bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoprotection of residual functional photosystem II units that survive illumination in the absence of repair, and their critical role in subsequent recovery
Authors: Sun Zhen‐Ling , Lee Hae‐Youn , Matsubara Shizue , Hope Alexander B. , Pogson Barry J. , Hong Young‐Nam , Chow Wah Soon
Published: October 2006

Photosystem II (PSII) complexes, which split water into oxygen, protons and electrons in photosynthesis, require light but are also inactivated by it. Recovery of PSII from photoinactivation requires de novo protein synthesis. PSII in capsicum leaf segments were photoinactivated in the absence of chloroplast‐encoded protein synthesis. At large photon exposures and despite the absence of repair, a residual fraction of PSII remained functional, being ca 0.08–0.2 depending on the ease of gas exchange in the tissue. This study revealed that the residual functional PSII was photoprotected by both (1) reaction‐center quenching of excitation energy by photoinactivated PSII even when little or no PSII activity was permitted, and (2) antenna quenching, which was dependent on a trans‐thylakoid pH gradient sustained mainly by linear electron transport and facilitated by the residual functional PSII complexes themselves. Significantly, little or no contribution to photoprotection of PSII was observed from cyclic electron flow around PSI. Further, the small residual functional PSII population was critical for recovery of the photoinactivated PSII complexes. Thus, photoinactivated and residual functional PSII complexes in leaves play a mutually beneficial role in each other’s ultimate survival.
Abscisic acid modulates polyamine metabolism under water stress in Arabidopsis thaliana
Authors: Alcázar Rubén , Cuevas Juan C. , Patron M. , Altabella Teresa , Tiburcio Antonio F.
Published: October 2006

Limited information is available concerning plant signal transduction pathways regulating polyamine (PA) metabolism in response to various abiotic stress conditions. To gain a new insight into this question, we have studied the possible role of abscisic acid (ABA) in the modulation of PA metabolism under water stress conditions in the model plant Arabidopsis thaliana. Transcriptome profiling of the PA‐biosynthetic gene family by real‐time quantitative reverse transcriptase polymerase chain reaction revealed that arginine decarboxylase 2 (ADC2), spermidine synthase 1 (SPDS1) and spermine synthase (SPMS) genes are highly induced by drought stress, and these responses are mostly impaired in ABA‐deficient (aba2‐3) and ABA‐insensitive (abi1‐1) mutants. These data, together with PA content analyses, indicate that ABA modulates PA metabolism at transcriptional and metabolite level in response to water stress.
Family‐focused treatment of the suicidal bipolar patient
Authors: Miklowitz David J , Taylor Dawn O
Published: October 2006

Objectives: Bipolar patients are at high risk for suicidal ideation and attempts. Suicidal behavior is correlated with poor family communication and/or high levels of intrafamilial conflict, particularly among adolescent bipolar patients. This article describes the application of family‐focused therapy (FFT) as an adjunct to pharmacotherapy in the management of suicidal ideation and behavior among bipolar patients.

Methods: We describe the empirical basis of FFT in studies of adult and adolescent patients. We then describe the manner by which the three modules of FFT – psychoeducation, communication skills training and problem solving – are adapted to address the clinical issues presented by suicidal bipolar adults or adolescents and their families.

Results: Key objectives of the treatment are to help the family recognize that suicidal behavior is a part of the pathophysiology of bipolar disorder but that it is also to some extent under environmental control. Thus, the family is in a unique position to develop and help assure the success of a suicide prevention contract. A case study of an adolescent with suicidal behavior is presented.

Conclusions: Future research should include a focus on: (i) cross‐cultural issues in suicide and bipolar disorder; and (ii) the adaptation of interventions shown to be effective in reducing suicidal behaviors in non‐bipolar populations.
Carnitine does not improve weight loss outcomes in valproate‐treated bipolar patients consuming an energy‐restricted, low‐fat diet
Authors: Elmslie Jane L , Porter Richard J , Joyce Peter R , Hunt Penelope J , Mann Jim I
Published: October 2006

Objectives:  Carnitine deficiency impairs fatty acid β‐oxidation and may partly explain weight gain in valproate‐treated patients. The aim of this study was to determine whether l‐carnitine supplementation improves weight loss outcomes in bipolar patients taking sodium valproate.

Methods:  Sixty bipolar patients with clinically significant weight gain thought to be related to sodium valproate, who had been taking sodium valproate for ≥6 months, were randomized to l‐carnitine (15 mg/kg/day) or placebo for 26 weeks, in conjunction with a moderately energy‐restricted, low‐fat diet. The primary outcome measure was weight change.

Results:  l‐carnitine had no effect on mean weight loss compared with placebo (−1.9 kg versus − 0.9 kg) (F = 0.778, df = 1,58, p = 0.381). The number of people in each group able to lose any weight was identical ( = 0, p = 1.0); more patients in the carnitine group (nine versus five) achieved a clinically significant weight loss (≥5%) but this was not statistically significant (p = 1.0, Fisher's exact test).

Conclusions:  At the dose prescribed in this study carnitine supplementation did not improve weight loss outcomes in valproate‐treated bipolar patients consuming an energy‐restricted, low‐fat diet.
Pilot sample of very early onset bipolar disorder in a military population moderates the association of negative life events and non‐fatal suicide attempt
Authors: Pettit Jeremy W , Paukert Amber L , Joiner Thomas E , Rudd M David
Published: October 2006

Objective:  To examine the moderating effects of very early onset diagnostic status (≤ 13 years) upon the association between life events and non‐fatal suicide attempt.

Methods:  Measures of negative life events, suicidal ideation and current suicide attempt were administered to 298 military‐based young adults at entry to treatment for suicidality. Current and lifetime diagnoses were assigned using the Diagnostic Interview Schedule. The predictive ability of negative life events for non‐fatal suicide attempt was examined separately for the total sample and for those with retrospectively determined histories of very early onset bipolar disorder (VEOBPD; n = 16), very early onset major depressive disorder (VEOMDD; n = 21) and very early onset anxiety disorder (VEOANX; n = 53).

Results:  Negative life events and suicide attempt were significantly and positively associated among those with no history of VEOBPD (OR = 1.30, 95% CI = 1.02–1.65, p < 0.05), including those with VEOMDD and VEOANX. Consistent with expectation, VEOBPD moderated the association between negative life events and suicide attempt (OR = 0.88, 95% CI = 0.78–0.99, p < 0.05), such that negative life events were non‐significantly and negatively associated with the presence of a suicide attempt (OR = 0.21, 95% CI = 0.04–1.02, p = 0.09) among patients with a history of VEOBPD.

Conclusions:  Despite similar rates of suicide attempt among all diagnostic groups, life stress did not contribute to attempt among those with VEOBPD. These findings are consistent with the severity and chronicity of VEOBPD. Potential explanations of these findings include a scarring effect on coping skills and increased sensitization to life stress.
Linear and nonlinear methods for analyses of cardiovascular variability in bipolar disorders
Authors: Voss A , Baier V , Schulz S , Bar KJ
Published: October 2006

Objectives:  Heart rate variability (HRV), blood pressure variability (BPV), and the assessment of baroreflex sensitivity are widely accepted methods for analyzing and characterizing cardiovascular regulation and for an enhanced risk evaluation in different diseases. As a result of the complexity of the investigated regulatory systems, univariate analyses do not often provide a convenient description of pathological changes in the cardiovascular regulation. Therefore, the application of a multivariate approach is preferable.

Methods:  We present principal methods of time‐domain, frequency‐domain, and nonlinear analyses of HRV, BPV as well as methods for coupling and interaction analyses.

Results:  Changes in autonomic nervous system (ANS) tone are known to accompany various mental disorders. Depressive patients frequently complain of symptoms of ANS dysfunction, such as dry mouth, diarrhea, and insomnia. These clinical observations propose the assumption of altered autonomic dysfunction in these patients. In contrast to these clinical assumptions, inconsistent results have been found in studies of HRV in depressive patients. This work therefore covers a brief review of the literature in respect to bipolar disorder and the rationale to study autonomic changes in such a psychiatric disease.

Conclusions:  Prospective studies of cardiovascular changes in mania and depression are needed to evaluate a psychopathological state in connection with cardiovascular changes and cardiac morbidity and mortality. These studies should consider BPV, coupling and interaction analyses, the application of nonlinear methods, and a multivariate approach in addition to the traditional analysis of HRV.
Approximate entropy as a measure of irregularity for psychiatric serial metrics
Authors: Pincus Steven M
Published: October 2006

Objectives:  The quantification of subtle patterns in sequential data, and their changes, has considerable potential utility throughout psychiatry, including the analyses of mood ratings, heart rate, respiratory, and electroencephalographic recordings.

Methods:  Approximate entropy (ApEn), a relatively recently developed statistic quantifying serial irregularity, has been applied in numerous studies throughout mathematics and other fields of study, especially biology.

Results:  We discussed applications of ApEn, both extant and potential, of most relevance to psychiatrists. We provided a mechanistic interpretation of lowered ApEn values, and discusses the relationship between ApEn and other (both classical and complexity) measures of serial dynamics. We also briefly discussed cross‐ApEn, a thematically similar quantification of two‐variable asynchrony that can aid in uncovering subtle disruptions in complicated network dynamics.

Conclusions:  ApEn and cross‐ApEn have significant potential to consequentially enhance present statistical methodologies of analysis of psychiatric data, in both clinical and in research settings.
Increased Calcium Deposits and Decreased Ca2+‐ATPase in Right Ventricular Myocardium of Ascitic Broiler Chickens
Authors: Li K. , Qiao J. , Zhao L. , Dong S. , Ou D. , Wang J. , Wang H. , Xu T.
Published: October 2006

Right ventricular hypertrophy and failure is an important step in the development of ascites syndrome (AS) in broiler chickens. Cytoplasmic calcium concentration is a major regulator of cardiac contractile function and various physiological processes in cardiac muscle cells. The purpose of this study was to measure the right ventricular pressure and investigate the precise ultrastructural location of Ca2+ and Ca2+‐ATPase in the right ventricular myocardium of chickens with AS induced by low ambient temperature. The results showed that the right ventricular diastolic pressure of ascitic broilers was significantly higher than that of control broilers (P < 0.01), and the maximum change ratio of right intraventricular pressure (RV ± dp/dtmax) of ascitic broilers was significantly lower than that of the controls (P < 0.01). Extensively increased calcium deposits were observed in the right ventricular myocardium of ascitic broilers, whereas in the age‐matched control broilers, calcium deposits were much less. The Ca2+‐ATPase reactive products were obviously found on the sarcoplasmic reticulum and mitochondrial membrane of the control right ventricular myocardium, but rarely observed in the ascitic broilers. The data suggest that in ascitic broilers there is the right ventricular diastolic dysfunction, in which the overload of intracellular calcium and the decreased Ca2+‐ATPase activity might be the important factors.
Endometrial Polyp in an African Wild Dog (Lycaon pictus)
Authors: Cho H. S. , Park N. Y.
Published: October 2006

An 8‐year‐old female African wild dog (Lycaon pictus) from a zoo in Gyeonggi province, Republic of Korea presented with a 3.0 × 2.0 × 2.5 cm in size, smooth‐surfaced, solitary pedunculated mass protruding into the uterine lumen. Microscopically, the mass was covered with epithelium, contained endometrial gland tissue, and was dilated in the vascularised stroma. Within the mass, there was extensive diffuse haemorrhage with several blood vessels apparently plugged with fibrin. At the base of the mass, the spaces lined with epithelium near the attachment of the stalk were interpreted to be glandular structures. There were segments of cuboidal epithelium found on the surface of the mass, which was similar to the lining the uterus. A diagnosis of an endometrial polyp was made based on the gross and histology findings. This is the first case report of a spontaneous endometrial polyp in an African wild dog.
Influence of Short‐term Confinement and Exercise on Tibia Development in Growing Pigs
Authors: Weiler U. , Salloum B. Abi , Claus R.
Published: October 2006

The influence of short‐term confinement and moderate exercise on tibia development was investigated in growing pigs (36–41 kg, 10 weeks at the beginning of the study). Animals were kept for 2 weeks either in individual crates of 0.8 m2 (‘confinement’, n = 4) or kept in groups of four animals in large crates of 5.6 m2 without (‘control’) or with additional exercise (30 min walking at 5 days/week; ‘exercise’). Bone density and morphological parameters were evaluated by computer tomography (CT). Periosteal apposition and longitudinal growth were determined after polychrome sequential labelling in weekly intervals. Cortical areas of the cross sections at the mid‐shaft and at 75% of the length of the bone measured distal to the carpus by CT were significantly correlated to each other (r = 0.70) and revealed a significant reduction in confined animals. This difference was explained by lower periosteal apposition rates in these animals compared with exercised and group‐housed pigs. Similarly longitudinal growth and the formation and calcification of spongiosa of the tibiae were inhibited by confinement. Thus, 2 weeks of confinement led to significant differences in bone growth and metabolism in young growing piglets when compared with animals with moderate activity.
ANTI‐OXIDANT EFFECTS OF ATORVASTATIN IN DEXAMETHASONE‐INDUCED HYPERTENSION IN THE RAT
Authors: Mondo Charles K , Yang Wan‐Song , Zhang Nan , Huang Ti‐Gang
Published: October 2006

Dexamethasone (Dex)‐induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide () production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in in Sprague‐Dawley (SD) rats, thereby reducing blood pressure.

Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 µg/kg per day, s.c.) or saline was started after 4 days in Ato‐treated and non‐treated rats and continued for 11–13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail‐cuff method. Endothelial function was assessed by acetylcholine‐induced vasorelaxation and phenylephrine‐induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi‐quantitative reverse transcription–polymerase chain reaction.

In rats treated with Dex alone, SBP was increased from 109 ± 2 to 133 ± 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 ± 2 to 119 ± 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial‐dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001).

Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex‐treated SD rats.
d‐DOPA IS UNIDIRECTIONALLY CONVERTED TOl‐DOPA BYd‐AMINO ACID OXIDASE, FOLLOWED BY DOPA TRANSAMINASE
Authors: Wu Mei , Zhou Xiang‐Jun , Konno Ryuichi , Wang Yong‐Xiang
Published: October 2006

Many studies have shown that administration ofd‐3, 4‐dihydroxyphenylalanine (d‐dopa) produces contralateral rotation in hemi‐parkinsonian animals comparable tol‐dopa, with less potency and slower onset. It was postulated thatd‐dopa was converted tol‐dopa to produce these effects.

To investigate the postulated chiral inversion ofd‐dopa tol‐dopa and the related mechanism, an enantiomeric separation method ford‐ andl‐dopa using HPLC was first established. Then, rat kidney homogenates containingd‐dopa orl‐dopa were incubated and subjected to HPLC to detect traces of respective enantiomer generation. The mechanism of the chiral inversion ofd‐dopa was explored by direct measurement of the production ofl‐dopa in kidney homogenates.d‐Dopa incubations containing different concentrations of an inhibitor ofd‐amino acid oxidase (DAAO) and an inhibitor of dopa transaminase were measured forl‐dopa generation using HPLC. The role of DAAO in the chiral inversion ofd‐dopa tol‐dopa was further investigated by using purified DAAO and mutant ddY/DAAO−mouse kidney lacking DAAO activity.

In rat kidney homogenate,d‐dopa was, indeed, converted tol‐dopa, whereasl‐dopa was not converted tod‐dopa. Sodium benzoate, a selective inhibitor of DAAO, blockedl‐dopa generation in a concentration‐dependant manner. In contrast with kidney homogenates of wild‐type ddY/DAAO+mice, those of mutant ddY/DAAO−mice lacking DAAO activity did not convertd‐dopa tol‐dopa unless exogenous DAAO protein was added. Conversely, when carbidopa, an inhibitor of dopa transaminase, was added to the homogenates, significant inhibition ofl‐dopa production was noted.

These results prove the proposal thatd‐dopa undergoes unidirectional chiral inversion and further suggest thatd‐dopa is first oxidatively deaminated by DAAO to its α‐keto acid and then transaminated by dopa transaminase tol‐dopa.
EFFECTS OF GENETIC POLYMORPHISMS OFCYP3A4,CYP3A5ANDMDR1ON CYCLOSPORINE PHARMACOKINETICS AFTER RENAL TRANSPLANTATION
Authors: Hu Yong‐Fang , Qiu Wen , Liu Zhao‐Qian , Zhu Li‐Jun , Liu Zhong‐Qi , Tu Jiang‐Hua , Wang Dan , Li Zhi , He Jun , Zhong Gan‐Ping , Zhou Gan , Zhou Hong‐Hao
Published: October 2006

The calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P‐glycoprotein (P‐gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P‐gp could be considered to result from genetic polymorphisms encoding their genes.

The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms ofCYP3A4,CYP3A5andMDR1on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients.

One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction–restriction fragment length polymorphism forCYP3A4*18A,CYP3A5*3andMDR1 C3435T.Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose‐adjusted trough blood concentrations (C0) were determined and compared among the different genotype groups.

The frequency of theCYP3A4*18A, CYP3A5*3andMDR1 C3435Tvariant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose‐adjusted C0inCYP3A5*1/*1genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1–26.8 ng/mL per mg per kg), inCYP3A5*1/*3patients (n = 34) it was 23.7 ng/mL per mg per kg (range 9.0–61.0 ng/mL per mg per kg) and forCYP3A5*3/*3patients (n = 66) it was 26.4 ng/mL per mg per kg (range 9.8–85.8 ng/mL per mg per kg;P = 0.012, Kruskal–Wallis test). Accordingly, cyclosporine dose‐adjusted C0was larger in CYP3A5 non‐expressors than expressors in the first week after renal transplantation. In addition, wild‐type homozygotes (n = 21) forMDR1 C3435Thad a slight but significantly lower dose‐adjusted C0compared with heterozygotes (n = 58): 17.7 (10.3–60.8) versus 26.4 (9.0–67.3) ng/mL per mg per kg, respectively (P = 0.014, Mann–WhitneyU‐test).

In conclusion, the present study shows that genetic polymorphisms inCYP3A5may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with theCYP3A5*3variant genotype require a low dose of cyclosporine to reach target levels compared with those with theCYP3A5*1allele.
ANTIHYPERGLYCAEMIC AND ANTIPEROXIDATIVE ROLES OF ACARBOSE IN TYPE 2 DIABETES MELLITUS ARE POSSIBLY MEDIATED THROUGH CHANGES IN THYROID FUNCTION
Authors: Rameshwar Jatwa , Anand Kar
Published: October 2006

The aim of the present study was to reveal the possible involvement of thyroid hormones in the antihyperglycaemic and antiperoxidative effects of acarbose.

The effects of acarbose on changes in serum concentration of thyroid hormones, insulin and glucose in dexamethasone‐induced type 2 diabetic mice were investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced glutathione (GSH) content and the activity of associated endogenous anti‐oxidant enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were investigated in renal and cardiac tissues, which are commonly affected in diabetes mellitus.

Although administration of dexamethasone (1.0 mg/kg, i.m., for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD and CAT.

When dexamethasone‐induced hyperglycaemic mice were treated with acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were increased and most of the abnormalities, including serum insulin and glucose levels, tissue LPO, SOD and CAT activity and GSH content, were reversed.

These findings suggest the involvement of thyroid hormones in the mode of action of acarbose in amelioration of type 2 diabetes mellitus.
ClC‐1 CHLORIDE CHANNEL: MATCHING ITS PROPERTIES TO A ROLE IN SKELETAL MUSCLE
Authors: Aromataris Edoardo C , Rychkov Grigori Y
Published: October 2006

ClC‐1 is a Cl− channel in mammalian skeletal muscle that plays an important role in membrane repolarization following muscular contraction. Reduction of ClC‐1 conductance results in myotonia, a state characterized by muscle hyperexcitability.

As is the case for other members of the ClC family, ClC‐1 exists as a dimer that forms a double‐barrelled channel. Each barrel, or pore, of ClC‐1 is gated by its own gate (‘fast’ or ‘single pore’ gate), whereas both pores are gated simultaneously by another mechanism (‘slow’ or ‘common’ gate).

Comparison of the biophysical and pharmacological properties of heterologously expressed ClC‐1 with the properties of the Cl− conductance measured in skeletal muscle strongly suggests that ClC‐1 is the major Cl− channel responsible for muscle repolarization. However, not all results obtained in experiments on whole muscle or muscle fibres support this notion.

In the present review we attempt to bring together the current knowledge of ClC‐1 with the physiology of skeletal muscle.
Bathymetry, biota and sediments on the Hirota Reef, Tane‐ga‐shima – the northernmost coral reef in the Ryukyu Islands
Authors: Ikeda Emiko , Iryu Yasufumi , Sugihara Kaoru , Ohba Hideo , Yamada Tsutomu
Published: October 2006

Abstract  Investigations were conducted on bathymetry, reef biota and sediments on the Hirota Reef, Tane‐ga‐shima, North Ryukyus, near the northern limit for coral‐reef formation. A bathymetric profile from shore to the reef edge was depicted along an approximately 420‐m transect on the Hirota Coast of this island. A total of 20 quadrats (1 m × 1 m) were analyzed along the profile at 10‐ or 20‐m intervals to clarify distribution of macrobenthos inhabiting the reef. The Hirota Reef is divided into four geomorphologic zones according to their depth, gradient, surface roughness, substrate and characteristic macrobenthos. They are, from shore to offshore, shallow lagoon, seaward reef flat, reef edge and reef slope. The shallow lagoon comprises a shoreward depression (∼160 m wide on the transect) with a sand/gravel bottom that inclines gently toward offshore, and a seaward patch zone (∼70 m wide). The patches (<2 m high) are covered with fleshy algae, coralline algae and hermatypic corals. The seaward reef flat (∼190 m wide) is a flat plane that is constructed by biogenic carbonates and is covered with turf algae, with hermatypic corals scattered. Although the seaward reef flat of the Hirota Reef cannot be differentiated into different geomorphologic zones, similar seaward reef flat areas in the Central and South Ryukyus can be clearly subdivided into inner reef flat, reef crest and outer reef flat. This difference may be attributed to a lower reef growth rate and/or the later reef formation of the Hirota Reef in Holocene time than the southern examples. The coral fauna on the Hirota Reef is delineated by low diversity and characterized by taxa typical of high‐latitude, non‐reefal communities. The algal flora consists of tropical to subtropical species associated with warm‐temperate species. These faunal and floral characteristics may be related largely to lower water temperature in Tane‐ga‐shima than those in typical coral‐reef regions.
Characterization of magnetic particles and magnetostratigraphic dating of shallow‐water carbonates in the Ryukyu Islands, northwestern Pacific
Authors: Sakai Saburo , Jige Mayumi
Published: October 2006

Abstract  Characterization of magnetic particles, and magnetostratigraphic dating, of Holocene and Pleistocene shallow‐water carbonates (the Ryukyu Group) in the Ryukyu Islands was carried out to infer the age of reef formation. Magnetic particles from these strata are dominated by fine‐grained, single‐domain magnetite/maghemite (40–140 nm in length). The magnetite crystals exhibit the size and morphologies characteristic of the magnetite formed by magnetotactic bacteria. No large multidomain grains were seen in transmission electron microscopy observations. The widespread presence of single‐domain magnetite in the Ryukyu Islands suggests that bacterial magnetites carry depositional remanent magnetization, which is stable enough for magnetostratigraphic dating and thereby for elucidating the evolution of shallow‐water carbonates. The polarity‐reversal sequence seen in a core taken from the Ryukyu Group correlates with the timescale of the Matuyama chron, including the Jaramillo subchron, Kamikatsura or Santa Rosa Excursions, through the Brunhes chron. These magnetostratigraphic results imply that the time of reef initiation in the Ryukyu Islands of the northwestern Pacific was earlier than in the Great Barrier Reef of the southwestern Pacific, where it started after the Brunhes–Matuyama boundary.
Organic facies and geochemical aspects in Neogene neritic sediments of the Takafu syncline area of central Japan: Paleoenvironmental and sedimentological reconstructions
Authors: Sawada Ken
Published: October 2006

Abstract  Organic petrological observations of kerogen macerals and organic geochemical analyses of carbon isotopes of kerogen macerals and biomarkers were conducted on Neogene neritic sediments of the Takafu syncline area of central Japan. The Senmi, Sakainomiya and Lower Shigarami Formations in that area were deposited at the neritic provinces on the southern edge of the paleo‐Japan Sea during the Late Miocene to Early Pliocene. Sedimentary organic matter in these formations was almost terrigenous in origin. Changes in kerogen maceral compositions reflect sedimentological and tectonic histories evaluated in previous studies from sedimentary facies and paleontology. It was found that carbon isotope ratios (δ13C) of kerogen macerals increased from −28‰ to −25‰ from the Sakainomiya to the lower part of the Lower Shigarami Formations. The cause of that increase was presumably the expansion of C4 plants into southwest Japan. The timing was concordant with that of the expansion of C4 plant grasslands in East Asia. The oxicity (oxic to anoxic) conditions of sea bottoms evaluated from pristane/phytane ratios varied. Particularly, in the lower part of the Senmi Formation, layers in which no steroid biomarkers could be detected were found, and had presumably formed under oxic conditions when strong biodegradation had occurred. Concentrations of regular (C27–C29) steranes and dinosteranes were higher in the Sakainomiya and Lower Shigarami Formations. This indicates that dinoflagellates‐dominant primary productions were higher at those stages. In addition, concentrations of diatomaceous biomarkers such as C26 norsterane increased from the Lower Shigarami Formation, thus adding diatoms to the major producers. Furthermore, similar associations between the increases of δ13C values of kerogen macerals and concentrations of diatomaceous biomarkers were observed in the Takafu syncline area. Thus, the expansion of C4 plants was possibly associated with the high production of diatom in the shallow‐marine areas of the paleo‐Japan Sea during the Neogene Period.
Sensitive high‐resolution ion microprobe U‐Pb ages of the Latest Oligocene‐Early Miocene rift‐related Hidaka high‐temperature metamorphism in Hokkaido, northern Japan
Authors: Usuki Tadashi , Kaiden Hiroshi , Misawa Keiji , Shiraishi Kazuyuki
Published: October 2006

Abstract  In order to define the timing of granulite facies metamorphism, sensitive high‐resolution ion microprobe (SHRIMP) U‐Pb analyses were performed on zircons of three pelitic granulites from the lower metamorphic sequence of the Hidaka Metamorphic Belt, southern central Hokkaido, Japan. Both rounded and prismatic zircons were found in the granulite samples. The rounded zircons had thin (10–20 µm) concentric overgrowth rims on detrital cores, while the prismatic zircons did not have detrital cores. Both the overgrowth rims on the rounded zircons and the entire prismatic zircons were formed under granulite facies metamorphism and consistently yield Latest Oligocene–Early Miocene ages (23.7 ± 0.4 Ma to 17.2 ± 0.5 Ma; 206Pb/ 238U ages (n = 31) with low Th/U ratios, mostly <0.1). The internal structure of zircons and their SHRIMP U‐Pb ages provide strong evidence in support of the granulite facies event occurring during the Latest Oligocene‐Early Miocene. The detrital cores of rounded zircons show a huge variety of ages; Mesoarchean to Paleoproterozoic, Paleozoic to Mesozoic and Paleogene. The interior and marginal portions of the Eurasian continent including cratonic areas are suggested for their source provenances. These wide variations in age suggest that the protolith of the granulites of the lower metamorphic sequence were deposited near the trench of the Eurasian continental margin during Paleogene. The protolith of the lower metamorphic sequence of the Hidaka metamorphic belt was thrust under the upper metamorphic sequence, which had already been metamorphosed in early Paleogene. The Latest Oligocene‐Early Miocene Hidaka high‐temperature metamorphic event is presumed to have been caused by asthenospheric upwelling during back‐arc rifting of the Kuril and Japan basins.
Treatment of functional dyspepsia with serotonin agonists: A meta‐analysis of randomized controlled trials
Authors: Hiyama Toru , Yoshihara Masaharu , Matsuo Keitaro , Kusunoki Hiroaki , Kamada Tomoari , Ito Masanori , Tanaka Shinji , Chayama Kazuaki , Haruma Ken
Published: October 2006

Background:  Functional dyspepsia (FD) is often treated with serotonin agonists; however, the efficacy of such agents has recently been questioned. The aim of this study was to perform a meta‐analysis of randomized controlled trials (RCTs) comparing serotonin agonists with other types of prokinetics in patients with FD.

Methods:  Included studies were RCTs that compared serotonin agonists, including cisapride and mosapride, with dopamine antagonists, including metoclopramide and domperidone, and an opiate agonist, trimebutine, in patients with FD. Studies were identified by searching the Medline database (January 1951 – January 2005) and Cochrane Library (Issue 4, 2004), and by manual searches. The difference in the probability of patients' responses between the serotonin agonists and control agents was used as a summary statistic for the treatment effect. Meta‐regression analysis was used to detect sources of heterogeneity.

Results:  Five studies were identified. In total, 467 subjects were assigned to a serotonin agonist arm, and 322 subjects were assigned to a control arm. In the overall analysis, the summary statistic was 0.019 (95% confidence interval [CI]: −0.055 to 0.093; P = 0.612), indicating that the patients' responses to serotonin agonists were similar to those to control agents. However, in the stratified meta‐analysis of cisapride and mosapride, mosapride had a 6.7% greater probability of producing a response compared with control agents (summary statistic: 0.067; 95% CI: 0.010–0.124; P = 0.021), whereas no significant effect was observed with cisapride.

Conclusion:  The data suggest that mosapride may be more effective than cisapride for the treatment of FD. Although FD is a chronic condition, efficacy was assessed over short periods in the studies used for the present meta‐analysis. Long‐term RCTs are needed to confirm the effect.
Hepatosplenic γδ T‐cell lymphoma following seven malaria infections
Authors: Hassan Rocío , Franco Sergio A. L. , Stefanoff Claudio Gustavo , Romano Sergio O. , Diamond Hilda R. , Franco Luiz G. P. , Seuánez Héctor N. , Zalcberg Ilana R.
Published: October 2006

Hepatosplenic γδ T‐cell lymphoma (HSTL) is a clinicopathological entity associated with an immunocompromised status in approximately 25% of patients. Herein is described a case of HSTL in a 53‐year‐old Brazilian man with seven previous malaria infections, initially misdiagnosed as a hyperreactive splenomegaly due to chronic malaria. A characteristic lymphoid infiltrate was observed in spleen, liver and bone marrow sinusoids/sinuses. Neoplastic cells had a CD45RO+, CD2+, CD7+, CD3+, CD5–, CD8+, CD56+, perforin+, FasL‐negative, T‐cell receptor (TCR)αβ‐negative, TCRγδ+ profile. Analyses of γ and δ TCR rearrangements confirmed diagnosis of γδ T‐cell lymphoma by detecting VγI/Vδ1‐Jδ1 clonal rearrangements. Sensitive polymerase chain reaction (PCR) for Plasmodium falciparum, Epstein–Barr virus and herpesvirus‐8 failed to demonstrate infection. The disease progressed to a fatal outcome following cutaneous infiltration and leukemic proliferation. The authors also comment on the association of lymphoma and infection, focusing on PCR diagnosis of TCRγ and δ clonal rearrangements and the presumed pathogenic events leading to HSTL in the context of chronic malaria infection. Initial lymphomagenic stages might not be direct consequences of antigenic stimulation of Vδ1 T‐cells, but might depend on interactions between γδ T and B cells during cooperative or regulatory responses to Plasmodium sp.
Unusual hemangioendothelioma of the liver with epithelioid morphology associated with marked eosinophilia: Autopsy case
Authors: Kimura Tokuhiro , Mukai Makio , Kaneko Yuko , Hirakata Michito , Okamoto Shinichiro , Sakamoto Michiie , Okada Yasunori , Ikeda Yasuo
Published: October 2006

Vascular neoplasms characterized by epithelioid endothelial cells consist of several different entities from benignity to high‐grade malignancy. Because of histological overlap between them, there is substantial difficulty in classifying them correctly. The present patient, a 33‐year‐old man, presented with hepatomegaly, striking eosinophilia and elevated serum interleukin‐5 level. Biopsy and autopsy revealed an unusual epithelioid vascular tumor in the liver, which is histologically distinct from epithelioid hemangioma, epithelioid hemangioendothelioma, or epithelioid angiosarcoma. The tumor cells had vasoformative and partly solid growth with no severe nuclear atypia and very low mitotic activity, and the histological features were similar to those of the entity recognized as hemangioendothelioma of bone. Organs other than the liver, for example the testes and bone, were also involved. This tumor should be considered in the differential diagnosis of severe eosinophilia.
Serology of Chlamydia pneumoniae in patients with chronic cough
Authors: KIM Woo Jin , LEE Hui Young , LEE Mi Eun , LEE Seung‐Joon
Published: October 2006

Objective and background:  Chronic cough is one of the more common respiratory symptoms. Controversy exists as to whether Chlamydia infection is associated with chronic cough. As such, the association of chronic cough with serological evidence of Chlamydia pneumoniae (C. P) infection and a systemic inflammatory marker was assessed.

Methods:  Thirty‐seven patients who visited Kangwon National University Hospital for chronic cough between September 2003 and August 2004 and 37 age‐matched healthy controls were evaluated for C. P. antibodies and C‐reactive protein. Chronic infection was defined as an IgG or IgA titre between 1:64 and 1:512, and acute infection was defined as IgM = 1:16 or IgG titre of = 1:512 or IgA = 1:512. A nasopharyngeal swab was evaluated for C. P. DNA using the polymerase chain reaction.

Results:  The median duration of cough was 3 months (1–240). Nineteen patients (49%) and 19 controls had titres consistent with chronic infection, and the titre difference was not significant (P = 0.592). Nine patients and two controls had titres consistent with acute infection (24.3% vs. 5.4%). Acute infection was significantly more prevalent in the patients with chronic cough (P = 0.023). There was no difference in the C‐reactive protein value (0.13 vs. 0.14, P = 0.84). Three patients were positive for C. P. DNA.

Conclusion:  Acute Chlamydia infection was more prevalent in patients with chronic cough, whereas chronic Chlamydia infection was not. There was no elevation of a systemic inflammatory marker in patients with chronic cough.
Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using high‐resolution computed tomography
Authors: FUJIMOTO Keisaku , KITAGUCHI Yoshiaki , KUBO Keishi , HONDA Takayuki
Published: October 2006

Objective and background:  The present study was performed to clarify the clinical characteristics of patients with COPD classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening (BWT) evaluated by chest high‐resolution CT.

Methods  A total of 172 patients with stable COPD (FEV1 < 80%) were examined by chest high‐resolution CT. Emphysematous changes and BWT were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without BWT (A phenotype), emphysema without BWT (E phenotype) and emphysema with BWT phenotype (M phenotype). The clinical characteristics were compared among the three phenotypes.

Results  The A phenotype showed a higher prevalence of those who had never smoked and patients with wheezing both on exertion and at rest, higher values of BMI and diffusing capacity for carbon mononide (DLCO), milder lung hyperinflation, and greater reversibility of airflow limitation responsive to β2‐agonist as compared with the E phenotype. The M phenotype showed a higher prevalence of patients complaining of a large amount of sputum, productive cough and wheezing, higher rate of exacerbation or hospitalization and greater reversibility of airflow limitation responsive to β2‐agonist as compared with the E phenotype.

Conclusions  These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to bronchodilators.
Skeletal muscles in chronic obstructive pulmonary disease: Deconditioning, or myopathy?
Authors: WAGNER Peter D.
Published: October 2006

Abstract:  In recent years, COPD has become increasingly thought of as a systemic disease affecting many tissues and organs in addition to the lungs. The skeletal muscles in particular have been the target of much research focusing on whether the universally observed exercise limitation reflects a systemic myopathic effect of COPD, or simply the consequences of extreme, long‐term inactivity. In this paper, the evidence is reviewed for COPD patients without loss of muscle mass and who are not taking systemic steroids. While altered levels of antioxidant defences (lower), circulating inflammatory biomarkers (higher) and anabolic hormones (lower) have been found in COPD, cause and effect remains to be established for the link of inflammation/oxidative stress to muscle dysfunction. Other evidence used to propose a myopathic state (early lactate release, reduced power output, lower metabolic enzyme capacities, greater phosphocreatine breakdown and slower phosphocreatine restoration after exercise, and altered fibre type distribution) also occur in normal subjects who are extremely inactive. Furthermore, intense small muscle mass training can normalize small muscle function in these patients. Based on these data, it remains to be shown that the muscles in COPD patients without loss of muscle mass are myopathic. The interesting discussion about systemic effects of COPD should not get in the way of systematic muscle training, which has been shown to be an effective component of rehabilitation.
Clinical aspects of epidermal growth factor receptor inhibitors: Benefit and risk
Authors: KATO Tefurumi , NISHIO Kazuto
Published: October 2006

Abstract:  Gefitinib and erlotinib are small molecules that selectively inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. Developmental studies of either drug have failed to show synergistic effects when combined with cytotoxic drugs as the first line treatment in patients with advanced non‐small cell lung cancer, but erlotinib has shown survival prolongation when compared with best supportive care in patients with recurrence. Female gender, adenocarcinoma histology and lack of smoking history are considered to be clinical factors predicting response. Being positive for EGFR mutations in exons 18–24 in cancer cells has a strong correlation with response. On the other hand, preceding idiopathic pulmonary fibrosis, male gender and history of smoking appear to be risk factors for EGFR tyrosine kinase inhibitor‐induced interstitial lung disease in the Japanese population. Reports on these factors predicting response or risk for interstitial lung disease have attracted great interest in the relation between cancer genetics and drugs, as well as the relation between ethnicity and genetics. In clinical practice, EGFR tyrosine kinase inhibitor should be prescribed with careful consideration and it is essential to assess benefit and risk of the drug.
Effectiveness of early budesonide intervention in Caucasian versus Asian patients with asthma: 3‐year results of the START study
Authors: TAN Wan C. , LAMM Carl J. , CHEN Yu‐Zhi , O’BYRNE Paul M. , PEDERSEN Søren , BUSSE William W. , OHLSSON Stefan V. , ULLMAN Anders , ANDERSSON Bertil , PAUWELS Romain A.
Published: October 2006

Objective and background:  Few studies have assessed the effectiveness of inhaled corticosteroid therapy exclusively in Asian patients with asthma. The present analysis compared the efficacy of early intervention with inhaled budesonide in Caucasian and Asian patients over the first 3 years of the inhaled Steroid Treatment As Regular Therapy in early asthma study.

Methods:  Patients aged 5–66 years with mild persistent asthma of ≤2 years’ duration were randomized to 3 years of double‐blind treatment with once‐daily budesonide 200 µg (for patients aged <11 years) or 400 µg administered via Turbuhaler or placebo, plus usual asthma therapy.

Results:  Budesonide significantly improved asthma outcomes in both Caucasian (n = 4661) and Asian (n = 1995) patients compared with reference therapy (placebo plus usual asthma therapy). Budesonide reduced the risk of a first severe asthma‐related event by 42% and 49% in Caucasian and Asian patients, respectively, over the 3‐year treatment period (P < 0.001 for both). Moreover, budesonide significantly increased symptom‐free days, decreased nights with sleeping problems, improved pre‐ and postbronchodilator FEV1 and reduced the need for additional asthma medications of particular drug classes compared with reference therapy. Except for differences in the patterns of use of additional asthma medications, outcomes with budesonide and overall adverse events were similar in the Caucasian and Asian patient populations.

Conclusion:  Inhaled budesonide administered once daily in Asian patients with recent‐onset, mild persistent asthma significantly improved asthma control and pulmonary function compared with reference therapy. Moreover, this effectiveness paralleled that observed in Caucasian patients.
Cost of treatment for multidrug‐resistant tuberculosis in South Korea
Authors: KANG Young Ae , CHOI Yong‐Jun , CHO Young‐Jae , LEE Sang Min , YOO Chul‐Gyu , KIM Young Whan , HAN Sung Koo , SHIM Young‐Soo , YIM Jae‐Joon
Published: October 2006

Objective and background:  Costs associated with multidrug‐resistant tuberculosis (MDR‐TB) are higher than those associated with drug‐susceptible TB because of the higher prices of second‐line anti‐TB drugs, the prolonged duration of treatment, greater productivity loss and higher mortality. The aim of this study was to estimate the cost of treatment for MDR‐TB according to the treatment strategy and prognosis in South Korea.

Methods:  We estimated the direct (medical and non‐medical) and indirect cost for the treatment of MDR‐TB according to the treatment strategies and prognosis: in medically treated, surgically treated and deceased patients groups. The same analyses were undertaken for drug‐susceptible TB for comparison. The patients with MDR‐TB or drug‐susceptible TB were randomly selected from the TB cohort of Seoul National University Hospital, Seoul, South Korea.

Results:  Direct costs per person were US$4000 (US$2527–4841) in the medically treated group, US$17 457 (US$10 133–26 418) in the surgically treated group and US$33 362 (US$25 386–40 338) in the deceased group. Total costs per person were US$15 856 (US$10 752–38 421), US$47 159 (US$20 587–77 622) and US$478 357 (US$257 377–777 778), respectively. For the patients with drug‐susceptible TB, the total cost ranged from US$1680 to US$7637 (median US$2166).

Conclusions:  The cost for the treatment of MDR‐TB is seven to 22 times that of managing the drug‐susceptible TB in South Korea. Considering the high cost, transmissibility and considerable fatality of MDR‐TB, there is a need to provide specific separate funding for multidrug‐resistant tuberculosis.