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J R Testa

Publications and source records attributed to J R Testa.

214 records · Page 12Linked to original sources
PubMed1981

Cytogenetic analysis of bone marrow and peripheral blood samples stored in fixative for several years.

We have developed a method which improves the spreading of chromosomes and permits banding analysis of cytogenetic samples of bone marrow and unstimulated peripheral blood which have been stored in fixative for up to 15 years. Metaphase cells had been harvested as usual and stored in fixative (acetic acid:methanol 1:3) at -15 C. The procedure includes 4-5 changes of fixative (acetic acid:ethanol 1:1). Next, cells are dropped onto a chilled, wet slide. The back of the slide is then rinsed with 70% ethanol and dried by ignition. C-, G-, Q-, or R-banding patterns can new be obtained with these specimens. The procedure is useful for reinvestigation of cytogenetic sample that were obtained prior to the development of banding techniques.

Acetates↗
PubMed1980

"Microgranular" acute promyelocytic leukemia: a distinct clinical, ultrastructural, and cytogenetic entity.

Three patients with acute leukemia, disseminated intravascular coagulation, and a specific acquired chromosome abnormality [t (15;17)] were found by transmission electron microscopy to have the typical distribution of granules seen in promyelocytes. However, the average granule sizes were 120, 170, and 180 nm, respectively, for the three patients, significantly less than the 250-nm resolution of light microscopy. We regard the leukemia in these three patients as comprising a distinct clinical, ultrastructural, and cytogenetic entity that we have chosen to call "microgranular" acute promyelocytic leukemia.

Adult↗
PubMed1980

Dysmyelopoietic syndrome: sequential clinical and cytogenetic studies.

Clinical and cytogenetic studies were done on 8 patients with dysmyelopoietic syndrome: 6 of these patients had refractory anemia with an excess of blasts (RAEB), and 2 patients had chronic myelomonocytic leukemia (CMML) according to the French-American-British classification. The ages of these 8 patients (3 female and 5 male) ranged from 45 to 70 yr (median, 61.5 yr). Seven of the 8 patients died 3-86 mo (median, 11 mo) after the onset of symptoms of hemorrhage or infections. Cytogenetic studies of bone marrow cells with the Q-banding technique showed clonal karyotypic abnormalities in 7 of the 8 patients (87.5%). Five of the 7 chromosomally abnormal patients had very complex karyotypes; all 7 patients, however, had at least 1 of 4 specific changes: -5 (or 5Q-), -7, +8, and +21. Three of the 7 patients with abnormal karyotypes had had some exposure to potential mutagenic/carcinogenic agents. Five of the 7 patients had serial cytogenetic analyses, 4 of which showed evolution of the karyotype to further complexity; in 2 cases, this coincided with the evolution of the disease into acute leukemia. The median survival time of patients whose initial cytogenetic samples showed both normal and abnormal metaphases was more than twice that of patients who had only abnormal metaphases initially (12 mo versus 4.5 mo).

Aged↗
PubMed1979

Chromosomal DNA cytophotometry in 20q- nonspecific myeloid disorders.

DNA cytophotometry was used to quantify the chromosomal alterations in the bone marrow and blood of three patients with nonspecific myeloid disorders. All patients possessed a population of cells with a morphologically abnormal chromosome 20, del(20)(qll). In two of the patients, the abnormal chromosome 20 showed nearly identical DNA measurements with a net loss of 0.37% of the total autosomal DNA in one patient and 0.38% in the second. The third patient had a net loss of only 0.25% of the autosomal DNA. Analysis of the DNA content of the long arm and short arm of the abnormal No. 20 indicated that all three cases had chromosomal material added to the short arm (0.10 to 0.14% of the autosomal DNA). About 0.50% of the autosomal DNA was deleted from the long arm in two of the patients; only 0.35% of the autosomal DNA was deleted from the long arm in the third case. Within the limit of resolution, there is no evidence that the material lost has been translocated intact to another chromosome. The origin of the 20q- chromosome as the result of an incomplete pericentric inversion is suggested.

Aged↗
PubMed1978

Cytogenetic patterns in acute nonlymphocytic leukemia.

Analysis of chromosomal banding patterns in acute nonlymphocytic leukemia (ANLL) reveals that approximately 50% of patients have an abnormal karyotype. Although there is substantial variability, certain nonrandom abnormalities occur, e.g., +8, -7, and the 8;21 translocation (often accompanied by loss of an X or Y chromosome). The 15;17 translocation appears to be highly specific for acute promyelocytic leukemia. These abnormalities usually are not seen in remission, but reappear in relapse, sometimes exhibiting further clonal evolution; a +8 is the most frequently observed evolutionary change. Patients with ANLL following treatment of a malignant lymphoma tend to have hypodiploid modal numbers and frequently show loss of a chromosome No. 5 or No. 7.

Acute Disease↗
PubMed1978

Correlation of clinical findings with quinacrine-banded chromosomes in 90 adults with acute nonlymphocytic leukemia: an eight-year study (1970-1977).

We observed chromosome-banding abnormalities in leukemic cells of 46 of 90 (51 per cent) adults with acute nonlymphocytic leukemia at initial hospital admission. The difference in survival between 37 treated patients with an initially normal karyotype (10 months) and 43 with an initially abnormal karyotype (four months) was significant (P less than 0.01). When patients were classified as having acute myelogenous leukemia or acute myelomonocytic leukemia, this difference in survival was even more pronounced. Of 16 treated patients with acute myelogenous leukemia and a normal karyotype, 11 (69 per cent) had a complete remission and a median survival of 13 months. Of eight patients with acute myelogenous leukemia in whom only abnormal metaphases were observed, none had a complete remission, and the median survival was only two months (P approximately 0.50). Remission rate and median survival were not significantly different in patients with acute myelomonocytic leukemia grouped according to initial karyotypes.

Adolescent↗
PubMed1978

Hypergranular promyelocytic leukemia (APL): cytogenetic and ultrastructural specificity.

Cytogenetic and ultrastructural findings were important diagnostic indicators of hypergranular promyelocytic leukemia (APL) in a patient whose bone marrow morphology appeared, by light microscopy, to be similar to that in acute myeloblastic leukemia (AML) with maturation. Peripheral blood smears and bone marrow specimens examined by light microscopy showed few cells with the numerous coarse, azurophilic granules typical of APL. Cytogenetic analyses, with several banding techniques, of cells from bone marrow and unstimulated peripheral blood revealed the 15;17 translocation, which has been observed only in APL. A reinterpretation of the reciprocal translocation, based on R banding, suggests that the breakpoints are distal to q24 in No. 15 and at or near the junction of q21 and q22 in No. 17. In addition, the patient had disseminated intravascular coagulation. The characteristic morphology of granules seen in APL was observed in this case only when transmission electron microscopy was used, since the granules were quite small. Since treatment for AML differs from that for APL, identification of the 15;17 translocation and ultrastructural evidence of granules represent valuable diagnostic aids for APL.

Adult↗
PubMed1978

Deletion of the long arm of chromosome 20 [del(20)(q11)] in myeloid disorders.

Detailed clinical and cytogenetic studies were performed in five patients who had abnormal hematopoiesis and an acquired deletion of an F-group chromosome. Cytogenetic analyses, with banding techniques, of cells from bone marrow, spleen, or unstimulated peripheral blood showed a partial deletion of the long arm of one chromosome 20 [del(20)(q11)] in all five patients. Three patients had myeloproliferative disorders of uncertain classification, the fourth had possible preleukemia, and the fifth had acute myelomonocytic leukemia. Although the five cases showed certain similarities, the clinical and hematologic findings seen with the 20q- abnormality were not specific. None of the patients showed evidence of polycythemia vera or idiopathic acquired refractory sideroblastic anemia, two diseases previously associated with the 20q-. Our studies indicate that the 20q- abnormality is not limited to diseases primarily affecting erythropoiesis but that it can be found in the broader spectrum of myeloid disorders. In polycythemia vera, the 20q- has sometimes been regarded as a possible result of previous therapy with cytotoxic agents; however, four of our patients were untreated when the deletion was first noted.

Aged↗
PubMedDate not supplied

Genome scanning detects amplification of the cathepsin B gene (CtsB) in transformed rat ovarian surface epithelial cells.

OBJECTIVE: To isolate a portion of the amplicon inferred to be present in a malignant rat tumor cell line, NuTu 26, by the presence of a homogeneously staining chromosomal region (hsr) and identify genes embedded within it. METHODS: Genome scanning was used to identify an EcoRI fragment (8.6 kbp) within the amplified region of the NuTu 26 genome using a recently identified rat repetitive sequence, OST17 as a probe. The 8.6 kbp amplified fragment was sequenced and used as starting material to obtain additional sequence information by screening a P1 clone-derived DNA library to identify any genes likely embedded in the amplicon. Use of the microdissected hsr as a probe for fluorescence in situ hybridization (FISH) and application of Southern, Northern, and Western blot analysis confirmed the amplification of this region in the NuTu 26 genome. RESULTS: The cathepsin B gene was within the amplicon of the hsr-containing marker chromosome of NuTu 26. FISH analysis and chromosomal banding further revealed that the marker chromosome was a derivative of chromosomes 4 and 15, i.e., der(15)t(4;15). CONCLUSION: Cathepsin B gene amplification may contribute to some aspect of the biology of ovarian cancer. This concept is strengthened by the finding that the gene is overexpressed frequently in independently transformed rat ovarian surface epithelial cells.

Animals↗
PubMedDate not supplied

Recent advances in the molecular analysis of human malignant mesothelioma.

PURPOSE: To evaluate the role of asbestos, somatic genetic alterations, and simian virus 40 (SV40) in the formation of malignant mesothelioma (MM). DESIGN: To review recent cytogenetic and molecular genetic advances in MM. RESULTS: Exposure to asbestos is a major factor contributing to the development of most MMs. The accumulation of recurrent cytogenetic deletions in most MMs suggests a multistep process in this malignancy characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Karyotypic, comparative genomic hybridization (CGH), and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific chromosomal regions within 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Positional candidate gene approaches have identified TSGs within two of these regions, i.e., CDKN2A at 9p21 and NF2 at 22q12, which are frequently altered in MMs. In addition, recent studies have demonstrated the presence and expression of SV40 in many MMs. Proposed mechanisms by which asbestos and SV40 contribute to the development of MM are reviewed. CONCLUSIONS: The identification of new TSGs involved in MM and understanding the role of these genes and of SV40 in the pathogenesis of this malignancy may lead to design of more effective therapeutic strategies.

Asbestosis↗
PubMedDate not supplied

Evaluation of techniques for increasing mitotic yield and chromosome length in leukemic cells.

Previously reported techniques for the culture of bone marrow and unstimulated peripheral blood for cytogenetic analysis were evaluated in patients with acute myelogenous leukemia (AML) or chronic myelogenous leukemia (CML). Samples were treated in the following manner: (1) cold synchronization (exposure to 4 C for eight hours, then incubation at 37 C for 14.5 hours [CML] or 16.5 hours [AML]); (2) cold synchronization plus Hoechst 33258 (as first treatment, with Hoechst 33258 added to a final concentration of 50 micrograms/ml for the last five hours of incubation; (3) methotrexate synchronization (methotrexate added to a final concentration of 10(-7) M, incubation at 37 C for 17 hours, then washing of cells and addition of thymidine to a final concentration of 10(-5) M for an additional 5 hours 15 minutes of incubation); and (4) controls (untreated, incubation at 37 C). All cultures were harvested simultaneously in the usual manner. Our results suggest that cold synchronization provides improvement in mitotic yield and chromosome length as well as in chromosomal morphology, as compared to the results obtained with cold synchronization plus addition of the fluorochrome Hoechst 33258, with methotrexate synchronization or with standard direct culture techniques. Cold synchronization can readily be applied to the routine laboratory culture of hematologic cells for cytogenetic analysis.

Bone Marrow↗