bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of proliferating (MiB‐1‐positive) cells in cervical smears of women infected with HIV is associated with clinical outcome: A study of Brazilian women
Authors: Boon Mathilde E. , van der Veen Gerrita , Barlow Yvonne , Graudenz Marcia Silveira , Kok Lambrecht P. 
Published: August 2002

AbstractThe hypothesis tested was that there is an association between the presence of proliferating (MiB‐1‐positive) cervical cells and clinical outcome of women infected with human immunodeficiency virus (HIV). Female partners (attending the Gynecology Outpatients Clinic of the University Hospital of Rio Grande, Brazil) of known HIV‐positive (HIV+) men were used for this pilot study. Among these women, 25 were also HIV+. Papanicolaou smears of these 25 HIV+ women and of 44 HIV− women were graded as negative, CIN I, CIN II, or CIN III, using neural network screening. MiB‐1 grading and HPV identification were also performed. The immune status of patients was determined using the current Centers for Disease Control classification. In agreement with the scientific literature, in these Brazilian women both CIN and HPV were associated with HIV. In the HIV+ women, the immune status tends to correlate with MiB‐1 grading. Also, in the one case in whom progression from CIN I to invasive cervical carcinoma was observed, the smear contained many MiB‐1‐positive cells. Staining cervical smears of HIV+ women is a simple procedure to get an indication of clinical outcome of the patient. Diagn. Cytopathol. 24:373–377, 2001. © 2001 Wiley‐Liss, Inc.
Cytologic features of tubular adenocarcinoma of the breast by aspiration biopsy
Authors: Cangiarella Joan , Waisman Jerry , Shapiro Richard L. , Simsir Aylin 
Published: August 2002

AbstractTubular adenocarcinoma is an invasive mammary adenocarcinoma associated with an excellent prognosis and a low incidence of axillary metastases. However, identification of tubular adenocarcinoma by fine‐needle aspiration (FNA) biopsy has proven difficult. One hundred five patients with documented “pure” tubular adenocarcinoma were diagnosed at Tisch Hospital from August of 1992 to December of 1998. Twenty‐one of these patients had an FNA before excision. We reviewed the smears of these cases and compared them with cases of fibroadenoma and fibrocystic change to identify criteria for diagnosis. Moderately to highly cellular smears with angular cellular clusters with sharp borders and oval cells outlining these clusters, dispersed single cells with minimal atypia, and the absence or paucity of dispersed bare oval nuclei in the background were features that suggest a diagnosis of tubular adenocarcinoma in our study. Attention to these features in combination with appropriate mammographic findings should preclude a false‐negative diagnosis in the majority of cases of tubular adenocarcinoma diagnosed by aspiration biopsy. We point to the presence of the peripheral perpendicular cells in the characteristic tubular arrays as an important clue to the diagnosis of tubular adenocarcinoma. Diagn. Cytopathol. 25:311–315, 2001. © 2001 Wiley‐Liss, Inc.
Gabapentin: A novel analgesic targeting voltage‐gated calcium channels
Authors: Sutton Kathy G. , Snutch Terrance P. 
Published: August 2002

AbstractGiven their vital roles in mediating neuronal excitability, it is not surprising that voltage‐gated calcium channels have been implicated in contributing to the development and maintenance of pain processes. Gabapentin, a synthetic analog of the neurotransmitter γ‐aminobutyric acid (GABA), is a clinically effective anticonvulsant recently shown to be efficacious also for a variety of neuropathic pain conditions. While its mechanism of action is incompletely understood, current evidence suggests that gabapentin does not directly interact with GABA receptors but rather modulates the activity of high threshold calcium channels. Although gabapentin binds to the calcium channel α2δ ancillary subunit, it remains to be determined whether this interaction solely accounts for its therapeutic effects. Drug Dev. Res. 54:167–172, 2002. © 2002 Wiley‐Liss, Inc.
Recent progress in the study of the intracellular functions of diadenosine polyphosphates
Authors: McLennan Alexander G. , Barnes Larry D. , Blackburn G. Michael , Brenner Charles , Guranowski Andrzej , Miller Andrew D. , Rovira Juan Manuel , Rotllán Pedro , Soria Bernat , Tanner Julian A. , Sillero Antonio 
Published: August 2002

AbstractRecent developments in the effort to understand the metabolism and function of the intracellular dinucleoside polyphosphates were described by nine speakers from some of the world’s leading laboratories in this field in a workshop at the Purines 2000 International Symposium on Nucleosides and Nucleotides held in Madrid in July, 2000. Topics were wide‐ranging and included phenotypic analyses of yeast mutants defective in enzymes of dinucleoside polyphosphate degradation, virally encoded catabolic enzymes, the structure and function of the Fhit tumor suppressor and Fhit‐nitrilase fusion proteins and the relationship of Fhit to human diadenosine triphosphate hydrolase, site‐directed mutagenesis of diadenosine tetraphosphate hydrolase, novel nucleotide analogs for studying hydrolase function, the synthesis of dinucleoside polyphosphates by ligases, and the possible roles of diadenosine tri‐ and tetraphosphates in insulin function and of diadenosine tetraphosphate in the heat‐shock response of Escherichia coli. The results presented and the ensuing discussions showed that, while considerable progress is being made in the field, it still has the capacity to tease and frustrate and produce the unexpected result. Drug Dev. Res. 52:249–259, 2001. © 2001 Wiley‐Liss, Inc.
Evolutionary thinking as a tool in pharmaceutical development
Authors: LeGrand Edmund K. 
Published: August 2002

AbstractThe rapidly expanding technologies involving chemical synthesis and screening, genomics, and bioinformatics are leading to the point where every gene product can be modulated as a therapeutic target. Thus, pharmaceuticals increasingly offer the potential to control disease processes. While great strides in understanding disease processes can come from this mechanistic approach (addressing “how?” questions), complete understanding is impossible without addressing the ultimate causation of disease processes. By addressing ultimate (“why?”) questions, evolutionary thinking provides a firm theoretical framework for all biological processes, including those relating to disease. Of practical relevance for pharmaceutical development is an increased awareness of evolved responses and potential consequences of bypassing these defenses. Examples involving reproductive medicine, components of the acute phase response, apoptosis, and axonal regeneration are discussed. Drug Dev. Res. 52:439–445, 2001. © 2001 Wiley‐Liss, Inc.
Third‐generation dihydropyridine‐type calcium channel blocker labedipinedilol‐B displays α/β‐adrenoceptor blocking activities
Authors: Yeh Jwu‐Lai , Tsai Chieh‐Ho , Liang Jhy‐Chong , Wu Jiunn‐Ren , Huang Yeun‐Chih , Chen Ing‐Jun 
Published: August 2002

AbstractThe pharmacological properties of labedipinedilol‐B {N‐[4‐[2‐hydroxy‐3‐(2‐methoxy‐1‐oxyethylaminobenzene) propoxy]‐benzyl]‐2,6‐dimethyl‐3,5‐dicarbomethoxy‐1,4‐dihydropyridine} were investigated in vivo and in vitro in comparison with labedipinedilol‐A. Intravenous labedipinedilol‐B (0.5, 1.0, and 3.0 mg kg–1), produced dose‐dependent hypotensive and bradycardia responses in pentobarbital‐anesthetized Wistar rats. Pretreatment with labedipinedilol‐B (1.0 mg kg–1, iv) also inhibited phenylephrine (10 μg kg–1)‐induced hypertensive and (–)isoproterenol (0.5 μg kg–1)‐induced tachycardia effects. In the isolated Wistar rat right and left atria and guinea pigs tracheal strips experiments, labedipinedilol‐B (10–7, 10–6, and 10–5 M) competitively antagonized the (–)isoproterenol‐induced positive chronotropic and inotropic effects and tracheal relaxation responses in a concentration‐dependent manner. The parallel shift to the right of the concentration–response curve of (–)isoproterenol suggested that labedipinedilol‐B was a β1/β2‐adrenoceptor competitive antagonist. Labedipinedilol‐B (10–7, 10–6, and 10–5 M) also prevented the rate‐increasing effects of increased extracellular Ca2+ (3.0–9.0 mM) in a concentration‐dependent manner. In the isolated rat aorta, labedipinedilol‐B (10–7, 10–6, and 10–5 M) competitively antagonized the CaCl2 and norepinephrine‐induced contractions with pKCa–1 and pA2 values of 8.02 ± 0.04 and 7.55 ± 0.05 in a concentration‐dependent manner. The parallel shift to the right of the concentration–response curves of norepinephrine suggested that labedipinedilol‐B was an α‐adrenoceptor competitive antagonist. Furthermore, labedipinedilol‐B, in an equal antagonist activity, inhibited norepinephrine‐induced phasic and tonic contraction. In the isolated rat aorta, labedipinedilol‐B also competitively antagonized CaCl2‐induced contractions and made the parallel shift to the right of the concentration–response curve of CaCl2. In cultured blood vessel smooth muscle cells (A7r5 cell lines), Bay K 8644‐induced intracellular calcium changes were decreased after application of labedipinedilol‐B, suggesting that the compound was a calcium channel blocker. The binding characteristics of labedipinedilol‐B were evaluated in [3H]CGP‐12177 binding to ventricle and lung and [3H]prazosin binding to brain membranes in rats. Labedipinedilol‐B also was evaluated in [3H]nitrendipine binding to brain membranes in rats. These results indicated that labedipinedilol‐B, similar to labedipinedilol‐A, has α‐adrenoceptor blocking, β‐adrenoceptor blocking, and calcium entry blocking activities in a single compound. We suggest that these two compounds represent a new generation of 1,4‐dihydropyridine‐type calcium channel blockers. Drug Dev. Res. 52:462–474, 2001. © 2001 Wiley‐Liss, Inc.
Synthesis of 1‐(2‐deoxy‐β‐D‐ribofuranosyl)‐2,4‐ difluoro‐5‐(2‐halo‐1‐hydroxyethyl)benzenes and related derivatives: “thymine replacement” analogs of deoxythymidine for evaluation as antiviral and anticancer agents
Authors: Naimi Ebrahim , Wiebe Leonard I. , Balzarini Jan , De Clercq Erik , Knaus Edward E. 
Published: August 2002

AbstractA group of unnatural 1‐(2‐deoxy‐β‐D‐ribofuranosyl)‐2,4‐difluorobenzenes having a variety of C‐5 substituents, designed as thymidine mimics, were synthesized for evaluation as antiviral and anticancer agents. The regiospecific addition of HOBr (generated from N‐bromosuccinimide in aqueous dioxane) across the 5‐vinyl substituent (4) afforded the corresponding 5‐[‐CH(OH)CH2Br] product (5), whereas reaction of 4 with iodine in the presence of iodic acid (HOI) yielded the 5‐[CH(OH)CH2I] product (6). The related 5‐[‐CH(OH)CHX2 (X = Br, I)] analogs (11, 12) were similarly prepared from the (E)‐5‐(2‐halovinyl) precursors (9, 10). Treatment of the 5‐[‐CH(OH)CH2X (X = Br, I)] compounds (5, 6) with NaOH in aqueous dioxane afforded the 5‐oxiranyl product (8). The 5‐[‐CH(OMe)CH2I] compound (7) was prepared by reaction of the 5‐vinyl compound (4) with ICl in MeOH (MeOI). This group of compounds (5–8, 11, 12) showed similar (marginal) activity against varicella‐zoster virus thymidine kinase positive (VZV/TK+) and thymidine kinase deficient (VZV/TK–) infected cells. Thus, the viral TK enzyme did not provide a gene therapeutic effect. This group of compounds, which were evaluated using a wide variety of antiviral assay systems [(herpes simplex virus HSV‐1, HSV‐2), varicella‐zoster virus (VZV), vaccinia virus, vesicular stomatitis, cytomegalovirus (CMV), and human immunodeficiency virus (HIV‐1, HIV‐2)], showed that these unnatural C‐aryl nucleoside mimics are inactive antiviral agents. Their failure to exhibit antiviral/anticancer activity could be due to the fact that they are not phosphorylated to the 5′‐monophosphate, or that incorporation of the active 5′‐triphosphate into DNA does not produce a cytotoxic effect, and/or that these C‐aryl nucleoside mimics do not act as inhibitors of thymidylate synthase, which may be required to produce a cytotoxic effect. Drug Dev. Res. 52:492–499, 2001. © 2001 Wiley‐Liss, Inc.
Developmental differences in temporal patterns and potentiation of isolation‐induced ultrasonic vocalizations: Influence of temperature variables
Authors: Kraebel Kimberly S. , Brasser Susan M. , Campbell James O. , Spear Linda P. , Spear Norman E. 
Published: August 2002

AbstractThe present study examined the relationship between the thermal environment and core body temperature in producing age‐related patterns of ultrasonic vocalizations (USVs). Implanted telemetry devices allowed on‐line measurement of core body temperature during an extended period of isolation and after maternal contact, both as a function of age and thermal environment. At 12 or 17 days of age, rat pups were isolated for 30 min in either a cool or a warm environment, returned home for 5 min, and then re‐isolatedj for 10 min. Number of USVs, body temperature, and behavioral activity were measured. During initial isolation in a cool environment, 12‐day‐olds displayed relatively stable patterns of ultrasounding and body temperature across time whereas older animals showed a time‐dependent increase in USV calling and in core temperature. During re‐isolation, 12‐day‐olds potentiated their USV calling at both ambient temperatures while 17‐day‐olds did not. The overall results suggest a strong dependence between USV calling, core body temperature, and ambient temperature during initial isolation at both ages—a finding in agreement with interpretations of USVs as an acoustic by‐product of thermal challenge. In contrast, during re‐isolation, USV calls, core body temperature, and ambient temperature functioned independently—a finding in agreement with interpretations of USVs as a representation of an emotional state. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 147–159, 2002. DOI 10.1002/dev.10022
Effects of chronic and acute methylphenidate hydrochloride (ritalin) administration on locomotor activity, ultrasonic vocalizations, and neuromotor development in 3‐ to 11‐day‐old CD‐1 mouse pups
Authors: Penner Marsha R. , McFadyen Melanie P. , Carrey Normand , Brown Richard E. 
Published: August 2002

AbstractThe present study examined the effects of chronic and acute treatment with methylphenidate hydrochloride (Ritalin) on isolation‐induced ultrasonic vocalizations, spontaneous locomotor activity, and neuromotor coordination in 3‐ to 11‐day‐old CD‐1 mouse pups. In Experiment 1, 3‐ to 11‐day‐old pups received daily injections of saline, 5 mg/kg or 20 mg/kg of methylphenidate hydrochloride, or no injection and were tested on postnatal Days 3, 5, 7, 9, and 11. Both doses of methylphenidate resulted in significant increases in locomotor activity at all ages, but had no significant effect on body weight, neuromotor development, or emission of ultrasonic vocalizations. In Experiment 2, pups were given a single dose of methylphenidate (5 or 20 mg/kg), saline, or no injection on one of postnatal Days 5, 7, 9, or 11. This acute methylphenidate treatment increased locomotor activity, but had no significant effects on ultrasonic vocalizations or neuromotor coordination. These results indicate that short‐term, chronic methylphenidate treatment elevates locomotor responses, but has no immediate effects on anxietylike responses or on the development of neuromotor behavior of CD‐1 mice in the first 11 days of life. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 216–228, 2001
Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats
Authors: Gallego Mónica , Casis Oscar 
Published: August 2002

AbstractBackgroundα‐Adrenergic stimulation regulates cardiac contractility by reducing repolarising K+ currents. Despite this, no published work exists on the effects of norepinephrine on isolated cardiac transient outward current, responsible for action potential duration in the rat and human. Besides, diabetes alters cardiac inotropic responses to sympathetic innervation, and this can result from altered responsiveness of the transient outward current to norepinephrine.MethodsTransient outward K+ current was measured using the whole‐cell configuration of the patch‐clamp technique. Myocytes were isolated from the right ventricle of healthy and streptozotocin‐induced diabetic rats.ResultsNorepinephrine, through α1‐adrenoceptors, reduces current amplitude in a concentration‐dependent way, with no effects on current kinetics or voltage dependence of inactivation. Diabetes reduces current amplitude and accelerates its inactivation process. Norepinephrine also reduces current amplitude in diabetic cells; however diabetes shifts to the right the concentration–response curve and reduces the maximum effect of the neurotransmitter.ConclusionsNorepinephrine reduces the amplitude of isolated ventricular transient outward K+ current with no effects on current properties in myocytes isolated from either healthy or diabetic hearts. Diabetes shifts the concentration–response curve; thus diabetic myocytes are more resistant to sympathetic regulation than are healthy cells. Copyright © 2001 John Wiley & Sons, Ltd.
Frizzled‐7 and limb mesenchymal chondrogenesis: Effect of misexpression and involvement of N‐cadherin
Authors: Tufan A. Cevik , Daumer Kathleen M. , Tuan Rocky S. 
Published: August 2002

AbstractProducts of the Frizzled family of tissue polarity genes have been identified as putative receptors for the Wnt family of signaling molecules. Wnt‐signaling is implicated in the regulation of limb mesenchymal chondrogenesis, and our recent study indicates that N‐cadherin and related activities are functionally involved in Wnt‐7a‐mediated inhibition of chondrogenesis. By using an in vitro high‐density micromass culture system of chick limb mesenchymal cells, we have analyzed the spatiotemporal expression patterns and the effects on chondrogenesis of RCAS retroviral‐mediated misexpression of Chfz‐1 and Chfz‐7, two Frizzled genes implicated in chondrogenic regulation. Chfz‐1 expression was localized at areas surrounding the cartilaginous nodules at all time points examined, whereas Chfz‐7 expression was limited to cellular aggregates during initial mesenchymal condensation, and subsequently was down‐regulated from the centers toward the periphery of cartilage nodules at the time of chondrogenic differentiation, resembling the pattern of N‐cadherin expression. Chondrogenesis in vitro was inhibited and limited to a smaller area of the culture upon misexpression of Chfz‐7, but not affected by Chfz‐1 misexpression. Analyses of cellular condensation and chondrogenic differentiation showed that the inhibitory action of Chfz‐7 is unlikely to be at the chondrogenic differentiation step, but instead affects the earlier precartilage aggregate formation event. At 24 hr, expression of N‐cadherin, a key component of the cellular condensation phase of chondrogenesis, was delayed/suppressed in Chfz‐7 misexpressing cultures, and was limited to a significantly smaller cellular condensation area within the entire culture at 48 hr, when compared with control cultures. Chfz‐1 misexpressing cultures appeared similar to control cultures at all time points. However, neither Chfz‐1 nor Chfz‐7 misexpression affected mesenchymal cell proliferation in vitro. These results suggest that Chfz‐7 is active in regulating N‐cadherin expression during the process of limb mesenchymal chondrogenesis and that Chfz‐1 and Chfz‐7 are involved in different Wnt‐signaling pathways. © 2002 Wiley‐Liss, Inc.
Gamma‐tubulin in chicken erythrocytes: Changes in localization during cell differentiation and characterization of cytoplasmic complexes
Authors: Linhartová Irena , Novotná Božena , Sulimenko Vadym , Dráberová Eduarda , Dráber Pavel 
Published: August 2002

AbstractThe mechanism of marginal band (MB) formation in differentiating erythroid cells is not fully understood, and the proteins involved in nucleation of MB microtubules are largely unknown. To gain insights into the function of γ‐tubulin in MB formation, we have followed its distribution in developing chicken erythrocytes and characterized soluble forms of the protein. In early stages of erythroid cells differentiation, γ‐tubulin was present in microtubule‐organizing centers, mitotic spindles, as well as on MB. Its subcellular localization changed in the course of differentiation, and in postnatal peripheral erythrocytes γ‐tubulin was found only in soluble forms. After cold‐induced depolymerization γ‐tubulin in erythroid cells formed large clusters that were not observed in matured cells, and re‐growth experiments demonstrated that γ‐tubulin was not present in distinct nucleation structures at the cell periphery. Soluble γ‐tubulin formed complexes of various size and large complexes were prone to dissociation in the presence of high salt concentration. Interaction of γ‐tubulin with tubulin dimers was revealed by precipitation experiments. γ‐Tubulin occurred in multiple charge variants whose number increased in the course of erythrocyte differentiation and corresponded with decreased binding to MB. The presented data demonstrate for the first time that γ‐tubulin is a substrate for developmentally regulated posttranslational modifications and that the binding properties of γ‐tubulin or its complexes change during differentiation events. © 2002 Wiley‐Liss, Inc.
Expression of Ol‐KIP, a cyclin‐dependent kinase inhibitor, in embryonic and adult medaka (Oryzias latipes) central nervous system
Authors: Nguyên Vân , Suárez Eva María Candal , Sharif Ariane , Joly Jean‐Stéphane , Bourrat Franck 
Published: August 2002

AbstractFrom an expression screen in a fish model, the medaka, we have isolated Ol‐KIP (Oryzias latipes‐kinase inhibitor protein), a new member of the KIP subfamily of cyclin‐dependent kinase (Cdk) inhibitors. We have analysed its expression in the developing and adult brain by in situ hybridization and by double labeling with Ol‐KIP mRNA and proliferating cell nuclear antigen (PCNA) antibodies. Ol‐KIP presents a complex expression pattern in several areas of the embryonic central nervous system, most often in close vicinity to proliferative neuroepithelia. We studied in great detail its expression in the optic tectum: Ol‐KIP is expressed in a ring‐shaped domain lying exactly between the proliferative and the postmitotic zones of this structure and is, therefore, potentially involved in cell cycle exit. In the adult CNS, Ol‐KIP expression persists in numerous nuclei, both close and distant from proliferative ventricular areas. So, Ol‐KIP expression is in part compatible with a sustained “stop signal” role for proliferation, but its expression in postmitotic zones suggests that KIP proteins may have late neuronal function(s), in addition to inhibiting Cdks. This first detailed study of the expression profile of a KIP gene in a nonmammalian vertebrate, thus, opens perspectives for analysing the role of these regulators in brain development and function. © 2001 Wiley‐Liss, Inc.