Human LBP-32/MGR is a repressor of the P450scc in human choriocarcinoma cell line JEG-3.

Steroid hormones regulate a wide range of physiologic functions in humans. The cholesterol side-chain cleavage enzyme P450scc regulates the initial step of biosynthesis of all steroid hormones. We investigated the expression of P450scc by studying a potential regulator of P450scc, LBP-32/MGR. Using a Northern blot, we found that LBP-32/MGR mRNA was expressed mainly in the human placenta. Using radiation hybrid mapping, we identified LBP-32/MGR on human chromosome 2p25. Recombinant LBP-32/MGR protein bound preferentially to a DNA fragment from the promoter of P450scc in vitro and exhibited clear nuclear localization in transfected cells. Luciferase reporter gene assays showed that LBP-32/MGR specifically repressed transcriptional activation of the human P450scc promoter. Because placental P450scc expression is essential for pregnancy and steroid biosynthesis, the placental expression and transcriptional repressor activity of LBP-32/MGR in JEG-3 cells suggest it has a role as a transcriptional modulator of steroid biosynthesis.

Genomic cloning, mapping, structure and promoter analysis of HEADPIN, a serpin which is down-regulated in head and neck cancer cells.

Headpin is a novel serine proteinase inhibitor (serpin) that is down-regulated in squamous cell carcinoma of the oral cavity and in squamous cell carcinoma cell lines of the head and neck. Using a panel of 18q21.3 YAC clones, we mapped and cloned the HEADPIN gene. The gene spans 10 kb and is composed of eight exons and seven introns. The genomic structure is identical with some other ovalbumin serpins (ov-serpins) in terms of the numbers, position and phasing of the intron/exon boundaries. HEADPIN was mapped within the serpin cluster in 18q21.3 between MASPIN and SCCA2 as follows: cen-MASPIN-HEADPIN-SCCA2-SCCA1-tel. The transcription start site was determined and the promoter activity of the 5'-flanking region was analyzed. Luciferase promoter assays in HaCaT cells showed that the -432 to -144 nucleotide region has functional promoter activity. The activity of the promoter/enhancer was not observed in head and neck cancer cell lines TU167 and UMSCC1 which lack headpin expression. These data suggest that the differential expression of headpin in normal and carcinoma-derived cells is regulated at the transcriptional level. Understanding the genomic organization and transcriptional regulation of the ov-serpins clustered within 18q21. 3 provides a critical framework for assessing their potential role in cancer.

Sensitivity of human glioma and brain cells to natural killer cell lysis. Effects of serum concentration, epidermal growth factor, and time in culture.

Using an in vitro monolayer natural killer (NK) cytolysis assay, the authors examined the effects of serum concentration and epidermal growth factor (EGF) on sensitivity to NK cytolysis. It was found that target cells cultured in high concentrations of serum (10% fetal bovine serum (FBS)) had higher cytotoxicity levels than those in low serum concentrations (0% to 0.5% FBS). Exposure of target cells to EGF had no effect on their sensitivity to NK cytolysis. Both glioma cell lines showed decreased NK cell sensitivity with longer times in culture. The results of cytofluorometric studies on these cell lines indicate that the differences in NK cell sensitivity may reflect the growth fraction of the target population and that a population with a higher proportion of cycling cells is more susceptible to lysis by NK cells. Whether it is possible to separate the proliferative rate of these cells from their NK cell sensitivity is unknown, but worthy of consideration.

Malignant melanoma arising within a burn scar case report and review of the literature.

Burn scar carcinomas, also called Marjolin's ulcers, are uncommon tumors that arise from an antecedent burn. Most burn scar carcinomas are diagnosed about 30 years after the burn, and most are well-differentiated squamous cell carcinomas. We report a case in which a squamous cell carcinoma developed within a burn scar on the cheek and then a malignant melanoma arose within the burn scar after the squamous cell carcinoma had been excised. We also review the available literature on burn scar carcinoma, covering the demographics, pathogenesis, diagnosis, prognosis, and treatment of the disease. Given the multifocality of this disease process, we advocate aggressive resection of the entire burn scar, as well as the tumor, to prevent the development of further cancers within the wound.

Initial report of primary sinusitis caused by an atypical pathogen (Mycobacterium chelonae) in an immunocompetent adult.

Primary sinonasal infections caused by atypical mycobacteria are rare. In fact, only four examples of a primary nontuberculous mycobacterial etiology of paranasal sinusitis have been cited in the literature. The patients in all these cases were infected with the human immunodeficiency virus and, by definition, they all had acquired immunodeficiency syndrome. We present a report of an immunocompetent adult with a history of chronic sinusitis who consistently and repeatedly manifested a fast-growing, nonpigmented, atypical mycobacterium of the Runyon group IV category: Mycobacterium chelonae. The patient was successfully treated over a 3-year period with a combination of antimicrobial agents, multiple limited endoscopic sinus surgeries, and eventually a total globe-sparing maxillectomy. At this time, the patient is disease-free and has received no further treatment. This case represents the first report of an immunocompetent adult host with a primary atypical mycobacterial infection of the paranasal sinuses. It also demonstrates the multimodal nature of the treatment of atypical mycobacterial infections. We also discuss the Byzantine classification scheme relative to atypical mycobacteria, the disease process in the immunocompromised host, and the various treatment options.

Fungal sinusitis.

Primary and secondary fungal sinusitis occurring in the immunocompromised patient is well documented, yet the incidence of fungal paranasal sinus infections is being increasingly reported in the immunocompetent host. This article will focus on some of the general principles regarding fungal sinusitis while examining the currently accepted classifications and clinical significance of fungal sinusitis in the literature.

Congenital aural atresia.

Congenital aural atresia is viewed by many physicians as a poorly characterized, arcane, clinical entity associated with a variety of hearing deficits. In fact, congenital aural atresia represents a disease spectrum predicated on the reliable embryological development of the first and second branchial apparatus. All degrees of microtia, canal atresia, and middle ear structure malformation are identified by this disease process. Many classification schemata have been proffered since the turn of the century to assist the otologist with a better means of assessing the patient's suitability as a surgical candidate. Clinical, audiological, and radiographic evaluation of congenital aural atresia is essential in selecting the appropriate candidates for surgery or hearing amplification. The high resolution CT scan has advanced the understanding and preoperative assessment of this condition. Surgical repair of the external ear and middle ear malformations is effective in properly selected patients. Essential background information, relevant embryology, patient evaluation, treatment, and current controversies related to congenital aural atresia are discussed.

Pediatric maxillofacial fractures.

Maxillofacial trauma in the pediatric population is a relatively infrequent occurrence. Studies have demonstrated consistently that 5% of all facial fractures occur in children. The low percentage of facial fractures in this age group has been attributed, in part, to the lack of full pneumatization of the sinuses until later in childhood. Review of the literature indicates that boys are more commonly affected than girls and that the majority of pediatric facial fractures occur in children between 6 and 12 years of age. Motor vehicle accidents, falls, and blunt trauma are responsible for the largest number of pediatric facial fractures. The most common site of facial fracture is the nose and dentoalveolan complex, followed by the mandible, orbit, and midface in most pediatric cohorts. Management of the mandible is often conservative owing to the high percentage of isolated condylar fractures in children. Open reduction and internal fixation of pediatric facial fractures is indicated in complex mandible, midface, and orbital fractures. The effect of rigid fixation on facial skeleton growth is not completely understood.

Increased mitochondrial DNA induces acquired docetaxel resistance in head and neck cancer cells.

Docetaxel is one of the most effective chemotherapeutic agents against cancer; nevertheless, some patients develop resistance. Unfortunately, their causes and mechanisms remain unknown. We created docetaxel-resistant DRHEp2 from human laryngeal cancer HEp2 and investigated the roles of mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) on docetaxel resistance. DRHEp2 had greatly increased mtDNA content. Reduction of mtDNA content in DRHEp2 by ethidium bromide treatment reduced the resistance. These results indicate the possible roles of mtDNA-coded enzymes in mitochondrial respiratory chain (MRC) in resistant mechanisms. Oligomycin A, an Fo-ATPase inhibitor, eliminated docetaxel resistance in DRHEp2; in contrast, inhibitors of other MRC did not. RNA interference targeted to Fo-ATPase d-subunit restored docetaxel-induced cytotoxicity to DRHEp2. These results indicate the roles of Fo-ATPase for resistant mechanisms. Docetaxel induced ROS generation in HEp2 but not in DRHEp2 and antioxidant pyrrolidine dithiocarbamate eliminated docetaxel-induced cytotoxicity, suggesting roles of ROS in docetaxel-induced cell death. Furthermore, inhibition of Fo-ATPase by Oligomycin A induced docetaxel-mediated ROS generation in DRHEp2. Taken together, DRHEp2 acquired docetaxel resistance through increasing Fo-ATPase, which led to diminish docetaxel-induced ROS generation and subsequently inhibited cell death. In conclusion, mtDNA plays an important role in developing docetaxel resistance through the reduction of ROS generation by regulating Fo-ATPase.

LDL accumulation in the grossly normal human iliac bifurcation and common iliac arteries.

We had previously used an electrophoretic transfer procedure to determine the topographic distribution of low density lipoprotein (LDL) accumulation in the aortic intima of normolipemic swine. In this present study we have employed a similar procedure to assess whether LDL-rich sites consistently demonstrate increased intimal thickening at the iliac bifurcation and common iliac arteries. The topographic distribution of LDL-rich sites was determined in the aortas of six subjects ranging in age from 16 to 36 years, by transferring LDL by electrophoresis from the tissue into an agarose gel containing anti-LDL, and then staining the immunofixed LDL in the gel for lipid. LDL-rich sites were found in all but two of these cases. On the basis of control studies establishing the level of nonspecific staining, we determined that the cutoff between LDL-rich and LDL-poor zones was 37 mg apoB protein/mm2 intimal surface area. Intimal thickening was found to be threefold greater in LDL-rich than in LDL-poor regions. These results confirm and extend earlier immunohistochemical studies suggesting a preferential accumulation of LDL at sites of intimal thickening in human arteries.

Neutral glycolipid composition of primary human brain tumors.

Neutral glycolipids (NGL) were isolated and quantitated in 98 primary human brain tumors; 19 low grade astrocytomas (LGA), 12 anaplastic astrocytomas (AA), 37 high grade astrocytomas (HGA), 18 oligodendroglial tumors, and 12 primitive neuroectodermal tumors (PNET). In 38 of these, the nature of the hexose in the cerebroside was determined using immunothin-layer chromatographic techniques. Galactosylceramide (GalCer) was the major ceramide monohexoside (CMH), and glucosylcerebroside never comprised more than 6% of this fraction in any tumor type. Furthermore, there was no correlation between the proportion of glucosylcerebroside and histological diagnosis. AA had the most characteristic neutral glycolipid pattern, with high levels of total lipid, total neutral glycolipid, CMH, and ceramide dihexoside (CDH) but low water contents. Consistent with this glycolipid composition is the finding that AA usually had neither ceramide trihexoside (CTH) nor globoside. Oligodendrogliomas were somewhat similar to AA in having high levels of CMH and infrequently having CTH or globoside. However, oligodendrogliomas had low water and total lipid contents. PNET had low levels of total lipid, total NGL, and CMH, but frequently contained CTH and globoside. LGA had high water contents but low levels of total lipid and CMH. HGA tended to have intermediate levels of almost all constituents analyzed, probably reflecting the pronounced cellular heterogeneity of these tumors. The frequent presence of GalCer in astrocytomas raises the possibility that some of these contain a population of cells that are related to the oligodendroglial lineage. However, the low amounts of GalCer and infrequent presence of sulfatide in PNET is consistent with their lack of differentiation toward oligodendrocytes. It will be of interest to determine if the neutral glycolipid patterns reported here will correlate with patient survival and be of prognostic significance.

Pesquisa do programa nacional de incentivo ao aleitamento materno. 1a.parte: Entrevistas com maes. / Research of the incentive national program of breast feeding. 1st Part: Interviews with mothers

Os resultados deste estudo serao publicados em tres documentos. O primeiro, resumido, e este, que corresponde as entrevistas com maes. Etapa I - Foi analisada a situacao do aleitamento materno em Sao Paulo e Recife metropolitanos. Entrevistaram-se 1.000 mulheres e os resultados mostram um desmame muito precoce, a maioria antes de um mes de idade, sendo introduzida cedo a mamadeira. As maes nao recebem informacoes sobre aleitamento materno. Analisou-se a opiniao das maes para parar ou continuar amamentando e os fatores que influenciam uma amamentacao mais prolongada. Entre eles destacam-se: introducao tardia da mamadeira, mamadas noturnas, informacoes sobre aleitamento materno recebidas pelas maes e outras

Pesquisa do Progama Nacional de Incentivo ao Aleitamento Materno. 2a.Parte: entrevistas com profissionais de saude e centros de saude. / Research the National Program for Breast Feeding Promotion. 2a. Part: interviews with health personnal and health centers

Pretende-se conhecer as condicoes do sistema de saude e dos profissionais de saude que influenciam o comportamento das mulheres quanto a amamentacao. Foram entrevistados 105 servicos de saude materno-infantil e 200 profissionais. Entre os resultados fica claro o desinteresse generalizado dos profissionais sobre a atualizacao cientifica quanto a amamentacao.No pre-natal tem-se omitido completamente o assunto amamentacao e a postura antialojamento conjunto e grande entre os administradores das maternidades. Nos servicos de puericultura o pessoal auxiliar desconhece conceitos de prevencao e nao sabe orientar sobre as intercorrencias comuns da lactacao. A presenca da industria de alimentos substitutos do leite materno e clara sobre os servicios infantis e o pediatra