bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnet and gradient coil system for low‐field EPR imaging
Authors: Rinard George A. , Quine Richard W. , Eaton Gareth R. , Eaton Sandra S. , Barth Eugene D. , Pelizzari Charles A. , Halpern Howard J.
Published: August 2002

Air‐core coils are more practical than iron‐core magnets for producing the required magnetic field distribution for electron paramagnetic resonance imaging at frequencies of a few hundred megahertz. An air‐core, air‐cooled magnet/gradient coil system is presented in this paper, which is optimum in the sense that mathematically it produces fields, which for the number of coils specified, are as uniform (for the magnet) and as linear (for the gradient coils) as is possible over a spherical volume. The magnet is four‐coil (eighth‐order), the z‐coordinate gradient coil system is two‐coil, Maxwell (fifth order), and the transverse gradient coils are four‐coil, Anderson (fifth order). The design tradeoffs included homogeneity and linearity specifications, compatibility with access needed for physiological studies, power requirements, and provisions for rapid scanning. Incremental adjustments of the positions of the magnet coils, based on uniformity measurements, facilitated the meeting of design specifications at a reasonable cost. The 81 cm magnet can operate continuously at 90 G and can scan to 140 G. A 15 cm diameter working volume has a homogeneity of about 40 ppm. Three‐dimensional gradient coils are designed for 10 G/cm. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 51–58, 2002.
Early gastric carcinoma with signet ring cell histology
Authors: Hyung Woo Jin , Noh Sung Hoon , Lee Jun Ho , Huh Jihun J. , Lah Ki Hyeok , Choi Seung Ho , Min Jin Sik
Published: August 2002

BACKGROUND

There has been much controversy surrounding the biologic behavior and prognosis of early stage gastric signet ring cell carcinoma (SRC). To clarify the biologic behavior of early stage gastric SRC (early SRC), we compared the clinicopathologic features and prognosis of early SRC with other histologic types.

METHODS

A total of 933 patients with early gastric carcinoma who had undergone gastrectomy from 1987 to 1995 were retrospectively analyzed. Among them, 263 patients with SRC were compared to 670 patients with other histologic types.

RESULTS

Younger patients more often had SRC than non‐SRC. Additionally, the proportion of females was greater in SRC than in non‐SRC. Signet ring cell carcinoma had a larger proportion of mucosa‐confined lesions and a lower rate of lymph node metastasis than non‐SRC. Even after stratifying the clinicopathologic characteristics, SRC showed a lower rate of lymph node metastasis than non‐SRC. When the lymph node metastasis rate was compared between SRC and undifferentiated histology other than SRC, SRC demonstrated a lower lymph node metastasis rate. Multivariate analysis showed that SRC histology was a negative independent risk factor for lymph node metastasis in early gastric carcinoma. The prognosis of SRC was significantly better than that of non‐SRC (P = 0.0104).

CONCLUSIONS

Early gastric carcinoma with SRC is a distinct type of gastric carcinoma in terms of clinicopathologic features and prognosis. The favorable prognosis and lower rate of lymph node metastasis in early SRC suggest that the patients with early gastric carcinoma with SRC could be candidates for less invasive surgeries for an improved quality of life. Cancer 2002;94:78–83. © 2002 American Cancer Society.
Survival after recurrence of Ewing Tumors
Authors: Rodriguez‐Galindo Carlos , Billups Catherine A. , Kun Larry E. , Rao Bhaskar N. , Pratt Charles B. , Merchant Thomas E. , Santana Victor M. , Pappo Alberto S.
Published: August 2002

BACKGROUND

Despite improved therapies, 30–40% of patients with Ewing tumors (ET) experience recurrence and have a poor prognosis. The authors analyzed factors prognostic of survival in patients with recurrent ET.

METHODS

The authors assessed the relation between postrecurrence survival (PRS) and demographic, disease, and treatment factors in 71 patients who experienced recurrent ET after treatment on one of three consecutive institutional protocols.

RESULTS

Thirty‐four patients (47.9%) had distant recurrence, 25 patients (35.2%) had local recurrence, and 12 patients (16.9%) had both distant and local recurrence at a median of 1.7 years after diagnosis. The probability of 5‐year PRS (± 1 standard error) was 17.7% ± 4.5%. Recurrence ≥ 2 years after diagnosis predicted a significantly better outcome (5‐year PRS, 34.9% ± 8.5%) compared with earlier recurrence (5.0% ± 2.8%; P < 0.001). Patients who had both local and distant recurrence fared worse (5‐year PRS, 12.5% ± 8.3%) compared with patients who had local recurrence alone (21.7% ± 7.8%) or distant recurrence alone (17.6 ± 6.1%). Among patients with local recurrence alone, those who underwent salvage with radical surgery had significantly higher 5‐year PRS estimates (31.4% ± 11.6%) compared with the other patients (9.1% ± 6.1%; P = 0.023). Pulmonary irradiation significantly improved the outcomes of patients with isolated pulmonary recurrence (5‐year PRS estimate, 30.3% ± 12.5% vs. 16.7% ± 10.8%, respectively; P = 0.018).

CONCLUSIONS

Although outcomes are generally poor after patients experience recurrence of ET, certain patient groups differ appreciably in their likelihood of survival. Patients who experience recurrence ≥ 2 years after diagnosis and patients who have local recurrence that can be treated with radical surgery and intensive chemotherapy have the most favorable outcomes. Cancer 2002;94:561–9. © 2002 American Cancer Society.
Lifestyle interference and emotional distress in family caregivers of advanced cancer patients
Authors: Cameron Jill I. , Franche Rene‐Louise , Cheung Angela M. , Stewart Donna E.
Published: August 2002

BACKGROUND

Providing end‐of‐life care at home to a family member with advanced cancer can have a negative impact on the emotional well‐being of the family caregiver. The current study examined the impact of providing care on lifestyle and emotional well‐being in a sample of caregivers to patients with advanced cancer. The mediation of lifestyle interference between the amount of care provided and emotional distress was specifically examined.

METHODS

Forty‐four family caregivers participated in a structured quantitative interview. Lifestyle interference was assessed by the Caregiving Impact Scale, amount of care provided was assessed by the Caregiver Assistance Scale, and emotional distress was assessed by the Profile of Mood States—Short Form. Pearson and partial correlations tested whether lifestyle interference mediated the relationship between caregiving assistance and emotional distress. Regression analyses determined overall correlates of emotional distress.

RESULTS

Three criteria, required to substantiate mediation, were met for total mood disturbance and the depression and tension subscales. An overall regression model identified education level and lifestyle interference to be significant and unique correlates of emotional distress.

CONCLUSIONS

The current results suggest that caregivers experience increased emotional distress, regardless of the amount of care provided, when limited in their ability to participate in valued activities and interests. In addition, caregivers with less than a high school education experience more emotional distress. Therefore, helping caregivers maintain valued aspects of their lifestyle should be an important element of home care. Cancer 2002;94:521–7. © 2002 American Cancer Society.
Higher doses of mitoxantrone among men with hormone‐refractory prostate carcinoma
Authors: Levine Ellis G. , Halabi Susan , Roberts John D. , Kaplan Ellen B. , Rago Randall , Atkins James N. , Vogelzang Nicholas J.
Published: August 2002

BACKGROUND

Mitoxantrone in combination with a low‐dose glucocorticoid has been shown to produce more favorable outcomes among men with hormone‐refractory prostate carcinoma than glucocorticoid alone. Therefore, the authors sought to determine the safety and activity of higher doses of mitoxantrone in combination with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and a glucocorticoid in preparation for a possible Phase III trial comparing standard to dose‐escalated mitoxantrone.

METHODS

This Phase II trial enrolled 45 patients from October 1996 to March 1998. Twenty‐one patients without pelvic irradiation (Arm I) received 21 mg/m2 of mitoxantrone every 3 weeks, and 24 patients who had received pelvic irradiation (Arm II) were given 17 mg/m2 on the same schedule. All patients received 40 mg of hydrocortisone in divided doses daily and GM‐CSF at 500 μg/daily for a minimum of 10 days per cycle beginning on the third day of the cycle.

RESULTS

In Arm I, 33% of assessable patients achieved a partial response, 50% had a ≥ 50% decline in their PSA, and 35% had a ≥ 75% decline in PSA values. The comparable numbers in Arm II were 24%, 48%, and 35%, respectively. The median survival times were 12 months in Arm I and 14 months in Arm II. Treatment had to be discontinued in 13% of patients because of thrombocytopenia. No other significant toxicities were encountered.

CONCLUSIONS

Higher doses of mitoxantrone (17 and 21 mg/m2) were associated with activity comparable to many estramustine combinations and generally were well tolerated. However, because the degree and frequency of thrombocytopenia were greater than that observed with standard dose mitoxantrone (12–14 mg/m2), and because the median survival is apparently comparable to standard dose mitoxantrone, this approach to HRPC cannot be recommended for Phase III testing. Cancer 2002;94:665–72. © 2002 American Cancer Society.

DOI 10.1002/cncr.10217
Vulvar melanoma
Authors: de Hullu Joanne A. , Hollema Harry , Hoekstra Harald J. , Piers Do A. , Mourits Marian J. E. , Aalders Jan G. , van der Zee Ate G. J.
Published: August 2002

BACKGROUND

The objective of this study was to evaluate the author's recent, preliminary experience with the sentinel lymph node procedure in patients with vulvar melanoma and to compare this experience with treatment and follow‐up of patients with vulvar melanomas who were treated previously at their institution.

METHODS

From 1997, sentinel lymph node procedure with the combined technique (99mTechnetium‐labeled nanocolloid and Patente Blue‐V) was performed as a standard staging procedure for patients with vulvar melanoma with a thickness > 1 mm and no clinically suspicious inguinofemoral lymph nodes. For the current study, clinicopathologic data from all 33 patients with vulvar melanoma who were treated between 1978 and 2000 at the University Hospital Groningen were reviewed and analyzed.

RESULTS

From January 1997 until December 2000, identification of sentinel lymph nodes was successful in all nine patients who were referred for treatment of vulvar melanoma. Three patients underwent subsequent complete inguinofemoral lymphadenectomy because of metastatic sentinel lymph nodes. In follow‐up, groin recurrences (in‐transit metastases) occurred in two of nine patients, both 12 months after primary treatment. Both patients had melanomas with a thickness > 4 mm and previously had negative sentinel lymph nodes. There was a trend toward more frequent groin recurrences in patients after undergoing the sentinel lymph node procedure (2 of 9 patients) compared with 24 historic control patients (0 of 24 patients; P = 0.06). Five of 33 patients developed local recurrences: Two patients had groin recurrences, and 11 patients developed distant metastases. Twelve patients died of vulvar melanoma. Seventeen patients with a median follow‐up of 66 months (range, 9–123 months) are currently alive (overall survival rate, 52%).

CONCLUSIONS

Although the numbers were small, this study showed that the sentinel lymph node procedure is capable of identifying patients who have occult lymph node metastases and who may benefit from lymphadenectomy for locoregional control and prevention of distant metastases. However, the data also suggest that the sentinel lymph node procedure may increase the risk of locoregional recurrences (in‐transit metastases), especially in patients with thick melanomas. The potential role of the sentinel lymph node procedure as an alternative method of lymph node staging in patients with vulvar melanoma needs further investigation only within the protection of clinical trials and probably should be restricted to patients with melanomas with intermediate thickness (1–4 mm). Cancer 2002;94:486–91. © 2002 American Cancer Society.
Episodic (breakthrough) pain
Authors: Mercadante Sebastiano , Radbruch Lukas , Caraceni Augusto , Cherny Nathan , Kaasa Stein , Nauck Friedemann , Ripamonti Carla , De Conno Franco ,   Steering Committee of the European Association for Palliative Care (EAPC) Research Network
Published: August 2002

BACKGROUND

Breakthrough pain is transitory exacerbation of pain that occurs in addition to otherwise stable persistent pain. The wide differences in estimation of incidence reported in literature are probably because of different settings and meanings attributed to the definition of breakthrough pain.

METHODS

A panel of experts met to establish the actual knowledge on breakthrough pain, according to the evidence in literature and experience. They agreed that episodic or transient pain could be a more simple and adequate term in most languages, including English, French, Italian, and Spanish.

RESULTS

A specific assessment and precise pain characterization are essential to plan the most appropriate treatments. Despite the relevance of this temporal pain pattern for the influence on the outcome and quality of life, few controlled studies have been performed to give evidence of a specific approach. Several experiences have reported the possible efficacy of different drugs, route of administration, and modalities of administration in different circumstances.

CONCLUSIONS

Prospective studies with previous treatments using similar terminologies are necessary to find the most convenient therapeutic intervention, according to the temporal pattern characteristics and the pain mechanism involved. Cancer 2002;94:832–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10249
Adjuvant chemohormonal therapy of high risk prostate carcinoma
Authors: Bagley Charles M. , Lane Robert F. , Blasko John C. , Grimm Peter D. , Ragde Haakon , Cobb Oliver E. , Rowbotham Ronald K.
Published: August 2002

BACKGROUND

Patients with T3 and/or N1 prostate carcinoma have poor cure rates. The authors sought to improve the relapse free, cancer specific survival of these patients by adding chemohormonal therapy to radiation.

METHODS

Twenty five men with clinical Stage III positive seminal vesicles or positive nodes received six courses of vinblastine, doxorubicin, and mitomycin with simultaneous radiation and permanent androgen deprivation. Prostate specific antigen (PSA) testing was the sole criterion for relapse. Median followup was 10.5 years.

RESULTS

Treatment was well tolerated. Patients received 91‐95% of each drug and all planned radiation. At 10 years the cumulative relapse free rate determined by continuously undetectable PSA levels was 73%, and the cumulative cancer specific survival was 81%. Of node‐positive patients, 82% were relapse‐free at 10 years.

CONCLUSIONS

The addition of chemotherapy to hormonal and radiation therapy is feasible and is accepted by most men when they are openly informed of their prognosis with conventional therapy. Results in the current small series appear excellent and may be superior to radiation plus hormones alone. Larger randomized studies are warranted. Cancer 2002; 94:2728–32. © 2002 American Cancer Society.

DOI 10.1002/cncr.10527
Physician factors in the timing of cancer patient referral to hospice palliative care
Authors: Lamont Elizabeth B. , Christakis Nicholas A.
Published: August 2002

BACKGROUND

Although physicians state that patients ideally should receive hospice care for 3 months before death, the majority of patients survive < 1 month in hospice care. In the current study, the authors attempted to determine whether the attributes of referring physicians were associated with the survival of terminally ill cancer patients in hospice.

METHODS

Using a prospective cohort study design, the authors observed the survival of 326 terminally ill cancer patients who were referred by 258 different physicians to 5 outpatient hospice programs in Chicago. The authors evaluated associations between patient, physician, and patient‐physician relationship factors and patient survival.

RESULTS

Of the 326 participating patients, 313 (96%) had known dates of death. For these patients, the median survival was 26 days. Controlling for patient demographic and disease factors, there were several physician factors found to be associated with the length of patient survival after hospice referral. For example, when a physician had referred ≥ 2 patients to hospice care in the previous 3 months, the patient survived 17 days longer in hospice compared with those patients whose physician referred fewer patients to hospice. When a physician estimated patient survival accurately (estimate obtained at the time of referral), the patient lived 20 days longer in hospice compared with those patients whose physicians made inaccurate survival estimates. The practice specialty of the physician also was found to be associated with patient survival after hospice referral, with patients referred by general internists and geriatricians living 18 days longer in hospice compared with those patients who were referred by oncologists.

CONCLUSIONS

In the current study, referring physician factors were found to be associated with the survival of terminally ill cancer patients after referral to hospice. Cancer 2002; 94:2733–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10530
Excitotoxic and metabolic damage to the rodent striatum: Role of the P75 neurotrophin receptor and glial progenitors
Authors: Hanbury Rose , Charles Vinod , Chen Er‐Yun , Leventhal Liza , Rosenstein Jeffrey M. , Mufson Elliott J. , Kordower Jeffrey H.
Published: August 2002

After injury, the striatum displays several morphologic responses that may play a role in both regenerative and degenerative events. One such response is the de novo expression of the low‐affinity p75 neurotrophin receptor (p75NTR), a gene that plays critical roles in central nervous system (CNS) cell death pathways. The present series of experiments sought to elucidate the cellular origins of this p75NTR response, to define the conditions under which p75NTR is expressed after striatal injury, and how this receptor expression is associated with neuronal plasticity. After chemical lesions, by using either the excitotoxin quinolinic acid (QA) or the complex II mitochondria inhibitor 3‐nitropropionic acid (3‐NP), we compared the expression of the p75NTR receptor within the rat striatum at different survival times. Intrastriatal administration of QA between 7 days and 21 days postlesion induced p75NTR expression in astrocytes that was preferentially distributed throughout the lesion core. P75NTR immunoreactivity within astrocytes was seen at high (100–220 nmol) but not low (50 nmol) QA doses. Seven and 21 days after 3‐NP lesions, p75NTR expression was present in astrocytes at all doses tested (100–1,000 nmol). However, in contrast to QA, these cells were located primarily around the periphery of the lesion and not within the lesion core. At the light microscopic level p75NTR immunoreactive elements resembled vasculature: but did not colocalize with the pan endothelium cell marker RecA‐1. In contrast, p75NTR‐containing astrocytes colocalized with nestin, vimentin, and 5‐bromo‐2‐deoxyuridine, indicating that these cells are newly born astrocytes. Additionally, striatal cholinergic neurons were distributed around the lesion core expressed p75NTR 3–5 days after lesion in both QA and 3‐NP lesions. These cells did not coexpress the pro‐apoptotic degradation enzyme caspase‐3. Taken together, these data indicate that striatal lesions created by means of excitotoxic or metabolic mechanisms trigger the expression of p75NTR in structures related to progenitor cells. The expression of the p75NTR receptor after these chemical lesions support the concept that this receptor plays a role in the initiation of endogenous cellular events associated with CNS injury. J. Comp. Neurol. 444:291–305, 2002. © 2002 Wiley‐Liss, Inc.
Effects of age on the glial cells in the rhesus monkey optic nerve
Authors: Sandell Julie H. , Peters Alan
Published: August 2002

The optic nerve is a circumscribed white matter tract consisting of myelinated nerve fibers and neuroglial cells. Previous work has shown that during normal aging in the rhesus monkey, many optic nerves lose some of their nerve fibers, and in all old optic nerves there are both myelin abnormalities and degenerating nerve fibers. The present study assesses how the neuroglial cell population of the optic nerve is affected by age. To address this question, optic nerves from young (4–10 years) and old (27–33 years) rhesus monkeys were examined by using both light and electron microscopy. It was found that with age the astrocytes, oligodendrocytes, and microglia all develop characteristic cytoplasmic inclusions. The astrocytes hypertrophy and fill space vacated by degenerated nerve fibers, and they often develop abundant glial filaments in their processes. Oligodendrocytes and microglial cells both become more numerous with age, and microglial cells often become engorged with phagocytosed debris. Some of the debris can be recognized as degenerating myelin, and in general, the greater the loss of nerve fibers, the more active the microglial cells become. J. Comp. Neurol. 445:13–28, 2002. © 2002 Wiley‐Liss, Inc.
Corticotropin‐releasing hormone‐synthesizing neurons of the human hypothalamus receive neuropeptide Y‐immunoreactive innervation from neurons residing primarily outside the infundibular nucleus
Authors: Mihály Emese , Fekete Csaba , Lechan Ronald M. , Liposits Zsolt
Published: August 2002

Immunohistochemical single‐ and double‐labeling studies were performed on the hypothalami of postmortem human brains to elucidate the distribution of corticotropin‐releasing hormone (CRH)‐immunoreactive (IR) neuronal elements and their interaction with the neuropeptide Y (NPY)‐ergic neuronal system. The great majority of CRH‐IR perikarya were found in the paraventricular nucleus (PVN), whereas a considerable number of CRH‐IR neurons were also observed in the periventricular and infundibular nuclei. The dorsomedial nucleus and the perifornical region contained only scattered CRH‐IR neurons. Dense CRH‐IR fiber networks were found throughout the hypothalamus. However, the medial preoptic, the dorsolateral part of the supraoptic, the suprachiasmatic, the ventromedial, and the different mammillary nuclei showed a relative paucity of fibers. The terminal fields of NPY‐IR axons overlapped the distribution of CRH‐IR neurons in the hypothalamus. NPY‐IR axon varicosities were juxtaposed to both dendrites and perikarya of the majority of CRH‐IR neurons residing in the paraventricular, periventricular, and infundibular nuclei. These neurons were frequently contacted by multiple NPY axons that either formed baskets around their perikarya or completely ensheathed the emanating CRH dendrites. Because NPY and agouti‐related protein (AGRP) are co‐contained in neurons of the human infundibular nucleus, we used AGRP as a marker of NPY fibers originating exclusively from the infundibular nucleus. Only a small proportion of CRH neurons in the PVN was contacted by AGRP‐IR axon varicosities, suggesting that NPY‐IR innervation of CRH neurons in the PVN derive mainly from regions outside the infundibular nucleus. The present morphological findings support the view that NPY regulates the CRH system of the human hypothalamus and therefore at least some of the effects of NPY on metabolic, autonomic, and endocrine functions may be mediated through CRH. J. Comp. Neurol. 446:235–243, 2002. © 2002 Wiley‐Liss, Inc.
Molecular characterization and cell‐specific expression of a Manduca sexta FLRFamide gene
Authors: Lu Dan , Lee Kyeong‐Yeoll , Horodyski Frank M. , Witten Jane L.
Published: August 2002

FMRFamide‐related peptides (FaRPs) are a large group of neuropeptides containing a common RFamide C‐terminus; they have been identified in vertebrates and invertebrates. We have isolated the cDNA that encodes three FaRPs in the tobacco hornworm, Manduca sexta, including the amidated decapeptide F10. The larger FaRPs are the partially processed precursors of F10, a neuropeptide belonging to the myosuppressin family of peptides. The presence of all three FaRPs in different tissues suggests differential utilization of typical dibasic processing sites and atypical processing sites C‐terminal to leucine residues. F10 mRNA was detected in the brain, nerve cord, and midgut, and the mRNA levels in the nervous system are dynamically regulated during development. In situ hybridization analysis localized the F10 mRNA to a variety of cell types within the central nervous system (CNS), a peripheral neurosecretory cell (L1), and midgut endocrine cells, which suggests diverse functions. Distribution of the F10‐containing neurons within the central nervous system is segment‐specific, and the developmental profile suggests that the F10 gene products may have stage‐specific functions. Molecular characterization of the F10 gene has provided insights into its regulation and cell‐specific distribution that will enhance our understanding of how these FaRPs modulate different physiological systems and ultimately behavior. J. Comp. Neurol. 446:377–396, 2002. © 2002 Wiley‐Liss, Inc.
GABAA receptor changes in δ subunit‐deficient mice: Altered expression of α4 and γ2 subunits in the forebrain
Authors: Peng Zechun , Hauer Birgit , Mihalek Robert M. , Homanics Gregg E. , Sieghart Werner , Olsen Richard W. , Houser Carolyn R.
Published: August 2002

The δ subunit is a novel subunit of the pentameric γ‐aminobutyric acid (GABA)A receptor that conveys special pharmacological and functional properties to recombinant receptors and may be particularly important in mediating tonic inhibition. Mice that lack the δ subunit have been produced by gene‐targeting technology, and these mice were studied with immunohistochemical and immunoblot methods to determine whether changes in GABAA receptors were limited to deletion of the δ subunit or whether alterations in other GABAA receptor subunits were also present in the δ subunit knockout (δ–/–) mice. Immunohistochemical studies of wild‐type mice confirmed the restricted distribution of the δ subunit in the forebrain. Regions with moderate to high levels of δ subunit expression included thalamic relay nuclei, caudate‐putamen, molecular layer of the dentate gyrus, and outer layers of the cerebral cortex. Virtually no δ subunit labeling was evident in adjacent regions, such as the thalamic reticular nucleus, hypothalamus, and globus pallidus. Comparisons of the expression of other subunits in δ–/– and wild‐type mice demonstrated substantial changes in the α4 and γ2 subunits of the GABAA receptor in the δ–/– mice. γ2 Subunit expression was increased, whereas α4 subunit expression was decreased in δ–/– mice. Importantly, alterations of both the α4 and the γ2 subunits were confined primarily to brain regions that normally expressed the δ subunit. This suggests that the additional subunit changes are directly linked to loss of the δ subunit and could reflect local changes in subunit composition and function of GABAA receptors in δ–/– mice. J. Comp. Neurol. 446:179–197, 2002. © 2002 Wiley‐Liss, Inc.
Differentiation and maturation of zebrafish dorsal root and sympathetic ganglion neurons
Authors: An Min , Luo Rushu , Henion Paul D.
Published: August 2002

The trunk neural crest of vertebrate embryos gives rise to dorsal root ganglion (DRG) sensory neurons and autonomic sympathetic neurons, among other derivatives. We have examined the development of DRG and sympathetic neurons during development in the zebrafish. We found that sensory neurons differentiate rapidly and that their overt neuronal differentiation significantly precedes that of sympathetic neurons in the trunk. Sympathetic neurons in different regions differentiate at different times. The most rostral population, which we call the cervical ganglion, differentiates several days before trunk sympathetic neurons. After undergoing overt neuronal differentiation, sympathetic neurons subsequently express the adrenergic differentiation markers dopamine β‐hydroxylase and tyrosine hydroxylase. A second population of adrenergic nonneuronal cells initially localized with cervical sympathetic neurons appears to represent adrenal chromaffin cells. In more mature fish, these cells were present in clusters within the kidneys. Individual DRG and sympathetic ganglia initially contain few neurons. However, the number of neurons in DRG and sympathetic ganglia increases continuously at least up to 4 weeks of age. Analysis of phosphohistone H3 expression and bromodeoxyuridine incorporation studies suggests that the increases in DRG and sympathetic ganglion neuronal cell number are due wholly or in part to the division of neuronal cells within the ganglia. J. Comp. Neurol. 446:267–275, 2002. © 2002 Wiley‐Liss, Inc.
Firing features and potassium channel content of murine spiral ganglion neurons vary with cochlear location
Authors: Adamson Crista L. , Reid Michael A. , Mo Zun‐Li , Bowne‐English Janet , Davis Robin L.
Published: August 2002

Neurons from varied regions of the central nervous system can show widely divergent responses to electrical stimuli that are determined by cell‐specific differences in ion channel composition. The well‐ordered and highly characterized peripheral auditory system allows one to explore the significance of this diversity during the final stages of postnatal development. We examined the electrophysiological features of murine spiral ganglion neurons in vitro at a time when recordings could be made from the cell bodies before myelination. These cells carry information about sound stimuli from hair cell receptors in the basilar membrane and are arranged tonotopically. Spiral ganglion neuron responses to depolarizing current injection were assessed with whole‐cell current clamp recordings from cells that were isolated separately from the apical and basal thirds of the mouse cochlea. These cells displayed systematic variation in their firing. Apex neurons (low frequency coding) showed longer latency, slowly adapting responses, whereas base neurons (high frequency coding) showed short latency, rapidly adapting responses to the same stimuli. This physiological diversity was mirrored by regional differences in ion channel content assessed immunohistochemically. Apex neurons had a preponderance of Kv4.2 subunits, whereas base neurons possessed greater levels of KCa, Kv1.1, and Kv3.1 subunits. Taken together, these results indicate that the distribution of a set of voltage‐gated potassium channels may relate specifically to a particular range of coding frequencies. These studies also suggest that intrinsic properties of spiral ganglion neurons can contribute to the characteristic responses of the peripheral auditory system. Their potential role in development and adult function is discussed. J. Comp. Neurol. 447:331–350, 2002. © 2002 Wiley‐Liss, Inc.
Retina of Bouton's skink (reptilia, scincidae): Visual cells, fovea, and ecological constraints
Authors: Röll Beate
Published: August 2002

Bouton's skink, Cryptoblepharus boutonii africanus, is a small, diurnal lizard living on outcrops along the coast of East Africa under high ambient light intensities. It is characterized by relatively large eyes (maximal diameter about 2 mm), with immovable eyelids forming a transparent spectacle and with a virtually constant pupil diameter. The single fovea in the central retina is well developed, with a clearly defined pit, which is relatively deep but not funnel‐shaped. The foveal pit is not devoid of the outer nuclear and outer plexiform layers; only the main part of the inner nuclear layer is displaced laterally, resulting in a pit with gradual sloping towards its edges. Thus, the fovea appears to be concaviclivate, as in the eyes of lacertids, varanids, and gekkonids. The central position of the foveae in these laterally placed scincid eyes corresponds with monocular fixation, e.g., of detected prey. C. boutonii has a pure‐cone retina containing single and double visual cells. The latter consist of two cells of unequal sizes. Yellowish oil droplets are present in single cones and the minor members of the double cones in all retinal regions. The visual cells of the different retinal regions do not differ in the ultrastructure of their components but differ considerably in size. The outer segments of the foveal cones are twice as long as those of the peripheral cones. Except for the pedicles, the diameters of the components of the visual cells decrease towards the fovea, resulting in an increase in visual acuity. J. Comp. Neurol. 436:487–496, 2001. © 2001 Wiley‐Liss, Inc.
Functional organization of the suprachiasmatic nucleus of Xenopus laevis in relation to background adaptation
Authors: Kramer Bianca M.R. , Welting Joyce , Berghs Constance A.F.M. , Jenks Bruce G. , Roubos Eric W.
Published: August 2002

The process of background adaptation in the toad Xenopus laevis is controlled by neurons in the suprachiasmatic nucleus (SC) that inhibit the release of α‐melanophore‐stimulating hormone from the neuroendocrine melanotrope cells in the pituitary gland. We have identified the structural and functional organization of different neuropeptide Y (NPY)‐containing cell groups in the Xenopus SC in relation to background adaptation. A ventrolateral, a dorsomedial, and a caudal group were distinguished, differing in location as well as in number, size, and shape of their cells. They also show different degrees of NPY immunoreactivity in response to different background adaptation conditions. In situ hybridization using a Xenopus mRNA probe for the exocytosis protein DOC2 revealed that melanotrope cells of black‐adapted animals have a much higher expression of DOC2‐mRNA than white‐adapted ones. This establishes that the degree of DOC2‐mRNA expression is a good parameter to measure cellular secretory activity in Xenopus. We show that in the ventrolateral SC group, more NPY‐positive neurons express DOC2‐mRNA in white‐ than in black‐adapted animals. In contrast, NPY‐positive neurons in the dorsomedial group have a high secretory activity under the black‐adaptation condition. We propose that in black‐adapted animals, NPY‐positive neurons in the ventrolateral group, known to inhibit the melanotrope cells in white‐adapted animals synaptically, are inhibited by NPY‐containing interneurons in the dorsmedial group. NPY‐positive neurons in the caudal group have similar secretory dynamics as the dorsomedial NPY neurons, indicating that they also play a role in background adaptation, distinct from that exerted by the ventrolateral and dorsomedial group. J. Comp. Neurol. 432:346–355, 2001. © 2001 Wiley‐Liss, Inc.
Immunocytochemical localization of opsin, visual arrestin, myosin III, and calmodulin in Limulus lateral eye retinular cells and ventral photoreceptors
Authors: Battelle Barbara‐Anne , Dabdoub Alain , Malone Michael A. , Andrews Anne W. , Cacciatore Chelsi , Calman Bruce G. , Smith W. Clay , Payne Richard
Published: August 2002

The photoreceptors of the horseshoe crab Limulus polyphemus are classical preparations for studies of the photoresponse and its modulation by circadian clocks. An extensive literature details their physiology and ultrastructure, but relatively little is known about their biochemical organization largely because of a lack of antibodies specific for Limulus photoreceptor proteins. We developed antibodies directed against Limulus opsin, visual arrestin, and myosin III, and we have used them to examine the distributions of these proteins in the Limulus visual system. We also used a commercial antibody to examine the distribution of calmodulin in Limulus photoreceptors. Fixed frozen sections of lateral eye were examined with conventional fluorescence microscopy; ventral photoreceptors were studied with confocal microscopy. Opsin, visual arrestin, myosin III, and calmodulin are all concentrated at the photosensitive rhabdomeral membrane, which is consistent with their participation in the photoresponse. Opsin and visual arrestin, but not myosin III or calmodulin, are also concentrated in extra‐rhabdomeral vesicles thought to contain internalized rhabdomeral membrane. In addition, visual arrestin and myosin III were found widely distributed in the cytosol of photoreceptors, suggesting that they have functions in addition to their roles in phototransduction. Our results both clarify and raise new questions about the functions of opsin, visual arrestin, myosin III, and calmodulin in photoreceptors and set the stage for future studies of the impact of light and clock signals on the structure and function of photoreceptors. J. Comp. Neurol. 435:211–225, 2001. © 2001 Wiley‐Liss, Inc.
Comparative fine structural distribution of endopeptidase 24.15 (EC3.4.24.15) and 24.16 (EC3.4.24.16) in rat brain
Authors: Fontenele‐Neto José Domingues , Massarelli Eduardo Ernst , Gurgel Garrido Paula Amaral , Beaudet Alain , Ferro Emer Suavinho
Published: August 2002

Endopeptidase 24.15 (EP24.15) and 24.16 (EP24.16) are closely related metalloendopeptidases implicated in the metabolism of several neuropeptides and widely expressed in mammalian brain. To gain insight into the functional role of these two enzymes in the central nervous system, we examined their cellular and subcellular distribution in rat brain by using electron microscopic immunogold labeling. In all areas examined, EP24.15 and EP24.16 immunoreactivity were observed in selective subpopulations of neuronal and glial cells. Subcellular localization of EP24.15 in neurons revealed that this enzyme was predominantly concentrated in the nucleus, whereas EP24.16 was almost exclusively cytoplasmic. The amount of EP24.15 found in the nucleus was inversely correlated with that found in the cytoplasm, suggesting that the enzyme could be mobilized from one compartment to the other. Within the cytoplasm, EP24.15 and EP24.16 immunoreactivity showed comparable distributional patterns. Both enzymes were detected throughout perikarya and dendrites, as well as within axons and axon terminals. In all neuronal compartments, EP24.15 and EP24.16 showed a major association with membranes of neurosecretory elements, including Golgi cisternae, tubulovesicular organelles, synaptic vesicles, and endosomes. However, whereas EP24.15 always faced the cytoplasmic face of the membranes, EP24.16 was observed on both cytoplasmic and luminal sides, suggesting that the latter was more likely to contribute to the processing of peptides or to the degradation of internalized ligands. Taken together, the present results suggest that EP24.15 could play a major role in the hydrolysis of intranuclear substrates, whereas EP24.16 would be predominantly involved in the processing and inactivation of signaling peptides. J. Comp. Neurol.438:399–410, 2001. © 2001 Wiley‐Liss. Inc.
Postnatal development of catecholamine inputs to the paraventricular nucleus of the hypothalamus in rats
Authors: Rinaman Linda
Published: August 2002

Adrenergic and noradrenergic neural projections to the paraventricular nucleus of the hypothalamus (PVN) contribute importantly to viscerosensory modulation of pituitary hormone secretion. Immaturity of ascending catecholamine pathways may partially underlie the documented hyporesponsiveness of PVN neurosecretory cells to certain interoceptive stimuli in rats during the first few weeks of postnatal development. To explore this possibility, the present study compared the distribution and number of dopamine‐β‐hydroxylase (DBH)‐ and phenylethanolamine‐N‐methyltransferase (PNMT)‐positive neurons projecting to the PVN in newborn and adult rats. In addition, a quantitative analysis of DBH‐ and PNMT‐immunoreactive fibers in the medial parvocellular subnucleus, dorsal division (PVNmpd) and posterior magnocellular subnucleus, lateral division (PVNpml) was performed in adult rats and in developing rats on postnatal day (P)1, P7, P14, and P21. The numbers of PVN‐projecting neurons in the A1, C1, A2/C2, C3, or A6 catecholamine cell groups were similar in newborn and adult rats, as were the proportions of PVN‐projecting neurons in each region that were PNMT‐positive. However, fewer PVN‐projecting neurons in the C1 and C3 regions expressed DBH immunolabeling in newborn rats compared to adults. DBH immunolabeling increased progressively in the PVNmpd and PVNpml between postnatal days P1 and P21, when adult‐like levels were achieved. Conversely, PNMT immunolabeling in the same PVN subdivisions was most dense at P1, gradually decreasing to adult‐like levels by P21. These dynamic developmental changes in catecholamine synthetic enzyme immunolabeling densities in the PVN may reflect functional changes in noradrenergic and adrenergic signaling capacity in rats during the first few weeks of postnatal development. J. Comp. Neurol. 438:411–422, 2001. © 2001 Wiley‐Liss, Inc.
Localization of the presynaptic cytomatrix protein Piccolo at ribbon and conventional synapses in the rat retina: Comparison with Bassoon
Authors: Dick Oliver , Hack Iris , Altrock Wilko Detlef , Garner Craig Curtis , Gundelfinger Eckart Dieter , Brandstätter Johann Helmut
Published: August 2002

In recent years significant progress has been made in the elucidation of the molecular assembly of the postsynaptic density at synapses, whereas little is known as yet about the components of the presynaptic active zone. Piccolo and Bassoon, two structurally related presynaptic cytomatrix proteins, are highly concentrated at the active zones of both excitatory and inhibitory synapses in rat brain. In this study we used immunocytochemistry to examine the cellular and ultrastructural localization of Piccolo at synapses in the rat retina and compared it with that of Bassoon. Both proteins showed strong punctate immunofluorescence in the outer and the inner plexiform layers of the retina. They were found presynaptically at glutamatergic ribbon synapses and at conventional GABAergic and glycinergic synapses. Although the two proteins were coexpressed at all photoreceptor ribbon synapses and at some conventional amacrine cell synapses, at bipolar cell ribbon synapses only Piccolo was present. Our data demonstrate similarities but also differences in the molecular composition of the presynaptic apparatuses of the synapses in the retina, differences that may account for the functional differences observed between the ribbon and the conventional amacrine cell synapses and between the photoreceptor and the bipolar cell ribbon synapses in the retina. J. Comp. Neurol. 439:224–234, 2001. © 2001 Wiley‐Liss, Inc.
Transforming growth factor‐α‐induced cellular changes in organotypic cultures of juvenile, amikacin‐treated rat organ of corti
Authors: Daudet Nicolas , Ripoll Chantal , Lenoir Marc
Published: August 2002

Hair cell losses in the mammalian cochlea following an ototoxic insult are irreversible. However, past studies have shown that amikacin treatment in rat cochleae resulted in the transient presence of atypical Deiters' cells (ACs) in the damaged organ of Corti. These ACs arise through a transformation of Deiters' cells, which produce, at their apical pole, densely packed microvilli reminiscent of early‐differentiating stereociliary bundles. The ACs do not, however, express typical hair cell markers such as parvalbumin or calbindin. The present study was designed to determine whether specific growth factors could influence the survival and differentiation of these ACs and stimulate hair cell regeneration processes in vitro. Apical‐medial segments of organ of Corti of juvenile amikacin‐treated rats were established as organotypic cultures, and the effects of epidermal growth factor (EGF), insulin‐like growth factor 1 (IGF‐1), transforming growth factor‐α (TGFα), and retinoic acid were studied using morphological and molecular approaches. Our results indicate that TGFα supports the survival of the damaged organ of Corti and influences ACs differentiation in vitro, possibly acting through reorganization of the actin cytoskeleton. These effects could be directly mediated through activation of the EGF receptor, which is expressed by supporting cells in the mature organ of Corti. TGFα does not, however, allow the ACs to progress towards a hair cell phenotype. J. Comp. Neurol. 442:6–22, 2002. © 2002 Wiley‐Liss, Inc.
Localization and characterization of NPY/PYY receptors in rat frontoparietal cortex during development
Authors: Leroux Philippe
Published: August 2002

Neuropeptide Y (NPY) is present in most cerebrocortical areas during fetal and postnatal development. In the rat frontal cortex, a dense radial fiber network containing NPY immunoreactivity is observed transiently as early as embryonic day 17 (E17) and disappears at the end of the first postnatal week. We have investigated the distribution of NPY receptors in the frontoparietal cortex at 13 stages of development, from E15 fetuses to adults, by in vitro autoradiography, using 125I‐pPYY as a radioligand. Quantitative receptor density was measured through all cortical layers at each developmental stage. Pharmacological identification of 125I‐pPPY binding sites was made by competition experiments using pNPY or [Leu31,Pro34]pNPY and pNPY13‐36, as selective competitors for Y1 and Y2 receptors, respectively. NPY receptors were first detected in the cerebral cortex at low densities at E19 in a thin layer of tissue corresponding to the inner half of the intermediate zone (IZ) and the upper ventricular zone (VZ). The neuroepithelium did not contain binding sites. High densities of sites were observed by E21 onward to P10 in the deep cortical layers corresponding to the IZ and layers V–VI. A decreasing gradient of receptor density was observed from layer VI to the marginal zone (layer I). The distribution of NPY receptors does not match with the perikarya of transient NPY‐immunoreactive neurons located in the cortical plate but does coincide with their axonal extension. The receptor density decreased abruptly between P10 and P12 in deep layers, whereas a moderate expression of binding sites is detected from P10 to P12 in layers I–III. By P14, the binding level was the lowest observed in the postnatal period. From P21 onward, receptors were observed in superficial layers I–III, and their density rose by two‐ to threefold up to adulthood. Competition studies indicated that the NPY receptors located in the deep cortical layers of the E21 or P1 rat cortex exhibit Y2 receptor type characteristics. The binding sites detected in the superficial layers from P10 to P12 rats also show Y2 receptors characteristics, unlike the NPY receptors in layers II–III of the adult, which behave like Y1 receptors. These data show that different NPY receptor types are successively expressed in specific layers during late gestation and early postnatal life in the rat frontoparietal cortex. J. Comp. Neurol. 442:35–47, 2002. © 2002 Wiley‐Liss, Inc.
Rotation shape functions for a low‐order quadrilateral plate element with mid‐side rotations
Authors: Crisfield M. A. , Tan D.
Published: August 2002

This short paper re‐visits an earlier paper by Nagtegaal and Slater in which a quadrilateral shell element was derived which used similar kinematics to that in the Morley facet shell. Because the paper seems to be relatively unknown and also is rather long and involved, we here concentrate on the plate‐bending aspects of the element and describe the shape functions. Copyright © 2001 John Wiley & Sons, Ltd.