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Biomedical subjects

E Henderson

Publications and source records attributed to E Henderson.

At least 145 records · Page 8Linked to original sources

Aberrant recombination events in B cell lines derived from a kappa-deficient human.

We have analyzed the structure of Ig kappa chain genes in B cell lines derived from a human individual who cannot synthesize any kappa chains, and whose Igs all contain lambda chains (1). We have characterized secondary DNA recombination events at two kappa alleles which have undergone misaligned V-J recombinations. One such secondary recombination has joined the flanking sequences of a V kappa and a J kappa 2 gene segment as if it were the reciprocal product of a V-J kappa 2 recombination, and resulted in the displacement of the recombined VJ kappa 1 gene segments from the C kappa locus. The non-rearranged form of the V kappa fragment which had recombined with the J kappa 2 flank was cloned. Nucleotide sequencing of this fragment identified a V kappa gene that differed by at least 38% from all previously sequenced human V kappa genes. The other V-J kappa segment analyzed has undergone a secondary recombination at a different site from that described above, at a site within the intervening sequence between the J kappa and C kappa gene segments, similar to the location of secondary recombinations which have occurred in lambda + B cell lines from mice and humans (2,3). These results prove that multiple recombinations can occur at one J kappa-C kappa locus.

B-Lymphocytes↗

Eubacteria, halobacteria, and the origin of photosynthesis: the photocytes.

The halobacteria and the photosynthetic members of the eubacteria have previously been classified in two separate urkingdoms--the archaebacteria and the eubacteria, respectively. They were thought to be no more closely related to each other than they each were to the eukaryotes. In accord with this earlier classification, photosynthesis was thought to have originated twice by independent events--once within the eubacteria and once within the archaebacteria. In this paper, however, using three-dimensional ribosome structure as a probe of evolutionary divergences, we show that the eubacteria and the halobacteria are more closely related to each other than they are to any other known organisms. The simplest interpretation of our data is that all extant photosynthetic cells are descended from a single common ancestor that possessed a primeval photosynthetic mechanism. Numerous data on the occurrence of related biochemical processes in halobacteria and eubacteria support this theory. Essential components of the photosynthetic apparatus, such as carotenoids, are present in both halobacteria and in eubacteria, including the nonphotosynthetic eubacteria, suggesting that photosynthesis could be a primitive property of both groups. Our data indicate that together the eubacteria and the halobacteria form a monophyletic group for which we propose the name "photocytes." If other techniques of phylogenetic analysis confirm this evolutionary tree, we propose that the photocytes be given urkingdom status.

Biological Evolution↗

Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III cancer and Leukemia Group B Study.

Patients with limited-stage small-cell carcinoma of the lung (SCCL) were randomly assigned to a four-drug chemotherapy program consisting of methotrexate, doxorubicin, cyclophosphamide, and CCNU (MACC) or to a regimen consisting of cyclophosphamide, CCNU, and vincristine alternated with Adriamycin (Adria Laboratories, Columbus, Ohio) and vincristine (CCV/AV). All patients received 4,500 cGy, in a split course, to the primary tumor, mediastinum, and supraclavicular lymph node drainage areas and 3,000 cGy to the whole brain. After four cycles of chemotherapy, patients were randomly assigned to chemotherapy plus methanol extractable residue of BCG (MER-BCG) or no MER-BCG. The complete response frequencies were similar for the two regimens (54% and 48%) as were the median survivals (12.0 and 11.5 months) and the two-year survival rates (15% and 17%). Immunotherapy with MER-BCG did not prolong the time to disease progression or improve survival. Women had a greater chance of achieving a complete remission independent of performance status. There was a complex interaction between sex and the chemotherapy regimens that may have important implications for the design and stratification of future trials in SCCL.

Antineoplastic Combined Chemotherapy Protocols↗

A new ribosome structure.

Ribosomes derived from the sulfur-dependent archaebacteria are structurally distinct from those types found in ribosomes from eubacteria, eukaryotes, and other archaebacteria. All four ribosome types share a common structural core, but each type also has additional independent structural features. In the smaller subunit derived from sulfur-dependent archaebacteria ("eocytes"), lobes, similar to those found at the base of the eukaryotic small subunits, and an archaebacterial bill, similar to those found on the smaller subunit of archaebacteria and eukaryotes, are present. On the larger subunit from sulfur-dependent archaebacteria, an eocytic lobe, eocytic gap, and eocytic bulge are present. These features, with the exception of the eocytic gap, are found in a slightly modified form on eukaryotic large subunits. These novel ribosomal properties are in general consistent with other molecular biological properties peculiar to these organisms.

Archaea↗

Eocytes: a new ribosome structure indicates a kingdom with a close relationship to eukaryotes.

Ribosomal large and small subunits are organized in four general structural patterns. The four types are found in ribosomes from eubacteria, archaebacteria, eukaryotes, and a group of sulfur-dependent bacteria ( eocytes ), respectively. All four ribosomal types share a common structural core, but each type also has additional independent structural features. The independent features include the eukaryotic lobes and the archaebacterial bill on the smaller subunit. On the larger subunit, they include the eocytic lobe, eocytic gap, and eocytic bulge and a modified central protuberance. These data are most parsimoniously fit by a single unrooted evolutionary tree. In this tree eocytes are closely related to eukaryotes, while archaebacteria and eubacteria are closest neighbors. The tree is consistent with currently known molecular biological properties and indicates that eocytes have a phylogenetic importance equal to that of the three known kingdoms. When other properties and molecular mechanisms of these organisms are better defined, we suggest that an appropriate kingdom name for this group would be the Eocyta .

Animals↗

99mTc-pyrophosphate imaging in patients with acute myocardial infarction: comparison of planar imaging with single-photon tomography with and without blood pool overlay.

To test the hypothesis that single-photon emission computed tomography (SPECT) of 99mTc-pyrophosphate (99mTc-PPi) with and without the overlay of tomographic blood pool scintigrams might detect small infarcts not identified by planar imaging, 52 patients were studied 3.2 +/- 2.0(SD) days after hospital admission for suspected acute myocardial infarction. Patients were chosen prospectively for tomographic study primarily, but not exclusively, because planar four-view imaging with 99mTc-PPi was either negative or equivocal. SPECT was performed with a commercial rotating detector system immediately after planar imaging on one occasion. Corresponding 99mTc-PPi and blood pool sections were mapped into opposite halves of a bichromic color table and displayed as an overlay. Planar images, SPECT and SPECT with blood pool overlay were interpreted separately and in random order without knowledge of clinical data. Seventeen patients had transmural infarcts (four anterior, 13 inferior), 19 had nontransmural infarcts, and 16 patients did not have acute myocardial infarction. The sensitivity of SPECT with blood pool overlay was significantly better than planar imaging for the entire group with myocardial infarction (97% vs 78%; p less than .025); this was primarily due to increased sensitivity in the detection of nontransmural myocardial infarction (95% vs 67%; p less than .05), although in one additional patient inferior transmural myocardial infarction was also detected by the SPECT overlay technique. The specificities of the SPECT overlay technique and planar imaging were not significantly different; however, receiver operating characteristic analysis showed enhanced observer confidence with the tomographic method. SPECT without overlay was intermediate in sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Werner's syndrome: proliferation in vitro of clones of cells bearing chromosome translocations.

Each of several cultures of Werner's syndrome (WS) fibroblasts and lymphoblasts examined was found to be composed of one or several clones of cells with mutated chromosome complements. Two "sister" fibroblasts cell lines (FCLs) that were derived from a mixture of explants cut from the same WS skin biopsy were found to have completely different rearranged chromosome complements. Daily observation of the skin explants from which these two sister FCLs were derived revealed not only that no more than a few fibroblasts ever migrated from a given explant but also that fibroblasts migrated from only a few of the explants. Two of three lymphoblastoid cell lines (LCLs), each probably developed as an independent clone from a different cell from the same WS blood sample, were mosaic, comprised of cells having both normal and rearranged chromosome complements. The third LCL studied, although nonmosaic, had a rearranged chromosome complement, but one that was completely different from those in the other two lines. Based on the observations described, hypotheses have been formulated to explain both the preponderance in long-term WS cultures of clones with mutated chromosome complements and the abbreviated lifespan characteristic of WS fibroblast cultures.

Adult↗

The Grange Inquiry.

Explore the source record for details and available documents.

Hospitals, Pediatric↗

Non-Hodgkin's lymphoma phenotyping: problems in the use of heterologous and monoclonal antibodies.

Cell suspensions or frozen sections of lymph node biopsies from 32 patients with non-Hodgkin's lymphoma (NHL) were studied for sheep erythrocyte (E)-binding under three conditions (Estandard, EAET, Egravity), Fc and C receptors, immunoglobulin (Ig) heavy and light chain class and reactivity with heterologous antisera to T cells (T-LCL), HLA-D (Ia-like) and common acute lymphocytic leukemia (c-ALL) antigens. Selected B and T cell lymphomas were also tested for reactivity with the monoclonal antibodies OKT 3, OKT 4, OKT 6, OKT 8, OKT 11A, Leu-1, Leu-2a, Leu-3a, Leu-4 and Leu-7. There were 26 B and 6 T lymphomas. Most B lymphomas were mu+ (81%), kappa+ (77%) and 31% were mu+ delta+. One of the T lymphomas arose in a patient with antecedent follicular small-cleaved (B) cell lymphoma. The most accurate marker for characterizing the immunologic phenotype in NHL was the clonal excess of kappa+ or lambda+ cells. Neither Estandard, EAET, Egravity or T-LCL were consistently reliable as sole reagents in identifying T-cell lymphomas, their individual scores often being lower than those of monoclonal pan-T cell reagents. HLA-D (Ia-like) antigen was noted in 89% of B and 50% of T lymphomas. The corresponding values for c-ALL antigen were 12 and 33%, respectively. The comparative scores in T-lymphomas between OKT 4 and Leu-3a for "helper-inducer" (HE) cells and OKT 8 and Leu-2a for "suppressor-cytotoxic" (SU) cells were not uniformly consistent. Four T lymphomas had a mixed HE/SU cell phenotype, one was HE, and another SU. Anti-T reactivity was detected in the neoplastic follicles of six of seven follicular lymphomas. The percentage of anti-T reactive cells within positive neoplastic follicles was usually small (5-15%) and of the same order as that noted within reactive lymphoid follicles (5-30%). High numbers (50-100%) of cells from five small lymphocytic B, three diffuse small cleaved cell B and six T cell lymphomas were also positive with one or more anti-T reagents, suggesting the presence of cross-reactive antigens that make phenotyping of lymphomas with monoclonal antibodies problematic. Reactivity with the monoclonal antibody Leu-7 (HNK-1), a putative NK-specific reagent, was seen in one of five B and three of five T lymphomas.

Antibodies, Monoclonal↗

Chloroflexus aurantiacus has 30S ribosomal subunits of the eubacterial type.

Ribosomal subunits from Chloroflexus aurantiacus were isolated and examined by sucrose gradient sedimentation, gel electrophoresis, and electron microscopy. The 30S subunits had all the characteristic structural features of other eubacterial 30S subunits. The data support the proposal that the absence of the archaebacterial bill is a valid phylogenetic marker of the eubacterial lineage.

Bacteria↗

Comparison of oral melphalan, CCNU, and BCNU with and without vincristine and prednisone in the treatment of multiple myeloma. Cancer and Leukemia Group B experience.

A total of 361 evaluable patients with previously untreated multiple myeloma were randomized to receive oral melphalan (0.15 mg/kg/day for seven days, followed by 0.05 mg/kg/day after recovery from the nadir of the leukocytes), BCNU (150 mg/m2 intravenously every six weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-week course of prednisone starting at 0.8 mg/kg for the first two weeks. At week 22, one-half of the patients were randomized to receive vincristine (1 mg/m2) and prednisone (0.6 mg/kg for seven days) every two months in addition to previous therapy. The melphalan treated patients showed a significantly higher overall objective response frequency (59%), according to Myeloma Task Force criteria, when compared to those treated with BCNU (40%) or CCNU (42%). The survivals for all patients were not statistically different for the three treatment programs. However, the good-risk patients treated with melphalan had significantly longer survival (P = 0.02) than the equivalent patients who received BCNU or CCNU. The addition of vincristine and prednisone at week 2 did not significantly increase the percentage of subsequent objective responses or prolong the subsequent survival of any treatment group. It is concluded that oral melphalan is superior to BCNU and CCNU in producing objective responses and in prolonging survival in good risk patients.

Antineoplastic Agents↗

Mapping evolution with ribosome structure: intralineage constancy and interlineage variation.

Ribosomal small subunits are organized in three general structural patterns that correspond to the eubacterial, archaebacterial, and eukaryotic lineages. Within each of these lineages, ribosomal structure is highly conserved. Small subunits from all three lineages share a common overall structure except for the following differences: (i) small subunits from archaebacteria and from the cytoplasmic component of eukaryotes both contain a feature on the head of the subunit, the archaebacterial bill, that is absent in eubacteria, and (ii) eukaryotic small subunits contain additional regions of density at the base of the subunit, the eukaryotic lobes, that are absent in archaebacteria and in eubacteria. We interpret the intralineage conservation of ribosomal three-dimensional structure as forming a phylogenetic basis for regarding archaebacteria, eubacteria, and eukaryotes as primitive lines. Although our data are separate and independent from those of Woese and Fox, they lend further support to their proposal [Woese, C. R. & Fox, G. E. (1977) Proc. Natl. Acad. Sci. USA 74, 5088-5090]. These data also provide a simple, rapid, and accurate method for classifying organisms and for identifying new lineages. Finally, interlineage variation of ribosomal structure is used to establish a rigorous framework for considering the evolution of these three lines.

Animals↗

Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study.

A randomized comparison of the relative efficacy and toxicity of daunorubicin (DNR) at 30 or 45 mg/sq m or adriamycin (ADM) at 30 mg/sq m, given on the first 3 days of a 7-day continuous infusion of cytosine arabinoside (ara-C) at 100 mg/sq m/day, shows the outcome to be dependent on anthracycline, dose, and patient age. DNR 45 is significantly better than DNR 30 or ADM 30 for inducing complete remissions (CR) in patients younger than 60 yr, (72%, 59%, 58% CRs, respectively). DNR 30 is better than DNR 45 or ADM 30 for inducing CR in patients older than 60 yr (47%, 31%, 35%, respectively). There was a corresponding shift in the induction mortality for the age, dose, and anthracycline groups. Adriamycin was significantly more toxic to the gastrointestinal tract than daunorubicin. The duration of complete remission, with cyclic courses of maintenance therapy, was independent of the patient's age, the dose, or choice of anthracycline used in induction, and of whether the maintenance courses were given every 4 wk or every 8 wk.

Adolescent↗