bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of the Perception of Different Severity Measures of Citrus Canker and the Relationships Between the Various Symptom Types
Authors: Bock C. H. , Parker P. E. , Cook A. Z. , Gottwald T. R.
Published: May 2008

Citrus canker is a disease of citrus and is caused by the bacterial pathogen Xanthomonas citri subsp. citri. Ways of managing the disease are being sought, and accurate, precise, reproducible disease assessment is needed for monitoring epidemics. The objective of this study was to investigate the characteristics of visual assessment of citrus canker symptoms compared with actual disease measured using image analysis (IA). Images of 210 citrus leaves with a range of incidence and severity of citrus canker were assessed by three plant pathologists (VR1-3) and by IA. The number of lesions (L), % area necrotic (%AN), and % area necrotic+chlorotic (%ANC) were assessed. The best relationships were found between %AN and %ANC (r2 = 0.41 to 0.87), and the worst between L and %AN (r2 = 0.27 to 0.66). Bland-Altman plots showed various sources of rater error in assessments, including under- and over-estimation, proportional error, and heterogeneity of variation dependent on actual disease magnitude. There was a tendency to overestimate area diseased, but not lesion counts, and this tendency was pronounced at lower disease severity, with a leaf having more lesions tending to be assessed as having greater area infected compared with a leaf with fewer lesions but equal actual area infected. The rater estimations of disease were less accurate or precise with increasing actual disease severity as indicated by the fit of a normal probability density function—the incidence of extreme values increases with increasing actual disease. For example, for %ANC the kurtosis of the distribution ranged from 17.92 to 1.18, 0.51, and 0.22 in actual disease category ranges of 0 to 10, 11 to 20, 21 to 30, and 31 to 40% area infected, respectively. The log variance of the estimates plotted against log actual disease for all three raters over two assessment occasions gave a linear relationship for L, %AN, and %ANC (r2 = 0.74, 0.65, and 0.74, respectively). Training should improve the accuracy, precision, and reproducibility of raters, and knowledge of the characteristics of disease assessment should help develop and target the training more appropriately and address specific causes and sources of error.
Phytophthora Database: A Forensic Database Supporting the Identification and Monitoring of Phytophthora
Authors: Park Jongsun , Park Bongsoo , Veeraraghavan Narayanan , Jung Kyongyong , Lee Yong-Hwan , Blair Jaime E. , Geiser David M. , Isard Scott , Mansfield Michele A. , Nikolaeva Ekaterina , Park Sook-Young , Russo Joseph , Kim Seong H. , Greene Matthew , Ivors Kelly L. , Balci Yilmaz , Peiman Masoomeh , Erwin Donald C. , Coffey Michael D. , Rossman Amy , Farr David , Cline Erica , Grünwald Niklaus J. , Luster Douglas G. , Schrandt Julia , Martin Frank , Ribeiro Olaf K. , Makalowska Izabela , Kang Seogchan
Published: May 2008

Phytophthora spp. represent a serious threat to agricultural and ecological systems. Many novel Phytophthora spp. have been reported in recent years, which is indicative of our limited understanding of the ecology and diversity of Phytophthora spp. in nature. Systematic cataloging of genotypic and phenotypic information on isolates of previously described species serves as a baseline for identification, classification, and risk assessment of new Phytophthora isolates. The Phytophthora Database (PD) was established to catalog such data in a web-accessible and searchable format. To support the identification of new Phytophthora isolates via comparison of their sequences at one or more loci with the corresponding sequences derived from the isolates archived in the PD, we generated and deposited sequence data from more than 1,500 isolates representing the known diversity in the genus. Data search and analysis tools in the PD include BLAST, Phyloviewer (a program for building phylogenetic trees using sequences of selected isolates), and Virtual Gel (a program for generating expected restriction patterns for given sequences). The PD also provides a customized means of storing and sharing data via the web. The PD serves as a model that easily can be adopted to develop databases for other important pathogen groups.
First Report of Puccinia kuehnii, Causal Agent of Orange Rust of Sugarcane, in Guatemala
Authors: Ovalle W. , Comstock J. C. , Glynn N. C. , Castlebury L. A.
Published: May 2008

In September 2007 at Masagua, Escuintla Department, Guatemala, uredial lesions that appeared different from those of brown rust were observed on a sugarcane (a complex hybrid of Saccharum L. species) cultivar (CP 72-2086) considered resistant to brown rust caused by Puccinia melanocephala Syd. & P. Syd. Samples were sent to the USDA-ARS Systematic Mycology and Microbiology Laboratory in Beltsville, MD for identification. Observed morphological features were consistent with P. kuehnii E.J. Butler and appeared similar to orange rust samples obtained from Florida in July (2). Uredinial lesions were hypophyllous, orange, and variable in size measuring 650 to 850 × 26 to 32 μm. Urediniospores were mostly obovoid to pyriform or broadly ellipsoidal, variable in size, 32 to 45 × 25 to 30 μm, and moderately echinulate with spines evenly distributed, 3 to 5 μm apart. Urediniospore walls were orange-to-light cinnamon brown, 1 to 2.5 μm thick with a pronounced apical wall and four to five equatorial pores. Telia and teliospores were not observed. The nuclear large subunit rDNA region of the rust infecting cv. CP 72-2086 (BPI 898289, GenBank Accession No. EU344904) and the ITS1, 5.8S, and ITS2 rDNA regions (GenBank Accession No. EU543434) were sequenced (1,3). DNA sequences matched sequences of P. kuehnii in GenBank and were distinct from known sequences of P. melanocephala available in GenBank (3). Thirteen cultivars were rated as to their relative resistance using severity of orange rust symptoms; CG 96–59, CG 96–135, CP 72–1312, CP 73–1547, and CP 88–1165 were resistant; CG 96–40, CG 98–121, CP 72–2086, CP 88–1508, and CP 89–2143 were intermediate; and CG 96–52, CG 98–0115, and SP 79–2233 were susceptible. Orange rust was previously reported in Florida (2), but to our knowledge, this is the second report of its occurrence in the Western Hemisphere.

References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) J. C. Comstock et al. Plant Dis. 92:175, 2008. (3) E. V. Virtudazo et al. Mycoscience 42:447, 2001.
First Report of Laurel Wilt Disease Caused by a Raffaelea sp. on Avocado in Florida
Authors: Mayfield A. E. , Smith J. A. , Hughes M. , Dreaden T. J.
Published: May 2008

Laurel wilt is a vascular disease of redbay (Persea borbonia (L.) Spreng.) and other plants in the family Lauraceae in the southeastern United States. It is caused by a fungus (Raffaelea sp.) that is vectored by a non-native insect of Asian origin, the redbay ambrosia beetle (Xyleborus glabratus Eichhoff) (1). Since the initial detection of the redbay ambrosia beetle near Savannah, GA in 2002, laurel wilt has caused widespread mortality of redbay in Georgia, South Carolina, and Florida (1). In September 2007, an avocado (Persea americana Mill.) tree planted approximately 10 years earlier in a residential neighborhood in Jacksonville, FL was discovered to be infected with laurel wilt. The crown was in various stages of decline, including upper branches that were dead and leafless, those with wilted and drooping foliage, and those with healthy foliage. Removal of bark from wilted branch sections revealed black-to-brown streaks of discoloration in the sapwood and a few ambrosia beetle holes from which the discoloration extended into the adjacent wood. A Raffaelea sp. was isolated from discolored wood samples by surface sterilizing wood chips by submersion in a 5% sodium hypochlorite solution for 30 s and plating them on cycloheximide streptomycin malt agar (2). Small subunit (18S) sequences from the rDNA were amplified by PCR and sequenced with primers NS1 and NS4 (3). BLASTn searches revealed homology to Raffaelea sp. C2203 (GenBank Accession No. EU123076, 100% similarity, e-value of 0.0, and a total score of 1,886), which is known to be the causal agent of laurel wilt (1). The small-subunit rDNA sequence for this isolate has been deposited into GenBank and has been assigned accession No. EU257806. Pathogenicity of the laurel wilt pathogen on Persea spp. in growth chamber trials has been previously demonstrated (1). Laurel wilt is of concern to the commercial avocado industry and is a potential threat to the Lauraceae elsewhere in the Americas.

References: (1) S. W. Fraedrich et al. Plant Dis. 92:215, 2008. (2) T. C. Harrington. Mycologia 73:1123, 1981. (3) T. J. White et al. Page 315 in: PCR Protocols, a Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, CA, 1990.
First Report of Blackleg of Ajuga multiflora Caused by Phoma multirostrata in China
Authors: Lou B. G. , Hu X. Q. , Wu L.
Published: May 2008

Ajuga multiflora Bunge (Labiatae) is an ornamental that is widely planted in gardens in southern China. Blackleg symptoms were observed on A. multiflora during the autumn of 2005 in the Hangzhou area, Zhejiang Province. A. multiflora had to be replaced by other landscape plants during the past 2 years because of a serious outbreak of the disease. When the plant is in continuous cultivation for more than 2 years, disease incidence is more than 80%. Brown water-soaked spots appeared initially on the base of the petioles. Blackleg lesions from multiple infections may coalesce. Lesions often expand rapidly along the petioles followed by wilting and drying of individual leaves, ultimately resulting in the death of plants. The disease can occur at any time of year, but is most severe during the flowering stage. A fungus was consistently isolated from symptomatic tissues on potato dextrose agar. After 14 days on SNA (synthetic low nutrient agar; 1.0 g of KH2PO4, 1.0 g of KNO3, 0.5 g of MgSO4·7H2O, 0.5 g of KCl, 0.2 g of glucose, 0.2 g of sucrose, and 20 g of agar per liter) medium, the fungus produced light olive-to-gray mycelium, and later, generated brown, globose to subglobose pycnidia with hyaline, unicellular, and ellipsoidal conidia. Diameter of pycnidia ranged from 163 to 260 μm (average 203 μm). Conidiophores measured 3.5 to 6.2 × 2.0 to 3.2 μm (average 5.4 × 2.3 μm). The fungus was identified as Phoma multirostrata (P.N. Mathur, S.K. Menon & Thirum) Dorenb. & Boerema based on its morphological characteristics (1). The fungus grew between 4 and 36°C and optimum growth was at 23°C. To fulfill Koch's postulates, 15 healthy 20-day-old A. multiflora seedlings were planted in sterile soil artificially infested with P. multirostrata, which was grown on a mixture (1:10 w/w) of corn meal and sand. Soil was amended with 20% (w/w) of inoculum mixture. Another 15 plants grown in noninfested soil served as controls. All plants were grown at 22 to 25°C in the greenhouse. After 5 to 7 days, inoculated plants showed symptoms closely resembling those seen on plants from the garden. P. multirostrata was isolated from the margins of necrotic tissues on diseased plants, but not from the control plants. To our knowledge, this is the first report of P. multirostrata causing blackleg of A. multiflora in China.

Reference: (1) B. C. Sutton. The Coelomycetes. CMI, Kew, Surrey, UK, 1980.
First Report of Citrus Canker Caused by Xanthomonas citri in Somalia
Authors: Balestra G. M. , Sechler A. , Schuenzel E. , Schaad N. W.
Published: May 2008

Xanthomonas citri (synonym = Xanthomonas axonopodis pv. citri) (3) has been reported in several countries in Africa (1) but not Somalia. During 2006 and 2007, hyperplasia-type lesions, often surrounded by a water-soaked margin and yellow halo, typical of citrus canker caused by X. citri were found on 8- to 10-year-old lime (Citrus limetta) and grapefruit (Citrus × paradisi Macfed.) trees in northern and southern Somalia, respectively. Ten leaf samples diagnosed presumptively as citrus canker by Xac ImmunoStrip test kits (Agdia, Elkhart, IN) were mailed to the USDA Foreign Disease-Weed Science Research Unit at Ft. Detrick, MD. To confirm the identification of X. citri, isolations were made from several lesions from each sample onto yeast-dextrose-CaCO3 (YDC) agar (2). Yellow, xanthomonad-like mucoid, convex colonies were purified and stored on YDC slants. Phenotypic tests were done as described (2), and real-time PCR assays were done using primers XCit8F and XCit5R with probe XCitP2 (N. W. Schaad, unpublished). For pathogenicity tests, cultures were grown overnight in liquid nutrient broth-yeast (4) medium adjusted to contain 1 × 105 CFU/ml and inoculated into leaves of lime seedlings with the blunt end of a 2-ml syringe. After 21 to 30 days in a lighted dew chamber (Model I-60DLM; Percival Scientific, Inc. Perry, IA) at 30/23°C day/night, symptoms were recorded. Cultures of sample S-1 (northern Somalia) from lime were phenotypically atypical of X. citri, PCR negative, and nonpathogenic. However, cultures of samples 3 to 7 (southern Somalia) from grapefruit were typical of X. citri and PCR positive; cultures 3 and 4 were tested for pathogenicity and produced erumpent lesions on lime. Isolations onto YDC agar resulted in typical mucoid, convex, yellow, PCR-positive colonies. To our knowledge, this is the first report of X. citri on citrus plants in Somalia. Strains S3 and S4 have been deposited in ICPB at Ft. Detrick, MD as ICPB 11650 and 11651, respectively.

References: (1) J. F. Bradbury. Guide to Plant Pathogenic Bacteria. CAB International, Egham, UK, 1986. (2) N. W. Schaad et al. Xanthomonas. Page 175 in: Laboratory Guide for Identification of Plant Pathogenic Bacteria. 3rd ed. N. W. Schaad et al. eds. American Phytopathological Society, St. Paul. MN. 2001. (3) N. W. Schaad et al. Syst. Appl. Microbiol. 29:690, 2006. (4) A. K. Vidaver. Appl. Microbiol. 15:1523, 1967.
Comparative Survival of Sclerotia of Sclerotinia minor and S. sclerotiorum
Authors: Wu B. M. , Subbarao K. V. , Liu Y.-B.
Published: May 2008

Survival of sclerotia of Sclerotinia minor and S. sclerotiorum was compared in irrigated fields during the summer in two major lettuce production areas in California. More than 50% sclerotia of S. sclerotiorum compared with 4 and 35% of S. minor remained viable after 24 weeks of burial at 15 and 5 cm depths, respectively, in the San Joaquin Valley while >80% of sclerotia survived in the Salinas Valley for both species. The results explain in part the lower infections from S. minor in the San Joaquin Valley. To identify factors that contribute to the rapid decline in the viability of sclerotia, the effects of soil moisture, temperature, and oxygen levels were studied in laboratory. More than 90% of sclerotia of both species survived for at least 3 months in sterilized dry soils at temperatures between 15 and 40°C. Soil moisture did not affect survival at 15 and 25°C. At 35°C, however, survival rates were significantly lower at high (–0.3 to –0.01 MPa) water potential than at low (<–1.0 MPa) water potential. Incubation under ultralow oxygen concentration (0.01%) significantly reduced survival of sclerotia in nonautoclaved moist soils at 25°C, with less than 2% sclerotia surviving over 4 weeks compared with about 45% sclerotia surviving at the ambient oxygen level (21%). The combination of high temperature, high soil moisture, and reduced oxygen in irrigated fields contribute to the lower survival of both Sclerotinia species and the responses of the two species to these conditions shape their relative geographical distribution.
Infection by Meloidogyne artiellia Does Not Break Down Resistance to Races 0, 1A, and 2 of Fusarium oxysporum f. sp. ciceris in Chickpea Genotypes
Authors: Navas-Cortés J. A. , Landa B. B. , Rodríguez-López J. , Jiménez-Díaz R. M. , Castillo P.
Published: May 2008

Fusarium oxysporum f. sp. ciceris, and the root-knot nematode Meloidogyne artiellia, coinfect chickpea crops in several countries of the Mediterranean Basin. The influence of root infection by M. artiellia on the reactions of chickpea genotypes with different reaction to infection with F. oxysporum f. sp. ciceris races 0, 1A, and 2 was investigated under controlled environmental conditions. Results demonstrated that co-infection of chickpea genotypes resistant to specific fungal races by M. artiellia did not influence the Fusarium wilt reaction of the plant, irrespective of the F. oxysporum f. sp. ciceris race assayed. However, in some of the assayed combinations, coinfection by both pathogens significantly affected the level of colonization by the fungus or reproduction of the nematode in the root system. Thus, coinfection of chickpea plants with Foc-0 and M. artiellia significantly decreased the level of colonization of the root system by F. oxysporum f. sp. ciceris in genotypes ‘CA 336.14.3.0’ and ‘PV 61’, but not in ‘ICC 14216 K’ and ‘UC 27’. Similarly, the nematode reproduction index was also significantly reduced by coinfection with Foc-0 in the four chickpea genotypes tested and inoculated with this race. Conversely, coinfection of chickpea plants with Foc-1A and M. artiellia significantly increased colonization of the root system by the fungus in all genotypes inoculated with this race, except for line BG 212. Altogether, we confirmed the complete resistance phenotype of ‘UC 27’ and ‘ICC 14216 K’ to Foc-0, and of ‘ICC 14216 K’ to Foc-1A and Foc-2, and demonstrated that this resistance was not modified by coinfection of the resistant plant with M. artiellia.
Fusarium Populations on Chinese Barley Show a Dramatic Gradient in Mycotoxin Profiles
Authors: Yang L. , van der Lee T. , Yang X. , Yu D. , Waalwijk C.
Published: May 2008

We report on a large gene bank of Fusarium isolates established by a broad survey conducted in 2005 in which infected barley ears were collected in 23 counties of seven provinces and two municipalities along the Yangtze River in China. In total, 1,894 single spore isolates were obtained. The isolates were characterized at the species level by a newly developed and robust set of diagnostic primers based on single nucleotide polymorphisms (SNPs) among members of the F. graminearum clade. In addition, we determined their chemotype using previously described polymerase chain reaction (PCR) primers. The results showed that in all regions F. asiaticum was the predominant species causing Fusarium head blight (FHB) on barley in China (N = 1,706), while in the upper valleys of the Yangtze River also F. graminearum sensu stricto, F. meridionale, and F. proliferatum were found. Major differences in the chemotypes were found in the F. asiaticum populations, from very high to exclusive nivalenol (NIV) chemotypes in the mountainous upper valleys of the Yangtze River to predominantly deoxynivalenol (DON) chemotypes in the middle and lower valleys. In contrast to the F. asiaticum isolates from three counties in Sichuan province, which were largely NIV producers (278 of 291), F. graminearum isolates from these sampling sites were for the vast majority (27 of 28) DON producers, indicating that despite sharing the same habitat, these sympatric species apparently have unique mycotoxin chemotypes.
A uniformly valid asymptotic solution for a transverse jet and its linear stability analysis
Authors: Kelly Robert E , Alves Leonardo S. de B
Published: May 2008

An expansion in terms of the ratio
λ
of the characteristic crossflow velocity
U
∞
to jet velocity
U
j
, where
λ
=
U
∞
/
U
j
≪1, is used to obtain a representation of the basic three-dimensional steady flow in the nearfield of a transverse jet at large Reynolds numbers and to study its dominant instability. The inviscid vortex sheet analysis of Coelho and Hunt is extended so as to include asymptotic analysis of the viscous shear layers forming along the boundaries of the jet. These not only allow for continuity of the velocity components but also create vorticity whose advection induces an
O
(
λ
) axial flow in the direction of the jet. A uniformly valid solution is then constructed for use in a stability analysis that concentrates on the effect of crossflow upon the dominant mode of the free jet. Both the characteristic frequency and growth rate of this mode are found to increase with
λ
, in qualitative agreement with recent experimental observations.
Evolved physiological responses of phytoplankton to their integrated growth environment
Authors: Behrenfeld Michael J , Halsey Kimberly H , Milligan Allen J
Published: May 2008

Phytoplankton growth and productivity relies on light, multiple nutrients and temperature. These combined factors constitute the ‘integrated growth environment’. Since their emergence in the Archaean ocean, phytoplankton have experienced dramatic shifts in their integrated growth environment and, in response, evolved diverse mechanisms to maximize growth by optimizing the allocation of photosynthetic resources (ATP and NADPH) among all cellular processes. Consequently, co-limitation has become an omnipresent condition in the global ocean. Here we focus on evolved phytoplankton populations of the contemporary ocean and the varied energetic pathways they employ to solve the optimization problem of resource supply and demand. Central to this discussion is the allocation of reductant formed through photosynthesis, which we propose has the following three primary fates: carbon fixation, direct use and ATP generation. Investment of reductant among these three sinks is tied to cell cycle events, differentially influenced by specific forms of nutrient stress, and a strong determinant of relationships between light-harvesting (pigment), photosynthetic electron transport and carbon fixation. Global implications of optimization are illustrated by deconvolving trends in the 10-year global satellite chlorophyll record into contributions from biomass and physiology, thereby providing a unique perspective on the dynamic nature of surface phytoplankton populations and their link to climate.
Association of adipose most abundant transcript 1 gene (apM1) with type 2 diabetes mellitus in a Chinese population: a meta‐analysis of case‐control studies
Authors: Li Shengbing , Li Ling , Li Ke , Qi Xiaoya , Hoekema Dale , Liu Hua , Yang Gangyi
Published: May 2008

Background  Polymorphisms of the adipose most abundant transcript 1 gene (apM1) may be closely associated with type 2 diabetes mellitus (T2DM) as described in several recent publications. In the present study, a meta‐analysis was performed to quantitatively analyse the association of apM1 polymorphisms with T2DM using previous case‐control studies in Chinese populations.

Research design and method  Several electronic databases were searched for relevant articles up to January 2007. After data collection and gene loci selection, a meta‐analysis was performed to assess heterogeneity, combine results and evaluate variations. Publication bias was examined by the Egger's linear regression test and fail‐safe number for P = 0·05 (Nfs0·05). Hardy–Weinberg equilibrium (HWE) test and different effect models were employed for the sensitivity analysis.

Results  The meta‐analysis for this study included 2379 subjects from nine studies. The distribution of SNP45TG + GG and SNP276GG polymorphisms of the apM1 was analysed. Results of these experiments revealed a significant association between the SNP45TG + GG and SNP276GG polymorphisms of apM1 with T2DM in Chinese populations (P ≤ 0·05). There was some heterogeneity in the SNP45TG + GG apM1 among these studies. The odds ratio (OR) of apM1 genotype SNP45TG + GG in T2DM was 1·59 when compared with controls (95% CI, 1·00–2·53, P = 0·05), and the OR for the wild‐apM1 genotype SNP276GG in T2DM was 1·26 (95% CI, 1·00–1·59, P = 0·05). The publication bias diagnostics and sensitivity analysis confirmed the reliability and stability of this meta‐analysis.

Conclusion  This apM1 polymorphism was found to be strongly associated with T2DM, and the SNP45TG + GG and SNP276GG forms of the apM1 increased risk for T2DM in Chinese populations.
Metabolic and cardiopulmonary effects of detraining after a structured exercise training programme in young PCOS women
Authors: Orio Francesco , Giallauria Francesco , Palomba Stefano , Manguso Francesco , Orio Marcello , Tafuri Domenico , Lombardi Gaetano , Carmina Enrico , Colao Annamaria , Vigorito Carlo
Published: May 2008

Objective  The aim of the present study was to determine if the favourable cardiopulmonary and metabolic benefits induced by exercise training (ET) programme are maintained after its cessation.

Patients  Thirty‐two young overweight polycystic ovary syndrome (PCOS) women matched for age and body mass index (BMI) with other 32 PCOS patients was enrolled. The first group [PCOS‐T (trained)] underwent 24‐week ET programme, whereas the second [PCOS‐DT (detrained)] underwent 12‐week ET programme followed by 12‐week detraining period.

Methods  At baseline, after 12‐ and 24‐week follow‐up, all PCOS women were studied for their hormonal (ovarian and adrenal androgens), metabolic (glucose and insulin) and lipid profile, and underwent cardiopulmonary exercise test.

Results  After the initial 12‐week ET programme, both PCOS‐T and PCOS‐DT groups, without differences between groups, showed a similar significant (P < 0·05) improvement in BMI, fasting insulin, areas under curve insulin (AUCINS), glucose and insulin AUC (AUCGLU/INS), high‐density lipoprotein‐cholesterol (HDL‐C), low‐density lipoprotein‐cholesterol (LDL‐C) and maximal oxygen consumption at cardiopulmonary exercise test (VO2max). At 24‐week follow‐up, PCOS‐T group showed a significant (P < 0·05) improvement in BMI, fasting insulin, AUCINS, AUCGLU/INS, LDL‐C, HDL‐C and VO2max, in comparison to baseline and 12‐week follow‐up. At same follow‐up visit, the all parameters resulted significantly (P < 0·05) worsened in PCOS‐DT group in comparison to 12‐week follow‐up and PCOS‐T group. In PCOS‐DT group, no parameter assessed at 24‐week follow‐up was significantly different in comparison with baseline.

Conclusion  In young PCOS women, 12‐week detraining resulted in a complete loss of the favourable adaptations obtained after ET.
Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal tumours
Authors: Unger Nicole , Serdiuk Inna , Sheu Sien‐Yi , Walz Martin K. , Schulz Stefan , Saeger Wolfgang , Schmid Kurt W. , Mann Klaus , Petersenn Stephan
Published: May 2008

Background  Somatostatin mediates its action through five receptor subtypes (sst1–5) that are widely distributed in various endocrine tissues and tumours. Because of the inhibitory effects of somatostatin, long‐acting analogues have been synthesized. In contrast to their well‐established use in neuroendocrine and pituitary tumours, little is known about their potential use in adrenal tumours.

Objective  We examined somatostatin receptor protein expression in adrenal tumours of various aetiologies. Immunostaining was performed with specific polyclonal antibodies for sst1–5.

Design  Seven benign and eight malignant pheochromocytomas (PHEOs), eight aldosterone‐secreting adenomas (APAs), nine cortisol‐secreting adenomas (CPAs), seven nonfunctioning adrenal tumours (NFAs) and 25 adrenal carcinomas (CAs) as well as eight normal adrenal glands were investigated.

Measurements  Staining pattern, distribution and subcellular localization of the somatostatin receptor subtypes were evaluated.

Results  In the majority of normal cortices the expression of sst1–5 was limited to the reticular zone. The medulla was predominantly positive for sst3. Most cortical adenomas were positive for all five subtypes. However, in the majority of these tumours, less than 30% of cells were positively stained. A high expression of sst4 was found in CPAs but only very few cortical carcinomas exhibited sst immunostaining. All benign PHEOs were positive for sst3. The majority presented with more than 60% of tumour cells stained. By contrast, only six out of eight malignant PHEOs were positive for sst3.

Conclusions  Somatostatin receptor subtypes are expressed in PHEOs as well as in tumours of the adrenal cortex with tumour‐specific distribution patterns. This may offer new diagnostic and therapeutic possibilities.
Safety of GH replacement in hypopituitary patients with nonirradiated pituitary and peripituitary tumours
Authors: Chung T. T. , Evanson J. , Walker D. , Akker S. A. , Besser G. M. , Monson J. P. , Grossman A. B. , Drake W. M.
Published: May 2008

Background  Published data suggest that growth hormone replacement (GHR) may be given safely to patients with hypopituitarism consequent upon a pituitary/peripituitary tumour. However, a preponderance of patients treated with external pituitary irradiation were included.

Objective  To assess the safety of GHR in nonirradiated pituitary/peripituitary tumour.

Design  Prospective audit.

Setting  Tertiary university referral centre.

Patients  We imaged prospectively the pituitary glands of 48 patients (18 males; mean age 51·6 years range 21–77) who had adult onset growth hormone deficiency (AO‐GHD) after appropriate treatment for a pituitary/peripituitary tumour but who did not receive external pituitary irradiation.

Intervention  All patients were treated with a dose titration regimen of GH to maintain serum IGF‐1 between the median and upper end of the age‐related reference range. Pituitary surveillance imaging was performed prior to the commencement of GHR, at 6–12 months and then yearly. For patients with secretory tumours, biochemical markers (cortisol and prolactin) were used as evidence of tumour recurrence.

Results  48 patients with median follow up since commencement of GHR was 38 months (range 9–104). Three patients were judged to have an apparent increase in tumour volume and/or marker, although only one was thought to be possibly GH related – a patient with a cystic chromophobe adenoma who demonstrated a marginal increase in residual tumour volume 4 years after commencement of GHR.

Conclusion  These data add to the growing body of evidence for the safety of GHR in hypopituitary patients consequent upon pituitary/peripituitary mass lesions and represents the first reported series in a heterogeneous group of nonirradiated patients.
GH receptor d3 polymorphism in Dutch patients with MPHD and IGHD born small or appropriate for gestational age
Authors: De Graaff L. C. G. , Meyer S. , Els C. , Hokken‐Koelega A. C. S.
Published: May 2008

Objective  GH acts through the GH receptor (GHR). The GHR gene contains a genetic polymorphism caused by a deletion of exon 3 (d3), with high frequency in the normal population. There is a continuing controversy whether the presence or absence of the exon 3 deletion (d3+ vs. d3–) affects the effect of GH in human growth.

Design, patients and measurements  For 144 patients with idiopathic isolated GH deficiency (IGHD, n = 72) or multiple pituitary hormone deficiency (MPHD, n = 72), amplification of the region around exon 3 of the GHR gene was performed. Clinical data and response to GH treatment were compared between GHR d3+and d3– IGHD and MPHD patients born either small for gestational age (SGA) or appropriate for gestational age (AGA).

Results  IGHD patients born SGA had a significantly higher d3+frequency (82%) than IGHD patients born AGA (35%, P = 0·006). Within the group of IGHD patients born SGA, d3– patients showed a slightly better spontaneous catch up growth before start of GH treatment than d3+ patients (1·1 ± 1·1 SD vs. 0·6 ± 1·1 SDS, P = 0·040) There was no difference in patients first year's response to GH treatment between GHR d3+ and d3– patients.

Conclusions  In IGHD and MPHD patients, response to GH treatment was independent of GHR genotype. GHR‐d3 was significantly more frequent among IGHD patients born SGA. As we are the third to report an association between birth size and GHR d3 status, it is conceivable that the GHR‐d3 might affect prenatal growth in IGHD patients by a yet unknown mechanism.
High‐density lipoprotein cholesterol, C‐reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiography
Authors: Alber H. F. , Wanitschek M. M. , De Waha S. , Ladurner A. , Suessenbacher A. , Dörler J. , Dichtl W. , Frick M. , Ulmer H. , Pachinger O. , Weidinger F.
Published: May 2008

Background  Although high‐density lipoprotein cholesterol (HDL‐C) and C‐reactive protein (CRP) are well‐established predictors for future cardiovascular events, little information is available regarding their correlation with the prevalence and severity of angiographically evaluated coronary artery disease (CAD).

Material and methods   Five thousand six hundred forty‐one consecutive patients undergoing coronary angiography for the evaluation of CAD were analysed. Cardiovascular risk factors were assessed by routine blood chemistry and questionnaire. CAD severity was graded by visual estimation of lumen diameter stenosis with significant stenoses defined as lumen diameter reduction of ≥ 70%. Coronary angiograms were graded as one‐, two‐ or three‐vessel disease, as nonsignificant CAD (lumen irregularities < 70%) or non‐CAD.

Results   HDL‐C (60·3 ± 18·5 vs. 51·9 ± 15·3 mg dL−1; P < 0·001) was higher and CRP was lower (0·65 ± 1·68 vs. 1·02 ± 2·38 mg dL−1; P < 0·001) in non‐CAD (n = 1517) compared to overall CAD patients (n = 4124). CAD patients were older (65·2 ± 10·5 years vs. 59·9 ± 11·4 years), more often diabetics (19·2% vs. 10·6%) and hypertensives (79·2% vs. 66·0%) and included more smokers (18·8% vs. 16·5%) (all P < 0·005). Low‐density lipoprotein cholesterol (124·5 ± 38·3 vs. 126·0 ± 36·3 mg dL−1; P = NS) was similar in overall CAD and non‐CAD patients with more statin users (43·4% vs. 27·9%; P < 0·001) among CAD patients. Comparing non‐CAD with different CAD severities using analysis of variance, results did not change substantially. In a multivariate analysis, HDL‐C and CRP remained independently associated with the prevalence of CAD. In addition, HDL‐C is also a potent predictor for the severity of CAD.

Conclusions   In this large consecutive patient cohort, HDL‐C and CRP are independently associated with the prevalence of CAD. In this analysis, HDL‐C is an even stronger predictor for CAD than some other major classical risk factors.
Inflammatory markers in relation to insulin resistance and the metabolic syndrome
Authors: Ingelsson E. , Hulthe J. , Lind L.
Published: May 2008

Background  Inflammation has repeatedly been demonstrated to be associated with the metabolic syndrome (MetS) and insulin resistance, but the relative importance of different aspects of the inflammatory process is largely unexplored.

Design  We measured circulating interleukins (IL‐1α, IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10); other cytokines (tumour necrosis factor‐α, interferon gamma and monocyte chemotactic protein‐1), cell adhesion molecules [vascular cell adhesion molecule‐1 (VCAM‐1), intercellular adhesion molecule‐1, E‐selectin, P‐selectin, l‐selectin], and systemic inflammation markers [C‐reactive protein (CRP) and leukocyte count] in 943 70 year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. We related these biomarkers to MetS and the homeostasis model assessment insulin resistance index (HOMA‐IR).

Results  In a multivariable model including all inflammatory markers conjointly together with sex, log VCAM‐1 [odds ratio (OR), 1·45; 95% confidence interval (CI), 1·22–1·72 per 1 SD increase; P < 0·0001], log E‐selectin (OR, 1·33; 95% CI, 1·12–1·57 per 1SD increase; P = 0·001), and log CRP (OR, 1·41; 95% CI, 1·20–1·66 per 1‐SD increase; P < 0·0001) were independently associated with MetS. These biomarkers were also independently associated with HOMA‐IR.

Conclusions  Among 17 inflammatory biomarkers, most of them previously not examined in relation to MetS and insulin resistance, VCAM‐1, E‐selectin and CRP demonstrated the strongest associations with MetS and insulin resistance in our community based sample of the elderly. The relative importance of these biomarkers in predicting the development of MetS, insulin resistance and cardiovascular disease needs to be further examined in a longitudinal setting.
Inhibitor Development
Authors: ASTERMARK J. , LACROIX‐DESMAZES S. , REDING M. T.
Published: May 2008

Summary.  The immune response to factor VIII and the development of inhibitory antibodies is a complex multi‐factorial process involving a variety of immune regulatory genes and cells, several of which have the potential to determine risk. A better understanding of the mechanisms involved will increase the likelihood of development of new therapeutic options for patients with hemophilia. This review summarizes genetic and non‐genetic risk factors currently under evaluation, and the potential modulative effect of the von Willebrand factor on factor VIII immuno‐ and antigenicity. In addition, the role of T‐regulatory cells in the pathogenicity of inhibitors will be discussed.
New images in haemophilia
Authors: MAUSER‐BUNSCHOTEN E. P. , JANSEN N. W. D. , DORIA A. S. , OLDENBURG J.
Published: May 2008

Summary.  New imaging techniques are valuable for the care of patients with haemophilia. On angiography it is shown that some bleedings in severely damaged joints or after implantation of prostheses are arterial. Effect of clotting factor is often poor. Selective catherization with embolization of the bleeding artery stops the bleed and is clinically effective. From 31 patients with severe haemophilia A or B, 62 knee radiographs were scored according to the Pettersson‐scoring system as well as with Knee Digital Image Analysis (KIDA). Using KIDA, good correlation was found for osteoporosis, irregular subchondral surface, narrowing of the joint space, deformity and incongruence. For each of the parameters within one point in the Pettersson score a large variation existed in KIDA grading. MRI is accurate for diagnosis of soft and osteochondral tissue. Nevertheless, it is costly and not very accessible. The use of parallel imaging is more feasible for assessment of multiple joints within a relatively short period of time. Although ultrasonography also holds the potential for being an adjunct to MRI it has the disadvantage that it is operator‐dependent. In a cohort of 124 chronically HCV infected haemophilia patients transient elastography was performed to measure liver stiffness. 57 (46%) had no or mild fibrosis, 18 (14.5%) moderate fibrosis and 49 severe or cirrhotic fibrosis. Transient elastography is safe and helpful to refer patients to antiviral therapy.
Management of carriers and babies with haemophilia
Authors: STREET A. M. , LJUNG R. , LAVERY S. A.
Published: May 2008

Summary.  Although up to 30% of babies born with haemophilia do not have a family history of the disorder, the remaining 70% are born in families where haemophilia has been diagnosed. It has been estimated that for each male with haemophilia, there are five potential female carriers. Such women will benefit from knowledge of both their genetic (mutation present or not) and phenotype (level of plasma factor activity) status. Genetic counselling services to provide information and testing, together with plasma factor measurement, should be offered where available to all women at risk of being carriers. It is critical that women know their plasma factor measurement as they may have mild haemophilia (factor 5–30%, reference range 50–150%) which requires management at times of medical and surgical procedures and following trauma. Close liaison between adult and paediatric haemophilia centres and obstetric–gynaecology units is important to ensure that clinical carers identify and address carriers’ needs. Genetic testing should be performed only after a potential carrier has been counselled and supported to receive such information. There is no coercion to accept such testing. An advantage of genetic testing is to then discuss pre‐implantation genetic diagnosis which is an ex‐viro form of prenatal diagnosis. This can assist couples at risk of having a child with haemophilia who wish to reduce their anxieties about reproduction. Approximately 4% of boys with haemophilia, born in countries with good maternal care, will have intracranial haemorrhage in the neonatal period. There are no high‐level evidence‐based guidelines for the management of delivery or of the newborn with haemophilia. Obstetricians or other birth attendants need to be advised of the possibility of delivery of a boy with haemophilia and seek support from a haemophilia specialist during the pregnancy. The mother can then be monitored and plans for delivery be developed between her medical consultants and discussed with her. It is always preferable for a carrier to know of her genetic and phenotypic status before becoming pregnant so that she is informed as to her options and requirements for safe delivery.
Haemophilia in the first years of life
Authors: LJUNG R. , CHAMBOST H. , STAIN A.‐M. , DIMICHELE D.
Published: May 2008

Summary.  Surgery in infants and young children with haemophilia, when preceded by accurate diagnosis and accompanied by safe and effective factor prophylaxis, is not associated with a significant risk of haemorrhage. Haemophilic newborns undergoing circumcision or major surgery prior to diagnosis and in the absence of appropriate haemostatic prophylaxis remain as a concern. Inhibitor development has replaced haemorrhage as the major surgical complication in the developed world, largely because of the intensity of treatment used to secure haemostasis. For that reason only, essential surgery should be performed. Intracranial haemorrhage (ICH) during the neonatal period affects 3.5–4.0% of all haemophilia boys in countries with a good standard of health care, which is considerably (40–80 times) higher than expected in the normal population. Because of the high frequency of sporadic cases, ICH in the neonatal period can only be partially prevented by improved carrier diagnosis and counselling. Infections and thrombosis are the major serious complications of central venous lines. Large differences are seen in the frequency of these complications, the most plausible explanations are probably related to the protocol used for device care, the quality of education and the compliance of the users, an issue addressed in an on‐going study.
Inhibition of Leydig Cell Function Through Hormonal Regulatory Mechanisms
Authors: Dufau Maria L. , Hsueh Aaron J. , Cigorraga Selva , Baukal Albert J. , Catt Kevin J.
Published: May 2008

The regulation of testicular endocrine function by hormonal mechanisms depends upon the integrated actions of gonadotropins (LH, FSH and prolactin) and steroids (estrogen and androgen) upon the Leydig cell. Withdrawal of gonadotropic support by hypophysectomy causes partial loss of LH receptors and testosterone responses, whereas cyclic AMP responses are normal or increased. Thus, the major effects of hypophysectomy are on processes beyond receptor activation and cyclic AMP formation. Treatment with FSH increases LH receptors and testosterone responses to hCG, and reduces the elevated cyclic AMP responses to hCG in vitro. In FSH‐treated hypophysectomized rats, direct inhibitory actions of estrogen upon LH receptors and testosterone responses are demonstrable, indicating that intratesticular regulation of androgen biosynthesis could be exerted by locally formed estrogen.

While low concentrations of LH are necessary for maintenance of Leydig cell function, elevation of plasma LH by treatment with LHRH or exogenous gonadotropin has a marked negative effect on LH receptors and subsequent steroidogenic responses. Such hormone‐induced loss of LH receptors leads to decreased sensitivity of the Leydig cell to gonadotropin, an effect that is most evident after subcutaneous treatment with hCG. More acute increases in plasma gonadotropin are followed by a post‐receptor lesion in the steroidogenic pathway, with loss of the maximum testosterone response during stimulation by gonadotropin or cyclic AMP in vitro. The retention of pregnenolone responses and the accumulation of progesterone and 17‐hydroxylated steroids in partially desensitized Leydig cells indicates that a transitory block of the 17–20 desmolase step is rcsponsible for the second lesion in receptor‐depleted Leydig cells. Thus, the negative effects of LH and hCG on Leydig cell responses result from the combination of receptor loss and enzymatic defect(s), attributable to the local inhibitory effects of steroids, such as estrogens, that are formed during the acute tcsticular response to gonadotropin.
Autoregulation of LH/hCG Receptors and Catabolism of hCG in Rat Testis
Authors: Huhtaniemi Ilpo , Rajaniemi Hannu , Martikainen Hannu , Tikkala Liisa
Published: May 2008

The number of free and occupied LH/hCG‐receptors in adult rat testes after subcutaneous injections of hCG was studied. When 3–10 IU of hCG was injected, there was initially (between 6 and 16 h) a significant increase in free binding sites, without detectable occupancy of receptors. Higher doses (100 and 1000 IU) induced a drop in the amount of free receptors which was explained by simultaneous receptor occupancy. Later (between 12 and 48 h) there was a pronounced net loss of both free and occupied binding sites. Gel filtration of radioactivity extracted from testicular tissue demonstrated that following the initial uptake [125I]hCG undergoes a cleavage to subunits and hydrolysis to peptide fragments and amino acids. The autoradiographic results suggest that the degradative processes take place in Leydig cells. The degradation of [125I]hCG was markedly reduced by simultaneous injection of an excess of unlabelled hormone, supporting the autoradiographic evidence of the degradation site of [125I]hCG.
Mechanism of Reversible Loss of Reproductive Capacity in a Seasonally‐Breeding Mammal
Authors: Bartke A. , Goldman B. D. , Bex F. J. , Dalterio S.
Published: May 2008

Reversible loss of fertility which occurs annually in seasonally‐breeding species appears due to changes in the release of pituitary hormones, the levels of gonadal hormone receptors and the sensitivity of the hypothalamic‐pituitary system to inhibition by gonadal steroids. In the golden hamster, exposure to a short photoperiod causes reduction in plasma prolactin (PRL) levels, loss of testicular LH receptors, and gonadal atrophy. Reduction in plasma PRL is probably not secondary to inhibition of testicular steroidogenesis because it cannot be induced by castration or reversed by administration of testosterone. Treatment of gonadally regressed hamsters with PRL increases testicular weight, spermatogenesis, concentration of LH receptors in the testis and plasma testosterone levels. Prolactin‐producing ectopic pituitary homografts prevent loss of LH receptors and delay gonadal regression in animals transferred from a long to a short photoperiod. Treatment of adult male hamsters with PRL can increase plasma FSH levels. It is concluded that changes in PRL release play an important role in mediating the effects of photoperiod on testicular activity in the golden hamster.
Further Characterization of Androgen Binding Protein in Epididymis and Blood
Authors: Musto Neal A. , Gunsalus Glen L. , Bardin C. Wayne
Published: May 2008

Androgen binding protein (ABP) has been purified and conclusively shown to have a subunit structure. Antibodies against purified ABP were utilized to detect an immunoreactive material in blood of male rats. It has been shown that this material binds steroid and is the same size as native ABP. Steroid binding by serum albumin has been shown to mask binding by ABP in blood.