Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin

A male infant with perineal hypospadias and a small phallus bound in chordee is described. Biochemical investigation at age 9 months after hCG stimulation revealed a testosterone to dihydrotestosterone (DHT) ratio of 40, a markedly elevated value suggestive of deficient steroid 5 alpha-reductase activity. The diagnosis of 5 alpha-reductase deficiency was confirmed by elevated urinary 5 beta/5 alpha-steroid metabolite ratios and demonstration of defective 5 alpha-reductase activity in cultured fibroblasts from the patient's scrotum and foreskin. Application of DHT cream to the patient's abdomen raised circulating levels of DHT to the adult male range. Two courses of DHT given nightly for 3 and 4 months resulted in phallic enlargement. Surgical release of the chordee and hypospadias repair have resulted in normal male appearance of the genitalia. This case illustrates the heterogeneity of the 5 alpha-reductase deficiency phenotype.     

Young Adults with Autism Spectrum Disorder and the Criminal Justice System

Journal of Autism and Developmental Disorders - This study describes charges, outcomes, and recidivism in both the juvenile and adult criminal justice systems (CJS) for young adults aged 17 to...     

A Randomized Pilot Study of a Phone-Based Mindfulness and Weight Loss Program

ABSTRACT

This study evaluated the feasibility and efficacy of integrating mindfulness training into a phone-based weight loss program to improve outcomes in those with high levels of emotional eating. Participants were 75 enrollees into an employer-sponsored weight loss program who reported high levels of overeating in response to thoughts and feelings. Seventy-five overweight and obese participants (92% female, 65% Caucasian, aged 26 to 68 years) were randomized to the new mindfulness weight loss program (n = 50) or the standard behavioral weight loss program (n = 25). Both programs consisted of 11 coaching calls with health coaches and registered dietitians with supplemental online materials. Satisfaction, engagement, and percent weight lost did not significantly differ for intervention vs. control at six months. Intervention participants had significantly better scores at six-month follow-up on mindful eating, binge eating, experiential avoidance, and one mindfulness subscale. Exploratory analyses showed that improvements on several measures predicted more weight loss in the intervention group. This pilot study found that integrating mindfulness into a brief phone-based behavioral weight loss program was feasible and acceptable to participants, but did not produce greater weight loss on average, despite hypothesized changes in mindful eating. Only one third of intervention participants reported participating in mindfulness exercises regularly. Mechanisms of change observed within the intervention group suggest that for adults with high levels of emotional eating those who embrace mindful eating and meditation may lose more weight with a mindfulness intervention.     

Characterization of non-human primate antisera to acute lymphoblastic leukemia (ALL): evidence for unique antigen(s) on childhood ALL of "T" phenotype

A non-human primate antiserum was prepared to acute lymphoblastic leukemia of T-cell phenotype (T-ALL) and, after absorptions with normal blood elements, reacted by immunofluorescence and microcytotoxicity to all the T-ALL tested. In addition, the antiserum reacted with cells from about 70% of the common ALL studied and immunoprecipitated the common ALL antigen of 100,000 daltons. However, when the anti-T-ALL serum was absorbed with with lymphoblasts from common ALL, it failed to react with common ALL lymphoblasts, yet reacted significantly with cells from patients with T-ALL phenotype and defined a 100,000-dalton membrane component not found on common ALL lymphoblasts. In addition, sequential immunoprecipitation of 125I-labeled T-ALL membranes by anti- common-ALL serum followed by anti-T-ALL serum detected the T-ALL membrane component of 100,000 daltons that was not found on common ALL. Thus, our results demonstrate the presence of of a unique human T-ALL antigen present on all T-ALL distinct from the common ALL antigen.     

Islet and beta cell volumes in offspring of severely diabetic (ketotic) chinese hamsters

Summary Chinese hamsters bred at the Upjohn Laboratory were studied at varying ages from 15 days to 19 months. Diabetic animals three to six months and those 10 to 19 months of age were glycosuric and hyper glycemic; there was ketonuria and ketonemia but blood glycerol and fasting plasma insulin levels were low when these values were compared with normal control animals of comparable ages. Using quantitative technics developed in our laboratory, the volumes of islets, beta cells and beta granules were diminished. The increase in volume of nongranular cells is progressive with duration of diabetes. Glycogen infiltration was observed in beta cells of these diabetic animals. — Although offspring (fifteen-day-old weanlings) of the mating of two severely diabetic (ketotic) animals were normoglycemic and glycosurie, their plasma insulin levels were higher than those of their controls. The islet volume was somewhat higher than that of the controls but the beta cells were degranulated both by light and electron microscopy; the beta cells exhibited glycogen infiltration. These results are consistent with the thesis that the primary defect is in insulin biosynthesis.

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Insel- und B-Zell-Volumen im Pankreas von Nachkommen schwer diabetischer chinesischer Hamster

Zusammenfassung Mit von den Autoren entwickelten morphometrischen Methoden wurde das B-Zell-Volumen im Pankreas chinesischer Hamster der Upjohn Kolonie bestimmt. Das Alter der untersuchten Tiere schwankte zwischen 15 Tagen und 19 Monaten. Die diabetischen Tiere waren entweder 3 – 6 oder 10–19 Monate alt. Sie waren hyperglykämisch und glykosurisch, teilweise bestand Ketonurie. Die Plasmainsulin- und Glyzerin-Konzentrationen im Gesamtblut waren niedriger als diejenigen gleichaltriger Normaltieren erniedrigt. Bei diabetisehen Tieren waren B-Zell- und-Granula-Volumen vermindert. Mit zunehmender Dauer des Diabetes nahm der Anteil der nicht granulierten B-Zellen zu. Die B-Zellen diabetischer Tiere zeigten Glykogeninfiltration. 15 Tage alte Nachkommen zweier ketotisch-diabetischer Eltern waren normoglykämisch, hatten aber im Vergleich zu gleichaltrigen Kontrolltieren erhöhte Plasmainsulin-Konzentrationen. Das Inselzellvolumen war gegenüber der Norm erhöht, aber die B-Zellen waren degranuliert und zeigten Glykogeninfiltration. Diese Resultate stimmen mit der Hypothese überein, daß der primäre Defekt, der beim chinesischen Hamster die Entwicklung eines diabetischen Syndroms zur Folge hat, die Biosynthese des Insulins betrifft.

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Le, volume des îlots de Langerhans et des cellules B du pancréas de la progéniture de hamsters chinois sévèrement diabetiques

Résumé Des hamsters chinois provenant de la colonie des Laboratoires Upjohn ont été étudiés à différents âges allant de 15 jours à 19 mois. On trouve une glycosurie et une hyperglycémie chez les animaux diabétiques de 3 à 6 mois et chez ceux de 10 à 19 mois. On observe également une cétonurie et une cétonémie, mais les taux de glycérol sanguin et les taux d'insuline plasmatique à jeun sont bas par comparaison à ceux détectés chez des témoins d'âge comparable. Le volume des îlots, des cellules et des granules, mesuré par des méthodes quantitatives élaborées dans notre laboratoire, est diminué. Le volume des cellules non-granulées augmente progressivement avec la durée du diabète. On observe une infiltration de glycogène dans les cellules B des animaux diabétiques. Bien que la progéniture, âgée de 15 jours, de deux animaux sévèrement diabétiques (avec cétose) ait des taux normaux de glycémie et une glycosurie, leur insulinémie est plus élevée que celle mesurée chez les témoins. Le volume de leurs îlots est un peu plus grand que celui des contrôles, mais, en microscopie optique et électronique, les cellules sont dégranulées et montrent une infiltration de glycogène. Ces résultats confirment l'hypothèse que le défaut primaire est au niveau de la biosynthèse de l'insuline.

     

Target direction rather than position determines oculomotor expectation in repeating sequences

Saccadic latencies to targets appearing to the left and right of fixation in a repeating sequence are significantly increased when a target is presented out of sequence. Is this because the target is in the wrong position, the wrong direction, or both? To find out, we arranged for targets in a horizontal plane occasionally to appear with an unexpected eccentricity, though in the correct direction. This had no significant effect on latency, unlike what is observed when targets appeared in the unexpected direction. That subjects learnt sequences of directions rather than simply positions was further confirmed in an experiment where saccade direction was a repeating sequence, but eccentricity was randomised. Latency was elevated when a target was episodically presented in an unexpected direction. Latencies were also elevated when targets appeared in the correct hemifield but at an unexpected direction (35° polar angular displacement from the horizontal, a displacement roughly equivalent in collicular spacing to our unexpected eccentricity), although this elevation was of a smaller magnitude than when targets appeared in an unexpected direction along the horizontal. Finally, we confirmed that not all changes in the stimulus cause disruption: an unexpected change in the orientation or colour of the target did not alter latency. Our results show that in a repeating sequence, the oculomotor system is primarily concerned with predicting the direction of an upcoming eye movement rather than its position. This is consistent with models of oculomotor control developed for randomly appearing targets in which the direction and amplitude of saccades are programmed separately.     

A 3-base pair deletion,c.9711_9713del,in DMD results in intellectual disability without muscular dystrophy

We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy.