bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II evaluation of docetaxel plus one‐day oral estramustine phosphate in the treatment of patients with androgen independent prostate carcinoma
Authors: Sinibaldi Victoria J. , Carducci Michael A. , Moore‐Cooper Sandra , Laufer Menachem , Zahurak Marianna , Eisenberger Mario A.
Published: August 2002

BACKGROUND

Recent clinical trials have shown antitumor activity with the combination of docetaxel plus estramustine phosphate (EMP) in the treatment of patients with androgen independent prostate carcinoma (AIPC). However, the most commonly employed treatment schedules with EMP have been associated with significant gastrointestinal, cardiovascular, and thromboembolic toxicity. The authors hypothesized that the therapeutic index of the combination of docetaxel plus EMP for patients with prostate carcinoma could be enhanced by reducing the incidence and severity of EMP‐associated toxicity, which could be accomplished by shortening the duration of exposure to EMP. To preserve the therapeutic synergism between docetaxel and EMP, they designed a regimen employing higher doses of oral EMP administered on the day of the docetaxel infusion.

METHODS

From June 1, 1998 through September 28, 2000, 42 patients with AIPC were registered to receive docetaxel (70 mg/m2 intravenously over 1 hour) and EMP (280 mg orally every 6 hours × 5 doses) every 21 days, up to a maximum of 6 cycles. Dexamethasone was administered prior to docetaxel and coumadin 2 mg orally every day was taken during the study treatment period. Patient characteristics included a median age of 68 years, a median Eastern Cooperative Oncology Group performance status of 1, a median prostate specific antigen (PSA) level at study entry of 110.5 ng/mL, and a median of 2 prior hormonal manipulations. Ten patients (25%) had received prior chemotherapy, and 14 patients (33%) had received prior palliative radiation therapy.

RESULTS

Forty patients were evaluable for response and toxicity. Eighteen patients (45%; 95% confidence interval, 29–62%) had a decline > 50% in PSA level that lasted > 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 4.0 months. Four of 20 patients (20%) had partial soft tissue responses. Ten of 17 symptomatic patients (59%) had improvement in pain. The median survival for all patients was 13.5 months. The most prominent Grade 3 and 4 toxicities were reversible myelosuppression and fatigue. Nausea, emesis, diarrhea, and peripheral edema were minimal. No thromboembolic or hepatic complications were seen.

CONCLUSIONS

Docetaxel plus 1 multidose day of oral EMP was active in patients with AIPC and was associated with an acceptable toxicity profile. Overall, the therapeutic index of this regimen compared favorably with regimens that employed a longer administration of EMP. Cancer 2002;94:1457–65. © 2002 American Cancer Society.

DOI 10.1002/cncr.10350
Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma
Authors: Rodríguez‐Alonso Andrés , Pita‐Fernández Salvador , González‐Carreró Joaquín , Nogueira‐March José Luis
Published: August 2002

BACKGROUND

Determination of prognosis factors associated with survival, recurrence, progression, and development of metastasis in T1 and T2a transitional cell carcinoma (TCC) of the bladder is discussed.

METHODS

A study was conducted of a group of 210 patients with primary bladder TCC at classification T1 (n = 175) and T2aN0M0 (n = 35). A total of 177 variables were studied in each patient. The monoclonal antibodies used were the following: DO7 (p53) and MIB‐1 (Ki‐67). Prognosis was obtained using Kaplan–Meier methodology and Cox proportional hazards model.

RESULTS

The average follow‐up period was 6.7 years. Cancer‐related survival rates at 5 and 10 years were 82.96% and 74.78%, respectively. The independent survival variables were the following: age and expression of p53. Recurrence free survival at 5 and 10 years stood at 51.80% and 42.71%, respectively. The independent recurrence variables were T2a classification, tumor multifocality, tumor size of greater than 3 cm, carcinoma in situ in random biopsy, and expression of Ki‐67. Progression free survival rates at 5 and 10 years were 75.31% and 69.16%, respectively. The independent progression variables were age, T2a classification, and expression of p53. Metastasis free survival rates at 5 and 10 years stood at 87.23% and 84.55%, respectively. The expression of p53 was the sole variable to provide an independent prediction of metastasis.

CONCLUSIONS

The expression of p53 clearly has an independent effect on the prediction of survival, progression and development of metastasis, showing a dose–response effect. Tumor multifocality and T2a classification are the variables that best predict recurrence. Cancer 2002;94:1677–84. © 2002 American Cancer Society.

DOI 10.1002/cncr.10376
The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease
Authors: DiRaimondo Francesco , Albitar Maher , Huh Yang , O'Brien Susan , Montillo Marco , Tedeschi Alessandra , Kantarjian Hagop , Lerner Susan , Giustolisi Rosario , Keating Michael
Published: August 2002

BACKGROUND

CD23 antigen is a cell surface protein considered important in the differentiation of chronic lymphocytic leukemia (CLL) from other lymphoid leukemias.

METHODS

To better clarify CD23 role as a diagnostic tool, the authors retrospectively evaluated clinical and laboratory features of 372 patients who were referred to M.D. Anderson Cancer Center with a diagnosis of CLL or B‐cell chronic lymphoproliferative disease.

RESULTS

Most of the patients (91%) were CD19+/CD5+. Only 6% of these CD19+/CD5+ patients were CD23−. Overall, CD23− patients had the worse prognostic features compared with CD23+ cases, including anemia (P = 0.03), massive splenomegaly (P = 0.000), high lactate dehydrogenase (P = 0.007), high β2‐microglobulin (P = 0.006), older age (P = 0.001), and male gender (P = 0.02). Surface immunoglobulin expression was moderate/strong in 19 (82%) patients, and FMC‐7 was positive in 22 (96%) patients. None of the 13 patients tested for CD10 expressed the antigen. Based on morphology, of the CD23, 16 (70%) were diagnosed with mantle cell leukemia (MCL) was diagnosed in 16 (70%) CD23− patients, 3 (13%) with splenic marginal‐zone leukemia, 3 (13%) with prolymphocytic leukemia (PLL) or PLL/CLL, and 1 (4%) with CLL. No cyclin D1 protein expression was noted by Western blot analysis in the one case that showed typical CLL morphology, and this patient did not require therapy. On the whole, the survival rate of CD23− patients was significantly worse than that of patients with CD23+. In contrast, 15 of 32 (49%) CD19+/CD5− patients were CD23−. CD23 negativity in this group was not associated with distinct clinical features or outcome. Eleven (73%) of these patients were classified as having splenic marginal‐zone lymphoma and 4 as having follicular lymphoma.

CONCLUSIONS

These data indicate that CD23 negativity is rare in typical B‐cell CLL, and CD23 negativity in patients with CD19+/CD5+ is suggestive of mantle cell leukemia a more aggressive disease with poor response to conventional therapy in which newer chemotherapy regimens such as hyper‐CVAD may be more effective. Cancer 2002;94:1721–30. © 2002 American Cancer Society.

DOI 10.1002/cncr.10401
Ethnic differences in survival among women with ovarian carcinoma
Authors: Barnholtz‐Sloan Jill S. , Tainsky Michael A. , Abrams Judith , Severson Richard K. , Qureshi Faisal , Jacques Suzanne M. , Levin Nancy , Schwartz Ann G.
Published: August 2002

BACKGROUND

Ovarian carcinoma is the leading cause of death among all female reproductive malignancies. There are substantial differences in age‐adjusted incidence rates and survival rates between Caucasian women and African‐American women. The objective of this study was to examine ethnic differences in survival after ovarian carcinoma in a population‐based sample of women.

METHODS

Thirteen thousand eighty‐three patients (12285 Caucasian women and 798 African‐American women) who were diagnosed with primary ovarian carcinoma from the population‐based Surveillance, Epidemiology, and End Results (SEER) Program were used for analysis. Odds ratios were used to estimate the association between prognostic variables and ethnicity. Chi‐square tests were used to determine the statistical significance of these associations (using two‐sided P values). Univariable and multivariable Cox proportional hazards models were used to assess survival differences.

RESULTS

African‐American women were significantly younger at the time of diagnosis, were more likely to be single, and were less likely to undergo site specific surgery compared with Caucasian women. In addition, the crude median survival for African‐American women was nearly 1 year less than for Caucasian women (22 months vs. 32 months, respectively; P < 0.0001). African‐American women were at a 30% increased risk of death from any cause when adjusting for all other prognostic variables that differed between the two ethnic groups.

CONCLUSIONS

African‐American women who are diagnosed with ovarian carcinoma are at a significant increased risk of death from any cause compared with Caucasian women who are diagnosed with ovarian carcinoma. Cancer 2002;94:1886–93. © 2002 American Cancer Society.

DOI 10.1002/cncr.10415
Site specific dependency of second primary cancer in early stage head and neck squamous cell carcinoma
Authors: Yamamoto Eiji , Shibuya Hitoshi , Yoshimura Ryo‐ichi , Miura Masahiko
Published: August 2002

BACKGROUND

A study was conducted to determine the site specificity of second primary cancer (SPC) following early (Stage I and II) squamous cell carcinoma of the head and neck (SCH) and its impact on prognosis.

METHODS

Between 1956 and 1999, 1,639 early stage SCHs in 1,609 patients were treated by radiotherapy at the authors' institution. The risk of additional respiratory and upper digestive tract (RUDT) carcinoma and the treatment outcome were reviewed for each SCH site. Second primary RUDT carcinomas were the second most common cause of death (113 cases) after death from primary SCH carcinomas (350 cases).

RESULTS

Among the 1,609 early stage SCH patients, 333 second primary cancers were documented in 258 patients, 235 (71%) of which were RUDT carcinomas. The risk of SPCs was 3.2% per year, and the risk of SPCs in the RUDT region was 2.3% per year. The risk of SPCs was almost two times higher in males (3.7% per year) than in females (2.2% per year). The highest risk of SPC was observed in the oro‐hypopharynx index cancer group (8.5% per year), and the lowest risks were observed in the epipharynx group (0% per year) and the maxillary sinus group (1.4% per year).

CONCLUSIONS

Different SPC risks according to the SCH site result in a different prognosis for each site of early stage SCH. Long‐term follow‐up care after the initial treatment for early SCH should be continued according to the site of the initial SCH. Cancer 2002;94:2007–14. © 2002 American Cancer Society.

DOI 10.1002/cncr.10444
Facing a prostate cancer diagnosis
Authors: Perczek Ruben E. , Burke Michael A. , Carver Charles S. , Krongrad Arnon , Terris Martha K.
Published: August 2002

BACKGROUND

The psychological adaptation to a cancer diagnosis is characterized by significant distress. Although distress levels in cancer patients have been reported to be the highest shortly after diagnosis and before treatment, few attempts have been made to study emotional adjustment during the diagnostic period of prostate cancer patients. This study's purpose was to determine whether differences in distress levels can be attributed to differences in diagnostic status, optimism, and/or coping strategies.

METHODS

This study followed patients across 4 weeks, from prebiopsy to 2 weeks postdiagnosis, using these two time points as measurements. Data were collected between 1995 and 1998 at the Miami and Palo Alto VA Medical Center urology clinics. Biopsies were performed on 101 men (ages 46–87) to determine whether prostate cancer was present. These men completed prebiopsy and postdiagnosis questionnaires.

RESULTS

Of optimism, coping, and cancer status, the only significant predictor of increased distress at postdiagnosis was dispositional avoidance at prebiopsy for both cancer and noncancer groups.

CONCLUSIONS

Although these findings complement other studies linking avoidance with increased distress, the similarities between the cancer and noncancer groups underscore the need to consider both of these groups during the first few weeks of the prostate cancer diagnostic process. Cancer 2002;94:2923–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10564
Complications from treatment for prostate carcinoma among men in the Detroit area
Authors: Schwartz Kendra , Bunner Scott , Bearer Ryan , Severson Richard K.
Published: August 2002

BACKGROUND

Aggressive treatment of early stage prostate carcinoma (PC) is limited primarily to two modalities: radical prostatectomy (RP) and external beam radiation therapy (RT). The authors conducted a population‐based study of Detroit area men with localized PC to determine the outcome of bowel, urinary, and sexual function after aggressive treatment.

METHODS

Men with PC were identified through the Metropolitan Detroit Cancer Surveillance System, a member of the National Cancer Institute Surveillance, Epidemiology, and End Results Program. Patients participated in interviews about their pretreatment bowel, urinary, and sexual function approximately 9 months after treatment. The same men were asked identical questions about their function an average of 2 years after treatment. Treatment outcomes were compared for men who underwent RP and men who received RT.

RESULTS

Of 501 men, 398 (79.4%) participated in both interviews, 304 of whom (76.4%) had localized PC and had been treated at least 1 year previously (median, 688 days). One hundred thirty men underwent RP, and 115 men received RT. The proportion of men in the RP group who reported an increase in incontinence symptoms was significant (53.8% compared with 19.2% in the RT group; P < 0.001). Men in the RT group reported increased loose stools between the pretreatment and post‐treatment interviews (5.2% vs. 29.6%; P < 0.001). Men in both the RT group and the RP group reported increases in impotence from 40% to > 75% (P < 0.001 for both). Men in the RT group were 3.6 times more likely to have bowel incontinence compared with men in the RP group (odds ratio [OR], 3.61; 95% confidence interval [95% CI], 1.54–8.47). Urinary incontinence (OR, 2.87; 95% CI, 1.52–5.44) and erection difficulty (OR, 3.98; 95% CI, 1.35–11.70) were more likely among men in the RP group.

CONCLUSIONS

Although patients may have recalled their baseline function as better than it was, the current results are consistent with other population‐based studies of treatment outcomes among men with localized PC. They indicate that the side effects associated with treatment are greater than those based on case series. Physicians and patients should be aware of these population‐based outcomes and should use them as part of the decision‐making process regarding the treatment options for men with PC. Cancer 2002;95:82–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10650
Neurons labeled from locomotor‐related ventrolateral funiculus stimulus sites in the neonatal rat spinal cord
Authors: Antonino‐Green Deborah M. , Cheng Jianguo , Magnuson David S.K.
Published: August 2002

Spinal cord/brainstem preparations from 5‐ to 8‐day‐old rats, maintained in vitro, were used to determine the cells of origin and regions of termination of fibers in the superficial ventrolateral funiculus (VLF) at a site from which rhythmic locomotor‐like activity can be induced. Rhythmic locomotor‐like activity was recorded from lumbar ventral roots after short trains of stimuli (50 Hz for 0.5–2 seconds) delivered to the VLF. Field potential mapping revealed that single VLF stimuli elicited responses in the ipsilateral ventrolateral medulla. Tract‐tracing experiments by using biocytin, pressure‐injected into the VLF, showed that only a small number of brainstem neurons were labeled and these were scattered bilaterally in the ventrolateral and lateral medulla. Dense concentrations of nerve terminals were found in the lateral reticular nucleus ipsilateral to the stimulation site. Labeled spinal cord neurons included a primary population of large cells distributed bilaterally in lamina VII from T13 to L4, with peak numbers in L2 ipsilaterally and in L3 contralaterally. Intracellular recordings revealed that some L2 and L3 neurons with rhythmic responses to VLF stimulation could be activated antidromically from the VLF, with latencies of less than 1.0 msec. These observations led us to speculate that the superficial VLF carries a locomotor‐related tract originating bilaterally in lumbar lamina VII and terminating in the ipsilateral medulla, including the lateral reticular nucleus. This pathway may be part of the spinoreticular or spinoreticulotectal pathway that has been described in many species, the function of which has only loosely been ascribed. J. Comp. Neurol. 442:226–238, 2002. © 2001 Wiley‐Liss, Inc.
Characterization of circular muscle motor neurons of the duodenum and distal colon in the Australian brush‐tailed possum
Authors: Konomi Hiroyuki , Meedeniya Adrian C.B. , Simula Maria E. , Toouli James , Saccone Gino T.P.
Published: August 2002

The motor innervation of the duodenum and distal colon remains uncharacterized within the same species. Our aim was to compare the projections and neurochemical properties of duodenal and distal colon circular muscle motor neurons. Circular muscle motor neurons were retrogradely traced by using a neural tracer in vitro, processed for choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity and then visualized by using indirect immunofluorescence. A mean of 372 ± 64 and 156 ± 23 neurons (mean ± SEM) were tracer‐labeled within the duodenum and colon, respectively. The ChAT+/NOS− neurons comprised 57.6 ± 6.6% and 39.6 ± 4.4% of all labeled cells in the duodenum and colon, respectively, and projected mainly in the oral direction. Of all labeled cells, the ChAT−/NOS+ neurons comprised 8.5 ± 2.3% in the duodenum and 46.6 ± 5.0% in the distal colon and projected mainly in the anal direction. Of the remainder, 20.6 ± 5.0% and 8.2 ± 2.4% were ChAT+/NOS+ and 13.2 ± 0.9% and 5.6 ± 1.4% were ChAT−/NOS− in the duodenum and distal colon, respectively. Within both regions, the distribution of the ChAT+/NOS− and ChAT−/NOS+ neurons are consistent with the ascending excitatory and descending inhibitory reflexes. The proportion of ChAT−/NOS+ neurons is greater within the colon in comparison with the duodenum. A considerable proportion of duodenal motor neurons were ChAT+/NOS+ and ChAT−/NOS−. These two classes may underlie nonperistaltic motor patterns, which predominate within the duodenum. These findings demonstrate regional differences in the innervation of intestinal circular muscle. J. Comp. Neurol. 443:15–26, 2002. © 2002 Wiley‐Liss, Inc.
Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey
Authors: Peters Alan , Sethares Claire
Published: August 2002

In the rhesus monkey, the myelin sheaths of nerve fibers in area 46 of prefrontal cortex and in splenium of the corpus callosum show age‐related alterations in their structure. The alterations are of four basic types. Most common is splitting of the dense line of myelin sheaths to accommodate electron dense cytoplasm derived from the oligodendroglia. Less common are splits of the intraperiod line to form balloons or blisters that appear to contain fluid, the occurrence of sheaths with redundant myelin, and thick sheaths that are almost completely split so that one set of compact lamellae is surrounded by another set. But despite these alterations in the sheaths, few nerve fibers show axonal degeneration. To quantify the frequency of the age‐related alterations in myelin, transversely sectioned nerve fibers from the splenium of the corpus callosum and from the vertical bundles of nerve fibers within area 46 were examined in electron photomicrographs. The material was taken from 19 monkeys, ranging between 5 and 35 years of age. It was found that the frequency of alterations in myelin sheaths from both locations correlates significantly with age. In area 46, the age‐related alterations also significantly correlate (P < 0.001) with an overall assessment of impairment in cognition, i.e., the cognitive impairment index, displayed by individual monkeys. The correlation is also significant when only the old monkeys are considered as a group. A similar result was obtained previously in our examination of the effects of age on the myelin sheaths of nerve fibers in primary visual cortex (Peters et al. [2000] J Comp Neurol. 419:364–376). However, in the corpus callosum the myelin alterations correlate significantly with only one component of the cognitive impairment index, namely the delayed nonmatching to sample task with a 2‐minute delay. It is proposed that age‐related myelin alterations are ubiquitous and that the correlations between their frequency and impairments in cognition occur because the conduction velocity along the affected nerve fibers is reduced, so that the normal timing sequences within neuronal circuits break down. J. Comp. Neurol. 442:277–291, 2002. © 2001 Wiley‐Liss, Inc.
Retinal organization in the bcl‐2‐overexpressing transgenic mouse
Authors: Strettoi Enrica , Volpini Maila
Published: August 2002

Naturally occurring cell death is believed to play a major role during the development of the nervous system in the establishment of neuronal architecture. Here we study the effects of cell death inhibition by using a transgenic mouse in which the powerful antiapototic gene bcl‐2 is expressed in neurons. The retina of this mouse reveals that the general neuronal plan has been maintained. However, bcl‐2 overexpression leads to altered frequencies of the major cell types in the retina. Thus, it is possible to estimate cell‐type‐specific rates of apoptosis by observing the increases in numbers of cells in the bcl‐2‐overexpressing transgenic mouse. J. Comp. Neurol. 446:1–10, 2002. © 2002 Wiley‐Liss, Inc.
Calcyon in the rat brain: Cloning of cDNA and expression of mRNA
Authors: Zelenin Sergey , Aperia Anita , Diaz Heijtz Rochellys
Published: August 2002

Calcyon is a 24 kD protein recently cloned from a human brain cDNA library and shown to interact with the dopamine receptor 1 (D1R) of D1‐like receptors. This interaction shifts the effector coupling of D1R to stimulate a calcium signaling pathway, without influencing the D1R‐adenylyl‐cAMP pathway. To obtain more knowledge about the potential role of calcyon in the brain, we cloned rat calcyon cDNA and studied its distribution in the brain. Northern blot analysis and RT‐PCR revealed that rat calcyon mRNA was expressed only in the brain. With the use of the in situ hybridization technique, we studied rat calcyon mRNA distribution in the brain and related it to the distribution of D1R and dopamine receptor 5 (D5R) mRNAs. Prominent calcyon mRNA signals were found in several brain regions, including hippocampus, hypothalamus, cerebellum, and medial prefrontal cortex. Less abundant calcyon mRNA expression was observed in the dorsal striatum region, where D1R mRNA is highly expressed and where D1R/cAMP‐DARPP‐32 signaling pathway is of great functional importance. The strongest expression of D5R mRNA was found in the hippocampus and cerebellum, where D1R mRNA expression was relatively low. In conclusion, rat calcyon appears to be a brain specific protein. There is a certain overlap between calcyon mRNA distribution and that of the D1R and D5 mRNAs, indicating that calcyon might be associated not only with D1R but also with D5R. J. Comp. Neurol. 446:37–45, 2002. © 2002 Wiley‐Liss, Inc.
Development of convergent synaptic inputs to subpopulations of autonomic neurons
Authors: Anderson Rebecca L. , Jobling Phillip , Matthew Sue E. , Gibbins Ian L.
Published: August 2002

Visceromotor neurons in mammalian prevertebral sympathetic ganglia receive convergent synaptic inputs from spinal preganglionic neurons and peripheral intestinofugal neurons projecting from the enteric plexuses. Vasomotor neurons in the same ganglia receive only preganglionic inputs. How this pathway‐specific pattern of connectivity is established is unknown. We have used a combination of immunohistochemical, ultrastructural, and electrophysiological techniques to investigate the development of synaptic inputs onto visceromotor and vasomotor neurons in the celiac ganglion of guinea pigs. Functional synaptogenesis occurred primarily from early fetal (F30–F35) to midfetal (F36–F45) stages, after the neurochemical differentiation of vasomotor and visceromotor neurons but before establishment of their electrophysiological phenotypes. Intestinofugal inputs were detected only on presumptive visceromotor neurons located primarily in medial regions of the ganglion. The number of ultrastructurally identified synaptic profiles increased in parallel with functional synaptogenesis, especially in medial regions, where dendritic growth rates also were higher. However, the expression of immunoreactivity to choline acetyltransferase in the terminals of inputs was very low until late fetal stages, after functional transmission already had been established. These results show that peripheral intestinofugal neurons directly establish appropriate functional connections with their target visceromotor neurons simultaneously with the development of functional preganglionic inputs to both visceromotor and vasomotor neurons. It seems likely that synaptogenesis occurs independently of the neurochemical differentiation of the target neurons but is closely related to the pathway‐specific dendritic development of those neurons. J. Comp. Neurol. 447:218–233, 2002. © 2002 Wiley‐Liss, Inc.
Distribution of postsynaptic GABAa receptor aggregates in the deep cerebellar nuclei of normal and mutant mice
Authors: Garin Nathalie , Hornung Jean‐Pierre , Escher Gérard
Published: August 2002

In the central nervous system, the aggregation of receptors is crucial for synapse formation and function. To study the role of presynaptic terminals in the maintenance of postsynaptic specializations, we analyzed the synaptic contacts between Purkinje cells and neurons of the deep cerebellar nuclei in two in vivo models: the Lurcher and Purkinje cell‐deficient (PCD) mutant mice. These mutants lose their Purkinje cells at different postnatal stages. By using confocal scanner microscopy and immunohistochemistry, we studied the distribution of the α subunit of the γ‐aminobutyric acid (GABA)A receptor (GABAARα1) and gephyrin, one of its anchoring proteins, in relation to the distribution of presynaptic markers, glutamic acid decarboxylase (GAD), or synaptophysin. In Lurcher the distribution of GABAA receptor aggregates on the membrane of postsynaptic neurons was not affected by the important loss of GAD‐positive terminals, whereas in PCD, the number of large GABAA receptor aggregates increased. In both mutants the number of aggregates of gephyrin decreased. Most of these remaining aggregates were clustered to form groups, some of which were in front of GAD‐positive terminals. This study shows, for the first time, the localization of GABAARα1 in Lurcher and PCD mutant mice. It clearly establishes that GABAARα1 and gephyrin are differentially affected by deafferentation. Because the receptor aggregates are maintained while the gephyrin aggregates are lost, as a result some receptor aggregates are not associated with any gephyrin. These two postsynaptic components appeared to be regulated by different mechanisms. J. Comp. Neurol. 447:210–217, 2002. © 2002 Wiley‐Liss, Inc.
Gonadal hormones are responsible for maintaining the integrity of spine synapses in the CA1 hippocampal subfield of female nonhuman primates
Authors: Leranth Csaba , Shanabrough Marya , Redmond D. Eugene
Published: August 2002

It is well established that gonadal hormonal manipulation results in morphologic changes in the rat hippocampus. The great similarities in the hippocampal formation between nonhuman primates and humans, as well as the differences in this structure between humans and rats, led to this investigation of whether hormonal manipulation in female subhuman primates influences pyramidal cell spine density in the CA1 hippocampal subfield, as it does in rats. African green monkeys (Cercopithecus aethiops sabaeus) were ovariectomized, and half of the animals received estrogen replacement therapy. One month later, the monkeys were killed. In the first group of experiments, pyramidal cell spines were analyzed on Golgi‐impregnated material taken from the CA1 hippocampal subfield. In the second experiment, unbiased electron microscopic stereologic calculations were performed to estimate the volumetric density of spine synapses in the same hippocampal subfield. Analysis of the Golgi‐impregnated material showed that the spine density of CA1 pyramidal cells is much lower in the ovariectomized animals than in ovariectomized and estrogen‐replaced monkeys. The unbiased, electron microscopic, stereologic calculation confirmed the light microscopic observation. The volumetric density (number of spine synapses/μ m3) of spine synapses was significantly lower (43.33%) in the ovariectomized animals than in ovariectomized and estrogen‐replaced monkeys. Because the hippocampus is involved in specific mnemonic functions, this observation highlights the importance of hormone replacement therapy in postmenopausal conditions. J. Comp. Neurol. 447:34–42, 2002. © 2002 Wiley‐Liss, Inc.
Neuroanatomical studies of period gene expression in the hawkmoth, Manduca sexta
Authors: Wise Sarah , Davis Norman T. , Tyndale Elizabeth , Noveral Jocelyne , Folwell Mary Grace , Bedian Vahe , Emery Ivette F. , Siwicki Kathleen K.
Published: August 2002

In the nervous system of the hawkmoth, Manduca sexta, cells expressing the period (per)gene were mapped by in situ hybridization and immunocytochemical methods. Digoxigenin‐labeled riboprobes were transcribed from a 1‐kb M. sexta
per cDNA. Monoclonal anti‐PER antibodies were raised to peptide antigens translated from both M. sexta and Drosophila melanogaster
per cDNAs. These reagents revealed a widespread distribution of per gene products in M. sexta eyes, optic lobes, brains, and retrocerebral complexes. Labeling for per mRNA was prominent in photoreceptors and in glial cells throughout the brain, and in a cluster of 100–200 neurons adjacent to the accessory medulla of the optic lobes. Daily rhythms of per mRNA levels were detected only in glial cells. PER‐like immunoreactivity was observed in nuclei of most neurons and glial cells and in many photoreceptor nuclei. Four neurosecretory cells in the pars lateralis of each brain hemisphere exhibited both nuclear and cytoplasmic staining with anti‐PER antibodies. These cells were positively identified as Ia1 neurosecretory cells that express corazonin immunoreactivity. Anti‐corazonin labeled their projections in the brain and their neurohemal endings in the corpora cardiaca and corpora allata. Four pairs of PER‐expressing neurosecretory cells previously described in the silkmoth, Anthereae pernyi, are likely to be homologous to these PER/corazonin‐expressing Ia1 cells of M. sexta. Other findings, such as widespread nuclear localization of M. sexta PER and rhythmic expression in glial cells, are reminiscient of the period gene of D. melanogaster, suggesting that some functions of per may be conserved in this lepidopteran species. J. Comp. Neurol. 447:366–380, 2002. © 2002 Wiley‐Liss, Inc.
Peripheral patterns of terminal innervation of vestibular primary afferent neurons projecting to the vestibulocerebellum in the gerbil
Authors: Purcell Ian M. , Perachio Adrian A.
Published: August 2002

Retrograde transganglionic labeling techniques with biotinylated dextran amine (BDA) were used to examine the terminal field structure and topographical patterns of innervation within the vestibular sensory end organs of vestibular primary afferent neurons projecting to the cerebellar uvula/nodulus and flocculus lobules in the gerbil. Robust, dark labeling in the cristae ampullares suggested that the vast majority of the terminals of afferent neurons were of the dimorphic type. The majority (94% to the uvula/nodulus and 100% to the flocculus) innervates the peripheral zones of each of the three semicircular canal cristae. Comparison of the type and distribution of terminals across the canalicular sensory neuroepithelium with morphophysiological studies in chinchilla suggests that the labeled population consists predominantly of peripheral terminal fields of lower‐to‐intermediate gain, more regularly firing, tonic afferents. For otolith organ‐related afferents, the uvula/nodulus receives strong inputs from primary otolith afferent neurons identified as dimorphic in type that predominately innervate the peristriolar zones of the utricular and saccular maculae. No direct otolith organ‐related inputs to the flocculus were observed. In contrast to the canal afferents, the types and locations of labeled otolith afferent terminals suggest that they largely consist of irregularly firing, high‐gain, phasic neurons. J. Comp. Neurol. 433:48–61, 2001. © 2001 Wiley‐Liss, Inc.
Structural abnormalities develop in the brain after ablation of the gene encoding nonmuscle myosin II‐B heavy chain
Authors: Tullio Antonella N. , Bridgman Paul C. , Tresser Nancy J. , Chan Chi‐Chao , Conti Mary Anne , Adelstein Robert S. , Hara Yoshinobu
Published: August 2002

Ablation of nonmuscle myosin heavy chain II‐B (NMHC‐B) in mice results in severe hydrocephalus with enlargement of the lateral and third ventricles. All B‐/B‐ mice died either during embryonic development or on the day of birth (PO). Neurons cultured from superior cervical ganglia of B‐/B‐ mice between embryonic day (E) 18 and P0 showed decreased rates of neurite outgrowth, and their growth cones had a distinctive narrow morphology compared with those from normal mice. Serial sections of E12.5, E13.5, and E15 mouse brains identified developmental defects in the ventricular neuroepithelium. On E12.5, disruption of the coherent ventricular surface and disordered cell migration of neuroepithelial and differentiated cells were seen at various points in the ventricular walls. These abnormalities resulted in the formation of rosettes in various regions of the brain and spinal cord. On E13.5 and E15, disruption of the ventricular surface and aberrant protrusions of neural cells into the ventricles became more prominent. By E18.5 and P0, the defects in cells lining the ventricular wall resulted in an obstructive hydrocephalus due to stenosis or occlusion of the third ventricle and cerebral aqueduct. These defects may be caused by abnormalities in the cell adhesive properties of neuroepithelial cells and suggest that NMHC‐B is essential for both early and late developmental processes in the mammalian brain. J. Comp. Neurol. 433:62–74, 2001. © 2001 Wiley‐Liss, Inc.
Muscarinic receptor M2 in cat visual cortex: Laminar distribution, relationship to γ‐aminobutyric acidergic neurons, and effect of cingulate lesions
Authors: Erisir Alev , Levey Allan I. , Aoki Chiye
Published: August 2002

Acetylcholine can have diverse effects on visual cortical neurons as a result of variations in postsynaptic receptor subtypes as well as the types of neurons and subcellular sites targeted. This study examines the cellular basis for cholinergic activation in visual cortex via M2 type muscarinic receptors in γ‐aminobutyric acid (GABA)‐ergic and non‐GABAergic cells, using immunocytochemical techniques. At light microscopic resolution, M2 immunoreactivity (‐ir) was seen in all layers except area and sublayer specific bands in layer 4. Subcellularly, M2‐ir occurred in both dendrites and terminals that form symmetric and asymmetric junctions. Layers 5 and 6 were characterized by axosomatic contacts that displayed labeling in the presynaptic component, and layer 6 displayed perikaryal postsynaptic staining, suggesting that corticofugal output neurons may be modulated particularly strongly via M2. Infragranular layers differed from the supragranular layers in that more labeled profiles were axonal than dendritic, indicating a dominant presynaptic effect by acetylcholine via M2 there. Unilateral cingulate cortex cuts caused reduction of cholinergic and noradrenergic fibers in the lesioned hemisphere at light microscopic resolution; at electron microscopic resolution, the synapse density and axonal M2 labeling were reduced, suggesting that M2 was localized presynaptically on extrathalamic modulatory inputs. Dual labeling with GABA in visual cortex layer 5 showed that half of M2‐labeled dendrites originated from GABAergic neurons. Given that only one‐fifth of all cortical dendritic profiles are GABAergic, this prevalence of dual labeling indicates an enrichment of M2 within GABAergic dendrites and, thus, implicates abundant postsynaptic action on GABAergic neurons via M2. In contrast, only one‐tenth of M2‐labeled terminals originated from GABAergic neurons, suggesting that the presynaptic action of acetylcholine via M2 receptors would be more selective for non‐GABAergic terminals. J. Comp. Neurol. 441:168–185, 2001. © 2001 Wiley‐Liss, Inc.
An averaged nodal deformation gradient linear tetrahedral element for large strain explicit dynamic applications
Authors: Bonet J. , Marriott H. , Hassan O.
Published: August 2002

This paper presents a new linear tetrahedral element that overcomes the shortcomings in bending dominated problems of the average nodal pressure element presented in Bonet and Burton (Communications in Numerical Methods in Engineering 1998; 14:437–439) Zienkiewicz et al. (Internatinal Journal for Numerical Methods in Engineering 1998; 43:565–583) and Bonet et al. (Internatinal Journal for Numerical Methods in Engineering 2001; 50(1):119–133). This is achieved by extending some of the ideas proposed by Dohrmann et al. (Internatinal Journal for Numerical Methods in Engineering 2000; 47:1549–1568) to the large strain nonlinear kinematics regime. In essence, a nodal deformation gradient is defined by weighted average of the surrounding element values. The associated stresses and internal forces are then derived by differentiation of the corresponding simplified strain energy term. The resulting element is intended for use in explicit dynamic codes (Goudreau and Hallquist, Computer Methods in Applied Mechanics and Engineering 1982; 33) where the use of quadratic tetrahedral elements can present significant difficulties. Copyright © 2001 John Wiley & Sons, Ltd.
Multiplicative multifractal modelling of long‐range‐dependent network traffic
Authors: Gao Jianbo , Rubin Izhak
Published: August 2002

We present a multiplicative multifractal process to model traffic which exhibits long‐range dependence. Using traffic trace data captured by Bellcore from operations across local and wide area networks, we examine the interarrival time series and the packet length sequences. We also model the frame size sequences of VBR video traffic process. We prove a number of properties of multiplicative multifractal processes that are most relevant to their use as traffic models. In particular, we show these processes to characterize effectively the long‐range dependence properties of the measured processes. Furthermore, we consider a single server queueing system which is loaded, on one hand, by the measured processes, and, on the other hand, by our multifractal processes (the latter forming a MFe/MFg/1 queueing system model). In comparing the performance of both systems, we demonstrate our models to effectively track the behaviour exhibited by the system driven by the actual traffic processes. We show the multiplicative multifractal process to be easy to construct. Through parametric dependence on one or two parameters, this model can be calibrated to fit the measured data. We also show that in simulating the packet loss probability, our multifractal traffic model provides a better fit than that obtained by using a fractional Brownian motion model. Copyright © 2001 John Wiley & Sons, Ltd.
Intramuscular low‐grade myxoid neoplasm with recurrent potential (cellular myxoma) of the lower extremity: Case report with cytohistologic correlation and review of the literature
Authors: Catroppo James F. , Olesnicky Ludmilla , Ringer Patrick , Goldenkranz Robert , Casas Victor , Wright Theodore
Published: August 2002

“Low‐grade myxoid neoplasm with recurrent potential” (cellular myxoma) is a term recently used to describe a subset of soft tissue lesions with histology intermediate between intramuscular myxoma and low‐grade myxofibrosarcoma or myxoid malignant fibrous histiocytoma (MFH), while resembling a deeper counterpart of superficial angiomyxoma. Their distinctive biological behavior is characterized by the potential to recur locally, in contrast to intramuscular myxoma, while having no potential to advance in grade or metastasize when compared to low‐grade myxofibrosarcoma. We present a cytohistological correlation for an intramuscular location of such a tumor in the lower extremity of a 49‐yr‐old male. Diagn. Cytopathol. 2002;26:301–305. © 2002 Wiley‐Liss, Inc.
Nested PCR for diagnosis of tuberculous lymphadenitis and PCR‐SSCP for identification of rifampicin resistance in fine‐needle aspirates
Authors: Gong Gyungyub , Lee Hungkyung , Hoon Kang Gyeong , Shim Yhoung‐hee , Huh Jooryung , Kwang Khang Shin
Published: August 2002

An accurate diagnosis of tuberculosis and multidrug resistance is important for the control of tuberculosis, which remains a major public health problem. Fine‐needle aspiration (FNA) has provided an alternative tool for bacterial examination. This study was performed to investigate the usefulness of one‐step polymerase chain reaction (PCR) and PCR‐SSCP as a routine test for the detection of Mycobacterium tuberculosis and rifampicin‐resistant strain in FNA. Ziehl‐Neelsen stain (Z‐N) and PCR were processed using the aspirates of tuberculous lymphadenitis for the detection of M. tuberculosis. PCR‐SSCP was done for the identification of rpoB mutation. M. tuberculosis was detected in 49/63 (77.8%) by PCR and 25/63 (39.7%) by Z‐N. There were 26 cases with PCR(+)/Z‐N(‐) and two cases with PCR(‐)/Z‐N(+). Twelve cases showed negativity against both. In 7/22 (31.8%), rpoB mutation was observed. In conclusion, PCR is more sensitive in the detection of M. tuberculosis in FNA than Z‐N. PCR‐SSCP could also be used in FNA in the prediction of multidrug resistance. Diagn. Cytopathol. 2002;26:228–231. © 2002 Wiley‐Liss, Inc.
Differential expression of the seven‐pass transmembrane cadherin genes Celsr1‐3 and distribution of the Celsr2 protein during mouse development
Authors: Shima Yasuyuki , Copeland Neal G. , Gilbert Debra J. , Jenkins Nancy A. , Chisaka Osamu , Takeichi Masatoshi , Uemura Tadashi
Published: August 2002

Drosophila Flamingo (Fmi) is an evolutionally conserved seven‐pass transmembrane receptor of the cadherin superfamily. Fmi plays multiple roles in patterning neuronal processes and epithelial planar cell polarity. To explore the in vivo roles of Fmi homologs in mammals, we previously cloned one of the mouse homologs, mouse flamingo1/Celsr2. Here, we report the results of our study of its embryonic and postnatal expression patterns together with those of two other paralogs, Celsr1 and Celsr3. Celsr1–3 expression was initiated broadly in the nervous system at early developmental stages, and each paralog showed characteristic expression patterns in the developing CNS. These genes were also expressed in several other organs, including the cochlea, where hair cells develop planar polarity, the kidney, and the whisker. The Celsr2 protein was distributed at intercellular boundaries in the whisker and on processes of neuronal cells such as hippocampal pyramidal cells, Purkinje cells, and olfactory neurons. Celsr2 is mapped to a distal region of the mouse chromosome 3. We discussed possible functions of seven‐pass transmembrane cadherins in mouse development. © 2002 Wiley‐Liss, Inc.
Early expression of endomucin on endothelium of the mouse embryo and on putative hematopoietic clusters in the dorsal aorta
Authors: Brachtendorf Gertrud , Kuhn Annegret , Samulowitz Ulrike , Knorr Ruth , Gustafsson Erika , Potocnik Alexandre J. , Fässler Reinhard , Vestweber Dietmar
Published: August 2002

Endomucin is a recently identified sialomucin that is specifically expressed on endothelium of the adult mouse. Here, we have analysed the expression of endomucin during development of the vascular system by immunohistochemistry by using three monoclonal antibodies (mAb). We demonstrate that two of the mAb, V.5C7 and V.1A7, recognize epitopes on the nonglycosylated protein, because they recognize the antigen when it is synthesized as a bacterial fusion protein and when it is in vitro translated in a membrane‐free reticulocyte lysate. During in vitro differentiation of embryonic stem cells to endothelial cells, endomucin is expressed at day 6 after onset of differentiation, 1 day later than PECAM‐1. During differentiation of the mouse embryo, endomucin is first detected at E8.0 in all embryonic blood vessels detectable at this stage but is absent in blood islands of the yolk sac. Analysing the paraaortic‐splanchnopleura (P‐SP) region and the aorta‐gonad‐mesonephros (AGM) region as sites of intraembryonic hematopoiesis, we found that endothelium of the dorsal aorta is brightly positive for endomucin at E8.5–9.0 and at E11.5. At later stages and in the adult aorta, endothelial staining is strongly reduced and confined to focal areas. Cell clusters associated with the luminal surface of the endothelium of the dorsal aorta could be stained for endomucin and for CD34. At a later stage (E15.5) single leukocytes in the lumen of large venules were stained for endomucin. We conclude that endomucin is an early endothelial‐specific antigen that is also expressed on putative hematopoietic progenitor cells. © 2001 Wiley‐Liss, Inc.
A meta‐analytic examination of the relationship between child sexual abuse and eating disorders
Authors: Smolak Linda , Murnen Sarah K.
Published: August 2002

Objective

This study had two goals. The first was to assess the magnitude and consistency of the relationship between child sexual abuse (CSA) and eating disorders (ED). The second was to examine methodological factors contributing to the heterogeneity of this relationship.

Method

Meta‐analysis was used to examine both questions. Fifty‐three studies were included in the analysis.

Results

A small, significant positive relationship between CSA and ED emerged. The relationship was marked by heterogeneity. Effect sizes were largest when CSA was the grouping variable, the Eating Disorders Inventory (EDI) or the Eating Attitudes Test (EAT) was used as the measure of eating disorders, and nonclinical groups were compared with clinical samples.

Discussion

Models of CSA and ED need to more clearly specify what aspects of ED (e.g., body image or binge eating) are most influenced by which types of CSA. These specific relationships then need to be examined empirically. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 31: 136–150, 2002; DOI 10.1002/eat.10008