bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Features and Outcome of Primary Effusion Lymphoma in HIV-Infected Patients: A Single-Institution Study
Authors: Simonelli Cecilia , Spina Michele , Cinelli Roberta , Talamini Renato , Tedeschi Rosamaria , Gloghini Annunziata , Vaccher Emanuela , Carbone Antonino , Tirelli Umberto 
Published: October 2003

Purpose: To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non-Hodgkin’s lymphomas (NHLs). Patients and Methods: From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the features and outcomes of 162 patients belonging to the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). Results: Among the 277 NHL patients, PEL was diagnosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demographic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly different from the outcome observed in the other two groups (PBLOC and IBL groups). Conclusion: PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients.
The Outcome of Liver Transplantation in Patients With Hepatocellular Carcinoma in the United States Between 1988 and 2001: 5-Year Survival Has Improved Significantly With Time
Authors: Yoo Hwan Y. , Patt Cary H. , Geschwind Jean-Francois , Thuluvath Paul J. 
Published: October 2003

Purpose: We hypothesized that the outcome of liver transplantation in patients with hepatocellular carcinoma (HCC) has improved over the past decade because of the application of published criteria for patient selection. In this study, we compared the outcome of liver transplantation in patients with and without HCC at different time periods using the United Network for Organ Sharing data. Patients and Methods: We excluded children, patients with multiple organ transplantation or retransplantation, and those with incomplete survival data. The study period was arbitrarily divided into three time intervals: 1987 to 1991, 1992 to 1996, and 1997 to 2001. Results: During the study period, 985 patients with HCC (HCC group), and 33,339 without HCC underwent liver transplantation (control group). Kaplan-Meier patient and graft survivals were significantly lower for the HCC group compared with the control group. Cox regression analysis (after adjusting for other confounding variables) confirmed a lower patient survival in the HCC group (1-year survival, 77.0% v 86.7%; hazard ratio [HR], 1.7; 95% CI, 1.5 to 2.0; P < .0001) compared with the control group (5-year survival, 48.2% v 74.7%; HR, 2.2; 95% CI, 1.9 to 2.4; P < .0001); HCC was an independent predictor of survival. Kaplan-Meier analysis showed a significant improvement in 5-year patient survival with time in patients with HCC (1987 to 1991, 25.3%; 1992 to 1996, 46.6%; 1997 to 2001, 61.1%; P < .0001). During the same period, there was only minimal improvement in survival among the control group. Conclusion: Five-year survival of patients transplanted for HCC is excellent, with a steady improvement in survival over the past decade. It is possible that the published criteria for patient selection may have contributed to the better outcome.
Dose-Dependent Switch in Response of Gonadotropin-Releasing Hormone (GnRH) Neurons to GnRH Mediated through the Type I GnRH Receptor
Authors: Xu Chun , Xu Xu-Zhi , Nunemaker Craig S. , Moenter Suzanne M. 
Published: October 2003

Abstract
Pulsatile release of GnRH provides central control of reproduction. GnRH neuron activity is likely synchronized to produce hormone pulses, but the mechanisms are largely unknown. One candidate for communication among these neurons is GnRH itself. Cultured embryonic and immortalized GnRH neurons express GnRH receptor type I (GnRHR-1), but expression has not been shown in adult GnRH neurons. Using mice that express green fluorescent protein (GFP) in GnRH neurons, we tested whether adult GnRH neurons express GnRHR-1. GFP-positive (n = 42) and -negative neurons (n = 22) were harvested from brain slices, and single-cell RT-PCR was performed with cell contents. Fifty-two percent of the GnRH neurons tested expressed GnRHR-1, but only 9% of non-GnRH hypothalamic neurons expressed GnRHR-1; no false harvest controls (n = 13) were positive. GnRHR-1 expression within GnRH neurons suggested a physiological ultrashort loop feedback role for GnRH. Thus, we examined the effect of GnRH on the firing rate of GnRH neurons. Low-dose GnRH (20 nm) significantly decreased firing rate in 12 of 22 neurons (by 42 ± 4%, P &lt; 0.05), whereas higher doses increased firing rate (200 nm, five of 10 neurons, 72 ± 26%; 2000 nm, nine of 13 neurons, 53 ± 8%). Interestingly, the fraction of GnRH neurons responding was similar to the fraction in which GnRHR-1 was detected. Together, these data demonstrate that a subpopulation of GnRH neurons express GnRHR-1 and respond to GnRH with altered firing. The dose dependence suggests that this autocrine control of GnRH neurons may be not only a mechanism for generating and modulating pulsatile release, but it may also be involved in the switch between pulse and surge modes of release.
Expression and Distribution of MAL2, an Essential Element of the Machinery for Basolateral-to-Apical Transcytosis, in Human Thyroid Epithelial Cells
Authors: Marazuela Mónica , Martín-Belmonte Fernando , García-López María Angeles , Aranda Juan F. , de Marco María C. , Alonso Miguel A. 
Published: October 2003

Abstract
Polarized transport of newly synthesized proteins to the apical surface of epithelial cells takes place by a direct pathway from the Golgi or by an indirect route involving the delivery of the protein to the basolateral surface, followed by its endocytosis and transport across the cell. The indirect pathway, named transcytosis, is also used to translocate external material across the cell. MAL, a raft-associated integral membrane protein required for the direct apical route, is known to be expressed in the thyroid epithelium. MAL2, a member of the MAL protein family, has been recently identified as an essential component of the machinery for the transcytotic route in human hepatoma cells. Herein, we have investigated the expression and distribution of MAL2 in the human thyroid. MAL2 mRNA species were detected in the thyroid. Immunohistochemical analysis of thyroid follicles indicated that, in contrast to MAL, which predominantly distributed to the Golgi region, MAL2 distributed to the apical membrane. Biochemical analysis in primary thyrocyte cultures indicated that MAL2 exclusively resides in raft membranes. Confocal immunofluorescence analysis of thyrocyte cultures revealed that MAL2 predominantly localized in a subapical endosome compartment that was positive for Rab11a. Alterations in MAL2 expression, distribution, and appearance were found in specific types of follicular cell-derived carcinomas. Although the role of MAL2 has not been directly addressed in this study, the simultaneous expression of MAL and MAL2 suggests that traffic to the apical membrane in thyrocytes may rely on MAL for the direct route and on MAL2 for the transcytotic pathway.
Does Cortisol Inhibit Pulsatile Luteinizing Hormone Secretion at the Hypothalamic or Pituitary Level?
Authors: Breen Kellie M. , Karsch Fred J. 
Published: October 2003

Abstract
Elevations in glucocorticoids suppress pulsatile LH secretion in sheep, but the neuroendocrine sites and mechanisms of this disruption remain unclear. Here, we conducted two experiments in ovariectomized ewes to determine whether an acute increase in plasma cortisol inhibits pulsatile LH secretion by suppressing GnRH release into pituitary portal blood or by inhibiting pituitary responsiveness to GnRH. First, we sampled pituitary portal and peripheral blood after administration of cortisol to mimic the elevation stimulated by an immune/inflammatory stress. Within 1 h, cortisol inhibited LH pulse amplitude. LH pulse frequency, however, was unaffected. In contrast, cortisol did not suppress either parameter of GnRH secretion. Next, we assessed the effect of cortisol on pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, duration, and frequency. Hourly pulses of GnRH were delivered to ewes in which endogenous GnRH secretion was blocked by estradiol. Cortisol, again, rapidly and robustly suppressed the amplitude of GnRH-induced LH pulses. We conclude that, in the ovariectomized ewe, cortisol suppresses pulsatile LH secretion by inhibiting pituitary responsiveness to GnRH rather than by suppressing hypothalamic GnRH release.
The Evolutionarily Conserved Gonadotropin-Releasing Hormone II Modifies Food Intake
Authors: Kauffman Alexander S. , Rissman Emilie F. 
Published: October 2003

AbstractGnRH is an evolutionarily conserved peptide of which there are multiple structural variants. One form, GnRH II, is the most widespread in vertebrates, but its primary function remains unclear. In female musk shrews, administration of GnRH II, but not GnRH I, reinstates mating behavior previously inhibited by food restriction. Because this finding suggests that the function of GnRH II may be linked to energetic status, we tested whether GnRH II directly affects food intake. Adult female musk shrews were maintained on ad libitum feeding or food restricted for 48 h, after which they were infused centrally with GnRH I (1 μg), GnRH II (1 μg), or saline. Food intake was recorded 90 min, and 3, 6, 24, and 48 h after infusion. GnRH II administration, but not saline or GnRH I, reduced 24-h food intake in ad libitum animals. Short-term food intake (90 min and 3 h) of both ad libitum and underfed shrews receiving GnRH II was also reduced by as much as 33%, relative to the food intake of saline-infused controls. GnRH I infusion did not affect short-term food intake differently than saline infusion in shrews fed ad libitum. In underfed females, GnRH I had an effect on short-term food intake that was intermediate to saline and GnRH II. We conclude that, in addition to its permissive role in regulating reproduction, GnRH II may also modulate food intake in mammals. Because GnRH II is present in primate brain, it may also serve a similar function in humans.
Androgens Promote Maturation and Signaling in Mouse Oocytes Independent of Transcription: A Release of Inhibition Model for Mammalian Oocyte Meiosis
Authors: Gill Arvind , Jamnongjit Michelle , Hammes Stephen R. 
Published: October 2003

Abstract
Normal fertility in females depends upon precise regulation of oocyte meiosis. Oocytes are arrested in prophase I of meiosis until just before ovulation, when meiosis, or maturation, is triggered to resume. Whereas sex steroids appear to promote maturation in fish and amphibians, the factors regulating mammalian oocyte maturation have remained obscure. We show here that, similar to lower vertebrates, steroids may play a role in promoting the release of meiotic inhibition in mammals. Specifically, testosterone induced maturation of mouse oocytes arrested in meiosis, as well as activation of MAPK and cyclin-dependent kinase 1 signaling. These responses appeared to be transcription independent and might involve signaling through classical androgen receptors expressed in the oocytes. Our results are the first to show that sex steroids can modulate meiosis in mammalian oocytes and suggest a model whereby dominant ovarian follicles in mammals may produce sufficient androgen and/or other steroids to overcome constitutive inhibitory signals and allow oocyte maturation and subsequent ovulation to occur.
Ebf gene function is required for coupling neuronal differentiation and cell cycle exit
Authors: Garcia-Dominguez Mario , Poquet Christophe , Garel Sonia , Charnay Patrick 
Published: October 2003

Helix-loop-helix transcription factors of the Ebf/Olf1 family have previously been implicated in the control of neurogenesis in the central nervous system in both Xenopus laevis and the mouse, but their precise roles have remained unclear. We have characterised two family members in the chick, and have performed a functional analysis by gain- and loss-of-function experiments. This study revealed several specific roles for Ebf genes in the spinal cord and hindbrain regions of higher vertebrates, and enabled their precise positioning along the neurogenic cascade.During neurogenesis, cell cycle exit appears to be tightly coupled to migration to the mantle layer and to neuronal differentiation. We show that antagonizing Ebf gene activity allows the uncoupling of these processes. Ebf gene function is necessary to initiate neuronal differentiation and migration toward the mantle layer in neuroepithelial progenitors, but it is not required for cell cycle exit. Ebf genes therefore appear to be master controllers of neuronal differentiation and migration, coupling them to cell cycle exit and earlier steps of neurogenesis.Mutual activation between proneural and Ebf genes suggests that besides their involvement in the engagement of differentiation, Ebf genes may also participate in the stabilisation of the committed state. Finally,gain-of-function data raise the possibility that, in addition to these general roles, Ebf genes may be involved in neuronal subtype specification in particular regions of the CNS.
The effect of elevated intraocular oxygen on organelle degradation in the embryonic chicken lens
Authors: Bassnett Steven , McNulty Richard 
Published: October 2003

SUMMARY
In the vertebrate lens, nuclei and other cytoplasmic organelles are degraded in fiber cells situated in the center of the tissue. This is believed to ensure the transparency of the tissue. The mechanism that triggers this process is unknown. We hypothesized that standing gradients of oxygen generated within the tissue may serve as a spatial cue for organelle degradation. To examine this possibility, we incubated fertilized chicken eggs under hyperoxic (50% O2) or normoxic (21% O2)conditions. Hyperoxic treatment was initiated on the seventh day of embryonic development (E7), five days before organelle degradation normally commences in the lens core. Hyperoxia was maintained until E17. Under normoxic conditions,the partial pressure of oxygen (PO) within the vitreous compartment was low. Direct measurement of PO using an optode oxygen sensor indicated values of 1.3 kPa and 0.4 kPa for the mid- and anterior vitreous, respectively. Similarly, treatment with pimonidazole, a bio-reductive hypoxia marker, led to the formation of immuno-positive protein adducts within the lens, suggesting that the embryonic lens is chronically hypoxic in situ. Following hyperoxic treatment, vitreous PO significantly increased, although pimonidazole staining in the lens was not markedly affected. Confocal microscopy of slices prepared from hyperoxic lenses revealed a significant increase in the size of the lens relative to age-matched normoxic controls. By E13, an organelle-free zone(OFZ) was present in the center of normoxic and hyperoxic lenses. However, in hyperoxic lenses, the OFZ was consistently smaller, and the distance from the lens surface to the border of the OFZ significantly larger, than in normoxic controls. These observations suggest that hyperoxia delays organelle breakdown and are consistent with a model in which hypoxia in the deep cortical layers of the normal lens serves as a trigger for the organelle loss process.
Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus
Authors: Donahue Seth W. , Vaughan Michael R. , Demers Laurence M. , Donahue Henry J. 
Published: October 2003

SUMMARY
Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.
Limits to sustained energy intake VI. Energetics of lactation in laboratory mice at thermoneutrality
Authors: Król E. , Speakman J. R. 
Published: October 2003

SUMMARYThe limits to sustained energy intake are important because of their implications for reproductive output, foraging behaviour and thermoregulatory capabilities. Recent attempts to elucidate the nature of the limits to sustained energy intake have focused on peak lactation, which is the most energetically demanding period for female mammals. The hypothesis that performance of lactating animals is limited peripherally by the capacity of mammary glands to produce milk has received the most attention. However, some empirical data cannot be explained by the peripheral limitation hypothesis. Here, we present a novel hypothesis that the limits to sustained energy intake at peak lactation are imposed by the capacity of the animal to dissipate body heat generated as a by-product of processing food and producing milk. To test the heat dissipation limit hypothesis we challenged reproducing MF1 laboratory mice (N=67) with a reduced potential heat flow between the animal and the environment by exposing them to 30°C (thermoneutral zone). We compared their food intake and reproductive output at peak lactation with animals studied previously at 21°C (N=71) and 8°C (N=15). Mice lactating at 30°C had a significantly lower mean asymptotic food intake (12.4 g day-1) than those at 21°C (23.5 g day-1) and 8°C (28.6 g day-1). On average, mice at 30°C raised significantly fewer (9.8) and smaller (6.1 g) pups than those at 21°C (11.3 pups; 7.0 g per pup) and smaller pups than those at 8°C(9.6 pups; 7.3 g per pup). Consequently, mean litter mass at 30°C (56.0 g)was significantly lower than at 21°C (77.1 g) and at 8°C (68.7 g). The mean rate of litter mass increase at 30°C (2.1 g day-1) was also lower than at 21°C (3.1 g day-1). The reduced food intake and low reproductive output in mice lactating at 30°C are consistent with the heat dissipation limit hypothesis.
Limits to sustained energy intake VII. Milk energy output in laboratory mice at thermoneutrality
Authors: Król E. , Speakman J. R. 
Published: October 2003

SUMMARYThe limits to sustained energy intake at peak lactation could be imposed peripherally, by the capacity of the mammary glands, or centrally, by the capacity of the animal to dissipate body heat generated as a by-product of processing food and producing milk. To distinguish between the two hypotheses,we examined milk energy output at peak lactation in MF1 laboratory mice exposed to 30°C (N=12), 21°C (N=10; published data)and 8°C (N=10; published data). The peripheral limitation hypothesis predicts that milk energy output will remain constant at different temperatures, while the heat dissipation limit hypothesis predicts a decline in milk energy output as temperature increases. Since estimates of milk energy output in small mammals can vary depending on the calculation method used, we evaluated the milk energy output of mice (N=24) using four different methods: (1) as the difference between metabolizable energy intake and daily energy expenditure of the female, (2) from female water turnover, (3) from pup water turnover and (4) from the energy budget of the litter. We assessed these four methods by comparing their accuracy, precision and sensitivity to changes in parameters involved in the calculations. Methods 1, 3 and 4 produced similar estimates of milk energy output, while those derived from female water turnover were significantly lower and more variable. On average, mice at 30°C exported significantly less energy as milk (87.7 kJ day–1) than mice at 21°C (166.7 kJ day–1) and 8°C (288.0 kJ day–1). This reduction in milk energy output at 30°C was caused by a significant decline in both milk flow (20.0 g day–1, 12.9 g day–1 and 8.5 g day–1 at 8°C, 21°C and 30°C, respectively) and gross energy content of milk (14.6 kJ g–1, 13.1 kJ g–1 and 10.5 kJ g–1 at 8°C, 21°C and 30°C, respectively). Milk produced at 30°C contained significantly less total solids (34.4%) than milk at 21°C (40.9%) and 8°C (41.5%) and significantly less fat(20.0%) than milk at 21°C (26.4%) and 8°C (30.3%). The reduced milk energy output in mice exposed to 30°C, paralleled by their reduced food intake and low reproductive output, argues against the peripheral limitation hypothesis and provides strong support for the heat dissipation limit hypothesis.