Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.
Oral myiasis is a rare condition caused by the invasion of tissues by larvae of flies. A case of gingival myiasis is presented in a 12-year-old boy with learning disability. The patient was unaware of the lesion, although it produced a swelling partially covering the teeth. The lesion was treated with ether, which forced the larvae out, and irrigated with warm saline solution. Follow-up examination revealed complete subsidence and healing of the lesion.
Osteomyelitis of jaws caused by infection with Mycobacterium tuberculosis is uncommon, especially in children. We present a case of tuberculous osteomyelitis in a young child. Its clinical presentation, with features similar to a dento-alveolar abscess, underline the importance of considering it in the differential diagnosis of jaw lesions. We discuss of the diagnostic techniques, management and preventive measures, and stress the importance of history taking during clinical examination.
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