bluuebunny/crossref_metadata_2025 huggingface dataset:
Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia
Authors: O'Brien Susan M. , Kantarjian Hagop M. , Thomas Deborah A. , Cortes Jorge , Giles Francis J. , Wierda William G. , Koller Charles A. , Ferrajoli Alessandra , Browning Mary , Lerner Susan , Albitar Maher , Keating Michael J.
Published: December 2003

BACKGROUND

The objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti‐CD52 monoclonal antibody, in patients with B‐cell chronic lymphocytic leukemia and residual disease after chemotherapy.

METHODS

Forty‐one patients received alemtuzumab 3 times weekly for 4 weeks. The first 24 patients received 10 mg per dose, and the next 17 patients received 30 mg. All patients received infection prophylaxis during therapy and for 2 months after treatment.

RESULTS

The overall response rate was 46%, including 39% of patients who received the 10 mg dose and responded versus 56% of the patients who received the 30 mg dose. The major reason for failure to respond was the presence of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of 29 patients (38%) achieved a molecular disease remission. The median time to disease progression had not been reached in responders with a median follow‐up of 18 months. Six patients remained in disease remission between 24–38 months after therapy. Infusion‐related events were common with the initial doses, but all such events were NCI Common Toxicity Criteria Grade 1–2. Infections were reported to occur in 15 patients (37%), and 9 of these infections were reactivation of cytomegalovirus. Three patients developed Epstein–Barr virus positive, large cell lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin.

CONCLUSIONS

Alemtuzumab produced significant responses in patients with residual disease after chemotherapy. Bone marrow disease was eradicated more frequently than lymph node disease, and molecular disease remissions were achieved. A randomized trial comparing alemtuzumab with observation after chemotherapy is indicated. Cancer 2003;98:2657–63. © 2003 American Cancer Society.
Imatinib mesylate in Philadelphia chromosome‐positive leukemia of childhood
Authors: Kolb E. Anders , Pan Qiulu , Ladanyi Marc , Steinherz Peter G.
Published: December 2003

BACKGROUND

Initial treatment for adult patients with Philadelphia chromosome‐positive (Ph[+]) chronic myelogenous leukemia (CML) now includes imatinib mesylate. However, to our knowledge, there are few data regarding imatinib safety, efficacy, and response monitoring in patients age < 18 years.

METHODS

In the current series, the authors report 5 consecutive patients ages 20 months to 12 years with Ph(+) leukemia who were treated with imatinib and evaluated for a response using cytogenetics, fluorescent in situ hybridization (FISH), and real‐time quantitative reverse transcriptase–polymerase chain reaction (RT‐PCR) on serial bone marrow aspirations. Doses of imatinib were escalated as tolerated from a starting dose of 400 mg/m2 (patients with a body surface area [BSA] < 1 m2) or 400 mg/day (patients with a BSA > 1 m2).

RESULTS

After the initiation of imatinib therapy, all 4 patients with CML were found to have no detectable Ph chromosome by cytogenetics (median of 198 days of imatinib therapy; range, 138–346 days), FISH (median of 285 days of imatinib therapy; range, 138–366 days), and real‐time RT‐PCR (median of 287 days of imatinib therapy; range, 224–366 days). One patient with Ph(+) acute mixed lineage leukemia achieved a morphologic disease remission with standard chemotherapy, but within 10 months had increasing Ph positivity in consecutive bone marrow aspirations. Imatinib was added to the intensive leukemia therapy, and within 26 days there were no detectable Ph(+) cells in the bone marrow. Mild thrombocytopenia was noted in two patients and transient mild hepatic toxicity was noted in one patient.

CONCLUSIONS

Imatinib mesylate was found to be effective in inducing undetectable residual disease in a small cohort of pediatric patients with Ph(+) leukemia. Further studies of the use of imatinib in childhood Ph(+) malignancies are needed. Cancer 2003;98:2643–50. © 2003 American Cancer Society.
The US's retreat from the Kyoto Protocol: an account of a policy change and its implications for future climate policy
Authors: Steurer Reinhard
Published: December 2003

In March 2001, President G.W. Bush announced that the United States had abandoned the ratification of the Kyoto Protocol. This paper describes the historical background as well as the political reasons and mechanisms behind the Bush administration's decision. Moreover, it deals with two alternative policy proposals, which have emerged at the US federal and the state level since then. The paper then highlights some important differences between EU and US climate change policies. The most important difference is that the EU wants global warming mitigation and the US, if necessary at all, is emphasizing the need to adapt to climate change. The paper concludes by suggesting that if a post‐Kyoto treaty wants to bring the US back on board it will need to address this difference. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
An adaptive virtual topology reconfiguration policy in multi‐wavelength optical Internet
Authors: Lee Kyunghee , Zhang Lin , Youn Chan‐Hyun
Published: December 2003

This paper studies the issues arising in the virtual topology reconfiguration phase of optical Internet networks. This reconfiguration process means to change a virtual topology in response to the changing traffic patterns in a higher layer. We formulate the optimal reconfiguration policy as a multi‐stage decision‐making problem to maximize the expected reward and cost function over an infinite horizon. To counter the continual approximation problem brought by heuristic approach, we take the traffic prediction into consideration. We further propose a new heuristic reconfiguration scheme called prediction based multi‐stage reconfiguration approach to realize the optimal reconfiguration policy based on predicted traffic. Simulation results show that our reconfiguration policy significantly outperforms the conventional one, while the required physical resources are limited. Copyright © 2003 AEI.
Disruption of the genomic imprint in trans with homologous recombination at Snrpn in ES cells
Authors: Tsai Ting‐Fen , Bressler Jan , Jiang Yong‐hui , Beaudet Arthur L.
Published: December 2003

Summary: In gene targeting studies of the Prader‐Willi syndrome (PWS)/Angelman syndrome (AS) domain in mouse ES cells, we recovered only recombinants with the paternal allele for constructs at exons 2 or 3 of the imprinted, maternally silenced Snurf‐Snrpn gene. These sites lie close to the imprinting center (IC) for this domain. In contrast, recombinants for Ube3a within the same imprinted domain were recovered with equal frequency on the maternal and paternal alleles. In addition, gene targeting of the paternal allele for Snurf‐Snrpn resulted in partial or complete demethylation in trans with activation of expression for the previously silenced maternal allele. The imprint switching of the maternal allele in trans is not readily explained by competition for trans‐acting factors and adds to a growing body of evidence indicating homologous association of oppositely imprinted chromatin domains in somatic mammalian cells. genesis 37:151–161, 2003. © 2003 Wiley‐Liss, Inc.
Generation of a germ cell nuclear factor conditional allele in mice
Authors: Lan Zi‐Jian , Xu Xueping , Cooney Austin J.
Published: December 2003

Summary: Two recombination steps in embryonic stem (ES) cells were adopted to generate a floxed Germ Cell Nuclear Factor (GCNF) allele. First, a targeting vector containing a loxP site upstream of exon 4, encoding the DNA binding domain (DBD), and a floxed NeoTK double selection cassette downstream of exon 4 was integrated into the GCNF locus by homologous recombination. Second, a Cre‐expressing vector was transiently introduced to remove the floxed NeoTK cassette via site‐specific recombination. Heterogeneous ES cell populations were found in a single colony after Cre transfection and were separated using an ES cell re‐pick step. Floxed GCNF mice were generated and had normal GCNF expression in the adult gonads. Using the Msx2Cre transgenic mice, the floxed GCNF can be completely deleted in the female germline. Taken together, the floxed GCNF mice were successfully generated and female germline deletion of the floxed GCNF allele was achieved using Msx2Cre mice. genesis 37:172–179, 2003. © 2003 Wiley‐Liss, Inc.
Electroporation of cynomolgus monkey embryonic stem cells
Authors: Furuya Masataka , Yasuchika Kentaro , Mizutani Ken‐ichi , Yoshimura Yasunori , Nakatsuji Norio , Suemori Hirofumi
Published: December 2003

Efficient genetic modification of primate embryonic stem (ES) cells is essential for the application for both basic and preclinical research. The transfection efficiency of primate ES cells is reportedly lower than that of mouse ES cells. Cynomolgus monkey ES cells provide a powerful model for understanding human development and disease. We evaluated electroporation as a method to introduce foreign genes into cynomolgus monkey ES cells. Our examination has allowed us to establish a protocol producing about 100 stably transfected clones from 107 cynomolgus monkey ES cells. Differences in efficiency, however, were observed for other ES cell lines. We compared the transcriptional activities of the PGK‐1, CMV, and SV40 promoters in cynomolgus monkey ES cells generating efficient G418 selection. Although the PGK‐1 and SV40 promoters efficiently drove neo gene expression, the CMV promoter was significantly less transcriptionally active in cynomolgus monkey ES cells. Using this electroporation method, we established fluorescent cynomolgus monkey ES cell lines. These cells may be useful tools for tracing grafted cells in transplantation studies using a variety of functional cells derived from cynomolgus monkey ES cells. genesis 37:180–187, 2003. © 2003 Wiley‐Liss, Inc.
Dlx5/6‐enhancer directed expression of Cre recombinase in the pharyngeal arches and brain
Authors: Ruest Louis‐Bruno , Hammer Robert E. , Yanagisawa Masashi , Clouthier David E.
Published: December 2003

Dlx5 and Dlx6, two members of the Distalless gene family, are required for development of numerous tissues during embryogenesis, including facial and limb development. This gene pair is expressed in tandem, transcribed toward each other and separated by a short intergenic region containing multiple putative enhancers. Targeted inactivation of Dlx5 and Dlx6 in mice results in multiple developmental defects in craniofacial and limb structures, suggesting that these genes are crucial for aspects of both neural crest and nonneural crest development. To further investigate potential developmental roles of Dlx5 and Dlx6, we used one of the Dlx5/6 intergenic enhancers to drive Cre recombinase expression in transgenic mice. Crossing Dlx5/6‐Cre transgenic mice with mice from the R26R strain results in β‐galactosidase staining in the apical ectodermal ridge, brain, and neural crest‐derived mesenchyme of the pharyngeal arches, with staining in term embryos observed in the facial skeleton and specific brain structures. However, in contrast to endogenous expression patterns of Dlx5 and Dlx6, Cre expression within the pharyngeal arches occurs during a very narrow window in early development. Our studies suggest that Dlx5/6‐Cre mice may prove useful both in further understanding the function and regulation of Distalless genes during development and in studies of gene function in conditional knockout mice. genesis 37:188–194, 2003. © 2003 Wiley‐Liss, Inc.
Neuropsychological correlates of hippocampal and rhinal cortex volumes in patients with mesial temporal sclerosis
Authors: O'Brien Catherine E. , Bowden Stephen C. , Bardenhagen Fiona J. , Cook Mark J.
Published: December 2003

Considerable progress has been made toward understanding the function of the primate rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices. However, translating animal models to human memory has been limited by the technological problems associated with characterizing neural structures in vivo. Functional correlates of hippocampal and rhinal cortex volume changes were examined in a sample of 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS; 33 left, 28 right). Patients were administered the Wechsler Adult Intelligence Scale (revised or third edition), the Wechsler Memory Scale (revised or third edition), and a spatial maze task. Neuropsychological data, together with rhinal cortex and hippocampal volumes, collected in our earlier study (O'Brien CE, Bowden SC, Whelan G, Cook MJ, unpublished observations), were analyzed using multiple regression. The only significant predictor of verbal memory function was the difference score between the volume of left hippocampus and the left PrC. Spatial maze scores were predicted by the bilateral sum of ErC volume. The difference score between the left hippocampus and left PrC volumes was the most powerful predictor of verbal episodic memory. Right hippocampal volume was not a significant predictor of nonverbal episodic memory. Verbal and nonverbal semantic memory were not significantly predicted by any combination of rhinal cortex structures. This quantitative study suggests a lateralized or material‐specific memory function for the left hippocampus and left PrC, in contrast to the bilateral role of the ErC. The left hippocampus and left PrC appear to act on verbal memory function through an opposing relationship. Finally, differentiation between hippocampal and subhippocampal components in terms of episodic and semantic memory, respectively, could not be supported by the current data. © 2003 Wiley‐Liss, Inc.
Conduction latency along CA3 hippocampal axons from rat
Authors: Soleng Anne F. , Raastad Morten , Andersen Per
Published: December 2003

Relatively few physiological studies have been carried out on intrahippocampal axons. We have recorded compound potentials from fiber groups and the activity of individual axons at 22–25°C to characterize the conduction in subsets of the broad fan‐shaped CA3 pyramidal axonal tree, including the Schaffer collaterals and longitudinal branches. The same wide axonal branching was indicated by antidromic activation of individual CA3 pyramidal cells. The average compound action potential latency from the CA3 to the CA1 area (Schaffer collaterals) increased by 4.16 ± 0.06 ms/mm separation between the stimulation and registration electrodes. The impulses spread 31% faster in the 45‐degree oblique temporal than in the transverse direction across CA1. The latency of the longitudinal axons in the CA3 area increased by 6.19 ± 0.19 ms/mm. More impressive than these direction‐dependent differences in latency were the large differences between individual axons running in the same direction. For both the longitudinal axons and the Schaffer collaterals, there was a broad distribution of antidromic latencies for a given distance between the stimulation and recording points. Typically, the fastest impulses arrived in half the time of the slowest. The distribution of compound action potential latencies between two points in the tissue could be made narrower by surgical restriction of the thickness and width of the preparation. By comparison, the cerebellar parallel fibers showed a narrower distribution of their latencies than the Schaffer collaterals. Because the cerebellar fibers run more straight than Schaffer collaterals, this suggested that some of the latency differences of the latter were due to differences in the path length of the axons. One consequence of our findings is that synchronous firing of neighboring CA3 pyramidal cells does not necessarily give synchronous inputs to common target CA1 neurons. © 2003 Wiley‐Liss, Inc.
Morphological and numerical analysis of synaptic interactions between neurons in deep and superficial layers of the entorhinal cortex of the rat
Authors: van Haeften Theo , Baks‐te‐Bulte Luciënne , Goede Peter H. , Wouterlood Floris G. , Witter Menno P.
Published: December 2003

Neurons providing connections between the deep and superficial layers of the entorhinal cortex (EC) constitute a pivotal link in the network underlying reverberation and gating of neuronal activity in the entorhinal‐hippocampal system. To learn more of these deep‐to‐superficial neurons and their targets, we applied the tracer Neurobiotin™ pericellularly in layer V of the medial EC of 12 rats. Labeled axons in the superficial layers were studied with light and electron microscopy, and their synaptic organization recorded. Neurobiotin‐labeled layer V neurons displayed “Golgi‐like” staining. Two major cell types were distinguished among these neurons: (1) pyramidal neurons with apical spiny dendrites traversing all layers and ramifying in layer I, and (2) horizontal neurons with dendrites confined to the deep layers. Labeled axons ramified profusely in layer III, superficially in layer II and deep in layer I. Analysis of labeled axon terminals in layers I–II and III showed that most synapses (95%) were asymmetrical. Of these synapses, 56% occurred with spines (presumably belonging to principal neurons) and 44% with dendritic shafts (presumably interneurons). A small fraction of the synapses (5%) was of the symmetrical type. Such synapses were mainly seen on dendritic shafts. We found in two sections a symmetrical synapse on a spine. These findings suggest that the deep to superficial projection is mainly excitatory in nature, and that these fibers subserve both excitation and feed‐forward inhibition. There is an additional, much weaker, inhibitory component in this projection, which may have a disinhibitory effect on the entorhinal network in the superficial layers. © 2003 Wiley‐Liss, Inc.
Differential neuronal fates in the CA1 hippocampus after hypoxia in newborn and 7‐day‐old rats: Effects of pre‐treatment with MK‐801
Authors: Grojean Stéphanie , Pourié Grégory , Vert Paul , Daval Jean‐Luc
Published: December 2003

The brain displays an age‐dependent sensitivity to ischemic insults. However, the consequences of oxygen deprivation per se in the developing brain remain unclear, and the role of glutamate excitotoxicity via N‐methyl‐D‐aspartate (NMDA) receptors is controversial. To gain a better understanding of the mechanisms involved in the cerebral response to severe hypoxia, cell damage was temporally monitored in the CA1 hippocampus of rat pups transiently exposed to in vivo hypoxia (100% N2) at either 24 h or 7 days of age. Also, the influence of a pre‐treatment with the NMDA receptor antagonist MK‐801 (5 mg/kg, i.p.) was examined. At both ages, morphometric analyses and cell counts showed hypoxia‐induced significant neuronal loss (30–35%) in the pyramidal layer, with injury appearing more rapidly in rats exposed at 7 days. Morphological alterations of 4,6‐diamidino‐2‐phenylindole (DAPI)‐labeled nuclei, DNA fragmentation patterns on agarose gels, as well as expression profiles of the apoptosis‐related regulatory proteins Bax and Bcl‐2 showed that apoptosis was prevalent in younger animals, whereas only necrosis was detected in hippocampi of rats treated at 7 days. Moreover, pre‐treatment with MK‐801 was ineffective in protecting hippocampal neurons from hypoxic injury in newborn rats, but significantly reduced necrosis in older subjects. These data confirm that hypoxia alone may trigger neuronal death in vivo, and the type of cell death is strongly influenced by the degree of brain maturity. Finally, NMDA receptors are not involved in the apoptotic consequences of hypoxia in the newborn rat brain, but they were found to mediate necrosis at 7 days of age. © 2003 Wiley‐Liss, Inc.
Induction of the avian coelom with associated vitelline blood circulation by Rauber's sickle derived junctional endoblast and its fundamental role in heart formation
Authors: Callebaut Marc , Van Nueten Emmy , Bortier Hilde , Harrisson Fernand
Published: December 2003

In histological sections through chicken blastoderms of different ages we describe the temporospatial relationship between junctional endoblast, the formation of blood islands (appearing first from a peripherally migrating mesoblastic blastema), and the formation of coelomic vesicles developing later in/and from a more superficially extending mesoblastic blastema (coelomic mesoblast). After unilateral removal of the Rauber's sickle‐derived junctional endoblast in early streak blastoderms (stage 2–4; Vakaet [1970] Arch Biol 81:387–426) and culture to stage 11 (Hamburger and Hamilton [1951] J Morphol 88:49–92), we observed that the early formation of the coelomic cavity was locally or totally disturbed in the operated area. Besides the simultaneous absence of blood islands, the coelomic vesicles did not form normally. Instead of regularly aligned coelomic vesicles, progressively forming the coelomic cavity by fusion, some voluminous irregular cavities appeared. Thus, the extent of the coelomic cavity was greatly reduced and the operated side was considerably smaller than the unoperated side. Furthermore, in the youngest operated blastoderms the cranial portion of the involved coelomic cavity (hemipericardial cavity) exhibited rudimentary development and usually did not reach the region of the foregut endoderm. This resulted in the absence of the myoepicardium and associated endocardium at this side. In another experiment, after removal of the junctional endoblast at one side of the chicken blastoderm, a fragment of quail junctional endoblast was placed isotopically. This resulted, after further in vitro culture, in the restoration of the formation of coelomic vesicles and accompanying subjacent blood islands in the immediate neighborhood of the apposed quail junctional endoblast. Also, the pericardium and primary heart tube developed normally. Similarly, by using the quail‐chicken chimera technique, we demonstrated that the splanchnic mesoderm cells of the pericardium develop in intimate association with the most cranial part of the junctional endoblast (derived from the Rauber's sickle horns). Our experiments indicate that the coelom and, in particular, the pericardium and primary heart tube form progressively (in time and space) under the inductory influence of Rauber's sickle and junctional endoblast. J. Morphol. 259:21–32, 2004. © 2003 Wiley‐Liss, Inc.
Blubber development in bottlenose dolphins (Tursiops truncatus)
Authors: Struntz D.J. , McLellan W.A. , Dillaman R.M. , Blum J.E. , Kucklick J.R. , Pabst D.A.
Published: December 2003

Blubber, the lipid‐rich hypodermis of cetaceans, functions in thermoregulation, buoyancy control, streamlining, metabolic energy storage, and locomotion. This study investigated the development of this specialized hypodermis in bottlenose dolphins (Tursiops truncatus) across an ontogenetic series, including fetuses, neonates, juveniles, subadults, and adults. Blubber samples were collected at the level of the mid‐thorax, from robust specimens (n = 25) that stranded along the coasts of North Carolina and Virginia. Blubber was dissected from the carcass and its mass, and the depth and lipid content at the sample site, were measured. Samples were prepared using standard histological methods, viewed by light microscopy, and digital images of blubber captured. Images were analyzed through the depth of the blubber for morphological and structural features including adipocyte size, shape, and numbers, and extracellular, structural fiber densities. From fetus to adult, blubber mass and depth increased proportionally with body mass and length. Blubber lipid content increased dramatically with increasing fetal length. Adult and juvenile blubber had significantly higher blubber lipid content than fetuses, and this increase was reflected in mean adipocyte size, which increased significantly across all robust life history categories. In juvenile, subadult, and adult dolphins, this increase in cell size was not uniform across the depth of the blubber, with the largest increases observed in the middle and deep blubber regions. Through‐depth counts of adipocytes were similar in all life history categories. These results suggest that blubber depth is increased during postnatal growth by increasing cell size rather than cell number. In emaciated adults (n = 2), lipid mobilization, as evidenced by a decrease in adipocyte size, was localized to the middle and deep blubber region. Thus, in terms of both lipid accumulation and depletion, the middle and deep blubber appear to be the most metabolically dynamic. The superficial blubber likely serves a structural role important in streamlining the animal. This study demonstrates that blubber is not a homogeneous tissue through its depth, and that it displays life history‐dependent changes in its morphology and lipid content. J. Morphol. 259:7–20, 2004. © 2003 Wiley‐Liss, Inc.
Effects of noradrenaline administration on the interrenal gland of the newt, Triturus carnifex: Evidence of intra‐adrenal paracrine interactions
Authors: Capaldo A. , Gay F. , Valiante S. , Laforgia V. , Varano L.
Published: December 2003

The existence of paracrine control of steroidogenic activity by adrenochromaffin cells in Triturus carnifex was investigated by in vivo noradrenaline (NA) administration. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the serum levels of aldosterone, NA, and adrenaline (A). In March and July, NA administration increased aldosterone release (from 187.23 ± 2.93 pg/ml to 878.31 ± 6.13 pg/ml in March; from 314.60 ± 1.34 pg/ml to 622.51 ± 2.65 pg/ml in July) from steroidogenic cells. The cells showed clear signs of stimulation, as evidenced by a strong reduction of lipid content. Moreover, NA administration decreased the mean total number of secretory vesicles in the chromaffin cells in March (from 7.24 ± 0.18 granules/μ2 to 5.57 ± 1.88 granules/μ2) and July (from 7.74 ± 0.74 granules/μ2 to 6.04 ± 1.13 granules/μ2). In March, however, when T. carnifex chromaffin cells contain both catecholamines, NA (3.88 ± 0.13 granules/μ2) and A (3.36 ± 0.05 granules/μ2) in almost equal quantities, NA administration reduced A content (1.29 ± 1.04 granules/μ2) in the chromaffin cells, enhancing adrenaline secretion (from 681.27 ± 1.83 pg/ml to 1527.02 ± 2.11 pg/ml). In July, when the chromaffin cells contain almost exclusively NA granules (NA: 7.42 ± 0.86 granules/μ2; A: 0.32 ± 0.13 granules/μ2), NA administration reduced the number of NA granules (5.45 ± 1.10 granules/μ2), thereby increasing noradrenaline release from the chromaffin cells (from 640.19 ± 1.65 pg/ml to 1217.0 ± 1.14 pg/ml). The results of this study indicate that NA influences the steroidogenic cells, eliciting aldosterone release. Noradrenalin effects on the chromaffin cells, increase of NA or A secretion, according to the period of chromaffin cell functional cycle, may be direct and/or mediated through the steroidogenic cells. The existence of intra‐adrenal paracrine interactions in T. carnifex is discussed. J. Morphol. 259:33–40, 2004. © 2003 Wiley‐Liss, Inc.
Pattern and rate of ovary differentiation with reference to somatic development in anuran amphibians
Authors: Ogielska Maria , Kotusz Agnieszka
Published: December 2003

The rate of somatic development of anuran amphibians is only roughly correlated with the rate of gonad differentiation and varies among species. The somatic stage of a tadpole often does not reflect its age, which seems to be crucial for gonad differentiation rate. We compared the morphology and differentiation of developing ovaries at the light and electron microscopy level, with reference to somatic growth and age of a female. Our observations were performed on 12 species of six families (Rana lessonae, R. ridibunda, R. temporaria, R. arvalis, R. pipiens, R. catesbeiana, Bombina bombina, Hyla arborea, Bufo bufo. B. viridis, Xenopus laevis, Pelobates fuscus) and compared with the results obtained by other authors. This allowed us to describe the unified pattern of anuran female gonad differentiation. Ovary differentiation was divided into 10 stages: I–III, undifferentiated gonad; IV, sexual differentiation; V, first nests of meiocytes; VI, first diplotene oocytes; VII–IX, increasing number of diplotene oocytes and decreasing number of oogonia and nests; X, fully developed ovary composed of diplotene oocytes with rudimental patches of oogonia. We distinguished three types of ovary differentiation rate: basic (most species), retarded (genus Bufo), and accelerated (green frogs of the subgenus Pelophylax genus Rana). J. Morphol. 259:41–54, 2004. © 2003 Wiley‐Liss, Inc.
A pair of rosette glands in the embryo and zoeal larva of an estuarine crab Sesarma haematocheir, and classification of the tegumental glands in the embryos of other crabs
Authors: Ikeda Hideki , Hirano Yuriko , Saigusa Masayuki
Published: December 2003

A pair of rosette glands (one of the tegumental glands in crustaceans) is present at the root of the dorsal spine of the thorax in mature embryos of the estuarine crab Sesarma haematocheir. Each rosette gland is spherical, 45–50 μm in diameter. This gland consists of three types of cells: 18–20 secretory cells, one central cell, and one canal cell. The secretory cells are further classified into two types on the basis of the morphology of secretory granules. There are 17–19 a cells, and only one b cell per rosette gland. An a cell contains spherical secretory granules of 2–3 μm in diameter. The granules are filled with highly electron‐dense materials near the nucleus but have lower electron‐density near the central cell. The secretory granules contained in the b cell have an irregular shape and are 1–1.5 μm in diameter. The density of the materials in the granules is uniform throughout the cytoplasm. The secretory granules contained in both the a and b cells are produced by the rough endoplasmic reticulum. Materials in the granules are exocytotically discharged into the secretory apparatus inside the secretory cell, sent to the extracellular channels in the central cell, and secreted through the canal cell. The rosette gland can be distinguished from the epidermal cells 2 weeks after egg‐laying and the gland matures just before hatching. Materials produced by this gland are secreted after hatching and secretion continues through five stages of zoeal larvae. These rosette glands were never found in the megalopal larva. Rosette glands are found in the embryos of Sesarma spp. and Uca spp. In other crabs, tegumental glands are also found at the same position as in the embryo of S. haematocheir, but the fine structure of their glands is largely different from that of the rosette gland. On the basis of the morphology of secretory cells (a–g cell types), the tegumental glands of a variety of crab embryos can be classified into four types, including rosette glands (type I–IV). The function of these tegumental glands is not yet known, but different types of the gland seem to reflect the phylogeny of the crabs rather than differences of habitat. J. Morphol. 259:55–68, 2004. © 2003 Wiley‐Liss, Inc.
Roles of actin networks in peristaltic squeezing of sperm bundles in Bombyx mori
Authors: Sahara Ken , Kawamura Naoko
Published: December 2003

Two types of sperm are produced in the silkworm, Bombyx mori. Nucleate eupyrene sperm is an ordinary sperm that contributes to fertilization, while anucleate apyrene sperm is considered to play important roles in assisting eupyrene sperm. At the very late stage of spermatogenesis, a phenomenon called “peristaltic squeezing” occurs in both types of sperm, whereby cytoplasm of the eupyrene and nuclei of the apyrene sperm are discarded from the posterior end, forming matured sperm. In this study, rhodamine‐phalloidin staining for actin was applied to sperm bundles. Before the start of peristaltic squeezing, actin filament networks are spread on the cyst cells and constrictions by the networks appear in several places of the bundles. Actin particles, which are later recognized as circlets, are localized within the bundles. Squeezing action by the networks occurs from the anterior region and transfers toward the posterior, eliminating cytoplasm together with circlets from the posterior end. It seems that actin filaments contribute to the peristaltic squeezing of the sperm bundles in Bombyx mori. J. Morphol. 259:1–6, 2004. © 2003 Wiley‐Liss, Inc.
Ovarian histology of the placentotrophic Mabuya mabouya (Squamata, Scincidae)
Authors: Gómez Duperly , Ramírez‐Pinilla Martha Patricia
Published: December 2003

Ovarian structure and folliculogenesis of females at different reproductive stages are described for the viviparous placentotrophic lizard Mabuya mabouya. The small ovaries have a thin wall formed by the ovarian epithelium and a thin tunica albuginea. One to two germinal beds that contain numerous oogonia and developing primordial follicles are derived from the ovarian epithelium and are next to the ovarian hilum. The ovarian cortex contains follicles at different stages of development, corpora lutea, and atretic follicles. The yolk nucleus and Balbiani complex were not evident in the ooplasm of previtellogenic follicles. The follicular epithelium of these follicles is polymorphic, as in other species of Squamata, but the larger cells are spherical and monolayered rather than pyriform. The zona radiata of the preovulatory follicles is less developed than in lecithotrophic species. These features suggest a decrease in metabolic and absorptive processes during follicular growth. In preovulatory follicles (1.5–1.8 mm diameter), primordial yolk vacuoles and small cortical granules are deposited in the ooplasm instead of fatty yolk platelets, so that only one stage of vitellogenesis is observed. Polyovular atretic follicles occur in some females. Follicular atresia is minimal for preovulatory follicles, but is more frequent in follicles with polymorphic epithelia. In the corpus luteum, the luteal tissue is formed from granulosa cells and luteolysis occurs during the late gastrula – late neurula embryonic stages. Thus, the maintenance of gestation from the pharyngula to preparturition stages seems to be related to secretion of extraluteal progesterone, possibly of placental origin. These observed ovarian features are related to the high degree of placental complexity of this species and show that the evolution of advanced placentotrophy in species of this lineage has been accompanied by concomitant changes in ovarian function. J. Morphol. 259:90–105, 2004. © 2003 Wiley‐Liss, Inc.
Studies of male sexual tubes in hermit crabs (crustacea, decapoda, anomura, paguroidea). I. Morphology of the sexual tube in Micropagurus acantholepis (Stimpson, 1858), with comments on function and evolution
Authors: Tudge Christopher , Lemaitre Rafael
Published: December 2003

The external morphology and internal structure of the male sexual tube of the hermit crab Micropagurus acantholepis, a member of the family Paguridae from Australian waters, is described in detail using histological thick sectioning and scanning and transmission electron microscopy techniques. This is the first in‐depth study of a sexual tube in the Paguroidea, a group where a remarkable number of genera (55.9% in the family Paguridae) with species having these intriguing sexual structures are known. In M. acantholepis a sexual tube is present on the left side, whereas only a gonopore is present on the right side. The tube is used for the delivery of spermatophores to the female and consists of a sheath of cuticular origin surrounding an internal, functional extension of the posterior vas deferens. Pedunculate spermatophores were observed within the lumen and partially extruding from the terminal opening of the tube in preserved specimens. The tube protrudes from the left coxa of the fifth pereopod as an elongate 3‐mm‐long, hollow, coiled structure with a terminal opening. Exteriorly the tube consists of a conspicuous thick chitinous cuticular ridge throughout its length, and a thin chitinous cuticle with sparse, regularly arranged simple setae. Interior to the cuticle, the tube contains loose connective tissue, secretory cells, oblique muscle, circular muscle, and epithelial cells. The latter cells line a central lumen that runs the length of the sexual tube. The morphology, cellular composition, and function of the tube are discussed. J. Morphol. 259:106–118, 2004. © 2003 Wiley‐Liss, Inc.
Modelling paired categorical outcomes in clinical trials
Authors: Dmitrienko Alex
Published: December 2003

The goal of this paper is to discuss methods for testing the homogeneity of treatment‐induced changes in trials with paired categorical responses. Widely used marginal homogeneity tests ignore the information contained in concordant pairs of observations and become highly underpowered for configurations of parameters encountered in real trials. This paper considers models for paired binary or ordinal outcomes based on both discordant and concordant pairs that provide a natural extension of marginal models. Likelihood‐ratio tests associated with these models are developed and are demonstrated to be at least as powerful as or more powerful than marginal homogeneity tests. The proposed models are easy to fit using standard statistical software. Copyright © 2003 John Wiley & Sons, Ltd.
An improved concordance correlation coefficient
Authors: Liao Jason J. Z.
Published: December 2003

It is often required to compare two measurements in medicine and other experimental sciences. This problem covers a broad range of data, and examples can be found in different industries. In this paper, a new index on measuring agreement is proposed, which is similar to Lin's concordance correlation coefficient but derived from a criterion which is more conceptually appealing and which offers improvements. An example is used to demonstrate the benefit of using the new index. Copyright © 2003 John Wiley & Sons, Ltd.
Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves on the cardiovascular system of anaesthetized rats
Authors: Dimo T. , Nguelefack T. B. , Tan P. V. , Yewah M. P. , Dongo E. , Rakotonirina S. V. , Kamanyi A. , Bopelet M.
Published: December 2003

The aim of this study was to investigate the hypotensive and cardiac effects of the neutral extract from Bidens pilosa leaves. Intravenous administration of the extract resulted in a biphasic dose‐related hypotensive activity. In normotensive rats (NTR), B. pilosa decreased systolic blood pressure by 18.26%, 42.5% and 30% at doses of 10, 20 and 30 mg/kg, respectively. In spontaneously hypertensive rats (SHR), the decrease in systolic blood pressure was 25.77%, 38.96% and 28.64% at the above doses, respectively. These doses induced hypotension by 27%, 34.13% and 18.73% respectively in salt‐loaded hypertensive rats. In NTR, B. pilosa reduced heart rate by 23.68% and 61.18% at doses of 20 and 30 mg/kg, respectively. The force of contraction of the heart was only affected at 30 mg/kg. The initial phase of hypotensive response was partially inhibited by atropine while propranolol increased this effect. These results suggest that B. pilosa exhibited its ﬁrst hypotensive effects by acting on the cardiac pump efﬁciency and secondly through vasodilation.
Relaxant effects of different fractions of essential oil from Carum copticum on guinea pig tracheal chains
Authors: Boskabady M. H. , Ramazani M. , Tabei T.
Published: December 2003

In previous studies, the relaxant and anticholinergic (functional antagonism), histamine(H1) inhibitory, and xanthine‐like activity effect of Carum copticum have been demonstrated on guinea pig tracheal chains. To investigate the effective component(s) of this plant, responsible for the observed bronchodilatory effect, fractionation of the essential oil from Carum copticum was carried out and the relaxant effects of different fractions were examined in this study. The bronchodilatory effect of different fractions of essential oil from Carum copticum and theophylline in comparison with ethanol was examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 µM methacholine in two different conditions including: non‐incubated tissues (group 2) and incubated tissues with 1 µM propranolol and 1 µM chlorpheniramine (group 3). In addition the relaxant effect of carvacrol was also examined on precontracted tracheal chains of guinea pig by 10 µM methacholine (group 4), (for each group, n = 5). In group 1 experiments, only theophylline and fraction 2 showed signiﬁcant relaxant effect compared to that of ethanol. Fraction 2 and 3 of essential oil from carum copticum showed potent and volume (concentration) dependent relaxant effects comparable to that of theophylline in groups 2 and 3 experiments. The relaxant effects of different volumes of these two fractions were signiﬁcantly higher than that of ethanol (p < 0.05 to p < 0.002 ). The volumes of fraction 1 showed relatively small relaxant effects in groups 2 and 3 experiments which were not signiﬁcantly different from that of ethanol. However, the relaxant effect of different volumes of fractions 2 and 3 obtained in group 2 experiments were not signiﬁcantly different from those of group 3 experiments. The volumes of fraction 4 did not show any relaxant effects. In addition volumes of carvacrol also showed comparable relaxant effect with those of fraction 2 and theophylline which was signiﬁcantly greater than that of ethanol. These results indicate that the relaxant effect of essential oil from carum copticum is mainly due to its fraction 2 which is presumably carvacrol and to lesser extent due to fraction 3, and their relaxant effects are not due to anticholinergic or β‐adrenegic stimulatory effects. Copyright © 2003 John Wiley & Sons, Ltd.
Cytotoxicity and antimicrobial activity of goniothalamin isolated from Bryonopsis laciniosa
Authors: Mosaddik M. Ashik , Haque M. Ekramul
Published: December 2003

The cytotoxicity and antimicrobial activity of goniothalamin isolated from Bryonopsis laciniosa was investigated. Goniothalamin showed potent cytotoxicity with LC50 values (5.03 µg/mL) comparable with the reference standard agent, gallic acid. It also showed weak antibacterial and signiﬁcant antifungal activity against a wide range of gram positive and gram negative bacteria and fungi. The antibacterial (minimum inhibitory concentration) effect against Bacillus cereus and Shigella shiga was found to be 64 µg/mL. Copyright © 2003 John Wiley & Sons, Ltd.
Antitumour potential of a polysaccharide‐rich substance from the fruit juice of Morinda citrifolia (Noni) on sarcoma 180 ascites tumour in mice
Authors: Furusawa Eiichi , Hirazumi Anne , Story Stephen , Jensen Jarakae
Published: December 2003

An immunomodulatory polysaccharide‐rich substance (Noni‐ppt) from the fruit juice of Morinda citrifolia has been found to possess both prophylactic and therapeutic potentials against the immunomodulator sensitive Sarcoma 180 tumour system. The antitumour activity of Noni‐ppt produced a cure rate of 25%–45% in allogeneic mice and its activity was completely abolished by the concomitant administration of speciﬁc inhibitors of macrophages (2‐chloroadenosine), T cells (cyclosporine) or natural killer (NK) cells (anti‐asialo GM1 antibody). Noni‐ppt showed synergistic or additive beneﬁcial effects when combined with a broad spectrum of chemotherapeutic drugs, including cisplatin, adriamycin, mitomycin‐C, bleomycin, etoposide, 5‐ﬂuorouracil, vincristine or camptothecin. It was not beneﬁcial when combined with paclitaxel, cytosine arabinoside, or immunosuppressive anticancer drugs such as cyclophosphamide, methotrexate or 6‐thioguanine. Noni‐ppt also demonstrated beneﬁcial effects when combined with the Th1 cytokine, interferon gamma, but its activity was abolished when combined with Th2 cytokines, interleukin‐4 or interleukin‐10, thereby suggesting that Noni‐ppt induces a Th1 dominant immune status in vivo. The combination of Noni‐ppt with imexon, a synthetic immunomodulator, also demonstrated beneﬁcial effects, but not when combined with the MVE‐2 copolymer, a high molecular weight immunomodulator. It was also not effective when combined with interleukin‐2 or interleukin‐12. Copyright © 2003 John Wiley & Sons, Ltd.
Opioid‐mediated modulation of calcium currents in striatal and pallidal neurons following reserpine treatment: Focus on kappa response
Authors: Spadoni Francesca , Martella Giuseppina , Martorana Alessandro , Lavaroni Franco , D'Angelo Vincenza , Bernardi Giorgio , Stefani Alessandro
Published: December 2003

Previous work has shown that enkephalins target N‐type calcium (Ca2+) channels in striatal and globus pallidus (GP) neurons, principally through activation of μ‐like receptors. Here, we examined the effects of selective μ, δ, and κ agonists on Ca2+ currents in striatal and GP neurons isolated from either control or reserpine‐treated rats. In cells from control rats DAMGO and dynorphin (DYN) inhibited high‐voltage‐activated (HVA) Ca2+ currents preferentially in “medium‐to‐small” GP cells (likely to correspond to parvalbumin‐negative cells). The κ response was elicited by several agonists (DYN 17, DYN 13, BRL, U50‐488‐H), U50‐488‐H being the most effective (>30% maximal inhibition). U50‐488‐H affected both ω‐CgTxGVIA‐sensitive and nimodipine‐sensitive Ca2+ conductances. The κ‐mediated effect (but not the μ response) was slow and blocked by chelerythrine, supporting the involvement of protein kinase C. In neurons from reserpinized rats we observed modest changes in the μ‐inhibited fraction in small GP cells and a dramatic reduction of the κ‐sensitive fraction in principal striatal cells. These data imply that aminergic depletion alters opiate transmission differentially in the indirect and direct pathways. The suppression of the κ response only in striatum reinforces the notion of an imbalance of endogenous opiates as relevant in extrapyramidal motor dysfunctions. Synapse 51:194–205, 2004. © 2003 Wiley‐Liss, Inc.