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Biomedical subjects

R L Baehner

Publications and source records attributed to R L Baehner.

At least 145 records · Page 8Linked to original sources
PubMed1978

In vitro functional capabilities of canine polymorphonuclear neutrophils collected simultaneously by continuous-flow centrifugation and continuous-flow filtration leukopheresis.

Polymorphonuclear neutrophils were simultaneously collected from dogs by continuous-flow centrifugation and continuous-flow filtration leukapheresis. In vitro studies were performed on cells obtained by the two methods as well as on control cells. Studies consisted of assessment of phagocytic capacity, degranulation, chemotaxis, hexose monophosphate (HMP) shunt activity, and bacterial killing. The cells obtained from the filter were metabolically more active than those harvested by centrifugation, as evidenced by increase in resting HMP shunt activity and dimunition in total available lysozyme-secreting activity compared to centrifuged cells. Despite their impaired phagocytic capacities, the filtered cells were able to kill Staphylococcus aureus as efficiently as the centrifuged cells. Both cell populations responded to chemotactic gradients equally.

Animals↗
PubMed1978

The lack of correlation of gallium (67Ga) scans with known prognostic indicators in childhood acute lymphocytic leukemia.

67Gallium-citrate scans were performed on 45 patients with acute lymphoblastic leukemia (ALL) at the time of diagnosis. The extent of uptake and distribution of gallium were compared to known prognostic indicators of age, initial white count, and bone marrow lymphoblast immune markers (T, B, and null cell). Selective increased uptake was noted in bone, kidney, liver/spleen, lymph nodes, or other sites in 29 patients, and 16 patients had "normal" scans. A scoring system giving one point for selective uptake in each organ system was used. Patients were grouped according to scores of zero, 1--2, and 3 or greater. There was no significant correlation found between total gallium scores and any of the three prognostic indicators. There was also no significant correlation when prognostic factors were compared to uptake in the individual organ systems except that T cell disease was associated with a significantly greater propensity for lymph node uptake. There was a suggestion that children with "normal" gallium scans may have a better long-term prognosis, since 6 of 7 nonrelapsers observed for longer than 18 months had scores of zero at diagnosis compared to 4 of 6 early deaths with scores greater than zero. This study indicates that the 67Ga scan does not significantly correlate with known prognostic indicators, with the possible exception of lymph node uptake in T cell disease, and its value as an independent indicator of long-term survival will require longer follow-up.

Adolescent↗
PubMed1978

Experience with "second-look" operations in pediatric solid tumors.

"Second-look" operations were performed in 32 infants and children with initially unresectable or recurrent solid tumors treated with combination chemotherapy and/or irradiation. Tumors were resectable in 26 of 32 cases (81%). These procedures often yielded information affecting staging and treatment. Disease-free survival was achieved in 18 of 32 patients (56%). Mortality was related to progressive disease in seven cases and opportunistic infections due to immunosuppression in three. Four additional patients are alive with evidence of persistent tumor. Second-look procedures were beneficial in patients with Wilms' tumor previously operated upon by a flank approach and in children with bilateral tumors. These procedures were particularly useful in children with stage III localized neuroblastoma and cases of metastatic neuroblastoma that respond to chemotherapy. Second-look operations were also useful in selected cases of rhabdomyosarcoma, teratoma, and Ewing's sarcoma. These observations suggest that combination chemotherapy has increased the use of second-look operations in a variety of less favorable (e.g. initially unresectable or recurrent) pediatric solid tumors.

Antineoplastic Agents↗
PubMed1978

Improvement of polymorphonuclear leucocyte oxidative and bactericidal functions in chronic granulomatous disease with 4-amino-4'-hydroxylaminodiphenyl sulphone.

In an effort to restore oxidant-dependent capabilities to chronic granulomatous disease (CGD) polymorphonuclear leucocytes (PMN), we studied a dapsone derivative, 4-amino-4'-hydroxylaminodiphenyl sulphone (DDS-NOH), known to generate H2O2. After incubation of CGD PMN with 0.2 and 1.0 mM DDS-NOH for 30 min, the rate of glucose-1-14C oxidation via hexose monophosphate (HMP) shunt increased 2--4-fold and that of iodination of ingested zymosan particles 1.5--2.7-fold. Both effects could be further enhanced by superoxide dismutase (SOD) but inhibited by catalase. In three patients, 0.2 mM DDS-NOH improved in vitro killing of Staph. aureus. DDS-NOH 0.02 mM induced capping of Concanavalin A (Con A) receptor complexes suggesting interference by the drug with microtubule-associated function. Thus, optimal concentrations of DDS-NOH may be employed as an oxidant to improve metabolic and bactericidal functions of PMN from patients with CGD.

Aminobiphenyl Compounds↗
PubMed1978

Effects of surface-active agents on neutrophil receptors.

An easily performed assay to identify the C3b and Fc receptors on human neutrophils was developed. Salmonella typhimurium were treated with fluorescein and then incubated in nonimmune fresh human serum, which led to C3b fixation via activation of the alternative pathway. Similarly, type II pneumococci were treated with fluorescein and opsonized with type-specific rabbit antiserum. Neutrophils bearing C3b and Fc receptors formed rosettes with the respective bacteria, which were easily readable because of their bright fluorescence. Incubation of neutrophils at 37 degrees C with C3-coated bacteria generated 54 +/ 4% C3b rosettes, whereas neutrophils incubated with immunoglobulin G-coated bacteria yielded 75 +/ 7% rosettes. Incubation at 4 degrees C inhibited the formation of C3b rosettes but not Fc rosettes. Heat inactivation of the fresh human serum at 56 degrees C for 30 min completely inhibited the formation of the C3b rosettes, and addition of heat-aggregated immunoglobulin G to the polymorphonuclear leukocyte blocked the ability of the polymorphonuclear leukocyte to bind immunoglobulin G-coated bacteria. Addition of 1.0 mM N-ethylmaleimide, 0.1 mg of trypsin per ml, 10 mM H2O2, O2- generated by xanthine-xanthine oxidase, and 8 times 10(-4) M hydrocortisone inhibited the C3b receptor, but did not inhibit the Fc receptor. In neutrophils, the selective effect of the various inhibitors suggests that the Fc and C3b receptors are distinct entities.

Binding Sites↗
PubMed1978

Role of microtubules in granulocyte adherence.

The adherence of human polymorphonuclear leukocytes (PMN) to nylon fibers is inhibited in a dose-dependent fashion by exposure in vitro of these cells to either colchicine or VM-26, both of which agents prevent microtubule assembly. Mean adherence of human PMN was 48% +/- 2%, following treatment with 10(-5) M colchicine or 10(-4) M VM-26 it was reduced to 31% +/- 2% and 7%, respectively. Peritoneal PMN obtained from mice and mink with Chediak-Higashi syndrome (CHS) thought to have a microtubule-membrane disorder affecting the PMN had a mean adherence of 29% +/- 3% and 40% +/- 8% compared to control values of 46% +/- 5% and 73% +/- 8%, respectively, from the mice and mink. Both ascorbic acid and bethanechol, shown previously to enhance microtubule assembly in humans with CHS, normalized granulocyte adherence in PMN obtained from mice with CHS. Cyclic nucleotide levels were not altered by treatment of human PMN with colchicine, nor did they differ between normal and CHS animals. Thus it appears that the state of microtubule assembly may directly affect the properties of the PMN plasma membrane without requiring alterations of cyclic nucleotides as an intermediary.

Animals↗
PubMed1978

In vitro characteristics of childhood leukemic monoblasts.

Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and matured to macrophages in vitro, either when adherent to glass slides or in feeder layer suspensions. Employing the double layer in vitro bone marrow culture technique, leukemic marrows from these children failed to produce colonies in culture in the presence or absence of normal feeder layers. Varying the concentration of leukemic cells in the feeder layers failed to augment colony growth from normal bone marrows. Although monoblasts were observed to mature to macrophages in vitro, no increase in colony stimulating factor activity was observed with aging of the feeder layers. These studies suggest that childhood leukemic monoblasts lack the ability to produce colony stimulating activity, differing in this respect from monoblastic leukemia in adults.

Adolescent↗
PubMed1978

Potentiation of polymorphonuclear leukocyte motile functions by 2,3-dihydroxybenzoic acid.

DHB potentiates PMN phagocytosis of opsonized lipopolysaccharide-coated PO droplets by 53% to 45% and chemotaxis by 36% to 10% at 10-3M and 10-4M concentrations, respectively. The effect is reversible in vitro. In the presence of DHB, PMNs released significantly less superoxide and H2O2 to the extracellular media but were able to oxidize 1-14C-glucose normally during phagocytosis. Although iodination of opsonized particles was decreased in the presence of DHB, the PMNs were able to kill Staphylococcus aureus 502A normally. These results support the hypothesis that directed cell movement and phagocytosis can be enhanced by protecting the PMN membrane against auto-oxidative damage from scavenging superoxide and H2O2 by means of DHB.

Cell Movement↗
PubMed1977

The effect of 2-deoxyglucose on guinea pig polymorphonuclear leukocyte phagocytosis.

The effects of 2-deoxyglucose (DOG), an inhibitor of glycolysis, on guinea pig polymorphonuclear leukocytes (PMN) obtained from peritoneal exudates was examined. ATP levels in PMN were reduced by 40% by one hour following an incubation with 2-deoxyglucose. When complement (C3) coated 14C-staphylococcus aureus, C3 coated lipopolysaccharide-paraffin oil droplets (LPS-PO), 14C-pneumococcus opsonized with IgG, or albumin coated paraffin oil droplets opsonized with IgG were added to cell suspensions containing DOG, the phagocytizing rate was 1,310+/-55 cpm/5 X 10(6) cells/15 minutes, 6+/-2 microng paraffin oil (PO)/10(7) cells/minute, 2,250+/-175 cpm/1 X 10(6) cells/20 minutes or 0.037+/-0.01 mg PO/10(7) cells/minute compared to control values of 5,970+/-275 cpm/5 X 10(6) cells/15 minutes, 35+/-3 microng PO/10(7) cells/15 minutes, 4,510+/-200 cpm/1 X 10(6) cells/20 minutes and 0.067+/-0.01 mg PO/10(7) cells/minute. In parallel studies the phagocytic index for latex was 0.74+/-0.28 in DOG compared to control of 2.36+/-1.13 and the phagocytic rate of albumin coated paraffin oil droplets was 0.029+/-0.01 mg PO/10(7) PMN/minute in DOG compared to control of 0.048 mg PO/10(7) cells/minute. When ATP levels were maintained by the simultaneous addition of 5 mM glucose or pyruvate to media containing DOG, latex ingestion was improved to 1.15+/-0.3 with glucose and 1.59+/-0.64 with pyruvate and albumin coated particles to 0.045+/-0.01 mg PO/10(7) PMN/minute with pyruvate. There was no improvement in the uptake of either the C3 dependent particles or IgG coated Pneumococci in media containing DOG and glucose and/or pyruvate. Following the removal of DOG from the extracellular medium and the addition of pyruvate or glucose, phagocytosis of C3 dependent LPS-PO was restored to normal values. Neither the binding of C3 or IgG coated particles to the PMN nor the lateral movement of glycoprotein utilizing concanavalin A capping was affected by DOG. Thus, the presence of DOG in the PMN containing adequate amounts of ATP will selectively and reversibly inhibit those surface events required for phagocytosis of C3 and IgG bound particles but not latex particles or albumin particles which non-specifically bind to PMN.

Adenosine Triphosphate↗
PubMed1977

Lack of correlation between blast cell size and length of first remission in acute lymphocytic leukemia in childhood.

The bone marrow from 55 children with acute lymphocytic leukemia diagnosed from April 1969 to June 1973 were evaluated for blast cell morphology and size. Sixteen marrows contained a predominance of macrolymphoblasts (greater than 12 mu), while the remainder contained mainly microlymphoblasts. There was no correlation between blast cell size and the known front-end prognostic indicators of age and initial white blood count, nor could blast cell size be used to predict the length of initial bone marrow remission.

Adolescent↗
PubMed1977

Interstitial pneumonitis in the immunologically suppressed child: an urgent surgical condition.

Thirty-eight children were evaluated for interstitial pneumonia by open lung biopsy. In most instances the patients were immunosuppressed as a result of cancer chemotherapy and irradiation. Pneumocystis carinii infection was the most common cause of pneumonitis (60.4%), especially in children with leukemia (78.3%). The clinical triad of hypoxemia, tachypnea, and a diffuse interstitial infiltrate on chest x-ray, is an indication for early open lung biopsy. Survival was 91.7% in cases of acute pneumocystis pneumonia, a significant improvement over previous reports. These observations strongly support the concept of early open lung biopsy in the management of diffuse interstitial pneumonitis in patients who are immunosuppressed.

Acute Disease↗
PubMed1977

Abnormal platelet function in Chediak-Higashi syndrome.

Platelets in an infant with Chediak-Higashi (C-H) syndrome without bleeding manifestations and not in the accelerated phase showed abnormal function consistent with storage pool disorder as shown by abnormal aggregation, decreased storage capacity and release of [14C]5-HT, low endogenous 5-HT, reduced ATP and ADP with an increased ATP/ADP ratio, increased specific radioactivity of ADP after [14C]adenine labelling, decreased release of adenine nucleotides after stimulation, impaired secretion of acid hydrolases despite normal stores, and decreased calcium content. Incorporation of [14C]adenine into metabolic pool adenine nucleotides was normal. Nucleotide conversion to hypoxanthine in stimulated platelets was mildly impaired. Platelet cyclic-AMP (c-AMP) was initially elevated, but even when c-AMP returned to normal levels after ascorbate treatment, platelet function was not improved. Elevated intracellular c-AMP was not solely responsible for the abnormal platelet function.

Adenosine Diphosphate↗