bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing the doxycycline yields different patterns of genomic recombination in brain neurons with a new inducible Cre transgene
Authors: Lindeberg J̇onas , Mattsson Ragnar , Ebendal Ted
Published: August 2002

We have developed a transgenic mouse expressing the Cre recombinase under control of a tetracycline‐responsive promoter. Using a CamKIIα‐driven tTA transgenic strain and a lacZ reporter mouse, we obtained the expected neuronal pattern of recombination in the olfactory lobe, cortex, striatum, hippocampus and Purkinje cells. Moreover, recombination can be completely abolished by feeding the mice doxycycline in their drinking water. We also show that it is possible to get a different pattern of recombination by changing the timing of the doxycycline‐mediated shutdown of Cre expression. By starting the doxycycline treatment at birth, we restrict recombination to striatum only. This approach should be applicable to other inducible transgenic strains, thus increasing the number of available tissue‐specific patterns for conditional knockouts. Also, our tetO‐Cre transgene can be combined with any of the increasing number of tetracycline transactivator transgenic strains to direct specifically inducible genomic recombination to several areas of the brain. © 2002 Wiley‐Liss, Inc.
Recovery of deficient cholinergic calcium signaling by adenosine in cultured rat cortical astrocytes
Authors: Ferroni Stefano , Marchini Cristina , Ogata Tadanori , Schubert Peter
Published: August 2002

The regulation of the cholinergic calcium signaling in astroglial cells is thought to play a crucial role in the pathogenesis of Alzheimer's disease. We investigated the action of the cell modulator adenosine on acetylcholine (Ach)‐mediated intracellular calcium ([Ca2+]i) transients in cultured rat cortical astrocytes using the Ca2+ imaging technique. The stable adenosine analog 2‐chloroadenosine (2ClA) potentiated the [Ca2+]i rise induced by activation of muscarinic Ach receptors by shifting ∼30‐fold the half‐effective Ach concentration. This 2ClA effect was maintained upon removal of extracellular Ca2+, indicating that Ach‐induced [Ca2+]i elevation was due mainly to Ca2+ mobilization from intracellular stores. Pharmacological studies demonstrated that the 2ClA action was mediated by A1 receptors. Incubation with pertussis toxin abrogated the 2ClA effect but left unchanged the [Ca2+]i rise produced by Ach alone. The [Ca2+]i response elicited by Ach alone was abolished upon blockade of muscarinic receptor subtypes that stimulate phospholipase C, whereas the [Ca2+]i elevation generated by the combined action of subthreshold Ach and 2ClA was not affected. Collectively, these results suggest that the impaired cholinergic signaling, the cardinal symptom of Alzheimer's disease, can be reinforced at the second messenger level by an alternative intracellular Ca2+ mobilizing path, which can be brought into play by the concomitant activation of A1 purinoceptors and muscarinic receptors negatively coupled to adenylyl cyclase. © 2002 Wiley‐Liss, Inc.
Identification of the amino acids on a neuronal glutamate receptor recognized by an autoantibody from a patient with paraneoplastic syndrome
Authors: Carlson Noel G. , Gahring Lorise C. , Rogers Scott W.
Published: August 2002

Autoantibodies from a patient with paraneoplastic disease were identified previously to bind to the glutamate receptor (GluR) subunit GluR5 and to function as potential allosteric modulators of receptor activity (Gahring et al. [1995] Mol Med 1:245–253). In the present study we have used deletion mapping and mutagenesis to define the residues in GluR5 bound by this autoreactivity. The autoantibody contact residues include residues K497, N508, K510, E512, and to a lesser extent Q507. Residues 507–512 confer autoantibody specificity of the autoreactivity to GluR5. These residues have been shown in crystallographic studies (Armstrong et al. [1998] Nature 395:913–917) to participate in a loop structure, whereas residue K497 is located on a beta‐strand. Notably, this binding spans tyrosine 504, a residue important in forming the agonist‐binding site. We propose that autoantibody binding of essential residues in this GluR5 autoantigenic region defines a subunit‐specific allosteric regulatory site on neuronal glutamate receptors and suggests how receptor dysfunction and region‐specific neuronal death in the brain can progress in certain autoimmune neurological diseases. J. Neurosci. Res. 63:480–485, 2001. © 2001 Wiley‐Liss, Inc.
Attenuation of malonate toxicity in primary mesencephalic cultures using the GABA transport blocker, NO‐711
Authors: Stokes Alan H. , Bernard Laura P. , Nicklas William J. , Zeevalk Gail D.
Published: August 2002

Cultured rat mesencephalic neurons were used to assess the effects of γ‐aminobutyric acid (GABA) transport blockers on toxicity caused by malonate, a reversible, competitive inhibitor of succinate dehydrogenase. Previous studies utilizing an ex vivo chick retinal preparation have shown that GABA release and cell swelling are early consequences of acute energy impairment and that GABA transport blockers attenuate this toxicity. The present results demonstrate that the nonsubstrate GABA transport blocker, NO‐711 (1 nM–1 μM), dose‐dependently protected cultured mesencephalic dopamine (DA) and GABA neurons from malonate‐induced toxicity. Similar protection was demonstrated with nipecotic acid (1 mM) and SKF89976A (100 nM), substrate and nonsubstrate GABA transport blockers, respectively. These compounds by themselves produced no signs of toxicity, although nipecotic acid caused a long‐term decrease in GABA uptake not associated with toxicity. Compounds which decrease intracellular reactive oxygen species (ROS) are protective in this model, but NO‐711 did not prevent the rise in intracellular ROS induced by malonate, indicating its protective effects were downstream of ROS production. Supplementation of malonate treated cultures with the GABAA agonist, muscimol (10 μM), increased the toxicity toward the DA and GABA neuron populations. Antagonists at the GABAA and glycine receptors provided partial protection to both the GABA and DA neurons. These findings suggest that the GABA transporter, GABAA, and/or glycine channels contribute to cell damage associated with energy impairment in this model. J. Neurosci. Res. 64:43–52, 2001. © 2001 Wiley‐Liss, Inc.
Purkinje cell degeneration in mice lacking the xeroderma pigmentosum group G gene
Authors: Sun Xue‐Zhi , Harada Yoshi‐Nobu , Takahashi Sentaro , Shiomi Naoko , Shiomi Tadahiro
Published: August 2002

Laboratory mice carrying the nonfunctional xeroderma pigmentosum group G gene (the mouse counterpart of the human XPG gene) alleles have been generated by using gene‐targeting and embryonic stem cell technology. Homozygote animals of this autosomal recessive disease exhibited signs and symptoms, such as postnatal growth retardation, reduced levels of activity, progressive ataxia and premature death, similar to the clinical manifestations of Cockayne syndrome (CS). Histological analysis of the cerebellum revealed multiple pyknotic cells in the Purkinje cell layer of the xpg homozygotes, which had atrophic cell bodies and shrunken nuclei. Further examination by an immunohistochemistry for calbindin‐D 28k (CaBP) showed that a large number of immunoreactive Purkinje cells were atrophic and their dendritic trees were smaller and shorter than in wild‐type littermates. These results indicated a marked degeneration of Purkinje cells in the xpg mutant cerebellum. Study by in situ detection of DNA fragmentation in the cerebellar cortex demonstrated that some deoxynucleotidyl transferase (TdT)‐mediated dUTP‐biotin in situ nick labeling (TUNEL)‐positive cells appeared in the granule layer of the mutant mice, but few cell deaths were confirmed in the Purkinje layer. These results suggested Purkinje cell degeneration in the mutant cerebellum was underway, in which much Purkinje cell death had not appeared, and the appearance of some abnormal cerebellar symptoms in the xpg‐deficient mice was not only due to a marked Purkinje cell degeneration, but also to damage of other cells. J. Neurosci. Res. 64:348–354, 2001. © 2001 Wiley‐Liss, Inc.
tert‐Butylhydroperoxide induces peroxynitrite‐dependent mitochondrial permeability transition leading PC12 cells to necrosis
Authors: Palomba Letizia , Sestili Piero , Cantoni Orazio
Published: August 2002

A short‐term exposure of PC12 cells to tert‐butylhydroperoxide, followed by recovery in fresh culture medium, causes cell death and the extent of this response progressively increases during the 120 min of post‐treatment incubation. Morphological and biochemical analyses of these cells revealed that the mode of cell death was necrosis. Cell killing induced by the hydroperoxide seems to be in part mediated by peroxynitrite because the lethal response was markedly and similarly reduced by the nitric oxide synthase inhibitor Nω‐nitro‐L‐arginine methylester and by scavengers of nitric oxide or peroxynitrite. This peroxynitrite‐dependent mechanism of cytotoxicity was blunted by antioxidants and inhibitors of mitochondrial permeability transition and the onset of cell death was preceded by mitochondrial depolarization and loss of cellular ATP. We conclude that tert‐butylhydroperoxide promotes peroxynitrite‐dependent PC12 cell necrosis causally linked to peroxidation of membrane lipids and mitochondrial permeability transition. J. Neurosci. Res. 65:387–395, 2001. © 2001 Wiley‐Liss, Inc.
Laminar variation in neuronal viability and trophic dependence in neocortical slices
Authors: Niblock Mary M. , Brunso‐Bechtold Judy K. , Riddle David R.
Published: August 2002

Organotypic slices are used frequently in studies of central nervous system development and function because they provide excellent experimental access with significant preservation of cellular context and relationships. Within a slice, however, a variety of factors may cause individual classes of neurons to respond differently to the culture environment. Differences in deafferentation, cellular maturation, trophic dependence and ongoing naturally occurring cell death may produce changes in the neuronal population that are transparent to the experimenter but that could affect experimental results significantly. In this study, we examined the distribution and prevalence of cell death among neurons in each cortical layer in organotypic slices. In addition, we assessed the ability of several neurotrophic factors to ameliorate neuronal death in each cortical layer. Within the first 24 hr in culture, there was striking laminar variation in the extent of neuronal death in culture, which could not be accounted for by the pattern of programmed cell death in vivo. In addition, neurons in the six layers of the neocortex differed in the degree to which they could be rescued by neurotrophic factors. These data suggest that differential neuronal death and rescue are important considerations in studies utilizing organotypic slices and may represent particularly confounding variables in studies of effects of trophic factors in such preparations. J. Neurosci. Res. 65:455–462, 2001. © 2001 Wiley‐Liss, Inc.
Bayesian hazard analysis of heavy precipitation in eastern Spain
Authors: Egozcue J.J. , Ramis C.
Published: August 2002

The hazard due to heavy daily rainfall in the Valencia region (eastern Iberian Peninsula) is analysed by using 30‐year records at 72 rain gauge stations. The proposed method is a Bayesian version of the commonly used point over threshold or exceedance methods. For each site, the occurrence of events in time are assumed to be Poisson distributed and the excesses over a selected high threshold are assumed to follow some generalized Pareto distribution. A large uncertainty about the type of distribution for the excesses is observed for each station and the preferred distribution changes from station to station. The large uncertainty in estimated occurrence probabilities or return periods suggests the use of Bayesian predictive occurrence probabilities as the main parameters describing the hazard. Two stations are selected for a detailed analysis. The whole database has been used to obtain predictive exceedance probability spatial distributions for thresholds of 150, 300 and 500 mm of daily precipitation. These maps confirm the most hazardous sites are placed at the northeast of the main mountain range of the region, where it is speculated that deep convection develops when humid northeasterly flows cross the coastal range. Copyright © 2001 Royal Meteorological Society
Transient climate simulation forced by natural and anthropogenic climate forcings
Authors: Bertrand Cédric , Ypersele Jean‐Pascal van
Published: August 2002

Numerical experiments have been carried out with a two‐dimensional sector‐averaged global climate model coupled to a diffusive ocean in order to assess the potential impact of four hypothesized mechanisms of decadal to century‐scale climate variability, both natural and anthropogenically induced: (1) solar variability; (2) variability in volcanic aerosol loading of the atmosphere; (3) anthropogenic increase of sulphate aerosols' concentration; (4) anthropogenic increase of greenhouse gas concentrations.

Our results suggest that neither the individual responses nor the combined natural or anthropogenic forcings allow one to reproduce all of the recorded major temperature fluctuations since the latter half of the 19th century. They show that these temperature variations are the result of both naturally driven climate fluctuations and the effects of industrialization.

By contrast, the dominant cause of decade‐to‐century‐scale variability of the 21st century is likely to be changes in atmospheric trace‐gas concentrations. Indeed, when the solar, volcanic, and tropospheric aerosols forcings used in our experiments are extended into the future, they are unable to counter the expected greenhouse warming. Copyright © 2002 Royal Meteorological Society.
Electrosynthesis, electrochemistry, and crystal structure of the tetracationic Zn-meso-tetrapyridiniumyl-β-octaethylporphyrin
Authors: GIRAUDEAU A. , LOBSTEIN S. , RUHLMANN L. , MELAMED D. , BARKIGIA K. M. , FAJER J.
Published: August 2002

Exhaustive electro-oxidation of ZnOEP in the presence of pyridine and Et 4 NPF 6 affords in high yield the new tetracationic porphyrin in which the four meso protons of ZnOEP are replaced by four pyridinium groups linked via their nitrogens: [ Zn -5,10,15,20-tetrakis(N-pyridiniumyl)-2,3,7,8,12,13,17,18-octaethylporphyrin]4+[Formula: see text], 1. The compound has been characterized by elemental analysis, 1 H NMR, and crystallography. The latter confirms the preparative electrosynthetic methodology and molecular structure of 1, and shows the porphyrin skeleton to adopt a severely nonplanar saddle conformation which minimizes steric crowding between the 12 peripheral substituents. As a consequence of the nonplanarity (and the high charge) of the complex, 1 exhibits significant red-shifts of the visible and Soret bands as well as a considerable broadening and loss of intensity of the latter. 1 first undergoes four one-electron reduction steps at the four pyridinium sites before the normal one-electron reduction of the porphyrin π-system.
Time‐resolved study of the photochemical reaction of 4‐dimethylaminobenzonitrile with carbon tetrachloride
Authors: Ma C. , Kwok W. M. , Matousek P. , Parker A. W. , Phillips D. , Toner W. T. , Towrie M.
Published: August 2002

The mechanism of 4‐dimethylaminobenzonitrile (DMABN) fluorescence quenching by carbon tetrachloride was studied using time‐resolved fluorescence, absorption and Raman techniques. Picosecond and nanosecond time‐resolved Raman spectra of DMABN and DMABN‐d6 were obtained in resonance with different electronic states to identify intermediates, their structure and time‐dependent dynamic changes. The quenching is attributed to intermolecular electron transfer between B‐state DMABN and carbon tetrachloride with a time constant of ∼500 fs leading to the formation of the DMABN radical cation as the initial intermediate followed by a ∼13 ps process yielding a DMABN Cl adduct as product with a lifetime longer than 50 ns. It is likely that the chlorine atom is located at the amino para‐ring position of the highly reactive DMABN radical cation. It is suggested that this reaction mechanism is general for other donor–aromatic–acceptor type DMABN derivatives. Copyright © 2001 John Wiley & Sons, Ltd.
Size dependence of the Raman spectra in an amorphous–nanocrystalline mixed phase: the glacial state of triphenyl phosphite
Authors: Hédoux Alain , Guinet Yannick , Descamps Marc
Published: August 2002

Raman scattering investigations on triphenyl phosphite, performed in both the low‐ and high‐wavenumber ranges, provide a detailed description of the glacial state. The latter can be described as a two‐phase (amorphous–nanocrystalline) system if it is prepared by isothermal aging in the 210–222 K temperature range. From two different procedures the nanocrystalline volume fraction can be determined in glacial states prepared in the above temperature range. The Raman spectra in the range 840–1640 cm−1 reveals that Ta = 224 K is a critical temperature from which the supercooled liquid isothermally transforms into a microstructure rather than nanocrystallized domains. In this case the volume of the non‐transformed supercooled liquid remaining in the intergranular space was estimated with respect to the volume of crystallized matter. Copyright © 2001 John Wiley & Sons, Ltd.
The arrival of postmodernist strategic theory: its academic manifestation and the development of a new modernist perspective
Authors: Woods Adrian , Joyce Paul
Published: August 2002

In this article different ways of conceptualizing strategic planning are explored, namely;

. Modern strategic planning with its emphasis on using scientific methods to find out about and programme the future.

. Postmodern strategic planning that calls into question the strategist's ability to know and programme the future.

. New modern strategic planning that stresses the importance of the strategist(s) interacting with other stakeholders and experimenting through strategic projects rather than planning from on high and then dictating changes which have been totally programmed—being able through foresight as opposed to forecasting to build a bridge from the present to the future.

From this the role of the strategist(s) in organizations as being charged with providing leadership through foresight and being able to forge different stakeholders together is explored.

Copyright © 2002 John Wiley & Sons, Ltd.
Strategic breakout in UK telecommunications: the case of Kingston Communications
Authors: Turner Colin
Published: August 2002

The progressive liberalization of the UK telecommunications sector has necessitated a strategic repositioning by its incumbent operators, British Telecommunications (BT) and Kingston Communications (KC), as they face up to increased competition within their traditional market places.

This repositioning has stimulated a process of strategic breakout, a framework derived from the author's on‐going examination of changes in the European telecommunications sector.

Amendments in the regulatory framework governing the industry has enabled firms to move into geographic and product markets from which they were previously excluded. However, they still face a residual regulatory framework that sustains a commitment by them to their base market principally through universal service obligations.

Such a scenario has the potential to create conflict and undermine strategic focus. This paper seeks to explore this conflict through the strategic repositioning of KC since its licence was last reviewed in July 1998. After exploring the process of strategic breakout, the framework is then applied to KC highlighting how the process, when interacting with the residual regulatory framework, creates the potential for strategic conflict.

Copyright © 2002 John Wiley & Sons, Ltd.
Search for predictors of cooking quality of marrowfat pea (Pisum sativum L) cultivars
Authors: Savage Geoffrey P , Savage Grace E , Russell Adrian C , Koolaard John P
Published: August 2002

The grain from 116 marrowfat pea breeding lines was assessed subjectively using current visual methods and then analysed objectively for L*a*b* colour, hydration capacity and cooking quality. The data show that the current method of selecting genotypes by subjective methods is not able to select marrowfat peas for specific processing uses. However, an objective measure, the −a* value of the dry grain, was a very good predictor (p < 0.001) for the hydrated and cooked green colour. Cultivars which have a high hydration coefficient may be more suitable for canning and deep frying because they hydrate to a larger size, while cultivars with a high bulk density and a darker green grain are more suitable for use as extrusion products.

© 2001 Society of Chemical Industry
Apoptosis and its correlation with proliferative activity in rectal cancer
Authors: Kim Young‐Ho , Lee Jun Haeng , Chun Hokyung , Nam Seok‐Jin , Lee Woo‐Yong , Song Sang Yong , Kwon O Jun , Hyun Jae Geun , Sung In Kyung , Son Hee Jung , Rhee Poong‐Lyul , Kim Jae J. , Paik Seung Woon , Rhee Jong Chul , Choi Kyoo Wan
Published: August 2002

Background and Objectives

Alterations in the normal control of apoptosis and cell proliferation are important factors in multistep colorectal carcinogenesis. The aim of this study was to determine the frequency of apoptosis and cell proliferation in rectal cancers and to examine their relationship to clinicopathological variables and expression of bcl‐2 and p53.

Methods

Terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick end labeling (TUNEL) staining and immunohistochemical staining for Ki‐67, bcl‐2, and p53 were performed on paraffin‐embedded tissue samples of 57 rectal cancers.

Results

There was a positive linear correlation between apoptotic index (AI) and proliferative index (PI) (γ = 0.276, P = 0.038). Both apoptosis and cell proliferation were more frequently found in rectal cancers with lymph node metastasis (P = 0.045 and 0.010, respectively). However, the ratio of AI and PI was not different by nodal status. There was no association between Dukes stage and AI or PI. The frequency of apoptosis was inversely related to the expression of bcl‐2, but was not related to the p53 status of rectal cancer. There were no association between cell proliferation and the expression of bcl‐2 or p53.

Conclusions

Our results suggest that the susceptibility to apoptosis in rectal cancer is clearly related to the proliferative activity and high turnover rate of tumor cells may contribute to lymph node metastasis. J. Surg. Oncol. 2002;79:236–242. © 2002 Wiley‐Liss, Inc.
FDG–PET sensitivity for melanoma lymph node metastases is dependent on tumor volume
Authors: Wagner Jeffrey D. , Schauwecker Donald S. , Davidson Darrell , Wenck Stacie , Jung Sin‐Ho , Hutchins Gary
Published: August 2002

Background and Objectives

The purpose of this study is to determine the tumor volume threshold for successful positron emission tomography (PET) imaging of melanoma nodal metastases.

Methods

Review of a clinical series of patients who had FDG–PET imaging of regional lymph node basins followed by lymphadenectomy. Lymph node tumor volumes were calculated from direct measurements of metastatic nodule(s) in formalin fixed specimens. PET scan interpretations were correlated with histology to determine sensitivity. Sensitivity was correlated with the aggregate lymph node tumor volume in the nodal basin and with AJCC stage group.

Results

Forty‐five patients with 49 pathologically positive regional nodal basins comprised the study group. Median total basin tumor volume was 28.3 mm3(range 0.004–22,879 mm3). FDG–PET sensitivity for detection of all tumor volumes was 0.49. The observed 90% sensitivity threshold for detection of nodal metastases was ≥ 78 mm3. PET sensitivity was 0.14 for detection of tumor volumes < 78 mm3. PET sensitivity differed by prescan AJCC stage: I—0.0; II—0.24; III—0.81; IV—1.0 (P < 0.001).

Conclusions

FDG–PET reliably detects lymph node tumor deposits greater than approximately 80 mm3 volume, but sensitivity falls rapidly below this. This amount of tumor is most likely to occur in patients with AJCC stage III or IV disease. J. Surg. Oncol. 2001;77:237–242. © 2001 Wiley‐Liss, Inc.
Correlation of human papillomavirus 16 and 18 with cervical neoplasia in histological typing and clinical stage in Taiwan: An in‐situ polymerase chain reaction approach
Authors: Shyu Jean‐Shiunn , Chen Cheng‐Jueng , Chiu Chia‐Chang , Huang Su‐Chin , Harn Horng‐Jyh
Published: August 2002

Background and Objectives:

In situ polymerase chain reaction (ISPCR) promises to considerably enhance our ability to detect a few copies of target nucleic acid sequences in fixed tissues and cells. The aim of this study was to investigate cervical carcinoma to determine the human papillomavirus (HPV) types on paraffin‐embedded tissue sections by ISPCR and standard in situ hybridization. The results will correlate the morphological characteristics of lesions with viral typing results..

Methods:

This study examined prevalence of HPV 16 and 18 DNA in biopsies from 85 cervical cancer patients by ISPCR, employing HPV 16, 18 consensus primers. There are 45 patients with squamous cell carcinomas, 13 with adenocarcinoma, 2 with adenosquamous carcinomas, 3 with small cell carcinomas, and 22 carcinoma in situ. The relation between the types of HPV detected, tumor type, and clinical stage were analyzed.

Results:

Fifty‐two of 85 biopsies were HPV 16‐ or 18‐positive, HPV 16 being the most prevalent type. Squamous cell carcinoma had a high prevalence of HPV 16 and adenocarcinoma had a high prevalence of HPV 18. HPV 18 was the predominant type among high clinical stage (III–IV) cases while HPV 16 and mixed HPV 16 with HPV18 were significantly correlated with low clinical stage (0–I–II).

Conclusion:

Our results indicate that certain malignant cervical tumor phenotypes and stages correlate with specific HPV type, and that ISPCR is a sensitive and fast method to detect HPV in these patients. J. Surg. Oncol. 2001;78:101–109. © 2001 Wiley‐Liss, Inc.
Chyle withdrawal from an implanted port in occult innominate vein stenosis
Authors: Kao Chiung‐Lun , Chang Jen‐Ping
Published: August 2002

Totally implantable venous devices are widely used for chemotherapy and parenteral nutrition. There have been many device‐associated complications reported in the literature. Herein, we report a case of chyle withdrawal from an implanted port that occurred secondary to occult innominate vein stenosis in a patient receiving chemotherapy for rectal cancer with lung metastasis. The port remained patent and functioning well after balloon angioplasty. J. Surg. Oncol. 2001;78:138–140. © 2001 Wiley‐Liss, Inc.
Attenuation by boron supplementation of the biochemical changes associated with thioacetamide‐induced hepatic lesions
Authors: Ali Shakir , Diwakar G. , Pawa Sonica , Siddiqui M.R. , Jain S.K. , Abdulla M
Published: August 2002

Acute hepatic failure is a severe complication induced by certain chemicals, drugs, or virus. Thioacetamide generally has been used for the study of hepatic failure in experimental animal model. The present study was aimed at to examine the role of boron in the pathogenesis of acute hepatic failure in rats. A single intraperitoneal injection of thioacetamide produced severe liver injury, as manifested by elevation in serum aminotransferases, alkaline phosphatase, and hepatic lipid peroxidation. Boron, when administered in the form of boric acid for three consecutive days followed by thioace‐tamide, attenuated thioacetamide‐mediated changes in the level of these biochemical parameters in a dose‐dependent manner. The effect of boron supplementation on the survival rates of rats treated with a lethal dose of thioacetamide was also determined and found to lower the mortality rates in the group of animals supplemented with boron followed by thioacetmide. The effects on biochemical parameters and the survival rates were dependent on the dose of boron administered as boric acid. It is concluded that boron provides protection against the thioacetamide‐induced acute hepatic failure in rats in a dose‐dependent manner. J. Trace Elem. Exp. Med. 15: 47–55, 2002. © 2002 Wiley‐Liss, Inc.
Dietary copper deficiency increases inducible nitric oxide synthase‐mediated vascular dilation in rat aorta
Authors: Gobejishvili Leila , Saari Jack T. , Adeagbo Ayotunde S.O. , Zhang Xiaodong , Schuschke Dale A.
Published: August 2002

The attenuation of endothelium‐dependent nitric oxide (NO)‐mediated vasodilation is a consistent finding in both conduit and resistance vessels during copper deficiency. However, there is often no effect on systemic blood pressure in experimental animals, suggesting that peripheral vascular resistance is not altered. We hypothesized that baseline vascular smooth muscle relaxation may be maintained by a chronic increase in inducible NO synthase (iNOS) expression, as has been documented in hearts of copper‐deficient rats. We used endothelium‐denuded rat aortic rings to examine the role of iNOS in the regulation of vascular reactivity during dietary copper deficiency. Male weanling rats were fed a copper‐adequate (CuA, 5.6 mg Cu/kg diet) or copper‐deficient diet (CuD, 0.33 mg Cu/kg diet) for 4 weeks. The induction of “functional” iNOS was indicated by a relaxation response to the NO precursor L‐arginine or to Cu,Zn‐superoxide dismutase (SOD), which preserves basal NO. Time to 50% relaxation in response to either compound was significantly shorter in the CuD than in the CuA aortas. The maximal relaxation response to L‐arginine was blocked by the iNOS inhibitor L‐NIL, and the relaxation response to Cu,Zn‐SOD was blocked by the NO‐sensitive guanylate cyclase inhibitor ODQ. Maximal activation of iNOS expression with lipopolysaccharide pretreatment did not cause a difference in vascular relaxation between dietary groups in response to L‐arginine. Expression of the iNOS protein in the aortas was also not different between groups. These results suggest that although there is no apparent increase in protein expression, copper deficiency increases baseline iNOS activity in the vascular wall. J. Trace Elem. Exp. Med. 15:85–95, 2002. © 2002 Wiley‐Liss, Inc.
Shock tube determination of the overall rate of NH2 + NO → products in the thermal De‐NOx temperature window
Authors: Song S. , Hanson R. K. , Bowman C. T. , Golden D. M.
Published: August 2002

The rate coefficient of the reaction NH2 + NO → products (R1) was determined in shock tube experiments using frequency‐modulation absorption spectroscopy for detection of NH2. Because of the sensitivity of the diagnostic system, very low reactant concentrations could be employed in order to reduce the influence of secondary reactions on the NH2 profiles. Benzylamine, C6H5CH2NH2, was used as a thermal source of the NH2 radicals in the experiments. To determine the reaction rate, a perturbation strategy was employed that is based on changes in the NH2 profiles when NO is added to the C6H5CH2NH2/Ar mixtures. The measured NH2 profiles were interpreted by detailed kinetic modeling to obtain the overall reaction rate of R1 in the temperature range 1262–1726 K. The lower temperature limit of the present study is in the middle of the Thermal De‐NOx temperature window. The present rate measurements are consistent with both our previous determination of the rate at higher temperatures and lower temperature data. A rate expression obtained by combining our higher temperature data and lower temperature data is
k1 = 6.83 × 1015 T−1.203 e106/T (K) cm3 mol−1 s−1
for the temperature range 200–2500 K. The estimated uncertainty of the rate coefficient is ±20%. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 715–721, 2001
Temporal changes of resource use, soil fertility and economic situation in upland Northwest Vietnam
Authors: Wezel A. , Luibrand A. , Thanh Le Quoc
Published: August 2002

Agricultural land in lowland Vietnam is scarce due to population growth. Hence, cultivation is increasingly practised on the steep upland slopes. Factors affecting resource use, soil fertility and household economics were studied in six villages of the Black Thai ethnic group in northwest Vietnam. Farmers were interviewed about their individual household situation. Yield development of major crops and cropping patterns in upland cultivation over the last 50 years were recorded in group discussions. In addition, soil fertility was analysed on different land‐use units.

Formerly predominant upland rice changed to maize and cassava production at present. Decreasing soil fertility and a shift from subsistence to market‐oriented production, facilitated by new maize varieties and better access to markets are major causes. The Black Thai farmers economy has improved in recent years. The decline in soil fertility is concealed by higher maize yields from new varieties, and soil fertility conservation ranks low among farmers' priorities. The improved economy of the individual households might be of short duration if farmers cannot be sensitized to new resource management options. These have to be developed in line with farmers' priorities and the fragile environment of Vietnam's uplands. Copyright © 2002 John Wiley & Sons, Ltd.
Diode‐pumped fiber lasers: A new clinical tool?
Authors: Jackson Stuart D. , Lauto Antonio
Published: August 2002

Background and Objective

Diode‐pumped fiber lasers are a compact and an efficient source of high power laser radiation. These laser systems have found wide recognition in the area of lasers as a result of these very practical characteristics and are now becoming important tools for a large number of applications. In this review, we outline the basic physics of fiber lasers and illustrate how a number of clinical procedures would benefit from their employment.

Study Design/Materials and Methods

The pump mechanisms, the relevant pump and laser transitions between the energy levels, and the main properties of the output from fiber lasers will be briefly reviewed. The main types of high power fiber lasers that have been demonstrated will be examined along with some recent medical applications that have used these lasers. We will also provide a general review of some important medical specialties, highlighting why these fields would gain from the introduction of the fiber laser.

Results/Conclusion

It is established that while the fiber laser is still a new form of laser device and hence not commercially available in a wide sense, a number of important medical procedures will benefit from its general introduction into medicine. With the number of medical and surgical applications requiring high power laser radiation steadily increasing, the demand for more efficient and compact laser systems providing this capacity will grow commensurately. The high power fiber laser is one system that looks like a promising modality to meet this need. Lasers Surg. Med. 30:184‐190, 2002. © 2002 Wiley‐Liss, Inc.
Laser‐tissue soldering with biodegradable polymer films in vitro: Film surface morphology and hydration effects
Authors: Sorg Brian S. , Welch Ashley J.
Published: August 2002

Background and Objective

Previous research introduced the concept of using biodegradable polymer film reinforcement of a liquid albumin solder for improvement of the tensile strength of repaired incisions in vitro. In this study, the effect of creating small pores in the PLGA films on the weld breaking strength is studied. Additionally, the effect of hydration on the strength of the reinforced welds is investigated.

Study Design/Materials and Methods

A 50%(w/v) bovine serum albumin solder with 0.5 mg/mL Indocyanine Green dye was used to repair an incision in bovine aorta. The solder was coagulated with an 806‐nm CW diode laser. A poly(DL‐lactic‐co‐glycolic acid) (PLGA) film was used to reinforce the solder (the controls had solder but no reinforcement). Breaking strengths were measured acutely and after hydration in saline for 1 and 2 days. The data were analyzed by ANOVA (P < 0.05) and multiple comparisons of means were performed using the Newman–Keuls test.

Results

The creation of pores in the PLGA films qualitatively improved the film flexibility without having an apparent adverse effect on the breaking strength, while the actual technique of applying the film and solder had more of an effect. The acute maximum average breaking strengths of some of the film reinforced specimens (114.7 g–134.4 g) were significantly higher (P < 0.05) than the acute maximum average breaking strength of the unreinforced control specimens (68.3 g). Film reinforced specimens were shown to have a statistically significantly higher breaking strength than unreinforced controls after 1‐ and 2‐day hydration.

Conclusions

Reinforcement of liquid albumin solders in laser‐assisted incision repair appears to have advantages over conventional methods that do not reinforce the cohesive strength of the solder in terms of acute breaking strength and after immersion in moist environments for short periods of time. Using a film with the solder applied to one surface only may be advantageous over other techniques. Lasers Surg. Med. 28:297–306, 2001. © 2001 Wiley‐Liss, Inc.
Optical‐thermal simulation of tonsillar tissue irradiation
Authors: Shah Rahul K. , Nemati Babak , Wang Lihong V. , Shapshay Stanley M.
Published: August 2002

Background and Objective

Despite laser applications targetted toward tonsillar tissue, there has been no characterization of underlying optical and thermal events during laser irradiation of tonsillar tissue.

Study Design/Materials and Methods

The optical properties of canine and human tonsils were determined at 805 nm (diode laser) and 1,064 nm (Nd:YAG laser). An optical‐thermal simulation was developed to predict the temperature rise in irradiated human tonsils.

Results

The optical properties of human and canine tonsillar tissue are similar at both wavelengths. The optical‐thermal simulation was validated and predicts that at 10 W and 1 minute of irradiation, the heat will be contained within the human tonsil. The diode laser causes more superficial heating than the Nd:YAG laser.

Conclusions

The safety of irradiating human tonsils was shown. The diode laser is superior to the Nd:YAG laser because less heat affects collateral structures. The optical‐thermal simulation detailed in this study can be used to predict the temperature rise in tissues undergoing irradiation. Lasers Surg. Med. 28:313–319, 2001. © 2001 Wiley‐Liss, Inc.
Production of narrow but deep lesions suitable for ablation of atrial fibrillation using a saline‐cooled narrow beam Nd:YAG laser catheter
Authors: Thomas Stuart P. , Guy Duncan J.R. , Rees Arianwun , Collins Lee , Ross David L.
Published: August 2002

Background and Objective

Lines of radiofrequency ablation for cure of atrial fibrillation are broad, and the consequent loss of atrial mass may impair atrial function and contribute to the risk of stroke. We studied whether Nd:YAG laser could produce deep but narrower lesions.

Study Design/Materials and Methods

Laser lesions were made in ventricular myocardium of nonperfused ovine hearts and at thoracotomy in dogs.

Results

Lesions were well demarcated, deep, and narrow. Saline irrigation prevented crater formation for energy levels below 200 J. Lesion depth increased with increasing duration of ablation (maximum 5.3 ± 0.8mm, P < 0.01). The depth to width ratio was >1 in all cases (maximum 2.5 ± 1.6). The narrowest lesions were made by using high power, short duration of exposure, and intermittent delivery.

Conclusions

Irrigated Nd:YAG laser can be used to make deep narrow myocardial lesions without crater formation. Laser ablation may be more suitable than radiofrequency ablation for intraoperative or catheter‐based cure of atrial fibrillation. Lasers Surg. Med. 28:375–380, 2001. © 2001 Wiley‐Liss, Inc.
Fluorescence spectroscopy of epithelial tissue throughout the dysplasia‐carcinoma sequence in an animal model: Spectroscopic changes precede morphologic changes
Authors: Coghlan Lezlee , Utzinger Urs , Richards‐Kortum Rebecca , Brookner Carrie , Zuluaga Andres , Gimenez‐Conti Irma , Follen Michele
Published: August 2002

Background and Objective

The hamster cheek pouch carcinogenesis model, using chronic treatments of dimethylbenz[α]anthracene (DMBA) was used as a model system to investigate changes in epithelial tissue autofluorescence throughout the dysplasia‐carcinoma sequence.

Study Design/Materials and Methods

Fluorescence emission spectra were measured weekly from 42 DMBA‐treated animals and 20 control animals at 337, 380, and 460 nm excitation. A subset of data in which histopathology was available was used to develop diagnostic algorithms to separate neoplastic and non‐neoplastic tissue. The change in fluorescence intensity over time was examined in all samples at excitation‐emission wavelength pairs identified as diagnostically useful.

Results

Algorithms based on autofluorescence can separate neoplastic and non‐neoplastic tissue with 95% sensitivity and 93% specificity. Greatest contributions to diagnostic algorithms are obtained at 380 nm excitation, and 430, 470, and 600 nm emission. Changes in fluorescence intensity are apparent as early as 3 weeks after initial treatment with DMBA, whereas morphologic changes associated with dysplasia occur on average at 7.5–12.5 weeks after initial treatment.

Conclusions

Fluorescence spectroscopy provides a potential tool to identify biochemical changes associated with dysplasia and hyperplasia, which precede morphologic changes observed in histologically stained sections. Lasers Surg. Med. 29:1–10, 2001. © 2001 Wiley‐Liss, Inc.
Near‐infrared photo‐excited emission from tissues treated at different temperature levels
Authors: Tang Jing , Zhang Gang , Zeng Fanan , Ho Ping Pei , Alfano R. R.
Published: August 2002

Background and Objective

There is a lack of methods to evaluate the extent of thermal treatment of biological tissue. The intensity of the near‐infrared (NIR) emission photo‐excitation was investigated from tissue undergoing different levels of heat treatment.

Study Design/Materials and Methods

Chicken muscle was heated in an oven at different temperature levels ranging from 40°C until burn‐off. The spectral emission intensity from these heat‐treated tissues was measured with a CCD camera and the intensity was calculated.

Results

The emission intensity increased proportionally with respect to the extent of treatment temperature until burning. Linear relationships between treatment temperature and the emission intensity from tissue samples were found in three temperature ranges: from 40 to 160°C, from 165 to 220°C, and from 225 to 250°C.

Conclusions

The change in tissue damage after heat treatment could be detected by measuring the NIR emission intensity from the thermally damaged tissues. Lasers Surg. Med. 29:18–22, 2001. © 2001 Wiley‐Liss, Inc.
Identification of cervical intraepithelial neoplasia (CIN) using UV‐excited fluorescence and diffuse‐reflectance tissue spectroscopy
Authors: Nordstrom Robert J. , Burke Louis , Niloff Jonathan M. , Myrtle James F.
Published: August 2002

Background and Objective:

The diagnostic potentials of ultraviolet‐excitation fluorescence spectroscopy and diffuse‐reflectance spectroscopy of tissue are assessed in a study to identify cervical intraepithelial neoplasia (CIN) in vivo. A multivariate algorithm is used to classify tissue into normal tissues, CIN I, and CIN II/III categories, based on spectral characteristics of biopsied tissue sites.

Study Design/Materials and Methods:

An optical instrument with the capability of measuring fluorescence and diffuse‐reflectance spectra from 120 locations uniformly distributed over the surface of the cervix is described. Using this device, these optical spectra of the cervix were measured on women referred for colposcopy due to an abnormal Pap smear.

Results:

UV fluorescence differentiates CIN II/III lesions from normal squamous tissue with a sensitivity and specificity of 91 and 93%, respectively. CIN I is distinguished from normal tissue with a sensitivity of 86% and a specificity of 87%.

Conclusion:

Optical spectroscopy shows promise for the detection of pre‐cancerous cervical lesions in vivo. The fluorescence and reflectance methods are complementary in their ability to differentiate different tissue types, making the use of the two techniques together more diagnostic than the use of either method separately. Lasers Surg. Med. 28:118–127, 2001. © 2001 Wiley‐Liss, Inc.
Confirmation of the mapping of a 12‐O‐tetradecanoylphorbol‐13‐acetate promotion susceptibility locus, Psl1, to distal mouse chromosome 9
Authors: Angel Joe M. , Caballero Manuel , DiGiovanni John
Published: August 2002

Susceptibility to two‐stage skin carcinogenesis in the mouse is affected by several genes. In addition, studies suggest that genes that modify the response of mice to skin tumor promotion by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) also may influence histologic changes in the skin as the result of TPA treatment. One TPA susceptibility locus, Psl1, previously was mapped to distal chromosome 9. The mapping of this locus was confirmed by marker‐based genotypic selection. Furthermore, Psl1 or a gene closely linked to Psl1 influenced epidermal hyperplasia and epidermal labeling index of mice treated with TPA. © 2001 Wiley‐Liss, Inc.
Chromosome 3p tumor‐suppressor gene alterations in cervical carcinomas
Authors: Herzog Christopher R. , Crist Keith A. , Sabourin Carol L. K. , Kelloff Gary J. , Boone Charles W. , Stoner Gary D. , You Ming
Published: August 2002

Loss of heterozygosity (LOH) on chromosome 3p is a common event in cervical cancer and typically occurs in a dispersed pattern involving several loci. This implies that more than one resident tumor‐suppressor gene is involved in the genesis of these tumors; however, specific targets remain to be identified. The region of 3p14.2‐pter encompasses a region of frequent loss and contains at least three tumor‐suppressor genes: fragile histidine triad (FHIT), transforming growth factor‐β receptor II (TβR‐II), and Von Hippel–Lindau. To identify those loci within 3p14.2‐pter that are important in cervical cancer, invasive tumors were first subjected to high‐density LOH analysis. With 25 microsatellite markers, LOH was detected in seven of 15 cervical carcinomas (47%). Losses always included markers mapping to 3p22, and markers at this location were exclusively lost in two tumors, implicating this as a site of a cervical tumor‐suppressor gene. Because it is a known tumor‐suppressor gene located at 3p22 and thus a potential target for inactivation in these tumors, the TβR‐II gene was subsequently screened for mutation and altered expression levels. Whereas no tumor‐derived mutations were detected in any of the tumors, six of ten tumors showed TβR‐II transcript levels reduced by ≥ 50% when compared with normal cervical epithelium. Nine of 15 (60%) tumors exhibited LOH at 3p22 or reduced expression of TβR‐II, suggesting that reduced TβR‐II levels contribute to cervical tumorigenesis. Two cases exhibited silent germline polymorphisms of TβR‐II: one corresponding to a C1167T transversion and the other to an A1266G transition. The FHIT gene, which is located at 3p14.2, also frequently incurred LOH and abnormal transcription in these tumors. LOH of FHIT was observed in five of the 15 tumors analyzed. Neither mutations nor homozygous deletions of FHIT were detected in the tumors. However, aberrantly short transcripts of the FHIT gene were evident in six of nine (67%) tumors. Only one of these also displayed LOH, indicating that this gene was altered in at least 10 of 15 (67%) tumors. These results provide evidence that the inactivation of two known tumor‐suppressor genes, TβR‐II and FHIT, on chromosome 3p is involved in cervical carcinogenesis. Mol. Carcinog. 30:159–168, 2001. © 2001 Wiley‐Liss, Inc.