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Biomedical subjects

H Winter

Publications and source records attributed to H Winter.

At least 37 records · Page 2Linked to original sources
PubMed2001

Childhood cancer in the south Asian population of England (1990-1992).

Cancer incidence in 1990-92 among English south Asian (residents with ethnic origins in India, Pakistan or Bangladesh) and non-south Asian children is compared. Standardized incidence ratios show significant overall excesses in south Asians (131), largely due to higher rates in south Asian boys, and specific excesses for leukaemia (141), lymphoid leukaemia (141), lymphoma (172) and hepatic tumours (375). Aetiological investigation is required.

Adolescent↗
PubMed2001

Spin-polarized electrons in collisions of multicharged nitrogen ions with a magnetized Fe(001) surface.

We report on the first spin-resolved energy spectra for the emission of electrons during grazing scattering of 150 keV multicharged nitrogen ions from a magnetized Fe(001) surface. A substantial spin polarization for KLL Auger electrons emitted in the final stage of the neutralization sequence during the interaction of multicharged ions with a metal surface is observed. We conclude from our data that the projectile L shell is dominantly populated by electrons from the conduction band of the target. For low energy electrons we find an increase of their spin polarization with an increase of the projectile charge.

Journal Article↗
PubMed2001

Kinetically assisted potential sputtering of insulators by highly charged ions.

A new form of potential sputtering has been found for impact of slow ( < or = 1500 eV) multiply charged Xe ions (charge states up to q = 25) on MgO(x). In contrast to alkali-halide or SiO2 surfaces this mechanism requires the simultaneous presence of electronic excitation of the target material and of a kinetically formed collision cascade within the target in order to initiate the sputtering process. This kinetically assisted potential sputtering mechanism has been identified to be present for other insulating surfaces as well.

Journal Article↗
PubMed2001

Detection of phospholipid oxidation in oxidatively stressed cells by reversed-phase HPLC coupled with positive-ionization electrospray [correction of electroscopy] MS.

Measurement of lipid peroxidation is a commonly used method of detecting oxidative damage to biological tissues, but the most frequently used methods, including MS, measure breakdown products and are therefore indirect. We have coupled reversed-phase HPLC with positive-ionization electrospray MS (LC-MS) to provide a method for separating and detecting intact oxidized phospholipids in oxidatively stressed mammalian cells without extensive sample preparation. The elution profile of phospholipid hydroperoxides and chlorohydrins was first characterized using individual phospholipids or a defined phospholipid mixture as a model system. The facility of detection of the oxidized species in complex mixtures was greatly improved compared with direct-injection MS analysis, as they eluted earlier than the native lipids, owing to the decrease in hydrophobicity. In U937 and HL60 cells treated in vitro with t-butylhydroperoxide plus Fe(2+), lipid oxidation could not be observed by direct injection, but LC-MS allowed the detection of monohydroperoxides of palmitoyl-linoleoyl and stearoyl-linoleoyl phosphatidylcholines. The levels of hydroperoxides observed in U937 cells were found to depend on the duration and severity of the oxidative stress. In cells treated with HOCl, chlorohydrins of palmitoyloleoyl phosphatidylcholine were observed by LC-MS. The method was able to detect very small amounts of oxidized lipids compared with the levels of native lipids present. The membrane-lipid profiles of these cells were found to be quite resistant to damage until high concentrations of oxidants were used. This is the first report of direct detection by LC-MS of intact oxidized phospholipids induced in cultured cells subjected to oxidative stress.

Animals↗
PubMed2001

Cu valency change induced by O doping in YBCPO.

An ab initio local spin density study of YBa2Cu3O6, YBa2Cu3O6.5, and YBa2Cu3O7 is presented. The method includes self-interaction corrections for the Cu d states, which enables a description of various valency configurations of both planar and chain Cu atoms. For YBa2Cu3O6 the antiferromagnetic and insulating state is described with planar (chain) Cu occurring in a divalent (trivalent) state. The evolution in the CuO2 plane from insulating to metallic behavior upon oxygenation is accomplished by the delocalization of the majority Cu d(x2-y2)-O2 p(x)-O3 p(y) band.

Journal Article↗
PubMed2001

Characterization of a cluster of human high/ultrahigh sulfur keratin-associated protein genes embedded in the type I keratin gene domain on chromosome 17q12-21.

Low stringency screening of a human P1 artificial chromosome library using a human hair keratin-associated protein (hKAP1.1A) gene probe resulted in the isolation of six P1 artificial chromosome clones. End sequencing and EMBO/GenBank(TM) data base analysis showed these clones to be contained in four previously sequenced human bacterial artificial chromosome clones present on chromosome 17q12-21 and arrayed into two large contigs of 290 and 225 kilobase pairs (kb) in size. A fifth, partially sequenced human bacterial artificial chromosome clone data base sequence overlapped and closed both of these contigs. One end of this 600-kb cluster harbored six gene loci for previously described human type I hair keratin genes. The other end of this cluster contained the human type I cytokeratin K20 and K12 gene loci. The center of the cluster, starting 35 kb downstream of the hHa3-I hair keratin gene, contained 37 genes for high/ultrahigh sulfur hair keratin-associated proteins (KAPs), which could be divided into a total of 7 KAP multigene families based on amino acid homology comparisons with previously identified sheep, mouse, and rabbit KAPs. To date, 26 human KAP cDNA clones have been isolated through screening of an arrayed human scalp cDNA library by means of specific 3'-noncoding region polymerase chain reaction probes derived from the identified KAP gene sequences. This screening also yielded four additional cDNA sequences whose genes were not present on this gene cluster but belonged to specific KAP gene families present on this contig. Hair follicle in situ hybridization data for single members of five different KAP multigene families all showed localization of the respective mRNAs to the upper cortex of the hair shaft.

Amino Acid Sequence↗
PubMed2001

Low-copy-number human transgene is recognized as an X inactivation center in mouse ES cells, but fails to induce cis-inactivation in chimeric mice.

X chromosome inactivation is initiated from a segment of the mammalian X chromosome called the X inactivation center. Transgenes from this region of the murine X chromosome are providing the means to identify the DNA needed for cis inactivation in mice. We recently showed that chimeric mice carrying transgenes from the human X inactivation center (XIC) region also provide a functional assay for human XIC activity; approximately 6 copies of a 480-kb human transgene (ES-10) were sufficient to initiate random X inactivation in cells of male chimeric mice (Migeon et al., 1999, Genomics, 59, 113-121). Now, we report studies of another human transgene (ES-5), which contains less than 300 kb of the human XIC region on Xq13.2 including an intact XIST locus and which has inserted in one or two copies into mouse chromosome 6. The ES-5 transgene is recognized as an X inactivation center in mouse embryonic stem cells, but is not sufficient to induce random X inactivation in somatic cells of highly chimeric mice. Human transgenes in chimeric mice provide a means to uncouple the key steps in this complex pathway and facilitate the search for essential components of the human XIC region.

Animals↗
PubMed2001

Human type I hair keratin pseudogene phihHaA has functional orthologs in the chimpanzee and gorilla: evidence for recent inactivation of the human gene after the Pan-Homo divergence.

In addition to nine functional genes, the human type I hair keratin gene cluster contains a pseudogene, phihHaA (KRTHAP1), which is thought to have been inactivated by a single base-pair substitution that introduced a premature TGA termination codon into exon 4. Large-scale genotyping of human, chimpanzee, and gorilla DNAs revealed the homozygous presence of the phihHaA nonsense mutation in humans of different ethnic backgrounds, but its absence in the functional orthologous chimpanzee (cHaA) and gorilla (gHaA) genes. Expression analyses of the encoded cHaA and gHaA hair keratins served to highlight dramatic differences between the hair keratin phenotypes of contemporary humans and the great apes. The relative numbers of synonymous and non-synonymous substitutions in the phihHaA and cHaA genes, as inferred by using the gHaA gene as an outgroup, suggest that the human hHaA gene was inactivated only recently, viz., less than 240,000 years ago. This implies that the hair keratin phenotype of hominids prior to this date, and after the Pan-Homo divergence some 5.5 million years ago, could have been identical to that of the great apes. In addition, the homozygous presence of the phihHaA exon 4 nonsense mutation in some of the earliest branching lineages among extant human populations lends strong support to the "single African origin" hypothesis of modern humans.

Amino Acid Sequence↗
PubMed2001

Expression of type I hair keratins in follicular tumours.

BACKGROUND: Hair keratins are specifically expressed in hair and nails. We previously demonstrated the expression of hair keratin basic 1 mRNA in pilomatrixomas. We recently developed a method for immunohistochemical staining of the group of acidic keratins, which have not yet been investigated in human tumours. OBJECTIVES: To study the expression of eight members of the type I hair keratin subfamily in pilomatrixomas and other skin tumours of follicular origin. METHODS: We performed immunohistochemistry on paraffin sections of formalin-fixed pilomatrixomas (40), trichoepitheliomas (10), trichoblastomas (10), desmoplastic trichoepitheliomas (10) and basal cell carcinomas (10), using antibodies against type I hair keratins hHa1, hHa2, hHa3-II, hHa4, hHa5, hHa6, hHa7 and hHa8 as well as cytokeratin CK17. RESULTS: While CK17 was found in almost all tumours investigated, hair keratins were exclusively expressed in pilomatrixomas. Their expression was restricted to areas of transitional cells, located between outer basophilic matricial cells and an inner zone of eosinophilic shadow cells. The most frequently and most strongly expressed hair keratins were hHa1, hHa2, hHa5 and hHa8, whereas hHa4 and hHa6 were only weakly expressed. No positive staining was observed with anti-hHa3-II and anti-hHa7 antibodies. Hair keratin expression in intermediate maturation stage pilomatrixomas resembled that of normal hair follicles, with early matricial and cuticular keratins hHa5 and hHa2 being expressed in lower transitional cells, followed by expression of early cortex keratins hHa1 and hHa8 in intermediate transitional cells and the late cortex keratins hHa4 and hHa6 in upper transitional cells. The latter were, however, seen only in a few intermediate maturation stage pilomatrixomas and were generally absent in late-stage pilomatrixomas. CONCLUSIONS: These changes in hair keratin expression patterns indicate that the maturation of pilomatrixomas towards large areas of shadow cells is associated with a gradual loss of differentiation-specific hair keratins. The complex hair keratin expression in pilomatrixomas is a further argument in favour of a hair matrix origin of this tumour.

Basal Cell Carcinoma↗
PubMed2001

Presurgical ultrasound-guided anchor-wire marking of soft tissue metastases in stage III melanoma patients.

BACKGROUND: Due to increased sensitivity of diagnostic procedures, soft tissue metastases in melanoma patients are frequently detected very early. However, small sizes, deep location, or position close to vulnerable structures could render subsequent surgery quite difficult. OBJECTIVE: To test the feasibility and effectiveness of presurgical ultrasound-guided anchor-wire marking of melanoma metastases. METHODS: We selected melanoma patients with cytologically proven metastases in clinical stage III which were either unfavorably located or which have failed removal by previous surgery. Anchor-wire marking was performed ultrasound guided and free-hand style without the use of local anesthesia. RESULTS: Twelve procedures in nine patients were well tolerated without any complications. In 11 cases the wire tip proved to be located within the tumor lesion; in one case the wire tip missed the target by less than 5 mm and thus was close enough to support appropriate surgery. Earlier, 3 of the 12 study lesions had undergone unsuccessful surgery. The median diameter of the removed metastases was 18.5 mm (range 7-30 mm). CONCLUSION: Ultrasound-guided anchor-wire marking of unfavorably located melanoma metastases is feasible and might facilitate subsequent surgery.

Adult↗
PubMed2000

Divergent roles for CD4+ T cells in the priming and effector/memory phases of adoptive immunotherapy.

The requirement for CD4(+) Th cells in the cross-priming of antitumor CTL is well accepted in tumor immunology. Here we report that the requirement for T cell help can be replaced by local production of GM-CSF at the vaccine site. Experiments using mice in which CD4(+) T cells were eliminated, either by Ab depletion or by gene knockout of the MHC class II beta-chain (MHC II KO), revealed that priming of therapeutic CD8(+) effector T cells following vaccination with a GM-CSF-transduced B16BL6-D5 tumor cell line occurred independently of CD4(+) T cell help. The adoptive transfer of CD8(+) effector T cells, but not CD4(+) effector T cells, led to complete regression of pulmonary metastases. Regression of pulmonary metastases did not require either host T cells or NK cells. Transfer of CD8(+) effector T cells alone could cure wild-type animals of systemic tumor; the majority of tumor-bearing mice survived long term after treatment (>100 days). In contrast, adoptive transfer of CD8(+) T cells to tumor-bearing MHC II KO mice improved survival, but eventually all MHC II KO mice succumbed to metastatic disease. WT mice cured by adoptive transfer of CD8(+) T cells were resistant to tumor challenge. Resistance was mediated by CD8(+) T cells in mice at 50 days, while both CD4(+) and CD8(+) T cells were important for protection in mice challenged 150 days following adoptive transfer. Thus, in this tumor model CD4(+) Th cells are not required for the priming phase of CD8(+) effector T cells; however, they are critical for both the complete elimination of tumor and the maintenance of a long term protective antitumor memory response in vivo.

Adoptive Transfer↗
PubMed2000

Energy transfer from fast atomic projectiles to a crystal lattice under channeling conditions

Neutral Ne atoms with keV energies are scattered under channeling conditions, i.e., at a glancing angle of incidence, from a LiF(001) surface. By means of a time-of-flight method with a pulsed neutral beam, energy distributions for scattered projectiles are obtained. We find for this specific system that the small energy transferred to the crystal lattice during channeling via binary collisions with large impact parameters dominates the dissipation of projectile energy, whereas all other excitations of the solid can be brought to a negligible level.

Journal Article↗
PubMed2000

Role of the 2D surface state continuum and projected band gap in charge transfer in front of a Cu(111) surface

Electron capture by Li+ and H projectiles in grazing scattering from Cu(111) and Cu(110) surfaces is studied experimentally and theoretically. Whereas data for Cu(110) can be described by established theoretical methods treating resonant charge transfer with a free-electron metal, data for Cu(111) show pronounced deviations from this approach. We interpret our observations by the effect of the projected L-band gap of the Cu(111) surface. In particular, the quantum states of reduced dimension (2D surface state continuum) play a dominant role in electron transfer.

Journal Article↗
PubMed2000

Unexpected behavior of the stopping of slow ions in ionic crystals

The energy loss of slow ions during grazing scattering from a LiF(100) surface as a function of the projectile atomic number Z1 is observed to show oscillations similar to those occurring in metals. A model of stopping of ions in an electron gas where screening is calculated from density functional theory reproduces well the experimental data. The same model gives good agreement with the energy loss obtained in transmission experiments performed with H and He projectiles. Analysis of these results allows us to gain new insights in the stopping of slow ions in ionic crystals.

Journal Article↗
PubMed2000

Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma.

Hybrid cell vaccination is a new cancer immune therapy approach that aims at recruiting T cell help for the induction of tumour specific cytolytic immunity. The vaccines are generated by fusion of the patients' tumour cells with allogeneic MHC class II bearing cells to combine the tumour's antigenicity with the immunogenicity of allogeneic MHC molecules. Safety and anti-tumour activity of this treatment were assessed in a clinical trial that has yielded one complete and one partial remission, and 5 cases of stable disease among 16 patients with advanced stage metastatic melanoma. As evidenced by histology, the vaccination induced T cell relocation into tumour nodules. Stable disease could be maintained by repeated booster injections for more than 24 months in some patients. The side effects were minor. Occasional occurrences of vitiligo spots after vaccination were indicative of a restricted therapy induced auto-immune reactivity. The results suggest that hybrid cell vaccination is a safe cancer immune therapy potentially effective for induction of acute anti-tumour response as well as long-term maintenance.

Adult↗
PubMed2000

Effect of the projected band gap on the formation of negative ions in grazing collisions from Cu surfaces.

The formation of negative ions (H-, O-, S-, F-, Cl-) is studied for grazing scattering of fast ions from Cu(110) and Cu(111) surfaces. In a detailed experimental and theoretical investigation we reveal that the projected L-band gap of the Cu metal affects charge transfer in a specific manner. From the analysis of the negative ion fractions as functions of projectile velocity we conclude that, for the Cu(111) surface the electronic 2D surface state continuum plays an essential role in the projectile-surface electron transfer.

Journal Article↗
PubMed2000

Characterization of a 300 kbp region of human DNA containing the type II hair keratin gene domain.

Screening of an arrayed human genomic P1 artificial chromosome DNA library by means of the polymerase chain reaction with a specific primer pair from the human type II hair keratin hHb5 yielded two P1 artificial chromosome clones covering approximately 300 kb of genomic DNA. The contig contained six type II hair keratin genes, hHb1-hHb6, and four keratin pseudogenes psihHbA-psihHbD. This hair keratin gene domain was flanked by type II epithelial keratins K6b/K6hf and K7, respectively. The keratin genes/pseudogene are 5-14 kbp in size with intergenic distances of 5-19 kbp of DNA and do not exhibit a single direction of transcription. With one exception, type II hair keratin genes are organized into nine exons and eight introns, with strictly conserved exon-intron boundaries. The functional hair keratin genes are grouped into two distinct subclusters near the extremities of the hair keratin gene domain. One subcluster encodes the highly related hair keratins hHb1, hHb3, and hHb6; The second cluster encodes the structurally less related hair keratins hHb2, hHb4, and hHb5. Reverse transcription-polymerase chain reaction shows that all hair keratin genes are expressed in the hair follicle. Pseudogene psihHbD is also transcriptionally expressed, albeit with alterations in splicing and frameshift mutations, leading to premature stop codons in the splice forms analyzed. Evolutionary tree analysis revealed a divergence of the type II hair keratin genes from the epithelial keratins, followed by their segregation into the members of the two subclusters over time. We assume that the approximately 200 kbp DNA domain contains the entire complement of human type II hair keratin genes.

Amino Acid Sequence↗