bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions and associations of paraoxonase gene cluster polymorphisms with myocardial infarction in a Pakistani population
Authors: Saeed M , Perwaiz Iqbal M , Yousuf FA , Perveen S , Shafiq M , Sajid J , Frossard PM
Published: January 2007

Polymorphisms of paraoxonase gene (PON) cluster have been investigated in numerous studies for their association with myocardial infarction (MI) but the results have been conflicting. Epistasis and gene–environment interactions at this locus could possibly modulate susceptibility toward MI and account for the discrepancies. We carried out a case–control study (211 MI patients and 370 control subjects) to test association of PON cluster polymorphisms with MI, their interactions with each other and with smoking. Genotyping was performed by PCR–restriction fragment length polymorphism based assays. The Q192R, C‐108T, and A148G polymorphisms were associated with MI. Two haplotypes consisting of C‐108T, C311S, and A148G, having allele frequencies of 0.17 and 0.14 in the control population, predisposed to MI (global haplotype statistic χ2 = 34.74, df = 15, p = 0.0027). Multifactor dimensionality reduction analysis showed a significant three‐locus model (p = 0.02) involving these three polymorphisms, suggesting a potential gene–gene interaction between PON1 and PON2. These polymorphisms also interacted with smoking, in a three‐locus and a four‐locus model (p = 0.01 and p = 0.05, respectively). Additionally, the R192 allele may advance the age‐at‐onset of MI. The PON cluster appears to be a susceptibility locus for MI in Pakistani population, and the susceptibility is modulated through gene–gene and gene–environment interactions.
Array comparative genomic hybridization for diagnosis of developmental delay – an exploratory cost‐consequences analysis
Authors: Newman WG , Hamilton S , Ayres J , Sanghera N , Smith A , Gaunt L , Davies LM , Clayton‐Smith J
Published: January 2007

A major application of array comparative genomic hybridization (aCGH) is to define a specific cause in children with undiagnosed learning and developmental disability (LDD). Medical notes for 46 consecutive patients selected for aCGH analysis by clinical dysmorphologists were abstracted for clinical investigations related to LDD and a cost‐consequences analysis was performed. aCGH analysis was completed in 36 cases and five diagnostic chromosomal anomalies were identified (13.8%). The number of investigations undertaken on each child varied. With aCGH estimated to cost £590 per case, if aCGH had been undertaken after negative standard initial tests for LDD investigation, the additional cost would be £2399 per positive case. If the cost of aCGH was reduced to £256 per case (∼€350), aCGH becomes cost neutral. All chromosomal anomalies detected by aCGH had a de Vries score of ≥5. If aCGH had only been used for individuals with a score of ≥5, the sensitivity increased to 21.7% yielding a cost of £1087 per positive case identified. Pre‐selection of cases for aCGH based on de Vries criteria has a major economic impact on introducing aCGH into clinical practice. Prospective studies are required to explore the long‐term costs and consequences of aCGH and identify when aCGH may provide the most benefit at least cost.
Nitric oxide promotes the progression of periapical lesion via inducing macrophage and osteoblast apoptosis
Authors: Lin S.‐K. , Kok S.‐H. , Lin L.‐D. , Wang C.‐C. , Kuo M. Y. P. , Lin C.‐T. , Hsiao M. , Hong C.‐Y.
Published: January 2007

This study aimed to elucidate the modulation by nitric oxide (NO) of the apoptosis of macrophages and osteoblasts, the essential cellular components in the development of periapical lesions. Lipopolysaccharide (LPS) induced prominent nitrite synthesis in J774 mouse macrophage cell lines. Exposure to LPS induced obvious apoptosis in J774 cells, whereas transient transfection with murine inducible nitric oxide synthase (iNOS), small interfering RNA (siRNA) diminished this effect. Tumor necrosis factor‐α (TNF‐α) and S‐nitroso‐N‐acetyl‐DL‐penicillamine (SNAP) (a NO donor) triggered apoptosis in UMR‐106 rat osteoblastic cell lines and a synergistic effect was noted when TNF‐α and SNAP were added to the medium together. Administration of siRNAs for c‐Fos and c‐Jun: components of activator protein‐1 (AP‐1) and transforming growth factor‐β1 attenuated the combined effect markedly. Terminal deoxynucleotidyl transferase‐mediated nick end‐labeling (TUNEL) stain in a rat model of induced periapical lesion showed positive apoptotic signals in macrophages and osteoblasts. Administration of NG‐monomethyl‐l‐arginine markedly diminished the extent of bone loss and the amounts of apoptotic macrophages and osteoblasts. In conclusion, NO mediates LPS‐stimulated apoptosis of macrophages. It also induces osteoblast apoptosis and augments the pro‐apoptotic effect of cytokines. Inhibition of NO synthesis in vivo attenuates apoptosis and the size of periapical lesions. Taken together, these results suggest that NO may promote the progression of periapical lesion by inducing the apoptosis of macrophages and osteoblasts.
Comparison of glucan‐binding proteins in cariogenicity of Streptococcus mutans
Authors: Matsumoto‐Nakano M. , Fujita K. , Ooshima T.
Published: January 2007

Streptococcus mutans has been implicated as a primary causative agent of dental caries in humans. Bacterial components associated with the adhesion phase of S. mutans include cell‐associated and cell‐free glucosyltransferases (GTFs), as well as protein antigen c and proteins that bind glucan. At least four types of S. mutans glucan‐binding protein (Gbp) have been identified; GbpA, GbpB, GbpC and GbpD. In the present study, GbpA‐, GbpB‐ and GbpC‐deficient mutants (AD1, BD1 and CD1, respectively) were constructed, and their cariogenic properties were evaluated by comparing them to those of their parent strain MT8148. All of the Gbp mutants showed lower levels of dextran binding, while the sucrose‐dependent adhesion levels of AD1 and CD1 were lower than in the parental strain. The expression of each GTF was detected in the Gbp mutants, however, they had lower levels of cell‐free‐GTF activity than the parental strain. On the other hand, in acid tolerance assays, BD1 was the most sensitive among all of the tested strains. These results suggest that GbpA and GbpC in S. mutans have strong relationships with cariogenicity, while GbpB may have another biological function.
Soluble products from Eikenella corrodens induce cell proliferation and expression of interleukin‐8 and adhesion molecules in endothelial cells via mitogen‐activated protein kinase pathways
Authors: Yumoto H. , Yamada M. , Shinohara C. , Nakae H. , Takahashi K. , Azakami H. , Ebisu S. , Matsuo T.
Published: January 2007

The periodontal vasculature is profoundly affected during the progression of periodontitis, and several specific bacteria are believed to be involved in this inflammatory disease. Eikenella corrodens is one of the common bacteria detected in periodontitis diseased lesions; however, the function of this organism in periodontitis is not well understood. In this study, we investigated the E. corrodens‐induced endothelial cell alteration and inflammation process that leads to leukocyte infiltration in inflamed regions. Soluble products from E. corrodens (EcSP) induced the gene expression and protein production of vascular endothelial growth factor in oral epithelial cells and human umbilical vein endothelial cells (HUVEC). Direct stimulation by EcSP also activated endothelial cell proliferation. Moreover, EcSP induced ERK1/2 (p44/42) and p38 mitogen‐activated protein kinase (MAPK) phosphorylation within 10–30 min in HUVEC, as demonstrated by Western blot analysis and up‐regulated intercellular adhesion molecule 1 (ICAM‐1), vascular cell adhesion molecule 1 (VCAM‐1), E‐selectin and interleukin‐8 (IL‐8) production demonstrated by reverse transcription–polymerase chain reaction and enzyme‐linked immunosorbent assay. The specific p38 MAPK inhibitor SB203580 reduced the expression of ICAM‐1, VCAM‐1 and IL‐8, whereas the blockade of p44/42 by MAPK kinase (MEK1) inhibitor, PD98059, inhibited only IL‐8 expression. Our results indicate that E. corrodens can trigger a cascade of events that induce inflammatory responses in periodontal tissue via the MAPK cascade and may promote chronic periodontitis without bacteria–cell contact.
Unilateral limited scleroderma‐like changes following formation of an arteriovenous fistula
Authors: Roberts Hugh , Curnow Paul A
Published: January 2007

A 55‐year‐old man presented with a 1‐year history of progressive skin thickening involving the right hand associated with Raynaud’s phenomenon, sclerodactyly and painful cutaneous ulcers. An arteriovenous fistula for haemodialysis had been formed on the same arm 2 years previously. There were no symptoms or signs of systemic sclerosis or involvement of the contralateral arm. The limb was clinically ischaemic, attributed to a vascular steal phenomenon from the arteriovenous fistula, superimposed on occlusive arterial disease. A revascularization procedure was performed, which resulted in substantial improvement in the sclerodactyly, Raynaud’s phenomenon and hand function. Tissue hypoxia is believed to be a contributing factor in the pathogenesis of scleroderma, and this case demonstrates scleroderma‐like changes in the setting of limb ischaemia.
Molecular genetics of bipolar disorder and depression
Authors: KATO TADAFUMI
Published: January 2007

Abstract  In this review, all papers relevant to the molecular genetics of bipolar disorder published from 2004 to the present (mid 2006) are reviewed, and major results on depression are summarized. Several candidate genes for schizophrenia may also be associated with bipolar disorder: G72, DISC1, NRG1, RGS4, NCAM1, DAO, GRM3, GRM4, GRIN2B, MLC1, SYNGR1, and SLC12A6. Of these, association with G72 may be most robust. However, G72 haplotypes and polymorphisms associated with bipolar disorder are not consistent with each other. The positional candidate approach showed an association between bipolar disorder and TRPM2 (21q22.3), GPR50 (Xq28), Citron (12q24), CHMP1.5 (18p11.2), GCHI (14q22‐24), MLC1 (22q13), GABRA5 (15q11‐q13), BCR (22q11), CUX2, FLJ32356 (12q23‐q24), and NAPG (18p11). Studies that focused on mood disorder comorbid with somatic symptoms, suggested roles for the mitochondrial DNA (mtDNA) 3644 mutation and the POLG mutation. From gene expression analysis, PDLIM5, somatostatin, and the mtDNA 3243 mutation were found to be related to bipolar disorder. Whereas most previous positive findings were not supported by subsequent studies, DRD1 and IMPA2 have been implicated in follow‐up studies. Several candidate genes in the circadian rhythm pathway, BmaL1, TIMELESS, and PERIOD3, are reported to be associated with bipolar disorder. Linkage studies show many new linkage loci. In depression, the previously reported positive finding of a gene–environmental interaction between HTTLPR (insertion/deletion polymorphism in the promoter of a serotonin transporter) and stress was not replicated. Although the role of the TPH2 mutation in depression had drawn attention previously, this has not been replicated either. Pharmacogenetic studies show a relationship between antidepressant response and HTR2A or FKBP5. New technologies for comprehensive genomic analysis have already been applied. HTTLPR and BDNF promoter polymorphisms are now found to be more complex than previously thought, and previous papers on these polymorphisms should be treated with caution. Finally, this report addresses some possible causes for the lack of replication in this field.
Glucose and lipid metabolism of long‐term risperidone monotherapy in patients with schizophrenia
Authors: MURASHITA MARI , INOUE TAKESHI , KUSUMI ICHIRO , NAKAGAWA SHIN , ITOH KOUICHI , TANAKA TERUAKI , IZUMI TAKESHI , HOSODA HIROSHI , KANGAWA KENJI , KOYAMA TSUKASA
Published: January 2007

Abstract  Risperidone has a relatively low risk of causing obesity and diabetes mellitus and is a first‐line treatment for schizophrenia. The aim of the present study was to investigate glucose and lipid metabolism, and feeding‐control parameters in schizophrenia patients treated with long‐term risperidone monotherapy. Fifteen patients with paranoid‐type schizophrenia who had been treated with risperidone and had Global Assessment of Function (GAF) scores >70 were selected and compared with healthy volunteers (n = 25). Single assessments of psychotic symptoms, side‐effects, Drug‐Induced Extrapyramidal Symptoms Scale (DIEPSS) score, bodyweight, body fat percentage and blood sampling were performed. Fasting blood glucose, insulin, hemoglobin A1c, homeostasis model assessment insulin resistance index (HOMA‐IR), total cholesterol, triglyceride, high density lipoprotein (HDL)‐, low density lipoprotein‐cholesterol, adiponectin, prolactin and feeding‐control parameters (ghrelin and leptin) were analyzed. The body fat percentage (P = 0.0018), body mass index (BMI) (P = 0.0150), fasting blood glucose (P = 0.0358), triglyceride (P = 0.0377), leptin (P = 0.0243), total ghrelin (P = 0.0067), active ghrelin (P = 0.0241) and prolactin (P < 0.0001) levels of patients treated with risperidone were significantly higher than those of healthy volunteers, while the HDL‐cholesterol level (P = 0.0222) was significantly lower. Although the patients had very mild psychiatric symptoms and maintained functionally high levels, the glucose and lipid parameters were significantly impaired compared to healthy volunteers. A high level of plasma ghrelin might increase appetite, leading to exacerbation of metabolic impairment.
Psychiatric comorbidity and gender difference among treatment‐seeking heroin abusers in Taiwan
Authors: CHIANG SHU‐CHUAN , CHAN HUNG‐YU , CHANG YUAN‐YING , SUN HSIAO‐JU , CHEN WEI J. , CHEN CHIH‐KEN
Published: January 2007

Abstract  The objectives of the present study were to estimate the psychiatric comorbidity of Taiwanese heroin users seeking treatment and to identify the gender differences in psychiatric comorbidity and drug use behavior. Subjects were interviewed using a structured questionnaire on drug use behavior and the Mini International Neuropsychiatric Interview for psychiatric disorders. Of the subjects, 58.5% of the male and 62.5% of the female subjects had at least one non‐substance‐use axis I psychiatric disorder or antisocial personality disorder. Compared to male subjects, female subjects were younger, were less educated, had higher rates of unemployment and had earlier onset of illicit drug use. Female subjects were 11‐fold more likely than male subjects to exhibit suicidal behavior. Among heroin abusers in the present study, female subjects were more widely exposed to unfavorable social factors and had substantially higher incidence of suicidal behavior than male subjects. Drug treatment centers should be aware of these gender differences and pay particular attention to comorbid depressive disorders and suicidal behavior of female heroin abusers.
Critical evaluation of the use of research tools in evaluating quality of life for people with schizophrenia
Authors: Hewitt Jeanette
Published: January 2007

ABSTRACT:  Schizophrenia may lead to impairments in many aspects of life, including physical, cognitive, and role functioning. The subjective quality of life of people with schizophrenia has been shown to be lower than in the general population and appropriate patient‐assessed health outcome measures are necessary to capture the distress and disability experienced by people living with a serious mental illness. Although psychiatry has been slow to become involved in quality of life measurement, the use of quality of life instruments has now been recognized as a means of evaluating the outcome of care interventions, in terms of symptoms and functioning. This paper evaluates the effectiveness of two widely used instruments: The Medical Outcomes Study Short Form Health Survey (SF‐36) and The Lancashire Quality of Life Profile (LQoLP) in terms of reliability and validity in measuring the quality of life of people with schizophrenia. The LQoLP appeared to be best suited for evaluation of care programmes, whereas the SF‐36 was more appropriate for medical trials, comparisons between patient groups, and assessment of the direct consequences of treatment on health and function. Subjective quality of life should, however, be considered to be distinct from clinical status and quality of life assessment should include the broadest range of indicators, to reflect the holistic ethos of mental health nursing.
Critique of Falloon and the Optimal Treatment Project
Authors: Hayman‐White Karla , Happell Brenda
Published: January 2007

ABSTRACT:  The Optimal Treatment Project advocated by Falloon has been demonstrated through the scientific research literature to be efficient and effective treatment strategies for people experiencing severe mental illness. For this reason, there is little critique of this approach. While the potential value of the project is acknowledged, it is important to identify the appropriateness of the model for specific services and to understand comprehensively the resources necessary for successful implementation. The aim of this paper is to review the literature in relation to the Optimal Treatment Project with a view to exploring the complexities associated with the model. It is concluded that the involvement of multiple stakeholders, including consumers of mental health services, should become an essential element of any implementation strategy.
Perceptions of the concept of health among nurses working in mental health services: A phenomenographic study
Authors: Jormfeldt Henrika , Svedberg Petra , Fridlund Bengt , Arvidsson Barbro
Published: January 2007

ABSTRACT:  A new understanding of the concept of health is needed to meet the goal of mental health nursing, which besides reducing disease is to strengthen the patient’s health. The aim of the present study was to describe perceptions of the concept of health among nurses working in mental health services. Twelve Swedish nurses working in mental health services were interviewed and data were analysed with a phenomenographic approach. The nurses expressed 10 perceptions, which constituted three description categories: autonomy, process, and participation. The result showed that health was more than absence of disease. Simultaneously, perceptions were expressed indicating that health was viewed as absence of disease, which implies that the concept is not sufficiently defined. The result emphasizes the need to clarify the concept of health if it is to be used as a goal in mental health nursing and to integrate a clarified definition of health at all hierarchical levels in mental health care services.
Family caregivers’ satisfaction with home care for mental illness in Taiwan
Authors: Tung Wei‐Chen , Beck Susan L.
Published: January 2007

ABSTRACT:  In Taiwan, family caregivers play a crucial role in the treatment of patients with mental illness. Attention to family caregivers’ satisfaction with home care for mental illness could have a significant impact on the well‐being of family caregivers, as well as on the health of the patients with mental illness for whom they care. A descriptive, cross‐sectional design has been used to assess the level of family caregivers’ satisfaction with home care for mental illness since the implementation of the National Health Insurance (NHI) in Taiwan, and to identify the family caregivers’ unmet needs for home care in cases of mental illness. Data were collected using the self‐administrated questionnaire completed by a convenience sample of 75 primary family caregivers of the patients with mental illness from a psychiatric hospital in Taipei, Taiwan. The result showed that most family caregivers were highly satisfied with home care provided to them and their relative with mental illness. Timeliness of home care provided in an emergency was the most prevalent unmet need. The implementation of the NHI has improved family caregivers’ perceptions of costs of home care services. There is a need to improve NHI policy and home care programmes to provide more holistic services for the patients with mental illness and their family.
Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration
Authors: Wang Jian‐Zhi , Grundke‐Iqbal Inge , Iqbal Khalid
Published: January 2007

Microtubule associated protein (MAP) tau is abnormally hyperphosphorylated in Alzheimer's disease (AD) and related tauopathies; in this form it is the major protein subunit of paired helical filaments (PHF)/neurofibrillary tangles. However, the nature of protein kinases and phosphatases and tau sites involved in this lesion has been elusive. We investigated self‐assembly and microtubule assembly promoting activities of hyperphosphorylated tau isolated from Alzheimer disease brain cytosol, the AD abnormally hyperphosphorylated tau (AD P‐tau) before and after dephosphorylation by phosphoseryl/phosphothreonyl protein phosphatase‐2A (PP‐2A), and then rephosphorylation by cyclic AMP‐dependent protein kinase (PKA), calcium, calmodulin‐dependent protein kinase II (CaMKII), glycogen synthase kinase‐3β (GSK‐3β) and cyclin‐dependent protein kinase 5 (cdk5) in different kinase combinations. We found that (i) dephosphorylation of AD P‐tau by PP‐2A inhibits its polymerization into PHF/straight filaments (SF) and restores its binding and ability to promote assembly of tubulin into microtubules; (ii) rephosphorylation of PP‐2A‐dephosphorylated AD P‐tau by sequential phosphorylation by PKA, CaMKII and GSK‐3β or cdk5, and as well as by cdk5 and GSK‐3β, promotes its self‐assembly into tangles of PHF similar to those seen in Alzheimer brain, and (iii) phosphorylation of tau sites required for this pathology are Thr231 and Ser262, along with several sites flanking the microtubule binding repeat region. Phosphorylation of recombinant human brain tau441 yielded similar results as the PP‐2A dephosphorylated AD P‐tau, except that mostly SF were formed. The conditions for the abnormal hyperphosphorylation of tau that promoted its self‐assembly also induced the microtubule assembly inhibitory activity. These findings suggest that activation of PP‐2A or inhibition of either both GSK‐3β and cdk5 or one of these two kinases plus PKA or CaMKII might be required to inhibit Alzheimer neurofibrillary degeneration.
Restored plasticity in a mouse model of neurofibromatosis type 1 via inhibition of hyperactive ERK and CREB
Authors: Guilding Clare , McNair Kara , Stone Trevor W. , Morris Brian J.
Published: January 2007

Patients with neurofibromatosis type 1 (NF1), resulting from neurofibromin gene mutations, frequently suffer from deficits in learning and spatial memory. Mice heterozygous for functional deletion of the NF1 gene (NF1+/– mice) also exhibit compromised spatial learning, and deficits in early‐stage hippocampal long‐term potentiation (LTP). Neurofibromin is a multifunctional protein which acts in part as an inhibitory constraint on Ras signalling, and the deficits in early‐stage LTP and spatial learning have been linked to Ras hyperactivation. However, the downstream targets of Ras hyperactivation that lead to cognitive disruption are unknown. The levels of activity of signalling molecules potentially downstream of Ras were therefore studied in NF1+/– mice. Elevated phospho‐ERK (pERK) levels were observed in the hippocampi from NF1+/– mice, while phospho‐Akt/PKB (pAkt) and phospho‐eIF4E (peIF4E) levels were unchanged relative to wild‐type mice. Hippocampal levels of phospho‐CREB (pCREB) were also increased, suggesting potential changes in late‐phase LTP in NF1+/– mice. Indeed, LTP was found to be impaired for at least 4 h following induction in NF1+/– mice, linking neurofibromin function with the long‐term maintenance of LTP. Remarkably, U0126, an inhibitor of ERK activation, at doses which reduced the hyperactive pERK levels in NF1+/– mice to the levels observed in control mice, caused a reduction in the deficits in early‐phase LTP and completely rescued the long‐term LTP deficits. In contrast to the abundant evidence that reductions in ERK activity lead to impaired plasticity, these data indicate that ERK hyperactivation in a partial model of type 1 neurofibromatosis leads to deficits in long‐lasting hippocampal plasticity.
Glycogen synthase kinase‐3 inhibition is integral to long‐term potentiation
Authors: Hooper Claudie , Markevich Vladimir , Plattner Florian , Killick Richard , Schofield Emma , Engel Tobias , Hernandez Felix , Anderton Brian , Rosenblum Kobi , Bliss Tim , Cooke Sam F. , Avila Jesús , Lucas José J. , Giese Karl Peter , Stephenson John , Lovestone Simon
Published: January 2007

Glycogen synthase kinase‐3 (GSK‐3) is a serine/threonine kinase regulating diverse cellular functions including metabolism, transcription and cell survival. Numerous intracellular signalling pathways converge on GSK‐3 and regulate its activity via inhibitory serine‐phosphorylation. Recently, GSK‐3 has been involved in learning and memory and in neurodegeneration. Here, we present evidence that implicates GSK‐3 in synaptic plasticity. We show that phosphorylation at the inhibitory Ser9 site on GSK‐3β is increased upon induction of long‐term potentiation (LTP) in both hippocampal subregions CA1 and the dentate gyrus (DG) in vivo. The increase in inhibitory GSK‐3β phosphorylation is robust and persists for at least one hour postinduction. Furthermore, we find that LTP is impaired in transgenic mice conditionally overexpressing GSK‐3β. The LTP deficits can be attenuated/rescued by chronic treatment with lithium, a GSK‐3 inhibitor. These results suggest that the inhibition of GSK‐3 facilitates the induction of LTP and this might explain some of the negative effects of GSK‐3 on learning and memory. It follows that this role of GSK‐3β in LTP might underlie some of the cognitive dysfunction in diseases where GSK‐3 dysfunction has been implicated, including Alzheimer's and other dementias.
Earliest spontaneous activity differentially regulates neocortical GABAergic interneuron subpopulations
Authors: De Lima Ana D. , Lima Beatriz D. , Voigt Thomas
Published: January 2007

Although less than one quarter of all neurons in the cerebral cortex are GABAergic, these neurons are morphologically diverse and their physiological complexity decisively moulds the network physiology. An important question is how different subpopulations of GABAergic neurons are regulated numerically during development. In rat neocortical cultures, neuronal precursors continue to divide, generating both GABAergic and non‐GABAergic neurons. In vitro generated GABAergic neurons form a population of uniquely small, mostly fusiform neurons that differ in size and morphology from older, in situ generated, large stellate GABAergic neurons. In a large series of experiments we investigated the impact of neuronal activity on the development of these two subpopulations of GABA interneurons present in cortical networks during the first 2 weeks in vitro. Here we show that a moderate increase in the generation of GABAergic neurons was achieved by blocking activity with tetrodotoxin, indicating that intrinsic spontaneous activity inhibits GABAergic neurogenesis in culture. Antagonists to ionotropic glutamate receptor and/or GABAA receptor did not significantly alter GABAergic generation but agonists to these receptors showed a time‐sensitive regulation of the size of small and large GABAergic neuronal subpopulations. Further, our results indicate that alterations of cell generation by activity manipulations might be overwritten by later activity effects on the survival of GABAergic cell populations.
Task‐dependent modulation of functional connectivity between hand motor cortices and neuronal networks underlying language and music: a transcranial magnetic stimulation study in humans
Authors: Sparing R. , Meister I. G. , Wienemann M. , Buelte D. , Staedtgen M. , Boroojerdi B.
Published: January 2007

Although language functions are, in general, attributed to the left hemisphere, it is still a matter of debate to what extent the cognitive functions underlying the processing of music are lateralized in the human brain. To investigate hemispheric specialization we evaluated the effect of different overt musical and linguistic tasks on the excitability of both left and right hand motor cortices using transcranial magnetic stimulation (TMS). Task‐dependent changes of the size of the TMS‐elicited motor evoked potentials were recorded in 12 right‐handed, musically naive subjects during and after overt speech, singing and humming, i.e. the production of melody without word articulation. The articulation of meaningless syllables served as control condition. We found reciprocal lateralized effects of overt speech and musical tasks on motor cortex excitability. During overt speech, the corticospinal projection of the left (i.e. dominant) hemisphere to the right hand was facilitated. In contrast, excitability of the right motor cortex increased during both overt singing and humming, whereas no effect was observed on the left hemisphere. Although the traditional concept of hemispheric lateralization of music has been challenged by recent neuroimaging studies, our findings demonstrate that right‐hemisphere preponderance of music is nevertheless present. We discuss our results in terms of the recent concepts on evolution of language and gesture, which hypothesize that cerebral networks mediating hand movement and those subserving language processing are functionally linked. TMS may constitute a useful tool to further investigate the relationship between cortical representations of motor functions, music and language using comparative approaches.
A population of human brain parenchymal cells express markers of glial, neuronal and early neural cells and differentiate into cells of neuronal and glial lineages
Authors: Rieske Piotr , Azizi S. Ausim , Augelli Brian , Gaughan John , Krynska Barbara
Published: January 2007

Glial fibrillary acidic protein (GFAP)‐positive cells derived from the neurogenic areas of the brain can be stem/progenitor cells and give rise to new neurons in vitro and in vivo. We report here that a population of GFAP‐positive cells derived from fetal human brain parenchyma coexpress markers of early neural and neuronal cells, and have neural progenitor cell characteristics. We used a monolayer culture system to expend and differentiate these cells. During the initial proliferative phase, all cells expressed GFAP, nestin and low levels of βIII‐tubulin. When these cells were cultured in serum and then basic fibroblast growth factor, they generated two distinct progenies: (i) βIII‐tubulin‐ and nestin‐positive cells and (ii) GFAP‐ and nestin‐positive cells. These cells, when subsequently cultured in serum‐free media without growth factors, ceased to proliferate and differentiated into two major neural cell classes, neurons and glia. In the cells of neuronal lineage, nestin expression was down‐regulated and βIII‐tubulin expression became robust. Cells of glial lineage differentiated by down‐regulating nestin expression and up‐regulating GFAP expression. These data suggest that populations of parenchymal brain cells, initially expressing both glial and neuronal markers, are capable of differentiating into single neuronal and glial lineages through asymmetric regulation of gene expression in these cells, rather than acquiring markers through differentiation.
Inhibition of Na+/K+ ATPase potentiates synaptic transmission in tactile sensory neurons of the leech
Authors: Scuri Rossana , Lombardo Paola , Cataldo Enrico , Ristori Chiara , Brunelli Marcello
Published: January 2007

Increasing evidence indicates that modulation of Na+/K+ ATPase activity is involved in forms of neuronal and synaptic plasticity. In tactile (T) neurons of the leech Hirudo medicinalis, Na+/K+ ATPase is the main determinant of the afterhyperpolarization (AHP), which characterizes the firing of these mechanosensory neurons. Previously, it has been reported that cAMP (3′,5′‐cyclic adenosine monophosphate), which mediates the effects of serotonin (5HT) in some forms of learning in the leech, negatively modulates Na+/K+ ATPase activity, thereby reducing the AHP amplitude in T neurons. Here, we show that a transient inhibition of Na+/K+ ATPase can affect the synaptic connection between two ipsilateral T neurons. Bath application of 10 nm dihydroouabain (DHO), an ouabain analogue, causes an increase in the amplitude of the synaptic potential (SP) recorded in the postsynaptic element when a test stimulus is applied in the presynaptic neuron. Iontophoretic injection of cAMP into the presynaptic T neuron also produces an increase of SP. Simulations carried out by using a computational model of the T neuron suggest that a reduction of the pump rate and a consequent depression of the AHP might facilitate the conduction of action potentials to the synaptic terminals. Moreover, nearly intact leeches injected with 10 nm DHO respond with a swimming episode more quickly to an electrical stimulation, which selectively activates T neurons exhibiting sensitization of swimming induction. Collectively, our results show that inhibition of Na+/K+ ATPase is critical for short‐term plasticity.
Capsaicin‐sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes
Authors: Gram Dorte X. , Ahrén Bo , Nagy Istvan , Olsen Uffe B. , Brand Christian L. , Sundler Frank , Tabanera René , Svendsen Ove , Carr Richard D. , Santha Peter , Wierup Nils , Hansen Anker J.
Published: January 2007

The system that regulates insulin secretion from β‐cells in the islet of Langerhans has a capsaicin‐sensitive inhibitory component. As calcitonin gene‐related peptide (CGRP)‐expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP‐containing primary sensory neurons is sensitive to capsaicin, the islet‐innervating sensory fibers may represent the capsaicin‐sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid type 1 transient receptor potential receptor (TRPV1) in CGRP‐expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin‐sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human type 2 diabetes mellitus. We found that CGRP‐expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non‐fasting, and mean 24‐h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP‐ and TRPV1‐coexpressing islet‐innervating fibers. These data indicate that CGRP‐containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet‐innervating capsaicin‐sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus.
Glutamatergic neurons are present in the rat ventral tegmental area
Authors: Yamaguchi Tsuyoshi , Sheen Whitney , Morales Marisela
Published: January 2007

The ventral tegmental area (VTA) is thought to play an important role in reward function. Two populations of neurons, containing either dopamine (DA) or γ‐amino butyric acid (GABA), have been extensively characterized in this area. However, recent electrophysiological studies are consistent with the notion that neurons that utilize neurotransmitters other than DA or GABA are likely to be present in the VTA. Given the pronounced phenotypic diversity of neurons in this region, we have proposed that additional cell types, such as those that express the neurotransmitter glutamate may also be present in this area. Thus, by using in situ hybridization histochemistry we investigated whether transcripts encoded by genes for the two vesicular glutamate transporters, VGluT1 or VGluT2, were expressed in the VTA. We found that VGluT2 mRNA but not VGluT1 mRNA is expressed in the VTA. Neurons expressing VGluT2 mRNA were differentially distributed throughout the rostro‐caudal and medio‐lateral aspects of the VTA, with the highest concentration detected in rostro‐medial areas. Phenotypic characterization with double in situ hybridization of these neurons indicated that they rarely co–expressed mRNAs for tyrosine hydroxylase (TH, marker for DAergic neurons) or glutamic acid decarboxylase (GAD, marker for GABAergic neurons). Based on the results described here, we concluded that the VTA contains glutamatergic neurons that in their vast majority are clearly non‐DAergic and non‐GABAergic.
New neurons in the vestibular nuclei complex after unilateral vestibular neurectomy in the adult cat
Authors: Tighilet Brahim , Brezun Jean Michel , Dit Duflo Sylvie Gustave , Gaubert Céline , Lacour Michel
Published: January 2007

Recent findings revealed a reactive neurogenesis after lesions and in several models of disease. After unilateral vestibular neurectomy (UVN), we previously reported γ‐aminobutyric acid (GABA)ergic neurons are upregulated in the vestibular nuclei (VN) in the adult cat. Here, we ask whether this upregulation of GABAergic neurons resulted from a reactive neurogenesis. To determine the time course of cell proliferation in response to UVN, 5‐bromo‐2′‐deoxyuridine (BrdU) was injected 3 h, 1, 3, 7, 15 and 30 days after UVN. We investigated the survival and differentiation in UVN cats injected with BrdU at 3 days and perfused 30 days after UVN. Results show a high number of BrdU‐immunoreactive nuclei in the deafferented VN with a peak at 3 days after UVN and a decrease at 30 days. Most of the newly generated cells survived up to 1 month after UVN and gave rise to a variety of cell types. Confocal analysis revealed three cell lineages: microglial cells (OX 42/BrdU‐immunoreactive cells); astrocytes [glial fibrillary acidic protein (GFAP)/BrdU‐immunoreactive cells]; and neurons (NeuN/BrdU‐immunoreactive cells). That UVN induced new neurons was confirmed by an additional marker (nestin) expressed by neural precursor cells. We show that most of the newly generated neurons have a GABAergic phenotype [glutamate decarboxylase (GAD)‐67/BrdU‐immunoreactive cells]. Morphological analysis showed two subtypes of GABAergic neurons: medium and small (30 vs. 10 µm, respectively). This is the first report of reactive neurogenesis in the deafferented VN in the adult mammalian CNS.
A honey bee Dscam family member, AbsCAM, is a brain‐specific cell adhesion molecule with the neurite outgrowth activity which influences neuronal wiring during development
Authors: Funada Masahiro , Hara Hiroaki , Sasagawa Hiromi , Kitagawa Yasuo , Kadowaki Tatsuhiko
Published: January 2007

The immunoglobulin superfamily (IgSF) has been indicated as functioning in the development and maintenance of nervous systems through cell–cell recognition and communication in several model invertebrates, Drosophila melanogaster and Caenorhabditis elegans. To further explore the functions of the IgSF in the brain of an invertebrate with more complex behavior, we identified and characterized a novel brain‐specific Dscam family member, AbsCAM, from honey bee (Apis mellifera). The level of the AbsCAM protein was high in newly hatched bees and was dramatically reduced with age. The AbsCAM protein level was constant among worker bees of the same age performing different tasks, suggesting that it was primarily determined by age and not task in adult brains. Two different AbsCAM transcripts (AbsCAM‐Ig7A and B) were generated by the alternative splicing of exon 11 encoding immunoglobulin domain 7 in an age‐dependent manner. AbsCAM was expressed in the major brain neuropils where the synaptic density was high. AbsCAM can mediate the isoform‐specific homophilic cell adhesion in vitro, and affected the axonal projections in Drosophila embryonic central nervous system and adult mushroom body by ectopic expression. Furthermore, AbsCAM promoted the neurite outgrowth of cultured neurons isolated from honey bee pupal brains. These results thus suggest that AbsCAM is the first honey bee IgSF implicated as functioning in neuronal wiring during honey bee brain development.
The role of Kif5B in axonal localization of Kv1 K+ channels
Authors: Rivera Jacqueline , Chu Po‐Ju , Lewis Tommy L. , Arnold Don B.
Published: January 2007

Here we present evidence that the kinesin, Kif5B, is involved in the transportation and axonal targeting of Kv1 channels. We show that a dominant negative variant of Kif5B specifically blocks localization to the axon of expressed, tagged versions of Kv1.3 in cultured cortical slices. In addition, the dominant negative variant of Kif5B blocks axonal localization of endogenous Kv1.1, Kv1.2, and Kv1.4 in cortical neurons in dissociated cultures. We also found evidence that Kif5B interacts with Kv1 channels. Endogenous Kv1.2 colocalized with Kif5B in cortical neurons and coimmunoprecipitated with Kif5B from brain lysate. The T1 domain of Shaker K+ channels has been shown to play a critical role in targeting the channel to the axon. We have three pieces of evidence to suggest that the T1 domain also mediates interaction between Kv1 channels and Kif5B: Addition of the T1 domain to a heterologous protein, TfR, is sufficient to cause the resulting fusion protein, TfRT1, to colocalize with Kif5B. Also, the T1 domain is necessary for interaction of Kv1.3 with Kif5B in a coimmunoprecipitation assay. Finally, dominant negative variants of Kif5B block axonal targeting of TfRT1, but have no effect on dendritic localization of TfR. Together these data suggest a model where Kif5B interacts with Kv1 channels either directly or indirectly via the T1 domain, causing the channels to be transported to axons.
Interactions between the environmental pathogen Listeria monocytogenes and a free‐living protozoan (Acanthamoeba castellanii)
Authors: Zhou Xiaohui , Elmose Jennifer , Call Douglas R.
Published: January 2007

Listeria monocytogenes can cause severe disease in animal hosts, but it has no recognized animal host reservoir. We tested the hypothesis that L. monocytogenes retains virulence traits to survive predation by amoebae and that listeriolysin O plays a crucial role in this process. Co‐culturing of L. monocytogenes and Acanthamoeba castellanii demonstrated that L. monocytogenes does not actively kill amoebae, but in the presence of amoebae, high bacterial population densities can be maintained over a period of at least 96 h. A gentamicin protection assay demonstrated that there is no significant difference in the ability to survive predation between serovars (4b versus 1/2a and 1/2c; P = 0.08) and between five species of Listeria (P = 0.14). Three of these species do not harbour the hly gene responsible for listeriolysin O production. A hly knockout strain had poorer survival compared with the parental strain (P = 0.04 at 24 h; P = 0.04 at 48 h; P = 0.02 at 72 h) and electron microscopy was consistent with a wild‐type strain being able to escape the phagosome whereas the hly knockout strain did not appear to have this ability. Thus, while there is weak evidence that listeriolysin O can contribute to improved survival after ingestion by amoebae, listeriolysin O does not appear to provide a significant selective advantage under the conditions of this study.
Diversity and biogeography of bacterial assemblages in surface sediments across the San Pedro Basin, Southern California Borderlands
Authors: Hewson Ian , Jacobson/Meyers Myrna E. , Fuhrman Jed A.
Published: January 2007

Sediment bacteria play important roles in the biogeochemistry of ocean sediments; however, factors influencing assemblage composition have not been extensively studied. We examined extractable sediment bacterial abundance, the composition of bacterial assemblages using a high‐throughput molecular fingerprinting approach, and several sediment biogeochemical parameters (organic matter content and alkaline phosphatase activity), along a 35 km transect from Point Fermin, Southern California, to Santa Catalina Island, across the approximately 900‐m‐deep San Pedro Basin. Automated rRNA intergenic spacer analysis (ARISA) demonstrated that in two spatially isolated shallow (approximately < 60 m, on opposite sides of the channel) sediment environments, assemblages were more similar to each other than to deeper communities. Distinct communities existed in deeper and shallower sediments, and stations within the deep basin over 2 km apart contained remarkably similar assemblage fingerprints. The relative contribution to total amplified DNA fluorescence of operational taxonomic units (OTUs) was significantly correlated to that of other OTUs in few comparisons (2.7% of total), i.e. few bacterial types were found together or apart consistently. The relative proportions within assemblages of only a few OTU were significantly correlated to measured physicochemical parameters (organic matter content and wet/dry weight ratio of sediments) or enzyme (alkaline phosphatase) activities. A low percentage of shared OTU between shallow and deep sediments, and the presence of similar, but spatially isolated assemblages suggests that bacterial OTU may be widely dispersed over scales of a few kilometres, but that environmental conditions select for particular assemblages.
Primary and metastatic perineal adenocarcinoma: aetiology and management
Authors: Leon R. , Ramesh A. , Wilson M. S. , O’Dwyer S. T.
Published: January 2007

Objective:  Adenocarcinoma of the perineum is unusual. This series of nine patients highlights the challenges of management.

Results:  Six male and three female patients aged 29–85 years presented to a single unit, five were T4 and three were T3 tumours. Pain and swelling in the perineum and perianal tissues remote from the anal canal occurred in six patients whilst three patients had chronic perineal fistulae, two of whom had longstanding Crohn's disease. In eight patients a primary adenocarcinoma was identified. One patient with fistulating perineal Crohn's disease had multifocal mucinous adenocarcinoma without evidence of a gastrointestinal primary. Radical multimodality treatment including long course chemo‐radiotherapy (CRT) and radical abdominoperineal resection was used in seven patients, four of whom required perineal reconstruction with myocutaneous flaps. Two patients had CRT without surgery, (one unresectable and one refused surgery). Negative resection margins were achieved in six out of seven patients. All seven patients undergoing resection were well palliated with relief of pain and currently four patients remain free of disease with only one patient developing further perineal disease remote from the surgical resection site.

Conclusion:  Perineal adenocarcinoma may be associated with an occult colorectal primary or chronic fistulae. Lower GI endoscopy and biopsies of nonhealing mucous producing fistulae should be undertaken to establish the diagnosis. Radical surgery often achieves local disease control.