Chromobacterium violaceum cellulitis and sepsis following cutaneous marine trauma.

Chromobacterium violaceum is a gram-negative bacillary organism that characteristically produces the purple pigment violacein. Documented as the cause of clinically relevant human infections in only 35 cases in the United States, C violaceum is particularly seen in patients with a history of cutaneous injury or trauma. We report the case of an 18-year-old woman who was struck by a propeller in a boating accident and sustained multiple deep lacerations of her right lower extremity. Shortly after admission to the hospital, the patient became frebrile and developed leukocytosis. Bacterial cultures revealed C violaceum, which demonstrated a characteristic purple pigment production on blood agar. Antimicrobial therapy was initiated, but 2 days after admission, the skin and subcutaneous tissue surrounding the patient's wounds became necrotic, necessitating an above-the-knee amputation of the right lower extremity (transfemoral amputation). The patient's condition improved after continued antimicrobial therapy and she was subsequently discharged in good health. This case represents a successful outcome of a rare but frequently fatal infection due to a morphologically and geographically distinct human pathogen.

Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer.

Ser/Thr protein phosphatase 5 (PP5) regulates several signaling-cascades that suppress growth and/or facilitate apoptosis in response to genomic stress. The expression of PP5 is responsive to hypoxia inducible factor-1 (HIF-1) and estrogen, which have both been linked to the progression of human breast cancer. Still, it is not clear if PP5 plays a role in the development of human cancer. Here, immunostaining of breast cancer tissue-microarrays (TMAs) revealed a positive correlation between PP5 over-expression and ductal carcinoma in situ (DCIS; P value 0.0028), invasive ductal carcinoma (IDC; P value 0.012) and IDC with metastases at the time of diagnosis (P value 0.0001). In a mouse xenograft model, the constitutive over-expression of PP5 was associated with an increase in the rate of tumor growth. In a MCF-7 cell culture model over-expression correlated with both an increase in the rate of proliferation and protection from cell death induced by oxidative stress, UVC-irradiation, adriamycin, and vinblastine. PP5 over-expression had no apparent effect on the sensitivity of MCF-7 cells to taxol or rapamycin. Western analysis of extracts from cells over-expressing PP5 revealed a decrease in the phosphorylation of known substrates for PP5. Together, these studies indicate that elevated levels of PP5 protein occur in human breast cancer and suggest that PP5 over-expression may aid tumor progression.

Solid-pseudopapillary tumor: a report of three cases in adult males diagnosed utilizing three different modalities.

Solid-pseudopapillary tumor of the pancreas is a rare neoplasm of uncertain origin with low malignant potential and often indolent behavior occurring predominantly in adolescent and young women. Here we report the cases of three adult males with pancreatic masses, one with metastasis, diagnosed as solid-pseudopapillary tumor by cytology, electron microscopy (EM), and routine histology. This neoplasm is uncommon in both males and adults and uncommonly metastasizes. The cases reported emphasize the utility of different diagnostic modalities, and here we review the diagnostic features by cytology, EM, and routine histology to correctly characterize this neoplasm. It is extremely important to correctly diagnose this indolent neoplasm due to the excellent prognosis with surgical resection.

Cantharidin-induced mitotic arrest is associated with the formation of aberrant mitotic spindles and lagging chromosomes resulting, in part, from the suppression of PP2Aalpha.

Cantharidin, a natural vesicant, inhibits the activity of several PPP family phosphatases, displays antitumor activity, and induces apoptosis in many types of tumor cells. However, the molecular mechanisms underlying the antitumor activity of cantharidin are not clear. Here, dose-response studies confirm a strong correlation between the suppression of phosphatase activity and cell death. Flow cytometry analysis indicates that before apoptosis, cantharidin delays cell cycle progression following DNA replication with no apparent effect on G(1)-S or S-G(2) phase progression. In contrast, studies with double thymidine-synchronized populations of cells indicate that cantharidin can rapidly arrest growth when added during G(2) or early M phase. Immunostaining indicates that cell cycle arrest occurs before the completion of mitosis and is associated with the appearance of aberrant mitotic spindles. Live cell imaging with time-lapse microscopy shows that cantharidin disrupts the metaphase alignment of chromosomes and produces a prolonged mitotic arrest, with the onset of apoptosis occurring before the onset of anaphase. To explore the contribution of individual phosphatases, antisense oligonucleotides and small interfering RNA were developed to suppress the expression of cantharidin-sensitive phosphatases. The suppression of PP2Aalpha, but not PP2Abeta, is sufficient to induce metaphase arrest, during which time lagging chromosomes are observed moving between the spindle poles and the metaphase plate. Immunostaining revealed slightly abnormal, yet predominately bipolar, mitotic spindles. Nonetheless, after a 10- to 15-hour delay, the cells enter anaphase, suggesting that an additional cantharidin-sensitive phosphatase is involved in the progression from metaphase into anaphase or to prevent the onset of apoptosis in cells arrested during mitosis.

Hypomelanosis of Ito associated with precocious puberty.

Hypomelanosis of Ito has been associated with precocious puberty in two cases. This study reports a third case involving a female with hypomelanosis of Ito including severe mental retardation and seizure disorder with autonomic symptoms (gastroesophageal reflux and asthma). At age 5 she developed vaginal discharge, thelarche, and adrenarche. Soon after, she died of pneumonia stemming from her neurologic deficits. A postmortem examination revealed normal gonads and endocrine organs. The breasts and vulva were prematurely developed. Central nervous system findings included megalencephaly, neuronal eosinophilic inclusions, leptomeningeal neuroglial heterotopias, and cortical dysplasia. Both previously reported cases of hypomelanosis of Ito associated with precocious puberty had abnormal gonads and responded to cyproterone acetate therapy, indicating a peripheral mechanism of precocious puberty (gonadotrophin-independent). The current case, which was autopsied, lacks significant gonadal pathology, and has extensive neurologic involvement that suggests that a central mechanism of precocious puberty (gonadotrophin-dependent) can also be associated with hypomelanosis of Ito.