bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear translocation of the transcription factor STAT3 in the guinea pig brain during systemic or localized inflammation
Authors: Rummel Christoph , Hübschle Thomas , Gerstberger Rüdiger , Roth Joachim
Published: February 2004

The purpose of the present study was to investigate a possible lipopolysaccharide (LPS)‐induced activation of brain cells that is mediated by the pleiotropic cytokine interleukin‐6 (IL‐6) and its transcription factor STAT3 during systemic or localized inflammation. In guinea pigs, intra‐arterial (i.a., 10 μg kg−1) or intraperitoneal (i.p., 30 μg kg−1) injections of bacterial LPS cause a systemic inflammatory response which is accompanied by a robust fever. A febrile response can also be induced by administration of LPS into artificial subcutaneously implanted Teflon chambers (s.c. 100 or 10 μg kg−1), which reflects an experimental model that mimics local tissue inflammation. Baseline plasma levels of bioactive IL‐6 determined 60 min prior to injections of LPS or vehicle amounted to 35–80 international units (i.u.) ml−1. Within 90 min of LPS injection, plasma IL‐6 rose about 1000‐fold in the groups injected i.a. or i.p., about 50‐fold in the group injected s.c. with 100 μg kg−1 LPS, and only 5‐fold in guinea pigs injected with the lower dose of LPS (10 μg kg−1). At this time point, a distinct nuclear translocation pattern of the transcription factor STAT3 became evident in several brain structures. Amongst those, the sensory circumventricular organs known to lack a tight blood–brain barrier such as the area postrema, the vascular organ of the lamina terminalis and the subfornical organ, as well as the hypothalamic supraoptic nucleus showed intense nuclear STAT3 signals in the i.a. or i.p. injected groups. In contrast a moderate (s.c. group, 100 μg kg−1), or even no (s.c. group, 10 μg kg−1), nuclear STAT3 translocation occurred in response to s.c. injections of LPS. These results suggest that STAT3‐mediated genomic activation of target gene transcription in brain cells occurred only in those cases in which sufficiently high concentrations of circulating IL‐6 were formed during systemic (i.a.. and i.p. groups) or localized (s.c. group, 100 μg kg−1) inflammation.
Capacitance measurements of exocytosis in mouse pancreatic α‐, β‐ and δ‐cells within intact islets of Langerhans
Authors: Göpel Sven , Zhang Quan , Eliasson Lena , Ma Xiao‐Song , Galvanovskis Juris , Kanno Takahiro , Salehi Albert , Rorsman Patrik
Published: February 2004

Capacitance measurements of exocytosis were applied to functionally identified α‐, β‐ and δ‐cells in intact mouse pancreatic islets. The maximum rate of capacitance increase in β‐cells during a depolarization to 0 mV was equivalent to 14 granules s−1, <5% of that observed in isolated β‐cells. β‐Cell secretion exhibited bell‐shaped voltage dependence and peaked at +20 mV. At physiological membrane potentials (up to ∼−20 mV) the maximum rate of release was ∼4 granules s−1. Both exocytosis (measured by capacitance measurements) and insulin release (detected by radioimmunoassay) were strongly inhibited by the L‐type Ca2+ channel blocker nifedipine (25 μm) but only marginally (<20%) affected by the R‐type Ca2+ channel blocker SNX482 (100 nm). Exocytosis in the glucagon‐producing α‐cells peaked at +20 mV. The capacitance increases elicited by pulses to 0 mV exhibited biphasic kinetics and consisted of an initial transient (150 granules s−1) and a sustained late component (30 granules s−1). Whereas addition of the N‐type Ca2+ channel blocker ω‐conotoxin GVIA (0.1 μm) inhibited glucagon secretion measured in the presence of 1 mm glucose to the same extent as an elevation of glucose to 20 mm, the L‐type Ca2+ channel blocker nifedipine (25 μm) had no effect. Thus, glucagon release during hyperglycaemic conditions depends principally on Ca2+‐influx through N‐type rather than L‐type Ca2+ channels. Exocytosis in the somatostatin‐secreting δ‐cells likewise exhibited two kinetically separable phases of capacitance increase and consisted of an early rapid (600 granules s−1) component followed by a sustained slower (60 granules s−1) component. We conclude that (1) capacitance measurements in intact pancreatic islets are feasible; (2) exocytosis measured in β‐cells in situ is significantly slower than that of isolated cells; and (3) the different types of islet cells exhibit distinct exocytotic features.
Spreading dilatation in rat mesenteric arteries associated with calcium‐independent endothelial cell hyperpolarization
Authors: Takano Hiromichi , Dora Kim A. , Spitaler Michaela M. , Garland Chris J.
Published: February 2004

Both ACh and levcromakalim evoke smooth muscle cell hyperpolarization and associated relaxation in rat mesenteric resistance arteries. We investigated if they could evoke conducted vasodilatation along isolated arteries, whether this reflected spreading hyperpolarization and the possible mechanism involved. Focal micropipette application of either ACh, to stimulate endothelial cell muscarinic receptors, or levcromakalim, to activate smooth muscle KATP channels, each evoked a local dilatation (88 ± 14%, n= 6 and 92 ± 6% reversal of phenylephrine‐induced tone, n= 11, respectively) that rapidly spread upstream (at 1.5 mm 46 ± 19%, n= 6 and 57 ± 13%, n= 9) to dilate the entire isolated artery. The local dilatation to ACh was associated with a rise in endothelial cell [Ca2+]i (F/Ft = 0= 1.22 ± 0.33, n= 14) which did not spread beyond 0.5 mm (F/Ft = 0= 1.01 ± 0.01, n= 14), while the local dilatation to levcromakalim was not associated with any change in endothelial cell [Ca2+]i. In contrast, ACh and levcromakalim both stimulated local (12.7 ± 1.2 mV, n= 10 and 13.5 ± 4.7 mV, n= 10) and spreading (at 2 mm: 3.0 ± 1.1 mV, n= 5 and 4.1 ± 0.7 mV, n= 5) smooth muscle hyperpolarization. The spread of hyperpolarization could be prevented by cutting the artery, so was not due to a diffusible agent. Both the spreading dilatation and hyperpolarization were endothelium dependent. The injection of propidium iodide into either endothelial or smooth muscle cells revealed extensive dye coupling between the endothelial cells, but limited coupling between the smooth muscle cells. Some evidence for heterocellular spread of dye was also evident. Together, these data show that vasodilatation can spread over significant distances in mesenteric resistance arteries, and suggest this reflects an effective coupling between the endothelial cells to facilitate [Ca2+]i‐independent spread of hyperpolarization.
A Putative Ca
2+
and Calmodulin-Dependent Protein Kinase Required for Bacterial and Fungal Symbioses
Authors: Lévy Julien , Bres Cécile , Geurts René , Chalhoub Boulos , Kulikova Olga , Duc Gérard , Journet Etienne-Pascal , Ané Jean-Michel , Lauber Emmanuelle , Bisseling Ton , Dénarié Jean , Rosenberg Charles , Debellé Frédéric
Published: February 2004

Legumes can enter into symbiotic relationships with both nitrogen-fixing bacteria (rhizobia) and mycorrhizal fungi. Nodulation by rhizobia results from a signal transduction pathway induced in legume roots by rhizobial Nod factors.
DMI3
, a
Medicago truncatula
gene that acts immediately downstream of calcium spiking in this signaling pathway and is required for both nodulation and mycorrhizal infection, has high sequence similarity to genes encoding calcium and calmodulin-dependent protein kinases (CCaMKs). This indicates that calcium spiking is likely an essential component of the signaling cascade leading to nodule development and mycorrhizal infection, and sheds light on the biological role of plant CCaMKs.
Local Ordering in the Pseudogap State of the High-
T
c
Superconductor Bi
2
Sr
2
CaCu
2
O
8+δ
Authors: Vershinin Michael , Misra Shashank , Ono S. , Abe Y. , Ando Yoichi , Yazdani Ali
Published: February 2004

We report atomic-scale characterization of the pseudogap state in a high-
T
c
superconductor, Bi
2
Sr
2
CaCu
2
O
8+δ
. The electronic states at low energies within the pseudogap exhibit spatial modulations having an energy-independent incommensurate periodicity. These patterns, which are oriented along the copper-oxygen bond directions, appear to be a consequence of an electronic ordering phenomenon, the observation of which correlates with the pseudogap in the density of electronic states. Our results provide a stringent test for various ordering scenarios in the cuprates, which have been central in the debate on the nature of the pseudogap and the complex electronic phase diagram of these compounds.
Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst
Authors: Hwang Woo Suk , Ryu Young June , Park Jong Hyuk , Park Eul Soon , Lee Eu Gene , Koo Ja Min , Jeon Hyun Yong , Lee Byeong Chun , Kang Sung Keun , Kim Sun Jong , Ahn Curie , Hwang Jung Hye , Park Ky Young , Cibelli Jose B. , Moon Shin Yong
Published: February 2004

Somatic cell nuclear transfer (SCNT) technology has recently been used to generate animals with a common genetic composition. In this study, we report the derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell morphology and cell surface markers and were capable of differentiating into embryoid bodies in vitro and of forming teratomas in vivo containing cell derivatives from all three embryonic germ layers in severe combined immunodeficient mice. After continuous proliferation for more than 70 passages, SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to the somatic nuclear donor cells. Although we cannot completely exclude the possibility that the cells had a parthenogenetic origin, imprinting analyses support a SCNT origin of the derived human ES cells.
IκB Kinase Is a Critical Regulator of Chemokine Expression and Lung Inflammation in Respiratory Syncytial Virus Infection
Authors: Haeberle Helene A. , Casola Antonella , Gatalica Zoran , Petronella Sharon , Dieterich Hans-Juergen , Ernst Peter B. , Brasier Allan R. , Garofalo Roberto P.
Published: February 2004

Respiratory syncytial virus (RSV) is the major etiologic agent of severe epidemic lower respiratory tract infections in infancy. Airway mucosal inflammation plays a critical role in the pathogenesis of RSV disease in both natural and experimental infections. RSV is among the most potent biological stimuli that induce the expression of inflammatory genes, including those encoding chemokines, but the mechanism(s) that controls virus-mediated airway inflammation in vivo has not been fully elucidated. Herein we show that the inoculation of BALB/c mice with RSV results in rapid activation of the multisubunit IκB kinase (IKK) in lung tissue. IKK transduces upstream activating signals into the rate-limiting phosphorylation (and proteolytic degradation) of IκBα, the inhibitory subunit that under normal conditions binds to the nuclear factor (NF)-κB complex and keeps it in an inactive cytoplasmic form. Mice treated intranasally with interleukin-10 or with a specific cell-permeable peptide that blocks the association of the catalytic subunit IKKβ with the regulatory protein NEMO showed a striking reduction of lung NF-κB DNA binding activity, chemokine gene expression, and airway inflammation in response to RSV infection. These findings suggest that IKKβ may be a potential target for the treatment of acute or chronic inflammatory diseases of the lung.
The AU-Rich RNA Recombination Hot Spot Sequence of
Brome Mosaic Virus
Is Functional in Tombusviruses: Implications for the Mechanism of RNA Recombination
Authors: Shapka Natalia , Nagy Peter D.
Published: February 2004

RNA recombination can be facilitated by recombination signals present in viral RNAs. Among such signals are short sequences with high AU contents that constitute recombination hot spots in
Brome mosaic virus
(BMV) and retroviruses. In this paper, we demonstrate that a defective interfering (DI) RNA, a model template associated with
Tomato bushy stunt virus
(TBSV), a tombusvirus, undergoes frequent recombination in plants and protoplast cells when it carries the AU-rich hot spot sequence from BMV. Similar to the situation with BMV, most of the recombination junction sites in the DI RNA recombinants were found within the AU-rich region. However, unlike BMV or retroviruses, where recombination usually occurred with precision between duplicated AU-rich sequences, the majority of TBSV DI RNA recombinants were imprecise. In addition, only one copy of the AU-rich sequence was essential to promote recombination in the DI RNA. The selection of junction sites was also influenced by a putative
cis
-acting element present in the DI RNA. We found that this RNA sequence bound to the TBSV replicase proteins more efficiently than did control nonviral sequences, suggesting that it might be involved in replicase “landing” during the template switching events. In summary, evidence is presented that a tombusvirus can use the recombination signal of BMV. This supports the idea that common AU-rich recombination signals might promote interviral recombination between unrelated viruses.
Analysis of the 3′
cis
-Acting Elements of Rubella Virus by Using Replicons Expressing a Puromycin Resistance Gene
Authors: Chen Min-Hsin , Frolov Ilya , Icenogle Joseph , Frey Teryl K.
Published: February 2004

A rubella virus (RUB) replicon, RUBrep/PAC, was constructed and used to map the 3′
cis
-acting elements (3′ CSE) of the RUB genome required for RUB replication. The RUBrep/PAC replicon had the structural protein open reading frame partially replaced by a puromycin acetyltransferase (PAC) gene. Cells transfected with RUBrep/PAC transcripts expressed the PAC gene from the subgenomic RNA, were rendered resistant to puromycin, and thus survived selection with this drug. The relative survival following puromycin selection of cells transfected with transcripts from RUBrep/PAC constructs with mutations in the 3′ CSE varied. The 3′ region necessary for optimal relative survival consisted of the 3′ 305 nucleotides (nt), a region conserved in RUB defective-interfering RNAs, and thus this region constitutes the 3′ CSE. Within the 3′ CSE, deletions in the ∼245 nt that overlap the 3′ end of the E1 gene resulted in reduced relative survivals, ranging from 20 to <1% of the parental replicon survival level while most mutations within the ∼60-nt 3′ untranslated region (UTR) were lethal. None of the 3′ CSE mutations affected in vitro translation of the nonstructural protein open reading frame (which is 5′ proximal in the genome and encodes the enzymes involved in virus RNA replication). In cells transfected with replicons with 3′ CSE mutations that survived antibiotic selection (i.e., those with mutations in the region of the 3′ CSE that overlaps the E1 coding region), the amount of replicon-specific minus-strand RNA was uniform; however, the accumulation of both plus-strand RNA species, genomic and subgenomic, varied widely, indicating that this region of the RUB 3′ CSE affects plus-strand RNA accumulation rather than minus-strand RNA synthesis.
Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine
Authors: Ranga Udaykumar , Shankarappa Raj , Siddappa Nagadenahalli B. , Ramakrishna Lakshmi , Nagendran Ramalingam , Mahalingam Marthandan , Mahadevan Anita , Jayasuryan Narayana , Satishchandra Parthasarathy , Shankar Susarla K. , Prasad Vinayaka R.
Published: February 2004

Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is correlated with increased monocyte migration to the brain, and the incidence of HAD among otherwise asymptomatic subjects appears to be lower in India than in the United States and Europe (1 to 2% versus 15 to 30%). Because of the genetic differences between HIV-1 strains circulating in these regions, we sought to identify viral determinants associated with this difference. We targeted Tat protein for these studies in view of its association with monocyte chemotactic function. Analyses of Tat sequences representing nine subtypes revealed that at least six amino acid residues are differentially conserved in subtype C Tat (C-Tat). Of these, cysteine (at position 31) was highly (>99%) conserved in non-subtype C viruses and more than 90% of subtype C viruses encoded a serine. We hypothesized a compromised chemotactic function of C-Tat due to the disruption of CC motif and tested it with the wild type C-Tat (CS) and its two isogenic variants (CC and SC) derived by site-directed mutagenesis. We found that the CS natural variant was defective for monocyte chemotactic activity without a loss in the transactivation property. While the CC mutant is functionally competent for both the functions, in contrast, the SC mutant was defective in both. Therefore, the loss of the C-Tat chemotactic property may underlie the reduced incidence of HAD; although not presenting conclusive evidence, this study provides the first evidence for a potential epidemiologic phenomenon associated with biological differences in the subtype C viruses.
High-Speed Micro-Thermal Focusing Field-Flow Fractionation of Micron-Size Particles
Authors: Ananieva Irina A. , Menshikova Anastasia Yu. , Evseeva Tatiana G. , Janča Josef
Published: February 2004

Micron-size polystyrene-based latex particles were separated by using new micro-thermal field-flow fractionation (micro-TFFF). The order of retention from the largest to the smallest particles that appears at high field strength and high flow rate corresponds to the focusing mechanism which itself is a consequence of the lift forces acting on the particles. The mechanism of steric exclusion can only be effective at low flow rates of the carrier liquid. Whenever high-speed separation was performed, the focusing effect clearly dominated the FFF mechanism. This application of micro-TFFF in focusing mode to the separation of the particles is the first one published. As a result, micro-TFFF thus became a very universal technique for the separation of synthetic and natural macromolecules and of particles of various origin and size up to large (micron-size) diameter.
Long term outcome up to 30 years after the Mustard or Senning operation: a nationwide multicentre study in Belgium
Authors: Moons P , Gewillig M , Sluysmans T , Verhaaren H , Viart P , Massin M , Suys B , Budts W , Pasquet A , De Wolf D , Vliers A
Published: February 2004

Objective: To assess long term outcome of patients who underwent Mustard or Senning repair for transposition of the great arteries up to 30 years earlier.

Design: Retrospective review of medical records.

Setting: The six university hospitals in Belgium with paediatric cardiology departments.

Patients: 339 patients were reviewed, of whom 124 underwent the Mustard procedure and 215 the Senning procedure. This represents almost the entire population of patients in Belgium with either simple or complex transposition.

Main outcome measures: Mortality, morbidity, functional abilities, social integration.

Results: Overall mortality was 24.2%. Early mortality (⩽ 30 days after surgery) accounted for 16.5%, late mortality for 7.7%. Actuarial survival of early survivors at 10, 20, and 30 years after surgery was 91.7%, 88.6%, and 79.3%, respectively. Patients in the Senning cohort had a slightly better survival rate than those in the Mustard cohort (NS). Baffle obstruction occurred more often after Mustard repair (15.3%) than after the Senning procedure (1.4%). Arrhythmia-free survival did not differ between the two cohorts, but was determined by the complexity of the transposition. Survivors of the Senning cohort had better functional status, and tended to engage in more sports activities.

Conclusions: The long term outcome for patients surviving the Mustard or Senning operation was favourable in terms of late mortality, morbidity, functional, and social status. Overall mortality in the Senning cohort did not differ from the Mustard group, but Senning patients had better functional status, greater participation in sports activities, and fewer baffle related problems.
Spilled gall stones during laparoscopic cholecystectomy: a review of the literature
Authors: Sathesh-Kumar T , Saklani A P , Vinayagam R , Blackett R L
Published: February 2004

Laparoscopic cholecystectomy is associated with spillage of gall stones in 5%–40% of procedures, but complications occur very rarely. There are, however, isolated case reports describing a range of complications occurring both at a distance from and near to the subhepatic area. This review looks into the various modes of presentation, ways to minimise spillage, treating the complications, and the legal implications.
Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9) polymorphism with bleeding complication
Authors: Malhi H , Atac B , Daly A K , Gupta S
Published: February 2004

Drug metabolism may be perturbed by genetically determined differences in the metabolic activity of cytochrome P450 enzymes. The authors encountered extensive bleeding in a patient receiving warfarin for anticoagulation after the introduction of celecoxib, an anti-inflammatory drug. As the CYP2C9 enzyme metabolises these drugs, it was determined whether variant alleles were responsible for altering warfarin handling. Genetic analysis established that the patient was a compound heterozygote with CYP2C9*2 and *3 variant alleles, which exhibit lower drug metabolising capacity and enhance susceptibility to drug toxicity.
Neonatal congenital microvillus atrophy
Authors: Pecache N , Patole S , Hagan R , Hill D , Charles A , Papadimitriou J M
Published: February 2004

Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with onset either in the first 72 hours of life (early onset) or at 6–8 weeks after birth (late onset). To date over 30 cases have been reported worldwide. The prognosis for this life threatening condition continues to be poor. Therapeutic agents like somatostatin and epidermal growth factor are either ineffective or of marginal benefit. Overall five year survival after small bowel transplantation is currently ∼50%. The following brief review is aimed towards helping neonatologists/perinatologists in the early diagnosis, and management of CMVA and in counselling the parents appropriately.
Clinical and laboratory observations of tuberculosis at a Mumbai (India) clinic
Authors: Gothi D , Joshi J M
Published: February 2004

Objectives

To study the positivity of sputum acid fast bacilli (AFB) smears in patients with pulmonary tuberculosis using 24 hour sputum collection. To detect HIV seropositivity in patients suffering from tuberculosis, and to analyse the pattern of tuberculosis disease in this subgroup. To determine the outcome of patients treated with directly observed therapy.

Setting

The tuberculosis referral unit of a tertiary care hospital.

Design

A total of 893 consecutive patients with tuberculosis, diagnosed between 1 November 2000 and 30 September 2002, were included in the study. An HIV test was performed in all patients, with adequate counselling and informed consent. Treatment was prescribed as per World Health Organisation treatment categories.

Results

Out of 893 patients with tuberculosis, 695 had pulmonary tuberculosis and 198 had extrapulmonary tuberculosis. Out of the 695 pulmonary tuberculosis patients, 673 (96.8%) were sputum smear AFB positive. Overall, 71 patients (8.0%) were HIV positive. The pattern of tuberculosis was the same in HIV seropositive and seronegative patients. Treatment outcome could be analysed in 112 out of 150 patients: 78 patients (70%) were declared cured or completed treatment.

Conclusions

Sputum smear AFB could be a very sensitive test when a large quantity of sputum is used. The presence of HIV coinfection does not alter the clinical presentation. Only 70% of patients treated were cured/completed treatment, in spite of a strict directly observed therapy.
Evaluation of flexible sigmoidoscopy as an investigation for “left sided” colorectal symptoms
Authors: Papagrigoriadis S , Arunkumar I , Koreli A , Corbett W A
Published: February 2004

Background

Colonoscopy is the best way of imaging the colon with concurrent biopsy and treatment. However it is expensive, requires full bowel preparation, and carries a risk of complications. Flexible sigmoidoscopy is an alternative way to investigate symptoms that raise the suspicion of a lesion of the rectum or left colon.

Aim of the study

To evaluate flexible sigmoidoscopy as the main investigation for “left sided” colorectal symptoms.

Methods

The clinical records of 317 patients who were assessed at a colorectal specialist clinic and were thought to have a suspicion of a lesion of the rectum or left colon were retrospectively reviewed. All patients had flexible sigmoidoscopy as the primary investigation. Primary outcome was the diagnostic yield of flexible sigmoidoscopy and secondary outcomes were any additional colonic investigations required, failure rates, and complication rates.

Results

Three hundred and sixteen patients who had flexible sigmoidoscopy with the above criteria were retrospectively analysed. Twenty four procedures (7.6%) had to be abandoned because of poor bowel preparation. The examination was considered complete when it reached the splenic flexure, which was the case in 205 cases (65%).

In 137 flexible sigmoidoscopies (43.3%) there were no abnormal findings. Of the remaining 179 a carcinoma of the rectum or colon was found in 28 cases (8.8%) and one or more polyps was found in 57 (18%) cases. On the basis of the findings it was calculated that 31% of the patients would require an additional investigation for further imaging of the right colon.

Discussion

Although flexible sigmoidoscopy has a high yield of pathologies when carried out by a specialist colorectal clinic, the presence of those pathologies makes the full imaging of the whole colon with an additional investigation necessary. Therefore the cost efficiency of flexible sigmoidoscopy is questionable. Although flexible sigmoidoscopy is indicated for certain patients, it cannot replace colonoscopy as the main investigation used by a specialist colorectal clinic.
A questionnaire survey of stress and bullying in doctors undertaking research
Authors: Stebbing J , Mandalia S , Portsmouth S , Leonard P , Crane J , Bower M , Earl H , Quine L
Published: February 2004

Background

Research is an increasingly important aspect of higher medical training for many doctors. Studies investigating sources of stress, isolation, and workplace bullying have not previously sought information in this setting.

Methods

An internet based questionnaire survey of doctors undertaking research (n = 259) was conducted to examine stressors and levels of job satisfaction in this potentially vulnerable group. In order to assess overall levels of satisfaction, we asked whether doctors would recommend their research post to a colleague.

Results

There was a statistically significant association between those who would not recommend their post to a colleague and those who had difficulties in arranging funding and in writing up (p<0.001). Further significant correlations were found between dissatisfaction with the post and lack of help, support, and advice from supervisors and colleagues, wanting to change supervisors, experience of the major categories of workplace bullying, and having an inadequate clinical commitment (p<0.001). When the significant variables were entered into a multivariate analysis, the results showed that dissatisfaction was associated with wanting to change supervisors and with a threat to professional status.

Conclusions

Stress and bullying are common in doctors undertaking research. These findings have important implications for medical training and for doctors choosing research projects. Setting up systems of support may have important benefits.
Co-occurrence of thyroid binding globulin excess and a pituitary macroadenoma containing thyroid stimulating hormone-producing cells
Authors: Soubhi Nizam M , Kennedy L
Published: February 2004

A patient is described in whom thyroid binding globulin (TBG) excess was found in association with a pituitary macroadenoma containing thyroid stimulating hormone (TSH)-producing cells, and the potential for diagnostic confusion arising from this unusual combination of endocrine disorders is discussed. The patient presented with visual field disturbance, and magnetic resonance imaging led to the diagnosis of a pituitary tumour. Raised levels of total thyroxine and triiodothyronine along with normal TSH levels suggested the possibility of a TSH-secreting pituitary adenoma. Immunostaining of the tumour removed at transsphenoidal surgery confirmed the presence of TSH-producing cells. When raised total thyroxine and triiodothyronine levels persisted postoperatively, the diagnosis of TBG excess was confirmed. Use of free, rather than total, thyroid hormone assays would almost certainly have prevented the diagnostic confusion concerning possible TSH-secreting pituitary adenoma, but may have resulted in the TBG excess being overlooked entirely.
Retired physicians: a survey study by the Turkish Medical Association
Authors: Gökçe-Kutsal Y , Özçakar L , Arslan Ş , Sayek F
Published: February 2004

Background

The aim of this study was to assess the quality of life of retired Turkish physicians. The focus was on their working conditions, their health status, and the impact of their disabilities on activities of daily life.

Methods

The survey was conducted using a 35 item questionnaire, which was distributed to the local medical chambers allied with the Turkish Medical Association and thereafter was mailed to retirees aged 65 years and older.

Results

Out of 680 physicians, 391 (57.5%) responded, and percentages are expressed according to the number of physicians answering each question. The ages of the physicians ranged between 65 years and 91 years with a mean of 72.57±5.22 years. Overall, 236 physicians (60.8%) were still actively carrying on their profession, and 152 (39.2%) were not. Of the physicians who were working, 0.8% classified their working conditions as very bad, 9.7% as unsatisfactory, 37.7% as satisfactory, 33.6% as good, and 18.2% as excellent. The number of physicians with a disability was 42 (11.8%). The number of days on which physicians were hindered in their daily tasks ranged between 0 and 30 days with a mean (SD) of 1.55 (4.88) days, and the amount of sick leave ranged between 0 and 365 days with a mean of 2.25 (21.08) days.

Conclusion

It is believed that planning for retirement in all its aspects should be a legitimate concern of all physicians. Recommendations for future retirees or the construction of guidelines for making this time of life enriching and a period of intellectual growth are awaited.
Echocardiography and the general physician
Authors: Heatlie G J , Giles M
Published: February 2004

Doctors from many medical specialties request echocardiography as part of their assessment of patients with a wide range of pathology. Recent advances in the technology and techniques of echocardiography are discussed. The role of echocardiography in acute medicine is reviewed and its place in general medicine is also discussed.
Poor outcome in primary intracerebral haemorrhage: results of a matched comparison
Authors: Barber M , Roditi G , Stott D J , Langhorne P
Published: February 2004

Background

Primary intracerebral haemorrhage (PICH) is associated with a poorer outcome than cerebral infarction. This study aimed to determine whether this is explained by the clinical severity of stroke.

Methods

An observational study of outcome in consecutive admissions with acute PICH and ischaemic stroke was undertaken. A nested case-control analysis, matched on a 1:2 basis for age, pre-stroke disability, early neurological impairment (Scandinavian Stroke Scale; SSS), and Oxfordshire Community Stroke Project classification was then performed. Follow up was at 30 days and at hospital discharge.

Results

Overall, 679 subjects were included in the analysis. Of these, 53 (8%) had PICH; this group had more severe initial neurological impairment (day 3 SSS 28 v 45 points, p<0.001) and a higher prevalence of total anterior circulation strokes (55% v 21%, p<0.001) than did the group admitted with ischaemic strokes. Outcomes were poorer in the PICH group, with 36% inpatient mortality and 68% of survivors having a day 30 modified Rankin Scale (MRS) of at least 3 (compared with 13% and 52%, respectively, in the ischaemic stroke group). Following matching for baseline clinical characteristics, the PICH group had a higher mortality, but this was not statistically significant; the day 30 MRS and institutionalisation rates in survivors were similar in the matched haemorrhage and infarct groups.

Conclusions

Compared with ischaemic stroke, PICH is associated with higher mortality and increased disability in survivors. The severity of clinical stroke is a major contributor to these poor outcomes; baseline characteristics, however, do not fully explain outcome differences.
Long uvula: an unusual cause of chronic cough
Authors: Pai V , Thomas H , Stewart C
Published: February 2004

Chronic cough is a distressing symptom for patients and parents in paediatric practice. Investigations of the child with persistent cough can be simple or complex depending on the underlying cause. There are some unusual reasons for chronic cough, which need to be kept in mind when investigating the cause. A case of a long, floppy uvula causing chronic cough through mechanical irritation of upper airway is reported.
Resolution of cryptosporidiosis with probiotic treatment
Authors: Pickerd N , Tuthill D
Published: February 2004

Cryptosporidium infection is usually self limited, but can be a life threatening illness in immunocompromised patients. Probiotics have been used successfully in the treatment of acute diarrhoea and they have also been shown to limit Cryptosporidium parvum infection in animal models. The first case of successful resolution of prolonged cryptosporidiosis with probiotic treatment is reported.
Body dysmorphic disorder
Authors: Veale D
Published: February 2004

Body dysmorphic disorder (BDD) is defined as a preoccupation with an “imagined” defect in one’s appearance. Alternatively, where there is a slight physical anomaly, then the person’s concern is markedly excessive. The preoccupation is associated with many time consuming rituals such as mirror gazing or constant comparing. BDD patients have a distorted body image, which may be associated with bullying or abuse during childhood or adolescence. Such patients have a poor quality of life, are socially isolated, depressed, and at high risk of committing suicide. They often have needless dermatological treatment and cosmetic surgery. The condition is easily trivialised and stigmatised. There is evidence for the benefit of cognitive behaviour therapy and selective serotonin reuptake inhibitors in high doses for at least 12 weeks, as in the treatment of obsessive-compulsive disorder. There is no evidence of any benefit of antipsychotic drugs or other forms of psychotherapy.
Felsenmeer persistence under non-erosive ice in the Torngat and Kaumajet mountains, Quebec and Labrador, as determined by soil weathering and cosmogenic nuclide exposure dating
Authors: Marquette Geneviève C , Gray James T , Gosse John C , Courchesne François , Stockli Lisa , Macpherson Gwen , Finkel Robert
Published: February 2004

Soil analyses and terrestrial cosmogenic nuclide exposure dating are combined and a conceptual model proposed to explain altitudinal weathering contrasts in high-latitude highlands. We show that summits in the Torngat and Kaumajet mountains were covered by ice during the Last Glacial Maximum, and that their felsenmeer cover probably survived multiple glaciation events. For similar lithologies, soils on felsenmeer covered summits are signigicantly more weathered than those below the felsenmeer limit, displaying higher concentrations of crystalline iron, amorphous aluminium, and silicium extracted with oxalate. Secondary minerals such as gibbsite and kaolinite occur in felsenmeer soils, whereas those formed in till lacked these secondary minerals.10Be and26Al exposure ages for nine of ten samples, from high-elevation tors and autochthonous felsenmeer blocks, range from 73 ± 6 to 157 ± 15 ka. By contrast, ages of 11.4 ± 1.0 and 11.7 ± 1.0 ka are measured for bedrock in the much lower Saglek zone, indicating extensive (>3 m) glacial erosion of this zone during Late Wisconsinan glaciation.26Al/10Be ratios demonstrate that exposure of the high-elevation surfaces was interrupted during at least one cosmic ray shielding event by either ice or till cover. In either case, Late Wisconsinan glaciers could not have extensively eroded these surfaces. Five erratics dated above the Saglek zone, including one in the felsenmeer zone, have exposure ages ranging from 11.6 ± 1.0 to 13.6 ± 0.7 ka. This indicates that valley and high-elevation ice persisted through the Younger Dryas Chron and provides further evidence that the highlands were not nunataks during the Late Wisconsinan period.
Late Wisconsinan buildup and wastage of the Innuitian Ice Sheet across southern Ellesmere Island, Nunavut
Authors: England John H , Atkinson Nigel , Dyke Arthur S , Evans David JA , Zreda Marek
Published: February 2004

During the Late Wisconsinan, a precursor of the Prince of Wales Icefield, southern Ellesmere Island, formed a prodigious ice divide of the Innuitian Ice Sheet. Initial buildup occurred after 19 ka BP, when the icefield advanced west (inland) across Makinson Inlet from margins similar to present. Subsequent reversal of flow to the east required ice divide migration to the west onto a plateau that is largely ice-free today. From this divide, a trunk glacier flowed eastward through Makinson Inlet to join the Smith Sound Ice Stream en route to nothern Baffin Bay. Westward flow from this divide filled Baumann Fiord, depositing a granite dispersal train that extends a further 600 km across the archipelago to the polar continental shelf. Deglaciation of most of Makinson Inlet occurred catastrophically at ~9.3 ka BP, forming a calving bay that thinned the Innuitian divide, thereby triggering deglaciation of most of Baumann Fiord by 8.5 ka BP. Ninety14C dates on Holocene shells and driftwood constrain deglacial isochrones and postglacial emergence curves on opposite sides of the former Innuitian divide. Isobases drawn on the 8 ka BP shoreline rise northwest towards Eureka Sound, the axis of maximum former ice thickness. Ice margins on Ellesmere Island were similar to present from ~5019 ka BP (spanning marine isotope stages 3 and 2). However, significant regional variation in ice extent during this interval is recorded by ice rafting from the Laurentide Ice Sheet into Baffin Bay. Later buildup of the Innuitian Ice Sheet occurred during the low global sea level that defines the last glacial maximum (18 ka BP). We also suggest that the Innuitian Ice Sheet was influenced by the buttressing and subsequent removal of the Greenland Ice Sheet along eastern Ellesmere Island.
DNA Mismatch Repair: Molecular Mechanisms and Biological Function
Authors: Schofield Mark J. , Hsieh Peggy
Published: February 2004

▪ Abstract  DNA mismatch repair (MMR) guards the integrity of the genome in virtually all cells. It contributes about 1000-fold to the overall fidelity of replication and targets mispaired bases that arise through replication errors, during homologous recombination, and as a result of DNA damage. Cells deficient in MMR have a mutator phenotype in which the rate of spontaneous mutation is greatly elevated, and they frequently exhibit microsatellite instability at mono- and dinucleotide repeats. The importance of MMR in mutation avoidance is highlighted by the finding that defects in MMR predispose individuals to hereditary nonpolyposis colorectal cancer. In addition to its role in postreplication repair, the MMR machinery serves to police homologous recombination events and acts as a barrier to genetic exchange between species.
The Bacterial RecA Protein as a Motor Protein
Authors: Cox Michael M.
Published: February 2004

▪ Abstract  The bacterial RecA protein plays a central role in the repair of stalled replication forks, double-strand break repair, general recombination, induction of the SOS response, and SOS mutagenesis. The major activity of RecA in DNA metabolism is the promotion of DNA strand exchange reactions. RecA is the prototype for a ubiquitous family of proteins but exhibits a few activities that some of its eukaryotic, archaeal, and viral homologs appear to lack. In particular, the bacterial RecA protein possesses an apparent motor function that is not evident in the reactions promoted by the eukaryotic Rad51 protein. This motor may be needed only in a subset of the DNA metabolism contexts in which RecA protein functions. Models for the coupling of DNA strand exchange to ATP hydrolysis are examined.
Simplification of rat intubation on inclined metal plate
Authors: Kastl Sigrid , Kotschenreuther U. , Hille B. , Schmidt J. , Gepp H. , Hohenberger W.
Published: February 2004

Small-animal intubation is often necessary during inhalation anesthesia to allow steady-state conditions for large operations and in vivo experiments in all fields of experimental surgery. In rats, placing an orotracheal tube is technically difficult primarily because of the small size of the subject and the lack of equipment specifically designed for this task. We describe a simple rat intubation technique in which the animal is suspended in dorsal recumbency on an inclined metal plate. The animal, anesthetized with ether, is fixed to a 70°-inclined metal plate in a dorsal position by means of a Mersilene ribbon hooked around the upper incisors. This method of positioning the animal is the most important step in the intubation process and further facilitates the technique already described by other authors. A human otoscope was used as a laryngoscope, intubation was performed using the Seldinger technique, and a 14-gauge intravenous catheter served as an endotracheal tube. This inexpensive technique is quickly learned and can be used in any laboratory. Safe and reliable airway management can thus be achieved, permitting in vivo examinations and operations.
An evaluation of case-based teaching: evidence for continuing benefit and realization of aims
Authors: Hudson J. N. , Buckley P.
Published: February 2004

A cross-sectional evaluation of case-based teaching (CBT), a novel physiology learning environment for medical undergraduates, revealed that second, third, and fourth year students, together with their tutors, valued CBT as an experience that met its three major aims. The initiative not only integrated physiology with related basic sciences and clinical medicine but importantly linked students’ developing knowledge of theory to practice. CBT was also valued by students as their first introduction to clinical skills, with most tutors believing that it was the nonthreatening environment that helped students gain confidence for their first “real patient” encounters. The greatest support for CBT came from third year medical students, at the crossroads between their preclinical and clinical environments. Fourth year students, now encountering real patients, had moved on to developing their skills in the hospital environment.
An introductory biology lab that uses enzyme histochemistry to teach students about skeletal muscle fiber types
Authors: Sweeney Lauren J. , Brodfuehrer Peter D. , Raughley Beth L.
Published: February 2004

One important goal of introductory biology laboratory experiences is to engage students directly in all steps in the process of scientific discovery. Even when laboratory experiences are built on principles discussed in the classroom, students often do not adequately apply this background to interpretation of results they obtain in lab. This disconnect has been described at the level of medical education ( 4 ), so it should not be surprising that educators have struggled with this same phenomenon at the undergraduate level. We describe a new introductory biology lab that challenges students to make these connections. The lab utilizes enzyme histochemistry and morphological observations to draw conclusions about the composition of functionally different types of muscle fibers present in skeletal muscle. We report that students were not only successful at making these observations on a specific skeletal muscle, the gastrocnemius of the frog Rana pipiens, but that they were able to connect their results to the principles of fiber type differences that exist in skeletal muscles in all vertebrates.
Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon
Authors: Kim Sylvia Jeewon , Cheung Sandy , Hellerstein Marc K.
Published: February 2004

We describe here a new technique for isolating nuclei from long-term label-retaining cells (LRCs), a subpopulation enriched with stem cells from colon, and for measuring their proliferation rates in vivo. A double-label approach was developed, combining the use of bromodeoxyuridine (BrdU) and 2H2O. Male Fisher 344 rats were administered BrdU in drinking water continuously for 2–8 wk. BrdU was then discontinued (BrdU washout), and animals ( n = 33) were switched to 2H2O in drinking water and killed after 2, 4, and 8 wk. Nuclei from BrdU-positive cells (LRCs) were collected by flow cytometry. The percentages of LRCs were 7 and 3.8% after 4 and 8 wk of BrdU washout, respectively. Turnover rates of LRCs were measured on the basis of deuterium incorporation from 2H2O into DNA of LRC nuclei, as determined by mass spectrometry. The proliferation rate of the LRCs collected was 0.33–0.90% per day (half-life of 77–210 days). Significant contamination from other potentially long-lived colon cells was excluded. In conclusion, this double-labeling method allows both physical isolation of nuclei from colon epithelial LRCs and measurement of their in vivo proliferation rates. Use of this approach may allow better understanding of mechanisms by which agents induce or protect against colon carcinogenesis.
Characterization of in vitro gutlike organ formed from mouse embryonic stem cells
Authors: Ishikawa Tadao , Nakayama Shinsuke , Nakagawa Tadashi , Horiguchi Kazuhide , Misawa Hiromi , Kadowaki Makoto , Nakao Akimasa , Inoue Soichiro , Komuro Terumasa , Takaki Miyako
Published: February 2004

Using an embryoid body (EB) culture system, we have made a functional organlike cluster: the “gut” from embryonic stem (ES) cells (ES gut). There are many types of ES clusters, because ES cells have a pluripotent ability to develop into a wide range of cell types. Before inducing specific differentiation by exogenously added factors, we characterized comprehensive physiological and morphological properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and exhibits spontaneous contractions [mean frequency: 13.5 ± 8.8 cycles per min (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth muscle cells were identified with electron microscopy. ICC frequently formed close contacts with the neighboring smooth muscle cells and occasionally formed gap junctions with other ICC. Widely propagating intracellular Ca2+ concentration oscillations were generated in the ES gut from the aggregates of c-Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in ICC, and electrical slow waves were recorded for the first time. These events were nifedipine insensitive, as in the mouse gut. Our present results indicate that the rhythmic pacemaker activity generated in ICC efficiently spreads to smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut. The present characterization of physiological and morphological properties of ES gut paves the way for making appropriate models to investigate the origin of rhythmicity in the gut.