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Biomedical subjects

D R Miller

Publications and source records attributed to D R Miller.

At least 235 records · Page 13Linked to original sources

Resistance of O-acetylated gonococcal peptidoglycan to human peptidoglycan-degrading enzymes.

Two naturally occurring forms of gonococcal peptidoglycan (PG) were tested for their susceptibility to human PG hydrolases. Purified 3H-labeled PG substituted extensively with O-acetyl derivatives (O-PG; from Neisseria gonorrhoeae FA19) and 14C-labeled O-acetyl-deficient PG (non-O-PG; from N. gonorrhoeae RD5) were mixed together and treated with either normal human sera (NHS) or with lysozyme purified from human polymorphonuclear leukocytes (PMN-LZ). The initial rate of hydrolysis of O-PG by NHS or by PMN-LZ was two- to fourfold less than that of its non-O-PG counterpart in the same tube. When the reactions were allowed to go to completion. NHS solubilized both PGs completely, whereas PMN-LZ solubilized all of the non-O-PG and left ca. 60% of the O-PG insoluble. The PMN-LZ-soluble fraction of O-PG consisted largely of glycosidically linked fragments with molecular weights greater than ca. 10(4), whereas the corresponding non-O-PG was degraded to lower-molecular-weight fragments, exclusively. At completion, NHS hydrolyzed both PGs to fragments whose size was equal to or smaller than that of the free disaccharide unit of PG, suggesting that human sera contain a peptide-splitting (amidase) activity and a glycosidase activity, in addition to that of the well-known muramidase. NHS also promoted the release of high-molecular-weight PG fragments from intact gonococci. The persistence of human hydrolase-resistant PG in the form of soluble macromolecular fragments may potentiate the biological effects of gonococcal PG in vivo.

Acetylation↗

Reduction in central nervous system leukemia with a pharmacokinetically derived intrathecal methotrexate dosage regimen.

During the period 1976-1981, 3241 children were enrolled on three major studies of acute lymphoblastic leukemia by participating institutions of the Children's Cancer Study Group. Each study included a different method of central nervous system (CNS) prophylaxis: (1) standard therapy with cranial irradiation, 2400 rads, and intrathecal methotrexate at 12 mg/m2 six times during consolidation (CCG-141); (2) a modification of CCG-141 in which the intrathecal methotrexate was initiated during induction (CCG-141A); and (3) a reduced cranial irradiation dose of 1800 rads with intrathecal methotrexate given at the same frequency as a CCG-141A, with or without maintenance intrathecal methotrexate, but with a dosage regimen derived from CNS volume considerations rather than based on body surface area (CCG-160 series). Strategy 3, a change in the intrathecal methotrexate dosage, has resulted in the lowest incidence of CNS leukemia to date (p less than 0.007). The cumulative 3-yr CNS relapse rate has decreased from 8%-10% to 2%-5% in average-risk patients (p less than 0.02; life table estimate) and from 23%-27% to 6% in high-risk patients (p less than 0.0002; life table estimate), despite a reduction in the cranial irradiation dose from 2400 to 1800 rads. Maintenance intrathecal chemotherapy has had a marginal effect among patients randomized to receive this additional therapy (p = 0.06). The overall outcome has been an increase in the continuous complete remission rate (p = 0.04) but not in the estimated 3-yr continuous hematologic remission or survival rates.

Acute Disease↗

[Genetic toxicity of methylmercuric chloride (CH3HgCl) on mitochondria of Saccharomyces cerevisiae].

Among the strains of the yeast Saccharomyces cerevisiae we investigated, the organic form of mercury:methylmercury (II) does not seem to induce any cytoplasmic mutant "petite colonie" rho-. However, it induces a significant number of the erythromycin-resistant mutant Eryr. A dose response is shown. These effects are discussed in the view of the part that discrete DNA lesions could take in the explanation of the mechanism of toxicity of the organomercurial.

DNA, Fungal↗

Effect of lithium carbonate plus oxymetholone vs. lithium alone on chemotherapy-induced myelosuppression.

To evaluate the possible additive leukocyte count-enhancing properties of lithium and oxymetholone, patients (1-21 years old) were randomized to receive lithium or lithium plus oxymetholone after chemotherapy. Seventy-one trials with lithium, 63 with both drugs, and 79 in the control group, were compared. White blood cell count and neutrophil nadirs were better in both treatment groups than in the controls (p = 0.001) but an additive effect of oxymetholone above and over lithium alone was seen only in patients under 15 years old (p = 0.05). The median duration of severe neutropenia (absolute neutrophil count less than 1000/cm3) was 6.2 days/patient in the control group but only 4.5 days/patient and 3.8 days/patient in the lithium and lithium plus oxymetholone groups, respectively (p = 0.0001). Both the lithium and lithium plus oxymetholone treatments had a modest platelet-sparing effect (p = 0.03). No difference in the hemoglobin nadirs was observed in the three groups. While the majority of the patients lost weight in the control and lithium-treated group, the patients on oxymetholone gained weight (median 1.25 kg) p = 0.00001. Lithium reduces the period of neutropenia after chemotherapy during which the patients may acquire infection. The addition of oxymetholone does not substantially lessen myelosuppression in most patients but improves the patients' appetite and weight.

Adolescent↗

Neuroblastoma, tuberous sclerosis, and subependymal giant cell astrocytoma.

A patient with Stage III paratesticular neuroblastoma diagnosed in infancy was treated with radiotherapy and chemotherapy. Typical depigmented "ash leaf" skin lesions of tuberous sclerosis appeared during early childhood. At 7 years of age he underwent craniotomy for a subependymal giant cell astrocytoma. The occurrence of neuroblastoma, tuberous sclerosis, and astrocytoma is unique, and supports the suggested relationship between neural crest tumors and hamartoma syndromes.

Brain Neoplasms↗

The NEOUCOM Cooperative Cataloging Service: development and review of the first four years.

The Basic Medical Sciences Library of the Northeastern Ohio Universities College of Medicine (NEOUCOM) provided a Cooperative Cataloging Service to fourteen of its affiliated hospitals' libraries since March 1978, using the OCLC system. Analysis of the first four years of service showed that the hospital libraries spent almost $30,000 to catalog more than 18,000 titles. Personnel expenses and other costs eclipsed the savings from a 31.3% duplication rate. Centralized bibliographic control control and the principal by-product of the service, a uniform, machine-related data base, provided the foundation for an on-line integrated library system to serve the consortium. The hospital libraries contributed 44% of the unique titles in this data base, which emphasis the need to share resources and continue cooperation.

Cataloging↗

[Some aspects of the genetic toxicity of methylmercury in yeasts].

Methylmercury chloride is a powerful inhibitor of the cell cycle in Yeasts. Its effect is reversible at low doses. It does not induce any nuclear mutation (at least among the ones we tested). Neither does it increase the amounts of intra and inter-genic conversions induced by a variety of mutagenic agents. However, in co-treatment with some carcinogens and mutagens, it causes a drastic depressive effect on survival.

Ascomycota↗

Immunoregulation by blasts from null cell and T-cell leukemias: help and suppression of T-cell proliferative responses to mitogens.

The immunoregulatory activity of bone marrow leukemic blasts from five patients with null-cell acute lymphoblastic leukemia (ALL) and two children with T-cell ALL was evaluated. Blasts were studied in co-culture for their effects on the proliferative responses of normal allogeneic peripheral blood lymphocytes to phytohemagglutinin. Mitomycin C-treated null cell ALL blasts from two of five children suppressed the proliferative responses of normal responder cells by 80% and 58% whereas those from two other children enhanced the responses by 118% and 31%. T-cell leukemic blasts from one patient with T-cell ALL exhibited helper cell activity (26%) and T-leukemic blasts from the other demonstrated suppressor cell activity (53%). The helper cell activity of leukemic blasts was associated with stimulating capacity of null blasts in one-way mixed lymphocyte reactions. In six of seven cases, incubation of blast cells with concanavalin A (20 microgram/ml) for 48 hours prior to co-culture with responder cells did not result in the generation of significant suppressor cell activity. Our study suggests that leukemic blasts from certain patients with 'null' and T-cell ALL may possess spontaneous helper or suppressor cell immunoregulatory activity. This functional heterogeneity of leukemic blasts may help in subclassifying the ALL.

Adolescent↗

Reaction of mercury with silver-tin dental amalgam alloy.

Electron diffraction evidence confirming the ordered orthorhombic crystal structure of the gamma phase of the silver-tin system has been obtained, and it has been established by optical metallography that an alloy with a composition corresponding to the dental amalgam alloy formula Ag3Sn (i.e., 26.85 wt % Sn) lies outside the single gamma phase field and in the duplex (gamma + Sn) phase field adjacent to it. Studies of the mechanism of the hardening reaction of single crystals of homogeneous gamma phase alloys with mercury were carried out using both scanning and transmission electron microscopy. Mercury attack occurred preferentially along well-defined planes in the single crystals. Using electron channeling and trace analysis techniques these planes of preferential attack were found to be [010] and [011], and from transmission electron microscopy of thin foils these were shown to be slip bands and deformation twins, respectively. In bicrystals of gamma phase material, preferential attack also occurred along grain boundaries. Similar preferential mercury attack, leading to the development of deep planar intrusions into the gamma phase material, was observed in an experimental dental amalgam prepared from a lathe-cut homogeneous gamma phase amalgam alloy. It is believed that the presence of such features would have important implications for the clinical performance of dental amalgam.

Chemical Phenomena↗

Contact-stimulated proliferation of cultured mouse epidermal cells by 3T3 feeder layers: inhibition of proliferation by 12-O-tetradecanoylphorbol-13-acetate (TPA).

Mouse epidermal cells can be subcultured at 31 degrees C onto an irradiated BALB/c 3T3 clone A31 feeder layer. A31 cells (supposedly derived from embryonic fibroblasts) were found to be specifically required for the optimal production of keratinizing epidermal colonies in secondary culture. This effect was not transmitted through the medium nor by the culture surface, since A31 cells plated on one end of a flask did not stimulate epidermal cell proliferation at the other end, even if the other end had previously held A31 cells. Epidermal cell contact with metabolizing A31 cells was probably necessary for the effect; fixed or freeze-thawed A31 cells were ineffective. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate, recently shown to interfere with contact-mediated transfer of label (metabolic cooperation) between Swiss 3T3 cells and cells of an established epidermal line in vitro, also blocked epidermal colony formation. The A31-epidermal cell interaction is apparently not a typical mesenchymal-epithelial interaction, since the basement membrane would prevent this contact in intact skin.

Animals↗

Immunoregulatory properties of childhood leukemias.

Investigation of in vitro humoral immune responses and immunoregulatory properties of leukemic cell was carried out in 17 children with acute leukemia prior to therapy. Leukemias were of the non-T, non-B-cell type in 13 patients and of T-cell origin in four. Bone marrow and peripheral blood cells consisted of 24-96% lymphoblasts and were generally deficient in surface Ig-positive cells. Induction of Ig secreting cells in response to pokeweed mitogen was markedly decreased in marrow and peripheral mononuclear cell cultures of leukemic patients. Co-culture of leukemic cells with normal lymphocytes led to marked deviations from the expected Ig secreting-cell response of the cell mixtures. The predominant effect was enhancement, as was the case with eight non-T, non-B-cell and one T-cell leukemia samples. Suppression of the Ig secreting-cell response was observed in only three instances, two with non-T, non-B-cell and one with T-cell leukemia samples. These findings implicate non-T, non-B as well as more differentiated leukemic cells in having the potential for modifying Ig production by B cells.

Adolescent↗

Immediate and long-term posttherapy neuropsychologic performance in children with acute lymphoblastic leukemia treated without central nervous system radiation.

Intellectual and neuropsychologic test performance was studied in 41 children with acute lymphoblastic leukemia within one year of completing multidrug therapy in which intrathecal methotrexate was the sole agent of central nervous system prophylaxis. To control for possible effects of intensive systemic chemotherapy and the disruptive psychosocial effects of treatment on psychometric test function, 33 children with embryonal rhabdomyosarcoma who had no CNS disease or treatment were similarly studied. All patients studied had been in continuous complete remission since diagnosis. Within each diagnostic group, patients were placed in a younger (less than 8 years) or an older (more than 8 years) group depending on age at the time of testing. No significant difference was found in intellectual function between the young ALL and ERMS groups or between the total ALL and ERMS groups. Further five-year follow-up of 12 of the youngest ALL patients showed no significant long-term change in intellectual or other specific neuropsychologic functions. Children with ALL who remained in continuous complete remission from diagnosis and who were treated with prophylactic intrathecal methotrexate and no CNS radiation did not have global or specific neuropsychologic impairment.

Adolescent↗

Granulocytic sarcoma of the clavicle.

Acute myeloblastic leukemia is suspected usually because of abnormalities of the peripheral blood or bone marrow. In some cases there may also be an extramedullary focus of leukemic cells called a chloroma or granulocytic sarcoma. On occasion, these tumor masses may precede any evidence of leukemia by months or years. They are often misdiagnosed as lymphomas or granulomas. We present here a case of acute myeloblastic leukemia that was preceded by a granulocytic sarcoma of the clavicle. The initial biopsy of the clavicle was thought to be consistent with Ewing's sarcoma. The patient was treated with systemic chemotherapy prior to gross marrow involvement. He has been in continuous complete remission 34 months after the start of chemotherapy and 44 months after the development of granulocytic sarcoma.

Bone Marrow↗