bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymptomatic bacteriuria in men with orthotopic ileal neobladders: possible relationship to nocturnal enuresis
Authors: Abdel‐Latif Mohamed , Mosbah Ahmed , Bahnasawy Magdy S. El , Elsawy Essam , Shaaban Atallah A.
Published: July 2005

The role of asymptomatic bacteriuria in patients with urinary diversion in general has been reported as having a significant role prognostically in several published studies. Authors from Mansoura, with considerable experience in the constructing the orthotopic ileal neobladder, have evaluated the incidence of asymptomatic bacteriuria in such patients prospectively, and have assessed its possible effect on neobladder function.

OBJECTIVE

To assess prospectively the incidence with time of asymptomatic bacteriuria in patients with orthotopic ileal neobladders, and the possible effect on neobladder function.

PATIENTS AND METHODS

In all, 47 patients (mean age 52.7 years, sd 8.7, range 31–68) with uncomplicated orthotopic ileal neobladders were prospectively evaluated. With no antibiotic manipulation, consecutive urine cultures were assessed monthly. Continence was assessed by direct information from the patients at each follow‐up visit.

RESULTS

Overall, 797 samples were cultured from the 47 patients (mean 17.6, sd 7.1). There was a steady decrease in the incidence of positive cultures, from 74.5%, to 35.6% and 6.7% at 1, 6 and 18 months, respectively. While there was persistently sterile urine in only eight patients (17%), 32 had occasional and seven had persistent bacteriuria. Escherichia coli was the commonest organism (76.6%) followed by Klebsiella pneumonia (15.7%); 54% of E. coli and 38% of K. pneumonia infections were sensitive to nitrofurantoin. Diurnal continence was achieved in 98% of the patients at 6 months after surgery. There was a gradual decrease in the frequency of nocturnal enuresis (NE) with time, from 87%, to 42%, 28% and 27% at 1, 6, 12 and 18 months, respectively. There was a significant correlation between the presence of bacteriuria and NE during the first 6 months, but it was not sustained after that. The age of the patients was also related significantly to the incidence of NE; at 6 months, only one of 18 men aged ≤ 50 years had NE, while 19 of 29 aged > 50 years had (P < 0.001). At 1 year all patients aged ≤ 50 years were nocturnally continent, while half of those aged > 50 years had NE (P = 0.001).

CONCLUSIONS

Ileal neobladders are associated with a high incidence of asymptomatic bacteriuria during the first year after surgery. There was spontaneous clearance of bacteriuria with time, with no antimicrobial manipulation. Soon after surgery there was a significant association between bacteriuria and NE. The effect of antimicrobials on patients with NE should be evaluated.
Vesicostomy revisited: the best treatment for the hostile bladder in myelodysplastic children?
Authors: Morrisroe Shelby N. , O'Connor R. Corey , Nanigian Dana K. , Kurzrock Eric A. , Stone Anthony R.
Published: July 2005

Vesicostomy is a well‐known management of the neuropathic bladder in children, and authors from Sacramento describe their experience with this in what they very appropriately name the “hostile bladder” of myelodysplastic children.

Other papers in this section suggest that inguinal hernia in female infants should act as a cue to check the sex chromosomes, evaluate nocturnal enuresis in children at 7.5 years old, and describe the efficacy of tolterodine as a first‐line treatment for non‐neurogenic voiding dysfunction in children.

OBJECTIVE

To evaluate the effects of vesicostomy on the urinary tract of myelodysplastic children in whom conservative bladder management with clean intermittent catheterization (CIC) has failed to preserve upper and lower urinary tract function.

PATIENTS AND METHODS

Sixteen children with myelodysplasia underwent vesicostomy. Indications included worsening hydronephrosis, vesico‐ureteric reflux (VUR), recurrent urinary tract infections (UTIs), and increasing renal insufficiency despite CIC and/or difficulty with CIC. The mean (range) age at vesicostomy was 36.5  (9–82) months and the follow‐up 7.4  (2–16) years.

RESULTS

Hydronephrosis resolved or improved in 12 of 14 children, the incidence of UTI decreased to one or fewer per year in 10, VUR resolved or improved in nine, and renal function improved or stabilized in six of seven patients. One patient initially presented with renal insufficiency and subsequently required dialysis despite vesicostomy. Complications occurred in three of 15 children, and included stomal stenosis and bladder calculi. The vesicostomy was closed in six patients after a mean of 4.4 (1.5–9) years. Four of these patients required concomitant bladder augmentation.

CONCLUSIONS

Vesicostomy in myelodysplastic children is effective in preventing and/or resolving the deleterious consequences of a ‘hostile’ bladder. The procedure is uncomplicated, well tolerated, reversible and should be considered in managing children in whom conservative management by CIC has failed.
Inguinal hernia in female infants: a cue to check the sex chromosomes?
Authors: Deeb Asma , Hughes Ieuan A.
Published: July 2005

OBJECTIVES

To review the clinical presentation of complete androgen insensitivity syndrome (CAIS) and assess the current practice of considering the diagnosis of CAIS in female infants presenting with inguinal hernia.

PATIENTS AND METHODS

AIS arises from target tissue resistance to the actions of androgens due to molecular abnormalities in the androgen receptor. Patients with CAIS are born with normal external female genitalia, and although inguinal hernias are uncommon in female infants, they are a well‐known presentation of CAIS. Such patients were identified from the Cambridge Intersex Database and details of presentation, presence and laterality of inguinal hernia and contents, and family history of CAIS, were recorded. A questionnaire detailing different indications for considering CAIS in female infants with a hernia was distributed to members of the British Association of Paediatric Surgeons and the British Society for Paediatric Endocrinology and Diabetes.

RESULTS

More than half of patients with CAIS presented with inguinal hernia, of which half were bilateral and a third contained gonads. Completed questionnaires were returned by 87 surgeons and 64 endocrinologists, and most of the surgeons and endocrinologists would consider CAIS in all female infants with a hernia. Bilateral hernias, hernias containing gonads and a family history of CAIS would prompt clinicians to consider the diagnosis.

CONCLUSION

Most clinicians agreed that CAIS should be considered in all female infants with inguinal hernia, as this is the commonest mode of presentation in childhood. Macroscopic inspection of the internal genital structures coupled, perhaps, with gonadal biopsy is recommended. Fluorescence in situ hybridization offers a rapid and reliable method to check the sex chromosomes. Liaison between the paediatric surgeon and endocrinologist is essential in management of infants with CAIS.
Nocturnal enuresis at 7.5 years old: prevalence and analysis of clinical signs
Authors: Butler Richard J. , Golding Jean , Northstone Kate ,   The ALSPAC Study Team
Published: July 2005

OBJECTIVE

To determine the prevalence of nocturnal enuresis (NE) in a large cohort of children at 7.5 years old, and to examine the frequency of variables such as gender, severity, associated elimination problems, and clinical signs within the identified group.

SUBJECTS AND METHODS

Of an original cohort of 13 971 infants alive at 12 months, 11 251 who were still active in the Avon Longitudinal Study of Parents and Children (ALSPAC) survey, were followed at 91 months. The mother or main carer was given a questionnaire which asked, amongst other items, about the presence and frequency of bedwetting, other elimination problems, and signs related to the wetting behaviour; 8269 (73.5%) questionnaires were returned and 8151 contained information on the frequency of bedwetting.

RESULTS

In all, 1260 children (15.5%) at 7.5 years wet the bed, but most wet once or less a week, and only 215 (2.6%) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria of NE (wetting at least twice a week). A higher prevalence was reported in boys than girls and 266 children (3.3%) had both daytime wetting and bedwetting, with 189 (2.3%) having both daytime soiling and bedwetting. Daytime urgency increased with severity of bedwetting and occurred in 28.9% of children with NE.

CONCLUSION

At 7.5 years old the incidence of bedwetting is high, but only 2.6% of this large population‐based sample wet at a frequency meeting the definition of NE. Although a small percentage of children had both daytime wetting and bedwetting, the evidence suggests that these are discrete problems. Amongst children with NE, indicators of bladder overactivity were present, supporting the view of heterogeneity and the importance of individual assessment in deciding on appropriate treatment.
Efficacy of tolterodine as a first‐line treatment for non‐neurogenic voiding dysfunction in children
Authors: Ayan Semih , Kaya Kemal , Topsakal Kahraman , Kilicarslan Hakan , Gokce Gokhan , Gultekin Yener
Published: July 2005

OBJECTIVE

To assess the effect of antimuscarinic treatment with tolterodine combined with behavioural modification as a first‐line treatment, before invasive investigation, in children with non‐neurogenic voiding dysfunction but no obvious anatomical or neurogenic cause.

PATIENTS AND METHODS

The study comprised 44 children presenting with voiding dysfunction (30 girls and 14 boys, mean age 7 years, range 5–14); all had a noninvasive evaluation consisting of a history, urine analysis, renal and bladder ultrasonography and physical examination, with specific emphasis on the voiding pattern. Anticholinergic treatment with tolterodine (1 mg twice daily) was started in all patients; they were also informed about conservative management, including timed voiding, double voiding and relaxation of the pelvic floor during voiding. At the start and after 3 months, the dysfunctional voiding symptom score (DVSS) was completed twice by all patients.

RESULTS

For all patients the mean (sd) DVSS was 14.0 (2.67) and 6.68 (3.67) before and after treatment, respectively; the difference was statistically significant (P < 0.001). The mean scores for girls and boys, respectively, were 13.8 (2.79) and 14.5 (2.44) before and 6.43 (3.79) and 7.50 (3.34) after treatment.

CONCLUSION

Tolterodine combined with behavioural modification for dysfunctional voiding in children with no neurological or anatomical abnormality can be recommended as a first‐line treatment before invasive evaluation. Additionally, the DVSS appears to provide accurate and objective data for monitoring the effect of treatment in such children.
The src‐family kinase inhibitor PP2 suppresses the in vitro invasive phenotype of bladder carcinoma cells via modulation of Akt
Authors: Chiang George J. , Billmeyer Brian R. , Canes David , Stoffel John , Moinzadeh Alireza , Austin Christina A. , Kosakowski Monika , Rieger‐Christ Kimberly M. , Libertino John A. , Summerhayes Ian C.
Published: July 2005

OBJECTIVE

To evaluate PP2 as a modulator of the cadherin/catenin complex in late‐stage bladder carcinoma cells, and to assess its potential invasion‐suppressor activity in this model.

MATERIALS AND METHODS

A panel of five human bladder carcinoma cells, characterizing late‐stage disease, was used to determine the concentration for 50% inhibition of PP2 in cell‐proliferation assays. Modulation of cadherin/catenin expression by PP2 was determined in Western blot analysis, with an assessment of the activation status of mitogen‐activated protein kinase and Akt signalling pathways. Altered invasive capacity linked to these variables was determined in standard in vitro invasion assays.

RESULTS

PP2 elicited concentration‐dependent growth inhibition in all bladder cell lines within the panel, with growth suppression recorded at 10–35 µmol/L PP2. Distinct morphological changes were recorded in cell lines exposed to PP2, accompanied by up‐regulation of plakoglobin expression in a subset of lines. Exposure of cells to PP2 resulted in inactivation of Akt in all cells and a concomitant reduction in in vitro invasive capacity.

CONCLUSIONS

These results show that PP2 inhibits bladder carcinoma cell growth and can modulate plakoglobin expression in a subset of cell lines. In addition, PP2 can suppress the in vitro invasive capacity of bladder carcinoma cells by modulating the activation status of Akt.
Sildenafil inhibits the formation of superoxide and the expression of gp47phox NAD[P]H oxidase induced by the thromboxane A2 mimetic, U46619, in corpus cavernosal smooth muscle cells
Authors: Koupparis Anthony J. , Jeremy Jamie Y. , Muzaffar Saima , Persad Raj , Shukla Nilima
Published: July 2005

OBJECTIVE

To assess the effect of sildenafil on superoxide formation and p47phox (the active subunit of NADPH oxidase) expression in cultured corpus cavernosal smooth muscle cells (CVSMCs).

MATERIALS AND METHODS

CVSMCs derived from rabbit penis were incubated with U46619 (thromboxane A2 analogue) with or without sildenafil for 1 or 16 h at 37°C. Superoxide dismutase‐inhibitable superoxide formation was assessed using the reduction of ferricytochrome c measured spectrophotometrically, and gp47phox assessed using Western blot analysis. The role of NAD[P]H oxidase and cGMP was further studied by using specific inhibitors of each.

RESULTS

Superoxide formation was significantly greater in cells incubated with U46619 after 1 and 16 h incubation than in controls, an effect blocked by NADP(H) oxidase inhibitors. These effects of U46619 were inhibited by sildenafil (1 and 10 nmol/L), which in turn were negated by the guanylyl cyclase inhibitor, ODQ; 10 nmol/L sildenafil inhibited p47phox expression induced by U46619.

CONCLUSIONS

Sildenafil is a potent inhibitor of superoxide formation in CVSMCs. This effect is mediated through the inhibition of PDE‐5 which in turn augments the inhibitory action of the NO‐cGMP axis on NAD[P]H oxidase expression and activity. This mechanism constitutes a new pharmacological action of sildenafil, consolidates the potential role of superoxide in ED, and indicates that thromboxane A2 may be an important mediator of intrapenile oxidative stress.
Loss of ryanodine receptor calcium‐release channel expression associated with overactive urinary bladder smooth muscle contractions in a detrusor instability model
Authors: Jiang Hai‐Hong , Song Bo , Lu Gen‐Sheng , Wen Qian‐Jun , Jin Xi‐Yu
Published: July 2005

OBJECTIVE

To investigate the changes in spontaneous bladder smooth muscle contractions that occur during detrusor instability (DI), and to test the possibility that altered function or expression of ryanodine receptors (RyRs) could account for the increased bladder contractions.

MATERIALS AND METHODS

After 8 weeks of partial bladder outlet obstruction, DI was confirmed in female experimental rats by filling cystometry. Muscle strips were dissected from freshly isolated bladders, and isometric tension recorded in strips from DI and normal bladders. The contractions were recorded during electrical stimulation or exposure to various agents. Western blot analysis was used to determine RyR expression in DI and normal bladder muscle.

RESULTS

In DI bladder muscle, spontaneous contractile activity persisted in the presence of blockers for known neurotransmitter receptors in the bladder wall. The RyR blocker ryanodine significantly increased the spontaneous contractile frequency in normal bladder strips, but failed to affect spontaneous contractions in DI muscle. Caffeine inhibited spontaneous contractile activity in both the DI and normal strips. After administering the l‐type Ca2+ channel antagonist nimodipine, the myogenic contractile activity was abolished in normal strips; in contrast, in DI strips, the amplitude of contractions was reduced but the frequency of contractions was unchanged. Western blot analysis showed that RyR expression was lower in DI muscle than in normal bladder muscle.

CONCLUSION

These results provide the first characterization of a loss of regulation of spontaneous contractile activity by RyRs in DI muscle associated with a significant decrease in RyR expression. RyRs in normal detrusor muscle act as negative‐feedback regulators of spontaneous contractile activity, presumably by releasing Ca2+ that activates Ca2+‐dependent K+ channels to decrease contractility. This mechanism might be weakened in DI muscle, resulting in spontaneous contractile overactivity.
Biosynthesis and differential processing of two pools of amyloid‐β precursor protein in a physiologically inducible neuroendocrine cell
Authors: Collin Rob W. J. , Van Den Hurk Wilhelmina H. , Martens Gerard J. M.
Published: July 2005

The amyloid‐β precursor protein (APP) is linked to Alzheimer's disease through its pathological proteolytic processing in the secretory pathway. Nevertheless, surprisingly little is known about the biosynthesis of endogenous APP. We therefore decided to investigate the intracellular fate of newly synthesized APP in a physiologically inducible neuroendocrine cell, the Xenopus intermediate pituitary melanotrope cell. We found that the level of both APP mRNA and protein was about threefold induced in the activated cells of black‐adapted animals. Intriguingly, two pools of APP were found, only one of which was up‐regulated. This induced pool became readily N‐ and subsequently O‐glycosylated and was eventually proteolytically processed by an α‐secretase‐like cleavage event resulting in a secreted N‐terminal and a cell‐associated C‐terminal APP fragment. Conversely, only the other (non‐induced, non‐glycosylated and uncleaved) pool became phosphorylated. Thus, we report on the biosynthesis of APP in a physiological context and illuminate the occurrence of two pools of APP, one of which is linked to neuroendocrine cell activation.
Literature Can Close the Fear Gap
Authors: RUSHDIE SALMAN
Published: July 2005

Post‐national literature is a new genre of writing for a new era beyond boundaries. In this section, we present interviews and comments adapted from conversations with authors from India, Iran, Lebanon, Turkey, Argentina, China and Austria—all but one of whom now live outside their countries, often writing in a language not their own.

Most of the conversations and interviews were conducted by Michael Skafidas, the former editor of Greek NPQ, in New York at the time of the PEN Festival of International Literature, organized by Salman Rushdie. Ha Jin was interviewed by Jehangir Pocha. Gao Xingjian's contribution is adapted from his lecture upon winning the Nobel Prize for Literature.
Serotonin transporter gene polymorphism (5‐HTTLPR) in patients with recurrent aphthous stomatitis
Authors: Victoria Junia Maria Netto , de Fátima Correia‐Silva Jeane , Pimenta Flávio Juliano , Kalapothakis Evanguedes , Gomez Ricardo Santiago
Published: July 2005

Background: Considerable evidence indicates that serotonergic mechanisms, particularly the serotonin transporter (5‐HTT) may be involved in psychological alterations. Recent findings have demonstrated that depression and stress are influenced by polymorphism of the promoter region of 5‐HTT (5‐HTTLPR) and that the short allele (S) is associated with reduced transcriptional efficiency resulting in reduced serotonin expression and uptake. As psychological and genetic factors have been implicated in the pathogenesis of recurrent aphthous stomatitis (RAS), the purpose of the present study was to investigate 5‐HTTLPR polymorphism in patients with RAS compared with control subjects.

Methods: Sixty‐nine consecutive subjects affected by minor and major forms of RAS and 70 healthy volunteers were genotyped at 5‐HTTLPR. The chi‐square test was used for statistical analysis.

Results: A significant increase in the genotype of SS (P = 0.05) and of the alleleS(P = 0.04) in the group of RAS were observed.

Conclusion: Our findings demonstrate that RAS patients have a tendency to show polymorphism associated with anxiety‐related traits.
Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea‐pigs
Authors: Mazzone Stuart B. , Mori Nanako , Canning Brendan J.
Published: July 2005

Cough initiated from the trachea and larynx in anaesthetized guinea‐pigs is mediated by capsaicin‐insensitive, mechanically sensitive vagal afferent neurones. Tachykinin‐containing, capsaicin‐sensitive C‐fibres also innervate the airways and have been implicated in the cough reflex. Capsaicin‐sensitive nerves act centrally and synergistically to modify reflex bronchospasm initiated by airway mechanoreceptor stimulation. The hypothesis that polymodal mechanoreceptors and capsaicin‐sensitive afferent nerves similarly interact centrally to regulate coughing was addressed in this study. Cough was evoked from the tracheal mucosa either electrically (16 Hz, 10 s trains, 1–10 V) or by citric acid (0.001–2 m). Neither capsaicin nor bradykinin evoked a cough when applied to the trachea of anaesthetized guinea‐pigs, but they substantially reduced the electrical threshold for initiating the cough reflex. The TRPV1 receptor antagonist capsazepine prevented the increased cough sensitivity induced by capsaicin. These effects of topically applied capsaicin and bradykinin were not due to interactions between afferent nerve subtypes within the tracheal wall or a direct effect on the cough receptors, as they were mimicked by nebulizing 1 mg ml−1 bradykinin into the lower airways and by microinjecting 0.5 nmol capsaicin into nucleus of the solitary tract (nTS). Citric acid‐induced coughing was also potentiated by inhalation of bradykinin. The effects of tracheal capsaicin challenge on cough were mimicked by microinjecting substance P (0.5–5 nmol) into the nTS and prevented by intracerebroventricular administration (20 nmol h−1) of the neurokinin receptor antagonists CP99994 or SB223412. Tracheal application of these antagonists was without effect. C‐fibre activation may thus sensitize the cough reflex via central mechanisms.
Baroreceptor reflex sensitivity in human neonates: the effect of postmenstrual age
Authors: Andriessen Peter , Oetomo Sidarto Bambang , Peters Chris , Vermeulen Barbara , Wijn Pieter F. F. , Blanco Carlos E.
Published: July 2005

We performed a cross‐sectional study in human infants to determine if indices of R–R interval variability, systolic blood pressure (SBP) variability, and baroreceptor reflex sensitivity change with postmenstrual age (PMA: gestational age + postnatal age). The electrocardiogram, arterial SBP and respiration were recorded in clinically stable infants (PMA, 28–42 weeks) in the quiet sleep state in the first days after birth. (Cross‐)spectral analyses of R–R interval series and SBP series were performed to calculate the power of low‐frequency (LF, indicating baroreceptor reflex activity, 0.04–0.15 Hz) and high‐frequency (HF, indicating parasympathetic activity, individualized between the p‐10 and p‐90 values of respiratory frequency) fluctuations, and transfer function phase and gain. The mean R–R interval, and LF and HF spectral powers of R–R interval series increased with PMA. The mean SBP increased with PMA, but not the LF and HF spectral powers of SBP series. In the LF range, cross‐spectral analysis showed high coherence values (> 0.5) with a consistent negative phase shift between R–R interval and SBP, indicating a ∼3 s lag in R–R interval changes in relation to SBP. Baroreceptor reflex sensitivity, calculated from LF transfer gain, increased significantly with PMA, from 5 (preterm) to 15 ms mmHg−1 (term). Baroreceptor reflex sensitivity correlated significantly with the (LF and) HF spectral powers of R–R interval series, but not with the LF and HF spectral powers of SBP series. The principal conclusions are that baroreceptor reflex sensitivity and spectral power in R–R interval series increase in parallel with PMA, suggesting a progressive vagal maturation with PMA.
Plague Bacteria Target Immune Cells During Infection
Authors: Marketon Melanie M. , DePaolo R. William , DeBord Kristin L. , Jabri Bana , Schneewind Olaf
Published: July 2005

The plague is caused by the bacterium
Yersinia pestis
. Plague bacteria are thought to inject effector Yop proteins into host cells via the type III pathway. The identity of the host cells targeted for injection during plague infection is unknown. We found, using Yop β-lactamase hybrids and fluorescent staining of live cells from plague-infected animals, that
Y. pestis
selected immune cells for injection. In vivo, dendritic cells, macrophages, and neutrophils were injected most frequently, whereas B and T lymphocytes were rarely selected. Thus, it appears that
Y. pestis
disables these cell populations to annihilate host immune responses during plague.
Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effects on proliferation and secretion
Authors: Bose Chhanda , Zhang Hailing , Udupa Kodetthoor B. , Chowdhury Parimal
Published: July 2005

The objectives of the present study were to determine the effect of nicotine on MAPK signaling and on the proliferation of AR42J cells as well as to assess the relationship between MAPK activation and exocrine secretion in these cells. AR42J cells were incubated with nicotine and analyzed for the activation of MAPK by Western blot analysis using their respective antibodies and confirmed by immunohistochemistry. The effect of nicotine on cell proliferation was determined by the spectrophotometric method, and cell function was assessed by cholecystokinin (CCK)-stimulated amylase release into the culture medium. Nicotine at a dose of 100 μM induced phospho-ERK1/2 activation maximally in 3 min compared with untreated cells. Furthermore, immunofluorescence study confirmed the nicotine-induced increase in translocation of phospho-ERK1/2 to the nucleus. Activation of phospho-ERK1/2 was inhibited by an ERK1/2 pathway inhibitor but not by a nicotine receptor antagonist. At the same dose, there was significantly enhanced proliferation of AR42J cells until 72 h without toxic effect, as the percentage of lactate dehydrogenase release remained unchanged. Other MAPKs, c-Jun NH2-terminal kinase 1/2 and p38 MAPK, were not affected by nicotine treatment. At a nicotine dose of 100 μM, the CCK-stimulated release of amylase was maximal at 6 min, and, although a nicotinic receptor antagonist inhibited this response, it was not inhibited by the ERK1/2 pathway inhibitor. We conclude that nicotine treatment induced activation of ERK1/2 and increased the proliferation of AR42J cells. The data further indicate that MAPK signaling by nicotine is independent of the secretory response.
Role of pressor mechanisms from the NTS and CVLM in control of arterial pressure
Authors: Moreira Thiago Santos , Sato Monica Akemi , Takakura Ana Carolina Thomaz , Menani José Vanderlei , Colombari Eduardo
Published: July 2005

In the present study, we investigated the effects of inhibition of the caudal ventrolateral medulla (CVLM) with the GABAAagonist muscimol combined with the blockade of glutamatergic mechanism in the nucleus of the solitary tract (NTS) with kynurenic acid (kyn) on mean arterial pressure (MAP), heart rate (HR), and regional vascular resistances. In male Holtzman rats anesthetized intravenously with urethane/chloralose, bilateral injections of muscimol (120 pmol) into the CVLM or bilateral injections of kyn (2.7 nmol) into the NTS alone increased MAP to 186 ± 11 and to 142 ± 6 mmHg, respectively, vs. control: 105 ± 4 mmHg; HR to 407 ± 15 and to 412 ± 18 beats per minute (bpm), respectively, vs. control: 352 ± 12 bpm; and renal, mesenteric and hindquarter vascular resistances. However, in rats with the CVLM bilaterally blocked by muscimol, additional injections of kyn into the NTS reduced MAP to 88 ± 5 mmHg and mesenteric and hindquarter vascular resistances below control baseline levels. Moreover, in rats with the glutamatergic mechanisms of the NTS blocked by bilateral injections of kyn, additional injections of muscimol into the CVLM also reduced MAP to 92 ± 2 mmHg and mesenteric and hindquarter vascular resistances below control baseline levels. Simultaneous blockade of NTS and CVLM did not modify the increase in HR but also abolished the increase in renal vascular resistance produced by each treatment alone. The results suggest that important pressor mechanisms arise from the NTS and CVLM to control vascular resistance and arterial pressure under the conditions of the present study.
Biomechanical and phenotypic changes in the vasospastic canine basilar artery after subarachnoid hemorrhage
Authors: Yamaguchi-Okada Mitsuo , Nishizawa Shigeru , Koide Masayo , Nonaka Yuichiro
Published: July 2005

Because it has been argued that active myogenic tone prolongs cerebral vasospasm for >2 wk after subarachnoid hemorrhage (SAH), we attempted to identify the mechanism that plays the main role in sustaining the prolonged cerebral vasospasm. We especially focused on the roles of biomechanical and phenotypic changes in the cerebral arteries in the mechanisms of prolonged vasospasm after SAH. We used the basilar arteries from a “two-hemorrhage” canine model to make serial measurements of maximal contraction capacity and arterial stiffness (papaverine-insensitive tone) until day 28. We also examined hematoxylin-eosin-stained vasospastic canine basilar arteries for histological changes and immunohistochemically examined them for expression of myosin heavy chain isoforms (SMemb, SM1, and SM2), which are markers of smooth muscle phenotypic changes. Changes in collagen concentration in canine basilar arteries were also measured. Angiographic cerebral vasospasm persisted until day 14 and then gradually diminished; artery diameter returned to the control diameters on day 28. Maximal contraction capacity decreased until day 21 and showed some recovery by day 28. Arterial stiffness, on the other hand, progressed until day 28. Histological examination revealed medial thickening and increased connective tissue until day 21 and a return to control findings by day 28. The increased connective tissue was not accompanied by changes in collagen concentration, suggesting a role of some other protein in the increase in connective tissue. Immunohistochemical studies with anti-SMemb, anti-SM1, and anti-SM2 antibodies showed enhanced expression of SMemb from day 7 to day 21 and disappearance of SM1 and SM2 on days 14 and 21. The changes in myosin heavy chain isoform expression returned to normal on day 28. The above results indicate that biomechanical and phenotypic changes may play a pivotal role in sustaining cerebral vasospasm for >2 wk after SAH, with minimal changes in active myogenic arterial tone.
Bradycardia Stimulates Vascular Growth During Gradual Coronary Occlusion
Authors: Lamping Kathryn G. , Zheng Wei , Xing Dezhi , Christensen Lance P. , Martins James , Tomanek Robert J.
Published: July 2005

Objective—

In cultured endothelium, stretch induces release of growth factors that contribute to angiogenesis. We tested the hypothesis that bradycardia, which prolongs ventricular diastolic filling time and volume, promotes collateral vessel growth.

Methods and Results—

An ameroid occluder was placed on coronary arteries of dogs with normal heart rates (AM) or bradycardia (55 bpm; AM+BC). A third group had normal heart rates and no ameroid (control [CON]). Four weeks after occluder placement, myocardial blood flow at rest and maximal vasodilation (adenosine) at equivalent heart rates and vascular morphometry of hearts were measured. In AM dogs, conductance (myocardial flow/diastolic pressure) of collateral-dependent myocardium was similar to collateral-independent myocardium during rest but increased to only one third of CON during maximal vasodilation. In contrast, in AM+BC dogs, conductance was similar in collateral-dependent and -independent regions during maximal vasodilation. Arteriolar length density in collateral-dependent myocardium was 80% greater in AM+BC than AM dogs. Capillary length density in collateral-dependent region of AM dogs was lower than CON but normal in AM+BC dogs. The angiopoietin receptor Tie-2 increased in collateral-dependent regions of AM and AM+BC groups, whereas vascular endothelial growth factor increased in collateral-dependent and -independent regions only in AM+BC dogs.

Conclusion—

Chronic bradycardia during gradual coronary artery occlusion facilitates angiogenesis/arteriogenesis in collateral-dependent myocardium and preserves maximal perfusion.
Mechanisms of the Inhibitory Effect of Epigallocatechin-3-Gallate on Cultured Human Vascular Smooth Muscle Cell Invasion
Authors: Cheng Xian Wu , Kuzuya Masafumi , Nakamura Kae , Liu Zexuan , Di Qun , Hasegawa Jun , Iwata Mitsunaga , Murohara Toyoaki , Yokota Mitsuhiro , Iguchi Akihisa
Published: July 2005

Objective—

Although we recently showed that the administration of catechins reduced the neointimal formation in a rat balloon-injury model, the precise molecular mechanisms are largely unknown. In the present study, we tried to determine these mechanisms using an in vitro SMC invasion system.

Methods and Results—

Boyden chamber assay was used to examine the effect of catechins on the invasive behavior of SMCs. The invasive activity of SMCs through collagen gel was restrained by EGCG in a concentration-dependent manner. The data from gelatin and collagen zymography and Western blot revealed that EGCG blocks the activation of pro-matrix metalloproteinase (MMP)-2 during an invasion assay and in the conditioned medium of cultured SMCs as well as the activities of MMP-2 and membrane type 1-MMP (MT1-MMP) even at 0.1 to 0.3 μmol/L of EGCG. EGCG was found to restrain MT1-MMP
cat
–dependent pro–MMP-2 activation. EGCG upregulated the expression of tissue inhibitor of MMP-2 (TIMP-2) protein. Reverse zymography showed that the increased TIMP-2 to expression was validated by an increased activity. The data from decreased TIMP-2 activity using its siRNA suggested that upregulation of TIMP-2 expression may be one of the major mechanisms for inhibition of SMC invasion by EGCG.

Conclusions—

These results indicate that EGCG targets multiple MMP-mediated SMC cellular events and provides a new major mechanism for the SMC invasion through upregulation of TIMP-2 expression to modulate MMP activity.
Targeted Delivery of Bone Marrow Mononuclear Cells by Ultrasound Destruction of Microbubbles Induces Both Angiogenesis and Arteriogenesis Response
Authors: Imada Takanobu , Tatsumi Tetsuya , Mori Yasukiyo , Nishiue Takashi , Yoshida Masayuki , Masaki Hiroya , Okigaki Mitsuhiko , Kojima Hiroyuki , Nozawa Yoshihisa , Nishiwaki Yasunobu , Nitta Noriko , Iwasaka Toshiji , Matsubara Hiroaki
Published: July 2005

Objective—

Ultrasound (US)-mediated destruction of contrast microbubbles causes capillary rupturing that stimulates arteriogenesis, whereas intramuscular implantation (im) of bone marrow mononuclear cells (BM-MNCs) induces angiogenesis. We therefore studied whether US-targeted microbubble destruction combined with transplantation of BM-MNCs can enhance blood flow restoration by stimulating both angiogenesis and arteriogenesis.

Methods and Results—

US-mediated destruction of phospholipid-coated microbubbles was applied onto ischemic hindlimb muscle and subsequently BM-MNCs were transfused. A significant enhancement in blood flow recovery after Bubble+US+BM-MNC infusion (34% increase,
P
<0.05) was observed compared with Bubble+US (25%). The ratio of capillary/muscle fiber increased by Bubble+US+BM-MNC-i.v (260%,
P
<0.01) than that in the Bubble+US group (172%), into which BM-MNCs were incorporated (angiogenesis). Smooth muscle α-actin–positive arterioles were also increased, and angiography showed augmented collateral vessel formation (arteriogenesis). Platelet-derived proinflammatory factors activated by Bubble+US induces the expression of adhesion molecules (P-selectin and ICAM-1), leading to the attachment of transplanted BM-MNCs on the endothelium. Flow assay confirmed that the platelet-derived factors cause the adhesion of BM-MNCs onto endothelium under laminar flow.

Conclusions—

This study demonstrates that the targeted delivery of BM-MNCs by US destruction of microbubbles enhances regional angiogenesis and arteriogenesis response, in which the release of platelet-derived proinflammatory factors activated by Bubble+US play a key role in the attachment of transplanted BM-MNCs onto the endothelial layer.
Becoming a Holistic Thinker: Training Effect of Oriental Medicine on Reasoning
Authors: Koo Minkyung , Choi Incheol
Published: July 2005

The authors hypothesized that training in Oriental medicine would make students think in a more holistic way. Study 1 found that students of Oriental medicine exhibited a cyclic expectation of future change, a key characteristic of holistic thinking, more than did students in other majors, such that the former, not the latter, believed that if something was going up or going down, it would reverse its direction in the future. Study 2 found that students in Oriental medicine also possessed a more complex causal belief and hence considered a greater amount of information in causal attribution than did students in other majors. More important, such a complex causal belief increased with the length of training in Oriental medicine. Implications and future research are discussed.
PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism
Authors: Walter Roland B. , Pirga Jason L. , Cronk Michelle R. , Mayer Sasha , Appelbaum Frederick R. , Banker Deborah E.
Published: July 2005

The peripheral benzodiazepine receptor (pBR) ligand, PK11195, promotes mitochondrial apoptosis and blocks P-glycoprotein (Pgp)-mediated drug efflux to chemosensitize cancer cells at least as well or better than the Pgp modulator, cyclosporine A (CSA). We now show that PK11195 broadly inhibits adenosine triphosphate (ATP)-binding cassette (ABC) transporters in hematologic cancer cell lines and primary leukemia-cell samples, including multidrug resistance protein (MRP), breast cancer resistance protein (BCRP), and/or Pgp. Ectopic expression models confirmed that pBR can directly mediate chemosensitizing by PK11195, presumably via mitochondrial activities, but showed that pBR expression is unnecessary to PK11195-mediated efflux inhibition. PK11195 binds plasma-membrane sites in Pgp-expressing cells, stimulates Pgp-associated adenosine triphosphatase (ATPase) activity, and causes conformational changes in Pgp, suggesting that PK11195 modulates Pgp-mediated efflux by direct transporter interaction(s). PK11195 and CSA bind noncompetitively in Pgp-expressing cells, indicating that PK11195 interacts with Pgp at sites that are distinct from CSA-binding sites. Importantly, PK11195 concentrations that were effective in these in vitro assays can be safely achieved in patients. Because PK11195 promotes chemotherapy-induced apoptosis by a pBR-dependent mitochondrial mechanism and broadly blocks drug efflux by an apparently pBR-independent, ABC transporter-dependent mechanism, PK11195 may be a useful clinical chemosensitizer in cancer patients.
Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma
Authors: Kundu Mondira , Compton Sheila , Garrett-Beal Lisa , Stacy Terryl , Starost Matthew F. , Eckhaus Michael , Speck Nancy A. , Liu P. Paul
Published: July 2005

Chromosomal rearrangements affecting RUNX1 and CBFB are common in acute leukemias. These mutations result in the expression of fusion proteins that act dominant-negatively to suppress the normal function of the Runt-related transcription factor 1 (RUNX)/core binding factor β (CBFβ) complexes. In addition, loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) have been identified in sporadic cases of acute myeloid leukemia (AML) and in association with the familial platelet disorder with propensity to develop AML (FPD/AML). In order to examine the hypothesis that decreased gene dosage of RUNX1 may be a critical event in the development of leukemia, we treated chimeric mice generated from Runx1lacZ/lacZ embryonic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an increased incidence of T-lymphoblastic lymphoma in Runx1lacZ/lacZ compared with wild-type chimeras and confirmed that the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can indeed predispose mice to hematopoietic malignancies.
Analysis of the function of E. coli 23S rRNA helix-loop 69 by mutagenesis
Authors: Liiv Aivar , Karitkina Diana , Maiväli Ülo , Remme Jaanus
Published: July 2005

Background

The ribosome is a two-subunit enzyme known to exhibit structural dynamism during protein synthesis. The intersubunit bridges have been proposed to play important roles in decoding, translocation, and the peptidyl transferase reaction; yet the physical nature of their contributions is ill understood. An intriguing intersubunit bridge, B2a, which contains 23S rRNA helix 69 as a major component, has been implicated by proximity in a number of catalytically important regions. In addition to contacting the small ribosomal subunit, helix 69 contacts both the A and P site tRNAs and several translation factors.

Results

We scanned the loop of helix 69 by mutagenesis and analyzed the mutant ribosomes using a plasmid-borne IPTG-inducible expression system. We assayed the effects of 23S rRNA mutations on cell growth, contribution of mutant ribosomes to cellular polysome pools and the ability of mutant ribosomes to function in cell-free translation. Mutations A1912G, and A1919G have very strong growth phenotypes, are inactive during in vitro protein synthesis, and under-represented in the polysomes. Mutation Ψ1917C has a very strong growth phenotype and leads to a general depletion of the cellular polysome pool. Mutation A1916G, having a modest growth phenotype, is apparently defective in the assembly of the 70S ribosome.

Conclusion

Mutations A1912G, A1919G, and Ψ1917C of 23S rRNA strongly inhibit translation. Mutation A1916G causes a defect in the 50S subunit or 70S formation. Mutations Ψ1911C, A1913G, C1914A, Ψ1915C, and A1918G lack clear phenotypes.
Welcome to Journal of Ethnobiology and Ethnomedicine
Authors: Pieroni Andrea , Price Lisa Leimar , Vandebroek Ina
Published: July 2005

Ethnobiology is a multidisciplinary field of study that draws on approaches and methods from both the social and biological sciences. Ethnobiology aims at investigating culturally based biological and environmental knowledge, cultural perception and cognition of the natural world, and associated behaviours and practices. Ethnomedicine is concerned with the cultural interpretations of health, disease and illness and also addresses the health care seeking process and healing practices. Research interest and activities in the areas of ethnobiology and ethnomedicine have increased tremendously in the last decade. Since the inception of the disciplines, scientific research in ethnobiology and ethnomedicine has made important contributions to understanding traditional subsistence and medical knowledge and practice. The Journal of Ethnobiology and Ethnomedicine (JEE) invites manuscripts and reviews based on original interdisciplinary research from around the world on the inextricable relationships between human cultures and nature, on Traditional Environmental Knowledge (TEK), folk and traditional medical knowledge, as well as on the relevance of the above for Primary Health Care (PHC) policies in developing countries.
Common mental disorders in a young urban population in Colombia
Authors: Harpham Trudy , Snoxell Simon , Grant Emma , Rodriguez Carlos
Published: July 2005

Background

There are few studies of mental ill health among young people in developing countries.

Aims

To measure the prevalence of common mental disorders among low-income young people in the city of Cali, Colombia and to examine associations with violence and social capital.

Method

The Self-Reporting Questionnaire was administered to 1057 young people aged 15–25 years. Social capital, violence, alcoholism and socio-demographic variables were also measured.

Results

We found 255 young people (24%) with common mental disorders. Being a woman, having limited education and experiencing high levels of violence were the main risk factors for common mental disorders. Social capital did not emerge as a risk factor.

Conclusions

A large burden of mental ill health among young people was found; this requires urgent interventions and more research on the mechanisms which link mental health and violence.
Introduction to ‘Early psychosis: abridge to the future’
Authors: Mcgorry Patrick , Nordentoft Merete , Simonsen Erik
Published: July 2005

Early intervention in psychiatry has taken a long time to emerge as a key strategy to reduce morbidity and mortality. In other fields of medicine it has received consistent support and great efforts are expended to educate the public about the value of early diagnosis and the benefits of timely intervention. There is finally substantial momentum behind similar endeavours in psychotic disorders, which, now they have reached ‘proof of concept’ stage, could begin to be extended across the spectrum of serious mental disorders. There is also ambivalence and resistance to this evidence-based reform which warrants careful analysis. The Third International Early Psychosis Conference proved to be a watershed and was the largest and most vibrant meeting to that point. This preface aims to set the scene for a selection of contributions, derived from the array of new evidence reported in Copenhagen, and recently fully updated.
Early detection and intervention in psychosis: an ethical paradigm shift
Authors: Mcglashan Thomas H.
Published: July 2005

This paper will first posit the rationale for intervention before onset, then outline the current usual practice of treating schizophrenia and the determinants ofthat practice. Recent developments that permit or demand a change in this practice will then be elaborated. The article concludes with an elaboration of the currently known risks and benefits of early intervention research. The ethics of early intervention are undergoing a paradigm shift, a shift that supports early intervention research as being necessary to bring empirical balance to territory that is currently overpopulated with zealous opinions.

Delcaration of interest

None.
Duration of untreated psychosis and its relationship to clinical outcome
Authors: Norman Ross M. G. , Lewis Shôn W , Marshall Max
Published: July 2005

Background

A major reason for interest in early intervention for psychotic disorders is the hypothesised relationship between longer duration of untreated psychosis (DUP) and poorer outcome of treatment.

Aims

To critically examine the evidence concerning DUP being related to treatment outcome and possible mediators of any such relationship.

Method

A systematic review of studies in which DUP is assessed and its relationship to treatment outcome is examined. In addition, studies relevant to possible neurotoxic effects of DUP were reviewed.

Results

The research is entirely of a correlational nature and, therefore, firm conclusions regarding causation are not possible. There is, however, substantial evidence of DUP being an independent predictor of treatment outcome, particularly remission of positive symptoms, over the first year or so of treatment. Findings regarding the possible neurotoxic effects of DUP are inconsistent.

Conclusions

There continues to be evidence consistent with DUP influencing aspects of treatment outcome. Non-correlational studies, such as quasi-experimental designs, could provide stronger evidence regarding causality.