bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification and characterization of a membrane‐bound enzyme complex from the sulfate‐reducing archaeon Archaeoglobus fulgidus related to heterodisulfide reductase from methanogenic archaea
Authors: Mander Gerd J. , Duin Evert C. , Linder Dietmar , Stetter Karl O. , Hedderich Reiner
Published: October 2003

Heterodisulfide reductase (Hdr) is a unique disulfide reductase that plays a key role in the energy metabolism of methanogenic archaea. The genome of the sulfate‐reducing archaeon Archaeoglobus fulgidus encodes several proteins of unknown function with high sequence similarity to the catalytic subunit of Hdr. Here we report on the purification of a multisubunit membrane‐bound enzyme complex from A. fulgidus that contains a subunit related to the catalytic subunit of Hdr. The purified enzyme is a heme/iron‐sulfur protein, as deduced by UV/Vis spectroscopy, EPR spectroscopy, and the primary structure. It is composed of four different subunits encoded by a putative transcription unit (AF499, AF501–AF503). A fifth protein (AF500) encoded by this transcription unit could not be detected in the purified enzyme preparation. Subunit AF502 is closely related to the catalytic subunit HdrD of Hdr from Methanosarcina barkeri. AF501 encodes a membrane‐integral cytochrome, and AF500 encodes a second integral membrane protein. AF499 encodes an extracytoplasmic iron‐sulfur protein, and AF503 encodes an extracytoplasmic c‐type cytochrome with three heme c‐binding motifs. All of the subunits show high sequence similarity to proteins encoded by the dsr locus of Allochromatium vinosum and to subunits of the Hmc complex from Desulfovibrio vulgaris. The heme groups of the enzyme are rapidly reduced by reduced 2,3‐dimethyl‐1,4‐naphthoquinone (DMNH2), which indicates that the enzyme functions as a menaquinol–acceptor oxidoreductase. The physiological electron acceptor has not yet been identified. Redox titrations monitored by EPR spectroscopy were carried out to characterize the iron‐sulfur clusters of the enzyme. In addition to EPR signals due to [4Fe‐4S]+ clusters, signals of an unusual paramagnetic species with g values of 2.031, 1.994, and 1.951 were obtained. The paramagnetic species could be reduced in a one‐electron transfer reaction, but could not be further oxidized, and shows EPR properties similar to those of a paramagnetic species recently identified in Hdr. In Hdr this paramagnetic species is specifically induced by the substrates of the enzyme and is thought to be an intermediate of the catalytic cycle. Hence, Hdr and the A. fulgidus enzyme not only share sequence similarity, but may also have a similar active site and a similar catalytic function.
Inhibition of glyceraldehyde‐3‐phosphate dehydrogenase by peptide and protein peroxides generated by singlet oxygen attack
Authors: Morgan Philip E. , Dean Roger T. , Davies Michael J.
Published: October 2003

Reaction of certain peptides and proteins with singlet oxygen (generated by visible light in the presence of rose bengal dye) yields long‐lived peptide and protein peroxides. Incubation of these peroxides with glyceraldehyde‐3‐phosphate dehydrogenase, in the absence of added metal ions, results in loss of enzymatic activity. Comparative studies with a range of peroxides have shown that this inhibition is concentration, peroxide, and time dependent, with H2O2less efficient than some peptide peroxides. Enzyme inhibition correlates with loss of both the peroxide and enzyme thiol residues, with a stoichiometry of two thiols lost per peroxide consumed. Blocking the thiol residues prevents reaction with the peroxide. This stoichiometry, the lack of metal‐ion dependence, and the absence of electron paramagnetic resonance (EPR)‐detectable species, is consistent with a molecular (nonradical) reaction between the active‐site thiol of the enzyme and the peroxide. A number of low‐molecular‐mass compounds including thiols and ascorbate, but not Trolox C, can prevent inhibition by removing the initial peroxide, or species derived from it. In contrast, glutathione reductase and lactate dehydrogenase are poorly inhibited by these peroxides in the absence of added Fe2+–EDTA. The presence of this metal‐ion complex enhanced the inhibition observed with these enzymes consistent with the occurrence of radical‐mediated reactions. Overall, these studies demonstrate that singlet oxygen‐mediated damage to an initial target protein can result in selective subsequent damage to other proteins, as evidenced by loss of enzymatic activity, via the formation and subsequent reactions of protein peroxides. These reactions may be important in the development of cellular dysfunction as a result of photo‐oxidation.
Molecular characterization of a novel nuclear transglutaminase that is expressed during starfish embryogenesis
Authors: Sugino Hiroyuki , Terakawa Yudai , Yamasaki Akiko , Nakamura Kazuhiro , Higuchi Yoshiaki , Matsubara Juro , Kuniyoshi Hisato , Ikegami Susumu
Published: October 2003

We report the constitution and molecular characterization of a novel transglutaminase (EC 2.3.2.13) that starts to accumulate specifically in the nucleus in the starfish (Asterina pectinifera) embryo after progression through the early blastula stage. The cDNA for the nuclear transglutaminase was cloned and the cDNA‐deduced sequence defines a single open reading frame encoding a protein with 737 amino acids and a predicted molecular mass of 83 kDa. A comparison of this transglutaminase with other members of the gene family revealed an overall sequence identity of 33–41%. A special sequence feature of this transglutaminase, which is not found in other transglutaminases, is the presence of nuclear localization signal‐like sequences in the N‐terminal region. Microinjection of hybrid constructs that encode the N‐terminal segment fused to reporter proteins into the germinal vesicle of an oocyte produced chimeric proteins by transcription‐coupled translation. It was found that the N‐terminal segment alone was sufficient to effect nuclear accumulation of an otherwise cytoplasmic protein. These results suggest that the nuclear accumulation of the transglutaminase may play an important role in nuclear remodeling during early starfish embryogenesis.
Investigations on Heterobasidion annosum s.lat. in central and eastern Asia with the aid of mating tests and DNA fingerprinting
Authors: Dai Y. ‐C. , Vainio E. J. , Hantula J. , Niemelä T. , Korhonen K.
Published: October 2003

To investigate the taxonomy of Heterobasidion in Eurasia, 49 specimens belonging to H. annosum sensu lato from Asia were identified with the aid of mating tests. Most of the specimens originated from north‐eastern and south‐western China and from the Altai region in southern Siberia, but a few isolates from Kirghizia, Japan and India were also tested. In addition to mating tests, the material from China was investigated with DNA fingerprinting. Heterobasidion annosum sensu stricto was identified only from the Altai region. Homokaryotic isolates from other specimens, except the Indian ones, were sexually compatible with H. parviporum, but they also showed a high degree of compatibility with H. abietinum and with the North American S group. The isolates from SW China (eastern Himalayas) mated with about equal frequency with the European strains of H. parviporum and H. abietinum. However, the DNA fingerprinting showed that these isolates were more closely related to H. parviporum, and hence they were tentatively included in this species. The North American S group was more distant from these Eurasian taxa. Four old isolates from India mated only weakly with the members of the H. annosum s.lat. According to the species concept presented, the distribution of H. parviporum extends from western Europe through southern Siberia to northern China, Japan and the eastern Himalayas. H. annosum s.str. is so far identified only from the Altai region outside Europe, and H. abietinum only from Europe.
Intratubular germ cell neoplasia of unclassified type occupying the whole testis accompanied by a small mature teratoma and metastatic choriocarcinoma and Sertoli cell‐only tubules in the other testis
Authors: Nakano Akinobu , Yoshida Manabu , Harada Takayuki , Araki Asuka , Pineda Liliam , Iijima Masaaki , Sezer Cem , Zhou Li , Maruyama Riruke
Published: October 2003

A 19‐year‐old man with mild mental retardation was diagnosed as having metastatic choriocarcinoma and a testicular tumor. Histopathological examination of the resected testis revealed the presence of a small lesion of mature teratoma but no trace of choriocarcinoma. The remaining seminiferous tubules were atrophic and lined by large atypical germ cells, which were diagnosed as intratubular germ cell  neoplasia  of  the  unclassified  type  (IGCNU).  A  small area with prominent tubules was also observed. Within this lesion, the tubules were dilated and contained several layers of cells with central necrosis. Immunohistological comparison  of  staining  for  several  biological  markers  (Ki‐67, c‐kit and placental alkaline phosphatase) between cells in the atrophic tubules and those in the dilated tubules indicated a progression of the latter cells to cells with a more proliferative ability. In the opposite testis, examined at autopsy after death due to metastatic choriocarcinoma, all seminiferous tubules were lined by Sertoli cells only. It was therefore assumed that the germ cell tumor of the combined histological type had primarily arisen in the background of IGCNU, and that choriocarcinoma had spontaneously regressed. The early onset of these testicular neoplastic lesions strongly indicates their occurrence under the genetic background of gonadal dysplasia, the Sertoli cell‐only syndrome. The possible relation of gonadal disease to mental retardation in this patient is also discussed.
Expression of estrogen receptors α and β in soft tissue sarcomas: Immunohistochemical and molecular analysis
Authors: Li Xiao‐Qiu , Hisaoka Masanori , Hashimoto Hiroshi
Published: October 2003

Sex hormones can regulate differentiation and growth of mesenchymal cells and their neoplastic counterparts. This study aims to investigate the expression status of estrogen receptors (ER), ERα and ERβ, in a variety of soft tissue sarcomas. One hundred and twenty soft tissue sarcomas were immunohistochemically examined for the expression of ERα and ERβ proteins. Fifty‐six tumors were further analyzed by reverse transcription–polymerase chain reaction (RT–PCR) and 30 tumors were further analyzed by in situ hybridization (ISH) assay for their gene expression. The expression level of ER proteins was assessed in correlation with clinicopathological parameters such as patients’ age, gender, and tumor Ki‐67 labeling index. Forty‐five (37.5%) tumors expressed ERα protein and 52 (43.3%) tumors expressed ERβ protein at variable levels. Both receptors were expressed with relatively high frequencies in several types of tumors (e.g. dermatofibrosarcoma protuberance, well‐differentiated liposarcoma, myxoid liposarcoma, and myxoid malignant fibrous histiocytoma). A positive correlation was seen between the expression levels of ERα and ERβ in the current series. Thirty‐one of the 42 informative cases examined by RT–PCR and 15 of the 16 informative tumors examined by ISH showed compatible results with those by immunohistochemistry. Neither gender nor age had a significant influence on the ER expression status. No significant correlation between the expression level of either type of ER and the tumor proliferation activity was identified. The results indicate that both ER isoforms are frequently expressed in certain subsets of soft tissue sarcomas, but their expression levels seem unrelated to the tumor proliferation activity.
Myxopapillary ependymoma with anaplastic features
Authors: Awaya Hirokazu , Kaneko Mayumi , Amatya Vishwa Jeet , Takeshima Yukio , Oka Shinichi , Inai Kouki
Published: October 2003

A case of myxopapillary ependymoma with anaplastic features in 15‐year‐old boy is reported. The tumor was located in the intradural space extending to the 12th thoracic to 2nd lumbar vertebral level. It was excised with the accompanying spinal arch of the T12 to L2 vertebra. At operation, the tumor was not attached to the surrounding soft and bony tissues. The tumor, measuring 49 × 19 × 15 mm, was brownish‐yellow in color and involved the conus medullaris and filum terminale. Histologically, the tumor was composed of biphasic features of a hypercellular papillary growth area and a hypocellular myxoid area. In the papillary growth area, ependymal rosettes and perivascular pseudorosettes were observed.  These  findings  were  consistent  with  those of a myxopapillary ependymoma, although multiple foci of punctate necrosis within the tumor and proliferation of endothelial cells showing glomeruloid structures were observed. Many mitotic figures were also observed. In addition, the Ki‐67 labeling index of tumor cells was 10.1%. These findings are unusual for myxopapillary ependymoma, and therefore, it appeared that the diagnosis of myxopapillary ependymoma with anaplastic features was appropriate.
Cytometrical image analysis for immunohistochemical hormone receptor status in breast carcinomas
Authors: Hatanaka Yutaka , Hashizume Kaoru , Nitta Kazuo , Kato Tomoyuki , Itoh Ichiro , Tani Yoichi
Published: October 2003

A cytometrical image analyzing method for nuclear protein was established using WinROOF, a commercially available, inexpensive software, to determine the status of both estrogen and progesterone receptors. Immunohistochemical evaluation of estrogen receptors (ER) and progesterone receptors (PR) was performed with the anti‐ER (clone 1D5) and the anti‐PR (clone PgR636), respectively, combined with dextran polymer reagent EnVision+, all of which are approved in vitro diagnostics in Japan. The immunostained results were captured as digital images in Windows, and then analyzed in WinROOF with macroinstructions for analyzing each captured area either immunolabeled with chromogen or counterstained with hematoxylin. This image analysis method graded the immunostained nuclei of carcinoma cells based on staining intensities, and calculated the labeling index (LI) for both ER and PR. Furthermore, the LI correlated highly with the results from a histology score (HSCORE) when 20 breast carcinomas were quantified. Regarding ER, when 20% in the LI was considered as the cut‐off point for positive, the positivity of ER in computer‐assisted analysis was 75% (15 of 20 cases), and was completely concordant with that of HSCORE‐based analysis. These results indicate that the cytometrical image analysis‐based quantification could be appropriately applied to the objective determination of the immunohistochemical status of both ER and PR.
Giant stercoral stone and catheterization difficulty
Authors: SUZUKI KAZUMI , SUGAYA YASUHIRO , TOKUE AKIHIKO
Published: October 2003

Abstract An unusual case of giant calcification in the midline of the pelvis is reported herein. An 84‐year‐old male, whose urination was managed by clean intermittent self‐catheterization (CIC), presented with catheter insertion difficulty. The patient had a history of transurethral operations for benign prostatic hyperplasia and small bladder stones. Kidney, ureter and bladder (KUB) X‐ray of post‐enhanced computed tomography (CT) suggested a giant ball‐shaped calcification in the bladder. A recurrent bladder stone was suspected. However, pelvic CT scan revealed that the giant calcification was, in fact, situated in the rectum. Thus, a diagnosis of giant stercoral stone was made. After the stone was removed manually, the patient had no difficulty in inserting the catheter. His prior complaint may have been caused by urethral bladder neck obstruction due to the giant stercoral stone.
Torsion of the epididymis: A rare cause of acute scrotum
Authors: RAVICHANDRAN S , BLADES RA , WATSON ME
Published: October 2003

Abstract Acute scrotum is a common clinical problem and establishing its etiology can be difficult, often necessitating scrotal exploration. We report here a very rare case of acute scrotum: torsion of the epididymis. Only one such case has been reported previously in the literature.
Down‐regulation of inducible nitric oxide synthase (iNOS) in rat with congenital hydronephrosis
Authors: ZHOU YUN , TAKAHASHI GO , YONAMINE KYOKO
Published: October 2003

Background: Most of our knowledge concerning obstructive uropathy has been derived mainly from surgically manipulated animal models, and the pathogenesis of congenital obstructive hydronephrosis is not fully elucidated. Nitric oxide (NO) acts as an important biological modulator with diverse physiological functions, which can be either toxic or protective depending on the situation. NO is synthesized from l‐arginine by nitric oxide synthase, and in the kidney iNOS is expressed spontaneously. The aim of our study is to investigate the expression of iNOS protein and its relationship with tubulointerstitial fibrosis and tubular cell apoptosis in congenital hydronephrosis.

Methods: We conducted histological studies on 18 kidneys of six‐week‐old‐rats from an inbred colony of congenital hydronephrosis with reference to the histological grading of the affected kidney, tubulointerstitial fibrosis, renal tubular atrophy, and tubular cell apoptosis. Renal transforming growth factor‐β1 (TGF‐β1) level was determined by a sandwich ELISA assay and the expression of iNOS was analyzed by western blotting.

Results: Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. Renal TGF‐β1 level was higher in hydronephrotic kidneys than normal control kidneys (364.81 ± 52.60 vs. 221.19 ± 22.53 pg/mg protein, P < 0.05). Tubular apoptotic score in hydronephrotic kidneys was also significantly higher than in the normal control kidneys (1.97 ± 0.42 vs. 0.14 ± 0.02/HPF, P < 0.01). The expression of iNOS protein was lower in the affected kidneys compared with the normal control kidneys (8.79 ± 0.78 vs. 14.00 ± 0.83 arbitrary unit, P < 0.01). There was a negative correlation between iNOS expression and histological grading in congenital hydronephrosis. The iNOS expression also correlated negatively with renal interstitial fibrosis, TGF‐β1 level and tubular cell apoptosis.

Conclusion: Our study confirmed the down‐regulation of iNOS expression in affected kidneys from rats with congenital hydronephrosis, in which the cytoprotective effect of NO may be lost or weakened.
Acid neutralization and bile acid binding capacity of hydrotalcite compared with other antacids: An in vitro study
Authors: MIEDERER S‐E , WIRTZ M , FLADUNG B
Published: October 2003

OBJECTIVE:  Antacids are used worldwide for the treatment of acid‐related conditions such as heartburn and gastro‐esophageal reflux disease. The present study investigated the in vitro acid neutralization and bile acid binding capacities of hydrotalcite compared with other antacids that are available in Germany and China. It has been reported that hydrotalcite is effective in the treatment of bile reflux gastritis because of its binding capacity to bile acids.

METHODS:  Hydrotalcite and other preparations of antacids were tested in a comparative in vitro study. The neutralization properties were determined with static and dynamic tests (preliminary antacid test, acid neutralization capacity (ANC) test, Rossett‐Rice (RR) test) and the bile acid binding test with a standardized commercial test kit (Merckotest bile acids).

RESULTS:  In the static and dynamic tests hydrotalcite 500 mg and some other antacids, such as magaldrate, almasilate, algedrate Mg hydroxide, Ca/Mg carbonate and calcium carbonate, demonstrated favorable ANC reflected by rapid onset and long duration of action, and high buffering capacity. In the RR test, a hydrotalcite dose of 1000 mg was able to keep the pH level above 3 for 76.9 min. The bile acid binding capacity test yielded that hydrotalcite had the highest binding potential to taurodeoxycholic acid, a lipophilic bile acid associated with cell and mucosa toxicity.

CONCLUSIONS:  Hydrotalcite has a rapid onset of action, a high buffering capacity and a long duration of action. In particular, hydrotalcite binds cytotoxic bile acids. These pharmacochemical properties make hydrotalcite a most suitable antacid.
Hepatoprotective effect of a curcumin/absinthium compound in experimental severe liver injury
Authors: MAROTTA F , SHIELD YR , BAMBA T , NAITO Y , MINELLI E , YOSHIOKA M
Published: October 2003

OBJECTIVE:  A preliminary in vitro study with hepatocyte culture showed that concentrations as low as 10 µg/mL of PN‐M001 are able to significantly mitigate CCl4 hepatocyte damage (P < 0.05) comparable to 100 µg/mL silymarin, and 100 µg/mL proved to be more protective than either silymarin 100 µg/mL or glycyrrhizin 10 µg/mL (P < 0.05).

METHODS:  Wistar rats were allocated into three groups: (A) 0.1 mL/100 g body weight (BW) mixture of CCl4 in olive oil (1 : 1 v/v) subcutaneous injection twice daily for 4 weeks; (B) as A, plus oral administration of 50 mg/kg of K‐17.22 dissolved in 5% glucose; (C) as B but with PN‐M001 given 1 week after the first injection of CCl4. Rats were killed at the end of the study and blood and liver samples were obtained.

RESULTS:  When compared with a control, group A showed a significant decrease of glutathione (GSH;>45%, P < 0.001) and oxidized GSH (GSSG; P < 0.01) liver content, a lower liver wet weight (P < 0.01) together with an increase of both transaminases (>15‐fold, P < 0.001) whereas groups B and C both showed only a mild increase in transaminases (<4‐fold, P < 0.05). Group A showed a significant decrease of Y‐protein fraction and of GST activity, as tested by both substrates (P < 0.01 vs control). However, both these parameters were reverted to normal by PN‐M001 (P < 0.05 vs A).

CONCLUSIONS:  These preliminary data suggest that PN‐M001 exerts a highly protective and prolonged effect (either preventive or therapeutic) on GSH depletion in CCl4‐induced liver injury, which suggests its potential use in the clinical setting.
Mast cells and neuropeptidergic terminals: Experimental studies of the mechanism of visceral hypersensitivity in irritable bowel syndrome
Authors: LI Zhao Shen , DONG Wen Zhu , ZOU Duo Wu , ZOU Xiao Ping , XU Guo Ming , ZHU Ai Yong , YIN Ning , GONG Yan Fang , SUN Zhen Xing , XU Can , MAN Xiao Hua
Published: October 2003

OBJECTIVE:  The failure of dysmotility to explain the symptoms of pain in irritable bowel syndrome (IBS) led to studies on visceral hypersensitivity. Mucosal mast cells (MC) may be one factor influencing the response of visceral afferents to mechanical and chemical stimuli because they are found in close proximity to gastrointestinal mucosal sensory nerve terminals containing neuropeptides and a bi‐directional pathway linking the central nervous system, gut and MC has been demonstrated.

METHODS:  The present study investigated the extent of MC and the neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), in the intestinal mucosa of patients with IBS, as well as the location of the MC. The MC and neuropeptidergic terminals were stained histochemically and immunohistochemically, respectively, neuropeptide concentrations were measured by radioimmunoassay (RIA), and the results were investigated qualitatively and quantitatively by color image analyzer. The structural relation between the MC and neuropeptide terminals was studied by ultramicroscopy using in situ embedding technique.

RESULTS:  In IBS, the number of MC in the terminal ileum, the ileocecal junction, and the ascending colon was significantly increased (P < 0.01), and the MC had great variations in their extent and size. Significantly increased concentrations of VIP and SP were found in the colon of IBS patients compared with controls. A correlation between mucosal MC and the SP(VIP)‐ergic terminals was found, and the MC were close to these terminals in the lamina propria, which demonstrated SP (VIP)‐ergic terminals.

CONCLUSIONS:  Mast cells and the neuropeptides of intestinal mucosa may play a central role in gut hypersensitivity, resulting in both the motor response and visceral perceptions that occur with IBS.
The prevalence of reduced zidovudine susceptibility in zidovudine‐naive, antiretroviral‐experienced HIV‐1‐infected patients
Authors: Gilleece Y , Torti C , Mandalia S , Gazzard BG , Pillay D , Pozniak AL
Published: October 2003

Objectives

There is increasingin vitroandin vivoevidence that reduced zidovudine (ZDV) susceptibility is generated by the selective pressure conferred by other nucleoside reverse transcriptase inhibitors (NRTIs). However, the degree to which this occurs in clinical practice remains unclear. We assessed phenotypic and genotypic resistance in ZDV‐naive patients with virological failure on stavudine (d4T)‐containing regimens, with particular reference to potential cross‐resistance between d4T and ZDV.

Methods

Patients were identified from a clinical database. Treatment history was confirmed by case note evaluation and discussion with patients. Genotypic and phenotypic analyses were undertaken by Virco (Virco BVBA, Mechelen, Belgium).

Results

Sixty‐seven drug‐experienced, ZDV‐naive patients who underwent a resistance test while failing a d4T‐containing regimen were identified. Of these patients, 23% had received three or more NRTIs and 42% at least one non‐nucleoside reverse transcriptase (RT) inhibitor; 22% had viruses with reduced d4T susceptibility (>1.8‐fold resistance), and 25% had viruses with reduced ZDV susceptibility (>4‐fold). The most frequently observed RT mutations were identified. A significant correlation was found between susceptibility to d4T and susceptibility to ZDV (r=0.36;P=0.003), and also between virtual resistance to d4T and that to ZDV (r=0.38;P=0.002).

Conclusions

A significant minority of d4T‐treated, ZDV‐naive patients were found to have viruses with reduced ZDV susceptibility, with a variable association with classical ZDV resistance mutations. These data suggest that cross‐resistance between d4T and ZDV may involve novel constellations of mutations. Correlations between d4T and ZDV susceptibilities and resistances further support cross‐resistance between NRTIs.
Epidemiological risk factors for hypersensitivity reactions to abacavir*
Authors: Easterbrook PJ , Waters A , Murad S , Ives N , Taylor C , King D , Vyakarnam A , Thorburn D
Published: October 2003

We investigated risk factors for hypersensitivity reactions (HSR) to abacavir in a case–control study. In a multivariate analysis, white race [odds ratio (OR), 5.16; 95% confidence interval (CI), 1.16–22.97] and a higher CD8 cell count at initiation of abacavir (>850 vs. ≤850 cells: OR, 3.74; 95% CI, 1.19–11.77) were found to be significantly associated with the development of HSR. Age, gender, stage of disease, prior antiretroviral exposure and type of concurrent antiretroviral therapy were not associated with HSR. Differences in predisposition to HSR according to ethnicity and baseline CD8 cell count may be explained by the reported MHC genetic associations with HSR.
Overcoming subjectivity in assessing facial lipoatrophy: is there a role for three‐dimensional laser scans?
Authors: Benn P , Ruff C , Cartledge J , Sauret V , Copas A , Linney A , Williams IG , Smith C , Edwards SG
Published: October 2003

Background

Prevalence and incidence rates of lipodystrophy vary widely and frequently rely upon self‐ and/or clinician reports. Currently no validated assessment tool for facial lipoatrophy is available.

Aims and objectives

To illustrate that assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. To evaluate the reproducibility of facial three‐dimensional surface laser scans.

Methods

Twenty‐three HIV‐positive men were recruited from an inner London HIV outpatient clinic in September 2001. CD4 count, viral load, antiretroviral history and body mass index were recorded. Patients and clinicians independently assessed the severity of facial lipoatrophy on a four‐point scale and the level agreement was measured. Seventeen of the 23 patients (73.9%) underwent two scans 1 week apart, which were then superimposed. The volume difference (mm3) and mean difference (mm) between the scans for five regions of the face were measured and compared with the self‐reported grade of facial lipoatrophy.

Results

For each pair of clinicians (P=0.03, 0.005 and 0.0002, respectively), and for one patient–clinician pair (P=0.004), there was a significant systematic difference between the two sets of gradings of facial lipoatrophy. The level of disagreement was generally higher for patients reporting facial lipoatrophy (n=17) compared to those not reporting it (n=6). The mean volume difference and mean difference between any region were within 200 mm3 and 0.25 mm, respectively. Reproducibility was unaffected by the self‐reported grade of facial lipoatrophy.

Conclusions

Assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. Three‐dimensional facial laser scans are reproducible and may provide an objective tool for monitoring changes in facial lipoatrophy.
Recurrence of Pneumocystis carinii pneumonia in an HIV‐infected patient: apparent selective immune reconstitution after initiation of antiretroviral therapy
Authors: Crothers K , Huang L
Published: October 2003

Although several studies have reported that it is safe to discontinue secondary Pneumocystis carinii pneumonia (PCP) prophylaxis in patients infected with HIV who experience a sustained immune response as a result of antiretroviral therapy, we describe a patient who developed recurrent PCP <3 months after discontinuing trimethoprim‐sulfamethoxazole prophylaxis. He developed disease despite a sustained CD4 T‐cell count above 200 cells/μL for more than 3 years while on antiretroviral therapy, as well as an apparent immune reconstitution against disseminated Mycobacterium avium complex (MAC) and Histoplasma capsulatum, for which he also discontinued therapy but without adverse effects. Thus, although increasing evidence continues to indicate that HIV‐infected patients receiving combinations of antiretroviral therapies may regain specific immunity against opportunistic infections, our patient's experience suggests that this immune recovery may be selective and incomplete.
Assessment of Skeletal Muscle Ventricle Tissue Blood Flow Using Positron Emission Tomography
Authors: Singh Tajinder P. , Greer Kevin , Muzik Otto , Hammond Robert L. , Stephenson Larry W. , Di Carli Marcelo F.
Published: October 2003

Abstract: In this pilot study, we assessed the feasibility of using positron emission tomography (PET) imaging for in vivo measurement of skeletal muscle ventricle (SMV) tissue blood flow. In 4 dogs, with SMVs prepared from their latissimus dorsi muscle, we quantified SMV tissue blood flow by PET and related it to the tissue flow measured by radiolabeled microspheres under similar physiologic conditions. The tissue blood flow was estimated in SMVs wrapped around a mandrel (not in circulation) at rest and during SMV stimulation (30 and 90 contraction‐cycles/min). SMV tissue perfusion was heterogeneous, especially during SMV contraction. Furthermore, there was a linear relationship between SMV tissue flows estimated by PET and those measured by microspheres. We conclude that in vivo imaging of SMV is feasible by PET. Quantification of SMV tissue blood flow by PET has promise as a means of assessing changes in blood flow, but further technical progress needs to be made before absolute flows can be reliably measured.
Efficacy of Nonwoven Fabric Bioreactor Immobilized with Porcine Hepatocytes for Ex Vivo Xenogeneic Perfusion Treatment of Liver Failure in Dogs
Authors: Naruse Katsutoshi , Sakai Yasuyuki , Lei Guo , Sakamoto Yoshihiro , Kobayashi Takashi , Puliatti Carmelo , Aronica Gaetano , Morale Walter , Leone Francesco , Qiang Shi , Ming Sue Gui , Ming Sun , Li Zhang , Chang Son Ji , Suzuki Motoyuki , Makuuchi Masatoshi
Published: October 2003

Abstract: We have developed a new bioartificial liver bioreactor filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF). In this study, we investigated the efficacy of our hybrid bioartificial liver system incorporating the NWF bioreactors and an immunoglobulin adsorbent column for perfusion treatment in a canine liver failure model. Xenogeneic perfusion treatment for operative canine liver failure models were performed for 3 h, and survival time, intracranial pressure, and blood and cerebrospinal fluid data were documented. Treatment was carried out without obstruction by immunological rejection when immunoglobulin adsorbent columns were used with the NWF bioreactors in combination. Dogs treated with this system exhibited a restricted increase of intracranial pressure and significant compensatory effects on blood and cerebrospinal amino acid imbalances as shown by a significant improvement of Fischer's ratio. On the other hand, relatively low capacity for ammonia elimination was shown as compared with homologous direct hemoperfusion.
Metabolic Alkalosis in a Hemodialysis Patient After Ingestion of a Large Amount of an Antacid Medication
Authors: Sahani Mandeep M. , Brennan John F. , Nwakanma Chukwuemeka , Chow May T. , Ing Todd S. , Leehey David J.
Published: October 2003

Abstract: A maintenance hemodialysis patient developed metabolic alkalosis in the absence of vomiting or nasogastric suction. The cause of the metabolic alkalosis was ingestion of an exogenous alkali in the form of Bromoseltzer. The metabolic alkalosis improved with hemodialysis using a low‐bicarbonate bath.
Coronary Artery Bypass Grafting for Dialysis Patients: Usefulness of Multiarterial Bypass
Authors: Nakayama Yoshihiro , Sakata Ryuzo , Ura Masashi
Published: October 2003

Abstract: This study assessed the efficacy of multiarterial bypass in coronary artery bypass grafting (CABG) in dialysis patients. Eighty dialysis patients who underwent CABG were divided into 2 groups. Group A consisted of 38 patients in whom the left internal thoracic artery and additional saphenous vein graft (SVG) had been used. Group B consisted of 42 patients in whom 2 or 3 arterial grafts and additional SVGs had been used. No mediastinitis was shown in either group. Actuarial survival rates, including all deaths, and estimated by cardiac deaths at 8 years, were 28% and 83%, respectively, in Group A and 93% and 100%, respectively, in Group B with a significant difference (p = 0.014 and 0.016, respectively). Cardiac event‐free rates at 8 years were 43% and 96% in Groups A and B, respectively, with a significant difference (p = 0.0016). Multiarterial grafting improved long‐term results after CABG for dialysis patients compared with single internal thoracic artery grafting with minimal complications related to graft harvesting.
The Change in Renal Replacement Therapy on Acute Renal Failure in a General Intensive Care Unit in a University Hospital and its Clinical Efficacy: A Japanese Experience
Authors: Hirayama Yoh , Hirasawa Hiroyuki , Oda Shigeto , Shiga Hidetoshi , Nakanishi Kazuya , Matsuda Kenichi , Nakamura Masataka , Hirano Takeshi , Moriguchi Takeshi , Watanabe Eizo , Nitta Masakazu , Abe Ryuzo , Nakada Takaaki
Published: October 2003

Abstract:  The aim of our study was to examine renal replacement therapies (RRT) that have been used for acute renal failure (ARF) in our intensive care unit (ICU) patients and to compare their outcomes. Sixteen patients who underwent intermittent hemodialysis (IHD), 14 patients who underwent continuous hemofiltration (CHF) in combination with IHD (CHF + IHD), and 38 patients who underwent continuous hemodiafiltration (CHDF) were evaluated. Regarding the effects of blood purification on hemodynamics and renal function, the percentage increase in blood pressure and percent rapid increase in urinary output were the greatest in the CHDF group. The hourly urinary output after the start of initial blood purification increased only in the CHDF group. The survival rate was significantly higher in the CHDF group. These results suggest that CHDF should be the first‐line therapy for patients with ARF and that we are moving in the right direction regarding the application of RRT to treat ARF in ICU patients.
Interactions Between Extracellular Stimuli and Excitation Waves in an Atrial Reentrant Loop
Authors: JOHNSON CHAD R. , BARR ROGER C.
Published: October 2003

Introduction: The interactions between extracellular stimuli and excitation waves propagating in a reentrant loop are a complex function of stimulus parameters, structural properties, membrane state, and timing. Here the goal was a comprehensive understanding of the mechanisms and frequencies of the major interactions between the advancing excitation wave and a single extracellular stimulus, separated from issues of anatomic or geometric complexity.

Methods and Results: A modernized computer model of a thin ring of uniform tissue that included a pair of extracellular stimulus electrodes (anode/cathode) was used to model one‐dimensional cardiac reentry. Questions and results included the following: (1) What are the major interactions between a stimulus and the reentrant propagation wave, and are they induced near the cathode or near the anode; and, for each interaction, what are the initiating amplitude range and timing interval? At the cathode, the well‐known mechanism of retrograde excitation terminated reentry; changes in timing or amplitude produced double‐wave reentry or phase reset. At the anode, termination occurred at different cells depending on stimulus amplitude. (2) Relatively how often did termination occur at the anode? For most stimulus amplitudes, termination occurred more often at the anode than at the cathode, although not always at the same cell. (3) With random timing, what is the probability of terminating reentry? Stimulation for 5 msec terminated reentry with a probability from 0% to approximately 10%, as a function of increasing stimulus amplitude.

Conclusion: A single extracellular stimulus can initiate major changes in reentrant excitation via multiple mechanisms, even in a simple geometry. Termination of reentry, phase shifts, or double‐wave reentry each occurs over well‐defined ranges of stimulus amplitude and timing. (J Cardiovasc Electrophysiol, Vol. 14, pp. ***‐***, October 2003)
Transvenous Biventricular Pacing in a Child after Congenital Heart Surgery as an Alternative Therapy for Congestive Heart Failure
Authors: BLOM NICO A. , BAX JEROEN J. , OTTENKAMP JAAP , SCHALIJ MARTIN J.
Published: October 2003

Cardiac resynchronization therapy improves short‐term and long‐term hemodynamics in adult patients with congestive heart failure and left bundle branch block. We describe the feasibility of transvenous biventricular pacemaker implantation in a 6‐year‐old child with heart failure and wide QRS complex after congenital heart surgery. Myocardial tissue Doppler imaging was used to demonstrate intraventricular dyssynchrony and resynchronization after cardiac resynchronization therapy. During 1‐year follow‐up, symptomatology and hemodynamic parameters improved. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1110‐1112, October 2003)
Clinical Significance and Contributing Factors of Long‐Term Variability in Induced Ventricular Tachyarrhythmias
Authors: HAYASHI MEISO , KOBAYASHI YOSHINORI , MORITA NORISHIGE , IWASAKI YU‐KI , OHMURA KAZUKO , ATARASHI HIROTSUGU , KATOH TAKAO , TAKANO TERUO
Published: October 2003

Introduction: Ventricular arrhythmias induced during electrophysiologic study (EPS) may vary over time, making arrhythmia induction studies unreliable. The aim of this prospective study was to clarify the clinical significance of long‐term variability in induced arrhythmias and to elucidate factors determining this variability.

Methods and Results: Three noninvasive EPSs were performed 1, 13, and 25 months after implantation of a cardioverter defibrillator in 40 patients with ventricular tachyarrhythmias, without a change in their antiarrhythmic drug regimens. The induced ventricular arrhythmias were categorized into five grades. Long‐term variability, which was defined as a variation in the grades during the three EPSs, was observed in 23 patients (group A) and not in the remaining 17 patients (group B). During the 2‐year period, spontaneous sustained ventricular arrhythmias developed in 15 patients (65%) in group A but in only 4 patients (24%) in group B (P = 0.01). Inducibility of sustained tachyarrhythmias was not associated with emergence of spontaneous arrhythmias. All patients also underwent thallium‐201 and iodine‐123‐metaiodobenzylguanidine (MIBG) scans to evaluate the extent of the regions showing normal thallium uptake with reduced MIBG uptake. Group A patients showed greater thallium/MIBG mismatched regions than did group B patients (P = 0.01). Logistic regression analysis revealed that long‐term variability (relative risk [RR] 7.55, P = 0.03), amiodarone therapy (RR 0.14, P = 0.04), and left ventricular ejection fraction <35% (RR 6.26, P = 0.04) were independent predictors of spontaneous arrhythmia occurrence.

Conclusion: In patients with ventricular tachyarrhythmias, long‐term variability in induced arrhythmias, but not the inducibility of arrhythmias, is associated with a higher incidence of spontaneous arrhythmias. Regional cardiac sympathetic denervation may be an important mechanism of this variability. These results also may explain why inducibility‐based antiarrhythmic drug testing does not predict patient prognosis. (J Cardiovasc Electrophysiol, Vol. 14, pp. ***‐***, October 2003)
Distal Right Ventricular Coil Position Reduces Defibrillation Thresholds
Authors: RASHBA ERIC J. , BONNER MATT , WILSON JOHN , SHOROFSKY STEPHEN R. , PETERS ROBERT W. , GOLD MICHAEL R.
Published: October 2003

Introduction: Understanding the factors that affect defibrillation thresholds (DFTs) has important implications both for optimization of defibrillation efficacy and for the design of new transvenous leads. The aim of this prospective study was to test the hypothesis that defibrillation efficacy is improved with the right ventricular (RV) coil in a distal position compared with a more proximal RV coil position.

Methods and Results: A novel defibrillation lead with three adjacent RV defibrillation coils (distal 0.8 cm, middle 3.7 cm, proximal 0.8 cm) was used for this study to permit comparison of DFTs with the proximal and distal RV coil positions without lead repositioning. In the distal RV configuration, the distal and middle RV coils were connected electrically as the anode for defibrillation. In the proximal RV configuration, the middle and proximal coils were the anode. A superior vena cava (SVC) coil and active can were connected electrically as the cathode (reversed polarity, RV→Can+SVC). In each patient, the DFT was measured twice using a binary search protocol with the distal RV and proximal RV configurations, with the order of testing randomized. The study cohort consisted of 31 subjects (mean age 65 ± 12 years, mean left ventricular ejection fraction 30% ± 16%, 81% male predominance). The mean delivered energy (8.2 ± 5.3 J vs 11.2 ± 6.1 J), leading‐edge voltage (335 ± 109 V vs 393 ± 118 V), and peak current (11.6 ± 5.2 A vs 14.9 ± 7.3 A) at DFT all were significantly lower with the distal RV configuration compared to the proximal RV configuration (P < 0.01 for all comparisons).

Conclusion: DFTs are significantly reduced with the distal RV configuration compared to the proximal RV configuration. Defibrillation leads should be designed with the shortest tip to coil distance that can be achieved without compromising ventricular fibrillation sensing. (J Cardiovasc Electrophysiol, Vol. 14, pp. ***‐***, October 2003)
Fasciculoventricular Pathways:
Authors: STERNICK EDUARDO BACK , GERKEN LUIZ MÁRCIO , VRANDECIC MÁRIO O. , WELLENS HEIN J.J.
Published: October 2003

Introduction: Fasciculoventricular tracts are considered a rare form of ventricular preexcitation. Few fasciculoventricular pathways have been reported, and none have been linked to a reentrant tachycardia.

Methods and Results: Four patients with fasciculoventricular bypass tracts underwent electrophysiologic evaluation. Two patients had a single fasciculoventricular pathway, one that inserted anteroseptally and the other in the left ventricle. Two patients also had an AV bypass tract, with anterograde conduction over the fasciculoventricular pathway during orthodromic AV reentrant tachycardia. After ablation of the AV pathways, the ECG during sinus rhythm and the electrophysiologic study showed ventricular preexcitation due to a fasciculoventricular bypass tract inserting into the right ventricle. Adenosine triphosphate was helpful in the diagnostic process.

Conclusion: Electrophysiologists should be able to make the differential diagnosis between a fasciculoventricular bypass tract and an anteroseptal accessory pathway to preclude potential harm to the AV conduction system if a fasciculoventricular pathway is targeted for catheter ablation.(J Cardiovasc Electrophysiol, Vol. 14, pp. ***‐***, October 2003)
Size‐ and density‐dependent reproductive success of bagworms, Metisa plana
Authors: Rhainds Marc , Gries Gerhard , Mat Min Mohd.
Published: October 2003

A study conducted in a Malaysian plantation of oil palm over 5 consecutive generations of bagworms, Metisa plana (Walker) (Lepidoptera: Psychidae), evaluated extent and causes of variability for 3 components of reproductive success: pupal mortality, mating success and fecundity. The population of M. plana in the experimental site exhibited cycles of 70–80 days with discrete generations. Females emerged before males during all generations. Relatively large proportions of M. plana did not reproduce, either because they did not survive as pupa or (for females) mate as adult. Occurrence of unmated female bagworms may be attributed to complex mating procedure, short lifespan of females, limited mating capacity of males, protogyny inducing female‐biased operational sex‐ratio, and/or flightlessness per se constraining mating success of females. Size attained at pupation is a significant component of reproductive success, with large individuals having greatest survival during pupal stage, mating success and fecundity. Population density also influenced reproductive success of M. plana: female and (to a lesser extent) male larvae on crowded palms attained small size at pupation; survival of pupae was density‐dependent during 2 generations for females and density‐independent during 5 generations for males; mating success of females was inverse density‐dependent during 4 generations. Size‐ and density‐dependent mating success of females may be attributed to mate choice by males, size‐dependent pheromone production by and longevity of females, and/or disorientation of mate‐seeking males around heavily infested palms. Long‐term studies are needed to determine whether and to what extent attributes of oil palm, seasonal fluctuations of abiotic factors and inter‐generational variations of reproductive success influence population dynamics of M. plana.