The importance of spatial scale in determining illusions of orientation

The twisted-cord illusion is a powerful demonstration of interaction between 1st-order (luminance-defined) and 2nd-order (contrast-defined) orientation processing. The perceived orientation of contrast-defined objects is pulled towards their 1st-order orientation content when the difference in orientation is small (Fraser effect), yet is pushed away from the 1st-order content at large orientation differences (Z?llner effect). Here we show that the relative spatial scale of carrier and envelope represents a decisive factor in determining the magnitude and direction of such interactions. We conclude that the perceived 2nd-order structure of a stimulus is biased by the properties of the 1st-order structure in a manner that depends on relative, rather than absolute spatial scale.     

Preparation of a monoclonal antibody to citrullinated epitopes: its characterization and some applications to immunohistochemistry in human brain

Using hybridoma technology, an IgM monoclonal antibody (mAb), designated as F95, was developed against a deca-citrullinated peptide (DCP) consisting of 10 citrulline residues and a carboxyl Gly-Gly-Cys through which DCP was covalently linked to an activated carrier protein, keyhole limpet hemocyanin (KLH). Clones were selected on the basis of not reacting with human unmodified and noncitrullinated myelin basic protein (MBP), MBP-C1, but reacting well with human citrullinated MBP (MBP-C8). When tested by ELISA, this mAb demonstrated minimal reactivity with human MBP-C1, varying reactivity with the C2-C5 isomers of human MBP, moderate binding with guinea pig MBP-C8, and strong reactivity with human MBP-C8. By ELISA, mAb F95 was directed predominantly against citrulline, not MBP, as revealed by its binding to DCP linked with activated KLH, bovine serum albumin (BSA), or ovalbumin (OA), but not with KLH, BSA, or OA alone. Immunohistochemistry of normal human brain demonstrated that F95 stained central nervous system myelin and a subset of astrocytes. Given the citrulline-directed features of mAb F95, this immunohistochemical pattern suggests that certain astroglial filaments expressing glial fibrillary acidic protein also contain citrulline-bearing components. These potentially implicate citrullinated proteins, notably in astroglial filaments, in a variety of normal and pathological neurobiological processes.     

Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators

OBJECTIVE: To determine whether linomide (roquinimex) is better than placebo in slowing the time to confirmed clinical worsening in patients with relapsing-remitting (RR) and secondary progressive (SP) MS. METHODS: In this 27-center, randomized, double-blind, placebo-controlled, multiple-dose, phase III trial, 715 patients with active RRMS (n = 90) or SPMS (n = 625) were randomized to receive either linomide (1.0, 2.5, or 7.5 mg orally daily) or placebo. Patients were evaluated at 3-month intervals clinically and with MRI. The planned primary outcome was the time to the development of "confirmed" clinical worsening (increase of >/= 1.0 Expanded Disability Status Scale [EDSS] score for an enrollment EDSS score /= 0.5 point for an enrollment EDSS score of >/= 5.5) not associated with an acute relapse. RESULTS: The trial was terminated 1 month after it became fully enrolled due to unanticipated serious cardiopulmonary toxicities (pericarditis, pleural effusion, myocardial infarction, and possible pulmonary embolism), pancreatitis, and death. Notable arthralgia, myalgia, bursitis, and facial and peripheral edema were common adverse events. The high dose of linomide (7.5 mg) was not well tolerated. The trial was too brief to determine unequivocal clinical benefits. Trends suggested an unconfirmed early effect on change in EDSS score at 6 months for the medium dose (2.5 mg daily). CONCLUSION: MS patients may be more prone to develop important linomide treatment-related adverse events than other previously studied patients. However, linomide may be a potentially more toxic drug than was suspected from observations made in smaller studies for other indications. Phase III trials may identify infrequent and important toxicities that may not be anticipated by phase I and II trials.     

Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.

BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis. METHODS: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-beta1 or TGF-beta2 plus TGF-beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. RESULTS: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P相似文献   

Neutrophil alkaline phosphatase (NAP) score in the diagnosis of hypophosphatasia

Hypophosphatasia is an inherited disease characterised by low tissue non-specific alkaline phosphatase (TNSALP) levels and skeletal defects. Diagnosis is usually made by measurement of serum total alkaline phosphatase (TALP, reference range 40-130 iu/l) and pyridoxal-5'-phosphate (PLP), and urine phosphoethanolamine (PEA). Neutrophil alkaline phosphatase (NAP) scores (reference range 20-150) have been reported to be low in isolated cases, but no comparison has been made of the diagnostic value of NAP, TALP, PEA and PLP in hypophosphatasia. We undertook such a comparison in six families with hypophosphatasia. In four families (Families 1, 2, 5, 6) with the adult type of hypophosphatasia, inherited as autosomal dominant, the NAP score and TALP (<40 iu/l), were low, <20 and <40 iu/l respectively, in all affected subjects, though the PEA and PLP were not consistently abnormal. In one of the two families (Family 3) with the autosomal recessive type of hypophosphatasia an affected subject had low NAP as well as low TALP, PLP and PEA. In another family (Family 4) one of the heterozygotes had a low NAP while the other had a normal NAP score (45). A child in this family had a normal TALP level. Her low NAP score (15) supported her to be a possible heterozygote. NAP score is readily available from most laboratories and may be diagnostically helpful in hypophosphatasia.     

Cocaine use in pregnancy in Amsterdam

To study the effects of cocaine use in pregnancy in Amsterdam, clinical data on cocaine-using pregnant women ( n = 21) and their offspring ( n = 23) were obtained retrospectively (1987–1994) at the Academic Medical Center, Amsterdam. Infants exposed to cocaine had a median gestational age of 39 weeks and a median birth weight of 3090 g. There were six preterm infants, two small-for-gestational-age infants and five infants with a small head circumference. Three infants had a congenital malformation. One infant (Potter's syndrome) died shortly before birth. One infant had congenital syphilis, four had intracerebral abnormalities on ultrasound and four had abnormal neurologic symptoms in the neonatal period. One infant died after 21 days of life. At follow-up four infants showed abnormal development. In 12 of the 23 infants (52%), one or more possible effects of cocaine were found.     

Variations in hyperacuity performance with age

The term hyperacuity has been applied to a group of stimuli which produce spatial thresholds smaller than those expected given the relatively large receptor spacing and the retinal image quality of the human eye. It is not yet firmly established whether hyperacuity performance declines with increasing age in the same way as most other measures of visual ability. This is perhaps due to the use of varying task configurations and criterion-dependent psychophysical techniques. The present study examines age-related performance in three different hyperacuity tasks using a criterion independent forced-choice method. Both displacement and bisection thresholds were found to increase with age, but there was no significant change in vernier acuity. This indicates that age has a differential effect on thresholds for various hyperacuities depending upon the task requirements. No significant age-related trend was observed in hyperacuity bias, which represents the difference between subjective and true physical alignment.