bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytologic differential diagnosis of myxoid and mucinous neoplasms of the sacrum and parasacral soft tissues
Authors: Layfield Lester J.
Published: April 2003

A diagnostically important group of lesions involving the sacrum, spinal canal, and parasacral soft tissues is characterized by a myxoid or mucinous background in cytologic smears. This group of myxoid/mucoid neoplasms includes chordoma, myxopapillary ependymoma, metastatic mucinous adenocarcinoma, and extraskeletal myxoid chondrosarcoma. Despite the similarity of the background substance, each neoplasm within this differential diagnosis has a characteristic composite set of morphologic and immunophenotypic features. Because many of these masses are not easily surgically biopsied, fine‐needle aspiration (FNA) is often used for their diagnosis. The private consultation records of the author and the cytology files of the University of Utah Department of Pathology were searched for all lesions arising in or around the sacrum. These cases were reviewed to determine which had a myxoid/mucinous background. Fourteen neoplasms were found and comprise the study set. Four of these cases had cell block material in addition to Diff‐Quik‐stained smears; a panel of antibodies, including cytokeratin, glial fibrillary acid protein (GFAP), S‐100 protein, and carcinoembryonic antigen (CEA), was performed on the cell block material. The smears were evaluated for cytologic features, including the presence of rosette‐like structures, physaliphorous cells, gland‐like structures, chondroid fragments, “signet ring” and “goblet” cells, as well as the character of the myxoid/mucinous background substance.

The cases included one myxopapillary ependymoma, 10 chordomas, two mucinous adenocarcinomas of colonic or gastric origin, and one myxoid chondrosarcoma. Physaliphorous cells were found to be highly specific for chordoma, while a fibrillary myxoid stroma containing cells with elongated cytoplasmic processes and cells lying in a rosette‐like pattern around central cores of myxoid to fibrillary stroma were highly characteristic of myxopapillary ependymoma. Fragments of a myxoid/chondroid matrix with lacunar‐like spaces strongly supported the diagnosis of myxoid chondrosarcoma. “goblet” or “signet ring” cells with a single distinct vacuole favored mucinous adenocarcinoma. There appear to be sufficient cytomorphologic features present within the FNA smears and cell block material to allow cytologic separation of the more common myxoid and mucinous neoplasms involving the sacral and parasacral tissues. Diagn. Cytopathol. 2003;28:264–271. © 2003 Wiley‐Liss, Inc.
A novel pattern of dimerization for 1, 4‐diphospha‐1,3‐butadienes
Authors: Ionkin Alex S. , Marshall William J.
Published: April 2003

A new example of [2+4] cycloaddition of the low‐coordinated diphospha‐analog of butadiene protected with a 2,4‐di‐tert‐butyl‐6‐methylphenyl group has been described. X‐ray structure investigations of monomer 4b and dimer 5a have been reported for the first time. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:231–234, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10123
Oxidation of thiols with metal nitrates supported on TAFF
Authors: Arroyo Gabriel , Osnaya Roberto , Cruz Tonatiuh , Londoño Amparo , Álvarez Cecilio , Delgado Francisco , Santiago Ricardo , Miranda René
Published: April 2003

Twelve thiols were readily oxidized to the corresponding disulfides by means of four metal nitrates supported on TAFF, a bentonitic clay, under mild conditions. However, in some cases, thioethers and other interesting by‐products were detected. Some of the disulfides showed antimicotical activities against Aspergillus fumigatus, Aspergillus niger, Aspergillus candidus, Microsporum gypseum, Candida albicans, and Cryptococcus neoformans © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:262–265, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10138
Myocutaneous versus thoraco‐abdominal flap cover for soft tissue defects following surgery for locally advanced and recurrent breast cancer
Authors: Deo S.V. Suryanarayana , Purkayastha Joydeep , Shukla Nootan K. , Asthana Sonal
Published: April 2003

Background and Objectives

Radical surgical extirpation in advanced breast cancer patients produces large defects that may not be suitable for primary closure. The primary aim in such cases is to achieve an adequate soft tissue cover expeditiously. Various methods, including skin graft, omentum, random flaps, and myocutaneous (MC) flaps, have been tried in the past; however, there is no consensus regarding the method of choice in such patients.

Methods

A retrospective analysis of the breast cancer database of a single surgical unit was performed to find out the incidence of advanced breast cancer patients requiring an additional surgical procedure for soft tissue cover. A comparative analysis of two major groups, “MC flaps” and “thoraco‐abdominal (TA) flaps,” was performed in relation to operative time, blood loss, morbidity, hospital stay, and final outcome.

Results

Forty (12.7%) out of 315 advanced breast cancer patients undergoing surgery required additional surgical procedures for soft tissue cover. MC flaps were used in 18 patients and TA flaps were used in 22 patients. The mean blood loss (192 ± 77 ml vs. 40 ± 19 ml), operating time (110 ± 20 minutes vs. 35 ± 7 minutes), and hospital stay (10 ± 4 days vs. 5 ± 2 days) were significantly less in the TA flap group.

Conclusions

The results of the current study show a significant diference in the blood loss, operating time, and hospital stay between patients requiring TA and MC flap for soft tissue cover following mastectomy. In view of its simplicity and better results, we recommend that the TA flap should be used as a first option flap in advanced breast cancer patients requiring skin cover. J. Surg. Oncol. 2003;83:31–35. © 2003 Wiley‐Liss, Inc.
Manual transport in Parkinson's disease
Authors: Hejduková Blanka , Hosseini Nasser , Johnels Bo , Ingvarsson Pall E. , Steg Göran , Olsson Torsten
Published: April 2003

We analyze hand dexterity in Parkinson's disease patients (PD) and control subjects using a natural manual transport task (moving an object from one place to another). Eight PD patients and 10 control subjects carried out the task repeatedly at maximum speed both in off and on medicated status. The movement parameters and the grip and load forces were recorded. Using the force and velocity signals, 10 subsequent phases of the transport movement were defined and their durations were measured. The difference between the control group and the test group in off and on was established statistically using non‐parametric methods. There was slowed reaching and a striking disturbance of establishing the precision grip in PD. The transport capabilities were impaired differentially. Although acceleration and reaching sufficient height of the lift were disturbed in PD subjects, transport of the object toward the target position was almost normal. A partial disturbance was observed when cancelling the grip. Dopaminergic medication improved only specific hand skills, especially establishment of the precision grip and one of the four transport phases. A long movement path was more sensitive for movement disturbance in Parkinson's disease than a short one.© 2003 Movement Disorder Society
Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease
Authors: Funkiewiez Aurélie , Ardouin Claire , Krack Paul , Fraix Valérie , Van Blercom Nadège , Xie Jing , Moro Elena , Benabid Alim‐Louis , Pollak Pierre
Published: April 2003

High‐frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow‐up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off‐drug/on‐stimulation; off‐drug/off‐stimulation; on‐drug/off‐stimulation; and on‐drug/on‐stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long‐term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD. © 2003 Movement Disorder Society
Influence of the network chain orientation on the fracture toughness of a mesogenic epoxy resin modified with CTBN
Authors: Harada Miyuki , Morimoto Mitsuhiko , Ochi Mitsukazu
Published: April 2003

A biphenol‐type epoxy resin, which had a mesogenic group in the backbone moiety, was modified with carboxy‐terminated butadiene acrylonitrile copolymer (CTBN) as a reactive elastomer, and its fracture toughness was measured. With the addition of CTBN, the fracture toughness of the biphenol‐type epoxy resin significantly increased and became significantly higher than that of a bisphenol A‐type epoxy resin modified with CTBN. The network chain orientation in the cured biphenol‐type epoxy resin system was clearly observed during the fracture process with polarized microscopy Fourier transform infrared measurements, although such a phenomenon was not observed in the bisphenol A‐type epoxy resin system. The high toughness of the cured biphenol‐type system was clearly due to the consumption of the mechanical energy by a large deformation of the matrix resin due to the orientation of the network chains during the fracture process. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1198–1209, 2003
Mechanical behavior of electrospun fiber mats of poly(vinyl chloride)/polyurethane polyblends
Authors: Lee Keun Hyung , Kim Hak Yong , Ryu Young Jun , Kim Kwan Woo , Choi Sun Woong
Published: April 2003

Various polyblends of poly(vinyl chloride) and polyurethane (PU) dissolved in a mixture of tetrahydrofuran and N,N‐dimethylformamide were produced by electrospinning, in different ratios, with several electrospinning conditions, and the relationship between morphology and mechanical behavior of the resulting fiber mats was examined in detail. The surface tension, viscosity, and electrical conductivity of polymer solutions affecting electrospinning were measured, and scanning electron microscopy (SEM) along with a universal testing machine were used to examine the family of polyblends under investigation. The SEM images demonstrated that point‐bonded structures in the fiber mats rose with increasing PU composition, and the mechanical properties of the fiber mats, as determined in a static tensile test, can be considered to have a strong effect by the point‐bonded structure. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1256–1262, 2003
Quantum imaging, quantum lithography and the uncertainty principle
Authors: Shih Y.
Published: April 2003

One of the most surprising consequences of quantum mechanics is the entanglement of two or more distant particles. The “ghost” image experiment demonstrated the astonishing nonlocal behavior of an entangled photon pair. Even though we still have question in regard to fundamental issues of the entangled quantum systems, quantum entanglement has started to play important roles in practical applications. Quantum lithography is one of the hot topics. We have demonstrated a prove‐of‐principle quantum lithography experiment recently. The experimental results have beaten the classical diffraction limit by a factor of two. This is a quantum mechanical two‐photon phenomenon but not a violation of the uncertainty principle.
Cytoprotective activity of Amla (Emblica ofﬁcinalis) against chromium (VI) induced oxidative injury in murine macrophages
Authors: Sai Ram M. , Neetu D. , Deepti P. , Vandana M. , Ilavazhagan G. , Kumar Devendra , Selvamurthy W.
Published: April 2003

The cytoprotective and immunomodulating properties of Emblica ofﬁcinalis (Amla) against chromium (VI) induced oxidative damage are reported. Chromium (VI) at 1 µg/mL concentration was highly cytotoxic. It enhanced free radical production and decreased reduced glutathione (GSH) levels and glutathione peroxidase (GPx) activity in macrophages. The presence of Amla resulted in an enhanced cell survival, decreased free radical production and higher antioxidant levels similar to that of control cells. Further, chromium (VI) treatment resulted in decreased phagocytosis and gamma‐interferon (γ‐IFN) production while Amla inhibited chromium induced immunosuppression and restored both phagocytosis and γ‐IFN production by macrophages signiﬁcantly. Copyright © 2003 John Wiley & Sons, Ltd.
Cu,Zn superoxide dismutase in Rhodotorula and Udeniomyces spp. isolated from sea water: cloning and sequencing the encoding region
Authors: Hernández‐Saavedra Norma Y.
Published: April 2003

The gene encoding the copper‐zinc superoxide dismutase enzyme (SODC or Cu,Zn‐SOD) has been cloned from several species of higher eukaryotes, but superoxide dismutase genes from moulds and yeast have not been studied extensively. Only 15 nucleotide sequences have been reported in the SwissProt, EMBL and GenBank data libraries. In general the presence of Cu,Zn‐SOD in cytosol, as well as Mn‐SOD in the mitochondrial matrix of yeast, has been accepted. The absence of Cu,Zn‐SOD in a pigmented yeast has been accepted as a general rule. Some authors suggest that the absence of Cu,Zn‐SOD in pigmented yeast is complemented by the presence of carotenoproteins that act as an extra mitochondrial antioxidant. In this report, we found that the absence of SODC is not a rule for pigmented yeast: Udeniomyces puniceus expresses an active SODC which responds to Cu2+ induction, as has been reported previously for non‐pigmented yeast. The encoding region of the sod1 gene was cloned from three species of pigmented marine yeast thorough genomic DNA PCR amplification. Fragments of 485–487 nucleotides were obtained, which contain information for theoretical products of 153–154 amino acids. In Rhodotorula mucilaginosa the deduced amino acid sequence shows that insertion of three bases (C112, A149 and C166) generates a stop codon at position 123 (TGA). For Rhodotorula graminis a single change (T for A) generates a stop codon at position 298. For both species, this non‐transcription of encoding sequence correlates with the absence of peptides or active proteins in cell homogenates. For U. puniceus, the cloned nucleotide sequence contains all necessary information to produce a functional protein, which correlates with activity detected in cell homogenates, both under normal conditions and by copper induction experiments. Finally, we clearly showed that the key factor in protection against oxidative stress on pigmented yeast is related not only to the presence of protective pigments but also to their amounts and spectra, as well as the presence and activity of SODC. The sod1 sequences reported in this paper have been deposited in the NCBI public data library under Accession Nos AY064723, AY064724 and AF301901. Copyright © 2003 John Wiley & Sons, Ltd.
Rapid Alzheimer‐like phosphorylation of tau by the synergistic actions of non‐proline‐dependent protein kinases and GSK‐3
Authors: Singh Toolsee J. , Haque Niloufar , Grundke-Iqbal Inge , Iqbal Khalid
Published: April 2003

Tau protein from Alzheimer disease (AD) brain is phosphorylated at eleven Ser/Thr‐Pro and nine Ser/Thr‐X sites. The former sites are phosphorylated by proline‐dependent protein kinases (PDPKs), the latter by non‐PDPKs. The identities of both the PDPKs and non‐PDPKs involved in AD tau hyperphosphorylation are still to be established. In this study we have analyzed the interactions between a PDPK (GSK‐3) and several non‐PDPKs (A‐kinase, C‐kinase, CK‐1, CaM kinase II) in the phosphorylation of one isoform (tau 39) of human tau. We found that the rate of phosphorylation of tau 39 by GSK‐3 was increased several‐fold if tau were first prephosphorylated by the non‐PDPKs. Further, several Alzheimer‐like epitopes in tau can be induced only slowly after phosphorylation of tau by GSK‐3 alone. After a prephosphorylation of tau by the non‐PDPKs, however, the rate of induction of these epitopes by GSK‐3 is increased several‐fold. These results suggest that one role of non‐PDPK‐catalyzed phosphorylation is the modulation of PDPK‐catalyzed phosphorylation of tau in AD brain.
GroES and the chaperonin‐assisted protein folding cycle: GroES has no affinity for nucleotides
Authors: Todd Matthew J. , Boudkin Olga , Freire Ernesto , Lorimer George H.
Published: April 2003

The E. coli chaperonin proteins, GroEL and GroES, assist in folding newly synthesized proteins. GroES is necessary for GroEL‐assisted folding under conditions where the substrate protein cannot spontaneously fold. On the basis of photolabelling of GroES with 8‐azido‐ATP, a role for nucleotide binding to GroES in chaperonin function was suggested [Martin, et al., Nature, 366 (1993) 279–2821]. We confirm the photolabelling of GroES with 8‐azido‐ATP. However, other proteins not known to contain nucleotide binding sites also become photolabeled suggesting that labeling is non‐specific. Using rigorous physical methods, isothermal calorimetry and equilibrium binding, no interaction between GroES and nucleotides could be detected. We conclude that GroES has no nucleotide binding site.
Cooperation of the molecular chaperone Ydj1 with specific Hsp70 homologs to suppress protein aggregation
Authors: Cry Douglas M.
Published: April 2003

Ydj1p, a cytosolic DnaJ homolog from Saccharomyces cerevisiae, is demonstrated to function as a molecular chaperone. Purified Ydj1p formed complexes with non‐native polypeptides and suppressed protein aggregation. Ydj1p cooperated with Ssa Hsp70 proteins in the prevention of protein aggregation. but not with the Ssb Hsp70 proteins. Cooperation between these different molecular chaperones was only observed in the presence of hydrolyzable ATP and correlated with the ability of Ydj1p to stimulate the ATPase activity of the Hsp70 homolog with which it was paired. The regulatory and chaperone activities of a eukaryotic DnaJ homolog thus act together to assist Hsp70 in modulating the conformation of proteins.
Mechanism of resistance to U‐90152S and sensitization to L‐697,661 by a proline to leucine change at residue 236 of human immunodeficiency virus type 1 (HIV‐1) reverse transcriptase
Authors: Fan Naisheng , Evans David B. , Rank Kenneth B. , Thomas Richard C. , Tarpley W.Gary , Sharma Satish K.
Published: April 2003

Bisheteroarylpiperazines (BHAPs) are highly specific inhibitors of human immunodeficiency virus type 1 (HIV‐1) reverse transcriptase (RT). BHAP‐resistant HIV‐1 is sensitized to other classes of nonnucleoside RT inhibitors and this has been primarily attributed to a proline‐to‐leucine substitution at amino acid 236 (P236L) of HIV‐1 RT. To understand the basis for the in vitro sensitization‐resistance phenomenon, single base pair mutations at amino acid P236 in HIV‐1 RT were introduced to obtain P236L, P236T, P236H, P236R, and P236A HIV‐1 RT mutants. Active HIV‐1 RT mutants H235W, D237T, and H235W/D237T/T240K, containing substitutions from HIV‐2 RT, were also cloned, expressed, and purified. Three BHAPs (U‐88204E, U‐87201E, and U‐90125S) and the pyridinone L‐697,661 were selected to quantitatively assess the effects of these amino acid substitutions on sensitization to L‐697,661 and resistance to the BHAPs. The HIV‐1 RT mutants bearing single (H235W; D237T) or multiple (H235W/D237T/T240K) HIV‐2 RT substitutions around the conserved P236 conferred little resistance or sensitization to these RT inhibitors. The inhibition profiles of the P236 HIV‐1 RT mutants demonstrated a direct correlation between sensitization to L‐697,661 and resistance to the BHAPs. These results suggest alterations in the shape of the binding pocket as the mechanism by which the P236L mutation confers resistance to the BHAPs and sensitization to L‐697,661.
Molecular cloning of a novel actin‐binding protein, p57, with a WD repeat and a leucine zipper motif
Authors: Suzuki Kensuke , Nishihata Jun , Arai Yuko , Honma Nakayuki , Yamamoto Kazuo , Irimura Tatsuro , Toyoshima Satoshi
Published: April 2003

A 57 kDa protein (p57) was obtained during the study on phosphatidylinositol‐specific phospholipase C. Its cDNA was isolated from calf spleen and human leukemia cell line HL60 libraries and cloned. In the primary structures of p57, they have two unique amino acid sequence motifs, a WD repeat and a leucine zipper motif. Furthermore, p57 shared sequence similarity (40%) with coronin, an actin‐binding protein responsible for chemotaxis, cell motility, and cytokinesis of Dictyostelium discoideum, which has only the WD repeat. p57 also showed an actin‐binding activity and was mainly expressed in immune tissues. From these results, we conclude that p57 is a coronin‐like novel actin‐binding protein in mammalian cells but may also have a different function from coronin.
Peroxynitrite stimulates vascular smooth muscle cell cyclic GMP synthesis
Authors: Tarpey M.M. , Beckman J.S. , Ischiropoulos H. , Gore J.Z. , Brock T.A.
Published: April 2003

Peroxynitrite stimulated the synthesis of cyclic GMP by rat aortic smooth muscle in a time‐ and dose‐dependent manner. Peak formation of cyclic GMP occurred at 1 min with 100 μM peroxynitrite and was inhibited by oxyhemoglobin. Peroxynitrite was less potent than nitric oxide in stimulating cyclic GMP synthesis. Peroxynitrite also enhanced endothelial‐dependent cyclic GMP synthesis, via generation of a long‐lived substance, which was prevented by inhibition of glutathione synthesis. These data show that peroxynitrite stimulates cyclic GMP synthesis, inferring production of low yields of nitric oxide or associated derivatives. Additionally, vascular exposure to peroxynitrite potentiates endothelial‐dependent activation of guanylate cyclase.
Protection against peroxynitrite‐dependent tyrosine nitration and α1‐antiproteinase inactivation by oxidized and reduced lipoic acid
Authors: Whiteman Matthew , Tritschler Hans , Halliwell Barry
Published: April 2003

Peroxynitrite, formed by combination of superoxide radical with nitric oxide, is a reactive tissue‐damaging species apparently involved in the pathology of several human diseases. Peroxynitrite nitrates tyrosine residues and inactivates α
1‐antiprotinase. We show that both lipoic acid and dihydrolipoic acid efficiently protect against damage by peroxynitrite. By contrast, other disulphides tested did not. The biological antioxidant effects of lipoate/dihydrolipoate may involve scavenging of reactive nitrogen species as well as reactive oxygen species.
The N‐terminal X‐X‐Pro sequence of the HIV‐1 Tat protein is important for the inhibition of dipeptidyl peptidase IV (DP IV/CD26) and the suppression of mitogen‐induced proliferation of human T cells
Authors: Wrenger Sabine , Reinhold Dirk , Hoffmann Torsten , Kraft Margot , Frank Rainer , Faust Jürgen , Neubert Klaus , Ansorge Siegfried
Published: April 2003

Recent data in the literature suggest that the HIV‐1 Tat(1–86) protein exhibits immunosuppressive effects. Moreover, Tat was found to interact with dipeptidyl peptidase IV (DP IV), which is identical to the T cell activation marker CD26. Here we show that the N‐terminal amino acid sequence of Tat is essential for the inhibition of DP IV‐catalyzed IL‐2(1–12) degradation. N‐terminal modification of Tat with rhodamine prevented inhibition of enzymatic activity of DP IV as well as suppression of DNA synthesis of mitogen‐stimulated human T cells. Moreover, natural peptides containing the X‐X‐Pro N‐terminal motif of Tat also inhibited DP IV activity. These data suggest the existence of endogenous immunomodulatory oligopeptides which influence immune cell proliferation and differentiation via DP IV as does HIV‐1 Tat.
The spectrin repeat folds into a three‐helix bundle in solution
Authors: Pascual Jaime , Pfuhl Mark , Rivas German , Pastore Annalisa , Saraste Matti
Published: April 2003

Spectrin, a major component of the membrane skeleton, is mainly composed of tandemly repeated segments of approx. 106 amino acids. We have undertaken the determination of the three‐dimensional structure of a chicken brain α‐spectrin repeat by heteronuclear multidimensional NMR. Sedimentation equilibrium demonstrates that this repeat is monomeric at the concentration used for NMR (1 mM). Its secondary structure was identified using a collection of sequential and medium range NOEs, chemical shifts, HN‐Hα coupling constants, and relaxation measurements. These data unequivocally demonstrate the presence of three long helices connected by two loops. A set of interhelical NOEs indicates that the helices assemble into a triple helical structure. Our results provide experimental evidence supporting the triple‐helical bundle proposed by modelling.
Aldehyde dismutase activity of human liver alcohol dehydrogenase
Authors: Svensson Stefan , Lundsjö Anders , Cronholm Tomas , Höög Jan-Olov
Published: April 2003

Human alcohol dehydrogenases of class I and class II but not class III catalyse NAD+‐dependent aldehyde oxidation in addition to the NADH‐dependent aldehyde reduction. The two reactions are coupled, i.e. the enzymes display dismutase activity. Dismutase activity of recombinantly expressed human class I isozymes β
1
β
1 and γ
2
γ
2, class II and class III alcohol dehydrogenases was assayed with butanal as substrate by gas chromatographic‐mass spectrometric quantitations of butanol and butyric acid. The class I γ
2
γ
2 isozyme showed a pronounced dismutase activity with a high k
cat, 1300 min−1, and a moderate K
m, 1.2 mM. The class I β
1
β
1 isozyme and the class II alcohol dehydrogenase showed moderate catalytic efficiencies for dismutase activity with lower k
cat values, 60–75 min−1. 4‐Methylpyrazole, a potent class I ADH inhibitor, inhibited the class I dismutation completely, but cyanamide, an inhibitor of mitochondrial aldehyde dehydrogenase, did not affect the dismutation. The dismutase reaction might be important for metabolism of aldehydes during inhibition or lack of mitochondrial aldehyde dehydrogenase activity.
Replacement of Gln280 by His in TM6 of the human ORL1 receptor increases affinity but reduces intrinsic activity of opioids
Authors: Mollereau Catherine , Moisand Christiane , Butour Jean-Luc , Parmentier Marc , Meunier Jean-Claude
Published: April 2003

The ORL1 (pioid eceptor‐ike) receptor is the G protein‐coupled receptor whose amino acid sequence is closest to those of opioid receptors. Residues that are conserved in ORL1 and the three types of opioid receptor, but also a residue, His in the sixth putative transmembrane (TM6) helix, which is present in all opioid receptor types but absent in ORL1, appear to play a key role in receptor recognition and/or activation. Here we have sought to create an opioid binding pocket in the non‐opioid ORL1 receptor by replacing residue Gln280 in its TM6 by the corresponding His residue of opioid receptors. The mutation affects neither the affinity of nociceptin ‐ the natural ORL1 agonist ‐ for the receptor, nor the potency of nociceptin to inhibit adenylyl cyclase via ORL1. In contrast, we find that a few opioid ligands, the agonists lofentanil, etorphine and dynorphin A, and especially the antagonists diprenorphine and nor‐BNI, bind the mutant Q280H receptor with substantially (5‐ to > 100‐fold) higher apparent affinity than they do the wild‐type receptor. Moreover, lofentanil and etorphine no longer act as pure agonists, as they do at the native ORL1 receptor, but are endowed with clear antagonist properties at the mutant receptor. The mutation Q280H, which increases affinity while decreasing intrinsic activity of opioids at ORL1, emphasizes the importance of the His residue for opioid recognition and activation.
Requirements for antibacterial and hemolytic activities in the bovine neutrophil derived 13‐residue peptide indolicidin
Authors: Subbalakshmi C. , Krishnakumari V. , Nagaraj R. , Sitaram N.
Published: April 2003

The antimicrobial and hemolytic activities of the 13‐residue peptide indolicidin (ILPWKWPWWPWRR‐NH2), present in bovine neutrophils, and its analogs have been determined with a view to gaining insight into the structural roles of tryptophan and proline. Peptides where proline was replaced by alanine and tryptophan by phenylalanine showed antibacterial activities comparable to that of indolicidin. The peptides do not exhibit a strong propensity to occur in either helical or β‐sheet conformation. The peptides also do not appear to exert their activity by permeabilizing the bacterial plasma membrane unlike other endogenous antibacterial peptides. The presence of tryptophan appears to be essential for hemolytic activity as the phenylalanine analog does not exhibit any hemolytic activity.
Inhibitor/fatty acid interactions with cytochrome P‐450 BM3
Authors: Macdonald Iain D.G. , Ewen Smith W. , Munro Andrew W.
Published: April 2003

The interaction of fatty acid substrate (palmitate) and inhibitor (metyrapone: 2‐methyl‐1,2‐di‐3‐pyridyl‐1‐propanone) with cytochrome P‐450 BM3 was analysed by UV‐visible and circular dichroism spectroscopy, and by surface‐enhanced resonance Raman scattering (SERRS). While visible spectroscopy provides information on the relative affinities of these compounds, SERRS provides additional novel data indicating palmitate‐induced structural changes in the haem environment. SERRS also demonstrates that binding of both palmitate and the large nitrogenous ligand metyrapone occurs simultaneously to P‐450 BM3 — highlighting the usefulness of this technique in probing haemoprotein active sites.
Differentiation‐dependent enhanced expression of protein phosphatase 2Cβ in germ cells of mouse seminiferous tubules
Authors: Kato Shunsuke , Kobayashi Takayasu , Kusuda Kazuyuki , Nishina Yukio , Nishimune Yoshitake , Yomogida Kentaro , Yamamoto Masayuki , Sakagami Hiroyuki , Kondo Hisatake , Ohnishi Motoko , Chida Naoki , Yanagawa Yuchio , Tamura Shinri
Published: April 2003

The presence of five distinct isoforms of protein phosphatase 2Cβ (PP2Cβ1∼‐5) is known. In this study, we demonstrate that the mRNA levels of PP2Cβ‐3, ‐4 and ‐5 and PP2Cβ protein level increased during the course of the first wave of spermatogenesis in neonatal mouse testis. Northern blot and in situ hybridization analyses revealed that PP2Cβ‐3, ‐4 and ‐5 were expressed predominantly in pachytene spermatocytes and in more highly differentiated germ cells. The substrate specificity of PP2Cβ‐4 determined with artificial substrates differed from those of PP2Cβ‐3 and ‐5, suggesting that the difference in the structure of PP2Cβ‐3, ‐4 and ‐5 reflect their unique physiological functions in testicular germ cells.
A framework for strategic service management
Authors: Kellogg Deborah L. , Nie Winter
Published: April 2003

A service framework is needed to foster strategic thinking in services. This paper introduces the service process/service package matrix to meet that need. The important feature of the service process is the degree of customer influence on the service process. The unique characteristic of the service package is that it consists of both tangible and intangible aspects. The service package is described by the degree of customization found in those tangible and intangible elements. Strategic competencies are identified and discussed along the service process dimension, the service package dimension, and the main diagonal of the matrix. Some existing strategic frameworks are embedded and incorporated in the matrix. Additionally, we formulate research propositions based on the matrix. Service firms can use this matrix to gain strategic insights by aligning the type of service package offered with the type of process used to create the service and to have a better understanding of their service operations strategy.
Acute‐phase α2‐macroglobulin in csf during development of the fetal rat
Authors: Panrucker D.E. , Dziegielewska K.M. , Lorscheider F.L. , Saunders N.R.
Published: April 2003

The concentration of acute phase α2‐macroglobulin (APα2M) was measured in the cerebrospinal fluid (csf) and plasma of fetal (12–22 days gestation) and neonatal (0–10 days post partum) rats. APα2M was detectable in the fetus as early as samples could be obtained (12 days) and increased in both fluids to reach a peak near the time of birth (17 mg/100 ml in csf and 168 mg/100 ml in plasma). During the neonatal period APα2M concentration declined markedly in both fluids. The results are compared with values for albumin and α‐fetoprotein in fetal rats. It was concluded that maintenance of the csf:plasma ratios for the three proteins are incompatible with an explanation of passive diffusion from plasma to csf. Other mechanisms to explain the occurrence of high concentrations of plasma proteins in fetal csf are discussed.
Survival of chick embryo sympathetic neurons in cell culture
Authors: Leah John , Kidson Chev
Published: April 2003

Changes in neuronal numbers during the development of the chick embryo paravertebral sympathetic nervous system have been examined using cell culture techniques. Early sympathetic ganglia contain predominantly cells having neuronal phenotypes and these increase in number until embryonic day 9. Subsequently there is a large decrease in the number of neurons and an increase in the population of non‐neuronal cells. This in vivo pattern is maintained when the neurons are grown in vitro, where Nerve Growth Factor more readily prevents the death of neurons cultured from 12‐day or older embryos than those from earlier stages of development.
Influence of nerve growth factor on developing dorso‐medial and ventro‐lateral neurons of chick and mouse trigeminal ganglia
Authors: Davies Alun , Lumsden Andrew
Published: April 2003

Trigeminal ganglia have been removed from five, six, seven and eight day chick embryos and explants of the dorso‐medial (DM) and ventro‐lateral (VL) parts of the maxillomandibular lobe were grown in tissue culture. Quantitative methods were used to assess the influence of nerve growth factor (NGF) on fiber outgrowth from these explants. At all ages outgrowth from DM explants was significantly greater than from VL explants, the difference being most pronounced between the extreme DM and VL poles of the maxillomandibular lobe. These observations are interpreted as indicating the existence of two distinct populations of neurons in terms of their response to NGF rather than the consequence of the asynchronous differentiation and maturation of the VL and DM neurons. A similar study of 10, 11 and 12 day embryonic mouse trigeminal ganglia revealed no significant difference in neurite outgrowth between DM and VL regions grown in the presence or absence of NGF.
Hypothalamic testosterone increase in the male rat at birth
Authors: Rhoda J. , Corbier P. , Roffi J.
Published: April 2003

In the male rat, a dramatic increase in serum testosterone occurs during the first 2 h of postnatal life. Since the hypothalamus is known to be an important site for sexual differentiation of the brain, this early testosterone surge was a good model to use to study the transfer of serum testosterone to the hypothalamus and cerebral cortex. Endogenous testosterone was measured by radioimmunoassay in the hypothalamus and the cerebral cortex of the foetus and newborn rats during the first 6 h following birth. In the male, hypothalamic testosterone increased between 0 h in utero and 2 h; in the males gonadectomized at 0 h in utero and killed at the age of 2 h, the testosterone surge was abolished, clearly indicating the testicular origin of this hormone in the neonate. The small testosterone increase in the cerebral cortex compared with that in the hypothalamus reflects a preferential uptake of this hormone by the hypothalamus of the newborn. In the female, hypothalamic testosterone slightly decreased between 0 h in utero and 6 h. These results are in agreement with the view that hypothalamic modifications form the basis for some behavioral and physiological changes attributed to the effect of perinatal hormonal stimulation.
Development of immunoreactive lhrh neurons in the fetal rat hypothalamus
Authors: Daikoku Shigeo , Maki Yuzo , Okamura Yoshihito , Tsuruo Yoshihiro , Hisano Setsuji
Published: April 2003

The ontogenesis of immunoreactive (ir) LHRH neurons was investigated in rats applying the double‐bridge PAP method of Vacca et al. (J. Histochem. Cytochem. 28, 297–307, 1980). Ir LHRH was first evident in the cell bodies confined in the ventromedial surface of the anterior part of the forebrain vesicles on day 16.5 of gestation. Only one or two cells, if any, were found in the brains examined; the cells are oval showing ir brown granules within the perikarya and also within the processes extended from both poles. On day 17.5 of gestation, a few ir cells appeared in the olfactory cortex, medial septum, medial preoptic area, diagonal band of Broca, and ventro‐lateral surface of the anterior hypothalamus, and, with development, their numbers increased gradually. During the prenatal period, no ir cell exists in the arcuate nucleus or in the medial‐basal hypothalamus. Beaded ir fibers appeared in the organum vasculosum of the lamina terminalis (OVLT) and in the external layer of the median eminence on 18.5 and 19.5 days of gestation, respectively. The present findings ascertain that the hypothalamic regulation of hypophysial gonadotrophic function exists during fetal period in rats.
Morphometry of GFA and vimentin positive astrocytes in grafted and lesioned cortex cerebri
Authors: Björklund Håkan , Dahl Doris , Olson Lars
Published: April 2003

The presence and morphology of GFA‐ and vimentin‐positive astrocytes were studied immunohistochemically in rats using smear preparations of single intraocular grafts of the cortex cerebri anlage and of cortex pieces grafted to eyes containing a previously grafted piece of the locus coeruleus area. Similarly, astrocytes were studied in lesioned cortex cerebri in situ. A high number of GFA and vimentin‐positive cells were found in smears of both types of cortex grafts as well as in smears of the lesioned cortex cerebri in situ. In contrast, only a limited number of GFA‐positive astrocytes were seen in smears of normal cortex. Using computerized image analysis, the two‐dimensional cell area and cell perimeter were found to be significantly increased in individual GFA‐positive astrocytes in both types of intraocular cortex grafts as well as in the lesioned cortex when compared to GFA‐positive astrocytes in normal cortex cerebri.

GFA‐positive cells in smears of cortex grafts from locus coeruleus‐cortex combinations had significantly smaller cell area and cell perimeter values compared to similar cells from single cortex grafts. A similar, although less pronounced difference was observed between vimentin‐positive cells from the same type of grafts. This suggests that the presence of the mature locus coeruleus graft in some as yet unknown way influences the development of the adjacent cortex graft towards a more normal astrocytic maturation. An additional finding was the large size difference between GFA‐ and vimentin‐positive cells in the intraocular grafts. Since most evidence indicates that vimentin‐positive cells are also GFA‐positive, this may indicate that the two intermediate filament systems have a partially different distribution within individual astrocytes.

It is concluded that computerized image analysis of smears processed for immunohistochemistry with antisera against GFA and vimentin is a useful technique for studies of astrocyte morphology in normal as well as experimentally perturbed CNS tissue. Cortex tissue that develops in contact with a locus coeruleus graft in the eye chamber show a significantly lesser degree of gliosis than cortex tissue developing in isolation in the eye.
Brain malformations in prenatal mice following acute maternal ethanol administration
Authors: Sulik Kathleen K. , Lauder Jean M. , Dehart Deborah B.
Published: April 2003

Acute maternal ethanol administration (two i.p. injections of 2.9 g ethanol/kg maternal body wt) to C57B1/6J mice during gastrulation stages of embryogenesis (gestational day 7) induces a spectrum of brain and facial malformations characteristic of those seen in the human Fetal Alcohol Syndrome. Scanning electron microscopic and light microscopic analyses of the brains of embryos of gestational days 11–14 demonstrate ventro‐medial forebrain deficiencies of varying degrees of severity in affected specimens. Even at the mild end of the spectrum, reductions in the size of the septal nuclei and the shape of the third ventricle are observed. As the severity of the effect increases, the septal nuclei disappear altogether, resulting in midline fusion of the corpora striata (basal ganglia). In such cases, the third ventricle is totally absent anteriorly (preoptic area) and significantly narrowed at more posterior levels, adjacent to the ventromedial nuclei. In addition, the hippocampal primordium is absent at levels which include the corpora striata, and septation of the cerebral cortex is incomplete. More posteriorly, at the level of the posterior commissure, the hippocampal primordium is present, but greatly reduced in size, and the entire brain is distinctly narrower in width. Still further posteriorly, at levels of the metencephalon which include the tectum and cerebellar plate, the cerebral aqueduct is significantly expanded, fusion of midline (raphe) structures is incomplete and the cerebellar plate does not extend as far medially as it does normally. Interestingly, these abnormalities are analogous to those observed in the holoprosencephaly series of malformations.

The results of the present study support our hypothesis that severe forms of the Fetal Alcohol Syndrome mimic certain aspects of the holoprosencephaly spectrum, and indicate that special attention should be paid to possible deficiencies in the septal nuclei and basal ganglia of children born to women who abuse alcohol. The fact that gross brain malformations can be induced in this animal model at a time corresponding to the third week of human gestation (a time when most women remain unaware of pregnancy) is of significance in terms of the possible prevention of alcohol‐induced birth defects and mental deficiency in man.
Growth of myenteric plexus explant cultures in a serum‐free, hormone‐supplemented culture medium
Authors: Saffrey M.J. , Burnstock G.
Published: April 2003

Explant cultures of the myenteric plexus from beneath the taenia coli of newborn guinea‐pig caeca were grown on glass substrates in a serum‐free, hormone‐supplemented culture medium. The growth of enteric neurons, glial cells and fibroblasts and their interactions in this medium were studied over 3 weeks in vitro, and compared with those of cells cultured in the presence of foetal calf serum and in serum‐free medium in the absence of added hormones. Enteric neurons, glial cells and fibroblasts survived in the serum‐free, hormone‐supplemented medium, but this was dependent on the presence of the hormone supplements and also on a brief initial period of exposure to serum‐supplemented medium.

The pattern of development of the cultures grown in serum‐free medium, however, differed markedly from that of cultures grown in serum‐supplemented medium: the numbers of enteric glial cells and fibroblasts were substantially reduced in the absence of serum; neurites grew extensively on the glass substrate rather than being restricted to a carpet of glial cells; and reaggregation of neurons and glial cells into compact groups resembling differentiated enteric ganglia did not occur.

This ability to grow enteric neurons in a defined chemical environment, without the presence of unknown serum components, thus offers an opportunity for detailed study of the effects of growth and trophic factors on neuronal survival, neurite outgrowth and neurochemical differentiation in the entericnervous system, and also for study of the factors involved in enteric ganglion formation.
Monoamine concentrations in brain regions of the developing rabbit
Authors: Crawford I.L. , Connor J.D. , Doller H.J.
Published: April 2003

Growth patterns in selected areas of rabbit brain were studied neurochemically by assaying for norepinephrine, dopamine and serotonin from the neonatal to adult stages of development. These measurements showed that the various monoamines reached adult concentrations at different rates within a brain region; each region had a unique pattern of amine development. Changes in content were most marked in the first 2 weeks of life. Concentration increases were pronounced for norepinephrine and serotonin in the hypothalamus and for dopamine in the caudate nucleus. By contrast, norepinephrine concentrations in the pons‐medulla and colliculi were relatively stable. The marked changes and differences in amine concentrations of maturing rabbit brain provide basic data on monoaminergic innervation of discrete regions and indicate the rabbit merits consideration in neurochemical and physiologic studies on the development of neurotransmission.
Development of substance P‐immunoreactive neurons in cranial sensory ganglia of the rat
Authors: Ayer‐LeLievre C.S. , Seiger Å.
Published: April 2003

Substance P‐like immunoreactivity has been observed in fetal and adult cranial sensory ganglia. It first appears at day 16 of gestation in sensory neurons of trigeminal, superior‐jugular, petrous and nodose ganglia, as well as in the autonomic myenteric plexus, and at day 17 in cervical dorsal root ganglion cells. Substance P immunoreactivity can be visualized much earlier (day 12) in the central nervous system. The ganglionic immunoreactivity subsequently increases during fetal life but drops at birth. The reactive material is first diffuse, then slowly becomes granular, and is mostly concentrated in coarse perinuclear inclusions in adult sensory neurons. Most substance P‐positive neurons in trigeminal and superior‐jugular ganglia are small, but medium‐sized and large positive neurons are also observed in the trigeminal, petrous and nodose ganglia.

Our observations give a precise picture of the development of substance P immunoreactivity in sensory neurons and are in general agreement with previous reports on some fetal and adult rat sensory ganglia. They indicate that in the rat, maturation of peripheral substance P‐containing sensory neurons is slower than that of central substance P neurons or equivalent sensory neurons in other species. The examination of fetal material allows the observation of numerous immunoreactive sensory neurons which cannot be visualized after birth. We hypothesize a possible different embryonic origin (neural crest or placodal) for small nociceptive and larger substance P‐containing neurons in rat cranial sensory ganglia.
Ganglioside glycosyltransferase activities in the cerebral hemispheres from developing rat embryos
Authors: Maccioni Hugo J.F. , Panzetta Pedro , Arrieta Daniela , Caputto Ranwel
Published: April 2003

The developmental patterns of three ganglioside glycosyltransferases were determined in the embryonic rat cerebral hemispheres from day 14 of gestation until birth. Considering the values of day 14 of gestation as 100%, the activity per μg of DNA at birth of the CMP‐NeuAc:GM3 sialosyltransferase decreased to 40%, that of UDP‐GalNAc:GM3 N‐acetylgalactosaminyltransferase increased to 230% and that of UDP‐Gal:GM2 galactosyltransferase showed minor variations. The changes in the activities of these enzymes correlated with the changes occurring in this embryonic period in the complexity of the oligosaccharide chain of gangliosides which result in a relative increase of gangliosides having the gangliotetraosyl backbone.