bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualization of poly(ether imide) and polycarbonate blending in an internal mixer
Authors: Lin Bin , Sundararaj Uttandaraman
Published: February 2004

The blending process of poly(ether imide)/polycarbonate (PEI/PC) was studied by visualization of blending in an internal mixer at 340°C. Distinct pellet deforming, softening, aggregation, stretching, bending, sheeting, and dispersing were seen during the blending process. By ramping the temperature of the barrel of the internal mixer, the process of pellet softening and deforming, and the phase‐inversion phenomenon were studied by examining the visualization results and the torque readings. It was found that a peak in torque occurred at the phase‐inversion point. It was also found that the blends are semitransparent at higher PEI composition (>80 wt %). SEM and TEM micrographs and DSC data verified the visualization result that PEI/PC blends are partially miscible at higher PEI compositions. The number‐average particle size was determined for the PEI/PC blends and it was found that the experimental results in the dilute solution limit for both PC drops and PEI drops did not match with the particle size predicted by Taylor's theory. The particle sizes at 15 wt % concentration were of the same order of magnitude as those calculated using Wu's correlation. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1165–1175, 2004
Expression of hypoxia‐inducible, membrane‐bound carbonic anhydrase isozyme XII in mouse tissues
Authors: Halmi Piia , Lehtonen Jonna , Waheed Abdul , Sly William S. , Parkkila Seppo
Published: February 2004

Carbonic anhydrase (CA) XII is a membrane‐associated enzyme that has been demonstrated to be normally expressed in some human tissues, to be upregulated in some cancers, and to be a hypoxia‐inducible gene product. In mouse, CA XII has been recently localized in the kidney. In the present study, we investigated CA XII gene and protein expression in other mouse tissues, with the kidney serving as a positive control for the reagents. The expression of CA XII mRNA was examined using polymerase chain reaction (PCR) amplification of commercial cDNAs produced from selected mouse tissues. A strong positive signal for CA XII mRNA was detected in the kidney, and weak signals were obtained in the testis and lung. Heart, spleen, liver, and skeletal muscle were negative. Immunohistochemical staining was performed using a mouse CA XII‐specific antibody and biotin‐streptavidin complex method. The results showed high expression of CA XII in the kidney, as expected. It was also highly expressed in the surface epithelial cells of the colon, whereas it was absent in the stomach, proximal small intestine, pancreas, liver, heart, and skeletal muscle. The maturing sperm cells showed a weak staining in a pattern that most probably indicates expression in the developing acrosomal membrane. The high expression in the kidney and colon suggests a role for CA XII in the maintenance of body ion and pH homeostasis in the mouse. However, the present findings demonstrated that CA XII has a very limited distribution in mouse tissues outside these two organs. Anat Rec Part A 277A:171–177, 2004. © 2004 Wiley‐Liss, Inc.
Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion
Authors: Crivellato Enrico , Belloni Anna , Nico Beatrice , Nussdorfer Gastone G. , Ribatti Domenico
Published: February 2004

Exocytosis is considered the main route of granule discharge in chromaffin cells. We recently provided ultrastructural evidence suggesting that piecemeal degranulation (PMD) occurs in mouse adrenal chromaffin cells. In the present study, we processed rat adrenal glands for transmission electron microscopy (TEM), and examined chromaffin cells for changes characteristic of PMD. Both adrenaline (A)‐ and noradrenaline (NA)‐storing cells express ultrastructural features suggestive of a slow and particulate mode of granule discharge. In adrenaline‐containing cells, some granules present enlarged dimensions accompanied by eroded or dissolved matrices. Likewise, a number of granules in NA‐releasing cells show content reduction with variably expanded granule chambers. Dilated, empty granule containers are recognizable in the cytoplasm of both cell types. Characteristically, altered granules and empty containers are seen intermingled with normal, resting granules. In addition, chromaffin granules often show irregular profiles, with budding or tail‐like projections of their limiting membranes. Thirty 150‐nm‐diameter membrane‐bound vesicles with a moderately electron‐dense or ‐lucent internal structure are observable in the cytoplasm of both cell types. These vesicles are seen among the granules and some of them are fused with the perigranule membranes in the process of attachment to or budding from the granules. These data add further support to the concept that PMD may be an alternative secretory pathway in adrenal chromaffin cells. Anat Rec Part A 277A:204–208, 2004. © 2004 Wiley‐Liss, Inc.
The dorsal lingual epithelium of Rhinoclemmys pulcherrima incisa (Chelonia, Cryptodira)
Authors: Josef Beisser Christian , Lemell Patrick , Weisgram Josef
Published: February 2004

This study employed light microscopic (LM), scanning electron microscopic (SEM), and transmission electron microscopic (TEM) methods to provide detailed morphological information on the histological and ultrastructural features of the dorsal tongue epithelium of Rhinoclemmys pulcherrima incisa. SEM revealed columnar papillae laterally, as well as papillae, which tend to have a ridge‐like appearance in the center of the tongue. LM and TEM showed three different zones of lingual epithelium: a stratified apical area with serous cells at the top of the papillae, a stratified lateral area with both serous and mucus cells, and an unstratified glandular area consisting of distinct glandular ducts with mucus cells. Comparison with morphological data from other turtles shows that the lingual epithelial structure in R. p. incisa is in accordance with that observed for other generalized omnivores which prefer a terrestrial lifestyle, thus matching the ecological information about this species. Anat Rec Part A 277A:227–235, 2004. © 2004 Wiley‐Liss, Inc.
Postnatal growth of cardiomyocytes in the left ventricle of the rat
Authors: Wulfsohn D. , Nyengaard J.R. , Tang Y.
Published: February 2004

We studied the development of myocytes and interstitium using perfusion‐fixed left ventricles obtained from normal female Wistar rats at 5 days (n = 5), 25 days (n = 5), and 125 days (n = 5) of age. Using design‐based stereological methods and light microscopy, we estimated the following parameters: volume of left ventricle made up by myocytes, myocyte nuclei, and interstitium; total numbers of myocyte and non‐myocyte nuclei; mean volumes of myocyte nuclei; the total volume, surface area, and length of fibers; and the mean star volumes of fibers. Some derived parameters were also calculated, namely, the mean myocardium volume per nucleus and the mean fiber cross‐sectional area. We found that postnatal myocyte growth after day 5 in the young rat is largely hypertrophic, while interstitial growth is hyperplastic. The increase in left ventricular mass was 10‐fold over the ages studied, whereas total length, surface area, and volume of fibers increased approximately 3‐, 8‐, and 11‐fold over the period. Relative rates of growth implied that fiber growth was dominated by an increase in length compared to other dimensions. The total number of myocyte nuclei (∼30 × 106) did not change between 5 and 25 days of age, but then almost doubled in 125‐day‐old rats. The number of non‐myocyte nuclei increased 9‐fold over the period studied in an exponential manner. The mean myocyte nucleus volume tripled between the ages of 5 and 25 days and then remained the same. The volume‐weighted mean nucleus volume was highly variable and showed no significant trend with age. Our results provide support for the claim made by some researchers that myocyte proliferation had ceased by day 5 after birth, but do not provide evidence for binucleation of myocytes between 5 and 25 days after birth. Reported numbers of myocyte nuclei express a net growth and do not rule out both myocyte death and creation throughout the early postnatal period. We clearly detect an increase in the number of myocyte nuclei from 25 to 125 days but are not able to state whether this increase reflects myocyte proliferation or myocyte binucleation. To determine this would require special double‐staining techniques to delineate intercalated discs and myocyte membranes. Our results agree very well with the limited data available from other studies that have used unbiased stereology. It is important to use unbiased designs that consider anisotropy as well as heterogeneity of the heart in sampling schemes, and to determine absolute quantities to avoid problems associated with interpreting changes in density (the “reference trap”). Anat Rec Part A 277A:236–247, 2004. © 2004 Wiley‐Liss, Inc.
Insect digestion: Potential applications in insect management
Authors: Oppert Brenda , Johnson Kelly
Published: February 2004

The papers assembled in this special issue were originally presented by researchers gathered at an informal symposium entitled “Insect Digestion: Potential Applications in Insect Management” at the National Meeting of the Entomological Society of America in Fort Lauderdale, Florida in November 2002. Although symposium participants and attendees clearly came from a diversity of backgrounds, they shared a common goal: to bring together their collective knowledge of insect digestive physiology and promote discussions of control methods that target insect digestion. The manuscripts published in this issue reflect the breadth of that knowledge. They include a structural and functional study of a peptide hormone that modulates digestion in mosquitoes, investigation of responses of Colorado potato beetle to transgenically expressed proteinase inhibitors, demonstration of the importance of phosphorous as a nutritive element of caterpillars, and phylogenetic analysis of insect trypsins and inhibitor resistance. The papers reinforce the notion that approaches to the study of insect digestion are as diverse as the insects we study, and it is our hope that this endeavor will promote new ideas for effective pest management tools.

The organizers would like to thank the Entomological Society of America for hosting the informal symposium, and to all who presented and attended. We are especially grateful to the Executive Editor of Archives of Insect Biochemistry and Physiology, David Stanley, and his editorial staff for making publication of this special issue possible.
Biochemical and cytoimmunological evidence for the control of Aedes aegypti larval trypsin with Aea‐TMOF
Authors: Borovsky Dov , Meola Shirlee M.
Published: February 2004

Trypsin and chymotrypsin‐like enzymes were detected in the gut of Aedes aegypti in the four larval instar and pupal developmental stages. Although overall the amount of trypsin synthesized in the larval gut was 2‐fold higher than chymotrypsin, both enzymes are important in food digestion. Feeding Aea‐Trypsin Modulating Oostatic Factor (TMOF) to Ae. aegypti and Culex quinquefasciatus larvae inhibited trypsin biosynthesis in the larval gut, stunted larval growth and development, and caused mortality. Aea‐TMOF induced mortality in Ae. aegypti, Cx. quinquefasciatus, Culex nigripalpus, Anopheles quadrimaculatus, and Aedes taeniorhynchus larvae, indicating that many mosquito species have a TMOF‐like hormone. The differences in potency of TMOF on different mosquito species suggest that analogues in other species are similar but may differ in amino acid sequence or are transported differently through the gut. Feeding of 29 different Aea‐TMOF analogues to mosquito larvae indicated that full biological activity of the hormone is achieved with the tetrapeptide YDPA. Using cytoimmunochemical analysis, intrinsic TMOF was localized to ganglia of the central nervous system in larvae and male and female Ae. aegypti adults. The subesophageal, thoracic, and abdominal ganglia of both larval and adult mosquitoes contained immunoreactive cells. Immunoreactive cells were absent in the corpus cardiacum of newly molted 4th instar larvae but were found in late 4th instar larvae. In both males and females, the intrinsic neurosecretory cells of the corpus cardiacum were filled with densely stained immunoreactive material. These results indicate that TMOF‐immunoreactive material is synthesized in sugar‐fed male and female adults and larvae by the central nervous system cells. Arch. Insect Biochem. Physiol. 55:124–139, 2004. © 2004 Wiley‐Liss, Inc.
Dietary phosphorus affects the growth of larval Manduca sexta
Authors: Perkins Marc C. , Woods H. Arthur , Harrison Jon F. , Elser James J.
Published: February 2004

Although phosphorus has long been considered an important factor in the growth of diverse biota such as bacteria, algae, and zooplankton, insect nutrition has classically focused on dietary protein and energy content. However, research in elemental stoichiometry has suggested that primary producer biomass has similar N:P ratios in aquatic and terrestrial systems, and phosphorus‐rich herbivores in freshwater systems frequently face phosphorus‐limited nutritional conditions. Therefore, herbivorous insects should also be prone to phosphorus limitation. We tested this prediction by rearing Manduca sexta larvae on artificial and natural (Datura wrightii leaves) diets containing varying levels of phosphorus (approximately 0.20, 0.55, or 1.2% phosphorus by dry weight). For both artificial and natural diets, increased dietary phosphorus significantly increased growth rates and body phosphorus contents, and shortened the time to the final instar molt. Caterpillars did not consistently exhibit compensatory feeding for phosphorus on either type of diet. The growth and body phosphorus responses were not explicable by changes in amounts of potassium or calcium, which co‐varied with phosphorus in the diets. Concentrations of phosphorus in D. wrightii leaves collected in the field varied over a range in which leaf phosphorus is predicted to affect M. sexta's growth rates. These results suggest that natural variation in dietary phosphorus is likely to affect the growth rate and population dynamics of M. sexta, and perhaps larval insects more generally. Arch. Insect Biochem. Physiol. 55:153–168, 2004. © 2004 Wiley‐Liss, Inc.
Coevolution of insect trypsins and inhibitors
Authors: Lopes A.R. , Juliano M.A. , Juliano L. , Terra W.R.
Published: February 2004

Many plant proteinase inhibitors have lysine at the P1 position, presumably to avoid hydrolysis by insect trypsins. Lepidopteran trypsins appear to have adapted to resist proteinase inhibitors through increased inhibitor hydrolysis and decreased binding to inhibitor hydrophilic reactive sites. Lepidopteran digestive trypsins prefer lysine at the P1 position and have substrate binding subsites more hydrophobic than trypsins from insects in other orders. All available sequences of sensitive and inhibitor‐insensitive insect trypsins were aligned with porcine trypsin, for which interactions with Kunitz and Bowman‐Birk inhibitor are known. After discounting conserved positions and positions not typical of sensitive or insensitive trypsins, the following residues were considered important to insect trypsin‐PI interactions (chymotrypsin numbering): 60, 94, 97, 98, 99, 188, 190, 213, 215, 217, 219, 228. These residues support the Neighbor Joining analysis tree branches separating sensitive and insensitive trypsin sequences. Primary sequences interacting with PIs are around the active site, with some forming part of the S1 (188, 217, 219 and 228) or S4 (99, 215) pockets. Arch. Insect Biochem. Physiol. 55:140–152, 2004. © 2004 Wiley‐Liss, Inc.
Colorado potato beetles compensate for tomato cathepsin D inhibitor expressed in transgenic potato
Authors: Brunelle France , Cloutier Conrad , Michaud Dominique
Published: February 2004

We reported earlier the importance of digestive cathepsin D‐like activity for initiating dietary protein hydrolysis in Colorado potato beetle, Leptinotarsa decemlineata Say [Brunelle et al. (1999) Arch. Insect Biochem. Physiol. 42:88–98]. We assessed here whether transgenic lines of potato (Solanum tuberosum L.) expressing a cathepsin D inhibitor (CDI) from tomato would show resistance to the beetle, or if the insect would compensate for the loss of cathepsin D activity after ingesting the recombinant inhibitor. Transgenic potato lines expressing tomato CDI were developed by Agrobacterium tumefaciens genetic transformation, and selected based on their relative amount of CDI. After confirming the absence of detectable visible effects of CDI on the plant's phenotype, diet assays with control and transgenic lines were carried out to assess the impact of the inhibitor on growth and development of the insect. Leaf consumption, relative growth rate, molting incidence, and digestive protease activity were monitored at 12‐h intervals over 132 h for 3rd‐instar larvae provided with transgenic potato foliage. Leaf consumption and relative growth rate were slightly reduced during the first 12 h for larvae fed CDI, but no significant differences were observed thereafter. In contrast, time for molting to the 4th larval stage was significantly longer for larvae fed modified plants, with developmental delays of ˜10 h (0.5 day) compared to control larvae. Recombinant CDI also had an impact on the insect's digestive physiology, readily inducing overproduction of digestive proteases (rubiscases), followed by a gradual decrease of total and pepstatin‐sensitive activity. Overall, these observations show the ability of Colorado potato beetle to compensate for the loss of cathepsin D activity by modulating its digestive protease complement in response to aspartate‐type inhibitors in the diet. From a practical viewpoint, these data stress the importance of devising improved strategies for the effective inhibition of insect digestive proteinases in vivo, based on the use of hybrid inhibitors active against different protease classes. Arch. Insect Biochem. Physiol. 55:103–113, 2004. © 2004 Wiley‐Liss, Inc.
Colorado potato beetles show differential digestive compensatory responses to host plants expressing distinct sets of defense proteins
Authors: Rivard Daniel , Cloutier Conrad , Michaud Dominique
Published: February 2004

Herbivorous insects fed plants expressing proteinase inhibitors (PIs) compensate for the loss of digestive proteolytic functions by producing novel proteinases. We assessed here whether such compensatory responses represent a general, non‐specific adaptation to defense‐related proteins in host plant tissues, or if distinct responses occur depending on the stress exerted on the plant. As a model, growth, development, and digestive proteases of the Colorado potato beetle (Leptinotarsa decemlineata Say) were monitored after feeding larvae with plants pre‐treated with either methyl jasmonate or arachidonic acid, two compounds inducing different sets of defense genes in potato. In brief, larvae fed plants treated with jasmonate or arachidonate were negatively affected compared to larvae fed non‐treated plants, suggesting the potency of both molecules to induce partial resistance to potato beetles in potato. On the other hand, larvae fed treated plants partially compensated for the presence of defense‐related proteins by adapting their digestive proteolytic system, both quantitatively and qualitatively. These compensatory processes varied depending on the treatment, the larvae fed arachidonate‐treated plants showing the most dramatic response. Compensation to jasmonate and arachidonate was also influenced by a cysteine PI from rice expressed in the plant, pointing out the possible indirect effects of recombinant defense proteins on naturally‐occurring plant–insect interactions. These observations, while showing the potential of jasmonate and arachidonate as inducers of partial resistance to the potato beetle in potato, also suggest that digestive compensation in herbivorous insects is determined, at least in part, by defense‐related compounds found in the plant in response to different stress stimuli or as a result of ectopic expression in transgenic plants. Arch. Insect Biochem. Physiol. 55:114–123, 2004. © 2004 Wiley‐Liss, Inc.
Synthesis, Anti‐inflammatory and Analgesic Synthesis, Anti‐inflammatory and Analgesic New 4(3H)‐Quinazolinone Derivatives
Authors: Yeşilada Akgül , Koyunoğlu Semra , Saygılıa Nezire , Kupeli Esra , Yeşilada Erdem , Bedir Erdal , Khanc Ikhlas
Published: February 2004

4(3H)‐Quinazolinone and pyrazole derivatives have been shown to have analgesic and anti‐inflammatory properties. In this study, 14 new 3‐methyl‐4(3H)quinazolinone derivatives bearing 2‐[1′‐phenyl‐3′‐(substituted‐phenyl)‐2′‐propenylidene]hydrazino or 2[5′‐(substituted phenyl)‐3′‐phenyl‐2′‐pyrazolin‐1′‐yl] groups have been synthesized with the aim of obtaining new analgesic and anti‐inflam matory leads. The structures were elucidated by means of UV, IR, 1H‐NMR, 13C‐NMR, mass spectroscopy, and elemental analysis data. The anti‐inflammatory activities of the synthesized compounds were determined by carrageenan‐induced hind paw edema test in mice. All the compounds showed statistically significant effects. For analgesic activity assessment, p‐benzoquinone‐induced writhing test was applied in mice. The results obtained were in accordance with the anti‐inflammatory activity tests.
Structure/Activity Investigations of 5‐Substituted 3‐Methylisoxazole[5, 4‐d]1, 2, 3‐triazin‐4‐one Derivatives
Authors: Jezierska Aneta , Maczyński Marcin , Koll Aleksander , Ryng Stanisław
Published: February 2004

The series of 5‐substituted 3‐methylisoxazole[5, 4‐d]1, 2, 3‐triazin‐4‐one derivatives was obtained by diazotization of 5‐amino‐3‐methylisoxazol‐4‐carboxylic acid hydrazide. The immunological activity of these compounds was investigated experimentally in several in vitro and in vivo assays in mice and human models. In the next step, quantum‐chemical investigations were performed using density functional theory with the B3LYP hybrid exchange‐correlation energy functional and 6‐31G(d, p) basis set. The Polarizable Continuum (SCRF/PCM) solvent model was also taken into account in order to show solvent influence on electron density and electrostatic potential around the exemplary molecules. Correlations between molecular structure and biological properties were found using a stepwise selection of scales for the multiple linear regression (MLR).
Thiirancarboxamides as Inhibitors of Papain
Authors: Bruno Gemma , Schirmeister Tanja
Published: February 2004

Derivatives of the thiirancarboxylic acid building‐block containing a peptide bond were synthesised and screened against the model cysteine protease papain. The most active of the series showed a second‐order rate constant of inactivation comparable to that of the parent compound. The insertion of a peptide moiety seems to compensate the lack of a free carboxylate interacting with the histidinium ion at the enzyme's active site.
Synthesis and NMDA‐Receptor Affinity of Ring and Side Chain Homologous Dexoxadrol Derivatives
Authors: Aepkers Marion , Wünsch Bernhard
Published: February 2004

The regioselectivity during transacetalization of benzophenone dimethyl acetal (4) with butane‐1, 2, 4‐triol (5) is controlled by the reaction conditions. Thermo‐dynamic control leads predominantly to the 1, 3‐dioxolane 6 whereas kinetic control favors the six‐membered acetal 7. The amines 2a—e and 3a—e are synthesized from the alcohols 6 and 7 and are investigated in receptor binding studies with radioligands for their affinity to the phencyclidine binding site of the NMDA—receptor. In both series the primary amines 2a and 3a show the highest NMDA—receptor affinity (2a: Ki = 3.38 μM; 3a: Ki = 1.45 μM). The NMDA receptor slightly prefers the 1, 3‐dioxane derivatives 3a and 3b compared to 2a and 2b (factor 2—3). Low interactions of the amines 3a and 3b with various receptor and reuptake systems indicate selectivity for the NMDA receptor. Surprisingly, the piperidine derivative 2e binds with high affinity at σ1‐receptors and, therefore, represents a novel lead compound for high affinity σ1‐receptor ligands.
The Synthesis and Anticonvulsant Activity of some ω‐Phthalimido‐N‐phenylacetamide and Propionamide Derivatives
Authors: Soyer Zeynep , Kılıc Fatma Sultan , Erol Kevser , Pabuccuoglu Varol
Published: February 2004

In this study, by combining anilide and N′, N′‐phthaloylglycinamide pharmacophores which are known to produce potent anticonvulsant compounds, sixteen ω‐phthalimido‐N‐phenylacetamide and propionamide derivatives bearing substituents at positions 2 or 2, 6 on N‐phenyl ring have been synthesized. The structural confirmation of the title compounds was achieved by interpretation of spectral and analytical data. The anticonvulsant activity of the title compounds was determined against maximal electroshock seizure at 100 mg/kg dose level in mice. The preliminary screening results indicated that ω‐phthalimido‐N‐phenylacetamide and propionamide nuclei have pronounced anticonvulsant activity against maximal electroshock seizure.
Recently Synthesized Class of Vinylphosphonates as Potent Matrix Metalloproteinase (MMP‐2) Inhibitors
Authors: Al‐Quntar Abed Al‐Aziz , Baum Ofir , Reich Reuven , Srebnik Morris
Published: February 2004

An in vitro evaluation of MMP‐2 inhibitors for a series of novel vinylphosphonic acids and phosphonic esters that contain various functional groups, shows that various types exhibit excellent efficiency, and points towards potent, promising compounds. Other types displayed relatively weak activity.
Sequential changes in plasma selenium concentration after cadaveric renal transplantation
Authors: Morris-Stiff G J , Oleesky D A , Smith S C , Jurewicz W A
Published: February 2004

Background

Previous investigations have shown that plasma selenium concentrations are significantly lower in patients with established chronic graft nephropathy (CGN) than in healthy transplant controls. The aims of this study were to determine when in the transplant process low selenium concentrations become apparent and to explore the relationship between selenium levels and risk factors for CGN.

Methods

Plasma selenium concentrations were measured in 40 patients (20 receiving cyclosporin, 20 receiving tacrolimus) undergoing transplantation. Samples were obtained immediately before transplantation and at 3, 6 and 12 months after transplantation.

Results

A low plasma selenium concentration was found in 30 patients at the time of transplantation but this had normalized in the majority of patients by 3 months. Plasma selenium concentrations at 3, 6 and 12 months were significantly higher than baseline values for both treatment arms, but were significantly lower at 3 months in patients who experienced either clinical acute rejection (CAR) or cytomegalovirus (CMV) infection during the preceding months.

Conclusion

Low plasma selenium concentrations are common at the time of transplantation but appear to normalize thereafter. The identification of low selenium levels in patients who experience CAR or CMV (two important risk factors for clinically apparent CGN) suggests that the relationship between selenium and CGN warrants further investigation.
Gene expression profiling of renal medullary carcinoma
Authors: Yang Ximing J. , Sugimura Jun , Tretiakova Maria S. , Furge Kyle , Zagaja Gregory , Sokoloff Mitchell , Pins Michael , Bergan Raymond , Grignon David J. , Stadler Walter M. , Vogelzang Nicholas J. , Teh Bin Tean
Published: February 2004

BACKGROUND

Renal medullary carcinoma is a rare kidney tumor with highly aggressive behavior. This tumor occurs exclusively in young patients with sickle cell trait or disease. To the authors' knowledge, very little is known to date regarding the underlying molecular genetics of this tumor, and no effective therapy has been established.

METHODS

The authors analyzed the gene expression profiles of 2 renal medullary carcinomas from patients with sickle cell trait using microarrays containing 21,632 cyclic DNA (cDNA) clones and compared them with the gene expression profiles of 64 renal tumors.

RESULTS

Based on global gene clustering with 3583 selected cDNAs, the authors found a distinct molecular signature of renal medullary carcinoma, which clustered closely with urothelial (transitional cell) carcinoma of the renal pelvis, rather than renal cell carcinoma (RCC). This finding of a significant difference in the gene expression patterns of renal medullary carcinoma compared with RCC suggests that this tumor should not be treated as a conventional RCC but, rather, as a special malignancy. This study also identified genes/proteins that may serve as biomarkers for renal medullary carcinoma or as potential targets of novel therapies. In addition, comparative genomic microarray analysis allowed the authors to predict the lack of chromosomal imbalances in this tumor.

CONCLUSIONS

To the authors' knowledge, the current study is the first molecular profiling of renal medullary carcinoma, a rare but highly aggressive kidney carcinoma. The genes that are expressed specifically in this tumor may lead to not only a better understanding of its molecular pathways and discoveries of novel diagnostic markers but also, more important, to effective therapeutic interventions. Cancer 2004;100:976–85. © 2004 American Cancer Society.
Low recurrence rate after surgery for dermatofibrosarcoma protuberans
Authors: DuBay Derek , Cimmino Vincent , Lowe Lori , Johnson Timothy M. , Sondak Vernon K.
Published: February 2004

BACKGROUND

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma with a propensity for local recurrence. Treatments with wide excision, Mohs surgery, and other approaches have been reported with widely variable local control rates. The objective of this study was to review the experience with a multidisciplinary approach employing wide excision and Mohs surgery selectively in the treatment of patients with DFSP at a single academic institution over the past 10 years.

METHODS

The records of 62 patients with 63 DFSP tumors who underwent wide excision, Mohs surgery, or a multidisciplinary combination approach from January 1991 to December 2000 were reviewed retrospectively. Primary endpoints included the ability to extirpate the DFSP lesion completely, the tumor recurrence rate, and the need for skin grafts or local tissue flaps. Additional objectives included defining surgical practice patterns at the authors' institution.

RESULTS

Sixty‐three DFSP lesions were removed from 62 patients. At a median follow‐up of 4.4 years, no local or distant recurrences were detected in any patient. Forty‐three lesions were treated with wide local excision, 11 lesions were treated with Mohs surgery, and 9 lesions were treated with a combination approach. Ninety‐five percent of lesions that were approached initially with wide local excision were cleared histologically. Two patients (5%) received postoperative radiation for positive margins after undergoing maximal excision. Eighty‐five percent of lesions that were approached initially with Mohs surgery were cleared histologically. The remaining 15% of lesions subsequently were cleared surgically with a wide excision. DFSP lesions that were approached initially with Mohs surgery tended to be smaller. Patients with head and neck lesions most often underwent Mohs surgery or were treated with a multidisciplinary combination approach (87%).

CONCLUSIONS

Wide local excision with careful pathologic analysis of margins was found to have a very low recurrence rate and was used for the majority of patients with DFSP lesions at the authors' institution. Wide local excision, Mohs surgery, and a multidisciplinary combination approach, selected based on both tumor and patient factors, were capable of achieving very high local control rates in the treatment of DFSP. The evolution of a multidisciplinary approach has provided a level of expertise that no single individual could achieve for the treatment of the full spectrum of DFSP lesions at the authors' institution. Cancer 2004;100:1008–16. © 2004 American Cancer Society.
Screening computed tomography
Authors: Fenton Joshua J. , Weiss Noel S.
Published: February 2004

BACKGROUND

Despite uncertain benefits and harms, screening computed tomography (CT) is being marketed to consumers in the U.S. One plausible harm is the detection and treatment of renal carcinoma cases that otherwise would have remained clinically silent during the patient's lifetime.

METHODS

After estimating the prevalence of preclinical renal carcinoma using meta‐analysis of five series of asymptomatic, middle‐aged Americans who received CT screening, the authors divided the prevalence by U.S. incidence rates of clinical renal carcinoma among persons of similar age. This calculation would estimate the mean duration of the detectable preclinical period (the “sojourn time”) of renal carcinoma if the incidence of preclinical and clinical renal carcinoma were equivalent.

RESULTS

The 5 series included 16,174 screenees (mean age range, 58–64 years; 61% male). The prevalence of asymptomatic renal carcinoma ranged from 0.11% to 0.76%; the pooled prevalence was 0.21% (95% confidence interval, 0.14–0.28%). The estimated mean sojourn time for renal carcinoma was between 3.7 years and 5.8 years among middle‐aged Americans.

CONCLUSIONS

Because most renal carcinomas grow slowly during the preclinical period, the authors' estimated mean sojourn time did not seem unduly long. Therefore, the incidence rate of clinical renal carcinoma most likely is a reasonable surrogate for the incidence rate of preclinical renal carcinoma, implying that most renal carcinomas detected by CT screening among middle‐aged Americans are likely to progress to clinical diagnosis. Cancer 2004;100:986–90. © 2004 American Cancer Society.
Redirected T‐cell cytotoxicity to epithelial cell adhesion molecule‐overexpressing adenocarcinomas by a novel recombinant antibody, E3Bi, in vitro and in an animal model
Authors: Ren‐Heidenreich Lifen , Davol Pamela A. , Kouttab Nicola M. , Elfenbein Gerald J. , Lum Lawrence G.
Published: February 2004

BACKGROUND

To redirect cytotoxic T cells to target a broad range of adenocarcinomas, the authors constructed a novel, recombinant, bispecific antibody, E3Bi, directed at the tumor‐associated antigen, epithelial cell adhesion molecule (EpCAM), and the CD3 receptor on T cells.

METHODS

T cells were prepared from healthy blood donors. The cytotoxicity of activated T cells (ATC) redirected to tumor cells by E3Bi was measured with in vitro 51Cr release assays. In vivo studies were performed in a severe combined immunodeficient (SCID)/Beige mouse xenograft model. Tumor‐bearing mice were treated with low doses (1 mg/kg) or high doses (10 mg/kg) of E3Bi along with ATC (2 × 109 cells/kg), and treatment efficacy was evaluated both by ex vivo tumor cell survival assay after in vivo treatments and by in vivo tumor growth delay studies.

RESULTS

In vitro, targeting the EpCAM‐overexpressing human tumor cell lines with E3Bi increased specific cytotoxicity of ATC by > 70% at an effector‐to‐target ratio of 2.5 (P < 0.001); this cytotoxicity was abolished competitively in the presence of an anti‐EpCAM monoclonal antibody. In contrast, E3Bi did not enhance ATC cytotoxicity toward the low EpCAM‐expressing tumor cell line. In ex vivo tumor cytotoxicity assays, a significant reduction in tumor cell survival (40% with low‐dose E3Bi; 90% with high‐dose E3Bi) was observed in E3Bi/ATC‐treated mice compared with control mice that were treated with ATC only. In addition, SCID/Beige mice xenografted with LS174T tumors demonstrated a significant tumor growth delay (P = 0.0139) after receiving E3Bi/ATC/interleukin 2 (IL‐2) compared with mice that received ATC/IL‐2 alone.

CONCLUSIONS

E3Bi specifically and very efficiently redirected T cells to destroy EpCAM‐overexpressing tumors both in vitro and in an animal model. These results suggest a therapeutic utility for E3Bi in the treatment of adenocarcinomas. Cancer 2004;100:1095–103. © 2004 American Cancer Society.
Birth characteristics and hepatoblastoma risk in young children
Authors: Reynolds Peggy , Urayama Kevin Y. , Von Behren Julie , Feusner James
Published: February 2004

BACKGROUND

Although hepatoblastoma is a very rare childhood cancer, its incidence appears to be rising, especially among children with very low birth weight. With the exception of documented correlations with certain congenital anomalies, the etiology of hepatoblastoma remains largely unknown.

METHODS

Using California's population‐based cancer registry, the authors identified 113 children ages birth–4 years with hepatoblastoma who were diagnosed between 1988 and 1997. Ninety‐nine of those 113 children (88%) were matched to a California birth certificate, and randomly selected controls from the same birth certificate files were matched to cases (4:1) according to the month and year of birth and gender. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression analyses.

RESULTS

A strikingly elevated risk of hepatoblastoma was found in children who were born with very low birth weight (< 1500 g; OR, 50.57; 95% CI, 6.59–387.97). A plot of the distribution by birth weight showed interesting peaks at birth weights < 1000 g and 3000–3499 g among cases. Children who weighed < 1000 g showed a statistically significant, linear trend toward being diagnosed at an older age (P = 0.036), which seemed to be explained in part by gestational age.

CONCLUSIONS

The results confirmed previously reported findings of an increased hepatoblastoma risk among children with very low birth weight and suggested that the etiology may differ between children with very low birth weight and children with normal birth weight. Cancer 2004;100:1070–6. © 2004 American Cancer Society.
A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status
Authors: Johnson Faye M. , Garden Adam , Palmer J. Lynn , Kies Merrill , Clayman Gary , Brumfield Brenda , Khuri Fadlo R. , Morrison William , Papadimitrakopoulou Vassiliki , Diaz Eduardo M. , Glisson Bonnie S.
Published: February 2004

BACKGROUND

Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1–3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5‐fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1–2N2–3M0 NPC.

METHODS

Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time‐concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy.

RESULTS

Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off‐study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases.

CONCLUSIONS

Although unlikely to be superior to cisplatin + 5‐fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk‐based approach examined in the current study merits further investigation. Cancer 2004;100:991–8. © 2004 American Cancer Society.
Survival among women with borderline ovarian tumors and ovarian carcinoma
Authors: Sherman Mark E. , Mink Pamela J. , Curtis Rochelle , Cote Timothy R. , Brooks Sandra , Hartge Patricia , Devesa Susan
Published: February 2004

BACKGROUND

Serous and mucinous ovarian tumors of low malignant potential (LMP‐S and LMP‐M, respectively) are noninvasive tumors that portend excellent survival when confined to the ovary. Comparison of the survival for women with LMP tumors staged as distant with women who have carcinoma may have important implications for diagnostic terminology and clinical management.

METHODS

The authors compared relative survival rates among patients diagnosed with ovarian tumors during the period 1988–1999 (with follow‐up through 2000) by histologic type, disease stage, tumor grade (for carcinomas), and patient age, using data from the Surveillance, Epidemiology, and End Results Program.

RESULTS

The overall relative survival rate at 10 years (± 1.96 standard errors) was 96.9% ± 2.3% for women with LMP‐S tumors, 30.4% ± 1.7% for women with serous carcinoma (CA‐S); 94.0% ± 3.1% for women with LMP‐M tumors, and 64.7% ± 3.4% for women with mucinous carcinoma (CA‐M). The survival rate at 10 years for women with distant‐stage LMP‐S tumors was 89.9% ± 5.3%, compared with 96.1% ± 8.6% for women with well differentiated, localized CA‐S. The survival rate for women with distant‐stage LMP‐M tumors at 5 years was 85.5% ± 9.0%, compared with 95.5% ± 3.4% for women with well differentiated, localized CA‐M (data for 10 years were limited). Mucinous ovarian neoplasms were associated with an excess of second malignancies of the digestive tract.

CONCLUSIONS

Relative survival among women with distant‐stage LMP tumors was not 100% and resembled the survival of women who had carcinoma exhibiting favorable prognostic features (localized stage). Future studies of women with high‐stage LMP tumors are required to clarify the pathogenesis of extraovarian lesions and their implications for management and prognosis. Cancer 2004;100:1045–52. Published 2004 by the American Cancer Society.
Parathyroid carcinoma: Evaluation and interdisciplinary management
Authors: Clayman Gary L. , Gonzalez Hernan E. , El‐Naggar Adel , Vassilopoulou‐Sellin Rena
Published: February 2004

BACKGROUND

A review of recent reports found a distinct clinical behavior pattern in the rare clinical entity of parathyroid carcinoma, although to the authors' knowledge information on oncogenetic changes, prognostic factors, and the potential benefits of adjuvant therapy remain fragmented and scarce. In this report, a composite review of the literature and The University of Texas M. D. Anderson Cancer Center (M. D. Anderson) experience are presented using the presentation of a patient to illustrate critical issues in the evaluation and interdisciplinary management of patients who are afflicted with this disease.

METHODS

The current study reflects a retrospective case review of patients who were diagnosed with parathyroid carcinoma, treated, and followed at M. D. Anderson from 1983 to 2002. To assure standardization of pathologic diagnosis as well as evaluations and interdisciplinary management, the investigators reviewed all cases using predetermined criteria within their specialties.

RESULTS

It is interesting to note that M. D. Anderson data showed classic pathologic features that were not always present in all parathyroid carcinomas (at most, some features were noted in 37% of patients). Other results of interest indicated local recurrence rates that appeared lower if adjuvant radiation was applied after initial surgery, independent of the type of surgery or disease stage. In the authors' experience, 70% of patient's tumors exhibited local invasion, although their 5‐year survival rate of 85% was consistent with that reported previously, and their 10‐year survival rate was somewhat higher at 77%.

CONCLUSIONS

Parathyroid carcinoma is a rare clinical entity that requires interdisciplinary evaluation and management. Comprehensive surgical excision of parathyroid carcinomas with verification of normalization of intraoperative parathyroid hormone levels should be sought. Cancer 2004;100:900–5. © 2004 American Cancer Society.
Development of potential anti‐cancer agents: Diazenes and derivatives
Authors: Čimbora‐Zovko Tamara , Bombek Sergeja , Košmrlj Janez , Kovačić Lidija , Polanc Slovenko , Katalinić Ana , Osmak Maja
Published: February 2004

The call for the discovery of more effective agents to treat cancer has become urgent. Recently, we have synthesized new compounds: diazenes. So far, we have demonstrated that several of them inhibited the growth of tumor cells, but their solubility and biological activity were relatively low. Therefore, new compounds have been synthesized to improve their solubility and biological efficacy. In the present study, we screened cytotoxicity of 26 new diazenes and their derivatives on human cervical carcinoma HeLa cells. The most active compound was tested also on human laryngeal carcinoma, breast adenocarcinoma, and glioblastoma cells, as well as on two drug‐resistant sublines derived from cervical and laryngeal carcinoma cells. Cytotoxicity of new compounds was determined using a colorimetric MTT assay. Results show that diazene SB‐681 was the most efficient one, reducing significantly survival of HeLa cells, with IC50 value of 16.3 μM. This compound applied in low doses inhibited also the growth of other cell lines tested, among which were two drug‐resistant cell lines. The observed activity could be explained by the influence of groups attached to the diazene functionality, namely 2‐chloroethylaminocarbonyl moiety and pentafluorophenyl moiety attached to the diazene nitrogen‐nitrogen double bond. Our data indicate that SB‐681 is a promising leading compound in the development of a novel class of antineoplastic agents. Drug Dev. Res. 61:95–100, 2004. © 2004 Wiley‐Liss, Inc.
An information filtering method for emergency management
Authors: Atoji Yusuke , Koiso Takashi , Nakatani Mie , Nishida Shogo
Published: February 2004

Information filtering is a function to select useful or interesting information for the user among a large amount of information. This function has become very important as network technology develops rapidly. This paper focuses on information filtering for emergency management. When a large‐scale disaster happens, the problem of information flood can be very serious because a great deal of information occurs in a short time and is sent to a person or an organization that is responsible for managing the situation.

In this paper, we first consider features of information in emergency situations, and propose an information filtering system for emergency management. The proposed system is composed of three parts: message structuring part, causal analysis part, and information classification part. A prototype system is developed and its effectiveness is evaluated by experiments. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 147(1): 60–69, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10233