Immune and mitogenic responses by BALB/c, C3H/HeJ, and nude mice to Brucella abortus bacterin and lipopolysaccharide.

The immunogenic and mitogenic properties of Brucella abortus 1119-3 bacterin (BA) and biologically active B. abortus lipopolysaccharide (BA-LPS) were studied using normal and athymic (nude) BALB/c and C3H/HeJ mice. Although BA stimulated 2-mercaptoethanol-sensitive (2-ME-S) primary and secondary antibody responses in all mice, nude mice, in contrast to normal BALB/c and C3H/HeJ mice, did not make substantial 2-mercaptoethanol-resistant (2-ME-R) antibody responses. Similarly, all mice injected with BA-LPS made 2-ME-S primary responses, and the secondary response of thymus-bearing mice contained a substantial 2-ME-R component. Collectively, these observations suggest that although both BA and BA-LPS can stimulate thymus-independent 2-ME-S antibody synthesis, thymus-derived cells are required for optimal immune responses containing a 2-ME-R component. The antibody responses of normal BALB/c and C3H/HeJ mice to BA and BA-LPS were qualitatively and quantitatively similar. Both BA and BA-LPS were mitogenic for spleen cells from normal and nude BALB/c and C3H/HeJ mice but not for thymus cells from normal BALB/c or C3H/HeJ mice, suggesting that both preparations are B-cell mitogens.     

Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

CD14-dependent airway neutrophil response to inhaled LPS: role of atopy

BACKGROUND: Inhaled endotoxin (LPS) is associated with airway neutrophilic (PMN) inflammation in both asthmatic and control subjects, with asthmatic subjects demonstrating possibly higher sensitivity. CD14 is the principal receptor mediating LPS responses in vivo. It is unknown whether constitutive CD14 can predict the magnitude of the PMN response after LPS inhalation and whether atopy plays a role in this response. OBJECTIVE: We sought to examine associations between constitutive airway CD14 expression and LPS-induced PMNs after 5 microg of LPS inhalation and to examine associations between markers of atopy (eosinophils and eosinophil cationic protein) and CD14 expression and LPS-induced PMNs. METHODS: Ten atopic asthmatic subjects and 8 healthy control subjects inhaled 0.9% saline and LPS (Escherichia coli 026:B6, 5 microg) separated by 3 weeks. Induced sputum was collected at 24 hours before and 6 hours after inhalation. Induced sputum was analyzed for total and differential cell counts and soluble markers (soluble [s]CD14, eosinophil cationic protein, IL8, and total protein). Flow cytometry was used to analyze membrane-bound CD14 expression. RESULTS: Significant associations were found between the LPS-induced PMN response (PMNs per milligram of sputum) and both constitutive sCD14 (R = 0.7, P =.005) and membrane-bound CD14 (R = 0.9, P =.01). Asthmatic subjects demonstrated significantly higher levels of constitutive sCD14 compared with control subjects, and baseline eosinophils were significantly associated with baseline sCD14 (R = 0.7, P =.01) and LPS-induced PMNs (R = 0.6, P =.03). CONCLUSION: Constitutive airway CD14 expression can predict the magnitude of the PMN response after inhaled LPS. Atopy appears to play a role in the level of CD14 expression and may contribute to LPS sensitivity in asthmatic subjects.     

Bone marrow origin of mucosal mast cells

Infection with the intestinal parasite Nippostrongylus brasiliensis stimulates an accumulation of mucosal mast cells (MMC) in the villi of the small intestine of normal but not athymic or W/Wv anemic mice. W/Wv mice are congenitally deficient in both MMC and skin and connective tissue mast cells (CTMC). Athymic mice have normal or elevated numbers of CTMC but are severely deficient in MMC. CTMC derive from the bone marrow. To determine the origin of MMC, athymic and W/Wv mice were given various hematopoietic or lymphoid tissues from normal littermate or beige mice and the MMC response to N. brasiliensis infection was evaluated. The MMC defect in athymic mice was repaired by grafts of thymus cells, thymus gland, or spleen cells, but not by bone marrow cells or anti-Thy 1-treated bone marrow or spleen cells. The MMC and CTMC defects of W/Wv mice were repaired by grafts of bone marrow, spleen cells, or anti-Thy 1-treated bone marrow or spleen cells. Neither the MMC nor the CTMC defect in W/Wv mice was repaired by grafts of thymus cells or thymus glands. These results indicate the following, MMC, like CTMC, derive from the bone marrow and not from the thymus. MMC require a thymic influence for development. Athymic mice possess bone marrow precursors for both MMC and CTMC but lack a thymus-dependent component necessary for MMC development. W/Wv mice lack both MMC and CTMC mast cell precursors but possess the thymus-dependent component required for MMC development.     

EEG effects of subcutaneous and intracerebroventricular injections of arginine vasopressin in the rat

Several studies have suggested that arginine vasopressin (AVP) may act centrally as a neurohormone or neuromodulator to produce electrophysiological and behavioral effects. However, there are few reports of EEG effects of AVP in unanesthetized, behaving animals. In the present study the EEG effects of behaviorally relevant subcutaneous (SC) doses of AVP (6 g/kg) known to raise blood pressure were compared to behaviorally relevant intracerebroventricular (ICV) doses (0.1–1.0 ng) and multiple toxic ICV doses (1.0 g) of AVP. Central injections of toxic doses of AVP produced behavioral arrest, bodily barrel rolling, and EEG slowing, but did not induce electrographic signs of seizure activity. Comparison of the spectral characteristics of the EEG revealed some similarities in the distribution of power between SC and the 1.0 ng ICV dose; whereas ICV doses of 0.1 and 0.5 ng produced power distributions that were different from those seen following saline or SC doses of AVP. The similarities in EEG activity between SC injections and the 1.0 ng ICV dose suggest a common brain state may be induced by the two routes of administration in those dose ranges.     

Sizes, laminar and topographic origins of cortical projections to the major divisions of the red nucleus in the monkey

The retrograde transport of horseradish peroxidase was used to study the topographic and laminar origins of the cortical projections to the parvocellular and the magnocellular divisions of the red nucleus in Macaca mulatta and Macaca fascicularis. Approximately 90% of the corticorubral projection is directed to the parvocellular division of the nucleus. Corticoparvocellular (CRp) neurons are pyramidally shaped, are smaller in size than corticospinal neurons, and are more numerous. They are found principally in sublamina Va of cytoarchitectonic areas 4 and 6, and in moderate quantities in sublamina Vb of posterior area 8 and area 5. In areas 4 and 6, the cells are grouped in clusters of three to 15 neurons each and are arranged in cellular bands of varying rostrocaudal thickness which course mediolaterally. With respect to functionally defined zones, CRp neurons are found throughout the supplementary motor area and the precentral motor cortex. In addition, they are found in parts of areas 5, 6, and 24 that project to these cortical motor areas, and that are thought to have "premotor" or movement-programming functions. The corticomagnocellular (CRm) projection arises principally from cells in sublamina Vb of the precentral arm and leg areas (area 4), and from adjacent parts of posterior area 6, CRm cells are pyramidally shaped, and their size distribution is bimodal, with peaks that correspond, respectively, to the modal diameters of CRp and of corticospinal neurons. These results and those of previous studies suggest that CRm neurons are involved principally in the control of hand and foot movements, with little effect on more proximal musculature. The massive CRp projection, however, is clearly part of a large cerebrocerebellar communication system, with motor and/or movement programming functions that have yet to be clearly defined.     

Effectiveness of a Universally Offered Chlamydia and Gonorrhea Screening Intervention in the Pediatric Emergency Department

PurposeAdolescents represent more than half of the newly diagnosed sexually transmitted infections in the U.S. annually. Emergency departments (EDs) may serve as an effective, nontraditional setting to screen for chlamydia/gonorrhea (CT/GC). The objective was to evaluate the effectiveness of a universally offered CT/GC screening program in two pediatric ED settings.MethodsThis was a prospective, delayed start pragmatic study conducted over 18 months in two EDs within the same academic institution among ED adolescents aged 14–21 years with any chief complaint. Using a tablet device, adolescents were confidentially informed of CT/GC screening recommendations and were offered screening. If patients agreed to CT/GC testing, a clinical decision support tool was triggered to inform the provider and order testing. The main and key secondary outcomes were the proportion of CT/GC testing and positive CT/GC test results in each respective ED.ResultsBoth EDs experienced modest but statistically significant increases in CT/GC testing post- versus pre-intervention (main: 11.5% vs. 7.9%; confidence interval [CI]: 2.9–4.2; p < .0001 and satellite: 3.8% vs. 2.6%; 95% CI: .7–1.7; p < .0001). Among those tested, the positivity rate at the main ED did not significantly change post- versus pre-intervention (24.1% vs. 23.2%; 95% CI: ?1.9 to 3.8; p = .71) but significantly decreased at the satellite ED (7.6% vs. 14.8%; 95% CI: ?12.2 to ?2.2; p = .01).ConclusionsA universally offered screening intervention increased the proportion of adolescents who were tested at both EDs and the detection rates for CT/GC at the main ED, but patient acceptance of screening was low.     

SARS-CoV-2 Serial Interval Variation,Montana, USA,March 1–July 31, 2020

We report mean severe acute respiratory syndrome coronavirus 2 serial intervals for Montana, USA, from 583 transmission pairs; infectors’ symptom onset dates occurred during March 1–July 31, 2020. Our estimate was 5.68 (95% CI 5.27–6.08) days, SD 4.77 (95% CI 4.33–5.19) days. Subperiod estimates varied temporally by nonpharmaceutical intervention type and fluctuating incidence.     

Safety and Efficacy of a Steroid Avoidance Immunosuppression Regimen in Renal Transplant Patients With De Novo or Preformed Donor-Specific Antibodies: A Single-Center Study

Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection.