Kartagener's syndrome and the syndrome of immotile cilia

Summary Kartagener's syndrome (KS) is a hereditary disease with typical symptoms of situs inversus, bronchiectasis, and chronic infections of the nasal mucosa. Autosomal recessive inheritance cannot be doubted on account of repeated observations of affected sibs and parental cansanguinity. The bronchopulmonary symptoms in sibs, however, cannot be explained by this mode of inheritance.Recent clinical findings and electron microscope investigations suggest that KS is a special form of manifestation within the immotile cilia syndrome. This disease combines the typical bronchial and nasal symptoms of KS with sterility in the male due to immotile sperm tails and, as a facultative symptom, situs inversus. Thus, sibs with bronchiectasis but without situs inversus are also classified under this syndrome. The symptoms mentioned are caused by an abnormal morphology of bronchial cilia and sperm tails, which can be demonstrated by electron microscopy. The dynein arms normally attached to the nine microtubular doublets and providing a normal ciliary movement are lacking.It is assumed that during early embryonic life ciliary beats in the growing embryo determine the type of laterality. When ciliary movements are absent laterality may develop fortuitously, thus effecting a situs inversus in about half the affected cases. The numerical evaluation of pedigrees from the literature supports this assumption.     

The Prader-Willi syndrome and the Angelman syndrome

The Prader-Willi syndrome and the Angelman syndrome are characterised by a complex clinical and behavioural phenotype resulting from loss of paternal or maternal expression, respectively, of genes located on the human chromosome 15q11-13. Different molecular mechanisms leading to this imbalance have been identified, including microdeletions, intragenic mutations, uniparental disomy and imprinting centre defects. Low copy repeat gene clusters are known to flank the 15q11-13 microdeletion. They predispose to unequal crossing-over events resulting in the deletion. Involvement of multiple disease genes is strongly suspected and traditional positional cloning techniques as well as animal models are used to identify the involved genes. In this review we include the present state of art and a delineation of future approach to study the candidate genes in these two syndromes.     

Crimino-biologic study of patients with the XYY syndrome and Klinefelter's syndrome

Summary 12 psychopathic patients with chromosome aberrations found among 480 individuals in two institutions for criminal psychopaths in Denmark have been crimino-biologically investigated. 5 of these individuals have Klinefelter's syndrome, 5 are of the XYY karyotype, 1 is 46,XY/47,XY ?Xq- mosaic, and the remaining one is 46, ?Xp-Y.The mean age at first offence is 18.5 years; 83% are recidivists with the mean number of sentences being 7.0. The criminal acts of 5 patients with the XYY syndrome consist mainly of petty thieving, indecency and arson. The criminal offences of 5 patients with Klinefelter's syndrome is mainly petty thieving, sexual offences and less violent crimes. The relationships between the individual criminal life curve, age at first offence, number of sentences, criminality among siblings, milieu factors, intelligence, and psychiatric diagnosis are discussed.Psychoinfantile personality is pronounced in 5 patients with Klinefelter's syndrome. Schizoid personality was remarkable in 3 patients with the XYY syndrome.

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Zusammenfassung 12 psychopathische Patienten mit Chromosomenaberrationen, die unter 480 Insassen von zwei Anstalten für kriminelle Psychopathen in Dänemark gefunden wurden, wurden kriminalbiologisch untersucht: 5 von ihnen hatten das Klinefelter-Syndrom, 5 zeigten den XYY-Karyotyp, 1 war 46, XY/47,XY,?Xq-Mosaik, der letzte war 46, ?Xp-Y.Das Durchschnittsalter bei dem ersten Vergehen war 18,5 Jahre; 83% wurden rückfällig; die durchschnittliche Zahl der Verurteilungen betrug 7,0. Die Vergehen der 5 Personen mit XYY-Syndrom bestanden vor allem aus geringfügigen Diebereien, Sittlichkeitsvergehen und Brandstiftung. Die Vergehen der 5 Patienten mit Klinefelter-Syndrom setzten sich vor allem zusammen aus geringfügigen Diebereien, sexuellen Vergehen und weniger gewaltsamen Vergehen. Die Beziehungen zwischen den individuellen Lebensläufen bezüglich der Kriminalität, dem Alter beim ersten Vergehen, der Zahl der Verurteilungen, der Kriminalität unter Geschwistern, den Milieufaktoren, der Intelligenz und der psychiatrischen Diagnose werden diskutiert. Bei 5 Patienten mit Klinefelter-Syndrom finden sich deutliche Zeichen einer psychoinfantilen Persönlichkeit. 3 Patienten mit XYY-Syndrom zeigten deutliche schizoide Züge.

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The author dedicates this paper to emeritus Prof. Dr. S. Yoshimasu on his 70th birthday.

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Stipendiat of the Alexander von Humboldt-Stiftung.     

The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome

We reviewed 36 patients with a deletion of the short arm of chromosome 10 and a partial DiGeorge syndrome. We compared the phenotypes observed in these del(10p) patients with the classical DiGeorge phenotype associated with del(22q11), pointing out both similarities and differences. Some features, such as sensorineural hearing loss, seem to be highly associated with a deletion of 10p but are absent in the classical DiGeorge spectrum caused by del(22q11).     

The lateral hypothalamic syndrome: Comparison with the syndrome of anorexia nervosa

The lateral hypothalamic syndrome of feeding disorders may not involve the hypothalamus per se, nor is it simply an impairment of feeding behavior. Recent work has forced revisions in traditional concepts regarding the role of the hypothalamus in the control of feeding. At present, it seems clear that hypothalamic damage disrupts nonspecific contributions to feeding behavior, by damaging dopaminergic and other fibers of passage coursing through the ventral diencephalon, and that the resultant aphagia reflects a general disruption of all voluntary behavior that includes feeding but is not restricted to it. Neurological dysfunctions such as akinesia, catalepsy, and sensory neglect are prominent and indicate a broad activational disorder reminiscent of Parkinson's disease. In the absence of a clear notion of how feeding is controlled by the brain, it seems premature to consider animals with experimental lesions in the hypothalamus (or elsewhere in the brain) as appropriate models of anorexia nervosa.     

Effector mechanisms of the autoimmune syndrome in the murine model of autoimmune polyglandular syndrome type 1

Mutations in the Aire gene result in a clinical phenomenon known as Autoimmune Polyglandular Syndrome (APS) Type I, which classically manifests as a triad of adrenal insufficiency, hypoparathyroidism, and chronic mucocutaneous infections. In addition to this triad, a number of other autoimmune diseases have been observed in APS1 patients including Sj?gren's syndrome, vitiligo, alopecia, uveitis, and others. Aire-deficient mice, the animal model for APS1, have highlighted the role of the thymus in the disease process and demonstrated a failure in central tolerance in aire-deficient mice. However, autoantibodies have been observed against multiple organs in both mice and humans, making it unclear what the specific role of B and T cells are in the pathogenesis of disease. Using the aire-deficient mouse as a preclinical model for APS1, we have investigated the relative contribution of specific lymphocyte populations, with the goal of identifying the cell populations which may be targeted for rational therapeutic design. In this study, we show that T cells are indispensable to the breakdown of self-tolerance, in contrast to B cells which play a more limited role in autoimmunity. Th1 polarized CD4(+) T cells, in particular, are major contributors to the autoimmune response. With this knowledge, we go on to use therapies targeted at T cells to investigate their ability to modulate disease in vivo. Depletion of CD4(+) T cells using a neutralizing Ab ameliorated the disease process. Thus, therapies targeted specifically at the CD4(+) T cell subset may help control autoimmune disease in patients with APS1.     

Immunogenetics of the polyglandular failure syndrome

Addison's disease, Graves' disease, thyroiditis, hypoparathyroidism, hypogonadism, diabetes mellitus, myasthenia gravis, vitiligo and pernicious anemia are included in the polyglandular failure syndrome. This review focuses on the association of these illnesses with specific human leukocyte antigens (HLA) and organ specific autoimmunity. The prevalence of HLA-B8, HLA-Bw15 and HLA-Dw3 is increased in these disorders. The HLA region of chromosome 6 controls multiple immune functions. The common HLA associations and evidence of autoimmunity in the polyglandular failure diseases suggests that gene products of chromosome 6 contribute to the pathogenesis of these disorders.     

Immunocorrective therapy of the traumatic syndrome

The effect of combined application of thymalin and plaferon in the prophylaxis and treatment of traumatic syndrome has been investigated in rats. The survival rate was taken as the criterion of efficiency, the mechanism of the effect obtained being estimated at the level of immunological protective factors. Traumatic shock was induced by Kennon's method in Wistar male rats weighing 200-250 g. Post-traumatic syndrome has been observed within 7 days. The combined application of thymalin and plaferon has increased the survival rate twice within the first 7 days. Immunomodulating effect of the combined application of thymalin and plaferon on the 7th day of traumatic syndrome was most marked at the level of total T-lymphocyte population, theophylline-sensitive T suppressors and lysozyme blood serum activity.     

Radiobiology of the acute radiation syndrome

Acute radiation syndrome or acute radiation sickness is classically subdivided into three subsyndromes: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. The time course and severity of clinical signs and symptoms are a function of the overall body volume irradiated, the inhomogeneity of dose exposure, the particle type, the absorbed dose and the dose rate. Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. Contemporaneously, many other radiation-induced effects has been described and all of them may lead to tissue injury with their corresponding signs and symptoms that can be expressed after short or long period of time. Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines.