The role of econazole in the management of oculomycosis

The possible role of econazole in the management of fungal eye infections is presented in this study. An animal model of oculomycosis was used to demonstrate the efficacy of econazole in an in vivo system both as a prophylactic and as a powerful therapeutic agent against sensitive fungal pathogens. In vitro tests on 114 ocular pathogenic fungal isolates exemplified the superiority of econazole to other available imidazoles.     

CD48 as a novel molecular target for antibody therapy in multiple myeloma

Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34(+) haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in-house anti-CD48 mAb induced mild antibody-dependent cell-mediated cytotoxicity and marked complement-dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti-CD48 mAb significantly inhibited tumour growth in severe combined immunodeficient mice inoculated subcutaneously with MM cells. Furthermore, anti-CD48 mAb treatment inhibited growth of MM cells transplanted directly into murine bone marrow. Finally and importantly, we demonstrated that the anti-CD48 mAb did not damage normal CD34(+) haematopoietic stem/progenitor cells. These results suggest that the anti-CD48 mAb has the potential to become an effective therapeutic mAb against MM.     

CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia

Permanent cure of acute myeloid leukemia (AML) by chemotherapy alone remains elusive for most patients because of the inability to effectively eradicate leukemic stem cells (LSCs), the self-renewing component of the leukemia. To develop therapies that effectively target LSC, one potential strategy is to identify cell surface markers that can distinguish LSC from normal hematopoietic stem cells (HSCs). In this study, we employ a signal sequence trap strategy to isolate cell surface molecules expressed on human AML-LSC and find that CD96, which is a member of the Ig gene superfamily, is a promising candidate as an LSC-specific antigen. FACS analysis demonstrates that CD96 is expressed on the majority of CD34(+)CD38(-) AML cells in many cases (74.0 +/- 25.3% in 19 of 29 cases), whereas only a few (4.9 +/- 1.6%) cells in the normal HSC-enriched population (Lin(-)CD34(+)CD38(-)CD90(+)) expressed CD96 weakly. To examine whether CD96(+) AML cells are enriched for LSC activity, we separated AML cells into CD96(+) and CD96(-) fractions and transplanted them into irradiated newborn Rag2(-/-) gamma(c)(-/-) mice. In four of five samples, only CD96(+) cells showed significant levels of engraftment in bone marrow of the recipient mice. These results demonstrate that CD96 is a cell surface marker present on many AML-LSC and may serve as an LSC-specific therapeutic target.     

A technique of tongue fixation after total mandibulectomy: the Oji spatula

When ameloblastoma presents late, as is often the case in Nigeria, it can affect the whole mandible. The treatment of choice is total mandibulectomy. The procedure may necessitate the resection of the musculature of the floor of the mouth to which a large portion of the tongue is attached. In our hospitals, immediate reconstruction is not undertaken for various reasons. Consequently, the musculature of the floor of the mouth cannot be reattached to a graft. The purpose of this paper is to illustrate a simple and patient-friendly method for fixation of the tongue after total mandibulectomy to achieve a secure airway. The tongue is tied to a wooden spatula, which stretches horizontally across the mouth. It is in contrast to the conventional technique of rigid fixation of the tongue to the pectoral muscle. This technique was used for 11 patients with large ameloblastomas. For the purpose of comparison, the conventional technique was used in 4 patients. The method of using a wooden spatula as a means of tongue fixation is known in the maxillofacial unit of the University of Nigeria Teaching Hospital, Enugu as the Oji spatula after the surgeon who developed it. All 11 patients tolerated this method well, but the 4 patients who had their tongues tied to the pectoral muscle complained of pain and discomfort. All the patients survived the procedure without postoperative blockage of the airway by the tongue. Follow-up for up to 6 months established that the patients had no respiratory problems.     

Prediction of Japanese cedar pollen emission in a snowy area--surveillance in Hirosaki City

Japanese cedar is the most common pollinosis allergen in Japan. Predictions of total pollen counts and the first 2 or more days of the Japanese cedar pollen season are beneficial to patients. We developed predictive methods for those 2 factors in Hirosaki. We conducted an atmospheric Japanese cedar pollen survey from 1996 to 2002 in Hirosaki and compared yearly data with the male flowering index counted in 50 cedar trees in the preceding autumn. The male flowering index correlated highly positively with total cedar pollen counts in regression analysis, indicating its usefulness in predicting total pollen counts. Although the number of days from January 1 to the first day of continuous pollen emission showed no correlation with the cumulative maximum temperature during these days, the number of days from the day of first detection of pollen emission (minimum of 1 particle per sq. cm) to the first day of continuous pollen emission correlated highly with the cumulative maximum temperature and cumulative amount of snowfall on these days, suggesting that it is possible to predict the first day of continuous pollen emission by the cumulated daily maximum temperature after the day of first detection of pollen emission.     

The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis.

The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless of disease subtypes. To characterize the expression pattern of WT1 during normal and neoplastic hematopoiesis, we generated a knock-in reporter green fluorescent protein (GFP) mouse (WT1(GFP/+)) and assayed for WT1 expression in normal and leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in none of the long-term (LT) hematopoietic stem cells (HSC) and very few (<1%) of the multipotent progenitor cells. In contrast, in murine leukemias induced by acute myeloid leukemia 1 (AML1)/ETO+TEL/PDGFbetaR or BCR/ABL, WT1 was expressed in 40.5 or 38.9% of immature c-kit(+)lin(-)Sca-1(+) (KLS) cells, which contained a subset, but not all, of transplantable leukemic stem cells (LSCs). WT1 expression was minimal in normal fetal liver HSCs and mobilized HSCs, both of which are stimulated for proliferation. In addition, overexpression of WT1 in HSCs did not result in proliferation or expansion of HSCs and their progeny in vivo. Thus, the mechanism by which expansion of WT1-expressing cells occurs in leukemia remains unclear. Nevertheless, our results demonstrate that the WT1(GFP/+) mouse is a powerful tool for analyzing WT1-expressing cells, and they highlight the potential of WT1, as a specific therapeutic target that is expressed in LSCs but not in normal HSCs.