bluuebunny/crossref_metadata_2025 huggingface dataset:
Is reduced female survival after mating a by-product of male-male competition in the dung fly Sepsis cynipsea?
Authors: Teuschl Y , Hosken DJ , Blanckenhorn WU
Published: October 2007

Background

In a number of species males damage females during copulation, but the reasons for this remain unclear. It may be that males are trying to manipulate female mating behaviour or their life histories. Alternatively, damage may be a side-effect of male-male competition. In the black scavenger or dung fly Sepsis cynipsea (Diptera: Sepsidae) mating reduces female survival, apparently because males wound females during copulation. However, this damage does not seem to relate to attempted manipulation of female reproduction by males. Here we tested the hypothesis that harming females during mating is an incidental by-product of characters favoured during pre-copulatory male-male competition. We assessed whether males and their sons vary genetically in their ability to obtain matings and harm females, and whether more successful males were also more damaging. We did this by ranking males' mating success in paired competitions across several females whose longevity under starvation was subsequently measured.

Results

As previously reported, our results show mating is costly for female S. cynipsea. However, variance in female longevity was not explained by male identity, family, body size, number of previous copulations, or copulation duration. Nevertheless, there was a positive correlation between the harm fathers inflicted on their mates (affecting female longevity) and the harm sons inflicted on theirs. Additionally, family identity significantly influenced male copulation success.

Conclusion

Our results indicate a heritable component of some yet unspecified male trait(s) that influence harm and mating success. However, there was no relationship between copulation success of fathers or sons and the mean longevity of their mates. We therefore found no support for harm being a side effect of traits favoured in pre-copulatory male-male competition.
Genetic polymorphisms of TLR3 are associated with Nasopharyngeal carcinoma risk in Cantonese population
Authors: He Jun-Fang , Jia Wei-Hua , Fan Qin , Zhou Xin-Xi , Qin Hai-De , Shugart Yin Yao , Zeng Yi-Xin
Published: October 2007

Background

Nasopharyngeal carcinoma is endemic in Southern China, displays a strong relationship with genetic susceptibility and associates with Epstein-Barr virus infection. Toll-like receptor 3 (TLR3) plays an important role in the antivirus response. Therefore, we examined the association between TLR3 gene polymorphisms and NPC susceptibility.

Methods

We performed a case-control study of 434 NPC cases and 512 healthy controls matched on age, sex and residence. Both cases and controls are of Cantonese origin from Southern China. Genetic variants in TLR3 were determined by polymerase chain reaction (PCR)-based DNA direct sequencing and four SNPs were genotyped in all samples.

Results

Our results showed that allele C for SNP 829A/C increased NPC risk significantly ((p = 0.0068, OR = 1.49, 95%CI:1.10–2.00). When adjusted for age, gender and VCA-IgA antibody titers, the NPC risk was reduced significantly among individuals who carried the haplotype "ATCT" compared to those who carried the most common haplotype "ACCT" (p = 0.0054, OR = 0.028; 95% CI (0.002–0.341).

Conclusion

The TLR3 polymorphisms may be relevant to NPC susceptibility in the Cantonese population, although the reduction in NPC risk is modest and the biological mechanism of the observed association merits further investigation.
Informal knowledge transfer in the period before formal health education programmes: case studies of mass media coverage of HIV and SIDS in England and Wales
Authors: Hilliard Nick , Jenkins Rebeka , Pashayan Nora , Powles John
Published: October 2007

Background

How advances in knowledge lead via behaviour change to better health is not well understood. Here we report two case studies: a rapid reduction in HIV transmission in homosexual men and a decline in Sudden Infant Death Syndrome (SIDS) that took place in the period before the relevant national education programmes commenced, respectively, in 1986 and 1991. The role of newspapers in transferring knowledge relevant to reducing the risk of AIDS and SIDS is assessed.

Methods

HIV

Searches were made of The Times (1981–1985), Gay News (1981–1984) and, for the key period of April to June 1983, of eight newspapers with the highest readership. Information on transmission route and educational messages were abstracted and analysed.

SIDS

Searches were made of The Times and the Guardian (1985–1991), The Sun (selected periods only, 1988–1991) and selected nursing journals published in England and Wales. Information on sleeping position and educational messages were abstracted and analysed.

Results

HIV

Forty-five out of 50 articles identified in newspapers described homosexuals as an at risk group. Sexual transmission of AIDS was, however, covered poorly, with only 7 (14%) articles referring explicitly to sexual transmission. Only seven articles (14%) associated risk with promiscuity. None of the articles were specific about changes in behaviour that could be expected to reduce risk. Gay periodicals did not include specific advice on reducing the number of partners until early 1984.

SIDS

Out of 165 relevant articles in The Times and 84 in the Guardian, 7 were published before 1991 and associated risk with sleeping position. The reviewed nursing journals reflected a pervasive sense of uncertainty about the link between SIDS and sleeping position.

Conclusion

Presumptively receptive audiences responded rapidly to new knowledge on how changes in personal behaviour might reduce risk, even though the 'signals' were not strong and were transmitted, at least partly, through informal and 'horizontal' channels. Advances in knowledge with the potential to prevent disease by behaviour change may thus yield substantial health benefits even without the mediation of formal education campaigns ('interventions'). Formal campaigns, when they came, did make important additional contributions, especially in the case of SIDS.
Coccidioidomycosis in the U.S. Military
Authors: CRUM‐CIANFLONE NANCY F.
Published: October 2007

Abstract:  Coccidioidomycosis has had an impact on the military since the discovery of the causative agent, Coccidioides immitis, over a century ago. The first reports of Coccidioides outbreaks affecting U.S. military personnel were reported by Smith and others during World War II. Since that time, numerous outbreaks and sporadic cases have occurred, affecting both the health and readiness of our armed forces. This article summarizes the impact of Coccidioides sp
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on our military troops with a review of the literature, a description of the experience at a tertiary referral hospital treating the disease, and a synopsis of incidence studies conducted at bases in the southwestern United States. The substantial effect that coccidioidomycosis has had on the military supports the development of both newer and more effective treatments as well as a Valley Fever vaccine for prevention of this disease.
Compensability of, and Legal Issues Related to, Coccidioidomycosis
Authors: HALEY LUANN
Published: October 2007

Abstract:  Legal issues that may develop when treating patients with coccidioidomycosis include allegations of medical malpractice, claims for workers' compensation benefits, and civil actions against business owners. In states where the disease is most prevalent, California recognizes cocci diodomycosis as a compensable condition, although Arizona does not. In civil actions, the state courts have not imposed liability on any business or institution for those that claim to have developed cocci diodomycosis on or near the premises of the business.
Expanding Understanding of Epidemiology of Coccidioidomycosis in the Western Hemisphere
Authors: LANIADO‐LABORIN RAFAEL
Published: October 2007

Abstract: Coccidioidomycosis is a disease of both national and worldwide importance that is most often diagnosed in nonendemic regions. The endemic region forCoccidioidesspp. lies exclusively in the Western Hemisphere.Coccidioidesspp. has long been identified in semiarid areas of the United States and Mexico, and endemic foci have been described in areas of Central and South America. Infection is usually the result of activities that cause the fungus to become airborne and inhaled by a susceptible host. Underlying medical diseases that affect T cell function are known to increase the risk of disseminated disease and include human immunodeficiency virus, cancer, and disease processes requiring transplantation and its subsequent immunosuppressive agents. In recent years the incidence of the coccidioidomycosis has increased in California and Arizona, which may be partially due to the massive migration of Americans to the Sunbelt states. To date the highest number of cases reported in Arizona was in 2004, when a total of 3,665 cases of coccidioidomycosis was reported, representing a 281% increase since 1997. Statistics on the prevalence and incidence of coccidioidomycosis in Latin America either are fragmentary or simply are not available.
Comparative Aspects of Coccidioidomycosis in Animals and Humans
Authors: SHUBITZ LISA F.
Published: October 2007

Abstract: Coccidioidesspp. appear capable of infecting all mammals and at least some reptiles. Development of disease as a result of infection is species‐dependent. Dogs seem to have a susceptibility similar to that of humans, with subclinical infections, mild‐to‐severe primary pulmonary disease, and disseminated disease. Whereas central nervous system disease in humans is typically meningitis, brain disease in dogs and cats takes the form of granulomatous parenchymal masses. Osteomyelitis is the most common form of disseminated disease in the dog, while skin lesions predominate in the cat. Orally administered azole antifungal agents are the backbone of therapy in animals as they are in humans.
State‐of‐the‐Art Treatment of Coccidioidomycosis
Authors: BLAIR JANIS E.
Published: October 2007

Abstract:  Coccidioidomycosis is a fungal infection common in the southwestern United States that is caused by the endemic Coccidioides species of fungus. Coccidioidal infections are generally manifested as self‐limited respiratory illnesses, but affected patients rarely present with coccidioidomycosis in extrapulmonary locations. Skin and soft‐tissue coccidioidomycosis may occur in 15% to 67% of patients with disseminated infection. Skin manifestations of coccidioidomycosis can either be reactive rashes, such as erythema multiforme or erythema nodosum associated with primary pulmonary infection, or they can be the result of extrapulmonary dissemination of the infection to the skin. As many as 90% of persons with disseminated infection to the skin have other extrapulmonary sites of infection, and the presence of coccidioidal skin lesions should prompt an investigation for other extrapulmonary foci of infection. Lymph nodes are a common site of extrapulmonary infection. Nearly every organ system and soft‐tissue have been described as infected with Coccididioides species, but subcutaneous abscesses, phlegmon, and sinus tracts are not uncommon and often are themselves the result of coccidioidal infection in neighboring lymph nodes, bones, or joints. A biopsy of the abnormal area is the most direct way to diagnose skin and soft‐tissue lesions. Fluconazole and itraconazole are preferred therapeutic agents, and surgical intervention may be required as an adjunctive measure. This article reviews the types and locations of disseminated infections, as well as diagnostic studies and treatment of this difficult‐to‐treat manifestation of coccidioidomycosis.
Coccidioidomycosis in California State Correctional Institutions
Authors: PAPPAGIANIS DEMOSTHENES ,   the COCCIDIOIDOMYCOSIS SEROLOGY LABORATORY
Published: October 2007

Abstract:  Coccidioidomycosis (CM) has been recognized in inmates of California State prisons since 1919, where it has been diagnosed in inmates of various correctional facilities inside and outside the known endemic areas. In recent years construction of new prisons within endemic areas has led to an increase in the number of cases of CM. In 2005 and 2006, the Pleasant Valley State Prison (PVSP) near Coalinga and Avenal State Prison (ASP) near Avenal on the western side of the San Joaquin Valley have been particularly affected. In 2005, our serologic testing yielded 150 new cases from PVSP and 30 from ASP. The incidence rate in 2005 for PVSP (population approximately 5,000) was at least 3,000 per 100,000, and this will be exceeded in 2006. Some cases diagnosed in early 2006 likely were infections that were acquired in 2005. Some cases are medically managed on site, but very ill inmates have had care in nonprison facilities. Precise numbers of patients who were hospitalized were not made available to the author. Estimates of the cost per patient have varied from $8,000 in the 1990s to $30,000 more recently. Thus, this disease has important medical, demographic, and financial implications for the state.
Dendritic Cell‐Based Vaccine against Coccidioides Infection
Authors: AWASTHI SHANJANA
Published: October 2007

Abstract: 
Coccidioides causes coccidioidomycosis in the southwestern United States. Its clinical manifestations range from the primary asymptomatic to progressive pulmonary and extrapulmonary disease. Because of endemicity, frequent relapse, and virulent nature of Coccidioides, there is an urgent need for the development of effective therapy or vaccine. It has been recognized from studies in human patients and in murine models that the divergence in their susceptibility to Coccidioides infection is related to differences in T cell response. Dendritic cells (DCs) are most potent antigen‐presenting cells that play a critical role in activating naïve T cells. On account of their unique immunostimulatory capacity, DCs have been used for the development of immunotherapy and vaccines against cancer and infectious diseases. We recently investigated the immunostimulatory potential of a DC‐based vaccine in a murine model against Coccidioides posadasii (C. posadasii). Our results suggest that DCs act as a potent adjuvant and activate protective responses in mice against C. posadasii.
Nuclear Labeling of Coccidioides posadasii with Green Fluorescent Protein
Authors: LI LEI , SCHMELZ MONIKA , KELLNER ELLEN M. , GALGIANI JOHN N. , ORBACH MARC J.
Published: October 2007

Abstract:  Coccidioidomycosis is a mild to life‐threatening disease in otherwise healthy humans and other mammals caused by the fungus Coccidioides spp. Understanding the development of the unique dimorphic life cycle of Coccidioides spp. and its role in pathogenesis has been an area of research focus. However, nuclear behavior during the saprobic and parasitic life cycle has not been studied intensively. In this study, green fluorescent protein (GFP) was fused to histone H1 and introduced into Coccidioides posadasii (C. posadasii) strain Silveira to monitor the nuclear behavior of the fungus during the saprobic and parasitic stages of the life cycle. We constructed an Agrobacterium tumefaciens–mediated transformation (ATMT) vector that had in its T‐DNA region a hygromycin‐resistance gene as well as the fused histone H1‐GFP gene under the control of the histone H3 promoter of C. posadasii. More than 30 hygromycin‐resistant transformants were obtained and 23 were purified to homozygosity through multiple passages of the original transformants on hygromycin‐containing media. One strain (VFC1420) transformed with a single copy of the fusion histone H1‐GFP gene was selected for cytological studies. Strong nuclear‐localized GFP signals were observed in arthroconidia, hyphae, as well as in spherules and endospores developed in vitro. Thus GFP can be used to study the expression pattern of potential virulence genes identified in serial analysis of gene expression (SAGE) or expressed sequence tags (EST) libraries, and could be a useful tool to monitor disease development in the murine model.
Characteristics of the Protective Subcellular Coccidioidal T27K Vaccine
Authors: JOHNSON SUZANNE M. , KEREKES KATHLEEN M. , LUNETTA JENNINE M. , PAPPAGIANIS DEMOSTHENES
Published: October 2007

Abstract:  While the whole killed spherule vaccine, protective in mice and monkeys, did not prevent coccidioidal disease in humans, the 27K vaccine, a soluble derivative, retains protective activity in mice with little irritant action. Gel filtration and anion exchange fractions of thimerosal‐inactivated spherules (T27K), when administered with alum adjuvant, also protect mice against lethal respiratory coccidioidal challenge. However, the superb protection afforded by T27K antigens is maintained for some 3 months, but may then diminish. This appears unrelated to the aging of the mice. Prolongation of the protective action may require addition of a different adjuvant or administration of booster doses of vaccine.
Diagnosis and Treatment of Ocular Coccidioidomycosis in a Female Captive Chimpanzee (Pan troglodytes)
Authors: HOFFMAN K. , VIDEAN E. N. , FRITZ J. , MURPHY J.
Published: October 2007

Abstract:  We report here the first documented case of ocular coccidioidomycosis in a chimpanzee (Pan troglodytes). In 1996, a 12‐year‐old female chimpanzee was undergoing treatment with an experimental triazole, BayR3783, for coccidioidomycosis when she was diagnosed with severe conjunctivitis in the right eye. Subsequent development of a coccidioidal granuloma of the ventral conjunctiva and anterior uvea was noted over the next several months, distorting the lens, iris, pupil, and sclera and progressing to uveitis. Treatment with BayR3783 and subconjunctival injections of triamcinolone were successful in reducing the ocular mass, but extensive damage was done to the lens and cornea. This case study provides an interesting comparison to ocular coccidioidomycosis cases observed in both humans and canines.
Amphotericin B and Coccidioidomycosis
Authors: JOHNSON ROYCE H. , EINSTEIN HANS E.
Published: October 2007

Abstract:  Prior to the 1950s no effective therapy for coccidioidomycosis existed. The advent of amphotericin B ushered in the therapeutic era for coccidioidomycosis. Until this time amphotericin B and its lipid congeners have been regarded as the “gold standard” of therapy for severe pulmonary and disseminated coccidioidomycosis. The availability of azoles and later triazoles for the past three decades have relegated the amphotericins into a rescue mode, used mainly in widely disseminated cases, azole intolerance, or when there are contraindications to Azoles, such as pregnancy. In meningitis the intrathecal use of amphotericin B is still used frequently by some clinicians alone or with a triazole. The newer lipid preparations, while more expensive, have significantly reduced toxicity, particularly nephropathy.
Assessment of Climate– Coccidioidomycosis Model
Authors: COMRIE ANDREW C. , GLUECK MARY F.
Published: October 2007

Abstract:  Understanding the predictive relationships between climate variability and coccidioidomycosis is of great importance for the development of an effective public health decision‐support system. Preliminary regression‐based climate modeling studies have shown that about 80% of the variance in seasonal coccidioidomycosis incidence for southern Arizona can be explained by precipitation and dust‐related climate scenarios prior to and concurrent with outbreaks. In earlier studies, precipitation during the normally arid foresummer 1.5–2 years prior to the season of exposure was found to be the dominant predictor. Here, the sensitivity of the seasonal modeling approach is examined as it relates to data quality control (QC), data trends, and exposure adjustment methodologies. Sensitivity analysis is based on both the original period of record, 1992–2003, and updated coccidioidomycosis incidence and climate data extending the period of record through 2005. Results indicate that models using case‐level data exposure adjustment do not suffer significantly if individual case report data are used “as is.” Results also show that the overall increasing trend in incidence is beyond explanation through climate variability alone. However, results also confirm that climate accounts for much of the coccidioidomycosis incidence variability about the trend from 1992 to 2005. These strongly significant relationships between climate conditions and coccidioidomycosis incidence obtained through regression modeling further support the dual “grow and blow” hypothesis for climate‐related coccidioidomycosis incidence risk.
Molecular Cloning and Expression of a cDNA Encoding a Coccidioides posadasii Cu,Zn Superoxide Dismutase Identified by Proteomic Analysis of the Coccidioidal T27K Vaccine
Authors: LUNETTA JENNINE M. , SIMMONS KEIRA A. , JOHNSON SUZANNE M. , PAPPAGIANIS DEMOSTHENES
Published: October 2007

Abstract:   Previous studies have demonstrated that the coccidioidal T27K vaccine preparation is protective in mice against respiratory challenge using Coccidioides posadasii (C. posadasii) arthroconidia. Proteomic methods have been employed to define the molecular components within the vaccine. This method has led to the identification of novel and previously uncharacterized coccidioidal proteins including a Cu,Zn superoxide dismutase. A two‐dimensional gel of the T27K vaccine was run and spots were excised for mass spectrometric analysis. One peptide was obtained from the T27K gel that matched a TIGR C. posadasii 2.0 gene index tentative consensus sequence, TC1072, which is similar to fungal Cu,Zn superoxide dismutase. Activity assays performed with native PAGE gels of the T27K vaccine showed that the vaccine contains superoxide dismutase. The cDNA encoding the enzyme has been cloned and sequenced and expressed as a recombinant protein.
Coccidioidomycosis in Rheumatology Patients
Authors: MERTZ LESTER E. , BLAIR JANIS E.
Published: October 2007

Abstract:  Coccidioidomycosis is a potentially serious fungal infection contracted in endemic areas of the desert southwestern United States. Limited information exists about its incidence and clinical course in patients with rheumatic diseases, who may be at higher risk of symptomatic or disseminated coccidioidomycosis because of either the rheumatic disease itself or its treatment. We analyzed the incidence and risk factors for symptomatic and complicated coccidioidomycosis in our academic rheumatology practice in central Arizona. Between January 1, 2000, and June 30, 2006, coccidioidomycosis was diagnosed in 1.9% of the overall practice and in 3.1–3.6% of patients with rheumatoid arthritis (RA). The annual incidence was 1% in patients recently diagnosed with RA and 2% among patients with recently initiated infliximab treatment. Coccidioidomycosis was identified only in patients with inflammatory rheumatic diseases and extrathoracic dissemination occurred only to joints in two patients. Corticosteroids, immunosuppressive medications, and tumor necrosis factor inhibitors (TNFIs) appeared to be risk factors for symptomatic, but not disseminated coccidioidomycosis.
Experimental Animal Models of Coccidioidomycosis
Authors: CLEMONS KARL V. , CAPILLA JAVIER , STEVENS DAVID A.
Published: October 2007

Abstract:    Experimental models of coccidioidomycosis performed using various laboratory animals have been, and remain, a critical component of elucidation and understanding of the pathogenesis and host resistance to infection with Coccidioides spp., as well as to development of more efficacious antifungal therapies. The general availability of genetically defined strains, immunological reagents, ease of handling, and costs all contribute to the use of mice as the primary laboratory animal species for models of this disease. Five types of murine models are studied and include primary pulmonary disease, intraperitoneal with dissemination, intravenous infection emulating systemic disease, and intracranial or intrathecal infection emulating meningeal disease. Each of these models has been used to examine various aspects of host resistance, pathogenesis, or antifungal therapy. Other rodent species, such as rat, have been used much less frequently. A rabbit model of meningeal disease, established by intracisternal infection, has proven to model human meningitis well. This model is useful in studies of host response, as well as in therapy studies. A variety of other animal species including dogs, primates, and guinea pigs have been used to study host response and vaccine efficacy. However, cost and increased needs of animal care and husbandry are limitations that influence the use of the larger animal species.
The Complex Immunology of Human Coccidioidomycosis
Authors: AMPEL NEIL M.
Published: October 2007

Abstract:  The human immune response during coccidioidomycosis is intimately involved with the development of delayed‐type hypersensitivity and cellular immunity. Sixty percent of those infected have no symptoms and benign outcome is generally associated with a specific cellular immune response to coccidioidal antigens. We have recently teased out the human pulmonary granulomatous response during coccidioidomycosis and noted that there are perigranulomatous clusters of lymphocytes consisting predominantly of B lymphocytes and CD4+ T lymphocytes. In other work, we have found that the mannose receptor as well as the toll‐like receptors TLR2 and TLR4 may have a role in recognizing glycosylated coccidioidal antigens. In addition, the IL‐12 receptor axis appears to be operative during antigen recognition and IL‐12p40 may be the active moiety. Finally, peripheral blood mononuclear cells from persons with disseminated coccidioidomycosis are able to respond to coccidioidal antigen when it is presented by a mature monocyte‐derived IL‐4‐generated dendritic cell (DC). These observations could be useful in the development of a human vaccine against coccidiodomycosis.
Coccidioidomycosis in Persons Infected with HIV‐1
Authors: AMPEL NEIL M.
Published: October 2007

Abstract:  Coccidioidomycosis is a recognized opportunistic infection in those with HIV‐1 infection. The major risk factor is immunodeficiency, particularly when the peripheral blood CD4 T lymphocyte count is below 250/μL. There are many manifestations of coccidioidomycosis during HIV‐1 infection, including diffuse, reticulonodular pneumonia, focal primary pneumonia, and disease disseminated beyond the thoracic cavity. Diagnosis is based on serology, culture and histopathologic identification. Two therapeutic modalities are currently available, the polyene antifungal amphotericin B and the triazole antifungals. Of the latter, the most experience is with the triazoles fluconazole and itraconazole. There are increasing data regarding drug interactions between triazoles and antiretroviral agents. The duration of treatment of coccidioidomycosis in those with HIV‐1 infection is not established and in many patients it is either prolonged or life‐long. Adherence to antiretroviral therapy is important in preventing recurrence.
The Application of Proteomic Techniques to Fungal Protein Identification and Quantification
Authors: ROHRBOUGH JAMES G. , GALGIANI JOHN N. , WYSOCKI VICKI H.
Published: October 2007

Abstract: The number of sequenced genomes has increased rapidly in the last few years, supporting a revolution in bioinformatics that has been leveraged by scientists seeking to analyze the proteomes of numerous biological systems. The primary technique employed for the identification of peptides and proteins from biological sources is mass spectrometry (MS). This analytical process is usually in the form of whole‐protein analysis (termed “top‐down” proteomics) or analysis of enzymatically produced peptides (known as the “bottom‐up” approach). This article will focus primarily on the more common bottom‐up proteomics to include topics such as sample preparation, separation strategies, MS instrumentation, data analysis, and techniques for protein quantification. Strategies for preparation of samples for proteomic analysis, as well as tools for protein and peptide separation will be discussed. A general description of common MS instruments along with tandem mass spectrometry (MS/MS) will be given. Different methodologies of sample ionization including matrix‐assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) will be discussed. Data analysis methods including database search algorithms and tools for protein sequence analysis will be introduced. We will also discuss experimental strategies for MS protein quantification using stable isotope labeling techniques and fluorescent labeling. We will introduce several fungal proteomic studies to illustrate the use of these methods. This article will allow investigators to gain a working knowledge of proteomics along with some strengths and weaknesses associated with the techniques presented.
The Public Health Need and Present Status of a Vaccine for the Prevention of Coccidioidomycosis
Authors: HECTOR RICHARD , RUTHERFORD GEORGE W.
Published: October 2007

Abstract:  Although the epidemiology of coccidioidomycosis has been well described, there is a paucity of recent data on the public health burden associated with this disease. Accordingly, California's Inpatient Hospital Discharge Data Set from 1997 to 2002 was used to calculate the incidence of hospitalization for coccidioidomycosis by county, year, age, race, ethnicity, and gender. The overall finding that coccidioidomycosis has a significant impact in endemic areas supports the conclusion that the need for a preventive vaccine is great. Investigators of the Valley Fever Vaccine Project (VFVP) have successfully identified a number of recombinant coccidioidal protein antigens and two attenuated mutant strains that have been evaluated as vaccines, demonstrating protective responses in murine models. Efforts to select and develop a vaccine for human clinical trials are in progress.
Coccidioidomycosis Infection in a Predominantly Hispanic Population
Authors: PENA‐RUIZ MIGUEL ANGEL , MEZA ARMANDO D. , MULLA ZUBER D.
Published: October 2007

Abstract:  In Texas there are limited data on the epidemiology of coccidioidomycosis. Our goal is to determine the prevalence of coccidioidomycosis in a county hospital in El Paso, Texas. The charts of all patients with coccidioidomycosis admitted to the hospital in the past 9 years was retrospectively reviewed statistical analysis performed. Forty‐one cases were identified, giving a prevalence of 3.2 cases per 10,000 discharges. Pneumonic consolidation occurred in 14 (44%), miliary pattern in 6 (19%) and cavitation in 6 (19%) cases. Pulmonary involvement occurred in 32 patients (78%) and meningeal involvement in 3 patients. Six patients had disseminated disease. The mortality rate was higher with disseminated disease (50% compared to 3.6%, P= 0.04). Four had concomitant pulmonary tuberculosis. Diabetes mellitus was found in 17 patients (41.4%), followed by HIV infection in 15 (36.5%). Patients with HIV had a higher incidence of disseminated disease (36.4% vs. 0%, P= 0.01). Four patients died, and the risk of death was increased in disseminated disease (P < 0.05). Coccidioiomycosis is not as frequent in El Paso, and for that matter in Texas, as in other states, but still has to be taken into consideration both in HIV and in diabetic patients.
Azole Therapy of Clinical and Experimental Coccidioidomycosis
Authors: STEVENS DAVID A. , CLEMONS KARL V.
Published: October 2007

Abstract:  The therapy of coccidioidomycosis has been an early target, both experimentally and clinically, for study of new members of the azole class of drugs, because of the recognition that coccidioidomycosis is one of the most difficult mycoses to treat, and because our research group and our collaborators have been eager to pioneer new therapies for this problem pathogen. There have been steady advances in the pharmacologic and antimicrobial properties of this class since the initial introduction of miconazole, and many patients with coccidioidomycosis have benefited. Perhaps the greatest contribution has been the development of well‐tolerated oral drugs that make possible prolonged courses of a conveniently administered agent, and perhaps the most impressive advance has been the utility of the agents in coccidioidal meningitis, at least as an adjunct to the polyenes. More potent agents are still required, so that complete biological cure can be attained in meningeal and nonmeningeal coccidioidomycosis.
The Population Biology ofCoccidioides
Authors: BARKER B. M. , JEWELL K. A. , KROKEN S. , ORBACH M. J.
Published: October 2007

Abstract: Studies of field‐ and patient‐derived isolates conducted over the past 75 years have provided a general picture of the population structure ofCoccidioides, the cause of coccidioidomycosis. Premolecular studies provided a general outline of the geographical range, epidemiology and distribution of the fungus. Recent studies based on molecular markers have demonstrated that the genus is comprised of two genetically diverse, and genetically isolated, species:Coccidioides immitisandC. posadasii. Both species are composed of biogeographically distinct populations. Structure for two of these populations (C. immitisfrom central California, andC. posadasiifrom southern Arizona) indicates that frequent genetic recombination occurs within the entire geographic range of each population, even though sex has never been observed in the genus. Outbreaks of coccidioidomycosis are not the result of the spread of a single clonal isolate, but are caused by a diversity of genotypes. Although it is now possible to match patient isolates to populations, the lack of apparent structure within each population and the current paucity of environmental isolates limit map‐based epidemiological approaches to understanding outbreaks. Therefore, a comprehensive database comprised of soil‐derived isolates from across the biogeographic range ofCoccidioideswill improve the utility of this approach. Appropriate collection of environmental isolates will assist the investigation of remaining questions regarding the population biology ofCoccidioides. The comparative genomics of representative genotypes from both species and all populations ofCoccidioideswill provide a thorough set of genetic markers in order to resolve the population genetics of this pathogenic fungus.
Coccidioidomycosis: Changing Perceptions and Creating Opportunities for Its Control
Authors: GALGIANI JOHN N.
Published: October 2007

Abstract:  The perceptions of coccidioidomycosis as a medical problem has undergone sequential and dramatic metamorphoses since its first description more than a century ago. First thought to be rare and lethal, coccidioidomycosis was subsequently found to be common and often mild. During World War II, its overall impact upon large populations came sharply into focus and the consequences for public health became clearer. Early treatments had significant limitations and toxicities, and therefore treatment of coccidioidomycosis was reserved for only the sickest patients. Since then, safer oral therapies have become commonplace. Despite their availability, there has been no investigation of their use in the less severe and much more common early infections. Even newer drugs such as nikkomycin Z, which might actually cure infections, until very recently have had trouble finding a sponsor to move it through clinical trials. Perceptions once formed by the understanding of coccidioidomycosis as a medical problem now appear to hinder the future study of newer therapeutic opportunities. It is suggested in this review that it is time to revisit and possibly change these perceptions if we are to improve our care of patients.
Public Health Surveillance for Coccidioidomycosis in Arizona
Authors: SUNENSHINE REBECCA H. , ANDERSON SHOANA , ERHART LAURA , VOSSBRINK ANNE , KELLY PETER C. , ENGELTHALER DAVID , KOMATSU KENNETH
Published: October 2007

Abstract:  Coccidioidomycosis or Valley Fever is a fungal disease that occurs primarily in the southwestern United States. Of the estimated 150,000 U. S. coccidioidomycosis infections per year, approximately 60% occur in Arizona, making this state the focal point for investigation of the disease. In this manuscript, we describe the epidemiology of coccidioidomycosis reported in Arizona over the last decade, hypotheses for the findings, and Arizona's response to the rising epidemic. Coccidioidomycosis surveillance data in Arizona consist of basic demographics of all laboratory and physician‐diagnosed cases, the reporting of which has been mandated by law since 1997. The rate of reported coccidioidomycosis has more than quadrupled over the last decade from 21 cases per 100,000 population in 1997 to 91 cases per 100,000 in 2006 (P < 0.001). Case rates in older age groups (≥65 years old) have more than doubled since 2000 (P < 0.001). These data demonstrate the rising coccidioidomycosis epidemic in Arizona, especially among the elderly. The increase in the numbers of reported cases can be partially explained by the institution of mandatory laboratory reporting in 1997, but the cause of the persistent rise after 1999 is unknown. Further investigation of coccidioidomycosis will not only assist with the development of public health interventions to control this disease in Arizona and the southwestern United States, but will also provide important information to prepare for a bioterrorism event caused by this select agent.
Molecular Identification of Coccidioides Isolates from Mexican Patients
Authors: CASTAÑÓN‐OLIVARES LAURA ROCÍO , GÜEREÑA‐ELIZALDE DIEGO , GONZÁLEZ‐MARTÍNEZ MARISELA ROCÍO , LICEA‐NAVARRO ALEXEI FEDOROVICH , GONZÁLEZ‐GONZÁLEZ GLORIA MARÍA , AROCH‐CALDERÓN ARTURO
Published: October 2007

Abstract:  Molecular studies of the genome of the fungus Coccidioides have demonstrated two nearly identical, but well‐identified species, Coccidioides immitis and C. posadasii, known as “California” and “non‐California” species, respectively. The objective of this study was to determine, through molecular methods, whether both species of Coccidioides are present in Mexican patients with coccidioidomycosis and to estimate, their geographical distribution in Mexico. We analyzed 56 clinical isolates of Coccidioides spp. from Mexican patients. Molecular identification of each strain was done by means of real time PCR using TaqMan® probes to amplify single nucleotide polymorphisms (SNPs) in four target sequences, loci, named proline 157, proline 174, hexokinase 149 and glucose‐synthase 192. SNP analysis identified two of the 56 isolates as Coccidioides immitis and the remaining 54 as C. posadasii. The dual probe assay that included proline 157, proline 174 and glucose‐synthase 192 gave consistent results on SNP differentiation between the two species. In contrast, the template matching hexokinase 149 gave negative results for any species in 34 samples. Our results did not show geographical overlap of the species, and they also confirmed that C. posadasii is the most frequent species in Mexico. A vast majority of C. posadasii strains were localized in the north‐central region of the country.
Laboratory Aspects in the Diagnosis of Coccidioidomycosis
Authors: SAUBOLLE MICHAEL A.
Published: October 2007

Abstract: Coccidioides immitisandCoccidioides posadasii, the two recognized causes of coccidioidomycosis, may be detected by direct microscopy, culture, and serologic documentation. Two useful stains include the Grocott methenamine silver (GMS) and the calcofluor white (CFW). Other useful stains used in histopathologic studies include hematoxylin‐eosin (H&E) and periodic acid Schiff (PAS). Nucleic acid amplification tests (NAATs) have been introduced for detection ofCoccidioidesspp. in specimens, but are not yet commercially available. Isolation ofCoccidioidesspp. by culture is not difficult as many fungal as well as routine bacteriologic media are available. For the safe isolation ofCoccidioidesspp., the laboratory should maintain a biological safety level 2 or 3. Identification ofCoccidioidesspp. uses the organisms’ phenotypic or genotypic characteristics. Phenotypic identification to genus level may be achieved by visualization of spherules in specimens and/or by the presence of arthroconidia in culture. Isolates may be confirmed asCoccidioidesspp. by molecular probes. Separation of species intoC. immitis and C. posadasiiis best achieved by specialized molecular techniques which are not normally available in routine clinical laboratories. Humoral antibodies can be used for the diagnosis and prognosis of coccidioidomycosis. Although positive serologic results may be helpful in the diagnosis of coccidioidomycosis, negative serologic results cannot be used to rule out the disease. Enzyme immunoassays (EIA) and immunodiffusion methods are commonly used for detection of both IgM and IgG antibody groups. Sequential complement fixation (CF) studies for IgG class of antibody are useful for the prognosis of coccidioidomycosis.
Pendred Syndrome in Two Galician Families: Insights into Clinical Phenotypes through Cellular, Genetic, and Molecular Studies
Authors: Palos Fernando , García-Rendueles María E. R. , Araujo-Vilar David , Obregon Maria Jesús , Calvo Rosa Maria , Cameselle-Teijeiro Jose , Bravo Susana B. , Perez-Guerra Oscar , Loidi Lourdes , Czarnocka Barbara , Alvarez Paula , Refetoff Samuel , Dominguez-Gerpe Lourdes , Alvarez Clara V. , Lado-Abeal Joaquin
Published: October 2007

Context: We studied two families from Galicia (northwest Spain) with Pendred syndrome (PS) and unusual thyroid phenotypes. In family A, the proposita had a large goiter and hypothyroxinemia but normal TSH and free T3 (FT3). In family B, some affected members showed deafness but not goiter.

Objective: Our objective was to identify the mutations causing PS and molecular mechanisms underlying the thyroid phenotypes.

Interventions: Interventions included extraction of DNA and of thyroid tissue.

Patients: Propositi and 10 members of the two families participated in the study.

Main Outcome Measures: Main outcome measures included SLC26A4 gene analysis, deiodinase activities in thyroid tissue, and c.416–1G→A effects on SLC26A4 splicing. In addition, a primary PS thyrocyte culture, T-PS2, was obtained from propositus B and compared with another culture of normal human thyrocytes, NT, by Western blotting, confocal microscopy, and iodine uptake kinetics.

Results: Proposita A was heterozygous for c.578C→T and c.279delT, presented with goiter, and had normal TSH and FT3 but low FT4 attributable to high type 1 and type 2 iodothyronine deiodinase activities in the goiter. Propositus B bore c.279delT and a novel mutation c.416–1G→A; some deaf relatives were homozygous for c.416–1G→A but did not present goiter. The c.279delT mutation was associated with identical haplotype in the two families. T-PS2 showed truncated pendrin retained intracellularly and high iodine uptake with low efflux leading to iodine retention.

Conclusions: c.279delT is a founder mutation in Galicia. Proposita A adapted to poor organification by increasing deiodinase activities in the goiter, avoiding hypothyroidism. Lack of goiter in subjects homozygous for c.416–1G→A was due to incomplete penetrance allowing synthesis of some wild-type pendrin. Intracellular iodine retention, as seen in T-PS2, could play a role in thyroid alterations in PS.
Long-Term Observation of 87 Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogs: Impact on Adult Height, Body Mass Index, Bone Mineral Content, and Reproductive Function
Authors: Pasquino Anna Maria , Pucarelli Ida , Accardo Fabiana , Demiraj Vitan , Segni Maria , Di Nardo Raffaella
Published: October 2007

Objective: We assessed in a retrospective unicenter study the impact of treatment with GnRH analogs (GnRHa) on adult height (AH), body mass index (BMI), bone mineral density (BMD), and reproductive function in girls with idiopathic central precocious puberty (ICPP).

Patients: Eighty-seven ICPP patients were treated with GnRHa for 4.2 ± 1.6 yr (range 3–7.9) and observed for 9.9 ± 2.0 yr (range 4–10.6 yr) after discontinuation of treatment; to estimate the efficacy better, 32 comparable ICPP untreated girls were analyzed.

Results: AH was 159.8 ± 5.3 cm, significantly higher than pretreatment predicted AH (PAH) either for accelerated or for average tables of Bayley and Pinneau. The gain in centimeters between pretreatment PAH and AH was 5.1 ± 4.5 and 9.5 ± 4.6 cm, respectively. Hormonal values and ovarian and uterine dimensions, reduced during treatment, increased to normal after 1 yr without therapy. Age of menarche was 13.6 ± 1.1 yr with an interval of 0.9 ± 0.4 yr after therapy. Menstrual pattern was normal. Six girls became pregnant and delivered normal offspring. BMI sd score for chronological age increased, but not significantly, before, during, and after therapy. BMD at discontinuation of treatment was significantly lower and increased to control values after gonadal activity resumption.

Conclusions: GnRHa treatment in ICPP is safe for the reproductive system, BMD, and BMI and helpful in reaching AH close to target height; however, the variability of individual responses suggests that one choose more parameters than increment in height, especially in girls with pubertal onset over 8 yr of age.
Abnormal Sex Chromosome Constitution and Longitudinal Growth: Serum Levels of Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein-3, Luteinizing Hormone, and Testosterone in 109 Males with 47,XXY, 47,XYY, or Sex-Determining Region of the Y Chromosome (SRY)-Positive 46,XX Karyotypes
Authors: Aksglaede Lise , Skakkebaek Niels E. , Juul Anders
Published: October 2007

Context: Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles.

Aim: The aim of the study was to evaluate the role of abnormal chromosome constitution for longitudinal growth in relation to reproductive hormones, IGF-I, and IGF binding protein (IGFBP)-3.

Setting: The study was conducted at an outpatient clinic, Copenhagen University Hospital.

Participants: Participants included 86 47,XXY males, 14 46,XX-males, and nine 47,XYY.

Main Outcome Measures: Standing and sitting height, serum levels of reproductive hormones, IGF-I, and IGFBP-3 were measured.

Results: In boys with 47,XXY and 47,XYY karyotypes, growth was accelerated already in childhood, compared with healthy boys. 46,XX-males were significantly shorter than healthy boys but matched the stature of healthy girls. In 47,XXY sitting height to height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal.

Conclusion: We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in circulating levels of IGF-I and IGFBP-3. The boys with 46,XX and 47,XXY karyotypes developed hypogonadism in puberty, but androgen secretion in 47,XYY boys remained normal. The abnormal stature of these patients may be a result of abnormal gene expression due to the underlying chromosome aberration resulting in excessive expression of growth-related genes.