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J R Downing

Publications and source records attributed to J R Downing.

97 records · Page 6Linked to original sources
PubMed1986

Diffuse large cell lymphoma in a patient with hairy cell leukemia: immunoglobulin gene analysis reveals separate clonal origins.

A 75-year-old man with hairy cell leukemia (HCL) was found to have an immunoblastic lymphoma of the small bowel. Immunologic and genotypic characterization of these neoplasms revealed both the HCL and the immunoblastic lymphoma to be of the B cell lineage. The HCL expressed the HCL-associated antigens detected by the monoclonal antibodies HC-1 and HC-2, whereas the immunoblastic lymphoma failed to react with these antibodies. In addition, surface immunoglobulin light chains could not be accurately determined for the hairy cells, whereas the immunoblastic lymphoma was shown to express only kappa immunoglobulin light chains. These immunophenotype differences were compatible with either the clonal evolution of the HCL into the immunoblastic lymphoma or a separate clonal origin for these two neoplasms. An analysis of tumor DNA by Southern blot hybridization revealed different heavy-chain and kappa light-chain gene rearrangements in these two malignancies. Thus the occurrence of the large cell lymphoma most likely represents the emergence of a second clonally unrelated B cell malignancy.

Aged↗
PubMed1980

Luteinizing hormone receptors and testosterone synthesis in two distinct populations of Leydig cells.

Dispersed cells from whole testes or from isolated interstitial tissue of mature rats, yielded two distinct populations of Leydig cells when subjected to centrifugation in a 0-40% metrizamide gradient. One population (I) was found in a fractions with a density of 1.085-1.117 g/cm3, and the other population (II) was found in fractions with a density of 1.128-1.145 g/cm3. Binding of 125I-labeled hCG by each population of cells indicated a single class of binding sites with the same high binding affinity and similar concentrations of binding sites per Leydig cell. Testosterone production per fmol gonadotropin receptor site in the absence of gonadotropin stimulation was similar for cells of each population. However, when cells from each population were incubated with increasing concentrations of hCG or dibutyryl cAMP, only Leydig cells from population II exhibited a marked increase in testosterone production. The low responsiveness of Leydig cells in population I did not appear to be a result of either damage to these cells or inhibition by non-Leydig interstitial cells in population I.

Animals↗
PubMed1980

A relationship between adenosine 5'-triphosphate and pregnenolone syntheses by ovarian mitochondria as demonstrated with aminoglutethimide.

Aminoglutethimide, an inhibitor of pregnenolone synthesis, was used to study the relationship between oxidative phosphorylation and steroidogenesis in ovarian mitochondria. In vitro addition of aminoglutethimide to mitochondria prepared from porcine corpora lutea resulted in a decrease in oxygen uptake and an increase in the ADP to oxygen ratio, with maximal changes occurring at a concentration of 300 microM. Similar decreases in oxygen uptake were seen when aminoglutethimide was added to ovarian mitochondria from untreated and PMS gonadotropin-treated immature rats and intact and hypophysectomized mature rats. Also, aminoglutethimide increased the ADP to oxygen ratio in ovarian mitochondria from PMS gonadotropin-treated immature rats and intact mature rats. The addition of aminoglutethimide to luteal mitochondria inhibited their [4-14C]cholesterol conversion activity but increased their ATP synthesis rate by 25%. It is concluded that inhibition of ovarian mitochondrial steroidogenesis by aminoglutethimide is accompanied by both a decrease in oxygen consumption and an increase in ATP synthesis.

Adenosine Triphosphate↗
PubMedDate not supplied

Disseminated intrathoracic desmoplastic small round-cell tumor: a case report.

PURPOSE: Recently recognized as a distinct clinicopathologic entity, desmoplastic small round-cell tumors typically affect young men. These aggressive tumors usually arise in the abdomen; other sites of primary disease have been described only rarely. We report the case of an extraabdominal primary tumor with widespread dissemination, including the subcutaneous tissue, a previously unrecognized metastatic site. PATIENT AND METHODS: We describe the case of a 16-year-old boy with a primary extraabdominal metastatic desmoplastic small round-cell tumor. RESULTS: Our patient had a primary intrathoracic desmoplastic small round-cell tumor and widespread dissemination involving the subcutaneous tissue, kidney, liver, bone, and lymph nodes. Histopathologic analysis found intense desmoplasia and polyphenotypic expression of neural, muscle, and epithelial markers. Reverse transcriptase-polymerase chain reaction analysis of fresh tumor tissue confirmed the characteristic EWS-WT1 transcript. CONCLUSIONS: Broader than originally anticipated, the clinical spectrum of desmoplastic small round-cell tumors continues to evolve. Primary intrathoracic tumors with soft-tissue dissemination and polyphenotypic expression should prompt suspicion of this malignancy. Molecular analysis of fresh tumor tissue is an important adjunct to diagnosing this rare neoplasm.

Adolescent↗
PubMedDate not supplied

Primitive neuroectodermal tumor of bone as a second malignant neoplasm in a child previously treated for acute lymphoblastic leukemia.

PURPOSE: Although rare, second malignant neoplasms (SMNs) are a devastating consequence of successful treatment of childhood cancer. The 15-year estimated risk of developing a second malignant neoplasm after treatment of childhood acute lymphoblastic leukemia (ALL) is 2.5%. Most of these neoplasms are central nervous system tumors. The risk of secondary acute myeloid leukemia has been negligible in most treatment regimens. Here, we report the first case of a primitive neuroectodermal tumor (PNET) in a patient treated for ALL. PATIENTS AND METHODS: A 15.7-year-old girl developed pain in her left leg 7 years after diagnosis of low-risk ALL. Imaging studies revealed lytic lesions in her left proximal tibia and several vertebra as well as metastatic nodules in both lungs. RESULTS: Immunocytochemical and molecular analyses led to the diagnosis of PNET. The treatment of this SMN was composed of combination chemotherapy with hematopoietic growth factor support and radiotherapy to the primary lesion and affected spine. The tumor recurred 5 months after the completion of treatment, and the patient is now undergoing salvage therapy composed of chemotherapy and radiotherapy. CONCLUSIONS: To our knowledge, this is the first report of PNET as an SMN after successful treatment of ALL.

Adolescent↗
PubMedDate not supplied

Acute lymphoblastic leukemia in a developing country: preliminary results of a nonrandomized clinical trial in El Salvador.

PURPOSE: To improve outcome and study biology of childhood acute lymphoblastic leukemia (ALL) in El Salvador. PATIENTS AND METHODS: Between January 1994 and December 1996, 153 children of El Salvador had newly diagnosed ALL treated in a collaborative program between Hospital Benjamin Bloom and St. Jude Children's Research Hospital (SJCRH). Therapy was based on a modified SJCRH protocol, with uniform remission induction (prednisone, vincristine, L-asparaginase) followed-up by consolidation with teniposide/cytarabine and/or high-dose methotrexate. Continuation treatment was risk-stratified: 123 patients assigned to the high-risk group received weekly rotational drug pairs, and 16 assigned to the standard-risk group received daily 6-mercaptopurine, weekly methotrexate, and monthly pulses of vincristine plus dexamethasone. High risk was defined as: DNA index < 1.16, age 12 months or younger, white blood cell count > or = 50 x 10(9)/L, T-cell immunophenotype, anterior mediastinal mass, central nervous system leukemia at diagnosis, or t(4;11), t(1;19), or t(9;22). Duration of the continuation treatment was 2.5 years in both groups. The median age at diagnosis of all patients was 4.8 (range I d-17 yrs), median leukocyte count was 15 (range 1-766) x 10(9)/L, and sex distribution was equal. RESULTS: Immunophenotypes were early beta-progenitor in 79%, T-cell in 3.9%, and inconclusive in 17% of cases. DNA index was <1.16 in 80.5% and was > or = 1.16 in 19.5% of the 123 known cases. For the analyzes, patients who refused therapy (abandoned treatment) were considered to have treatment failure as of their last follow-up dates. Complete remission was achieved in 126 of 151 (82.4%) patients (11 abandoned therapy during induction). The overall 4-year event-free survival (EFS) rate +/- 1 standard error was 48 +/- 6%. The 4-year EFS rates in patients at high-risk and standard-risk were 46 +/- 7% (n = 121) and 69 +/- 15% (n = 16), respectively (P = 0.20). When patients who refused further treatment are censored, the corresponding 4-year estimates of EFS are 51 +/- 8% and 75 +/- 14%, respectively. CONCLUSIONS: These results suggest that the biology of childhood ALL in El Salvador appears to be similar to that seen in the United States. Risk-directed chemotherapy can successfully be used in developing countries, but risk factors must be carefully determined and applied.

Adolescent↗