Draft Genome Sequence of Streptomyces sp. Strain C8S0, Isolated from a Highly Oligotrophic Sediment.

Streptomyces spp. are prolific bacteria producing bioactive metabolites. We present the draft genome sequence of Streptomyces sp. strain C8S0, which was isolated from a highly oligotrophic sediment from the Cuatro Cienegas Basin (Mexico). The whole-genome assembly comprised 6,898,902 bp, with 18 biosynthetic gene clusters, including those for nonconventional terpenes, nonribosomal peptides, and polyketides.

Electrochemical strategy to scout 1,4-naphthoquinones effect on voltage gated potassium channels.

Naphthoquinone (NQ) was tested on voltage-gated ion channels expressed in Xenopus laevis oocytes. The activity of potassium Shaker channel with Inactivation domain Removed (ShIR) was not affected; in contrast, NQ diminished Kv1.3 currents. A current decrease was barely observed with the oxidant H(2)O(2). These findings suggested that redox properties were involved in the naphthoquinone-Kv1.3 channel interaction. NQ and some derivatives (NQs) were characterized in DMSO and physiological (ND-96) media by cyclic voltammetry. A typical two-stage mono-electronic reduction mechanism was observed in DMSO, while a one-stage bi-electronic reduction process was found in ND-96 medium. NQs with the lowest and the highest redox potential values were tested on both channels. Voltage-clamp recordings showed that inhibition of Kv1.3 was dependent on NQs redox potential. Results demonstrated that structural features (aromaticity and substituents prone to hydrogen bonds formation) of NQs were also important. This effect could be explained by interactions of some channel residues with NQs that contribute to favor their reduction process in the protein surroundings. The electrochemical strategy presented to simulate the cellular environments (aqueous and non-aqueous) that NQs may face, is an important contribution to pre-select (in a fine and simple way) the best redox compounds for electrophysiological testing.

Gastrointestinal autonomic nerve tumors in the pediatric population: a report of four cases and a review of the literature.

BACKGROUND: Gastrointestinal autonomic nerve tumors (GANTs) are a subpopulation of gastrointestinal stromal tumors (GISTs) that are characterized by ultrastructural features resembling enteric autonomic nerve cells, without epithelial, Schwannian, or smooth muscle differentiation. Delineation of the clinicopathologic features of GANT in the pediatric population is lacking. METHODS: The clinicopathologic and outcome data for four pediatric patients with GANT are presented. The data from these patients and four previously reported pediatric patients are summarized and compared with data for GANT in adults. RESULTS: All four cases occurred in females at a mean age of 12.5 years. The primary tumor site was the stomach in all cases, and the mean tumor size was 6.3 cm. Immunocytochemical and ultrastructural examination were essential in distinguishing GANT from GIST in all cases by identifying features of neural origin (neuron specific enolase in all four cases, NFP in three cases, S-100 in two cases, dense core neurosecretory granules in all four cases, and neuritelike processes in all four cases), while failing to identify features of myogenic origin (no desmin, smooth muscle actin, myofilaments, or dense bodies were found in any of the cases). Primary treatment was surgical, with chemotherapy administered to 1 patient at the time of recurrence. All patients are alive after a mean follow-up of 60 months (range, 8 months to 9 years). CONCLUSIONS: Similarities of pediatric GANT to GANT in adults include the need for a high index of suspicion for diagnosis; comparable histopathologic, immunohistochemical, and ultrastructural features; and surgery as the primary therapy. Distinguishing features in children may be a prevalence among females in the second decade, a predominance of smaller gastric tumors, and a positive prognostic value of younger age.

Symptomatic splenic hamartoma: case report and literature review.

An 11-year-old girl with low-grade fever, night sweats, thrombocytopenia, and an 8-year history of progressive splenomegaly underwent an elective splenectomy. Pathologic diagnosis was multiple splenic hamartoma. The patient's symptoms resolved after the splenectomy. Since first described by Rokitansky in 1861, approximately 140 cases of splenic hamartoma have been described in the literature. Most of the splenic hamartomas were discovered incidentally. A minority of these lesions were associated with hematologic symptoms such as pancytopenia, anemia, and thrombocytopenia. Only 20 of the reported cases of splenic hamartoma occurred in pediatric patients. However, compared with the adult patients, nearly half of these cases in pediatric patients was associated with symptoms. Splenectomy and partial splenectomy have relieved these symptoms. With advances in imaging, splenic hamartomas are being discovered with increasing frequency. A multimodal radiologic work-up has enabled some cases of splenic hamartoma to be diagnosed preoperatively. Inclusion of this benign entity in the differential diagnoses of symptomatic splenomegaly in a pediatric patient is important in the preoperative management and counseling of the patient and family. In patients who have discrete lesions, consideration of this entity preoperatively may avoid total splenectomy.

Neuroblastoma presenting as acute monoblastic leukemia.

PURPOSE: We report a 5-year-old boy with stage 4 neuroblastoma initially diagnosed as having acute monoblastic leukemia (FAB M5A, AMoL), based on bone marrow morphology, histochemistry, immunocytochemistry, immunophenotyping and cytogenetics, all consistent with AMoL. The patient also had circulating blasts at diagnosis. After failing initial therapy for AMoL and because of concerns about residual blasts with a clumped appearance in the bone marrow, urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) and N-myc amplification in tumor cells were evaluated and found to be positive, resulting in the diagnosis of neuroblastoma. Abdominal computerized tomography showed a left adrenal mass. A review of 10 reported cases of neuroblastoma with leukemic features showed that seven of them were misdiagnosed as having leukemia, and in six of the seven, the diagnosis of neuroblastoma was made postmortem. CONCLUSION: Neuroblastoma may be confused with acute leukemia, even with the use of modern techniques.

Renal cell carcinoma metastatic to the gallbladder or prostate: two case reports.

Although metastatic renal cell carcinoma (RCC) is not uncommon, dissemination to the gallbladder or prostate is very rare. We present 1 case of RCC with synchronous metastasis to the gallbladder and 1 case of RCC with metachronous metastasis to the prostate. These cases illustrate the propensity of RCC for unpredictable presentation and unusual sites of metastases. The first case also illustrates the benefit of adjuvant nephrectomy with excision of a solitary metastasis. Patterns of RCC metastases and flow cytometric analysis of RCC are discussed.

Malignant melanoma of soft parts involving the head and neck region: review of literature and case report.

Malignant melanoma of soft parts (MMSP) was originally described as a distinct entity by Enzinger in 1965 and was termed "clear cell sarcoma of tendons and aponeuroses" because of its association with tenosynovial structures. It has been shown immunophenotypically and ultrastructurally that this tumor is derived from neuroectoderm and shares a number of features with cutaneous melanoma. Over 95% of MMSPs present in the extremities, with the head and neck region (1.9%) being an unusual site. This study presents an additional case of MMSP of the head and neck region involving the posterior cervical region in a 15-year-old Hispanic male and reviews the literature on MMSP. Ultrastructural examination showed rudimentary cell attachments, smooth cell membranes, discontinuous basal lamina, scanty glycogen, and occasional premelanosomes in some tumor cells. Cytogenetic analysis showed a reciprocal translocation between the long arms of chromosomes 12 and 22 [t(12:22)(q13;q12.2)], characteristic for MMSP and not seen in cutaneous melanoma. Survival in MMSP has been correlated with tumor size, tumor necrosis, and ploidy status. Overall reported clinical outcome for this tumor is as follows: died of disease, 45%; alive with disease, 23%; no evidence of disease, 30%; and died of other causes, 2%. MMSP represents a distinct entity with a characteristic ultrastructural appearance and a tumor defining cytogenetic translocation.

Allelic imbalance in gastric cancer: an affected site on chromosome arm 3p.

In order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we performed an allelotype study on 78 gastric adenocarcinomas from a population composed largely of Texan Hispanics and Anglos, two ethnic groups that have a ratio of incidence rates of gastric cancer of approximately 2:1. In total, 42 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome. These included several markers linked to known tumor suppressor genes (TP53, APC, DCC, RB1, and BRCA1). Sites showing quantitative allelic imbalance (AI) greater than 30% were located on 3p (36%), 11q (31%), 12q (38%), 13q (33%), 17p near TP53 (74%), and 17q near BRCAI (32%). Among the 22% of cases showing microsatellite instability (MI), a subset (4 of 17) showed instability at 59% or more of sites tested. No ethnic bias was detected in cases showing MI or in cases with AI at sites with rates of AI above 30%. Tumors of the intestinal subtype were significantly more likely than diffuse tumors to show AI at DI3S170 (P = 0.01). A deletion map of chromosome arm 3p was prepared for tumors with AI at D3S1478. These data indicate that a tumor suppressor gene on chromosome arm 3p is involved in the development of a subset of gastric cancers.

Novel germline mutation of the p53 tumor suppressor gene in a child with incidentally discovered adrenal cortical carcinoma.

PURPOSE: We report a case of adrenal cortical carcinoma in an infant, which was incidentally discovered by renal sonography after a urinary tract infection. The previous death of a sibling after rhabdomyosarcoma in infancy prompted a search for a heritable p53 tumor suppressor gene mutation in this family. PATIENTS AND METHODS: Starting with frozen adrenal carcinoma tissue, polymerase chain reaction (PCR) amplification followed by direct sequencing of exons 4-8 of p53 was used to search for a mutation. When a mutation was identified in exon 6 of the tumor p53 sequence, PCR amplification and direct sequencing of exon 6 alone was then performed on DNA from peripheral blood lymphocytes (PBLs) of all immediate family members to determine whether a germline mutation was present. A different set of primers was used by a second laboratory at our institution to independently confirm the presence of the mutation in the adrenal carcinoma and in paraffin-embedded rhabdomyosarcoma tissue of the deceased sibling. RESULTS: A C-to-T transition was identified at a CpG site in codon 196 resulting in a change from arginine to a stop codon (CGA to TGA). The identical mutation, present as the sole p53 allele in the tumor DNA samples and in the heterozygous state with wild type p53 allele in DNA from PBLs (germline), was found in the adrenal carcinoma, the rhabdomyosarcoma, and the PBLs of the tumor-bearing child and her healthy father and 5-year-old brother. This nonsense mutation of p53 has never before been reported in the germline. The extended pedigree showed only one known additional cancer. CONCLUSIONS: A novel germline p53 mutation was identified by investigation of a sibling pair with cancers associated with the Li-Fraumeni syndrome in a family with an otherwise negative history for cancer. The implications of this case for identification of carriers of p53 germline mutations and their clinical management are discussed.

Hepatoblastoma: a rare pediatric neoplasm.

The differential diagnosis of an abdominal mass in an infant or young child includes hepatoblastoma. This rare embryonal neoplasm of the liver is linked to several congenital abnormalities and may be associated with maternal occupational exposure to metal fumes, petroleum products, or paints. Alpha-fetoprotein is a useful tumor marker that may also be elevated with hepatocellular carcinoma. The relatively better prognosis of hepatoblastoma, if completely resected, mandates its differentiation from hepatoma. The fetal subtype of hepatoblastoma seems to represent a "favorable" histology pattern.

Giant bilateral xanthogranulomas in a child: case report.

Symptomatic xanthogranulomas are rare lesions that most commonly occur in adults. A case of giant bilateral xanthogranulomas in a 6-year-old boy, who remains without tumor recurrence 9 years after resection, is presented. The operative management of these unusually large lesions is discussed. The pathogenesis of xanthogranulomas is reviewed as it relates to the presentation of these lesions in the pediatric population.

Childhood undifferentiated leukemia with early erythroid markers and c-myb duplication.

Ultrastructural, flow cytometric, and molecular studies were performed on leukemia cells from bone marrow and pleural effusion of a 6-year-old boy diagnosed with undifferentiated (MO) leukemia, using routine histology and immunostains at diagnosis and relapse. Ultrastructurally, surface and/or intracellular ferritin particles were present on or in some blasts and the majority of blasts contained identifiable acid ferrocyanide reactive inorganic iron comparable to that seen in normal early erythroblasts. The cells lacked other evidence of differentiation, including diaminobenzidine-reactive or immunoreactive hemoglobin. Flow cytometric analysis of malignant cells showed a lack of lymphoid or myeloid markers. Anti-transferrin receptor antibody was positive on 93% of cells and antibody to glycophorin A reacted with 23% of cells. RNA blot analysis of leukemia cells with myeloperoxidase (MPO) showed an absence of appreciable levels of MPO mRNA. Chromosome analysis showed 51,XY, t(1;16)(p31;q24), +6, +10, +15, +19, +21. The oncogene c-myb, which is specifically expressed and regulated in hematopoietic cells and produces a DNA-binding protein responsible for myeloid differentiation, was found to be duplicated in the patient's tumor cells. Expression of c-jun, N-ras, c-myc, and p53 was normal. The data indicate that the malignant cells in this patient are of early erythroid lineage at diagnosis and relapse and that classification of cell lineage can be enhanced by ultrastructural Prussian blue staining. The failure of this otherwise undifferentiated leukemia to express or evolve into a myeloid phenotype is biologically and clinically distinct from previously described cases of erythroid and myeloid leukemia and may represent a previously unidentified phenotype which should be included in the spectrum of 'undifferentiated' childhood leukemia.

Cytogenetic and molecular evaluation of clinically aggressive esthesioneuroblastoma.

We report a 16-year-old boy with esthesioneuroblastoma that presented with a unilateral tumor extending to the maxillary sinus and periorbital region. Despite initial therapy with gross resection, 5,682 cGy to the tumor bed and chemotherapy, the patient subsequently had a rapid local recurrence with distant metastases. Immunocytochemical, ultrastructural, cytogenetic, and molecular techniques were performed to determine if this tumor was biologically similar to childhood neuroblastoma. Urinary excretion of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were markedly elevated. Chromogranin and neuron specific enolase immunostaining of tumor cells was positive, as seen in neuroblastoma. Electron microscopic studies showed cells that were closely packed and connected by occasional cell junctions. The cell cytoplasm contained moderate amounts of filaments and microtubules. Numerous electron dense granules were observed; however, these granules lacked distinct nucleoids and generally reacted strongly for acid phosphatase, indicating a lysosomal rather than a secretory function. Tumor cells contained near-pseudotetraploid chromosomes, with all chromosomes represented at least three times, and chromosome 5 was present in multiples of eight. Clonal structural abnormalities included 2q+ and 5q+ and multiple double minutes. Northern blot analysis revealed both c-myc and N-myc expression; however, N-myc amplification was not demonstrated, and c-myc expression appeared increased, unlike cases of rapidly progressive neuroblastoma. These results suggest that despite biologic similarities to neuroblastoma in catecholamine excretion and some ultrastructural features, molecular genetic abnormalities differ in this comparatively aggressive case of estesioneuroblastoma.

Immunophenotyping of childhood astrocytomas with a library of monoclonal antibodies.

Immunophenotype (IP) analysis of 14 childhood glial tumors was performed with a library of 16 monoclonal antibodies (MAbs) using biotin-streptavidin-alkaline phosphatase immunohistochemical detection technique. Presence of glial or neuronal differentiated cells within the tumors was evaluated with MAbs against cell-lineage-specific markers: high-, medium- and low-molecular-weight neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP). Intense expression of GFAP was demonstrated in 14/14 astrocytomas. The three NFs were detected in 10-50% of the cells in 6/14 cases. The pan-neuro-ectodermal antigen defined by MAb UJ 13/A was present in 7/14 astrocytomas on more than 10% of the cells. Thy-1 was expressed in 14/14 tumors on more than 50% of their cells. The GQ ganglioside antigen detected by MAB A2B5, was found in 12/14 tumors. Shared antigens exist among morphologically benign and malignant glial tumor cells and leukocytes detectable with the following four MAbs: Thy-1, PI 153/3, UJ 308 and anti-HLe, common leukocyte antigen (CLA). CLA-expressing cells were demonstrated in 8/12 astrocytomas, and in 4/12 cases more than 90% of the cells were positive. We have shown that cells within childhood astrocytomas can express neuronal IP. The most common expressed phenotype for glial tumors was: GFAP+, Thy-1+, A2B5+, UJ 167.11+, UJ 223.8+, NF (H,M)+, UJ 13/A+, UJ 127.11-, and NF (L)-.

Postoperative chemotherapy for primary intracranial germ cell tumor.

Two children with primary intracranial mixed germ cell tumors are described who were successfully treated by partial resection of the tumor followed by sequential combination chemotherapy without radiation therapy. The chemotherapy consisting of VP-16 and cisplatin alternating with vincristine, methotrexate, and bleomycin resulted in apparent complete response after 6 to 7 months of treatment. Disease-free remission has continued 30-34 months off therapy. A small residual mass in one patient continues to decrease in size on magnetic resonance imaging and is presumed to represent postsurgical change rather than malignant tumor. This report demonstrates that chemotherapy may be effective in primary germ cell tumors of the suprasellar and pineal regions and could be considered for primary treatment instead of radiotherapy.

Disseminated primitive neuroectodermal tumor: diagnosis using immunocytochemistry, electron microscopy, and molecular probes.

A patient with a disseminated small cell tumor presented with hyperuricemia, gingival hypertrophy, lymphadenopathy, and bone marrow replacement with tumor cells. Initial histologic examination and clinical presentation were consistent with presumed marker silent lymphoma/leukemia. Despite initial treatment with and response to lymphoma/leukemia therapy the patient relapsed in the testis, bone marrow, pancreas, and skin whereupon subsequent and retrospective immunocytochemical, ultrastructural, cytogenetic, and molecular analysis led to the diagnosis of primitive neuroectodermal tumor (PNET). Despite extensive investigation and autopsy no primary site of tumor could be found demonstrating that PNET should be considered in the differential diagnosis of disseminated small cell tumors without an apparent primary.

Glioblastoma multiforme masquerading as a pleomorphic xanthoastrocytoma.

Since its first description by Kepes in 1979, pleomorphic xanthoastrocytoma (PXA) has been considered a tumor with a benign course. Two cases are presented here that support the concept that PXA may be more accurately considered part of a spectrum of astrocytomas that occasionally may act aggressively. These cases represent astrocytomas with PXA components and are characterized by meningeal proximity, a high number of mitoses, and subsequently aggressive clinical behavior. The importance of recognizing the potential of a "benign" PXA to transform into a malignant entity has obvious implications for the therapeutic management of these tumors.

Terminal deoxynucleotidyl transferase negative acute lymphoblastic leukemia in two offspring of mothers exposed to diethylstilbestrol (DES) in utero.

We report two children with leukemia who were born to diethylstilbestrol (DES)-exposed mothers. The children were 2 and 6 years old at diagnosis and the lymphoblasts expressed the unusual terminal deoxynucleotidyl transferase negative phenotype. Both children completed induction and maintenance therapy and are alive 6 and 4 years from diagnosis. The role of DES as a transplacental carcinogen is reviewed, and a hypothesis for the target cell interaction is proposed.

Vasculopathic hepatotoxicity associated with E-Ferol syndrome in low-birth-weight infants.

A fatal syndrome characterized by progressive clinical deterioration with unexplained thrombocytopenia, renal dysfunction, cholestasis, and ascites developed in certain infants throughout the United States who had received E-Ferol, an intravenous vitamin E supplement. We reviewed the clinical course of all 36 infants from one (index) nursery who had received E-Ferol, which contains 25 units per milliliter of dl-alpha-tocopheryl acetate solubilized with 9% polysorbate 80 and 1% polysorbate 20. The syndrome was recognized in eight of the 36 infants; affected infants had a lower birth weight (less than 1,200 g) and had received a higher total dose of E-Ferol for longer periods than the unaffected cases. We reviewed autopsy-derived tissue from 20 infants (six from the index nursery and 14 from three other collaborating nurseries) who had received the intravenous vitamin E preparation in a reported dose of 25 to 137 units/kg/day for six to 45 days between October 1983 and March 1984. The hepatic histology in the affected cases indicated a progressive injury characterized initially by Kupffer cell exfoliation, central lobular accumulation of cellular debris, and centrally accentuated panlobular congestion. Prolonged exposure to E-Ferol was associated with progressive intralobular cholestasis, inflammation of hepatic venules, and extensive sinusoidal veno-occlusion by fibrosis. We propose that vasculocentric hepatotoxicity is the basis for the observed clinical syndrome that represents the cumulative effect of one or more of the constituents of E-Ferol.

Interventricular fibroma and cystic renal dysplasia in a newborn.

A newborn twin presented with a cardiac tumor; at autopsy microcystic dysplasia was found in the kidneys. The histology of the renal cysts were not unlike those found in many multisystem syndromes (e.g., Schwartz-Jampel, Ehlers-Danlos, and Jeune's asphyxiating thoracic dystrophy). No evidence of tuberous sclerosis or other phakomatoses were found. This case may alert other observers to carefully look for cystic dysplasia of the kidneys or other organs in association with cardiac tumors.