolution of carditis was delayed in CIITA-deficient animals compared with controls. Moreover, CIITA-deficient mice developed B. burgdorferi-specific IgG2b Abs, and sera from these animals passively protected naive C3H/HeN mice from challenge inoculation and cleared B. burgdorferi from 2 day-infected C.B.17 SCID mice. These data suggest that CD4+ T cells and MHC class II-mediated responses are not required for the generation of protective Abs or the regression of arthritis, but may be important in the resolution of Lyme carditis in mice.     

Measurements of HDO between 4719 and 5843 cm-1

Fourier transform spectrometer data of heavy water vapor were obtained at resolutions of 0.01 and 0.02 cm-1. The spectra were analyzed to obtain line center frequencies and line strengths of HD16O from 4719 to 5843 cm-1. The analysis included 1700 assigned lines of the (011)-(000), (200)-(000), (120)-(000), and (021)-(010) bands. This is the first report of assignments in the weak (120)-(000) band which borrows much of its strength from the (200)-(000) band. The measurements provided in this work are a marked improvement over the HDO listing presently available on the HITRAN database in the spectral region. Copyright 1997 Academic Press. Copyright 1997Academic Press     

Erythema migrans-like rash illness at a camp in North Carolina: a new tick-borne disease?

BACKGROUND: Borrelia burgdorferi, the causative agent of Lyme disease, has never been isolated from a patient thought to have acquired Lyme disease in any southeastern state. OBJECTIVE: To investigate 14 cases of an erythema migrans (EM)-like rash illness that occurred during 2 summers at an outdoor camp in central North Carolina in an effort to determine the etiologic, epidemiological, and clinical aspects of this illness. METHODS: Using active surveillance, we identified cases of clinically diagnosed EM in residents and staff of the camp. We collected clinical and demographic information; history of exposure to ticks; acute and convalescent serum antibodies to B. burgdorferi, Rickettsia rickettsii, and Ehrlichia chaffeensis; and cultures for spirochetes from biopsy specimens of skin lesions. Serum samples from a group of residents and staff who did not develop rashes were tested for the same antibodies. We speciated ticks removed from people and collected from vegetation. RESULTS: We identified 14 cases of EM-like rash illness during the 2 summers. Of the 14 case-patients, 10 had associated mild systemic symptoms and 1 had documented fever. All 14 case-patients had removed attached ticks, and 8 remembered having removed a tick from the site where the rash developed a median of 12 days earlier (range, 2-21 days). One tick removed from the site where a rash later developed was identified as Amblyomma americanum, the Lone Star tick; 97% of ticks collected from vegetation and 95% of ticks removed from people were A. americanum. No spirochetes were isolated from skin biopsy specimens. Paired serum samples from 13 case-patients did not show diagnostic antibody responses to B. burgdorferi or other tick-borne pathogens. CONCLUSIONS: This investigation suggests the existence of a new tick-associated rash illness. We suspect that the disease agent is carried by A. americanum ticks. In the southern United States, EM-like rash illness should no longer be considered definitive evidence of early Lyme disease.     

6-Hydroxycatecholine, a choline-mimicking analogue of the selective neurotoxin, 6-hydroxydopamine

The purpose of this prospective study was to verify whether the percentage area of lung occupied by lowest attenuation values on high-resolution computed tomography (HRCT) scans reflects microscopic emphysema and to compare this quantification with the information yielded by the most widely used pulmonary function tests (PFT). Preoperative HRCT scans were obtained with 1-cm intervals in 38 subjects. With a semiautomatic evaluation procedure, the percentage areas occupied by attenuation values inferior to thresholds ranging from -900 Hounsfield units (HU) to -970 HU were calculated for the lobe or lung to be resected. Emphysema was microscopically quantified by using a computer-based method, measuring the perimeters and interwall distances of alveoli and alveolar ducts. The strongest correlation was found for -950 HU. As a second step, we evaluated possible correlations between PFT and microscopic measurements. Finally, considering the microscopic measurements as a standard, we tried to investigate their relationships with each of the PFT and with the relative area occupied by attenuation values lower than -950 HU for both lungs. This revealed that the diffusing capacity for carbon monoxide associated with HRCT quantification is sufficient to predict microscopic measurements. We concluded that the percentage area of lung occupied by attenuation values lower than -950 HU is a valid index of pulmonary emphysema.     

Evaluation of a "lexically assign, logically refine" strategy for semi-automated integration of overlapping terminologies

Visually evoked potentials (VEPs) measured under conditions of retinal image stabilization that minimized the influences of visual masking and smearing were averaged from electroencephalographic records measured from striate cortex of three cats. The amplitudes of the VEPs increased around saccade initiation. The grating-evoked potentials obtained at different times relative to the saccade exhibited changes in waveform shape that could be attributed to a saccade-evoked potential. The changes in the shape of the waveform were reasonably accounted for by the summation of the grating-evoked potential (produced when the cat did not make a saccade) and an appropriately timed saccade-evoked potential. The fundamental amplitudes of the residual potentials were computed and found to vary across the time course of the saccade. These observations suggest that there are other influences besides visual masking that are exerted early in the visual pathway to modulate visual processing during saccadic eye movements. A corollary discharge process is the most likely candidate to exert these influences.     

Complex intracranial aneurysms: combined operative and endovascular approaches

OBJECTIVE: Endovascular management of complex intracranial aneurysms is increasingly being considered as an alternative to standard surgical clipping. However, little attention has been paid to the complementary nature of surgery and endovascular therapy. METHODS: Between September 1992 and May 1997, 12 patients with complex intracranial aneurysms were treated with combined operative and endovascular methods. Seven patients demonstrated subarachnoid hemorrhage (two of Grade II, two of Grade III, and three of Grade IV). Five patients demonstrated unruptured aneurysms, i.e., three giant aneurysms (one vertebrobasilar junction aneurysm, one middle cerebral artery bifurcation aneurysm, and one internal carotid artery-ophthalmic artery aneurysm), one large internal carotid artery-ophthalmic artery aneurysm, and one middle cerebral artery serpentine aneurysm. Management strategies involved either surgery followed by endovascular therapy (S-E; n = 5) or endovascular therapy followed by surgery (E-S; n = 7). S-E paradigms included aneurysm exploration followed by endovascular treatment (S-E1; n = 3), partial aneurysm clipping followed by endovascular aneurysm packing (S-E2; n = 1), and extracranial-to-intracranial bypass followed by endovascular parent vessel occlusion (S-E3; n = 1). E-S paradigms included superselective angiography followed by surgical clipping (E-S1; n = 2), Guglielmi detachable coil partial dome packing followed by delayed surgical clipping (E-S2; n = 2), proximal temporary vessel balloon occlusion followed by aneurysm clipping (E-S3; n = 2), and proximal permanent vessel occlusion followed by surgical aneurysm decompression for mass effect treatment (E-S4; n = 1). RESULTS: Eleven aneurysms (92%) were completely eliminated. The remaining aneurysm was 90% obliterated and remained quiescent at the 34-month follow-up examination, despite presenting with subarachnoid hemorrhage. No patient experienced repeat bleeding (follow-up period, 23+/-28 mo). There were no deaths. One patient achieved a fair outcome (Glasgow Outcome Scale score of III); all other patients experienced excellent outcomes (Glasgow Outcome Scale score of I). In all cases, the aneurysm management paradigm chosen had a positive effect on definitive therapy. CONCLUSION: Several factors can contribute to the complexity of intracranial aneurysms. Management strategies that combine operative and endovascular techniques in a complementary way, for the best possible outcomes for these patients, can be designed accordingly.     

Endothelial cell injury caused by Candida albicans is dependent on iron

MRL-lpr/lpr mice spontaneously develop manifestations of autoimmunity including arthritis, vasculitis, and glomerulonephritis. The paramagnetic molecule nitric oxide has been implicated as an effector molecule in initiation and propagation of these inflammatory conditions. In this study, we utilized electron paramagnetic resonance spectroscopy to directly detect nitrosylated protein complexes as products of nitric oxide in whole blood and in kidneys of MRL-lpr/lpr mice. Electron paramagnetic resonance spectra of blood samples from MRL-lpr/lpr mice showed nitrosyl hemoglobin species. Amounts of blood nitrosyl hemoglobin in MRL-lpr/lpr mice were significantly increased as compared to age-matched control mice. Electron paramagnetic resonance spectra of MRL-lpr/lpr kidney tissue exhibited a signal characteristic of a dinitrosyl-iron-dithiolate complex at g approximately 2.04. Formation of nitrosylated nonheme protein in diseased kidneys is associated with development of glomerulonephritis in the autoimmune mice. The presence of nitrosylated nonheme protein indicates the formation of nitric oxide within the kidneys of the diseased mice signifying in situ renal nitric oxide formation.     

Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase

We have previously demonstrated that interleukin-4 (IL-4) induces tyrosine phosphorylation of a protein closely related or identical to the c-fes proto-oncogene product (FES) and association of this protein with the IL-4 receptor alpha chain (IL-4R alpha). IL-4 is known to induce association of phosphatidylinositol-3 (PI3) kinase with the IL-4R alpha. Since FES contains the consensus motifs for PI3 kinase binding, we tested the possibility that FES may associate with PI3 kinase upon IL-4 stimulation. We demonstrate herein that IL-4 stimulation induced rapid association of FES or a related protein with PI3 kinase in mouse T-cell lines. We also show an association of human FES (hFES) with the src homology 2 (SH2) domain of PI3 kinase in a COS7 cell expression system. The in vitro PI3 kinase assay using COS7 cells suggested that hFES partly contributes to the association between the hIL-4R alpha and PI3 kinase. We have further identified the important region in the cytoplasmic domain of the hIL-4R alpha for association of tyrosine-phosphorylated hFES with the hIL-4R alpha and SH2 domain of PI3 kinase using a COS7 cell expression system. These results suggest that FES or a related protein/PI3 kinase pathway may play a role in the pleiotropic effects of IL-4.