bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of alpha hemoglobin stabilizing protein (AHSP) as a genetic modifier in patients with β thalassemia
Authors: Viprakasit Vip , Tanphaichitr Voravarn S. , Chinchang Worrawut , Sangkla Pakarat , Weiss Mitchell J. , Higgs Douglas R. 
Published: January 2004

Abstract
Although β thalassemia is considered to be a classic monogenic disease, it is clear that there is considerable clinical variability between patients who inherit identical β globin gene mutations, suggesting that there may be a variety of genetic determinants influencing different clinical phenotypes. It has been suggested that variations in the structure or amounts of a highly expressed red cell protein (alpha hemoglobin stabilizing protein [AHSP]), which can stabilize free α globin chains in vitro, could influence disease severity in patients with β thalassemia. To address this hypothesis, we studied 120 patients with Hb E-β thalassemia with mild, moderate, or severe clinical phenotypes. Using gene mapping, direct genomic sequencing, and extended haplotype analysis, we found no mutation or specific association between haplotypes of AHSP and disease severity in these patients, suggesting that AHSP is not a disease modifier in Hb E-β thalassemia. It remains to be seen if any association between AHSP and clinical severity is present in other population groups with a high frequency of β thalassemia. (Blood. 2004;103:3296-3299)
Very low levels of donor CD18+ neutrophils following allogeneic hematopoietic stem cell transplantation reverse the disease phenotype in canine leukocyte adhesion deficiency
Authors: Bauer Thomas R. , Creevy Kate E. , Gu Yu-chen , Tuschong Laura M. , Donahue Robert E. , Metzger Mark E. , Embree Lisa J. , Burkholder Tanya , Bacher John D. , Romines Chris , Thomas Marvin L. , Colenda Lyn , Hickstein Dennis D. 
Published: January 2004

Abstract
Children with the severe phenotype of the genetic immunodeficiency disease leukocyte adhesion deficiency or LAD experience life-threatening bacterial infections because of molecular defects in the leukocyte integrin CD18 molecule and the resultant failure to express the CD11/CD18 adhesion molecules on the leukocyte surface. Hematopoietic stem cell transplantation remains the only definitive therapy for LAD; however, the degree of donor chimerism and particularly the number of CD18+ donor-derived neutrophils required to reverse the disease phenotype are not known. We performed nonmyeloablative hematopoietic stem cell transplantations from healthy matched littermates in 9 dogs with the canine form of LAD known as CLAD and demonstrate that in the 3 dogs with the lowest level of donor chimerism, less than 500 CD18+ donor-derived neutrophils/μL in the peripheral blood of the CLAD recipients resulted in reversal of the CLAD disease phenotype. These results demonstrate the value of a disease-specific, large-animal model for identifying the lowest therapeutic level required for successful cellular and gene therapy. (Blood. 2004;103:3582-3589)
The Attitudes of Cancer Patients and Their Families Toward the Disclosure of Terminal Illness
Authors: Yun Young Ho , Lee Chang Geol , Kim Si-young , Lee Sang-wook , Heo Dae Seog , Kim Jun Suk , Lee Keun Seok , Hong Young Seon , Lee Jung Suk , You Chang Hoon 
Published: January 2004

Purpose To ascertain the attitude of cancer patients and their families toward disclosure of terminal illness to the patient. Patients and Methods We constructed a questionnaire that included demographic and clinical information and delivered it to 758 consecutive individuals (433 cancer patients and 325 families that have a relative with cancer) at seven university hospitals and one national cancer center in Korea. Results 380 cancer patients and one member from each of 281 families that have a relative with cancer completed the questionnaire. Cancer patients were more likely than family members to believe that patients should be informed of the terminal illness (96.1% v 76.9%; P < .001). Fifty percent of the family members and 78.3% of the patients thought that the doctor in charge should be the one who informs the patient. Additionally, 71.7% of the patients and 43.6% of the family members thought that patients should be informed immediately after the diagnosis. Stepwise multiple logistic regression indicated that the patient group was more likely than the family group to want the patient to be informed of the terminal illness (odds ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61 to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41). Conclusion Our findings indicated that most cancer patients want to be informed if their illness is terminal, and physicians should realize that the patient and the family unit may differ in their attitude toward such a disclosure. Our results also reflect the importance of how information is given to the patient.
Outcome of Elderly Patients With Recurrent or Metastatic Head and Neck Cancer Treated With Cisplatin-Based Chemotherapy
Authors: Argiris Athanassios , Li Yi , Murphy Barbara A. , Langer Corey J. , Forastiere Arlene A. 
Published: January 2004

Purpose To evaluate the outcome of elderly patients with head and neck cancer undergoing palliative chemotherapy. Patients and Methods We analyzed combined data from two mature phase III randomized trials conducted by the Eastern Cooperative Oncology Group (ECOG; trial E1393, which compared cisplatin plus paclitaxel at two dose levels, and trial E1395, which compared cisplatin plus fluorouracil to cisplatin plus paclitaxel) to evaluate the toxicity, objective response rates, and survival of patients 70 years or older versus their younger counterparts. All patients had previously untreated recurrent or metastatic squamous cell carcinoma of the head and neck and ECOG performance status 0 or 1. Results Fifty-three elderly patients were enrolled from a total of 399 eligible participants (13%). Elderly patients had similar objective response rates (28% v 33%) and median time to progression (5.25 v 4.8 months) compared with younger patients. The median survival was 5.3 v 8 months (Wilcoxon P = .06; log-rank P = .17) and the 1-year survival 26% v 33% for elderly and younger patients, respectively. Elderly patients had a significantly higher incidence of severe nephrotoxicity, diarrhea, and thrombocytopenia. A higher rate of toxic deaths was noted in the elderly but did not reach statistical significance (13% v 8%; P = .29). Conclusion Elderly patients were underrepresented in these studies. Fit elderly patients with recurrent or metastatic head and neck cancer sustained increased toxicities with cisplatin-based doublets but had comparable survival outcomes compared with younger patients. Strategies to ameliorate toxicities should be pursued in the elderly.
In Boys with Abnormal Developmental Tempo, Maturation of the Skeleton and the Hypothalamic-Pituitary-Gonadal Axis Remains Synchronous
Authors: Flor-Cisneros Armando , Leschek Ellen W. , Merke Deborah P. , Barnes Kevin M. , Coco Marilena , Cutler Gordon B. , Baron Jeffrey 
Published: January 2004

The primary mechanism that initiates puberty is unknown. One possible clue is that pubertal maturation often parallels skeletal maturation. Conditions that delay skeletal maturation also tend to delay the onset of puberty, whereas conditions that accelerate skeletal maturation tend to hasten the onset of puberty. To examine this relationship, we studied boys with congenital adrenal hyperplasia (n = 13) and familial male-limited precocious puberty (n = 22), two conditions that accelerate maturational tempo, and boys with idiopathic short stature (n = 18) in which maturational tempo is sometimes delayed.
In all three conditions, the onset of central puberty generally occurred at an abnormal chronological age but a normal bone age. Boys with the greatest skeletal advancement began central puberty at the earliest age, whereas boys with the greatest skeletal delay began puberty at the latest age. Furthermore, the magnitude of the skeletal advancement or delay matched the magnitude of the pubertal advancement or delay. This synchrony between skeletal maturation and hypothalamic-pituitary-gonadal axis maturation was observed among patients within each condition and also between conditions. In contrast, the maturation of the hypothalamic-pituitary-gonadal axis did not remain synchronous with other maturational processes including weight, height, or body mass index.
We conclude that in boys with abnormal developmental tempo, maturation of the skeleton and the hypothalamic-pituitary-gonadal axis remains synchronous. This synchrony is consistent with the hypothesis that in boys, skeletal maturation influences hypothalamic-pituitary-gonadal axis maturation.
Dysmetabolic Syndrome in a Man with a Novel Mutation of the Aromatase Gene: Effects of Testosterone, Alendronate, and Estradiol Treatment
Authors: Maffei Laura , Murata Yoko , Rochira Vincenzo , Tubert Gloria , Aranda Claudio , Vazquez Marcela , Clyne Colin D. , Davis Susan , Simpson Evan R. , Carani Cesare 
Published: January 2004

We present the fourth case of an adult man (29 yr old) affected by aromatase deficiency resulting from a novel homozygous inactivating mutation of the CYP19 (P450arom) gene. At first observation, continuing linear growth, eunuchoid body proportions, diffuse bone pain, and bilateral cryptorchidism were observed. The patient presented also a complex dysmetabolic syndrome characterized by insulin resistance, diabetes mellitus type 2, acanthosis nigricans, liver steatohepatitis, and signs of precocious atherogenesis. The analysis of the effects induced by the successive treatment with high doses of testosterone, alendronate, and estradiol allows further insight into the roles of androgens and estrogens on several metabolic functions. High doses of testosterone treatment resulted in a severe imbalance in the estradiol to testosterone ratio together with the occurrence of insulin resistance and diabetes mellitus type 2. Estrogen treatment resulted in an improvement of acanthosis nigricans, insulin resistance, and liver steatohepatitis, coupled with a better glycemic control and the disappearance of two carotid plaques. Furthermore, the study confirms previous data concerning the key role of estrogens on male bone maturation, at least in part, and regulation of gonadotropin secretion. The biopsy of the testis showed a pattern of total germ cell depletion that might be due to the concomitant presence of bilateral cryptorchidism. Thus, a possible role of estrogen in male reproductive function is suggested but without revealing a direct cause-effect relationship.Data from this case provide new insights into the role of estrogens in glucose, lipid, and liver metabolism in men. This new case of aromatase deficiency confirms previous data on bone maturation and mineralization, and it reveals a high risk for the precocious development of cardiovascular disease in young aromatase-deficient men.
Anti-Müllerian Hormone Serum Concentrations in Normoovulatory and Anovulatory Women of Reproductive Age
Authors: Laven Joop S. E. , Mulders Annemarie G. M. G. J. , Visser Jenny A. , Themmen Axel P. , de Jong Frank H. , Fauser Bart C. J. M. 
Published: January 2004

Anti-Müllerian hormone (AMH) concentrations correlate with the number of antral follicles as well as age and constitute an endocrine marker for ovarian aging. In normogonadotropic anovulatory infertile women [World Health Organization (WHO) class 2], the number of early antral follicles is usually increased. To investigate whether AMH concentrations are increased, serum levels in 128 WHO 2 women were compared with those in 41 normoovulatory premenopausal women of similar age.Serum AMH concentrations are significantly (P &lt; 0.001) elevated in WHO 2 patients [median, 7.6 μg/liter (range, 0.1–40.0)], compared with controls [median, 2.1 μg/liter (0.1–7.4)]. In 106 patients presenting with polycystic ovaries (PCOs) (≥12 follicles/ovary measuring 2–9 mm and/or an ovarian volume &gt; 10 ml), AMH levels were elevated [9.3 μg/liter (1.8–40.0)], compared with 22 patients without PCOs [6.4 μg/liter (0.1–22.1)] (P &lt; 0.0001). In WHO 2 patients, AMH concentrations correlated with features characteristic for polycystic ovary syndrome such as LH concentrations (r = 0.331; P = 0.0001), testosterone levels (r = 0.477, P = 0.0001), mean ovarian volume (r = 0.421; P = 0.0001), and the number of ovarian follicles (r = 0.308; P = 0.0001). AMH levels correlated well with age in WHO 2 patients (r = −0.248; P = 0.002) as well as in controls (r = −0.465; P = 0.005). However, the relative decline in AMH with age is less pronounced in WHO 2 patients. In a subset of patients no significant correlation was found between AMH serum concentrations and the FSH response dose, the duration of stimulation, and the total number of ampoules of FSH used.In conclusion, serum AMH concentrations are elevated in WHO 2 women, especially in those patients exhibiting PCOs. Because AMH concentrations correlated well with other clinical, endocrine, and ultrasound markers associated with polycystic ovary syndrome, AMH may be used as a marker for the extent of the disease. A less pronounced AMH decrease over time in these women may suggest retarded ovarian aging. The latter hypothesis, however, should be confirmed by longitudinal studies.
Effect of ketoprofen and its enantiomers on the renal disposition of methotrexate in the isolated perfused rat kidney
Authors: Karpf D M , Kirkegaard A L , Evans A M , Nation R L , Hayball P J , Milne R W 
Published: January 2004

Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit the renal tubular secretion of methotrexate. However, the relative contribution of the active S- and inactive R-enantiomers is unknown. This study examined the effect of racemic ketoprofen and its enantiomers on the renal disposition of methotrexate in the isolated perfused rat kidney (IPK). Nineteen kidneys were divided between a control and three treatment groups. Controls were perfused with methotrexate alone (25 μg mL−1, n = 5) over three 30-min periods. Treatment groups were perfused with methotrexate (25 μg mL−1) for the first period, followed by a second period of methotrexate (25 μg mL−1) plus R- (n = 5), S- (n = 5) or RS-ketoprofen (n = 4) at 25 μg mL−1, and a third period of methotrexate (25 μg mL−1) plus R-, S- or RS-ketoprofen (50 μg mL−1). Perfusate and urine were collected over 10-min intervals. Methotrexate was measured by HPLC and its binding in perfusate by ultrafiltration. The clearance ratio (CR) for methotrexate was obtained by dividing the renal clearance by the product of its fraction unbound and the glomerular filtration rate. During control experiments, there was no significant change in the CR over 90 min. R-, S- and RS-ketoprofen at 50 μg mL−1 reduced the CR of methotrexate significantly, but there was no difference between the three groups. While the enantiomers of ketoprofen reduced the renal excretion of methotrexate, the interaction was not enantioselective.
Electrogenic proton-regulated oxalate/chloride exchange by lobster hepatopancreatic brush-border membrane vesicles
Authors: Gerencser George A. , Robbins Frank , Zhang Jianliang , Ahearn Gregory A. 
Published: January 2004

SUMMARYThe transport of [14C]oxalate (Ox2–) by epithelial brush-border membrane vesicles (BBMV) of lobster (Homarus americanus) hepatopancreas, formed by a magnesium precipitation technique, was stimulated by an outward Cl– gradient (in &gt;out). By contrast, Ox2– uptake was not enhanced by an inward Na+ or K+ transmembrane gradient. Generation of an inside-positive membrane potential by K+ in the presence of valinomycin stimulated Ox2–/Cl– exchange,while an inside-negative membrane potential generated by K+ efflux in the presence of valinomycin inhibited this process. Neither Ox2–/Ox2– nor Ox2–/SO42– transport exchange were affected by alterations of transmembrane potential. An inwardly directed proton gradient, or the presence of low bilateral pH, enhanced Ox2–/Cl– exchange, yet the H+gradient alone could not stimulate Ox2– uptake in Cl–-equilibrated BBMV or in vesicles lacking internal Cl–. The stilbenes 4-acetamido-4′-isothiocyanotostilbene-2,2′-disulfonic acid (SITS)and 4,4′-diisothiocyano-2,2′-disulfonic stilbene (DIDS) strongly inhibited Ox2–/Cl– exchange. Oxalate influx occurred by a combination of carrier-mediated transfer, exhibiting Michaelis–Menten kinetics, and nonsaturable `apparent diffusion'. Apparent kinetic constants for Ox2–/Cl–exchange were Kt=0.20 mmol l–1 and Jmax=1.03 nmol l–1 mg–1protein 7 s–1. 36Cl– influx into oxalate-loaded BBMV was stimulated by an inside-negative transmembrane potential compared with short-circuited vesicles. These results suggest that Ox2–/Cl– exchange in crustacean hepatopancreatic BBMV occurred by an electrogenic carrier mechanism exhibiting a 1:1 flux ratio that was modulated by an external proton-sensitive regulatory site.
Water calcium concentration modifies whole-body calcium uptake in sea bream larvae during short-term adaptation to altered salinities
Authors: Guerreiro Pedro M. , Fuentes Juan , Flik Gert , Rotllant Josep , Power Deborah M. , Canario Adelino V. M. 
Published: January 2004

SUMMARYWhole-body calcium uptake was studied in gilthead sea bream larvae(9–83 mg) in response to changing environmental salinity and[Ca2+]. Calcium uptake increased with increased fish size and salinity. Fish exposed to calcium-enriched, diluted seawater showed increased calcium uptake compared with fish in diluted seawater alone. Calcium uptake was unchanged in Na+-enriched, diluted seawater. Overall,[Ca2+], and not salinity/osmolarity per se, appears to be the main factor contributing to calcium uptake. By contrast, drinking was reduced by a decrease in salinity/osmolarity but was little affected by external [Ca2+]. Calculations of the maximum contribution from drinking-associated calcium uptake showed that it became almost insignificant(less than 10%) through a strong decrease in drinking rate at low salinities(0–8‰). Diluted seawater enriched in calcium to the concentration present in full-strength seawater (i.e. constant calcium, decreasing salinity)restored intestinal calcium uptake to normal. Extra-intestinal calcium uptake also benefited from calcium addition but to a lesser extent.
Vocal mechanics in Darwin's finches: correlation of beak gape and song frequency
Authors: Podos Jeffrey , Southall Joel A. , Rossi-Santos Marcos R. 
Published: January 2004

SUMMARYRecent studies of vocal mechanics in songbirds have identified a functional role for the beak in sound production. The vocal tract (trachea and beak)filters harmonic overtones from sounds produced by the syrinx, and birds can fine-tune vocal tract resonance properties through changes in beak gape. In this study, we examine patterns of beak gape during song production in seven species of Darwin's finches of the Galápagos Islands. Our principal goals were to characterize the relationship between beak gape and vocal frequency during song production and to explore the possible influence therein of diversity in beak morphology and body size. Birds were audio and video recorded (at 30 frames s–1) as they sang in the field, and 164 song sequences were analyzed. We found that song frequency regressed significantly and positively on beak gape for 38 of 56 individuals and for all seven species examined. This finding provides broad support for a resonance model of vocal tract function in Darwin's finches. Comparison among species revealed significant variation in regression y-intercept values. Body size correlated negatively with y-intercept values, although not at a statistically significant level. We failed to detect variation in regression slopes among finch species, although the regression slopes of Darwin's finch and two North American sparrow species were found to differ. Analysis within one species (Geospiza fortis) revealed significant inter-individual variation in regression parameters; these parameters did not correlate with song frequency features or plumage scores. Our results suggest that patterns of beak use during song production were conserved during the Darwin's finch adaptive radiation, despite the evolution of substantial variation in beak morphology and body size.
Modular organization of the silkmoth antennal lobe macroglomerular complex revealed by voltage-sensitive dye imaging
Authors: Ai Hiroyuki , Kanzaki Ryohei 
Published: January 2004

SUMMARY
We succeeded in clarifying the functional synaptic organization of the macroglomerular complex (MGC) of the male silkmoth Bombyx mori by optical recording with a voltage-sensitive dye. Sensory neurons in the antennae send their axons down either the medial nerve (MN) or lateral nerve(LN), depending on whether they are located on the medial or lateral flagella. Pheromone-sensitive fibers in the MN are biased towards the medial MGC, and those in the LN are biased towards the lateral MGC in the antennal lobe. In our optical recording experiments, the postsynaptic activities in the MGC were characterized by pharmacological analysis. Postsynaptic activities in the MGC were separated from sensory activities under Ca2+-free conditions,and subsequently the inhibitory postsynaptic activities were separated by applying bicuculline. We found that the inhibitory postsynaptic responses always preceded the postsynaptic responses separated under Ca2+-free conditions. Moreover, the excitatory postsynaptic activities were calculated by subtracting the inhibitory potentials from the posysynaptic activities separated under Ca2+-free conditions. When the MN was stimulated, the amplitudes of the excitatory postsynaptic activities in the central toroid, the medial toroid and the medial cumulus were selectively higher than those in the other areas. By contrast, when the LN was stimulated, excitatory postsynaptic activities were evoked in areas in both the lateral toroid and the lateral cumulus. The inhibitory postsynaptic activities were equally distributed throughout the whole MGC. These data suggest that there is a modular organization to the MGC such that information from the two main branches of the antenna is segregated to different sub-regions of the MGC glomeruli.
Purification and cDNA cloning of the ovigerous-hair stripping substance(OHSS) contained in the hatch water of an estuarine crab Sesarma haematocheir
Authors: Gusev Oleg , Ikeda Hideki , Okochi Tetsushi , Lee Jae Min , Hatakeyama Masatsugu , Kobayashi Chiyoko , Agata Kiyokazu , Yamada Hidenori , Saigusa Masayuki 
Published: January 2004

SUMMARY
The egg attachment system of an estuarine crab Sesarma haematocheir is formed on the maternal ovigerous hairs just after egg laying, and slips off these hairs just after hatching. The stripping is caused by an active factor that we call OHSS (ovigerous-hair stripping substance),which is released by the embryo upon hatching. OHSS was purified, and its active form had a molecular mass of 25 kDa. The cDNA of OHSS cloned from an embryonic cDNA library was 1759 bp long, encoding 492 amino acids in a single open reading frame (ORF). The C-terminal part of the predicted protein was composed of a trypsin-like serine protease domain, with homology to counterparts in other animals of 33–38%. The predicted protein (54.7 kDa) secreted as a zymogen may be cleaved post-translationally, separating the C-terminal from the N-terminal region. The OHSS gene was expressed in the embryo at least 2 weeks before hatching. Expression was also detected in the zoea larva 1 day after hatching and in the brain of the female. However, it was not detected in the muscle, hepatopancreas or ovigerous seta of the female. Ultrastructural analysis indicated that the material investing maternal ovigerous hair, i.e. the outermost layer (E1) of the egg case, is attached at the special sites (attachment sites) arranged at intervals of 130–160 nm on the hair. It is suggested that OHSS acts specifically at these sites, lysing the bond with the coat, thus disposing of the embryo attachment system. This enables the female to prepare the next clutch of embryos without ecdysis.