Imaging proliferation in vivo with [F-18]FLT and positron emission tomography

Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.     

Increased calpain expression in activated glial and inflammatory cells in experimental allergic encephalomyelitis

In demyelinating diseases such as multiple sclerosis (MS), myelin membrane structure is destabilized as myelin proteins are lost. Calcium-activated neutral proteinase (calpain) is believed to participate in myelin protein degradation because known calpain substrates [myelin basic protein (MBP); myelin-associated glycoprotein] are degraded in this disease. In exploring the role of calpain in demyelinating diseases, we examined calpain expression in Lewis rats with acute experimental allergic encephalomyelitis (EAE), an animal model for MS. Using double-immunofluorescence labeling to identify cells expressing calpain, we labeled rat spinal cord sections for calpain with a polyclonal millicalpain antibody and with mAbs for glial (GFAP, OX42, GalC) and inflammatory (CD2, ED2, interferon gamma) cell-specific markers. Calpain expression was increased in activated microglia (OX42) and infiltrating macrophages (ED2) compared with controls. Oligodendrocytes (galactocerebroside) and astrocytes (GFAP) had constitutive calpain expression in normal spinal cords whereas reactive astrocytes in spinal cords from animals with EAE exhibited markedly increased calpain levels compared with astrocytes in adjuvant controls. Oligodendrocytes in spinal cords from rats with EAE expressed increased calpain levels in some areas, but overall the increases in calpain expression were small. Most T cells in grade 4 EAE expressed low levels of calpain, but interferon gamma-positive cells demonstrated markedly increased calpain expression. These findings suggest that increased levels of calpain in activated glial and inflammatory cells in EAE may contribute to myelin destruction in demyelinating diseases such as MS.     

Primary cysts of the iris pigment epithelium. Clinical features and natural course in 234 patients

OBJECTIVE: To describe the clinical characteristics, natural course, and complications of a large group of patients with primary iris pigment epithelium (IPE) cysts. DESIGN: Observational case series. PARTICIPANTS: Two hundred thirty-four patients with primary IPE cysts participated. RESULTS: Primary IPE cysts were classified as central in 6 patients (3%), midzonal in 50 patients (21%), peripheral in 170 patients (73%), and dislodged in 8 patients (3%). Central (pupillary) IPE cysts were found only in males, peripheral IPE cysts were found most often in females (69%), and no gender predilection was detected for midzonal and dislodged IPE cysts. Central and peripheral IPE cysts occurred in young patients (mean age, 20 and 33 years, respectively), whereas midzonal and dislodged IPE cysts were seen in slightly older patients (mean age, 52 and 45 years, respectively). Central IPE cysts were visible when the pupil was not dilated and appeared most often as a round or collapsed brown lesion arising from the pupillary margin, most commonly superonasally. Midzonal IPE cysts were brown and fusiform, best visualized after pupillary dilation. Peripheral IPE cysts produced a characteristic bulging in the iris stroma near the iris root, but they were directly visible in only 78% of cases. After wide dilation and patient and slit-lamp positioning, they appeared as a round clear lesion behind the iris, most often in the inferotemporal quadrant. Finally, dislodged IPE cysts appeared as a brown oval lesion, free floating in the anterior chamber (12%) or in the vitreous (12%), or fixed in the anterior chamber angle (75%). One hundred twenty-four patients (53%) were followed for a mean of 35 months (range, 3 months-19 years). In these patients, complications associated with IPE cysts included lens subluxation in one case (1%), iritis in one case (1%), focal cataract in two cases (2%), glaucoma in two cases (2%), and corneal touch in five cases (4%). CONCLUSION: Primary IPE cysts have characteristic clinical features that serve to differentiate them from intraocular malignancies. Most cysts have a benign clinical course, and treatment is rarely necessary.     

Depression and self-medication with nicotine: The modifying influence of the dopamine D4 receptor gene.

This study evaluated whether there are genetic subgroups of depressed individuals who are more or less predisposed to engage in self-medication smoking practices. Smokers (N?=?231) completed self-report questionnaires of depression and smoking practices and were genotyped for the dopamine D4 (DRD4) gene. A significant interaction (DRD4 Genotype?×?Depression) was found for stimulation smoking and negative-affect reduction smoking. Specifically, these smoking practices were significantly heightened in depressed smokers homozygous for the short alleles of DRD4 but not in those heterozygous or homozygous for the long alleles of DRD4. These preliminary results suggest that the rewarding effects of smoking and the beneficial effects of nicotine replacement therapy for depressed smokers may depend, in part, on genetic factors involved in dopamine transmission. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A semiconserved residue inhibits complex formation by stabilizing interactions in the free state of a theophylline-binding RNA

The theophylline-binding RNA aptamer contains a 15 nucleotide motif that is required for high-affinity ligand binding. One residue within this RNA motif is only semiconserved and can be an A or C. This residue, C27, was disordered in the previously determined three-dimensional structure of the complex, suggesting that it is dynamic in solution. 13C Relaxation measurements are reported here, demonstrating that C27 is highly dynamic in the otherwise well-ordered RNA-theophylline complex. A synthetic complex with an abasic residue at position 27 was found to exhibit wild-type binding affinity (Kd approximately 0.2 microM), indicating that the base of residue 27 is not directly involved with theophylline binding. Surprisingly, the U27 and G27 RNAs were found to bind theophylline with low affinity (Kd values > 4 microM). NMR spectroscopy on the U27 RNA revealed the presence of an A7-U27 base pair in the free RNA that prevents formation of a critical base-platform structural motif and therefore blocks theophylline binding. Similarly, a protonated A7H+-C27 base pair forms in the absence of theophylline at low pH, which explains the unusual pH dependence of theophylline binding of the C27 RNA aptamer. Thus the weak binding for various nucleotides at position 27 arises not from unfavorable interactions in the RNA-theophylline complex but instead from stable interactions in the free state of the RNA that inhibit theophylline binding.     

School children's use of computers and teachers' education in computer ergonomics

A national survey to investigate the education of teachers in computer-related ergonomics was carried out by postal questionnaire. The use of computers by primary school children (age 4-12 years) was also investigated. Data were collected from a random sample of 25% (n = 830) of primary schools in the Republic of Ireland. Questionnaires (n = 1863) were returned from 416 schools giving a response rate of 50.1%. Almost all schools (99.7%) had computers for children's use. The computers were most often (69.8%) used in the classroom. The majority (56.3%) of children worked in pairs. Most teachers (89.6%) had received computer training, but few (17.6%) had received ergonomics information during the training. Respondents were not satisfied with their current knowledge of ergonomics. Over 90% stated that they would like to receive further information by printed format or during a training course, rather than by computer (web or CD-ROM).     

Zinc absorption in Crohn's disease

Zinc deficiency is a potential complication of Crohn's disease and we have searched for evidence of this and assessed the possibility that malabsorption of zinc might be a cause. Serum zinc concentrations in 33 patients suffering from Crohn's disease were significantly lower than in 58 normal control subjects (9 . 18 +/- 2 . 3 mumol compared with 13 . 6 +/- 1 . 73 mumol, P < 0 . 0005). Serum zinc correlated well with serum albumin concentrations and the low serum zinc may simply reflect the low serum albumin. Thus its value as an indicator of zinc deficiency is poor. We studied zinc absorption in seven patients with Crohn's disease and compared it with the results obtained previously in five normal subjects using a new technique involving a short-lived isotope of zinc (69mZn). Plasma appearance curves, constructed after an oral dose of isotope, and disappearance curves, after an intravenous dose, were used in a deconvolution computer programme to calculate zinc absorption. Compared with normal subjects, zinc absorption was considerably impaired in patients with Crohn's disease (range 9--45%, compared with 38--75%). This abnormality is a potential cause of zinc deficiency in patients with Crohn's disease.     

Videographic and histologic comparison of Nd:YAG and diode laser contact transscleral cyclophotocoagulation

We performed contact transscleral cyclophotocoagulation in two human autopsy eyes with continuous-wave Nd:YAG and diode lasers. Duration of exposure was two seconds, and powers were 4 to 7.3 W with the Nd:YAG laser and 1.75 to 2.5 W with the diode laser. In both procedures, we used hand-held quartz fiberoptic contact probes for energy delivery. Tissue responses were viewed with high-magnification videographic recording technique to analyze the real-time laser effects. The treated tissues were then studied by light microscopy. We observed different tissue responses both videographically and histologically. Nd:YAG laser lesions were characterized by prominent tissue whitening and contraction of the ciliary epithelium, while the diode laser lesions had less whitening and the tissue contraction appeared to be deeper in the ciliary body. The histologic correlate was coagulation and disruption of the ciliary epithelium and little effect on the underlying ciliary muscle with the Nd:YAG laser, while the diode laser had less effect on the ciliary epithelium but caused a significant coagulative response in the ciliary muscle. Comparative trials are needed to establish the clinical significance of these videographic and histologic observations.     

Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22

(1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri-Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.