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Biomedical subjects

R L Baehner

Publications and source records attributed to R L Baehner.

At least 127 records · Page 7Linked to original sources
PubMed1979

Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia.

Hemoglobin (Hb) Indianapolis is an extremely labile beta-chain variant, present in such small amounts that it was undetectable by usual techniques. Clinically, it produces the phenotype of severe beta-thalassemia. Biosynthetic studies showed a beta:alpha ratio of 0.5 in reticulocytes and about 1.0 in marrow after a 1-h incubation. These results, similar to those seen in typical heterozygous beta-thalassemia, suggested that betaIndianapolis was destroyed so rapidly that its net synthesis was essentially zero. To examine the kinetics of globin synthesis, reticulocyte incubations of 1.25--20 min were performed with [3H]leucine. The betaIndianapolis:beta A ratio at 1.25 min was 0.80 suggesting that beta Indianapolis was synthesized at a near normal rate. At 20 min, this ratio was 0.46 reflecting rapid turnover of beta Indianapolis. The erythrocyte ghosts from these incubations contained only betaIndianapolis and alpha-chains, and the proportion of betaIndianapolis decreased with time, indicating loss of betaIndianapolis. Pulse-chase studies showed little change in beta A:alpha ratio and decreasing betaIndianapolis:alpha and betaIndianapolis:beta A with time. The half-life of betaIndianapolis in the soluble hemoglobin was approximately equal to 7 min. There was also rapid loss of beta Indianapolis from the erythrocyte membrane. From these results, it may be inferred that betaIndianapolis is rapidly precipitated from the soluble cell phase to the membrane, where it is catabolized. Heterozygotes for beta 0-thalassemia usually have minimal hematologic abnormalities, whereas heterozygotes with betaIndianapolis, having a similar net content of beta-chain, have severe disease. The extremely rapid precipitation and catabolism of betaIndianapolis and the resulting excess of alpha-chains, both causing membrane damage, may be responsible for the severe clinical manifestations associated with this variant. It seems likely that other, similar disturbances in the primary sequence of globin polypeptide chains may produce clinical findings similar to those seen with hemoglobin Indianapolis and thus produce the phenotype of severe beta-thalassemia.

Adolescent↗
PubMed1979

Membrane fluidity in human and mouse Chediak-Higashi leukocytes.

Polymorphonuclear leukocytes from humans and mice with the Chediak-Higashi syndrome were characterized by spin label electron spin resonance spectrometry. Our results suggest that cells from afflicted mice and humans have membranes more fluid than controls. Order parameters for a spin label that probes near the membrane surface were 0.652 for normals and 0.645 for two Chediak-Higashi patients. Cells from Chediak-Higashi mice showed similar differences, as did isolated plasma membrane fractions. An increased membrane fluidity was also detected with a spin label that probes deeper in the bilayer. In vitro treatment of Chediak-Higashi mouse cells with 0.01 M ascorbate increased the order parameter to normal levels. In vitro incubation of mouse Chediak-Higashi cells with glucose oxidase increased the order parameter, similar to the effect of ascorbate. This increase was abolished when catalase was added to the incubation medium. In vitro incubation with dibutyryl cyclic guanosine monophosphate (1 muM to 0.1 mM) did not normalize order parameters. These results indicate that fluidity of Chediak-Higashi cell membranes was affected by treatments expected to alter the oxidation: reduction potential of the environment but was not affected by treatments expected to alter the ratio of intracellular cyclic nucleotides. The latter treatment would affect microtubule assembly. Therefore, it appears that the membrane fluidity abnormalities as demonstrated by electron spin resonance and the earlier demonstrated microtubule dysfunctions characteristic of Chediak-Higashi cells are coexisting defects and are probably not directly related.

Animals↗
PubMed1979

Utilization of liposomes for correction of the metabolic and bactericidal deficiencies in chronic granulomatous disease.

IgG-coated liposomes containing glucose oxidase (GO) in order to provide a means of generating H2O2 were prepared. Leukocytes from patients with chronic granulomatous disease (CGD) which are lacking a means of generating H2O2, ingested the IgG-coated liposomes and metabolic oxidative deficiencies of glucose-1-14C oxidation and iodination were normalized. Both of these activities have been shown to depend upon the availability of H2O2 within polymorphonuclear leukocytes. Improvement in the capacity to kill Staphylococcus aureus by chronic granulomatous disease leukocytes were observed under similar conditions. Thus, it is possible to restore the oxidative metabolic capacities to CGD leukocytes by the introduction of glucose oxidase containing liposomes to these cells.

Adult↗
PubMed1979

Effects of a chemotactic factor, N-formylmethionyl peptide, on adherence, superoxide anion generation, phagocytosis, and microtubule assembly of human polymorphonuclear leukocytes.

FMLP promoted microtubule assembly in PMNs at concentrations which were chemotactic for the cells. At higher concentrations than those required for chemotaxis, FMLP enhanced the adherence of PMNs to nylon glass fibers. With colchicine, PMN adherence was inhibited, but upon exposure to FMLP, PMN adherence could be restored. The effect of FMLP on PMN adherence was transitory and was no longer evident by 5 min. At concentrations similar to those employed in the adherence studies. FMLP induced the cells to briefly generate O-2, since ferricytochrome C reduction was no longer evident by 5 min. Pretreatment of the PMNs with cytochalasin B enhanced the release of O-2 by PMNs exposed to FMLP. On the other hand, there was no effect of FMLP on phagocytosis of C3-coated particles. These results suggest that FMLP induces responsive cells to develop a hyperadherent plasma membrane which is largely independent on microtubule control. Since oligopeptides similar of AMLP are formed in bacteria, it is likely that the action of N-formylated peptides is important in regulating the inflammatory response.

Cell Adhesion↗
PubMed1979

Evaluation of bone-marrow scanning with technetium-99m sulfur colloid in pediatric oncology.

Eighty-six technetium-99m sulfur colloid (Tc-SC) bone-marrow scans in 56 pediatric oncology patients were reviewed. The distribution of the sulfur colloid was similar to that in adult bone marrow in normal children older than 10 yr, and involved progressively more marrow of the extremities in normal children under 10 years of age. After irradiation or chemotherapy there was an extension of the Tc-SC to peripheral marrow sites. There was also diminished uptake of the tracer in sites corresponding to irradiated areas. In most patients there was recovery of these defects by 6 mo after completion of therapy. Tumor replacement of the marrow was reflected in the scans, and the extent of the scan defect paralleled the course of the disease. In four patients, despite normal bone scans and radiographs, marrow-scan abnormalities due to tumor replacement were present and confirmed by needle aspiration and/or biopsy. In two other patients, the marrow-scan abnormality preceded radiographic and histologic evidence of tumor metastasis. Two patients who responded clinically showed persistent defects; biopsy in one revealed fibrosis. Technetium-99m sulfur colloid bone-marrow scanning appears to be a sensitive monitor of marrow alteration caused by metastases, irradiation damage, or tissue fibrosis in children receiving treatment for cancer.

Adolescent↗
PubMed1979

Correlation of the FAB morphologic criteria and prognosis in acute lymphocytic leukemia of childhood.

The bone marrows at the time of initial diagnosis of 101 children with acute lymphocytic leukemia diagnosed from April 1969 to December 1974 were evaluated employing the FAB morphologic classification. The group with L1 morphology and a significantly improved duration of first remission and survival when compared to the L2--L3 morphologic groups. Both groups were similar in age and initial level of WBC, indicating that the morphologic classification has prognostic significance in childhood ALL when age and initial WBC were considered together as prognostic risk factors. The L1 morphologic groups survival for the low- and moderate-risk groups was significantly better than for the L1 high-risk group and for the L2--L3 groups.

Adolescent↗
PubMed1979

The use and limitation of labeled staphylococcal protein A for study of antineutrophil antibodies.

Antineutrophil antibodies can be detected following their attachment to neutrophils by employing labeled staphylococcal protein A (SPA). Radiolabeled SPA provides a sensitive means for identifying the presence of IgG restricted to subclasses IgG1, IgG2, and IgG4 that will specifically bind to neutrophils and that are found in the serum of patients with isoimmune and autoimmune neutropenia. However, SPA bound to the Fc region of IgG does not interfere with the attachment of IgG to the Fc domain of the neutrophil. Fluorescein-labeled SPA, in turn is useful in monitoring the functional consequences of antibody attachment to the surface of polymorphonuclear leukocytes (PMN). Both heterologous and isoimmune antisera induced lateral movement of surface antigens into polar-capped pseudopodia. The formation of such pseudopodia may facilitate leukoagglutination and the subsequent removal of sensitized cells from the circulation.

Animals↗
PubMed1979

Isolated pulmonary leukemic relapse following successful bone marrow transplant in a child with acute lymphoblastic leukemia.

Leukemic relapse and interstitial pneumonitis are common complications for leukemic patients following bone marrow transplantation. We present the case of a successful bone marrow transplantation patient who developed an interstitial infiltrate on chest roentgenogram 212 days post-transplant that was diagnosed by open lung biopsy and found to be a leukemic relapse of the lung parenchyma. No extrapulmonary sites were involved and the infiltrate cleared in three weeks with systemic chemotherapy. Pulmonary function tests continued to demonstrate restrictive disease. The patient remained in remission for nine months following pulmonary relapse on systemic chemotherapy. This patient illustrates an unusual site of leukemic relapse and the importance of open lung biopsy in the diagnosis of the immunosuppressed patient with a pulmonary infiltrate.

Adolescent↗
PubMed1979

Role of membrane vitamin E and cytoplasmic glutathione in the regulation of phagocytic functions of neutrophils and monocytes.

Neutrophils and monocytes are the prime defenders of the body against suppurative bacterial and fungal infections. To accomplish their role in inflammation, they must respond appropriately to chemotactic signals elaborated from complement and bacteria. This response predictably results in the adherence and subsequent directed movement of the phagocytes toward the infected area where they recognize opsonized microbes. Attachment of the microbes to the membrane of the cell leads to their ingestion and subsequent demise, principally by the reduced oxygen by-product H2O2, which is generated by the neutrophils and monocytes during phagocytosis. Optimal killing requires the translocation of granule myeloperoxidase into the phagocytic vacuole containing the bacteria and a suitable halide ion. Degranulation is controlled, in part, by assembled microtubules whereas ingestion requires assembly of submembrane microfilaments. Deficiency states resulting from vitamin E results in diminished membrane-related chemotaxis and ingestion, whereas depletion of cellular GSH results in defective microtubule assembly preventing the normal increase in adherence, chemotaxis, degranulation, and microbicidal activity of the phagocytic cells. Deficiency states resulting in dysfunction of the microtubule system include neutrophil glutathione synthetase deficiency, rodent glutathione peroxidase deficiency, and the Chediak-Higashi syndrome.

Cell Membrane↗
PubMed1979

Oxidative metabolic responses of rabbit pulmonary alveolar macrophages.

During phagocytosis of opsonized lipopolysaccharide-coated paraffin oil droplets, rabbit alveolar macrophages reduced nitroblue tetrazolium, which effect was in part inhibitable with the use of superoxide dismutase. Exposure of cytochalasin-B-treated rabbit alveolar macrophages to opsonized zymosan led to the generation of superoxide, as quantitated by ferricytochrome C reduction. It was found that nitroblue tetrazolium in the presence of ferricytochrome C could in turn serve as scavenger of superoxide during stimulation of cytochalasin-B-treated rabbit alveolar macrophages. Following challenge with either opsonized zymosan or the membrane perturbant digitonin, rabbit alveolar macrophages released hydrogen peroxide into the extracellular medium. Employment of the surface membrane stimulant phorbol myristrate acetate led to activation of the hexose monophosphate shunt, which activity could be further enhanced in the presence of superoxide dismutase or attenuated in the presence of catalase. These studies demonstrate that rabbit alveolar macrophages release superoxide and hydrogen peroxide during surface membrane perturbation. In turn, hydrogen peroxide generation can stimulate the hexose monophosphate shunt.

Animals↗
PubMed1978

An outbreak of pneumocystis pneumonia in children with acute lymphocytic leukemia.

Between Jan 1 and Oct 31, 1975, a cluster of ten cases of pneumocystis pneumonia occurred in children with acute lymphocytic leukemia (ALL) at the James Whitcomb Riley Hospital for Children in Indianapolis. The risk of infection appeared to be related to the intensity of chemotherapy. Furthermore, illness developed in nine of the ten patients between 30 and 100 days after initiation of therapy, suggesting a period of heightened susceptibility to infection. An indirect immunofluorescent test was used to detect antipneumocystis antibodies in serum samples collected from patients with pneumocystis pneumonia and their contacts. Members of the Riley Hospital staff who had close contact with infected children had a higher prevalence of elevated antibody titers (7/12) than other staff members (2/22; P = .004) or parents of infected patients (0/8; P = .01). This suggests that transmission of pneumocystis may occur within the hospital environment.

Adolescent↗