Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

BACKGROUND: Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. METHODS: Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. RESULTS: Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. CONCLUSIONS: Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.     

Reduced secretion of gastric inhibitory polypeptide in turner patients with impaired glucose tolerance

There is a well documented increase in the incidence of abnormal glucose tolerance in patients with Turner syndrome. To elucidate the pathophysiology of this phenomenon, we studied the serum concentrations of gastric inhibitory polypeptide (GIP) — as probably the most important hormonal factor of the entero-insular axis — in relation to impaired glucose tolerance in this syndrome. Oral glucose tolerance tests were performed in 12 Turner patients with simultaneous determination of plasma glucose, insulin and GIP. An impaired glucose tolerance (iGT) was found in four patients with a chronological age between 12.3 and 14.9 years. These patients were compared with found Turner patients of similar age and weight and a normal glucose tolerance (nGT). The highest insulin level occurred 90 min after stimulation in the patients with iGT compared to 30 min in the nGT group. Interestingly, the total areas under the insulin curves were not different. Stimulated plasma GIP concentrations and the areas under the GIP curves wer significantly lower in iGT compared to nGT patients. A disturbed entero-insular axis might contribute to the delayed — rather than diminished — release of insulin in patients with Turner syndrome and impaired glucose tolerance.Deceased February 21, 1987     

Klassifikation von Kopfschmerzen

In 2003 the International Headache Society (IHS) published the second edition of the International Classification of Headache Disorders. Diagnostic criteria for no less than 206 separate headache diagnoses are presented in the parts (I) primary headaches, (II) secondary headaches and (III) cranial neuralgia, central and primary facial pain. The headaches are classified according to the etiology in case of the secondary headaches and according to the phenomenology in case of the primary headaches. It is the task of the headache specialist to identify the correct headache diagnose with the smallest effort possible. Both, the differentiation between secondary and primary headaches and the differentiation between the various primary headaches are of equal importance.     

Bestimmung der Bindung von Trijodthyronin an Serumproteine mittels Dextran-Gel-Filtration

Zusammenfassung 1. Es wird eine Methode zur gleichzeitigen Bestimmung des sog. freien und des proteingebundenen Anteils von in vitro zugesetztem L-Trijodthyronin-¹³¹Jod im Serum mittels Dextran-Gel-Filtration angegeben. In der beschriebenen Form ist diese Technik für die routinemäßige Anwendung in der Klinik zur Bestimmung der Bindungs- und Transportverhältnisse von Trijodthyronin geeignet.2. In sog. Verdrängungsversuchen wurde nichtmarkiertes Trijodthyronin dem Inkubationsgemisch von Serum und L-Trijodthyronin-¹³¹Jod zugesetzt. Die zugesetzten Trijodthyroninmengen erschöpfen die Gesamtbindungskapazität der Serumproteine in dem gewählten Konzentrationsbereich keineswegs. Im Gegensatz zum Verhalten der prozentualen Anteile des sog. freien und des proteingebundenen Trijodthyronins steigt die absolute Menge des proteingebundenen Trijodthyronins dabei steil an. Man findet eine Kurve, die nicht einer einfachen Sättigunskurve entspricht, sondern eine Resultante aus Sättigungskurven verschiedener Trijodthyronin-bindender Proteine und Verdrängungskurven kompetitiv gebundener Substanzen (z.B. Thyroxin) darstellt.3. Dextran-Gel wirkt nicht als einfaches Molekülsieb für Trijodthyronin. Es greift vielmehr durch Adsorptionsvorgänge kompetitiv in die Serumproteinbindungsverhältnisse des Trijodthyronins ein. Die physiologische Bedeutung des sog. freien Anteils an Trijodthyronin wird diskutiert.4. Die Methode zur Bestimmung des proteingebundenen Jods (PB¹²⁷I) mittels alkalischer offener Veraschung (Barker) wurde technisch vereinfacht und bezüglich ihrer Reproduzierbarkeit untersucht. Die¹³¹Jodausbeute aus zugesetztem L-Thyroxin-¹³¹Jod lag bei diesem Verfahren bei ca. 80%.

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Summary 1. A method allowing the simultaneous determination in serum of the socalled free and the protein bound part of 1-triiodothyronine-¹³¹I added in vitro, using dextran gel filtration, is presented. Assessment of serum protein binding and transport of triiodothyronine can be conveniently performed for clinical purposes by this procedure.2. In socalled discharge experiments non-labelled triiodothyronine is added to incubation mixtures of serum and l-triiodothyronine-¹³¹I. The amount of added triiodothyronine did not exhaust the total binding capacity of serum proteins for triiodothyronine. In contrast to the behaviour of the percentages of socalled free and protein bound triiodothyronine the absolute amount of protein bound triiodothyronine was rising linearly with rising concentrations of triiodothyronine added. The curve obtained was interpreted as resulting from saturation curves of different triiodothyronine binding proteins and discharge curves of competitively bound substances, e.g. thyroxine.3. Dextran gel is not acting merely as molecular sieve for triiodothyronine, but rather competing actively with serum proteins for triiodothyronine, adsorbing the latter. The physiological rôle of the socalled free triiodothyronine is discussed.4. With addition of l-thyroxine-¹³¹I 80% of¹³¹iodine was recovered, when the method ofBarker for determination of serum protein bound¹²⁷iodine (open alkaline ashing) was used.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.

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Herrn Prof. Dr. Dr. h. c.Carl Krauspe in Verehrung zum 70. Geburtstag gewidmet.     

Molecular and cytogenetic characterization of a non-mosaic isodicentric Y chromosome in a patient with Klinefelter syndrome

We report on an adult male with Klinefelter phenotype and an isodicentric Y chromosome (47,XX,+idic(Y)(q12)), a combination which has to the best of our knowledge not been reported before. The patient was hospitalized in forensic psychiatry because of repeated delinquency, aggressive, aberrant and inappropriate behavior, and borderline intelligence. Molecular cytogenetic studies (FISH) showed that the SRY gene was present on both ends of the idicY, while there was only one signal for the Yq subtelomere probe. Molecular investigations by multiplex PCR, using STS markers covering the short and long arm of the Y chromosome did not indicate a deletion of Y chromosomal material. Molecular investigations of STR markers located on Xp22.3 and Xq28 indicated paternal origin of the additional X chromosome and an error in paternal meiosis I. Results of FISH analysis and molecular investigations are compatible with a phenotype as described for individuals with a 48,XXYY karyotype and support the findings that isodicentric Y chromosomes are frequently accompanied by other sex chromosomal abnormalities.     

Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy

Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.Subject terms: Cardiovascular diseases, Development, Medical genetics, Medical genomics     

Failure of BCL-2 up-regulation in proximal tubular epithelial cells of donor kidney biopsy specimens is associated with apoptosis and delayed graft function

SUMMARY: In renal transplantation, postischemic acute renal failure (ARF) develops in more than 20% of patients. We investigated whether tubular epithelial cells obtained from donor kidneys without subsequent ARF express a different pattern of survival genes, compared with cells from kidneys exhibiting ARF. Donor kidney biopsy specimens were obtained before transplantation from eight recipients of cadaveric kidneys with primary graft function (CAD-PF), eight patients with biopsy-proven ARF without rejection (CAD-ARF), and eight recipients of living donor kidneys with primary graft function (LIV). One thousand proximal tubular epithelial cells per biopsy specimen were isolated by laser capture microdissection. Quantitative analysis of apoptosis and the apoptosis regulatory genes Bcl-2, Bcl-xL, and Bax were performed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling staining and real-time PCR, respectively. Primary cultures of human proximal tubular epithelial cells served as calibrator. The number of apoptotic cells was significantly higher in CAD-ARF compared with LIV and CAD-PF (1.5 +/- 1.1% [p < 0.05] vs. 0.3 +/- 0.2% vs. 0.4 +/- 0.2%; mean +/- SD). The apoptosis inhibitors Bcl-2 and Bcl-xL were significantly up-regulated in renal tubular cells of recipients without ARF compared with CAD-ARF. The ratios of Bcl-2/GAPDH normalized to calibrator were as follows: LIV 48 +/- 30, CAD-PF 38 +/- 55, and CAD-ARF 5 +/- 7 (p < 0.05). The corresponding ratios for Bcl-xL were as follows: LIV 6 +/- 6, CAD-PF 5 +/- 3, and CAD-ARF 1 +/- 1 (p < 0.05). No difference in the expression of the proapoptotic Bax could be observed. These data suggest that failure of proximal tubular cells to respond to injury by up-regulation of survival factors from the Bcl-2 family contributes to postischemic ARF in patients after cadaveric renal transplantation.