Fatal Disseminated Herpes Simplex in a very premature neonate

Herpes Simplex Virus infections (HSV) are ubiquitous. The neonatal HSV infection (NHSV) is rare. The incidence is estimated globally at only 10.3 per 100,000 births, but it can cause devastating disease in premature infants. Both HSV-1 and HSV-2 can be the etiologic agents in this type of vertically transmittted NHSV infection. Here we describe the pathological findings from a complete autopsy of a very low birth weight infant who succumbed to the infection despite early institution of antiviral treatment. We urge more awareness of this disease with continued surveillance; every effort should be taken to make an early diagnosis and thus prevent this devastating disease

Fatal Disseminated Herpes Simplex in a very premature neonate

Herpes Simplex Virus infections (HSV) are ubiquitous. The neonatal HSV infection (NHSV) is rare. The incidence is estimated globally at only 10.3 per 100,000 births, but it can cause devastating disease in premature infants. Both HSV-1 and HSV-2 can be the etiologic agents in this type of vertically transmittted NHSV infection. Here we describe the pathological findings from a complete autopsy of a very low birth weight infant who succumbed to the infection despite early institution of antiviral treatment. We urge more awareness of this disease with continued surveillance; every effort should be taken to make an early diagnosis and thus prevent this devastating disease

A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component

Background/Objectives We have demonstrated the presence of Candida cell surface amyloids that are important in aggregation of fungi and adherence to tissue. Fungal amyloid was present in invasive human candidal infections and host serum amyloid P component (SAP) bound to the fungal amyloid. SAP is a protease-resistant glycoprotein that binds avidly to amyloid and interferes with host defence, especially against bacterial pathogens for which neutrophils are important. In this study, we investigated whether biofilm of fungal amyloid and SAP was a feature of other disseminated fungal infections. Methods Tissue specimens from 15 autopsies were systematically evaluated with multiple histochemical stains including thioflavin T and Congo red (dyes that stain amyloid), as well as antibody to SAP. We studied specimens with disseminated aspergillosis, mucormycosis and coccidioidomycosis. The structure of the lesions, host inflammatory cells and the presence of fungal amyloid and SAP were determined. Results The structure of the lesions was characteristic in aspergillosis (‘starburst’) and mucormycosis (closely apposed bundles of hyphae). Host inflammatory cells were absent or few in number within these lesions. In Coccidioides lesions, host inflammation was sparse as well. Fungal amyloid was a prominent feature of all lesions along with abundant SAP bound to hyphae and spherules. Fungal amyloid and SAP perhaps contributed to persistence in caseous necrosis lesions. SAP also bound to Aspergillus and Mucorales amyloid in vitro. Conclusions A biofilm including amyloid and SAP is present in invasive fungal infections. This biofilm may dampen host defence leading to the characteristic sparse inflammatory reaction found in these infections

Peptide Detection of Fungal Functional Amyloids in Infected Tissue

Many fungal cell adhesion proteins form functional amyloid patches on the surface of adhering cells. The Candida albicans Agglutinin-like sequence (Als) adhesins are exemplars for this phenomenon, and have amyloid forming sequences that are conserved between family members. The Als5p amyloid sequence mediates amyloid fibril formation and is critical for cell adhesion and biofilm formation, and is also present in the related adhesins Als1p and Als3p. We have developed a fluorescent peptide probe containing the conserved Als amyloid-forming sequence. This peptide bound specifically to yeast expressing Als5p, but not to cells lacking the adhesin. The probe bound to both yeast and hyphal forms of C. albicans. Δals1/Δals3 single and double deletion strains exhibited reduced fluorescence, indicating that probe binding required expression of these proteins. Additionally, the Als peptide specifically stained fungal cells in abscesses in autopsy sections. Counterstaining with calcofluor white showed colocalization with the amyloid peptide. In addition, fungi in autopsy sections derived from the gastrointestinal tract showed colocalization of the amyloid-specific dye thioflavin T and the fluorescent peptide. Collectively, our data demonstrate that we can exploit amyloid sequence specificity for detection of functional amyloids in situ

Do Pentraxins Bind to Fungi in Invasive Human Gastrointestinal Candidiasis?

Tissue from 13 autopsy cases with invasive gastrointestinal candidiasis was studied for the binding of the pentraxins, C-reactive protein (CRP), pentraxin 3 (PTX3), and serum amyloid P component (SAP) to fungal surfaces. Invasive candidal infection was demonstrated using a hematoxylin and eosin stain and a Gomori methenamine silver stain (GMS). Immunohistochemistry was performed with CRP and PTX3 monoclonal antibodies and did not demonstrate CRP or PTX3 bound to fungi (0 of 13 cases), although CRP was extensively deposited on human tissue. A polyclonal antibody to SAP showed that SAP was bound to fungi in 12 of 13 cases. Although all three pentraxins have been reported to bind to fungi or bacteria, only SAP was bound to filamentous and yeast forms of Candida in human tissue, as detected by immunohistochemistry. SAP was abundantly present on fungi and may have affected the host innate immune response to the invading fungi.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Patients Who Take Home Their Surgical Pathology Specimens: A Preliminary Study

Patients regularly request to take possession of their human tissues after they have become surgical pathology specimens. To date, few formal research studies have examined the prevalence of this practice or the reasoning patients’ request that their specimens to be returned to them. This study interviews patients from 2015 to 2017 at one US academic medical center who requested their surgical pathology specimens. Of the 22 eligible patients, 8 patients agreed to be interviewed. Interviews lasted 10 to 30 minutes and included 5 questions. The questions were: (1) What motivated your decision to obtain your surgical pathology specimen, (2) What, if anything, did you do with your specimen, (3) What were positive aspects of your experience, (4) What were negative aspects of your experience, (5) What can the pathology department change to better support patients who request their surgical pathology specimens? Verbatim transcripts were generated and a mixed-methods analysis was performed. The type of specimens included products of conception, placenta and cord, costal cartilage and ribs, loop explant recorder, pacemaker, below knee amputation, and cervix, uterus, Fallopian tubes, and ovaries. The dominant themes included adversity, medical interest, souvenir, cultural beliefs, and curiosity. Subthemes included becoming whole in the afterlife, preservation, my body, restoration, honoring, and regret. In conclusion, pathologists can expand their role as patient advocates and advance patient-centered pathology by supporting patient’s individual needs, motivations, and goals, when they request their surgical pathology specimens

Serum Amyloid P Component and Systemic Fungal Infection: Does It Protect the Host or Is It a Trojan Horse?

It is a striking observation that tissue of patients invaded by the deep mycoses often lacks evidence of an inflammatory response. This lack of host response is often attributed to neutropenia secondary to chemotherapy. However, systematic studies do not support this simplistic explanation. However, invasive fungal lesions are characterized by abundant fungal functional amyloid, which in turn is bound by serum amyloid P component (SAP). We postulate that SAP is important in the local immune response in invasive fungal infections. The interaction between fungal functional amyloid, SAP, and the immune response in deep mycoses is discussed.Open Access Journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Cardiac Sarcoidosis Masquerading as Right Ventricular Dysplasia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73517/1/j.1460-9592.2003.t01-1-00217.x.pd

Als5p expressing S. cerevisiae cells stained with fluorescent peptides.

<p><i>S. cerevisiae</i> harboring an empty vector (A,C) or expressing Als5p (B, D) were stained with amyloid peptide (200 µg/ml; A, B) or a scrambled-sequence peptide of identical composition (200 µg/ml; C, D). Lower micrographs are bright field images. All scale bars are 30 µm.</p