Three new families with arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is a rare condition with autosomal recessive inheritance characterized by connective tissue abnormalities. The most specific clinical findings are cardiovascular anomalies including tortuosity, lengthening, aneurysm, and stenosis formation of major arteries. Also ventricular hypertrophy is frequently present. Other anomalies are skin hyperextensibility and cutis laxa, joint laxity or contractures of the joints, and inguinal herniae. Histology shows disruption of elastic fibers of the media. These features suggest that ATS is a connective tissue disorder. A biochemical or molecular defect has not yet been identified. We describe here nine additional ATS patients from three consanguineous Moroccan families and review a total of 35 patients with this uncommon condition.     

Congenital malformation of the feet with low body height

Among 75 members of a Danish family, 12 were found with a syndrome not previously described. Clinically, the syndrome consists of low body height and rigid flat feet, with weight-bearing pain in the feet. Radiologically, the deformation of the feet is a medial synostosis between the talus and the calcaneus combined with ankle joint dysplasia. The cause of the syndrome is most probably an autosomal dominant gene with complete penetrance. No linkage was found of the gene to 18 marker genes.     

Age-related accumulation of congophilic fibrillar inclusions in endocrine cells

Summary Intracellular fibrillar congophilic inclusions are well known as neurofibrillary tangles in neurons and as Biondi bodies in choroid plexus epithelial cells. Recently similar amyloid-like inclusions in adrenal cortical cells were described (Eriksson and Westermark 1990). This study on 150 adrenal glands confirms these observations. In our material the age-related accumulation of congophilic inclusions starts earlier (in the sixth decade) and reaches a higher incidence (42.7%). We found similar intracellular inclusions in other endocrine organs, for example in the anterior lobe of the pituitary, in the cells of parathyroid glands and in Sertoli cells. The age-related incidence of these fibrillar inclusions in the pituitary was 68%; the co-incidence with interstitial amyloid deposits was 49.5%. Thus the intracellular accumulation of congophilic fibrils in old age is a widespread phenomenon and occurs not only in neurons but also in endocrine cells (adrenal, pituitary and parathyroid glands) and in active secretory cells (choroid plexus and Sertoli cells).     

Beeinflussung der Atemsteigerung bei Muskelarbeit durch partiellen neuromuskulären Block (Tubocurarin)

Zusammenfassung In 17 Versuchen erhielten 7 Versuchspersonen 0,09–0,16 (Mittel 0,13) mg Tubocurarin/kg i.v. Vor und nach der Injektion wurde die gleiche Muskelarbeit geleistet (Beinarbeit; O₂-Aufnahme etwa das dreifache des Ruheumsatzes). Gemessen wurden Atemzeitvolumen, alveolarer O₂- und CO₂-Druck, Blutdruck und Pulsfrequenz. Die Curaredosen führten zu einer Erschwerung der Arbeit, beeinträchtigten jedoch nicht die Atmung.Bei gleicher Muskelarbeit ventilierte die Mehrzahl der Versuchspersonen, vor allem im Beginn der Arbeit, unter Curare mehr als bei der Kontrollarbeit ohne Curare. Am deutlichsten war dies bei denjenigen Versuchspersonen ausgeprägt, die schon ohne Curare im Beginn der Arbeit eine plötzliche Steigerung der Ventilation zeigten.Es wird angenommen, daß unter Curare die gleiche Muskelarbeit mit einer verstärkten motorischen Innervation geleistet wird. Die dabei beobachtete Ventilationssteigerung wird als weiteres Argument für einen Einfluß der motorischen Innervation auf die Atemzentren angesehen.Mit 3 TextabbildungenHerrn Professor Dr. Hans Winterstein zum 80. Geburtstag gewidmet.     

Histological and cytological criteria in the diagnosis of malignant melanomas by cryostat sections

Summary Although cryostat sections in general allow a distinction to be made between malignant melanomas and other pigmented lesions in clinically doubtful cases, the differential diagnosis may be difficult. The histological and cytological criteria taken into account can be classified as major, minor, and insufficient. Knowing the diagnostic value of each makes a conventionally established diagnosis safer. Variance analysis does not contribute to the problem but it can nevertheless be shown that the evaluation of six major criteria makes a quick and reliable cryostat section diagnosis possible. If these results are confirmed in a prospective study it would be a decisive step on the way to a quicker and safer cryostat section diagnosis of malignant melanoma, even for the less experienced histopathologist.The results published here were presented in part at the DDG meeting 1980 at Westerland/SyltWe are grateful to Miss Schubert, Institute of Biomathematics of the University of Munich, for the statistical evaluations     

Insulin inhibits amyloid beta-induced cell death in cultured human brain pericytes

Amyloid-beta (Abeta) deposition in the cerebral arterial and capillary walls is one of the characteristics of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type. In vitro, Abeta1-40, carrying the "Dutch" mutation (DAbeta1-40), induced reproducible degeneration of cultured human brain pericytes (HBP), by forming fibrils at the cell surface. Thus, this culture system provides an useful model to study the vascular pathology seen in Alzheimer's disease. In this study, we used this model to investigate the effects of insulin on Abeta-induced degeneration of HBP, as it has been mentioned previously that insulin is able to protect neurons against Abeta-induced cell-death. The toxic effect of DAbeta1-40 on HBP was inhibited by insulin in a dose-dependent matter. Insulin interacted with Abeta and inhibited fibril formation of Abeta in a cell-free assay, as well as at the cell surface of HBP. Our data indicate that the formation of a fibril network is essential for Abeta-induced cell death in HBP. Additionally, insulin may be involved in the regulation of Abeta fibrillization in AD.     

Isolation and RNA-binding analysis of NAD+-isocitrate dehydrogenases from Kluyveromyces lactis and Schizosaccharomyces pombe

Krebs cycle NAD⁺-isocitrate dehydrogenase (Idh) binds to the 5-UTRs of all mitochondrial mRNAs in Saccharomyces cerevisiae. We hypothesize that this leader-binding activity plays a role in translational regulation, thereby linking mitochondrial biogenesis to the need for respiratory function. Analysis of effects of leader binding on mitochondrial translation is complicated by the involvement of the enzyme in mitochondrial metabolism. We have therefore searched for an Idh altered in RNA binding, but retaining full enzyme activity. Idh from Kluyveromyces lactis and Schizosaccharomyces pombe was partially purified and examined for the ability to bind Cox2 mRNA. Sch. pombe Idh, like the S. cerevisiae enzyme, has high affinity for both its own, K. lactis and S. cerevisiaeCOX2 leaders. In contrast, Idh purified from K. lactis shows only low affinity for all mRNAs tested. To determine what distinguishes K. lactis Idh from S. cerevisiae Idh, genes encoding the two subunits of Idh in K. lactis were cloned and sequenced. Sequence comparison revealed high levels of similarity throughout the proteins, in particular in regions involved in enzyme activity, co-factor and regulator binding. Non-conserved residues between the subunits from the two yeasts are candidates for involvement in the interaction with RNA. Received: 19 January 2000 / 24 March 2000     

Characterization of FMR1 proteins isolated from different tissues

FMR1 protein expression was studied in different tissues. Inhuman, monkey and murine tissues, high molecular mass FMR1 proteins(67–80 kDa) are found, as shown in lymphobiastoid celiiines. The identity of these proteins was confirmed by theirabsence in tissues from patients with the fragile X syndromeand a FMR1 knock-out mouse. An IIe367Asn substitution in theFMR1 protein did not aiter the transiation, processing and localizationof FMR1 proteins in lymphoblastoid cells from a patient carryingthis mutation. All the high molecular mass FMR1 proteins isolatedfrom normal lymphoblastoid cells and cells from the patientwith the IIe367Asn substitution were able to bind RNA. However,the FMR1 proteins of the patient had reduced affinity for RNAbinding at high salt concentrations. In some human, monkey andmurine tissues low molecular mass FMR1 proteins (39–41kDa) were found, which had the same N terminus as the 67–90kDa isoforms, but differ in their C terminus and are thereforemost likely the result of carboxy-terminal proteolytic cleavage.These low molecular mass FMR1 proteins did not bind RNA, incontrast with the high molecular mass FMR1 proteins. The significanceof these low molecular mass proteins remains to be studied.