Interventions to promote the implementation of pressure injury prevention measures in nursing homes: A scoping review.

AIMS: To identify studies and the content of the interventions that have facilitated the implementation of pressure injury (PI) prevention measures in nursing home settings. DESIGN AND METHOD: A scoping review methodology was employed. The author has carried out the following steps successively: Identified this scoping review's questions, retrieved potentially relevant studies, selected relevant studies, charted the data, summarised the results, and consulted with stakeholders from nursing homes in China. DATA SOURCES: Six electronic databases and three resources of grey literature-PubMed, CINAHL, Web of Science Core Collection, Embase, Cochrane Central Register of Controlled Trials, Psych INFO, Open Grey, MedNar, ProQuest Dissertations, and Theses Full Texts were searched from January 2002 through May 2022. RESULTS: Forty articles were included, among which the primary interventions were quality improvement, training and education, evidence-based practice, device-assisted PI prophylaxis, nursing protocols, and clinical decision support systems. Twenty-three outcome indicators were summarised in 40 articles, which included 10 outcome indicators, seven process indicators, and six structural indicators. Furthermore, only five articles reported barriers in the process of implementing interventions. CONCLUSION: The common interventions to promote the implementation of PI prevention measures in nursing homes are quality improvement, training, and education. Relatively limited research has been conducted on evidence-based practice, clinical decision support systems, device-assisted PI prophylaxis, and nursing protocols. In addition, there is a paucity of studies examining the impediments to implementing these measures and devising targeted solutions. Therefore, it is recommended that future studies include analysis and reporting of barriers and facilitators as part of the article to improve the sustainability of the intervention. IMPACT: This article reminds nursing home managers that they should realise the importance of implementation strategies between the best evidence of PI prevention and clinical practice. Also, this review provides the types, contents, and outcome indicators of these strategies for managers of nursing homes to consider what types of interventions to implement in their organisations. TRIAL AND PROTOCOL REGISTRATION: The protocol of this scoping review was published as an open-access article in June 2022 (Yang et al., 2022).

[68Ga-PSMA-I&T PET/CT for assessment of tumor burden in primary lesions of treatmentnaïve prostate cancer].

OBJECTIVE: To investigate the value of 68Ga-labeled prostate specific membrane antigen (PSMA) PET/CT for assessing tumor load in primary lesions for risk stratification and predicting metastasis of newly diagnosed prostate cancer (PCa). METHODS: We retrospectively analyzed the data of 36 patients (mean age 71.3 ± 8.6 years, range 56 to 89 years) with newly diagnosed PCa undergoing 68Ga-PSMA-I&T PET/CT from June 2018 to July 2019. SUVmax and SUVmean of the primary lesions were measured, and the primary PSMA tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were automatically measured and calculated in all the patients. The correlations of primary SUVmax, PSMA-TV, and TL-PSMA with PSA and Gleason score (GS) were analyzed, and SUVmax, PSMA-TV and TL-PSMA of the primary lesions were compared among different PCa subgroups. RESULTS: SUVmax, PSMA-TV and TL-PSMA of the primary lesions were all correlated with PSA and GS (P < 0.05). PCa subgroup analysis showed that SUVmax, PSMA-TV and TL-PSMA were all significantly higher in patients with PSA >20 ng/mL than in those with PSA ≤20 ng/mL (P < 0.001), and were higher in patients with a GS ≥8 than in those with a GS ≤7 (P < 0.001). PSMA-TV and TL-PSMA were significantly higher in patients with tumor metastasis than in those without metastasis (P < 0.001), while SUVmax did not differ significantly with tumor metastasis. SUVmax (P=0.002), PSMA-TV (P < 0.001), and TL-PSMA (P < 0.001) were all significantly higher in high-risk group than in low-to moderate-risk group. CONCLUSION: PSMA-TV and TL-PSMA of 68Ga-PSMA-I&T PET/CT have potential value in predicting risk stratification and metastasis of newly diagnosed PCa.

[Efficiency and safety of peptide receptor radionuclide therapy in the treatment of metastatic neuroendocrine tumors].

The clinical data of 14 patients with neuroendocrine tumors who received Peptide Receptor Radionuclide Therapy (PRRT) from December 2018 to May 2021 were retrospectively analyzed. Among them, 2 patients demonstrated proprogressive disease, 2 patients had partial response, and 10 patients had stable disease. Grade 1-2 myelosuppression occurred in 5 patients. and 1 patient became grade 3 myelosuppression，which recovered to grade 2 after symptomatic treatment. No grade 2 or higher treatment-related renal toxicity was observed in any of the patients. PRRT is efficacy and no significant side effects for unresectable metastatic neuroendocrine tumors.

[Medium- and long-term outcomes of cardiac assist devices after coronary artery bypass grafting in left ventricular dysfunction patients].

Objective: To evaluate the medium-and long-term outcomes of cardiac assist devices after coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction. Methods: From January 2012 to May 2018, a total of 127 patients with low left ventricular ejection fraction (LVEF) value (≤40%) undergoing CABG in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Zhengzhou University were selected. Meanwhile, another 2 454 cases with LVEF>55% were also enrolled as controls. Clinical data of intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) application were compared and analyzed. All patients were followed up at the Outpatient Clinic at different time points (3 and 6 months after surgery, then every year). Results: Compared to the control group, IABP usage (10.2% vs 0.8%), ECMO usage (6.3% vs 0.3%) and the mortality (4.7% vs 0.7%) were higher (all P<0.05) in the left ventricular dysfunction group. Additionally, Intensive Care Unit stay [(50±12) h vs (33±10) h] and the hospital stay after surgery [(15±3) d vs (11±4) d] was longer in the left ventricular dysfunction group (all P<0.05). In the left ventricular dysfunction group, LVEF at 3, 6 month and 1 year was (48±8)%, (51±9)%, and (55±9)%, respectively, and then maintained stable. Conclusions: Patients with left ventricular dysfunction who received coronary artery bypass grafting had a high rate of cardiac assist devicesuse, however, optimal perioperative management can save the lives of some patients, whose medium-and long-term outcome are good. Therefore, it is worthy of being recommended in clinical practice.

Effect of bradykinin on rats with thromboangiitis obliterans through PI3K/Akt signaling pathway.

OBJECTIVE: To explore the effect of bradykinin on rats with thromboangiitis obliterans (TAO) through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathway. MATERIALS AND METHODS: The female Wistar rats were injected with lauric acid via the femoral artery to establish the TAO model, and they were randomly divided into control group (healthy rats), model group (TAO rats) and bradykinin group (TAO rats injected with bradykinin B2 receptor-specific inhibitor). The control was set in each group before the operation. The level of serum bradykinin in each group was detected via enzyme-linked immunosorbent assay (ELISA), and the reactive oxygen species (ROS) level, Caspase-3 activity and PI3K/Akt protein concentration in vascular tissues were measured via ELISA, Western blotting, ROS assay, and Caspase-3 activity assay, respectively. Moreover, the specific therapeutic mechanism of bradykinin was analyzed. RESULTS: In control group, the intima of the lower extremity venous tissues was smooth, the extima had no evident changes, and there was no inflammatory cell invasion around the arteries and veins. In model group, there was massive inflammatory cell invasion into the lower extremity venous tissues. In bradykinin group, fibrosis and atrophy occurred in venous tissues, the extima was thickened without fibrosis, and there was phagocytosis of neutrophils and mononuclear macrophages around the arteries and veins, as well as massive inflammatory infiltration. The PI3K/Akt protein concentration in lower extremity venous tissues was the highest in control group and the lowest in bradykinin group, and there were statistically significant differences (p<0.01). At 24 h after administration of doxorubicin (DOX), the level of ROS in lower extremity venous tissues was higher in bradykinin group than that in model group (p<0.05), and it was also higher in model group than that in control group (p<0.05). Besides, the activity of Caspase-3 in lower extremity venous tissues was significantly increased in bradykinin group compared with that in model group and control group, while it was slightly higher in model group than that in control group (p<0.05). CONCLUSIONS: The low expression of bradykinin can promote TAO in rats by the mechanism that it inhibits the PI3K/Akt signaling pathway to raise the oxidative stress level, thereby aggravating TAO.

[The situation and related factors of satisfaction of HIV-infected people towards the follow-up management of primary medical and health care institutions in rural areas of Jiangxi Province].

The HIV-infected people were investigated for their satisfactory situation towards the follow-up management of primary medical and health care institutions in Xinjian County, Yushan County and Guixi City of Jiangxi Province from January to July 2018 and related factors were also analyzed. The total score of the Infected Patients' Follow-up Management Satisfaction Scale higher than 59 was defined as the satisfactory. 75.68% of 259 infected patients were satisfied with the follow-up management. Compared to farmers and other follow-up modes, non-farmers (OR=10.72, 95%CI: 2.07-55.63), and patients receiving follow-up service in responsible institutions (OR=6.44, 95%CI: 3.12-13.30) were more satisfied with follow-up management.

[Follow-up of people living with HIV/AIDS by primary health care institutions in rural area of Jiangxi province].

Objective: To understand the current status of follow up of people living with HIV/AIDS by health service at grass root in rural area of Jiangxi province and related factors, and provide references for the promotion of the follow up by grass root health service. Methods: People living HIV/AIDS aged ≥18 years and diagnosed before 31 December 2017 in 6 townships of Xinjian, Yushan counties and Guixi city were included in the study in Jiangxi province. They had been followed up for more than one time after the first epidemiologic survey. The information about their demographic characteristics and HIV infection status were collected by using self-designed questionnaire. Univariate and multivariate logistic regression analyses were conducted to identify the factors that influencing the acceptance of follow up by grass root health service. Results: Of the 373 surveyed HIV infected subjects aged (53.06±16.15) years, 261 were males (70.0%, 261/373). Among the surveyed subjects, the illiteracy and people who received only primary school education accounted for 54.7% (204/373). The rate of follow up of the HIV infected subjects by grass root health service was 55.8% (208/373), and those through heterosexual contact were 58.5% (190/325). The multivariate regression analysis showed that the acceptance of follow up by grass root health service was higher in those who were farmers (OR=7.36, 95%CI: 2.52-21.45), had family support (OR=16.01, 95%CI: 2.25-49.73), didn't worry about discrimination (OR=12.97, 95%CI: 4.75-35.42), trusted health care provider (OR=5.07, 95%CI: 2.19-11.76) and showed AIDS symptoms (OR=10.58, 95%CI: 2.25- 49.73). Conclusions: The performance of follow up of people living with HIV/AIDS by grass root health service was well, suggesting it is a feasible management model. Being famer or not, family member supporting or not, worry about discrimination or not, trusting health care provider or not and showing AIDS symptoms or not were the main factors influencing the acceptance of follow up by grass root health service.

[Sivelestat alleviates nonalcoholic steatohepatitis in mice through inhibiting activation of Kupffer cells].

Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance). Results: Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor necrosis factor -α; (4) significantly reduced mRNA levels of CD68 and F4/80; and (5) reduced expression of CD68 in the liver. Conclusion: Sivelestat alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting the activation of Kupffer cells.

Evolving telehealth reimbursement in Australia.

Video-based consultation is the only telehealth service reimbursed by the Medicare Benefits Schedule in Australia, but the uptake of telehealth is still low and inconsistent. There is a clear need for the development of appropriate medical evidence to support implementation of telehealth services. With the ubiquitous use of mobile phones, mobile health becomes important in facilitating health services and impacting clinical outcomes anywhere.

[Establishment and evaluation of a mouse model of nonalcoholic steatohepatitis-related hepatocellular carcinoma].

OBJECTIVE: To establish an apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) double-knockout (ApoE(-/-)/LDLR(-/-)) mouse model of nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) induced by high-fat and high-cholesterol (HFHC) diet. METHODS: ApoE(-/-) knockout mice were crossed with LDLR(-/-) knockout mice to obtain ApoE(-/-)/LDLR(-/-) mice. The ApoE(-/-)/LDLR(-/-) mice mated with each other, and the offspring were injected with low-dose streptozotocin (STZ) at 2-3 days after birth. Some mice were fed with HFHC diet after weaning as the model group (n = 15), and some mice were fed with normal diet as the control group (n = 15). Mice were sacrificed at the end of weeks 10, 16, and 20 (5 mice at each time point). The body weight was measured. Liver tissue and blood were collected to measure biochemical parameters, evaluate the pathological changes in the liver tissue by HE staining, oil red O staining, and Masson staining, and detect the expression of glypican-3 (a marker of HCC) by immunohistochemical staining. RESULTS: The model group had significantly higher levels of fasting blood glucose and total cholesterol than the control group (P < 0.01). Serum levels of alanine aminotransferase, aspartate aminotransferase, and total triglyceride gradually increased with time in the model group; at week 20, there were significant differences in above three indices between the two groups (P < 0.05). HE staining showed that compared with the control group at the corresponding time point, the model group developed sequential histological changes: NASH at week 10, dysplastic nodules at week 16, and early HCC at week 20. Oil red O staining showed that in the model group, the degree of liver steatosis increased within 10 weeks and gradually decreased later. Masson staining demonstrated that the model group developed pathological changes: mild perisinusoidal fibrosis at week 16 and bridging fibrosis around tumors at week 20. HE staining, oil red O staining, and Masson staining showed that no histological or pathological changes were found in the control group. Glypican-3 was detected in the nodules at week 16 and in the cytoplasm of HCC cells at week 20 in the model group. CONCLUSION: The mouse model of NASH-related HCC can be developed by giving STZ injection to neonatal ApoE(-/-)/LDLR(-/-) mice and feeding them with HFHC diet after weaning for 20 weeks. Early HCC may develop directly from NASH.

The guiding significance of NT-proBNP and PCT levels in mechanical ventilator of patients with chronic respiratory failure.

OBJECTIVE: To analyze the guiding significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) and procalcitonin (PCT) level in mechanical ventilator used for patients with chronic respiratory failure. PATIENTS AND METHODS: Eighty-two patients with simple chronic respiratory failure who were treated by mechanical ventilator were selected for this study. They were treated offline after they reached the standards of spontaneous breathing trial, and were divided into two groups: 1- the successful offline group with 59 patients and 2- the failure group with 23 patients. Differences of NT-proBNP and PCT levels, oxygenation index, average heart rate and mean arterial pressure between two groups were compared. RESULTS: The NT-proBNP and PCT levels in the failure group were significantly higher than those in the success group, while oxygenation index was significantly lower in the success group. All differences were statistically significant (p<0.05). Comparison of average heart rate and mean arterial pressure between two groups showed no statistically significant difference (p>0.05). CONCLUSIONS: Through multi-factor regression analyses we observed that NT-proBNP and PCT levels were independent risk factors for guiding the success rate of offline (p<0.05). Spontaneous breathing trial in combination with NT-proBNP and PCT levels improved the success rate of offline.

[Identification and verification of the candidate proteins that interact and collaborate with ATF3 in inhibiting hepatocarcinogenesis].

OBJECTIVE: To identify and verify proteins that interact and collaborate with ATF3 in inhibiting hepatocarcinogenesis. METHODS: Immunoprecipitation (IP), co-IP and protein spectrum analysis were used to identify the protein which interacted with ATF3 in HepG2. Immunohistochemistry (IHC) and Western blot (WB) were used to detect the expression pattern of ATF3 and its candidate interacting proteins in liver tissue. RESULTS: The protein expression differences were detected by IP in two HepG2 groups. The experimental group was infected by lentiviral vector with ATF3 over-expression and the control group was infected by mock-vehicle. Several protein bands with expression diversity were analyzed by protein spectrum, which revealed several candidate proteins that may be related with ATF3. Peptide sequences were analyzed by Mascot software and NCBI database. Combined with the existing literature and our study results, Gelsolin (GSN) was identified as a protein closely interacting with ATF3 and confirmed by co-IP, IHC and WB. CONCLUSIONS: GSN is identified and verified as an interacting protein with ATF3. ATF3 may function as a suppressor of liver cancer via protein-protein interactions with Gelsolin.

Mapping forested wetlands in the Great Zhan River Basin through integrating optical, radar, and topographical data classification techniques.

Knowledge of the spatial extent of forested wetlands is essential to many studies including wetland functioning assessment, greenhouse gas flux estimation, and wildlife suitable habitat identification. For discriminating forested wetlands from their adjacent land cover types, researchers have resorted to image analysis techniques applied to numerous remotely sensed data. While with some success, there is still no consensus on the optimal approaches for mapping forested wetlands. To address this problem, we examined two machine learning approaches, random forest (RF) and K-nearest neighbor (KNN) algorithms, and applied these two approaches to the framework of pixel-based and object-based classifications. The RF and KNN algorithms were constructed using predictors derived from Landsat 8 imagery, Radarsat-2 advanced synthetic aperture radar (SAR), and topographical indices. The results show that the objected-based classifications performed better than per-pixel classifications using the same algorithm (RF) in terms of overall accuracy and the difference of their kappa coefficients are statistically significant (p<0.01). There were noticeably omissions for forested and herbaceous wetlands based on the per-pixel classifications using the RF algorithm. As for the object-based image analysis, there were also statistically significant differences (p<0.01) of Kappa coefficient between results performed based on RF and KNN algorithms. The object-based classification using RF provided a more visually adequate distribution of interested land cover types, while the object classifications based on the KNN algorithm showed noticeably commissions for forested wetlands and omissions for agriculture land. This research proves that the object-based classification with RF using optical, radar, and topographical data improved the mapping accuracy of land covers and provided a feasible approach to discriminate the forested wetlands from the other land cover types in forestry area.

Clinical review: Intravenous glucocorticoids for Graves' orbitopathy: efficacy and morbidity.

CONTEXT: The administration of iv glucocorticoid pulses has been advocated as a treatment approach for patients with inflammatory and moderate to severe Graves' orbitopathy (GO). This review offers an update on this controversial regimen. EVIDENCE ACQUISITION: PubMed and the MeSH-Database were searched (with no temporal limit) for the following topics: management of active and severe GO; glucocorticoid therapy of GO; iv glucocorticoid administration; mechanism and pharmacokinetics of iv glucocorticoids; and adverse events, morbidity, and mortality of iv glucocorticoids. The articles were evaluated according to their setting and study design. EVIDENCE SYNTHESIS: All randomized and uncontrolled trials, consensus statement, systematic reviews, and meta-analyses dealing with the efficacy and morbidity of iv glucocorticoids in GO were identified. CONCLUSIONS: The current first-line treatment for active, moderate-to-severe GO is a 12-wk course of high-dose iv glucocorticoid pulses. The response rate of this regimen is approximately 80%. Intravenous glucocorticoids have a statistically significant advantage over oral treatment and cause significantly fewer adverse events. However, major side effects related to preexisting diseases, administered dose, and treatment schedule have been reported. The morbidity and mortality of iv glucocorticoid therapy are 6.5 and 0.6%, respectively. Thus, careful patient selection is warranted. Before iv glucocorticoid administration, patients should be screened for recent hepatitis, liver dysfunction, cardiovascular morbidity, severe hypertension, inadequately managed diabetes, and glaucoma. The cumulative dose should not exceed 8 g, and with the exception of sight-threatening GO the single doses preferably should not be administered on consecutive days. Monthly monitoring during subsequent treatment is warranted.

Dose of intravenous steroids and therapy outcome in Graves' orbitopathy.

BACKGROUND AND AIM: Several trials have proved the efficacy of intravenous (IV) steroids in Graves' orbitopathy (GO). However, the impact of administered dose and therapy schedule has not been assessed yet. SUBJECTS AND METHODS: Nine randomized and 14 non-randomized controlled trials of IV steroids in GO were evaluated according to the applied single and cumulative doses with respect to outcome, efficacy on clinically relevant issues and adverse events. RESULTS: High single (1 g per day) and cumulative (>6 g) doses of IV steroids are superior to lower single (0.5 g/d) and cumulative (<5 g) doses with respect to therapy response (84 vs 75%; p=0.034 and 83 vs 77%; ns, respectively), improvement of eye symptoms (87 vs 75%, p=0.052 and 85 vs 71%; ns, respectively) and disappearance of diplopia (32 vs 27%; ns and 48 vs 27%; p=0.08, respectively). Decrease of both clinical activity score (3 vs 2.5 points and 2.5 vs 3, ns) as well as proptosis (-1.4 vs -1.2 mm, ns and 1.5 vs 1.2, ns) are similar in both groups. However, high single and/or cumulative doses are accompanied with a 2-fold higher rate of adverse events (56 vs 28%; p<0.001 and 52 vs 33%; p=0.034, respectively). CONCLUSIONS: Tailoring the IV steroid dose to severity of GO can be concluded and implies that a prospective randomized trial comparing different doses of IV steroids in active/severe GO is keenly warranted.

Umbilical cord blood transplantation in adult myeloid leukemia.

Allogeneic hematopoietic stem cell (HSC) transplantation is a life-saving procedure for hematopoietic malignancies, marrow failure syndromes and hereditary immunodeficiency disorders. However, wide application of this procedure is limited by availability of suitable human leucocyte antigen (HLA)-matched adult donors. Umbilical cord blood (UCB) has been increasingly used as an alternative HSC source for patients lacking matched-HSC donors. The clinical experience of using UCB transplantation to treat pediatric acute leukemias has already shown that higher-level HLA-mismatched UCB can be equally as good as or even better than matched HSC. Recently, large registries and multiple single institutional studies conclusively demonstrated that UCB is an acceptable source of HSCs for adult acute leukemia patients who lack HLA-matched donors. These studies will impact the future clinical allogeneic stem cell transplantation for acute myeloid leukemia (AML), which is the most common acute leukemia in adults. UCB has unique advantages of easy procurement, absence of risk to donors, low risk of transmitting infections, immediate availability, greater tolerance of HLA disparity and lower-than-expected incidence of severe graft-versus-host disease. These features of UCB permit successful transplantation available to almost every patient who needs it. We anticipate that using UCB as a HSC source for allogeneic transplantation for adult AML will increase dramatically over the next 5 years, by expanding the available allogeneic donor pool. Clinical studies are needed with focus on disease-specific UCB transplantation outcomes, including AML, acute lymphoblastic leukemia, and lymphoma.

A study on Notch signaling in human breast cancer.

Breast cancer is one of the leading causes of cancer death in women. The Notch family of proteins plays crucial roles in determining cell fates such as proliferation, differentiation and apoptosis. A role for Notch signaling in human breast cancer has been suggested by the development of adenocarcinomas in the murine mammary gland. However, it is not clear currently whether Notch signaling is frequently expressed and activated in breast cancers. Here we show that Notch signaling is overexpressed and highly activated in breast cancers. More significantly, the attenuation of Notch signaling by gamma-secretase inhibitor can inhibit the proliferation of breast cancer cells by both causing cell cycle arrest and apoptosis. Thus, targeting Notch signaling may be of therapeutic value in breast cancers.

In vivo staphylococcal superantigen-driven polyclonal Ig responses in mice: dependence upon CD4(+) cells and human MHC class II.

Staphylococcal enterotoxin (SE) B and seven other staphylococcal superantigens (SAg), despite promoting vigorous Ig production in human peripheral blood mononuclear cell cultures, are exceedingly poor at eliciting Ig responses in cultures of spleen cells from C57BL/10J (B10) or C3H/HeJ mice. In contrast, SEB elicits Ig responses in cultures of spleen cells from human MHC class II-transgenic mice. Whereas i.p. administration of SEB (0.2-20 microg) to non-transgenic B10 mice elicits very weak in vivo Ig responses, identical treatment of CD4(+) cell-intact (but not CD4(+) cell-depleted) human MHC class II-transgenic mice elicits dramatic increases in both splenic Ig-secreting cells and serum Ig levels. Over a 2-week period, the SEB-induced in vivo Ig responses peak and then plateau or fall in association with a preferential increase in splenic CD8(+) cells. Nevertheless, in vivo depletion of CD8(+) cells has no sustained effect on SEB-driven Ig responses. Taken together, these observations demonstrate that the effects of SAg on in vivo humoral immune responses are highly CD4(+) cell dependent, are substantially CD8(+) cell independent and can be successfully investigated using human MHC class II-transgenic mice. This model system may be useful in investigating the polyclonally activating effects of microbial products (prototypic environmental insults) on the development of systemic autoimmunity.