Clinicopathologic correlates of loss of heterozygosity in Wilms' tumor: A preliminary analysis

Wilms' tumor-specific loss of heterozygosity (LOH) for DNA markers located at chromosomes 11p13, 11p15, 16q, and 1p has been reported to occur in a minority of Wilms' tumors. We hypothesized that tumors classified by region of LOH would exhibit specific clinicopathologic patterns. We have therefore determined the constitutional and tumor genotypes for markers at 11p13, 11p15, 16q, and 1p in a large series of Wilms' tumor patients who were registered on a Pediatric Oncology Group study and on the National Wilms' Tumor Study, to determine whether tumor-specific LOH for any of these regions was associated with any specific phenotype. Of 286 cases, 27% had LOH at both 11p13 and p15 (BOTH), 3% at 11p13 only, 8% at 11p15 only, and 62% at neither. Significant associations were found between younger age at diagnosis and LOH for BOTH, but not for 11p15 only, and between the presence of intralobar nephrogenic rests and LOH for BOTH. The incidence of nephrogenic rests (all types combined) and of bilateral tumors was the same in tumors with or without LOH. There was a negative association between anaplastic histology and LOH for 11p. There was no association between LOH on 11p and outcome as assessed by relapse-free and overall survival. The associations between age at diagnosis and LOH are interpreted as suggesting the existence of a Wilms' tumor locus on 11p in addition to WT1 at 11p13 and the putative WT2 at 11p15. LOH for chromosome 16q was identified in 17% of 204 tumors and was associated with a significantly worse outcome. Outcome for patients with LOH for 1p was also worse but not significantly so. © 1996 Wiley-Liss, Inc.     

Tracking an occluded visual target with sequences of saccades

Gaze behavior during visual tracking consists of a combination of pursuit and saccadic movements. When the tracked object is intermittently occluded, the role of smooth pursuit is reduced, with a corresponding increase in the role of saccades. However, studies of visual tracking during occlusion have focused only on the first few saccades, usually with occlusion periods of less than 1 second in duration. We investigated tracking on a circular trajectory with random occlusions and found that an occluded object can be tracked reliably for up to several seconds with mainly anticipatory saccades and very little smooth pursuit. Furthermore, we investigated the accumulation of uncertainty in prediction and found that prediction errors seem to accumulate faster when an absolute reference frame is not available during tracking. We suggest that the observed saccadic tracking reflects the use of a time-based internal estimate of object position that is anchored to the environment via fixations.     

Developmental potentialities and surface antigens of mouse teratocarcinoma x lymphoid cell hybrids

Hybrids between PCC4-aza 1 teratocarcinoma cells and either thymus cells (PcT and RPcT hybrids) or Lc lymphocytic leukemia cells (PcLc hybrids) are carcinoma cells and when injected into hosts they produce tumors which are teratocarcinomas. PcT and RPcT hybrid tumors are well differentiated and include a large variety of somatic tissues. In most PcLc tumors, neuroectoderm differentiation is predominant. Like the PCC4 parental cells, PcT, RPcT, and PcLc hybrids carry F9 embryonic antigens and do not express perceptible amounts of H-2 alloantigens. Nonexpression of the H-2^d haplotype of the thymus cell parent in PcT hybrids is not due to the loss of chromosome 17 which carries the major histocompatibility complex.A preliminary account of some of these results has been presented at the XIVth International Congress of Genetics, Moscow, August 1978.     

Levonorgestrel-releasing intrauterine device-wearing women express contraceptive glycodelin A in endometrium during midcycle: another contraceptive mechanism?

Intrauterine devices (IUDs) exert contraceptive action by interfering with sperm transport, ovum development, fertilization and implantation. Glycodelin A (GdA) is a uterine glycoprotein that has local contraceptive activity by inhibiting sperm-egg binding. GdA is normally absent from endometrium during the fertile midcycle and it is not expressed until the fifth postovulatory day. The phase of menstrual cycle addressed in this study covers the phase when conception is most likely to follow an unprotected intercourse and when GdA is normally absent. We present here evidence that levonorgestrel-releasing IUD (LNg- IUD) is accompanied by 'inappropriate' expression of GdA in endometrium between days 7 and 16 of the menstrual cycle (six out of six cases). The same was also found in copper-releasing IUD (Cu-IUD)-wearing women, but less frequently (four out of 11 cases, P < 0.0345, Fisher's exact test). In-situ hybridization localized GdA mRNA into endometrial glands in the midcycle endometrium, confirming the cellular site of synthesis. Based on the potent inhibitory activity of GdA on sperm-egg binding, the presence of GdA in uterine glands of IUD wearers may lead to prior exposure of sperm to contraceptive GdA, thus contributing to the contraceptive activity of the IUD.      

Ensemble discharge from Golgi tendon organs of cat peroneus tertius muscle

1. The responses of individual tendon organs of the cat peroneus tertius muscle to motor-unit contractions were recorded in anesthetized cats during experiments in which all the Ib-afferent fibers from the muscle had been prepared for recording in dorsal root filaments. This was possible because the cat peroneus tertius only contains a relatively small complement of approximately 10 tendon organs. 2. Motor units of different physiological types were tested for their effects on the whole population of tendon organs in the muscle. Effects of unfused tetanic contractions were tested under both isometric and anisometric conditions. Each motor unit activated at least one tendon organ, and each tendon organ was activated by at least one motor unit. Individual slow-type units were found to act on a single or two receptors, whereas a fast-type unit could activate up to six tendon organs. 3. In one experiment, the effects of 8 motor units on 10 tendon organs were examined. One fast-twitch, fatigue resistant (FR)-type unit acted on six tendon organs, of which four were also activated by another FR unit. The contraction of each unit, on its own, elicited a range of individual responses, from weak to strong. The discharge frequencies of individual responses displayed no clear relation with the strength of contraction, nor did they accurately represent the shape of force profiles. But when all the discharges were pooled, a fairly good correspondence appeared between variations of contractile force and variations of averaged discharge frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of muscle shortening on the responses of cat tendon organs to unfused contractions

1. The discharges from individual Golgi tendon organs of peroneus tertius and brevis muscles were recorded in anesthetized cats. Responses to unfused isometric contractions of single motor units and combinations of motor units were compared with responses to contractions eliciting muscle shortening (i.e., shortening contractions). 2. In 75% of the examined instances, the effect of muscle shortening during unfused contractions was a slight decrease in tendon organ activation, in keeping with the reduction of contractile tension recorded at the muscle tendon. In other instances there was either no change in tendon organ response or, in less than 10% of instances, a slight increase For two motor units eliciting similar activation of a given tendon organ under isometric conditions, the effect of shortening contraction was not necessarily the same. 3. The reductions observed in tendon organ discharges upon muscle shortening were less than proportional to the reductions of contractile tension and difficult to correlate with the properties of motor units, as determined under isometric conditions. The present observations suggest three main reasons for this lack of relation. 4. The first reason depended on the properties of motor units, in that the relation between length changes and tension changes was not the same for all units. Two motor units developing similar isometric tensions did not necessarily produce the same degree of muscle shortening. Some units produced relatively significant shortening without much loss of tension. 5. Second, the dynamic sensitivity of tendon organs is known to exert a major influence on their responses to isometric unfused contractions, accounting for 1:1 driving of discharge during tension oscillations and high frequency bursts upon abrupt increase of tension. Although less tension was produced and the rate of tension development was slower in shortening contractions, similar manifestations of the dynamic sensitivity of tendon organs were observed. In such cases, the responses of tendon organs were the same whether or not the muscle shortened during contraction. 6. Third, when several motor units were stimulated in combination, the unloading influences of in-parallel units were facilitated by muscle shortening so that unloading effects, which were hardly visible under isometric conditions became evident during shortening contractions.     

Effects of social status and moderate alcohol consumption on mammary gland and endometrium of surgically postmenopausal monkeys

OBJECTIVE: To evaluate the effects of social subordination stress and chronic moderate alcohol consumption on indices of breast and endometrial cancer risk. DESIGN: Forty-six adult, ovariectomized, cynomolgus monkeys (Macaca fascicularis) were trained to voluntarily drink a placebo or a two-drink/day equivalent of ethanol (0.5 g/kg), 5 days a week for 26 months, the latter resulting in average blood alcohol levels of 42 mg/100 mL. Indices of cell proliferation and sex steroid receptor abundance were measured. RESULTS: Compared with dominants, socially subordinate females had increased cell proliferation and proportions of glandular (P < 0.02) and epithelial tissue (P = 0.009) and less stroma (P < 0.02) in endometrium, and increased tissue thickness in breast (P < 0.05). There was no evidence of increased risk of breast or endometrial cancer with chronic moderate alcohol consumption, as indicated by markers of cell proliferation and sex steroid receptor abundance. Chronic moderate alcohol consumption did not effect circulating sex steroid concentrations (all P > 0.10). The adipocyte hormones leptin and adiponectin were correlated with indices of cell proliferation and sex steroid receptor abundance. CONCLUSIONS: These observations suggest that social status was more important than chronic moderate alcohol consumption in endometrial and breast biology of surgically postmenopausal females. Endogenous sex steroid metabolism was not significantly affected by chronic moderate alcohol exposure consistent with the lack of estrogen-like effects on breast and endometrium. Social subordination stress was associated with initial cellular changes that may increase endometrial cancer risk. Ovariectomized cynomolgus monkeys may be a useful model for the study of effects of social factors and obesity on breast and endometrial cancer risk.     

Symptom presentation and outcome of cognitive-behavioral therapy for obsessive-compulsive disorder

Previous researchers have classified obsessive-compulsive disorder (OCD) patients by the themes of their obsessions and compulsions (e.g., washing, checking); however, mental compulsions have not been adequately assessed in these studies. The authors conducted 2 studies using a large sample of OCD patients (N=132). In the 1st study, they categorized patients on the basis of symptom presentation, giving adequate consideration to mental compulsions. Five patient clusters were identified: harming, contamination, hoarding, unacceptable thoughts, and symmetry. Mental compulsions were most prevalent among patients with intrusive, upsetting religious, violent, or sexual thoughts. In the 2nd study, they compared response to cognitive-behavioral therapy across symptom categories, finding poorer outcomes among patients with hoarding symptoms compared with those with other symptom themes.