Development of contrast sensitivity and temporal-frequency selectivity in primate lateral geniculate nucleus

We studied the development of spatial contrast-sensitivity and temporal-frequency selectivity for neurons in the monkey lateral geniculate nucleus. During postnatal week 1, the spatial properties of P-cells and M-cells are hardly distinguishable, with low contrast-sensitivity, sluggish responses, and poor spatial resolution. The acuity of P-cells improves progressively until at least 8 months, but there is no obvious increase in their maximum contrast-sensitivity with age. The contrast sensitivity of M-cells is already clearly higher than that of P-cells by 2 months, and at 8 months of age this characteristic difference between M- and P-cells approaches the adult pattern. There is a major increase in responsiveness during the first 2 postnatal months, especially for M-cells, the peak firing rate of which rises fivefold, on average, between birth and 2 months. Many P-cells in the neonatal and 2-month-old animals did not give statistically reliable responses to achromatic gratings, even at the highest contrasts: this unresponsiveness of P-cells might result from low gain and/or chromatic opponency. The upper limit of temporal resolution in the neonate is low--about one-third of that in the adult. Among M-cells, the improvement in temporal resolution, like that in contrast sensitivity, is rapid over the first 2 months, followed by a slower change approaching the adult value by 8 months of age. The development of contrast sensitivity, responsiveness and temporal tuning are little affected, if at all, by binocular deprivation of pattern vision from birth for even a prolonged period.     

Reengineering a surgical service line: focusing on core process improvement

Integrating principles from a variety of theory has led to the development of a conceptual framework for reengineering in a clinical care delivery setting to improve the value of services provided to the customer. A conceptual framework involving the identification of three high level core processes to reengineer can provide clarity and focus for clinicians to begin directing reengineering efforts. Those core processes are: clinical management of the patient's medical needs, patient operational processes to support the clinical processes, and administrative decision-making processes to support the implementation of the clinical and operational processes. Improvement in any one of these areas has the potential to increase value, but the concurrent targeting of these core processes for reengineering has provided a synergy that has accelerated the achievement of the desired outcomes in the area of surgical services.     

Identification of a gene that causes primary open angle glaucoma

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.     

Glass-ionomer cements in restorative dentistry

This article reviews the current status and future prospects for glass-ionomer materials. These materials are of two chemical types: the older, self-hardening cements, which set by an acid-base neutralization reaction to give relatively brittle materials; and the newer, resin-modified cements, which set partly by polymerization and partly by neutralization. Compared with the self-hardening cements, the latter materials have improved esthetics, improved resistance to moisture, and greater toughness. Both types of glass-ionomer cement bond well to enamel and dentin and release a clinically useful amount of fluoride. They have been used in a variety of applications: as liners or bases, for luting of stainless steel crowns, for Class V restorations in permanent teeth, and for Class II and Class III restorations in primary teeth. The resin-modified glass-ionomers are particularly promising for these latter uses, although it is too early to be sure whether their long-term durability is sufficient. Self-hardening glass-ionomer materials are likely to retain specific niches of clinical application, including in their metal-reinforced and cermet-containing forms.     

Suppression of MHC class II expression by human class II trans-activator constructs lacking the N-terminal domain

The class II trans-activator (CIITA) is a bi- or multi-functional domain protein which plays a critical role in the expression of MHC class II genes. We report that removal of the N-terminal 151 amino acids, encompassing all of the acidic domain but leaving intact the proline/serine/threonine-rich domain, results in a mutant protein with potent suppressive properties for MHC class II expression. HeLa cells stably or transiently transfected with mutant CIITA constructs showed up to 99% suppression of MHC class II antigen induction by IFN-gamma and marked suppression of HLA-DRA mRNA expression. Transient transfection of a B lymphoma line resulted in up to 89% reduction of constitutive MHC class II expression within 5 days and suppression of HLA-DRA mRNA synthesis.     

Exclusion of BMP6 as a candidate gene for cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized skeletal dysplasia in humans that has been mapped to the short arm of chromosome 6. We report linkage of a CCD mutation to 6p21 in a large family and exclude the bone morphogenetic protein 6 gene (BMP6) as a candidate for the disease by cytogenetic localization and genetic recombination. CCD was linked with a maximal two-point LOD score of 7.22 with marker D6S452 at theta = 0. One relative with a recombination between D6S451 and D6S459 and another individual with a recombination between D6S465 and CCD places the mutation within a 7 cM region between D6S451 and D6S465 at 6p21. A phage P1 genomic clone spanning most of the BMP6 gene hybridized to chromosome 6 in band region p23-p24 using FISH analysis, placing this gene cytogenetically more distal than the region of linkage for CCD. We derived a new polymorphic marker from this same P1 clone and found recombinations between the marker and CCD in this family. The results confirm the map position of CCD on 6p21, further refine the CCD genetic interval by identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a candidate gene.     

Activation of the mitogen-activated protein kinase pathway is involved in and sufficient for megakaryocytic differentiation of CMK cells

Activation of the mitogen-activated protein (MAP) kinase pathway has been associated with both cell proliferation and differentiation. Constitutively activated forms of Mek (MAP kinase/Erk kinase) and Erk (MAP kinase) have been previously shown capable of inducing differentiation or proliferation in nonhematopoietic cells. To specifically examine the role of Erk activation in megakaryocytic growth and development, we activated the MAP kinase pathway by the transfection of constitutively activated Mek or Erk cDNA into a human megakaryoblastic cell line, CMK, by electroporation. The CMK transfectant clones that expressed constitutively activated Mek or Erk showed morphologic changes of differentiation. Transfected cells also showed expression of mature megakaryocytic cell surface markers. The MAP kinase pathway was also activated by treatment of the hematopoietic cells with a cytokine that activates Erk. The treatment of CMK cells with stem cell factor (SCF ) caused MAP kinase activation and induced differentiation by the expression of mature megakaryocytic cell surface markers. The effects of the SCF treatment were inhibited by pretreatment with a specific inhibitor of the MAP kinase pathway, PD98059. In this report, we conclude that activation of the MAP kinase pathway was both necessary and sufficient to induce differentiation in this megakaryoblastic cell line.     

Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Difference limens for formant patterns of vowel sounds

Studies of thresholds for discrimination of formant frequency variation in synthetic vowel sounds have been predominantly limited to variations in a single formant. Here, differences limens (DLs) are presented for multiformant variations expressed in measures of delta F and as distances in the auditory-perceptual space (APS) proposed by J. D. Miller [J. Acoust. Soc. Am. 85, 2114-2134 (1989)]. DLs for four subjects were estimated along 102 synthetic vowel continua representing five patterns of formant variation [(1) single variation in F1; (2) single variation in F2; (3) parallel simultaneous variation in F1 and F2; (4) opposing simultaneous variation in F1 and F2; and parallel simultaneous variation in F1, F2, and F3] and 17 within- or between-category vowel sounds. Minimal uncertainty methodology was employed utilizing an adaptive up-down procedure with a cued, two-interval forced-choice (2IFC) task. The results of this experiment reflect smaller DLs for both single- and multiple-formant changes than have been found in the past and also suggest that discrimination of parallel multiformant variation is significantly better than opposing multiformant or single-formant variation.     

Establishment and neurite outgrowth properties of neonatal and adult rat olfactory bulb glial cell lines

Two glial cell types surround olfactory axons and glomeruli in the olfactory bulb (OB) and may influence synapse development and regeneration. OB astrocytes resemble type-1 astrocytes, and OB ensheathing cells resemble non-myelinating Schwann cells. We have produced clonal OB astrocyte and ensheathing cell lines from rat neonatal and adult OB cultures by SV40 large T antigen transduction. These cell lines have been characterized by morphology, growth characteristics, immunophenotype, and ability to promote neurite outgrowth in vitro. Neonatal and adult ensheathing cell lines were found to support higher neurite outgrowth than OB astrocyte lines. Neonatal OB astrocyte lines were of two types, high and low outgrowth support. The low support astrocyte lines express J1 and a chondroitin sulfate-containing proteoglycan as do astrocytes encircling the neonatal glomeruli in vivo. The adult OB astrocyte cell lines supported lower levels of outgrowth than adult ensheathing cell lines. These results are consistent with a positive role for ensheathing cells in OB synapse regeneration, in vivo. Further, based on our results, we hypothesize that ensheathing cells and high-outgrowth astrocytes facilitate axon growth in vivo, while low outgrowth astrocytes inhibit axon growth and may facilitate glomerulus formation.