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Glutamate (Glu) is considered the most important excitatory amino acid neurotransmitter in the mammalian Central Nervous System. Zinc (Zn) is co-released with Glu during synaptic transmission and interacts with Glutamate receptors and transporters. We performed binding experiments using [3H]MK-801 (NMDA), and [3H]Fluorowillardine (AMPA) as ligands to study Zn-Glutamate interactions in rat cortical synaptic membranes. We also examined the effects of mercury and lead on NMDA or AMPA receptors. Zinc at 1 nM, significantly potentiates [3H]MK-801 binding. Lead inhibits [3H]MK-801 binding at micromolar concentrations. At millimolar concentrations, Hg also has a significant inhibitory effect. These effects are not reversed by Zn (1 nM). Zinc displaces the [3H]FW binding curve to the right. Lead (nM) and Hg (μM) inhibit [3H]FW binding. At certain concentrations, Zn reverses the effects of these metals on [3H]FW binding. These specific interactions serve to clarify the role of Zn, Hg, and Pb in physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Efforts to translate, package, and diffuse HIV/AIDS research into practice have gained momentum with the Centers for Disease Control and Prevention's (CDC's) launch of three projects: the Prevention Research Synthesis Project, which identifies evidence-based interventions studies; the Replicating Effective Programs Project, which supports the translation of evidence-based interventions into materials suitable for use in local prevention programs; and the Diffusion of Effective Behavioral Interventions Project, which moves behavioral interventions into full-scale practice across the United States. This article describes the CDC's fast-track process of translation, packaging, and diffusion of an HIV intervention for Hispanic/Latino injection drug users, the Modelo de Intervención Psicomédica conducted by the Diffusion of Effective Behavioral Interventions Project in collaboration with a CBA organization and the original researchers. [ABSTRACT FROM AUTHOR]

Objective: Despite children's unique vulnerability, clinical guidance and resources are lacking around the use of radiation medical countermeasures (MCMs) available commercially and in the Strategic National Stockpile to support immediate dispensing to pediatric populations. To better understand the current capabilities and shortfalls, a literature review and gap analysis were performed., Methods: A comprehensive review of the medical literature, Food and Drug Administration (FDA)-approved labeling, FDA summary reviews, medical references, and educational resources related to pediatric radiation MCMs was performed from May 2016 to February 2017., Results: Fifteen gaps related to the use of radiation MCMs in children were identified. The need to address these gaps was prioritized based upon the potential to decrease morbidity and mortality, improve clinical management, strengthen caregiver education, and increase the relevant evidence base., Conclusions: Key gaps exist in information to support the safe and successful use of MCMs in children during radiation emergencies; failure to address these gaps could have negative consequences for families and communities. There is a clear need for pediatric-specific guidance to ensure clinicians can appropriately identify, triage, and treat children who have been exposed to radiation, and for resources to ensure accurate communication about the safety and utility of radiation MCMs for children. (Disaster Med Public Health Preparedness. 2019;13:639-646).

The effects of two valerian extracts (aqueous and hydroalcoholic) were investigated through [(3)H]Glutamate ([(3)H]Glu) and [(3)H]Fluorowillardine ([(3)H]FW) receptor binding assays using rat synaptic membranes in presence of different receptor ligands. In addition, the extract stability was monitored spectrophotometrically. Both extracts demonstrated interaction with ionotropic glutamate receptors (iGluRs). However, the extracts displayed considerable differences in receptor selectivity. The hydroalcoholic extract selectively interacted with quisqualic acid (QA), group I metabotropic glutamate receptor (mGluR) ligand, while the aqueous extract did not alter the binding of QA. The stability of the extracts was examined during several weeks. Freshly prepared extract inhibited 38-60% of [(3)H]FW binding (AMPA). After 10 days, the aqueous extract inhibited 85% of [(3)H]FW binding while the hydroalcoholic extract markedly potentiated (200%) [(3)H]FW binding to AMPA receptors. Thus, our results showed that factors such as extraction solvent and extract stability determine the selectivity for glutamate receptor (GluR) interactions.

Blinded review has been shown to be an excellent method to detect disagreements and errors and improve performance in gynecologic cytology. Preliminary studies suggest it may be valuable in surgical pathology. We reviewed 5,000 sequential outpatient surgical pathology biopsy cases without knowledge of the original diagnosis or history and compared the results with those of the original diagnosis. Complete agreement was obtained in 91.12% of cases. The technique of blinded review of surgical pathology biopsy material had a sensitivity of more than 99%, failing to identify an abnormality in 19 cases. Although there was a significant level of diagnostic disagreement (444 cases), primarily due to differences in diagnostic thresholds (292 cases), diagnoses that resulted in a change in the original report (true errors) were present in only 5 cases, and only 4 were clinically significant. This clinically significant error rate of 0.08% is significantly lower than previously published error rates. Blinded review is a sensitive (99%) and effective method to identify areas of disagreement and errors in surgical pathology biopsy material. The relatively high rate of disagreement found with blinded review coupled with the very low rate of error highlights the substantial potential for bias in nonblinded reviews.

Recent reports suggest that the finding of lobular neoplasia (atypical lobular hyperplasia [ALH] or bular carcinoma in situ [LCIS]) in breast core needle biopsy specimens may be associated with an increased risk of both ductal carcinoma in situ (DCIS) or invasive carcinoma at excision. We reviewed our breast core biopsy material to see if we could confirm this finding. from 4,297 biopsies, 71 cases of lobular neoplasia lone and 35 cases of lobular neoplasia associated with typical ductal hyperplasia were identified. Biopsy follow-up revealed DCIS or invasive carcinoma in none of 6 cases of ALH, none of 9 cases of LCIS, and DCIS in 1 of 11 cases with both atypical ductal hyperplasia and LCIS. Our results suggest that patients with lobular eoplasia in breast core biopsy specimens are not at increased risk of either DCIS or invasive carcinoma at excision, and patients with this finding and no other linical or pathologic indications for biopsy can be llowed up rather than routinely undergo excision.

Artifactual distortion of hematopoietic elements in histologic preparations and smears of bone marrow aspirates simulating metastatic small cell carcinoma has been recently described. The clinical, pathologic, and immunohistochemical features in 12 such cases have been studied by us. In all these cases, bone marrow smears and histologic sections showed multiple small clusters of atypical, hyperchromatic cells suspicious for metastatic small cell carcinoma. Immunohistochemical stains showed focal positivity of the suspicious cells for leukocyte common antigen (LCA), anti-hemoglobin A (Hem A) and anti-erythrocyte membrane antigen (ERM), and negative staining for epithelial membrane antigen (EMA) and neuron specific enolase (NSE). Clinical follow-up of two years did not demonstrate any evidence of a primary small cell carcinoma in the lung or elsewhere. Comparison of these 12 cases with four cases of transbronchial biopsy-proven metastatic small cell carcinoma to the bone marrow showed that this artifact had a tendency to be located at the periphery of the marrow particles, unlike the true metastatic carcinoma cells which were predominantly found within the marrow particles and replacing the hematopoietic elements. The results of our immunohistochemical studies appear to indicate that these cells correspond to aggregated nuclei and cytoplasmic remnants from erythroid as well as myeloid and lymphoid cells. The main importance of identifying this artifact lies in avoiding confusion with metastatic small cell carcinoma, a distinction that may be very difficult to establish on morphologic grounds alone. Immunohistochemical stains and a thorough clinical follow-up are necessary for arriving at the correct diagnosis.

To study the effect of the inflammatory mediator hydrogen peroxide (H2O2) on airway ciliary activity, we measured ciliary beat frequency (CBF) in cultured tracheal explants from sheep. Addition of H2O2 (10(-8) to 10(-4) M) produced a concentration-dependent mean (+/- SEM) decrease in CBF between 11.1 +/- 0.4% (P less than 0.01) and 100 +/- 0% (P less than 0.001); at each concentration, the maximal effect was reached by 20 to 25 min. Between 10(-8) and 10(-6) M H2O2, the decrease in CBF was reversible, lactate dehydrogenase (LDH) release was not significantly increased, and major morphologic lesions were not seen. At higher concentrations of H2O2, incomplete recovery of CBF (10(-5) M) or irreversible ciliostasis (10(-4) M) developed, and a significant increase in LDH and morphologic lesions were present. Catalase (2,000 U/ml) and H-7 (10(-5) M), a protein kinase inhibitor, abolished cilioinhibition produced by H2O2 at 10(-6) M and lower concentrations but not at 10(-5) M and higher concentrations. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, caused a dose-dependent (10(-11) to 10(-5) M), reversible decrease in CBF; this effect was abolished by H-7. We suggest that at nonlethal concentrations, H2O2 inhibits the beat frequency of airway epithelial cilia reversibly, through the activation of second messengers, including protein kinase C. This mechanism might contribute to the previously demonstrated impairment of mucociliary clearance in airway inflammation.

Fine-needle aspiration (FNA) cytology of lymph nodes in malignant lymphoma is fraught with difficulty. In certain clinical situations, cytology has been documented to be useful in patients with malignant lymphoma. The intent of our investigation was to determine the accuracy of a multiparameter approach in diagnosing lymphoma. We reviewed the results of FNA cytology combined with the immunocytochemistry and, in some cases, the Southern blots of aspirated cell suspensions obtained from 86 suspected lymphoma patients who subsequently underwent surgical biopsy of the aspirated site. In four cases, in which FNA was unable to retrieve sufficient material for diagnosis, the histology showed extensive fibrosis. When the FNA diagnoses were compared with the histologic diagnoses, the diagnosis concurred in 69 cases (56 malignant lymphomas, 12 reactive, 1 atypical lymphoid proliferation). There was one false-positive, six false-negatives, and eight cases diagnosed as atypical lymphoid proliferation. Overall accuracy was 91%. There were two types of false-negative cases: those in which a diagnosis of another malignancy or unspecified malignant neoplasm was made and those that were diagnosed as reactive when the histology showed lymphoma. In seven cases, the DNA rearrangement studies of the antigen receptor genes were successfully performed on the aspirated cells and were useful in establishing lineage and clonality of both B and T lymphoid cells. Our study indicated that the use of a multiparameter approach in the diagnosis of malignant lymphoma by FNA enhanced the accuracy of diagnosis of the non-Hodgkin's lymphomas. In Hodgkin's disease, no benefit was derived from the approach.

School-age children in Chile received 30 g of wheat-flour biscuits daily through a National School Lunch Program. To improve iron nutrition, these biscuits were fortified with 6% of a bovine hemoglobin concentrate. Hemoglobin iron bioavailability, measured with a double isotope technique, showed that heme-iron absorption in fortified biscuits was high (19.7%). In a pilot field trial, a cohort of 215 school-children received fortified biscuits (30 g) daily during two school periods, and their iron nutrition status was compared with that of children who received non-fortified biscuits (n = 212). Acceptability of both types of biscuits was excellent. Initially, both groups had comparably good iron nutrition. The fortified children presented higher mean ferritin values at the end of the first and second school periods. Good iron stores (serum ferritin greater than or equal to 20 micrograms/lt) were present in 92% and 79% of the fortified and control subjects, respectively (P less than 0.004). The high-iron bioavailability, the good organoleptic characteristics and the biological effect on iron nutriture make this product an appealing alternative to combat iron deficiency.

A 72-year-old woman presented with the sudden onset of multiple, large, firm, subcutaneous nodules in her right arm and left thigh. Biopsy of the lesions revealed a septal and lobular panniculitis of unknown cause. The lesions regressed spontaneously without therapy over a period of a few weeks. A follow-up review of the microscopic slides from the biopsy disclosed a lymphohistiocytic and plasma cell proliferation with lymphophagocytosis by histiocytes, the characteristic morphological features of sinus histiocytosis with massive lymphadenopathy. This diagnosis was further supported by the immunocytochemical demonstration of S100 protein reactivity within the histiocytic cells. A seven-year follow-up has failed to reveal any evidence of recurrence or progression of the disease. Sinus histiocytosis with massive lymphadenopathy should be entertained in the differential diagnosis of cutaneous lesions presenting with septal and lobular panniculitis.

Primary clear cell tumors of the breast are rare neoplasms. Traditionally, their differential diagnosis has included lipid-rich, glycogen-rich, and secretory carcinomas of the breast. Although clear cell myoepithelial tumors of the salivary gland and skin have been reported, a primary clear cell myoepithelial carcinoma of the breast has not been previously described. We report a case of clear cell myoepithelial neoplasm of the breast showing an infiltrative histologic growth pattern highly suggestive of carcinoma. Electron microscopy showed evidence of myoepithelial differentiation manifested by cytoplasmic microfilaments with randomly dispersed fusiform densities in conjunction with specialized membrane junctions and remnants of basal membrane. Immunohistologically, the tumor cells were positive for actin, keratin, and S-100 protein. This tumor should be included in the differential diagnosis of the clear cell neoplasms of the breast.