2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 ...to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.
A PCR assay for the sensitive detection of a transforming fragment of herpes simplex virus type 2 (HSV-2) was developed. Oligonucleotide primers were selected in Xho-2, a transforming region of the ...BglII N fragment of HSV-2. The assay reached a sensitivity endpoint of 10 copies of the Xho-2 subfragment and did not show cross-reactivity with other herpesviruses, including HSV-1. All 42 HSV-2 isolates scored positive in the assay. The Xho-2 PCR assay was evaluated with 216 clinical specimens and the and the results were compared with those of cell culture. The best protocol for processing specimens contained in viral transport medium included a centrifugation step followed by cell lysis. Of the 107 specimens positive for HSV-2 by culture, 105 were PCR positive (sensitivity, 98.1%). For one of the two falsely negative samples, beta -globin as well as sequences from the HSV-2 DNA polymerase gene could not be amplified. The other sample scored positive in both of these reactions but was indeterminate in duplicate tests by Xho-2 PCR. Two of 109 HSV-2 culture-negative specimens tested positive in the PCR assay (specificity, 98.2%). The latter two samples tested positive in a PCR test for the HSV-2 DNA polymerase gene. This novel tool was shown to be sensitive and specific for HSV-2 sequences and should allow for the investigation of the role of HSV-2 in genital cancers.
The pathologic and clinical features of 31 cases of childhood non‐Hodgkin's lymphoma (NHL) were reviewed retrospectively using Rappaport's classification and a modification of the Ann Arbor staging ...system. Twenty‐nine (93.5%) of the patients had diffuse and 2 (6.5%) had nodular lymphoma. Diffuse histiocytic lymphoma accounted for 10 cases (32.3%), diffuse undifferentiated for 9 (29%), and diffuse lymphocytic, poorly differentiated for 5 (16.1%). Five cases (16.1%) were unclassifiable. No cases of well‐differentiated lymphocytic or mixed cell lymphoma were found. A modified classification was attempted, which included also large basophilic cell (LBC), convoluted T‐lymphocytic (CTL), and Burkitt's lymphomas. These pathologic subgroups accounted for 35.4%, 16.1%, and 6.5% of the cases, respectively. The patients were almost equally divided between clinically localized and generalized stages, and their survival was stage‐dependent. The overall survival was 32.3%; the 3‐year survival was 50% for Stages I and II, compared to 7.7% for Stages III and IV. The gastrointestinal tract was the most common site of origin. In 22% of the cases, the disease originated in extra‐lymphatic tissues. Central nervous system involvement occurred in 10 of 31 children (32%), and a leukemic picture developed in 6 of 31 (19%). The CTL lymphomas were confined to the mediastinum, whereas the LBC lymphomas arose mostly in Waldeyer's ring and Peyer's patches. We conclude that the extent of the disease as determined by clinical staging has prognostic significance in childhood NHL. The prognostic value of the histological classification could not be clearly established from our data.
Of 227 cases of pediatric non‐Hodgkin's lymphoma with adequate histopathologic material for review, 72 (32%) were classified as diffuse “histiocytic” lymphoma (DHL). These cases were further divided ...into different morphologic subtypes according to the Lukes—Collins classification, and the National Cancer Institute Working Formulation, to ascertain whether there were any significant prognostic differences among the different subtypes. The results of our study showed that 40 patients were classified as immunoblastic lymphomas, and 32 were called large follicular center cell (FCC) tumors. Of the 40 patients with immunoblastic histology, 19 had morphologic features of the clear cell type and were interpreted as consistent with T‐immunoblastic lymphomas; an additional two had polymorphous features also consistent with T‐cell type: 17 had plasmacytoid features, and were morphologically classified as B‐immunoblastic lymphomas; two could not be subtyped. Of the 32 patients with morphologic features of FCC lymphomas, 29 were classified as large noncleaved type, and three as large cleaved type. A clinicopathologic analysis showed that 90% of the patients obtained complete remission, and there were no significant differences in complete remission rate among the different morphologic subtypes of DHL. The estimated five year disease‐free survival for all patients was over 70%, with no failure after the second year; and there were no significant differences in the disease‐free survival among the different subtypes. The only clinical differences that we found, were that patients with lymphomas of FCC (large noncleaved) type (1) were younger (P = 0.01); (2) had less nodal involvement (P = 0.03); and (3) had more organ involvement (P < 0.01). We conclude that the morphologic subclassification of DHL in children currently has limited clinical prognostic significance. Cancer 59:1138‐1142, 1987.
We present the discovery and a detailed multi-wavelength study of a strongly-lensed luminous infrared galaxy at z=0.816. Unlike most known lensed galaxies discovered at optical or near-infrared ...wavelengths, this lensed source is red, which the data presented here demonstrate is due to ongoing dusty star formation. The overall lensing magnification (a factor of 17) facilitates observations from the blue optical through to 500 micrometers, fully capturing both the stellar photospheric emission as well as the reprocessed thermal dust emission. We also present optical and near-IR spectroscopy. These extensive data show that this lensed galaxy is in many ways typical of IR-detected sources at z approximates 1, with both a total luminosity and size in accordance with other (albeit much less detailed) measurements in samples of galaxies observed in deep fields with the Spitzer telescope. Its far-infrared spectral energy distribution is well-fit by local templates that are an order of magnitude less luminous than the lensed galaxy; local templates of comparable luminosity are too hot to fit. Its size (D approximately 7 kpc) is much larger than local luminous infrared galaxies, but in line with sizes observed for such galaxies at z approximates 1. The star formation appears uniform across this spatial scale. Thus, this lensed galaxy, which appears representative of vigorously star-forming z approximates 1 galaxies, is forming stars in a fundamentally different mode than is seen at z approximates 0.
Short interspersed elements (SINEs) are mobile elements that contribute to genomic diversity through the addition of genetic material. Recent genomic analyses have vastly augmented our knowledge of ...both human- and canine-specific SINEs. SINEC_Cf is a major SINE of the canid family that has undergone recent expansion and is thought to be present in half of all genes. To date, only three phenotypes of the domestic dog have been attributed to a SINE. One of these is merle, a coat pattern characterized by patches of full color on a diluted background and associated with ocular and auditory anomalies. A SINEC_Cf in the SILV gene causes merle patterning by altering the cDNA transcript and has unique characteristics that are likely responsible for the random nature of the phenotype.
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