The first case of human protothecosis caused by Prototheca zopfii in Japan.

This report describes a fatal case Prototheca zopfii genotype 2 infection in an immunosuppressed patient. The patient was a 62-year-old housewife who presented general malaise in April 2011. Hairy cell leukemia was highly suspected. Chemotherapy was started because the patient developed severe pancytopenia in October 2011. Itraconazole capsules (100 mg/day) and trimethoprim (320 mg/day) plus sulfamethoxazole (1600 mg/day) combinations were orally administered for prophylaxis of fungal infections. Of BacT/ALERT 3D FA aerobic culture bottles and FN anaerobic culture bottles, only FA aerobic blood culture bottles produced positive reactions when the patient developed fever in January 2012. Gram-staining of blood culture bottles revealed Gram-negative elliptical sporangia. Culturing on Sabouraud dextrose agar produced smooth and creamy white, yeast-like colonies. Partial DNA sequences of the nuclear 18S rDNA and 28S rDNA D1/D2 domains of the isolated strain were identical to those of P. zopfii genotype 2. The MICs and minimal lethal concentrations of antifungals revealed that it was susceptible to amphotericin B and itraconazole. The patient died, at which time plasma (1 â†’ 3)-ß-D-glucan was positive (131 pg/mL).

Primary lateral sclerosis: upper-motor-predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration--immunohistochemical and biochemical analyses of TDP-43.

Primary lateral sclerosis (PLS) is clinically defined as a disorder selectively affecting the upper motor neuron (UMN) system. However, recently it has also been considered that PLS is heterogeneous in its clinical presentation. To elucidate the association of PLS, or disorders mimicking PLS, with 43-kDa TAR DNA-binding protein (TDP-43) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive frontotemporal atrophy. In the present study, the distribution and severity, and biochemical profile of phosphorylated TDP-43 (pTDP-43) in the brains and spinal cords were examined immunohistochemically and biochemically. Pathologically, in both cases, frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) was evident, with the most severe degeneration in the motor cortex. An important feature in both cases was the presence of Bunina bodies and/or ubiquitin inclusions, albeit very rarely, in the well preserved lower motor neurons. The amygdala and neostriatum were also affected. pTDP-43 immunohistochemistry revealed the presence of many positively stained neuronal cytoplamic inclusions (NCIs) and dystrophic neurites/neuropil threads in the affected frontotemporal cortex and subcortical gray matter. By contrast, such pTDP-43 lesions, including NCIs, were observed in only a few lower motor neurons. pTDP-43 immunoblotting revealed that fragments of ∼25-kDa were present in the cortices, but not in the spinal cord in both cases. Genetically, neither of the patients had any mutation in the TDP-43 gene. In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper-motor-predominant amyotrophic lateral sclerosis with FTLD-TDP.