Ring-chromosom 18

Zusammenfassung Wir berichten über einen Patienten mit Ring-Chromosom 18, dessen klinische Symptomatik durch Dystrophie, Minderwuchs, stato-motorische und geistige Retardierung, Mikrocephalie, Dyskranie, Mittelgesichtsdysplasie mit carpshaped mouth, Hypertelorismus, Epikanthus, Ohrmuschelanomalien, Ohrkanalstenose, beeinträchtigtes Hören, spindelförmige Finger, Muskelhypotonie, kongenitalen Herzfehler, vermehrte Wirbelbildung auf den Fingerbeeren und fehlenden IgA-Mangel ausgezeichnet ist. Phänische Merkmale der bisher publizierten Fälle mit 18r, 18p-und 18q-werden zusammengestellt und untereinander verglichen. Ein klar umrissenes 18 Ring-Syndrom läßt sich unseres Erachtens nicht abgrenzen. Alle beschriebenen 18r-Fälle zeigen klinisch Übergänge zu den Symptomkomplexen von 18p-und 18q-Patienten, so daß wir von einem 18p-/18q-—Deletionssyndrom sprechen möchten.

---

Ring chromosome 1818p-/18q-—Deletion-syndrome

Summary We report a patient with ring chromosome 18, whose clinical symptoms are characterized by dystrophy, short stature, psychomotorical retardation, microcephalus dyscrania, mid-face dysplasia with carpshaped mouth, hypertelorism, epicanthus, dysplasia of the external ears, stenosis of the ear canals, hearing loss, spindle-shaped fingers, hypotonia of the muscles, congenital heart defect, increased numbers of whorles on the fingertips; there is no IgA-deficiency. The phenotypical symptoms of previously published cases with 18r, 18-and 18q-are summarized and discussed. In our opinion delineation of a separate 18 ring syndrome is not justified. All the 18r cases described in the literature clinically overlap with the 18p-and 18q-patients; we therefore suggest to call it an 18p-/18q-deletion-syndrome.

---

---

Die cytogenetischen Untersuchungen wurden mit Unterstützung durch die Deutsche Forschungsgemeinschaft durchgeführt.     

白细胞介素18

白细胞介素-18(IL-18)是新发现的细胞因子,具有多种生物学功能.IL-18能促进外周血单个核细胞产生干扰素-γ(IFN-γ)、IL-2、粒细胞巨噬细胞集落刺激因子(GM-CSF)等细胞因子,增强天然杀伤细胞(NK细胞)的细胞毒作用.IL-18结构上与IL-1相似,而功能更接近IL-12,IL-18与IL-12均能诱导Th1细胞产生IFN-γ,存在协同效应,但它们的作用途径不同.IL-18在抗感染抗肿瘤等方面有着潜在的应用前景,并与自身免疫性疾病的发病密切相关.     

Mouse Chromosome 18

Chair of Committee for Mouse Chromosome 18     

Chromosome number 18

Summary 4 cases of ? chromosome abnormality, referred to this department in the past 3 months, have shown an aberrant complement of chromosome 18. Chromosome 18 has been identified using a modification of Seabright's (1971) method of banding human chromosomes.

---

Zusammenfassung Vier Fälle mit fraglicher Chromosomen-Anomalie, die während der vergangenen 3 Monate an diese Abteilung überwiesen wurden, zeigten ein abnormes Chromosom Nr. 18. Chromosom 18 wurde mit Hilfe einer Modifikation von Seabright (1971) für die Darstellung von Bandenmustern identifiziert.

---

---

Supported in part by United Sheffield Hospitals Research Grant Code 309.     

Trisomy 18q

Summary A 2-month-old male infant with partial trisomy 18, 46,XY,der(4),t(4;18)(q35;q21.1)mat, was presented. Except for atypical facies, he had many of the significant signs of full trisomy 18. Phenotype-karyotype correlations based on the data of our case and those from the literature were discussed. Major features of trisomy 18, such as congenital heart disease, early death, and external malformations, appear to be consistently related to the trisomic state of 18q21. Characteristic congenital heart diseases in trisomy 18 were polyvalvular disease in 100%, membranous ventricular septal defect, patent ductus arteriosus, and high take-off of the right coronary ostium. Pathology of the heart did not differ between full and partial 18-trisomy cases.     

Interleukin-18.

Interleukin (IL)-18 is a newly discovered cytokine, structurally similar to IL-1, with profound effects on T-cell activation. This short review summarizes the present knowledge on IL-18, to give an insight into the future perspectives for its possible use as vaccine adjuvant. Formerly called interferon (IFN) gamma inducing factor (IGIF), IL-18 is the new name of a novel cytokine that plays an important role in the T-cell-helper type 1 (Th1) response, primarily by its ability to induce IFNgamma production in T cells and natural killer (NK) cells. Mice deficient in IL-18 have suppressed IFNgamma production despite the presence of IL-12 IL-18 is related to the IL-1 family in terms of structure, receptor family, and function. In terms of structure, IL-18 and IL-1beta share primary amino acid sequences of the so-called "signature sequence" motif and are similarly folded as all-beta pleated sheet molecules. Also similar to IL-1beta, IL-18 is synthesized as a biologically inactive precursor molecule lacking a signal peptide which requires cleavage into an active, mature molecule by the intracellular cysteine protease called IL-1beta-converting enzyme (ICE, also called caspase-1). The activity of mature IL-18 is closely related to that of IL-1. IL-18 induces gene expression and synthesis of tumor necrosis factor (TNF), IL-1, Fas ligand, and several chemokines. The activity of IL-18 is via an IL-18 receptor (IL-18R) complex. This IL-18R complex is made up of a binding chain termed IL-18Ralpha, a member of the IL-1 receptor family previously identified as the IL-1 receptor-related protein (IL-1Rrp), and a signaling chain, also a member of the IL-1R family. The IL-18R complex recruits the IL-1R-activating kinase (IRAK) and TNFR-associated factor-6 (TRAF-6) which phosphorylates nuclear factor kappaB (NFkappaB)-inducing kinase (NIK) with subsequent activation of NFkappaB. Thus on the basis of primary structure, three-dimensional structure, receptor family, signal transduction pathways and biological effects, IL-18 appears to be a new member of the IL-1 family. Similar to IL-1, IL-18 participates in both innate and acquired immunity.     

18p- Mosaicism

Summary The case of a 5-month-old male infant with 18p- mosaic, who has intractable seizures and severe ophthalmological abnormalities in addition to many clinical manifestations usually described in the 18p- syndrome, is reported. The proportions of abnormal cells are 7–8% in blood and 55% in skin. About 35% of the short arm of chromosome 18 is deleted. To our knowledge the present report is the fifth one of 18p- mosaic. The main interest of this case resides in the fact that it shows a serious clinical picture despite the low proportion of abnormal cells in blood and the small degree of deletion of the short arm of chromosome 18.     

Partial monosomies 18

Summary This paper contains a survey of clinical and chromosome data of about 170 patients with partial monosomies 18 (18p-; 18q-; 18r). Cases with karyotype (18q-) show a very distinct malformation syndrome. The symptoms of (18r) cases are in-between those of (18p-) and (18q-).

---

Zusammenfassung Diese Arbeit gibt eine Übersicht über klinische Daten und Chromosomenbefunde bei ungefähr 170 Patienten mit partieller Trisomie (18p-; 18q-; 18r). Fälle mit dem Karyotyp (18q-) zeigen das charakteristischste Mißbildungs-Syndrom. Die Symptome von (18r)-Patienten nehmen eine Mittelstellung zwischen solchen mit 18p- und 18q- ein.

     

A time-resolved fluoroimmunoassay for 18-oxocortisol and 18-hydroxycortisol. Development of a monoclonal antibody to 18-oxocortisol

Patients with primary aldosteronism and with glucocorticoid-suppressible aldosteronism excrete in the urine excessive amounts of the hybrid steroids 18-hydroxycortisol and 18-oxocortisol. The measurement of these steroids aids in the differential diagnosis of various adrenal disorders. We have produced mouse monoclonal antibodies against 18-oxocortisol and polyclonal antibodies against 18-hydroxycortisol and describe a time-resolved fluoroimmunoassay (TR-FIA) technique for the measurement of these steroids in the urine. We have also compared this assay with an ELISA technique for these compounds. We also describe the preparation of in-house Eu(III)-labeled avidin and an enhancement solution and compared to a commercially available Eu(III)-labeled streptavidin and enhancement solutions. The monoclonal antibodies against 18-oxocortisol are sensitive and have a high level of specificity. The TR-FIA technique using in-house prepared reagents or commercial ones were indistinguishable from each other, but at a significant saving. The TR-FIA technique was more sensitive and had a greater precision than the ELISA technique for both steroids.     

Prenatal diagnosis of a de novo satellited chromosome 18 (18ps) associated with 18p deletion

De novo satellited non-acrocentric chromosomes are very rare findings in prenatal diagnosis. Here we report the first case of a de novo 18ps, associated with del(18p), detected at prenatal diagnosis. A 37 years old woman underwent Chorionic Villus Sampling (CVS) for advanced maternal age. Cytogenetic analysis on direct CVS preparation (CVSc) revealed a male karyotype with a nonfamilial satellited 18ps and a reciprocal translocation t(17;19)(P11.1;q11) of maternal origin. The mesenchimal CVS culture (CVSm) showed a mosaic of cell lines with various involvement of chromosome 18: 18ps [36/70]/ r(18) [25/70]/ del(18p) [3/70]/ -18 [6/70]. Amniotic fluid cells (AFC) confirmed the homogeneous karyotype found at CVSc. The molecular cytogenetic characterization, performed on AFC, allowed the following diagnosis: 46,XY, +15, dic(15;18)(p11.1;p11.2), t(17;19)(p11.1;q11)mat. ish dic(15;18)(tel 18p-, D15Z1+, wcp18-, wcp 18+, D18Z1+, tel 18q+). The foetal autopsy disclosed subtle facial dysmorphisms and corpus callosum hypoplasia. In case of prenatal detection of de novo terminal ectopic NORs an accurate cytogenetic and molecular analysis should be performed in order to rule out subtle unbalancements.