Low section of the rectum during laparoscopic total mesorectal excision using the Contour device. Technical report.
Explore the source record for details and available documents.
Equipment Design↗
Biomedical subjects
P Hernandez
Publications and source records attributed to P Hernandez.
The discovery of moriniafungin, a novel sordarin derivative produced by Morinia pestalozzioides.
A novel sordarin derivative, moriniafungin (1), containing a 2-hydroxysebacic acid residue linked to C-3' of the sordarose residue of sordarin through a 1,3-dioxolan-4-one ring was isolated from the fungus Morinia pestalozzioides. Isolation of moriniafungin employed a highly specific bioassay consisting of a panel of Saccharomyces cerevisiae strains containing chimeric eEF2 for Candida glabrata, Candida krusei, Candida lusitaniae, Crytpococcus neoformans, and Aspergillus fumigatus as well as wild type and human eEF2. Moriniafungin exhibited an MIC of 6 microg/mL versus Candida albicans and IC(50)'s ranging from 0.9 to 70 microg/mL against a panel of clinically relevant Candida strains. Moriniafungin was shown to inhibit in vitro translation in the chimeric S. cerevisae strains at levels consistent with the observed IC(50). Moriniafungin has the broadest antifungal spectrum and most potent activity of any natural sordarin analog identified to date.
Antifungal Agents↗
The impact of depressive symptoms on the functional status of inner-city patients with asthma.
BACKGROUND: Functional deficits are common in patients with asthma. If there is cooccurring depression, these deficits may be more severe and/or more persistent. OBJECTIVE: This study was undertaken to determine 1) the prevalence and severity of depressive symptoms in a sample of inner-city patients being treated for asthma and 2) the impact of these symptoms on functional status. METHODS: Three hundred seventeen enrollees in an inner-city asthma program were evaluated using the health status questionnaire and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and at 3- and 6-month follow-ups. Two groups were created based on patients' CES-D baseline scores, using a commonly used cutpoint to define "caseness" for depression. The two groups were compared using ANOVA, chi2, and the general linear model for repeated measures. RESULTS: Of the sample, 55.01% had a CES-D score greater than the cutpoint for depression. The mean was 29.3 +/- 11.95, well above the scores commonly used to indicate the presence of depression. The depressed group had lower scores on many measures of functional capacity at baseline; whereas both depressed and nondepressed patients improved over time on the physical performance measure (the physical performance measure subscale of the health status questionnaire), the mean score for the depressed group was consistently lower. CONCLUSIONS: The prevalence of depressive symptoms was greater than expected. Depression was persistent and had a major impact on functional capacity. Routine depression screening may be especially important in inner-city patients and other groups thought to be at increased risk for poor outcome.
Adolescent↗
Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine.
MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.
Adjuvants, Immunologic↗
Weak and strong hydrogen-bonding patterns in the structure of 2, 4-bis(2-hydroxybenzoyl)-2,3-dihydro-1H-pyrido
The title compound, C(25)H(19)NO(4)S, (IV), was produced by a cyclocondensation reaction similar to that which had previously produced an unexpected product, thus giving a novel route for such reactions. The structure of (IV) contains two S(6) motifs formed by strong intramolecular O-H.O hydrogen bonds. Weak C-H.O hydrogen bonds form primary C(11), R(1)(2)(7) and R(2)(2)(8) motifs which combine to form a complex three-dimensional network.
Journal Article↗
[Pivotal role of axonal adhesion molecules in central nervous system myelination].
Close relationship between neurons and oligodendrocytes seems to be of the greatest importance during oligodendrocyte maturation and myelin formation within central nervous system. Two major factors are likely to play the decisive role in CNS myelination--adhesion molecules and electrical activity. It has been shown, both in vitro and in vivo, that blocking or stimulating electrical activity may inhibit or induce myelination respectively. The fact that even in culture oligodendrocytes myelinate solely axons and not other cellular processes present within CNS as well as the finding that normal myelin sheath compaction is encountered only around axons suggest that close interaction between oligodendrocytes and neurons is required for normal myelin formation. Adhesion molecules are most likely involved in this interaction by not only bringing the axon and the glial cell close to each other but also by transducing signals to initiate myelination. The neural cell adhesion molecule (NCAM) is a candidate molecule that could regulate axon/glial cell interaction. It is abundantly present in all growing fiber tracts of the developing CNS. Since its polysialylated from (PSA-NCAM) has been shown to disappear from axonal surface as myelination progresses and that its removal increases 4 to 5 fold myelination, it is thought to be a negative factor for myelin formation. These observations may have important implications in therapeutic strategies in demyelinating disorders like multiple sclerosis.
Axonal Transport↗
IL-2 plasmid therapy of murine ovarian carcinoma inhibits the growth of tumor ascites and alters its cytokine profile.
We have evaluated whether i.p. murine ovarian tumors could be treated with an IL-2 plasmid DNA complexed with the cationic lipid, (+/-)-N-(2-hydroxyethyl)-N,N-dimethyl-2, 3-bis(tetradecyloxy)-1-propanaminium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). Reporter gene studies were initially conducted in which mice bearing i.p. murine ovarian teratocarcinoma (MOT) were injected i.p. with reporter gene plasmid DNA (pDNA):DMRIE/DOPE. Histochemical analyses revealed that transfection occurred primarily in the tumor cells of the ascites, with only a minority of other ascitic cells or surrounding tissues transfected. IL-2 levels in the MOT ascites were determined after i. p. injection of either IL-2 pDNA:DMRIE/DOPE or recombinant IL-2 protein. IL-2 was detected in tumor ascites for up to 10 days after a single i.p. injection of IL-2 pDNA:DMRIE/DOPE, but was undetectable 24 h after a single i.p. injection of IL-2 protein. In an antitumor efficacy study, MOT tumor-bearing mice injected i.p. with IL-2 pDNA:DMRIE/DOPE on days 5, 8, and 11 after tumor cell implant had a significant inhibition of tumor ascites (p = 0.001) as well as a significant increase in survival (p = 0.008). A cytokine profile of the MOT tumor ascites revealed that mice treated with IL-2 pDNA:DMRIE/DOPE had an IL-2-specific increase in the levels of IFN-gamma and GM-CSF. Taken together, these findings indicate that i. p. treatment of ovarian tumors with IL-2 pDNA:DMRIE/DOPE can lead to an increase in local IL-2 levels, a change in the cytokine profile of the tumor ascites, and a significant antitumor effect.
Animals↗
Antitumor effects of interferon-omega: in vivo therapy of human tumor xenografts in nude mice.
The antitumor effect of the type I IFN, IFN-omega, was evaluated in both in vitro and in vivo studies of human cancer. For these studies, the cDNA for human IFN-omega was cloned into a eukaryotic expression plasmid DNA (pDNA) driven by the cytomegalovirus promoter. Supernatants from UM449 cells transfected in vitro with IFN-omega pDNA had antiproliferative effects on 11 of 13 human tumor cell lines. For in vivo studies, nude mice were implanted s.c. with one of the following human tumors: NIH: OVCAR-3 ovarian carcinoma, A375 melanoma, or A431 epidermoid carcinoma. Direct intratumoral injection of 100 microg of a IFN-omega pDNA DMRIE/DOPE complex (1:1 DNA:DMRIE mass ratio) for 6 consecutive days resulted in a significant reduction in the tumor volume of NIH: OVCAR-3 ovarian carcinoma or A375 melanoma (P = 0.02). IFN-omega pDNA delivered by i.m. injection also had an antitumor effect. Nude mice bearing s.c. A431 epidermoid carcinoma and injected i.m. with 100 microg of IFN-omega pDNA, twice per week for 3 weeks, had a significant reduction in tumor volume (P = 0.009). These results demonstrate for the first time that IFN-omega can have in vivo antitumor effects in several models of human cancer.
Animals↗
Biochemistry and pharmacology of rabbit cardiac growth hormone (GH) receptors.
In this report we present the first in-depth description of the biochemical and pharmacological properties of rabbit cardiac GH receptors. The apparent M(r)'s of the [125I]human (h) GH-receptor complexes were 380, 205, 90, 62, 52 and 38 kDa as demonstrated by an autoradiograph of affinity-labelled cardiac GH receptors separated under non-reducing conditions by SDS PAGE. The [125I]hGH-cardiac GH receptor complexes were disulfide-linked since the M(r)s of the complexes diminished to 170, 116, 97, 71, 45 and 38 kDa under reducing conditions, indicating the presence of multiple receptors, receptor-associated macromolecules or receptor and ligand in various ratios. The pharmacology of cardiac GH receptors is not typical of GH receptors present in other tissues. In radio receptor assays, both bovine GH and ovine prolactin were 50-fold and 100-fold less potent, respectively, than unlabelled hGH, in blocking the binding of [125I]hGH to cardiac binding sites and were, therefore, extremely weak antagonists. Similarly, neither bovine GH nor ovine prolactin blocked the [125I]hGH affinity-labelling of cardiac GH receptors compared to equivalent doses of unlabelled hGH. Parameters which characterize the kinetics for the association, dissociation and equilibrium binding of [125I]hGH to cardiac GH receptors were ascertained. Association kinetics for the binding of [125I]hGH to heart GH receptors exhibited a maximum specific binding at 17 h and 25 degrees C. The association of [125I]hGH to heart GH receptors was reversible with approximately 15 h required for half of the specifically bound [125I]hGH to dissociate. The coupling of [125I]hGH to heart GH receptors was optimum at pH 6 and the strength of the equilibrium binding, as measured by the ED50, was approximately 2 ng/ml. These data indicate that the cardiac GH receptors are pharmacologically distinct and that there is a M(r) heterogeneity in the [125I]hGH receptor complexes.
Animals↗
A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon alpha.
A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c. B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m. with mIFN-alpha pDNA. In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene.
Animals↗
Development of a blocking ELISA for screening antibodies to porcine rubulavirus, La Piedad Michoacan Virus.
A blocking enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies to porcine rubulavirus (La Piedad Michoacan Virus [LPMV]) in serum samples from pigs. The test, based on a monoclonal antibody against the LPMV hemagglutinin-neuraminidase glycoprotein, had a sensitivity of 99% and a specificity of 97%. The results of this test were in agreement with those obtained by an indirect ELISA and hemagglutination inhibition, indirect immunofluorescence, and virus neutralization tests. The blocking ELISA is considered the most suitable test for routine screening for antibodies against LPMV.
Animals↗
Parotid and central nervous system relapse during complete hematologic remission in acute promyelocytic leukemia.
Explore the source record for details and available documents.
Adolescent↗
Cartilage and serum levels of nitric oxide in patients with hip osteoarthritis.
OBJECTIVE: To assess whether nitric oxide (NO) is related to cartilage deterioration resulting from osteoarthritis, NO concentrations were analyzed in normal and deteriorated areas of cartilage obtained from femur heads of patients with primary hip osteoarthritis (HOA). METHODS: The concentration of NO in macroscopically deteriorated and non-deteriorated cartilage of femoral heads of patients with HOA at hip replacement surgery was analyzed spectrophotometrically. Serum NO levels were also determined in 16 ambulatory patients with hip OA and in healthy volunteers. RESULTS: NO levels of non-deteriorated areas of femoral head cartilage were significantly lower (3.82+/-1.30 micromol/l; mean +/- SD) than levels of deteriorated cartilage areas (11.07+/-6.48 micromol/l; p<0.01). The surgery HOA group showed serum NO levels (2.64+/-0.32 micromol/l; p<0.0001 vs. healthy group) similar to the ambulatory HOA group levels (2.56+/-0.56 micromol/l; p<0.0001 vs. healthy group). Serum NO concentrations in healthy volunteers were 1.37+/-0.55 micromol/l. CONCLUSION: This study shows increased NO levels in joint cartilage of patients with hip OA. This increase was not homogeneously distributed, but the higher NO levels were found in macroscopically deteriorated areas. The data also suggest that high NO serum levels found in patients with hip OA may be due to joint cartilage destruction.
Aged↗
Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression in the synovial tissue of rabbits with antigen arthritis and in cultured synovial cells.
Since IL-8 and MCP-1 are chemoattractant proteins that participate in the recruitment of inflammatory cells into the arthritic joint, we examined the effects of tenidap, a new anti-inflammatory drug of the oxindole family, on IL-8 and MCP-1 expression in the joints of rabbits with acute antigen arthritis. The model was induced by injecting 5 mg/ml ovalbumin into the knees of 20 preimmunized rabbits. Animals were randomized into two groups: treated with tenidap (15 mg/kg per 12 h), or untreated. The effect of tenidap treatment was evaluated on chemokine production in synovial membranes of rabbits with arthritis and in cultured monocytic and synovial cells (SC). By immunoperoxidase staining, chemokines were localized in the synovial tissue. Chemokine messenger RNA levels in the synovial membranes and in cultured cells were analysed by reverse transcription-polymerase chain reaction (RT-PCR). At the end of the study, tenidap significantly reduced neutrophil infiltration into the joint cavity (27+/-4 x 10(6) cells/ml versus 45+/-6 x 10(6) cells/ml in untreated; P<0.05), and synovial effusion (134+/-15 microl versus 236+/-19 microl in untreated; P<0.005). Untreated rabbits showed synovial membrane up-regulation in mRNA expression of IL-8 and MCP-1 (11- and seven-fold versus healthy rabbits, respectively) that was markedly decreased by tenidap (two- and three-fold versus healthy rabbits, respectively). IL-8 and MCP-1 were localized in the synovial tissue in a perivascular pattern and areas of the interstitium and lining, mostly coinciding with cell infiltration. Tenidap also reduced the accumulation of IL-8 and MCP-1 proteins. In cultured synovial and monocytic cells, tumour necrosis factor-alpha (TNF-alpha) elicited an increase in gene expression of IL-8 (four- and nine-fold, respectively) and MCP-1 (nine- and four-fold, respectively) that was significantly reversed in both cell types by 10 microM tenidap. These results suggest that the beneficial effect of tenidap in acute antigen arthritis could be related to the down-regulation in gene expression and synthesis of IL-8 and MCP-1, two key chemokines involved in the recruitment of inflammatory cells.
Acute Disease↗
Antiproliferative effects of N1,N4-dibenzylputrescine in human and rodent tumor cells.
Polyamines (putrescine, spermidine and spermine) increase in proliferating tissues and are essential for cellular growth and cell division processes. We had previously shown that alkyl substituted putrescines can inhibit cell proliferation. We now tested the effects of the (N(alpha),N(omega)-dibenzyl derivatives of the simple diamines putrescine, cadaverine and 1,3-diaminopropane on the growth of three human squamous cell carcinoma (SCC) lines and a rat hepatoma (H-4-II-E) cell line. Survival assays were measured by treating exponentially-growing SCC cultures with N1,N4-dibenzylputrescine (DBP) (270 microM) or a rat hepatoma cell culture with DBP (100 microM) for 48 hrs. Inhibition of cell growth was measured either by the colony forming assay or by cell counting. DBP inhibited proliferation of the rat hepatoma (H-4-II-E) cell line and induced cytotoxicity when used at a concentration of 100 microM for >48 hrs. N1,N5-dibenzylcadaverine (DBC) also induced cytotoxicity at a similar concentration, while N1,N3-dibenzyl-1,3-diaminopropane (DBPr) was a much weaker inhibitor of cell growth. Inhibition of cell growth by DBP resulted in marked modifications of cell morphology, such as vacuole formation, decrease in size, pycnosis, change in staining behavior toward trypan blue and lack of adherence. DBP was also growth inhibitory in the three human SCC cell lines tested. The concentration of DBP required to achieve growth inhibition of SCC cells could be dramatically decreased in the presence of N1,N4-bis(buta-2,3-dienyl)butanediamine, a specific inhibitor of polyamine oxidase (PAOI). Moreover, although the presence of PAOI only prevented the oxidation (debenzylation) of approximately 20% of intracellular DBP over a 5-day period, it produced a 5-fold increase in the inhibition of cell proliferation by DBP. DBP (and DBC) inhibited putrescine uptake by rat hepatoma (H-4-II-E) cells in what appears to be a competitive reaction. A tenfold excess of putrescine over DBP did not inhibit the antiproliferative or cytotoxic effects of the latter. DBP administered for 72 hrs. depleted intracellular levels of putrescine, spermidine and spermine in the SCC lines by 50-100% of control values. It was found that DBP inhibited nucleic acid and protein synthesis at an early stage of cell proliferation, hence its growth inhibitory effect may be related to inhibition of the synthesis of macromolecules.
3T3 Cells↗
A comparative study on the use of virus and antibody detection techniques for the diagnosis of La Piedad Michoacan paramyxovirus (LPMV) infection in pigs.
La Piedad Michoacan paramyxovirus (LPMV) is newly recognized paramyxovirus that has been associated with neurologic and reproductive disorders in pigs in Mexico. To date, no comparative study of methods for the diagnosis of infection with this virus has been published. In this study, we identified tissues containing maximum virus load to optimize virus isolation procedures, and we compared this method to a rapid diagnostic test employing immunostaining of impression smears for LPMV antigens. In addition, several of the available tests for detecting LPMV antibodies were compared for their sensitivity in detecting seroconversion. Pigs used for the study of virus load in tissues and serologic studies were inoculated at 17 days of age with 10(7.00) TCID50 of LPMV. Serial blood samples were collected from selected pigs, and selected pigs were necropsied over a 14-day period. Pigs used in the investigation comparing standard virus isolation techniques to immunostaining of impression smears were inoculated at 3 days of age as described above and necropsied over an 8-day period. The results demonstrate that in the 17-day-old pigs maximum virus titers were detected in olfactory bulb at 5 days postinoculation (PI) and in midbrain at 9 days PI. In addition, the most consistent recovery of high titer virus was from tonsil (3-9 days PI) and olfactory bulb (4-9 days PI). Immunostaining of impression smears was as sensitive as virus isolation when selected tissues (lung, midbrain, olfactory bulb) were compared, with virus detected by both methods in 11/13 samples and in 1 sample each by immunostaining and virus isolation, respectively. All of the serology tests investigated detected seroconversion in pigs by 8 days PI. The identification of target organs where highest virus titers are found combined with immunofluorescent methods for the detection of LPMV antigens and a comparative study of the available serologic tests should facilitate the selection of techniques suitable for any laboratory to diagnose LPMV infection in pigs.
Animals↗
Childcare needs of female street vendors in Mexico City.
This article reports on strategies developed by female street vendors (vendedoras ambulantes) in Mexico City to ensure the care of their young children in the absence of a specific and operational government policy to fulfil this need. The information concerning child care and health was gathered by a survey of 426 street traders selected by multi-stage random cluster sampling in four of the administrative districts (delegaciones politicas) of Mexico City during 1990. It was found that, as mothers of young children, street vendors most frequently looked after their children personally on the street or left them with other members of the family. Related factors were availability of alternative child care providers in the family, the age of the children and working conditions of the mother. Children who remained on the streets with their mothers suffered more frequently from gastro-intestinal diseases and accidents than the national average. The incidence of acute respiratory diseases, however, was similar in the cases of maternal care in the street and care by family members in another environment. Existing public health measures show a greater concern for the health of food consumers than that of workers in this area. Current public policy seeks to regulate street vending activities and to concentrate traders in ad hoc areas and facilities. Our research results document the need for actions that can contribute to an improvement in the care and health conditions of these young children.
Child Care↗
High dose rate brachytherapy for the local control of endobronchial carcinoma following external irradiation.
BACKGROUND: External irradiation is an established palliative treatment for patients with inoperable lung cancer. However, persistent or recurrent symptoms due to local disase are common following external irradiation. The impact of high dose rate (HDR) brachytherapy in the palliative management of patients with local sequelae of residual or recurrent endobronchial lung carcinoma following external irradiation was investigated. METHODS: A prospective cohort of 29 patients (19 men, mean age 65 years) underwent HDR brachytherapy for inoperable lung cancer. All patients had completed external irradiation at least one month before entry into the study (mean (SD) dose 4400 (1481) cGy, completed 12.9 (21.3) months previously). Patients underwent outpatient bronchoscopic placement of 1-3 HDR brachytherapy catheters for delivery of 750-1000 cGy of intraluminal irradiation every two weeks on 1-3 occasions. Prospective evaluation before and four weeks after completion of HDR brachytherapy included assessment of indices of level of function, symptoms, extent of atelectasis (chest radiography), and bronchoscopic determination of degree of endobronchial obstruction. RESULTS: One hundred and eighteen catheters were placed in 81 treatments. Eleven of the 26 patients who underwent repeat bronchoscopy showed a reduction in the degree of endobronchial obstruction; five of 18 patients had radiographic improvement in the extent of atelectasis. Positive response rates ranged from 25% for signs and symptoms related to pneumonitis to 69% for haemoptysis. Performance status improved in 24% of patients. Two patients died before completion of the study protocol. Short term complications included one episode of non-fatal, massive haemoptysis, five of minor haemoptysis, and one pneumothorax. CONCLUSIONS: HDR brachytherapy may improve the degree of endobronchial obstruction, atelectasis, symptoms, and level of function with minimal short term complications in patients with recurrent or residual symptomatic disease following external irradiation.
Adult↗