Atypical teratoid rhabdoid tumours (ATRTs)-a 21-year institutional experience.

PURPOSE: Atypical teratoid/rhabdoid tumours (ATRTs) are malignant embryonal tumours of childhood that affect the central nervous system (CNS). We aim to determine which factors, including patient age, extent of resection (EOR), presence of distal metastasis and use of adjuvant therapies, affect overall survival in children with atypical teratoid/rhabdoid tumours (ATRTs) treated at this single centre. METHODS: Retrospective cohort review of patients with histological diagnosis of ATRT treated over 21 years (1999-2020) was conducted. Data on demographics, tumour location, presence of metastasis, use of adjuvant therapy, extent of resection (EOR), complications, neurological outcome post-surgery, and overall survival were collected. Kaplan-Meier survival analysis was performed. RESULTS: A total of 45 children (mean age 2 years) underwent 64 operations. 25 patients were <1 year of age. Gross-total resection (GTR) pre-adjuvant therapy was achieved in 15, near-total resection (NTR) in 15, subtotal resection (STR) in 9, and biopsy in 6 children. Most children had good neurological outcomes post-operatively (28/45 with GOS 5). Fourteen patients survived longer than 4 years. Survival analysis showed a significant difference in median survival in favour of GTR and localised disease. There was no significant difference in median survival between patients <1 year vs >1 year of age (p=0.84). CONCLUSION: We find that presence of metastasis was an important factor in poor survival in patients with ATRT. GTR, where possible, may confer significant survival benefit in ATRT. Children aged <1 year appear to have performed as well as those >1 year and therefore should still be considered for radical surgery.

Visual outcomes and predictors in optic pathway glioma: a single centre study.

BACKGROUND/AIMS: Optic pathway gliomas (OPGs) may cause progressive visual loss despite chemotherapy. Newer, less toxic treatments might be given earlier, depending on visual prognosis. We aimed to investigate the prognostic value of visual evoked potentials (VEP) and optical coherence tomography (OCT). METHODS: A retrospective study of OPG patients (treated 2003-2017) was conducted. Primary outcome was PEDIG category visual acuity in better and worse eyes (good < = 0.2, moderate 0.3-0.6 and poor > = 0.7 logMAR). Binary logistic regression analysis was used to identify predictors of these outcomes. RESULTS: 60 patients (32 Neurofibromatosis type 1 [NF1] and 28 sporadic) had median presentation age 49 months (range 17-183) (NF1) and 27 months (range 4-92) (sporadic). Median follow up was 82 months (range 12-189 months). At follow up 24/32 (75%) of NF1 children and 14/28 (50%) of sporadic children had good better eye visual acuity and 11/32 (34%) of NF1 children and 15/28 (54%) of sporadics had poor worse eye acuity. Mean peripapillary retinal nerve fibre layer (RNFL) thickness predicted good better eye final acuity (OR 0.799, 95%CI 0.646-0.987, p = 0.038). Presenting with visual symptoms (OR 0.22 95% CI 0.001-0.508, p = 0.017) and poorer VEP scores (OR 2.35 95% CI 1.1-5.03, p = 0.027) predicted poor worse eye final acuity. 16 children had homonymous hemianopias at follow up, predicted by poor presenting binocular VEP score (OR 1.449 95%CI 1.052-1.995, p = 0.02). CONCLUSIONS: We found that both RNFL thickness on OCT and VEP were useful in predicting future visual acuity and vision and potentially in planning treatment. We had a high prevalence of homonymous hemianopia.

Renal tumor biopsies are associated with a low complication rate.

BACKGROUND: Due to the high incidence of benign lesions in renal masses, numerous studies have been performed to clarify the value of core needle biopsies. The aim of the present study was to describe the complication rate after renal tumor biopsies (RTB), in order to make recommendations on observation after the procedure. MATERIALS AND METHODS: Data from all patients who underwent percutaneous ultrasound-guided RTB between February 2013 and October 2016 due to CT verified solid renal masses were prospectively collected and kept in a well-maintained database. Complications were collected retrospectively and classified according to the Clavien-Dindo (CD) classification system. RESULTS: Data from 224 consecutive patients were retrieved. Thirteen patients underwent unilateral repeat biopsies and three patients underwent bilateral biopsies; thus, a total of 240 procedures were analyzed. A total of 124 patients (51.7%) were discharged within 4 hours after the RTB procedures and 110 patients (45.8%) were discharged within 24 hours. The remaining six patients (2.5%) were hospitalized for more than 1 day, all due to co-morbidities which were unrelated to the procedure. In total, five patients (2.1%) experienced post-biopsy complications: one case of iatrogenic pneumothorax, one case of spontaneously resolving hematuria and three cases of fever. All complications were CD ≤2 and all patients with complications were discharged within 24 hours, except for one patient who was hospitalized for 3 days due to management of bone pain. No correlation was found between the number of biopsies and complication rate. CONCLUSION: The overall complication rate following ultrasound-guided biopsies of renal tumors was low and all complications were mild. Given the current evidence, it is believed that ultrasound-guided RTB can be done as an outpatient procedure without the need for hospitalization.

Core needle biopsy clarify the histology of the small renal masses and may prevent overtreatment.

PURPOSE: The purpose of the study was to evaluate the diagnostic accuracy of core biopsy in small renal masses ≤ 4 cm in response to the rising prevalence of renal masses. METHODS: Data from 129 consecutive patients who underwent biopsies of solid renal masses of ≤ 4 cm were prospectively collected between September 2014 and January 2017. In cases with inconclusive biopsies, a repeat biopsy was recommended. Histology from surgical specimens was used as gold standard to evaluate the accuracy of renal biopsies. RESULTS: The initial biopsies revealed malignancy in 77 patients (59.7%) and benign histology in 35 patients (27.1%), whereas 17 (13.2%) were inconclusive. Fifty-six patients with malignant histology underwent either partial or radical nephrectomy according to the physicians' recommendation, while two patients with benign histology requested surgery. In all cases, the biopsy diagnosis was confirmed upon final histopathology. Of the inconclusive cases, six underwent repeat biopsies all with benign histology. Further, three patients opted for immediate partial nephrectomy with benign oncocytoma in two and renal cell carcinoma in the third. The remaining eight patients opted for follow-up CT scans with no sign of progression with a minimum of 6-month follow-up. No biopsy related complications were reported in the first 30 days after RTB. Overall, the treatment strategy changed in 45 of 129 (35%) patients due to biopsy results. This was either due to benign findings or due to the discovery of non-renal cell cancers. CONCLUSION: Core needle biopsies of solid renal masses ≤ 4 cm have excellent accuracy and may be used to select the correct treatment. Importantly, they may serve to prevent overtreatment of benign tumors.

Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure.

OBJECTIVES: Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF. DESIGN: Prospective, observational study including 155 consecutive patients with chronic HF. In addition, 100 patients with stable CAD without HF and 33 matched healthy individuals were included as controls. Plasma levels of TMAO and its precursors choline and betaine were measured, and associations with symptoms, aetiology and transplant-free survival in the patients with HF were explored. RESULTS: Plasma levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were elevated in patients with chronic HF compared to control subjects, with the highest levels in patients with New York Heart Association (NYHA) classes III and IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or betaine, was associated with reduced transplant-free survival: approximately 50% of patients in the upper tertile of TMAO levels died or received a heart transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio 2.24, 95% confidence interval 1.28-3.92, P = 0.005). CONCLUSIONS: TMAO levels were elevated in patients with HF and associated with NYHA class, ischaemic aetiology and adverse outcomes. Future studies should focus on gut microbiota, dietary composition and intestinal dysfunction in relation to TMAO levels and clinical outcome in HF.

The "bacterial heterodisulfide" DsrC is a key protein in dissimilatory sulfur metabolism.

DsrC is a small protein present in organisms that dissimilate sulfur compounds, working as a physiological partner of the DsrAB sulfite reductase. DsrC contains two redox active cysteines in a flexible carboxy-terminal arm that are involved in the process of sulfite reduction or sulfur(1) compound oxidation in sulfur-reducing(2) or sulfur-oxidizing(3) organisms, respectively. In both processes, a disulfide formed between the two cysteines is believed to serve as the substrate of several proteins present in these organisms that are related to heterodisulfide reductases of methanogens. Here, we review the information on DsrC and its possible physiological partners, and discuss the idea that this protein may serve as a redox hub linking oxidation of several substrates to dissimilative sulfur metabolism. In addition, we analyze the distribution of proteins of the DsrC superfamily, including TusE that only requires the last Cys of the C-terminus for its role in the biosynthesis of 2-thiouridine, and a new protein that we name RspA (for regulatory sulfur-related protein) that is possibly involved in the regulation of gene expression and does not need the conserved Cys for its function. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference.

Osteoprotegerin levels predict mortality in patients with symptomatic aortic stenosis.

OBJECTIVES: To examine the prognostic value of osteoprotegerin (OPG) levels in relation to all-cause mortality in patients with symptomatic severe aortic stenosis (AS). DESIGN: We measured plasma OPG levels in 136 patients with symptomatic severe AS and investigated associations with transvalvular gradients, valve area, valve calcification (using ultrasonic backscatter analysis as an estimate) and measures of heart failure. Then, we assessed the prognostic value of elevated plasma OPG in determining all-cause mortality (n = 29) in these patients. RESULTS: Elevated OPG was poorly correlated with the degree of AS but was associated with increased backscatter measurements and impaired cardiac function. Furthermore, OPG was associated with all-cause mortality in patients with symptomatic AS, even after adjustment for conventional risk markers. The strongest association was obtained by using a combination of high levels of both OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP), suggesting that these markers may reflect distinct pathways in the development and progression of AS. CONCLUSION: The level of circulating OPG is significantly associated with all-cause mortality alone and in combination with NT-proBNP in patients with severe symptomatic AS.

Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis.

OBJECTIVE: Matrix Gla protein (MGP) is a calcification inhibitor and alterations in circulating MGP have been observed in different populations characterized by vascular calcification. We hypothesized that patients with calcific valvular aortic stenosis (AS) would have dysregulated circulating MGP levels. DESIGN AND SUBJECTS: We examined plasma levels of nonphosphorylated carboxylated and undercarboxylated MGP (dp-cMGP and dp-ucMGP, respectively) in 147 patients with symptomatic severe AS and in matched healthy controls. MAIN OUTCOME MEASURES: We further investigated the relationship between MGP levels and aortic pressure gradients and valve area by echocardiography and measures of heart failure. Finally, we assessed the prognostic value of elevated plasma dp-ucMGP level in relation to all-cause mortality in patients with AS. RESULTS: We found markedly enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with symptomatic AS. Although only weak correlations were found with the degree of AS, circulating dp-ucMGP was associated with cardiac function and long-term mortality in multivariate analysis. CONCLUSIONS: A dysregulated MGP system may have a role in the development of left ventricular dysfunction in patients with symptomatic AS.

5-HT4-elicited positive inotropic response is mediated by cAMP and regulated by PDE3 in failing rat and human cardiac ventricles.

BACKGROUND AND PURPOSE: The left ventricle in failing hearts becomes sensitive to 5-HT parallelled by appearance of functional G(s)-coupled 5-HT(4) receptors. Here, we have explored the regulatory functions of phosphodiesterases in the 5-HT(4) receptor-mediated functional effects in ventricular muscle from failing rat and human heart. EXPERIMENTAL APPROACH: Extensive myocardial infarctions were induced by coronary artery ligation in Wistar rats. Contractility was measured in left ventricular papillary muscles of rat, 6 weeks after surgery and in left ventricular trabeculae from explanted human hearts. cAMP was quantified by RIA. KEY RESULTS: In papillary muscles from postinfarction rat hearts, 5-HT(4) stimulation exerted positive inotropic and lusitropic effects and increased cAMP. The inotropic effect was increased by non-selective PDE inhibition (IBMX, 10 microM) and selective inhibition of PDE3 (cilostamide, 1 microM), but not of PDE2 (EHNA, 10 microM) or PDE4 (rolipram, 10 microM). Combined PDE3 and PDE4 inhibition enhanced inotropic responses beyond the effect of PDE3 inhibition alone, increased the sensitivity to 5-HT, and also revealed an inotropic response in control (sham-operated) rat ventricle. Lusitropic effects were increased only during combined PDE inhibition. In failing human ventricle, the 5-HT(4) receptor-mediated positive inotropic response was regulated by PDEs in a manner similar to that in postinfarction rat hearts. CONCLUSIONS AND IMPLICATIONS: 5-HT(4) receptor-mediated positive inotropic responses in failing rat ventricle were cAMP-dependent. PDE3 was the main PDE regulating this response and involvement of PDE4 was disclosed by concomitant inhibition of PDE3 in both postinfarction rat and failing human hearts. 5-HT, PDE3 and PDE4 may have pathophysiological functions in heart failure.

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study.

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985--1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6-5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8-8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.

Genomic profiling of malignant melanoma using tiling-resolution arrayCGH.

Malignant melanoma is an aggressive, heterogeneous disease where new biomarkers for diagnosis and clinical outcome are needed. We searched for chromosomal aberrations that characterize its pathogenesis using 47 different melanoma cell lines and tiling-resolution bacterial artificial chromosome-arrays for comparative genomic hybridization. Major melanoma genes, including BRAF, NRAS, CDKN2A, TP53, CTNNB1, CDK4 and PTEN, were examined for mutations. Distinct copy number alterations were detected, including loss or gain of whole chromosomes but also minute amplifications and homozygous deletions. Most common overlapping regions with losses were mapped to 9p24.3-q13, 10 and 11q14.1-qter, whereas copy number gains were most frequent on chromosomes 1q, 7, 17q and 20q. Amplifications were delineated to oncogenes such as MITF (3p14), CCND1 (11q13), MDM2 (12q15), CCNE1 (19q12) and NOTCH2 (1p12). Frequent findings of homozygous deletions on 9p21 and 10q23 confirmed the importance of CDKN2A and PTEN. Pair-wise comparisons revealed distinct sets of alterations, for example, mutually exclusive mutations in BRAF and NRAS, mutual mutations in BRAF and PTEN, concomitant chromosome 7 gain and 10 loss and concomitant chromosome 15q22.2-q26.3 gain and 20 gain. Moreover, alterations of the various melanoma genes were associated with distinct chromosomal imbalances suggestive of specific genomic programs in melanoma development.

Modulation of chemokine gene expression in CD133+ cord blood-derived human mast cells by cyclosporin A and dexamethasone.

We have recently developed a protocol for generating huge numbers of mature and functional mast cells from in vitro differentiated umbilical cord blood cells. Using CD133 as a positive selection marker to isolate haematopoietic progenitors we routinely expand the number of recovered cells at least 150-fold, which vastly exceeds the yields of conventional protocols using CD34+ cells as a source of progenitors. Taking advantage of the large quantities of in vitro differentiated mast cells, here we assess at the levels of transcription and translation the kinetics of chemokine gene induction following receptor mediated mast cell activation or following pharmacological activation of specific signal transduction cascades that become activated upon classical FcepsilonRI receptor crosslinking. We demonstrate that chemokine genes encoding IL-8, MCP-1, MIP-1alpha, and MIP-1beta are induced with different kinetics and with different amplitudes in a receptor activation dependent manner, and that these events can be mimicked using pharmacological agents which activate distinct signal transduction pathways. These findings were corroborated by adding immunomodulators such as cyclosporin A and dexamethasone prior to mast cell activation. Finally, we demonstrate that the same modulators added after mast cell activation can differentially quench ongoing chemokine gene induction. Thus, considering the vast yields of mast cells, our protocol is valuable not only for studying regulation of gene expression in mast cells in general, but also as an experimental tool to develop better and more balanced treatments of mast cell related disorders.

Human mast cells express receptors for IL-3, IL-5 and GM-CSF; a partial map of receptors on human mast cells cultured in vitro.

BACKGROUND: Mast cells have long been recognized as the principal cell type that initiates the inflammatory response characteristic of acute allergic type 1 reactions. Our goal has been to further characterize maturation of progenitors to mast cells. METHODS: Mast cells were cultured from human cord blood derived CD133(+) progenitors. Mast cell function was tested using histamine release. During differentiation mast cells surface marker expression was monitored by flow cytometry. RESULTS: CD133(+) progenitors expressed the early haematopoietic and myeloid lineage markers CD34, CD117, CD13 and CD33. Mature mast cells expressed CD117, CD13 and CD33, and expression of the high affinity immunoglobulin E receptor FcepsilonRI increased during culture. Cytokine receptors interleukin (IL)-5R, IL-3R, granulocyte-macrophage-colony stimulating factor (GM-CSF)R and IL-18R were expressed at high levels during maturation. Chemokine receptors CXCR4 and CXCR2 were highly expressed on both newly purified CD133(+) cells and mature cells. CONCLUSION: Human mast cells can be cultured from a CD34(+)/CD117(+)/CD13(+)/CD33(+) progenitor cell population in cord blood that is tryptase and chymase negative. Developing and mature mast cells express a wide range of chemokine and cytokine receptors. We found high levels of expression of CD123, IL-5R and GM-CSF receptors, also found on eosinophils and basophils, and high levels of expression of the receptor for the inflammatory cytokine IL-18.

Lectins interact differentially with purified human eosinophils, cultured cord blood-derived mast cells and the myeloid leukaemic cell line AML14.3D10: induction of interleukin-4 secretion is conserved among granulocytes, but is not proportional to agglutination or lectin-glycoprotein interaction.

BACKGROUND: Atopy is closely associated with the cellular T helper type-2 (Th2) phenotype, that is dominated by the pleiotrophic cytokine IL-4. The cellular source of IL-4 has yet to be determined, although basophils have been proposed. Eosinophils and mast cells are likely contenders investigated here, and the eosinophil-like leukaemia line AML14.3D10 is compared to eosinophils as an in vitro culturable model for eosinophils. Lectins can cross-link-specific surface glycoproteins and are found in the ingested (processed foods) and inhaled (airborne pollen grains) human environment. Therefore it is of interest to determine whether lectins can elicit the release of IL-4 from Th2-associated granulocytes other than basophils. METHOD: This study investigated the ability of eosinophils, AML14.3D10 and mast cells to secrete preformed IL-4 in response to stimulation with lectins, and explored molecular mechanisms underlying the interaction. RESULTS: Purified eosinophils and basophils, and cultured mast cells and AML14.3D10 cells were incubated with 1 micro m lectin. Agglutination was scored by microscopy. IL-4 secretion was measured by enzyme-linked immunosorbent assay. Biotinylated lectins were used to determine binding to cells by flow cytometry and in lectin blots of sodium dodecyl sulphate (SDS) gels. DISCUSSION: Purified human eosinophils, AML14.3D10 cells and cultured mast cells secrete IL-4 with a pattern similar to that found in basophils when stimulated with a panel of reactive and unreactive lectins. The lectin SNA induces IL-4 secretion from mast cells and basophils, but not from eosinophils or AML14.3D10. Eosinophils appear to secrete only pre-formed IL-4, whereas mast cells may synthesize IL-4 on ligation with the lectin LCA. Lectins that agglutinate the granulocytes investigated do not necessarily induce secretion of IL-4. Lectins that elicit secretion of IL-4 bind more to eosinophils than unreactive lectins as determined by flow cytometry and lectin blotting of SDS gels. CONCLUSION: As granulocytes with functions related to that of basophils, eosinophils, AML14.3D10 and cultured mast cells respond to stimulation with lectins similarly to basophils. This emphasizes the possibility that eosinophils and mast cells may be linked in their cellular heritage as the cellular partners, and lectins as ligands, may contribute to the maintenance of a Th2-favoured microenvironment that is thought to underlie the allergic march.

Leydig cell tumour--a rare testicular tumour.

Although Leydig cell tumour is a rare tumour which constitutes only 1-3% of all testicular tumours, still it is in the focus of interest because of the difficulties in determining its exact nature and subsequently the type of treatment and follow-up. We report a case of Leydig cell tumour with a review of the related literature.

In vivo role of adenosine-5'-phosphosulfate reductase in the purple sulfur bacterium Allochromatium vinosum.

Adenosine-5'-phosphosulfate (APS) reductase participates in the oxidation of sulfite to APS in Allochromatium vinosum. Oxidation of sulfite via the APS pathway yields ATP through substrate-level phosphorylation. An alternative enzyme for the oxidation of sulfite to sulfate, sulfite:acceptor oxidoreductase, has also been reported in Ach. vinosum. Oxidation of sulfite through this enzyme does not yield ATP. APS reductase is expressed constitutively in Ach. vinosum, suggesting that it performs an important role in this organism. However, studies carried out with batch cultures of an APS reductase mutant showed little or no differences in growth or in the rates of substrate oxidation when compared to the wild-type, therefore questioning the role of this enzyme. In an attempt to establish whether the ATP gain derived from APS-reductase-mediated oxidation of sulfite is relevant for energy-limited cultures, we compared growth of the wild-type SM50 and the APS-reductase-deficient mutant D3 when grown in continuous culture under different degrees of illumination. Little differences in the specific growth rates of the two strains were observed at light-limiting irradiances, suggesting that the ATP gained during sulfite oxidation through the APS reductase pathway does not constitute a significant energy input. However, at saturating irradiances, wild-type Ach. vinosum grew considerably faster than the mutant. Increasing the irradiance even further resulted in inhibition of the wild-type strain down to the level of the APS reductase mutant. The implications of these results are discussed.

Physical therapist management of tuberculous arthritis of the elbow.

BACKGROUND AND PURPOSE: Tuberculous arthritis is not commonly seen by physical therapists in the United States. The purpose of this case report is to describe a case of tuberculous arthritis of the elbow. CASE DESCRIPTION: The patient was a 36-year-old man referred for physical therapy evaluation and intervention for chronic elbow pain. After an evaluation and a trial of physical therapy, the patient was referred back to a primary care provider for additional tests to rule out systemic pathology. An open debridement of synovium and biopsy of the capitellum and radial head was positive for acid-fast bacilli, which was later identified as Mycobacterium tuberculosis. OUTCOMES: The patient was placed on a 4-drug antituberculosis regimen that resolved all patient complaints and restored full elbow function. DISCUSSION: Tuberculous arthritis has characteristic findings during examination and in diagnostic tests. Although tuberculous arthritis is uncommon, it should be considered when patients have chronic or vague musculoskeletal complaints.

"ADP sulfurylase" from Thiobacillus denitrificans is an adenylylsulfate:phosphate adenylyltransferase and belongs to a new family of nucleotidyltransferases.

During AMP-dependent sulfite oxidation by some sulfur bacteria, the liberation of sulfate from adenosine-5'-phosphosulfate (APS) is catalyzed by APS:phosphate adenylyltransferase (APAT). Here we report the first biochemical and genetic characterization of APAT. We isolated this enzyme from the chemolithoautotroph Thiobacillus denitrificans and cloned the corresponding gene. The enzyme is homodimeric with 41,387-Da subunits and exhibits a specific activity of 2100 micromol min(-1) mg(-1). The K(m) values are K(m(APS)) = 300 microM and K(m(P(i))) = 12 mM. Catalysis occurs by a ping-pong mechanism with a covalently bound AMP as reaction intermediate. The arsenolysis of APS, but not of ADP, CDP, GDP, UDP, or IDP, is also catalyzed, indicating a specific and unidirectional function. The former enzyme name ADP-sulfurylase implies that the reverse reaction is catalyzed; therefore, this name should not be used any longer. Histidine modification of APAT results in complete inactivation that can be suppressed by substrate addition. APAT is highly similar to galactose-1-phosphate uridylyltransferase and also related to Ap(4)A phosphorylase. Active site residues of galactose-1-phosphate uridylyltransferase are conserved in APAT and Ap(4)A phosphorylase, suggesting a histidine as the nucleotide-binding residue in all three enzymes, which together form a new family of nucleotidyltransferases.