Multiple brain abscesses caused by Salmonella enteritidis in a neonate: successful treatment with ciprofloxacin.
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Brain Abscess↗
Biomedical subjects
L Thomas
Publications and source records attributed to L Thomas.
Migration of human melanoma cells on hyaluronate is related to CD44 expression.
Phenotypic and functional aspects of melanoma-hyaluronate interactions were investigated by studying the expression of CD44, cell migration, and transmembrane penetration of human melanoma cell lines on hyaluronate-coated substrates. Expression of CD44 was tested by flow cytometry on seven human melanoma cell lines. Strong reactivity with anti-CD44 monoclonal antibody was observed in four of seven of the cell lines. Migration studies of CD44(+) cell lines on hyaluronic acid- and chondroitin-6-sulfate-coated substrates, using time-lapse video-microscopy, showed a dramatic dose-dependent increase in migration rate on hyaluronate but not on chondroitin-6-sulfate. Moreover, CD44(-) cell lines showed no modification in migration rate on either substrate. Addition of soluble hyaluronate produced a dose-dependent inhibition of acceleration of CD44(+)cells on hyaluronate-coated substrates, whereas addition of chondroitin-6-sulfate had no effect. Migration inhibition experiments with soluble CD44 (CD44 receptor globulin) also showed specific blocking of the migration of CD44(+) cells on hyaluronate. Haptotactic invasion was increased in CD44(+) cell lines through hyaluronate-coated polycarbonate membranes, whereas no change was detected on chondroitin-6-sulfate-coated membranes. CD44(-) cell lines showed no response to either type of coating. In the melanoma cell lines tested, the expression of CD44 correlated with in vitro migration and invasiveness on hyaluronate substrates. Taken together, our data are consistent with the suggestion that CD44 may play a role in stimulating in vivo aggressiveness of tumors through hyaluronate-rich stroma.
Cell Movement↗
Role of integrin alpha 2 beta 1 (VLA-2) in the migration of human melanoma cells on laminin and type IV collagen.
The random cell migration of four human melanoma cell lines on laminin and type IV collagen-coated substrates was studied by video time-lapse image analysis and compared to the expression of a number of beta 1 integrins including alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1 using flow cytometry. These integrins were heterogeneously expressed in the four cell lines tested with three of four lines expressing alpha 2 beta 1. The melanoma cell line that did not express alpha 2 beta 1 exhibited weak attachment and low cell migration rate on both laminin and type IV collagen, whereas the other melanoma cell lines showed an increase in attachment and mean cell migration rate in a dose-dependent manner on the matrix molecules (p < 0.001). The enhanced migration seen in the three cell lines could be specifically inhibited by function blocking anti-beta 1 and anti-alpha 2 monoclonal antibodies (p < 0.001) but not by function blocking anti-alpha 3 and anti-alpha 6 monoclonal antibodies. Image analysis of the cells before and after treatment with anti-beta 1 and anti-alpha 2 MoAb indicated that the inhibition of migration did not result in detectable cell detachment, retraction of cell processes, or other significant cell-shape change. Taken together, the findings suggest that the observable enhanced migration on laminin and type IV collagen of a number of human melanoma cell lines is largely mediated by integrin alpha 2 beta 1.
Antibodies, Monoclonal↗
Murine mast cells attach to and migrate on laminin-, fibronectin-, and matrigel-coated surfaces in response to Fc epsilon RI-mediated signals.
We have examined the possibility that mouse bone marrow-derived cultured mast cells (BMCMC) have the capacity to attach to and migrate on extracellular matrix components in vitro through the use of time lapse videography. Unactivated mast cells did not display significant interaction with slide flasks coated with either 3% BSA or collagen IV, and Fc epsilon RI-mediated activation of BMCMC did not appreciably increase their attachment and migratory characteristics. Both activated and unactivated BMCMC adhered to surfaces coated with a synthetic IKVAV laminin polypeptide, but this association resulted in the immobilization of the cells to the substrate. BMCMC did not adhere to surfaces coated with laminin, fibronectin or matrigel until Fc epsilon RI-mediated activation, after which they displayed rapid, random movement on these surfaces. Cells continually interacted with laminin, fibronectin or matrigel by flattening, interspaced by periods of movement as rounded cells with small pseudopodia. The mean velocity of BMCMC on laminin, fibronectin or matrigel was similar and averaged approximately 180 microns/hr. The mean velocity of BMCMC on these three substrates was not significantly different from the mean velocity of monocytes on laminin. The movement of BMCMC on these substrates demonstrated a directional tendency. In summary, these results demonstrate that mast cells activated through Fc epsilon RI are capable of attachment to and motion on components of extracellular matrix, and demonstrate one mechanism by which mast cells may migrate to areas of inflammation and wound repair.
Amino Acid Sequence↗
Acute toxicological effects of ingested tooth whiteners in female rats.
Tooth whiteners are considered as cosmetic agents to be used for bleaching teeth. Since tooth whitener may be swallowed during the whitening procedure, studies were conducted to determine whether ingestion of tooth whitener containing carbamide peroxide resulted in toxic effects. Adult female rats were used, and vaginal smears were examined daily to determine whether the animals were ovulating. Following an overnight fast, a single bolus of a commercial tooth whitener (5 g of tooth whitener/kg fasting body weight) was administered by gavage. Control rats received de-ionized water. After 2 h, mean respirations per min of animals receiving the tooth whitener Quik Start (contains 35% carbamide peroxide) decreased from 169 to 55, and body temperature decreased from 38.4 to 34 degrees C. Other distress signs included: labored breathing, loss of righting reflex, partial eye closure, bloody urine, and incontinence. Three of 22 animals (3/22) died within 48 h, of gastric hemorrhaging. Eight/10 rats stopped ovulating. At necropsy 2 weeks post-dosing, 10/19 animals had grossly bloated stomachs, and mucosal necrosis was observed histologically in 3. Animals receiving White & Brite or Nu-Smile (containing 10 or 15% carbamide peroxide, respectively) exhibited similar but milder symptoms. The data indicate that ingestion of large doses of commercial preparations of tooth whiteners may be acutely toxic, sometimes fatal, to female laboratory rats.
Animals↗
5-Bromo-2-deoxyuridine regulates invasiveness and expression of integrins and matrix-degrading proteinases in a differentiated hamster melanoma cell.
Cell interactions with the extracellular matrix play a critical role in regulating complex processes such as terminal differentiation and tumor progression. In these studies we describe a melanoma cell system that should be useful in addressing the regulation of cell-matrix interactions and the roles they play in regulating differentiation and cell invasiveness. CS (suspension)-1 melanoma cells are relatively well differentiated: they are melanotic, responsive to melanocyte-stimulating hormone, and express TA99, a melanosome membrane differentiation marker. Their repertoire of integrin receptors for extracellular matrix ligands is limited; in particular, they lack receptors for vitronectin, accounting for the observation that they are nonadherent when cultured in the presence of serum. CS-1 cells are noninvasive as well, and express low levels of both metalloproteinases and activated plasminogen activators. Treatment of these cells with melanocyte-stimulating hormone causes them to increase melanin production and assume an arborized phenotype, suggesting that it promotes their further differentiation. In contrast, treatment of CS-1 with the thymidine analog 5-bromodeoxyuridine, converts them to a highly invasive cell population (termed BCS-1) that loses its differentiated properties and responsiveness to melanocyte-stimulating hormone, acquires a broad integrin repertoire (including vitronectin receptors), and expresses elevated levels of metalloproteinases and activated urokinase. From these observations and findings of others on BrdU treatment of other developmental lineages, we hypothesize that BrdU both suppresses differentiation and promotes invasiveness of CS-1 cells. The demonstrated manipulability of CS-1 cells should make them extremely useful for studying the regulation of both terminal differentiation and tumor progression in the melanocyte lineage.
Animals↗
[CD44, the hyaluronic acid cell receptor. Its role in neoplastic invasion and metastatic dissemination].
The CD44 group of transmembrane glycoproteins encompasses several isoforms expressed in a variety of tissues. All isoforms are encoded by the same gene on chromosome 11 and are formed by alternative splicing of their mRNA. CD44 isoforms belong to the family of cell adhesion molecules and to the sub-family of the hyaladherins in consideration of their affinity for hyaluronate and their structural homology with the cartilage link protein. The standard form of CD44, CD44H exhibits a high affinity for hyaluronate, plays a role in the uptake and degradation of this glycosaminoglycan and participates in cell locomotion in its presence. In physiology, CD44H plays a role in the homing of lymphocytes into Peyer's patches, in organogenesis and in the degradation of hyaluronate in lung or lymphoid tissue. In pathology, CD44H probably enhances the tumorigenic properties of some lymphomas and melanomas. The variant form CD44E exhibits low affinity for hyaluronate and its role in cell-cell adhesion in epithelia is suspected. The variant form CD44V (or CD44M) confers metastatic properties to rat carcinoma cells and is expressed in human breast and colorectal cancer and in adenomatous polyps.
Antigens, Surface↗
Role of beta-1 integrins in organ specific adhesion of melanoma cells in vitro.
BACKGROUND: Recent data suggest that the extracellular matrix of organs and heterogeneous integrin expression of tumor cells may influence metastasis distribution. EXPERIMENTAL DESIGN: Three human melanoma cell lines were characterized for integrin expression, in vitro binding to cryostat sections of different organs, and ability to generate experimental metastases in triple immunodeficient mice. RESULTS: The three cell lines exhibited heterogeneous expression of integrins, binding to cryostat sections, and organ colonization. A primary melanoma cell line (PM-WK) did not give rise to experimental metastases, showed scant or mild attachment to only a few organ tissue sections, and showed absent or minimal expression of alpha-integrin subunits tested (VLA 1-6) and alpha v beta 3. In contrast, two lymph node derived lines exhibited distinct patterns of organ colonization: MM-RU colonized only the lungs and expressed predominantly alpha 2 beta 1 and alpha v beta 3 integrin, whereas MM-AN colonized lung and extrapulmonary sites including pancreas and subcutaneous brown fat and expressed predominantly alpha 2 beta 1 and alpha 6 beta 1 integrin. In vitro, MM-RU exhibited marked attachment to lung, brown fat, kidney, and adrenal with no binding to liver, pancreas, brain, or muscle tissue sections, whereas MM-AN had a similar binding profile but with additional attachment to liver and pancreas. Function blocking anti-beta 1 monoclonal antibody inhibited the attachment of MM-RU and MM-AN cells to these tissues (p < 0.001), whereas function blocking anti-alpha 5 and an unrelated monoclonal antibody (HLA class I) did not. Function blocking anti-alpha 2 monoclonal antibody inhibited MM-RU cell adhesion (p < 0.001) but not MM-AN adhesion. However, the function blocking monoclonal antibody alpha 6 beta 1 significantly inhibited the binding of MM-AN to these tissues. CONCLUSIONS: These data suggest that alpha 2 beta 1 and alpha 6 beta 1 mediate differential melanoma cell attachment to organ tissue sections in vitro and that differences in integrin expression of these melanoma cells may be involved in differential organ colonization in vivo.
Animals↗
[The use of monoclonal antibodies in the study of ion transporting pumps].
The active ion transport is related to some vital functions for the normal eukaryotic cell metabolism. The study of transport mechanism and its regulation is a fundamental problem in cellular biology. The production of monoclonal antibodies (AcM) let us to have a probe, with large specificity, for the study of the localization, distribution and function of carrier proteins in the epithelium, as well as the study of its molecular structure, synthesis and assembling in the cell. The quality of a monoclonal antibody depends of the proper selection of each step to follow in the course of its production. In this article, we examine the strategy more currently used in the production of monoclonal antibodies and its direct use in the ionics pump's morphological, biochemical and physiological study.
Animals↗
[Syringoma and trisomy 21].
Two cases of syringoma associated with trisomy 21 are reported. The first case concerned a 29-year old trisomic woman with multiple syringomas of the eyelids, and the second case concerned a 44-year old trisomic woman with disseminated but not eruptive syringomas. The syringoma-trisomy 21 associated is not fortuitous, being 31 times more frequent than in the general population. The "usual" location of syringomas on the eyelids has given rise to many reports, but disseminated syringomas have been reported in only four cases.
Down Syndrome↗
[Is there a place for 2nd look laparotomy in the treatment of ovarian cancers?].
The charts of 147 patients with advanced ovarian cancers responding completely (CR) or partially (PR > 50%) to a primary cisplatin-based chemotherapy are reviewed. All fulfilled our criterias to undergo second-look laparotomy. One hundred patients (group A) underwent second-look laparotomy and 47 patients (group B) other features of control: laparoscopy 37 patients, clinical control ten patients. Apart metastatic spread more frequent in group B (A vs B = 10 vs 32%) and tumor grade 1 more frequent in group B (A vs B = 33 vs 49%), the two groups were well balanced concerning tumor characteristics and treatment features. All patients had received a complementary treatment after the second-look procedures. With a median follow-up of 86 months in group A and 104 months in group B, no difference was found in overall nor in recurrence-free survival. Within group A, 34 patients had achieved pathologic proved complete remission. Their 5-year survival was 73% with an incidence of recurrence of 32%. Second-look laparotomy was found an invasive technique with a 15% operative morbidity. Its therapeutic apport seems absent and the diagnostic role limited to indication of radiotherapy in CR patients. Second-look laparotomies should be reserved to trials evaluating its proper place but should not be used systematically to assess tumor response to chemotherapy. The good 5-year survival of the CR mi group suggest the beneficial impact of complementary treatment, but prospective trials are needed to evaluate the place of this treatment.
Adult↗
[Thomson-type congenital poikiloderma with reduced DNA repair capacity].
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Abnormalities, Multiple↗
Successful treatment of adult's Langerhans cell histiocytosis with thalidomide. Report of two cases and literature review.
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Adolescent↗
[Loose anagen hair syndrome].
A typical case of loose anagen hair syndrome in a 4-year old girl is reported here. The key signs of this disease are the absence of hair cut since infancy, an easy and painless uprooting of the hairs and a 100 p. 100 anageneity of the hairs with distorted bulbs on trichograms. There is no known treatment of this anomaly. Cosmetically, the course of the disease is usually favourable, but abnormal trichograms and fragility of the hairs persist in adulthood. A brief review of the literature concerning this probably underestimated condition is presented.
Alopecia↗
An overview of current research into diabetes.
1. Current research into diabetes will influence a decade of change in care and treatment. 2. Several new oral drugs are currently under development to treat non-insulin dependent diabetes. 3. Clinical trials are underway into new routes to deliver insulin therapy.
Diabetes Mellitus↗
Frequent loss of heterozygosity on chromosome 14 occurs in advanced colorectal carcinomas.
The current model for colorectal tumorigenesis defines four specific mutations (activation of a ras proto-oncogene and inactivation of the APC, p53 and DCC tumor-suppressor genes) that accumulate in a colonic epithelial cell as it progresses towards a carcinoma. However, further mutations must be needed for progression to malignancy because advanced adenomas have been observed with all four of these mutations. Loss of heterozygosity (LOH) for 11 loci spanning the distal portion of the long arm of chromosome 14 was studied in 89 sporadic colorectal adenocarcinomas and 25 adenomas. The overall rate of LOH in carcinomas was 53% (46/86 informative carcinomas). The smallest region of overlap (SRO) of deletions includes the markers D14S19 to D14S20. No LOH was seen in the 18 informative adenomas examined. There was a significant trend towards higher levels of LOH within the SRO in advanced Dukes' stages (P = 0.016). Since frequent loss of heterozygosity in a specific region of a chromosome may reflect the inactivation of a tumor-suppressor gene located there, these data suggest that a gene involved in the progression of colonic neoplasia may reside on the distal portion of the long arm of chromosome 14, and that its inactivation may be a critical event in this process.
Adenocarcinoma↗
Inhibition of membrane fusion in vitro via cyclin B but not cyclin A.
It is now clear that complexes of cdc2 kinase with "mitotic" cyclins regulate the transition between the G2 phase of the cell cycle and mitosis and that membrane traffic in mammalian cells is arrested during mitosis. Using a cell-free assay, we have previously reported that the fusion of early endosomes is, in fact, inhibited via the cdc2 kinase (Tuomikoski, T., Felix, M.-A., Dorée, M., and Gruenberg, J. (1989) Nature 342, 942-945). In the present paper, we show that this in vitro inhibition occurs efficiently only when the kinase activity is specifically evoked by a cyclin of the B-type but not by cyclins of the A-type. In addition, high resolution two-dimensional gel analysis revealed that the kinases associated with A- and B-type cyclins exhibit different substrate preferences. These data suggest that the complexes of the cdc2 kinase with different cyclins may control specific events of the cell cycle.
Animals↗
Metastatic tumors to the orbit--management and prognosis.
In a retrospective study the records of 34 consecutive cases with tumors metastatic to the orbit were reviewed with special attention to the management and prognosis of these patients. The primary tumor site was the breast in 20 patients, prostate in 5, kidney in 2 and skin in 2. The remaining 5 patients had other primary tumour sites. The symptoms of orbital metastasis preceded the detection of the primary tumor in 8 cases (24%). Twenty patients died after a mean interval of 25 months following the diagnosis of the orbital metastasis. This study gives a summary of the clinical features of these patients. With improved methods of treatment it was possible to obtain a relief of orbital symptoms in 24 patients (71%). Although the life expectancy of these patients remains poor, treatment can result in symptomatic relief and in an improvement in the quality of life, which is the main goal in the management of these patients.
Adult↗