The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis.

In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices to adhere to stroma. However, analyses of a potential role for hemidesmosomes and their components in mammary epithelial tissue morphogenesis have never been attempted. MCF-10A cells are a spontaneously immortalized line derived from mammary epithelium and possess a number of characteristics of normal mammary epithelial cells including expression of hemidesmosomal associated proteins such as the two bullous pemphigoid antigens, alpha 6 beta 4 integrin and its ligand laminin-5.

A population-based study of the usefulness of screening for neuroblastoma.

Background: Neuroblastoma has many characteristics which suggest that preclinical detection might improve outcome. The Quebec Neuroblastoma Screening Project was initiated to determine whether mass screening could reduce mortality in a large cohort of infants. As an early endpoint, we report whether screening could reduce the incidence of poor-prognosis neuroblastoma in children with advanced-stage disease over 1 year of age.

Molecular typing for investigating an outbreak of Candida krusei.

Invasive infections due to Candida krusei are often observed in immunocompromised patients who have received prior therapy with fluconazole, although infection has also occurred in patients in the absence of this antifungal agent. From August 25 through September 19, 1995, we identified four patients with C. krusei fungemia on our hematology/oncology unit.

Biological monitoring of workers' exposure to bromine.

The use of serum bromine concentration (SeBr) as a measure of exposure was examined in an occupational cohort. Associations with work site, department type, chemical handling, and occupation, as proxy measures of exposure, were studied. SeBr was associated with all of these measures.

Metastatic osteosarcoma of the kidney presenting as renal hemorrhage.

Purpose: Renal osteosarcoma may arise as a metastasis from a primary bone osteosarcoma or as a primary renal tumor. Metastatic renal osteosarcoma has been found at autopsy in approximately 10% of patients who die of this disease.

Patient And Methods: A case report of a young Chinese patient presenting with acute onset of renal infarction and hemorrhage from a renal metastasis of osteosarcoma is presented, as well as a review of the literature.

The monetary costs of childhood cancer to the families of patients.

The medical costs of cancer treatment are well described, but there are few reports of expenses incurred by families of children with malignant disease. The objective of this study was to describe the monetary costs borne by families of patients with childhood cancer and to determine whether these costs represent an important component of the burden of illness. Families completed a prospective diary survey about daily expenses incurred during each sample week of therapy.

Methylation of estrogen and progesterone receptor gene 5' CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors.

Hormonal factors have a profound influence on the development, treatment, and outcome of breast cancer. The absence of steroid hormone receptors is highly correlated with resistance to antihormonal treatments. Work in cultured human breast cancer cell lines has shown that the absence of estrogen receptor (ER) gene expression in ER- cells is associated with extensive methylation of the ER gene 5' CpG island, and treatment with agents that demethylate the ER gene CpG island results in the production of functional ER protein.

Stimulation and inhibition of human mammary epithelial cell duct morphogenesis in vitro.

We previously determined that normal human mammary epithelial cells (HMECs) placed on the basement membrane-like substance Matrigel form structures, whereas malignant breast cells do not (1). In the present study, we determined that the structures formed by normal cells on Matrigel resembled breast ducts in vivo by electron microscopy, and the process of their formation recapitulated what is known of duct formation in vivo. We therefore used this model to study less well-understood aspects of breast morphogenesis.

Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers.

Exposure to asbestos, particularly members of the amphibole subgroup (crocidolite, amosite), is associated with the development of malignant mesothelioma and lung cancer. Although management of asbestos in buildings and increased regulation of asbestos in workplace settings are viable approaches to the prevention of disease, the prognosis of asbestos-associated tumors is generally dismal. Moreover, although a vast amount of information is available on the responses of cells and tissues to fibers, understanding the pathogenesis of asbestos-associated malignancies is hampered by the complexity of and differences between various fiber types.

Preoperative strategies in the management of Wilms tumor.

Prenephrectomy therapy is well tolerated and results in easier operations, with significantly fewer tumor ruptures during surgery, and a favorable stage distribution as determined by the surgical specimen. As in other solid tumors of childhood, acceptable disease-free and actual survival figures with a minimum of early, intermediate, and late complications remain the aim of this strategy.

Expression of hemidesmosomes and component proteins is lost by invasive breast cancer cells.

Hemidesmosomes are multiprotein structures that attach basal cells of stratified epithelia to basement membranes. Although normal human breast epithelia are not stratified, we observed expression of electron-dense hemidesmosomes and hemidesmosome protein components by breast epithelial and myoepithelial cells at the basal lamina in vivo. Primary cultured normal human breast epithelial cells also contained hemidesmosomes and component proteins, and could be used as a model for hemidesmosome assembly and regulation.

Phytic acid, an iron chelator, attenuates pulmonary inflammation and fibrosis in rats after intratracheal instillation of asbestos.

Reactive oxygen species, especially iron-catalyzed hydroxyl radicals (.OH) are implicated in the pathogenesis of asbestos-induced pulmonary toxicity. We previously demonstrated that phytic acid, an iron chelator, reduces amosite asbestos-induced .

Free radical DNA adduct 8-OH-deoxyguanosine affects activity of Hpa II and Msp I restriction endonucleases.

8-OH-deoxyguanosine can diminish the ability of the restriction endonucleases Hpa II and Msp I to cleave DNA. The exact position of the adduct within the recognition site appears to determine the extent of the effect.

Hospice and palliative care: attitudes and practices of the physician faculty of an academic hospital.

It has been suggested that physicians, particularly in academic hospitals, are resistant to the hospice approach to palliative care for terminally ill patients. It is of interest, therefore, to assess the attitudes and practices of the physician faculty of an academic hospital where a hospice program has been in existence for more than 10 years. This was assessed with two faculty surveys.

[Retinopathy and serum uric acid in diabetics].

Low serum uric acid (UA) levels have been reported in diabetics. In a group followed for 15 years it was reported that low UA levels preceded the onset of diabetic retinopathy. We studied 95 consecutive diabetic clinic patients between July and September 1992.

DNA adduct 8-hydroxyl-2'-deoxyguanosine (8-hydroxyguanine) affects function of human DNA methyltransferase.

8-Hydroxyl-2'-deoxyguanosine (also referred to as 8-hydroxyguanine [8-OH-dG] or 7,8-dihydro-8-oxoguanine), a common DNA adduct resulting from injury to DNA via reactive oxygen species, affects the in vitro methylation of nearby cytosine moieties by the human DNA methyltransferase. The exact position of 8-OH-deoxyguanosine relative to a CpG dinucleotide appears important to this effect. Our data indicate that 8-OH-deoxyguanosine diminishes the ability of the methyltransferase to methylate a target cytosine when the 8-OH-deoxyguanosine is one or two nucleotides 3' from the cytosine, on the same strand.

Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma.

DEAD box proteins are putative RNA helicases that have been implicated in cellular processes involving alteration of RNA secondary structure, such as translation initiation and splicing. These proteins share eight conserved amino acid motifs, including Asp(D)-Glu-(E)-Ala(A)-Asp(D) which is part of a more extended motif. Recently, we have shown that the novel DDX1 gene containing a DEAD box motif maps to the same chromosome band as MYCN at 2p24 and is co-amplified with MYCN in retinoblastoma cell lines.

Sequential changes in serum iron and ferritin in patients undergoing high-dose chemotherapy and radiation with autologous bone marrow transplantation: possible implications for treatment related toxicity.

In an effort to define the pattern of iron flux during high-dose chemotherapy or chemo/radiotherapy, we prospectively measured serum iron, iron binding capacity, and ferritin in patients undergoing autologous bone marrow transplantation for various malignancies. Sequential measurement of serum iron from days -7 to +12 was carried out in 88 evaluable patients, and simultaneous measurement of iron, ferritin, and total iron binding capacity was carried out in 32 patients. We found that there was a predictable rise in serum iron on day -2 or -3, and that this was accompanied by an increase in the saturation of transferrin.

Asbestos causes DNA strand breaks in cultured pulmonary epithelial cells: role of iron-catalyzed free radicals.

Asbestos causes pulmonary fibrosis and various malignancies by mechanisms that remain uncertain. Reactive oxygen species in part cause asbestos toxicity. However, it is not known whether asbestos-induced free radical production causes alveolar epithelial cell (AEC) cytotoxicity by inducing DNA strand breaks (DNA-SB).

[Cost of insulin-dependent diabetes vs cost of its prevention].

Accumulating evidence suggests that insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease which can be predicted from immunologic markers. Encouraging results of recent IDDM prevention trials with insulin raises the question of cost benefit of such procedures, in addition to the obvious medical benefit. We estimated the expected cost benefit of national screening and preventive efforts in Israel (population 5 million in 1993).