Magnetic resonance imaging T1 indices of the brain as biomarkers of inhaled manganese exposure.

Excessive exposure to manganese (Mn) is linked to its accumulation in the brain and adverse neurological effects. Paramagnetic properties of Mn allow the use of magnetic resonance imaging (MRI) techniques to identify it in biological tissues. A critical review was conducted to evaluate whether MRI techniques could be used as a diagnostic tool to detect brain Mn accumulation as a quantitative biomarker of inhaled exposure. A comprehensive search was conducted in MEDLINE, EMBASE, and PubMed to identify potentially relevant studies published prior to 9 May 2022. Two reviewers independently screened identified references using a two-stage process. Of the 6452 unique references identified, 36 articles were retained for data abstraction. Eligible studies used T1-weighted MRI techniques and reported direct or indirect T1 measures to characterize Mn accumulation in the brain. Findings demonstrate that, in subjects exposed to high levels of Mn, deposition in the brain is widespread, accumulating both within and outside the basal ganglia. Available evidence indicates that T1 MRI techniques can be used to distinguish Mn-exposed individuals from unexposed. Additionally, T1 MRI may be useful for semi-quantitative evaluation of inhaled Mn exposure, particularly when interpreted along with other exposure indices. T1 MRI measures appear to have a nonlinear relationship to Mn exposure duration, with R1 signal only increasing after critical thresholds. The strength of the association varied depending on the regions of interest imaged and the method of exposure measurement. Overall, available evidence suggests potential for future clinical and risk assessment applications of MRI as a diagnostic tool.

Biomarkers for occupational manganese exposure.

Long-term inhalation exposure to manganese (Mn) metal or its inorganic compounds can result in manganism or subclinical neurofunctional deficits. Studies have described affected workers in Mn dioxide mining, Mn-containing ore crushing and milling facilities, manufacturing of dry-cell batteries, Mn steel and alloy production plants, and in welders. The objective of this study was to critically review existing evidence on the reliability of potential biomarkers of Mn exposure, specifically the relationship between inhalation exposure to Mn particulates in different occupational settings and Mn concentrations in blood and other biological fluids and tissues, with a particular focus on whole blood as a potentially useful medium for measuring internal tissue dose. We also examined available evidence on the relationship between Mn levels in blood and adverse clinical and subclinical neurotoxic outcomes. Three bibliographic databases were searched for relevant studies and identified references were screened by two independent reviewers. Of the 6338 unique references identified, 76 articles were retained for data abstraction. Findings indicate that the relationships between Mn in blood and both external Mn exposure indices and neurofunctional impairments are limited and inconsistent. Different sources of exposure to Mn compounds, heterogeneity in the methodological approaches, and inadequate reporting of essential information limited direct comparison of the reported findings. Among the Mn-exposure biomarkers considered in this review - including biomarkers in blood, plasma, serum, erythrocytes, urine, bone, toenails, fingernails, hair, saliva - biomarkers in whole blood may provide to be most useful in Mn biomonitoring and risk assessment.

Re-Envisioning the Culture of Undergraduate Biology Education to Foster Black Student Success: A Clarion Call.

The purpose of this paper is to present an argument for why there is a need to re-envision the underlying culture of undergraduate biology education to ensure the success, retention, and matriculation of Black students. The basis of this argument is the continued noted challenges with retaining Black students in the biological sciences coupled with existing research that implicates science contexts (i.e., the cultural norms, values, and beliefs manifesting through policies and practices) as being the primary source of the challenges experienced by Black students that lead to their attrition. In presenting this argument, we introduce the Re-Envisioning Culture Network, a multigenerational, interdisciplinary network comprised of higher education administrators, faculty, staff, Black undergraduate students majoring in biology, Black cultural artists, community leaders, and STEM professionals to work together to curate and generate resources and tools that will facilitate change. In introducing the REC Network and disseminating its mission and ongoing endeavors, we generate a clarion call for educators, researchers, STEM professionals, students, and the broader community to join us in this endeavor in fostering transformative change.

Antibodies against granule proteins activate neutrophils in vitro.

Polymorphonuclear leukocyte (PMN) respiratory burst was stimulated by heterologous antibodies against PMN granule proteins but not by control antibodies. Fluorescence-activated cell sorter (FACS) analysis of activated PMN demonstrated the presence of two primary granule proteins, proteinase 3 (PR-3) and cationic protein 57 (CAP-57) at the membrane surface. The presence of myeloperoxidase (MPO) at the cell surface of primed and unprimed PMN was confirmed by immunoelectron microscopy. Priming doses of recombinant tumor necrosis alpha (rTNF alpha) enhanced the rate of superoxide (O2-) production by these antibodies and increased the amount of surface protein accessible to these antibodies. Anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificities for PMN granule proteins are present in patients with Wegener's granulomatosis, polyarteritis nodosa, and idiopathic and crescentic glomerulonephritis. The demonstration that antibodies against granule proteins activate PMN supports the hypothesis that the vasculitis seen in these diseases is due in part to PMN mediated oxidative injury following PMN stimulation by ANCA.

Ultrastructural localization of tartrate-resistant, purple acid phosphatase in rat osteoclasts by histochemistry and immunocytochemistry.

The intracellular localization of the tartrate-resistant purple acid phosphatase in osteoclasts of developing rat bone has been determined immunocytochemically using an antiserum to the purified bone-derived purple acid phosphatase. The localization of the immunoreactivity was compared with the results of enzyme histochemistry using p-nitrophenylphosphate as substrate and 10 mM tartrate. Both methods revealed the presence of the enzyme in numerous vesicles of various sizes up to 2-3 microns in diameter and in granules. There was no immunoreactivity in the Golgi apparatus, and tartrate completely inhibited the histochemical activity of this organelle. No consistent extracellular activity could be detected, nor was any reaction product observed at the ruffled border. The localization of the tartrate-resistant purple acid phosphatase in osteoclasts is consistent with an intracellular function for this enzyme.

Focal microsatellite mutations in relatives with prostatic adenocarcinoma.

Instability of short tandem repeat sequences, microsatellite instability (MI), has been reported to play an important role in the tumorigenesis of various adenocarcinomas, including prostatic adenocarcinoma. Although prostate cancer is not widely recognized as a heriditary cancer, familial clustering is well known. To investigate the frequency of microsatellite instability in familial prostatic adenocarcinomas we analyzed archival tumor tissue from seven paired first degree relatives with prostatic adenocarcinoma. Twelve dinucleotide, nine trinucleotide, six tetranucleotide repeats and the CAG repeat of the androgen receptor gene were screened for MI. Solitary mutations were observed in four separate cases (28.6%) and widespread somatic alterations were not identified. No statistical correlation to pathological characteristics was determined. Our data indicate that microsatellite instability is an uncommon phenomenon in prostatic adenocarcinoma within first degree relatives. Those changes present appear to manifest as focal mutations in contrast to the more global changes seen in MI.

Educational desert or oasis? An educator's trek to Outer Mongolia.

Mongolia has long been associated with isolation from the western world. Sandwiched between Russia on the north and China on the south, it is little known and little understood. Now split into two separate nations, Inner Mongolia is under the control of Red China, and Outer Mongolia under the control of Russia. Outer Mongolia has a population of 1.3 million and is about one-fifth the size of the United States. Education follows the Russian (communist) model and, of course, has a Five-Year Plan. Since World War II the literacy rate has jumped to 90%, and has received recognition by UNESCO for its efforts. Mongolian schools are on a two-track system, one for those going into trades or agriculture, and the other for those going on to higher education and the professions. Considering the Mongolian economic structure, its geography, and the nature of its people, it can be said that they have done a good job of educating their people.

Physical and chemical properties of anaesthetic agents (with an appendix on the manufacture of isoflurane).

The physical and chemical requirements of today's modern inhalation anaesthetic agents have resulted in the production of compounds that closely approach those of the ideal agent. As medical science develops and defines the need for better drug characteristics, the complexity of the research problems for the organic chemist is intensified. Many of the inhalation anaesthetic agents in use 30 yr ago would not pass a clinical investigator screen today, and would be rejected as inhalation anaesthetic agents. An outline of the manufacture of isoflurane is given as an Appendix to this paper.

Salt, Water and Oilseed Proteins Affect Brine Content of Sausages.

Brine contents of commercial sausage products ranged from 3.7 to 5.9% and were different among brands. Frankfurters to which either isolated soy or cottonseed protein isolate were added had greater process shrinkage values and higher moisture, lower fat and lower brine contents than did controls. Frankfurters prepared with oilseed proteins had higher (P < .05) process shrinkage percentages, higher moisture percentages and lower brine contents than did controls (all-meat). Although not significant among all comparisons, as in-going (lb per 100 lb raw meat) salt levels increased from 2.5 to 3.0 to 3.5 lb, brine contents increased regardless of level of added water (25, 30, and 35 lb per 100 lb of meat). Within added-salt levels, brine content generally decreased with increasing level of in-going water but these differences were not significant (P > .05). At the beginning and end of a 6-week storage period, frankfurters with high brine contents (4.50-5.25%) had lower total microbial numbers than did frankfurters with low (2.50-3.49%) or medium (3.50-4.49%) brine contents. Because of simplicity, brine content determinations may be further developed as a practical tool for predicting product performance of cured sausages.

Use of proliferative markers Ki-67 (MIB-1) and proliferating cell nuclear antigen (PC10) in transitional cell carcinoma of the renal pelvis.

Segmental renal resection and improved endourological techniques have resulted in conservative treatment options for transitional cell carcinoma of the renal pelvis. These techniques have increased the need for more objective measures of biological behavior. We applied two immunohistochemical markers of cellular proliferation, proliferating cell nuclear antigen (PCNA; PC10) and Ki-67 (MIB-1), to 58 archival cases of renal pelvic transitional cell carcinomas and correlated the percentage of positive cells to grade, stage, and survival, and to one another; mitotic counts (mitoses/10 high-power fields) were also performed. Expression of PCNA showed a significant difference between grades 1, 2, and 3 tumors (P = 0.05) and between superficial (Ta, T1) and invasive tumors (T2-4) (P = 0.02). There was a significant overlap, however, in the percentage of cells staining between the grades as well as the stages. PCNA staining did not correlate with survival and did not identify a subset of patients with low-stage, low-grade tumors with a poorer prognosis. The Ki-67 score exhibited a stronger correlation with grade (P = 0.001), and there was a trend of increasing Ki-67 expression with higher stage tumors, but this did not reach statistical significance (P = 0.10). Ki-67 showed comparable findings to PCNA with regard to survival and overlap in staining between the grades and stages. Mitotic counts did correlate with grade (P = 0.003) but not stage or survival. This study demonstrates that cellular proliferation, as determined by the immunohistochemical markers, Ki-67 and PCNA, is related to grade and, to a lesser extent, stage, but the use of these markers as measures of biological behavior in clinical practice may be limited.

Effect of Reduction and Replacement of Sodium Chloride on Rancidity Development in Raw and Cooked Ground Pork.

Ground pork (raw and cooked) was treated with NaCl, KCl or MgCl2 at ionic strengths of either 0.70 or 0.35, and stored at 4 or -20°C. Regardless of storage temperature, NaCl and MgCl2 increased rancidity of both raw and cooked samples, whereas KCl increased rancidity of raw samples only. In raw pork samples, NaCl increased rancidity the most. In cooked samples, MgCl2 increased rancidity more than NaCl when samples were stored at 4°C, but the opposite was true for samples stored at -20°C. Discoloration was most severe for raw, frozen samples treated with NaCl. Replacement of NaCl with KCl was most effective for decreasing rancidity in both raw and cooked samples.

Some characteristics of an exceptionally potent inhaled anesthetic: thiomethoxyflurane.

The authors sought to test whether a deviation existed for the correlation between anesthetic potency and the oil/gas partition coefficient at an extreme of lipid solubility. For thiomethoxyflurane, the sulfur analog of methoxyflurane, the oil/gas partition coefficient was 7230 +/- 50 SEM, and MAC (minimum alveolar concentration of thiomethoxyflurane required for anesthesia) in 4 dogs was 0.035 +/- 0.008 percent of 1 atm. This agrees with the potency predicted by the lipid solubility, although thiomethoxyflurane is 7 1/2 times more potent than methoxyflurane, to date the most potent available anesthetic. Thiomethoxyflurane water/gas and blood/gas partition coefficients were 5.4 +/- 0.3 and 68.1 +/- 1.5, respectively. The latter coefficient accords with the prolonged recovery associated with this agent. Renal and hepatic blood chemistries measured on the 1st and 7th days following anesthesia showed only small changes from preanesthetic values.