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Biomedical subjects

J Roche

Publications and source records attributed to J Roche.

At least 37 records · Page 2Linked to original sources
PubMed2002

Malaria vectors in Bioko Island (Equatorial Guinea): PCR determination of the members of Anopheles gambiae Giles complex (Diptera: Culicidae) and pyrethroid knockdown resistance (kdr) in An. gambiae sensu stricto.

Anopheles gambiae sensu lato Giles, 1902 and Anophelesfunestus Giles, 1900 are the main malaria vectors on the island of Bioko (Equatorial Guinea). This study was carried out to determine: a) members of the An. gambiae complex that may be present on the island of Bioko and, b) the sensitivity of An. gambiae sensu stricto to pyrethroids. The analysis by PCR detected the presence of An. gambiae s.s. as the major vector of the complex and the "forest chromosomal form" was demonstrated by cytogenetic analysis. The presence of Anopheles melas in the southwest, north and southeast of the island justifies its study as a vector. The molecular characterization of pyrethroid knockdown resistance (kdr) showed that the populations of An. gambiae s.s. were sensitive and no mutations were found. This fact justifies the implementation on a large scale of pyrethroid-impregnated bednets within the framework of the Malaria Control Program of Equatorial Guinea.

Animals↗
PubMed2001

Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B.

Semaphorins SEMA3B and its homologue SEMA3F are 3p21.3 candidate tumor suppressor genes (TSGs), the expression of which is frequently lost in lung cancers. To test the TSG candidacy of SEMA3B and SEMA3F, we transfected them into lung cancer NCI-H1299 cells, which do not express either gene. Colony formation of H1299 cells was reduced 90% after transfection with wild-type SEMA3B compared with the control vector. By contrast, only 30-40% reduction in colony formation was seen after the transfection of SEMA3F or SEMA3B variants carrying lung cancer-associated single amino acid missense mutations. H1299 cells transfected with wild-type but not mutant SEMA3B underwent apoptosis. We found that lung cancers (n = 34) always express the neuropilin-1 receptor for secreted semaphorins, whereas 82% expressed the neuropilin-2 receptor. Because SEMA3B and SEMA3F are secreted proteins, we tested conditioned medium from COS-7 cells transfected with SEMA3B and SEMA3F and found that medium from wild-type SEMA3B transfectants reduced the growth of several lung cancer lines 30-90%, whereas SEMA3B mutants or SEMA3F had little effect in the same assay. Sequencing of sodium bisulfite-treated DNA showed dense methylation of CpG sites in the SEMA3B 5' region of lung cancers not expressing SEMA3B but no methylation in SEMA3B-expressing tumors. These results are consistent with SEMA3B functioning as a TSG, the expression of which is inactivated frequently in lung cancers by allele loss and promoter region methylation.

Animals↗
PubMed2001

Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23).

The mixed lineage leukemia, MLL, gene is frequently rearranged in patients with secondary leukemia following treatment with DNA topoisomerase II inhibitors. By FISH and Southern blot analyses we identified a rearrangement in the MLL gene due to a novel t(3;11)(q28;q23) chromosomal translocation in a patient who developed AML-M5 3 years after treatment for a follicular lymphoma. Through inverse PCR, the LPP (lipoma preferred partner) gene on 3q28 was identified as the MLL fusion partner. LPP contains substantial identity to the focal adhesion protein, zyxin, and is frequently fused to HMGIC in lipomas. The breakpoint occurred in intron 8 of MLL and LPP. Two in-frame MLL-LPP transcripts, which fuse MLL exon 8 to LPP exon 9, were detected by RT-PCR, although the smaller of these contained a deletion of 120 bp from the MLL sequence. The predicted MLL-LPP fusion protein includes the A/T hook motifs and methyltransferase domain of MLL joined to the two last LIM domains of LPP. A reciprocal LPP-MLL transcript, predicted to include the proline-rich and leucine zipper motifs, and the first LIM domain of LPP were also detected by RT-PCR. In summary, LPP is a newly identified MLL fusion partner in secondary leukemia resulting from topoisomerase inhibitors. The MLL-LPP and LPP-MLL predicted proteins contain many of the features present in other MLL rearrangements.

Adult↗
PubMed2001

The role of semaphorins in lung cancer.

The semaphorins are a family of secreted, transmembrane, and membrane-associated proteins initially identified as causing the repulsion of nerve growth cone guidance. However, subsequent experiments have demonstrated that they can induce retraction in non-neural cells and affect the development of non-neural organs. Two related secreted semaphorins, SEMA3F and SEMA3B, were isolated from a recurrent 3p21.3 homozygous deletion region in small-cell lung cancer (SCLC) cell lines. Moreover, a functionally related molecule, Roundabout/DUTT1, was identified as the target of a more proximal chromosome 3p deletion also involving SCLCs. Based on current data, it is likely that the loss of these semaphorins or Roundabout may affect cell migration, metastasis, and apoptosis. In addition, receptors for the secreted semaphorins, neuropilin-1 and neuropilin-2, have been shown to function as coreceptors for a subset of vascular endothelial growth factor (VEGF) isoforms and related growth factors. Since semaphorins and VEGF bind antagonistically to neuropilins, their loss is likely to facilitate angiogenesis. In lung cancer specimens, antibody staining against SEMA3F has been shown to correlate with stage and histologic subtypes with more aggressive tumors showing increased VEGF and decreased SEMA3F staining. This review is focused on a basic understanding of these pathways with an emphasis on their role in lung cancer.

Journal Article↗
PubMed2000

Altered HOX and WNT7A expression in human lung cancer.

HOX genes encode transcription factors that control patterning and cell fates. Alterations in HOX expression have been clearly implicated in leukemia, but their role in most other malignant diseases remains unknown. By using degenerate reverse transcription-PCR and subsequent real-time quantitative assays, we examined HOX expression in lung cancer cell lines, direct tumor-control pairs, and bronchial epithelial cultures. As in leukemia, genes of the HOX9 paralogous group and HOXA10 were frequently overexpressed. For HOXB9, we confirmed that elevated RNA was associated with protein overexpression. In some cases, marked HOX overexpression was associated with elevated FGF10 and FGF17. During development, the WNT pathway affects cell fate, polarity, and proliferation, and WNT7a has been implicated in the maintenance of HOX expression. In contrast to normal lung and mortal short-term bronchial epithelial cultures, WNT7a was frequently reduced or absent in lung cancers. In immortalized bronchial epithelial cells, WNT7a was lost concomitantly with HOXA1, and a statistically significant correlation between the expression of both genes was observed in lung cancer cell lines. Furthermore, we identified a homozygous deletion of beta-catenin in the mesothelioma, NCI-H28, associated with reduced WNT7a and the lowest overall cell line expression of HOXA1, HOXA7, HOXA9, and HOXA10, whereas HOXB9 levels were unaffected. Of note, both WNT7a and beta-catenin are encoded on chromosome 3p, which undergoes frequent loss of heterozygosity in these tumors. Our results suggest that alterations in regulatory circuits involving HOX, WNT, and possibly fibroblast growth factor pathways occur frequently in lung cancer.

Blotting, Western↗
PubMed2000

First determination of generalized polarizabilities of the proton by a virtual compton scattering experiment

Absolute differential cross sections for the reaction ep-->epgamma have been measured at a four-momentum transfer with virtuality Q2 = 0.33 GeV2 and polarization epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high-resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.

Journal Article↗
PubMed2000

Semaphorin SEMA3F localization in malignant human lung and cell lines: A suggested role in cell adhesion and cell migration.

Semaphorins/collapsins are a family of secreted and membrane-associated proteins involved in nerve growth cone migration. However, some are expressed widely in adult tissues suggesting additional functions. SEMA3F/H.SemaIV was previously isolated from a 3p21.3 homozygous deletion region in human lung cancer. We studied SEMA3F cellular localization using our previously characterized anti-SEMA3F antibody. In normal lung, SEMA3F was found in all epithelial cells at the cytoplasmic membrane and, to a lesser extent, in the cytoplasm. In lung tumors, the localization was predominantly cytoplasmic, and the levels were comparatively reduced. In non-small-cell lung carcinomas, low levels correlated with higher stage. In all tumors, an exclusive cytoplasmic localization of SEMA3F correlated with high levels of vascular endothelial growth factor and was related to the grade and aggressiveness. This suggests that vascular endothelial growth factor might compete with SEMA3F for binding to their common receptors, neuropilin-1 and -2 and might contribute to SEMA3F delocalization and deregulation in lung tumor. In parallel studies, SEMA3F distribution was examined in cell cultures by confocal microscopy. Marked staining was observed in pseudopods and in the leading edge or ruffling membranes of lamellipods or cellular protrusions in motile cells. SEMA3F was also observed at the interface of adjacent interacting cells suggesting a role in cell motility and cell adhesion.

Adenocarcinoma↗
PubMed2000

The potential utility of the Semi-Nested Multiplex PCR technique for the diagnosis and investigation of congenital malaria.

We report three cases of congenital malaria involving two malarial immune mothers living in Spain. Diagnostic PCR and Genotyping PCR for merozoite surface proteins 1 and 2 were essential to show that mothers and new-borns had different Plasmodium population parasites at the moment of the delivery, and that the infection was acquired earlier in gestation by transplacental transmission. In the first case the Plasmodium species founded in both, mother and child were different. Malaria in the twins showed a mixed infection (P. falciparum plus P. malariae) while the mother presented a P. falciparum infection. These facts were confirmed studying the polymorphisms for MSP1 and MSP2. Blood samples of the newborns were analyzed an half hour after delivery excluding the possibility of re-infection by mosquito bite and indicating a vertical transmission during pregnancy.

Adult↗
PubMed1999

Distribution of semaphorin IV in adult human brain.

The semaphorins comprise a family of secreted and membrane bound proteins that influence development of the nervous system as well as non-neural organs. H.SemaIV was originally isolated from a homozygously deleted region involving a subset of small cell lung cancers, a neuroendocrine derived neoplasm. To investigate H.SemaIV expression, specific polyclonal antibodies directed against a unique polypeptide (amino acids 758-773) were developed and their specificity confirmed. In cell lines, H.SemaIV staining was observed in cytoplasmic granules. In the normal adult human brain, we noted three general characteristics of H.SemaIV expression. H.SemaIV was strongly present in specific nuclei or in neuronal regions arranged in defined subnuclear structures. It was also present in neurons but not glial cells or ependymocytes. Lastly, H.SemaIV was not present in cell bodies, but rather in fibers and nerve terminals. Interestingly, an altered pattern of staining was detected in brains of three patients with Alzheimer's disease.

Adult↗
PubMed1999

Usefulness of seminested multiplex PCR in surveillance of imported malaria in Spain.

The use of a new PCR-based method for the diagnosis of malaria in the Spanish Malaria Reference Laboratory has promoted an increase in confirmed cases of malaria. From August 1997 to July 1998, a total of 192 whole-blood samples and 71 serum samples from 168 patients were received from the hospitals of the Spanish National Health System. Most of the patients came from west-central African countries (85%). This molecular method showed more sensitivity and specificity than microscopy, detecting 12.4% more positive samples than microscopy and 13% of mixed infections undetectable by Giemsa stain. Plasmodium falciparum was the main species detected, with 68% of the total positive malaria cases, followed by Plasmodium malariae (29%), Plasmodium vivax (14%), and Plasmodium ovale (7%), including mixed infections in all cases. This report consists of the first wide, centralized survey of malaria surveillance in Spain. The reference laboratory conducted the analysis of all imported cases in order to detect trends in acquisition. The use of a seminested multiplex PCR permitted confirmation of the origins of the infections and the Plasmodium species involved and confirmation of the effectiveness of drug treatments. This PCR also allowed the detection of the presence in Spain of primaquine-tolerant P. vivax strains from west-central Africa, as well as the detection of a P. falciparum infection induced by transfusion.

Child, Preschool↗
PubMed1999

Aml1/ETO and Pml/RARA rearrangements in a case of AML-M2 acute myeloblastic leukemia with t(15;17).

We report a case of acute myeloid leukemia FAB-type 2 with a translocation t(15;17)(q22;q12) On the basis of the cytological findings, a translocation t(8;21)(q22;q22) was suspected. FISH analyses using specific probes for t(15;17) and t(8;21) detected both PML/RARalpha and AML1/ETO rearrangements in a few percentage of cells. This case demonstrates the complexities that may occur between cytology and cytogenetic findings and the usefulness of FISH methods to detect an AML1/ETO rearrangement only suspected by cytological examination of bone marrow smears.

Adult↗
PubMed1999

Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea.

A semi-nested, multiplex polymerase chain reaction (PCR) based on the amplification of the sequences of the 18S small subunit ribosomal RNA (ssrRNA) gene was tested in a field trial in Equatorial Guinea (a hyperendemic focus of malaria in west central Africa). The method uses a primary PCR amplification reaction with a universal reverse primer and two forward primers specific for the genus Plasmodium and to mammals (the mammalian-specific primer was included as a positive control to distinguish uninfected cases from inhibition of the PCR). The second amplification is carried out with the same Plasmodium genus-specific forward primer and four specific reverse primers for each human Plasmodium species. The PCR amplified products are differentiated by fragment size after electrophoresis on a 2% agarose gel. Four villages from three regions of the island of Bioko (Equatorial Guinea) and two suspected Plasmodium vivax-P. ovale infections from the hospital of Malabo were tested by microscopy and PCR. The PCR method showed greater sensitivity and specificity than microscopic examination and confirmed the existence of a focus of P. vivax infections in Equatorial Guinea suspected by microscopic examination. It also provided evidence of several mixed infections, mainly P. falciparum and P. malariae, the two predominant species causing malaria in Equatorial Guinea.

Animals↗
PubMed1999

Prevalence of intestinal parasite infections with special reference to Entamoeba histolytica on the island of Bioko (Equatorial Guinea).

The prevalence of intestinal parasitic infections was assessed (1993 through 1995) among two different groups of persons on the island of Bioko, Equatorial Guinea. In the first group, parasitologic examinations were performed on stool specimens from a household-based sample of 557 dwellers from the rural area of the island. In the second group, 1,633 inpatients and outpatients at the General Hospital of Malabo (the capital of the country) were studied. All age groups were represented in both groups. The average prevalence of the most common protozoan and helminthic intestinal infections in rural and urban areas, respectively, was as follows: Entamoeba histolytica/E. dispar (14.9% and 32.7%, respectively), Giardia lamblia (7.2% and 8.6%), Ascaris lumbricoides (45.8% and 31.4%), and Trichuris trichiura (25.7% and 36.4%). Seventy-nine sera from patients with amebic liver abscess (suspected by ultrasonography) were studied by an immunohemagglutination assay, with 44 (56%) showing anti-E. histolytica titers > or = 1:32. Of these 79 sera, 71 were studied by an enzyme immunoassay, 86% of which were positive with titers > or = 1:64. This study showed that parasitic infections in Equatorial Guinea represent a major health problem.

Animals↗
PubMed1998

Unusual lesions of the internal auditory canal.

Acoustic neuromata (AN) account for nearly 90 per cent of internal auditory canal (IAC) and cerebello-pontine angle (CPA) tumours. The second most common tumour is meningioma. Rare lesions include primary cholesteatoma, facial neuroma, lipoma, angioma and various cysts. Two cases of IAC tumour are presented, one of hamartoma in which smooth muscle was prominent and the other of lymphangioma. Of interest are the specific clinical and radiological features associated with these lesions.

Adolescent↗
PubMed1998

Imaging destructive lesions of the petrous apex.

Cholesterol granuloma and cholesteatoma are the two most common destructive lesions of the petrous apex. Arachnoid cyst is less common. These three expansile lesions are often indistinguishable on clinical grounds. Cholesterol granulomas can be treated effectively through internal drainage into the mastoid cavity or middle ear. Cholesteatomas, however, are managed by more aggressive and complicated removal, which often mandates the sacrifice of hearing. Symptomatic arachnoid cysts are amenable to simple surgical drainage. Therefore, accurate preoperative recognition on computed tomography (CT) and magnetic resonance imaging (MRI) is important in planning proper treatment. Thirteen cases of destructive lesions of the petrous apex are analyzed. The authors' experience illustrates that the "typical" CT and MRI radiographic features are diagnostic in some cases, but not in all. In this study the pathologic findings have been correlated with the radiologic features on both MRI and CT.

Adolescent↗
PubMed1998

Development and implementation of a breast and cervical cancer screening program in urban and rural Alaska.

Early detection of breast and cervical cancers represents the single best strategy to effect the reduction of associated morbidity and mortality. The State of Alaska identified a need to establish a service delivery system which would assure the availability of breast and cervical cancer screening services for women who are low income, under- and uninsured, and from racial/ethnic minorities. In March 1995 the Alaska Breast and Cervical Cancer Early Detection Program (AK-BCCEDP) began funding breast and cervical cancer screening services through the Centers for Disease Control and Prevention, National Breast and Cervical Cancer Early Detection Program. The purpose of AK-BCCEDP is to establish a comprehensive service delivery strategy which includes screening, tracking, referral, follow-up, public education, quality assurance, surveillance, coalition building/partnering, and evaluation. During the first year of services (March 1, 1995, to February 29, 1996) 651 women were screened for breast and cervical cancer. Higher than expected numbers of breast cancer were detected. Of the 651 women screened, four were diagnosed with invasive breast cancer and three were diagnosed with high-grade squamous intraepithelial lesions.

Adolescent↗