Dental agenesis patterns of permanent teeth in Apert syndrome

Dental agenesis may either occur as an isolated trait (non-syndromic) or as a component in a congenital syndrome. The aim of the present study was to identify the prevalence of dental agenesis for each type of tooth and to look for dental agenesis patterns in persons with Apert syndrome. Serial panoramic radiographs of 23 individuals (five male patients and 18 female patients) were examined. Third molars were excluded. The prevalence of agenesis for at least one tooth was 34.8%. Up to two missing teeth were found for individuals with Apert syndrome. Maxillary lateral incisors and mandibular second premolars were the most frequently missing teeth. Four different dental agenesis patterns of the entire dentition were identified by using the tooth agenesis code (TAC). Two patterns occurred more frequently, both of which were symmetrical. One involved the simultaneous absence of teeth 12 and 22, and the other showed agenesis of teeth 35 and 45. In conclusion, patients with Apert syndrome were found to exhibit a high prevalence of dental agenesis. All dental agenesis patterns in which more than one tooth was missing were symmetrical.     

Trastuzumab cotreatment improves survival of mice with PC-3 prostate cancer xenografts treated with the GRPR antagonist 177Lu-DOTAGA-PEG2-RM26

Gastrin-releasing peptide receptors (GRPRs) are overexpressed in prostate cancer and are suitable for targeted radionuclide therapy (TRT). We optimized the bombesin-derived GRPR-antagonist PEG₂-RM26 for labeling with ¹⁷⁷Lu and further determined the effect of treatment with ¹⁷⁷Lu-labeled peptide alone or in combination with the anti-HER2 antibody trastuzumab in a murine model. The PEG₂-RM26 analog was coupled to NOTA, NODAGA, DOTA and DOTAGA chelators. The peptide-chelator conjugates were labeled with ¹⁷⁷Lu and characterized in vitro and in vivo. A preclinical therapeutic study was performed in PC-3 xenografted mice. Mice were treated with intravenous injections (6 cycles) of (A) PBS, (B) DOTAGA-PEG₂-RM26, (C) ¹⁷⁷Lu-DOTAGA-PEG₂-RM26, (D) trastuzumab or (E) ¹⁷⁷Lu-DOTAGA-PEG₂-RM26 in combination with trastuzumab. ¹⁷⁷Lu-DOTAGA-PEG₂-RM26 demonstrated quantitative labeling yield at high molar activity (450 GBq/μmol), high in vivo stability (5 min pi >98% of radioligand remained when coinjected with phosphoramidon), high affinity to GRPR (K_D = 0.4 ± 0.2 nM), and favorable biodistribution (1 hr pi tumor uptake was higher than in healthy tissues, including the kidneys). Therapy with ¹⁷⁷Lu-DOTAGA-PEG₂-RM26 induced a significant inhibition of tumor growth. The median survival for control groups was significantly shorter than for treated groups (Group C 66 days, Group E 74 days). Trastuzumab together with radionuclide therapy significantly improved survival. No treatment-related toxicity was observed. In conclusion, based on in vitro and in vivo characterization of the four ¹⁷⁷Lu-labeled PEG₂-RM26 analogs, we concluded that ¹⁷⁷Lu-DOTAGA-PEG₂-RM26 was the most promising analog for TRT. Radiotherapy using ¹⁷⁷Lu-DOTAGA-PEG₂-RM26 effectively inhibited tumor growth in vivo in a murine prostate cancer model. Anti-HER2 therapy additionally improved survival.     

Stimulation of glutamine synthetase activity by excitatory amino acids in astrocyte cultures derived from aged mouse cerebral hemispheres may be associated with non-n-methyl-d-aspartate receptor activation

We have been using glial cells derived from aged mouse cerebral hemispheres (MACH) at several passages to study the responsiveness of astrocytes to microenvironmental signals in culture. In the present study, we examined the effects of excitatory amino acids on the activity of glutamine synthetase, a marker for astrocytes. MACH glia cell passages 25 to 29 were used. Culture groups were Dulbecco's modified Eagle's medium +10% fetal bovine serum (control); glutamate 100 μM; γ-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA) 50 μM; kainic acid 10 μM; N-methyl-d-aspartate (NMDA) 10 μM. In all treated groups glutamine synthetase activity was significantly higher than in controls. We speculate that this increase represents an enhanced differentiation of immature astrocytes. In a second series, we examined the effects of glutamate receptor antagonists on glutamine synthetase activity as follows. MACH cultures were treated with glutamate 100 μM in combination with either L(+)-2-amino-3-phosphonopropionic acid (L-AP3; 50 μM); D(−)-2-amino-5-phosphonopentanoic acid (D-AP5; 50 μM) or 6,7-dinitroquinoxaline-2,3-dione (DNQX; 50 μM). The increase in GS activity produced by glutamate was exhibited by the non-selective NMDA receptor antagonist, DNQX, but not by the metabotropic receptor antagonist, L-AP3 or a selective NMDA receptor antagonist, D-AP5. We also found that in cultures treated with glutamate, a number of astrocytes resembled “reactive astrocytes” morphologically. These astrocytes were absent in cultures treated with glutamate + DNQX. The findings provide supportive evidence that astrocytes from aged mouse cerebral hemispheres respond to excitatory amino acids and that this response is mediated by non-NMDA receptor activation.     

Behavioral treatment of autistic persons: A review of research from 1980 to the present

Studies evaluating behavioral treatment of autism from 1980 to the present were reviewed. Studies included were published in journal articles and utilized behavioral methodology. A total of 251 studies were included in the review. Each study was analyzed for target behaviors and behavioral techniques implemented. Target behaviors were divided into categories, which included aberrant behaviors, social skills, language, daily living skills, and academic skills. Behavioral techniques were classified as positive, negative, extinction, or combined. Results were presented for each category. Recent trends in the treatmen literature were also reviewed, and recommendations for future research were presented.     

The use of conditional probability analysis to identify a response chain leading to the occurrence of eye poking

In contrast to the literature on shaping adaptive behavior chains, few applied studies have described procedures for identifying and treating behavior chains involving problem behavior such as self-injury. The present study expands upon past work by conducting a conditional probability analysis and within-session analysis to identify a response chain leading to the occurrence of self-injurious behavior. Based on the hypothesis that stereotypy and self-injury constituted a response chain, the effects of blocking stereotypy were examined. Reductions in both self-injury and in response effort for treatment implementation were observed.