bluuebunny/crossref_metadata_2025 huggingface dataset:
Chirality inversion in the bilirubin molecular exciton
Authors: Boiadjiev Stefan E. , Lightner David A.
Published: August 2002

The bichromophoric pigment bilirubin acts as a molecular exciton in its UV‐visible and circular dichroism (CD) spectroscopy. In both polar and nonpolar solvents, an optically active analog, (βR,β′R)‐dimethylmesobilirubin‐XIIIα (1), exhibits intense bisignate CD Cotton effects in the region of its long wavelength UV‐vis absorption near 400 nm: Δϵ + 337, Δϵ − 186 (CHCl3), and Δϵ + 285, Δϵ − 177 (CH3OH). However, introduction of an amine into a CHCl3 solution of 1 causes the Cotton effect signs to become inverted, e.g., after addition of NH3, Δϵ − 345, Δϵ + 243, and after addition of ethylene diamine, Δϵ − 420, Δϵ + 299. The sign inversions imply inversion of molecular chirality of the bilirubin and the phenomenon appears to be general for amines, including α,ω‐diamines. 1,8‐Diaminooctane was found to be more effective than longer or shorter chain analogs in producing CD sign inversion. Chirality 13:251–257, 2001. © 2001 Wiley‐Liss, Inc.
Drastic change of local stiffness distribution correlating to cell migration in living fibroblasts
Authors: Nagayama Masafumi , Haga Hisashi , Kawabata Kazushige
Published: August 2002

Sequential images of the local stiffness distribution of living fibroblasts (NIH3T3) were captured under a culture condition using scanning probe microscopy in a force modulation mode. We found a clear relation between cell migration and local stiffness distribution on the cell: When cells were stationary at one position, the stiffness distribution of their cellular surface was quite stable. On the other hand, once the cells started to move, the stiffness in their nuclear regions drastically decreased. Possible explanations for the correlation between the cell migration and the cell stiffness are proposed. Cell Motil. Cytoskeleton 50:173–179, 2001. © 2001 Wiley‐Liss, Inc.
Selective accumulation of the high molecular weight neurofilament subunit within the distal region of growing axonal neurites
Authors: Yabe Jason T. , Wang Feng‐Song , Chylinski Teresa , Katchmar Timothy , Shea Thomas B.
Published: August 2002

Axonal maturation in situ is accompanied by the transition of neurofilaments (NFs) comprised of only NF‐M and NF‐L to those also containing NF‐H. Since NF‐H participates in interactions of NFs with each other and with other cytoskeletal constituents, its appearance represents a critical event in the stabilization of axons that accompanies their maturation. Whether this transition is effected by replacement of “doublet” NFs with “triplet” NFs, or by incorporation of NF‐H into existing doublet NFs is unclear. To address this issue, we examined the distribution of NF subunit immunoreactivity within axonal cytoskeletons of differentiated NB2a/d1 cell and DRG neurons between days 3–7 of outgrowth. Endogenous immunoreactivity either declined in a proximal‐distal gradient or was relatively uniform along axons. This distribution was paralleled by microinjected biotinylated NF‐L. By contrast, biotinylated NF‐H displayed a bipolar distribution, with immunoreactivity concentrated within the proximal‐ and distal‐most axonal regions. Proximal biotinylated NF‐H accumulation paralleled that of endogenous NF immunoreactivity; however, distal‐most biotinylated NF‐H accumulation dramatically exceeded that of endogenous NFs and microinjected NF‐L. This phenomenon was not due to co‐polymerization of biotin‐H with vimentin or α‐internexin. This phenomenon declined with continued time in culture. These data suggest that NF‐H can incorporate into existing cytoskeletal structures, and therefore suggest that this mechanism accounts for at least a portion of the accumulation of triplet NFs during axonal maturation. Selective NF‐H accumulation into existing cytoskeletal structures within the distal‐most region may provide de novo cytoskeletal stability for continued axon extension and/or stabilization. Cell Motil. Cytoskeleton 50:1–12, 2001. © 2001 Wiley‐Liss, Inc.
Cisplatin, fludarabine, and cytarabine
Authors: Seymour John F. , Grigg Andrew P. , Szer Jeff , Fox Richard M.
Published: August 2002

BACKGROUND

Based on in vitro synergism, the combination of cytarabine (ara‐C) and cisplatin is the basis of many salvage regimens for patients with aggressive non‐Hodgkin lymphoma (NHL). However, patients with previously refractory disease are significantly less likely to respond, stimulating the search for novel salvage regimens. In vitro, fludarabine enhances the cytotoxicity of both ara‐C and cisplatin, increasing ara‐C incorporation into DNA and inhibiting repair of platinum/DNA adducts, suggesting that the combination of cisplatin, fludarabine, and ara‐C (PFA) may have clinical utility.

METHODS

A Phase‐II study of a 96‐hour continuous infusion of cisplatin with two timed‐sequential couplets of fludarabine and ara‐C together with granulocyte‐colony stimulating factor was performed in 45 patients with previously refractory, histologically aggressive or mantle cell NHL.

RESULTS

Patients had predominantly diffuse large cell and/or immunoblastic NHL or its variants (80%), or they had mantle cell lymphoma (18%). Overall, 93% of patients had previously refractory disease, with a median International Prognostic Index score of 3. A median of 2 cycles per patient were delivered (range, 1–4 cycles) with significant myelosuppression; there were medians of 2 days of neutropenia < 0.5 × 109/L (range, 0–12 days) and 3 days of thrombocytopenia < 20 × 109/L (range, 0–24 days). This was more severe in older patients and was cumulative with successive cycles. Thirty‐five percent of cycles were complicated by infections, nausea and emesis were prominent, but other nonhematologic toxicity was mild. Peripheral blood progenitor cells were mobilized adequately after the first cycle, but collections were impaired after more prolonged therapy. The overall response rate was 48% (7% of patients had complete responses, and 41% of patients had partial responses), with one toxic death due to tumor‐lysis syndrome. Patients with mantle cell lymphoma were more likely to respond than patients with other histologies (88% vs. 39%, respectively; P = 0.019), although three of eight patients had relapsed rather than refractory disease. The median remission duration was 4 months, with 28% of potentially eligible patients able to proceed to subsequent high‐dose therapy. The actuarial 2‐year survival rates were 20% ± 6% overall and 50 ± 18% for patients with mantle cell lymphoma.

CONCLUSIONS

Given the adverse outlook for these patients, the results are promising, particularly for patients with mantle cell lymphoma, and suggest that the addition of fludarabine as a potential biochemical modulator may enhance the activity of cisplatin and ara‐C. This is associated with significant cumulative (but manageable) myelosuppression. This paradigm, in which a nuceloside analogue is used to inhibit the repair of platinum/DNA adducts, also may be applicable for the treatment of patients with other types of platinum‐sensitive tumors. Cancer 2002;94:585–93. © 2002 American Cancer Society.

DOI 10.1002/cncr.10240
Patterns of gastric atrophy in intestinal type gastric carcinoma
Authors: El‐Zimaity Hala M. T. , Ota Hiroyoshi , Graham David Y. , Akamatsu Taiji , Katsuyama Tsutomu
Published: August 2002

BACKGROUND

Multifocal atrophic gastritis (MAG) is currently considered a precancerous lesion leading to intestinal type gastric carcinoma. The current study aimed to describe the topography of atrophy in stomachs with early gastric carcinoma.

METHODS

Resected stomachs from patients with intestinal type gastric carcinoma were routinely processed, sectioned (an average of 108 sections/stomach), and stained with a triple stain. Sections were scored on a visual analog scale for Heliobacter pylori and intestinal metaplasia. The type of epithelium (antral, oxyntic, transitional) was recorded. Atrophy was defined as the loss of normal glandular components and included intestinal metaplasia and/or pseudo‐pyloric metaplasia of the corpus. Pseudo‐pyloric metaplasia was identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum.

RESULTS

Sixteen stomachs with intestinal type gastric carcinoma were examined. In none of the specimens examined was MAG (independent foci of atrophy) identified. In the majority (88%), atrophy was present as a continuous sheet. Islands of intestinal metaplasia (multifocal intestinal metaplasia) were present within a sheet of pseudo‐pyloric metaplasia. A few specimens (12%) had a non‐atrophic corpus with almost total replacement of antral epithelium with intestinal metaplasia. Multifocal dysplasia distant from the original tumor was found both in areas with and without intestinal metaplasia.

CONCLUSIONS

Contrary to popular belief, atrophy in intestinal type gastric carcinoma is not present as independent foci, but rather as a continuous sheet. Previous studies failed to identify pseudo‐pylori metaplasia as a marker for atrophy. Cancer 2002;94:1428–36. © 2002 American Cancer Society.

DOI 10.1002/cncr.10375
The clinical use of bone resorption markers in patients with malignant bone disease
Authors: Coleman Robert E.
Published: August 2002

BACKGROUND

Advanced tumors often metastasize to bone, resulting in a variety of skeletal complications. Bisphosphonates are potent inhibitors of osteoclast‐mediated bone resorption that reduce the incidence and delay the onset of skeletal complications and reduce the need for radiation and surgery. Biochemical markers of bone resorption have been identified that can augment the imaging techniques used to diagnose bone metastases and assess response to bisphosphonate therapy.

METHODS

In the current study, the available literature regarding bone resorption markers is reviewed and the clinical relevance of these data with respect to the treatment of bone metastases discussed.

RESULTS

Urinary calcium and hydroxyproline have been widely used to assess bone metabolism, but do not appear to be well correlated with clinical outcome in patients with bone metastases. Several unique breakdown products of Type I collagen (including pyridinium crosslinks, pyridinoline, and deoxypyridinoline) and peptide‐bound crosslinks (N‐telopeptide and C‐telopeptide) are more specific and sensitive markers of bone resorption. N‐telopeptide and C‐telopeptide have been identified as the most sensitive biochemical markers currently available for detecting bone metastases and for assessing response to therapy or disease progression.

CONCLUSIONS

To the author's knowledge markers of bone resorption have not yet been recommended for routine clinical use. However, further research is needed to define their potential role in the diagnosis of bone metastases, the assessment of disease progression and response to bisphosphonate therapy, and predict the rate of bone loss and the potential for fracture. Suppression of bone resorption markers in response to bisphosphonate therapy appears to correlate with clinical outcome in patients with both osteolytic and blastic bone lesions; therefore, the goal of bisphosphonate therapy should be to suppress markers of bone resorption. Cancer 2002;94:2521–33. © 2002 American Cancer Society.

DOI 10.1002/cncr.10522
Uridine phosphorylase is a potential prognostic factor in patients with oral squamous cell carcinoma
Authors: Miyashita Hitoshi , Takebayashi Yuji , Eliason James F. , Fujimori Fumihiro , Nitta Yasutaka , Sato Atsushi , Morikawa Hidehiro , Ohashi Akira , Motegi Katutoshi , Fukumoto Manabu , Mori Shiro , Uchida Takafumi
Published: August 2002

BACKGROUND

Uridine phosphorylase (UPase) catalyzes the reversible phosphorolysis of uridine to uracil. The expression levels and the enzymatic activity of UPase are reported to be higher in human solid tumors than in adjacent normal tissues. However, to the authors' knowledge the clinical significance of UPase expression as determined by immunohistochemical analysis has not been demonstrated in human malignancies.

METHODS

The authors prepared the antibody against UPase, examined the staining of UPase in 72 cases of oral squamous cell carcinoma (SCC) with immunohistochemical analysis using the antibody, and analyzed its relation to clinical and pathologic factors.

RESULTS

UPase stained mainly within the invasive edges of tumors and macrophages. UPase‐positive staining was observed in 56 of the 72 tumors (77.8%). High staining of UPase (defined as > 50% of cells in a tumor biopsy that are positive for UPase) in primary tumors frequently was associated with the presence of metastasis to lymph nodes (P = 0.007 by the Fischer exact test) and with lower overall survival (P = 0.03 by the log‐rank test).

CONCLUSIONS

The high rate of UPase staining in biopsies from patients with oral SCC may be a prognostic marker for these individuals. Cancer 2002;94:2959–66. © 2002 American Cancer Society.

DOI 10.1002/cncr.10568
Sentinel lymph node biopsy in patients with ductal carcinoma in situ
Authors: McMasters Kelly M. , Chao Celia , Wong Sandra L. , Martin Robert C. G. , Edwards Michael J.
Published: August 2002

Sentinel lymph node (SLN) biopsy for the treatment of ductal carcinoma in situ (DCIS) is not necessary and generally should be limited to those patients with a core needle biopsy diagnosis of DCIS who are undergoing mastectomy. Used in this way, SLN biopsy will spare the majority of patients with occult invasive tumor the need for axillary lymph node dissection.
Mental health in men treated for early stage prostate carcinoma
Authors: Litwin Mark S. , Lubeck Deborah P. , Spitalny G. Mark , Henning James M. , Carroll Peter R.
Published: August 2002

BACKGROUND

The current study was conducted to assess posttreatment changes in the mental components of health related quality of life in prostate carcinoma patients during the two years following diagnosis and management with radical prostatectomy, pelvic irradiation, or watchful waiting.

METHODS

The authors studied the mental domains of general health related quality of life in 452 men recently diagnosed with early stage prostate carcinoma and treated with radical prostatectomy, pelvic radiation, or watchful waiting. Outcomes were assessed with the RAND 36‐Item Health Survey, a validated health‐related quality of life instrument that includes four mental domains. To minimize the influence of potentially confounding factors, the authors adjusted for age, comorbidity, prostate specific antigen (PSA) at diagnosis, and biopsy Gleason score. All subjects were drawn from CaPSURE™, a national, longitudinal cohort.

RESULTS

By 6–12 months after treatment, the active treatment groups began to show differences in mental health and vitality. By 15 months, surgery and radiation patients scored differently in all four mental domains. Over time, the gaps between mental domain scores grew wider among the treatment groups, with surgery patients performing the best, radiation patients performing the worst, and watchful waiting patients falling in between.

CONCLUSIONS

The mental health profiles differ for patients undergoing surgery, radiation, or watchful waiting for early stage prostate carcinoma. Men with more serious disease, as evidenced by higher PSA levels or more aggressive histology, tended to worry more about it. Older men performed better, while sicker men performed worse, even though the older men tended to be sicker. Cancer 2002;95:54–60. © 2002 American Cancer Society.

DOI 10.1002/cncr.10651
Glial fibrillary acidic protein expression and promoter activity in the inner ear of developing and adult mice
Authors: Rio Carlos , Dikkes Pieter , Liberman M. Charles , Corfas Gabriel
Published: August 2002

The intermediate filament glial fibrillary acidic protein (GFAP) is a classic marker for several types of glial cells, including astrocytes and nonmyelinating Schwann cells. The pattern of expression of GFAP in the postnatal murine inner ear, from postnatal day 3 (P3) to P38, was studied by anti‐GFAP immunostaining in wild‐type mice as well as in two lines of transgenic mice expressing either β‐galactosidase (LacZ) or green fluorescent protein (GFP) under the control of the GFAP promoter. Analysis of protein and promoter activity shows that several classes of supporting cells in the sensory epithelia, as well as Schwann cells and satellite cells express GFAP. Early after birth, all cochlear supporting cells express GFAP, in a gradient decreasing in intensity from base to apex. After P15, GFAP expression in the organ of Corti is mostly restricted to supporting cells of the inner hair cell area (i.e., inner border and inner phalangeal cells) and outer hair cell area (i.e., Deiters' cells). A small population of limbic cells also showed expression in a base‐to‐apex gradient. In the vestibular organs, high expression was detected in supporting cells in extrastriolar regions of the utricular macula and in the canal ampullae, with weaker staining in the saccular macula. These results suggest that supporting cells of the inner ear have important similarities to glial cells and may play roles similar to those of astrocytes or Schwann cells in supporting the normal development and maintenance of neurons and sensory cells of the inner ear. J. Comp. Neurol. 442:156–162,2002. © 2002 Wiley‐Liss, Inc.
Adult‐like complexity of the larval antennal lobe of D. melanogaster despite markedly low numbers of odorant receptor neurons
Authors: Python François , Stocker Reinhard F.
Published: August 2002

We provide a detailed analysis of the larval head chemosensory system of Drosophila melanogaster, based on confocal microscopy of cell‐specific reporter gene expression in P[GAL4] enhancer trap lines. In particular, we describe the neuronal composition of three external and three pharyngeal chemosensory organs, the nerve tracts chosen by their afferents, and their central target regions. With a total of 21 olfactory and 80 gustatory neurons, the sensory level is numerically much simpler than that of the adult. Moreover, its design is different than in the adult, showing an association between smell and taste sensilla. In contrast, the first‐order relay of the olfactory afferents, the larval antennal lobe (LAL), exhibits adult‐like features both in terms of structure and cell number. It shows a division into approximately 30 subunits, reminiscent of glomeruli in the adult antennal lobe. Taken together, the design of the larval chemosensory system is a “hybrid,” with larval‐specific features in the periphery and central characteristics in common with the adult. The largely reduced numbers of afferents and the similar architecture of the LAL and the adult antennal lobe, render the larval chemosensory system of Drosophila a valuable model system, both for studying smell and taste and for examining the development of its adult organization. J. Comp. Neurol. 445:374–387, 2002. © 2002 Wiley‐Liss, Inc
Ultrastructural characterization of the accessory lobes of Lachi in the lumbosacral spinal cord of the pigeon with special reference to intrinsic mechanoreceptors
Authors: Rosenberg Jörg , Necker Reinhold
Published: August 2002

The lumbosacral spinal cord of birds is unique among vertebrates in that segmentally organized accessory lobes protrude from the ventrolateral spinal cord into the vertebral canal. Recently, it has been suggested that these lobes may be part of an extralabyrinthine sense organ of equilibrium. For a better understanding of such a function, a complete analysis of the structural basis was performed by means of electron microscopy. The lobes consist of multipolar neurons, myelinated and unmyelinated axons, glia‐derived glycogen cells, glial cells, and capillaries. The dorsal part of the lobe is covered by a loose mesh of pia mater. Ventrolaterally, an arachnoidal trabecle is in close contact with the lobe. Extracellular lacunae extend from the periphery deep into each lobe. The lacunae are separated from the subarachnoidal space by a loose mesh of processes of the glycogen cells with its basal lamina. The lacunae are filled by a network of processes of glycogen cells, glial cell, dendrites, and small axons. Both neuronal somata and dendrites are contacted by numerous axon terminals that form rather uniform synapses. Finger‐like processes emerge from both the somata and the dendrites. The dendrites branch deeply into the extracellular lacunae and form lateral ramifications, which consist of narrow stalks with serially arranged bulbous portions, from which finger‐like processes emerge. Finger‐like processes are well‐known elements in mechanotransduction. Glycogen cells and lacunae may contribute to transmission of hydrostatic pressure changes during movements of the body. J. Comp. Neurol. 447:274–285, 2002. © 2002 Wiley‐Liss, Inc.
Apoptosis of spinal interneurons induced by sciatic nerve axotomy in the neonatal rat is counteracted by nerve growth factor and ciliary neurotrophic factor
Authors: Oliveira Alexandre L.R. , Risling Mårten , Negro Alessandro , Langone Francesco , Cullheim Staffan
Published: August 2002

We have previously shown that not only motoneurons and dorsal root ganglion cells but also small neurons, presumably interneurons in the spinal cord, may undergo apoptotic cell death as a result of neonatal peripheral nerve transection in the rat. With the aid of electron microscopy, we have here demonstrated that apoptosis in the spinal cord is confined to neurons and does not involve glial cells at the survival time studied (24 hours). To define the relative importance of the loss of a potential target (motoneuron) and a potential afferent input (dorsal root ganglion cell) for the induction of apoptosis in interneurons in this situation, we have compared the distributions and time courses for TUNEL labeling, which detects apoptotic cell nuclei, in the L5 segment of the spinal cord and the L5 dorsal root ganglion after sciatic nerve transection in the neonatal (P2) rat. In additional experiments, we studied the effects on TUNEL labeling of interneurons after treatment of the cut sciatic nerve with either ciliary neurotrophic factor (CNTF) to rescue motoneurons or nerve growth factor (NGF) to rescue dorsal root ganglion cells. The time courses of the TUNEL labeling in motoneurons and interneurons induced by the lesion show great similarities (peak at 8–48 hours postoperatively), whereas the labeling in dorsal root ganglion cells occurs later (24–72 hours). Both CNTF and NGF decrease the number of TUNEL‐labeled interneurons, but there is a regional difference, in that CNTF preferentially saves interneurons in deep dorsal and ventral parts of the spinal cord, whereas the rescuing effects of NGF are seen mainly in the superficial dorsal horn. The results are interpreted as signs of a trophic dependence on both the target and the afferent input for the survival of interneurons neonatally. J. Comp. Neurol. 447:381–393, 2002. © 2002 Wiley‐Liss, Inc.
Primates exposed to cocaine in utero display reduced density and number of cerebral cortical neurons
Authors: Lidow Michael S. , Song Zan‐Min
Published: August 2002

This study examined the effects of cocaine use during the second trimester of pregnancy on cerebral neocortical volume and density, and total number of neocortical neurons and glia in offspring. We also evaluated the extent of postnatal recovery of cytoarchitectural abnormalities previously observed in the neocortex of two‐month‐old primates born from cocaine‐treated mothers (Lidow [1995] Synapse 21:332–334). Pregnant monkeys received cocaine orally (20 mg/kg/day) from the 40th to 102nd days of pregnancy (embryonic day [E]40–E102). On E64 and E65, the animals were injected with [3H]thymidine. Cerebral hemispheres of the offspring were examined at three years of age. We found a reduction in the neocortical volume and density and total number of neocortical neurons. The observed reduction in neuronal number within the neocortex was not accounted for by the increase in the number of neurons in the white matter of cocaine‐exposed animals, because the number of these “extra” neurons was equal to only half that of missing neurons. We detected no significant changes in the number of neocortical glia. The cytoarchitectural abnormalities in the neocortex of prenatally cocaine‐exposed three‐year‐old monkeys closely resembled previously described neocortical abnormalities in similarly exposed two‐month‐old animals: the neocortex lacked a discernible lamination; the majority of the cells labeled by [3H]thymidine injected during neocortical neuronogenesis did not reach their proper position within the cortical plate. Therefore, postnatal maturation is not associated with significant improvement in neocortical organization in primates prenatally exposed to cocaine. There was, however, a postnatal recovery of low glial fibrillary acidic protein (GFAP) immunoreactivity previously observed in 2‐month‐old cocaine‐exposed animals. J. Comp. Neurol. 435:263–275, 2001. © 2001 Wiley‐Liss, Inc.
Thalamo‐cortical connections of areas 3a and M1 in marmoset monkeys
Authors: Huffman Kelly J. , Krubitzer Leah
Published: August 2002

The present investigation is part of a broader effort to examine cortical areas that contribute to manual dexterity, reaching, and grasping. In this study we examine the thalamic connections of electrophysiologically defined regions in area 3a and architectonically defined primary motor cortex (M1). Our studies demonstrate that area 3a receives input from nuclei associated with the somatosensory system: the superior, inferior, and lateral divisions of the ventral posterior complex (VPs, VPi, and VPl, respectively). Surprisingly, area 3a receives the majority of its input from thalamic nuclei associated with the motor system, posterior division of the ventral lateral nucleus of the thalamus (VL), the mediodorsal nucleus (MD), and intralaminar nuclei including the central lateral nucleus (CL) and the centre median nucleus (CM). In addition, sparse but consistent projections to area 3a are from the anterior pulvinar (Pla). Projections from the thalamus to the cortex immediately rostral to area 3a, in the architectonically defined M1, are predominantly from VL, VA, CL, and MD. There is a conspicuous absence of inputs from the nuclei associated with processing somatic inputs (VP complex). Our results indicate that area 3a is much like a motor area, in part because of its substantial connections with motor nuclei of the thalamus and motor areas of the neocortex (Huffman et al. [2000] Soc. Neurosci. Abstr. 25:1116). The indirect input from the cerebellum and basal ganglia via the ventral lateral nucleus of the thalamus supports its role in proprioception. Furthermore, the presence of input from somatosensory thalamic nuclei suggests that it plays an important role in somatosensory and motor integration. J. Comp. Neurol. 435:291–310, 2001. © 2001 Wiley‐Liss, Inc.
Morphological identification of nitric oxide sources and targets in the cat oculomotor system
Authors: Moreno‐López Bernardo , Escudero Miguel , De Vente Jan , Estrada Carmen
Published: August 2002

Nitric oxide (NO) production by specific neurons in the prepositus hypoglossi (PH) nucleus is necessary for the correct performance of eye movements in alert cats. In an attempt to characterize the morphological substrate of this NO function, the distribution of nitrergic neurons and NO‐responding neurons has been investigated in different brainstem structures related to eye movements. Nitrergic neurons were stained by either immunohistochemistry for NO synthase I or histochemistry for reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. The NO targets were identified by cyclic guanosine monophosphate (cGMP) immunohistochemistry in animals treated with a NO donor immediately before fixation of the brain. Connectivity between cells of the NO‐cGMP pathway was analyzed by injections of the retrograde tracers horseradish peroxidase or fast blue in different structures. The motor nuclei commanding extraocular muscles did not contain elements of the NO‐cGMP pathway, except for some scattered nitrergic neurons in the most caudal part of the abducens nucleus. The PH nucleus contained the largest number of nitrergic cell bodies and a rich neuropil, distributed in two groups in medial and lateral positions in the caudal part, and one central group in the rostral part of the nucleus. An abundant cGMP positive neuropil was the only NO‐sensitive element in the PH nucleus, where no cGMP‐producing neuronal cell bodies were observed. The opposite disposition was found in the marginal zone between the PH and the medial vestibular nuclei, with a large number of NO‐sensitive cGMP‐producing neurons and almost no nitrergic cells. Both nitrergic and NO‐sensitive cell bodies were found in the medial and inferior vestibular nuclei and in the superior colliculus, whereas the lateral geniculate nucleus contained nitrergic neuropil and a large number of NO‐sensitive cell bodies. Some of the cGMP‐positive neurons in the marginal zone and medial vestibular nucleus projected to the PH nucleus, predominantly to the ipsilateral side. These morphological findings may help to explain the mechanism of action of NO in the oculomotor system. J. Comp. Neurol. 435:311–324, 2001. © 2001 Wiley‐Liss, Inc.
Neurokinin‐1 receptor‐immunoreactive neurons of the ventral respiratory group in the rat
Authors: Wang Hong , Stornetta Ruth L. , Rosin Diane L. , Guyenet Patrice G.
Published: August 2002

The rostral end of the ventral respiratory group (VRG) contains neurons that are intensely neurokinin‐1 receptor (NK1R) immunoreactive (ir). It has been theorized that some of these cells might be critical to respiratory rhythmogenesis (Gray et al. [1999] Science 286:1566–1568). In the present study we determined what major transmitter these NK1R‐ir cells make and whether they are bulbospinal or propriomedullary. NK1R‐ir neurons were found in the VRG between Bregma levels −11.7 and −13.6 mm. The highest concentration was found between Bregma −12.3 and −13.0 mm. This region overlaps with the pre‐Bötzinger complex (pre‐BötC) as it was found to contain many pre‐inspiratory neurons, few E2‐expiratory neurons, and no I‐incremental neurons. VRG NK1R‐ir neurons contain neither tyrosine hydroxylase (TH) nor choline acetyl‐transferase (ChAT) immunoreactivity, although dual‐labeled neurons were found elsewhere within the rostral medulla. GAD67 mRNA was commonly detected in the ventrolateral medulla (VLM) but rarely in the NK1R‐ir neurons of the pre‐BötC region (6 % of somatic profiles). GlyT2 mRNA was commonly found in the pre‐BötC region but rarely within NK1R‐ir neurons (1.3 %). Up to 40% of VRG NK1R‐ir neurons were retrogradely labeled by Fluoro‐Gold (FG) injected in the contralateral pre‐BötC region. Some NK1R‐ir VRG neurons located caudal to Bregma −12.6 mm were retrogradely labeled by FG injected in the spinal cord (C4–C5, T2–T4). In sum, NK1R immunoreactivity is present in many types of ventral medullary neurons. Within the VRG proper, NK1R‐ir neurons are concentrated in an area that overlaps with the pre‐BötC. Within this limited region of the VRG, NK1R‐ir neurons are neither cholinergic nor catecholaminergic, and very few are γ‐aminobutyric acid (GABA)ergic or glycinergic. The data suggest that most NK1R‐ir neurons of the pre‐BötC region are excitatory. Furthermore, the more rostral NK1R‐ir cells are propriomedullary, whereas some of the caudal ones project to the spinal cord. J. Comp. Neurol. 434:128–146, 2001. © 2001 Wiley‐Liss, Inc.
An efficient gradient‐based optimization algorithm for mechanical systems
Authors: Kegl M. , Butinar B. J. , Kegl B.
Published: August 2002

This paper describes an optimization algorithm based on a special convex approximation technique and a robust numerical solution procedure. The employed approximation technique involves automatic adjustability in order to ensure good convergence properties. Additionally, it guaranties convexity and a special form of the approximate problems. Consequently, these problems can be transformed into very simple and quasi‐unconstrained dual problems which are solved by a robust and reliable numerical solution procedure. A few examples illustrate the use of the algorithm. Copyright © 2002 John Wiley & Sons, Ltd.
Systemic attachment theory and therapeutic practice: a proposal
Authors: von Sydow Kirsten
Published: August 2002

The fundamentals of attachment theory and family systems theory are outlined in this paper. Theoretical strengths and weaknesses of both approaches are discussed. First, the similarities of both approaches are analysed (focus on family relationships; focus on normal as well as disturbed development; status as metatheoretical perspectives). Then, the differences are outlined (empirical consolidation versus speculative theory development; integration versus abandonment of the concept of ‘personality’; normativity versus non‐normativity; deficit orientation versus resource orientation; dyadic versus triadic view; focus on past and present time versus focus on present and future). Finally, an integrative proposal of a systemic attachment theory is presented. It includes the following main positions: (1) Attachment needs are inborn and of vital importance for humans of all ages. (2) Relationship experiences are internalized and shape the personality. (3) Inner working models of attachment tend to remain stable, but it is possible to change them through new relationship experiences. (4) Attachment can be conceptualized as having an intrapsychic as well as an interpersonal dimension. (5) Internal models and interpersonal relationships influence each other. (6) Focus on normativity and resource orientation. (7) Focus on the present and future, with limited consideration of the past. (8) Sensitivity for losses and ‘inherited trauma’. (9) Triadic view. Research implications (focus on triadic interactions, on inner working models of attachment, and on interrelationships between both) and clinical‐psychotherapeutic implications are derived from this proposal. Bowlby's (1979) recommendations for individual therapy are extended to couples/family therapy and supplemented by a competence‐based basic attitude, flexibility of therapy setting, sensitivity for ‘inherited trauma’ and sensitivity for complex triadic relationships. Copyright © 2002 John Wiley & Sons, Ltd.
Basic bifurcation analysis of a hysteresis oscillator
Authors: Storace Marco , Bizzarri Federico
Published: August 2002

This paper carries out a basic bifurcation analysis of a ‘smooth’ version of a recently proposed piecewise‐linear oscillator based on hysteresis. The analysis is made referring mainly to two circuit parameters particularly easy to vary in a laboratory implementation of the circuit. By resorting to both analytical and numerical analyses, some local and global bifurcations of the dynamics of the oscillator are pointed out. The reported results completely agree with PSPICE simulations and experimental measures. Copyright © 2001 John Wiley & Sons, Ltd.
Aligning experimental design with bioinformatics analysis to meet discovery research objectives
Authors: Kane Michael D.
Published: August 2002

The utility of genomic technology and bioinformatic analytical support to provide new and needed insight into the molecular basis of disease, development, and diversity continues to grow as more research model systems and populations are investigated. Yet deriving results that meet a specific set of research objectives requires aligning or coordinating the design of the experiment, the laboratory techniques, and the data analysis. The following paragraphs describe several important interdependent factors that need to be considered to generate high quality data from the microarray platform. These factors include aligning oligonucleotide probe design with the sample labeling strategy if oligonucleotide probes are employed, recognizing that compromises are inherent in different sample procurement methods, normalizing 2‐color microarray raw data, and distinguishing the difference between gene clustering and sample clustering. These factors do not represent an exhaustive list of technical variables in microarray‐based research, but this list highlights those variables that span both experimental execution and data analysis. Cytometry 47:50–51, 2002. © 2001 Wiley‐Liss, Inc.
Interferometry in flow to sort unstained X‐ and Y‐chromosome‐bearing bull spermatozoa
Authors: van Munster Erik B.
Published: August 2002

Background

It was found earlier that the difference in volume between unstained X‐ and Y‐chromosome‐bearing sperm heads could be detected using interference microscopy in visible light. This could be the basis for an alternative to the conventional method to sort X and Y sperm, which uses DNA staining and ultraviolet (UV)‐excitation that may be harmful to sperm cells. A novel technique is introduced combining interferometry with flow cytometry.

Materials and Methods

Interference optics were built into an existing flow cytometer/cell sorter and used to sort fresh unstained bull sperm cells on the basis of their head volume. Sorted fractions were stained with a DNA stain, and reanalyzed using the conventional method.

Results

Purities between 60–66% were found in both X‐ and Y‐enriched fractions. It was possible to sort up to 300 cells per second. The system was found to be less sensitive to the orientation of sperm cells than the conventional method.

Conclusions

Interferometry can be combined with flow cytometry and used to obtain significantly enriched fractions of X‐ and Y‐bearing sperm without staining and UV light. Sorting speeds and purities at this point, however, are much lower than with the conventional method. Cytometry 47:192–199, 2002. © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration biopsy of liver masses: Diagnostic value and reproducibility of cytological criteria
Authors: Granados Rosario , Aramburu Jose A. , Murillo Nieves , Camarmo Encarnación , de la Cal Miguel A. , Fernandez‐Segoviano Pilar
Published: August 2002

There are many helpful cytological criteria for the diagnosis of liver fine‐needle aspiration biopsies (FNABs), but none of them are pathognomonic of primary or metastatic tumors. We analyzed the diagnostic value and reproducibility of 28 cytological parameters in FNABs from 140 hepatic masses, including 29 benign lesions, 49 hepatocellular carcinomas (HCCs), and 62 metastatic tumors, encompassing 48 adenocarcinomas (ACAs). Five different observers evaluated each sample, and the interobserver and intraobserver agreement was studied. Multivariable analysis showed that the criteria more closely associated with malignancy were irregular nuclear contour, three‐dimensional cell groups, and atypical naked nuclei. Capillaries separating tumor cells and granular cytoplasm were strongly associated with HCCs, while eccentrically placed nuclei and necrosis were most commonly seen in ACAs and in metastatic tumors. The intraobserver and interobserver agreement was excellent for the final cytological diagnosis, and there was fair to very good interobserver agreement for 22 of the 28 criteria studied. Architectural features were less reproducible than pure cytological criteria. Intraobserver variability was not influenced by the years of experience in the field. A precise and strict definition of terminology rendered a better reproducibility of the cytological criteria. Diagn. Cytopathol. 25:365–375, 2001. © 2001 Wiley‐Liss, Inc.
Intracytoplasmic and intranuclear Reinke's crystals in a testicular Leydig‐cell tumor diagnosed by fine‐needle aspiration cytology: A case report with review of the literature
Authors: Jain M. , Aiyer H.M. , Bajaj P. , Dhar S.
Published: August 2002

We report on the cytopathologic findings of a Leydig‐cell tumor of the testis in a young adult male with no evidence of endocrine dysfunction. The preoperative diagnosis was based on fine‐needle aspiration cytology (FNAC) alone, which was subsequently confirmed on histopathology. The present case was of interest on account of the paucity of literature regarding the cytodiagnosis of this lesion. In addition, the finding of intracytoplasmic lipofuscin pigment and several intracytoplasmic as well as intranuclear Reinke's crystals served to clinch the diagnosis on FNA. Therefore, the use of FNAC, especially in the presence of diagnostic Reinke's crystals, may vitiate the need for more invasive biopsy procedures in the preoperative diagnosis of testicular Leydig‐cell tumors. Diagn. Cytopathol. 2001;25:162–164. © 2001 Wiley‐Liss, Inc.
Antiarrhythmic drug development: Historical review and future perspective
Authors: Pugsley Michael K.
Published: August 2002

Cardiac ion channels represent the traditional target for antiarrhythmic drug development. Although channel‐selective drugs are effective in treating supraventricular arrhythmias, they are less effective against life‐threatening ventricular arrhythmias, and some are proarrhythmic. Paradoxically, the one exception, amiodarone, which uniquely suppresses ventricular fibrillation without proarrhythmia, is one of the least channel‐selective drugs currently available (and thus has extracardiac side effects). Thus, antiarrhythmic drug development has become becalmed. This review describes the history of antiarrhythmic drug development, considers antiarrhythmic drugs to date, and provides an overview of current novel therapeutic areas of drug development in an attempt to introduce some of the articles contained within this focused issue of Drug Development Research. Models (for preclinical antiarrhythmic drug assessment) and mechanisms (of drug action and arrhythmia suppression) are the themes of this issue. Drug Dev. Res. 55:3–16, 2002. © 2002 Wiley‐Liss, Inc.
Maternally separated rats show deficits in maternal care in adulthood
Authors: Lovic Vedran , Gonzalez Andrea , Fleming Alison S.
Published: August 2002

Although there is considerable research on the phenomenology, neuroendocrinology, neuroanatomy, and sensory control of maternal behavior, little is known about the influences of early postnatal and postweaning experiences on the development of maternal behavior. The purpose of this study was to assess how early life separation from the mother rat affects development of the offspring's juvenile and adult maternal behavior. From postnatal Days 1 to 17, 3 female rats within each litter were separated (SEP) from the mother and the rest of the litter for 5 hr daily while 3 of their sisters were not maternally separated (NSEP). On postnatal Day 21, all subjects were weaned and randomly assigned to one of three juvenile conditions. One female from both SEP and NSEP groups was either isolated (I), given a social conspecific (S), or given 1‐ to 4‐day‐old pups (P) for 5 consecutive days. Maternal behavior of SEP and NSEP animals was assessed and recorded on each of the 5 days. Once all animals reached adulthood, they were mated, gave birth, and were assessed for their maternal behavior. We found that the effects of maternal separation on juvenile maternal‐like behaviors were minimal. On the other hand, maternal separation reduced adult maternal licking and crouching over pups. In addition, there was a significant interaction between postnatal and juvenile experience on maternal crouching in maternal animals. These results are discussed in terms of the variety of possible behavioral, endocrine, and neurochemical mechanisms that mediate the effects of early life experiences on adult maternal behavior. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 19–33, 2001
Response of adolescent bonnet macaques to an acute fear stimulus as a function of early rearing conditions
Authors: Rosenblum Leonard A. , Forger Caroline , Noland Siobhán , Trost Ronald C. , Coplan Jeremy D.
Published: August 2002

When primate infants are reared during the first half‐year of life in an environment in which their mothers face uncertain requirements for food procurement (variable foraging demand [VFD]), long‐lasting behavioral and neurodevelopmental consequences ensue, including increases in timidity and social subordinance as well as alterations in stress‐related neuroendocrine profiles. We examined the nature and persistence of the effects of VFD rearing by exposing VFD‐reared and normally reared adolescent bonnet macaques to a mild fear‐provoking stimulus 2 years after the end of differential rearing. VFD‐reared subjects at baseline were less gregarious than normally reared monkeys. VFDs also were considerably less responsive to the fear stimulus, and their behavior and affect returned to baseline levels more quickly than normally reared subjects. The extent and persistence of the sequelae of VFD rearing suggest parallels with predisposing factors in human anxiety disorders. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 40–45, 2001
Morphogenetic domains in the yolk syncytial layer of axiating zebrafish embryos
Authors: D'Amico Leonard A. , Cooper Mark S.
Published: August 2002

The yolk syncytial layer (YSL) of the teleostean yolk cell is known to play important roles in the induction of cellular mesendoderm, as well as the patterning of dorsal tissues. To determine how this extraembryonic endodermal compartment is subdivided and morphologically transformed during early development, we have examined collective movements of vitally stained YSL nuclei in axiating zebrafish embryos by using four‐dimensional confocal microscopy. During blastulation, gastrulation, and early segmentation, zebrafish YSL nuclei display several highly patterned movements, which are organized into spatially distinct morphogenetic domains along the anterior‐posterior and dorsal‐ventral axes. During the late blastula period, with the onset of epiboly, nuclei throughout the YSL initiate longitudinal movements that are directed along the animal‐vegetal axis. As epiboly progresses, nuclei progressively recede from the advancing margin of the epibolic YSL. However, a small group of nuclei is retained at the YSL margin to form a constricting blastoporal ring. During mid‐gastrulation, YSL nuclei undergo convergent‐extension behavior toward the dorsal midline, with a subset of nuclei forming an axial domain that underlies the notochord. These highly patterned movements of YSL nuclei share remarkable similarities to the morphogenetic movements of deep cells in the overlying zebrafish blastoderm. The macroscopic shape changes of the zebrafish yolk cell, as well as the morphogenetic movements of its YSL nuclei, are homologous to several morphogenetic behaviors that are regionally expressed within the vegetal endodermal cell mass of gastrulating Xenopus embryos. In contrast to the cellular endoderm of Xenopus, the dynamics of zebrafish YSL show that a syncytial endodermal germ layer can express a temporal sequence of morphogenetic domains without undergoing progressive steps of cell fate restriction. © 2001 Wiley‐Liss, Inc.