Developmental regulation of metabotropic glutamate receptor 1 splice variants in olfactory bulb mitral cells

Alternative splicing of the metabotropic glutamate receptor 1 (mGluR1) receptor gene generates two major receptor isoforms, mGluR1a and mGluR1b, differing in intracellular function and distribution. However, little is known on the expression profiles of these variants during development. We examined the mRNA expression profile of mGluR1a/b in microdissected layers and acutely isolated mitral cells in the developing mouse olfactory bulb. This analysis showed that the two mGluR1 variants are differentially regulated within each bulb layer. During the first postnatal week, the mGluR1a isoform replaces GluR1b in the microdissected mitral cell layer (MCL) and in isolated identified mitral cells, coinciding with a developmental epoch of mitral cell dendritic reorganization. Although mGluR1a mRNA is expressed at high levels in both the adult external plexiform layer (EPL) and MCL, Western blotting analysis reveals a marked reduction of the mGluR1a protein in the MCL, where mitral cell bodies are located, and strong labeling in the EPL, which contains mitral cell dendrites. This suggests that there is increased dendritic trafficking efficiency of the receptor in adult. The temporal and spatial shift in mGluR1b/a expression suggests distinct roles of the mGluR1 isoforms, with mGluR1b potentially involved in the early mitral cell maturation and mGluR1a in dendritic and synapse function.     

Randomized controlled trials of the efficacy of lung cancer screening by sputum cytology revisited

BACKGROUND:

Two randomized controlled trials of lung cancer screening initiated in the 1970s, the Johns Hopkins Lung Project and the Memorial Sloan‐Kettering Lung Study, compared 1 arm that received annual chest X‐ray and 4‐monthly sputum cytology (dual‐screen) to a second arm that received annual chest X‐ray only. Previous publications from these trials reported similar lung cancer mortality between the 2 groups. However, these findings were based on incomplete follow‐up, and each trial on its own was underpowered to detect a modest mortality benefit.

METHODS:

The authors estimated the efficacy of lung cancer screening with sputum cytology in an intention‐to‐screen analysis of lung cancer mortality, using combined data from these trials (n = 20,426).

RESULTS:

Over ½ of squamous cell lung cancers diagnosed in the dual‐screen group were identified by cytology; these cancers tended to be more localized than squamous cancers diagnosed in the X‐ray only arm. After 9 years of follow‐up, lung cancer mortality was slightly lower in the dual‐screen than in the X‐ray only arm (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74‐1.05). Reductions were seen for squamous cell cancer deaths (RR, 0.79; 95% CI, 0.54‐1.14) and in the heaviest smokers (RR, 0.81; 95% CI, 0.67‐1.00). There were also fewer deaths from large cell carcinoma in the dual‐screen group, although the reason for this is unclear.

CONCLUSIONS:

These data are suggestive of a modest benefit of sputum cytology screening, although we cannot rule out chance as an explanation for these findings. Cancer 2009. © 2009 American Cancer Society.     

Effects of hypoxemia on gastrointestinal blood flow and gastric emptying in the newborn piglet

The effects of severe hypoxemia on gastrointestinal (GI) blood flow and gastric emptying were studied in nine 2- to 4-day-old piglets which were mechanically ventilated while receiving nitrous oxide anesthesia. Each animal was studied during a control period of oxygenation (PaO2 91 +/- 8 torr), 35 min of hypoxemia (PaO2 29 +/- 1 torr), and a recovery period (PaO2 90 +/- 5 torr) (mean +/- SEM). During each study period, the animal received a 10% dextrose test meal with phenol red marker (22 ml/kg), gastric residual volumes were determined at 10-min intervals over 30-min study periods using a dye dilution double sampling technique, and GI blood flow (radionuclide-labeled microspheres), O2 delivery, O2 extraction, and O2 consumption were measured at the end of the 30-min period. Hypoxemia resulted in decreased blood flow to the following GI organs: stomach, jejunal and ileal mucosa-submucosa, and colon decreased 62, 31, and 35%, respectively (p less than 0.05). Jejunal and ileal muscularis blood flow remained unchanged. Oxygen delivery and consumption by GI tract decreased 79 and 58%, respectively; whereas oxygen extraction of GI tract increased 115%. Values returned toward baseline levels during the recovery period. The hypoxemic gastric emptying pattern showed significantly greater gastric residuals at 20 min compared to the 10-min value (p less than 0.05). This pattern was different than that observed during control and recovery periods. We conclude that severe hypoxemia results in decreased GI blood flow, tissue oxygenation, and an altered gastric emptying pattern. These observations may have clinical significance for feeding infants following an hypoxemic episode.     

Pregnancy protein-1 in the serum of patients with diseases of the breast

Pregnancy-specific beta 1-glycoprotein (SP1) was assayed by enzyme immunoassay in serum from 32 patients with breast diseases (11 mastopathies, 6 benign tumors and 15 breast cancers). Healthy blood donors were used as control group. There were significant differences between the SP1-serum concentrations of patient group (mastopathies, benign tumors, breast cancer) and the control group (p less than 0.001). The SP1-values of the groups with mastopathies, benign tumors and breast cancer did not differ significantly. Elevated SP1-concentrations were found in 4 of 11 patients with mastopathy, in 3 of 6 patients with benign tumor and in 10 of 15 patients with breast cancer versus 1 of 24 blood donors. With the help of SP1 determination in serum of 5 breast cancer patients before operation and 6 months post operation we did not found a correlation with further clinical course.     

One-year outcomes after photodynamic therapy in patients with age-related macular degeneration with poor baseline visual acuity

Background Photodynamic therapy with verteporfin (PDT) has been demonstrated in randomized controlled trials to be a safe and effective therapy for choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD). Limited information is available on the prognosis with PDT for patients who fell outside the inclusion criteria for the clinical trials, however. The purpose of this study is to describe the clinical course of patients with CNV lesions in AMD treated with PDT, with baseline visual acuities sufficiently poor to warrant exclusion from previous randomized trials.Methods Retrospective case series. Ten consecutive patients with CNV secondary to exudative AMD treated with PDT with baseline visual acuity less than 34 ETDRS letters were followed for 1 year. The main outcome was median change in visual acuity on the ETDRS chart.Results The median change in acuity over 12 months was + 13 letters. All patients lost <3 lines of ETDRS acuity, and eight of ten patients (80%) gained at least one line of vision, over 12 months.Conclusions In our series, patients with low visual acuity at baseline appeared to respond to PDT on both visual acuity and fluorescein angiographic measurements. PDT treatment may be considered for selected patients with these baseline characteristics.Proprietary relationships: Dr. Potter has acted as a consultant to Novartis Ophthalmics and QLT Inc.; neither company provided funds or input to this report.This material was presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology, 2003.     

Immunohistochemical localization of protein 3-nitrotyrosine and S-nitrosocysteine in a murine model of inhaled nitric oxide therapy

Inhaled nitric oxide (INO) therapy is currently used clinically to selectively dilate the pulmonary vasculature and to help treat persistent pulmonary hypertension and bronchopulmonary dysplasia in the neonate. However, in the presence of oxygen or superoxide, nitric oxide forms potentially harmful reactive nitrogen species. Using an experimental mice model, we examined the effects of concurrent hyperoxia and INO on protein tyrosine nitration and cysteine S-nitrosylation in pulmonary tissue. Data showed enhanced 3-nitrotyrosine staining within the airway epithelium and alveolar interstitium of mice lungs treated with hyperoxia, which did not increase significantly with INO administration. Within the alveolar interstitium, 3-nitrotyrosine staining was localized to macrophages. S-Nitrosocysteine staining in airway epithelium was significantly enhanced with INO administration regardless of oxygen content. These data suggest that the formation of protein S-nitrosocysteine is the major protein modification during administration of INO.