Mature, dormant spores of a marine bacillus, SG-1, bound and oxidized (precipitated) manganese on their surfaces. The binding and oxidation occurred under dormant conditions, with mature spores suspended in natural seawater. These heat-stable spores were formed in the absence of added manganese in the growth medium. The rate and amount of manganese bound by SG-1 spores was a function of spore concentration. Temperatures greater than 45 degrees C, pH values below 6.5, or the addition of EDTA or the metabolic inhibitors sodium azide, potassium cyanide, and mercuric chloride inhibited manganese binding and oxidation. However, SG-1 spores bound and oxidized manganese after treatment with glutaraldehyde, formaldehyde, ethylene oxide gas, or UV light, all of which killed the spores. Manganese oxidation never occurred in the absence of manganese binding to spores. The data suggest that Mn2+ was complexed by a spore component, perhaps an exosporium or a spore coat protein: once bound, the manganese was rapidly oxidized.
Utilizing hyaline membranes and proliferative pneumonitis as evidence of pulmonary oxygen toxicity, the lung changes in 21 patients (19 injured, two inhaled smoke) who died after oxygen therapy are correlated with the intensity and duration of oxygen administration. Diffuse pneumonitis inducing hypoxaemia was found in 10 (or 11) subjects, and in nine of them it was associated with the breathing of high concentrations of oxygen (60 to 100%) for at least two days. In at least eight subjects the pneumonitis contributed to death, and two others who survived for weeks had extensively fibrosed lungs. The breathing of 40% oxygen for a sufficient time seems to be a threshold for dangerous lung effects, since one patient developed a diffuse pneumonitis and another a partly-diffuse partly-focal pneumonitis while exposed to this concentration. Those respiring oxygen concentrations between 25 and 40% for days developed either subclinical focal lung lesions or had no relevant lung changes.
BACKGROUND: Cytomegalovirus may replicate within the lungs both of recipients of transplants and of patients infected with the human immunodeficiency virus (HIV). A hypothesis formulated by this group was that a host damaging immune response might be provoked by cytomegalovirus infection and cause a severe pneumonitis in recipients of allogeneic transplants, whereas the progressive impairment of cellular immunity in patients with HIV disease would preclude a damaging immune response in the lungs, and thus protect these patients from severe cytomegalovirus pneumonitis. This study set out to discover whether severe cytomegalovirus pneumonitis arises in HIV infected patients. METHODS: Data were prospectively collected on severity of pneumonitis and infectious agents identified in consecutive respiratory episodes in HIV infected patients undergoing diagnostic bronchoalveolar lavage during 20 months. RESULTS: Eighty five episodes of pneumonitis occurred in 68 patients. Cytomegalovirus was identified as the only infectious agent in nine episodes (nine patients). Seven of the episodes were mild; all these patients had CD4 counts below 0.1 x 10(9)/1. The remaining two episodes were severe and ventilatory support was required. In both cases the CD4 counts were above 0.2 x 10(9)/1 and HIV infection appeared to have been acquired shortly before presentation. CONCLUSION: Although rare, severe cytomegalovirus pneumonitis may occur in HIV infected patients. Both patients with severe pneumonitis in this series had relatively well preserved immune function. These findings support the hypothesis that severe cytomegalovirus pneumonitis is an immunopathological condition.
Yersinia pestis has a flea-mammal-flea transmission cycle, and is a zoonotic pathogen that causes the systemic diseases bubonic and septicaemic plague in rodents and humans, as well as pneumonic plague in humans and non-human primates. Bubonic and pneumonic plague are quite different diseases that result from different routes of infection. Manganese (Mn) acquisition is critical for the growth and pathogenesis of a number of bacteria. The Yfe/Sit and/or MntH systems are the two prominent Mn transporters in Gram-negative bacteria. Previously we showed that the Y. pestis Yfe system transports Fe and Mn. Here we demonstrate that a mutation in yfe or mntH did not significantly affect in vitro aerobic growth under Mn-deficient conditions. A yfe mntH double mutant did exhibit a moderate growth defect which was alleviated by supplementation with Mn. No short-term energy-dependent uptake of 54Mn was observed in this double mutant. Like the yfeA promoter, the mntH promoter was repressed by both Mn and Fe via Fur. Sequences upstream of the Fur binding sequence in the yfeA promoter converted an iron-repressible promoter to one that is also repressed by Mn and Fe. To our knowledge, this is the first report identifying cis promoter elements needed to alter cation specificities involved in transcriptional repression. Finally, the Y. pestis yfe mntH double mutant had an ~133-fold loss of virulence in a mouse model of bubonic plague but no virulence loss in the pneumonic plague model. This suggests that Mn availability, bacterial Mn requirements or Mn transporters used by Y. pestis are different in the lungs (pneumonic plague) compared with systemic disease.
The deposition of manganese in a water distribution system with manganese-related "dirty water" problems was studied over a 1-year period. Four monitoring laboratories with Robbins biofilm sampling devices fitted to the water mains were used to correlate the relationship among manganese deposition, the level of manganese in the water, and the chlorination conditions. Manganese deposition occurred by both chemical and microbial processes. Chemical deposition occurred when Mn(II) not removed during water treatment penetrated the filters and entered the distribution system, where it was oxidized by chlorine and chlorine dioxide used for disinfection. Microbial deposition occurred in areas with insufficient chlorination to control the growth of manganese-depositing biofilm. At 0.05 mg of Mn(II) per liter, the chemical deposition rate was much greater than microbial deposition. Significant deposition occurred at 0.03 mg of manganese per liter, and dirty water complaints were not eliminated until manganese levels were continuously less than 0.02 mg/liter and chlorination levels were greater than 0.2 mg/liter. A guideline level of 0.01 mg of manganese per liter is recommended.
Pneumonitis was induced in calves by exposure to aerosols of Micropolyspora faeni with or without prior sensitization of the animals by subcutaneous injection of antigen. The pneumonitis primarily involved centrolobular areas and was characterized by alveolar septal thickening and loss of air space by cellular infiltration. Vasculitis and focal haemorrhage occurred in certain individuals and haemoproteinaceous exudate appeared within septa and alveolar lumina. The pneumonitis was compared with human farmer's lung, pneumonitis of housed cattle and other experimental hypersensitivity pneumonitides.
Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI). Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT) and dopamine receptor D1 (D1R) levels were reduced and dopamine receptor D2 (D2R) levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed “rescue response” with beneficial influence on motor impairment due to low iron status.
The current practice of providing manganese supplementation to neonates on long term parenteral nutrition is leading to a high incidence of hypermanganesaemia. Magnetic resonance imaging (MRI) studies in adults on long term manganese parenteral nutrition have shown changes in TI weighted MRI images and similar findings in a neonate receiving trace element supplementation are reported here. Whole blood manganese concentration in the infant was 1740 nmol/l (or 8.3 times upper reference limit). In all neonates on long term parenteral nutrition with evidence of cholestatic liver disease so far investigated, the whole blood manganese concentrations were > 360 nmol/l (reference range 73-210). Manganese supplementation to patients on long term parenteral nutrition requires reappraisal, particularly in those who develop cholestatic liver disease associated with parenteral nutrition.
Manganese-enhanced magnetic resonance imaging (MEMRI) provides a powerful tool to study multi-synaptic circuits in vivo, and thereby to link information about neural structure and function within individual subjects. Making the best use of MEMRI in monkeys requires minimizing manganese-associated neurotoxicity, maintaining sensitivity to manganese-dependent signal changes, and mapping transport throughout the brain without a priori anatomical hypotheses. Here, we performed intracortical injections of isotonic MnCl2, comparisons of pre- and post-injection scans, and voxel-wise statistical mapping. Isotonic MnCl2 did not cause cell death at the injection site, damage to downstream targets of manganese transport, behavioral deficits, or changes in neuronal responsiveness. We detected and mapped manganese transport throughout cortical-subcortical circuits by using voxel-wise statistical comparisons of at least 10 pre- and 2 post-injection scans. We were able to differentiate between focal and diffuse projection fields and to distinguish between the topography of striatal projections from orbitofrontal and anterior cingulate cortex in a single animal. This MEMRI approach provides a basis for combining circuit-based anatomical analyses with simultaneous single unit recordings and/or fMRI in individual monkeys. Such studies will enhance our interpretations of functional data and our understanding of how neuronal activity is transformed as it propagates through a circuit.
orbitofrontal cortex; anterior cingulate cortex; striatum; neuroanatomy; tract tracing; non-human primate
To test the hypothesis that in dark-adapted diabetic mice subnormal manganese uptake in the outer retina can be ameliorated with exogenous 11-cis-retinal intervention.
Three groups were studied: age-matched controls and mice that had been diabetic for 3 months with and without acute, systemic 11-cis-retinal treatment administered 30 min before the manganese injection. Mice in each group were examined with manganese-enhanced magnetic resonance imaging (MEMRI) to assess central intraretinal manganese uptake and extraocular muscle manganese uptake. Bodyweights and glycated hemoglobin were determined.
Both diabetic groups had lower bodyweights and higher glycated hemoglobin levels relative to controls; no differences in these parameters between diabetic groups were noted. No substantial differences in muscle uptake were noted between any of the groups. Diabetes produced a subnormal intraretinal uptake of manganese; acute exogenous 11-cis-retinal significantly corrected only outer retinal uptake, although not to control levels.
The present results provide for the first time evidence that raises the possibility of a critical role of 11-cis-retinal, a key participant of the visual cycle, in diabetes-evoked outer retinal dysfunction.
Manganese intoxication has been described in children on long
term parenteral nutrition presenting with liver and nervous system
disorders. Cases are reported of a brother and sister on long term
parenteral nutrition with hypermanganesaemia and basal ganglia
manganese deposition, detected by magnetic resonance imaging (MRI),
without overt neurological signs. Following reduction of manganese
intake, basal ganglia manganese was monitored by repeated MRI, and
neurological and developmental examinations. An MRI intensity index of
the globus pallidus declined over a three year period from 0.318 and
0.385 to 0.205 and 0.134 with concomitant falls in whole blood
manganese from 323 and 516 to 226 and 209 nmol/l (normal range,
73-210 nmol/l). Unlike adult experience these children developed
normally without neurological signs. In conclusion, deposited manganese
is removed from neural tissue over time and the prognosis is good when
neurological manifestations and liver disease are absent.
When cultured anaerobically in a chemically defined medium that was treated with Chelex-100 to lower its trace metal content, Streptococcus mutans OMZ176 had no apparent requirement for manganese or iron. Manganese or iron was necessary for aerobic cultivation in deep static cultures. During continuous aerobic cultivation in a stirred chemostat, iron did not support the growth rate achieved with manganese. Since the dissolved oxygen level in the chemostat cultures was higher than the final level in the static cultures, manganese may be required for growth at elevated oxygen levels. In medium supplemented with manganese, cells grown anaerobically contained a low level of superoxide dismutase (SOD) activity; aerobic cultivation increased SOD activity at least threefold. In iron-supplemented medium, cells grown anaerobically also had low SOD activity; aerobic incubation resulted in little increase in SOD activity. Polyacrylamide gel electrophoresis of the cell extracts revealed a major band and a minor band of SOD activity in the cells grown with manganese; however, cells grown with iron contained a single band of SOD activity with an Rf value similar to that of the major band found in cells grown with manganese. None of the SOD activity bands were abolished by the inclusion of 2 mM hydrogen peroxide in the SOD activity strain. S. mutans may not produce a separate iron-containing SOD but may insert either iron or manganese into an apo-SOD protein. Alternatively, iron may function in another activity (not SOD) that augments the defense against oxygen toxicity at low SOD levels.
Human herpesvirus 6 (HHV-6)-associated encephalitis or pneumonitis has been reported in immunocompetent and immunosuppressed individuals. Several MRI studies in patients with HHV-6-associated encephalitis have been presented. However, to the best of our knowledge, no studies describing thin-section CT imaging in patients with HHV-6-associated pneumonitis have been reported. Here we describe a case of HHV-6-associated encephalitis and pneumonitis that developed after bone marrow transplantation. Thin-section CT images of the chest revealed ground-glass attenuation, consolidation and centrilobular nodules in both lungs.
Trehalose dimycolate is a glycolipid component of the cell walls of mycobacteria, nocardia, and corynebacteria. When trehalose dimycolate is injected into certain strains of mice, they develop interstitial pneumonitis that is characterized by mononuclear cell infiltration of the alveolar walls, intra-alveolar hemorrhages, and in some animals, granuloma formation. The disorder is seldom fatal, and in approximately 4 weeks, the lungs are normal. There is strong evidence that T lymphocytes are essential for production of interstitial pneumonitis by trehalose dimycolate, but little is known about the mechanisms of lung injury in this model. The experiments described in this report were conducted to identify the roles of the various cells that accumulate in the lungs of mice with this form of interstitial pneumonitis. We found that Mac3+ macrophages were the first cells to appear in the alveolar walls. Increases in the number of L3T4+ T lymphocytes, Lyt2+ T lymphocytes, and surface-immunoglobulin-positive lymphocytes followed, but significant increases in the number of lymphoid cells were not observed until day 7, when the pulmonary lesions were well developed. Treatment of the mice with cyclophosphamide or anti-T-cell sera significantly reduced the number of lymphoid cells in the alveolar walls but did not affect the number of Mac3+ cells and did not affect development of intra-alveolar hemorrhages. Treatment with poly(I.C) significantly decreased the number of Mac3+ cells in the lungs, and these mice did not develop pulmonary hemorrhages. We conclude that although development of pulmonary lesions in trehalose dimycolate-treated mice is a T-cell-dependent process, macrophages are also essential and are more directly involved in production of the lung injury. We postulate that the lung lesions are the direct effect of macrophage-produced cytokines, such as tumor necrosis factor.
Four adults had varicella pneumonitis. All developed respiratory symptoms within a week of the exanthem. Cough and/or dyspnea, cyanosis and chest pain were common. Radiological signs of disease were more marked than physical signs. A slight polymorphonuclear leukocytosis and normal sputum culture were usual. One man with mild symptoms recovered. Two women, one pregnant, had severe symptoms and died. A second man succumbed to secondary bacterial pneumonia. The lungs in fatal cases showed interstitial pneumonitis with mononuclear cell infiltrate, focal areas of necrosis, and acidophilic inclusion bodies in two cases. Patients received oxygen, antibiotics and, in one instance, corticosteroid therapy. The value of antibiotics and corticosteroid treatment is questionable. Use of gamma globulin in preventing varicella pneumonitis is mentioned and residual pulmonary changes are discussed.
BACKGROUND: Low dose methotrexate has become established in the treatment of refractory rheumatoid arthritis. Until recently it has been considered that the use of a low dose regimen (< 20 mg/week) would avoid the pulmonary toxicity associated with the higher doses prescribed in malignant disease. Although initial experience with low dose methotrexate was encouraging, an increasing number of cases of an acute, life threatening pneumonitis are being reported in patients with refractory rheumatoid arthritis. PATIENTS: Since 1984 43 patients with refractory rheumatoid arthritis have been established on low dose methotrexate in the Oxford Health District. Five of these patients have subsequently developed acute methotrexate induced pneumonitis. The clinical and radiological features of these cases are described and previous reports reviewed. RESULTS: Five patients having low dose methotrexate treatment developed acute pneumonitis. Presentation was subacute and dominated by constitutional features. Respiratory symptoms developed insidiously but progressed rapidly with increasing dyspnoea associated with severe hypoxia. Chest radiographs were non-specific, showing diffuse interstitial infiltration and alveolar shadowing. Microbiological investigation gave negative results. In all cases methotrexate was discontinued and high dose corticosteroids started, with rapid clinical and radiological improvement. After withdrawal of steroid both clinical and radiological resolution was maintained at follow up. CONCLUSION: Acute pneumonitis is an uncommon but serious adverse effect of low dose methotrexate treatment for refractory rheumatoid arthritis. The initial presentation is non-specific and a high index of suspicion is required as respiratory failure may develop rapidly. Management depends on exclusion of infection, withdrawal of methotrexate, and high dose corticosteroid treatment. Full supportive treatment is indicated as the prognosis in such patients is good.
BACKGROUND--A study was performed to identify the clinical, radiographic, and histopathological features of interstitial pneumonitis in patients infected with the human immunodeficiency virus. METHODS--A retrospective review was made of the case notes, chest radiographs, and histopathological results of seven HIV-1 antibody positive patients with symptomatic diffuse pulmonary disease and a pathological diagnosis of non-specific interstitial pneumonitis. RESULTS--All patients had dyspnoea, with or without cough, and chest radiographs showing diffuse infiltrates. The arterial oxygen tension ranged widely from 5.9 to 13.1 kPa. The initial clinical diagnosis was Pneumocystis carinii pneumonia in most cases. The pathological diagnosis was made by transbronchial biopsy in one case and by open lung biopsy in six cases. The interstitial pneumonitis consisted of a patchy lymphocytic infiltrate composed of B cells in focal aggregates and T cells in a more diffuse distribution. The T cell population was a mixture of CD4+ and CD8+ cells. The histological findings contrast with the more extensive infiltrate of predominantly CD8+ lymphocytes seen in HIV-associated lymphocytic interstitial pneumonitis which occurs mainly in children. The condition ran a subacute course. Three patients spontaneously improved and three improved with steroid therapy. Long term survival was less than three years, the prognosis being determined by other infective or neoplastic complications. CONCLUSIONS--Non-specific interstitial pneumonitis usually presents with an illness resembling Pneumocystis carinii pneumonia but occurs when the CD4 and total lymphocyte counts are still preserved. The pneumonitis resolves spontaneously or responds to steroids, and does not itself lead directly to the patient's death. It does, however, appear to mark a downturn in the course of HIV infection.
Although the cause and development of most inflammatory and fibrotic interstitial lung diseases are unknown, both the antigenic stimuli and the immunopathogenic mechanisms that produce the syndrome of hypersensitivity pneumonitis have been well described. Hypersensitivity pneumonitis is a group of related inflammatory and fibrotic interstitial lung diseases that result from hypersensitivity immune reactions to the repeated inhalation of antigens derived from fungal, bacterial, animal protein, and reactive chemical sources. Immune complex-induced inflammatory reactions initiate acute lung injury; T cell-mediated hypersensitivity reactions perpetuate it and induce chronic inflammatory, granulomatous, and fibrotic responses in the interstitium of the lungs. Because the natural history of many interstitial lung diseases of unknown causes involves the progressive evolution through these same phases, knowledge about immune pathogenesis gained from studies of hypersensitivity pneumonitis may provide a way to understand the causes and development of other interstitial lung diseases.
Manganese-enhanced magnetic resonance imaging (MRI) is a surrogate method to measure calcium content in nervous system since manganese physiologically follows calcium. Manganese is detectable in MRI and therefore visualizes structures and cell populations that actively regulate calcium. Since calcium is actively recruited for the transmission of action potentials, our purpose is to validate manganese-enhanced MRI for detection of changes in lumbar nerves related to nociception. A neuropathic pain model was created by chronic constrictive injury of the left sciatic nerve of Sprague-Dawley rats. Behavioral measurements, using von Frey’s tests, confirmed the presence of significant allodynia in the left hind limb of animals in the injured group. T1-weighted fast spin echo images were obtained of the lumbar cord and plexus of animals with injured left sciatic nerve and uninjured animals (control) scanned in a 7 Tesla magnet after intraperitoneal manganese chloride administration four weeks after surgery. Lumbar nerve roots and sciatic nerves in the injured group show increased normalized manganese-enhanced MRI signal, representing manganese enhancement, compared to the control group. In conclusion, animals with neuropathic pain in the left hind limb show increased manganese uptake in not only the injured sciatic nerve but also in the contralateral uninjured sciatic nerve on manganese-enhanced MRI in vivo. Although poorly understood, this finding corroborates ex vivo finding of bilateral nociceptive-related molecular changes in the nervous system of unilateral pain models.
Manganese-enhanced magnetic resonance imaging; chronic constrictive injury; sciatic nerve injury; neuropathic pain; animal model
Paramagnetic manganese can be employed as a calcium surrogate to sensitize the magnetic resonance imaging (MRI) technique to the processing of calcium during the bone formation process. At low doses, after just 48 h of exposure, osteoblasts take up sufficient quantities of manganese to cause marked reductions in the water proton T1 values compared with untreated cells. After just 24 h of exposure, 25 μM MnCl2 had no significant effect on cell viability. However, for mineralization studies 100 μM MnCl2 was used to avoid issues of manganese depletion in calvarial organ cultures and a post-treatment delay of 48 h was implemented to ensure that manganese ions taken up by osteoblasts is deposited as mineral. All specimens were identified by their days in vitro (DIV). Using inductively coupled plasma optical emission spectroscopy (ICP-OES), we confirmed that Mn-treated calvariae continued to deposit mineral in culture and that the mineral composition was similar to that of age-matched controls. Notably there was a significant decrease in the manganese content of DIV18 compared with DIV11 specimens, possibly relating to less manganese sequestration as a result of mineral maturation. More importantly, quantitative T1 maps of Mn-treated calvariae showed localized reductions in T1 values over the calvarial surface, indicative of local variations in the surface manganese content. This result was verified with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). We also found that ΔR1 values, calculated by subtracting the relaxation rate of Mn-treated specimens from the relaxation rate of age-matched controls, were proportional to the surface manganese content and thus mineralizing activity. From this analysis, we established that mineralization of DIV4 and DIV11 specimens occurred in all tissue zones, but was reduced for DIV18 specimens because of mineral maturation with less manganese sequestration. In DIV25 specimens, active mineralization was observed for the expanding superficial surface and ΔR1 values were increased due to the mineralization of small, previously unmineralized areas. Our findings support the use of manganese-enhanced MRI (MEMRI) to study well-orchestrated mineralizing events that occur during embryonic development. In conclusion, MEMRI is more sensitive to the study of mineralization than traditional imaging approaches.
Manganese-enhanced magnetic resonance; imaging; Osteoblasts; Mineralization; Calvaria; Laser ablation inductively coupled plasma; mass spectrometry
The first gene causing early-onset generalized dystonia with brain manganese accumulation has recently been identified. Mutations in the SLC30A10 gene, encoding a manganese transporter, cause a syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia.
We present 10-year longitudinal clinical features, MRI data, and treatment response to chelation therapy of the originally described patient with a proven homozygous mutation in SLC30A10.
The patient presented with early-onset generalized dystonia and mild hyperbilirubinemia accompanied by elevated whole-blood manganese levels. T1-sequences in MRI showed hyperintensities in the basal ganglia and cerebellum, characteristic of manganese deposition. Treatment with intravenous disodium calcium edetate led to clinical improvement and reduction of hyperintensities in brain imaging.
We wish to highlight this rare disorder, which, together with Wilson's disease, is the only potentially treatable inherited metal storage disorder to date, that otherwise can be fatal as a result of complications of cirrhosis. © 2012 Movement Disorder Society
dystonia; hypermanganesemia; cirrhosis; polycythemia; SLC30A10
In the absence of manganese, rapidly metabolizable carbohydrates such as glucose or glycerol are not completely metabolized by Bacillus subtilis growing in a nutrient sporulation medium: 3-phosphoglyceric acid (3PGA) accumulates inside the cells, growth stops at a low cell titer, and normal sporulation remains suppressed (no prespore septa). Upon the addition of manganese, 3PGA disappears, growth resumes, and normal sporulation takes place. These effects results from a specific manganese requirement of phosphoglycerate phosphomutase which catalyzes the interconversion of 3PGA and 2-phosphoglyceric acid (2PGA). Other metal ions cannot replace manganese, for which the enzyme has an apparent Km of 0.22 mM.
An iron-oxidizing factor was identified in the spent culture medium of the iron- and manganese-oxidizing bacterial strain Leptothrix discophora SS-1. It appeared to be a protein, with an apparent molecular weight of approximately 150,000. Its activity could be demonstrated after fractionation of the spent medium by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A spontaneous mutant of L. discophora SS-1 was isolated which excreted neither manganese- nor iron-oxidizing activity, whereas excretion of other proteins seemed to be unaffected. Although the excretion of both metal-oxidizing factors was probably linked, the difference in other properties suggests that manganese and iron oxidation represent two different pathways. With a dot-blot assay, it was established that different bacterial species have different metal-oxidizing capacities. Whereas L. discophora oxidized both iron and manganese, Sphaerotilus natans oxidized only iron and two Pseudomonas spp. oxidized only manganese.
The cation requirements for fruiting body formation in the myxobacterium Stigmatella aurantiaca on agarose were determined. Calcium alone caused the cells to aggregate into interconnecting ridges. Under these conditions, stalk formation was severely depressed but sporangia frequently formed. The combination of magnesium and manganese was necessary for optimal formation of discrete aggregates (rather than ridges) and stalks. Manganese inhibited sporangium development. The inclusion of calcium into the magnesium-manganese medium overcame the inhibition by manganese and stimulated the production of multiple sporangia.
A non-invasive method to image the mass and/or function of human pancreatic islets is needed to monitor the progression of diabetes, and the effect of therapeutic interventions. As yet, no method is available for this purpose, which could be applied to in situ human islets. Animal and in vitro studies have documented that manganese infusion could improve the magnetic resonance imaging (MRI) of the endocrine pancreas. Here, we have tested whether a similar approach could discriminate diabetic and non-diabetic patients. In vitro, human isolated islets readily incorporated manganese. In vivo, 243 manganese-enhanced magnetic resonance imaging (MEMRI) examinations were reviewed, including 41 examinations which were run on 24 patients with type 2 diabetes and 202 examinations which were run on 119 normoglycemic patients. The results show that MEMRI discriminates type 2 diabetics from non-diabetic patients, based on the signal enhancement of pancreas.
MEMRI; MRI; diabetes; imaging; manganese