Modeling the initiation of Ewing sarcoma tumorigenesis in differentiating human embryonic stem cells.

Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. However, despite the well-established role of EWS-FLI1 in tumor initiation, the development of models of Ewing sarcoma in human cells with defined genetic elements has been challenging. Here, we report a novel approach to model the initiation of Ewing sarcoma tumorigenesis that exploits the developmental and pluripotent potential of human embryonic stem cells. The inducible expression of EWS-FLI1 in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. Furthermore, these cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth, which is a hallmark of Ewing sarcoma tumors.

An evaluation of efficacy of ultrasonography in the diagnosis of head and neck swellings.

OBJECTIVE: The aim of this study was to evaluate the efficacy of ultrasonography in the diagnosis of swellings in the head and neck regions. METHODS: For this study, 70 cases with clinically obvious swellings in head and neck regions were selected randomly. The ultrasonographic features considered were shape, boundary, echo intensity, ultrasound architecture of lesion, posterior echoes and ultrasound characteristic of tissues. Intergroup comparisons were made between four different types of swellings: inflammatory; cystic; benign; and malignant. RESULTS: A comparison was made between benign and malignant neoplasms, and the criteria of boundary, echo intensity and ultrasound architecture of lesions are statistically significant as the P-value is <0.05. The comparison of inflammatory swellings and malignant neoplasms shows that criteria of boundary and ultrasound architecture of lesions are statistically significant. The comparison of cystic swellings and benign neoplasms concluded that only the criterion of ultrasound characteristics of tissues is statistically significant. The comparison of inflammatory swellings and benign neoplasms shows that the criteria of boundary and echo intensity are statistically significant. The comparison of inflammatory swellings and cystic swellings concluded that the criteria of boundary, shape, echo intensity, posterior echoes and ultrasound characteristics of tissues are statistically significant. The comparison of cystic swellings and malignant neoplasms concluded that the criteria of ultrasonography, boundary, shape, echo intensity, ultrasound architecture of lesion, posterior echoes and ultrasound characteristics of tissues are statistically significant as the P-value is <0.05. CONCLUSION: It can be concluded that clinical diagnosis had a sensitivity and accuracy of 85.7% and ultrasonographic diagnosis had a sensitivity and accuracy of 98.5%.

Rapidly maturing juvenile ossifying fibroma: a case report.

This report describes an unusual case of juvenile ossifying fibroma (JOF) in a 16-year-old female patient with a clinical presentation of a single large, well-circumscribed swelling on left side of the palate. Ossifying fibromas are normally slow growing benign lesions. Radiographically they can present as radiolucent, mixed or radiopaque lesions depending on the degree of maturity. A period of at least 6 years is required for the lesion to pass from the radiolucent to radiopaque stage. All previously reported cases of JOF have been either radiolucent or mixed density lesions, but our case is unusual because the lesion had shown apparently rapid transformation into an almost complete radiopaque stage at a very early age.

Oral health status and alveolar bone loss in treated leprosy patients of central India.

A descriptive cross sectional study was carried out, in a group of 160 leprosy patients treated with multi drug therapy. The patients with age group of 25 to 60 year were considered. Out of 160 patients 50 patients were selected by simple random sampling technique for radiological assessments. Intra-oral periapical radiographs (6 for each patient) were taken. The paralleling long cone technique was used and radiographs were attached with grids so as to enable measuring the bone height. The grid was spaced in 1 mm marking and placed directly over the film. Clinical examination revealed that Prevalence of dental caries was 76.25% and periodontal disease was 78.75%. Mean DMFT score was 2.26. Mean OHI-S score was 3.50. Score for Gingival index was 1.60 and average loss of gingival attachment was 1.2 mm. Radiographic findings showed mean alveolar bone loss in maxillary anterior region to be 5.05 mm and in maxillary posterior region it was 4.92 mm. Alveolar bone loss in mandibular anterior region was 4.35 mm and in mandibular posterior region was 5.14 mm. Overall Dental Health Status of the leprosy patients was poor and needed more attention for dental care. There was also an increase in the alveolar bone loss, which was generalized. This bone loss could be due to advance stage of the disease or late approach to rehabilitation center, these patients also had peripheral neuropathy leading to hand and feet deformity in the form of claw hand or ulcer on hand, making maintenance of oral hygiene difficult.

Comparative evaluation of gustatory function between postmenopausal women and age-matched men.

OBJECTIVE: The aim of the study was to compare the gustatory function between postmenopausal women and age-matched men. SUBJECTS AND METHODS: During a period of 4 months, 30 postmenopausal women and 30 age-matched men were prospectively evaluated for gustatory function. Each subject was given a symptoms questionnaire for self-assessment of taste function. Then, whole mouth taste test was performed in which the quality identification and intensity ratings of taste solutions were measured. RESULTS: Regarding correct quality identification, the results were statistically non-significant (P > 0.05). As far as the intensity judgments are concerned, significant difference exists between postmenopausal women and age-matched men. Intensity of taste perception for sucrose was significantly lower in postmenopausal women than intensity of taste perception for other tastes (P < 0.05). One of the noticeable findings is that 15 (50%) postmenopausal women reported a change in dietary habits; all expressed liking for sweeter food. CONCLUSION: Postmenopausal women appeared to have a reduced perception of sucrose, which can alter eating habits, such as intake of more sweet foods, whereas no significant difference is observed in taste perception of NaCl, citric acid and quinine hydrochloride between postmenopausal women and age-matched men. Fifteen (50%) postmenopausal women stated fondness for sweet taste.

Orofacial lesions in treated central Indian leprosy patients: a cross sectional study with review of literature.

OBJECTIVE: The goal of this study was to evaluate the orofacial lesions in treated leprosy patients. PATIENTS AND METHODS: 160 treated patients at Maharogi Seva Samithi, Warora were examined clinically. RESULTS: Of 160 patients studied, 140 (87.5%) was of lepromatous types, 100 patients presented with depressed nasal bridge, 64 presented with hypopigmented macules on face. Intraoral examination revealed tongue abnormalities as a most common finding, with fissured tongue being the commonest feature. CONCLUSION: We conclude that though active lesions of leprosy are not present, manifestations such as fissured tongue may remain in treated leprosy patients.

Deposition of salicylic acid into hamster sebaceous.

In an earlier paper, we identified vehicles that are miscible with sebum, using differential scanning calorimetry (DSC). In this paper, the potential of these vehicles to deliver salicylic acid (SA) into the sebum-filled follicles of hamster ears is examined. The main objective of this study is to correlate the melting transitions of a model sebum with the follicular delivery of SA, using two different types of vehicles (fatty and polar). Generally, the fatty vehicles show higher deposition than the polar vehicles. Follicular delivery of salicylic acid correlates well with its solubility in the respective vehicles. This extent of deposition also shows a relationship with the effect of the vehicle on thermal behavior of the model sebum. The nature of the relationship depends on the vehicle (polar or fatty) tested. We conclude that DSC could be used to identify appropriate vehicles for drugs whose follicular delivery depends on solubility. The results also suggest that delivery into the sebaceous glands occurs by two different mechanisms, depending upon the polarity of the vehicle and the physicochemical properties of the drug. The results of these experiments are further extended to investigate follicular delivery of SA from two different types of oil-in-water emulsion formulations. From these studies we conclude that either increasing the volume of the oil phase or changing the emulsion to a water-in-oil emulsion would increase follicular deposition. Our research highlights the role of sebum, its compatibility with drug molecules, and vehicle selection in the transport of drugs into the follicles. The overall results of these experiments provide a reasonable understanding of the mechanisms underlying the transport of drugs to, and subsequently through, the sebaceous follicle.

Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts.

CPT-11, a DNA topoisomerase I inhibitor, has demonstrated clinical activity in colorectal cancer. Flavopiridol, a cyclin-dependent kinase inhibitor, is rapidly emerging as a chemotherapy modulator. To enhance the therapeutic index of CPT-11 in colon cancer, we studied the combination of these two drugs in relatively resistant human colon cancer cells, Hct116. Exposure of parental Hct116 cells to clinically achievable concentrations of SN-38 (the active metabolite of CPT-11) induces p21 and a G(2) arrest. However, these conditions fail to induce apoptosis. In contrast, Hct116 cells that are p21 deficient (p21-/- Hct116) readily undergo apoptosis after treatment with SN-38. In this study we show that the parental Hct116 cells can be sensitized to undergo apoptosis by the addition of flavopiridol after SN-38 treatment. The induction of apoptosis was greatest with sequential therapy consisting of SN-38 followed by flavopiridol. Clonogenic assays also showed greatest inhibition with this sequence. Sequential treatment with SN-38 followed by flavopiridol was associated with higher activation of caspase-3 and greater cleavage of both p21 and XIAP, an inhibitor of apoptosis, compared with other treatment schedules. CPT-11 induced some tumor regressions but no complete responses in the p21-intact Hct116 xenografts. CPT-11 with flavopiridol more than doubled tumor regression, compared with CPT-11 alone, and produced a 30% complete response rate. Our studies indicate that CPT-11 induces cell cycle arrest rather than cell death and that flavopiridol, by activating the caspase cascade, cleaves the inhibitors of apoptosis and sensitizes the cells to undergo cell death. Thus, flavopiridol combined with CPT-11 may provide a completely new therapeutic approach in the treatment of colon cancer.

Flavopiridol increases sensitization to gemcitabine in human gastrointestinal cancer cell lines and correlates with down-regulation of ribonucleotide reductase M2 subunit.

As a single agent, gemcitabine (2',2'-difluorodeoxycytidine) has shown minimal activity against gastrointestinal malignancies with only a modest improvement in survival in patients with pancreatic cancer. Recently, gemcitabine resistance has been associated with the up-regulation of mRNA and protein levels of the ribonucleotide reductase M2 subunit (RR-M2), a rate-limiting enzyme in DNA synthesis that is cell cycle regulated. In this study we show that flavopiridol, a cyclin-dependent kinase inhibitor, enhances the induction of apoptosis by gemcitabine in human pancreatic, gastric, and colon cancer cell lines. As determined by quantitative fluorescence microscopy, flavopiridol enhanced gemcitabine-induced apoptosis 10-15-fold in all of the cell lines tested in a sequence-dependent manner. This was confirmed by poly(ADP-ribose) polymerase cleavage and mitochondrial cytochrome c release. Colony formation assays confirmed the apoptotic rates, showing complete suppression of colony formation only after exposure to sequential treatment of G(24)-->F(24). This is associated with suppression of the RR-M2 protein. This appears to be related to down-regulation of E2F-1, a transcription factor that regulates RR-M2 transcription and hypophosphorylation of pRb. The proteasome inhibitor PS-341 could restore the protein levels of E2F-1 in G(24)-->F(24) treatment indicating that E2F-1 down-regulation is attributable to its increased degradation via ubiquitin-proteasome pathway. This also resulted in restoration of RR-M2 mRNA and protein. These results indicate that flavopiridol in gemcitabine-treated cells inhibits parts of the machinery necessary for the transcription induction of RR-M2. Thus, combining flavopiridol with gemcitabine may provide an important and novel new means of enhancing the efficacy of gemcitabine in the treatment of gastrointestinal cancers.

Differential scanning calorimetry studies of sebum models.

Human sebum is a mixture of triglycerides, fatty acids, wax esters, squalene, cholesterol, and cholesterol esters. P. acnes, a bacterium that is normally found on the skin, hydrolyzes certain triglycerides to fatty acids, thereby changing the sebum composition. The objective of this study was to examine the physical state of a model sebum and the effect of variations in its composition on its physical properties including (a) the carbon chain length of the components, (b) the ratio of unsaturated to saturated components, and (c) the ratio of triglycerides to fatty acids. A model sebum mixture was prepared based on a composition reported in the literature and evaluated by differential scanning calorimetry (DSC). Since cholesterol and cholesterol esters contribute insignificantly to sebum composition, they were not included. Squalene was kept constant (13%), while the concentration of the rest of the components was varied. Variations of sebum were prepared by dissolving all components in a 3:1 chloroform-methanol mixture for uniformity. Subsequently the solvent was evaporated at room temperature. The samples were then analyzed using DSC. Four distinct endotherms (namely, Mp-1, Mp-2, Mp-3, and Mp-4) were observed between -50 degrees C and 100 degrees C. Mp-1 and Mp-2 occurred below 0 degrees C and were contributed by unsaturated components. Mp-3 and Mp-4, which represent the saturated components, occurred above 30 degrees C. Thus, at normal skin temperature (skin surface temperature is 32 degrees C), sebum contains both a solid and a liquid phase. All the transition temperatures increased with an increase in carbon chain length for the same ratio of unsaturation to saturation. A replacement of unsaturated components with corresponding saturated components led to a decrease in the transition temperatures for the former (Mp-1 and Mp-2) and an increase in the transition temperatures for the latter (Mp-3 and Mp-4). Replacement of triglycerides with corresponding fatty acids (mimicking the action of anaerobic bacteria) caused an increase in Mp-2 and a decrease in Mp-4. In all cases, the final melting temperature (Mp-4) was greater than the temperature of the human skin surface (32 degrees C); thus components contributing to these endotherms are still solids at skin temperature. All variations in the sebum model led to mixtures of solids and liquids at skin temperature. Considering a reduction in Mp-3 and/or Mp-4 to represent sebum "fluidization," it was achieved by a decrease in carbon chain length, an increase in unsaturation, or a substitution of triglycerides by corresponding fatty acids. Preferential enrichment with the saturated species will lead to enrichment of solids versus liquids in the sebum, presumably making it difficult for the liquid phase to dissolve the solids. It seems plausible that perturbation of the balance of solid and liquid components of sebum, such as by P. acnes action, may lead to blockage of the follicle. Future research will investigate strategies to dissolve and/or liquify the solid phase of sebum.

Huanglian, A chinese herbal extract, inhibits cell growth by suppressing the expression of cyclin B1 and inhibiting CDC2 kinase activity in human cancer cells.

Huanglian is an herb that is widely used in China for the treatment of gastroenteritis. We elected to determine whether huanglian could inhibit tumor cell growth by modulating molecular events directly associated with the cell cycle. Huanglian inhibited tumor growth and colony formation of gastric, colon, and breast cancer cell lines in a time- and dose-dependent manner. Cell growth was completely inhibited after 3 days of continuous drug exposure to 10 microg/ml of herb. This degree of growth inhibition was significantly greater than that observed with berberine, the major constituent of the herb. The inhibition of cell growth by huanglian was associated with up to 8-fold suppression of cyclin B1 protein. This resulted in complete inhibition of cdc2 kinase activity and accumulation of cells in G(2). The mRNA expression of cyclin B1 was not changed after huanglian treatment. There was no change in the protein expression of cyclins A or E. Therefore, the effect of huanglian on inhibiting tumor growth seems to be mediated by the selective suppression of cyclin B1, which results in the inhibition of cdc2 kinase activity. Inhibition of cyclin dependent kinase (cdk) activity is emerging as an attractive target for cancer chemotherapy. Huanglian represents a class of agents that can inhibit tumor cell growth by directly suppressing the expression of a cyclin subunit that is critical for cell cycle progression. These results indicate that traditional Chinese herbs may represent a new source of agents designed for selective inhibition of cyclin dependent kinases in cancer therapy.

The in vivo effect of bryostatin-1 on paclitaxel-induced tumor growth, mitotic entry, and blood flow.

Pretreatment of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1 enhances the cytotoxicity of most chemotherapeutic agents. However, in the case of paclitaxel, this effect has been shown in vitro to be best achieved when bryostatin-1 follows (rather than precedes) paclitaxel treatment. With combination trials of bryostatin-1 and paclitaxel planned for clinical trials and with only in vitro data available regarding drug sequence, we elected to undertake an in vivo study evaluating the effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing mouse model and to correlate this effect to cell cycle events, tumor metabolism, and tumor blood flow. At the maximum tolerated i.p. dose, bryostatin-1 at 80 microg/kg resulted in a small but significant increase in tumor doubling time (4.2 +/- 0.3 days) compared with control tumors (3.0 +/- 0.3 days; P < 0.01). Mice treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every 12 h for three doses, weekly for 3 weeks, had a tumor doubling time of 23.4 +/- 1.7 days. Mice pretreated with i.p. bryostatin-1 (80 microg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg every 12h for three doses) weekly for 3 weeks had a tumor doubling time of 9.7 +/- 1.1 days. This was significantly less (P < .001) than paclitaxel alone, which indicated an inhibitory effect by bryostatin-1 on paclitaxel therapy. In comparison, tumor-bearing mice that were treated with the same dose but with the sequence of paclitaxel followed by bryostatin-1 had a tumor doubling time of 29.6 +/- 0.6 days. This was significantly greater than the tumor doubling times for any condition tested (P < 0.01), demonstrating the sequence dependence of this combination. The efficacy of paclitaxel is dependent on mitotic entry, a step that requires activation of p34cdc2 kinase activity. Treatment with paclitaxel in vivo increased p34 cdc2 kinase activity in the mouse mammary tumors, whereas administration of bryostatin-1 before paclitaxel prevented the p34cdc2 kinase activation by paclitaxel. This was further evaluated in vitro by flow cytometry in MKN-74 human gastric cancer cells. As determined by MPM-2 labeling, which identifies cells in mitosis, pretreatment with bryostatin-1 prevented paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been reported to induce changes in muscle metabolism and to decrease muscle blood flow. These events could impact on the interaction of bryostatin-1 with paclitaxel. Using proton-decoupled phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy in vivo, bryostatin-1 at 80 micro1g/kg induced a decrease in both intratumoral pH and high-energy phosphates. In vivo perfusion studies, using dynamic enhanced NMR imaging with gadolinium diethylenetriamine pentaacetic acid, also demonstrated decreased tumor blood flow. These studies suggest that the inhibition of tumor response to paclitaxel by bryostatin-1 is multifactorial and includes such diverse factors as inhibition of cell entry into mitosis, a decrease in pH and energy metabolism, and a decrease in tumor blood flow. These results indicate that, as this combination enters Phase I clinical trials, the sequence of paclitaxel followed by bryostatin-1 will be critical in the clinical trial design.

Flavopiridol, a cyclin-dependent kinase inhibitor, prevents spindle inhibitor-induced endoreduplication in human cancer cells.

Defects in cell cycle checkpoints can lead to chromosome abnormality, aneuploidy, and genomic instability, all of which can contribute to tumorigenesis. Recent studies and data presented in this study indicate that cells with compromised G1 checkpoint endoreduplicate and become polyploid in response to microtubule inhibitors. Previous studies have shown that polyploid cells are unstable and lose chromosomes randomly to give aneuploidy. In this study, we show that endoreduplication and polyploidation can be prevented by inhibiting the cyclin-dependent kinases (Cdks) by flavopiridol, a synthetic flavone presently undergoing phase II clinical trials. In our initial studies, we treated MCF-7 cells with paclitaxel, which results in the arrest of cells in G1 with 4n DNA content (pseudo G1). This was coincident with increased p53 and p21 protein expression and decreased cyclin E/Cdk2 kinase activity. In contrast, G1 checkpoint-compromised MDA-MB-468 (p53-/- and pRb-/-) and p21-/- HCT116 do not arrest in the pseudo G1 state after exposure to microtubule inhibitors and enter in the S phase with 4n DNA content. More than 60% of MDA-MB-468 cells accumulate with >4n DNA content after 72 h of nocodazole treatment. The MPM-2 labeling showed that 8n cells also undergo mitosis. These cells display deregulated and persistent activation of cyclin E/Cdk2 and cyclin B1/cdc2 kinase activity. Administration of flavopiridol after mitotic block results in the arrest of cells in the pseudo G1 state and the dramatic decrease in cells containing >4n DNA content in MDA-MB-468 cells. The cyclin E/Cdk2 and cyclin B1/cdc2 kinase activities remained low after exit from mitosis. Furthermore, pRb was hypophosphorylated after the addition of flavopiridol in p21-deficient HCT116 cells, indicating the arrest of cells at the pseudo G1 state. Based on these studies, we propose that flavopiridol preserves the genomic stability by preventing endoreduplication and polyploidy and thus has the potential to be used as a chemopreventive agent to prevent the occurrence of neoplasia.

Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells.

Although in the past 10 years paclitaxel has emerged as a successful drug in cancer therapy, the overall response rate to this drug in patients with advanced metastatic disease remains low. Therefore, an understanding of the mechanism of the effect of paclitaxel on inducing apoptosis and the discovery of new ways to enhance the effect of paclitaxel will be critical to improving the therapeutic efficiency of this drug. In the present studies, we have determined that the cyclin-dependent kinase inhibitor flavopiridol significantly enhances paclitaxel-induced apoptosis in the human gastric and breast cancer cell lines MKN-74 and MCF-7. Flavopiridol enhances paclitaxel-induced apoptosis only when administered after paclitaxel treatment. The activation of caspases, specifically caspase 3, is enhanced by flavopiridol on paclitaxel-treated cells. In accordance with this, poly(ADP-ribose) polymerase cleavage is enhanced in combination therapy relative to single-agent paclitaxel. The induction of apoptosis, activation of caspase 3, and poly(ADP-ribose) polymerase cleavage in treatment regimens with paclitaxel and paclitaxel followed by flavopiridol were reversed by treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, which supports the notion that caspases are the executioners of apoptosis in these processes. Paclitaxel alone causes transient mitotic arrest with activation of cdc-2 kinase. Cells exit mitosis in a specific time window without cytokinesis, with a decrease in cdc-2 kinase activity and MPM-2 labeling. Flavopiridol accelerates the mitotic exit when administered after paclitaxel treatment in association with a more rapid decrease in MPM-2 labeling. In contrast, pretreatment with flavopiridol prevents cells from entering mitosis by inhibiting cdc-2 kinase activity, thus antagonizing the paclitaxel effect. Therefore, in this study we show that potentiation of paclitaxel-induced apoptosis by flavopiridol is highly sequence dependent, such that mitotic entry and cdc-2 kinase activation by paclitaxel must precede flavopiridol therapy, and the synergistic effect of flavopiridol on paclitaxel-treated cells is due to enhancement in caspase activation.

Role of the transcription factor AP-1 in melanoma differentiation (review).

Although the molecular details remain to be elucidated, temporal changes in gene expression that result in discrete biochemical alterations and growth arrest are primary determinants of terminal cell differentiation. The control of gene expression is inextricably associated with proteins that can initiate or inhibit gene transcription. Specific genes contain within their promoter regions, DNA sequences that permit the binding of transactivating and transinhibiting proteins that can initiate or suppress transcription, respectively. Activating protein-1 (AP-1), a dimeric complex consisting of proteins encoded by the Jun and Fos gene families, is a transcription factor induced by a variety of signals, including those eliciting proliferation, differentiation and programmed cell death (apoptosis). We presently review the potential role of AP-1 proteins in differentiation with specific emphasis on melanoma differentiation.

Mouse surfactant protein-D. cDNA cloning, characterization, and gene localization to chromosome 14.

Surfactant protein-D (SP-D) is a collectin found associated with surfactant in the lung. SP-D has also been functionally characterized as an opsonin for diverse microorganisms and a chemoattractant for phagocytic cells. To determine the structure of mouse SP-D, we isolated and characterized clones from a B6/CBAF1J strain lung cDNA library using a PCR-derived genomic probe. The deduced sequence predicts a 19-amino acid signal sequence, a 25-amino acid long NH2 terminus with two cysteines, followed by an uninterrupted collagen domain with 59 Gly-X-Y repeats. Next, a short "neck" domain of 28 amino acids, with a potential to form trimeric alpha-helical coiled coil is found ending in a COOH-terminal 125-amino acid carbohydrate recognition domain. The mature mouse SP-D protein of 355 amino acids shows strong homology to rat (92% identity), human (76%), and bovine (72%) SP-D amino acid sequences. Northern blot and RT-PCR analysis revealed that the mouse SP-D gene is expressed predominantly in lung and, surprisingly, also in heart, stomach, and kidney but not in brain. In contrast, mouse surfactant protein-A (SP-A) mRNA expression was found to be restricted to lung. Human lung and stomach, but not heart or liver, were found to express SP-D mRNA, as determined by PCR. The mouse SP-D gene (Sftp4) has been localized to chromosome 14 (to a region syntenic to human chromosome 10), closely linked to the genes for other collagenous lectins, mannose-binding protein-A (MbI1), and SP-A (Sftp1).

Steroid injection versus conservative treatment of anisometropia amblyopia in juvenile adnexal hemangioma.

Because of serious side effects, the indications for intralesional steroid injection of adnexal hemangiomas are unclear. Of 23 children with such lesions who were examined over a period of 9 years, 9 had no evidence of amblyopia and needed no intervention. Five required steroids intralesionally and/or systemically because of threatened occlusion of the pupillary axis. The remaining 9 were considered at risk of anisometropic amblyopia because of induced astigmatism: 5 received injections and 4 were treated with glasses and/or patching alone. The visual, refractive, and cosmetic results of the injected and conservatively managed anisometropes were similar. We recommend that steroid injection be reserved for patients with threatened occlusion of the visual axis and for those with severe astigmatism or amblyopia refractory to conservative management.