Altered Brain Structure in Infants with Turner Syndrome.

Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period.

Neoplasia and granulomas surrounding microchip transponders in Damaraland mole rats (Cryptomys damarensis).

Damaraland mole rats (Cryptomys damarensis) are among the longest-living rodents, with a maximum longevity of approximately 16 years. As one of the few mammals termed eusocial, these animals have been used in behavioral, genetic, metabolic, and physiologic research at the University of Connecticut since 1997. For individual identification at 3 to 4 months of age, mole rats were subcutaneously implanted with microchip transponders (11 mm in length) in the dorsal cervical region. In 2007, 2 of the 90 implanted adults, 10-year-old and 9-year-old females, developed subcutaneous masses at the site of the implant. Histopathological and immunohistochemical examinations revealed amelanotic melanoma and fibrosarcoma, respectively, with metastasis of the amelanotic melanoma. In 2008, a total of 3 adult males were castrated as part of a sex behavior study; 3 months later, all 3 castrated males developed subcutaneous masses around their implants, whereas none of the noncastrated males had masses. After an additional 9 months, these masses were found to be granulomas. To the authors' knowledge, this is the first report of neoplasia in this species. Both the tumors and the granulomas surrounded the microchip transponder.

Distribution of oxytocin in the brain of a eusocial rodent.

Naked mole-rats are highly social rodents that live in large colonies characterized by a rigid social and reproductive hierarchy. Only one female, the queen, breeds. Most colony members are non-reproductive subordinates that work cooperatively to rear the young and maintain an underground burrow system. Little is known about the neurobiological basis of the complex sociality exhibited by this species. The neuropeptide oxytocin (Oxt) modulates social bonding and other social behaviors in many vertebrates. Here we examined the distribution of Oxt immunoreactivity in the brains of male and female naked mole-rats. As in other species, the majority of Oxt-immunoreactive (Oxt-ir) cells were found in the paraventricular and supraoptic nuclei, with additional labeled cells scattered throughout the preoptic and anterior hypothalamic areas. Oxt-ir fibers were found traveling toward and through the median eminence, as well as in the tenia tecta, septum, and nucleus of the diagonal band of Broca. A moderate network of fibers covered the bed nucleus of the stria terminalis and preoptic area, and a particularly dense fiber innervation of the nucleus accumbens and substantia innominata was observed. In the brainstem, Oxt-ir fibers were found in the periaqueductal gray, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract, and nucleus ambiguus. The high levels of Oxt immunoreactivity in the nucleus accumbens and preoptic area are intriguing, given the link in other rodents between Oxt signaling in these regions and maternal behavior. Although only the queen gives birth or nurses pups in a naked mole-rat colony, most individuals actively participate in pup care.

Mammalian photoperiodic system: formal properties and neuroendocrine mechanisms of photoperiodic time measurement.

Photoperiodism is a process whereby organisms are able to use both absolute measures of day length and the direction of day length change as a basis for regulating seasonal changes in physiology and behavior. The use of day length cues allows organisms to essentially track time-of-year and to "anticipate" relatively predictable annual variations in important environmental parameters. Thus, adaptive types of seasonal biological changes can be molded through evolution to fit annual environmental cycles. Studies of the formal properties of photoperiodic mechanisms have revealed that most organisms use circadian oscillators to measure day length. Two types of paradigms, designated as the external and internal coincidence models, have been proposed to account for photoperiodic time measurement by a circadian mechanism. Both models postulate that the timing of light exposure, rather than the total amount of light, is critical to the organism's perception of day length. In mammals, a circadian oscillator(s) in the suprachiasmatic nucleus of the hypothalamus receives photic stimuli via the retinohypothalamic tract. The circadian system regulates the rhythmic secretion of the pineal hormone, melatonin. Melatonin is secreted at night, and the duration of secretion varies in inverse relation to day length; thus, photoperiod information is "encoded" in the melatonin signal. The melatonin signal is presumably "decoded" in melatonin target tissues that are involved in the regulation of a variety of seasonal responses. Variations in photoperiodic response are seen not only between species but also between breeding populations within a species and between individuals within single breeding populations. Sometimes these variations appear to be the result of differences in responsiveness to melatonin; in other cases, variations in photoperiod responsiveness may depend on differences in patterns of melatonin secretion related to circadian variation. Sites of action for melatonin in mammals are not yet well characterized, but potential targets of particular interest include the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei. Both these sites exhibit uptake of radiolabeled melatonin in various species, and there is some evidence for direct action of melatonin at these sites. However, it appears that there are species differences with respect to the importance and specific functions of various melatonin target sites.

Common dermatoses of the male genitalia. Recognition of differences in genital rashes and lesions is essential and attainable.

Dermatoses of the male genitalia can be confusing to identify and difficult to diagnose and treat. Rashes and lesions that occur on other areas of the body can be hard to recognize when they appear on the genitalia. In this article, Dr Goldman reviews the common dermatoses, presents defining characteristics, and suggests treatment options.

Genetic and environmental influences on short-day responsiveness in Siberian hamsters (Phodopus sungorus).

Siberian hamsters are photoperiodic rodents that typically exhibit several physiological changes when exposed to a short-day photoperiod. However, development of the winter phenotype in short days is largely conditional on prior photoperiod history: Hamsters that have been reared in an exceptionally long day length (18 L) do not usually exhibit the winter phenotype after transfer to short days, whereas animals reared under "moderately" long days (16 L) are more variable in responsiveness to subsequent short-day exposure, with 20% to 30% generally failing to exhibit winter-type responses. Hamsters reared exclusively in an "intermediate" day length (14 L) are almost uniformly responsive to short photoperiod. In the present study, the authors examine the influence of photoperiod history on short-day responsiveness in a breeding line of hamsters that has been subjected to artificial selection for resistance to the effects of short days. The results demonstrate that photoperiod history is an important determinant of short-day responsiveness in both random-bred (UNS) hamsters and animals artificially selected and bred for nonresponsiveness to short photoperiod (PNR). The PNR hamsters have a reduced requirement for long-day exposure to evoke a state of unresponsiveness to short days. The results are discussed in relation to possible significance for the origin of population and species differences in photoperiod responsiveness.

Herpes serology for dermatologists.

Serologic tests for antibodies to herpes simplex virus (HSV) have traditionally played a limited role in the treatment of patients with genital herpes. The epidemiological gold standard has been the Western blot analysis, which is only available in a few research centers and is expensive. The gold standard of diagnosis for HSV infection has been viral culture. Diagnosis by viral culture has severely underestimated the number of individuals infected. The majority of patients who are seropositive for herpes simplex virus type 2 (HSV-2) by Western blot analysis are unaware of their symptoms (unrecognized infection) or have subclinical infection. These patients are unlikely to present for culture. Enzyme-linked immunosorbent assay (ELISA) for the serologic diagnosis of herpes has been available for many years but suffers from poor sensitivity and specificity. Reliable, convenient serologic tests for antibodies that distinguish between prior infection with HSV-1 and HSV-2 have recently become commercially available.

Lichenoid drug reaction due to sildenafil.

Lichenoid drug eruptions are difficult to distinguish from lichen planus. Determining the offending agent is complicated by the proliferation of lifestyle medications that the patient may not consider a medication. A case of lichenoid drug eruption due to sildenafil, which was taken for sexual enhancement, is presented.

Circadian rhythms of locomotor activity in naked mole-rats (Heterocephalus glaber).

A wide variety of organisms exhibit various circadian rhythms in their behavior and physiology. Circadian rhythms are regulated by internal clocks that are generally entrained primarily by the environmental light:dark (L:D) cycle. There have been few studies of circadian rhythms in fossorial species that inhabit an environment where day-night variations are minimal and where exposure to light occurs infrequently. In this study, circadian patterns of wheel-running activity were examined in naked mole-rats (Heterocephalus glaber). Naked mole-rats are fossorial and eusocial, living in colonies of 60-70 animals with only one breeding female. Most individual mole-rats that ran on wheels (65%) exhibited robust circadian rhythms of locomotor activity, entrained to various L:D cycles, and free-ran in constant darkness (DD) with taus averaging 23.5 h. The remainder of the animals either free-ran or were arrhythmic under the various L:D cycles. Mole-rats generally failed to entrain to non-24-h T-cycles with period lengths ranging from T=23 h to T=25 h. There was considerable inter-individual variation in the circadian patterns of locomotor activity in naked mole-rats as is observed in other subterranean mammals that have been studied. In contrast to the results obtained when mole-rats were individually housed with access to running wheels, circadian rhythms of general locomotor activity were typically not observed for animals monitored while they were housed in a colony setting. However, clear nocturnal rhythms of general locomotor activity were displayed by four males while residing in their home colonies. Two of these males exhibited the physical appearance of a disperser morph - subordinate individuals that are believed to leave their home colonies to achieve reproductive opportunities elsewhere. All four of these males were among the largest males in their respective colonies. These results demonstrate that although naked mole-rats are not frequently exposed to light, the species has retained the capacity to exhibit locomotor patterns of circadian rhythmicity and has the ability to entrain to 24-h L:D cycles. The possible adaptive function of this circadian capacity is discussed.

Circadian rhythms of body temperature and metabolic rate in naked mole-rats.

Body temperature (T(b)) and metabolic rate (O(2) consumption) were measured continuously in naked mole-rats. Circadian rhythms were observed for both parameters. Body temperature increased at the end of the light phase in a 12L:12D cycle in three of four animals. The remaining animal exhibited a freerunning rhythm of T(b). When animals had access to running wheels, the time of elevated T(b) coincided closely with the time of increased running wheel activity. Rhythms of T(b) continued following removal of the wheels, but the duration of increased T(b) was decreased as compared to the duration of T(b) elevation in the presence of wheels. Metabolic rate was increased at the same circadian phase as the increase in T(b) and running wheel activity. These observations extend our earlier findings on circadian rhythms of locomotor activity in naked mole-rats and suggest that the circadian system may have significant physiological functions in this subterranean rodent.

The circadian timing system and reproduction in mammals.

Circadian systems in a wide variety of organisms all appear to include three basic components: 1) biological oscillators that maintain a self-sustained circadian periodicity in the absence of environmental time cues; 2) input pathways that convey environmental information, especially light cues, that can entrain the circadian oscillations to local time; and 3) output pathways that drive overt circadian rhythms, such as the rhythms of locomotor activity and a variety of endocrine rhythms. In mammals, the circadian system is employed in the regulation of reproductive physiology and behavior in two very important ways. 1) In some species, there is a strong circadian component in the timing of ovulation and reproductive behavior, ensuring that these events will occur at a time when the animal is most likely to encounter a potential mate. 2) Many mammals exhibit seasonal reproductive rhythms that are largely under photoperiod regulation; in these species, the circadian system and the pineal gland are crucial components of the mechanism that is used to measure day length. The rhythm of pineal melatonin secretion is driven by a neural pathway that includes the circadian oscillator(s) in the suprachiasmatic nuclei. Melatonin is secreted at night in all mammals, and the duration of each nocturnal episode of melatonin secretion is inversely related to day length. The pineal melatonin rhythm appears to serve as an internal signal that represents day length and that is capable of regulating a variety of seasonal variations in physiology and behavior.

Factors influencing metabolic rate in naked mole-rats (Heterocephalus glaber).

Naked mole-rats (Heterocephalus glaber) are fossorial, eusocial mammals that live in colonies averaging about 70 individuals. Metabolic regulation is of particular interest in this species because it is one of only two naturally occurring small mammals that are hairless. Further, relative to other small mammals, naked mole-rats exhibit low body temperature (Tb) and weak capacity to maintain Tb above the ambient temperature (Ta). The present study examined effects of Ta, norepinephrine (NE), and chronic food restriction on O2 consumption (as a measure of metabolism) in naked mole-rats. Studies were performed in both awake and anesthetized animals. Metabolic rate decreased with increasing T. over the range of 23-34 degrees C in awake mole-rats, whereas in anesthetized animals rates of O2 consumption were very low over this entire range of Ta and tended to increase with increasing Ta. Injections of NE led to rapid increases in metabolic rate at all Tas in anesthetized subjects and also at Ta = 34 degrees C in awake mole-rats. However, at Tas of 29 and 23 degrees C, awake subjects given NE showed little stimulation of O2 consumption beyond the already elevated baseline rates observed at these Tas. During chronic restriction of food to 60-70% of their normal daily consumption mole-rats exhibited decreased rates of metabolism; metabolic rate was not altered following several hours of acute food deprivation. Food consumption remained somewhat decreased after a period of chronic food restriction, even when animals were returned to ad lib conditions. However, body weights returned to prerestriction values, despite the continued reduction in ad lib food intake. These observations suggest that mole-rats may be capable of long-lasting metabolic adaptations as a means to cope with restricted food supply. These findings are discussed in relation to adaptation of this fossorial species to a habitat where food has a patchy distribution. Naked mole-rats, with their several unusual thermoregulatory and behavioral features, provide an intriguing model for studies of mammalian metabolic regulation.

The Siberian hamster as a model for study of the mammalian photoperiodic mechanism.

The Siberian hamster has been a useful model for studies of mammalian photoperiodism for a number of reasons: 1) Siberian hamsters are hardy animals that are easily maintained and bred in the laboratory. 2) The species exhibits a large number of seasonal, photoperiod-driven, pineal-dependent responses. Thus, the Siberian hamster is an excellent species in which to examine whether several different types of photoperiod responses share similar mechanistic features with respect to their control by MEL. Are all the responses cued to the duration of the nocturnal MEL peak? Does MEL act at a single site to influence all the types of responses, or are there separate MEL target sites for different responses? 3) Juvenile Siberian hamsters exhibit an unusually rapid (for mammals) response to photoperiod change or to MEL treatments, making them ideal subjects for certain types of photoperiod-related studies. 4) Populations of Siberian hamsters show individual variations in photoperiod responsiveness, and the differences are at least partly heritable. These hamsters also exhibit strong influences of environmental history on short day responsiveness. Thus, the species may be a valuable model for the investigation of both genetic and environmental influences on the photoperiodic mechanism. 5) Siberian hamsters have proved to be useful animals in which to study maternal influences on the developing photoperiodic mechanism of the fetus.

Nontraditional staffing models in long-term care.

Regardless of the primary care model used in the long-term care facility, each of the three approaches offers quality care improvement and greater consistency for residents at reduced costs. Of the three, an all licensed nursing staff model could best meet the higher acuity levels of residents and the disintegrating availability of qualified nursing assistants. If nurses are unable to "sell" this model to administration, it may be helpful to pilot the concept one one unit for a period of time and compare resident, family, and staff satisfaction with that of a similar unit. Also, it is critical to compare the financial implications, including cost per resident per day and rate of staff turnover, to weigh the model's effectiveness. This small sampling of five facilities indicates the average cost per resident per day is $10 less when using either the primary team or all licensed staff models than in facilities of comparable size. Hospitals have already passed the time when they have had to work smarter, leaner, and more efficiently. Can long-term care facilities afford not to do the same?

Circadian patterns of locomotor activity and body temperature in blind mole-rats, Spalax ehrenbergi.

A wide variety of organisms exhibit circadian rhythms, regulated by internal clocks that are entrained primarily by the alternating cycle of light and darkness. There have been few studies of circadian rhythms in fossorial species that inhabit a microenvironment where day-night variations in most environmental parameters are minimized and where exposure to light occurs only infrequently. In this study, daily patterns of locomotor activity and body temperature (Tb) were examined in adult blind mole-rats (Spalax ehrenbergi). These fossorial rodents lack external eyes but possess rudimentary ocular structures that are embedded in the Harderian glands and covered by skin and fur. Most individual mole-rats exhibited circadian rhythms of locomotor activity, but some animals were arrhythmic. Individuals that did exhibit robust rhythms of locomotor activity also showed rhythms of Tb. In most cases, Tb was highest during the phase of intense locomotor activity. Locomotor activity rhythms could be entrained to light:dark cycles, and several mole-rats exhibited entrainment to non-24-h light cycles (T-cycles) with period lengths ranging from T = 23 h to T = 25 h. Some individuals also showed entrainment to daily cycles of ambient temperature. There was considerable interindividual variation in the daily patterns of locomotor activity among mole-rats in virtually all the conditions of environmental lighting and temperature employed in this study. Thus, whereas it appears likely that photic cues have a significant role in the entrainment of circadian rhythms in mole-rats, the amount of variability in rhythm patterns among individuals appears to be much greater than for most species that have been studied.

Pustular and erythrodermic psoriasis complicated by acute respiratory distress syndrome.

BACKGROUND: The pustular and erythrodermic types of psoriasis have been associated with a number of systemic complications, including congestive heart failure and pneumonia. Acute respiratory distress syndrome (ARDS) refers to acute noncardiogenic pulmonary edema with hypoxemia of various causes and has been attributed to pulmonary capillary leak. Recently, 4 cases of generalized pustular or erythrodermic psoriasis have been described associated with a pulmonary capillary leak syndrome. OBSERVATIONS: We describe 2 additional patients, 1 with pustular and erythrodermic psoriasis and 1 with erythrodermic psoriasis; who developed ARDS. Radiographic findings, pulmonary capillary wedge pressures, echocardiograms, and, in one case, an open lung biopsy specimen, were consistent with the diagnosis of ARDS. In neither case could we document any of the common causes of acute respiratory failure. CONCLUSIONS: Generalized pustular and erythrodermic psoriasis may be complicated by ARDS. The pathogenesis of this complication is unclear, but proinflammatory cytokines may be involved.

Anterior pituitary release of prolactin is inhibited by exposure to short photoperiod.

The potential regulatory sites responsible for the decrease of circulating prolactin (PRL) levels shown by many photoperiodic mammals following prolonged exposure to short days was investigated in Siberian hamsters that had been maintained under a stimulatory, long-day photoperiod, and in hamsters that had been shifted to a nonstimulatory, short-day photoperiod for 8-10 weeks. The ability of anterior pituitary fragments (AP) from each of these groups to release prolactin was evaluated in pituitary tissue cultured alone and also in pituitary tissue co-cultured with hypothalamic fragments (HF), using a perifusion tissue culture system. The perfusate from these cultures was collected every 1/2 h for 8 h, and was assayed for basal levels of prolactin using radioimmunoassay. For AP tissue cultured alone, there was a robust reduction in prolactin release by the fragments harvested from short-day housed animals. In AP tissue harvested from long-day exposed animals, co-culture with either long- or short-day HF did not induce significant changes in basal PRL release. Similarly, co-culture with short-day HF did not significantly alter PRL release in short-day APs. However, there was a significant increase in release when short-day APs were co-cultured with long-day HF. These results suggest a direct effect of photoperiod on PRL synthesis and/or release at the level of the pituitary. However, the altered responsiveness of short-day pituitaries could be the result of previous, chronic inhibitory hypothalamic input during short-day exposure. A follow-up study was conducted to investigate the ability of vasoactive intestinal peptide (VIP) to stimulate PRL release from long- and short-day APs. Results indicated that the ability of VIP to stimulate PRL release is both photoperiod and dose dependent.

Pleiotropic expression of heterologous cytokine/receptor genes in HTLV-1 associated diseases: candidate TRS for chimeric gene therapy.

DNA motifs that encode for specific transcriptional regulatory sequences (TRS) when engineered adjacent to the structural protein coding domain of a suicide enzyme can provide cell-lineage specific protein expression. The disparate up-regulation of several genes in adult T-cell leukemia (ATL) versus HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), seropositive carriers (SPC) and uninfected normals may reflect events at the molecular level related to leukemogenesis or to processes maintaining the heme-oncologic phenotype. Further, the genetic transduction of cytokine and receptor genes uniquely associated with ATL may provide targets for the development of leukemia-specific gene therapies aimed at exploiting differences in the production of certain growth factors and growth factor receptors. Comparisons of the transcriptional and translational levels of interleukin-2 receptor alpha chain (IL-2R alpha), transforming growth factor-beta 1 (TGF-beta 1) and intracellular adhesion molecule-1 (ICAM-1) in ATL, HAM/TSP, and SPC and in several control populations revealed selectively up-regulated expression in ATL. We evaluated the feasibility of using lymphoid-specific TRS to activate herpes simplex virus thymidine kinase (HSVtk) to achieve selective cytotoxicity in leukemias expressing terminal deoxynucleotidyl transferase (TdT). Selective and efficient leukemic cell killing was produced and suggests that similar chimeric gene constructs containing TRS elements for IL-2R alpha, TGF-beta 1, or ICAM-1 may prove useful in designing gene therapies to treat ATL.