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Biomedical subjects

H Lazarus

Publications and source records attributed to H Lazarus.

At least 73 records · Page 4Linked to original sources
PubMed1978

Controlled substances registration for nonlicensed physicians.

Changes in drug laws and the addition of many formerly uncontrolled drugs to the controlled substances list has caused some concern about the registration of nonlicensed physicians. The question is, how does the recent medical school graduate obtain authorization to use the controlled substances he may need in the course of his postgraduate training at the hospital? The University of Alabama Hospitals, Birmingham, have answered the question with an effective system for hospital registration of nonlicensed physicians.

Alabama↗
PubMed1978

Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion.

We applied a recently developed and more direct technic to diagnose thalassemia syndromes associated with deletion of particular globin structural genes and to assess a fetus at risk for one of those conditions, deltabeta-thalassemia. The method allows assessment of the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA. Cellular DNA fragments produced by cleavage using two specific restriction endonucleases are separated on the basis of size by agarose-gel electrophoresis, and the distribution of specific sequences among the DNA fragments determined by molecular hybridization. We observed the total deletion of alpha-globin genes in homozygous alpha-thalassemia (hydrops fetalis with hemoglobin Bart's) and the deletion of particular beta and beta-like sequences in cases homozygous for hereditary persistence of fetal hemoglobin and deltabeta-thalassemia. Analysis of amniotic-fluid cell DNA from a fetus at risk for deltabeta-thalassemia demonstrated the feasibility of these improved methods for antenatal diagnosis. The molecular studies confirmed the diagnosis predicted by analysis of fetal blood and established at birth.

Adult↗
PubMed1978

Restricted classes of immunoglobulin produced by a lymphoid cell line from a patient with agammaglobulinemia.

Restricted expression of immunoglobulin by a long-term B lymphoid cell line derived from a patient with X-linked agammaglobulinemia is reproted. The patient had peripheral blood B lymphocytes with surface IgD and IgM. Culture of the B cells in vitro with mitogens did not stimulate immunoglobulin secretion, although pokeweed mitogen stimulation resulted in the development of cytoplasmic IgD and IgM. The lymphoid cell line established from these B lymphocytes primarily bore surface IgD, with a small population of cells also bearing surface IgM. These cells also had cytoplasmic immunoglobulin, primarily IgD. The cell line did not have a cytoplasmic pool of immunoglobulin for export and did not secrete immunoglobulin. This B lymphoid cell line is an in vitro analogue of the arrest in differentiation of the patient's B lymphocytes. The IgD-bearing phenotype may represent a normal transitional stage in the differentiation of B lymphocytes.

Adolescent↗
PubMed1978

Bone marrow-derived lymphoid cell lines from patients with agammaglobulinemia.

In vitro infection with Epstein-Barr virus of bone marrow-derived (B) lymphocytes from blood of patients with X-linked or common varied agammaglobulinemia resulted in the establishment of long-term B-lymphoid cell lines (LCL). LCL were established only with B lymphocytes from patients whose B cells failed to respond to in vitro mitogenic stimulation. In contrast, lymphocytes from patients without small B lymphocytes or with B cells that synthesized but failed to secrete Ig failed uniformly to establish LCL. Analysis of the "nonsecretory" B lymphocytes demonstrated the presence of receptors for C3b and C3d as well as surface Ig, but absence of detectable receptors for Epstein-Barr virus. All of the six cell lines that were established formed rosettes with EAC3 but not with sheep erythrocytes. Four of the six LCL were principally surface IgD bearing and did not synthesize detectable Ig for secretion. Two of the cell lines were indistinguishable from cell lines from normal individuals: they had surface IgG, A, M, and D and synthesized and secreted Ig.

Adolescent↗
PubMed1978

Two functionally distinct subpopulations of human T cells that collaborate in the generation of cytotoxic cells responsible for cell-mediated lympholysis.

A human thymus-dependent differentiation antigen, TH2 was defined by a rabbit anti-human T cell serum absorbed with autologous B lymphoblasts and leukemic cells bearing T cell markers from a patient with chronic lymphocytic leukemia. Anti-TH2 reacted specifically with thymus-derived lymphoid cells and exhibited two distinct profiles of reactivity with normal peripheral T cells as detected by indirect immunofluorescence on a FACS I. Isolation of strongly reactive, TH2+, from weakly reactive, TH2- T cells by fluorescence-activated cell sorting revealed that the TH2+ subset contained most of the killer activity in cell-mediated lympholysis (CML), but had a diminished response in MLC and a suboptimal or negligible proliferative response to soluble antigens (mumps, PPD, tetanus toxoid). In contrast, the TH2- subset contained markedly less killer activity but amplified cytotoxicity by TH2+ cells and exhibited a proliferative response to both alloantigen and soluble antigens that was often significantly greater than the response by unseparated T cells. The relevance of these findings to previously described human T cell subsets and to functional subpopulations of murine T cells is discussed.

Absorption↗
PubMed1978

Characterization of a unique cell line (LAZ 221) from human acute lymphocytic ("null" cell) leukemia.

A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the "null" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines.

Adult↗
PubMed1977

Cystine requirement of continuous human lymphoid cell lines of normal and leukemic origin.

A number of continuous, human lymphoid cell lines from healthy and leukemic donors have been studied. Those from healthy individuals were found to be cystine prototrophs (cys+), while those from leukemic donors were observed to be cystine auxotrophs (cys-). The former can grow in either cystine or cystathionine-containing media. The latter grow only in cystine-containing medium. The former contain readily measurable levels of cystathionase, the last enzyme in the mammalian cysteine biosynthetic pathway, while the latter contain much less of this activity. The apparent molecular weight, overall charge, pH versus activity, Km, and [pyridoxal phosphate] versus activity properties of the enzyme from both cell types were indistinguishable. No soluble cystathionase inhibitor could be detected in cys- cell lines. Thus, it is reasonable to hypothesize that those leukemic cell lines studied synthesize less active cystathionase protein than their cys+ counterparts and that this difference in enzyme production underlies the differential growth properties in cystathionine-containing medium.

Animals↗
PubMed1977

Detection, isolation, and functional characterization of two human T-cell subclasses bearing unique differentiation antigens.

A heterologous antihuman T-cell serum (anti-TH1), raised against purified peripheral T cells, and absorbed with an autologous Ig+ line, was shown to bind specifically to T- but not to B-lymphoid cells by both a complement-dependent cytotoxic assay and indirect immunofluorescence. Whereas 90% fetal thymocytes and thymocytes were killed by anti-TH1 and complement, a consistently restricted population (50-60%) of peripheral T cells from several normal donors were lysed, indicating that anti-TH1 is directed against one or more thymus-specific antigens which are lost or reduced on a subpopulation of human T cells in the periphery. Functional analysis of the unreactive (TH1-) and reactive (TH1+) T-cell subclasses demonstrated that TH1- cells mounted a good proliferative response to a battery of specific soluble antigens (mumps, PPD, tetanus toxoid) but neither responded in MLC, nor elaborated LMF in response to tetanus toxoid. In contrast TH1+ cells proliferated in MLC and elaborated LMF but did not respond by 3H-incorporation to soluble antigens. The relevance of these findings to human T-cell functions in vivo and to previously described functional subclasses of murine T cells is discussed.

Antilymphocyte Serum↗
PubMed1977

Synthesis of mono- and bifunctional alpha-methylene lactone systems as potential tumor inhibitors.

Synthetic nono- and bifunctional alpha-methylene lactone derivatives including deoxyvernolepin and kihydrodeoxyvernolepin were tested as inhibitors of the growth of CCRF-CEM human lymphoblastic leukemia cells in culture. The range of ID-50 values for compounds 1-7 (ca. 10(-5)-10(-6)M) was roughly comparable to the doses observed earlier in the CCRF-CEM cell system with synthetic alpha-methylene-gamma-butyrolactones. Of significance is that dihydrodeoxyvernolepin and deoxyvernolepin were at least an order of magnitude more active than natural vernolepin.

Animals↗
PubMed1977

Methotrexate analogues. 9. Synthesis and biological properties of some 8-alkyl-7,8-dihydro analogues.

A series of 8-alkyl-7,8,-dihydromethotrexate analogues was prepared by direct alkylation of 7,8-dihydromethotrexate, after pilot studies were performed with simpler pteridines. These compounds are tested for in vitro inhibitory activity against Lactobacillus casei and as enzyme inhibitors against dihydrofolate reductase and thymidylate synthetase derived from this organism. All of the analogues were less inhibitory toward dihydrofolate reductase than was methotrexate but were more inhibitory toward thymidylate synthetase. The analogues were also evaluated for in vitro inhibitory activity against the CCRF-CEM human lymphoblastic leukemia cells. In vivo against the L-1210 leukemia in mice, several of the analogues exhibited some antileukemic activity.

Animals↗
PubMed1977

A facile method of purification of neocarzinostatin, an antitumor protein.

A three-step column chromatographic method for the purification of neocarzinostatin (NCS) from a crude preparation was described. The purified material was homogeneous by acrylamide gel electrophoresis, isoelectric focusing, amino terminal analysis, and immunologic criteria. Purified NCS was 40 times as active in the inhibition of growth of Sarcina lutea and twice as active against CCRF-CEM human leukemia cells in vitro as was the starting material. When assayed against P388 and L1210 mouse leukemias in vivo, the purified material showed a median increase in life-span of 119 and 72%, respectively.

Amino Acids↗
PubMed1977

In vitro inhibition of human leukemic cells (CCRF-CEM) by agarose-immobilized neocarzinostatin.

Neocarzinostatin (NCS) is an acidic protein (molecular weight, 10,700) isolated from Streptomyces carzinostaticus that has antitumor activity both in model rodent systems and in humans. In vitro it inhibits the growth of a human lymphoblastic leukemic cell line (CCRF-CEM) at a very low concentration (the amount of drug that causes a 50% inhibition of growth compared to control cultures as extrapolated from a dose-response curve (ID50), 2.4 X 10(-9) M). We covalently coupled NCS to the N-hydroxysuccinimide ester of agarose and obtained a product that, by a variety of biochemical and immunological criteria, has been demonstrated to be devoid of any free or loosely bound NCS. Agarose-bound NCS, which is unable to enter cells because of its size, retains a significant amount of inhibitory activity (ID50, 6 to 15 X 10(-9) M) and is also capable of inhibiting tritiated deoxythymidine incorporation into CCRF-CEM cells. Since agarose-bound NCS cannot enter mammalian cells, the above findings indicate that NCS is able to exert its toxic effects by binding to or reacting with receptors on the cell membrane.

Animals↗
PubMed1976

A new sutureless technique for skin closure.

A sutureless wound-closure device was used in 150 patients. The average time spent to effect skin closure was reduced; removal was easy; skin apposition was satisfactory; and patient response was favorable. Sutureless tape closures eliminate the disadvantages of invasive skin closures. The device described provides secure tape adhesion to the skin and does not cover the wound. It can be easily applied, adjusted, and removed, in addition to serving as a protective splint to the healing wound. This method can reduce operative time of skin closure with highly satisfactory cosmetic results.

Adolescent↗
PubMed1976

Absence of messenger RNA and gene DNA for beta-globin chains in hereditary persistence of fetal hemoglobin.

The relative amounts of alpha-amd beta-globin mRNA and globin gene DNA were measured in reticulocyte RNA and lymphocyte DNA of an individual with homozygous hereditary persistence of fetal hemoglobin whose red blood cells contain 100% fetal hemoglobin (hb F: alpha2gamma2.) Molecular hybridization assays used as probes full-length DNA copies of human alpha- and beta-globin messenger RNA. The results of these hybridization assays demonstrated the expected amounts of alpha-globin mRNA and gene DNA, but absence of beta-globin mRNA and absence of beta-globin gene DNA. In the individual studied, hereditary persistence of fetal hemoglobin is associated with total deletion of the beta-globin structural gene.

Child↗