A case of apparent trisomy 21 without the Down''s syndrome phenotype.

We describe a case of apparent trisomy 21 that does not fulfill the criteria for the clinical diagnosis of Down's syndrome (DS). Our patient was subjected to karyotype analysis and found to have full, non-mosaic trisomy 21 in both blood lymphocytes and skin fibroblasts, while examination of the term placenta, which was performed earlier in the course of a different study, had shown mosaicism (73%) for trisomy 21. FISH analysis showed no obvious rearrangement of the DS chromosomal region in any of the chromosomes 21. Molecular analysis using polymorphic markers on chromosome 21 verified the existence of trisomy for the entire long arm of the chromosome and showed that the origin of the extra chromosome was maternal and was probably the result of a mitotic error. In contrast with the above, the clinical evaluation using the Jackson checklist of 25 signs failed to establish the diagnosis of DS. We believe that our patient might present mosaicism in other tissues that are not available for analysis and can be regarded as an extreme example in the continuous spectrum of karyotype phenotype associations in mosaic cases.     

The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.     

Therapeutic and diagnostic applications of minor histocompatibility antigen HA-1 and HA-2 disparities in allogeneic hematopoietic stem cell transplantation: a survey of different populations.

Minor histocompatibility antigens (mHags) HA-1 and HA-2 are encoded by biallelic loci, with immunogenic variants, HA-1H and HA-2V, which induce strong HLA-A2-restricted alloreactive T-cell responses, and nonimmunogenic counterparts, HA-1R and HA-2M, which represent functional null alleles that are poorly presented by HLA class I molecules. HA-1 and HA-2 are potential targets of selective graft-versus-leukemia and graft-versus-tumor reactivity after allogeneic hematopoietic stem cell transplantation (HSCT); however, these applications are restricted to a limited number of patients. Here, we show that a far more frequent application of HA-1 and HA-2 disparity relies on their use as markers for the state of host chimerism after allogeneic HSCT. We have determined allelic frequencies of 29.3% and 70.7% for HA-1H and HA-1R, respectively, and of 83.7% and 16.3% for HA-2V and HA-2M, respectively, in >200 healthy individuals from northern Italy. Similar frequencies were observed in nearly 100 patients affected by hematologic malignancies or solid tumors, thus showing that HA-1 and HA-2 variability are not associated with the presence of cancer. On the basis of these data, we predict that HA-1 and HA-2 can be used in 32.8% and 23.5% of Italian transplant patients, respectively, as markers for the state of host chimerism, whereas exploitation of disparity for these mHags for targeted immunotherapy will be possible in 10.7% and 1.1% of Italian patients, respectively. Retrospective HA-2 typing of bone marrow aspirates obtained from a patient during complete remission or recurrence of acute myeloid leukemia after haploidentical HSCT showed the feasibility of using HA-2 as a surrogate marker for disease monitoring. Because of an apparent north-south gradient for HA-1 allelic frequencies, with higher frequencies for the HA-1H variant reported in white populations from Southern Europe as compared with Northern Europe and North America, the diagnostic applicability of HA-1 disparity will be slightly more frequent in transplant patients from the north. Taken together, our data show that determination of HA-1 and HA-2 variability can be an important parameter for the selection of allogeneic stem cell donors, in particular for patients affected by hematologic malignancies without a tumor-specific molecular marker.     

Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease

Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD.     

Cotinine levels in follicular fluid and serum of IVF patients: effect on granulosa-luteal cell function in vitro

Cigarette smoking is accepted as a risk factor for pregnancybut its effect on fertility is uncertain. In this study we determinedthe concentration of cotinine, a nicotine metabolite, in follicularfluid and serum from women participating in an In-vitro fertilizationand embryo transfer (IVF-ET) programme. Cotinine was undetectableIn serum and follicular fluid of non-smokers but ranged from<5 to 371 ng/ml in follicular fluid and from 24 to 245 ng/mlin serum of smokers. Granulosa-luteal cells, obtained from IVFpatients and cultured for 4 days, secreted progesterone and,when an aromatizable androgen was added, oestradiol-17. Theaddition of cotinine or nicotine did not alter progesteroneor oestradlol-17 secretion. However, the presence of cotininein follicular fluid of women smokers provides evidence for accessof at least one component of cigarette smoke to the developinggamete and the cells of the follicle. Further work is requiredto determine whether fertllity is compromised by the presence,In follicular fluid, of contaminants derived from cigarettesmoke.     

Extrinsic risk factors for compromised blood flow in the vertebral artery: anatomical observations of the transverse foramina from C3 to C7

The vertebral artery (VA) is often involved in the occurrence of complications after spinal manipulative therapy. Due to osteophytes compressing the VA anteriorly from the uncinate process or posteriorly from the facet complex, the VAs are susceptible to trauma in the transverse foramina. Such altered anatomical configurations are of major clinical significance, as spinal manipulations may result in dissection of the VA with serious consequences for the blood supply to the vertebrobasilar region. The purpose of this study is to describe numerous structural features of the third to seventh cervical vertebrae in order to contribute to the understanding of pathological conditions related to the VA. The minimal and maximal diameter of 111 transverse foramina in dry cervical vertebrae were studied. The presence of osteophytes and their influence on the VA were evaluated at the vertebral body and at the superior and inferior articular facets. The diameter of the transverse foramina increased from C3 to C6, while the transverse foramina of C7 had the smallest diameter. At all levels the mean dimensions of the left foramina were greater than those of the right side. Osteophytes from the uncinate process of C5 and C6 vertebrae were found in over 60% of dry vertebrae. Osteophytes from the zygapophyseal joints were more frequent at C3 and C4 vertebrae. About half of the osteophytes of the uncinate and of the superior articular process partially covered the transverse foramina. This was less common with those of the inferior articular facets. Osteophytes covering the transverse foramen force the VAs to meander around these obstructions, causing narrowing through external compression and are potential sites of trauma to the VAs potentially even leading to dissection. We strongly advocate that screening protocols for vertebrobasilar insufficiency (VBI) be used prior to any manipulation of the cervical spine and should include not only extension and rotation but any starting position from which the planned manipulation will be performed.     

Proctolin-related material in the mouse brain as revealed by immunohistochemistry

By use of a specific antiserum against the insect peptide proctolin we were able to identify proctolin-immunoreactive neurons in the mouse brain. These nerve cells belong to the nuc. mesencephalicus n. trigemini. Furthermore, the antiserum stained very few nerve fibers with varicosities in the immediate neighborhood of the roof of the third ventricle. The chemical identity of the immunoreactive material with genuine proctolin remains to be elucidated.     

Angiostrongylose bei Mensch und Tier

Zusammenfassung Die vorliegende Arbeit gibt eine Übersicht über den Stand der Angiostrongylose-Forschung. Von den bisher bekannten 16 Angiostrongylus-Arten haben drei eine medizinische Bedeutung: Der Rattenparasit A. cantonensis (Chen, 1935), Dougherty 1946 ist im südostasiatisch-pazifischen Raum Erreger einer eosinophilen Meningoenzephalitis des Menschen. A. costaricensis Morera und Céspedes, 1971, eine kürzlich in Costa Rica bei Haus- und Baumwollratten festgestellte Art, kann sich in den Mesenterialgefäßen des Menschen ansiedeln und Gefäßthrombosen und Darmentzündung hervorrufen. Eine Humanpathogenität des Fleischfresserparasiten A. vasorum (Baillet, 1866) läßt sich nach den heutigen Kenntnissen nicht ausschließen; als Ursache für zentralnervöse Erkrankungen des Menschen kommt dieser Parasit jedoch höchstwahrscheinlich nicht in Betracht, da die Larven auch im spezifischen Endwirt nicht in das Zentralnervensystem einwandern. Über A. vasorum werden folgende, zum Teil unveröffentlichte Forschungsergebnisse mitgeteilt: In der Schweiz wurden Fälle autochthoner Angiostrongylose des Hundes festgestellt und die Nacktschneckenart Arion rufus als natürlicher Zwischenwirt ermittelt. Neue experimentelle Zwischenwirte sind die Landschneckenarten Deroceras agreste, D. laeve und Vitrea diaphana sowie die Süßwasserschneckenarten Anisus leucostomus und Lymnaea tomentosa. Von verschiedenen Labortierarten ist nur die Nilratte, Arvicanthis niloticus, für A. vasorum empfänglich, in der sich der Parasit bis zur Geschlechtsreife entwickelt. Hunde lassen sich nach den Untersuchungen von Neff (1971) oral, intraduodenal, intraperitoneal, intravenös, subkutan und perkutan durch die skarifizierte Haut infizieren.

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Angiostronglyosis in man and animals

Summary A review is given on the present state of angiostrongylosis research. From the 16 known Angiostrongylus species three are of medical importance: A. cantonensis (Chen, 1935), Dougherty, 1946, a parasite of rats, may produce meningoencephalitis of man in the Pacific area and South-East Asia. A second species A. costaricensis Morera and Céspedes, 1971 was recently reported from house rats and cotton rats in Costa Rica; it can parasitize the mesenteric blood vessels of man leading to thrombosis and enteritis.According to our present knowledge, the possibility of a pathogenic effect by the parasite of carnivores A. vasorum (Baillet, 1866) to humans may not be fully dismissed. However, the parasite has no cerebral migration in its normal hosts and it is unlikely that it would produce a disease of the central nervous system in man.The authors discuss their partly unpublished data on A. vasorum. The occurrence of autochthonous angiostrongylosis was established in Switzerland transmitted by the slug Arion rufus. The slugs, Deroceras agreste and D. laeve, the terrestrial snail Vitrea diaphana and freshwater snails, Anisus leucostomus and Lymnaea tomentosa were found to be suitable as new experimental intermediate hosts. From many laboratory animals only the Nilerat, Arvicanthis niloticus, was found to be susceptible to the parasite reaching sexual maturity in that host. Experiments carried out by Neff (1971) showed that dogs can be successfully infected per os, through intraduodenal, intraperitoneal, intravenous and subcutaneous injections, or through the percutaneous route by application of infective larvae to the scarified skin.

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Nach einem Vortrag an der VI. Tagung der Dtsch. Ges. für Parasitologie, am 10.–12.4. 1972 in Hannover.