bluuebunny/crossref_metadata_2025 huggingface dataset:
A pulsed and continuous wave 250 MHz electron paramagnetic resonance spectrometer
Authors: Quine Richard W. , Rinard George A. , Eaton Sandra S. , Eaton Gareth R.
Published: August 2002

A 250 MHz electron paramagnetic resonance (EPR) spectrometer was constructed to be an engineering test facility for in vivo EPR imaging of physiological samples and for protein structure determination. Innovations relative to prior low‐frequency EPR spectrometers include a four‐coil, air‐core magnet and gradient coils, a crossed‐loop resonator, dynamic Q‐switching to decrease dead time in pulsed EPR, and a narrow‐band bridge based on circulators. The automatic frequency control system uses a signal separate from the EPR signal to make the frequency control independent of the radiofrequency (RF) phase. The design incorporates multiple excitation and signal paths to facilitate testing of a variety of resonators, two magnets, and both a locally built console described here and a Bruker console. Plug‐in cards in the bridge facilitate using reflection or crossed‐loop resonators in continuous wave or pulsed EPR modes. In the locally built console there is a microprocessor‐controlled interface unit to handle magnetic field modulation and scan, tuning display, and other functions. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 59–91, 2002.
Transforming growth factor‐β1 as a useful serologic marker of small hepatocellular carcinoma
Authors: Song Byung‐Cheol , Chung Young‐Hwa , Kim Jung A. , Choi Won‐Beom , Suh Dong Dae , Pyo Seung Il , Shin Jung Woo , Lee Han Chu , Lee Yung Sang , Suh Dong Jin
Published: August 2002

BACKGROUND

Although alpha‐fetoprotein (AFP) is a useful serologic marker of hepatocellular carcinoma (HCC), it has been reported insufficiently sensitive in detecting small HCCs. Plasma transforming growth factor‐β1 (TGFβ1) has been reported to be elevated in HCC patients compared with liver cirrhosis patients. It has been reported that TGFβ1 mRNA was overexpressed in HCC, especially in patients with small HCC and well‐differentiated HCC compared with patients with liver cirrhosis. The current study investigated the usefulness of TGFβ1 compared with AFP in the diagnosis of small HCCs.

METHODS

Thirty‐eight patients with small HCC (≤ 3 cm), 31 patients with liver cirrhosis only, and 23 normal volunteers were studied. Using plasma TGFβ1 and serum AFP levels measured at the time of diagnosis, the sensitivities and specificities were calculated in the diagnosis of small HCCs.

RESULTS

Plasma TGFβ1 and serum AFP levels were significantly higher in patients with small HCC than in those with liver cirrhosis. In diagnosing small HCCs, the cut‐off values of plasma TGFβ1 and serum AFP were 800pg/mL and 200ng/mL, respectively, where the specificities were over 95%. At the cut‐off level of plasma TGFβ1 and serum AFP, the sensitivities were 68% and 24%, respectively.

CONCLUSIONS

The current results suggest that TGFβ1 may be a useful serologic marker in detecting HCCs earlier because it shows higher sensitivity than, with specificity as, AFP in the diagnosis of small HCCs. Cancer 2002;94:175–80. © 2002 American Cancer Society.
Self‐assessment in cancer patients referred to palliative care
Authors: Strömgren Annette S. , Goldschmidt Dorthe , Groenvold Mogens , Petersen Morten Aa. , Jensen Pernille T. , Pedersen Lise , Hoermann Linda , Helleberg Carsten , Sjogren Per
Published: August 2002

BACKGROUND

Research in palliative care is considered difficult due to the poor health of patients. However, patient‐provided data are essential for a thorough description of patient symptomatology and for the evaluation of care.

METHODS

The authors examined the feasibility of a questionnaire‐based study using the European Organization for Research and Treatment of Cancer quality‐of‐life instrument EORTC QLQ‐C30, the Edmonton Symptom Assessment System (ESAS), and the Hospital Anxiety and Depression Scale (HADS) in cancer patients who were receiving palliative care. This report describes the symptomatology of participating patients and examines differences in symptomatology between patients in three palliative care functions: inpatient, outpatient, and palliative home care.

RESULTS

Of 267 eligible patients who were referred to a department of palliative medicine, initial self‐assessment questionnaires were obtained from 176 patients (65.9%). The 91 nonparticipants were older and had lower Karnofsky Performance status (KPS) values than the participants. Almost all participating patients suffered from impaired role function and physical function and had high levels of pain, fatigue, and other symptoms. According to the HADS, 47% of patients suffered from depression. Outpatients had better scores than inpatients and patients in palliative home care for physical function, role function, cognitive function, depression, and inactivity.

CONCLUSIONS

It is possible to carry out a questionnaire‐based study of symptomatology in consecutive cancer patients in palliative care, achieving rather complete data from the participants. The symptomatology in these patients was very pronounced. The questionnaires were able to detect clinically important differences between places of service. Cancer 2002;94:512–20. © 2002 American Cancer Society.
Immunohistochemical analysis and in situ hybridization of cyclooxygenase‐2 expression in intraductal papillary‐mucinous tumors of the pancreas
Authors: Niijima Mitsuoki , Yamaguchi Taketo , Ishihara Takeshi , Hara Taro , Kato Kazuki , Kondo Fukuo , Saisho Hiromitsu
Published: August 2002

BACKGROUND

The objective of this study was to investigate COX‐2 expression in intraductal papillary‐mucinous tumor of the pancreas (IPMT) using immunohistochemical staining (IH) and in situ hybridization (ISH).

METHODS

Immunohistochemical staining of COX‐2 was performed using samples from 42 patients with IPMT (hyperplasia, 10; adenoma, 13; noninvasive adenocarcinoma, 13; invasive adenocarcinoma, 6) and from 10 patients with ductal pancreatic adenocarcinoma, 10 with chronic pancreatitis, and 6 normal pancreatic tissues as controls. Also, COX‐2 was determined in five patients with IPMT noninvasive adenocarcinoma, in whom all histologic types, hyperplasia, adenoma, and adenocarcinoma were observed in the same excised specimens. Furthermore, IH of proliferating cell nuclear antigen (PCNA) was performed, and the labeling index (LI) was calculated to investigate the correlation with COX‐2. To confirm COX‐2 mRNA, the authors performed ISH in 20 IPMT patients.

RESULTS

COX‐2 was positive in 0%, 0%, and 10% of pancreatic duct epithelial cells from normal pancreatic tissue, chronic pancreatitis, and IPMT hyperplasia, respectively. Whereas it was positive in 69%, 77%, 67%, and 80% of IPMT adenoma, IPMT noninvasive adenocarcinoma, IPMT invasive adenocarcinoma, and ductal pancreatic adenocarcinoma, respectively, showing significant differences between IPMT hyperplasia and IPMT adenoma or IPMT adenocarcinoma (noninvasive and invasive adenocarcinoma). In the same patient, COX‐2 was negative in the hyperplasia region but positive in adenoma and adenocarcinoma regions, showing results reflecting the progression of the disease. In the COX‐2 negative group, PCNA‐LI was 19.2 ± 17.9%, and 33.5 ± 15.7% in the positive group, a significant difference. On ISH, COX‐2 mRNA was expressed in three of four and seven of eight COX‐2 positive patients with IPMT adenoma and adenocarcinoma, respectively.

CONCLUSIONS

COX‐2 was highly expressed in adenoma and adenocarcinoma in IPMT, showing a relation to the histologic grade of IPMT. Cancer 2002;94:1565–73. © 2002 American Cancer Society.

DOI 10.1002/cncr.10358
Helping patients with localized prostate carcinoma manage uncertainty and treatment side effects
Authors: Mishel Merle H. , Belyea Michael , Germino Barbara B. , Stewart Janet L. , Bailey Donald E. , Robertson Cary , Mohler James
Published: August 2002

BACKGROUND

The objective of this study was to test the efficacy of an individualized uncertainty management intervention delivered by telephone to Caucasian and African‐American men with localized prostate carcinoma and directed at managing the uncertainties of their disease and treatment.

METHODS

The authors delivered a psychoeducational intervention by phone to men with prostate carcinoma, with or without supplemented delivery to a close family member, that was directed at managing uncertainty and improving symptom control. One hundred thirty‐four Caucasian men and 105 African‐American men were assigned randomly to one of two approaches to delivering the intervention or to the control condition. Men entered the study immediately after surgical treatment or in the first 3 weeks of radiation therapy. Trained nurses delivered the intervention through weekly phone calls for 8 weeks.

RESULTS

The authors found that the majority of intervention effects were from baseline to 4 months postbaseline, when treatment side effects are most intense. Both Caucasian men and African‐American men who received either one of the two approaches for delivering the intervention improved in the two uncertainty management methods of cognitive reframing and problem solving. Similarly, when the intervention groups were combined, men who received the intervention also improved significantly in control of incontinence by 4 months postbaseline. Decreases in the number of treatment side effects differed by time and treatment/ ethnic group interactions as did satisfaction with sexual functioning.

CONCLUSIONS

This is one of the first tests of a psychoeducational intervention among men with prostate carcinoma and was the first test that included a sufficient number of African‐American men to test by ethnic group. Therefore, replication of these findings is advised. Cancer 2002;94:1854–66. © 2002 American Cancer Society.

DOI 10.1002/cncr.10390
Tumor specific gene expression profiles in human leiomyosarcoma
Authors: Shmulevich Ilya , Hunt Kelly , El‐Naggar Adel , Taylor Ellen , Ramdas Latha , Labordé Pilar , Hess Kenneth R. , Pollock Raphael , Zhang Wei
Published: August 2002

Leiomyosarcomas are malignant smooth muscle tumors characterized by a spectrum of histopathologic features and clinical behavior. Gene expression profiling of leiomyosarcomas may identify differential gene signatures that may allow for the clinical stratification of the tumors. Typically, surgical specimens from these tumors are large and manifest a variegated macroscopic appearance. Because of their large size at the time of diagnosis, sufficient tissue is available for regional and clonal heterogeneity assessment. However, if the gene expression profiles of samples taken from different locations in the tumors are drastically different, biologic classification on the basis of random sample analysis may not be adequate. Therefore, to assess intertumor and intratumor heterogeneity, the authors performed a gene expression study using leiomyosarcoma specimens from three excised sarcomas from an equal number of different patients. Comparisons between tumor and normal samples from the three patients as well as between carefully mapped peripheral and core specimens from the same tumor (excised from one of the patients), were performed. Analysis of the expression profiles demonstrated minimal intratumor variations compared with intertissue variations, indicating homogeneous tumor specific gene expression profiles. The authors also identified genes that are expressed differentially in tumor and normal tissue. Cancer 2002;94:2069–75. © 2002 American Cancer Society.

DOI 10.1002/cncr.10425
Phase II study of methotrexate, vinblastine, doxorubicin, and cisplatin in patients with squamous cell carcinoma of the upper respiratory or alimentary passages of the head and neck
Authors: Okuno Scott H. , Mailliard James A. , Suman Vera J. , Edmonson John H. , Creagan Edward T. , Nair Suresh , Levitt Ralph , Kugler John W.
Published: August 2002

BACKGROUND

The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population.

METHODS

Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4‐week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival.

RESULTS

Thirty‐six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33–60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1‐year progression free survival rate was 17% (95% CI, 8–36%). The median survival was 49 weeks, and the 1‐year survival rate was 43% (95% CI, 29–63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1‐year progression free survival rate was 14% (95% CI, 5–39%), and median survival was 24 weeks, and the 1‐year survival rate was 36% (95% CI, 21–63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1‐year progression free survival rate was 23% (95% CI, 9–62%), the median survival was 54 weeks, and the 1‐year survival rate was 54% (95% CI, 33–89%).

CONCLUSIONS

Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck. Cancer 2002;94:2224–31. © 2002 American Cancer Society.

DOI 10.1002/cncr.10442
Prognostic relevance of immunohistochemically detected lymph node micrometastasis in patients with gastric carcinoma
Authors: Lee Eungseok , Chae Yangseok , Kim Insun , Choi Jongsang , Yeom Bomwoo , Leong Anthony S.‐Y.
Published: August 2002

BACKGROUND

Micrometastases consisting of one to a few cells in lymph nodes resected during gastrectomy are difficult to identify using conventional hematoxylin and eosin (H&E) stains. It has been shown that immunostaining for cytokeratins is effective in detecting lymph node micrometastasis in a variety of human tumors, but only a few previous reports demonstrated its use in the treatment of patients with early and advanced gastric carcinoma, and those reports had conflicting results.

METHODS

In this study, 3625 regional lymph nodes that were dissected in gastrectomy specimens from 153 patients with early‐stage gastric carcinoma (46 patients) and advanced gastric carcinoma (107 patients) were immunostained with the anticytokeratin cocktail AE1/3 for micrometastasis (median, 23 lymph nodes; range, 8–66 lymph nodes). Micrometastasis (MM) was defined as a single tumor cell or clusters of tumor cells that were missed on conventional examination with H&E stains but were detected by immunostaining with broad‐spectrum anticytokeratin antibodies.

RESULTS

Lymph node metastasis (LNM) was detected in 609 lymph nodes (17%) by H&E staining. MM was identified in another 191 of the remaining lymph nodes (6.3%) from 75 patients. Twenty‐eight of those patients were up‐staged. There was a significant correlation between MM and depth of tumor invasion (P < 0.01). Patients with MM had a decreased 5‐year survival rate (49%) compared with patients without MM (76%) for both early and advanced gastric carcinoma. The effect of MM on survival was most pronounced for patients in the Stage I and LNM negative group.

CONCLUSIONS

Immunohistochemical examination using broad‐spectrum anticytokeratin antibodies increased the detection rate of LNM and had a significant impact on staging and survival in patients with gastric carcinoma. Cancer 2002;94:2867–73. © 2002 American Cancer Society.

DOI 10.1002/cncr.10562
Breast and cervical carcinoma screening practices among women in rural and nonrural areas of the United States, 1998–1999
Authors: Coughlin Steven S. , Thompson Trevor D. , Hall H. Irene , Logan Pamela , Uhler Robert J.
Published: August 2002

BACKGROUND

Prior studies have suggested that women living in rural areas may be less likely than women living in urban areas to have had a recent mammogram and Papanicolau (Pap) test and that rural women may face substantial barriers to receiving preventive health care services.

METHODS

The authors examined both breast and cervical carcinoma screening practices of women living in rural and nonrural areas of the United States from 1998 through 1999 using data from the Behavioral Risk Factor Surveillance System. The authors limited their analyses of screening mammography and clinical breast examination to women aged 40 years or older (n = 108,326). In addition, they limited their analyses of Pap testing to women aged 18 years or older who did not have a history of hysterectomy (n = 131,813). They divided the geographic areas of residence into rural areas and small towns, suburban areas and smaller metropolitan areas, and larger metropolitan areas.

RESULTS

Approximately 66.7% (95% confidence interval [CI] = 65.8% to 67.6%) of women aged 40 years or older who resided in rural areas had received a mammogram in the past 2 years, compared with 75.4% of women living in larger metropolitan areas (95% CI = 74.9% to 75.9%). About 73.0% (95% CI = 72.2% to 73.9%) of women aged 40 years or older who resided in rural areas had received a clinical breast examination in the past 2 years, compared with 78.2% of women living in larger metropolitan areas (95% CI = 77.8% to 78.7%). About 81.3% (95% CI = 80.6% to 82.0%) of 131,813 rural women aged 18 years or older who had not undergone a hysterectomy had received a Pap test in the past 3 years, compared with 84.5% of women living in larger metropolitan areas (95% CI = 84.1% to 84.9%). The differences in screening across rural and nonrural areas persisted in multivariate analysis (P < 0.001).

CONCLUSIONS

These results underscore the need for continued efforts to provide breast and cervical carcinoma screening to women living in rural areas of the United States. Cancer 2002; 94:2801–12. © 2002 American Cancer Society.

DOI 10.1002/cncr.10577
Carcinoma detection at the breast examination center of Harlem
Authors: Liberman Laura , Freeman Harold P. , Chandra Sukanya , Stein Amanda L. , Mccord Colin , Godfrey Diana , Dershaw D. David
Published: August 2002

BACKGROUND

Breast carcinoma is one of the leading causes of excess mortality rates in Harlem, an inner‐city neighborhood with the highest mortality rates and worst life expectancy in New York City. This study reports the results of a breast carcinoma screening and diagnostic program in Harlem.

METHODS

Retrospective review was performed of a database of 49,750 visits to the Breast Examination Center of Harlem from 1995 to 2000. During this period, 181 breast carcinomas were diagnosed in 178 women. The medical records of these 178 women were reviewed to determine the method of detection, stage, and treatment.

RESULTS

Among these women, 89% were black or Hispanic, 45% had no medical insurance, and 38% had incomes below federal poverty guidelines. Breast carcinoma stage, known for 167 carcinomas, was Stage 0 in 38 (23%), Stage I in 38 (23%), Stage II in 63 (38%), Stage III in 24 (14%), and Stage IV in 4 (2%). Fifty‐six cases (34%) were minimal breast carcinomas. Of 181 breast carcinomas, 122 (67%) were palpable and 59 (33%) were nonpalpable, detected only by mammography in asymptomatic women. Nonpalpable, as opposed to palpable, breast carcinomas were significantly more likely to be ductal carcinoma in situ (30 of 55 [54%] vs. 8 of 112 [7%], P < 0.0000001) or minimal breast carcinoma (39 of 55 [71%] vs. 17 of 112 [15%], P = 0.0000001) and were more likely to be treated with breast‐conserving surgery (47 of 56 [84%] vs. 76 of 110 [69%], P < 0.04).

CONCLUSIONS

A breast carcinoma screening and diagnostic program has been established in Harlem, a traditionally underserved area in New York City. Early, curable breast carcinomas were detected but outreach remains a challenge, particularly for the uninsured. Cancer 2002;95:8–14. © 2002 American Cancer Society.

DOI 10.1002/cncr.10640
Synaptic protein expression by regenerating adult photoreceptors
Authors: Yang Haidong , Standifer Kelly M. , Sherry David M.
Published: August 2002

Regeneration of functionally normal synapses is required for functional recovery after degenerative central nervous system insults and requires proper expression and targeting of presynaptic proteins by regenerating neurons. The reconstitution of presynaptic terminals by regenerating adult neurons is poorly understood, however. We examined the intrinsic ability of regenerating adult retinal photoreceptors to reconstitute properly differentiated presynaptic terminals in the absence of target contact. The expression and localization of vesicle‐associated membrane protein (VAMP), synaptic vesicle protein 2 (SV2), synaptophysin, synapsin I, and synaptosomal‐associated protein of 25 kDa (SNAP‐25) was assessed immunocytochemically. Photoreceptor terminals in the intact retina contain VAMP, SV2, synaptophysin, and SNAP‐25, but not synapsin I. Isolated, regenerating adult photoreceptors intrinsically expressed the proper complement of synaptic vesicle proteins in the absence of target contact: VAMP, SV2, and synaptophysin were present at all stages of regenerative growth; synapsin I was never expressed. At early stages of regenerative growth, VAMP, SV2, and synaptophysin were diffusely localized in the cell, with prominent VAMP labeling distributed along the plasma membrane. SV2 and synaptophysin rapidly localized to regenerated terminals, but VAMP accumulated much more slowly, indicating that these proteins are trafficked independently. In contrast, labeling for SNAP‐25, which is associated with the presynaptic plasma membrane, was undetectable in regenerating photoreceptors, suggesting that SNAP‐25 expression is target‐regulated. Thus, regenerating photoreceptors can intrinsically regulate the expression of the proper set of synaptic vesicle proteins. Proper expression of other presynaptic proteins, such as SNAP‐25, and proper subcellular localization of synaptic proteins such as VAMP, however, may require extrinsic cues such as target contact. J. Comp. Neurol. 443:275–288, 2002. © 2002 Wiley‐Liss, Inc.
Firing properties of axotomized central nervous system neurons recover after graft reinnervation
Authors: Benítez‐Temiño Beatriz , De La Cruz Rosa R. , Pastor Ángel M.
Published: August 2002

Axotomy produces changes in the electrical properties of neurons and in their synaptic inputs, leading to alterations in firing pattern. We have considered the possibility that these changes occur as a result of the target deprivation induced by the lesion. Thus, we have provided a novel target to axotomized central neurons by grafting embryonic tissue at the lesion site to study the target dependence of discharge characteristics. The extracellular single‐unit electrical activity of abducens internuclear neurons was recorded in the alert behaving cat in control, after axotomy, and after axotomy plus the implantation of cerebellar primordium. As recently characterized (de la Cruz et al. [2000] J. Comp. Neurol. 427:391–404), firing alterations induced by axotomy included an overall decrease in firing rate and a loss of eye‐related signals, i.e., eye position and velocity neuronal sensitivities, that do not resume to normality with time. The grafting of a novel target to the injured abducens internuclear neurons restored the normal firing and sensitivities as recorded in the majority of units. To study the reinnervation of the implant, we performed anterograde labeling with biocytin combined with electron microscopy visualization. Axons of abducens internuclear neurons grew into the transplant sprouting into granule cell and molecular layers, as characterized by the immunostaining for γ‐aminobutyric acid and calbindin D‐28k. Ultrastructural examination of labeled axons and boutons revealed the establishment of synaptic contacts, mainly axodendritic, with different cell types of the grafted cerebellar cortex. Therefore, these data indicate that axotomized central neurons resume to normal firing after the reinnervation of a novel target. J. Comp. Neurol. 444:324–344, 2002. © 2002 Wiley‐Liss, Inc.
Nociceptin/orphanin FQ and opioid receptor‐like receptor mRNA expression in dopamine systems
Authors: Norton Camille S. , Neal Charles R. , Kumar Suneel , Akil Huda , Watson Stanley J.
Published: August 2002

Although nociceptin/orphanin FQ (N/OFQ) influences dopamine (DA) neuronal activity, it is not known whether N/OFQ acts directly on DA neurons, indirectly by means of local circuitry, or both. We used two parallel approaches, dual in situ hybridization (ISH) and neurotoxic lesions of DA neurons by using 6‐hydroxydopamine (6‐OHDA), to ascertain whether N/OFQ and the N/OFQ receptor (NOP) mRNA are expressed in DA neurons in the ventral tegmental area (VTA) and substantia nigra compacta (SNc). In the VTA and SNc, small populations (∼6–10%) of N/OFQ‐containing neurons coexpressed mRNA for tyrosine hydroxylase (TH), the rate‐limiting enzyme for DA synthesis. Similarly, very few (1–2%) TH‐positive neurons contained N/OFQ mRNA signal. A majority of NOP‐positive neurons (∼75%) expressed TH mRNA and roughly half of the TH‐containing neurons expressed NOP mRNA. Many N/OFQ neurons (∼50–60%) expressed glutamic acid decarboxylase 65 and 67 mRNAs, markers for γ‐aminobutyric acid (GABA) neurons. In the 6‐OHDA lesion studies, NOP mRNA levels were nearly 80 and 85% lower in the VTA and SNc, respectively, on the lesioned side. These lesions appear to lead to compensatory changes, with N/OFQ mRNA levels approximately 60% and 300% higher in the VTA and SNc, respectively, after 6‐OHDA lesions. Finally, N/OFQ‐stimulated [35S]guanylyl‐5′‐O‐(γ‐thio)‐triphosphate levels were decreased in the VTA and SNc but not the prefrontal cortex after 6‐OHDA lesions. Accordingly, it appears that N/OFQ mRNA was found largely on nondopaminergic (i.e., GABA) neurons, whereas NOP mRNA was located on DA neurons. N/OFQ is in a position to influence DA neuronal activity by means of the NOP located on DA neurons. J. Comp. Neurol. 444:358–368, 2002. © 2002 Wiley‐Liss, Inc.
Light‐ and electron‐microscopic analysis of vasoactive intestinal polypeptide‐immunoreactive amacrine cells in the guinea pig retina
Authors: Lee Eun‐Jin , Park Sung‐Hee , Kim In‐Beom , Kang Wha‐Sun , Oh Su‐Ja , Chun Myung‐Hoon
Published: August 2002

Vasoactive intestinal polypeptide (VIP) is a neuroactive substance that is expressed in both nonmammalian and mammalian retinas. This study investigated the morphology and synaptic connections of VIP‐containing neurons in the guinea pig retina by immunocytochemistry, by using antisera against VIP. Specific VIP immunoreactivity was localized to a population of wide‐field and regularly spaced amacrine cells with processes ramifying mainly in strata 1 and 2 of the inner plexiform layer (IPL). Double‐label immunohistochemistry demonstrated that all VIP‐immunoreactive cells possessed γ‐aminobutyric acid immunoreactivity. The synaptic connectivity of VIP‐immunoreactive amacrine cells was identified in the IPL by electron microscopy. The VIP‐labeled amacrine cell processes received synaptic input from other amacrine cell processes and bipolar cell axon terminals in strata 1 to 3 of the IPL. The most frequent postsynaptic targets of VIP‐immunoreactive amacrine cells were other amacrine cell processes in strata 1 to 3 of the IPL. Synaptic outputs to bipolar cells were also observed in strata 1 to 3 of the IPL. In addition, ganglion cell dendrites were also postsynaptic to VIP‐immunoreactive neurons in the sublamina a of the IPL. These studies show that one type of VIP‐immunoreactive amacrine cells make contact predominantly with other amacrine cell processes. This finding suggests that VIP‐containing amacrine cells may influence inner retinal circuitry, thus mediating visual processing. J. Comp. Neurol. 445: 325–335, 2002. © 2002 Wiley‐Liss, Inc.
Nigral and pallidal inputs to functionally segregated thalamostriatal neurons in the centromedian/parafascicular intralaminar nuclear complex in monkey
Authors: Sidibé Mamadou , Paré Jean‐François , Smith Yoland
Published: August 2002

In primates, thalamostriatal projections from the centromedian (CM) and parafascicular (Pf) nuclei are strong and organized according to a strict pattern of functional connectivity with various regions of the striatal complex. In turn, the CM/Pf complex receives a substantial innervation from the internal globus pallidus (GPi). In this study, we demonstrate that the substantia nigra pars reticulata (SNr) also provides a massive input to Pf in monkeys. These pallidothalamic and nigrothalamic projections provide routes whereby information can flow in functional loops between the basal ganglia and the intralaminar nuclear group. To understand better the anatomical organization and the degree of functional specificity of these loops, we combined retrograde and anterograde labeling methods from functionally defined regions of the striatum and GPi/SNr to determine the relationships between thalamostriatal neurons and basal ganglia afferents. Together with previous studies, our data suggest the existence of tightly connected functional circuits between the basal ganglia and the CM/Pf in primates: 1) A “sensorimotor” circuit links together the medial two‐thirds of CM, the postcommissural putamen, and the ventrolateral part of the caudal GPi; 2) a “limbic” circuit involves the rostral one‐third of Pf, the ventral striatum, and the rostromedial pole of GPi; and 3) an “associative”circuit exists between the caudal two‐thirds of Pf, the caudate nucleus, and the SNr. An additional “associative” circuit that involves the caudate‐receiving territory of GPi (dorsal one‐third), the dorsolateral Pf (Pfdl), and the precommissural putamen was also disclosed. In conclusion, findings of this study provide additional evidence for the high degree of functional specificity of the thalamostriatal system through which CM/Pf may provide attention‐specific sensory information important for conditional responses to the primate striatum. J. Comp. Neurol. 447:286–299, 2002. © 2002 Wiley‐Liss, Inc.
Distribution of tyrosine hydroxylase (TH) and dopamine β‐hydroxylase (DBH) immunoreactivity in the central nervous system of two chondrostean fishes (Acipenser baeri and Huso huso)
Authors: Adrio Fátima , Anadón Ramón , Rodríguez‐Moldes Isabel
Published: August 2002

To obtain a better understanding of the evolution of the brain catecholaminergic systems of fishes, we have examined the distribution of catecholamine‐synthesizing enzymes in two species of sturgeon (Acipenser baeri and Huso huso) using antibodies against tyrosine hydroxylase (TH) and dopamine‐β ‐hydroxylase (DBH; only analyzed in Acipenser). Both sturgeons showed TH‐immunoreactive (THir) neurons widely distributed in most regions of the brain, the highest number of THir cells being located in the forebrain (olfactory bulb, preoptic area, and posterior tuberculum). THir cells were also seen in other forebrain areas (retrobulbar area, dorsal and ventral telencephalic areas, hypothalamus, ventral thalamus, pretectal area) and in the brainstem (locus coeruleus, viscerosensory area, caudal reticular formation, and area postrema). Immunoreactive fibers and varicosities showed a wide distribution, being particularly abundant in the diencephalon and mesencephalon. DBH‐immunoreactive (DBHir) cells were observed in the anterior tuberal nucleus, where these cells were TH‐negative, and in the locus coeruleus and the caudal rhombencephalon (vagal reticular formation), where the DBHir cells were also THir. DBHir fibers were scarce in the telencephalon and very abundant in the diencephalon, mesencephalon, and rhombencephalon. The comparative analysis of the catecholaminergic systems of chondrosteans and those observed in other groups of fishes and tetrapods indicate a similar organization of many nuclei, as well as characteristics that are probably primitive, such as the presence of a large number of forebrain catecholaminergic groups. J. Comp. Neurol. 448:280–297, 2002. © 2002 Wiley‐Liss, Inc.
Distribution of vesicular glutamate transporter mRNA in rat hypothalamus
Authors: Ziegler Dana R. , Cullinan William E. , Herman James P.
Published: August 2002

Two isoforms of the vesicular glutamate transporter, VGLUT1 and VGLUT2, were recently cloned and biophysically characterized. Both VGLUT1 and VGLUT2 specifically transport glutamate into synaptic vesicles, making them definitive markers for neurons using glutamate as a neurotransmitter. The present study takes advantage of the specificity of the vesicular transporters to afford the first detailed map of putative glutamatergic neurons in the rat hypothalamus. In situ hybridization analysis was used to map hypothalamic distributions of VGLUT1 and VGLUT2 mRNAs. VGLUT2 is clearly the predominant vesicular transporter mRNA found in the hypothalamus; rich expression can be documented in regions regulating energy balance (ventromedial hypothalamus), neuroendocrine function (preoptic nuclei), autonomic tone (posterior hypothalamus), and behavioral/homeostatic integration (lateral hypothalamus, mammillary nuclei). Expression of VGLUT1 is decidedly more circumspect and is confined to relatively weak labeling in lateral hypothalamic regions, neuroendocrine nuclei, and the suprachiasmatic nucleus. Importantly, dual‐label analysis revealed no incidence of colocalization of VGLUT1 or VGLUT2 mRNAs in glutamic acid decarboxylase (GAD) 65‐positive neurons, indicating that GABA neurons do not express either transporter. Our data support a major role for hypothalamic glutamatergic neurons in regulation of all aspects of hypothalamic function. J. Comp. Neurol. 448:217–229, 2002. © 2002 Wiley‐Liss, Inc.
Neural substrates for tongue‐flicking behavior in snakes
Authors: Martínez‐Marcos Alino , Ubeda‐Bañón Isabel , Halpern Mimi
Published: August 2002

Snakes deliver odorants to the vomeronasal organ by means of tongue‐flicks. The rate and pattern of tongue‐flick behavior are altered depending on the chemical context. Accordingly, olfactory and vomeronasal information should reach motor centers that control the tongue musculature, namely, the hypoglossal nucleus (XIIN); however, virtually nothing is known about the circuits involved. In the present work, dextran amines were injected into the tongue of garter snakes (Thamnophis sirtalis) to identify the motoneurons of the XIIN. Tracers were then delivered into the XIIN to identify possible afferents of chemical information. Large injections into the XIIN yielded retrograde labeling in two chemosensory areas: the medial amygdala (MA) and the lateral posterior hypothalamic nucleus (LHN). Smaller injections only yielded labeled neurons in the LHN. In fact, the MA, which receives afferents from the accessory olfactory bulb, the rostroventral lateral cortex, and the nucleus sphericus, projects to the LHN. Injections into the MA did not show terminal labeling in the XIIN but in an area lateral to it. However, injections into the LHN gave rise not only to labeled fibers in the XIIN but also to retrograde labeling in the MA, thus confirming the chemosensory input to LHN. Injecting different fluorescent tracers into the tongue and into the LHN corroborated the projection from the LHN to the XIIN. The present report investigates further connections of the olfactory and vomeronasal systems and describes the afferent connections to XIIN in a nonmammalian vertebrate. The circuit for tongue‐flicking behavior described herein should be evaluated using functional studies. J. Comp. Neurol. 432:75–87, 2001. © 2001 Wiley‐Liss, Inc.
Descending supraspinal pathways in amphibians. II. Distribution and origin of the catecholaminergic innervation of the spinal cord
Authors: Sánchez‐Camacho Cristina , Marín Oscar , Smeets Wilhelmus J.A.J. , Ten Donkelaar Hans J. , González Agustín
Published: August 2002

Immunohistochemical studies with antibodies against tyrosine hydroxylase, dopamine, and noradrenaline have revealed that the spinal cord of anuran, urodele, and gymnophionan (apodan) amphibians is abundantly innervated by catecholaminergic (CA) fibers and terminals. Because intraspinal cells occur in all three orders of amphibians CA, it is unclear to what extent the CA innervation of the spinal cord is of supraspinal origin. In a previous study, we showed that many cell groups throughout the forebrain and brainstem project to the spinal cord of two anurans (the green frog, Rana perezi, and the clawed toad, Xenopus laevis), a urodele (the Iberian ribbed newt, Pleurodeles waltl), and a gymnophionan (the Mexican caecilian, Dermophis mexicanus). To determine the exact site of origin of the supraspinal CA innervation of the amphibian spinal cord, retrograde tracing techniques were combined with immunohistochemistry for tyrosine hydroxylase in the same sections. The double‐labeling experiments demonstrated that four brain centers provide CA innervation to the amphibian spinal cord: 1.) the ventrolateral component of the posterior tubercle in the mammillary region, 2.) the periventricular nucleus of the zona incerta in the ventral thalamus, 3.) the locus coeruleus, and 4.) the nucleus of the solitary tract. This pattern holds for all three orders of amphibians, except for the CA projection from the nucleus of the solitary tract in gymnophionans. There are differences in the strength of the projections (based on the number of double‐labeled cells), but in general, spinal functions in amphibians are controlled by CA innervation from brain centers that can easily be compared with their counterparts in amniotes. The organization of the CA input to the spinal cord of amphibians is largely similar to that described for mammals. Nevertheless, by using a segmental approach of the CNS, a remarkable difference was observed with respect to the diencephalic CA projections. J. Comp. Neurol. 434:209–232, 2001. © 2001 Wiley‐Liss, Inc.
Laminar organization of the pyramidal cell layer of the subiculum in the rat
Authors: Ishizuka Norio
Published: August 2002

The distribution of neurons in the subiculum of the rat that give rise to subcortical connections was studied using retrograde labeling with horseradish peroxidase conjugated to wheat germ agglutinin. Injections were made into the anteroventral thalamic nucleus, the medial mammillary nucleus, the nucleus accumbens, and the lateral septal nucleus. To facilitate the analysis, the hippocampal formation with adjacent cortices were “flattened,” which allowed the cutting of sections perpendicular to the full septotemporal axis. Cells projecting to the anteroventral thalamic nucleus (AV cells), the medial mammillary body (MMB cells), and the nucleus accumbens (ACC cells) were observed consistently throughout the entire septotemporal (dorsoventral) and transverse extent of the subiculum (from field CA1 of the hippocampus to the presubiculum). In the transverse plane, the three kinds of projection cells were arranged in a laminar fashion: The AV cells were observed in the deepest portion of the subicular pyramidal cell layer, the ACC cells were observed in the most superficial portion of the layer, and the MMB cells were observed in the middle portion of the layer. Although this laminar arrangement was observed at all septotemporal levels of the subiculum, it was most apparent at the septal level. At more temporal levels, the “laminae” shifted such that the superficially located ACC cells were more prominent in the proximal half of the subiculum, whereas the AV cells were shifted toward the distal half of the subiculum. The average size of somata of the AV cells was 72.3 μm2, that of the ACC cells was 105.2 μm2, and that of the MMB cells was 121.8 μm2. The connectional and cytoarchitectonic data indicate that there is a distinct sublamination of the subicular pyramidal cell layer, suggesting that the subiculum may be analogous to the infragranular layer (layers V and VI) of the isocortex. J. Comp. Neurol. 435:89–110, 2001. © 2001 Wiley‐Liss, Inc.
Quantitative analysis of the dendrites of sacral preganglionic neurons in the cat
Authors: Morgan Charles W. , Ohara Peter T.
Published: August 2002

Quantitative analyses were performed on the dendrites and somata of 25 electrophysiologically identified preganglionic neurons (PGN) obtained from the sacral spinal cord of the cat by intracellular injection of Neurobiotin or horseradish peroxidase. Total dendritic length and surface area were measured for each dendrite. The sizes of the stem dendrites measured at their base were positively correlated with the sizes of the entire tree and numbers of end branches. Total surface area of somata and dendrites averaged 39,138 μm2; 90.7% of that was from the dendrites. To obtain measurements of the relative contributions of PGN dendrites to specific regions of the spinal cord, the percentage of each dendrite occupying eight spinal cord regions was recorded. Sixty‐three percent of the dendrites projected dorsal to their somata, whereas an average of 33.3% of dendrites were located in the white matter, most of them in the lateral and dorsolateral funiculi. The neurons within this sample formed a continuum with some neurons having a large percentage of dendrites in lamina I but little in the white matter, whereas at the other end of the continuum were cells with the reverse configuration. The intermediate neurons had dendrites in both locations. Taken together, these data indicate a heterogeneous population of PGN in the lateral band of the sacral parasympathetic nucleus. J. Comp. Neurol. 437:56–69, 2001. © 2001 Wiley‐Liss, Inc.
Bipolar cell diversity in the primate retina: Morphologic and immunocytochemical analysis of a new world monkey, the marmoset Callithrix jacchus
Authors: Chan Tricia L. , Martin Paul R. , Clunas Nathan , Grünert Ulrike
Published: August 2002

The aim of this study was to identify the bipolar cell types in the retina of a New World monkey, the common marmoset, and compare them with those found in the Old World macaque monkey. Retinal whole‐mounts, sections, or both, were stained by using DiI labeling and immunohistochemical methods. Semithin sections were analyzed by using quantitative methods. We show that the same morphologic types of bipolar cell as described for the Old World macaque monkey by Boycott and Wässle (Boycott and Wässle [1991] Eur. J. Neurosci. 3:1069–1088) are present in marmoset retina: two types of midget bipolar cells, six type of diffuse bipolar cells, a blue cone bipolar cell, and one type of rod bipolar cell. The pattern of staining with different immunohistochemical markers (“fingerprint”) of each bipolar cell type in marmoset was also the same as described for macaque, with one exception: the flat midget bipolar cell (FMB) class is labeled by antibodies to recoverin in macaque but is labeled by antibodies to CD15 in marmoset. The labeled FMB cells in marmoset make contact with multiple cone photoreceptors throughout most of the extrafoveal retina. The spatial density of bipolar cells in marmoset is shown to be sufficient to support one‐to‐one connectivity of midget bipolar and ganglion cells in the fovea and to allow for parallel pathways to ganglion cells throughout the retina. Quantitative differences in the morphology and receptor connectivity between marmoset and macaque can be related to differences in cone and rod photoreceptor density between the species. We conclude that bipolar cell diversity is a preserved feature of the primate retina. J. Comp. Neurol. 437:219–239, 2001. © 2001 Wiley‐Liss, Inc.
Immunohistochemical localization of 3β‐hydroxysteroid dehydrogenase and 5α‐reductase in the brain of the African lungfish Protopterus annectens
Authors: Mathieu Maura , Mensah‐Nyagan Ayikoe Guy , Vallarino Mauro , Do‐Régo Jean‐Luc , Beaujean Delphine , Vaudry David , Luu‐The Van , Pelletier Georges , Vaudry Hubert
Published: August 2002

The localization of the enzymes responsible for the biosynthesis of neurosteroids in the brain of dipnoans has not yet been determined. In the present study, we investigated the immunohistochemical distribution of 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 5α‐reductase (5α‐R) in the brain and pituitary of the African lungfish Protopterus annectens by using antibodies raised against type I human 3β‐HSD and type I human 5α‐R. The 3β‐HSD and 5α‐R immunoreactivities were detected in cell bodies and fibers located in the same areas of the lungfish brain, namely, in the pallium, thalamus, hypothalamus, tectum, and periaqueductal gray. Identification of astrocytes, oligodendrocytes, and neurons with antisera against glial fibrillary acidic protein, galactocerebroside and neurofilaments revealed that, in the lungfish brain, 3β‐HSD immunolabeling is expressed exclusively by neurons, whereas the 5α‐R‐immunoreactive material is contained in both neurons and glial cells. In the pituitary gland, 3β‐HSD‐ and 5α‐R‐like immunoreactivity was localized in both the pars distalis and the pars intermedia. The present study provides the first immunocytochemical mapping of two key steroidogenic enzymes in the brain and pituitary of a lungfish. These data strongly suggest that neurosteroid biosynthesis occurs in the brain of fishes, as previously shown for amphibians, birds, and mammals. J. Comp. Neurol. 438:123–135, 2001. © 2001 Wiley‐Liss, Inc.