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Biomedical subjects

C Reading

Publications and source records attributed to C Reading.

At least 37 records · Page 2Linked to original sources

Further novel metabolites of the paraherquamide family.

Four novel metabolites of a Penicillium strain, IMI 332995, which has previously been reported to produce paraherquamide and a number of related metabolites, are herein described. VM55596 is the first N-oxide to be found in this family of compounds. Unusual oxidative substitution is also seen in VM55597. VM55599 appears to be the first documented example of the hexacyclic indole species that have long been postulated as biosynthetic precursors of metabolites of the brevianamide, paraherquamide and marcfortine families.

Animals↗

Polyclonal hematopoiesis in interferon-induced cytogenetic remissions of chronic myelogenous leukemia.

Interferon (IFN) therapy of early chronic myelogenous leukemia (CML) frequently produces partial or complete cytogenetic remission of the disease. Patients with complete cytogenetic remission often continue on therapy for several years with bone marrow showing only diploid (normal) metaphases. We studied hematopoiesis in five female patients with major cytogenetic remissions from CML during IFN therapy. Clonality analysis using the BstXI PGK gene polymorphism showed that granulocytes were nonclonal in all patients during cytogenetic remission. BCR region studies showed rearrangement only in the one patient whose remission was incomplete at the time of sampling. Granulopoiesis is nonclonal in IFN-induced remissions of CML and may be derived from normal hematopoietic stem cells.

Clone Cells↗

Differentiation and maturation of growth factor expanded human hematopoietic progenitors assessed by multidimensional flow cytometry.

Non-adherent cord blood and bone marrow mononuclear cells were analyzed by multiparameter flow cytometry before and at day 2, 4, 7, and 11 of culture in recombinant interleukin 3 (IL-3) and granulocyte colony-stimulating factor (G-CSF, cord blood) or stem cell factor (SCF), IL3 and granulocyte-macrophage colony-stimulating factor (GM-CSF, BM) to assess the differentiation and maturational pathway of myeloid cells. Before cell culture cord blood contained progenitor cells (CD34+) in various differentiation stages (CD38(-)----CD38bright), mature lymphocytes, monocytes, and neutrophils, but no immature neutrophils and immature monocytes. During cell culture, all CD34+ cells acquired the CD38 antigen between day 2 and 5 of cell culture, the CD34 antigen was lost between day 5 and 11 of cell culture. Differentiation of cells into the myeloid cell lineage was characterized by the acquisition of both CD33 and CD71. The latter is indicative for the active proliferation of these cells. Maturation of the cells into the neutrophilic pathway was indicated by the acquisition of first the CD15 antigen followed by CD11b and CD16 respectively. Whereas maturation of the cells into the monocytic pathway was indicated by the acquisition of first CD11b followed by CD14 and a dim expression of both CD15 and CD16. In normal bone marrow, cells of various maturational stages are already present before cell culture. During cell culture differentiation of cells into the myeloid lineage and maturation of the cells along the monocyte and neutrophilic lineage followed identical pathways as was observed before cell culture. Differentiation and maturational pathways of cord blood and adult bone marrow were identical. The results confirm the surface-antigen-defined pathways of myeloid cell differentiation described previously for non-cultured normal bone marrow aspirates. The detailed assessment of cell maturation and differentiation of cultured cells by multidimensional flow cytometry permits the determination of the specific effects of various recombinant human growth factors on myeloid cells.

Antigens, CD↗

Effect of deoxyribonucleic acid ploidy status on survival of patients with carcinoma of the endometrium.

This retrospective study was performed to determine the clinical usefulness of deoxyribonucleic acid (DNA) ploidy and the amount of DNA in the nucleus of the tumor cell on the prognosis of patients with carcinoma of the endometrium. Five year follow-up study was obtained for 121 patients. Flow cytometric analysis was used to determine tumor cell ploidy from paraffin-embedded specimens. Patients were grouped according to ploidy, clinical stage and grade and whether or not they received postoperative radiation. The data were subjected to a Cox proportional hazards regression analysis, and only ploidy status and clinical stage were significantly associated with survival time. Of the 121 patients observed, 44.6 per cent were aneuploid and 55.4 per cent, euploid. Preliminary chi-square analysis indicated a strong survival advantage to those patients with euploid endometrial carcinoma. The over-all five year survival rate for patients with aneuploid tumors was 53.7 per cent, as opposed to 80.6 per cent for patients with euploid tumors (p less than 0.01). Eighty-seven patients were Stage I, 39 aneuploid, 48 euploid. The five year survival rate for patients with Stage I aneuploid was 71.8 versus 85.4 per cent for those who were euploid. Twenty-one patients were Stage II; seven aneuploid and 14 euploid. The five year survival rate for aneuploid patients was 14.3 versus 85.7 per cent for euploid patients. The over-all five year survival rate for those with Stage I and II was 85.5 per cent euploid and 63.0 per cent aneuploid, p less than 0.05. Patients with Stage III or IV had poor outcome regardless of ploidy status. These data show that patients with euploid Stage I and II carcinoma of the endometrium have a significant survival advantage over patients with aneuploid tumors. We, therefore, believe that ploidy status may be used to facilitate the determination of prognosis in carcinoma of the endometrium.

Adenocarcinoma↗

Molecular analysis of retroviral transduction in chronic myelogenous leukemia.

We have developed a polymerase chain reaction (PCR) assay for detection of integrated retroviral transgenomes containing the neo G418 resistance gene in colonies (40 cells or more) grown in G418 selection after exposure to the neo-positive retrovirus LNL6. This assay also provides for simultaneous characterization of these colonies as belonging to a chronic myelogenous leukemic (bcr-abl positive) or nonleukemic population (bcr-abl negative). Using these techniques, we assessed transduction of the LNL6 retrovirus into the normal and leukemic cells of a blast-crisis chronic myelogenous leukemia (CML) patient. This work was designed to support the use of the LNL6 retroviral marker to help identify the origin of relapse after autologous marrow infusion. The data from these experiments show that the majority of CML blast crisis cells that, following exposure to the LNL6 virus, produce colonies under rigorous G418 selection are indeed transduced by the virus, as shown by the presence of the neo retroviral gene. Most of these colonies are also shown to be leukemic by PCR detection of the bcr-abl RNA. This demonstrates the feasibility of the study of CML marrow for retroviral marking. These procedures will be of use in establishing if relapse arises from leukemic blasts which contaminate purged autologous bone marrow infused following intensive therapy for leukemia.

Base Sequence↗

Activation of class I HLA expression by TNF-alpha and gamma-interferon is mediated through protein kinase C-dependent pathway in CML cell lines.

The combination of tumour necrosis factor alpha (TNF alpha) and gamma-interferon induced transcription of class I HLA genes in chronic myelogenous leukaemia (CML) cell lines through the formation of a complex between nuclear proteins and the transcriptional enhancers associated with these genes. Although gamma-interferon or TNF-alpha stimulated expression of class I HLA antigens in the EM2 and K562 CML cell lines when used alone, the effect of the combination of TNF-alpha and gamma-interferon was greater than that observed with either agent alone. The induction of class I HLA expression by gamma-interferon and TNF-alpha was inhibited completely by the isoquinoline sulfonamide H7, an inhibitor of protein kinase C. We conclude that the enhancement of the gamma-interferon induced transcriptional activation of class I HLA gene expression by TNF-alpha involves a protein kinase C-dependent pathway.

Base Sequence↗

A microassay for the determination of iodide and its application to the measurement of the iodination of proteins and the catalytic activities of iodo compounds.

A microassay system based on the effect of the catalytic Sandell-Kolthoff reaction of iodide on the oxidation of arsenic(III) by cerium(IV) was developed to measure iodine-containing compounds. This rapid assay uses small quantities of reagents, is suitable for use with a photometric microplate reader, can test many samples simultaneously, and eliminates problems associated with the use of radiolabeled compounds to measure iodination. It can detect picogram quantities of iodide. We report the use of this assay to measure the conjugation of an iodine-containing hapten (iodinated Bolton-Hunter reagent, IBHR) to ovalbumin and human serum albumin. It has proven to be excellent for studying the relative molar catalytic activity of the iodine-containing compounds IBHR, thyroxine, 4-iodophenol, and lithium 3,4-diiodosalicylate. The interference by azide on the assay was investigated.

Ammonium Sulfate↗

Hot flushes are induced by thermogenic stimuli.

Hot flushes were caused by hot drinks, alcohol, radiant heaters and thermal blankets in men undergoing treatment for carcinoma of the prostate and in menopausal women. Avoiding or changing these commonplace stimuli appears to reduce the frequency of flushing.

Aged↗

The content of tumor DNA as an indicator of prognosis in patients with T1N0M0 and T2N0M0 carcinoma of the breast.

To determine if the flow cytometric measurement of the content of the tumor DNA could provide prognostic information in T1N0M0 and T2N0M0 carcinoma of the breast, we isolated nuclei from paraffin-embedded tumor specimens from 128 consecutive patients who underwent modified radical mastectomy and were found to have a T1 or T2N0M0 carcinoma of the breast. The content of DNA of the nuclei was determined by flow cytometry. Although the average tumor size was not significantly different, 17 of 56 patients with aneuploid tumors died of cancer compared with 2 of 72 with euploid tumors. The 10-year overall actuarial survival rate of the euploid and aneuploid groups was 72% and 67%, respectively (p less than 0.02). A hazards model of the data shows that the DNA content of the tumor is the most significant indicator of prognosis, with a 2.25-fold increased risk of death for patients with aneuploid tumors. These data show that the tumor DNA content can be used to identify a group of patients with T1 or T2N0M0 carcinoma of the breast with the same prognosis as a group of patients without carcinoma of the breast that would be unlikely to benefit from adjuvant therapy.

Adult↗

The effects of clavulanic acid and sulbactam on beta-lactamase biosynthesis.

Clavulanic acid and sulbactam were tested as inducers of beta-lactamase in 21 strains of Gram-negative bacteria. beta-Lactamase synthesis was inducible in all these strains, as demonstrated by the increased enzyme activities obtained when cells were grown in the presence of 10 mg/l of cefoxitin, the increase varying from 11- to 734-fold However, at the same concentration, neither inhibitor induced significant amounts of beta-lactamase, except in one strain of Providencia rettgeri, where both were potent inducers. When steps were taken to overcome the inhibitory effects of clavulanic acid and sulbactam, they were still found to be ineffective inducers. We conclude that, at therapeutic concentrations, clavulanic acid and sulbactam are generally poor inducers of beta-lactamase. Amoxycillin and ampicillin induced more beta-lactamase than the inhibitors, but were much less effective than cefoxitin, except for the strain of Prov. rettgeri.

Clavulanic Acids↗

Sympathetic nervous system and dysfunction of the lower urinary tract.

Careful clinical and investigative protocols allow the identification of a homogeneous group of patients with prostatodynia or 'anxious bladder syndrome' (underactive detrusor function). Psychophysiological studies and urodynamic measurements in such patients demonstrate remarkably consistent results, which, whilst lending support to the hypothesis that the sympathetic nervous system may effect bladder and urethral function, do not offer objective proof that adrenergic mechanisms are directly responsible for the observed dysfunctional state. observed dysfunctional state.

Humans↗

Inhibition of the beta-lactamases of Branhamella catarrhalis by clavulanic acid and other inhibitors.

The beta-lactamases of Branhamella catarrhalis Ravasio and strain 1908 were readily inhibited by low concentrations of sulbactam, beta-halopenicillanic acids, MM 13902 and clavulanic acid. More detailed studies on the interaction of the Ravasio beta-lactamase with clavulanic acid demonstrated that the enzyme had high affinity for the inhibitor (Ki = 0.07 mumol/L) and was rapidly inhibited (t1/2 = 21 sec, kinhib. = 0.033/sec). Two types of enzyme-inhibitor complex were formed, a transiently stable species (t1/2 = 5.3 minutes at pH 7.3 and 37 degrees C) and a more stable species (t1/2 approximately equal to 2 hours at pH 7.3 and 37 degrees C). Irreversible inactivation of the enzyme was not achieved. Permeability studies on whole cells showed that beta-lactam antibiotics and beta-lactamase inhibitors readily penetrated the outer membrane of B. catarrhalis.

Cell Membrane Permeability↗