Effects of homeobox genes on the differentiation of photoreceptor and nonphotoreceptor neurons

PURPOSE: The homeobox genes Pax6 and Chx10 are diffusely expressed in proliferating, undifferentiated retina neuroepithelial cells. Distinct, topographically specific expression patterns emerge, however, as postmitotic cells become organized into layers. The hypothesis that the product of each gene may be necessary for the differentiation of particular nonphotoreceptor neuron subsets and that their absence may be required for progenitor cells to differentiate as photoreceptors was tested in this study. METHODS: Neural retinas from 5-day-old chick embryos were dissociated, cultured at low density, and cotransfected with a plasmid expressing the green fluorescent protein (GFP) reporter gene, and a plasmid expressing Pax6, Chx10, Optx2, or the control gene lacZ. After further culture, the cells were fixed and processed for the detection of cell-specific markers. RESULTS: Nonphotoreceptor neurons increased threefold with Chx10 and almost sixfold with Pax6, compared with cells transfected with lacZ. The frequency of GFP(+) cells immunoreactive with the ganglion cell-specific antibody RA4 was unchanged by Chx10, but was increased twofold by Pax6. Conversely, Chx10 and Pax6 expression diminished the photoreceptor population to approximately 35% and 15% of control values, as determined by morphologic analysis, visinin immunocytochemistry, and peanut lectin binding. Optx2 had some inhibitory effects on photoreceptor differentiation, which were accompanied by marked increases in the frequency of morphologically undifferentiated cells. CONCLUSIONS: These results are consistent with the hypothesis that Chx10 and Pax6 promote the differentiation of nonphotoreceptor neurons while inhibiting the differentiation of photoreceptor cells.     

Functional comparison of DCs generated in vivo with Flt3 ligand or in vitro from blood monocytes: differential regulation of function by specific classes of physiologic stimuli

Dendritic cells (DCs) are a family of leukocytes that initiate T- and B-cell immunity against pathogens. Migration of antigen-loaded DCs from sites of infection into draining lymphoid tissues is fundamental to the priming of T-cell immune responses. In humans, the major peripheral blood DC (PBDC) types, CD1c+ DCs and interleukin 3 receptor-positive (IL-3R+) plasmacytoid DCs, are significantly expanded in vivo with the use of Flt3 ligand (FL). DC-like cells can also be generated from monocyte precursors (MoDCs). A detailed comparison of the functional potential of these types of DCs (in an autologous setting) has yet to be reported. Here, we compared the functional capacity of FL-expanded CD1c+ PBDCs with autologous MoDCs in response to 3 different classes of stimuli: (1) proinflammatory mediators, (2) soluble CD40 ligand trimer (CD40L), and (3) intact bacteria (Escherichia coli). Significant differences in functional capacities were found with respect to changes in phenotype, migratory capacity, cytokine secretion, and T-cell stimulation. MoDCs required specific stimuli for the expression of functions. They responded vigorously to CD40L or E coli, expressing cytokines known to regulate interferon-gamma (IFN-gamma) in T cells (IL-12p70, IL-18, and IL-23), but required prostaglandin E2 (PGE2) during stimulation to migrate to chemokines. In contrast, PBDCs matured in response to minimal stimulation, rapidly acquired migratory function in the absence of PGE2-containing stimuli, and were low cytokine producers. Interestingly, both types of DCs were equivalent with respect to stimulation of allogeneic T-cell proliferation and presentation of peptides to cytotoxic T lymphocyte (CTL) lines. These distinct differences are of particular importance when considering the choice of DC types for clinical applications.     

Comparison of nickel patch test reactivity in phases of the menstrual cycle

BACKGROUND: In earlier studies, it has been shown that severity of some diseases varies with menstrual cycle. Severity of skin diseases such as atopic dermatitis, lupus erythematosus, infections due to herpes virus, urticaria and acne were also reported to increase in the premenstrual phase. Effect of estradiol on the cellular immune system was investigated and it was found to depress the cellular immune response. In our study, we investigated whether nickel patch test reactivity was different during phases of the menstrual cycle and whether there was an increase in sensitivity to nickel during the premenstrual cycle in nickel-sensitive women. METHODS: The study consisted of 30 women who had a history of nickel sensitivity. Finn Chamber nickel patch test was applied to all 30 women by dividing them into two groups of 15 and applying the test first on days 7-10 and then on days 20-24 of the menstrual cycle or vice versa. RESULTS: The reactions of both the groups on days 20-24 were more severe than those on days 7-10 even though the results were not statistically significant. CONCLUSIONS: Estrogens not only impair the skin barrier but also have a negative impact on the immune system. Estradiol has been proved to suppress cellular immunity. In a few studies conducted to date, the relationship between phases of the menstrual cycle and the severity of patch test reactivity has been examined with equivocal results. In our study, we observed that the presence of reactions due to nickel sensitivity was independent of the phases of the menstrual cycle. Nevertheless, we would like to point out the fact that the reactions seen in the second phase of the menstrual cycle were more severe than those seen in the first phase.     

Short-course preoperative radiation therapy for operable rectal cancer

BACKGROUND: Short course neoadjuvant radiation has been shown to provide improved local control of rectal cancer in a clinical trial population even in the presence of standardized surgical techniques. However, this use of hypofractionated radiotherapy has been limited in North America owing to concerns over toxicity.METHODS: Patients considered to have locally advanced rectal carcinoma received a radiation dose of 25 Gy given in five fractions to the posterior pelvis. Definitive surgery was then performed within 2 weeks. Retrospective analysis was performed. RESULTS: Sixty-three patients, of whom 60 were assessable, were treated with preoperative short course radiotherapy at the British Columbia Cancer Agency between 1991 and 1998, and 97% proceeded to R0 resection. Local recurrence developed in 3 patients (5%). Five-year actuarial overall and relapse-free survival rates for the group were 71% and 69%, respectively. The actuarial rates of relapse-free survival by stage at 5 years were stage 1 83%, stage II 75%, stage III 62%, and stage 4 0%. Eleven patients (18%) experienced a postoperative complication.CONCLUSION: Short course preoperative radiotherapy for operable rectal cancer can be delivered to a general population and produce high pelvic control rates with acceptable toxicity.     

A comparison of liquid-based cytology with conventional cytology.

OBJECTIVE: To evaluate the 2 methods of cytologic screening to detect abnormalities of the cervical epithelium. METHODS: This study with 3 groups of women was performed at Selcuk University Meram Medical School between January 2004 and March 2006. In one group (paired sample for specimen collection) women were screened with conventional cytology; in another group (paired sample for specimen collection) they were screened with liquid-based cytology; and in the third group (split sample for specimen collection) they were screened by both methods. RESULTS: The rate of unsatisfactory results was lower in the liquid-based than in the conventional cytology group (6.1% vs. 2.6%; P<0.05). More smears containing atypical squamous cells of undetermined significance were detected by the liquid-based method, but the difference was not statistically significant. Also, no statistically significant differences between liquid-based and conventional cytology were observed in the detection of other epithelial abnormalities (P>0.05). CONCLUSION: The liquid-based and conventional cytology methods were found to be equivalent in the detection of cervical epithelial abnormalities.     

Mite-sensitive asthma of childhood: Trial of avoidance measures

A trial of the effects of measures designed to reduce exposure to house-dust mites was performed on 14 children with mite-sensitive asthma. These measures reduced mite infestation of the beds and were associated with clinical improvement of asthmatic symptoms. Immunological studies revealed a tendency for levels of total serum IgE to fall during the course of the trial, but no such changes were apparent in the levels of anti-mite specific serum IgE. Possible reasons for this discrepancy are discussed.The conclusion of the study is that the use of a plastic mattress cover and the other inexpensive and harmless avoidance measures described should be advised for all asthmatic children with evidence of mite-sensitivity before resort to drug prophylaxis or hyposensitization procedures.     

Acute Isovolemic Anemia Does Not Impair Peripheral or Central Nerve Conduction

Background: Previous studies have found subtle slowing of responses in tests of addition and digit-symbol substitution during acute severe isovolemic anemia to a hemoglobin concentration of 5 g/dl in healthy unmedicated humans. In this study, the authors tested the hypothesis that such changes relate to the slowing of afferent neural traffic.

Methods: The median nerve was stimulated at the wrist in seven healthy unmedicated volunteers before and after induction of acute isovolemic anemia to a nadir hemoglobin concentration of 5.1 +/- 0.3 g/dl (mean +/- SD). Times for neural impulses to travel from the stimulus site to the brachial plexus, cervical spinal cord, and cerebral cortex were measured using somatosensory evoked potentials. Tests were repeated during acute anemia with the subject breathing oxygen. As a control for time and intrasubject variation, the testing was repeated on a separate day when anemia was not produced at times equivalent to those on the experimental day.

Results: Induced acute severe isovolemic anemia decreased nerve conduction latencies from the wrist to the contralateral cerebral cortex (i.e., to the N20 peak) by 2.3 +/- 1.6% compared with values at a mean hemoglobin concentration of 12.7 g/dl (P < 0.01). These decreased latencies were due solely to an increased peripheral conduction velocity, from the wrist to the brachial plexus (P < 0.05), and were not altered when subjects breathed oxygen (P > 0.05). Conduction velocity from the brachial plexus or cervical spinal cord to the cerebral cortex did not change with acute anemia (P > 0.05). Latencies did not differ on the control day among the times of testing (all P > 0.05), nor did they differ at baseline between the control and experimental days (all P > 0.05).     

Parathyroid adenomas evaluated by Tl-201/Tc-99m pertechnetate subtraction scintigraphy and high-resolution ultrasonography

Thallium-201/technetium-99m pertechnetate subtraction scintigraphy of the parathyroid glands was performed in a prospective study of 33 patients who had undergone bilateral neck exploration for elevated serum calcium and serum parathyroid hormone levels. In 31 cases, the Tl-201/Tc-99m subtraction technique yielded an overall sensitivity of 81%, specificity of 99%, and accuracy of 94% for identifying solitary parathyroid adenomas. Tl-201/Tc-99m subtraction scintigraphy correctly identified 73% of parathyroid adenomas weighing less than 499 mg, 79% of those weighing 500-1,499 mg, and 100% of adenomas weighing more than 1,500 mg. In a subgroup of 24 patients with solitary parathyroid adenomas who underwent both scintigraphy and high-resolution sonography, the sensitivity, specificity, and accuracy of both procedures were similar.