Biomedical subjects
Publications and source records attributed to L M Williams.
Pulmonary veno-occlusive disease (PVOD) was diagnosed in an adult following chemotherapy and bone marrow transplantation (BMT) for acute lymphoblastic leukemia. A medical literature review showed only three previous reports of PVOD following BMT occurring in children but no prior cases in adults.
The pars tuberalis is a structurally distinct region of the adenohypophysis, the function of which has been unclear for decades. Recent studies, which demonstrate the localization of melatonin receptors on the pars tuberalis, suggest a photoperiodic function. The principal cell type of the pars tuberalis is morphologically distinct from others in the pituitary and is thought to secrete a specific product. In support of this, evidence is emerging that ovine pars tuberalis cells secrete a factor ('tuberalin') that exerts hormonal control over both gene expression and prolactin release from the pars distalis lactotrophs. These data in conjunction with physiological studies, which show that photoperiodically driven cycles in prolactin secretion can occur in the absence of an intact hypothalamic-pituitary axis, suggest that the function of the pars tuberalis is to act as an endocrine intermediate in the photoperiodic effects of melatonin on prolactin secretion. Studies of the cellular biochemistry of the ovine pars tuberalis suggest that the main function of melatonin is to prevent or terminate transcriptional and translational activation by an unidentified factor (Stim X). On the basis of these physiological and biochemical studies, a hypothetical model is proposed to account for the mechanism of photoperiodic regulation of prolactin secretion by melatonin.
To define the hormonal influences that are directly involved in the hair follicle cycles of animals with differing patterns of fibre growth and moulting, we have investigated the possible presence of IGF-I and melatonin receptors on the dermis and hair follicles of cashmere and Angora goats, sampled in February. March and June, using quantitative in vitro autoradiography. The presence of IGF-I receptors in the dermis of both breeds of goat was determined using cryostat sections incubated with 50 pM 125I-labelled IGF-I in the presence or absence of 50 nM IGF-I. Sections of the growing tip of deep antlers concerning the cartilaginous zone, a tissue known to contain high concentrations of specific IGF-I receptors, were used as a positive control. As the production of antler velvet uniquely involves the generation of hair follicles de novo, the presence of IGF-I receptors in the velvet-producing region was also investigated. In both breeds of goat, specific 125I-IGF-I binding was localised over the inner and outer root sheath, the matrix, the germinal matrix, the dermal papilla and the sebaceous glands and satisfied the basic kinetic criteria considered to be representative of a specific IGF-I receptor. Analysis of saturation isotherms using a one-site binding model revealed dissociation constants (Kd) in the range 0.1-0.9 nM and theoretical maximal numbers of binding sites (Bmax) between 21.4 and 45.6 fmol/mg tissue. Kd and Bmax values derived from cashmere and Angora goats sampled at different times of the year did not differ significantly between breeds or sampling times. Specific 125I-IGF-I binding was also localised to the developing follicles on the deer antler dermis. The presence of melatonin receptors within the goat dermis was also investigated. Sections were incubated with 100 pM 2-[125I]iodomelatonin with or without 0.1 microM melatonin, along with sections of sheep pars tuberalis which are known to contain high levels of high-affinity melatonin receptors. No displaceable 2-[125I]iodomelatonin binding was found on any sections of the cashmere or Angora skin analysed. It is therefore concluded that melatonin receptors are not present on the hair follicles or associated structures. IGF-I receptors are present on the hair follicle and sebaceous gland and may be involved in the growth of both seasonally and non-seasonally produced fibre and in the development of antler velvet.
Pineal melatonin hormonally transduces photoperiod to influence daily and seasonal cycles in most vertebrates (1, 2). Evidence of melatonin receptors throughout the brain of several fish species (3-5), particularly in retinorecipient structures, also indicates a role in visual processing. Despite the absence of solar light many deepsea organisms show seasonality (6-8). The presence of central melatonin receptors was investigated by quantitative in vitro autoradiography in the deep-sea fish Coryphaenoides (Nematonurus) armatus. Specific, time-dependent, saturable, high affinity and guanine nucleotide sensitive, 2-[125I]iodomelatonin binding was found over the mid-brain tegmentum and hindbrain. Competing ligand potency was iodomelatonin > melatonin >> 5-HT. Although C.(N.) armatus has well developed eyes no 2-[125I]iodomelatonin binding occurred in optic tectum, cerebellum or hypothalamus. Thus melatonin involvement in processing of visual information and control of seasonal physiology via hypothalamic areas appears to be absent in this species. The presence of central G-protein coupled receptors indicates a function for melatonin unrelated to solar light.
This study provides evidence that some adults who claim to have recovered memories of sexual abuse recall actual events that occurred in childhood. One hundred twenty-nine women with documented histories of sexual victimization in childhood were interviewed and asked about abuse history. Seventeen years following the initial report of the abuse, 80 of the women recalled the victimization. One in 10 women (16% of those who recalled the abuse) reported that at some time in the past they had forgotten about the abuse. Those with a prior period of forgetting--the women with "recovered memories"--were younger at the time of abuse and were less likely to have received support from their mothers than the women who reported that they had always remembered their victimization. The women who had recovered memories and those who had always remembered had the same number of discrepancies when their accounts of the abuse were compared to the reports from the early 1970s.
The existence of a biosocial mechanism for inhibiting incest through early caretaking contact was explored in a comparison between incestuous fathers and a nonincestuous control sample. Low involvement in caretaking was found to be a risk factor for incest, even after controlling for other predisposing conditions. However, it appeared that caretaking has its effect by enhancing more general parental feelings and capacities, rather than by inhibiting a father's sexual interest in the daughter, as proposed in the original biosocial theory.
In the sheep, it has been shown that the pars tuberalis of the pituitary may mediate the photoperiodic control of seasonal changes in prolactin secretion. High concentrations of melatonin receptors are present on the ovine pars tuberalis and melatonin is known to inhibit forskolin-stimulated cyclic AMP production in this tissue. Other hormonal inputs to the ovine pars tuberalis have not yet been identified. In the rat mRNA for the IGF-I receptor has been identified in the pars tuberalis using in situ hybridization. In order to define whether IGF-I may influence the function of the ovine pars tuberalis the presence of receptors for IGF-I has been investigated. Using in vitro autoradiography specific [125I]IGF-I binding was found in high concentrations over the ovine pars tuberalis particularly associated with certain of the capillaries. Homogenate receptor assays showed saturable specific binding of [125I]IGF-I with a mean dissociation constant (Kd) of 0.5 +/- 0.1 nM (n = 4). Competition studies revealed a rank order of potency of IGF-I > IGF-II > > > insulin, in displacing [125I]IGF-I binding, indicative of a mixed population of IGF-I and IGF-II/mannose-6-phosphate receptors and insulin-like growth factor binding proteins (IGFBPs). Cross-linking of [125I]IGF-I to pars tuberalis membrane homogenates and analysis by SDS-PAGE under reducing conditions confirmed the presence of both IGF-I receptors and binding proteins. Autophosphorylation of a 97 kDa substrate, compatible with the beta-sub-unit of the IGF-I receptor, was increased in the presence of IGF-I, indicating the existence of functional IGF-I receptors on the ovine pars tuberalis. In contrast in the rat [125I]IGF-I binding was restricted to the median eminence region of the brain and was not detectable over the pars tuberalis.
2-(125I)iodomelatonin binding has been mapped and characterized in the brain and pituitary of the male laboratory rat using quantitative in vitro autoradiography. Specific binding was defined as that completely displaced in the presence of 1 microM melatonin. In the brain high levels of binding were localized over the suprachiasmatic nucleus (SCN), the area postrema (AP), and the spinal tract of the trigeminal nerve (Sp5). Lower densities of binding were found over the medial preoptic area (MPA), the septohypothalamic nuclei (SHy), the anterior hypothalamic area (AHA), the nuclei of the lateral olfactory tract (LOT), the paraventricular (PV), anteroventral (AV) and intermediodorsal (IMD) nuclei of the thalamus, the medial region of the lateral habenular (Lhb), the nuclei of the stria medullaris (SM), the basolateral (BL) and medial (ME) amygdaloid nuclei, the ventromedial nuclei (VMH), the arcuate nuclei (Arc), the subiculum of the hippocampus (S) and the lateral mammillary nuclei (LM). High levels of binding were also present over the pars tuberalis of the pituitary (PT) and the anterior and posterior cerebral arteries (CA). In both neuronal and non-neuronal areas, specific binding was time dependent and partially reversible in the presence of 1 microM melatonin. Binding was also saturable and of high affinity with dissociation constants (Kd) in the low picomolar range and was significantly inhibited in the presence of 10(-4)M guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) and 150 mM NaCl in all regions examined, indicating the presence of high affinity G-protein coupled melatonin receptors.
A study is reported using the 'negative priming' paradigm to examine individual differences in cognitive inhibition in relation to distinct features of schizotypy. Seventy psychology students completed four measures of schizotypy, selected to index specific schizotypal traits: the Schizotypy Scale (STA), the Magical Ideation (MI) Scale, the Revised Social Anhedonia (SoA) Scale and the Physical Anhedonia (PhA) Scale. The priming paradigm was based on that of Beech, McManus, Baylis & Agar (1991), including conventional repeat and semantic priming conditions as well as repeat and semantic negative priming conditions, but differed in terms of task and stimuli. Cluster analysis of STA scores revealed a four-cluster solution reflecting 'very low', 'moderately low', 'moderately high' and 'very high' STA scores. Cluster analysis of MI, SoA, and PhA Scale scores also revealed four clusters. The first cluster comprised those with low scores on all scales. The remaining three clusters were distinguished by those with high MI, high SoA, and high PhA Scale scores, respectively. Those with high STA, MI, and SoA scale scores showed a significantly reduced, or reversed, repeat and semantic negative priming effect compared to those with moderately low STA scores and those low on all scales, respectively. An unexpected finding was that participants with high and moderately high STA scores as well as those with high MI and SoA scores revealed an inhibitory rather than facilitatory conventional repeat priming effect. It is concluded that weakening of inhibitory processes may be associated with a strong presence of schizotypal features related to dimensions of positive schizophrenic symptomatology, whereas schizotypal traits that parallel purely negative schizophrenic symptoms are not linked to reduced inhibition unless there is also a presence of 'positive' schizotypal features. The association of some schizotypal traits with an inhibitory repeat priming effect indicates that stimuli and task differences have a bearing on the attentional processes underlying priming effects for these participants. Thus, Beech et al.'s 'reduced-inhibition' model of schizophrenic symptomatology may require refinement.
This is an exploration of whether stressful life events were related to 200 couples' marital quality after four or five years of marriage. Implications for measuring influence of stressful life events on marital quality are discussed.
A combination of in vitro autoradiography and membrane homogenate receptor assays has been used to localize and characterized 2-[125I]iodomelatonin binding sites in the brain of the rainbow trout (Onchorhynchus mykiss). Specific 2-[125I]iodomelatonin binding, defined as that displaced by 1 microM melatonin, increased linearly with increasing protein concentration in membrane homogenates of whole trout brain. Specific binding was both time and temperature dependent and reversible in the presence of 1 microM melatonin. Binding was saturable at between 100-150 pM 2-[125I]iodomelatonin and Scatchard analysis of saturation isotherms revealed a dissociation constant (Kd) of 15.00 +/- 0.95 pM and a maximum receptor number (Bmax) of 42.35 +/- 2.70 fm/mg protein (n = 16). Addition of 10(-4) M GTP gamma S (an analogue of guanosine triphosphate) to saturation isotherms apparently reduced the Bmax by 75% on average with no apparent change in the affinity of the binding. Scatchard analysis of saturation isotherms generated from whole brain membrane homogenates of trout kept on long days (15 hr light:9 hr dark) and killed either during the midlight or middark phase showed no significant differences in either the Kd or the Bmax of 2-[125I]iodomelatonin binding, although a robust rhythm in melatonin concentration was confirmed in these fish. Displacement of 2-[125I]iodomelatonin binding with increasing concentrations of competing ligands gave an order of potency of 2-iodomelatonin > melatonin >> 5-HT. Localization of specific central 2-[125I]iodomelatonin binding in the rainbow trout showed high levels of binding associated with neuronal areas involved in the processing of visual signals, particularly the optic tectum and nucleus rotundus.(ABSTRACT TRUNCATED AT 250 WORDS)
One hundred twenty-nine women with previously documented histories of sexual victimization in childhood were interviewed and asked detailed questions about their abuse histories to answer the question "Do people actually forget traumatic events such as child sexual abuse, and if so, how common is such forgetting?" A large proportion of the women (38%) did not recall the abuse that had been reported 17 years earlier. Women who were younger at the time of the abuse and those who were molested by someone they knew were more likely to have no recall of the abuse. The implications for research and practice are discussed. Long periods with no memory of abuse should not be regarded as evidence that the abuse did not occur.
A convenient and sensitive method has been developed for measuring changes in protein synthesis in discrete areas of the brain and pituitary of conscious freely moving rats. A single injection of high-concentration low-specific activity L-[35S]methionine is given to flood amino acid precursor pools, thereby equalizing the specific activity of the L-[35S]methionine throughout the tissue. Unincorporated L-[35S]methionine is removed from cryostat sections by treatment with perchloric acid (2%) before quantitative autoradiography. The sensitivity of this technique is demonstrated by the detection of changes in protein synthesis in regions of the brain and pituitary after systemic administration of interleukin-1 beta, a cytokine that has centrally mediated effects but which is not thought to cross the blood-brain barrier. Areas of the brain found to exhibit significant increases in protein synthesis were the subfornical organ, the choroid plexus, the medial habenular, the dentate gyrus, and the anterior and posterior lobes of the pituitary. In the brain, the cingulate cortex and the pineal gland showed significant decreases in the rate of protein synthesis.
The pineal hormone, melatonin, is important in the timing of seasonal reproduction in the sheep. Melatonin of maternal origin readily crosses the placenta; its function in the fetal sheep is, however, unclear. To gain an insight into the role of melatonin in ovine development we have identified specific melatonin receptors throughout gestation using 2-[125I]iodomelatonin and quantitative in vitro autoradiography. Specific binding was found at the earliest time studied at 30 days of gestation, over the developing thyroid (term = 145 days). At 31 days of gestation specific labelling was found over the thyroid and pituitary glands, the spinal nerves, nasal cavity and developing bronchi. This binding was diminished by over 50% in the presence of 10(-4) M GTP gamma S (an analogue of guanosine triphosphate) indicating that the 2-[125I]iodomelatonin binding at this early stage of gestation represents a receptor coupled to a regulatory G-protein. By 40 days of gestation specific binding was found over the nasal epithelium, cochlear epithelium, regions of the brain, especially the hind brain and the vestibulocochlear and glossopharyngeal nerves, and both the pars distalis and pars tuberalis of the pituitary. As gestation proceeded, labelling over the pars distalis appeared to become more scattered in nature while that on the pars tuberalis remained consistent. Saturation studies of both the neuronal and pituitary binding sites at 121 days of gestation and in the newborn lamb revealed a single class of high-affinity binding sites with Kd values in the picomolar range. Also at 121 days of gestation, binding over the fetal pars tuberalis was diminished in a dose-dependent manner by GTP gamma S, again confirming that specific binding is indicative of a receptor coupled to a regulatory G-protein. These data demonstrate a potential for sensitivity to melatonin from early in gestation, as well as the developmentally specific expression of the melatonin receptor in certain tissues, and suggest a wider role for melatonin in ovine fetal development than previously considered.
1. The four stereoisomeric ephedrines and four oxazolidines formed by reaction of each ephedrine isomer with salicylaldehyde were tested for their ability to increase locomotor activity in rats. 2. All ephedrine isomers except (-)pseudoephedrine increased locomotor activity; the order of potency was (-)ephedrine > (+) pseudoephedrine > (+) ephedrine. 3. All oxazolidine derivatives increased locomotor activity except (-)pseudoephedrine oxazolidine. 4. The oxazolidines derived from (-) and (+) ephedrine were slightly more active than their parent drugs. (+) Pseudoephedrine oxazolidine was less active than its parent. 5. Half-lives of hydrolysis were measured for the oxazolidines in aqueous buffer, ephedrine oxazolidines hydrolyze faster than pseudoephedrine oxazolidines.
A review of 45 studies clearly demonstrated that sexually abused children had more symptoms than nonabused children, with abuse accounting for 15-45% of the variance. Fears, posttraumatic stress disorder, behavior problems, sexualized behaviors, and poor self-esteem occurred most frequently among a long list of symptoms noted, but no one symptom characterized a majority of sexually abused children. Some symptoms were specific to certain ages, and approximately one third of victims had no symptoms. Penetration, the duration and frequency of the abuse, force, the relationship of the perpetrator to the child, and maternal support affected the degree of symptomatology. About two thirds of the victimized children showed recovery during the first 12-18 months. The findings suggest the absence of any specific syndrome in children who have been sexually abused and no single traumatizing process.
Osmotic-swelling experiments were conducted on a variety of preparations of "uniform" unilamellar vesicle systems. The synthetic lipid preparations included both vesicles produced by extrusion through polycarbonate ultrafiltration membranes and vesicles produced by the pH-adjustment method. The vesicles were monitored by photon correlation spectroscopy during swelling as the osmolarity of the external solution was decreased. Contrary to our previously reported results [Aurora, T. S., Li, W., Cummins, H. Z., & Haines, T. H. (1985) Biochim. Biophys. Acta 820, 250-258; Li, W., & Haines, T. H. (1986) Biochemistry 25, 7477-7483; Li, W., Aurora, T. S., Haines, T. H., & Cummins, H. Z. (1986) Biochemistry 25, 8220-8229; Haines, T. H., Li, W., Green, M., & Cummins, H. Z. (1987) Biochemistry 26, 5439-5447] large unilamellar vesicles produced from acidic lipids by the pH-adjustment technique were highly polydisperse and did not swell in a manner that permitted the computation of a Young's modulus, presumably due to the polydispersity. Also contrary to our previous reports, membranes derived from bovine submitochondrial particles did not produce evidence of swelling when subjected to similar protocols. Analysis of osmotic swelling of extruded unilamellar vesicles has allowed us to assign Young's moduli for bilayers of dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol, in the range (5-8) x 10(8) and (3-6) x 10(8) dyn/cm2, respectively. The diameters and polydispersites obtained with electron microscopy and photon correlation spectroscopy were compared directly and with computer-modeling techniques. While excellent agreement was obtained for distributions with low polydispersity (approximately greater than 0.1), serious disagreement was found when the polydispersity exceeded approximately 0.2.
Independent isolates of HIV-1 differ widely in their tropisms for CD4-positive T-cell lines. This study demonstrates that tropisms of 10 different HIV-1 isolates also differ widely, as much as 1000-fold, for normal peripheral blood lymphocytes (PBLs) cultured from any given donor. This could only be reproducibly demonstrated by end point titrations. In addition, the degree of susceptibility of PBLs from 12 random donors to productive infection by any given HIV-1 isolate also varied in a reproducible pattern from donor to donor, with some donors relatively resistant to one or a few isolates. The HIV susceptibility pattern of each donor was manifested at the level of the CD4 lymphocyte and it segregated within a family, conclusively demonstrating that it was genetically determined.