We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.

Community-associated MRSA strains have emerged as a significant cause of sepsis in neonates hospitalized in NICU since birth and have caused disseminated infection with substantial morbidity and mortality.

Background Intrauterine herpes simplex virus (HSV) infection often is omitted from descriptions of neonatal HSV disease. Previous characterizations of intrauterine HSV infection limit manifestations to the triad of cutaneous, central nervous system (CNS), and ophthalmologic findings. We report 3 cases of intrauterine HSV infection and provide a contemporary literature review of this disease. Methods Cases published between 1963 and January 2009 were identified. Selected cases fit the clinical description of intrauterine HSV infection, had manifestations present at birth, and had virologic confirmation of infection. Results This review yielded 64 cases, 3 of which were our own, of intrauterine HSV infection. Less than one-third fit the typical triad. Of the patients with cutaneous findings at birth, 24 (44%) had manifestations other than vesicles or bullae. Confirmation of HSV infection by culture of cutaneous lesions present at birth was delayed beyond 72 hours after birth in 15 patients and occurred at a median of 10 days of age. Nine of these patients had lesions at birth that were neither vesicles nor bullae, and 14 cases were confirmed by culture of new vesicles. Conclusions More than two-thirds of reported cases do not present with the typical triad. Cutaneous findings are not limited to vesicles or bullae. A high index of suspicion and recognition of varied cutaneous manifestations is necessary to diagnose infants with intrauterine HSV infection.

The posttranslational translocation of proteins across the endoplasmic reticulum (ER) membrane in yeast requires ATP hydrolysis and the action of hsc70s (DnaK homologues) and DnaJ homologues in both the cytosol and ER lumen. Although the cytosolic hsc70 (Ssa1p) and the ER lumenal hsc70 (BiP) are homologous, they cannot substitute for one another, possibly because they interact with specific DnaJ homologues on each side of the ER membrane. To investigate this possibility, we purified Ssa1p, BiP, Ydj1p (a cytosolic DnaJ homologue), and a GST-63Jp fusion protein containing the lumenal DnaJ region of Sec63p. We observed that BiP, but not Ssa1p, is able to associate with GST-63Jp and that Ydj1p stimulates the ATPase activity of Ssa1p up to 10-fold but increases the ATPase activity of BiP by Ͻ2-fold. In addition, Ydj1p and ATP trigger the release of an unfolded polypeptide from Ssa1p but not from BiP. To understand further how BiP drives protein translocation, we purified four dominant lethal mutants of BiP. We discovered that each mutant is defective for ATP hydrolysis, fails to undergo an ATP-dependent conformational change, and cannot interact with GST-63Jp. Measurements of protein translocation into reconstituted proteoliposomes indicate that the mutants inhibit translocation even in the presence of wild-type BiP. We conclude that a conformation-and ATP-dependent interaction of BiP with the J domain of Sec63p is essential for protein translocation and that the specificity of hsc70 action is dictated by their DnaJ partners. INTRODUCTIONThe first step in secretory protein biogenesis, the translocation of newly synthesized polypeptides across the endoplasmic reticulum (ER) membrane, is a highly intricate, multistep process (for reviews, see Corsi and Schekman, 1996;Rapoport et al., 1996;Johnson, 1997). Protein translocation may occur in one of two ways, either cotranslationally or posttranslationally. In cotranslational translocation, nascent secretory polypeptides are targeted to the ER membrane before translation is complete. Posttranslational translocation proceeds after the secretory polypeptide has been fully synthesized and released from the ribosome. In either case, various proteins in the cytosol, in the ER membrane, and in the lumen of the ER are required for protein translocation. Among these are members of the 70-kDa class of heat shock cognate proteins (Hsc70s).Hsc70s consist of a highly conserved N-terminal ATPase domain and a variable C-terminal region that mediates peptide binding and can act as molecular chaperones by disallowing the aggregation of exposed hydrophobic regions and preventing nonproductive folding pathways (for review, see Gething et al., 1995). Homologues of the bacterial DnaJ molecular chaper- ‡ Corresponding author: Department of Biological Sciences, University of Pittsburgh, 267 Crawford Hall, Pittsburgh, PA 15260. E-mail address: jbrodskyϩ@pitt.edu.© 1998 by The American Society for Cell Biology 3533 one activate the ATPase activity of hsc70s, can present polypeptide substrates...

To study the evolution of hemophagocytic syndrome (HPS) in children, we performed a retrospective review of 19 patients (median age, 17.4 months) in whom an infectious diseases consultation was requested at Texas Children's Hospital during the period of September 1991 through September 2001. Clinical findings consistent with HPS most frequently presented during days 6-14 of illness, concomitant with laboratory abnormalities. Fever was present for a median of 19 days before the diagnosis of HPS. Elevated serum lactate dehydrogenase and ferritin levels were noted in all patients. An infectious agent was identified in 42% of patients; 16% were found to have immunologic or vasculitic disease. HPS is a rare but often fatal disease that can initially present as fever of unknown origin with varying clinical findings, and it can be recognized by physicians who are familiar with the evolution of HPS. It is likely that many of these cases remain undiagnosed because of the HPS's rapidly fatal course.

Though CA was the single most common species, NAC species collectively have emerged as the predominant pathogens responsible for candidemia in non-neonatal patients at our institution. Risk factors, clinical features, and outcomes were not different between the 2 groups.

CoNS ISD occurred in smaller, more premature infants than SA and was IVC associated in a minority of cases. Hypoxia and hypotension were the only presenting features that differentiated CoNS and SA. SA-associated morbidity was substantial, but SA infection carried no greater risk of death (5%) than CoNS.

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