A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction

PURPOSE: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.     

N-terminal truncated insulin-like growth factor-I in human urine

Urinary insulin-like growth factor-I (IGF-I) from healthy human subjects was examined using two antisera directed toward the whole molecule (WM) and the N-terminal of IGF-I. Pooled urine samples from normal adults were dialyzed, lyophilized, then subjected to Sephacryl S-200 chromatography. The gel filtration profile of immunoreactive IGF-I measured by RIA using WM antiserum showed two peaks. Of the total IGF-I, approximately 40% was free, and the rest was present as a 50-kilodalton complex. To characterize the IGF-I forms present in those two peaks, antibody capture enzyme-linked immunoassays (EIA) using the two antisera were established for detection of intact IGF-I and N-terminal-truncated IGF-I variants. The WM antibody recognizes intact IGF-I and des(1-3)-IGF-I, an N-terminal-truncated variant, equally well, whereas the N-terminal IGF-I antibody recognizes intact IGF-I, but not des(1-3)-IGF-I (< 1% cross-reactivity). As both antibodies show similar cross-reactions with IGF-II, the difference between IGF-I levels recognized by the two antisera was considered to indicate the presence of N-terminal-truncated IGF-I variants. Of the free immunoreactive IGF-I in the urine, 64% was not recognized by N-terminal IGF-I antiserum and was considered to represent N-terminal-truncated IGF-I. In contrast, only 6% of the IGF-I present in the 50-kilodalton fraction was truncated. Urine samples from normal human subjects were analyzed by RIA with WM antiserum and EIA with both WM and N-terminal IGF-I antisera after extraction of IGF-I from binding proteins. IGF-I values measured by EIA with the WM antiserum correlated well with those values obtained by RIA using WM antiserum (r = 0.98; P < 0.001). The total urinary IGF-I level measured by EIA with the WM antiserum was 216.0 +/- 41.1 ng/L (mean +/- SEM), and 35.2 +/- 6.1% of this was considered to represent N-terminal-truncated IGF-I. Using an immobilized biotinylated peptide corresponding to the N-terminal six amino acids of IGF-I, we detected proteolytic activity toward the N-terminal of IGF-I in all four human serum samples tested. In contrast, only two of seven urine samples had detectable protease activity, and in these samples, activity was very low compared to that in serum.(ABSTRACT TRUNCATED AT 400 WORDS)     

Study of humidifying oxygen with 0.1 copper sulfate solution

The 0.1/dL copper sulfate solution may be used to replace distilled water for humidifying oxygen. It can reduce the carrier rate and prolong the using time. There is little copper-ion in the oxygen while the 0.5/dL copper sulfate solution were used continuously for 9 days. The oxygen humidified by copper sulfate solution has no peculiar smell. The solution is cheap, easy to make, and has broad bacteriostatic spectrum.     

Gilbert''s syndrome and Ramadan: exacerbation of unconjugated hyperbilirubinemia by religious fasting

A now 14-year-old boy underwent orthotopic heart transplantation at the age of 13 for anthracycline cardiomyopathy which was a sequela of polychemotherapy for embryonal teratocarcinoma at the age of 1 year. Despite perioperative cerebellar infarction with signs of herniation which required emergency right cerebellar hemispherectomy the long-term course after 18 months turned out to be favorable with complete medical and psychosocial rehabilitation.     

Both Epstein-Barr viral nuclear antigen 2 (EBNA2) and activated Notch1 transactivate genes by interacting with the cellular protein RBP-J kappa

The Epstein-Barr viral nuclear antigen 2 (EBNA2) plays a key role during establishment and maintenance of B cell immortalization after Epstein-Barr virus (EBV) infection. EBNA2 acts as a transactivator of cellular and viral genes. We studied two EBNA2 regulated viral promoters (TP1 promoter and LMP/TP2 promoter) in detail to learn more about the molecular mechanisms of EBNA2-mediated transactivation. In both promoters we could identify at least one binding site for the cellular repressor protein RBP-J kappa. EBNA2 is tethered to the EBNA2 responsive promoter elements by interaction with this cellular protein. Although necessary, the binding of RBP-J kappa is not sufficient for EBNA2-mediated transactivation. At least two further cellular proteins, which are different in the studied promoters are important for efficient transactivation. The identification of RBP-J kappa as central mediator of EBNA2 transactivation suggested an interference of EBNA2 with the highly conserved Notch receptor signal transduction pathway. We could show that an activated form of the Notch receptor can transactivate a reporter construct containing a hexamer of the two RBP-J kappa binding sites of the TP1 promoter supporting the idea that EBNA2 acts as a functional equivalent of an activated Notch receptor.     

Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency

Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate disturbed brain myelination in 18q- syndrome, a disorder characterized by mental retardation, dysmorphic features, and growth failure. T1-weighted and dual spin-echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps were created for 20 patients and 12 controls. MRI demonstrated abnormal brain white matter in all patients. White matter T1 and T2 relaxation times were significantly prolonged in patients compared to controls at all ages studied, suggesting incomplete myelination. Chromosome analysis using fluorescence in situ hybridization techniques showed that all patients with abnormal MRI scans and prolonged white matter T1 and T2 relaxation times were missing one copy of the myelin basic protein (MBP) gene. The one patient with normal-appearing white matter and normal white matter T1 and T2 relaxation times possessed two copies of the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral myelination in 18q- is associated with haploinsufficiency of the gene for MBP.