bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial mutations may drive Y chromosome evolution
Authors: Gemmell Neil J. , Sin Frank Y. T.
Published: August 2002

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which impair male fertility and ultimately lead to a reduction in the effective population size (Ne) and consequently the variability of the Y chromosome. BioEssays 24:275–279, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10062
Multifunctional regulatory proteins that control gene expression in both the nucleus and the cytoplasm
Authors: Wilkinson Miles F. , Shyu Ann‐Bin
Published: August 2002

The multistep pathway of eukaryotic gene expression involves a series of highly regulated events in the nucleus and cytoplasm. In the nucleus, genes are transcribed into pre‐messenger RNAs which undergo a series of nuclear processing steps. Mature mRNAs are then transported to the cytoplasm, where they are translated into protein and degraded at a rate dictated by transcript‐ and cell‐type‐specific cues. Until recently, these individual nuclear and cytoplasmic events were thought to be primarily regulated by different RNA‐ and DNA‐binding proteins that are localized either only in the nucleus or only the cytoplasm. Here, we describe multifunctional proteins that control both nuclear and cytoplasmic steps of gene expression. One such class of multifunctional proteins (e.g., Bicoid and Y‐box proteins) regulates both transcription and translation whereas another class (e.g., Sex‐lethal) regulates both nuclear RNA processing and translation. Other events controlled by multifunctional proteins include assembly of spliceosome components, spliceosome recycling, RNA editing, cytoplasmic mRNA localization, and cytoplasmic RNA stability. The existence of multifunctional proteins may explain the paradoxical involvement of the nucleus in an RNA surveillance pathway (nonsense‐mediated decay) that detects cytoplasmic signals (premature termination codons). We speculate that shuttling multifunctional proteins serve to efficiently link RNA metabolism in the cytoplasmic and nuclear compartments. BioEssays 23:775–787, 2001. © 2001 John Wiley & Sons, Inc.
IR spectra and IR spectral maps of individual normal and cancerous cells
Authors: Diem Max , Chiriboga Luis , Lasch Peter , Pacifico Anthony
Published: August 2002

The IR microspectra for individual normal and cancerous cells are reported at a spatial resolution that permits a distinction between the nuclear and cytoplasmic regions. The observed spectra reveal large differences in the spectral contributions of RNA, DNA, and phospholipids: metabolically inactive cells show spectral patterns of proteins only, whereas actively dividing cells also show spectral signatures of nucleic acids and phospholipids. These spectral variations are independent of the state of health of a cell. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 349–353, 2002
In vitro degradation of a polymeric dye (Poly R‐478) by manganese peroxidase
Authors: Moreira M. T. , Palma C. , Mielgo I. , Feijoo G. , Lema J. M.
Published: August 2002

The aim of this study is the evaluation of the enzymatic action of the ligninolytic enzyme manganese peroxidase (MnP), through a suitable addition of H2O2, as a feasible system for the in vitro degradation of complex structures. For this purpose, a highly recalcitrant polymeric dye (Poly R‐478) was selected as a model compound. An amperometric technique was used to determine the H2O2 requirement in the decolorization by nonpurified MnP. Two H2O2 supply strategies—fed‐batch (every hour) or semicontinuous (every 5 min)—were applied. The addition of H2O2 in pulses led to a limited decolorization after the pulses and the instantaneous consumption or decomposition of H2O2. Therefore, this way of addition may limit the actual H2O2 concentration in the reaction mixture. In contrast, the semicontinuous strategy maintained lower and prolonged concentrations of H2O2, which allowed a clearly greater decolorization (48% after 2 h). In addition, the effect of Mn+2 concentration on the decolorization efficiency was investigated to establish the optimal application of the MnP‐oxidative system. The enzymatic treatment provoked not only the destruction of the chromophoric groups but also a noticeable breakdown of the chemical structure of the dye. In experiments with pure enzyme, MnP proved to be the main factor responsible for the dye decolorization. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 362–368, 2001.
Inhibiting apoptosis in mammalian cell culture using the caspase inhibitor XIAP and deletion mutants
Authors: Sauerwald Tina M. , Betenbaugh Michael J. , Oyler George A.
Published: August 2002

Lower yields and poorer quality of biopharmaceutical products result from cell death in bioreactors. Such cell death may occur from necrosis but is more commonly associated with apoptosis. During the process of programmed cell death or apoptosis, caspases become activated and cause a cascade of events that eventually destroy the cell. XIAP is the most potent caspase inhibitor encoded in the mammalian genome. The effectiveness of XIAP and its deletion mutants was examined in two cell lines commonly utilized in commercial bioreactors: Chinese hamster ovary (CHO) and 293 human embryonic kidney (293 HEK) cells. CHO cells undergo apoptosis as a result of various insults, including Sindbis virus infection and serum deprivation. In this study, we demonstrate that 293 HEK cells undergo apoptosis during Sindbis virus infection and exposure to the toxins, etoposide and cisplatin. Two deletion mutants of XIAP were created; one containing three tandem baculovirus iaprepeat (BIR) domains and the other containing only the C‐terminal RING domain, lacking the BIRs. Viability studies were performed for cells expressing each mutant and the wild‐type protein on transiently transfected cells, as stable pools, or as stable clonal cell populations after induction of apoptosis by serum deprivation, Sindbis virus infection, etoposide, and cisplatin treatment. Expression of the wild‐type XIAP inhibited apoptosis significantly; however, the XIAP mutant containing the three BIRs provided equivalent or improved levels of apoptosis inhibition in all cases. Expression of the RING domain offered no protection and was pro‐apoptotic in transient expression experiments. With the aid of an N‐terminal YFP fusion to each protein, distribution within the cell was visualized, and the wild‐type and mutants showed differing intracellular accumulation patterns. While the wild‐type XIAP protein accumulated primarily in aggregates in the cytosol, the RING mutant was enriched in the nucleus. In contrast, the deletion mutant containing the three BIRs was distributed evenly throughout the cytosol. Thus, protein engineering of the XIAP protein can be used to alter the intracellular distribution pattern and improve the ability of this caspase inhibitor to protect against apoptosis for two mammalian cell lines. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 704–716, 2002; DOI 10.1002/bit.10154
Metabolic control of recombinant protein N‐glycan processing in NS0 and CHO cells
Authors: Baker Kym N. , Rendall Mark H. , Hills Anna E. , Hoare Michael , Freedman Robert B. , James David C.
Published: August 2002

Chinese hamster ovary and murine myeloma NS0 cells are currently favored host cell types for the production of therapeutic recombinant proteins. In this study, we compared N‐glycan processing in GS‐NS0 and GS‐CHO cells producing the same model recombinant glycoprotein, tissue inhibitor of metalloproteinases 1. By manipulation of intracellular nucleotide‐sugar content, we examined the feasibility of implementing metabolic control strategies aimed at reducing the occurrence of murine‐specific glycan motifs on NS0‐derived recombinant proteins, such as Galα1,3Galβ1,4GlcNAc. Although both CHO and NS0‐derived oligosaccharides were predominantly of the standard complex type with variable sialylation, 30% of N‐glycan antennae associated with NS0‐derived TIMP‐1 terminated in α1,3‐linked galactose residues. Furthermore, NS0 cells conferred a greater proportion of terminal N‐glycolylneuraminic (sialic) acid residues as compared with the N‐acetylneuraminic acid variant. Inclusion of the nucleotide‐sugar precursors, glucosamine (10 mM, plus 2 mM uridine) and N‐acetylmannosamine (20 mM), in culture media were shown to significantly increase the intracellular pools of UDP‐N‐acetylhexosamine and CMP‐sialic acid, respectively, in both NS0 and CHO cells. The elevated UDP‐N‐acetylhexosamine content induced by the glucosamine/uridine treatment was associated with an increase in the antennarity of N‐glycans associated with TIMP‐1 produced in CHO cells but not N‐glycans associated with TIMP‐1 from NS0 cells. In addition, elevated UDP‐N‐acetylhexosamine content was associated with a slight decrease in sialylation in both cell lines. The elevated CMP‐sialic acid content induced by N‐acetylmannosamine had no effect on the overall level of sialylation of TIMP‐1 produced by both CHO and NS0 cells, although the ratio of N‐glycolylneuraminic acid:N‐acetylneuraminic acid associated with NS0‐derived TIMP‐1 changed from 1:1 to 1:2. These data suggest that manipulation of nucleotide‐sugar metabolism can promote changes in N‐glycan processing that are either conserved between NS0 and CHO cells or specific to either NS0 cells or CHO cells. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 73: 188–202, 2001
The response of GS‐NS0 myeloma cells to pH shifts and pH perturbations
Authors: Osman Jason J. , Birch John , Varley Julie
Published: August 2002

The perceived sensitivity of animal cells to hydrodynamic shear has limited agitation and aeration at large‐scale. This makes it difficult to ensure adequate mixing of the vessel contents and may lead to inhomogeneities in operational parameters such as temperature, dissolved oxygen concentration, and especially pH. The effect of pH shifts and pH perturbations on the cellular responses, in batch culture, of a GS‐NS0 mouse myeloma cell line, expressing a recombinant antibody, was investigated. In addition, the effect of extreme pH on the structure of the purified antibody product was studied using isoelectric focusing. The fermentation pH value was shifted abruptly from pH 7.3 to pH values ranging from 6.5 to 9.0. Culture pH was maintained at this new value for the remainder of the fermentation. All pH shifts of above 0.2 units caused a transient increase in apoptosis. However, cultures shifted to pH values between 7.0 and 8.0 continued to grow and the apoptotic fraction returned to initial levels. Cultures shifted to pH values above pH 8.0 and below pH 7.0 did not recover resulting in culture death. For example, a shift to pH 8.5 caused accumulation of cells in the G2/M phase of the cell cycle followed by apoptotic death. After the pH shift, maximum specific growth rate was observed over the range pH 7.3 to 7.5 and maximum viable cell number was seen at pH 7.3. Maximum volumetric antibody production, resulting from increased culture longevity, was seen at pH 7.0. It was also observed that glucose consumption increased with increasing pH. In a separate set of experiments cells were subjected to a single pH perturbation ranging in duration from 0 to 600 minutes. Exposure of cells to a pH value greater than 8.5 for more than 10 minutes caused a decrease in the proportion of viable cells and induced a lag in cell growth. At very low pH (6.5) similar effects were seen, but only for extended perturbations (600 min). However, after recovery from the pH perturbation, growth, product secretion and metabolism all returned to original levels. Incubation of the antibody, at the range of pH values investigated, indicated no alterations in the structure of the antibody as determined by the isoelectric focusing pattern. © 2001 John Wiley & Sons Inc. Biotechnol Bioeng 75: 63–73, 2001.
Importance of dissection in learning anatomy: Personal dissection versus peer teaching
Authors: Johnson James H.
Published: August 2002

Two studies or approaches to time savings in teaching gross anatomy were implemented and tested. Personal dissection vs. peer teaching of the upper and lower extremities revealed subtle effects of dissection on examination performance. Although peer teaching was generally successful, students preferred to dissect for themselves, lacking confidence in being taught by other students. ANOVA and multiple range tests carried out on the examination means indicated no difference between each student's scores on upper and lower extremity questions. However, subtle effects were reflected in significant differences (P < 0.05) in both ratio (upper%/lower%) and difference (upper%–lower%) between each student's percent scores on upper extremity and lower extremity questions, indicating enhanced performance on the extremity dissected. Students dissecting both extremities were intermediate in both ratio and difference, and not significantly different from either the “upper” or “lower” extremity groups. A questionnaire indicated that students who dissected only one extremity would have preferred to have dissected both extremities, and, contrary to overall examination performance, disagreed that they had learned both extremities at a satisfactory level. Although documenting adequate learning with time savings, the results are consistent with the contention that hands‐on dissection enhances learning and confidence in the subject matter, because examination performance as well as personal satisfaction was enhanced on the extremity that was dissected. Clin. Anat. 15:38–44, 2002. © 2002 Wiley‐Liss, Inc.
The effect of calcitonin treatment on plasma nitric oxide levels in post‐menopausal osteoporotic patients
Authors: Taş Nihal , Aricioglu Aysel , Erbas Deniz , Özcan Serpil
Published: August 2002

Several recent studies have revealed a wide role for nitric oxide (NO) in bone metabolism. Low doses of NO cause bone resorption, but higher doses of NO inhibit bone resorbing activity. Cytokines are potent stimulators of NO production. NO is a very short‐lived molecules. It exists for only 6–10 s only before it is converted by oxygen and water into the end‐products nitrates and nitrites. Osteoporosis is a metabolic bone disease, characterized by a decreased amount of bone and increased susceptibility to fracture. NO may be involved as a mediator of bone disease such as post‐menopausal osteoporosis. Calcitonin is a peptide hormone that inhibits bone resorption. The function of calcitonin in some cells is often unclear. In this study 30 post‐menopausal osteoporotic women of ages ranging between 55 and 59 years without systemic diseases and free of any drug therapy were included. Twenty of them, randomly chosen, were treated with calcium (500 mg day−1)+calcitonin (nasal spray 100 U day−1) and the other 10 women (control group) were treated with calcium only. This treatment was applied for 6 months and NO values were measured in each of the two groups before and after treatment. Our findings demonstrate that NO regulates osteoclastic bone resorption activity in association with calcitonin. Copyright © 2001 John Wiley & Sons, Ltd.
State Governance Patterns for Community Colleges
Authors: Lovell Cheryl D. , Trouth Catherine
Published: August 2002

This chapter describes state governance patterns for community colleges and current and emerging policy issues affecting governance.
Percutaneous repair of abdominal aortic aneurysms using the AneuRx stent graft and the percutaneous vascular surgery device
Authors: Howell Marcus , Doughtery Kathy , Strickman Neil , Krajcer Zvonimir
Published: August 2002

Endovascular exclusion of abdominal aortic aneurysms (AAAs) was developed in an effort to treat patients who were at high risk for complications following standard surgical repair. Stent grafts used for endovascular repair of AAAs require the use of large‐bore sheaths and surgical exposure of the common femoral arteries (CFAs). To decrease the invasiveness of AAA repair, we attempted to perform the procedure percutaneously utilizing the Prostar XL Percutaneous Vascular Surgery Device and the preclose technique. Thirty patients underwent an attempted percutaneous AAA repair. These patients were followed prospectively to assess the success of the procedure. Twenty‐eight patients (93%) had successful percutaneous repair of both CFA access sites. One patient had inadequate hemostasis of the 22 Fr CFA entry site and one patient had inadequate hemostasis of the 16 Fr CFA entry site. Both of these CFA sites underwent open surgical repair. The rate of successful repair of the 22 Fr CFA access site was 29 of 30 (96%); for the 16 Fr CFA access site, 29 of 30 (96%). No in‐hospital groin complications were seen. The procedure time was 105 ± 21 min. The estimated blood loss was 90.6 ± 50 cc. The hemoglobin loss was 1.54 ± 0.89 mg/dL and the hematocrit loss was 5.04% ± 2.8%. Complete percutaneous endoluminal AAA repair is feasible using the preclose technique. CFAs with sheaths up to 22 Fr can be safely and successfully accessed and repaired percutaneously using this technique. This method provides secure hemostasis and reduces the invasiveness of procedures requiring large‐bore sheaths. Cathet Cardiovasc Intervent 2002;55:281–287. © 2002 Wiley‐Liss, Inc.
The Plant Ontology™ Consortium and Plant Ontologies
Authors:   The Plant Ontology™ Consortium
Published: August 2002

The goal of the Plant Ontology™ Consortium is to produce structured
controlled vocabularies, arranged in ontologies, that can be applied to plant‐based
database information even as knowledge of the biology of the relevant plant
taxa (e.g. development, anatomy, morphology, genomics, proteomics) is accumulating
and changing. The collaborators of the Plant Ontology™ Consortium (POC)
represent a number of core participant database groups. The Plant Ontology™
Consortium is expanding the paradigm of the Gene Ontology™ Consortium
(http://www.geneontology.org).
Various trait ontologies (agronomic traits, mutant phenotypes, phenotypes,
traits, and QTL) and plant ontologies (plant development, anatomy [incl. morphology])
for several taxa (Arabidopsis, maize/corn/Zea mays and rice/Oryza)
are under development. The products of the Plant Ontology™ Consortium
will be open‐source. Copyright © 2002 John Wiley & Sons, Ltd.
The complete mitochondrial genome of Yarrowia lipolytica
Authors: Kerscher Stefan , Durstewitz Gregor , Casaregola Serge , Gaillardin Claude , Brandt Ulrich
Published: August 2002

We here report the complete nucleotide sequence of the 47.9 kb mitochondrial (mt) genome from the obligate aerobic yeast Yarrowia lipolytica. It encodes, all on the same strand, seven subunits of NADH:ubiquinone oxidoreductase (ND1‐6, ND4L), apocytochrome b (COB), three subunits of cytochrome oxidase (COX1, 2, 3), three subunits of ATP synthetase (ATP6, 8 and 9), small and large ribosomal RNAs and an incomplete set of tRNAs. The Y. lipolytica mt genome is very similar to the Hansenula wingei mt genome, as judged from blocks of conserved gene order and from sequence homology. The extra DNA in the Y. lipolytica mt genome consists of 17 group 1 introns and stretches of A+T‐rich sequence, interspersed with potentially transposable GC clusters. The usual mould mt genetic code is used. Interestingly, there is no tRNA able to read CGN (arginine) codons. CGN codons could not be found in exonic open reading frames, whereas they do occur in intronic open reading frames. However, several of the intronic open reading frames have accumulated mutations and must be regarded as pseudogenes. We propose that this may have been triggered by the presence of untranslatable CGN codons. This sequence is available under EMBL Accession No. AJ307410. Copyright © 2001 John Wiley & Sons, Ltd.
Therapy choices among older patients with lung carcinoma
Authors: Rocha Lima Caio Max S. , Herndon James E. , Kosty Michael , Clamon Gerald , Green Mark R.
Published: August 2002

BACKGROUND

Despite a greater risk of malignancy and a higher cancer mortality rate for patients age > 65 years, bias in accruing older patients to clinical trials persists. The results from two National Cancer Institute‐approved cooperative group trials (Cancer and Leukemia Group B trial 8931 [CALGB 8931] and CALGB 9130) were analyzed retrospectively to determine the participation, tolerance of treatment, and outcome of patients age > 70 years.

METHODS

Five hundred fifteen patients with locally advanced or metastatic nonsmall cell lung carcinoma participated in two separate, randomized, Phase III clinical trials conducted by CALGB. Retrospective evaluation of patients by four distinct age cohorts (< 50 years, 50–59 years, 60–69 years, and > 70 years) was carried out to determine differences in toxicity, response, and survival.

RESULTS

No patients age > 80 were entered on either study, even though there was no age restriction in the study eligibility criteria. No significant differences were seen in response, survival, or continuation of treatment based on age cohort. Significantly increased leukocyte toxicity was seen in older cohorts without a concomitant increase in severe or worse infectious events.

CONCLUSIONS

No patients age > 80 were entered on either trial despite their potential eligibility. Patients in the oldest cohort showed no negative impact of age on treatment tolerance, response to treatment, or survival. The aggregate clinical judgment of patients and physicians can identify septuagenarians who should not be denied active consideration for aggressive management of their advanced nonsmall cell lung carcinoma. Cancer 2002;94:181–7. © 2002 American Cancer Society.
Diffuse malignant epithelial mesotheliomas of the peritoneum in women
Authors: Kerrigan Scott A. J. , Turnnir Rael T. , Clement Philip B. , Young Robert H. , Churg Andrew
Published: August 2002

BACKGROUND

The behavior of diffuse peritoneal mesotheliomas in women and the possible relation between tumor morphology and outcome are uncertain. Reported survival has ranged from < 1 month to > 14 years, and a previous study found that tumor morphology could not be used reliably for predicting outcome. The authors examined the behavior of diffuse epithelial peritoneal mesotheliomas in women and the possible relation between pathologic features and outcome.

METHODS

Twenty‐five female patients with diffuse peritoneal epithelial malignant mesotheliomas were divided into two groups: those who survived for < 4 years (60%) and those who survived for > 4 years (40%). Both groups were compared in terms of age, presentation, treatment, survival, tumor architecture, mitotic rate, necrosis, nuclear grade, and immunohistochemical profile.

RESULTS

Patients in the two groups were similar in terms of age at diagnosis (median ages, 50.7 years and 49.9 years), presentation, initial tumor burden, and treatment. In both groups, the most common initial clinical presenting features were ascites and abdominal pain. The tumors typically took the form of multiple nodules measuring < 1.5 cm in greatest dimension. Slightly less than 50% of patients in both groups received some form of chemotherapy or radiation therapy after undergoing tumor‐reductive surgery or biopsy. Overall survival ranged from 1 month to 15 years. The median survival was 12 months in the group of women who survived for < 4 years and 7 years in the group of women who survived for > 4 years. Overall, 10 of 25 patients survived for ≥ 5 years. One patient was alive with disease 15 years after diagnosis. Although there was a suggestion that the tumors in patients with short survival more often had solid architecture and high‐grade nuclei, these findings were not significant statistically. The frequency of necrosis and the mitotic activity were the same in both groups.

CONCLUSIONS

The spectrum of diffuse epithelial peritoneal mesotheliomas in women includes tumors that are highly aggressive and behave much like pleural mesotheliomas, although a sizeable number of tumors, unlike the pleural tumors, are relatively indolent. However, because there do not appear to be morphologic features that reliably identify favorable tumors versus unfavorable tumors, aggressive therapy for all women with diffuse peritoneal mesotheliomas may be warranted. Cancer 2002;94:378–85. © 2002 American Cancer Society.
HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process
Authors: Vincent‐Salomon Anne , Jouve Michel , Genin Pascal , Fréneaux Paul , Sigal‐Zafrani Brigitte , Caly Martial , Beuzeboc Philippe , Pouillart Pierre , Sastre‐Garau Xavier
Published: August 2002

BACKGROUND

The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process.

METHODS

HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post‐CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2–T4,N1–N2 breast carcinoma and were treated by preoperative anthracycline‐based CT and then underwent surgery. The second group included 44 patients with metastatic breast carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2 status was determined by immunohistochemistry using an anti‐p185HER/neu monoclonal antibody and was classified as overexpressed or not overexpressed.

RESULTS

Among the patients who received preoperative CT, HER2 overexpression was observed in 15 of 59 patients (25%). A complete pathologic response was observed in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining residual tumors and was no longer detectable in 2 tumors. In addition, the 29 tumors with no HER2 overexpression before CT remained negative after treatment. In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two patients who had low levels of HER2 overexpression in their primary tumors, no staining was observed in the secondary tumor (one pulmonary tumor and one liver tumor). There were no tumors in which the overexpression of HER2 was found only in the metastasis.

CONCLUSIONS

The current study showed that, in most patients, HER2 overexpression was unchanged after CT and in metastatic sites. No HER2 negative primary tumors became HER2 positive after patients received CT or during the metastatic process. In a few patients, a diminution in the level of HER2 expression was observed after CT or in secondary tumors. This may have been due to a transitory state of altered tumor cells or to the selection of HER2 negative tumor cells clones. Cancer 2002;94:2169–73. © 2002 American Cancer Society.

DOI 10.1002/cncr.10456
Neurochemical organization of the human basal ganglia: Anatomofunctional territories defined by the distributions of calcium‐binding proteins and SMI‐32
Authors: Morel Anne , Loup Fabienne , Magnin Michel , Jeanmonod Daniel
Published: August 2002

The distribution of the calcium‐binding proteins calbindin‐D28K (CB), parvalbumin (PV) and calretinin (CR), and of the nonphosphorylated neurofilament protein (with SMI‐32) was investigated in the human basal ganglia to identify anatomofunctional territories. In the striatum, gradients of neuropil immunostaining define four major territories: The first (T1) includes all but the rostroventral half of the putamen and is characterized by enhanced matriceal PV and SMI‐32 immunoreactivity (‐ir). The second territory (T2) encompasses most part of the caudate nucleus (Cd) and rostral putamen (PuT), which show enhanced matriceal CB‐ir. The third and fourth territories (T3 and T4) comprise rostroventral parts of Cd and PuT characterized by complementary patch/matrix distributions of CB‐ and CR‐ir, and the accumbens nucleus (Acb), respectively. The latter is separated into lateral (prominently enhanced in CB‐ir) and medial (prominently enhanced in CR‐ir) subdivisions. In the pallidum, parallel gradients also delimit four territories, T1 in the caudal half of external (GPe) and internal (GPi) divisions, characterized by enhanced PV‐ and SMI‐32‐ir; T2 in their rostral half, characterized by enhanced CB‐ir; and T3 and T4 in their rostroventral pole and in the subpallidal area, respectively, both expressing CB‐ and CR‐ir but with different intensities. The subthalamic nucleus (STh) shows contrasting patterns of dense PV‐ir (sparing only the most medial part) and low CB‐ir. Expression of CR‐ir is relatively low, except in the medial, low PV‐ir, part of the nucleus, whereas SMI‐32‐ir is moderate across the whole nucleus. The substantia nigra is characterized by complementary patterns of high neuropil CB‐ and SMI‐32‐ir in pars reticulata (SNr) and high CR‐ir in pars compacta (SNc) and in the ventral tegmental area (VTA). The compartmentalization of calcium‐binding proteins and SMI‐32 in the human basal ganglia, in particular in the striatum and pallidum, delimits anatomofunctional territories that are of significance for functional imaging studies and target selection in stereotactic neurosurgery. J. Comp. Neurol. 443:86–103, 2002. © 2002 Wiley‐Liss, Inc.
Organization of cutaneous ventrodorsal and rostrocaudal axial lines in the rat hindlimb and trunk in the dorsal horn of the spinal cord
Authors: Takahashi Yuzuru , Chiba Tanemichi , Sameda Hiroaki , Ohtori Seiji , Kurokawa Masahiro , Moriya Hideshige
Published: August 2002

The somatotopic organization of cutaneous primary afferents projecting to the dorsal horn of the rat spinal cord was investigated. The fluorescent neurotracer, 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI) was applied to cutaneous incisions made along ventrodorsal axial lines (VDALs) or rostrocaudal axial lines (RCALs) of the trunk and hindlimb. DiI‐induced fluorescent zones appeared in laminae I‐III of the dorsal horn in the transverse section. Several fluorescent zones appeared at different mediolateral portions after tracer application to VDALs. After tracer was applied to RCALs, a single zone of fluorescence was observed. Serial transverse sections were used to reconstruct fluorescent zones in lamina II and to illustrate the rostrocaudally elongated band‐like projection fields in a horizontal plane. In the horizontal plane, the fluorescent zones of VDALs were reconstructed to band‐like projection fields. These fields were arranged mediolaterally and extended rostrocaudally for approximately the length of one spinal cord segment or less. The fluorescent zones of RCALs were reconstructed to one band‐like projection field. This field extended rostrocaudally over several spinal cord segments. Cutaneous afferents from the ventral median line of the trunk, tail, hindlimb, sole, and ventral side of the digits projected to the medial margin of the dorsal horn. Cutaneous afferents from the dorsal median lines projected to the lateral margin of the dorsal horn. By analyzing the pattern of the body surface regions and the VDALs and RCALs, the central projection fields of body surface regions could be hypothesized, based on the central projection fields of the individual VDAL and RCAL afferents. Thus, we established a detailed dorsal view map of the central projection fields of cutaneous primary afferents. J. Comp. Neurol. 445:133–144, 2002. © 2002 Wiley‐Liss, Inc.
Excitatory synaptic inputs on myenteric Dogiel type II neurones of the pig ileum
Authors: Cornelissen Wim , De Laet Ann , Kroese Alfons B.A. , van Bogaert Pierre‐Paul , Scheuermann Dietrich W. , Timmermans Jean‐Pierre
Published: August 2002

The synaptic input on myenteric Dogiel type II neurones (n = 63) obtained from the ileum of 17 pigs was studied by intracellular recording. In 77% of the neurones, electrical stimulation of a fibre tract evoked fast excitatory postsynaptic potentials (fEPSPs) with an amplitude of 6 ± 5 mV (mean ± S.D.) and lasting 49 ± 29 ms. The nicotinic nature of the fEPSPs was demonstrated by superfusing hexamethonium (20 μM). High‐frequency stimulation (up to 20 Hz, 3 seconds) did not result in a rundown of the fEPSPs, and did not evoke slow excitatory or inhibitory postsynaptic potentials. The effects of neurotransmitters, possibly involved in these excitatory responses, were investigated. Pressure microejection of acetylcholine (10 mM in pipette) resulted in a fast nicotinic depolarisation in 67%(18/27) of the neurones (13 ± 9 mV, duration 7.0 ± 7.2 seconds) as did 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP) application (10 mM; 14 ± 10 mV, duration 4.1 ± 2.8 seconds) in 76%of the cells. The fast nicotinic response to acetylcholine was sometimes (6/27) followed by a slow muscarinic depolarisation (8 ± 4 mV; duration 38.7 ± 10.8 seconds). Immunostaining revealed 5‐hydroxytryptamine hydrochloride (5‐HT)‐ and calcitonin gene‐related peptide (CGRP)‐positive neuronal baskets distributed around and in close vicinity to Dogiel type II neuronal cell bodies. Microejection of 5‐HT (10 mM) resulted in a fast nicotinic‐like depolarisation (12 ± 6 mV, duration 3.0 ± 1.3 seconds) in 4 of 8 neurones tested, whereas microejection of CGRP (20 mM) gave rise to a slow muscarinic‐like depolarisation (6 ± 2 mV, duration 56.0 ± 27.5 seconds) in 8 of 12 neurones tested. In conclusion, myenteric Dogiel type II neurones in the porcine ileum receive diverse synaptic input. Mainly with regard to the prominent presence of nicotinic responses, these neurones behave contrary to their guinea pig counterparts. J. Comp. Neurol. 432:137–154, 2001. © 2001 Wiley‐Liss, Inc.
The Co‐evolution of cooperation and complexity in a multi‐player, local‐interaction prisoners' dilemma
Authors: Albin Peter S. , Foley Duncan K.
Published: August 2002

Agents located on a 20 × 20 toroidal lattice play a Prisoners' Dilemma game with their Moore neighbors, adopting policies of cooperation and defection that depend only on their own action and the number of cooperators in the neighborhood in the last round of the game. These policies (“characters”) are encoded in 19‐bit strings, which are subjected to evolution according to a genetic algorithm, with selection based on the cumulative scores of the agents in the neighborhood over 10 rounds of the basic game. Simulations examine the evolution of the population of characters over 1000 generations. Even with selection disabled, the genetic algorithm organizes the population into a small number of surviving characters clustered in spatially homogeneous regions. Selection for fitness rapidly achieves uniform cooperation. The characters evolved cooperate on the initial play, continue to cooperate when five or more of their neighbors cooperate, tend to defect defensively when they have cooperated and most of their neighbors have defected, and switch back to cooperation when five or more neighbors cooperate. When selection operates at the level of the whole society, however, the diversity of the population rapidly collapses, a single character predominates, and the cooperativeness of the dominating character is a matter of chance, so that there is no systematic tendency to evolve cooperation. © 2001 John Wiley & Sons, Inc.
Monoclonal antibody FMC7 detects a conformational epitope on the CD20 molecule: Evidence from phenotyping after rituxan therapy and transfectant cell analyses
Authors: Serke Stefan , Schwaner Ingo , Yordanova Maya , Szczepek Agnes , Huhn Dieter
Published: August 2002

Numerous studies have reported that monoclonal antibody (mAb) FMC7 detects an antigen present on only a subset of circulating B lymphocytes. In particular, this mAb may distinguish typical B‐cell chronic lymphocytic leukemia (FMC7 negative) from other types of B‐cell non‐Hodgkin lymphoma (B‐NHL; FMC7 positive). We treated patients with B‐NHL with Rituxan, a chimeric CD20 mAb, and observed abrogation of staining not only with prototype CD20 mAb B‐1 but also with mAb FMC7. To investigate the relation between antigens CD20 and FMC7, we performed mutual blocking studies that showed mutual inhibition of FMC7 and CD20. In addition, FMC7 modulated CD23 expression and confirmed the presence of mAb B‐1 in B‐lymphoblastoid cell lines CESS and JVM. Transient transfection of myeloid cell line K562 with plasmid containing CD20‐encoding cDNA produced de novo expressions of CD20 and FMC7. Our data indicate that FMC7 binds to a particular conformation of the CD20 antigen, probably to a multimeric CD20 complex. We assume that FMC7 stains positively only when CD20 antigen is present in high densities and in the postulated multimeric complex formation. Cytometry (Comm. Clin. Cytometry) 46:98–104, 2001. © 2001 Wiley‐Liss, Inc.
Detection of MRP functional activity: Calcein AM but not BCECF AM as a multidrug resistance‐related protein (MRP1) substrate
Authors: Olson Douglas P. , Taylor Barbara J. , Ivy S. Percy
Published: August 2002

Resistance to anticancer drugs has been attributed to an array of cellular changes. The multidrug resistance‐related protein (MRP1) is an efflux pump whose overexpression confers resistance to several classes of drugs, such as the anthracyclines, epipodophyllotoxins, and vinca alkaloids. These drugs are mainstays in cancer therapy. MRP1 overexpression is hypothesized to be a causative agent of clinical treatment failure. Consistently accurate methods for detecting this protein are necessary to further understand its biology and delineate its possible clinical relevance. Flow cytometric analysis of multidrug resistance (MDR) is a valuable method to evaluate both antigen expression and function. Using flow cytometry, we assayed MRP1 functional activity in pediatric leukemic blasts and an array of MDR+ and WT cell lines. We conclude that calcein AM, when used in a retention assay with MRP1‐specific modulators, is able to reliably detect MRP functional activity. 2′‐7′‐bis(2‐carboxyethyl)‐5(6)‐carboxyfluorescein (BCECF AM) transport is not indicative of MRP1 overexpression. Cytometry (Comm. Clin. Cytometry) 46:105–113, 2001. © 2001 Wiley‐Liss, Inc.
Subgrouping and grading of soft‐tissue sarcomas by fine‐needle aspiration cytology: A histopathologic correlation study
Authors: Palmer Hal E. , Mukunyadzi Perkins , Culbreth Wanda , Thomas James R.
Published: August 2002

To evaluate the accuracy and reproducibility of subgrouping and grading soft‐tissue sarcomas by fine‐needle aspiration biopsy (FNAB), a blind review was conducted of 84 FNAB specimens from 77 malignant and 7 benign soft‐tissue lesions. Cytomorphologic subgroups included 31 spindle‐cell, 24 pleomorphic, 11 myxoid, 7 epithelioid/polygonal, 3 small round cell, and 8 nondiagnostic cases. Malignancies included one lymphoma and 41 primary, 15 recurrent, and 20 metastatic soft‐tissue sarcomas. Adequacy was defined as a majority of slides with at least 5 clusters of 10 unobscured cells. Five originally false‐negative cases were considered nondiagnostic on review. Sarcoma was recognized in 59 of 64 adequate cases (92%) with available histology; however, the specific histopathologic subtype was identified in only 9 cases (14%). Benign myxoid and spindle‐cell lesions were difficult to separate from low‐grade sarcomas in 4 cases, and a B‐cell lymphoma with sclerosis mimicked a low‐grade myxoid sarcoma. The assigned cytologic grade accurately reflected the histologic grade in 90% of sarcomas when segregated into high and low grades. Pleomorphic, small round cell, and epithelioid/polygonal subgroups corresponded to high‐grade sarcomas in all cases with only minor noncorrelations. Major grading noncorrelations occurred in 50% of myxoid and 9% of spindle‐cell sarcomas. Therefore, attention should be given to specimen adequacy, and caution should be exercised when attempting to grade myxoid and spindle‐cell sarcomas by FNAB. Diagn. Cytopathol. 24:307–316, 2001. © 2001 Wiley‐Liss, Inc.
Comparison of ThinPrep and TriPath PREP liquid‐based preparations in nongynecologic specimens: A pilot study
Authors: Michael Claire W. , McConnel James , Pecott James , Afify Alaa M. , Al‐Khafaji Basim
Published: August 2002

ThinPrep (TP) and TriPath PREP (TriP) are two liquid‐based cytologic preparations that produce a thin layer of cells. This study compares the diagnostic accuracy and different cytomorphologic alterations produced by these preparations in nongynecologic specimens. Samples from 10 urines (3 urothelial carcinomas and 7 negative), 4 positive serous fluids, and 7 fine‐needle aspirates (FNAs) were prepared by both techniques. FNAs represented one each of: Hashimoto's thyroiditis (HT), hyperplastic colloid nodule (HCN), Hodgkin's lymphoma, liposarcoma, chondrosarcoma, squamous‐cell carcinoma (SCC) metastatic to the lymph node, and carcinoid tumor. All 5 participants, none of whom had prior knowledge of the clinical history or histologic diagnosis, reviewed and interpreted the slides.

Both techniques produced a clean background and were equally accurate in urines, serous fluids, and three FNAs. TriP was slightly more accurate in four FNAs: HCN and HT where colloid and lymphocytes were better represented, SCC where keratin and malignant cells were more readily identified among lymphocytes, and carcinoid which was easier to evaluate on TriP due to less cellular shrinkage and more dispersion of cells between aggregates. TP preparations had more cell shrinkage, and the chromatin was harder to evaluate. Both techniques produced artificial aggregations of lymphocytes, but TriP had a more evenly dispersed single‐cell population between aggregates, rendering them easier to evaluate for atypia. TP produced fragmentation of large sheets that were flattened, while TriP contained larger branching sheets in a three‐dimensional (3‐D) configuration. TP produced a true monolayer of cells that were all spread at the same plane, while in TriP the cells were spread at slightly different planes, requiring frequent focusing of the viewed plane.

While both techniques are acceptable for diagnostic purposes, they both introduce new cytomorphologic alterations that pathologists need to recognize. TriP seems superior to TP in FNAs specimens where preservation of architecture and cellular integrity are important considerations. Diagn. Cytopathol. 25:177–184, 2001. © 2001 Wiley‐Liss, Inc.
Correlates of subjective and objective binge eating in binge‐purge syndromes
Authors: Kerzhnerman Irina , Lowe Michael R.
Published: August 2002

Objective

Research has begun to challenge the idea that a large amount of food is a diagnostically relevant distinction in classifying binge eating. This study examined the relationship between both objective and subjective (i.e., feeling out of control while eating an appropriate amount of food) binge eating frequency and factor analytically derived measures of dieting and psychopathology.

Method

Participants were 40 women who were admitted for inpatient treatment for bulimia nervosa, anorexia nervosa, binge‐purge type, or eating disorder not otherwise specified with binge‐purge symptoms.

Results

Controlling for subjective binge frequency, neither the psychopathology nor the dieting factors were related to objective binge frequency. Controlling for objective binge frequency, dieting, but not psychopathology, was related to subjective binge frequency. There was no correlation between frequency of subjective and objective binge eating.

Discussion

The results are discussed in light of research on restrained eating. Implications for diagnosis and the role of loss of control in defining binge behavior are also discussed. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 31: 220–228, 2002; DOI 10.1002/eat.10026
Postnatal depression, eating, exercise, and vomiting before and during pregnancy
Authors: Abraham Suzanne , Taylor Alan , Conti Janet
Published: August 2002

Objective

To examine the postnatal distress and the eating, exercise, and weight losing behavior of women before and during pregnancy.

Method

The subjects were healthy women who had given birth to a singleton healthy baby in the week before the study. They were drawn from two consecutive series of mothers of babies whose birth weights were either ≤2,500 g or >2,500 g. A total of 181 women were interviewed using a standardized interview modified for pregnancy and related behaviors. They also completed the Edinburgh Postnatal Distress Questionnaire.

Results

Regression analysis produced a final model containing variables that made a unique contribution to predicting the level of distress of women in the week following childbirth. The model accounted for 25% of the variance and included four variables that were associated with greater distress: fear of weight gain before and during pregnancy, being distracted by thoughts of food during pregnancy, being afraid of gaining more weight than the pregnancy would explain, and vomiting more frequently during the first 3–4 months of pregnancy. A fifth variable accounted for less distress, that is, participating in low‐intensity exercise for reasons of shape and weight during months 3–4 of pregnancy. Other variables associated with distress only in the preliminary analysis were maternal age, binge eating, and vomiting before pregnancy. The most distressed mothers were suffering from an eating disorder at the time of pregnancy. The binge and/or purge type of eating disorder was associated with more distress than a food restriction type.

Discussion

Postnatal distress is associated with body weight and shape concerns, with disordered eating before and during pregnancy, and with vomiting during pregnancy. The protective role of low‐intensity exercise during early pregnancy needs to be explored. Women with eating disorders should be considered at risk for postnatal problems. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 29: 482–487, 2001.
Probabilistic critical excitation for MDOF elastic–plastic structures on compliant ground
Authors: Takewaki Izuru
Published: August 2002

Earthquake ground motions and their effects on structural responses are very uncertain even with the present knowledge. It is therefore desirable to develop a robust structural design method taking into account these uncertainties. Critical excitation approaches are promising and a new random critical excitation method is proposed for MDOF elastic–plastic shear‐building structures on compliant ground. The power (area of power spectral density (PSD) function) and the intensity (magnitude of PSD function) are fixed and the critical excitation is found under these restrictions. In contrast to linear elastic structures, transfer functions and simple expressions for response evaluation cannot be defined in elastic–plastic structures and difficulties arise in describing the peak responses except by laborious elastic–plastic time‐history response analysis. Statistical equivalent linearization is used to estimate the elastic–plastic stochastic peak responses approximately. The critical excitation responses are obtained for several examples and compared with those of the corresponding recorded earthquake ground motion. Copyright © 2001 John Wiley & Sons, Ltd.