bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of dermoscopic and histopathologic features and their correlations in pigmented basal cell carcinomas
Authors: Demırtaşoǧlu M , İlknur T , Lebe B , Kuşku E , Akarsu S , Özkan Ş
Published: September 2010

Background  Because of their clinical similarities, pigmented basal cell carcinomas (BCCs) can be confused with melanocytic pigmented lesions especially with melanoma. Since special dermoscopic features have been described for pigmented BCCs, dermoscopy is accepted as a useful tool for the diagnosis of pigmented BCCs.

Objective  To investigate dermoscopic and corresponding histopathologic features of BCCs and to evaluate their correlations in pigmented BCCs.

Methods  In this study, 32 pigmented BCCs in 30 patients whose diagnoses were confirmed with clinical and histopathologic features were included. Before the histopathologic evaluation, the lesions were analysed for dermoscopic features. Histopathologic correlations of dermoscopic features of BCCs and the localization of pigment accumulation in tumour mass were investigated.

Results  In addition to ulceration, large grey‐blue ovoid nests, multiple grey‐blue globules, maple leaf areas and arborizing telangiectasia; dermoscopically yellow‐brown, whitish‐yellow, and black‐dark brown colour showed statistically significant correlation with their histopathologic counterparts (P < 0.05). Whitish veil, which is among dermoscopic features of BCCs, did not show significant correlation with its histopathologic counterpart (P > 0.05). It was histopathologically determined that pigmentation is found within the tumour mass as well as in the tumour stroma and in the hyperplastic epidermal melanocytes.

Conclusions  Ulceration, large grey‐blue ovoid nests, multiple grey‐blue globules, maple leaf‐like areas and arborizing telangiectasia, which are specific dermoscopic features for the diagnosis of pigmented BCC, were found to correlate with their histopathologic counterparts. In conclusion, dermoscopy can be described as a valuable tool for the diagnosis of pigmented basal cell carcinomas.
The safety of hydroquinone
Authors: Nordlund JJ , Grimes PE , Ortonne JP
Published: September 2010

Hydroquinone is one of the most effective molecules for the treatment of hyperpigmentary disorders, with over 40 years of efficacy and safety data. Concerns over its safety have been raised because of the fact that it is a derivative of benzene and because of the long‐term side‐effects observed with cosmetic products containing high concentrations of hydroquinone. However, despite 40–50 years use of hydroquinone for medical conditions, there has not been a single documented case of either a cutaneous or internal malignancy associated with this drug. This article reviews the evidence for the safety of hydroquinone in the treatment of hyperpigmentation conditions.
Basal cell carcinoma of the nasolabial fold: an apparently ‘benign’ tumour that often needs complex surgery
Authors: Garcia L , Nagore E , Llombart B , Sanmartin O , Botella‐Estrada R , Requena C , Jorda E , Guillen C
Published: September 2010

Background  Location of the tumour is a well‐known prognostic factor for recurrence of basal cell carcinoma (BCC). We have observed that tumours located in the nasolabial fold may deserve a particular attention.

Objective  The aim of this study is to evaluate the behaviour of BCC located on the nasolabial fold in comparison to a control group of patients with BCC in lower risk sites, and to detect characteristics which may imply a more complicated treatment or the consideration of adjuvant treatment.

Methods  A series of 24 patients with BCC located on the nasolabial fold were retrospectively recruited from our database of Mohs surgery from January 1997 to December 2000. A control group of 37 patients with BCC located on the cheek or forehead were selected from the same database. The differences between both groups in clinical, surgical and histological terms were evaluated.

Results  BCC on the nasolabial fold presented with shorter evolution time from first symptom, had a smaller size, had been less frequently treated before and showed mostly non‐aggressive histologic subtype, but needed more surgical stages and more complex reconstruction.

Conclusion  We have observed that BCC on the nasolabial fold, despite presenting with better clinical and histological features, needed more complicated surgery. In our opinion, this location warrants a particular attention and further prospective studies should be made to corroborate our findings.
Verruca vulgaris: pulsed dye laser therapy compared with salicylic acid + pulsed dye laser therapy
Authors: Akarsu S , Ilknur T , Demirtaşoǧlu M , Özkan Ş
Published: September 2010

Background  In recent years, lasers have been used in verruca therapy and some successful results have been obtained in some types of verruca. In some of these laser studies, peeling processes have been used to increase penetration.

Objective  This study aimed to compare the effects of pulsed dye laser (PDL) therapy with the effects of PDL therapy following salicylic acid (SA) application. The purpose of the SA application is to increase the laser penetration by decreasing the hyperkeratosis of verruca vulgaris.

Methods  This controlled study included 66 lesions from 19 patients enrolled in the study. PDL was applied to 33 lesions following 30% SA application twice a day for 5 days, and the remaining 33 lesions underwent PDL therapy. PDL was administered in both groups at 4‐week intervals varying from one to five sessions. In the comparison of these two groups, the changes in verruca dimensions were recorded in width × length × height (mm3), and the results of the therapy were evaluated statistically.

Results  In both PDL and SA + PDL groups, the regressions observed in the size of the lesions were statistically significant at the end of the fifth session compared with those observed at the onset of the therapy (P < 0.05). At the end of the fifth session, the difference between the two groups was not statistically significant (P = 0.451); however, the clearance rate in the SA + PDL group was more statistically significant than that in the PDL group after the second session (P = 0.049). The complete clearance rate in the SA + PDL group was 54.6% after the second session, but 66.4% in the PDL group only after the fifth session. Complete clearance in the SA + PDL group was observed after 2.2 sessions, and in the PDL group after 3.1 sessions (P < 0.05).

Conclusions  Although there was no difference between the clearance rate of the SA + PDL group and that of the PDL group after the fifth session, adding SA to PDL decreased the number of sessions to a large extent.
Evidence of a marked 25‐hydroxyvitamin D deficiency in patients with congenital ichthyosis
Authors: Ingen‐Housz‐Oro S , Boudou P , Bergot C , Ibrahim F , Souberbielle JC , Dubertret L , Blanchet‐Bardon C
Published: September 2010

Background  Vitamin D is essential for bone mineralization, and its deficiency may be the cause of skeletal fractures and osteomalacia. Geographical or ethnic factors may modulate the cutaneous synthesis of vitamin D. We hypothesized that major changes in keratinization may similarly alter the cutaneous synthesis of vitamin D.

Objectives  To explore calciotrophic hormones, parameters of bone remodelling and bone mineral density (BMD) in nine patients with non‐bullous congenital ichthyosis.

Patients and methods  Six patients were European, three were North African. Four had received acitretin over a long period of time. A complete biological investigation, including serum and urinary calcium and phosphorus, calciotrophic hormones [intact parathyroid hormone (iPTH), 25‐hydroxyvitamin D (25‐(OH)D) and 1,25‐dihydroxyvitamin D (1,25‐(OH)2D)], bone formation and resorption markers, was performed on all patients during the winter season and repeated among four patients after summer. BMD was measured in all patients.

Results  All patients had a marked 25‐(OH)D deficiency, clearly below the deficiency threshold of 25 nmol/L. Patients from North Africa had a greater deficiency than European patients, perhaps because of the difference in skin pigmentation. iPTH remained normal in European patients but was elevated among the North Africans. After sun exposure, an improvement in vitamin status was visible in only one patient. Bone formation and resorption markers remained normal. Femoral neck osteodensitometry indicated values near the osteopaenic threshold in two young North African females. No deleterious effect of retinoids on vitamin D metabolism was observed.

Conclusion  Patients, and in particular pigmented patients, with congenital ichthyosis present a severe deficiency in vitamin D. Care provided to protect the skeletal future of these patients involves measuring BMD and prescribing supplementation.
Psychological distress and coping strategies in patients with psoriasis: the PSYCHAE Study
Authors: Finzi A , Colombo D , Caputo A , Andreassi L , Chimenti S , Vena G , Simoni L , Sgarbi S , Giannetti A ,   for the PSYCHAE Study Group
Published: September 2010

Objective  Our objectives were to determine the prevalence of psychological distress in a large sample of Italian patients with psoriasis; to establish whether disease severity and psychological distress are associated; to identify the strategies employed to cope with psoriasis; to evaluate the coping strategies employed by dermatologists; and to identify potential predictors of psychological distress.

Design  Cross‐sectional.

Setting  Thirty‐nine Italian dermatology centres.

Subjects  One thousand five hundred and eighty (1580) patients with psoriasis.

Methods  Minor psychological distress was evaluated using the General Health Questionnaire‐12 (GHQ‐12) and major psychopathological distress using the Brief Symptom Inventory (BSI); coping strategies were evaluated using the Brief COPE questionnaire; disease severity was evaluated using the body surface area index.

Results  Patients were aged 44 ± 13 years (mean ± SD) and were mainly men (57%). Minor psychological distress was present in 46% of patients and major psychopathological distress in 11% of them. Both minor (54% vs. 40%, P < 0.0001) and major (17% vs. 7%, P < 0.0001) distress were more frequent in women than in men. The psychological status of women was worse than that of men independently from the extension of psoriasis. There was no association between the presence of distress and the treatment prescribed by dermatologists. Planning and active coping were the strategies most commonly employed by patients to cope with psoriasis, but there were between‐gender differences. Most dermatologists employed a ‘problem‐orientated’ attitude in caring for patients.

Conclusions  (i) Psychological distress was relatively frequent in our patients with psoriasis; (ii) female gender was the most important predictive factor for psychological distress; (iii) there was no association between psoriasis severity and psychological distress; (iv) planning and active coping were the coping strategies most frequently employed by patients; and (v) most dermatologists employed a problem‐orientated attitude in caring for patients.
New lifestyle drugs and somatoform disorders in dermatology
Authors: Harth W , Seikowski K , Hermes B , Gieler U
Published: September 2010

An increasing number of healthy individuals make use of ‘lifestyle’ drugs, such as nootropics, psychopharmaca, hormones and eco‐drugs. In this respect, the fact that many people try to improve their outer appearance, solve their ‘cosmetic problems’, influence their rate of hair growth and altogether delay, halt or even reverse the natural ageing process has become a relevant matter for the practising dermatologist. Lifestyle drugs in dermatology are taken in an attempt to increase personal life quality by means of attaining a certain, psychosocially defined beauty ideal. They are not taken to manage a medically identifiable, well‐defined disease. Often, patients suffering from somatoform disorders, such as hypochondriac disorders, body dysmorphic disorders, somatization disorders or persistent somatoform pain disorders, may spontaneously ask physicians, in particular dermatologists and plastic surgeons, to prescribe them lifestyle drugs. Typically, patients repeatedly present with alleged ‘physical symptoms’ that turn out to be subjective complaints without any underlying identifiable medical disease. The use of lifestyle drugs without any proper medical indication may lead to a chronification of the emotional disorders that had ultimately been the cause of the patients’ request for such drugs. Such disorders may need to be treated promptly with psychotherapy and/or appropriate psychopharmacotherapy, and the choice of the treatment requires an accurate differential diagnostic approach.
Developmental trajectories of reading development and impairment from ages 3 to 8 years in Chinese children
Authors: Lei Lin , Pan Jinger , Liu Hongyun , McBride‐Chang Catherine , Li Hong , Zhang Yuping , Chen Lang , Tardif Twila , Liang Weilan , Zhang Zhixiang , Shu Hua
Published: September 2010

Background:  Early prediction of reading disabilities in Chinese is important for early remediation efforts. In this 6‐year longitudinal study, we investigated the early cognitive predictors of reading skill in a statistically representative sample of Chinese children from Beijing.

Method:  Two hundred sixty‐one (261) native Chinese children were administered seven language‐related skills over three years between the ages of 3 and 6 years. Performances on these skills were then examined in relation to subsequent word reading accuracy and fluency. Individual differences in developmental profiles across tasks were then estimated using growth mixture modeling.

Results:  Four developmental trajectories were classified – the typical (control), catch‐up (with low initial cognitive performances but adequate subsequent reading), literacy‐related‐cognitive‐delay (with difficulties in morphological awareness, phonological awareness, and speeded naming and subsequent word recognition), and language‐delay (relatively low across all tasks) groups.

Conclusion:  Findings suggest that the combination of phonological awareness, rapid naming and morphological awareness are essential in the early prediction of later reading difficulties in Chinese children.
Prenatal maternal stress programs infant stress regulation
Authors: Davis Elysia Poggi , Glynn Laura M. , Waffarn Feizal , Sandman Curt A.
Published: September 2010

Objective:  Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.

Methods:  The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36 + weeks’ gestational age. Infant cortisol and behavioral responses to the painful stress of a heel‐stick blood draw were evaluated at 24 hours after birth. The association between prenatal maternal measures and infant cortisol and behavioral stress responses was examined using hierarchical linear growth curve modeling.

Results:  A larger infant cortisol response to the heel‐stick procedure was associated with exposure to elevated concentrations of maternal cortisol during the late second and third trimesters. Additionally, a slower rate of behavioral recovery from the painful stress of a heel‐stick blood draw was predicted by elevated levels of maternal cortisol early in pregnancy as well as prenatal maternal psychosocial stress throughout gestation. These associations could not be explained by mode of delivery, prenatal medical history, socioeconomic status or child race, sex or birth order.

Conclusions:  These data suggest that exposure to maternal cortisol and psychosocial stress exerts programming influences on the developing fetus with consequences for infant stress regulation.
Effects of 2,3‐butanedione monoxime (BDM) on calcium channels expressed in Xenopus oocytes
Authors: Allen T. J. A. , Mikala G. , Wu X.‐P. , Dolphin A. C.
Published: September 2010

We examine the actions of a chemical phosphatase, 2,3‐butanedione monoxime (BDM), on endogenous and expressed Ca2+ channel currents in Xenopus oocytes. In previous studies on L‐type Ca2+ channel currents in cardiomyocytes and dorsal root ganglia, the inhibitory effects of BDM were attenuated by activation of protein kinase A.

Ba2+ currents (IBa) through a human wild‐type L‐type Ca2+ channel complex (i.e. hα1C, α2‐δa and hβ1b) are inhibited by BDM with an IC50 of 16 mM, with 10 mM producing a 36.1 ± 2.2 % inhibition. IBa through endogenous oocyte N‐type Ca2+ channels, upregulated by exogenous α2‐δa and hβ1b subunits, are inhibited to a similar degree by BDM.

To examine whether the action of BDM is dependent on PKA‐dependent phosphorylation, a clone of hα1C deficient in all five serine PKA consensus sites (hα1C‐SA5) was co‐expressed with α2‐δa and the human cardiac hβ3 subunit, which naturally lacks PKA consensus sites. This complex exhibited a sensitivity to BDM that was similar to the wild‐type complex, with 10 mM BDM producing 31.6 ± 1.5 % inhibition.

As limited proteolysis upregulates Ca2+ channels in cardiomyocytes and renders them less sensitive to BDM, experiments were performed with a carboxyl terminus deletion mutant, hα1C‐Δ1633. IBa through this subunit showed a sensitivity to BDM that was similar to the wild‐type complex, with 10 mM BDM producing 31.3 ± 1.4 % inhibition. However, co‐expression with α2‐δa and hβ3 subunits reduced potency, and is reflected by an increased IC50 of 22.7 mM.

The actions of BDM were examined on a rat brain rbA‐1 Ca2+ channel clone, α1A, co‐expressed with α2‐δb and β1b subunit homologues from rat brain. BDM inhibited the current through this channel complex to a similar degree to that seen for cardiac wild‐type channels, with 10 mM BDM causing a 33.1 ± 3.5 % inhibition.

The effects of BDM were compared at two holding potentials, ‐80 and ‐30 mV, using the hα1C‐Δ1633, α2‐δa and hβ3 subunit combination. At ‐30 mV BDM is more potent with 10 mM BDM reducing IBa by 39.8 ± 2.7 %, compared with 20.8 ± 2.2 % at ‐80 mV.

The data suggest that BDM may not exert its inhibitory action by means of a chemical phosphatase effect, but by channel block. The similar potency observed between α1C, α1A and endogenous (N‐type) channels may help point towards a possible site of action; differences with the carboxyl deletion mutant may help further to define a locus of interaction.
The human Na+–glucose cotransporter is a molecular water pump
Authors: Meinild A.‐K. , Klaerke D. A. , Loo D. D. F. , Wright E. M. , Zeuthen T.
Published: September 2010

The human Na+‐glucose cotransporter (hSGLT1) was expressed in Xenopus laevis oocytes. The transport activity, given by the Na+ current, was monitored as a clamp current and the concomitant flux of water followed optically as the change in oocyte volume.

When glucose was added to the bathing solution there was an abrupt increase in clamp current and an immediate swelling of the oocyte. The transmembrane transport of two Na+ ions and one sugar molecule was coupled, within the protein itself, to the influx of 210 water molecules.

This stoichiometry was constant and independent of the external parameters: Na+ concentrations, sugar concentrations, transmembrane voltages, temperature and osmotic gradients.

The cotransport of water occurred in the presence of adverse osmotic gradients. In accordance with the Gibbs equation, energy was transferred within the protein from the downhill fluxes of Na+ and sugar to the uphill transport of water, indicative of secondary active transport of water.

Unstirred layer effects were ruled out on the basis of experiments on oocytes treated with gramicidin or other ionophores. Na+ currents maintained by ionophores did not lead to any initial water movements.

The finding of a molecular water pump allows for new models of cellular water transport which include coupling between ion and water fluxes at the protein level; the hSGLT1 could account for almost half the daily reuptake of water from the small intestine.
Activation of pulmonary C fibres by adenosine in anaesthetized rats: role of adenosine A1receptors
Authors: Hong Ju‐Lun , Ho Ching‐Yin , Kwong Kevin , Lee Lu‐Yuan
Published: September 2010

Intravenous administration of adenosine (Ado) to patients can cause dyspnoea, chest discomfort and bronchoconstriction. To assess the role of vagal pulmonary C fibres in evoking these adverse reactions, the effect of Ado on single pulmonary C fibres was studied in anaesthetized and artificially ventilated rats.

Right‐atrial injection of Ado (320 μg kg−1) activated 68 % (73/107) of pulmonary C fibres; the total number of action potentials during a period of 15 s increased from a baseline of 0.2 ± 0.1 impulses to a peak of 16.4 ± 2.6 impulses (P< 0.01,n= 107) after Ado. Inosine, the metabolite of Ado, did not activate any of eleven C fibres tested in six rats. Furthermore, C fibres were activated only by right‐atrial and not by left‐ventricular injection of the same dose of Ado.

Unlike the immediate and transient stimulation of C fibres by capsaicin, the C fibre stimulation by Ado had a latency of 6.5 ± 0.3 s (range, 3‐18 s) and lasted longer.

The stimulation of C fibres by Ado was significantly attenuated by pretreatment with aminophylline, a non‐selective Ado receptor antagonist, was completely prevented by 1,3‐dipropyl‐8‐cyclopentylxanthine, an Ado A1receptor antagonist, but was unaffected by 3,7‐dimethy‐1‐propargylxanthine, an A2receptor antagonist. None of these Ado receptor antagonists prevented capsaicin‐induced C fibre stimulation.

In conclusion, Ado stimulates pulmonary C fibre terminals through an activation of A1receptors. The stimulation of pulmonary C fibres may play an important role in Ado‐induced adverse respiratory effects.
Serotonin reduces synaptic excitation in the superficial medial entorhinal cortex of the rat via a presynaptic mechanism
Authors: Schmitz Dietmar , Gloveli Tengis , Empson Ruth M. , Draguhn Andreas , Heinemann Uwe
Published: September 2010

The superficial layers II and III of the entorhinal cortex, which form the main cortical input to the hippocampus, receive a large serotonergic projection from the raphe nuclei and express 5‐HT receptors at high density. Here, we studied the effects of serotonin on the intrinsic properties and excitatory synaptic transmission of the superficial medial entorhinal cortex.

Intracellular and patch clamp recordings revealed that serotonin hyperpolarized only one‐third of the cells, approximately, through a potassium conductance via a GTP‐dependent process.

Serotonin depressed mixed as well as isolated α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐ propionic acid receptor (AMPAR)‐ and N‐methyl‐D‐aspartic acid receptor (NMDAR)‐mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCsapproximately 40 % reduction with 1 μM serotonin).

The effect of serotonin on EPSPs/EPSCs was similar in whole‐cell versus intracellular recordings; it did not require intracellular GTP and was not visible in glutamate applications to excised patches. Miniature EPSCs recorded in the presence of tetrodotoxin and bicuculline were reduced in frequency, but not altered in amplitude.

The effects of serotonin on intrinsic properties and EPSPs were partially mimicked by 5‐HT1A receptor agonists (±)‐8‐hydroxy‐2‐(di‐n‐propylamino)tetralin hydrobromide (8‐OH‐DPAT) and 5‐carboxamido‐tryptamine maleate (5‐CT), and reduced by 5‐HT1A receptor antagonists S‐(‐)‐5‐fluoro‐8‐hydroxy‐DPAT hydrochloride (S‐UH‐301), 1‐(2‐methoxyphenyl)‐4‐[4‐(2‐phthalimido)butyl]piperazine hydrobromide (NAN‐190) and spiperone.

We conclude that serotonin potently suppresses excitatory synaptic transmission via 5‐HT1A receptors in layers II and III of the medial entorhinal cortex by a presynaptic mechanism.
The effects of extracellular and intracellular pH on intracellular Ca2+ regulation in guinea‐pig detrusor smooth muscle
Authors: Wu C. , Fry C. H.
Published: September 2010

Intracellular pH (pHi) and intracellular [Ca2+] ([Ca2+]i) were measured during changes to superfusate PCO2 and/or [NaHCO3]. Changes to superfusate PCO2 produced sustained changes to pHi and [Ca2+]i, while changes to [NaHCO3] altered only extracellular pH (pHo).

Carbachol or caffeine induced a transient rise of [Ca2+]i due to Ca2+ release from an intracellular store. This Ca2+ transient was reduced by extracellular acidosis, but increased by intracellular acidosis. Alkalosis in either compartment produced opposite effects to acidosis. Changes to the Ca2+ transient mirrored those to phasic tension previously reported in this preparation.

A raised superfusate [K+] also induced a Ca2+ transient, due to transmembrane influx of Ca2+. This transient was depressed by extracellular acidosis, but unaffected by changes to pHi. The L‐type Ca2+ current was similarly affected by changes to pHo, but not by alteration of pHi.

The results suggest that extracellular acidosis depresses the Ca2+ transient by reducing transmembrane influx through the L‐type Ca2+ channel. The increase in the carbachol‐ and caffeine‐induced Ca2+ transients by intracellular acidosis is due to enhancement of Ca2+ uptake into intracellular stores as a result of a raised resting [Ca2+]i.
Intrasarcomere [Ca2+] gradients and their spatio‐temporal relation to Ca2+sparks in rat cardiomyocytes
Authors: Tanaka Hikaru , Sekine Toshiyuki , Kawanishi Toru , Nakamura Ryu , Shigenobu Koki
Published: September 2010

Line‐scan analyses of spontaneous Ca2+sparks, non‐propagating local rises in Ca2+concentration, and the early phase of Ca2+transients in cardiomyocytes were performed with a rapid‐scanning laser confocal microscope (Nikon RCM8000) and fluo‐3.

On electrical stimulation, points at which rise in Ca2+began earliest were observed at regular spacings of 1.82 ± 0.26 μm (mean ± s.d.) along the longitudinal axis of the cell. The points were heavily stained with di‐2‐ANEPEQ, which stains the T‐tubules, indicating that they were at the Z‐line.

The points where spontaneous Ca2+sparks originated coincided with the points which showed faster Ca2+elevation, i.e. the Z‐line.

In some cases where a Ca2+spark had occurred within about 30 ms before the evoked Ca2+transient, fast elevation of Ca2+was not observed at the corresponding Z‐line, indicating the presence of a refractory period in Ca2+release from the SR.

The present results provide visual evidence for Ca2+release from the junctional sarcoplasmic reticulum in cardiomyocytes. The presence of a refractory period in Ca2+release after Ca2+sparks provided new evidence that the normal Ca2+transient may be the summation of Ca2+sparks.
Intracellular calcium and Na+‐Ca2+ exchange current in isolated toad pacemaker cells
Authors: Ju Yue‐Kun , Allen David G.
Published: September 2010

Single pacemaker cells were isolated from the sinus venosus of cane toad (Bufo marinus) in order to study the mechanisms involved in the spontaneous firing rate of action potentials. Intracellular calcium concentration ([Ca2+]i) was measured with indo‐1 to determine whether [Ca2+]i influenced firing rate. A rapid transient rise of [Ca2+]i was recorded together with each spontaneous action potential. [Ca2+]i at the peak of systole was 655 ± 64 nM and the minimum at the end of diastole was 195 ± 15 nM.

Reduction of extracellular Ca2+ concentration from 2 to 0.5 mM caused a reduction in both systolic and diastolic [Ca2+]i and the spontaneous firing rate also gradually declined.

Application of the acetoxymethyl (AM) ester of BAPTA (10 μM), in order to increase intracellular calcium buffering, caused a decline in systolic and diastolic [Ca2+]i. The firing rate declined progressively until the cells stopped firing after 10‐15 min. At the time that firing ceased, the diastolic [Ca2+]i had declined by 141 ± 38 nM.

In the presence of ryanodine (2 μM), which interferes with Ca2+ release from the sarcoplasmic reticulum, the systolic and diastolic [Ca2+]i both declined and the firing rate decreased until the cells stopped firing. At quiescence diastolic [Ca2+]i had declined by 93 ± 20 nM.

Exposure of the cells to Na+‐free solution caused a rise in [Ca2+]i which exceeded the systolic level after 4.8 ± 0.3 s. This rise is consistent with Ca2+ entry on a Na+‐Ca2+ exchanger.

Rapid application of caffeine (10‐20 mM) to cells clamped at ‐60 mV caused a rapid increase in [Ca2+]i which then spontaneously declined. An inward current with a similar time course to that of [Ca2+]i was also generated. Application of Ni2+ (5 mM) or 2,4‐dichlorobenzamil (25 μM) reduced the amplitude of the inward current produced by caffeine by 96 ± 1 % and 74 ± 10 %, respectively. In a Na+‐free solution the caffeine‐induced current was reduced by 93 ± 7 %.

Under a variety of circumstances the diastolic [Ca2+]i showed a close association with pacemaker firing rate. The existence of a Na+‐Ca2+ exchanger and its estimated contribution to inward current during the pacemaker potential suggest that the Na+‐Ca2+ exchange current makes a contribution to pacemaker activity.
The effect of length on the relationship between tension and intracellular [Ca2+] in intact frog skeletal muscle fibres
Authors: Claflin Dennis R. , Morgan David L. , Julian Fred J.
Published: September 2010

The relationship between tension and intracellular calcium concentration ([Ca2+]i) in intact frog skeletal muscle fibres was determined at two fibre lengths, corresponding to mean sarcomere lengths (SL) of 2.2 and 2.9 μm. Tension and [Ca2+]i were recorded during the slow decline of tension following stimulation in the presence of cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca2+‐uptake pump inhibitor. [Ca2+]i was estimated by injecting the K+ salt form of the fluorescent dye fura‐2 into the fibres. Experimental temperature was 3.0 °C.

At a SL of 2.2 μm, where thick and thin filaments fully overlap, the [Ca2+]i corresponding to 50 % tension generation ([Ca2+]50) was 1.09 ± 0.02 μM (mean ± s.e.m., n= 61 contractions). At a SL of 2.9 μm, where overlap is approximately 50 %, the [Ca2+]50 was significantly lower, 0.69 ± 0.02 μM (n= 22 contractions). This is in agreement with previous results from skinned fibres.

The relationship between tension and [Ca2+]i was very steep, as reported previously from experiments at a SL of 2.2 μm in which the membrane permeant acetoxymethyl ester form of fura‐2 was used. The fall in tension from 90 to 10 % occurred in 0.12 ± 0.01 pCa units (mean ± s.e.m., n= 61) for a SL of 2.2 μm and 0.17 ± 0.01 pCa units (n= 22) for a SL of 2.9 μm, corresponding to Hill coefficients of 15.4 and 10.9, respectively.

We conclude that the increase in sensitivity of tension to [Ca2+] that occurs in skinned skeletal muscle fibres upon stretch also occurs in intact fibres, that the steepness of the relation between tension and [Ca2+]i in intact fibres reported previously cannot be attributed to the use of the acetoxymethyl ester form of fura‐2 to report [Ca2+]i, and that the steepness decreases as myofilament overlap decreases.
Cytoskeletal targeting of calponin in differentiated, contractile smooth muscle cells of the ferret
Authors: Parker Christopher A. , Takahashi Katsuhito , Tang Jay X. , Tao Terence , Morgan Kathleen G.
Published: September 2010

Biochemical and quantitative image analysis methods were used to investigate the anatomical basis for the previously described agonist‐induced redistribution of calponin.

At 140 nm resolution, the quantitative distribution of calponin in resting cells was statistically indistinguishable from that of filament bundles containing α‐smooth muscle actin and myosin, but was significantly different from that of filaments containing β‐non‐muscle actin. Conversely, in stimulated cells, the distribution of calponin was not significantly different from that of β‐actin filaments in the subplasmalemmal cell cortex but was significantly different from the distribution of α‐actin‐ and myosin‐containing filamentous bundles.

The distribution of calponin significantly differed from that of the intermediate filament proteins vimentin and desmin as well as that of the dense body protein α‐actinin either by ratio analysis of the subcellular distribution or by colocalization analysis.

The imaging results, although limited to 140 nm spatial resolution, suggested the hypothesis that the agonist‐induced redistribution involves the binding of calponin to isoform‐specific actin filaments. This hypothesis was tested by quantifying the relative affinity of calponin for purified α‐ and β‐actin. Light scattering measurements showed that calponin induces bundle formation with β‐actin more readily than α‐actin, indicating that calponin may be preferentially sequestered by β‐actin under appropriate conditions.

These results are consistent with a model whereby agonist activation decreases calponin's binding to filaments, but the tighter binding to β‐actin filaments results in a spatial redistribution of calponin to the submembranous cortex.
Spatio‐temporal receptive fields in carp retinal horizontal cells
Authors: Umino Osamu , Ushio Tomomi
Published: September 2010

The dynamics of the receptive fields of retinal horizontal cells were examined by applying a spatio‐temporal modulated light signal to the retina.

The spatio‐temporal receptive fields of both cone‐ and rod‐driven horizontal cells, estimated through cross‐correlation between the modulated light signal and the cells’ responses, showed their receptive fields (the space‐dependent component) to be reduced in size with time.

In cone‐driven horizontal cells, the reduction in receptive field size was initially small but then rapidly became prominent with time. The time to peak of the time‐dependent component of spatio‐temporal receptive fields did not depend on the distance from the centre.

Application of a small amount of Co2+, an agent blocking the cone‐driven horizontal cells’ feedback action on cones, or GABA, resulted in a reversal of the time‐dependent shrinkage of receptive fields to time‐dependent expansion.

In rod‐driven horizontal cells, the receptive field shrinkage was slow. The time to peak of the time‐dependent component decreased with the distance from the centre.

Image processing experiments examining the response pattern in the horizontal cell layer (neural image) to a moving square of light showed smudging of the neural image when the time‐dependent receptive field expansion was present, while there was essentially no smudging under conditions of receptive field shrinkage.
Role of spinal premotoneurones in mediating corticospinal input to forearm motoneurones in man
Authors: Pauvert V. , Pierrot‐Deseilligny E. , Rothwell J. C.
Published: September 2010

Evidence was sought to support the suggestion that corticospinal input can be relayed to motoneurones (MNs) via a population of interneurones (premotoneurones) in the cervical cord, and that this pathway operates in parallel with the direct monosynaptic pathway.

Single motor units were recorded in forearm muscles and post‐stimulus time histograms (PSTHs) of their firing pattern were constructed during voluntary activation. Weak transcranial magnetic stimulation of the contralateral motor cortex was used to produce a small facilitation in the PSTH. We then examined how the size of this peak was affected by low threshold electrical stimulation of either the homonymous muscle nerve or the musculo‐cutaneous nerve at various interstimulus intervals (ISIs).

Homonymous nerve stimulation had the following characteristics: (a) the cortical peak was facilitated when stimuli were timed so that both inputs arrived simultaneously at the MN; (b) the amount of facilitation was only slightly greater than the sum of the effects of each stimulus given alone; and (c) facilitation affected even the earliest bins of the cortically evoked peak. These three features are consistent with a monosynaptic input onto the MN from both sources.

Stimulation of the musculo‐cutaneous nerve (which has no monosynaptic connections with forearm MNs) had no effect at similar timings. It (a) produced facilitation only at longer intervals corresponding to an extra central delay of 4‐6 ms; (b) always gave a significantly larger facilitation than expected from the algebraic sum of the effects of each stimulus given alone; and (c) never affected the earliest bins of the cortical peak. These features are compatible with interaction of peripheral and cortical inputs at a population of premotoneurones.

These results confirm the suggestion that premotoneurones mediate part of the cortical command to MNs innervating forearm muscles.

Excitation is followed by an inhibition which may almost completely suppress the cortical peak. It is suggested that cortical and musculo‐cutaneous volleys also converge onto inhibitory interneurones projecting to the premotoneuronal pool.
Detection of movements of the human forearm during and after co‐contractions of muscles acting at the elbow joint
Authors: Wise A. K. , Gregory J. E. , Proske U.
Published: September 2010

We report here observations on the effects of muscle contraction history on thresholds for the detection of movements at the elbow joint of human subjects. Detection thresholds were measured in the direction of flexion or extension to movements of the relaxed forearm at a speed of 0.2 deg s−1 with the elbow at 90 deg.

As reported previously, thresholds for movements in the direction of extension were lower than in the direction of flexion after a conditioning co‐contraction of elbow muscles with the arm flexed by 30 deg from its mid‐position (hold‐short). After a co‐contraction with the arm held extended by 30 deg (hold‐long), thresholds were lower in the direction of flexion.

Here we have made two additional observations. Thresholds for movements of the passive forearm after a co‐contraction at the 90 deg test position (hold‐test) were low, both in the direction of flexion and extension. Secondly, when thresholds were measured while subjects were carrying out a co‐contraction of forearm muscles (15‐20 % maximum voluntary contraction), thresholds were much higher.

It is concluded that muscle contraction history is an important factor to consider when making measurements of movement thresholds at the relaxed elbow joint. It is speculated that during an active contraction increases in muscle spindle discharges evoked by fusimotor activity lead to the rise in movement detection threshold.
SOME EFFECTS OF SPINAL CORD LESIONS ON EXPERIENCED EMOTIONAL FEELINGS
Authors: Hohmann George W.
Published: September 2010

In structured interviews, 26 adult males with spinal cord lesions at varying levels were asked to compare certain of their emotional feelings before and after injury. The investigator, himself a paraplegic, knew all subjects well. The major findings follow.

Significant decreases in experienced feelings of anger, sexual excitement, fear, and an over‐all estimate of change were found.

A significant increase in feelings of sentimentality was reported.

Although spinal cord lesions decrease some emotional feelings, overt emotional behavior may continue to be displayed.

Support was offered for the belief that disruption of the autonomic nervous system and its afferent return causes notable changes in experienced emotional feelings. A trend was noted which suggests that the more extensive the disruption, the greater the decrease in some emotional feelings.
A SHIELDED SOUND‐ATTENUATING CHAMBER
Authors: Lee Bernard
Published: September 2010

An electrically shielded sound‐attenuating chamber for psychophysiological work which was constructed of readily available building supplies is described.
AFFECT, VERBALIZATION, AND DIRECTIONAL FRACTIONATION OF AUTONOMIC RESPONSES
Authors: Campos Joseph J. , Johnson Harold J.
Published: September 2010

An experiment was designed to evaluate the effects of pleasantness and un‐pleasantness and instructions to verbalize on directional fractionation of autonomic response. Degrees of pleasant and unpleasant stimulation were presented to Ss under two verbalization instruction conditions. Something like directional fractionation was found for the very unpleasant no‐verbalization condition only, but the pattern disappeared upon the addition of a later‐verbalization requirement. More generally, it was found without exception that conditions of no verbalization are accompanied by cardiac deceleration, regardless of degree or of quality of affect, while later verbalization conditions produce cardiac acceleration, again regardless of degree or quality of affect. The authors conclude that verbalization instructions are important for determining the degree and direction of cardiac activation.
CONDITIONING OF THE ELECTRODERMAL ORIENTING RESPONSE
Authors: Gale Elliot N. , Stern John A.
Published: September 2010

The present study demonstrates that the orienting response (OR) to the conditional stimulus can be conditioned with a delayed differential conditioning paradigm. Controls utilized were two “sensitization” and one backward‐trace differential conditioning group. Conditioned ORs, conditioned anticipatory responses, and conditioned responses at latency of unconditioned response in the absence of the unconditioned stimulus were all demonstrated. In the backward conditioning group the amplitude of the OR to the tone preceded by shock was lower than that found for any other group. Refractoriness of the peripheral components of the electrodermal response (EDR) are invoked to account for this finding.
A METHOD TO ESTABUSH ELECTRICALLY GOOD CONTACTS WITH UNRESTRAINED RATS
Authors: Doerr Hans O.
Published: September 2010

A technique for implanting chronically indwelling recording‐stimulating electrodes in rats has been developed. It allows recording of bioelectrical potentials and/or administration of specified amounts of electrical shock with unrestrained animals.
Concomitant Heart Rate and Eyeblink Pavlovian Conditioning in Human Subjects as a Function of Interstimulus Interval
Authors: Prescott Louisa , Durkin Martin , Furchtgott Ernest , Powell D.A.
Published: September 2010

Pavlovian heart rate and eyeblink conditioning were simultaneously assessed in human subjects. Tone durations of 0.6, 1.1, and 2.1 s were employed in separate groups of subjects as the conditioned stimulus. A 100‐ms corneal airpuff, which served as the unconditioned stimulus, overlapped the last 100 ms of the tone in each group, thus producing interstimulus intervals of 0.5, 1.0, and 2.0 s. Other groups of pseudoconditioning subjects received explicitly unpaired tone and airpuff presentations of identical durations but in a pseudorandom sequence so that they never occurred together. The best eyeblink conditioning was observed in the group with the .5‐s interstimulus interval, although the 1.0‐s group also demonstrated some evidence of eyeblink conditioning. The group with the 2.0‐s interstimulus interval showed a lower overall rate of conditioned response occurrence and the highest rate of pseudoconditioned responding. The conditioned heart rate response in all three conditioning groups consisted of cardiac decelerations, but tone‐evoked cardiac accelerations were observed in the pseudoconditioning groups. The magnitude of the cardiac deceleration was comparable in all three conditioning groups.
Cardiac Autonomic Mechanisms Associated with Borderline Hypertension under Varying Behavioral Demands: Evidence for Attenuated Parasympathetic Tone but Not for Enhanced Beta‐Adrenergic Activity
Authors: Grossman Paul , Brinkman Annemiek , De Vries Johan
Published: September 2010

Elevated blood pressure in psychophysiological studies of borderline hypertension is frequently attributed to the effects of increased sympathetic tone, and with few exceptions, the potential parasympathetic contributions have not been considered. Furthermore, of the investigations that have addressed vagal influences upon blood pressure, most have employed invasive pharmacological assessment of parasympathetic tone.

In this study, cardiac parasympathetic and beta‐adrenergic influences in borderline hypertension were evaluated noninvasively employing respiratory sinus arrhythmia as a vagal index and pree‐jection period as a sympathetic index of cardiac functioning. Subjects were 30 borderline hypertensive and 23 normotensive males (age range, 24–45 years). The ECG, blood pressure, impedance cardiography, and respiration were measured during two baselines (initial and post‐task), a memory‐comparison reaction time task, the cold pressor, and CO2‐rebreathing.

Results indicated tonic differences between groups in all cardiovascular variables across tasks, with the exception of pre‐ejection period, which showed no group effects at all. Hypertensives additionally manifested somewhat heightened systolic blood pressure reactivity and attenuated cardiac parasympathetic responsivity to specific tasks.

Our findings provide no support for an exaggerated cardiac beta‐adrenergic tonic level or reactivity in borderline hypertensives. On the other hand, the consistently lower magnitude of respiratory sinus arrhythmia in our hypertensives suggests that reduced parasympathetic control may be involved in the pathophysiology of hypertension.
Analysis of Pattern‐Reversal Visual Evoked‐Potential Topography: Replicability in Normal Subjects and Comparisons with Alzheimer's Disease
Authors: Pollock Vicki E. , Cliff Norman
Published: September 2010

This paper reports two studies using multivariate analysis to aid the interpretation of crosscoherence of multiple electrode sites in evoked potential responses. In the first study, the replicability of principal components and multidimensional scaling was evaluated by applying both methods to pattern‐reversal visual evoked potentials recorded from 28 scalp sites in two subgroups of sex‐ and age‐matched healthy subjects, and then comparing the results. Four dimensions replicated in the two initial multidimensional scaling solutions and appeared to reflect differences in: 1) anterior versus posterior scalp areas, 2) laterality, 3) separation of frontal and occipital sites from other scalp regions, and 4) proximal versus distal placements. The initial principal components did not match well in the two groups, but rotation to congruence improved their replicability and ultimately yielded axes similar to those of the multidimensional scaling dimensions. In the second study, Alzheimer's disease and sex‐ and age‐matched control subjects were evaluated. The four axes identified were the same as those described above, but after the solutions were rotated to align them, the group differences appeared negligible. Examination of the components and dimensions from both studies showed some consistent departures from being merely reflectors of site location, and the apparently visual dimension appeared clearly in all four groups. Judged on the basis of initial interpretability and replicability of the solutions, the results suggest that multidimensional scaling, with appropriate transformation, may provide an effective tool for analyzing pattern‐reversal visual evoked‐potential topography.
The association between lithium carbonate and smooth pursuit eye tracking among first‐episode patients with psychotic affective disorders
Authors: GOODING DIANE C. , IACONO WILLIAM G. , KATSANIS JOANNA , BEISER MORTON , GROVE WILLIAM M.
Published: September 2010

The association between treatment with lithium carbonate and smooth pursuit eye tracking performance was investigated in first‐episode patients with psychotic affective disorders. The horizontal pursuit performance of patients with major depression and bipolar disorder who were receiving lithium carbonate was contrasted with that of patients not receiving lithium carbonate. In addition, the accuracy and quality of pursuit eye tracking was examined in bipolar patients whose lithium status changed from the time of initial testing to the time of retest 10 months later. For the combined group of depressed and bipolar patients, treatment with lithium carbonate was not associated with worse pursuit performance. Bipolar disordered patients on lithium did not differ in tracking proficiency from those not on lithium; bipolar patients whose lithium status changed from intake to retest also did not display a significant change in pursuit performance.