bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of exogenous surfactant on gas exchange and compliance in rabbits after meconium aspiration
Authors: Robinson Tonya W. , Roberts Andrew M. 
Published: August 2002

AbstractSuccess in using adjunctive surfactant therapy for meconium aspiration has been inconsistent. We tested the hypothesis that the ability of exogenous surfactant to improve gas exchange and pulmonary compliance after meconium aspiration is related to the method of surfactant administration. In anesthetized rabbits (2.4 ± 0.16 kg body weight), an endotracheal tube (ETT) was placed in the lower trachea, and the lungs were ventilated mechanically. After a control period, filtered meconium (3–5 mL/kg) was instilled through the ETT. Group 1 (n = 5) was not given surfactant. Thirty minutes after meconium instillation, group 2 (n = 5) was given a bolus of bovine surfactant (Beractant, 4 mL/kg) through the ETT, and group 3 (n = 5) was given an infusion of Beractant (4 mL/kg for 1 hr) through the side‐port of the ETT.Thirty minutes after meconium instillation, tracheal pressure increased by 8 ± 1 cm H2O (mean ± SEM), dynamic compliance decreased by 0.36 ± 0.07 mL/cm H2O/kg, arterial PO2 (PaO2) decreased by 49 ± 6.0 mmHg, arterial PCO2 (PaCO2) increased by 12 ± 2.4 mmHg, and arterial pH (pHa) decreased by 0.09 ± 0.02. After 3 hr of exposure to meconium, tracheal pressure was significantly (P < 0.001) lower in group 3 compared to groups 1 or 2. PaO2 remained below baseline in all groups. Group 3 had a significantly (P = 0.001) higher dynamic compliance than groups 1 or 2. Likewise, static compliance was higher for group 3 compared to groups 1 or 2, with the greatest difference at low lung volume. Mean arterial blood pressure, pulse rate, PaCO2, and pHa were not significantly different between groups.These results suggest that continuous infusion of exogenous surfactant is more effective than bolus administration in improving pulmonary function after meconium aspiration. Pediatr Pulmonol. 2002; 33:117–123. © 2002 Wiley‐Liss, Inc.
Snoring and obstructive sleep apnea in Thai school‐age children: Prevalence and predisposing factors
Authors: Anuntaseree Wanaporn , Rookkapan Korpong , Kuasirikul Surachai , Thongsuksai Paramee 
Published: August 2002

AbstractWe studied the prevalence of habitual snoring and its associations with tonsillar size, allergic rhinitis, obesity, and parental smoking, as well as prevalence of obstructive sleep apnea (OSAS) in a sample of 1,142 children aged 6–13 years (mean, 7.25 ± 0.58) from seven randomly selected schools in Hat yai, Southern Thailand.Eighty‐five (8.5%) of the children were habitual snorers; the prevalence was the same in boys and girls. Significant and independent association was present between snoring and allergic rhinitis with an odds ratio of 5.27 (95% CI, 1.57–17.77). The odds ratio was significantly increased to 2.65 (CI, 1.31–5.39), 5.72 (CI, 2.67–12.25), and 11.06 (CI, 1.91–63.84) in children with tonsillar size of 2+ , 3+ , and 4+ , respectively. Of the 85 habitual snorers, 69 could be contacted by telephone call or by hospital visit. Eight of these were reported to have at least one of the following symptoms: difficulty breathing during sleep, stop breathing at night, restless sleeping and frequent awakening, sleeping with the head tipped back, and a tendency to breathe through the mouth rather than the nose. Polysomnographic studies in these 8 children demonstrated an apnea/hypopnea index of 0.6–4.7 per hr. Seven children met the criteria for OSAS. Thus, our estimate of the prevalence of OSAS among Thai schoolchildren was 7/1,008 (0.69%).We have shown that the prevalence of habitual snoring was 8.5%, and the prevalence of OSAS in a sample of Asian school‐age children in Southern Thailand was 0.69%, which was similar to that observed in Western populations. An association of snoring with tonsillar size or allergic rhinitis was demonstrated. All but one of the snoring children with sleep‐related symptoms had OSAS, but all were mild cases. Pediatr Pulmonol. 2001; 32:222–227. © 2001 Wiley‐Liss, Inc.
Elevated serum progastrin‐releasing peptide (31–98) in metastatic and androgen‐independent prostate cancer patients*
Authors: Yashi Masahiro , Muraishi Osamu , Kobayashi Yutaka , Tokue Akihiko , Nanjo Hiroshi 
Published: August 2002

AbstractBACKGROUNDIncreases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin‐releasing peptide (ProGRP), a carboxy‐terminal region common to three subtypes of precursors for gastrin‐releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor.METHODSIn 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme‐linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate‐specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow‐up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin‐A (CgA) in tissue samples from several subjects.RESULTSWe found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen‐independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen‐dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA.CONCLUSIONSThe clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen‐independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone. Prostate 51: 84–97, 2002. © 2002 Wiley‐Liss, Inc.
Silencing of π‐class glutathione S‐transferase in MDA PCa 2a and MDA PCa 2b cells
Authors: Vidanes Genevieve M. , Paton Vince , Wallen Eric , Peehl Donna M. , Navone Nora , Brooks James D. 
Published: August 2002

AbstractBACKGROUNDLoss of expression of the glutathione S‐transferase‐π (GSTP1) is the most common genetic alteration described in human prostate cancer, occurring in virtually all tumors regardless of grade or stage. Of the available human prostate cancer cell lines, only LNCaP mirrors this phenotype. We investigated whether the prostate cancer cell lines MDA PCa 2a and MDA PCa 2b share this phenotype.METHODSGSTP1 protein and mRNA levels were assessed in the MDA PCa 2a and MDA PCa 2b cell lines by Western and Northern blot. DNA methylation was evaluated by Southern blot analysis of genomic DNA digested with the methylation‐sensitive restriction enzymes BssHII, NotI, and SacII. Re‐expression of GSTP1 was determined by RT‐PCR following treatment with 5‐azacytidine, a DNA methyltransferase inhibitor, and/or the histone deacetylase inhibitor trichostatin A (TSA).RESULTSLike all human prostatic carcinomas in vivo, both the MDA PCa 2a and 2b cell lines lack protein and mRNA expression of GSTP1. This lack of expression is associated with methylation in the GSTP1 gene promoter. Treatment with the methyltransferase inhibitor 5‐azacytidine resulted in re‐expression of GSTP1. By itself, TSA did not result in re‐expression of GSTP1, nor did it augment expression induced by 5‐azacytidine.CONCLUSIONSMDA PCa 2a and 2b appear to be useful models of human prostatic carcinoma in that they lack expression of GSTP1 due to gene silencing via promoter methylation. Inhibition of histone acetylation does not appear to affect GSTP1 expression. Prostate 51: 225–230, 2002. © 2002 Wiley‐Liss, Inc.
Mixed lineage kinase (MLK) family members are not involved in androgen regulation of prostatic proliferation or apoptosis*
Authors: Gao Jin , Isaacs John T. 
Published: August 2002

AbstractBACKGROUNDOnce paracrine growth factors are secreted by androgen receptor expressing prostatic stromal cells, they diffuse across the basement membrane of glandular acini, where they bind to epithelial cell surface receptors. This binding stimulates signaling pathways that regulate both the rate of proliferation and apoptosis of prostate epithelial cells. In the present studies, the role of mixed lineage kinases (MLKs) in these signaling processes were studied using a pharmacological approach.METHODSThe indolocarbazole CEP‐1347 (KT 7515) is a potent inhibitor of kinase activity of MKLs. Male rats were treated with CEP‐1347 (1 mg/kg of body weight/day) to determine whether inhibition of the MLKs can prevent androgen ablation (i.e. castration) induced apoptosis of prostatic epithelial cells, using as indexes total ventral prostatic DNA content and the percentage of ventral prostatic epithelial cells whose DNA can be terminal transferase end‐labeled. In addition, animals previously castrated a week earlier were treated daily with either vehicle or CEP‐1347 and exogenous androgen replacement to induce the proliferative re‐growth of the prostatic epithelial cells. After 1 week of treatment, the total ventral prostatic DNA content in the vehicle vs. CEP‐1347 groups was compared.RESULTSUsing the National Center for Bio‐Informatics data bank, MLK2, MLK3, and DLK members of the MLK family are expressed by the normal prostate. Inhibition of the MLKs with CEP‐1347 did not affect the kinetics of apoptosis of prostatic epithelial cells induced by androgen ablation. In addition, such MLK inhibition did not prevent androgen replacement induced proliferative regrowth of the prostate epithelium in castrated animals.CONCLUSIONSSignaling through the MLK family is not involved in either the androgen‐induced proliferation or the androgen ablation‐induced apoptosis of prostatic epithelial cell in the rat. Prostate 48:67–70, 2001. © 2001 Wiley‐Liss, Inc.
Activation of latent protease function of pro‐hk2, but not pro‐PSA, involves autoprocessing
Authors: Denmeade Samuel R. , Lövgren Janita , Khan Saeed R. , Lilja Hans , Isaacs John T. 
Published: August 2002

AbstractBACKGROUNDHuman glandular kallikrein 2 (hK2) and prostate‐specific antigen (PSA) are members of an extensive kallikrein family of proteases. Both proteases are secreted as zymogens or proenzymes containing a seven amino acid propeptide that must be proteolytically removed for enzymatic activation. The physiological proteases that activate pro‐hK2 and pro‐PSA are not known.METHODSThe pro‐hK2 peptide sequence is Val‐Pro‐Leu‐Ile‐Gln‐Ser‐Arg (VPLIQSR). For PSA, the amino acid sequence of the propeptide is Ala‐Pro‐Leu‐Ile‐Leu‐Ser‐Arg (APLILSR). Fluorescent substrates were made by coupling these peptide sequences to 7‐amino‐4‐methylcoumarin (AMC). The hydrolysis of the VPLIQSR‐AMC and APLILSR‐AMC substrates by hK2, PSA, and a panel of purified proteases was determined.RESULTSHK2 readily cleaved the pro‐hK2 peptide substrate VPLIQSR‐AMC with a rate of hydrolysis that was ∼ 8‐fold higher than an equimolar amount of purified trypsin. HK2 also had the highest hydrolysis rate from among a group of other trypsin‐like proteases. In contrast, neither hK2 nor PSA was able to appreciably cleave the pro‐PSA substrate APLILSR‐AMC. The pro‐PSA substrate was most readily hydrolyzed by urokinase and trypsin.CONCLUSIONSHK2 can hydrolyze the pro‐hK2 substrate suggesting that maturation of pro‐hK2 to enzymatically active hK2 involves autoprocessing. As expected, PSA, a chymotrypsin‐like protease, was unable to hydrolyze either of the propeptide substrates. Therefore, it is unlikely that PSA can auto‐process its own enzymatic function. HK2 has trypsin‐like specificity but was unable to hydrolyze the pro‐PSA substrate. These results raise the possibility that an additional processing protease may be required to fully process PSA to an enzymatically active form. Prostate 48:122–126, 2001. © 2001 Wiley‐Liss, Inc.
Expression of a human cell adhesion molecule, MUC18, in prostate cancer cell lines and tissues
Authors: Wu Guang‐Jer , Varma Vijay A. , Wu Mei‐Whey H. , Wang Shur‐Wern , Qu Pengpeng , Yang Hsiuchin , Petros John A. , Lim So Dug , Amin Mahul B. 
Published: August 2002

AbstractBACKGROUNDOver expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non‐metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues.METHODSRT‐PCR and Western blot analyses were used to analyze the expression of MUC18 mRNA and protein in four human prostate cancer cell lines, cultured primary normal prostate epithelial cells, normal prostate and malignant prostate tissues. Immunohistochemistry was used to determine the expression of MUC18 antigen in prostatic tissues at different stages of malignancy.RESULTSHuman MUC18 mRNA and protein was expressed in three different prostate cancer cell lines (TSU‐PR1, DU145, and PC‐3), but not in one prostate cancer cell line (LNCaP.FGC). HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from either cultured primary normal prostatic epithelial cells or the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high‐grade PIN and prostatic carcinomas and in cells of a lymph node metastasis compared to that in normal or benign hyperplastic epithelium (BPH).CONCLUSIONSWe therefore conclude that MUC18 is expressed at higher levels in pre‐malignant and malignant prostatic epithelium, including metastasis. We suggest that over‐expression of MUC18 may be a new marker of human prostate cancer and also implicates its possible role in development and progression of prostate cancer. Prostate 48:305–315, 2001. © 2001 Wiley‐Liss, Inc.
Structural determinants of binding and specificity in transforming growth factor–receptor interactions
Authors: Shah Parantu K. , Buslje Cristina Marino , Sowdhamini R. 
Published: August 2002

AbstractTransforming growth factor (TGF‐β) protein families are cytokines that occur as a large number of homologous proteins. Three major subgroups of these proteins with marked specificities for their receptors have been found—TGF‐β, activin/inhibin, and bone morphogenic protein. Although structural information is available for some members of the TGF‐β family of ligands and receptors, very little is known about the way these growth factors interact with the extracellular domains of their cell surface receptors, especially the type II receptor. In addition, the elements that are the determinants of binding and specificity of the ligands are poorly understood. The structure of the extracellular domain of the receptor is a three‐finger fold similar to some toxin structures. Amino acid exchanges between multiply aligned homologous sequences of type II receptors point to a residue at the surface, specifically finger 1, as the determinant of ligand specificity and complex formation. The “knuckle” epitope of ligands was predicted to be the surface that interacts with the type II receptor. The residues on strands β2, β3, β7, β8 and the loop region joining β2 and β3 and joining β7 and β8 of the ligands were identified as determinants of binding and specificity. These results are supported by studies on the docking of the type II receptor to the ligand dimer–type I receptor complex. Proteins 2001;454:408–420. © 2001 Wiley‐Liss, Inc.
Protein sequence threading: Averaging over structures
Authors: Russell Anthony J. , Torda Andrew E. 
Published: August 2002

AbstractMultiple sequence alignments are a routine tool in protein fold recognition, but multiple structure alignments are computationally less cooperative. This work describes a method for protein sequence threading and sequence‐to‐structure alignments that uses multiple aligned structures, the aim being to improve models from protein threading calculations. Sequences are aligned into a field due to corresponding sites in homologous proteins. On the basis of a test set of more than 570 protein pairs, the procedure does improve alignment quality, although no more than averaging over sequences. For the force field tested, the benefit of structure averaging is smaller than that of adding sequence similarity terms or a contribution from secondary structure predictions. Although there is a significant improvement in the quality of sequence‐to‐structure alignments, this does not directly translate to an immediate improvement in fold recognition capability. Proteins 2002;47:496–505. © 2002 Wiley‐Liss, Inc.
Ionic network at the C‐terminus of the β‐glycosidase from the hyperthermophilic archaeon Sulfolobus solfataricus: Functional role in the quaternary structure thermal stabilization
Authors: Cobucci‐Ponzano Beatrice , Moracci Marco , Di Lauro Barbara , Ciaramella Maria , D'Avino Rossana , Rossi Mosé 
Published: August 2002

AbstractBiochemical, crystallographic, and computational data support the hypothesis that electrostatic interactions are among the dominant forces in stabilizing hyperthermophilic proteins. The thermostable β‐glycosidase from the hyperthermophile Sulfolobus solfataricus (Ssβ‐gly) is an interesting model system for the study of protein adaptation to high temperatures. The largest ion‐pair network of Ssβ‐gly is located at the tetrameric interface of the molecule; in this paper, key residues in this region were modified by site‐directed mutagenesis and the stability of the mutants was analyzed by kinetics of thermal denaturation. All mutations produced faster enzyme inactivation, suggesting that the C‐terminal ionic network prevents the dissociation into monomers, which is the limiting step in the mechanism of Ssβ‐gly inactivation. Moreover, the calculated reaction order showed that the mechanism of inactivation depends on the mutation introduced, suggesting that intermediates maintaining enzymatic activity are produced during the inactivation transition of some, but not all, mutants. Molecular models of each mutant allow us to rationalize the experimental evidence and give support to the current theories on the mechanism of ion pair stabilization in proteins from hyperthermophiles. Proteins 2002;48:98–106. © 2002 Wiley‐Liss, Inc.
Molecular engineering of a polymer of tetrameric hemoglobins
Authors: Fronticelli Clara , Arosio Daniele , Bobofchak Kevin M. , Vasquez Gregory B. 
Published: August 2002

AbstractWe have engineered a recombinant mutant human hemoglobin, Hb Prisca β(S9C+C93A+C112G), which assembles in a polymeric form. The polymerization is obtained through the formation of intermolecular SS bonds between cysteine residues introduced at position β9, on the model of Hb Porto Alegre (β9Ser → Cys) (Bonaventura and Riggs, Science 1967;155:800–802). Cβ93 and Cβ112 were replaced in order to prevent formation of spurious SS bonds during the expression, assembly, and polymerization events. Dynamic light scattering measurements indicate that the final polymerization product is mainly formed by 6 to 8 tetrameric hemoglobin molecules. The sample polydispersity Q = 0.07 ± 0.02, is similar to that of purified human hemoglobin (Q = 0.02 ± 0.02), consistent with a good degree of homogeneity. In the presence of strong reducing agents, the polymer reverts to its tetrameric form. During the depolymerization process, a direct correlation is observed between the hydrodynamic radius and the light scattering of the system, which, in turn, is proportional to the mass of the protein. We interpret this to indicate that the hemoglobin molecules are tightly packed in the polymer with no empty spaces. The tight packing of the hemoglobin molecules suggests that the polymer has a globular shape and, thus, allows estimation of its radius. An illustration of an arrangement of a finite number of tetrameric hemoglobin molecules is presented. The conformational and functional characteristics of this polymer, such as heme pocket conformation, stability to denaturation, autoxidation rate, oxygen affinity, and cooperativity, remain similar to those of tetrameric human hemoglobin. Proteins 2001;44:212–222. © 2001 Wiley‐Liss, Inc.
Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness shared by cysteine‐rich motifs
Authors: Campion Stephen R. , Ameen Abdullah S. , Lai Longsheng , King Jeniffer M. , Munzenmaier Tracy N. 
Published: August 2002

AbstractThis report describes the application of a simple computational tool, AAPAIR.TAB, for the systematic analysis of the cysteine‐rich EGF, Sushi, and Laminin motif/sequence families at the two‐amino acid level. Automated dipeptide frequency/bias analysis detects preferences in the distribution of amino acids in established protein families, by determining which “ordered dipeptides” occur most frequently in comprehensive motif‐specific sequence data sets. Graphic display of the dipeptide frequency/bias data revealed family‐specific preferences for certain dipeptides, but more importantly detected a shared preference for employment of the ordered dipeptides Gly–Tyr (GY) and Gly–Phe (GF) in all three protein families. The dipeptide Asn–Gly (NG) also exhibited high‐frequency and bias in the EGF and Sushi motif families, whereas Asn–Thr (NT) was distinguished in the Laminin family. Evaluation of the distribution of dipeptides identified by frequency/bias analysis subsequently revealed the highly restricted localization of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme conservation in the consensus sequence of all three sequence families. The similar employment of the high‐frequency/bias dipeptides in three distinct protein sequence families was further correlated with the concurrence of these shared molecular determinants at similar positions within the distinctive scaffolds of three structurally divergent, but similarly employed, motif modules. Proteins 2001;44:321–328. © 2001 Wiley‐Liss, Inc.
Self‐repair of biological fibers catalyzed by the surface of a virus crystal
Authors: Kuznetsov Yu. G. , Malkin A. J. , McPherson A. 
Published: August 2002

AbstractHelical fibers, presumably proteinaceous and of microbial origin, have been visualized by atomic force microscopy on the surfaces of crystals of satellite tobacco mosaic virus. If the crystals are growing, then the fibers are incorporated intact into the crystal lattice. If broken on the crystal surface, then within a few minutes, the fibers self‐reassemble to reestablish continuity. This, we believe, is the first observation of such a crystal surface–catalyzed repair of a biological structure. The surfaces of virus crystals provide ideal workbenches for the visualization and manipulation of nanoscale objects, particularly extended structures such as these fibers. Proteins 2001;44:392–396. © 2001 Wiley‐Liss, Inc.