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101.
102.
Leonard E. Weisman Gerald W Fischer Philip Marinelli Val G. Hemming John R. Pierce Stephen M. Golden and Carl C. Peck 《Vox sanguinis》1989,57(4):243-248
Intravenous immunoglobulin (IVIG) may be a therapeutic adjunct to antibiotic treatment of neonatal infections. We examined the pharmacokinetics and safety of IVIG in human neonates. Thirty neonates with suspected sepsis were randomly assigned either to a treatment (receiving either 250, 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group. The 500 mg/kg dose produced a rise in total IgG for greater than 8 and in group B streptococcus (GBS) type-specific IgG for greater than 4-14 days. The type-specific antibody elevation varied with the amount of pathogen-specific antibody and dose of IVIG. Pharmacokinetic analysis suggests a Vdss of 42 ml/kg, Cl of 3.0 ml/kg/day, a biphasic elimination curve, and a terminal elimination half-life of 24.2 days. No toxicity was observed. These data may be valuable in determining optimal dosing schedules for IVIG in treating or preventing neonatal infections. 相似文献
103.
The unaffected skin of eighteen patients with dermatitis herpetiformis (D.H.), twenty-two patients with cœliac disease (C.D.), and eight controls were examined using direct immunofluorescence and class-specific fluorescein-conjugated anti-human IgA, IgM, and IgG antisera. All eighteen patients with D.H. showed IgA deposits in the skin: in seventeen the deposits were only found in the dermal papillæ, whilst in one it was found in a continuous line below the basement membrane, confirmed by immuno-electronmicroscopy. IgM deposits were also found in the dermal papillæ in three patients with D.H. and IgG deposits below the basement membrane in one patient. In cœliac disease, however, only one of the twenty-two patients showed papillary IgA deposits and one had continuous IgM deposits. These immunoglobulin deposits in D.H. and C.D. seem to be on the reticulin of the dermal papillæ. It is suggested that in D.H. there is a fault of the reticulin in the skin and small intestine, whilst in cœliac disease it is present in the small intestine but not in the skin. The reticulin cross-reacts with gluten complexes to give rise to an immunological reaction. In support of this hypothesis we have demonstrated cross-reactivity between gluten and reticulin. 相似文献
104.
Zhen Lu Angelica Ortiz Ioannis I. Verginadis Amy R. Peck Farima Zahedi Christina Cho Pengfei Yu Rachel M. DeRita Hongru Zhang Ryan Kubanoff Yunguang Sun Andrew T. Yaspan Elise Krespan Daniel P. Beiting Enrico Radaelli Sandra W. Ryeom J. Alan Diehl Hallgeir Rui Constantinos Koumenis Serge Y. Fuchs 《The Journal of clinical investigation》2021,131(10)
Intercellular biomolecule transfer (ICBT) between malignant and benign cells is a major driver of tumor growth, resistance to anticancer therapies, and therapy-triggered metastatic disease. Here we characterized cholesterol 25-hydroxylase (CH25H) as a key genetic suppressor of ICBT between malignant and endothelial cells (ECs) and of ICBT-driven angiopoietin-2–dependent activation of ECs, stimulation of intratumoral angiogenesis, and tumor growth. Human CH25H was downregulated in the ECs from patients with colorectal cancer and the low levels of stromal CH25H were associated with a poor disease outcome. Knockout of endothelial CH25H stimulated angiogenesis and tumor growth in mice. Pharmacologic inhibition of ICBT by reserpine compensated for CH25H loss, elicited angiostatic effects (alone or combined with sunitinib), augmented the therapeutic effect of radio-/chemotherapy, and prevented metastatic disease induced by these regimens. We propose inhibiting ICBT to improve the overall efficacy of anticancer therapies and limit their prometastatic side effects. 相似文献
105.
Rebecca S. Hofford Tanner J. Euston Rashaun S. Wilson Katherine R. Meckel Emily G. Peck Arthur Godino Joseph A. Landry Erin S. Calipari TuKiet T. Lam Drew D. Kiraly 《The Journal of neuroscience》2021,41(7):1553
Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no Food and Drug Administration (FDA)-approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony stimulating factor (G-CSF) as a neuroactive cytokine that alters behavioral response to cocaine, increases synaptic dopamine release, and enhances cognitive flexibility. Here, we investigate the role of G-CSF in affecting extinction and reinstatement of cocaine-seeking and perform detailed characterization of its proteomic effects in multiple limbic substructures. Male Sprague Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured. Quantitative assessment of changes in the proteomic landscape in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were performed via data-independent acquisition (DIA) mass spectrometry analysis. Administration of G-CSF during extinction accelerated the rate of extinction, and administration during abstinence attenuated cue-induced cocaine-seeking. Analysis of global protein expression demonstrated that G-CSF regulated proteins primarily in mPFC that are critical to glutamate signaling and synapse maintenance. Taken together, these findings support G-CSF as a viable translational research target with the potential to reduce drug craving or seeking behaviors. Importantly, recombinant G-CSF exists as an FDA-approved medication which may facilitate rapid clinical translation. Additionally, using cutting-edge multiregion discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.SIGNIFICANCE STATEMENT Pharmacological treatments for psychostimulant use disorder are desperately needed, especially given the disease''s chronic, relapsing nature. However, there are currently no Food and Drug Administration (FDA)-approved pharmacotherapies. Emerging evidence suggests that targeting the immune system may be a viable translational research strategy; preclinical studies have found that the neuroactive cytokine granulocyte-colony stimulating factor (G-CSF) alters cocaine reward and reinforcement and can enhance cognitive flexibility. Given this basis of evidence we studied the effects of G-CSF treatment on extinction and reinstatement of cocaine seeking. We find that administration of G-CSF accelerates extinction and reduces cue-induced drug seeking after cocaine self-administration. In addition, G-CSF leads to downregulation of synaptic glutamatergic proteins in medial prefrontal cortex (mPFC), suggesting that G-CSF influences drug seeking via glutamatergic mechanisms. 相似文献
106.
BackgroundMonitoring of white cell counts during clozapine treatment leads to cessation of therapy if levels fall below pre-determined values. Reductions in white cell counts, driven by lower levels of lymphocytes, have been observed with coronavirus disease 2019 (COVID-19). Neutropenia during COVID-19 has not been reported. We present data for 56 patients who were taking clozapine and had COVID-19.MethodsWe included patients who were taking clozapine at the time they tested positive for COVID-19. We compared absolute neutrophil counts, lymphocyte counts and white cell counts between baseline and the first week of infection, and baseline and the second week of infection.ResultsWe observed reductions in absolute neutrophil counts (p = 0.005), lymphocyte counts (p = 0.003) and white cell counts (p < 0.001) between baseline and the first 7 days of COVID-19. All cell counts had returned to baseline levels by days 8 to 14. Six patients experienced neutropenia (absolute neutrophil counts < 2.0 × 109/L) and of those, 4 underwent mandatory cessation of clozapine. For 3 patients, clozapine treatment had been established for more than 6 months with no previous neutropenia, neutrophil levels returned to baseline within 2 weeks and no further neutropenia was observed on restarting treatment.LimitationsThis was a retrospective chart review; larger cohorts are required. Clozapine plasma levels were largely not measured by clinicians.ConclusionThese data strongly suggest that mild neutropenia in the acute phase of COVID-19 in patients who are well established on clozapine is more likely to be a consequence of the virus than of clozapine treatment. 相似文献
107.
Min Joo Choi Won Suk Choi Hye Seong Jun Yong Choi Jong-Hyun Kim Yae-Jean Kim Eun Young Cho Dong-Hyun Kim Hyesook Park Heeyoung Lee Nam Joong Kim Joon Young Song Hee Jin Cheong Sang Il Kim Kyong Ran Peck 《Journal of Korean medical science》2021,36(23)
BackgroundThis study presents a framework for determining the allocation and distribution of the limited amount of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsAfter analyzing the pandemic strategies of the major organizations and countries and with a literature review conducted by a core panel, a modified Delphi survey was administered to 13 experts in the fields of vaccination, infectious disease, and public health in the Republic of Korea. The following topics were discussed: 1) identifying the objectives of the vaccination strategy, 2) identifying allocation criteria, and 3) establishing a step-by-step vaccination framework and prioritization strategy based on the allocation criteria. Two rounds of surveys were conducted for each topic, with a structured questionnaire provided via e-mail in the first round. After analyzing the responses, a meeting with the experts was held to obtain consensus on how to prioritize the population groups.ResultsThe first objective of the vaccination strategy was maintenance of the integrity of the healthcare system and critical infrastructure, followed by reduction of morbidity and mortality and reduction of community transmission. In the initial phase, older adult residents in care homes, high-risk health and social care workers, and personal support workers who work in direct contact with coronavirus disease 2019 (COVID-19) patients would be prioritized. Expansion of vaccine supply would allow immunization of older adults not included in phase 1, followed by healthcare workers not previously included and individuals with comorbidities. Further widespread vaccine supply would ensure availability to the extended adult age groups (50–64 years old), critical workers outside the health sector, residents who cannot socially distance, and, eventually, the remaining populations.ConclusionThis survey provides the much needed insight into the decision-making process for vaccine allocation at the national level. However, flexibility in adapting to strategies will be essential, as new information is constantly emerging. 相似文献
108.
Dawn Peck Amy White Gisele Pino April Studinski Meghan Strenk Randi Gadea Jennifer Gannon Bryce Heese Esperanza Font-Montgomery Tracy Klug Jennifer Burton George Hoganson Devin Oglesbee Dimitar Gavrilov Dietrich Matern Kimiyo Raymond Piero Rinaldo Silvia Tortorelli 《Molecular genetics and metabolism》2021
109.
110.
TS Suhardja L Bae EZ Seah P Cashin DG Croagh 《Annals of the Royal College of Surgeons of England》2015,97(8):568-573