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Biomedical subjects

B Lange

Publications and source records attributed to B Lange.

At least 109 records · Page 6Linked to original sources
PubMed1989

Isolation and characterization of an alginate lyase from Klebsiella aerogenes.

The bacterium Klebsiella aerogenes (type 25) produced an inducible alginate lyase, whose major activity was located intracellularly during all growth phases. The enzyme was purified from the soluble fraction of sonicated cells by ammonium sulfate precipitation, anion- and cation-exchange chromatography and gel filtration. The apparent molecular weight of purified alginate lyase of 28,000 determined by gel filtration and of 31,600 determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the active enzyme was composed of a single polypeptide. The alginate lyase displayed a pH optimum around 7.0 and a temperature optimum around 37 degrees C. The purified enzyme depolymerized alginate by a lyase reaction in an endo manner releasing products which reacted in the thiobarbituric acid assay and absorbed strongly in the ultraviolet region at 235 nm. The alginate lyase was specific for guluronic acid-rich alginate preparations. Propylene glycol esters of alginate and O-acetylated bacterial alginates were poorly degraded by the lyase compared with unmodified polysaccharide. The guluronate-specific lyase activity was applied in an enzymatic method to detect mannuronan C-5 epimerase in three different mucoid (alginate-synthesizing) strains of Pseudomonas aeruginosa. This enzyme which converts polymannuronate to alginate could not be demonstrated either extracellularly or intracellularly in all strains suggesting the absence of a polymannuronate-modifying enzyme in P. aeruginosa.

Chromatography, Gel↗
PubMed1989

Detection of minimal disease in hematopoietic malignancies of the B-cell lineage by using third-complementarity-determining region (CDR-III)-specific probes.

Approximately 80% of hematopoietic malignancies of the B-cell lineage carry only one or two immunoglobulin heavy chain gene rearrangements indicating their clonal origin. These rearrangements due to the recombination of various variable, diversity, and joining regions of the heavy-chain gene segments during B-cell commitment result in a region called complementarity-determining region III (CDR-III). This region, which encompasses the diversity region of the heavy-chain segment, because of extensive somatic mutations, provides a DNA-encoded signature specific for each B-cell clone. CDR-III sequences were obtained from DNA of pre-B-cell acute lymphoblastic leukemia by using suitable primers and the polymerase chain reaction. The sequences were used to generate diagnostic probes that hybridized only to the amplified CDR-III of leukemic cells from which the sequences were derived. With these probes, leukemic cells could be detected when diluted 1:10,000 with other cells. By cloning the amplified CDR-III into recombinant libraries residual leukemic cells were accurately quantitated in bone-marrow samples from repeated relapses and remissions in one case of acute lymphoblastic leukemia. During a clinical remission lasting greater than 7 mo, malignant cells were present in marrow at greater than 1 per 1000 cells. These findings indicate that custom-made diagnostic probes will be useful in accurate quantitation of malignant cells in acute lymphoblastic leukemia patients in clinical remission and will allow investigation of the biological significance of low or high numbers of residual leukemic cells in evolution of that disease.

Alleles↗
PubMed1989

Natural killing of varicella-zoster virus (VZV)-infected fibroblasts in normal children, children with VZV infections, and children with Hodgkin's disease.

We studied mononuclear cell (MNC)-mediated natural killing (NK) of varicella-zoster virus (VZV)-infected fibroblasts in normal children, children with VZV infections, and children with Hodgkin's disease. NK activity was tested in 18 hr 51Cr release assays. NK activity for adults was significantly higher than that for children 1-3 years old or 4-6 years old (p less than 0.05). Serological status did not affect NK activity. NK activity in normal children was not increased 4-6 weeks after immunization with varicella vaccine. Seven normal children with natural varicella showed significantly higher NK activity against VZV-infected and uninfected targets. Eight immunosuppressed children with herpes zoster showed significantly reduced NK activity within 72 hours of the onset of herpes zoster. However, their NK activity rose to the normal level one to two weeks later. Children with Hodgkin's disease had low NK activity. These results suggested that NK cells might play an initial defensive role in VZV infections, and that low NK activity in immunocompromised hosts might contribute to their high incidence of herpes zoster.

Adolescent↗
PubMed1989

Chronopharmacokinetics of oral methotrexate and 6-mercaptopurine: is there diurnal variation in the disposition of antileukemic therapy?

The chronopharmacokinetics of the orally administered antileukemic drugs, 6-mercaptopurine and methotrexate, were examined in 13 children with acute lymphoblastic leukemia (ALL) to establish if there is a pharmacokinetic basis for the lower relapse rate associated with administration of these agents in the evening. Children with ALL in complete remission had plasma drug concentrations monitored for 8 h following an oral dose of either methotrexate or 6-mercaptopurine administered in the morning (8 a.m.) and the evening (8 p.m.). Total drug exposure to oral methotrexate, as measured by the mean area under the plasma concentration-time curve (AUC), was 2.75 microM.h following the morning dose and 2.77 microM.h in the evening. For 6-mercaptopurine, the mean morning AUC (198 ng.h/ml) was higher than that following the evening dose (167 ng.h/ml) (p greater than 0.05); but compared to the wide interpatient variability observed with this drug, this 20% difference is not likely to be clinically significant. These results indicate that the suggested benefit of evening drug administration is not likely to be a result of diurnal variation in drug disposition.

Administration, Oral↗
PubMed1988

Prediction of outcome of decompression for carpal tunnel syndrome.

45 patients (55 hands) with carpal tunnel syndrome treated surgically have been studied. Painful nocturnal paraesthesiae occurred in patients with short histories and was a good prognostic feature. Electromyography proved of value in assessing motor lesions and the degree of the process. The first sign of muscle involvement was fibrillation potential. In longer histories, an increased amount of polyphasic potentials and reduced voluntary pattern was seen. The reduced pattern is reversible in cases of short duration and the absence of muscle wasting. In cases with marked alteration and signs of chronic muscle degeneration, the prognosis for pain is good, but not so for the neurological deficit. The nerve conduction velocity improved quickly after decompression of the median nerve in accordance with the complaints of the patient. Electrophysiological methods proved their value in staging and follow-up.

Adult↗
PubMed1988

Biologic characteristics and treatment of acute nonlymphocytic leukemia in children. Report of the ANLL Strategy Group of the Childrens Cancer Study Group.

Today approximately 75 per cent of children with ANLL can be induced into a complete remission and approximately 40 per cent will have an event-free survival for more than 3 years, irrespective of whether they received a bone marrow transplantation or chemotherapy after induction. In order to achieve these results very intensive therapy is required. The morbidity and mortality of treatment are high. The length of therapy needed after induction of remission is not known. Whether or not maintenance therapy is required is perhaps related most directly to the intensity of the therapy employed. Similarly, the role of bone marrow transplantation in patients in first remission, treatment of CNS leukemia, and treatment of chloromas are controversial. There is general agreement that WBCs over 100,000, acute monoblastic leukemia in infants less than 2 years of age, and certain chromosomal abnormalities are associated with a poor prognosis. Although there has been a dramatic improvement in the treatment of ANLL over the past 15 years, stratification of therapy based on biologic parameters, and alteration of treatment based on the early responses to treatment may be required before further advances will be made.

Acute Disease↗
PubMed1988

Prognostic significance of "short-term" effects of chemotherapy on MYC and histone H3 mRNA levels in acute leukemia patients.

We have found that administration of chemotherapy alters expression of growth-regulated genes in leukemia blast cells. To determine if such changes might be correlated with therapeutic outcome, we studied steady-state mRNA levels of MYC and histone H3 in the leukemic blasts of patients just prior to and 24 hr after the administration of the first doses of antileukemic drug therapy. Among nine patients with acute myelogenous leukemia, mRNA levels of MYC and histone H3 were reduced in five patients, and hematologic remission was achieved in three of these individuals. No remission was obtained in the four patients without reduction in MYC and histone H3 mRNA. Among acute lymphocytic leukemia patients, the mRNA levels of MYC and/or histone H3 were reduced by the therapy in seven of nine patients. A complete hematologic remission was obtained in five of them, and a partial remission was obtained in the other two. No remission was obtained in the patients in which MYC and H3 mRNA levels were unaffected by the therapy. These studies are of interest because they suggest that a decrease in the mRNA levels of MYC and histone H3 24 hr after a single dose of antineoplastic drugs may predict which patients will achieve complete remission; lack of reduction in these mRNAs correlates with failure to achieve remission. In addition, these studies also provide further proof of the heterogeneity of altered growth regulation among human leukemias.

Antineoplastic Agents↗
PubMed1988

Ethical or legal perceptions by dental practitioners.

Perplexing ethical and legal concerns cross health professions and reach into many professions and vocations. Confidentiality is crucial not only to the health professional and the patient, but also to the lawyer and client, and the investigative reporter and the source. Reporting poor work or whistleblowing is a dilemma not only for dentists and other health care professionals, but also for the engineer, architect, and federal employee, among others. This survey of the ethical or legal perceptions of the dental practitioner supports two conclusions: perplexing situations are perceived as predominantly ethical rather than legal problems and the factor of age (number of years in practice) might affect this trend toward the ethical consideration of complicated issues. Understanding the nature of these and other perplexing situations requires that dental practitioners step beyond the confines of their practice and the boundaries of the dental profession to search for more effective ways of dealing with, and therefore living with, the realities of their practice.

Age Factors↗
PubMed1987

Recombinant human macrophage colony-stimulating factor (M-CSF) requires subliminal concentrations of granulocyte/macrophage (GM)-CSF for optimal stimulation of human macrophage colony formation in vitro.

Human macrophage colony-stimulating factor (M-CSF or CSF-1), either in purified or in recombinant form, is able to generate macrophagic colonies in a murine bone marrow colony assay, but only stimulates small macrophagic colonies of 40-50 cells in a human bone marrow colony assay. We report here that recombinant human granulocytic/macrophage colony stimulating factor (rhGM-CSF) at concentrations in the range of picograms enhances the responsiveness of bone marrow progenitors to M-CSF activity, resulting in an increased number of macrophagic colonies of up to 300 cells. Polyclonal antiserum against M-CSF did not alter colony formation of bone marrow progenitors incubated with GM-CSF at optimal concentration (1-10 ng/ml) for these in vitro assays. Thus, GM-CSF at higher concentrations (nanogram range) can by itself, elicit macrophagic colonies, and at lower concentrations (picogram range) acts to enhance the responsiveness of these progenitors to M-CSF.

Animals↗
PubMed1987

Establishment and characterization of an undifferentiated human T leukemia cell line which requires granulocyte-macrophage colony stimulatory factor for growth.

A human leukemia cell line (TALL-101) was established from the bone marrow of a patient with an undifferentiated acute T cell leukemia using the conditioned medium (CM) of the human T cell leukemia virus (HTLV) II-transformed human cell line J-LB1. Immunofluorescence analysis on the original leukemic cells indicated the presence of T cell markers (Leu-1, Tdt, and T11); however, the established TALL-101 cell line expressed only antigens commonly present on progenitor cells, thymocytes, and myelomonocytic cells, but not on mature T cells. A high percentage of TALL-101 cells displayed the Tac antigen which was down-regulated upon incubation in the presence of recombinant human (rH) interleukin 2 (IL 2). Interferon (IFN)-gamma induced the appearance of class II histocompatibility leukocyte antigens (HLA) and of a T cell marker (3A1), and enhanced the expression of transferrin receptors on these cells. Further evidence for a T cell lineage of the TALL-101 cell line was provided by both chromosomic and genotypic analysis showing a translocation in chromosome 14 typical of T cell leukemias, and a rearrangement of the T-beta receptor locus. The growth-promoting activity in the J-LB1-CM was identified as granulocyte-macrophage colony stimulatory factor (GM-CSF), a growth factor which stimulates proliferation of normal myelomonocytic cells and other progenitor cells, but not known to have an effect on T cells. Dose response curves of [3H]thymidine incorporation and growth indicated that TALL-101 cells were sensitive to very low concentrations of rHGM-CSF, 5 ng/ml inducing maximal proliferation in chemically defined medium. The TALL-101 cell line is strictly GM-CSF-dependent for growth: upon depletion of GM-CSF from the culture medium, the cells stop proliferating immediately and die within 1 to 2 wk. The overall data, showing that GM-CSF is able to support the growth of a highly undifferentiated T cell leukemia, strongly suggests that this factor might have similar growth promoting effects on other immature T cell leukemias, and possibly, on normal T cell progenitors.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Differential diagnosis of syndromes with abnormal respiration (tachypnea-apnea).

Abnormal respiration with episodic tachypnea-apnea can occur in several syndromes (particularly, the Rett, Joubert, Mohr and Dandy-Walker syndromes). These syndromes are briefly reviewed. In the Rett syndrome, in contrast to in most other genetically determined syndromes, the onset of breathing abnormalities does not occur in the neonatal period.

Abnormalities, Multiple↗
PubMed1987

Growth factor requirements of childhood acute leukemia: establishment of GM-CSF-dependent cell lines.

Eight permanent cell lines were established from cells of 50 consecutive patients with childhood acute leukemia. Three cell lines required growth factor-containing conditioned media. Analysis using blocking antisera and recombinant granulocytic macrophage (GM) colony-stimulating factor (CSF) identified GM-CSF as a growth factor required to establish the latter three cell lines and necessary for their continuous proliferation in chemically defined medium. Two of the GM-CSF-dependent cell lines were derived from patients with undifferentiated T- and a biphenotypic B-myelomonocytic leukemia, which suggests that GM-CSF might maintain proliferation of leukemias originating from immature progenitor cells. Cytogenetic analysis indicated that all established leukemic cell lines were aneuploid, with six lines containing chromosomal alterations related to those observed in the leukemic cells of the patient. Two patients did not have an abnormal clone identified in the marrow but did yield an aneuploid cell line. These studies indicate that GM-CSF-dependent leukemic cell lines can be established in a fraction of childhood leukemia. These cell lines lend themselves to studies aimed at the evaluation in vitro of the role of growth factors in controlling proliferation and differentiation of leukemic cells.

Acute Disease↗
PubMed1986

Childhood Ki-1 lymphoma presenting with skin lesions and peripheral lymphadenopathy.

We describe a large-cell lymphoma of activated lymphoid cells in six children and adolescents. The presenting clinical features of regressing skin lesions and peripheral lymphadenopathy, sinus infiltration of lymph nodes, and infrequent tumor cell erythrophagocytosis resulted in initial diagnoses of malignant or regressing atypical histiocytosis in five cases. Binucleate and multinucleate tumor cells, sometimes with prominent eosinophilic nucleoli, resembled Reed-Sternberg (RS) cells and occasionally were found in a cytoarchitectural milieu that was consistent with a diagnosis of Hodgkin's disease (HD). The tumor cells did in fact express the HD-associated antigen Ki-1, but unlike most types of HD, the RS-like cells expressed common leukocyte antigen and were negative for Leu-M1. A T cell origin for the malignant cells was demonstrated with monoclonal antibodies in two cases, by focal staining for nonspecific esterase in one case, and by rearrangement of the beta-chain genes for the T cell receptor in a fourth case. These studies provide further evidence that some cases previously interpreted as malignant or regressing atypical histiocytosis and some types of HD are actually T cell disorders.

Adolescent↗