bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostaglandin D2 Receptors Control Osteoclastogenesis and the Activity of Human Osteoclasts
Authors: Durand Marianne , Gallant Maxime A , de Brum-Fernandes Artur J
Published: February 2008

We recently showed that human osteoblasts synthesize prostaglandin D2 (PGD2) and express both DP and CRTH2 receptors. Activation of the DP receptor decreased osteoprotegerin production, whereas activation of the CRTH2 receptor induced osteoblast chemotaxis and decreased RANKL expression. Our objectives in this study were to determine the presence, distribution, and action of these receptors in the functions of human osteoclasts and in osteoclastogenesis. Immunohistochemistry was used to detect the presence of DP and CRTH2 in in vitro–differentiated human osteoclasts in culture and in osteoclasts in situ. The effects of the activation of PGD2 receptors on the cytoskeleton were determined by fluorescence microscopy. Specific agonists and antagonists allowed the study of the roles of these receptors on bone resorption and osteoclast differentiation. Our results show that in vitro–differentiated human osteoclasts and authentic fetal osteoclasts express both DP and CRTH2 receptors, as shown by immunocytochemistry. Similar results were obtained in osteoclasts from normal, osteoporotic, pagetic, and osteoarthritic adult bone tissues. Stimulation of osteoclasts with PGD2 induced a robust reorganization of the cytoskeleton with a decrease in the number of cells presenting actin rings and an increase of lamellipodia, effects mediated by the DP and CRTH2 receptors, respectively. PGD2 showed an inhibitory effect on bone resorption activity acting through the DP receptor. In vitro osteoclastogenesis from peripheral blood mononuclear cells cultured in the presence of RANKL and macrophage-colony stimulating factor was decreased by activation of either DP or CRTH2 receptors. These results suggest that PGD2 receptors could be useful targets in certain bone diseases because their specific activation/inhibition leads to a decrease in osteoclastogenesis and to inhibition of bone resorption by osteoclasts.
Assessment of the 10-Year Probability of Osteoporotic Hip Fracture Combining Clinical Risk Factors and Heel Bone Ultrasound: The EPISEM Prospective Cohort of 12,958 Elderly Women
Authors: Hans Didier , Durosier Claire , Kanis John A , Johansson Helena , Schott-Pethelaz Anne-Marie , Krieg Marc-Antoine
Published: February 2008

This study aimed to develop a hip screening tool that combines relevant clinical risk factors (CRFs) and quantitative ultrasound (QUS) at the heel to determine the 10-yr probability of hip fractures in elderly women. The EPISEM database, comprised of ∼13,000 women ≥70 yr of age, was derived from two population-based white European cohorts in France and Switzerland. All women had baseline data on CRFs and a baseline measurement of the stiffness index (SI) derived from QUS at the heel. Women were followed prospectively to identify incident fractures. Multivariate analysis was performed to determine the CRFs that contributed significantly to hip fracture risk, and these were used to generate a CRF score. Gradients of risk (GR; RR/SD change) and areas under receiver operating characteristic curves (AUC) were calculated for the CRF score, SI, and a score combining both. The 10-yr probability of hip fracture was computed for the combined model. Three hundred seven hip fractures were observed over a mean follow-up of 3.2 yr. In addition to SI, significant CRFs for hip fracture were body mass index (BMI), history of fracture, an impaired chair test, history of a recent fall, current cigarette smoking, and diabetes mellitus. The average GR for hip fracture was 2.10 per SD with the combined SI + CRF score compared with a GR of 1.77 with SI alone and of 1.52 with the CRF score alone. Thus, the use of CRFs enhanced the predictive value of SI alone. For example, in a woman 80 yr of age, the presence of two to four CRFs increased the probability of hip fracture from 16.9% to 26.6% and from 52.6% to 70.5% for SI Z-scores of +2 and −3, respectively. The combined use of CRFs and QUS SI is a promising tool to assess hip fracture probability in elderly women, especially when access to DXA is limited.
Vitamin D Insufficiency: Disease or No Disease?
Authors: Hansen Karen E , Jones Andrea N , Lindstrom Mary J , Davis Lisa A , Engelke Jean A , Shafer Martin M
Published: February 2008

Vitamin D insufficiency (VDI) is widely reported. In patients with normal PTH, the diagnosis rests on increases in fractional calcium absorption (FCA) when 25(OH)D increases above 30 ng/ml. However, estimates of increased FCA after correction of VDI vary dramatically, depending on study methods. We used a dual stable calcium isotope to clarify the impact of vitamin D repletion on FCA in postmenopausal women with VDI. We hypothesized that FCA would increase with vitamin D repletion. We studied postmenopausal women with VDI [25(OH)D = 16–24 ng/ml] and an estimated calcium intake ≤1100 mg daily. Exclusion criteria included hypercalcemia, hypercalciuria, renal insufficiency, nephrolithiasis, gastrointestinal disorders, osteomalacia, prior adult fragility fracture, baseline T-score < −3.0, and use of medications known to interfere with vitamin D or calcium metabolism. Each woman underwent inpatient FCA studies before and after correction of VDI. We used ergocalciferol 50,000 IU/d for 15 days to achieve vitamin D repletion. During each study, women consumed their typical diet. They ingested 44Ca orally with breakfast and received 42Ca intravenously. We collected urine for 24 h and measured its calcium isotope content by mass spectrometry. Eighteen women completed the study; all but two had normal PTH. During the first and second FCA studies, their mean 25(OH)D level was 22 ± 4 and 64 ± 21 ng/ml, respectively (p < 0.001). Subjects' average FCA was 24 ± 7% initially and 27 ± 6% after vitamin D repletion (p = 0.04). Thus, FCA increased by 3 ± 1% with correction of VDI. Postmenopausal women with VDI experience small FCA increments with vitamin D therapy. In existing literature, this small change in FCA does not associate with lower fracture rates or consistently higher bone mass. Future studies should ascertain whether small FCA increments favorably affect the skeleton.
Mechanisms of the Anabolic Effects of Teriparatide on Bone: Insight From the Treatment of a Patient With Pycnodysostosis
Authors: Chavassieux Pascale , Karsdal Morten Asser , Segovia-Silvestre Toni , Neutzsky-Wulff Anita V , Chapurlat Roland , Boivin Georges , Delmas Pierre D
Published: February 2008

Pycnodysostosis is an extremely rare genetic osteosclerosis caused by cathepsin K deficiency. We hypothesized that teriparatide, a potent anabolic agent used in the treatment of osteoporosis, might reduce skeletal fragility by activating bone turnover. We studied a typical case of pycnodysostosis in a 37-yr-old woman who exhibited short stature, skull and thorax deformities, and a history of severe fragility fractures. Cathepsin K gene sequencing was performed. Before and after 6 mo of 20 μg/d teriparatide, biochemical markers of bone turnover were measured, and 3D bone structure and microarchitecture was assessed in vivo by HR-pQCT. Qualitative and quantitative analysis of transiliac bone biopsies were performed, and the degree of mineralization was evaluated by quantitative microradiography. In vitro assessment of bone resorption was performed after separation and differentiation of CD14+ monocytes from peripheral blood. Bone structure assessed by HR-pQCT on the radius and tibia showed augmentation of cortical and trabecular density. Transiliac bone biopsy showed highly increased bone mass (+63% versus age- and sex-matched controls), a decrease in bone remodeling without evidence of active osteoblasts, and a severe decrease in the dynamic parameters of bone formation (mineralizing surfaces, −90% and bone formation rate, −93% versus age- and sex-matched controls). This depressed bone turnover probably explained the increased degree of mineralization. The presence of a novel missense mutation leading to an A141V amino acid substitution confirmed a genetic defect of cathepsin K as the cause of the disease. The deficiency of active osteoclasts was confirmed by an in vitro study that showed a decreased concentration of CD14+ monocytes (the precursor of osteoclasts) in blood. These osteoclasts had low resorptive activity when incubated on bone slices. After 6 mo of teriparatide, the structure, microarchitecture, and turnover of bone—assessed by HR-pQCT, histology, and bone turnover markers—remained unchanged. Our data strongly suggest that some features of the osteoclastic phenotype—that are absent in pycnodysostosis—are a prerequisite for the anabolic effect of PTH on osteoblasts.
Compromised Bone Marrow Perfusion in Osteoporosis
Authors: Griffith James F , Yeung David KW , Tsang Polly H , Choi Kai C , Kwok Timothy CY , Ahuja Anil T , Leung Kwok S , Leung Ping C
Published: February 2008

A link between bone blood flow and osteoporosis may exist. Outside of the spine, the proximal femur is the most common site of osteoporotic fracture and is also an area prone to avascular necrosis and fracture nonunion. This study of the proximal femur investigates the relationship between BMD, bone marrow fat content, bone perfusion, and muscle perfusion. One hundred twenty healthy female subjects (mean age, 74 yr; age range, 67–89 yr) underwent DXA examination of the hip, proton MR spectroscopy, and dynamic contrast-enhanced MR imaging of the right proximal femur, acetabulum, and adductor thigh muscle. In all bone areas examined (femoral head, femoral neck, femoral shaft, acetabulum), perfusion indices (maximum enhancement, enhancement slope) were significantly reduced in subjects with osteoporosis compared with subjects with osteopenia or normal BMD. Adductor muscle perfusion was not affected by change in BMD. As marrow perfusion decreased in the proximal femur, marrow fat increased (r = 0.827). This increase in fat content seemed to account for the decrease in marrow perfusion more than a reduction in BMD. For normal BMD subjects, perfusion parameters in the femoral head were one third of those in the femoral neck or shaft and one fifth of those in the acetabulum. Perfusion throughout the proximal femur is reduced in osteoporotic subjects compared with osteopenic and normal subjects. This reduction in perfusion only affects bone and not those tissues outside of bone with the same blood supply. As bone perfusion decreased, there was a corresponding increase in marrow fat.
HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE
Authors: Zhou Zheng , Han Jun-Yan , Xi Cai-Xia , Xie Jian-Xin , Feng Xu , Wang Cong-Yi , Mei Lin , Xiong Wen-Cheng
Published: February 2008

High-mobility group box 1 (HMGB1), a nonhistone nuclear protein, is released by macrophages into the extracellular milieu consequent to cellular activation. Extracellular HMGB1 has properties of a pro-inflammatory cytokine through its interaction with receptor for advanced glycation endproducts (RAGE) and/or toll-like receptors (TLR2 and TLR4). Although HMGB1 is highly expressed in macrophages and differentiating osteoclasts, its role in osteoclastogenesis remains largely unknown. In this report, we present evidence for a function of HMGB1 in this event. HMGB1 is released from macrophages in response to RANKL stimulation and is required for RANKL-induced osteoclastogenesis in vitro and in vivo. In addition, HMGB1, like other osteoclastogenic cytokines (e.g., TNFα), enhances RANKL-induced osteoclastogenesis in vivo and in vitro at subthreshold concentrations of RANKL, which alone would be insufficient. The role of HMGB1 in osteoclastogenesis is mediated, in large part, by its interaction with RAGE, an immunoglobin domain containing family receptor that plays an important role in osteoclast terminal differentiation and activation. HMGB1-RAGE signaling seems to be important in regulating actin cytoskeleton reorganization, thereby participating in RANKL-induced and integrin-dependent osteoclastogenesis. Taken together, these observations show a novel function of HMGB1 in osteoclastogenesis and provide a new link between inflammatory mechanisms and bone resorption.
Serum Biomarker Profile Associated With High Bone Turnover and BMD in Postmenopausal Women
Authors: Bhattacharyya Sudeepa , Siegel Eric R , Achenbach Sara J , Khosla Sundeep , Suva Larry J
Published: February 2008

Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the identification of the individual proteins, this protein fingerprint may provide a novel approach to evaluate high bone turnover states.
Semantics as lexicography
Authors: Geurts Bart
Published: February 2008

Over the past few decades, the interpretation of language has gradually come to be accepted as a subject deserving its own academic regalia, such as conferences, journals, and university chairs. The definition of the emerging field of inquiry is, as yet, very moot. It is not even decided that it is a single field, rather than several related ones, and whether it (or they) should be subsumed under linguistics, psychology, or somewhere else. But there is a measure of consensus about the kind of topics the fledgling discipline is supposed to address. Here are a few examples:
NSM and the meaning of color words
Authors: Kay Paul
Published: February 2008

Uwe Durst (D) is to be commended for a clear exposition of the Natural Semantic Metalanguage (NSM) theory of Anna Wierzbicka (W) and her associates. In addition to laying out clearly the assumptions of the NSM theory, D states that

The …NSM model… has turned out to be a most useful theoretical and methodological framework for semantic analysis in various linguistic… domains.
NSM: Theoretical, methodological and applicational problems
Authors: Koptjevskaja-Tamm Maria , Ahlgren Inger
Published: February 2008

0. Introduction

Durst's paper is a well-written and clear survey of the Natural Semantic Metalanguage (NSM) model. However, it strikes us as somewhat over-enthusiastic and slightly simplistic: alternative positions and voices are not present, there is often no deep argumentation for or against a certain position, problems and complications are very seldom mentioned.
Servant of two masters? NSM and semantic explanation
Authors: Riemer Nick
Published: February 2008

1. Introduction

Uwe Durst opens his helpful précis with the claims that NSM ‘has turned out to be a most useful theoretical and methodological framework for semantic analysis’, and that it ‘is free from various shortcomings of other semantic frameworks.’ Since the insights of NSM scholars into the details of many semantic domains have frequently been acknowledged, the theory's usefulness for semantic description need scarcely be doubted. I would like to suggest, however, that Durst's second claim is more questionable. Not only is NSM subject to shortcomings of its own distinctive stripe, but it inherits others from the approach to semantic analysis characteristic of linguistics generally, of which, in the last analysis, it is only a particularly forthright exemplar. NSM's most significant problems, then, are just the problems of semantics in general, seen as part of the would-be scientific project of linguistics. These problems are not always obvious from Durst's survey, and in this commentary I will indicate some of the most interesting. Given the space available, I will not discuss the universality of NSM's proposed primitives, perhaps the issue which has most often stimulated discussion. I will also only address the lexical semantics aspects of NSM. These are, in any case, at the theory's core, and since analogous issues arise in its treatment of other topics, the omission from this commentary of any discussion of the NSM approach to morphology, cultural scripts, pragmatics, and the like is, I trust, appropriate.
Listen: Sequenzielle und prosodische Struktur einer kommunikativen Praktik – eine Untersuchung im Rahmen der Interaktionalen Linguistik
Authors: Selting Margret
Published: February 2008

I describe the construction of lists in my corpus of conversations in, mostly, Northern Standard German. With respect to the general structure of listing and lists, I will show the following points:

(i) Listing is always an embedded practice; lists are normally middle parts of a larger three-component structure that consists of

(a) the projection component, projecting more-to-come, i. e. a multiunit turn to be constructed, either a pre-detailing and/or a general formulation;

(b) the list itself, preferably three-parted, suggesting the items as part of either a closed or an open number of list items, as a practice of detailing;

(c) the gestalt closure, i. e. a post-detailing component, completing the structure around the list.

(ii) We should distinguish between (a) closed lists that suggest a closed number of items, and (b) open lists that suggest an open number of items. These classes of lists are produced with different kinds of practices. It seems to be the prosody that is used to suggest the intended kind of list, irrespective of its syntactic embedding.

(iii) Lists may be produced with different kinds of, albeit similar, intonation contours. But it is not so much the particular intonation contour that is constitutive of lists, but a variety of similar contours plus the repetition of the chosen contour for at least some or even all of the list items. Furthermore, intonation is deployed to suggest the interpretation of a potential final list item as either a list completer or as another item of the list with some kind of gestalt closure still to come.

I will show that intonation is indeed one of the methodically used constitutive cues that makes the production and structuring of lists recognizable for recipients.
Measurement of Rates of Delayed Hydride Cracking (DHC) in Zr-2.5Nb Alloys—An IAEA Coordinated Research Project
Authors: Coleman Christopher E. , Inozemtsev Victor V.
Published: February 2008

Values of DHC rates in Zr alloys are sensitive to measurement procedures. A standard method has been developed at the laboratories of AECL and evaluated in a round-robin involving ten IAEA member states. Two test materials were used—Zr-2.5Nb pressure tubes in the cold-worked (CANDU™) and heat-treated (RBMK) conditions. Cracks were grown from fatigued starter cracks in the axial direction on the axial-radial plane of the original tubes. To obtain the maximum value of Vc, specimens were heated to dissolve all their hydrogen, then cooled at 1 to 3°C/min to the test temperature before loading at 15 MPa√m. Although the start of cracking was detected by potential drop, the extent of cracking was measured directly on the crack faces. The values of incubation time to the start of cracking were highly variable but Vc was well behaved. The values of Vc were normally distributed with a range varying from a factor of 1.2 to 5.2. At 250°C the mean value of Vc from 80 specimens of cold-worked material was 8.9(±1.12)×10-8 m/s and from 41 specimens of heat-treated material the mean value of Vc was 3.3(±0.64)×10-8 m/s. Tests were also done at six other temperatures between 144 and 283°C, using up to 22 specimens at each temperature. Both materials had an Arrhenius-type temperature dependence, Vc= A exp(-Q/RT). The use of strictly defined and coordinated experimental procedures gave a consistent set of Vc values, allowing effective comparison of results obtained in different national laboratories and resulting in good correlations between the DHC velocity values and differences in strength, crystallographic texture, and distribution of β-phase in the test materials.
Effects of Pt Surface Coverage on Oxidation of Zr and Other Materials
Authors: Anghel Clara , Hultquist Gunnar , Limbäck Magnus , Szakalos Peter
Published: February 2008

Certain elements, including noble metals, are identified to influence corrosion behavior of many metals in high-temperature water/steam and O2. We have previously reported effects of porous Pt coatings on the thermal oxidation of Zr, Fe, Ni, Cr, and GaAs in O2. Effects of Pt on oxidation of Zircaloy-2 in H2O have also been observed at temperatures near 400°C. An enhanced oxidation rate is observed in all of the studied systems upon a sufficiently high surface Pt-particle density. Even more interesting, low Pt-particle density in most cases leads to a decreased oxidation rate. In the case of Zr and Zircaloy-2 the beneficial effect of Pt is stronger when hydrogen is present in the metal substrate and in the oxide layer. From 18O/SIMS experiments it is concluded that, for a sufficiently high Pt-particle density on the surface, enhanced transport of dissociated oxygen, On− (n=0; 2), towards the oxide/metal interface occurs in all of the studied systems. An oxygen spillover from Pt particles to the adjacent surface is a known phenomenon in catalysis and partly explains the results observed also in the current study of oxidation of Zr-based materials. Such a spillover involves a high surface diffusivity of dissociated oxygen, On−, which results in an increased gradient of On− across the oxide scale. In turn, the high oxygen gradient enhances the transport of oxygen towards the substrate/oxide-interface. This shows that not only diffusivity but also an effective activity of dissociated oxygen at the external oxide surface influences the oxidation rate. Naturally, the effects of Pt are maximized when small (nm-sized) and evenly distributed Pt particles are present on the surface. In our presentation a summary of obtained results of Pt additions on different materials will be given with suggested interpretations. Especially, the observed beneficial combination of Pt and hydrogen in the oxidation of Zr-based materials is discussed with a possible mechanistic explanation. Parallels are also drawn to the potential effect of Noble Metal Chemical Application (NMCA), used in a large fraction of the U.S. BWRs, on the corrosion resistance of Zr-based claddings.
Electrochemical Techniques in Corrosion: Status, Limitations, and Needs
Authors: Frankel Gerald S.
Published: February 2008

The corrosion of metals occurs primarily by electrochemical processes involving metal oxidation and simultaneous reduction of some other species. The fundamental understanding of these processes has allowed the development of a number of electrochemical techniques for the study of the corrosion phenomena and assessment of the corrosion rate. In fact, electrochemical techniques are so ingrained in the field that many practitioners think of corrosion rates first in terms of current density rather than thickness or mass loss per unit time. Standard approaches for electrochemical corrosion rate determination are commonly used in the field for on-line monitoring of systems and facilities. Electrochemistry also provides powerful tools for developing fundamental understanding of corrosion phenomena. However, there are some limitations to the abilities of current electrochemical techniques and some needs for the future. This paper describes the status of electrochemical techniques, their limitations, where non-electrochemical methods are required, and future needs in the field.
Liver Function Tests of Workers Exposed to Toluene and Toluene/Dimethylformamide at Low Concentrations
Authors: Wang Da‐Hong , Horike Tokushi , Mizuuchi Hidetsugu , Ishii Kunihiko , Zhen Li‐Xue , Taketa Kazuhisa
Published: February 2008

Liver Function Tests of Workers Exposed to Toluene and Toluene/Dimethylformamide at Low Concentrations: Da‐Hong Wang, et al. Department of Public Health, Okayama University Medical School—The purpose of our study was to analyse the results of liver function tests of workers exposed to toluene or to toluene/dimethylformamide (DMF) at levels below 100 ppm of toluene [(previous Occupational Exposure Limits of the Japan Society for Occupational Health); 10 ppm of DMF] in comparison with those of the reference group in order to see whether these solvents had any effect on the liver at levels generally considered to be safe. Our results suggested that occupational exposure to toluene below previous Occupational Exposure Limits of the Japan Society for Occupational Health lowered serum glutamic‐pyruvic transaminase (GPT) and gamma‐glutamyl transpeptidase (7‐GTP) activities significantly in males. On the other hand, serum levels of GPT and 7‐GTP in the female toluene‐ exposed group were significantly higher than those in the control group. Median Body Mass Index (BMI) levels and alcohol consumption did not show any significant difference between toluene‐exposed subjects and the controls, suggesting that toluene exposure or other unknown life‐style factors were likely to have more effects on the difference of serum GPT and 7‐GTP levels between toluene‐exposed and control subjects. Serum GPT activity in the DMF/tolu‐ ene‐exposed group was significantly higher than that in the toluene‐exposed group, and DMF exposure was considered to play a role in increasing the serum GPT activity in the DMF/toluene‐exposed male group. The present results that the decreased serum GPT and 7‐GTP levels in the toluene‐exposed male group necessitate performing further epidemiological and experimental studies to investigate the possible hepatic effect of toluene exposures at levels generally considered to be safe.
Effects of Low‐Dose Solvents on the Blood of Art Restorers
Authors: Tomei Francesco , Baccolo Tiziana Paola , Papaleo Bruno , Biagi Marco , Signorini Stefano , Persechino Benedetta , Rosati Maria Valeria
Published: February 2008

Effects on the Blood among Art Restorers: Francesco Tomei, et al. Department of Occupational Medicine, University of Rome “La Sapienza”—Restoration of art works is usually assessed from an artistic viewpoint, and little attention is paid to the restorers’ health. There appear to be no specific published reports. Art restoration is a craftsman's job, often done by students as part of their art courses, and they are exposed to low doses of a hard‐to‐classify range of different substances. This study employed a protocol designed for use in the workplace to check whether art restoration work had effects on the blood of the young people doing it. We studied 65 art restorer students and teachers, most of them young, who did different types of restoration work: on stone and archaeological findings, frescoes, paintings on wood and canvas, paper and parchment, plaster, fabrics, metals, wood or painted linings. Seventy‐one non‐exposed workers were compared as controls. We found significant reductions in RBC, Hb and Ht among exposed workers but no change in WBC. These findings suggest there may be problems in the effect on the blood of art restorers exposed to low doses of solvents. It would appear useful for these workers to undergo periodic blood screening tests, and the protocol we employed appeared suitable for identifying subjects at risk in their workplace.
Dose‐Response Relationship for Hand‐Arm Vibration Syndrome
Authors: Futatsuka Makoto
Published: February 2008

Dose‐Response Relationship for Hand‐ Arm Vibration Syndrome: Makoto Futatsuka. Department of Public Health, Kumamoto University School of Medicine—Dose‐effect relationships for hand‐arm vibration involve relating a complex physical agent to the production of a variable and a not fully understood set of disorders. The physical agent, vibration, may be of variable magnitude, frequency, direction and duration; it is often intermittent and may contain shocks. The method of holding a tool, its physical characteristics, the ambient temperature and other factors may effect the severity of vibration exposure. The first occurrence of white finger is the effect of hand‐arm vibration most usually considered in dose‐response relationships. Neither the identification nor the diagnosis of this disorder is always reliable and it may not be the only significant adverse effect of exposure to hand‐arm vibration. Data from cross‐sectional studies show that the prevalence of white finger generally increases with increases in the vibration magnitude. The frequency weighting often employed in vibration measurement standard is loosely based on studies of subjective response to vibration and has a velocity characteristic over this frequency range. There have been few studies of the influence of vibration exposure duration on the development of relevant signs and symptoms. In a cohort of persons exposed to the same vibration, the mean latency increases with increasing duration of exposure until all persons are affected. It is becoming common for the daily exposure to vibration to be assessed on a so‐called energy basis and expressed as an equivalent 8h exposure or an equivalent 4h exposure. This time‐dependency is convenient because it enables exposures to be quantified by means of root‐mean‐square averaging.
Medical Costs of Cigarette Smoking among Employees in a Company
Authors: Osaki Yoneatsu , Anada Kimiko , Minowa Masumi
Published: February 2008

Medical Costs of Cigarette Smoking among Employees in a Company: Yoneatsu Osaki, et at. Department of Epidemiology, Institute of Public Health—We analyzed the association between smoking status and medical costs for employees in a company to determine the direct influence of smoking on medical costs. Data on smoking status and cigarette consumption per day were linked to data on individual medical costs. Data for 1,381 persons out of 1,531 employees in a given age group were analyzed. The age range and mean age of the subjects were 30‐75 and 41.5 + 7.4 years old, respectively.

The proportion of employees who received any medical care was not significantly different among smokers, ex‐smokers, and non‐smokers. Although the average per capita costs (hereafter referred to as population average costs) by age group were not significantly different by smoking status, the medical costs for smokers tended to be lower than those of ex‐smokers and non‐smokers. When the medical costs per employee who received any medical care were compared among the three smoking status groups, a similar association was observed. No significant dose‐response relationship between cigarette consumption and medical costs was observed statistically.

These results indicate that medical costs for smokers are not higher than those for other smoking status groups. These results do not support antismoking measures in the workplace, but may be due to a small sample size, because no cases of death or malignant respiratory disease with the accompanying higher medical costs were observed during the study. A large sample study observing a direct relationship between smoking status and medical costs is therefore required for a more appropriate example of the harmfulness of smoking in the workplace.
Development of Pulmonary Lesions Following Acute Exposure to Diborane in Male ICR Mice
Authors: Uemura Takamoto
Published: February 2008

Develompment of Pulmonary Lesions Following Acute Exposure to Diborane in Male ICR Mice: Takamoto Uemura. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—In order to investigate the sequential development of respiratory injuries following acute exposure to diborane, male ICR mice were exposed to 15 ppm diborane for four hours and histo‐ pathological, hematological and serum biochemical examinations were conducted immediately, one day, three days and two weeks after exposure. Immediately after exposure, polymorphonuclear neutrophil infiltration of the bronchiolar lumens was observed. On the following day, macrophages had infiltrated into the alveolar and bronchiolar lumen. Multifocal and disseminated inflammatory obstructive changes, edema and congestion diffusely developed at the respiratory bronchiolus, and were diagnosed as diffuse panbronchiolitis (DPB)‐like lesions. These changes progressed most severely on day 3, and lung weight significantly increased with the severity of the pulmonary lesions. Transmission electron microscopy revealed deposition of fine fibrillar materials in the alveoli sacs immediately after exposure and phagocytosis of the materials by macrophages on day 3. At two weeks, few inflammatory cells in the bronchiolar lumen remained, and peribronchiolar thickening was disseminated at almost the same sites where DPB‐like inflammatory foci had been detected. These sequential changes in the histopathological observations from this study corroborated very well with the clinical signs and symptoms of human acute diborane poisoning cases reported in the 1960s. No significant changes in the nasal cavity or major bronchi were detected at any time. No particular trends were identifiable in the blood biochemistry findings. Further studies are necessary to elucidate the pathogenetic mechanism responsible for the respiratory organ damage caused by diborane.
Coal Workers’ Pneumoconiosis and Related Risk Indices
Authors: Niu Qiao , Liu Tianwang , Li Tang , Tang Hanchao , Bai Yuanping , Gao Tianshu
Published: February 2008

Coal Workers’ Pneumoconiosis and Related Risk Indices: Qiao Niu, et al. Department of Public Health, Shanxi Medical College—Cross sectional epidemiological studies were carried out in three coal mines (Mines A, B and C), that produce differnt types of coal in order to examine the relationship between the prevalence of coal workers’ pneumoconiosis (CWP) and factors contributing to the development and seriousness of CWP. Seven factors were taken into consideration and two of them were calculated as “risk indices”. They concerned composition (including carbon, ash, volatile content of coal, free silica in coal dust and rock dust) and exposure factors (including dust concentration, duration of exposure and type of operation). Composition factors were: carbon 90%, ash 23.13%, volatile content 13.85%, free silica in coal dusts 2.58% and free silica in rock dusts 32.88% in Mine A. Carbon 82%, ash 8%, volatile content 28.5%, free silica in coal dusts 5.90% and free silica in rock dusts 33.0% in Mine B. Carbon 94%, ash 20.46%, volatile content 10.76%, free silica in coal dusts 2.04% and free silica in rock dusts 24.04% in Mine C. Differences in the coal dust concentration over a period of 20 to 30 years were not significant in the three mines. The rock dust concentration in Mine B was much higher than those in the other two mines. The CWP prevalence was 2.22% in Mine A, 13.20% in Mine B and 1.86% in Mine C. Analysis has shown that both composition and exposure factors were related to CWP prevalence, but the strength of the relationship between the factors was different in the three mines, especially in Mine B, where there was a high CWP prevalence, and the association of CWP with free silica and high volatile content was strong. It was interesting that, though the rank of coal in Mine B was much lower than those in Mine A and Mine C, the prevalence of CWP in Mine B was much higher than those in Mine A and Mine C. This result was in contrast with those reported before. The calculation of risk indices indicated that there was a positive correlation between the risk indices and exposure duration.
A Research in the Effects of Active Listening on Corporate Mental Health Training
Authors: Kubota Shinya , Mishima Norio , Ikemi Akira , Nagata Syohji
Published: February 2008

A Research in the Effects of Active Listening on Corporate Mental Health Training: Shinya Kubota, et al. Department of Mental Health, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health—The effects of mental health training for corporate administrators, using Active Listening (Experiential Listening) as a major method was investigated. Sixty subjects took part in the mental health training program which consisted of 2 two‐day workshops (a total of 30 hr). The workshop program consisted of a lecture on stress, techniques of relaxation, the practice of Active Listening, and sharing of personal communication experiences in the workplace. Questionnaires which measured the Type A behavior pattern and the effects of Active Listening were collected in the first and last training sessions. The results showed significant differences in the degree of listening in the workplace in six of 27 items in the listening questionnaire and significant differences in three of seven items in the Type A questionnaire. Active Listening training seems to promote the attitudes of “listening genuinely” or “listening seriously” to workers. The practice of better listening may decrease the characteristics of the Type A behavior pattern such as “being busy” or “making others busy.” The mental health method focusing on Active Listening is discussed as a useful training technique for corporate mental health.
Trends in Major Occupational Injuries in Different Industrial Divisions in Taiwan during 1983‐1993
Authors: Chang Yu‐Chen , Wang Jung‐Der
Published: February 2008

Trends in Major Occupational Injuries in Different Industrial Divisions in Taiwan during 1983‐1993: Yu‐Chen Chang, et al. Department of Family Medicine, Tainan Municipal Hospital

Objectives

The purpose of this study was to examine the time trend in occupational injuries in main industrial divisions in Taiwan from 1983 through 1993 with newly developed quantification methods.

Methods

Data concerning deaths and permanent disabilities caused by occupational injuries were retrieved from the computer files of Taiwan's Labor Insurance Bureau and statistical analyses were performed by using the indices of the cumulative injury rate for from 1 5 to 64 years of age (CIR15_64), modified severity index (MSI), proportion of potential workdays lost (PPWDL) and foregone earnings lost.

Results

Mining and quarrying was the most risky industry, when expressed in both frequency and severity. The mean rates over the 1 1 year period were as follows: disabling frequency rate, 24.0; incidence rate, 0.012 (yr −1); CIR15_64, 0.491; disabling severity rate, 7,591.7; modified severity index, 22.5; and the PPWDL, 3.72 (10−3). In terms of frequency, incidence rate and CIR15‐64, manufacturing was second and agriculture third. With regard to severity, MSI and PPWDL, agriculture ranked second and construction ranked third. The overall trend in occupational injuries in Taiwan has steadily improved in the past decade. All indicators of human capital loss in 1993 were nearly down to one third of those reported in 1983. The estimated potential salary lost in all industries of 1993 was 584.6 million US dollars.

Conclusions

Mining and quarrying was still ranked the most risky industry during 1983‐93. We have demonstrated that CIR15_64, MSI, PPWDL and foregone earnings lost supplemented disabling frequency and severity rates in the aspect of human capital loss. There was a consistently improved trend in occupational injuries in Taiwan during 1983‐93.
Testicular and Hematopoietic Toxicity of 2‐Bromopropane, a Substitute for Ozone Layer‐Depleting Chlorofluorocarbons
Authors: Ichihara Gaku , Asaeda Nobuyuki , Kumazawa Toshihiko , Tagawa Yoshiaki , Kamijima Michihiro , Yu Xiaozhong , Kondo Hidetaka , Nakajima Tamie , Kitoh Junzoh , Yu II Je , Moon Young Hahn , Hisanaga Naomi , Takeuchi Yasuhiro
Published: February 2008

Testicular and Hematopoietic Toxicity of 2‐Bromopropane, a Substitute for Ozone Layer‐Depleting Chlorofluorocarbons: Gaku Ichihara, et al. Department of Hygiene, Nagoya University School of Medicine—In 1995r unexpected amenorrhea, oligozoospermia and anemia were discovered in Korean workers exposed to solvents containing 2‐bromopropane which was a substitute for chlorofluorocarbon. We aimed to determine experimentally the testicular and hematopoietic toxicity of 2‐bromopropane in male rats. Thirty‐six Wistar male rats were divided into four groups of nine each. The rats were exposed to 300r 1,000 and 3,000 ppm 2‐bromopropane or only fresh air, respectively, 8 hr a day, 7 days per week. The 300 ppm and 1,000 ppm groups were exposed for 9 weeks, but the 3,000 ppm group's exposure was discontinued and three rats in this group were dissected after 9‐11 days’ exposure because of serious illness. The others were dissected at the end of the experiment. At 300 ppm or over, the testicular and epididymal weights per body weight, epididymal sperm count, motile sperm percentage and the number of erythrocytes and platelets had decreased compared to the control. Histopathologically, all types of germ cells decreased in the 300 ppm group. Germ cells were absent but Sertoli cells still remained in the 1,000 ppm and 3,000 ppm groups at the end of the experiment. Spermatogonia were absent and the number of spermatocytes decreased in the 3,000 ppm group rats sacrificed after 1 1 days’ exposure. Sertoli cell vacuolations were marked in two of these three rats. Bone marrow was hypocellular in the 1,000 ppm group and in all the rats in the 3,000 ppm group. These results clearly showed that 2‐bromopropane had a testicular and hematopoietic toxicity in male rats.
Minamata Disease from the Viewpoint of Occupational Health
Authors: Nomura Shigeru , Futatsuka Makoto
Published: February 2008

Minamata Disease from the Viewpoint of Occupational Health: Shigeru Nomura, et al. Department of Public Health, Kumamoto University School of Medicine—Minamata disease is a neurological disorder caused by methyl mercury poisoning which occurred as the result of ingestion of large quantities of fish and shellfish polluted by industrial waste water in Minamata and Niigata, Japan. More than 40 years have passed since the epidemic was first reported in 1956 in Minamata. Inorganic mercury used as a catalyst in the acetaldehyde process had methylated inside the factory and had then been discharged into Minamata Bay. The waste from the acetaldehyde process continued to pour into the bay until 1968. In the process of researching possible causal elements, the Minamata Disease Study Group of the Kumamoto University School of Medicine found that the clinical and pathological findings in cases of Minamata disease coincided with certain cases of methyl mercury poisoning in England reported in 1940 by D. Hunter and D. S. Russell and which were published in a monograph on occupational toxicology in 1958. The English cases involved the poisoning of workers in a factory producing methyl mercury pesticide. It is clear that occupational poisoning can provide an important guide for the investigation into the cause of an environmental disease such as Minamata disease but there are differences between the two types of poisoning as they occur under different conditions. Occupational poisoning is a direct poisoning of workers which occurs under certain conditions, whereas Minamata disease involves the poisoning of the entire population of a contaminated area, including embryos, the aged and those who are already suffering from other diseases. When these points are considered, it becomes clear that although Minamata disease and occupational poisoning coincide with each other in some respects, they do not in others.
Use of Kinetic and Mechanistic Data in Species Extrapolation of Bioactivation: Cytochrome P‐450 Dependent Trichloroethylene Metabolism at Occupationally Relevant Concentrations
Authors: Lipscomb John C. , Garrett Carol M. , Snawder John E.
Published: February 2008

Use of Kinetic and Mechanistic Data in Species Extrapolation of Bioactivation: Cytochrome P‐450 Dependent Trichloroethylene Metabolism at Occupationally Relevant Concentrations: John C. Lipscomb, et al. United States Air Force, Armstrong Laboratory, Toxicology Division—Trichloroethylene (TRI) is an industrial solvent and environmental contaminant; therefore exposure to TRI occurs in diverse human populations. TRI causes hepatocellular carcinoma in B6C3F1 mice, but not rats; this suggests that TRI may be metabolized differently in the two species. We investigated the metabolism of TRI and the effect of TRI on enzymatic activities indicative of specific cytochrome P450 (CYP) forms in hepatic microsomes from mice, rats and humans. Studies in microsomes estimated Michaelis‐ Menten kinetic parameters by saturation analysis. Km values were 35.4, 55.5 and 24.6 μM and V values were 5,425, 4,826 and 1,440 pmol/min/mg in pooled mouse, rat and human microsomes, respectively. TRI (1,000 ppm) inhibited CYP2E1 dependent activity in all three species and BROD activity in mice and rats; TRI (1,000 ppm) increased CYP1A1/1A2 activity, and had no effect on CYP2A activity. Inhibition studies with mouse hepatic microsomes demonstrated that TRI was a competitive inhibitor of CYP2E1, with K of 50 ppm. TRI noncompetitively inhibited CYP2B‐dependent activities in the rat and mouse. Preincubation of microsomes with TRI and NADPH decreased the absorbence of CO‐bound CYP in all three species, but the dose‐dependence was most evident in mouse hepatic microsomes. These results have quantified the interspecies difference in CYP‐dependent TRI bioactivation and indicate that under both equivalent and occupationally relevant (hepatic) exposure conditions the human is at less risk of forming toxic CYP‐derived TRI metabolites.
Occupational Leukoderma in Workers Engaged in 4‐(p‐Hydroxyphenyl)‐2‐Butanone Manufacturing
Authors: Fukuda Yoshiharu , Nagano Megumi , Futatsuka Makoto
Published: February 2008

Occupational Leukoderma in Workers Engaged in 4‐(p‐Hydroxyphenyl)‐2‐Butanone Manufacturing: Yoshiharu Fukuda, et al. Department of Public Health, Kumamoto University School of Medicine—Occupational leukoderma was found to be caused by exposure to depigmentation agents. This is the first report associated with the depigmenting activity of 4‐(p‐Hydroxyphenyl)‐2‐butanone and its crude products. The purpose of this paper is to present three cases of occupational leukoderma in the upper extremities of workers engaged in the manufacturing of 4‐(p‐Hydroxyphenyl)‐2‐butanone. Two workers had symptoms of dermatitis in the same areas before depigmentation. An epidemiological study, their clinical courses and results of phototesting suggest that these cases of leukoderma were due to exposure to 4‐(p‐ hydroxyphenyl)‐2‐butanone and its crude products.